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Content Medical Journal (2014) Vol. 20, No. 2

Original articleThe importance of asthma control test (ACT) in asthma control level assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77Belma Paralija

Assessing the level of dental care to the prevalence of dental caries among school children in Central Bosnia Canton . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81Aida Šaban, Sead Karakaš, Orhan Šaban, Nejra Džananović, Marina Delić–Šarac, Suvada Švrakić, Ognjen Riđić

Gender comparison of serum asymmetric dimethylarginine and C-reactive protein concentration in patients with diabetes mellitus type 2 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85Asija Začiragić, Berina Hasanefendić, Nesina Avdagić, Orhan Lepara, Nermina Babić, Jasminko Huskić, Nedžad Mulabegović

Comparative analyses of the effect of surgical weakening of inferior oblique muscle overaction on binocularity . . . 91 Jasmina Alajbegović–Halimić, Denisa Zvizdić, Haris Tanović

Incidence and risk factors of complications after tonsillectomy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96Lana Sarajlić, Adnan Kapidžić, Jusuf Šabanović, Haris Tanović, Igor Gavrić, Ismar Rašić

Efficiency of conservative treatment of postpartum hemorrhages caused by uterine atony . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99 Mohamad Abou El-Ardat, Zulfo Godinjak, Nermin Hadžić, Naima Imširija, Aida Dizdarević, Eldar Mehmedbašić, Armina Rovčanin

Psychiatric comorbidity among opiate addicts on methadone substitution treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102 Rasema Okić

Imbalanced values of highly reactive molecule nitric oxide in schizophrenia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 106Amra Memić, Abdulah Kučukalić, Lilijana Oruč, Jasminko Huskić

Epidemiological and clinical characteristics of childhood lymphoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 110Edo Hasanbegović, Nermana Čengić, Meliha Sakić, Adela Tunić, Senada Mehadžić

Secondary osteoporosis in hospital sample . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116Ksenija Miladinović, Narcisa Vavra-Hadžiahmetović, Slavica Šakota, Damir Čelik, Haris Tanović

Professional articleMost common etiologies of neurogenic laryngeal paralysis in middle-aged patients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120Mirjana Gnjatić, Daniela Kesić Mijić, Tatjana Barać, Svjetlana Trifunović

Surgery and endoscopic treatment in children with vesicoureteral reflux . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 124Murat Berisha, Nexhmi Hyseni, Salih Grajqevci, Sejdi Statovci, Ali Aliu

Blood pressure oscilation during carotid endarterectomy in superficial cervical plexus block . . . . . . . . . . . . . . . . . . . . . . . . . . 127Dragan Milošević, Darko Golić

Case reportUterine anomalies and pregnancy outcome: uterus unicornis cum cornum rudimentarium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 130Lejla Imširija, Naima Imširija, Mohamad Abou El-Ardat, Fatima Gavrankapetanović

Hemorrhagic fever with renal syndrome and coexisting hantavirus pulmonary syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132 Duško Anić, Emina Vukas, Almira Kadić

Review article

Surgical treatment of traumatic flail chest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134 Dušan Janičić, Bojan Gulić, Zoran Roljić, Velibor Škrbić

Instructions to authors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 136

Uputstva autorima . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 138

Medical Journal (2014) Vol. 20, No. 2, 77 - 80 Original article

The importance of asthma control test (ACT) in asthma control level assessment

Značaj astma kontrol testa (ACT) u određivanju kontrole astmeBelma Paralija*

Clinic of Pulmonary Diseases, Clinical Centre University of Sarajevo, Bolnička 25, 71000 Sarajevo, Bosnia and Herzegovina

*Corresponding author

ABSTRACT

Introduction: GINA guidelines recommend asthma treatment ac-cording to asthma control level. Aim: to assess asthma control level using Asthma control test (ACT) questionnaire and FEV1 measure-ment. Patients and methods: the patients diagnosed with bronchial asthma, who attended asthma school in the period from 2010 to 2011 at the Clinic of Pulmonary Diseases, were included in this study. At first ACT questionnaire was self completed by patients. ACT con-tains five questions, regarding the frequency of daily symptoms, night symptoms, reliever use, the potency of daily activities performance in the last 4 weeks, as well as patient asthma assessment by their own. Each answer was scored from 1 (poor control) to 5 (good control) and the scores were added to give a final score with a maximum of 25 points. The range of 20-24 points was considered as good asthma control. A cutoff score of 19 or less identified patients with poorly controlled asthma. Furthermore, the pulmonary function test was performed, and FEV1 values in percent were particularly notified. Results: 38.96% of the total number of examined patients (n=154) were males, and 61.04% females. Total asthma control (25 points) was achieved in 1.95% patients; good control in 30 patients (19.48%), while 78.57% of patients achieved less than 20 points, that means poorly controlled asthma, which is directly in connection with the increased risk of asthma exacerbation. 61.04% of patients achieved FEV1 of 60-80% predicted values; less than 60% of FEV1 was notified in 28.57% of patients. FEV1 higher than 80% of the predicted values was notified in 10.39% of patients. 48.76% of patients with poorly controlled asthma found their asthma good (4 points) and totally con-trolled (5 points). Conclusion: ACT questionnaire is a simple tool for assessing asthma control with/or without pulmonary function testing. It rathershortens the time needed for symptom assessment, identifies the patients with uncontrolled asthma as well as facilitates physicians ability to follow patient’s progress with treatment.

Key words: asthma control questionnaire, asthma control

SAŽETAK

Uvod: GINA smjernice preporučuju liječenje astme u odnosu na razinu njene kontrole. Ciljevi istraživanja: primjenom astma kon-trol testa (ACT) i mjerenjem FEV1 odrediti stepen kontrole astme. Pacijenti i metode: u studiji su učestvovali pacijenti sa dijagnozom bronhijalne astme, a obuhvaćeni programom astma škole u periodu od 2010-2011. godine na Klinici za plućne bolesti. ACT upitnik, koji su sami pacijenti popunjavali, sastavljen je od pet pitanja, a ona se odnose na učestalost dnevnih, noćnih simptoma astme, korištenje inhalatora brzog djelovanja, mogućnost obavljanja dnevnih aktiv-nosti u posljednje 4 sedmice, a na kraju subjektivna ocjena astme od strane samog pacijenta. Svaki odgovor je bodovan ocjenom od 1 (loša kontrola) do 5 (dobra kontrola), sa mogućim maksimalnim rezultatom od 25 bodova. Rezultat od 20-24 boda se smatrao do-brom, a ispod 20 bodova lošom kontrolom astme. Nakon toga je pacijentima urađeno ispitivanje plućne funkcije, a posebno su regis-trovane vrijednosti postignutog FEV1 u procentualnim vrijednostima. Rezultati: od ukupnog broja ispitivanih pacijenata (n=154) 38.96% su osobe muškog, a 61.04% ženskog spola. Potpunu kontrolu astme (25 bodova) je postiglo 1.95% pacijenata; dobru kontrolu 30 pacije-nata (19.48%), a rezultat ispod 20 bodova je zabilježen kod 78.57% pacijenata, što podrazumijeva lošu kontrolu bolesti, koja je direkt-no povezana sa povećanim rizikom od egzacerbacije astme. 61.04% pacijenata je postiglo FEV1 od 60-80%; ispod 60% vrijednost FEV1 je postiglo 28.57% pacijenata, a 10.39% pacijenata FEV1 iznad 80%. 48.76% pacijenata sa lošom kontrolom astme smatra da je njihova astma dobro (4 boda) i potpuno pod kontrolom (5 bodova). Zak-ljučak: ACT upitnik je jednostavno sredstvo za praćenje kontrole astme u kombinaciji sa/ili bez testiranja plućne funkcije. Znatno sk-raćuje vrijeme potrebno za procjenu simptoma i identificira pacijente sa nekontrolisanom astmom i olakšava dalje praćenje napretka u li-ječenju pacijenta.

Ključne riječi: astma kontrol test, kontrola astme

INTRODUCTION

Asthma is a chronic inflammatory disease of the airways that causes recurring episodes of wheezing, breathlessness, chest tight-

ness and coughing, particularly at night or in the early morning. Asthma control is assessed by symptoms, activities of daily living and quality of life. It also includes the likelihood of loss of control, exacerbations, decline in respiratory function, and the side-effects

of treatment. The primary goals of asthma management are: 1) to achieve and maintain control of symptoms and 2) to prevent asthma exacerbations. In many cases, it is also possible to improve and/or maintain respiratory function, to retain normal activity levels, to prevent the development of irreversible airway narrowing and to prevent deaths from asthma. Clearly, it is also desirable to avoid short and long-term adverse events from asthma medication. GINA guidelines also recommend asthma treatment according to asthma control level (1). ACT is a patient self-assessment tool of asthma control (2, 3). ACT was developed by Nathan et al., in 2004 and was described as a patient-based tool for identifying patients with poorly controlled asthma. ACT contains five questions, regarding the frequency of daily symptoms, night symptoms, reliever use, the potency of daily activities performance in the last 4 weeks, as well as patient asthma assessment by their own (2). Objectives of the study: to assess asthma control level using ACT and FEV1 measurement.

MATERIALS AND METHODS

The patients diagnosed with bronchial asthma, who attended asthma school in the period from 2010 to 2011 at the Clinic of Pul-monary Diseases, were included in this study. At first ACT question-naire was self completed by patients.

ACT (Figure A) contains five questions, regarding the frequency of daily symptoms, night symptoms, reliever use, the potency of daily activities performance in the last 4 weeks, as well as patients asthma assessment by their own. Each answer was scored from 1 (poor control) to 5 (good control) and the scores were added to give a final score with a maximum of 25 points. The range of 20-24 points was considered as good asthma control. A cutoff score of 19 or less identified patients with poorly controlled asthma. Further-more, the pulmonary function test was performed, and FEV1 values in percent were measured.

RESULTS

The total of 154 patients were examined. Out of total number of the examined patients 38.96% (n=60) were males, and 61.04% (n=94) females. There was a significant difference in sex distribution in favour of females (χ2=7.506; df=1; p=0.006) (Figure 1).

Analysis of age group distribution reported that the most common age group was of 45-54 years (n=42). There was a significant differ-ence in the number of the examined patients related to the age group (χ2=23.74; df=5; p=0.001) (Figure 2).Figure A

78 B. Paralija

!

Figure 1 Sex distribution of examined patients.

Figure 2 Distribution of examined patients according to age groups.

The results of ACT questionnaire, that was self completed by patients, are presented in Figure 3. Total asthma control (25 points) was achieved in 3 patients (1.95%); good control in 30 patients (19.48%), and 121 patient (78.57% ) achieved less than 20 points, that means poorly controlled asthma, which is directly in connection with increased risk of asthma exacerbation. There was a significant difference in the number of patients according to the ACT score (χ2=141; df=1; p=0.001).

90 patients (61.04%) achieved FEV1 of 60-80% of the predict-ed values; less than 60% FEV1 was notified in 42 patients (28.57%). FEV1 higher than 80% of the predicted values was notified in 22 pa-tients (10.39%). There was significant difference (χ2 =47.58; df=2; p<0.05) (Figure 4).

The positive significant correlation between ACT results and FEV1 values is presented in Figure 5, that was proved by Pearson correlation (r=0.834; p=0.001).

The total number of patients with ACT score <20 points (poor-ly controlled asthma) was 121 (100%). Of all patients with poorly controlled asthma, 48.76% (n=59) of patients found their asthma good (4 points) (n=42; 34.7%) and totally controlled (5 points) (n=17; 14.05%) (Table 1).

DISCUSSION

Females are more affected by asthma than males as reported in the literature (4). In our study there was also significant difference in sex distribution in favour of females. The individuals over 34 years are commonly affected by asthma (4,5). ACT is a patient self-assessment tool of asthma control (2,3). ACT was developed by Nathan et al., in 2004. In their article the development of the ACT was described as a patient-based tool for identifying patients with poorly controlled asthma. Methods of the study: a 22-item survey was administered to 471 patients with asthma in the offices of asthma specialists. The specialists’ rating of asthma control after spirometry was also collected. Results: five items were selected from regression analyses. The internal consis-tency reliability of the 5-item ACT scale was 0.84. ACT scale scores discriminated between groups of patients differing in the specialist’s rating of asthma control (F=34.5, p<.00001), the need for change in patient’s therapy (F=40.3, p<.00001), and percent predicted FEV1 (F=4.3, p=.0052). As a screening tool, the overall agreement between ACT and the specialists’ rating ranged from 71% to 78% depending on the cut points used, and the area under the receiver operating characteristic curve was 0.77. The authors have conclud-ed that results reinforce the usefulness of a brief, easy to administer, patient-based index of asthma control (ACT is clinically validated against spirometry and specialist assessment) (2). In the literature, ACT has been reported as reliable (test-retest reliability was 0.77). Internal consistency is also proved (Cronbach’s α=0.84-0.85 (crossectionally); 0.79 (longitudinally). Test validity: it correlates with specialists’ rating of asthma control determined based on history, physical examination and FEV1. The minimally important difference is 3 points between two groups or for changes over time. It has some limitations: it has a multidimensional construct, however does not include objective measures of airway caliber (6). In our study the positive significant correlation between ACT re-sults and FEV1 values was proved by Pearson correlation (r=0.834; p=0.001).

The importance of asthma control test (ACT) in asthma control level assessment 79

Figure 4 Results of FEV1 values.

Figure 5 Correlation of ACT results and FEV1 values.

Figure 3 Results of ACT questionnaire.

PATIENTS OVERALLSELF-ASSESSMENT OF ASTHMA CONTROL

NUMBER OF PATIENTS n

%

GOOD CONTROL (4 points)

42 34.71

TOTALLY CONTROLLED (5 points)

17 14.05

NOT CONTROLLED (1-3 points)

62 51.24

TOTAL (n=121) 100%

Table 1 Patients overall self-assessment of asthma control in the group with poorly controlled asthma (according to ACT score).

Other authors evaluated the reliability and validity of the ACT in a longitudinal study of asthmatic patients new to the care of an asth-ma specialist (the total number of patients 313). Internal consisten-cy reliability of the ACT was 0.85 (baseline) and 0.79 (follow-up). Test-retest reliability was 0.77. Criterion validity was demonstrated by significant correlations between baseline ACT scores and base-line specialists’ ratings of asthma control (r=0.52, p<.001) and ACQ scores (r=-0.89, p<.001). Discriminant validity was demonstrated, with significant (p<.001) differences in mean ACT scores across pa-tients differing in asthma control, pulmonary function, and treatment recommendation. Responsiveness of the ACT to changes in asthma control and lung function was demonstrated with significant correla-tions between changes in ACT scores and changes in specialists’ rat-ings (r=0.44, p<.001), ACQ scores (r=-0.69, p<.001), and percent predicted FEV1 values (r=0.29, p<.001). An ACT score of 19 or less provided optimum balance of sensitivity (71%) and specificity (71%) for detecting uncontrolled asthma. The authors proved the ACT as reliable, valid and responsive to changes in asthma control over time in patients new to the care of asthma specialists. A cutoff score of 19 or less identifies patients with poorly controlled asthma (3). The ACT was responsive to change at the initiation of asthma treatment and was useful for the initiation of asthma treatment (7). It was recognized by the National Institutes of Health (NIH) in its 2007, Asthma guidelines (8). Other authors also support their use in clinical decision making (9). In the survey of other authors, 54% of New Zealand patients with asthma were not controlled (10). In our study 78.57% of pa-tients achieved less than 20 points according to the ACT scale, that means poorly controlled asthma, which is directly in connection with increased risk of asthma exacerbation. The researches have showed that asking specific questions is much more likely to pick up uncontrolled symptoms. In reality, lots of people think their asthma is better controlled than it actually is (11). In our study, of all patients with poorly controlled asthma, 48.76% of patients found their asthma good (4 points) and totally controlled (5 points).

CONCLUSIONS

ACT is a simple tool for assessing asthma control with/or with-out pulmonary function testing. There’s positive significant correla-tion between ACT results and FEV1 values. It’s a patient-based tool for identifying patients with poorly controlled asthma (a cutoff score of 19 or less). Results reinforce the usefulness of a brief, easy to administer, patient-based index of asthma control, that rather short-ens the time needed for symptoms assessment. Clinical implications; In a clinical setting the ACT should be a useful tool to help physicians identify patients with uncontrolled asthma and facilitate their ability to follow patients’ progress with treatment. Recommendations; be-fore alteration of drug therapy, the following should be considered:

1) Is the diagnosis correct? 2) Are there any correctable trigger fac-tor (including occupation)? 3) Does the patient have allergic rhinitis (treatment of those may help asthma control)? 4) Is there patient‘s compliance with the existing therapy? 5) Is the patient able to use his/her inhaler properly?

Conflict of interest: none declared.

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Reprint requests and correspondence:Paralija Belma, MD, PhDClinic of Pulmonary DiseasesClinical Centre University of SarajevoBardakčije 9071 000 SarajevoBosnia and HerzegovinaPhone: +387 33 444 343Email: [email protected]

80 B. Paralija

Medical Journal (2014) Vol. 20, No. 2, 81- 84 Original article

Assessing the level of dental care to the prevalence of dental caries among school children in Central Bosnia Canton

Procjena nivoa stomatološke njege s obzirom na rasprostranjenost karijesa kod djece školskog uzrasta u Kantonu Srednja BosnaAida Šaban1*, Sead Karakaš2, Orhan Šaban3, Nejra Džananović4, Marina Delić–Šarac4, Suvada Švrakić5, Ognjen Riđić6 1Primary Health Center Travnik, 72270 Travnik, Bosnia and Herzegovina; 2Public Health Institute of the Central Bosnia Canton, 72270 Travnik, Bosnia and Herzegovina; 3Public Institution Hospital Travnik, 72270 Travnik, Bosnia and Herzegovina; 4Institute of Clinical Immunology, Clinical Center University of Sara-jevo, Bolnička 25, 71000 Sarajevo, Bosnia and Herzegovina; 5Department for Quality Improvement and Safety of Health Services, Clinical Center University of Sarajevo, Bolnička 25, 71000 Sarajevo, Bosnia and Herzegovina; 6International University of Sarajevo, Management and Leadership studies, Hrasnička cesta 15, 71210 Ilidža, Bosnia and Herzegovina.


ABSTRACT

By promoting the proper oral hygiene and maintaining the same, the formation of cavities, and thus, associated oral hygiene compli-cations can be minimized. By examining the level of dental care with an impact on oral hygiene the important results will be obtained, which can be useful through the analysis of policies, guidelines and activities in promoting the oral hygiene. The study was designed as a cross-sectional study. The survey instrument was used for the survey interview and clinical examination of the mouth and teeth to provide data on the oral health of the examined children. The Survey instrument consisted of observation units in selected schools in the stage of choice within these departments-selected groups of students. At the same time, this suggested our decision to use the application of two-phased stratified sample of compatible groups. A dental examination was carried out and the survey of 804 prima-ry school students, where 355 students were from the urban and 449 students from the rural schools. The obtained results showed that, in elementary schools in Central Bosnia Canton, the “Decayed, Missing and Filled Teeth” (abr. DMFT) index was fairly uniform. Ac-cording to the results of examinations, we could see that the num-ber of visits to the dentist was more common, among respondents, from urban than the rural areas. This finding can be directly related to statements and results from the part of the socio-economic sta-tus, where we had the answers on the availability of and closeness to the dentist, as well as the possession of automobile and financial capabilities, all of which were much less prevalent in rural areas than urban. The largest number of respondents stated that they feared dental visits. This finding represents a remarkable health-promotion problem, which we, as health /dental care workers and the society, as a whole, must further analyze and improve upon.

Key words: prevention, dental caries, school children

SAŽETAK

Promocijom pravilne oralne higijene i održavanje iste na-stanak karijesa, a samim time i komplikacija u oralnoj higijeni, svodi se na minimum. Ispitivanjem nivoa stomatološke zaštite uz utjecaj na oralnu higijenu dobit će se značajni pokazatelji koji nam mogu korisiti kroz analizu politika, smjernica i aktivnosti u promicanju oralne higijene. Istraživanje je dizajnirano kao studija presjeka. Kao instrument istraživanja bila je korištena anketa-in-tervju, kao i stomatološki pregled usta i zuba za dobijanje poda-taka o oralnom zdravlju ispitivane djece. Izvršilo se anketiranje svih jedinica posmatranja u izabranim školama i u etapi izbora u okviru njih izabrana odjeljenja-skupina učenika. Ovo istovreme-no znači opredjeljenje za primjenu dvoetapnog stratifikovanog uzorka kompatibilnih skupina. Izvršen je stomatološki pregled i anketiranje 804 učenika osnovnih škola, pri čemu je 355 učeni-ka iz urbanih škola, a 449 učenika iz ruralnih škola. Dobijeni su rezultati koji govore da je vrijednost KEP indeksa u osnovnim školama na području Srednjobosanskog kantona prilično ujedna-čena. Prema rezultatima ispitvanja možemo vidjeti da je broj po-sjeta zubaru mnogo češći kod ispitanika iz urbane nego iz ruralne sredine, što može biti u direktnoj vezi s izjavama i rezultatima iz dijela o socioekonomskom statusu, gdje smo imali odgovore o dostupnosti i blizini posjete zubaru kao i posjedovanju automo-bila i f inansijskim mogućnostima koje su mnogo manje u rural-nim sredinama nego urbanim. Najveći broj ispitanika izjavio je da se plaši posjete stomatologu, što predstavlja izuzetan zdrav-stveno-promotivni problem koji zdravstveni profesionalci iz ove oblasti moraju analizirati i dalje unapređivati.

Ključne riječi: prevencija, zubni karijes, školska djeca

INTRODUCTION

Dental caries is a chronic disease that progresses very slowly and the symptoms are difficult to detect. Sometimes it takes a year from the start of the process, until the first symptoms occur. Fi-nally, the decay of tooth is manifested at the affected substances (i.e. enamel, dentin and tooth root) (1). From the idea that worms caused tooth decay, which occurred 200 years before Christ, until today, there were numerous theories about the process of decay. Today, it is considered that the caries disease is caused by many different organisms, most notably Streptococcus mutants’. Important epidemiological evidence links Streptococcus mu-tants with caries. The numerous laboratory studies have shown the ability of these types of streptococci to produce lactic acid, which causes demineralization of enamel (2). Dental plaque plays an im-portant role in caries development, which is a soft, hard discernible layer, which firmly adheres to the wall of the tooth. Since the pa-tient cannot wash it off, it must be mechanically removed. Plaque begins to form immediately after tooth brushing. First, it creates a thin surface coating (called “pellicle”), which becomes inhabited by bacteria. Bacteria develop using the metabolic products and other ingredients from saliva and food. Full plaque formation ends in about seven days (3). By exploiting carbohydrates, the bacteria in dental plaque produce acids, which in contact with the enamel leads to its demineralization. At the beginning, while still working on immature plaque (i.e. somewhat clean teeth), it is possible that the processes of regen-eration or enamel re-mineralization can occur by the various saliva ingredients. De-mineralization and re-mineralization processes take place until the plaque is not mature. Mature plaque, on one hand, prevents the flow of saliva to the teeth, and on the other hand, does the same to the inside of plaque. Bacteria can reach the small molecules of sucrose (sugar), which acidic decomposition products maintain the degree of plaque acidity (pH), with the critical value of 5.2, which favors the formation of dental caries (eng. carries gen-esis). The result is irreversible enamel de-mineralization, in other words, this represent compensatory mechanisms within the oral cavity, which cannot be treated. This development marks the be-ginning of creation of initial caries lesions (initial damage) (4). Tooth decay is caused by damage to the hard bone tissue, which leads to their softening and destruction. A child is born with a sterile oral cavity. Colonization of the oral environment microorganisms must be prevented because they are normal inhabitants of the oral cavity and are responsible for the development of the immune system of the child. Streptococcus mutants group, to inhabit the eruption of the first teeth, are usually transmitted directly from mother to the child (vertical transmission) (5). Cavities can also be called a dental disease that begins at the surface and spreads to the core, or pulp, and it is reflected in the gradual destruction of enamel and then the dentin. Factors that cause tooth decay, as well as the theory that explains the origin and evolution suggest that caries may be close-ly related to the general state of the organism (6). New theories about the origin of caries explain the resistance of tooth decay in the presence of physiological balance in the system of blood-tooth-sa-liva. If you damage the function of this system, which is unique, as a whole, you will create a new pathological condition - dental caries. The anatomical-morphological and pathological and clinical terms

may vary, such as: enamel caries or the start of the first degree car-ies. The effects of acids that form the first fermentation are subject to organic substance enamel. As the result of this process, we can notice the lime-white dot that is clearly different from the surround-ing yellowish-white healthy tissue. At this stage, the sensitivity to physical stimuli, such as, cold, hot, sour and/or sweet does not exist or is very weak. This decay of enamel occurs in fissures and pits or on the smooth surfaces of teeth. Dentine caries is the second level of caries. The most common cause of the spread of the process is enamel. It manifests itself as a relatively narrow opening in the enamel, which covers the edges of a cavity in dentin. Dentin damage consists of a cavity that is formed due to the loss of tissue. Softened dentin is free of mineral salts and its organic structure is changed by the microbes (7). In this dentin we can detect the presence of various types of microorganisms, such as, lactobacilli or micrococ-cus. The so-called zone invasion occurs as amended, below softened dentin zone or in the area of ducts filled with microbes and tissue that are completely softened and destroyed. Dentine caries can ex-ist without subjective complaints. It is revealed by careful examina-tion or by the sensitivity to cold, less warm and moderately sour and sweet food or water. Penetrating cavities in some cases represent a rapid evolution in the direction of the pulp and reach fast the pulping chamber. This flow of decay is seen in dairy and permanent teeth. Cavities are usually localized to premolar and molar fissure. Circular decay is a special type of dental caries, in its course, localization and outcome. It occurs in young children, as early as the second year of age. It covers dairy upper front teeth. It starts on the labial surfaces as the murky green stain that spreads circularly around the neck of the tooth, and dentin, and then continues to completely destroys the crown of the tooth. It is very likely caused by the frequent effect of carbohydrates (i.e. sweetened dummy) and various endogenous and exogenous influences. If left untreated, it spreads to the pulp and leads to its illness. The further progress of the disease may lead to changes at the top of the tooth root and damage to the sur-rounding tissue (8). Treatment consists of preventing caries and it plays a significant role in a way to take care of the mouth and teeth. Wash your mouth and teeth using toothbrush and toothpaste, in the morning and evening, preferably after each meal. It is useful to know that if sugar remains long in contact with the teeth, it causes caries. The preventive measures include early detection of initial damage, which is why it is recommended to have a dental check-up every six months, or at least once a year (9).


To test the level of dental care unit we used the questionnaire and dental examination. We surveyed 804 students in elementa-ry school, where 355 students were from the urban schools and 449 students from the rural schools. The study was designed as a cross-sectional study. The survey instrument was used for the sur-vey interview and clinical examination of the mouth and teeth to provide data on the oral health of children examined. The survey was comprised of observation units in selected schools at the stage of choice, within these departments-selected groups of students. We also utilized a two-phased stratified sample of compatible groups.

82 A. Šaban et al.

Planned pattern in all municipalities was satisfactorily achieved.In general, all elections units were covered by the sample. The units of analysis, as seen from the sample project, were envisaged as a random expected size, and therefore the realization of samples of special importance for each analytical unit was achieved. In addition to numerical methods in the analysis of the results of this study graphical analysis methods were also used, namely:

- Bar charts, horizontal and vertical parallel to the presentation of the structure and characteristics within and between individual municipalities,

- Circular charts for displaying the structure,- Combination charts for showing the structure of those units of

analysis that have analyzed characteristic,- Graphs to show the confidence interval for the probability

p=95%, in which we should expect that it will move its value in the basic group and the obtained values from the sample.

Work methods and plan of action:1. Creation of questionnaires and publicity materials and2. Education of working team members. The members were fa-

miliar with the available data on oral hygiene habits and their impact on oral health, various techniques and tools for proper oral hygiene, and tools and techniques for the determination of OHI (index oral hygiene).

3. Data were collected by conducting surveys in classrooms (one class from each age group selected within primary schools) and filling out questionnaires with the assistance of members of the survey team in order to help determining the status and oral hygiene index.

4. At the end, data analysis and evaluation was performed.

RESULTS

Assessment of the level of dental care was conducted on the basis of dental surveys carried out at urban schools in Travnik, Kali-bunar, then in rural schools in Guča Gora, Turbe, Mehurići, Karaula and Vitovlje. It was based on KEP index, the number of healthy teeth with fillings, extracted teeth, as well as the insight into the state of oral hygiene of each child. On the basis of responses to a group of questions related to the method of maintaining daily oral hygiene, the number of visits to the dentist, knowledge of proper brushing, and generalized oral hygiene, the following results were obtained:

According to the table listed above, we can see that the DMFT index, in elementary schools in Central Bosnia Canton was fairly uni-form. The lowest value of 2.9, in girls, was measured at the Primary school Guča Gora – Travnik, while the girls in elementary school at Kalibunar had the largest value of 4.8. KEP value index. In boys, that value was the largest at the elementary school in Travnik, with the measured value of 4.4, while the youngest boys from the Primary school at Vitovlje, had the value of 3.3.

DISCUSSION

By posing a group of questions related to the status of oral hy-giene in patients we received the insights about their state of oral milieu. Therefore, we could clearly see that a large number of re-spondents had not learned how to wash their teeth properly and how to maintain the oral hygiene. A large number of respondents had already visited the dentist, but on average 1-3 times. This find-ing represents a very worrying fact that a large number of respon-dents from the urban areas visited a dentist in the projects 7-9 times, compared to significantly less number by children from rural areas. Fear of the dentist was observed in both groups in the same pro-portion. A disturbing fact was that a very small number of respon-dents received any advice from a dentist or some pharmacological substances to improve the oral hygiene milieu. Poor enlightenment and promotion of oral hygiene certainly affected the answers to the question of how many times a day the respondents brushed their teeth, and the largest number of respondents reported twice a day, while the large number of respondents from the urban areas made irregular oral hygiene milieu (10). Oral hygiene habits among prima-ry school students cannot receive the most positive assessment, due to the fact that the answers and the results of the survey showed otherwise (11). As the important factor can be considered a large number of unenlightened subjects, 18.25% in the urban environ-ment, which stated that they were not familiar with regular brushing and nobody showed them the proper way of brushing (12). As a predominant factor in this troubling development could also be con-sidered a poor oral hygiene promotion, due to the large number of respondents who were not familiar with the means to strengthen teeth totaling 79.62% (out of which 35.5% from the urban areas and 44.12% from the rural areas) (13).

CONCLUSION

According to the examinations’ results, we could clearly see that the number of visits to the dentist was more common among re-spondents from the urban than the rural areas, a finding which can be directly related to statements and results linked to respondents’ socio-economic status, where we had the answers on the availability of dental services and closeness to the dentists, as well as having a motor vehicles and financial capabilities that were much less avail-able in the rural, as opposed to the urban areas. Most of the respon-dents stated that they feared dental visits, which poses a remarkable health-promotion problem, on which the scientists and legislators must conduct a further research and information campaigns in order to further analyze and improve the overall state of the oral health. Most of the respondents in both urban and rural areas stated that

Assessing the level of dental care to the prevalence of dental caries among school children in Central Bosnia Canton 83

Elementary School (E.S.) Sex Caries Filings Extractions Fissures sealed DMFT

MŽMŽMŽMŽMŽMŽMŽ

E.S. ¨TRAVNIK¨ Travnik

E.S. ¨KALIBUNAR¨ Travnik,Total: 29

E.S. ¨Karula¨ Travnik, Total: 48

E.S. ¨Guča Gora¨ Travnik Total 55

E.S. ¨Turbe¨ Travnik Total: 145

E.S. ¨Viovlje¨ Travnik Total 45

E.S. „Mehurići“ Travnik Total 156

18414223629192926885722328076

31021337114328473214886263610573

3162063594732432813295263311679

18416225930193216825722308484

189200010000100

4,44,14,24,84,14,14,22,94

4,13,34,53,83,2

Table 1 Summary overview of analyzed data.

Rural areas 1 – 10% 2- 25% 3 – 45% 4 – 15% 5 – 5% Urban areas 1 – 15% 2 – 15% 3 – 55% 4 – 15% 5- 10%

no one had addressed a diet supplements or educated about proper nutrition, which helps in developing teeth and preservation of good oral hygiene.


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parent education: Parent and patient responses. Pediatr Dent. 2010 July – Aug; 32

(4): 295-303.

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for 2010 and beyond. Dent Clin North Am. 2010 Jul; 54(3):423-40.

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Reprint requests and correspondence: Aida Šaban, DMDPrimary Health Care Center TravnikVezirska 172270 TravnikBosnia and HerzegovinaPhone: +387 61 848 698Email: [email protected]

84 A. Šaban et al.

Our contribution to the reduction of cardiovascular diseases in Bosnia and Herzegovina!Naš prilog redukciji kardiovaskularnih bolesti u Bosni i Hercegovini!

Gender comparison of serum asymmetric dimethylarginine and C-reactive protein concentration in patients with diabetes mellitus type 2

Spolna usporedba koncentracije asimetričnog dimetilarginina i C-reaktivnog proteina u serumu pacijenata sa dijabetes melitusom tip 2Asija Začiragić1*, Berina Hasanefendić2, Nesina Avdagić1, Orhan Lepara1, Nermina Babić1, Jasminko Huskić1, Nedžad Mulabegović3 1Department of Human Physiology, Faculty of Medicine University of Sarajevo, Čekaluša 90, 71000 Sarajevo, Bosnia and Herzegovina, 2Department of Clinical Chemistry and Biochemistry, Clinical Center University of Sarajevo, Bolnička 25, 71000 Sarajevo, Bosnia and Herzegovina, 3Institute of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine University of Sarajevo, Čekaluša 90, 71000 Sarajevo, Bosnia and Herze-govina.


ABSTRACT

Previous studies have shown that asymmetric dimethylarginine (ADMA) as a marker of endothelial dysfunction, and C-reactive pro-tein (CRP) as a marker of chronic low-grade inflammation have signifi-cant impact on development and progression of cardiovascular disease (CVD), and on diabetes mellitus-associated vascular impairment. Fur-thermore, studies have shown increased CVD risk in diabetic women compared to diabetic men but overall reasons for greater augmentation of CVD risk in diabetic women are still not fully understood. The aim of the present study was to conduct gender comparison of serum ADMA and CRP concentration in type 2 diabetic patients as well as in healthy subjects. Serum ADMA concentration was determined by ELISA meth-od and high-sensitivity CRP was determined by immunonephelometry in 60 patients (30 male, 30 female) with diabetes mellitus type 2 (DMT2) and in 60 healthy individuals (30 male, 30 female). Results of our re-search have shown increased serum ADMA concentration in female compared to male patients with DMT2 (p=0.011). Likewise, statistically significantly higher ADMA concentration was determined in female com-pared to male control subjects (p=0.028). In female patients with DMT2 we determined significantly higher serum CRP values compared to male patients with DMT2 (p=0.001). Moreover, significant increase in serum CRP levels was observed in female compared to male healthy control subjects (p=0.017). Results of the present study have shown higher values of serum ADMA and CRP concentration in female compared to male patients with DMT2. Obtained results suggest that more pro-nounced endothelial dysfunction and chronic low-grade inflammation in diabetic women compared to diabetic men could be one of the possible explanations for increased cardiovascular morbidity and mortality in fe-male patients with DMT2. Longitudinal studies with larger sample size are warranted for the confirmation of the observed findings.

Key words: asymmetric dimethylarginine, C-reactive protein, en-dothelial dysfunction, gender, diabetes mellitus type 2

SAŽETAK

Prethodne studije su pokazalale da asimetrični dimetilarginin (ADMA) kao marker endotelne disfunkcije i C-reaktivni protein (CRP) kao marker hronične inflamacije niskog stepena imaju znača-jan uticaj na razvoj i progresiju kardiovaskularnih bolesti (KVB), kao i na dijabetes-povezana vaskularna oštećenja. Nadalje, studije su po-kazale povećan rizik od KVB kod žena u poređenju sa muškarcima sa dijabetes melitusom tip 2 (DMT2) iako opšti razlozi povećanja KV rizika kod žena sa DMT2 još uvijek nisu u potpunosti shvaćeni. Cilj ove studije bio je provesti spolnu usporedbu koncentracije ADMA i CRP u serumu pacijenata sa DMT2, kao i kod zdravih ispitanika. Kon-centracija ADMA u serumu određena je ELISA metodom, a koncen-tracija visoko-senzitivnog CRP u serumu je određena imunonefelo-metrijom kod 60 pacijenata (30 muškaraca, 30 žena) sa DMT2 i 60 zdravih osoba (30 muškaraca, 30 žena). Rezultati našeg istraživanja su pokazali povećanu koncentraciju ADMA u serumu pacijentica sa DMT2 u poređenju sa pacijentima oboljelim od DMT2 (p=0.011). Također, statistički signifikantno veća koncentracija ADMA određe-na je u serumu ispitanica u poređenju sa ispitanicima kontrolne grupe (p=0.028). U serumu pacijentica sa DMT2 utvrdili smo sig-nifikantno veću koncentraciju CRP u poređenju sa pacijentima obol-jelim od DMT2 (p=0.001). Signifikantan porast koncentracije CRP u serumu opažen je i kod ispitanica u poređenju sa ispitanicima kon-trolne grupe (p=0.017). Dobijeni rezultati sugeriraju da bi izraženija endotelna disfunkcija i hronična inflamacija niskog stepena kod žena u poređenju sa muškarcima sa DMT2 mogla biti jedno od mogućih objašnjenja povećanog kardiovaskularnog morbiditeta i mortaliteta kod pacijentica oboljelih od DMT2. Longitudinalne studije sa većim uzorkom ispitanika su neophodne u cilju potvrđivanja opaženih nala-za.

Ključne riječi: asimetrični dimetilarginin, C-reaktivni protein, en-dotelna disfunkcija, spol, dijabetes melitus tip 2


INTRODUCTION

Asymmetric dimethylarginine (ADMA) is a naturally occurring endogenous inhibitor of nitric oxide (NO) synthase (1). Defined referent values of ADMA in blood are in a range from 0.36 to 1.17 μmol/L and gender dependent correlation between ADMA and age has been shown (2). Since its discovery in 1992 many features of ADMA properties have been reported but the most significant one remains reduction of NO production which consequently leads to endothelial dys-function. Results of numerous studies conducted in recent years have demonstrated that endothelial dysfunction has central role in pathophysiology of atherosclerosis (3). In many of those studies ADMA was used as non-invasive marker of endothelial dysfunction. Increased plasma value of ADMA has been associated with hyper-tension, hypercholesterolemia, insulin resistance and diabetes. Fur-thermore, in the last decade ADMA has been suggested as potential cardiovascular risk factor (4). C-reactive protein (CRP) is currently most studied and best val-idated biomarker of inflammatory processes. In a study by Shine et al. (5) determined median serum CRP concentration in healthy adult volunteer blood donors was 0.8 mg/L, the 90th percentile was 3.0 mg/L, and the 99th percentile was 10 mg/L. Majority of studies have confirmed that age, gender and body mass index have influence on CRP basal concentration (6). Measurement of CRP considerably contributes to monitoring of the response on inflammation and infection treatment, screening of organ diseases, as well as in detection of infection in immunosu-pressed individuals (7). Recent findings have also shown importance of CRP as a marker of systemic low-grade inflammation. This chron-ic condition is characterized by moderate CRP increase in blood without classical signs of inflammation. Numerous metabolic diseas-es that are annotated with cellular stress and metabolic dysfunction are frequently accompanied by chronic low-grade inflammation (8). Furthermore, majority of studies have confirmed important role of CRP in cardiovascular risk assessment. According to existing guide-lines, individuals with CRP values < 1 mg/L are considered to be in low, those with CRP values 1-3 mg/L in moderate and those with CRP values > 3 mg/L in high cardiovascular risk (9). It is now widely accepted that endothelial dysfunction and chronic low-grade inflammation have pivotal impact in diabetogen-esis. Impaired endothelium-dependent vasodilatation has been in-variably demonstrated in patients with diabetes. This is partly due to the frequent association of this disease with other cardiovascular risk factors, including obesity, dyslipidemia and hypertension. Based on recent reports, mechanisms leading to endothelial damage in di-abetes, independent of the damage due to other cardiovascular risk factors include insulin resistance, hyperglycemia, as well as systemic low-grade inflammation (10). Higher risk of cardiovascular disease in adult diabetics than in the general population of the same age has been well document-ed (11). Although many studies indicate that female diabetics are at greater CVD risk and mortality than male diabetics, the relative risk varies among studies, and the basis for the sex difference remains inconclusive (12, 13). Recent study by Kautzky-Willer et al. (14) reported that women with diabetes mellitus type 2 (DMT2) had worse cardiovascular risk

profile and achieved therapeutic goals less frequently than did men. Conversely, results from the Barbanza Diabetes study showed no difference in medium-term prognosis, with regard to mortality and cardiovascular morbidity, between male and female diabetics from the same geographical area, despite the presence of clinical differ-ences between the sexes (15). Currently, the influence of gender on CVD morbidity and mortality especially in diabetic patients remains one of the most controversial medical topics. Majority of studies reported increased ADMA and CRP con-centration in patients with DMT2 (16, 17). However, studies that investigated influence of gender on serum ADMA and CRP level in patients with diabetes mellitus are limited. Thus, the aim of the pres-ent study was to conduct gender comparison of serum ADMA and CRP concentration in type 2 diabetic patients as well as in apparently healthy subjects.


Subjects: we recruited 60 patients with diabetes mellitus type 2 (30 male, 30 female), as defined by American Diabetes Associ-ation (18), who regularly attend the Out-Patient Family Medicine Clinic „Višnjik“ in Sarajevo. All patients were receiving antidiabetic and antihypertensive therapies and some were receiving antilipid-emic drugs and/or aspirin for at least 6 previous months. Exclusion criteria was the presence of sustained acute and chronic infections, malignancy, hepatic or renal disease, diabetic retinopathy and ne-phropathy, and other endocrine dysfunctions. The control group consisted of 60 apparently healthy subjects (30 male, 30 female) with no history of DMT2, other endocrine dysfunctions, hyperlipid-emia, hypertension, or coronary heart diseases. None of the con-trol subjects had received any medication (hormone replacement therapy, corticosteroids, vitamin supplements, antioxidant formu-lations and thiazolidinediones) which might affect insulin resistance and/or endothelial function and none of the subjects were current smokers and consumers of alcohol. Blood sampling: blood was collected in the morning after an overnight fast after a 30-min rest in a semi-recumbent position. Sam-pling was done without stasis, using the vacutainer technique. Blood chemistry analysis: serum ADMA concentration was de-termined by ELISA method (machine STAT FAX 2100, USA) at the Department of Physiology and Biochemistry, Faculty of Medicine University of Sarajevo. ADMA ® - ELISA kit (DLD Diagnostika GmbH, Hamburg, Germany) was used as reagent. ADMA standards range from 0.1 to 5.0 µmol/L and the detection limit for ADMA with the use of this method is 0.05 µmol/L. Serum CRP was de-termined particle- enhanced immunonephelometry with the use of BN II analyzer. CardioPhase high-sensitivity CRP (DADE BEHRING, Marburg, Germany) was used as a diagnostic reagent. CardioPhase hs-CRP consists of a suspension of polystyrene particles coated with mouse monoclonal antibodies to CRP. Reference interval for CRP with the use of this method is from 0 to 5 mg/L, and the lower limit of CRP detection is 0.18 mg/L. The total cholesterol (TC), HDL-cholesterol (HDL-C), and triglyceride levels were measured with the use of standard enzymatic methods. The LDL-cholester-ol (LDL-C) levels were calculated using the Friedewald formula. Glycated hemoglobin (HbA1c) was measured by an immunotur-bidimetric method (TINIA; Siemens Healthcare Diagnostics Ltd,

86 A. Začiragić et al.

Camberley, United Kingdom). Normal range was 4.8-6.0%. All bio-chemical tests, except for ADMA determination, were performed at the Department of Clinical Chemistry and Biochemistry, Clinical Center University of Sarajevo. BMI, WHR and BP measurements: height was measured with stadiometer and weight with a Toledo self-zeroing weight scale. From these two measurements, Body Mass Index (BMI) for each subject was calculated (weight in kilograms divided by height in square meters). To determine waist to hip ration (WHR), the stan-dardized clinician tape was placed around the narrowest part of the waist and then placed around the widest part of the hips. The ratio was determined by dividing the waist measurement by the hip mea-surement. Three supine blood pressure recordings were made after a 5-min rest using an Omron 705c oscillometric device. The mean of the second and third readings was used. Hypertension was defined as having a systolic blood pressure (SBP) ≥ 140 mmHg and/or a diastolic blood pressure (DBP) ≥ 90 mmHg. The study was approved by the Ethics Committee of the Med-ical Faculty University of Sarajevo. Written informed consent was obtained from all subjects. Investigations were carried out in accor-dance with the Declaration of Helsinki as revised in 2000. Statistical analysis: Shapiro -Wilk normality test was used to test the distribution of variables. Normally distributed data are present-ed as mean ± SEM and skewed variables as median and interquartile ranges. An unpaired Student t-test or Mann-Whitney U-test was used to compare the difference between two groups, as appropri-ate. A p value of less then 0.05 was considered statistically signifi-cant. The software used was SPSS for Windows (version 17.0; SPSS, Chicago, IL, USA).

RESULTS

The basic characteristics of the study participants by gender are reported in Table 1. Statistically significant difference was observed between male and female subjects of the control group in age and in values of SBP and glycated hemoglobin (p<0.01). Furthermore, statistically significant difference was also observed between male

and female subjects of the control group in values of BMI, WHR and DBP (p<0.05). Significant difference in values of fasting glucose, total cholesterol, triglycerides, LDL-cholesterol and HDL-cholester-ol between male and female subjects of the control group was not observed. In patients with diabetes mellitus type 2, female patients had higher values of SBP and LDL-cholesterol compared with to male diabetic patients (p<0.05). Significant difference in age and in values of BMI, WHR, DBP, fasting glucose, glycated hemoglobin, total cholesterol, triglycerides, and HDL-cholesterol between male and female patients with type 2 diabetes mellitus was not observed. Data are presented as mean ± SEM. CG men: control group men; CG women: control group women; DMT2 men- male patients with diabetes mellitus type 2; DMT2 women- female patients with diabetes mellitus type 2. BMI: Body Mass Index; WHR: waist-hip ration; SBP: systolic blood pressure; DBP: diastolic blood pressure; FG: fasting glucose; HbA1c: glycated hemoglobin; TC: total choles-terol; TG: triglycerides; HDL-C: HDL-cholesterol; LDL-C: LDL-cho-lesterol.

∆ p<0.01 – compared to male control subjects§ p<0.05 – compared to female control subjects◊ p<0.05 – compared to male control subjects• p<0.05 – compared to male diabetic patients

Figure 1 shows the median and inter-quartile range of serum ADMA concentration in male subjects of the control group (0.60; 0.50-0.70 μmol/L) and in female subjects of the control group (0.70; 0.57-0.80 μmol/L). Serum ADMA concentration in female subjects of the control group was statistically significantly higher compared to male subjects of the control group (p=0.028). Furthermore, the median and inter-quartile range of serum ADMA concentration in

male patients with diabetes mellitus type 2 (1.45; 0.90-1.70 μmol/L) and in female patients with diabetes mellitus type 2 (1.65; 1.20-2.00 μmol/L) are also presented in Figure 1. Serum ADMA concentra-tion in female diabetic patients was statistically significantly higher compared to male diabetic patients (p=0.011). The solid horizontal lines denote the median value, the box represents the 25% and 75% inter-quartile ranges and the whiskers represent minimum and maximum values.

CG male – male subjects of the control group (n=30)CG female – female subjects of the control group (n=30)

Gender comparison of serum asymmetric dimethylarginine and C-reactive protein concentration in patients with diabetes 87

Variables

CG men n=30

CG women n=30

DMT2 men n=30

DMT2 womenn=30

Age (years) 49.97±1.37 58.40±0.92 56.26±1.29 57.10±1.18

BMI (kg/m2) 29.04±0.45§ 27.68±0.45 31.03±0.83 29.88±1.02

WHR

0.84±0.02 0.89±0.01 0.94±0.01 0.93±1.01

SBP (mmHg) 117.47±2.40 133.33±3.02 134.50±2.55 142.83±2.86

DBP (mmHg) 78.83±1.23 83.67±1.45 83.00±1.61 86.17±1.53

FG (mmol/L) 5.25±0.14 5.42±0.15 8.90±0.49 8.16±0.59

HbA1c (%) 5.49±0.04 5.78±0.49 7.48±0.23 7.33±0.28

TC (mmol/L) 5.68±0.18 5.30±0.19 5.76±0.16 5.89±0.17

TG (mmol/L) 1.65±0.14 1.64±0.14 2.30±0.19 2.76±0.24

HDL-C (mmol/L) 1.34±0.06 1.35±0.05 1.16±0.06 1.13±0.05

LDL-C (mmol/L) 3.57±0.15 3.51±0.19 3.57±0.17 4.06±0.18

Table 1 Summary overview analyzed data. Gender com-parison of basic characteristics in controlling subjects and patients with diabetes mellitus type 2.

!

Figure 1 Serum asymmetric dimethylarginine concentra-tion in male and female subjects of the control group and in male and female patients with diabetes mellitus type 2.

DMT2 male – male patients with diabetes mellitus type 2 (n=30)DMT2 female - female patients with diabetes mellitus type 2 (n=30) * - compared to male subjects of the control group ** - compared to male patients with diabetes mellitus type 2 p - probability

Figure 2 shows the median and inter-quartile range of serum CRP concentration in male subjects of the control group (0.75; 0.47-1.60 mg/L) and in female subjects of the control group (1.50; 0.87-2.72 mg/L). Serum CRP concentration in female subjects of the control group was statistically significantly higher compared to male subjects of the control group (p=0.017). Furthermore, the median and inter-quartile range of serum CRP concentration in male patients with diabetes mellitus type 2 (1.20; 0.70-3.52 mg/L) and in female patients with diabetes mellitus type 2 (4.10; 1.57-8.15 mg/L) are also presented in Figure 2. Serum CRP concentration in female diabetic patients was statistically significantly higher com-pared to male diabetic patients (p=0.001). The solid horizontal lines denote the median value, the box rep-resents the 25% and 75% inter-quartile ranges and the whiskers rep-resent minimum and maximum values.

CG male – male subjects of the control group (n=30)CG female – female subjects of the control group (n=30)DMT2 male – male patients with diabetes mellitus type 2 (n=30)DMT2 female - female patients with diabetes mellitus type 2 (n=30) * - compared to male subjects of the control group ** - compared to male patients with diabetes mellitus type 2 p - probability

DISCUSSION

Few studies have so far investigated influence of gender on se-rum ADMA concentration. Schulze et al. (2) determined positive correlation between ADMA and age which was influenced by gen-der in healthy subjects. Namely, in this study it was observed that women up to 50 years of age had lower ADMA values compared to men of the same age group, while women over 50 had higher ADMA values compared to men of the same age group. Authors

concluded that beginning of menopause in women results in signif-icant increase of serum ADMA levels. Furthermore, clinical studies reported lower ADMA values in postmenopausal women who were taking hormonal supplement therapy with estrogens (19). Results of our research have shown increased serum ADMA concentration in female compared to male patients with DMT2. Likewise, higher ADMA concentration was determined in female compared to male control subjects. The mean age of our female DMT2 patients was over 50, so our results confirm influence of menopause on ADMA increase in women compared to men of the same age group. None of our female DMT2 patients have taken hormonal supplement therapy so we exclude possible influence of estrogens on the obtained results. Given that the influence of gender on serum ADMA concen-tration in patients with DMT2 has not been extensively investigated so far we are limited in comparison of our results with the results of other authors. However, recent study by Anderssohn et al. (20) reported that sex was independent determinant of plasma ADMA concentration in patients with DMT2. Interestingly, findings of this study did not support previously reported associations or causal re-lationship between ADMA and features of diabetes or cardiovascu-lar disease. Significantly higher serum CRP concentration, as well as other proinflammatory markers, has been found in women with metabolic syndrome compared to men with the same condition. In healthy subjects included in this study gender difference in serum CRP con-centration was not observed (21). Hu et al. (22) investigated wheth-er gender had influence on association between CRP and risk for diabetes development. Results of this study have shown that high CRP levels are associated with increased risk for DMT2 both in men and in women, but this association was more markedly present in women. Saltevo et al. (23) reported increased serum CRP concen-tration in women compared to men with DMT2. In female patients with DMT2 we have determined significantly higher serum CRP values compared to male patients with DMT2. The obtained results are in accordance with other studies in which influence of gender on serum CRP concentration in type 2 diabetic patients was assessed (23, 24). Moreover, in our study significant increase in serum CRP levels was observed in female compared to male healthy control subjects. Observed CRP increase in female compared to male patients with DMT2 might be explained by obesity which is generally more frequently seen in women as a result of higher percentage of body fat (25). Adipose tissue cells are known to produce among others pro-inflammatory adipokines such as Interleukin-6 and Tumor Ne-crosis Factor-alpha which are the most potent stimulators of hepat-ic CRP synthesis. Novel findings suggest that adipose tissue is the key regulator of serum CRP concentration. Accumulation of body fat leads to increased production of adipose pro-inflammatory cy-tokines which in turn leads to increased serum CRP concentration (26). Furthermore, possible interaction between sex hormones and inflammation should also not be excluded. Studies have shown increased cardiovascular disease (CVD) risk in diabetic women compared to diabetic men and available data point to the conclusion that cardiovascular risk modification and treatment is of the at most importance in diabetic patients, especial-ly in women (27).


!

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Figure 2 Serum C-reactive protein concentration in male and female subjects of the control group and in male and female patients with diabetes mellitus type 2.

Based on current evidence cardiovascular risk factors are more severe, more common and more likely to cluster in diabetic women than in diabetic men. Furthermore, disparities in accessibility, qual-ity and, possibly, effectiveness of care in diabetic women have also been documented (28). However, overall reasons for greater aug-mentation of CVD risk in diabetic women are still not fully under-stood. We have previously reported increased values of both ADMA and CRP in patients with DMT2 compared to healthy control sub-jects (29, 30). In the attempt to assess the role of endothelial dys-function and chronic low-grade inflammation as possible culprits for reported gender difference in CVD risk we have conducted gender comparison of serum ADMA and CRP concentration in patients with DMT2. Results of the present study have shown elevated concentration of serum ADMA and CRP in diabetic women com-pared to diabetic men. Both of these compounds are thought to have significant impact on CVD development and progression, and on diabetes mellitus-associated vascular impairment (31). Obtained results suggest that one of the possible explanations for augmented CVD risk in diabetic women might be the observed gender differ-ence in an increase of endothelial dysfunction and chronic low-grade inflammation markers in DMT2 patients. Due to a small patient sam-ple of the present investigation, the obtained results require confir-mation in larger, longitudinal studies. However, if our findings are to be supported in the future, then gender specific guidelines for CV risk factors detection and correction as well as measures for decrease of cardiovascular morbidity and mortality in patients with DMT2 should include therapeutic interventions for reduction of se-rum ADMA and CRP concentration.

CONCLUSION

The risk of cardiovascular disease in diabetes mellitus type 2 is markedly influenced by gender. Results of the present study have shown higher values of serum ADMA and CRP concentration in female compared to male patients with DMT2. Although the mech-anisms leading to a greater augmentation of CVD risk in diabetic women remain largely unknown one of the possible explanations might be more pronounced endothelial dysfunction and low-grade inflammation in diabetic women compared to diabetic men. Longitu-dinal studies with larger sample size are warranted for confirmation of the obtained results.


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Reprint requests and correspondence:Asija Začiragić, MD, PhDDepartment of Human Physiology Faculty of Medicine University of SarajevoČekaluša 9071000 SarajevoBosnia and HerzegovinaPhone: +387 33 226 472Fax: +387 33 203 670Email: [email protected]



INTRODUCTION

Hypertropia or eye elevation, in most of the cases is caused by inferior muscle overaction (IOOM). Inferior oblique muscle overac-tion (IOOA) may be primary or secondary. Primary hyperfunction of inferior oblique muscle is characterized by elevation of the eye in adduction, with smaller or minor vertical deviation in the primary position, with smaller or minor torticolis and negative Bielschowsky test. Secondary hyperfunction of oblique muscle is caused by ipsilat-eral or contralateral paresis of superior oblique muscle, when we, also, have the eye elevation in adduction, but vertical deviation is present in primary position too, with strong torticolis and positive Bielschowsky test. Hypertropia can be isolated or combined with

other types of deviations, so more than 50% of patients with hor-isontal strabismus have the vertical deviation too. Primary inferior oblique overaction is mainly combined with horizontal deviations, according to Parks, with congenital esotropias 65% i 35% with inter-mitent exotropia. Can be present on one or both eyes simetrically (1,2,3,4). Surgeries of weakening of inferior oblique muscle are done because of functional, but the estetic reasons too. The variety of surgical procedure have been performed including: recession, hang-back recession, myotomy, myectomy, anterior transposition, nasal transposition, denervation and muscle fixation. Myotomy is simplier version of myectomy, not technically complicated and easy to per-form; freed oblique muscle is cutted-down, and bonds are freed, after cauterisation. Recession is, according to many authors, the

Comparative analyses of the effect of surgical weakening of inferior oblique muscle overaction on binocularity

Komparativna analiza efekta hirurškog slabljenja hiperfunkcije donjeg kosog mišića na binokularni vid

Jasmina Alajbegović–Halimić1*, Denisa Zvizdić1, Haris Tanović2

1Clinic of Ophtalmology, Clinical Center University of Sarajevo, Bolnička 25, 71000 Sarajevo, Bosnia and Herzegovina, 2Clinic of General and Abdominal Surgery, Clinical Center University of Sarajevo, Bolnička 25, 71000 Sarajevo, Bosnia and Herzegovina


ABSTRACT

Inferior oblique overaction (IOOA) can be primary or second-ary, isolated or combined with other types of horizontal deviation, mostly with esotropias (ET). Surgical weakening of inferior oblique muscle overaction means several techniques like: recession, myoto-my, myectomy, anteroposition etc. Goals: we analysed the effect of inferior oblique muscle surgical weakening to binocular vision, com-paring two groups of patients with primary hypertropia. Material and methods: in retrospective study, we observed 33 patients who were subject to the surgical procedure of weakening inferior muscle overaction by two methods; recession and myotomy. Results: out of 33 patients, 57.6% were male and 42.4% female patients with the average age of 10.6±7.5 (in range of 4–36). There was 33.3% of isolated primary hypertropias, and 66.7% combined with esotro-pias. The recession was done in 23 (69.9%) patients and myotomy in 10 (30.1%). Good and stabile binocular vision postoperativly was achieved in 65.2% of patients, on whom the recession of oblique muscle was done, which was statistically significant with significance level of p<0.05. Conclusion: effect of surgical weakening of the infe-rior oblique muscle overaction, considering the binocularity, proved better in patients treated with the inferior oblique muscle recession.

Key words: comparation, weakening, inferor oblique muscle, bin-ocularity

SAŽETAK

Hiperfunkcija donjeg kosog mišića (IOOA) može biti primarna ili sekundarna, izolovana ili udružena sa drugim vrstama horizontalnog ot-klona, najviše sa ezotropijama (ET). Hirurško slabljenja pojačane funk-cije donjeg kosog mišića, podrazumijeva nekoliko tehnika kao što su; retropozicija, miotomija, miektomija, anteropozicija itd. Ciljevi: Anali-zirali smo efekat hirurškog slabljenja donjeg kosog mišića na binokularni vid komparirajući dvije grupe pacijenata koji su imali njegovu pojačanu funkciju ili hipertropiju. Materijal i metode: U 5–godišnjoj retrospektiv-noj studiji observirali smo 33 pacijenta kod kojih je rađena hirurška pro-cedura slabljenja pojačane funkcije donjeg kosog mišića metodom ret-ropozicije i miotomije. Rezultati: Od 33 pacijenta, bilo je 57.6% muških i 42.4% ženskih pacijenata sa prosječnom starosnom dobi od 10.6±7.5 (u rasponu od 4–36). Izolovanih primarnih hipertropija bilo je 33,3%, a udruženo sa ezotropijama 66.7%. Kod 23 (69.9%) pacijenta rađena je retropozicija, a kod 10 (30.1%) miotomija. Dobar i stabilan binokular-ni vid postoperativno imalo je 65.2% pacijenata kod kojih je rađena retropozicija donjeg kosog mišića, što je bilo statistički signifikantno izraženo stepenom vjerovatnoće p<0.05. Zaključak: Efekat slabljenja pojačane funkcije donjeg kosog mišića, obzirom na binokularni vid, bio je bolji kod pacijenata gdje je rađena retropozicija donjeg kosog mišića.

Ključne riječi: komparacija, slabljenje, donji kosi mišić, binokularni vid


best method of inferior oblique muscle weakening, and according to Parks dominant to all other methods. Isolated muscle is recessed 2 mm laterrally and 3 mm temporally or more towards lateral edge of insertion of inferior rectus muscle. By this method, recession can be addopted and dosed in accordance with the hyperfunction degree; for 1+ overaction, the inferior oblique muscle is recessed 6 mm; for 2+ overaction 10 mm and for 3+ overaction 14 mm, which is the maximum recession (2,3,4). But, the decission on choosing the surgical procedure is individual and based on personal experience of a surgeon (3). Indications for these surgeries, whether inferior oblique overaction is primary or secondary or associated with the V pattern, are to treat hypertropia, diplopia, binocular vision compro-mise in the field of adduction, torticollis, and to improve cosmetic appearance. However, these surgeriees may have effect not only on vertical deviation, but also on horizontal deviations in varying degrees (4). When the hyperfunction is unilateral, usualy the only one muscle is weakened, and if the hyperfunction is bilateral, weak-ening procedure is done both-sided. Also, inferior oblique muscle weakening procedure, in case of existence of horizontal deviation, is done at the same time with correction of horizontal deviation (3,4). During and after surgery, more or less regardless of a procedure, the possible surgery and post-surgery complications must be con-sidered. One of them is intraoperative and postoperative bleeding and hemathoma in orbit,” adherent syndroma”, postoperative and continued hyperfunction of IOM, hypotropia, internal ophthalmo-plegia etc (3,4,5,6,7).


Retrospectivelly, study was performed in the period from Janu-ary 2007 to December 2013 at the Clinic of Ophtalmology, Clinical Center University of Sarajevo. We evaluated a total of 33 patients suffering from primary inferior oblique muscle overaction, isolated or combined with esotropia. Other forms of horisontal deviations were not considered. In all patients, the preoperative and postop-erative angle of horizontal esodeviation and vertical deviation was measured, with the prism cover test or Krimsky test, on primary position and 9 diagnostic gaze positions. Binocularity was tested in accordance with the Lang and Titmus fly tests 3, 6 and 12 months after the surgery. Patients were divided into two groups: in one group, depending on vertical deviation, the weakening of inferior muscle overaction was done by recession and in other by miotomy. Horizontal deviation was done at the same time or separatelly with vertical deviation, and depending on the case, it was done by bime-dial recession or combined unilateral recess–resect procedure. The data shown in a table are based on the number of cases, percent-age, arithmetic mean, standard deviation, median, and rangewere presented as descriptive statistics for quantitative data. Qualitative data are summarized using frequency and percentages. For testing of predicted hypothesis and prooving the goals, we used the Hi-square test, Student’s test and Pearson’s or Spearman’s correlation coefficient test. Results were accepted as statistically significant on the significance level of, p<0,05. Data were analyzed by using statis-tic software IBM Statistics SPSS v21.0 (Chicago, Illinois, USA). The procedures are confirmed with the tenets of the Declaration of Hel-sinki.

RESULTS

We analysed a total of 33 patients, of which 19 (57.6%) were males and 14 (42.4%) females. According to the type of surgery, we found that number of male patients was higher than female in total number and in recession group, while in a myotomy group the number of male and female patients was equal. Statistical analysis shows that there is no statistically significant difference of the pa-tients based on sex distribution, p>0,05 (Table 1). Analysis of average age during the surgery shows that the av-erage age of the patients subject to surgery was 10.6±7.5 (age 4 to 36), and that the patients in the recession group were old-er, with the average age of 12.4±8.1 (age 5 to 36), compared to patients in myotomy group with average age of 6.5±3.8 (age 4 to 17). Statistical analysis shows the significant differ-ence in average age during the surgery in accordance to type of surgery presented with significance level of p<0,05 (Table 1).

Out of 33 patients, 11 (33.3%) had isolated primary inferior oblique muscle overaction and 22 (66.7%) patients had it combined with esodeviation. All patients in the myotomy group had esotropia (100%). In the recession group, we had almost equal distribution of patients with esotropia 12 (52.2%) and hypertropia, only 11 (47.8%), which is statistically significant, p=0.007 (Table 2).

The most commonly performed surgery was inferior oblique muscle recession, which was done in 23 (69.9%) cases and myoto-

92 J. Alajbegović–Halimić et al.

Sex / Type of surgery Type of surgery Total No

Recession Myotomy Sex Male N 14 5 19

% 60,9 50,0 57,6 Female N 9 5 14

% 39,1 50,0 42,4 Total N 23 10 33

% 100,0 100,0 100,0 Age in surgery time / Type of surgery

Age N X SD SG Minimum

Maximum

Recession 23 12,4348 8,06128 1,68089 5,00 36,00

Myotomy 10 6,5000 3,80789 1,20416 4,00 17,00

Total 33 10,6364 7,51173 1,30762 4,00 36,00

Table 1 Sex and age of patients according to type of surgery. Sex distribution is not statistically significant (p>0.05), age distribution statistically significant (p<0.05).

Type of deviation/*Type of surgery procedure Type of surgery

22

66,7 11

33,3

Total value 33 100,0

Recession

Of the 33 patients, 19 (57,7 %) underwent unilateral weekening procedure and 14 (42,42%) bilateral surgery.

Total

10100,000,010100,0

Myotomy1252,21147,823100,0

N%N%N%

Hyperfunction MOIwith esotropia

Only hyperfunctionMOI

Type ofdeviation

Table 2 Type of deviation based on type of surgical pro-cedure χ2=7.174; p=0.007.

Comparative analyses of the effect of surgical weakening of inferior oblique muscle overaction on binocularity 93

my in 10 (30,1%) cases. Out of 33 patients, 19 (57.7%) underwent unilateral weakening procedure and 14 (42.42%) bilateral surgery (Table 2). Average value of preoperative angle of esodeviation was 16.3±9.8 (range 0-35). Those values were more statistically signifi-cant in the myotomy group (22.4±5.3; range 14-30), as compared to the patients in the recession group, presented on significance level of, p<0.05. Postoperative angle of esodeviation was much smaller in total number of patients and, on average, it was 3.2±3.8 (range -6 to 13), and still higher in the myotomy group (4.5±3.3; range -2 to 10), compared to ones in the recession group (2.6±3.9; range -6 to 13), but without statistically significant difference in respect to a surgery type, p>0.05 (Table 3).

Preoperative angle of vertical deviation in a total number of pa-tients was, on average, 7.5±3.9 (range 3-20) and it was higher in the recession group (8.7±4.3; range 3-20), compared to patients in the myotomy group (5.9±2.7; range 4-13), but without statistically sig-nificant difference in respect to a type of surgery, p>0.05. After the surgery, vertical deviation angle was smaller, and, on average, it was 1.4±0.96 (range 0-4) in the total number of patients, while the val-ues at certain types of surgery were 1.5±0.8 (range 0-3) in patients from the myotomy group, and 1.3±1.0 (range 0-4) with the patients in the recession group, but without statistically significant difference, in respect to a type of surgery, p>0.05 (Table 4).

Binocular vision was at 65.2% in the recession group, and at 20% of the patients in myotomy group, which is statistically significant shown with significance level of p<0.05 (Table 5).

In the myotomy group we still had overaction in 2 (6.1%) cases with residual angle of vertical deviation. In 1 (4.3%) case in the recession group, we had postoperative hypotropy, and we believed it to be “adhesive syndroma”. Statistical analysis shows that there is no sig-nificant difference in a number of re-operations, in respect to a type of surgery, p>0.05. Analysis of correlation between binocular vision and other an-alysed parameters showed that, beside statistically significant cor-relation, the following factors have the strongest effect on binocular vision: older age of patients undergoing surgery (r=0.734), lower value of preoperative esotropia deviation angle (r=-0.568), isolat-ed hyperfunction of IOM (r=0.429), recession as a type of surgery procedure (r=-0.416), and smaller postoperative vertical deviation angle (r=-0.39). Other parameters did not show any statistically im-portant influences (Table 6).

DISCUSSION

Inferior oblique muscle overaction (IOOA) may be primary or secondary and very often combinated with horisontal deviations, mostly with esodeviations. In our cases, we had a total of 33 pa-tients, of which 33.3% had only inferior oblique overaction, and

N X SD SG Minimum Maximum

23Recession 13,6957 10,15084 2,11660 ,00 35,00

Type of deviation/*Type of surgery procedure

Postoperative angle of Esodeviation

10Myotomy 22,4000 5,25357 1,66132 17,00 30,00

23Total 16,3333 9,75214 1,69763 ,00 35,00


23Recession 2,6087 3,92821 ,81909 -6,00 13,00

10Myotomy 4,5000 3,27448 1,03548 -2,00 10,00

33Total 3,1818 3,79518 ,66066 -6,00 13,00

Table 3 Preoperative and postoperative horisontal an-gle of deviations t=6.508; p=0.016.


23Recession 8,2609 4,25566 ,88737 3,00 20,00

Preoperative vertical angle of deviation

Postoperative angle of Esodeviation

10Myotomy 5,9000 2,68535 ,84918 4,00 13,00

33Total 7,5455 3,96146 ,68960 3,00 20,00


23Recession 1,3043 1,01957 ,21260 ,00 4,00

10Myotomy 1,5000 ,84984 ,26874 ,00 3,00

33Total 1,3636 ,96236 ,16753 ,00 4,00

Table 4 Preoperative and postoperative horisontal an-gle of deviations t=6,508; p=0.016.

Correlation coefficient towards binocular vision Stereovision Type of surgery ro -,416*

p ,016 Sex ro -,149

p ,409 Age in surgery time ro ,734**

p ,000 Type of deviations ro ,429*

p ,013 Esodeviation preoperative ro -,568**

p ,001 Esodeviation postoperative ro -,314

p ,075 Vertical deviation preoperative ro ,240

p ,179 Vertical deviation postoperative ro -,390*

p 0,025 Reoperation ro -,262

p ,141 *. Correlation signifi cant on a level p<0,05 **. Correlation signifi cant on a level p<0,01

Table 6 Correlation coefficient towards binocular vision.

Type of deviation/*Type of surgery procedure Type of surgery

22

66,7 11

33,3

Total value 33 100,0

Recession

Of the 33 patients, 19 (57,7 %) underwent unilateral weekening procedure and 14 (42,42%) bilateral surgery.

Total

10100,000,010100,0

Myotomy1252,21147,823100,0

N%N%N%

Hyperfunction MOIwith esotropia

Only hyperfunctionMOI

Type ofdeviation

Table 5 Binocular vision based on a type of surgery χ2=5,705; p=0,021.

66.7% inferior oblique muscle overaction with esotropias. Analysis of average age of patients in respect to the type of surgery, shows that the average age of the patients who underwent the surgery was 10.6±7.5 (range 4-36 years of age), which was statistically signifi-cant, presented on significance level of p<0.05. Wilson and Parks found primary overaction of the inferior oblique muscle in 72% of patients with congenital esotropia at an average age of 3.6 years, 34% of patients with accommodative es-otropia at an average age of 5.2 years, and 32% of patients with intermittent exotropia, also at an average age of 5.2 years (7). Weakening surgery for IOOA either primary or secondary in-cludes recession, disinsertion, myectomy, tenotomy, myotomy and anteriorization. The most commonly performed inferior oblique muscle weakening procedures are inferior oblique myectomy and inferior oblique muscle recession. The surgical decision appears to be primarily based on individual experience and preference (7,9). The aim of all these surgeries is to release IOOA and reduce related vertical deviations. In previous studies, we found the data of better usage of recession, as a modern method of weakening of inferior oblique muscle which is usually compared with myectomy or transposition, and not with myotomy. We did not find enough data on binocularity in any of the studies. Based on our analysis, according to binocularity, we showed that stereo vision was present in 65.2% of patienats in the recession group, and in 20% of patients in the myotomy group, which was statistically significant, presented on significance level of, p<0.05. If we analyse correlation between stereo vision and other parameters, we can see that, beside statisti-cally significant correlation, the following factors have the strongest influence on stereo vision: older age of patients, smaller deviation angle before the surgery, isolated hyperfunction of inferior oblique muscle, type of surgery – recession, and smaller angle of vertical deviation postoperativly. Other parameters did not show statisti-cally strong influence. The need for repeated surgery occurred in 2 (6.1%) patients out of a total number of patients, when we still had overreaction. In 1 (4.3%) case, we had postoperative hypot-ropy, and we believed it was the so called adhesive syndroma, but statistical analysis showed that there was no significant difference in repeating the surgeries in respect to type of a surgery, what was significance with, p>0.05. Parks found inferior oblique muscle recession to be the most ef-fective procedure. He observed a persistent inferior oblique muscle overaction in 37% of patients and inferior oblique muscle underac-tion in 8% of patients after an inferior oblique muscle myectomy and 13% incidence of inferior oblique muscle adhesive syndrome when the myectomy was performed at the inferior oblique muscle insertion (2,3,4,5,7). After the surgery, the angle of vertical deviation decreased, and was, on average 1.4±0.96 degrees. In myotomy group it was 1.5±0.8 (range 0-3), in recession group 1.3±1.0 (range 0-4), but without statistically significant difference in respect to a type of sur-gical procedure, p>0.05. Cooper and Sandall found that a measured recession will de-crease the hyperdeviation by 6.88 prism dioptries in primary posi-tion and by 12.3 prism dioptries in the field of action of the overact-ing inferior oblique muscle. They analyzed recession and myotomy group, but there is no data about binocularity (8). Shipman and Burke had total of 23 patients, 12 myectomies and

11 recessions and follow-up period of 12 months. All but one pa-tient had demonstrable binocular single vision. The average preop-erative hyperdeviation in contralateral gaze was 26.5 prism dioptres in the myectomies and 20 prism dioptres in the recessions. This was reduced at 12 months postoperatively to 1.75 prism dioptres in the myectomies and to 3 prism dioptres in the recessions. Both proce-dures were largely self-grading, so that the larger the preoperative hyperdeviation, the greater the effect of surgery (9). Sekeroglu et al. did the qualitative analysis at 76 patienrs, 30 male and 36 female, average age 11(1-49). Out of 76 patients, 54.5% had secondary hyperfunction of IOM, and 45% primary hy-perfunction of IOM. Three surgery procedures were done: 8.5% anteriorization, 43.9% tenotomy and 7.6% recession. They did not found any difference between different types of surgery in terms of horisontal deviations correcting effect. Unfortunatelly, there was no data about binoculararity (10). Ehrt et al. had retrospective studys of 234 patients in the age of 2-81, during the period of 9 years, where the quantitative analysis IOM weakening effect by recession, and described reduction of ver-tical deviation from 25 degreses to 6. They propose this method as safe and suitable, but with smaller risk from consecutive hypotropia and limited elevation, which they got in one case (11). Risović et al. in their study had 79, divided into two groups: first as a primary overaction IOM, and other and disociated vertical de-viation. Binocular vision was found in 67% of patients from the first group and 55.6% patients from the second group, but without big statistically significant difference between the groups (12).

CONCLUSIONS

The intention of the present study was not to evaluate effect of weakening of inferior oblique muscle on horisontal deviation, but to investigate its effect to condition of binocular vision. In this re-gard, the better results were achieved by applying recession as the method of inferior oblique muscle weakening. Recession is safe and effective procedure to eliminate inferior oblique overaction and can be dosed and adopt to overaction. But, when planning the surgery of inferior oblique muscle weakening, the knowledge and experi-ence regarding its influence on horizontal deviation and binocularity is needed, as well as dosing and possible operative and postopera-tive complications.


REFERENCES

1. Dorn V, Čelić M. Strabizam i nistagmus. Zagreb: Medicinska naklada 2004;153,

460-62.

2. Parks MM. Study of the weakening surgical procedures for eliminating overaction

of the inferior oblique. Trans Am Ophthalmol Soc.1971;69:163-87.

3. Parks MM. Atlas of Strabismus Surgery. Philadelphia, Pa: Harper & Row; 1983.

4. Parks MM. The weakening surgical procedures for eliminating overaction of the

inferior oblique muscle. Am J Ophthalmol. 1972 Jan;73(1):107–22.

5. Parks MM. Causes of the Adhesive Syndrome. Symposium on strabismus. Trans-

actions of the New Orleans Academy of Ophthalmology. The C.V. Mosby Com-

pany: St.Louis,1978;269–279.

6. Kenneth W. Wright, M.D., Peter H. Spiegel, M.D., and Lisa S. Thompson, M.D.

Handbook of Pediatric Strabismus and Amblyopia. New York: Springer Science;

94 J. Alajbegović–Halimić et al.

2006. Am Orthopt J. 2006;56:200-1

7. Wilson ME, Parks MM. Primary inferior oblique overaction in congenital esotro-

pia, accommodative esotropia, and intermittent exotropia. Ophthalmology. 1989

Jul;96(7):950–5; discussion 956-7.

8. Cooper EL, Sandall GS. Recession versus free myotomy at the insertion of the

inferior oblique muscle. J Pediatr Ophthalmol 1969; 6: 6–10.

9. Shipman T, Burke J. Unilateral inferior oblique muscle myectomy and recession

in the treatment of inferior oblique muscle overaction: a longitudinal study. Eye

(Lond). 2003 Nov;17(9):1013–8.

10. Taylan Sekeroglu H, Dikmetas O, Sanac AS, Sener EC, Arslan U. Inferior Oblique

Muscle Weakening: Is it possible to quantify its effect on horisontal deviations? J

Ophthalmol. 2012;2012:813085.

11. Ehrt O, Beki Y, Boergen KP. Effect of inferior oblique recession in strabismus adduc-

torius. Strabismus. 2002 Jun;10(2):63-8.

12. Risović D, Petrović L, Kosanović–Jaković N, Misailović K, Stanković B, Erić-Marinković

J. Binocular vison and vertical strabismus. Vojnosanit Pregl. 2007 Feb;64(2):109-15.

Reprint requests and correspondence:Jasmina Alajbegović-Halimić, MD, PhDClinic of OphtalmologyClinical Center University of SarajevoBolnička 2571 000 SarajevoBosnia and HerzegovinaPhone: + 387 33 297 191Fax: + 387 33 663 668Email: [email protected]

Cholesterol (mmol/L) 150 200 250 300 mg/dL

10 year risk of fatal CVD in high risk regions of Europe

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Comparative analyses of the effect of surgical weakening of inferior oblique muscle overaction on binocularity 95

INTRODUCTION

Tonsillectomy is one of the most common surgeries and ac-counts for about half of all surgical procedures in children (1).Mortality and morbidity after tonsillectomy are usually result of post-operative bleeding. In addition to the bleeding, the most com-mon complications include infection, pain, nausea and vomiting (2). Complications of tonsillectomy also include; pain, bleeding, respira-tory obstruction, pulmonary edema, uvulo-pharyngeal insufficiency, nasopharyngeal stenosis, pulmonary abscess, Horner’s syndrome, optic neuritis, meningitis, septicemia, cerebral abscess, palsy of glosofaringealnog nerve, recurrent laryngeal nerve palsy, salivatory fistul from the submaxillary glands, mediastinitis, subcutaneous em-physema, pulmonary emphysema, Eagle syndrome, aspiration of a

foreign body such as an extractes tooth gauze, or tonsillar tissue, cervical vertebral complications such as Grisel ‘s syndrome, retro-pharyngeal abscess, amputation of uvula, pseudoaneurism of lingual arteries, necrotizing fasciitis and death. The most common serious complication of tonsillectomy is delayed hemorrhage that occurs in 2-4% of patients after surgery (3, 4). Generally it can be expected that some patients need to be re-admitted to the hospital bacause of pain control and treating dehydration in cases of decreased oral fluid intake due to post-operative pain (5). The aim of this article is; 1. to define major complications of tonsillectomy and to determine its incidence; 2. to determine pos-sible connection between age, gender and season of operation and possible complications; 3. to determine possible connection be-tween ABO-blood type and bleeding after tonsillectomy.

Incidence and risk factors of complications after tonsillectomy

Učestalost i riziko faktori komplikacija poslije tonzilektomije

Lana Sarajlić1*, Adnan Kapidžić2, Jusuf Šabanović1, Haris Tanović1, Igor Gavrić1, Ismar Rašić1

1Clinic of General and Abdominal Surgery, Clinical Center University of Sarajevo, Bolnička 25, 71000 Sarajevo, Bosnia and Herzegovina, 2Clinic of Otorhinolaryngology, Clinical Centre University of Sarajevo, Bolnička 25, 71000 Sarajevo, Bosnia and Herzegovina


ABSTRACT

Tonsillectomy is one of the most common surgeries and ac-counts for about half of all surgical procedures in children. Mortality and morbidity after tonsillectomy are usually result of post-opera-tive bleeding. In addition to the bleeding, the most common com-plications include infection, pain, nausea and vomiting. Aim of the study was todefine major complicarions of tonsillectomy and to de-termine its incidence possible connection between the age, gender, season of operation, ABO blood type and possible complications. Primary and secondary bleeding were observed as major complica-tions; primary bleeding occurred in 2% of both group subjects, and secondary hemorrhage in 2% of patients from the studied and 4% of the control group patients. The largest number of complications was observed in the older age respondent groups (23-30 years), and during the summer. There was no statistically significant associa-tion between the occurrence of complications and the respondents gender. Of the total number of postoperative bleeding the largest number was registered in O blood group patients, while one bleed-ing in patient with A and B blood group respectively. The difference was statistically significant.

Key words: tonsillectomy, risk factors, complications

SAŽETAK

Tonzilektomija spada među najčešće operativne zahvate i čini oko polovinu svih hirurških procedura kod djece. Mortalitet i morbiditet nakon tonzilektomije su najčešće posljedica postope-rativnog krvarenja. Pored krvarenja, najčešće komplikacije uklju-čuju infekciju, bol, mučninu i povraćanje Cilj studije je definisati najčešće komplikacije tonzilektomije i utvrditi njihovu učestalost, ispitati moguću povezanost dobi, spola, godišnjeg doba u kojem se izvodi operacija, ABO krvne grupe i komplikacija poslije ton-zilektomije. Od komplikacija su zapažena primarna i sekundarna krvarenja. Primarna su se javila u 2% ispitanika obje skupine, a sekundarno krvarenje u 2% ispitanika ispitivane i 4% ispitanika kontrolne skupine. Najveći broj komplikacija je uočen kod starije dobne skupine ispitanika (23-30 godina) te u ljetnom periodu. Nije bilo statistički značajne povezanosti između pojave kompli-kacija i pola ispitanika. Od ukupnog broja postoperativnih krva-renja najveći broj je bio kod ispitanika sa O krvnom grupom, a po jedno krvarenje je bilo kod ispitanika A i B krvne grupe. Razlika je bila statistički značajna.

Ključne riječi: tonzilektomija, riziko faktori, komplikacije



100 patients was included in the study that was designed as a prospective cohort study.Inclusion criteria;

- patients after tonsillectomy,- age between 7 and 30,- both gender.

Exclusion criteria;- failure to follow the research plan,- irregular control,- serious side effects.

RESULTS

In the study group there were 23 (46%) male and 27 female (54%) subjects. Of the total number of subjects in the control group 21 (42%) were male and 29 (58%) were female. Chi-square test showed that there was no statistically significant difference in the gender structure of respondents between the groups; χ2=0.161; p=0.420. Analysis of the age structure of the respondents in this research showed that the middle age of the control group was 14:30 ± 7.71 years, while the middle age of the tested subjects was 16:14 ± 7.81 years. Anova test showed that there was no statistically sig-nificant difference in the age structure of respondents between the examined groups, F=1.404 ; p=0.239. Subjects were divided into three age groups; 7-14 years, 15-22 years and 23-30 years. The largest number of respondents from both groups belonged to the 7-14 age group, specifically 64% of the control group subjects

and 50% of studied group subjects. Chi-square test showed that there was no statistically significant difference in the age structure of the respondents between the two groups, χ2=2.28;p=0.131. By analyzing the frequency of complications in relation to the age group it was found that majority of complications occurred in patients aged 23-30 years, 2 in the control and 2 in the study group. There was statistically significant difference in the incidence of com-plications in relation to age groups, χ2=9012; p=0029. There was no statistically significant difference in the incidence of complications in relation to gender, p=0.477. There was statistically significant difference in the incidence of complications in relation to the season in which the operation was performed, and majority of com-plications occurred in summer, p<0.05 (Figure 1, Figure 2, Table 1).

DISCUSSION

In the 2007 International Journal of Otolaryngology, Fioer-entino et al. published a retrospective study that included 1464 patients, which aim was to investigate the prevalence of post-ton-sillectomy bleeding. Results showed that the secondary bleeding occurred in 41 (2.8%) patients. Majority; 20 (70.7%) did not re-quire active treatment and the remaining 12 (29.2%) required a further surgical treatment to achieve adequate hemostasis. In 4.9% patients bleeding was highly abundant and required transfusion (6). Collison et al. (2000) published a study in ENT Journal, which included 430 patients and studied the incidence and risk factors of tonsillectomy. The incidence of bleeding was 4%. Variables asso-ciated with bleeding were: the season in which operations were performed (most bleeding was observed in the late spring and summer), age, length of execution procedures (over 35 minutes), estimated blood loss during surgery, and the use of steroids. The variables that were investigated, and were not statistically associ-ated with bleeding, were gender, indication for surgery, concur-rent illness, personal and familial history of bleeding, preoperative coagulation profile, length of stay in hospital and the size of the tonsils (7). In the 2010 International Journal of Paediatric Otorhinolaryn-gology, Leonard et al. published a study with 303 patients, and investigated the association of ABO blood group and bleeding after tonsillectomy. Researchers have tried to demonstrate that

Incidence and risk factors of complications after tonsillectomy 97

Figure 1 The highest percentage of respondents from both groups was without complications. Among compli-cations primary bleeding occurred in 2% of the subjects from both groups, and secondary bleeding occurred in 2% of the tested patients and in 4% of the control group pa-tients.

Figure 2 Of the total number of postoperative bleeding (n=5), the majority occurred in patients with O blood group (n=3), and in one patient with A and one with B blood group. The difference was statistically significant.

Relative risk 1,500095% CI 0,2561 to 8,7854z statistic 0,450Significance level P = 0,030NNT (Benefit) 100,00095% CI 30,072 (Harm) to ∞ to 18,778 (Benefit)

Table 1 The relative risk of possible complications was 1.5 times higher in the control as compared to the expe-rimental group.

patients with 0 blood group have several problems associated with thrombosis and may be more prone to bleeding. That blood type indicates the reduction of the expression of Von Willebrand factor of coagulation. Results of the study showed that 63% of respon-dents in whom the secondary bleeiding occurred were 0 blood group. Although the study could not prove causality, the results showed that patients with this blood group are prone to second-ary bleeding after tonsillectomy in comparision to the patients of other blood groups (8).

CONCLUSION

Primary and secondary bleeding were observed as major com-plications; primary occurred in 2% of both group patients, and sec-ondary hemorrhage in 2% of the studied and in 4% of the control group patients. The highest number of complications was observed in the older age group of respondents (23-30 years), and during the summer. There was no statistically significant association between the occurrence of complications and gender of the respondents. Of the total number of postoperative bleeding the largest number was registered in patients with O blood group, and one bleeding in patient with A and B blood group respectively. The difference was statistically significant.


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1. Rivas Lacarte M. Tonsillectomy as a major outpatient procedure. Prospective 8-year

study: indications and complications. Comparison with inpatients. Acta. Otorrino-

laringol. Esp. 2000 Apr;51(3):221-7.

2. Kim MK, Lee JW, Kim MG, Ha SY, Lee JS, Yeo SG. Analysis of prognostic factors

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Reprint requests and correspondence:Lana Sarajlić, MDClinic of General and Abdominal SurgeryClinical Center University of SarajevoBolnička 25 71000 SarajevoBosnia and HerzegovinaPhone: +387 61 262 330Email: [email protected]

98 L. Sarajlić et al.


Medical Journal (2014) Vol. 20, No. 2, 99 -101 Original article

Efficiency of conservative treatment of postpartum hemorrhages caused by uterine atony

Efikasnost konzervativnog tretmana postpartalne hemoragije uslijed atonije uterusa

Mohamad Abou El-Ardat*, Zulfo Godinjak, Nermin Hadžić, Naima Imširija, Aida Dizdarević, Eldar Mehmedbašić, Armina Rovčanin

Clinic of Gynecology and Obstetrics, Clinical Center University of Sarajevo, Patriotske lige 80, 71000 Sarajevo, Bosnia and Herzegovina


ABSTRACT

Uterine atony leads to heavy blood loss caused by lack of uter-ine muscle contraction after placenta expulsion. Around 80% of women with postpartum hemorrhage have some of the risk fac-tors: over-distended uterus due to multiple pregnancy, fetal mac-rosomia, polyhidramnios or protracted labor. Active management of the third stage of labor can reduce hemorrhages. Oxytocics are routinely administered intravenously as they are associated with the minimal side effects. Other conservative methods include manu-al uterine compression for at least 15 minutes, bladder catheter-izing, and administration of methylergometrine, misoprostol, or 15-methyl Prostaglandin F2α. Research objective was to analyze the effects of conservative treatments and the success rate of medica-mentous treatment of postpartum hemorrhage caused by uterine atony. Cross-sectional prospective – retrospective study included 30 respondents, who gave birth at the Clinic of Obstetrics Clinical Center University of Sarajevo. All respondents have been diagnosed with uterine atony. Depending on the therapy administered (intra-venous ergometrine, intramuscular prostine 15-M and intravaginal misoprostol), the respondents were classified into three test groups. No difference in parity was detected among the patients, and the primiparae were the least represented (p=0.401). In patients who had ergometrine administered, the bleeding stopped in 40% of the cases. Prostine 15-M showed a success rate of 60%, whereas the patients who received the first dose of misoprostol showed a suc-cess rate of 90%. The patients who had ergometrine administered intravenously stopped bleeding within 30 minutes, which is longer than in the two other tested groups (p<0.05). The patients who used Prostine 15-M stopped bleeding after approximately 21.16 minutes, and the patients who were administered misoprostol vag-inally stopped bleeding within ca 22.44 minutes. The second and the third group did not show any statistically significant difference between the bleeding duration periods (p=0.554). Recent clinical, written and obstetrics experience suggests using misoprostol as an effective, simple and cheap drug to stop and control PPH. Miso-prostol will prevent many urgent primary postpartum hemorrhages caused by uterine atony and reduce the number of maternal deaths.

Key words: uterine atony, postpartum hemorrhage, misoprostol

SAŽETAK

Atonija uterusa dovodi do pretjerana gubitka krvi zbog neodgo-varajuće kontrakcije uterusa nakon rađanja posteljice. Oko 80% žena s postpartalnom hemoragijom ima neki od rizičnih faktora: prera-stegnutost uterusa uzrokovana višeplodnom trudnocom, fetalnom makrosomijom, polihidramnijon ili protrahiranim porođajem. Aktiv-no vođenje treceg porođajnog doba može smanjiti gubitak krvi. Ru-tinski se daje oksitocin intravenski kao sredstvo prvog izbora zbog malog broja nuspojava. Ostale konzervativne metode su manualna uterina kompresija barem 15 minuta, pražnjenje mokracnog mjehura kateterom, a mogu se dati i metilergometrin, misoprostol ili 15-me-til-prostaglandin F2-α. Cilj istraživanja je bio analizirati efekte konzer-vativnog tretmana i uspješnost medikamentozne terapije u tretma-nu postpartalne hemoragije uzrokovana atonijom uterusa. Kliničko deskriptivna prospetkivno-retrospektivna studija je obuhvatila 30 ispitanica koje su se porodile na Akušerskoj klinici Kliničkog centra Univerziteta u Sarajevu. Istraživanje je obuhvatilo 30 ispitanica kod kojih je postavljena dijagnoza atonije uterusa. U odnosu na primje-njenu terapiju intravenskog ergometrina, intramuskularnog prostina 15-M i intravaginalnog misoprostola, sve ispitanice su podjeljene u tri ispitivane skupine. Između ispitivanih skupina nije usta-novljena razlika u paritetu, te su primipare bila najmanje zastupljenije (p=0.401). Kod ispitanica kod kojih je apliciran ergometrin u 40% slučajeva došlo je do prestanka krvarenja, taj procenat kod ispitanica koje su primile prostin 15-M iznosio je 60% dok je kod ispitanica koje su primile prvu dozu misoprostola uspješnost je iznosila 90%. Ispitanice kod kojih je aplici-ran ergometrin intravenozno, prestale su da krvare nakon 30 min, što je statistički značajno duže u odnosu na druge dvije ispitivane skupine (p<0.05). Ispitanice koje su primile prostin 15-M prestale su da krvare nakon prosječno 21.16 min, a ispitanice koje su primile misoprostol intravaginalno prosječno 22.44min. Između druge i treće ispitivane skupine nije ustanovljena statistički značajna razlika u dužini trajanja krvarenja (p=0.554). Dosadašnja klinička, literaturna i akušerska isku-stva sugeriraju primjenu misoprostola kao uspješan, jednostavam i jef-tin lijek u zaustavljanju i kontrolisanju PPH. Primjenom misoprostola prevenira se veliki broj urgentnih primarnih postpartalnih hemoragija zbog atonije uterusa te kasnije materalni morbiditet i mortalitet.

Ključne riječi: atonija uterusa, postpartalna hemoragija, misoprostol

INTRODUCTION

Uterine atony leads to heavy blood loss caused by lack of uter-ine muscle contraction after placenta expulsion. Around 80% of women with postpartum hemorrhage have some of the risk factors: over-distended uterus due to multiple pregnancy, fetal macrosomia, polyhidramnios or protracted labor (1). Research has shown that PPH rates depend on several factors, inter alia: blood loss measure-ments, monitoring during the third stage of labor (use of uteroton-ics, massage of the uterus, controlled withdrawal of the umbilical cord), obstetrics interventions (episiotomy, childbirth methods). The results depend on the characteristics of the population (size of the population, parity, urban/rural environment, etc.). Clinical workers usually visually estimate blood losses, but this method can underestimate the postpartum blood loss by 30 to 50% (2). Typical symptoms of this condition are continuous or temporary bleeding from the (soft) uterus (1). The first step to reduce PPH is to de-termine the main cause. Uterine atony is diagnosed by means of bimanual palpation, whereas initial treatment includes massage of the uterine corpus and administration of intravenous oxytocin. Man-ual compression of the uterus enables doctors to determine the amount of lost blood and the uterine muscle tone. Soft uterus is usually subject to palpation, whereas the fundus is further away. In case of heavy bleeding, and if the uterus is contracted, vaginal lacer-ations or retained placenta need to be excluded. This can easily be done by performing a vaginal exam using a speculum and ultrasound (to search for placenta residues). Active management of the third stage of labor can reduce hemorrhages. Oxytocics are routinely administered intravenously as they are associated with the minimal side effects. Other conservative methods include manual uterine compression for at least 15 minutes, bladder catheterizing, and administration of methylergometrine, misoprostol, or 15-methyl Prostaglandin F2α. Even though conservative methods are success-ful in majority of the PPH cases, sometimes hysterectomy cannot be avoided (3). The aim of this article was to analyze the effects of conservative treatments and the success rate of medicamentous treatment of postpartum hemorrhage caused by uterine atony.


Cross-sectional prospective-retrospective study included 30 respondents, who gave birth at the Clinic of Obstetrics and Gynea-cology of the Clinical Center University of Sarajevo. All respondents have been diagnosed with uterine atony. Depending on the thera-py administered (intravenous ergometrine, intramuscular prostine 15-M and intravaginal misoprostol), the respondents were classified into three test groups. Due to profuse bleeding, each patient was manually examined, after which drugs were administered. In patients who did not respond to the treatment, the therapy was repeated or other uterotonic administered. Statistical evaluation included all three groups of patients. Basic demographic data are presented in the tables provided herein. We tested the arithmetic mean value (x), the standard deviation value (s), the standard error value (Sx) and the median. A chi-squared test (x²-test) was used for all three inde-pendent samples, and the quantitative results were analyzed using ANOVA. The significance rate was p<0.05.

RESULTS

The research included 30 patients who satisfied the crite-ria. They were separated into three groups. The chi-squared test showed statistical variances in parity of all patients, and that the groups were dominated by multiparae or pluriparae in relation to primiparae (p=0.025). However, no variance in parity was detected among the patients, and the primiparae were the least represented (p=0.401) (Table 1). Table 2 shows the effects of the first dose of drugs administered in patients with postpartum hemorrhage caused by uterine atony. In patients who had ergometrine administered, the bleeding stopped in 40% of the cases. Prostine 15-M showed a success rate of 60%, whereas the patients who received the first dose of misoprostol showed the success rate of 90%. The Chi-squared test showed a statistically significant variance in stopping the hemorrhage com-pared to the therapy administered, χ2=5.203; df=1; p=0.023 (Table 2). After the drugs were administered, we measured the time need-ed for bleeding to stop. The patients whose bleeding stopped after the first dose of drugs were subject to these measurements. The patients who had ergometrine administered intravenously stopped bleeding within 30 minutes, which is longer than in the two oth-er tested groups (p<0.05). The patients who used Prostine 15-M stopped bleeding after approximately 21.16 minutes, and the pa-tients who were administered misoprostol vaginally stopped bleed-

100 M. Abou El-Ardat et al.

Groups Total

Parity

PrimiparaeCount 1 1 1 3% 10.0% 10.0% 10.0% 10.0%Count 7 4 3 14% 70.0% 40.0% 30.0% 46.7%Count 2 5 6 13% 20.0% 50.0% 60.0% 43.3%Count 10 10 10 30% 100.0% 100.0% 100.0% 100.00% Χ2=1,832; df=4; p=0.401 X2=7,400; df=2; p=0.025

Group I(ergometrine)

Group II(Prostine 15-M)

Group III(misoprostol)

Multiparae

Pluriparae

Total

Table 1 Parity overview of patients.

Groups Total

Blee

ding

sto

pped

NoCount 6 4 1 11% 60.0% 40.0% 10.0% 36.7%Count 4 6 9 19% 40.0% 60.0% 90.0% 63.3%Count 10 10 10 30% 100.0% 100.0% 100.0% 100.00%

χ2=5,203; df=1; p=0,023

Group I(ergometrine)

Group II(Prostine 15-M)

Group III(misoprostol)

Yes

Total

Table 2 Success rate in stopping the hemorrhage depending on the therapy administered.

ing within ca 22.44 minutes. The second and the third group did not show any statistically significant difference between the bleeding duration periods (p=0.554) (Table 3).

DISCUSSION

Postpartum hemorrhage (PPH) is loss of blood estimated to be >500 ml after vaginal delivery, or >1000 ml after C-section within 24 hours after delivery. Etiologically speaking, it is a lack of the uterine myotamponade (so called “live ligature”), or thrombotamponade in coagulopathies. Early or primary postpartum hemorrhage (PPPH) occurs within 24 hours after delivery and is caused by uterine atony/hypotony, retained secundines or their fragments (fragments of cot-yledon, membrane, or placenta), forms of invasive malplacentation (placenta accretafocalis, placenta increta, percreta), cervical lacera-tions, disseminated intravascular coagulopathy (DIC), rupture and uterus inversion (4-6). This study included patients who suffered from postpartum hemorrhages due to uterine atony. The findings showed that the highest incidence of postpartum hemorrhage oc-curred in multiparae and that in only 10% of primiparae the uterine atony was detected. PPH is obstetric hemorrhage that causes high number of maternal death. PPH causes death of 125.000 (7) wom-en every year, especially in the developing countries (8, 9). If PPH is timely detected and therapy administered, the recovery rates are higher. However, availability of drugs and work routines of obste-tricians are often a decisive factor in solving these problems. Having evaluated administration of various drugs, the research showed that the drugs available today have different effects on PPH. Detailed analysis of conservative methods showed that misoprostol is much more effective in treatment of postpartum hemorrhage than ergo-metrine and Prostine 15-M.

CONCLUSION

Recent clinical, written and obstetrics experiences suggest using misoprostol as an effective, simple and cheap drug to stop and con-trol PPH. Misoprostol will prevent many urgent primary postpartum hemorrhages caused by uterine atony and reduce the number of maternal deaths.


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1. Kainer F, Hasbargen U. Emergencies associated with pregnancy and delivery: peri-

partum hemorrhage. DtschArztebl Int. 2008 Sept;105(37):629-38.

2. Sloan NL, Durocher J, Aldrich T, Blum J, Winikoff B. What measured blood loss tells

us about postpartum bleeding: a systematic review. BJOG. 2010 Jun;117(7):788-800.

3. Rahman SS, Myers JE, Gillham JC, Fitzmaurice R, Johnston TA. Post partum hemor-

rhage secondary to uterine atony, complicated by platelet storage pool disease and

partial placenta diffusa: a case report. Cases J. 2008 Dec 13;1(1):393.

4. Kainer F, Schiessl B, Kastner R. Geburtshilfliche Notfälle. GeburtshFrauenheilkd Re-

fresher 2003; 28:161–84.

5. El-Rafaey H, Rodeck C. Post-partum hemorrhage: definitions, medical and surgical

management. A time for change. Br Med Bull. 2003;67:205–17.

6. Römer TH, Mallmann, Straube W. Pschyrembel Wörterbuch Therapie in Gynäkol-

ogie und Geburtshilfe. Berlin: W. de Gruyter. 2001;159.

7. Hayman RG, Arulkumaran S, Steer PJ. Uterine compression sutures: surgical man-

agement of postpartum hemorrhage. ObstetGynecol 2002 Mar;99(3):502–6.

8. Allam MS, B-Lynch C. The B-Lynch and other uterine compression suture tech-

niques. Int J Gynaecol Obstet. 2005 Jun;89(3):236-41. Epub 2005 Apr 19.

9. Akhter C, Begum MR, Kabir Z, Rashid M, Laila TR, Zabeen F. Use of a condom to

control massive postpartum hemorrhage. MedGenMed. 2003 Sep 11;5(3):38.

Reprint requests and correspondence:Mohamad Abou El-Ardat, MDClinic of Gynecology and Obstetrics Clinical Center University of Sarajevo Patriotske lige 8171000 SarajevoBosnia and HerzegovinaPhone: +387 33 250 285Email: [email protected]

Efficiency of conservative treatment of postpartum hemorrhages caused by uterine atony at the clinic for obstetrics 101

N Mean Std.Dev Std.Error 95% Confidence Interval for Mean Minimum Maximum

4 30.00 3.16 1.58 24.96 35.03 26.00 33.00

6 21.16 1.72 0.70 19.35 22.97 19.00 24.00

9 22.44 2.35 0.78 20.63 24.25 18.00 26.00

Group I

Group II

Group III

Lower Bound Upper Bound

Table 3 Duration of bleeding after therapy.

INTRODUCTION

Psychiatric comorbidity or dual diagnosis among heroin addicts have been the subject of numerous studies and indicate significant presence of these disorders among them. Several large epidemiological studies indicate that approximately

50% of patients addicted to drugs and alcohol also have some other psychiatric disorders (1,2,3). Majority of these are personality disor-ders, anxiety and depressive disorder (1,2). According to the studies carried out by Leshner, Volkow and Brook it was found that the dual diagnosis among opiate addicts was present in 30% - 60% of cas-es (4,5,6). Some other authors mentions mood disorder, antisocial

Psychiatric comorbidity among opiate addicts on methadone substitution treatment

Psihijatrijski komorbiditet opijatskih ovisnika na metadonskoj supstitucionoj terapiji

Rasema Okić *

Institute for Alcoholism and Substance Abuse of Canton Sarajevo, Bolnička 25, 71000 Sarajevo, Bosnia and Herzegovina


ABSTRACT

Introduction: opiate addiction as a chronic, relapsing disorder is almost never alone, but in comorbid relation with other mental disorders. Therefore, the goal of this study was to verify the pres-ence of psychiatric comorbidity among opiate addicts in methadone substitution therapy (MST) and to examine differences in the prev-alence of mental disorders between the two groups of patients. Material and methods: study included a sample of 100 opiate ad-dicts in the MST at the Centre for Addiction Diseases in Zenica, from June to December 2011. Respondents were divided into two groups: G1 (50 respondents): stable patients - whose tests for psy-choactive substance - PAS in urine were negative for the past six months or more and G2 (50 respondents): unstable patients on tests of PAS positive urine six or more months in the therapeutic process. The respondents of both sexes, at the age between 20-47, were included in the substitution program for the period from one to five years. Daily doses of methadone ranged from 5 to 100 mg. The instruments used in the study were Pompidou forms of treated addicts with basic information about the respondents and MINI - International psychiatric interview for the major psychiat-ric disorders at Axis I of the DSM-IV and ICD-10. Results: in both groups we found a high prevalence of mental disorders, particular-ly antisocial personality disorder, 85% among unstable patients and 72% among stable patients. Other psychiatric disorders were also present in both groups of patients: hypomanic and manic episodes, panic disorder, anxiety, depressive disorder and OCD. Analysis of the MINI test total score showed a significant difference between the two groups with p=0.0043 (p<0.05), but not on the individu-al subscales, where p> 0.05. Conclusion: psychiatric comorbidity is frequent among opiate addicts, regardless of the current therapeutic response they show. Comorbidity represents an aggravating factor in the therapeutic process and requires a comprehensive, long-term psychiatric care, on the path to long-term stabilization of addicts.

Keywords: psychiatric comorbidity, opiate addiction, methadone therapy

SAŽETAK

Uvod: opijatska ovisnost kao kronični, recidivirajući poremećaj, gotovo nikada nije usamljena, već je u komorbiditetnoj relaciji sa drugim mentalnim poremećajima. Stoga je cilj ove studije utvrditi prisustvo psihijatrijskog komorbiditeta kod opijatskih ovisnika koji su u programu metadonske supstitucione terapije (MST), te ispitati razlike u zastupljenosti mentalnih poremećaja između dvije ispitivane grupe pacijenata. Materijal i metode: ispitivanje je vršeno na uzorku od 100 opijatskih ovisnika na MST u Centru za bolesti ovisnosti u Zenici, od juna do decembra 2011 godine. Ispitanici su podijeljeni u dvije grup: G1(50 ispitanika): stabilni pacijenti - na testovima na psihoaktivne supstance-PAS u urinu negativni zadnjih šest i više mjeseci i G2 (50 ispitanika): nestabilni pacijenti na testovima na PAS u urinu pozitivni šest i više mjesec u terapijskom procesu. Među ispitanicima su zastupljena oba spola, starosna dob je od 20 do 47 godina, a u programu supstitucije su od jedne do pet godina. Dnevne doze metadona koje su od 5 mg do 100 mg. Korišteni instrumenti u istraživanju su Pompidou obrazac liječenih ovisnika sa osnovnim podacima o ispitaniku i MINI – Međunarodni psihijatrijski intervju za glavne psihijatrijske poremećaje iz Osi I DSM-IV i ICD-10. Rezultati: u obje ispitivane skupine našli smo visoku zastupljenost psihičkih poremećaja, osobito antisocijalni poremećaj ličnosti, 85% među nestabilnim pacijentima, odnosno 72% među stabilnim pacientima. I drugi psihički poremećaji su zastupljeni u obje grupe ispitanika: hipomanične i manične epizode, poremećaj panike, anksioznost, depresivni poremećaji i OCD. U ukupnom skoru na MINI testu analiza pokazuje signifikantnu razliku između dvije ispitivane grupe sa p=0,0043 (p<0.05), ali ne i na pojedinim subskalama, gdje je p>0.05. Zaključak: psihijatrijski komorbiditet je vrlo zastupljen kod opijatskih ovisnika, bez obzira na trenutni terapijski odgovor koji oni daju. Komorbiditet predstavlja otežavajuću okolnost u terapijskom procesu i zahtijeva sveobuhvatnu, dugoročnu psihijatrijsku skrb, na putu ka dugoročnoj stabilizaciji ovisnika.

Ključne riječi: psihijatrijski komorbiditet, opijatska ovisnost, metadonska terapija


behavior and anxiety disorders as often present in heroin addicts, which has an impact on their therapeutic outcome (7). When assessing the patient and its mental status it is important to identify short-term and long-term opiate effects and withdrawal symptoms that may resemble symptoms of other mental disorders (3). Such cases require special attention in terms of differential di-agnosis, when it is necessary to discern the primary disorder among addiction, intoxication or objective development of endogenous psychoses. Acute mood changes, primarily anxiety and depressive disorders occur during opiate withdrawal (8). Patients in the methadone substitution treatment (MST), with psychiatric comorbidity have a significantly higher risk of frequent hospitalizations caused by additional drug use, than patients without comorbidity, but they receive lower doses of methadone for safety reasons. Increasing doses of methadone among these patients car-ries high risks of overdose and/or lethal outcome. In patients who are at higher doses of methadone Axis l comor-bidity is less present than in patients at lower doses of methadone (9). The presence of dual diagnosis and severity of psychopathology are closely related to therapeutic outcome in terms of further drug use, family and social problems and their employment status (10).


Respondents in the survey are long term heroin addicts on meth-adone substitution therapy (MST) at the Centre for Addiction Treat-ment in Zenica, treated from June to December 2011. The sample included 100 patients, divided into two groups: G1-stable patients in substitution (at screening urine tests negative for opiate substances) and G2-unstable patients in the therapeutic process (at screening urine tests positive for opiate substances) in a period of sixth months and more. The source of data was medical documentation (individual pa-tient file with daily doses of methadone and the results of screening tests) and International Pompidou form for treated addicts. The pa-tients of both sexes, at the age between 20-47 were included in the MST program for the period from one to five years. Daily dose of methadone in the sample ranged from 5 to 100 mg. Exclusion criteria related to: voluntarily interruption of treatment by the patient, imprisonment, change in the therapeutic direction (de-toxification, joining Therapeutic Community) or changing substituent.The instruments used in the study are: treated addicts form, which represents the “identity card” of the patient, with personal data, some of which were used in this study (age, gender, level of education), and MINI - International Neuropsychiatric Interview. It is designed as a compact structured interview for the major Axis I psychiatric disorders from the DSM-IV and ICD-10 classifications. It is a short structured scale based on which it is possible to diagnose psychiatric disorders according to the DSM-IV and ICD -10 for multicenter clinical and epi-demiological studies. The instrument is divided into modules in accor-dance with the observed diagnostic categories. Statistical data are presented by the absolute number, relative number (percentage), the mean and standard deviation in accor-dance with the type of data. Statistical evaluation was performed by Chi-Square and Student’s t test. Test results where p<0.05 or at the confidence level of 95% were considered as statistically significant All data were analyzed using SPSS statistical software ver. 14 for Windows.

RESULTS

Of the total number of respondents (100) 57% used heroin intra-venously, 28% by “sniffing”, and 15% in “other” manner (Figure 1). Gender structure indicates that 92 respondents (92%) were males and eight (8%) females. The mean age in the stable patients group (G1) was 31.59±7.9 and in the unstable (G2) 31.74±7.3 years. The mean daily dose of methadone in group of stable (G1) patients was 46.5±25.2 and in the unstable addicts (G2) it was 40.48±17.68 (Table 1).

The results obtained from the MINI test were interpreted as the sum of answers on all items where the lower limit was 190 points, according to which there was no psychopathological deviations. However, score above 190 indicates the presence of one or more psychiatric disorders. Therefore, the table shows that the mean of the stable patients was 222.90±20.15 and in the unstable group it was 235.92±24.15, which indicated to a possible presence of one or more psychiatric disorders in both groups (Table 2).

Results presented in Table 3 show that: the most represented mental disorders in both groups of addicts were antisocial person-ality disorder: 72% in the therapeutic stable group of patients and 85% in the unstable group, followed by hypomanic episodes in 56% of stable and 62% of unstable group of patients (36% of respon-dents had hypomanic episodes and in 26% of cases manic episodes were found), panic disorder in 54% of stable and 47% of unstable patients, and generalized anxiety disorder in 42% of stable and 50%

Psychiatric comorbidity among opiate addicts on methadone substitution treatment 103

Figure 1 Manner of heroin use.

G1 (N=50) G2 (N=50) p

Age 31.59±7.9 31.74±7.3 t=0.0986 0.9217

Gender Male 47 (94%) 45 (90%) chi=0.136 0.7124

Female 3 (6%) 5 (10%)

Mean methadone dose 46.5± 25.19 40.48± 17.68 t=1.3832 0.1698

Table 1 Differential characteristics of the tested groups G1 and G2 (age, sex, dose of methadone).

N Mean Std. deviation Std. Error of mean

Min. Max.

MINI test

G1 50 222.90 20.15 2.85 191 269

G2 50 235.92 24.15 3.35 203 310

Total 100 229.54 23.11 2.29 191 310

Table 2 Mean score of the MINI test in groups of stable and unstable patients.

of MST unstable patients. Depressive disorder was observed in 26% of stable and 36% of unstable patients. The analysis shows that there is a significant difference in to-tal MINI score between the groups with t=2.9271 and p=0.0043 (p<0.05), but without statistically significant difference in the indi-vidual subscales among the groups with p>0.05.

DISCUSSION

In this study, we found a high prevalence of dual diagnosis, or psychiatric comorbidity among heroin addicts in MST. Numerous studies worldwide have shown that more than half of opiate addicts (11,1) has a personality disorder (in our study 75%), anxiety and depression. Although anxiety and depressive disorders are often as-sociated, we established a higher frequency of anxiety than depres-sive disorders (stable patients 42% of them with anxiety and 26% of them with depression, or unstable patients - 50% of them with anxiety and 36% of them were depressed addicts) in both groups. Interestingly, a study conducted in northern Italy (1,2) on 1090 pa-tients showed the presence of dual psychiatric diagnoses in 506 pa-tients (52.7%). For some psychiatric disorders such as depression the most common risk factors are: gender, presence of the diagnosis from the DSM-IV Axis I, taking any psychotropic drugs, abuse of benzo-diazepines and methadone dose above 100 mg/day (12). True, in our sample the highest dose of methadone which patients receive was 100mg, and also the presence of depressive disorders was reg-istered in less than 50% of the cases. Prevalence of psychiatric disor-ders was up to ten times higher in patients in MST than in the general population, and 2-3 times higher than among potential addicts who are still experimenting or have harmful substance use but are not included in pharmacotherapy (13). Exploring psychiatric comorbidity among patients on MST Ngo et al. found a significantly higher risk for frequent hospitalizations in patients with comorbidity, than among patients without comorbid-ity (14), which is something that we encounter in our daily work. Patients that also use heroin are treated with lower doses of meth-adone, mainly for safety reasons, and the risk of over doses. Thus, the patients in our sample are under dosed in relation to the Euro-pean average. Axis-I comorbidity is declining among patients with higher doses of methadone (9). Particular attention should be given to the daily methadone dose and duration of substitution treatment. Panni et al. observed patients who were in substitution for more than a year and found a significant presence of serious psychiatric disorder, which required a

comprehensive psychiatric care (3). In this study we cannot help but raise the question of the suf-ficiency of daily doses of methadone. For example, studies have shown that methadone in adequate doses provides effects of reliev-ing anxiety, depression and psychotic symptoms. Monotherapy with methadone generally is not the only, or sufficient therapeutic agent, because of the presence of psychopathology that seriously desta-bilizes the patient and affects the treatment outcome. Methadone maintenance with adequate doses definitely leads to a reduction of the physical symptoms and psychological distress (15). The literature references talks about the average doses of meth-adone in patients with comorbidity in order to achieve stabilization from 80 mg up to 150 mg/day, and in case of drug addicts with-out comorbidity the optimal dose should be from 49 mg up to 99 mg/day (11). In our sample the methadone doses were significantly lower in both groups, G1 - 46.5±25.2 and G2 - 40.48±17.6. It is possible that patients under dose is an important factor of instability and patient demands for the introduction of additional psychiatric treatment, but also increase of the methadone dose. Medium-high doses of methadone reduce physical symptoms and psychological problems (15). Of course, we must emphasize the duration of the addiction substitution treatment program. Wondering about rapid stabiliza-tion and long-term quality abstinence, and insisting on a lower dose of methadone are the most common mistakes and unrealistic con-templations of the patients and their families. CONCLUSION In this study we found a high prevalence of psychiatric disorders among opiate addicts in MST. Statistically significant difference was no-ticed based on the total score of mental disorders (p<0.05) among stable and unstable patients, but it did not exist in the case of individual subscales (p>0.05). This leads us to the conclusion that in/stability of the patient in the therapeutic process is variable, and it depends on many other factors, such as the daily methadone dose, treatment dura-tion, as well as frequency of hospitalizations, additional psychiatric care, but also a range of socio-economic parameters, which can be subject of the future research.


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104 R. Okić

G1 (N=50) G2 (N=50) G1 (N=50) G2 (N=50) Student's t

p

MINI test - total score 222.90± 20.151 235.92± 24.150 2,9271 0,0043

Depression 13.32± 4.053 14.33± 4.647 13 (28%) 18 (36%) 0,6291 0,5342

Hippomanic episodes 17.74± 3.795 19.08± 4.558 28 (56%) 31 (62%) 1,2197 0,2276

Panic disorder 25.44± 7.605 25.40± 7.701 26 (52%) 24 (47%) 0,0185 0,9853

Agoraphobia and social phobias

07.04± 1.603 07.10± 1.902 17 (345) 12 (24%) 0,0919 0,9274

OCD 06.80± 1.641 07.12± 1.875 10 (20%) 15 (30%) 0,4386 0,665

General anxiety 12.16± 3.661 12.60± 3.599 22 (26%) 25 (38%) 0,4149 0,6802

Antisocial personality disorder

17.84± 3.893 18.50± 3.269 36 (72%) 42 (85%) 0,4182 0,814

Table 3 Frequency of mental disorders by the MINI test in the groups G1 and G2.

Arch Gen Psychiatry. 2002 Nov;59(11):1039-44.

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bidity in methadone maintained patients. J Addict Dis.1998;17(3):75-89.

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of illnesses. Presentation Abstracts. The 6th European Association of Addiction

Therapy, 2009, Ljubljana.

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chic structure of substance abuse and addictions: Should anxiety, mood and im-

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methadone maintenance population. Aust N Z J Psychiatry. 2001 Oct;35(5):601-5.

14. Ngo HT, Tait RJ, Hulse GK. Hospital psychiatric comorbidity and its role in heroin

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nance. J.Psychopharmacol. 2011 Jun;25(6):774-82.

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wellbeing and somatic markers in methadone substitution. Evaluation of 61 heroin

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Reprint requests and correspondence:Rasema Okić, MD, PhDInstitute for Alcoholism and Substance Abuse of Canton SarajevoBolnička 25 71000 SarajevoBosnia and HerzegovinaPhone: +387 61 798 809 Fax: +387 33 264 106Email: [email protected]

Psychiatric comorbidity among opiate addicts on methadone substitution treatment 105

Bosnia and Herzegovina versions of Guidelines for Patients!Bosanskohercegovačka verzija Vodiča za pacijente!

Imbalanced values of highly reactive moleculenitric oxide in schizophrenia

Vrijednosti visoko reaktivne molekule nitričkog oksida kod shizofrenije

Amra Memić1*, Abdulah Kučukalić1, Lilijana Oruč1, Jasminko Huskić2

1Clinic of Psychiatry, Clinical Center University of Sarajevo, Bolnička 25, 71000 Sarajevo, Bosnia and Herzegovina, 2Institute of Physiology and Biochemistry,

Faculty of Medicine, University of Sarajevo, Čekaluša 90, 71000 Sarajevo, Bosnia and Herzegovina


ABSTRACT

For many years, despite many studies it is not clear whether in-creased or reduced level of nitric oxide (NO) has some role in the path physiology of schizophrenia (Sch). Our goalwas to investigate whether the serum levels of NO differ between patients suffering from schizophrenia and healthy controls, and to determine whether NO level among patients is in correlation with negative and positive symptoms of schizophrenia. The study population consisted of 50 pa-tients hospitalized at the Psychiatric Clinic of the Sarajevo University Clinical Center and 50 healthy controls. The best lifetime diagnostic criteria was done based on DSM-IV criteria for Sch confirmed by Structured Clinical Interview (SCID 1). NO concentration in serum was determined by classic colorimetric Griess reaction. Conversion of nitrate into nitrite was done with elementary zinc. Our results showed that the level of NO, in the group of patients with positive symptoms (36.74±4.41) was statistically significantly higher (p<0.0001), and also that the concentration of NO in the group of patients with negative symptoms (33.62±4.69) was higher than in the control group with statistically significant differences (p<0.002), while there was no statis-tically significant difference based on type of the symptoms (p>0.05).These results suggest that there is a difference in NO synthesis in pa-tients with positive and negative forms of schizophrenia.

Key words: nitric oxide, schizophrenia, positive and negative symptoms

SAŽETAK

Već duži niz godina, bez obzira na mnoge studije, nije jasno da li povećane ili smanjene vrijednosti nitričkog oksida (NO) imaju ulogu u patofiziologiji shizofrenije (Sch). Ciljnam je bio istražiti da li je nivo nitričkog oksida u serum u različit između grupe pacijenata koji boluju od shizofrenije i kontrolne zdrave skupine i utvrditi da li je nivo NO između pacijenata u korelaciji sa negativnim i pozitivnim simptomima bolesti. U istraživanje je bilo uključeno 50 pacijenata koji su bili hospitalizirani na Psihijatrijskoj klinici, KCUS, i 50 zdravih kontrola. Doživotno najbolja procjena dijagnoze je dodijeljena prema DSM-IV kriterijima (SCID I). Koncentracija nitričnog oksida (NO) u serumu određena je konverzijom nitrata (NO-

3) u nitrite (NO-2) pomoću

elementarnog cinka, a zatim mjerenjem koncentracije NO-2

(µmol/L) kolorimetrijski pomoću pripremljenog Greiss reagensa. Naši rezultati su pokazali da je koncentracija nitričkog oksida, kod grupe pacijenata oboljelih od shizofrenije sa pozitivnim simptomima u kliničkoj slici (36.74±4.41), veća i statistički signifikantna (p<0.0001), a koncentracija NO kod grupe pacijenata sa negativnim simptomima (33.62 ± 4.69) je veća u odnosu na kontrolnu grupu ali bez statistički značajne razlike (p<0.002). Ovi rezultati sugeriraju da postoji razlika u nivou NO između grupe pacijenata sa dominacijom pozitivnih u odnosu na negativne simptome bolesti.

Ključne riječi: nitrički oksid, shizofrenija, pozitivni i negativni simptomi

INTRODUCTION

During the last decade and nowadays nitric oxide (NO) is a cen-tral topic and in focus of many scientific research papers, as well as the possible role of oxidative stress and free radicals in the patho-physiology of schizophrenia (Sch)(1), since the etiopathogenesis mechanisms in schizophrenia still remains unknown. Schizophrenia is a serious mental illness, that is the most specific constellation of symptoms that reflect the particular existential context of the indi-vidual while maintaining a consistent core in terms of stable, diag-nostically relevant characteristics. This means that the schizophrenic manifestations in terms of content show the richness of individual differences, preserving stable patterns related to the onset of dis-

ease, manifestation and course of illness (2). The constellation of symptoms is more important rather than a single symptom, because there is not one symptom, which is present in all patients. In mod-ern biological research during the last decade psychopathological symptoms are grouped into two types, often three, which overlap in the clinical picture (3). NO is one of the most important signal-ing molecule involved in many cellular events in the cardiovascular, immune and nervous systems (4), both in physiological and patho-logical functions, such as the interesting features that has neuro-protective, while the high concentrations of pure NO neurotoxic feature (5,6). First facts about the role of the NO came to light during demonstration of NMDA (N-methyl D-aspartate) glutamate receptor stimulation and noticed the release of a molecule that had


a similarity to the endothelial-derived relaxation factor (EDRF), and shortly thereafter established that EDRF is identical to the NO (7,8). Activation of N-methyl-D-aspartate (NMDA) receptor leads to an increase in intracellular calcium that stimulates the enzyme constitu-tive nitric oxide synthase (NOS), one of the three iso forms of the enzyme responsible for the formation of NO, which catalyze the oxidation of L-arginine to L-citrulline and NO (9). In recent stud-ies with Nogo-A, a myelin-associated protein, it was possible to demonstrate in patients with schizophrenia more marked increases in nNOS/iNOS activity (but not in their expression) in the right, rather than left hemisphere, that is the disturbed asymmetry in cor-tical N-methyl-D-aspartate (NMDA) receptor-nitric oxide synthase (NOS) pathway, which is reported as dysfunctional in schizophrenia (10). Maia-de-Oliveira et al. (2012) showed significantly higher levels of NO in patients with schizophrenia in comparison to the control group, which is often associated with antipsychotic drugs that af-fect the increase of nitric oxide plasma and/orserum level (11). For many years, despite many studies it is still not clear whether increase or deficit of NO has some role in the pathophysiology of schizo-phrenia, and Issy et al. (2013) tried to solve this dilemma with the effects of NO/cGMP increase on sensory and motor gating modu-lation during dopamine hyperfunction as a possible target for drug development, and it seems that the amphetamine-disruptive effect is tied to an increase in NO and not to the increase in cGMP (12). Minutolo et al. (2012) found a correlation between PANSS score and nitrate levels, but it is unclear whether nitric oxide is related to the severity of schizophrenia, because nitrate levels are also affected by antipsychotic treatment (13). It is well known that the role of NO is associated with other psychiatric entities such as bipolar af-fective disorder, and more recently with major depressive disorder (5,14). Akpinar et al. (2013) in their research on patients suffering from major depression indicate that serum levels of NO are elevat-ed and that increased serum levels of NO may be associated with psychomotor retardation but not with the course or severity of the disease (15). Nakano et al. (2010) indicated to a significant decline in levels of nitric oxide in schizophrenic patients compared to the control group, but prior to treatment with risperidone, after which increase in the levels of NO was observed, and suggested that nitric oxide was one of the possible candidates that could be linked to the pathophysiology of negative symptoms of schizophrenia (16). All the above mentioned authors agree that a potentially new treat-ment strategy for alleviating social dysfunction in schizophrenia may be NO synthase inhibition, as Wass et al. (2009) confirmed in their study that a significant clinical facts in the pathophysiology of schizo-phrenia and the role of nitric oxide is still unclear (17,18,19). The goal of this study was, primarily to determine whether there was a difference between the level of nitric oxide in the blood serum of patients with schizophrenia and in the serum of healthy control group, and secondly to determine whether there was a difference between the level of NO in the serum of patients with positive psy-chotic symptomatology and in the group of patients with negative symptoms, and correlation with the same.


This prospective clinical study and partially descriptive con-

trolled study sample consisted of patients from the Clinic of Psychi-atry, Clinical Center University of Sarajevo, who were taking stable doses of the neuroleptics for at least 8 weeks prior to the involve-ment in the study and who gave their written informed consent to participate in the study after a detailed explanation of the study pro-cedures. Fifty patients (N=50) with schizophrenia and fifty (N=50) healthy subjects participated in this study. A DSM-IV diagnosis of schizophrenia (20) was established on the basis of independent clin-ical interviews and the patients’ psychopathology was assessed with the Scale for the Assessment of Negative Symptoms and the Scale for the Assessment of Positive Symptoms (21). Patients and controls with history of psychiatric and chronic diseases such as diabetes mellitus, hypertension, neurology diseases, inflammatory or gastro-enterohepatology diseases were excluded from the study. Fifteen milliliters of venous blood was taken from the patients and controls. The concentration of NO in blood was determined by measure-ment of nitrate and nitrite using colorimetric Greiss reaction (22). The concentration of NO in serum was determined by conversion of nitrate (NO¯3) to nitrite (NO¯2) using elemental zinc and then colorimetric measurement of nitrite (NO¯2) (µmol/L). We took 1 mL of blood, added 8 mg of elemental zinc dissolved in 0.4 mL of deionized water, 0.032 ml 5% CH3COOH (acetic acid) and 2 mL deionized water. The sample was mixed for 5 min using vortex at room temperature and centrifuged 2.5 min at 700 rpm. After that 1 mL of supernatant and 1 mL of Greiss reagent was mixed for 10 min in vortex at room temperature. After 10 min of mixing we measured light absorption (optical density) with spectrophotometer at 546 nm. The concentration of nitrate and nitrite was determined from a standard curve with known concentrations of NaNO2 (1.56 µmol–100 µmol). Distilled water was uses as a blank test to which Griess reagent was added.

Statistical analysis

Excel and SPSS version 15 for Windows was used for the statis-tical analyses of data. Categorical variables were compared using the Chi square test and contingency tables. Where appropriate, correla-tions were used to determine the association between continuous variables and to determine the Pearson correlation coefficient. The hypothesis was tested using the paired Student t test. All results are presented in tables and figures by type of variables.

RESULTS

The demographics characteristics of the two groups are shown in Table 1. Analysis by Chi square test and Student t-test indicate that significant difference exist, as expected, in employment status and education level between the two groups (p<0.05), but not in respect to gender, mean age and marital status (p>0.05). The serum NO levels in the group of patients with schizo-phrenia (35.8±3.37) were significantly higher than in the control group(15.545±0.87) (Figure 1). We used the paired t-test to com-pare the difference of serum NO level between sch and control group and we got statistical significance at p=0.000, CI (13.31 to 27.29), t (5.863).

Imbalanced values of highly reactive molecule nitric oxide in schizophrenia 107

Our results showed that the level of nitric oxide, in the group of patients suffering from schizophrenia with positive symptoms (36.74±4.41), was higher and statistically significant (p<0.0001), and the concentration of NO in the group of patients with negative symptoms (33.62±4.69) was greater than in the control group also with statistically significant differences (p<0.002). However, no sta-tistically significant difference or correlation (rho=0.074; p=0.055) was found between patients with positive or negative symptoms (Figure 2).

DISCUSSION

Serum nitric oxide levels in the group of patients suffering with schizophrenia were significantly higher than in the healthy controls which is consistent with the results of Necat et al. (23), but not in

accordance with the results of Nakano et al. (16) when their results are compared with other studies that have different result explained with preparation of blood prior to the Greiss reaction such as sam-ple handling and storage procedures, stability of reaction interme-diates formation of more than one dye, pH, temperature and with repeated sample freezing and repeated dilution. The level of nitric oxide was higher in the group of patients with the prevalence of positive symptoms of schizophrenia, compared to a group of patients with negative symptoms but without statistically significant differences, which is in line with the results of studies of Suzuki et al. (24). In this study it is important to note that the in-volved patients underwent long-term treatment with antipsychotics inducing NOS2 mRNA in various regions of the brain, so there is a possibility that antipsychotic treatment increased NOS activity in the previous research subjects which somewhat justifies the above mentioned facts. Along these lines of evidence, Nakaki et al. (25) ar-gued that excessive NO production may lead to neurodegeneration and the formation of enduring negative symptoms in the brains of patients with the deficit form of schizophrenia, which partly explains the negative symptoms of schizophrenia (26). Type II, which former-ly classified schizophrenia as negative, unproductive form, is a form of schin in which there is hyperactivity of the central dopaminergic activity, characterized by negative symptoms (alogia, atimia, anhe-donia, social withdrawal, apathy and abulia) (27). Specifically, there are no clear indicators that fully differentiated positive and nega-tive type of disease (28,29,30,31), especially as different varieties of representation may occur at different stages of the disease. We speculate that the discrepancies reflect the heterogeneous psychotic condition of patients. The disadvantage of this research would also be a control group of drug free schizophrenic patients, which we have not been able to include, as well as determining the level of nitric oxide from the group of patients who were on typical rather than in the group of patients on atypical antipsychotics. We also could not observe the difference in changes of NO level before and after the treatment. These results suggest that we could not predict the response to antipsychotic therapy on serum NO levels. Contro-versial results exist when the question is whether the level of Nitric oxide is higher or lower in patients with schizophrenia compared to the control group. Taken all together the role of nitric oxide in schizophrenia might be very complicated.

CONCLUSION

The present study suggests that schizophrenic patients differ from control subjects in levels of NO. We found no significant differ-ences in the group of patients with negative symptoms and control subjects. In addition, our study indicates that there is a significant positive correlation between NO and the group of patients with positive symptoms and the control group. Our preliminary findings of increased serum NO in patients with Sch indicate its potential role in pathophysiology of this severe psychiatric disorder. Howev-er, those results are preliminary and have to be confirmed in a larger size sample. Bearing in mind heterogeneity in symptom expression, course and treatment our future study has to be focused on re-search of this particular characteristics and NO role in ethiopathol-ogy of Sch.

108 A. Memić et al.

Figure 2 NO levels based on type of symptoms.

Control Sch t/chi

Gender Male 18 (36.0%) 15 (30.0%) 2=0.407

p=0.523 Female 32 (64.0) 35 (70.0%)

Age 35.56±10.84 38.4±12.5 t=1.639

p=0.105

Marital

status

Married 23 (46.0%) 21 (42.0%) 2=0.171

p=0.918 Single 24 (48.0%) 26 (52.0%)

Divorced 3 (6.0%) 3 (6.0%)

Employment

Employed 39 (78.0%) 9 (18.0%) 2=38.850

p=0.0001 Unemployed 11 (22.0%) 29 (58.0%)

Retired 0 (0%) 24 (50.0%)

Education

Elementary

school

4 (8.0%) 11 (22.0%)

2=15.675

p=0.001 High school 21 (42.0%) 32 (64.0%)

College 7 (14.0%) 2 (4.0%)

Faculty 18 (36.0%) 5 (10.0%)

Table 1 Demographic characteristics.

Figure 1 NO serum levels.

Imbalanced values of highly reactive molecule nitric oxide in schizophrenia 109


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Reprint requests and correspondence:Amra Memić, MD, MSc Clinic of PsychiatryClinical Center University of SarajevoBolnička 2571000 Sarajevo Bosnia and HerzegovinaEmail: [email protected]

Epidemiological and clinical characteristics of childhood lymphoma

Epidemiološke i kliničke karakteristike limfoma dječije dobiEdo Hasanbegović*, Nermana Čengić, Meliha Sakić, Adela Tunić, Senada Mehadžić

Pediatric Clinic, Clinical Center University of Sarajevo, Patriotske lige 81, 71000 Sarajevo, Bosnia and Herzegovina


ABSTRACT

Introduction: lymphomas are the primary neoplasias of the lym-phatic system, which are usually manifested by painless enlargement of the lymph nodes.In children, the third most common malignan-cy are lymphomas, after leukemias and brain tumors. They repre-sent 10-13% of newfound malignancies in children. There has been progress in the last 20 years as a diagnostic as well as therapeutic. Despite the progress of genetics, molecular biology and immunol-ogy, and their significant results, causes of these diseases have not yet been identified. Aim: the aim of this study is to evaluate the basic epidemiological and clinical characteristics of childhood lym-phoma at the Hematooncology Department of Pediatric Clinic of the Sarajevo University Clinical Center (CCUS) in a ten year period. Patients and methods: the study included 58 patients, of both gen-der, aged 0 through 15, with diagnosis of lymphoma at the Hema-tooncology Department of the Pediatric Clinic of CCUS, during the period from January 1st 2004 to December 31st 2013. The retro-spective study of patients with lymphoma in childhood was con-ducted. The results were presented using tables and charts, with number of cases and percentages. Statistical analysis of significant differences was performed using Fisher and Chi - square test. The values of p<0.05 or on the level reliability of 95% were considered statistically significant. Results: our study included 58 patients, 37 (63.80%) boys and 21 (36.20%) girls. It showed a higher percentage prevalence of boys compared to girls. Most patients were in the age group of 8-15 years, 38 (65.50%) patients. The leading symptom of lymphoma in childhood was lymphadenopathy, which was pre-sented in 45 (77.58%) patients, followed by subfebrile temperature in 19 (32.75%), paleness in 16 (27.59%), hepatosplenomegaly in 13 (22.41%), and weight loss in 12 (20.69%) patients. The following elevated values were noted: LDH in 16 patients with HL and 14 with NHL, and Cu in 15 patients with HL and 10 with NHL. Most patients with HL were diagnosed in stage II of disease, 12 (37.50%) patients, and 11 (34.40%) in stage IV. Most patients with NHL were diagnosed in stage II, 13 (50%), and 8 (30.80%) in the IV stage. Af-ter leukemias (157 patients – 39.20%), lymphomas were the second malignancies in children, represented with 14.50% of all malignancies diagnosed at the Pediatric Clinic. Each year, an average 5.8 of new cases has ocurred and majority of them (10 new cases) in 2013. Ten-year survival of patients with HL was 87.50% and 80.77% with NHL. Conclusion: lymphomas are the second malignancies in chil-dren at the Pediatric Clinic of CCUS. Most patients are in the age group of 8-15 years, with higher percentage prevalence of boys compared to girls. Clinical diagnostic methods and modern therapy at the Pediatric Clinic contribute to the good prognosis for patients suffering from lymphoma in childhood. The survival rates of pa-tients are similar to those in the international centres.Keywords: Lymphoma, Hodgkin’s, Non Hodgkin’s

SAŽETAK

Uvod: limfomi su primarne neoplazije limfnog sistema koje se najčešće manifestiraju bezbolnim povećanjem limfnih čvorova. Predstavljaju 10-13% novootkrivenih malignoma dječije dobi. Nakon leukemija i tumora mozga, limfomi se nalaze na trećem mjestu po učestalosti maligniteta dječije dobi. Primjetan je napredak u zadnjih 20 godina kako dijagnostički, tako i terapijski. Bez obzira što su genetika, molekularna biologija i imunologija napredovali i dali značajne rezultate, uzroci nastanka ovih oboljenja još uvijek nisu utvrđeni. Cilj rada: cilj rada je evaluirati osnovne epidemiološke i kliničke karakteristike limfoma dječije dobi na Hematoonkološkom odjelu Pedijatrijske klinike Kliničkog centra Univerziteta u Sarajevu u desetogodišnjem periodu. Isptanici i metode: istraživanjem je obuhvaćeno 58 pacijenta, oba spola, u dobi od 0-15 godina, kod kojih je dijagnostikovan limfom na Pedijatrijskoj klinici KCUS-u u periodu od 01.01.2004. do 31.12.2013. Sprovedena je retrospektivna analiza oboljelih od limfoma dječije dobi. Dobiveni rezultati su predstavljeni tabelarno i grafički, brojem i procenatualnom vrijednošću. Fišerovim i Hi-kvadrat testom je testirana razlika od normalne distribucije, a kao statistički značajna razlika smatran je (p<0,05). Rezultati: Od ukupno 58 pacijenata oboljelih od limfoma dječije dobi, bilo je 37 (63.80%) dječaka i 21 (36.20%) djevojčica, što pokazuje da dječaci više oboljevaju od djevojčica. Najviše oboljelih bilo je u dobnoj skupini od 8 - 15 godina i to 38 (65,50%). Vodeći simptom limfoma dječije dobi je limfadenopatija, koja je bila prisutna kod 45 (77.58%) pacijenata, zatim subfebrilnost kod 19 (32.75%), blijedilo kod 16 (27.59%), hepatosplenomegalija kod 13 (22.41%), te gubitak tjelesne težine kod 12 (20.69%) pacijenata. Kod 16 pacijenata sa HL i 14 pacijenata sa NHL, bile su povišene vrijednosti LDH, a Cu u serumu kod 15 pacijenata sa HL i 10 pacijenata sa NHL. Najviše pacijenata oboljelih od HL-a je dijagnosticirano u II stadiju bolesti i to 12 (37.50%), a u IV stadiju 11 (34.40%) pacijenata. Najviše pacijenata oboljelih od NHL-a je dijagnosticirano u II stadiju i to 13 (50%), te u IV stadiju 8 (30.80%). Nakon leukemija (157 pacijenata – 39.20%), limfomi su na drugom mjestu malignih oboljenja kod djece. Predstavljaju 14.50% svih maligniteta dijagnosticiranih na Pedijatrijskoj klinici KCUS-u. Godišnje se prosječno javlja 5.8 novooboljelih, a najviše ih je bilo 2013. godine i to 10 (17.20%). Desetogodišnje preživljavanje oboljelih od HL iznosilo je 87.50%, a u slučaju NHL 80.77%. Zaključak: limfomi su na drugom mjestu malignih oboljenja kod djece na Pedijatrijskoj klinici KCUS-u. Najviše oboljelih je u dobnoj skupini od 8–15 godina. Više obolijevaju dječaci. Kliničko – dijagnostičke metode i savremena terapija na Pedijatrijskoj klinici doprinose dobroj prognozi za pacijente oboljele od limfoma dječije dobi. Stope preživljavanja naših pacijenata odgovaraju istim u svjetskim centrima.

Ključne riječi: Limfom, Hodgkin, Non Hodgkin


INTRODUCTION

In the general population, neoplasms in children represent 1% of all malignancies. By cause of death, they are in second place right af-ter the accidents, with a prevalence of 10.60%. In children, the most common neoplasms are: leukemias, brain tumors and lymphomas. Lymphomas are the primary neoplasias of the lymphatic system, which are usually manifested by painless enlargement of the lymph nodes. They represent 10 - 13% of newfound malignancies in chil-dren. Lymphomas are divided into Hodgkin’s lymphoma (HL) and Non-Hodgkin’s lymphoma (NHL) which are so different diseases in epidemiology, biology, diagnostic approach, treatment and progno-sis, that they are treated quite separately. NHL represent about 60% of children’s lymphomas (1, 2). Hodgkin’s lymphoma is the most common malignant lympho-ma, characterized by hyperplasia fields of lymphoid tissue in which there are Reed-Sternberg (RS) cells. It usually starts as a painless lymphadenopathy, usually in the neck, and later the disease expands to other lymph nodes and may cause infiltration extra - lymphatic organs and tissues. Lymph nodes are much bigger and stronger than in benign lymphadenopathy, which is usually seen in children. Gener-al symptoms such as fever > 38 ° C, body weight loss > 10% in the last 6 months, night sweats, itchy skin, also called B symptoms, are not so common in children (3). The etiology of the disease is not clear. Most likely, it is import-ant influence of genetic predisposition and environmental factors, of which important socio-economic and infectious factors are im-portant once. In almost 75% of the examples of HL in childhood it is possible to prove the involvement of Epstein-Barr virus. In order to determine the treatment, the stage of the disease is determined on the basis of diagnostic biopsy and anatomical distribution. Intra-ab-dominal disease is normally diagnosed radiologically (ultrasound, CT, MRI) (3). Four types of HL are differentiated histopathologically: lympho-cyte predomination, nodular sclerosis, mixed cellularity and lym-phocyte depletion. The most favorable prognosis has lymphocyte predomination, and the least favorable lymphocyte depletion. Lym-phocyte depletion is rarein children (4, 5). The treatment of HL in the last 40 years has dramatically im-proved. With the combination therapy, which includes chemothera-py and radiotherapy, permanent cure is achieved in 80% of patients. The most frequently applied protocols for the treatment of HL in children are: ABVD (Adryamicin, Bleomycin, Vincristine, DTIC), ChlVPP (Chlorambucil, Vinblastine, Procarbasid, Pronison), COPP (Ciclofosfamid, Oncovin, Procarbazine, Pronison) (4, 5). Non-Hodgkin’s lymphomas (NHL) are clonal malignancies of lymphocytes. NHL are heterogeneous group of lymphoproliferative neoplasms marked by the emergence of malignantly altered lym-phocytes in the lymph node, and rarely primary in other organs.It is characterized by rapid growth, early dissemination and a high de-gree of malignancy. Extremely rare occurs in children under 2 years, after which the frequency increases gradually during childhood. The peak is reached between 7-10 years. NHL is 2-3 times more fre-quent in boys than in girls (6, 7, 8). According to the cell lines it belongs to, Non-Hodgkin’s lym-phoma is divided into B-NHL and T-NHL group. The World Health Organization (WHO) has classified NHL in children at four main

types: B-cell Non-Hodgkin’s lymphoma (Burkitt and non-Burkitt’s lymphoma), diffuse large B-cell lymphoma, lymphoblastic lympho-ma, anaplastic large cell lymphoma. Five-year survival in patients who were diagnosed with NHL under twenty years was 86% (6, 7, 8). The aims of this study was to evaluate the basic epidemiological and clinical characteristics of childhood lymphoma at the Hema-tooncology Department of the Pediatric Clinic of Sarajevo (CCUS) over the period of ten years.


The study included children diagnosed with malignant lymphoma (Hodgkin’s and Non-Hodgkin’s lymphoma), at the Hematooncolo-gy Department of the Pediatric Clinic of CCUS, during the period from January 1st 2004 to December 31st 2013. Total of 58 patients were subject to the analysis, 37 boys and 21 girls, aged 0 - 15 years. The retrospective study of patients with lymphoma in childhood was conducted. The data (clinical and laboratory parameters) were collected by studying the medical records of patients, and trial was conducted through a questionnaire. The results were presented us-ing tables and charts, with number of cases and percentages. Statisti-cal analysis of significant differences was performed using Fisher and Chi square test. The values of p<0.05 or on the level reliability of 95% were considered statistically significant. The following was analyzed: • genderandageof patientswithHodgkin’s(HL)andNonHod-

gkin’s lymphoma (NHL) • theratioof patientswithHLandNHLtowardsothermalignant

diseases in childhood• distributionof patientswithHLandNHLbytheyearof occur-

rence• distribution of patients with HL and NHL by the cantons of

FB&H• clinicalfeaturesof patients• laboratoryparameters• histopathologicclassification• classificationaccordingtothedegreeof lymphomaspreading.

RESULTS

Table 1 shows the gender distribution of children with HL or NHL in ten year period. Malignant lymphoma was diagnosed in 58 patients, 37 (63.80%) boys and 21 (36.20%) girls. There was a sta-tistically significant difference between the groups of boys and girls with NHL (p=0.006; Chi-square=7.538).

Epidemiological and clinical characteristics of childhood lymphoma 111

Lymphoma

HL%NHL%Total%

1753,10

2076,90

3763,80

1546,90

623,10

2136,20

32100,00

26100,00

58100,00

0,724

0,006

0,125

7,538

Boys Girls Total p-value Chi-squaretest χ2

Table 1 Gender distribution of children with lymphoma.

Table 2 shows the age distribution of children with malignant lymphoma. Most of the patients were in the age group of 8 - 15 years, precisely 38 patients (65.50%). There was a statistically sig-nificant difference in the total morbidity of malignant lymphoma between the age group of 2 - 7 years and 8 - 15 years (p=0.018; Chi-square=5.586) and morbidity of HL between the age group of 2 - 7 and 8 - 15 years (p=0.013, Chi-square=6.125).

Figure 1 shows the number of patients with malignant diseases treated at the Pediatric Clinic in a ten year period. The total number of malignancies was 401, of which most were leukemias, 157 pa-tients (39.20%), followed by lymphomas, in 58 patients (14.50%).

Table 3 shows the number of new cases of malignant lymphoma per year in the period 2004 - 2013. Most patients with HL were registered in 2005, 7 patients (21.90%) and with NHL in 2013, 6 (23.10%) patients. Table 4 shows the number of patients with malignant lymphoma by the cantons of the Federation of Bosnia and Herzegovina and Brčko District. Sarajevo Canton led with 16 (27.60%) patients, fol-lowed by Tuzla Canton with 15 (25.90%) and Zenica-Doboj Canton with 10 (17.20%) patients.

Table 5 shows the representation of symptoms in malignant lymphoma patients. The most frequent symptoms related to lymph-adenopathy (HL in 26, NHL in 19 patients), subfebrile temperature (HL in 9, NHLin 10 patients), paleness (HL in 11, NHL in 5 patients) and hepatosplenomegaly (HL in7, NHL in 6 patients). There was no statistically significant difference between the number of HL and NHL patients with these symptoms. Table 6 shows nonspecific laboratory parameters. In 16 patients with HL and 14 with NHL levels of LDH were elevated, and Cu serum levels in 15 patients with HL and 10 with NHL. There was no statistically significant difference between laboratory parameters and the type of lymphoma.

112 E. Hasanbegović et al.

Year

HL

%

NHL

%

Total

%

5

15,60

3

11,50

8

13,80

2004

7

21,90

2

7,70

9

15,50

2005

6

18,80

2

7,70

8

13,80

2006

4

12,50

4

15,40

8

13,80

2007

0

0,00

1

3,80

1

1,70

2008

1

3,10

2

7,70

3

5,20

2009

1

3,10

2

7,70

3

5,20

2010

4

12,50

2

7,70

6

10,30

2011

0

0,00

2

7,70

2

3,40

2012

4

12,50

6

23,10

10

17,20

2013

32 (3,20)

100,00

26 (2,60)

100,00

58 (5,80)

100,00

Total

Table 3 Distribution of patients by the year of occurrence.

Figure 1 The distribution of malignant diseases in the peri-od 2004 – 2013.

Canton

Una-SanaPosavina

TuzlaZenica-Doboj

Bosnian PodrinjeCentral Bosnia

Herzegovina-NeretvaWest Herzegovina

SarajevoCanton 10

Brčko DistrictTotal

Number and percentage of patientsHL % NHL % Total %3088042060132

9,400,0025,0025,000,0012,506,200,0018,800,003,10

100,00

40720210100026

15,400,0026,907,700,007,703,800,0038,500,000,00

100,00

7015100630160158

12,100,0025,9017,200,0010,305,200,0027,600,001,70

100,00

Table 4 Distribution of patients with HL and NHL by the cantons of FB&H.

26794771132231

19310865560155

0,2970,2060,8190,2480,7820,5640,1340,317n/a

0,5640,480,102

SymptomatologyLymphadenopathyLoss of appetite

Subfebrile temperatureWeakness

HepatosplenomegalyWeight loss

PalenessCough

Dryness of the oral mucosaExcessive sweating

Pain in the abdomenPain in the bones

HL NHL p-value

Table 5 Clinical signs and symptoms of patients with malig-nant lymphoma.

164515

141410

0,7150,180,7390,75

Laboratory parametersLDH

FERRITINBETA 2 GLOBULIN

Serum Cu

HL NHL p-value

Table 6 Laboratory parameters.

!! !! !!

Total p - value

Age

0 - 1years

Chi- squaretest χ2

2 - 7years

8 - 15yearsLymphoma

HL%NHL%Total%p- valueChi- square test χ2

000000

n/a

928,10

1142,30

2034,500,6550,2

2371,90

1557,70

3865,500,1941,684

32100,00

26100,00

58100,00

0,013

0,433

0,018

6,125

0,615

5,586

Table 2 Age distribution of children with lymphoma.


Figure 2 shows number of patients in relation to histopathologi-cal type of Hodgkin’s lymphoma. Most patients with HL belonged to the histopathological type of nodularsclerosis, 16 (50.0%) patients and to mixed cellularity, 11 (34.40%) patients. There was statistical-ly significant difference between the frequency of histopathological classifications of patients with HL (p=0.01, p<0.05). Figure 3 shows the relationship between the two histopatho-logical types of non-Hodgkin’s lymphoma. B-NHL was presentin the majority of patients, 16 patients (61.50%) compared to T-NHL which was present in 10 (38.50%) patients. There was no statistical-ly significant difference between the incidence of histopathological classifications of patients with NHL (p=0.239, p>0.05).

Figure 4 shows the number of patients classified according to the Ann Arbor staging classification of Hodgkin’s lymphoma. Most patients were diagnosed in stage II, 12 patients (37.50%), followed by the 11 patients (34.40%) in stage IV and 9 (28.10%) in stage III. There was no statistically significant difference between clinical stag-es of HL (p=0.804, p> 0.05).

Figure 5 shows the number of patients classified according to the clinical stage of disease progression. Most patients were diag-nosed in stage II, 13 patients (50%) and 8 (30.80%) in stage IV. There was no statistically significant difference between clinical stages of NHL (p=0.152, p> 0.05). Figure 6 shows the ten year survival rate of patients with HL in the 2004 - 2013 period, which was 87.50%.

Figure 7 shows the ten year survival rate of patients with NHL in the 2004 - 2013 period, which was 80.77%.

DISCUSSION In our study, malignant lymphoma was diagnosed in 58 patients, 37 (63.80%) boys and 21 (36.20%) girls. HL was diagnosed in 32 pa-tients, 17 boys (53.10%) and 15 girls (46.90%), which corresponds to the literature stating approximately equal ratio of morbidity in boys and girls. NHL was diagnosed in 26 children, 20 boys (76.90%) and 6 girls (23.10%). Statistical analysis performed by using Fisher and Chi-square test showed that there was a significant difference between the number of boys and girls (p=0.006; Chi-square= 7.538) suffering from NHL.

p=0.01, p< 0,05 Figure 2 Histopathological classification of Hodgkin’s lym-phoma (HL).

p=0.239, p > 0,05Figure 3 Histopathological classification of Non-Hodgkin’s lymphoma (NHL).

Figure 6 The ten-year survival rate of patients with HL in the period 2004 - 2013.

Figure 7 The ten-year survival rate of patients with NHL in the period 2004 - 2013.

p=0.804, p > 0.05Figure 4 Classification of Hodgkin’s lymphoma (HL) ac-cording to the clinical stage of disease progression (Ann Ar-bor staging classification of Hodgkin’s lymphoma).

p=0.152, p > 0.05Figure 5 St. Jude’s classification of Non-Hodgkin’s lympho-ma (NHL) according to the clinical stage of disease pro-gression.

Pourtsidis A, Pedrosa MF et al. reported 2,5-3 times more af-fected boys compared to girls, aged up to 15 years (9, 10). The highest number of patients was in the 8 through 15 age group, 38 children (65.50%). This group included 23 patients (71.90%) with HL and 15 (57.70%) patients with NHL. In the 2-7 age group, there were 20 patients, which was 34.50% of all patients. Of these, 9 patients were with HL (28.10%), and 11 (42.30%) with NHL. Statistical analysis showed that there was a significant differ-ence (p=0.013; Chi-square=6.125) between the age groups of pa-tients with HL, as well as the difference between the age groups of the total number of patients (p=0.018, Chi-square=5.586), which corresponds to the literature. Howard SC, Metzger ML et al. stated that the greatest incidence of HL and NHL was in the age group of 2-10 years, rarely occured before the age of two, and more often after the age of ten (11). There was no statistically significant difference between the age groups of patients with NHL (p=0.43, Chi-square=0.615) in our study. Total of 401 patient was treated of malignancies. Majority of them were treated of leukemia, 157 patients (39.20%), followed by lymphoma, 58 (14.50%), brain tumors 41 (10.20%), neuroblastoma 38 (9.50%), other tumors 30 (7.50%), sarcoma 29 (7.20%), nephro-blastoma 26 (6.50%) and 22 (5.50%) patients were treated of bone tumors. Konja J et al. reported that in the world, the highest number of children were suffering from leukemia, followed by brain tumors in the second place and malignant lymphomas in the third place (12). Our results do not correspond to the results of the cited literature.The main reason for discrepancies lies in the fact that this research covered a small area, in this case, the Federation of Bosnia and Her-zegovina and the Brčko District. Therefore, to cover a larger area, e.g. Southeastern Europe, it is assumed that the results would be consistent with the pre-mentioned literature, i.e. lymphomas would be in the third place. Most new cases of malignant lymphoma were diagnosed in 2013, 10 (17.20%), in 2005, 9 patients (15.50%), 8 (13.80%) in 2004, 2006, 2007, and, 6 (10.30%) patientsin 2011. In other years, the number of new cases did not exceed 5 per year, even in 2008 there were nonew cases of HL, and only 1 case of NHL was registered. Majority of new cases of HL, 7 patients (21.90%), were registered in 2005, and of NHL in 2013, 6 (23.10%) patients. The total num-ber of patients with lymphoma in the Federation of B&H and the Brčko District for the period of 10 years amounted to 58 patients, anaverage of 5.8 patients per new case. Incidence for the same area amounted to 2.32 per million out of the total number of population (according to the assessment FB&H and the Brčko District have 2.5 million people), or 0.232 per 100 000 population. Children’s Cancer Institute Australia, headed by Baade PD stated that in Australia for the period of 1997-2006, the number of new registered cases was an average of 62 per year, and the total number of patients for a period of 10 years amounted to 620. The incidence of childhood lymphoma for the same period of 10 years in Australia was 2.70% per 1 million population, or 0.270 per 100 000 population (if we take that Australia has about 23 million population). Thus, it can be concluded that the incidence of childhood lymphoma in the FB&H and the BD is less than in Australia for 0.38% per million population, or 0.038 per 100 000 population (13). According to our data, out of

total of 500 000 children aged 0-15 years in the FB&H and the BD 5.8 suffer from lymphoma, the incidence per 100 000 is 1.38, and 13.80 per million. Of the eleven observed regions, patients from seven regions approached the Hematooncology Department of the Pediatric Clinic. There were no cases of malignant lymphoma registered in Bosnian Podrinje, Posavina, West Herzegovina Canton and Canton 10. Majority of patients were from Sarajevo Canton, specifically 16 or 27.60%, 15 or 25.90% of them were from Tuz-la Canton, 10 or 17.20%, from Zenica-Doboj Canton 7 or 12.10% from Una-Sana Canton, 6 or 10.30% from Central Bosnia Canton, 3 or 5.20% from Herzegovina-Neretva Canton, and 1 or 1.70% of patients were from the Brčko District. The numbers do not indicate a special concentration of patients in certain cantons except for Sa-rajevo Canton, where 16 patients were registered (10 patients with NHL and 6 with HL). These results are largely attributed to demo-graphic factors. The main clinical symptom dominant in HL and NHL was pain-less enlargement of the lymph nodes (lymphadenopathy). In chil-dren with HL lymphadenopathy it was present in 26 cases, and in children with NHL in 19 cases. After lymphadenopathy, the most common associated symptoms were subfebrile temperature: HL 9, NHL 10; hepatosplenomegaly: HL 7, NHL6; and weight loss: HL 7, NHL 5 (all these symptoms occured equally). The difference be-tween HL and NHL was noted in the occurrence of symptoms such as loss of appetite, paleness, weakness, cough and pain in the bones. Thus, for example, in HL: 7 patients suffered from loss of appetite and 11 from paleness, compared to NHL where 3 patients suffered from loss of appetite and 5 from paleness. The symptoms in NHL occurred more symptomatologically such as weakness in 8 patients, cough in 6, pain in the bones in 5 patients, compared to HL where cases of weakness were registered in 4 patients, coughin 3 and pain in the bones 1 patient. The difference was evident, but not so rele-vant for statistically significant difference. Schwartz CL, Büyükpakmukcu M, et al. reported that the most common symptoms of lymphoma were lymphadenopathy, fever, loss of appetite, weight loss, weakness with night sweating and itch-iness of the skin (1, 14). The following non-specific laboratory parameters of lymphoma were monitored: lactate dehydrogenase (LDH), ferritin, β2-globulin and cuprum (Cu) in serum (2). The increase in their values indicated to the worsening of the disease and its activity. LDH was elevated in 16 cases of HL and in 14 cases of NHL. Ferritin was elevated in 4 patients with HL and in 1 patient with NHL. β2-globulin was elevat-ed in five patients with HL and in 4 with NHL, and Cu serum levels in 15 patients with HL and 10 patients with NHL. There was no sta-tistically significant difference between the two groups of patients. The study conducted by Sanjay Vinjamaram MD et al. found that laboratory parameters in NHL such as LDH, β2-globulin, serum Cu were significant during the screening test, in monitoring the effects of therapy to the final cure. Ye QD, Pan C, et al. confirmed that laboratory parameters in HL, LDH, serum Cu, ferritin, β2-globulin were very important for prognosis, course and outcome of disease. These two studies showed that these laboratory parameters for both, HL and NHL, played a very important role in monitoring the disease and that there was no statistically significant difference be-tween subtypes of lymphoma, which is consistent with our research (15, 16).

114 E. Hasanbegović et al.

From the point of pathohistology REAL (Revised Europe-an-American Lymphoma) classification is currently in use, modified and accepted by the World Health Organization (WHO), which dif-fers nodular form of lymphocyte predomination and classical Hod-gkin’s lymphoma. Classical HL is divided into nodular sclerosis, lymphocyte pre-domination, mixed cellularity and lymphocyte depletion. It was noticed that most cases had nodular sclerosis, 16 cases (50.0%), followed by mixed cellularity in 11 patients (34.4%), while the lym-phocyte predomination and depletion were represented in a small-er number. There was statistically significant difference between the incidence of histopathologic classifications of patients with HL (p=0.01, p<0.05). Obralić et al. reported that the most common was nodular type, with the representation of 40-70%, followed by mixed cellularity (30-50%), lymphocyte predomination (5-10%) and lymphocyte depletion with 1-5% (17). Our results correlate with the results in the international literature. Out of 26 patients with NHL, 16 (61.50%) had B-NHL, and 10 patients (38.50%) T-NHL. Murphy SB, et al reported the inci-dence of B-NHL > 60%, or more precisely (65-70%), and of T-NHL <40%, or more precisely (30-35%) (18). The results of our study are approximate to the relevant literature. According to the clinical stage of disease progression, Hodgkin’s lymphoma was classified by the Ann Arbor classification system. Majority of new cases were diagnosed in stage II of disease, 12 (37.50%), then in stage IV, 11 (34.40%), and in stage III 9 patients (28.10%). There was not diag-nosed cases of HL in the first stage. Xing PY et al. noted that patients diagnosed with HL were 28.40% in stage I, 34.80% in stage II, 19.70% and 17.10% in stage III and IV (19). According to our research, most of Hodgkin’s lympho-ma (HL) was diagnosed in stage II and IV, while based on interna-tional literature, HL in children was most represented in the first and second stage. According to the clinical stage of disease progression, non-Hodgkin’s lymphoma was classified by St. Jude’s classification system. The highest number of new cases were diagnosed at the time when they were already in stage II of disease, 13 (50%). There were 8 (30.80%) patients in stage IV and 5 (19.20%) in stage III. Adamson P, Murphy et al. reported the results according to stages: I (18%), II (21%), III (43%) and IV (18%) (20). Non-Hodgkin’s lymphoma (NHL) according to our results was the most represented in the second stage, while according to rele-vant international literature, NHL was the most common in stage III.In our study, ten-year survival of patients with HL was 87.50% and 80.77% with NHL. These results were approximate to the data that Lee SH, Xing PY, et al. noted (21, 19).

CONCLUSION

Lymphomas are the second malignancies in children at the Pe-diatric Clinic of CCUS. Most patients are in the age group of 8-15 years, with higher percentage prevalence of boys compared to girls. Clinical diagnostic methods and modern therapy at the Pediatric Clinic contribute to the good prognosis for patients suffering from lymphoma in childhood. The survival rates of patients are similar to those in international centres.


REFERENCES

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3. Saunders C. Hsu, Monika L. Metzger, Melissa M. Hudson et al. Comparison of

Treatment Outcomes of Childhood Hodgkin Lymphoma in Two US Centers and a

Center in Recife, Brazil. Pediatric Blood Cancer 2007;49:139-144.

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2002; 122: 718-727.

5. Thomson AB, Wallace WHB. Treatment of paediatric Hodgkin’s disease: a balance

of risks. Eu J Cancer 2002 Mar; 38(4): 468-77.

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management. Indian Pediatrics 2001 Jun; 38(6): 583-8.

7. Cairo MS et al. Non-Hodgkin lymphoma in children. In Kufe DW. Cancer medicine

E. 6. London: BC Decker Inc, 2003; 374-87.

8. Hasanbegović E, Šabanović S. The results of Hodgkin lymphoma treatment in chil-

dren in the period 1997.-2006. Bosn J Basic Med. 2008 Feb;8(1): 72-5.

9. Pourtsidis A, Doganis D, Baka M, Bouhoutsou D, Varvoutsi M, Synodinou M, et al

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ma. Pediatr Hematol Oncol. 2013 Sep; 30(6): 532-6

10. Pedrosa MF, Pedrosa F, Lins MM, Pontes Neto NT, Falbo GH. Non-Hodgkin’s lym-

phoma in childhood: clinical and epidemiological characteristics and survival analysis

at a single center in Northeast Brazil. J Pediatr (Rio J). 2007 Nov-Dec; 83(6): 547-54.

11. Cairo MS et al. Non-Hodgkin lymphoma in children. In Kufe DW. Cancer medicine

E. 6. London: BC Decker Inc, 2003; 374-87.

12. J. Konja i sur. Maligni limfomi. Paediatr Croat 2006; 50 (Supl 1): 198-202.

13. BaadePD, Youlden DR, Valery PC, Hassall T, Ward L, Green AC et al, Trends

in incidence of childhood cancer in Australia, 1983–2006.Br J Cancer. 2010 Feb

2;102(3):620-6; Average annual incidence for lymphoma, 1997-2006; British Journal

of Cancer (2010) 102, 620–626.

14. Schwartz CL. The management of Hodgkin disease in the young child. Curr Opin

Pediatr. 2003 Feb; 15(1): 10-6.

15. Sanjay Vinjamaram, MD, MPH. Diagnosis signs and symptoms, laboratory studies in

a patient with suspected NHL. Sep 20 2006;24(27):4418-25.

16. Ye QD, Pan C, Xue HL, Chen J, Zhou M, Jiang H, Shen SH, Tang YJ, Wang JM. De-

partment of Hematology/Oncology, Shanghai Children’s Medical Center, Shanghai

Jiaotong University School of Medicine, Shanghai 200127, China.

17. Obralić N. Limfomi: Morbus Hodgkin, non-Hodgkin limfomi. U Mušanović M, Obralić

N: Onkologija. Bošnjački institut, Sarajevo, Bosna i Herzegovina, 2002; 373-396.

18. Murphy SB. Classification, staging and results of treatment of childhood non-Hod-

gkin’s lymphomas in adults. Semi Oncol 1980 Sept; 7(3):332-9.

19. Xing PY, Shi YK, He XH, Zhou LQ, Dong M, Yang JL, Liu P. Clinical analysis of child-

hood and adolescent Hodgkin’s lymphoma: a report of 88 cases. Zhonghua Zhong

Liu Za Zhi. 2012 Sep; 34(9): 692-7. doi: 10.3760/cma.j.issn.0253-3766.2012.09.011.

20. Adamson P, Bray F, Costantini AS, Tao MH, Weiderpass E, Roman E. Time trends in

the registration of Hodgkin and non-Hodgkin lymphomas in Europe. Eur J Cancer

2007 Jan;43(2):391-401.

21. Lee SH, Yoo KH, Sung KW, Ko YH, Lee JW, Koo HH. Department of Pediatrics,

Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Re-

public of Korea. Pediatr Blood Cancer. 2013 Nov;60(11):1842-7. doi: 10.1002/

pbc.24695. Epub 2013 Jul 16.

Reprint requests and correspondence:Edo Hasanbegović, MD, PhDPediatric ClinicClinical Center University of SarajevoPatriotske lige 81, 71000 SarajevoBosnia and HerzegovinaPhone: +387 33 566 448Email: [email protected]


Secondary osteoporosis in hospital sample

Sekundarna osteoporoza u bolničkom uzorkuKsenija Miladinović1*, Narcisa Vavra-Hadžiahmetović1, Slavica Šakota1, Damir Čelik1, Haris Tanović2 1Clinic of Physical and Rehabilitation Medicine, Clinical Center University of Sarajevo, Bolnička 25, 71000 Sarajevo, Bosnia and Herzegovina, 2Clinic of General and Abdominal Surgery, Clinical Center University of Sarajevo, Bolnička 25, 71000 Sarajevo, Bosnia and Herzegovina


ABSTRACT

Introduction: secondary osteoporosis still remains subdiag-nosed entity. According to previous studies in certain diseases such as multiple sclerosis, spinal cord lesion, diabetes mellitus, rheuma-toid arthritis, malignomas, chronic kidney disease, as well as in con-dition after hysterectomy, diagnosis and treatment of secondary osteoporosis is very important. Objective: the aim of this study was to analyze the pattern of hospital patients who had the diseases where development of secondary osteoporosis was expected. Ma-therial and Methods: out of all medical records of the patients who were treated at the inpatient Clinic of Physical and Rehabilitation Medicine (n=531) from November 2012 to November 2013, the patients who had the diseases, where development of secondary osteoporosis was expected, were selected, and these were: mul-tiple sclerosis, spinal lesion, diabetes mellitus, rheumatoid arthritis, malignant disease, chronic kidney disease, as well as condition after hysterectomy. Patients were divided in two groups. The first group (I) consisted of patients to whom secondary osteoporosis was diag-nosed and treated, and the second group (II) consisted of patients to whom diagnostic procedures for secondary osteoporosis were not performed, although according to clinical picture and to primary disease they were potential candidates. Results: out of total num-ber of hospitalized patients (n=531), 13.2% (n=70) had the diseases where development of secondary osteoporosis was expected. In 20% of these patients secondary osteoporosis was diagnosed and treated, and they presented the first group (I). In this group the most frequent disease was spinal lesion, presented by 57.1% (n=8), followed by multiple sclerosis and rheumatoid arthritis with 14.3% (n=2) each, then chronic kidney disease and malignant disease with 7.1% (n=1) each. Male patients formed 42.8% (n=6) of this group. The second group (II) was presented by 80% of selected patients (n=56) with primary disease where development of secondary osteoporosis was expected, but they were not diagnosticaly pro-cessed. In this group the most frequent disease was multiple sclero-sis, presented by 39.3% (n=22), followed by malignoma with 26.76% (n=15), then spinal lesion and diabetes mellitus with 10.7% (n=6) each, condition after hysterectomy with 8.8% (n=5) and rheumatoid arthritis with 3.6% (n=2). Ratio between males and females was 1:1. Conclusion: patients with certain diseases, like multiple sclerosis, spinal cord lesion, diabetes mellitus, rheumatoid arthritis, malignant disease, chronic kidney disease, as well as condition after hysterec-tomy, regardless of stage and time of disease occurance, demand higher attention for secondary osteoporosis diagnostic processing.

Key words: secondary osteoporosis, diagnostic processing

SAŽETAK

Uvod: sekundarna osteoporoza je još uvijek subdijagnosticiran entitet. Dosadašnje studije pokazuju da je dijagnoza i liječenje sekundarne osteoporoze veoma važno kod odredjenih bolesti kao što su: multipla skleroza, spinalna lezija, diabetes melitus, reumatoidni artritis, malignomi, hronične bolesti bubrega, kao i stanje nakon histerektomije. Cilj: ova studija je imala za cilj da analizira uzorak bolničkih pacijenata koji su imali bolesti gdje se očekuje razvoj sekundarne osteoporoze. Materijal i metode: iz medicinske dokumentacije svih pacijenata koji se hospitalizirani na Klinici za fizijatriju i rehabilitaciju Univerzitetskog Kliničkog Centra u Sarajevu (n=531) od novembra 2012. do novembra 2013. godine, izdvojeni su pacijenti koji su imali bolesti kod kojih se očekivao razvoj sekundarne osteoporoze, a to su bile: multipla skleroza, spinalna lezija, diabetes melitus, reumatoidni artritis, malignomi, hronične bolesti bubrega, kao i stanje nakon histerektomije. Pacijenti su zatim podijeljeni u dvije grupe. Prvu grupu (I) su sačinjavali oni pacijenti kod kojih je dijagnosticirana i tretirana sekundarna osteoporoza, a drugu grupu (II) pacijenti kod kojih nisu provedene dijagnostičke procedure za sekundarnu osteoporozu, iako su po kliničkoj slici i primarnoj bolesti bili potencijalni kandidati da je imaju. Rezultati: od ukupnog broja hospitaliziranih pacijenata (n=531), 13.2% (n=70) je imalo primarnu bolest kod koje se očekuje razvoj sekundarne osteoporoze. Kod 20% od ovih pacijenata sekundarna osteoporoza je bila dijagnosticirana i tretirana, (grupa I). U ovoj grupi najčešća primarna bolest je bila spinalna lezija, 57.1% (n=8), praćena sa multiplom sklerozom i reumatoidnim artritisom, 14.3% (n=2) svaka, zatim sa hroničnom bubrežnom bolešću i malignitetima, 7.1% (n=1) svaka. Muškarci su sačinjavali 42.8% (n=6) ove grupe. Grupa II je bila predstavljena sa 80% selektiranih pacijenata (n=56) koji su imali primarne bolesti kod kojih se očekivao razvoj sekundarne osteoporoze, ali im nije uradjena dijagnostika za postojanje iste. U ovoj grupi najčešća primarna bolest je bila multipla skleroza, 39.3% (n=22), praćena sa malignomima, 26.76% (n=15), zatim sa spinalnom lezijom i diabetes melitusom sa 10.7% (n=6) svaka, stanjem nakon histerektomije sa 8.8% (n=5) i reumatoidnim artritisom sa 3.6% (n=2). Odnos žena i muškaraca je bio 1:1. Zaključak: pacijenti sa odredjenim oboljenjima kao što su multipla skleroza, spinalna lezija, diabetes melitus, reumatoidni artritis, malignomi, hronične bolesti bubrega, kao i stanje nakon histerektomije, bez obzira na stadij bolesti, zahtijevaju više inicijative za dijagnosticiranje sekundarne osteoporoze.

Ključna riječ: sekundarna osteoporoza, dijagnostičke procedure


INTRODUCTION

Osteoporosis that results from having another disease or condi-tion or from the treatment of another condition is called second-ary osteoporosis. Secondary osteoporosis remains a diagnostic and therapeutic challenge as it frequently affects patient populations, e.g. premenopausal women or younger men who are usually not target populations for routine screening for osteoporosis. A variety of diseases or conditions can increase bone loss and/or fall risk, such as: rheumatoid arthritis and other rheumatological conditions, neurological disorders (stroke, multiple sclerosis, spinal lesion, Parkinson’s disease, cerebral palsy, neuropathy), malabsorp-tion syndromes, sex hormone deficiency, primary hyperparathyroid-ism, chronic kidney disease, chronic liver disease, diabetes, chronic obstructive pulmonary disease or hyperthyroidism. Medications that can cause bone loss, falls and/or fractures are: synthetic glucocorti-coids (e.g. prednisone), breast cancer drugs, prostate cancer drugs, “heartburn” drugs, excessive thyroid hormone replacement, anti-sei-zure and mood-altering drugs, blood pressure medication, diuretics, prostate drugs, and others drugs. Management of secondary osteo-porosis includes treatment of the underlying disease, modification of medications known to affect the skeleton, and specific anti-osteopo-rotic therapy. It is very important to diagnose and treat secondary osteoporosis, otherwise falls and fractures, as well as visceral and heterotopic calcu-losis, reduce already compromised quality of life of these patients. Osteoporosis related to rheumatoid arthritis and oth-er rheumatological conditions; an inflammatory disease of the joints, rheumatoid arthritis (RA) is often treated with glucocorticoids, usually prednisone. Pain and loss of joint function can lead to inactiv-ity, which can further contribute to bone loss. Research suggests that osteoclast activity and bone resorption is increased at the affected sites. During the pathological processes, inflammatory cytokines such as TNF (tumor necrosis factor) are largely produced from inflamed synovium and cause activation of osteoclasts deviated from bone re-modeling cycle. (1) Osteoporosis in RA is characterized by bone loss in the hip and the radius, while the axial bone is relatively preserved. Bisphosphonates are well known to be effective for not only treat-ment but also prevention of glucocorticoid-induced osteoporosis. In addition to rheumatoid arthritis, ankylosing spondylitis has been associ-ated with bone loss. Several other rheumatologic conditions may affect the joints, resulting in poor balance and increased risk of falls, including lupus, psoriatic arthritis and severe osteoarthritis of the hip or knee. Osteoporosis related to multiple sclerosis; multiple scle-rosis (MS) is disorder characterized by acute episodes of neurolog-ical defects leading to progressive disability. Patients with MS have multiple risk factors for osteoporotic fractures, such as progressive immobilization, long-term glucocorticoids treatment or vitamin D deficiency. The duration of motor disability appears to be a major contributor to the reduction of bone strength. The long term immo-bilization causes a marked imbalance between bone formation and resorption with depressed bone formation and a marked disruption of mechanosensory network of tightly connected osteocytes due to increase of osteocyte apoptosis. Vertebral BMD is affected to a lesser degree than femoral BMD. Patients with higher level of disability have also higher risk of falls that combined with a bone loss increases the frequency of bone fractures. The low BMD in MS patients involve

both sexes. (3) The physical as well as pharmacological interventions which can counteract the bone remodeling imbalance, particularly osteocyte apoptosis, are promising for prevention and treatment of osteopo-rosis in patients with MS. Osteoporosis related to spinal lesion; osteoporosis induced by spinal lesion (SL) is, actually, inevitable complication, which begins to develop already tenth day after occurrence of spinal lesion, reach-es its maximum after 4-6 months, then stabilizes after 12-16 months. It occurs predominantly in the pelvis and the lower extremities, and is found in 60-90% of patients with SL. (4) Mechanism of spinal lesion induced osteoporosis development is complex. Initially it has been studied in the light of altered metabolism of calcium and hypercal-cemia, associated hypercalcuria and the loss of load. Multifactorial mechanism of its formation, both in acute and in chronic phase of SL, is examined in detail only in the last ten years. In addition to neu-rological changes caused by spinal cord lesion, especially interruption of pathways which are involved in bone innervation, affection factors may include abnormalities of blood flow in infralesion levels that in-fluence bone cell differentiation, and hormonal changes that generate metabolic bone disorder. In the chronic phase of SL osteoporosis is balanced by increasing bone mineral density in regions of the body that are burdened by their own weight, like upper extremities and the spine, and even by greater demineralization of regions that are chronically without a load, such as pelvis and lower extremities. Oste-oporosis induced by SL has been successfully treated with physical as well as pharmacological interventions which can counteract the bone remodeling imbalance, such as bisphosphonates or denosumab. Osteoporosis related to malignant disease; patients with cancer may be at risk for secondary osteoporosis related to cancer therapies, particularly therapies that impair gonadal function. Patients with cancers such as breast or prostate cancer who have been treated with hormone deprivation therapies or anti-cancer agents for certain periods of time frequently manifest reduced bone mass or pathologi-cal fractures during their clinical course. These are likely due to an im-balance between osteoblastic bone formation and osteoclastic bone resorption. (5) Bone should be carefully monitored in these patients. Identifying which patients with cancer are at risk for bone mineral density loss is important, and beside patients with breast or prostate cancer, may include adults with other tumors and some survivors of pediatric malignancies. (6) Osteoporosis among cancer survivors is higher in elderly subjects and in female cancer survivors (95%). In male cancer survivors, underweight and lower calcium intake are risk factors. (7) Administration of some agents, such as bisphosphonates or denosumab, may be necessary to maintain bone mineral density and protect pathological fractures in these cancer patients. Osteoporosis related to diabetes mellitus; diabetes mel-litus is a risk factor for osteoporotic fractures. Patients with recent onset of type 1 diabetes mellitus may have impaired bone formation because of the absence of the anabolic effects of insulin and amylin, whereas in long-standing type 1 diabetes mellitus, vascular compli-cations may account for low bone mass and increased fracture risk. Patients with type 2 diabetes mellitus display an increased fracture risk despite a higher BMD, which is mainly attributable to the increased risk of falling. (8) Strategies to improve BMD and to prevent osteo-porotic fractures in patients with type 1 diabetes mellitus may include optimal glycemic control and aggressive prevention and treatment of

Secondary osteoporosis in hospital sample 117

vascular complications. Patients with type 2 diabetes mellitus (T2DM) may additionally benefit from early visual assessment, regular exercise to improve muscle strength and balance, and specific measures for preventing falls, as well as from calcium and vitamin D rich diet. The prevalence of low BMD in males with T2DM is 59.1% according to recent study (9). Osteoporosis related to chronic kidney disease; changes in mineral metabolism and bone structure develop early in the course of chronic kidney disease and worsen with progressive loss of kid-ney function. Chronic kidney disease (CKD) includes abnormalities of calcium, phosphorus, parathyroid hormone, or vitamin D, abnor-malities in bone turnover, mineralization, volume, linear growth, or strength, and vascular or other soft tissue calcification (10). Patients with chronic kidney disease may have other bone diseases (osteopo-rosis, vitamin D deficiency) either before or after developing kidney disease. It is difficult to diagnose osteoporosis in the setting of CKD. This is particularly relevant for the aging population, where fragility fractures, reduced glomerular filtration rate (GFR), and low bone mineral density are more prevalent. There are multiple reasons why this differentiation is important, not the least of which is that man-agement of osteoporosis versus the spectrum of bone diseases in patients with CKD differ vastly. Osteoporosis related to hysterectomy; it is very well known that osteoporosis and increased risk of bone fractures are associat-ed with hysterectomies. This has been attributed to the modulatory effect of estrogen on calcium metabolism, and the drop in serum es-trogen levels after menopause can cause excessive loss of calcium leading to bone wasting. Strategies to improve BMD and to prevent fracture are based on hormone replacement therapy (HRT), calcium and vitamin D, or other type of drugs for osteoporosis.


Out of all medical records of the patients who were treated at the Clinic of Physical and Rehabilitation Medicine (n=531) from No-vember 2012 to November 2013, the patients who had the diseases where development of secondary osteoporosis was expected were selected, and these were: multiple sclerosis, spinal lesion, diabetes mellitus, rheumatoid arthritis, malignant disease, chronic kidney dis-ease, as well as condition after hysterectomy. Patients were divided in two groups. The first group consisted of patients whom second-ary osteoporosis was diagnosed and treated (I). The second group (II) consisted of patients whom diagnostic procedures for secondary osteoporosis presence were not performed, although according to clinical picture and to primary disease they were potential candidates.

RESULTS

Out of total number of hospitalized patients (n=531), 13.2% (n=70) had the diseases where development of secondary osteopo-rosis was expected (Figure 1). In 20% of these patients secondary osteoporosis was diagnosed and treated, and they presented the first group (I) (Figure 2). In this group the most frequent disease was spinal lesion, present-ed by 57.1% (n=8), followed by multiple sclerosis and rheumatoid arthritis with 14.3% (n=2) each, then chronic kidney disease and ma-lignoma with 7.1% (n=1) each (Figure 3).

Male patients formed 42.8% (n=6) of this group.

The second group (II) was presented by 80% of selected patients (n=56) with primary disease where development of secondary os-teoporosis is expected, but they were not diagnosticaly processed (Figure 2).

In this group the most frequent disease was multiple sclerosis, pre-sented by 39.3% (n=22), followed by malignoma with 26.8% (n=15),

then spinal lesion and diabetes mellitus with 10.7% (n=6) each, con-dition after hysterectomy with 8.8% (n=5) and rheumatoid arthritis with 3.6% (n=2) (Figure 4). Ratio between males and females was 1:1.

118 K. Miladinović et al.

Figure 1 Percantage of patients with diseases in wich devel-opment of secondary osteoporosis is expected.

Figure 2 Percantage of patients with diagnosed ant treated secondary osteoporosis and of patients who were not diag-nosticaly processed.

Figure 3 Diseases related to diagnosed and treated second-ary osteoporosis.

Secondary osteoporosis in hospital sample 119

DISCUSSION

Secondary osteoporosis is characterized by low bone mass with microarchitectural alterations in bone leading to fragility fractures in the presence of an underlying disease or medication. An open-minded approach with a detailed history and physical examination combined with first-line laboratory tests are aimed at identifying clinical risk factors for fractures, osteoporosis-inducing drugs, and underlying endocrine, gastrointestinal, hematologic, or rheumatic diseases, which then need to be confirmed by specific and/or more invasive tests. Bone mineral density should be assessed with bone densitometry at the hip and spine. Lateral X-rays of the thoracic and lumbar spine should be performed to identify or ex-clude prevalent vertebral fractures which may be clinically silent. (11) In our hospital sample 20% of patients (I group) were diagnosed and treated for secondary osteoporosis, and 80% of patients (II group) (n=56), with primary disease where development of secondary os-teoporosis was expected, were not diagnosticaly processed. The most frequent primary disease in group I was spinal lesion, present-ed by 57.1% (n=8), followed by multiple sclerosis and rheumatoid arthritis with 14.3% (n=2) each, then chronic kidney disease and malignoma with 7.1% (n=1) each. Rather high percentage (80%) of patients were not diagnosticaly processed for secondary osteopo-rosis, even though they had primary disease where development of secondary osteoporosis was expected. The most frequent disease in this group (II) was multiple sclerosis, presented by 39.3% (n=22), followed by malignoma with 26.76% (n=15), then spinal lesion and diabetes mellitus with 10.7% (n=6) each, hysterectomy with 8.8% (n=5) and rheumatoid arthritis with 3.6% (n=2). Patients with MS have multiple risk factors for osteoporotic frac-tures, such as progressive immobilization, long-term glucocorticoids treatment or vitamin D deficiency. The analysis of a registry of 9029 patients with MS in the USA found that 27.2% responders reported low bone mass, and more than 15% of responders reported a history of fracture. (3) In our sample multiple sclerosis was presented with 14.3% in the first (I) group of patients and with 39.3% in the second group (II). Osteoporosis induced by spinal lesion (SL) is found in 60-90% of patients with. (4) In our analysis the most frequent primary disease was spinal lesion in group I, presented by 57.1% (n=8). In the second group osteoporosis induced by SL was presented by 10.7% (n=6). The adverse effects of diabetes mellitus have just recently been acknowledged. In fact, patients with type 1 diabetes mellitus have a

12-fold higher risk of sustaining osteoporotic fractures, compared with non-diabetic controls. (12) In our sample diabetes mellitus was not presented in the first group (I) at all, and in the second group it was presented by 10.7% (n=6). Several cross-sectional studies doc-umented a lower mineral bone density in patients with RA, with a two-fold increase in osteoporosis compared to age and sex matched controls. (2) In the first group (I) of selected patients in our analy-sis rheumatoid arthritis was presented with 14.3% (n=2), and in the second group (II) with 3.6% (n=2). It is very important to prevent and treat bone loss after hysterectomy because of high risk for os-teoporotic fractures. Our hospital sample showed that there were 8.8% (n=5) of women with hysterectomy in the second (II) group of patients, and that condition was not present in the first group (I).

CONCLUSION

Patients with certain diseases, like multiple sclerosis, spinal cord le-sion, diabetes mellitus, rheumatoid arthritis, malignant disease, chron-ic kidney disease, as well as condition after hysterectomy, regardless of stage and time of disease occurance, demand higher attention for secondary osteoporosis diagnostic processing.


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Figure 4 Diseases related to diagnosticaly not processed secondary osteoporosis.

Most common etiologies of neurogenic laryngeal paralysis in middle-aged patients

Najčešći uzroci neurogenih paraliza larinksa kod pacijenata srednje životne dobiMirjana Gnjatić1*, Daniela Kesić Mijić2, Tatjana Barać3, Svjetlana Trifunović2

1Ear, Nose and Throat Clinic, Clinical Center Banja Luka, 12 beba 1, 78000 Banja Luka, Bosnia and Herzegovina; 2Outpatient Department Banja Luka, Sime Matavulja bb, 78000 Banja Luka, Bosnia and Herzegovina; 3Department of Gastroenterology, Clinical Center Banja Luka, 12 beba 1, 78000 Banja Luka, Bosnia and Herzegovina


ABSTRACT

Introduction: a large number of causes lead to neurogenic laryn-geal paralysis, which is expressed as impairment of certain laryngeal muscles function and manifested as hoarseness and dysphonia. Neu-rogenic laryngeal paralyses are the matter of interest and research for otolaryngologists, because of complex etiology, precise evaluation, as well as diagnostics, and especially because of the long and complicated treatment. Aim: determine the prevalence of etiological factors and symptoms of unilateral and bilateral neurogenic paralysis of the larynx (gender, age) and their differences. Materials and methods: we have performed a three-year prospective study in the Clinical Center Banja Luka which included 110 patients in Ear, Nose and Throat Clinic, Clin-ical Center Banja Luka. The patients were monitored in the phoniatric cabinet where, the types of paralysis were determined by means of the endo-videostrobescope, and etiological causes by means of the questionnaires. The obtained results were analyzed by using standard statistical methods - X² test, Student test. Results: the study included a total of 110 patients, of which 70.9% were females and 29.9% males. It appeared that 92 patients had unilateral vocal cord paralysis while 18 had bilateral, mainly in the female population. Complications after the thyroid gland surgery were the leading etiologic factor in the de-velopment of bilateral neurogenic paralysis of the larynx. Conclusion: our research resulted in a conclusion that the leading factor in the life threatening bilateral paralysis development is a thyroid gland surgery (due to the increase in malignant disease of the thyroid gland, which is an additional risk for surgical treatment), as well as the operation risks.

Keywords: neurogenic laryngeal paralysis, unilateral paralysis, bilater-al paralysis, etiology

SAŽETAK

Uvod: veliki je broj uzročnika neurogenih paraliza larinksa, koje se očituju kao smanjenom funkcijom određenih laringealnih mišića, a koja se manifestuje kao promuklost i disfonija. Neurogene paralize larinksa su predmet interesovanja i istraživanja otorinolaringologa zbog svoje kompleksne etiologije, potrebne precizne evaluacije, di-jagnostičke obrade, a posebno zbog duge i komplikovane terapije.Cilj rada: odrediti prevalence etioloških faktora i simptoma jednos-trane i obostrane neurogene paralize glasnica u larinksu (pol, dob) i njihove razlike. Materijal i metode: trogodišnja prospektivna studija je sprovedena u Kliničkom Centru u Banjaluci koja je uključivala 110 pacijenata Otorinolaringološke klinike, Kliničkog Centra Banjaluka. Pacijenti su praćeni u fonijatrijskom kabinetu, gdje su, endovideos-troboskopskom metodom, određivani tipovi paraliza i, kroz upit-nike, utvrđeni etiološki uzroci. Dobijeni rezultati su obrađeni stan-dardnim statističkim metodama – X2 test, Studentov test. Rezultati: Ukupan broj pacijenta u ovoj studiji iznosio je 110, od čega je 70.9% bilo ženskog, a 29.9% muškog pola. Pokazalo se da su 92 pacijen-ta imali jednostranu, a 18 obostranu paralizu glasnica – pretežno u ženskoj populaciji. Komplikacije nakon operacije štitne žlijezde su bile vodeći faktor u razvoju obostranih neurogenih paraliza glasni-ca larinksa. Zaključak: naše istraživanje nas je dovelo do zaključka da vodeći faktor u razvoju obostrane paralize glasnica, a koji može i ugroziti život pacijenta, jeste operacija štitne žlijezde (zbog pov-ećanog maligniteta štitnjače što predstavlja dodatan rizik pred hiruški zahvat), kao i operativni rizici.

Ključne riječi: neurogena laringealna paraliza, jednostrana parali-za, obostrana paraliza, etiologija

INTRODUCTION

Larynx, as one of the functionally most perfect human organs, with its highly specialized features sounds as an intellectually con-scious being. From the time of Hippocrates (460-370 BC) it was observed that denervation of the larynx had life-threatening con-sequences (1,2,3,4). A large number of causes lead to neurogenic laryngeal paralysis, which can be seen as a failure of certain functions of laryngeal muscle and heard as hoarseness, dysphonia. The most common causes of laryngeal paralysis are: 1) goiter of the thyroid gland 2) thyroid surgery 3) thoracic surgery 4) neurological caus-

es 5) prolonged intubation 6) lung cancer 7) esophageal cancer 8) idiopathic paralysis. Neurogenic laryngeal paralyses are the matter of interest and research for otolaryngologists, because of complex etiology, precise evaluation, as well as diagnostics, and especially be-cause of the long and complicated treatment (5,6). Neurogenic laryngeal paralysis (unilateral and bilateral vocal cord paralysis), along with numerous other disorders, is one of the most common reasons for occurrence of vocal dysfunction that causes hoarseness. About 1/3 of the total population during certain period of life experiences hoarseness. Control of phoniatric function be-gins on the cerebral cortex, depends upon respiratory musculature,

Medical Journal (2014) Vol. 20, No. 2, 120 - 123 Professional article

the state of the lungs and expiratory air flow through the trachea and larynx and the vocal cords, and also depends of n. recurrensa function innervated by opening and closing of the glottis (7-12). Among the most common causes of vocal paralysis are neck and chest injuries, goiter, thyroid tumors, cancers of the esopha-gus and lung, as well as complications after their surgery. Causes of neurogenic laryngeal paralysis can also be metastasis in the lymph nodes as well as aortic aneurysm, viral infections, prolonged intuba-tion and idiopathic neurogenic paralysis (cases where etiologic origin factor has not been determined). The main symptoms of unilateral (one-sided) paralysis of the larynx are hoarseness/dysphonia and difficulty in swallowing/dysphagia, while in bilateral paralysis more pronounced are breathing disturbances (dyspnea) due to narrowing of the airway caused by the vocal cords position. Position of the vocal cords determines the degree of glottal occlusion, which affects the respiratory function and the degree of hoarseness (10,11,12). The aim of this article is to determine the prevalence and etio-logical factors and symptoms of unilateral and bilateral neurogenic paralysis of the larynx (gender, age) and their differences.


We performed a three-year prospective study, which included 110 patients an Ear, Nose and Troath Clinic, Clinical Center of Ban-ja Luka, who were monitored through phoniatric examination. The data were analyzed by using standard statistical methods. The differ-ences between the groups were compared by using the χ2 contigen-cy test. For the purpose of comparison of the average values of pa-rameters, we used the Student test for independent samples and non-parameter Mann-Whitney test (the values with p<0,05 were taken as statistically significant). For the purpose of determining the degree of the observed parameters correlation, we applied the Pearson parameter correla-tion. All results are presented in the tables and figures below.

RESULTS

The total number of patients included in this study was 110, of which 70.9% were females and 29.9% males. In our study, we have found that 83.64% were unilateral neurogenic vocal cord paralysis, against 16.36% of bilateral paralysis, as shown in Figure 1.

Etiology of laryngeal paralysis was demonstrated in 99 patients, while the remaining 11 patients were classified as idiopathic larynge-al paralysis. The age group that was involved in the study included the pa-tients between 25 and 83 years of age and it appeared that the pa-ralysis of the vocal cords larynx was predominantly found in the middle-aged patients, as shown in Table 1.

Bilateral paralysis of the vocal cords was found in 18 patients, predominantly in women - 16 patients (88.8%), as shown in Figure 2.

Complications after surgery of the thyroid gland were leading etiologic factor in the development of bilateral neurogenic laryngeal paralysis, as shown in Figure 3.

Age rate Frequency

Absolute Relative

26 -35 7 6.36% 36 - 45 15 13.63%

46 - 55 14 12.72% 56 - 65 32 29.09%

66 - 75 26 23.63% 76 - 85 16 14.54%

Total 110 100%

Table 1 Age distribution.

Most common etiologies of neurogenic laryngeal paralysis in middle-aged patients 121

Figure 1 Localization of the involvement of the vocal cords.

Figure 2 Gender distribution of bilateral paralysis.

Figure 3 Etiology of bilateral paralysis.

Based on the statistical data processing, we noticed that there was a statistically significant difference among the etiological causes of disease (p<0.01).

Unilateral neurogenic paralysis occurs much more frequently in women (62/30), as shown in Figure 4, rather than in men. There-fore, the difference in the gender distribution is highly significant (p<0.01).

Carcinoma of the lung, specifically thorax surgery, led to the disease in 12 (13%) patients. In patients included in our study some less common causes of neurogenic unilateral laryngeal paralysis were observed, such as: thoracic surgery (5.43%), neurological causes (2.1%), prolonged intubation (5.43%), esophageal carcinoma 2 (2.1%), and insulin-dependent diabetes mellitus (7.61%), Table 2.

DISCUSSION

Based on the results, we found out that the occurrence of uni-lateral neurogenic paralysis was more common on the left than on the right side. Left-sides paralyses were observed in 49 patients (53%), compared to 43 right-sided paralyses. We observed numer-ous etiological factors for the development of unilateral paralysis of the larynx in a group of patients with known etiology of the disease. Unilateral paralyses, according to the gender distribution, were twice as often in women than in men. The damages to the left n.laryngeusa reccurensa are far worse and much more frequent than damage to the right n. laringeusa rec-curensa, as shown in the results of our work, where we obtained statistically significant more frequent incidence of left-sided paral-ysis. In most cases we were able to clearly determine the etiologic cause of the paralysis. However, the cause of unilateral neurogenic paralysis has not been determined in 19 patients. Determined etio-logical cause of unilateral neurogenic laryngeal paralysis was statisti-cally more common than idiopathic cause of this disease. Exploring the causes of neurogenic paralysis of the larynx, we concluded that surgeries on the thyroid was the most common cause of the dis-ease. This can be interpreted by consequences that initially led to the primary disease (for example, infiltration of nerves by malignant thyroid tumors, as well as compromised nerves vascularization due to physical pressure of the present tumor), hence the risks of surgi-cal intervention in the thyroid gland and the possibility of intraoper-ative injuries to the corresponding neural structures. Our study has shown that surgery of the thyroid gland is the leading etiologic factor in the development of neurogenic paralysis. In our patients it was present in 35.45% of cases as an etiological factor, followed by goiter of the thyroid gland in 14.55%, idiopathic paralysis in 10% of cases, which is consistent with the studies de-veloped by other authors from the region (13, 14, 15, 16, 17, 18, 19). Development of the thyroid surgery has drawn attention to the possibility of neurological disturbance on larynx, which frequently follows this type of surgery. According to the research of various authors, such are Tucker HM (1986), Denis D,and Kasshimae H. (1989) and many other later on, the increase in the number of pa-tients with bilateral larynx paralyses continues. A group of American authors dealing with similar issues within the States, where the data point to neck and cervical spine injuries, mostly occurred in traffic accidents, as one of the leading etiological factors in the development of neurogenic paralysis, in 1.27 – 2.7% of the cases, thyroid surgery 2.1%, heart surgery 1.4%, esophageal carcinoma 1.3%, prolonged intubation 1.8% (data from 2009). In the cases where we were unable to determine the etiology of neurogenic paralysis, we assumed its etiological cause could be a neurotropic virus or an allergic toxic mechanism.

CONCLUSIONS Our research resulted in a conclusion that the leading factor in the development of life-threatening bilateral paralysis, and the most common reason, is thyroid gland surgery, increasing due to the ma-lignant disease growth, as well as the operation risks. Our study has shown that the complications of the thyroid gland surgery are the

Etiology of unilateral paral ysis

Frequency

%

Thyroid surgery Thyroid goiter Idiopathic Vir al infection Diabetes Post operative thyroid cancer Thoracic surgery Prolonged intubation Lung cancer Esophageal carcinoma Thyroid carcinoma CVI (n eurologic) Chondrosarcoma Diabetes Miocardiopathy Resection of trachea Total

27151187

4

5

5

3

2

0

1171

0

92

29.3516.3011.96

8.707.61

4.35

5.43

5.43

3.26

2.17

0.00

1.091.097.611.09

0.00

100.00

Table 2 Distribution of etiological factors of unilateral la-ryngeal paralysis.

122 M. Gnjatić et al.

Figure 4 Gender distribution of unilateral paralysis.

leading etiological factor in the neurogenic laryngeal paralysis devel-opment. The frequency of neurogenic unilateral larynx paralysis is highly significant in relation to the cause of paralysis. This significant difference is caused by a large number of resulting paralyses follow-ing the thyroid surgery.


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Reprint requests and correspondence:Mirjana Gnjatić, MD, PhDClinic of ENTClinical Centar Banja Luka12 beba 178000 Banja Luka, RSBosnia and HerzegovinaPhone: +387 65 541 777Email: [email protected]


Most common etiologies of neurogenic laryngeal paralysis in middle-aged patients 123

Surgery and endoscopic treatment in childrenwith vesicoureteral reflux

Operativni i endoskopski tretman djecesa vezikoureteralnim refluksom Murat Berisha*, Nexhmi Hyseni, Salih Grajqevci, Sejdi Statovci, Ali Aliu

Pediatric Surgery Clinic, University Clinical Center, Prishtina, Kosovo


ABSTRACT

Introduction: vesicoureteral reflux (VUR) is a pathologic entity with different forms of therapeutic management. The aim of this study is to compare and analyze surgical and endoscopic treatment of children with VUR (from grade II to IV). Also, medical charts of children with VUR will be analyzed with special focus on results of endoscopic sur-gery. Methods: from 2000 to 2013, 44 children with RVU (61 urethers) were surgically treated. Endoscopic surgery in our Center has started in 2009. In the period 2009-2013, 55 children with RVU were treated with endoscopic surgery (78 urethers). Three months postoperatively avoiding cystourethrogram (VCUG) was performed. Results: 44 pa-tients were surgically treated (ureterocystoneostomia sec.Cohen) and average hospitalisation was 6 days. The average age of patients was 6.5 years. In 7 cases (15.9%) we had postoperative complications. 55 pa-tients were treated with endoscopic surgery, and average hospitalisa-tion was 1 day. In 6 patients (6.6%) endoscopic surgery with deflux was done twice, while in three patients (8.5%) it was done 3 times, because of recurrence. The average age of those patients was 5.2 years. Con-clusion: the endoscopic surgery of the VUR is much easier for both the pediatric surgeon and the patient. We suggest that endoscopic surgery should be offered to all children with grade II to IV VUR. We strongly recommend the endoscopic surgery to the majority of VUR cases that come to our Center.

Key words: vesicoureteral reflux, pediatric urology

SAŽETAK

Uvod: vezikoureteralni refluks (VUR) je patološka jedinica sa različitim vrstama terapijskih zahvata.Cilj ove studije je da se uporedi i analizira operativni i endoskopski tretman djece sa VUR-om (od II do IV stepena). Također, izvršit će se analiza liječničkih grafikona djece sa VUR-om sa fokusom na rezultatima endoskopskih zahvata. Metode: u periodu od 2000. do 2013. godine, 44 djece sa RVU (61 ureter) je liječeno operativnim zahvatom. U našem Centru endoskopski zahvati počeli su se primjenjivati u 2009. godini. U periodu od 2009. do 2013. godine, 55 djece sa RVU-om je liječeno primjenom endoskopskog zahvata (78 uretera). Tri mjeseca nakon zahvata urađen je cystourethrogram (VCUG). Rezultati: 44 pacijenta podvrgnuta su hirurškom zahvatu (ureterocystoneostomia sec.Cohen) i njihova hospitalizacija je trajala u prosjeku 6 dana. Pacijenti su u prosjeku imali 6.5 godina. U 7 slučajeva (15.9%) došlo je do postoperativnih komplikacija. 55 pacijenata je tretirano primjenom endoskopskog zahvata, i hospitalizacija ovih pacijenata trajala je u prosjeku 1 dan. Kod 6 pacijenata (6.6%) endoskopski zahvat sa defluksom je obavljen dva puta, dok je taj zahvat kod tri pacijenta (8.5%) obavljen 3 puta, zbog vraćanja bolesti. Prosječna starosna dob tih pacijenata je bila 5.2 godine. Zaključak: endoskopska metoda tretiranja VUR-a je mnogo lakša i za hirurga i za pacijenta. Predlažemo da bi se sva djeca kod kojih je dijagnosticiran od II do IV stepena VUR-a trebala podvrgnuti endoskopskom zahvatu. Zalažemo se za to da se većini pacijenata sa dijagnosticiranim VUR-om koji dođu u naš Centar predloži endoskopski zahvat, kao metod liječenja.

Ključne riječi: vezikoureteralni refluks, pedijatrijska urologija

INTRODUCTION

Vesicoureteral reflux (VUR) is a common problem encoun-tered in urological practice. Traditionally, if medical management with low-dose antibiotic prophylaxis failed, the only alternative was open surgery. Recently, promising results with subureteral injection of dextranomer/hyaluronic acid copolymer (Deflux) have renewed interest in the endoscopic treatment of VUR (1). Endoscopic treat-ment (ET) was pioneered by O’Donnell and P. Puri when they pre-sented their first report in 1982(2). ET of VUR in children has now become an acceptable alternative to open ureteral re-implantation for the treatment of pediatric VUR (3). In humans, one method for assessing VUR is avoiding cystourethrogram (VCUG), in which a catheterized bladder is filled with radiopaque contrast under fluo-roscopy (4). Early diagnosis is very important to reduce and prevent complications (5). The prevalence of VUR in children with a history

of symptomatic urinary tract infection (UTI) varies between 30% and 50% in different publications (6). Bilateral reflux resolves at a slower ratethan unilateral reflux (7). In 1952, Hutch, carried out the first re-implantation of ureter in humans (8). In last ten years, since Deflux (dextranomer hyaluronic acid copolymer) was approved by the Food and Drug Administration (FDA), endoscopic surgery is the first treatment of children with RVU (9).


This study includes children treated for RVU and the data were obtained from histories of patients of our center. The surgical treat-ment of children with RVU in our center started since 1999. We are the only center in the country that treats RVU in children. The diagnosis of these children was correct and was found out through physical, laboratory and radiological examinations. Radiological


examinations used to verify the diagnosis were as follows: ultra-sonography, voiding cystourethrogram (VCUG), and radionuclide cystogram (RNC). The RVU treatment with open surgery consists of re-implanting of the ureter with a reflux. Whereas the RVU treat-ment with endoscopic surgery is carried out by injecting, through cystoscopy, Deflux in the subureteral part (sub-mucosa) of ureter that has a reflux (10).

RESULTS

From 1999 to 2013, 99 children were treated. Following the op-eration, children were observed for approximately 24 months. Until 2009 all children with RVU were treated by open surgery (ureter re-implantation). Since 2009, our center has started treating the pa-thology in question with endoscopic surgery (Deflux injection). 44 patients were treated with open surgery (61 ureters) whereas 55 children were treated with endoscopic surgery (78 ureters). There were complications in relation to treating the RVU with open sur-gery. 7 children (15.9%) with RVU treated with open surgery suf-fered postoperative complications. On the other hand, there were no complications in cases with endoscopic treatment, apart from some repeated treatments. The first treatment with endoscopic sur-gery was successful in 46 children (83.4%). In order to cure them from RVU, 6 children (16.6%) had to undergo endoscopic treatment twice whereas 3 children (8.5%) underwent the treatment three times (Figure 1). Children treated with open surgery were hospital-ized for 7 days, received parenteral therapy, had a urinary catheter and suffered postoperative hematuria. Whereas children treated with endoscopic surgery had no complications, the treatment was repeated in some cases, they were hospitalized for one day, received per os therapy, no hematuria, no urinary catheter. When it comes to open surgery, the average duration of intervention was 180 minutes and average stay in hospital was 6 days, whereas in case of endo-scopic surgery the average duration of intervention was 25 minutes and only one day stay in the hospital. There was a huge difference of RVU treatment with open surgery and endoscopic surgery, but they were both successful.

DISCUSSION

In a survey of parents whose children suffered from VUR, 95% of them said they preferred endoscopic surgery, compared to 5% who were in favor of open surgery. This was also expressed by Capozza et al. in their study of 2003 (11). The biggest difference of endoscopic surgery is minimal postoperative pain and quick heal-ing (12). The study presents huge differences of these methods for treatment of RVU in children. A characteristic of open surgery was

as follows: long stay in hospital, postoperative pain, limited move-ments, whereas a characteristic of endoscopic surgery was as fol-lows: short stay in hospital, no postoperative pain, no limited move-ments. In our center, the success rate of children with RVU that were treated with endoscopic surgery was 83.6% and this shows that the success rate in case of our patients is similar to the one of other centers, referring to some studies such as Pinto et al. (13) that reported the success rate of 84%, while Puri et al. (14) reported success rate of 96%. Capozza et al. have shown that non-function-ing of bladder (neurogenic bladder) is a risk factor for the failure of endoscopic surgery (15). Therefore, our Center does not even think of endoscopic surgery in cases of children with neurogenic bladder and RVU. Children treated with the RVU in our Center are observed for 2 years, whereas according to Chertin et al., minimum observation time of these children should be 3 years (9). In general, the reported rate of big complications caused by endoscopic sur-gery is too low and is favored in parallel to open surgery (16).

CONCLUSION

The treatment of children with RVU with open surgery and en-doscopic surgery is successful in our center. Endoscopic surgery is easier and more feasible for pediatric surgeons and patients. Endo-scopic surgery has more advantages than open surgery. The advan-tages of endoscopic surgery are: short hospital stay, absent of post-operative complications and high success rate. Endoscopic surgery is preferred as the first line of RVU treatment.


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Children with Severe Vesicoureteral Reflux: 10-year Prospective Study of Medical

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Figure 1 Outcome of endoscopic correction of VUR.

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Reprint requests and correspondence:Murat Berisha, MD, MScClinic of Pediatric SurgeryUniversity Clinical CenterSt. Rexhep KrasniqiKulla III-k-II-5PrishtinaKosovoPhone: +381 44 116 512 Email: [email protected]

126 M. Berisha et al.



Blood pressure oscilation during carotid endarterectomy in superficial cervical plexus block

Oscilacije krvnog pritiska tokom karotidne endarterektomije u superficijalnom bloku cervikalnog pleksusaDragan Milošević*, Darko GolićClinic of Anesthesia and Intensive Care, Clinical Center Banja Luka, Zdrave Korde 1, 78000 Banja Luka, Bosnia and Herzegovina


ABSTRACT

Carotid endarterectomy (CEA) is a surgical procedure per-formed to remove deposits of fat, called plaque, from the carotid arteries in the neck. Two main arteries, one on each side of the neck, deliver blood and oxygen to the brain. Plaque occurs in sub-intimal layer in large and medium arteries as people get older, de-pending on the lifestyle and hereditary facors. The plaque build up is a vascular disease called atherosclerosis. When this happens, the arteries narrow and that condition is called stenosis. During carotid endarterectomy, a surgeon removes the plaque, corrects narowing, and allows normal flow of blood and oxygen to brain. The goal of our work was examination of hemodynamic stability and oscillation of blood pressure during operation procedure.

Key words: blood pressure, cervical plexus block, carotid endar-terectomy

SAŽETAK

Karotidna endarterektomija (CEA) je hirurška procedura čijim izvođenjem se uklanja plak iz karotidnih arterija vrata. Dvije glavne karotidne arterije, svaka sa po jedne strane vrata dopremaju krv i kiseonik do mozga. Plak se stvara na intimi velikih i srednjih arterija u poznijim godinama u zavisnosti od životnih navika i hereditarnih faktora. Tako nastaje vaskularno oboljenje nazvano ateroskleroza. Njenim razvojem lumen arterija se sužava i dolazi do stenoze. Tokom karotidne endarterektomije uklanja se plak, ispravlja stenoze te omogućuje normalan protok krvi odnosno kiseonika do mozga. Cilj ovog rada je ispitivanje hemodinamske stabilnosti pacijenta i oscilacija krvnog pritiska za vrijeme operativnog zahvata.

Ključne riječi: krvni pritisak, blok cervikalnog pleksusa, karotidna endarterektomija

INTRODUCTION

The choice of anesthesia for CEA is still disputable (1,2). Tra-ditionally, CEA has been performed in general anesthesia (GA). Surgeons find it less stressful, the operation does not need to be rushed, patient movement is avoided, and there is a theoretical ben-efit – reduced cerebral metabolic requirements. However, GA has some disadvantages, major of them is mandatory, additional and expensive cerebral blood flow monitoring equipment (2,3). When CEA is performed in regional anaesthesia, cerebral blood flow mon-itoring is superior (3). Yet, there are certain disadvantages of region-al anesthesia. It proved to be more stressful for both surgeons and patients, patient movement is present, haemodynamic instabillity may occur and airway protection is poor (4).


Superficial cervical plexus block was performed in fifty patients, all subjected to carotid endarterectomy. Patients fall in categories II or III according to ASA classification. Average age was 63 years. Comorbidity: diabetes mellitus 40% (20), transitor ishemic attack/

stroke 46% (23), myocardial infarction 24% (12), arrhythmia 28% (14), chronic bronchitis/asthma 38% (19). Out of total number of patient, 90% of them were smokers and positive family history of carotid disease was observed in 36% (18). Thirty four (68%) cas-es were with contralateral occlusion. For premedication, midazol-am (3-5 mg) and fentanil (50-100 mcg) were used and lidocain 1,6 -1,8% - 20 ml. All patients received oxygen by mask 2-3 lit./min, and manitol 20% 100-150 ml routine. On average, duration of op-eration procedure was 82 min, and the average duration of ACC clamping was 16 min. Our choice of anesthetic provide approximate

Figure 1 The landmarks and performing of superficial cer-vical plexus block.

90 min. analgesia. We performed continuous monitoring of NIBP, oxygen saturation level, heart rate, ECG (II lead), and verbal/motor response, especially during clumping and postoperative period. The landmark for superficial cervical plexus block performing was pos-terior border of m. sternocleidomastoideus, connection point be-tween top and middle third of line connecting processus mastoideus and midpoint of clavicula. We used redirection needle technique – infiltration of anastetic directly, cranial and caudal than puncture site, 0.5 – 1 cm deep under the skin (Figure 1).

RESULTS

Results are presented statistically by means of values, graphics and tables. The most important were: • Heartratewaschangedinallpatients,-12to+22%according

to preoperative values, in five cases bradycardia occurred (40/min) during preparation – glomus caroticum irritation (atropine i.v. administration).

• Bloodpressurewas increased in40cases (80%), systolic from10,7% to 40%, diastolic 12.5 to 35%. Average increase was 16,5%, for systolic, 18% for diastolic, and 9.9% for mean arterial pressure. In three cases we detected decrease of blood pres-sure, systolic up to 23.7%, and diastolic up to 9.1% (Figure 2,3,4).

Hemodynamic variability according to collateral circulation shows high correlation between increasing pressure and poor devel-oped contralateral circulation, particularly in cases where we used antihypertensive medication as shown in Table 1 and 2.

DISCUSSION

There is a strong evidence in literature about preservation of physiological protective mechanism in loco-regional anesthesia in carotid endarterectomy (5). Combining NIRS spectrometry and jug-ular venous oxymerty McCleary demonstrated that preservation of cerebral circulation during cross clumping period of commuis carot-id artery, depending on reflex increasing blood pressure and heart rate, was not registered in general anesthesia (6). This discovery is supporeted by Wellman who recorded significantly lower incidence of ischemic changes on EEG intraoperatively in regional anesthesia, 6.3% vs 15.7% in general anesthesia (7). Sympatic nervous system reaction, which is suppressed by general anesthetics, is responsible for the blood preassure increase. This suppression is dose depen-dent, so it is possible to preserve this reflex reaction in „light“ gener-al anesthesia as found by Roizen, explaining some cases of increased blood pressure in general anesthesia (8). It seems that some parts of reticular formation in medula (with possible similar zone trought

Figure 2 Preoperative blood pressure.

Figure 4 Postoperative blood pressure.

Figure 3 Intraoperative blood pressure increased in 80%, during cross clumping phase 72%, antihipertensive drug used in 36% (urapidil).

Figure 5 Average values of all pressures in different stages of surgery show tendency of blood pressure increase especially in cross-clumping period, and decrease in post clumping period.

Condition of collateral branches

p* Poor (N=16; 32.0%) Good (N=34; 68.0%) Mean Std. Deviation Mean Std. Deviation

Preoperative systolic 145.0 14.085 136.6 15.088 0.068 Preoperative diastolic 91.4 7.780 84.6 7.024 0.003 Preoperative mean 111.3 8.647 104.2 8.611 0 .0 0 9 Clumping systolic 167.3 8.379 152.9 12.717 0 .0 0 0 Clumping diastolic 104.4 11.735 96.8 10.005 0 .0 2 2 Clumping mean 122.8 6.605 119.2 13.328 0.312 * t -test for independent samples

Hemodynamic variables in patients under superficial cervical block

Table 1 Hemodynamic variables in patients under super-ficial cervical block.

Table 2 Hemodynamic variables in patients under super-ficial cervical block, I.V. antihipertensive agens (urapidil) administered.

Condition of collateral branches

p* Poor (N=13; 81.25%) Good (N=3; 18.75%)

Mean Std. Deviation Mean Std. Deviation

Preoperative systolic 145.8 12.449 161.3 25.541 0.130 Preoperative diastolic 91.2 8.019 91.7 5.686 0.919 Preoperative mean 110.4 9.260 119.7 15.308 0.183 Clumping systolic 169.0 6.916 164.0 12.288 0 .0 4 0 Clumping diastolic 105.8 12.683 97.0 3.606 0 .0 6 6 Clumping mean 124.1 6.525 142.7 33.232 0 .0 5 0 Release systolic 158.4 12.332 144.0 20.881 0.128 Release diastolic 101.5 7.644 92.0 6.083 0.065 Release mean 116.5 10.325 117.7 6.807 0.852 Postoperative systolic 158.5 10.658 148.3 14.224 0.178 Postoperative diastolic 101.8 13.596 93.0 6.557 0.304 Postoperative mean 118.5 10.548 112.0 12.288 0.367 * t-test for independent samples

Hemodynamic variables in patients under superficial cervical block, I.V. antihiper-tensive agens (urapidil) administered

128 D. Milošević et al.

the brain tissue), especially sensitive on hypoxia and cessation of circulation (cross clumping period), have important role in this reflex response. Preservation of cerebrovascular physiological mechanism during loco-regional anesthesia can prevent occurrence of ischemic damage in endarterectomy. This claim is confirmed by Calvey who in his clinical research measured concentration of protein S 100 (glia cell degradation product) in jugular vein sample, and results were compared with series of psychometrics tests. The results show sig-nificantly higher concentrations of S 100 protein, and worse psycho-metrics capabilities in group of patients with general anesthesia for endarterectomy compared to cervical plexus block group (9). In our investigation there was significant increase of blood pres-sure especially in cross clumping period as preserved reflex for cere-bral blood flow maintenance. We tolerated the increase up to 25% from preoperative (baseline) values, because the further increase would have negative effect on cardiovascular system.

CONCLUSION

Based on our results, we can conclude that superficial cervical plexus block is a low cost, simple and reliable kind of anesthesia for carotid endarterectomy, providing a good hemodynamic stability, and cerebral perfusion monitoring. Using this type of anesthesia, we avoid all potential complications and side effect of general endo-tracheal anesthesia. The reflex increase of blood pressure in cross -clamping period was tolerated up to 25% of preoperative values, which is considered useful for cerebral perfusion maintenance via collateral blood vessels.


REFERENCES

1. McCleary AJ, Maritati G, Gough MJ. Carotid endarterectomy; Local or General

anesthesia? Eur J Vasc Surg 2001;22 1-12.

2. Fioriani P, Sbarigia E, Speziale F, Antonini M, Fiorani B, Rizzo L, et al: General an-

esthesia versus cervical block and perioperative complications in carotid vascular

suregry. Eur J Vasc Endovasc Surg 1997 Jan; 13(1):37-42.

3. Meliere D, Desgrangers P, Alaire E, Cron J, Berhalad D, D’Audiffret A, et al. Sur-

gery of the internal carotide: locoregional or general anesthesia? Ann Chir. 2000

Jul;125(6):530-8.

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terectomy Br J Anaesth. 2000 Jun;84(6):797-800.

5. Stoneham MD, Thompson JP. Arterial pressure managment and Carotid Endarter-

ectomy. Br J Anaesth. 2009 Apr; 102(4): 442 – 52.

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fects of regional and general anesthesia on cerebral metabolism during carotid end-

arterectomy. Eur J Vasc Surg 1996 Aug; 12(2):173-81.

7. Wellman BJ, Loftus CM, Kresowik TF, Todd M, Granner MA. The differences in EEG

changes during endarterectomy in local vs general anesthesia. Neurosurgery. 1998

Oct; 43(4):769-73.

8. Roizen MF. Anesthesia goals for operations to prevent cerebrovascular insufficien-

cy. Clinical Neuroanesthesia 2nd Ed. New York: Churchill Livingstone, 103-122.

9. Calvey TAJ, Bollom P, Cruickshakk J. et al. Difference in cognitive function and pro-

tein S100 production after carotid endarterectomy under local or general anesthe-

sia. Br J Surg. 2000;87:490.

Reprint requests and correspondence:Dragan Milošević MD, MScClinic of Anesthesia and Intensive CareClinical Center Banja LukaZdrave Korde 1 78000 Banja Luka, RSBosnia and HerzegovinaPhone: +387 51 343 238Email: [email protected]

Blood pressure oscilation during carotid endarterectomy in superficial cervical plexus block 129

Uterine anomalies and pregnancy outcome: uterus unicornis cum cornum rudimentarium

Ishod trudnoće kod anomalije uterusa: uterus unicornis cum cornum rudimentarium Lejla Imširija*, Naima Imširija, Mohamad Abou El-Ardat, Fatima Gavrankapetanović

Clinic of Obstetrics, Clinical Center University of Sarajevo, Patriotske lige 81, 71000 Sarajevo, Bosnia and Herzegovina


ABSTRACT

Congenital uterus anomalies are most often diagnosed during clinical examination and even more frequently during delivery or at the end of instrumental termination of pregnancy. A pregnant woman from Sarajevo, born in 1978, was admitted to the Clinic of Obstetrics in 37 weeks of pregnancy. In her previous pregnancy, during a caesarean delivery, the patient was diagnosed with uterus unicornis cum cornum rudimentarium. Due to this anomaly both pregnancies resulted in breech presentation. Regular obstetric con-trols and monitoring biometrics of the fetus and its presentation could result in full term pregnancy and a mature newborn delivery.

Key words: uterine anomaly, caesarean section, breech presentation

SAŽETAK

Kongenitalne anomalije uterusa se najčešće dijagnosticiraju to-kom kliničkog pregleda, a još češće, pri porodu ili instrumentalnom dovršetku pobačaja. Trudnica iz Sarajeva, rođena 1978. godine primljena je na Klinici za porodiljstvo u 37. sedmici trudnoće. U prethodnoj trudnoći, tokom carskog reza, ustanovljeno je da paci-jentica ima uterus unicornis cum cornum rudimentarium. Zbog ove anomalije u obje trudnoće bila je karlična prezentacija ploda. Adek-vatnim akušerskim nadzorom, praćenjem biometrije ploda i njegove prezentacije, trudnoća se može izvesti do kraja, te se na svijet može donjeti zrelo novorođenče.

Ključne riječi: anomalija materice, carski rez, karlična prezentacija

INTRODUCTION

Congenital uterus anomalies and frequency of their occurrence primarily depend on the tested sample and applied diagnostic meth-ods. The congenital uterus anomalies are most often diagnosed during clinical examination and even more frequently during delivery or at the end of the instrumental termination of pregnancy (1). A large num-ber of congenital anomalies remain undetected. The most important methods for diagnosing congenital anomalies are ultra-sound examina-tions, especially at the beginning of pregnancy, hysterosalpingography, and combined laparoscopy and hysteroscopy (2). Nowadays, the ap-plication of magnetic resonance and three dimensional images result in precise detection of uterus abnormality (3). Congenital uterus anomalies mainly occur in partial fusion of the mullerian ducts or in lack of the fusion. The most common anomalies relate to those connected to the uterus body, cervix and vagina anom-alies are less common, while anomalies of ovary and fallopian tubes are uncommon (4). The American Society for Reproductive Medicine (ASRM) anomaly classification, based on intensity and level of fusion or lack of the mullerian ducts fusion, along with the Buttram and Gib-bons classifications, is the most frequently used classification of the uterus anomalies (5). Based on Buttram and Gibbons classification uterus anomalies are divided into 6 groups. The first group relates to agnesis and hypoplasia of any organ; II group involve one-sided aplasia

(uterus unicornis, semiuterus) or hypoplasia with rudimentary horn (uterus unicornis cum cronu rudimentario); III group is uterus duplex or didelphys, usually with vagina septa or duplex; IV group is bicor-poreal uterus, which can be total or partial or only uterus arcuatus; V group is aplastic uterus (total or partial); VI group relates to a special syndrome of various changes in women reproductive organs (5). Only a small number of obstetricians, working in large institutions with a large number of pregnant women and deliveries, is privileged to see gravid uterus unicornis able to carry out the pregnancy in full term (6).

CASE REPORT

A pregnant woman from Sarajevo, born in 1978, was admitted to the Clinic of Obstetrics in 37 weeks of pregnancy. Prior to this preg-nancy the patient had one miscarriage and a delivery which resulted in cesarean section in 34 weeks of pregnancy due to premature rapture of membranes and breech presentation. She gave birth to a baby boy which was hospitalized at the Pediatric Ward of the Clinic. During the pregnancy the patient was regularly monitored and subjected to regu-lar obstetric examinations. Prior to a delivery and at the beginning of the third trimester she was diagnosed with breech presentation which remained until delivery. Due to the breech presentation and uterus unicornis cum cornum rudimentum diagnosed during the previous caesarian delivery, the second delivery also ended in caesarian section.

Medical Journal (2014) Vol. 20, No. 2, 130 - 131 Case report

A caesarian section was performed in 37 weeks of gestation. Elective caesarian delivery was performed in general anesthesia. The fetus extraction was somewhat difficult due to breech presentation and narrow space in the uterus horn. Hemorrhage was normal for this type of surgical intervention and the uterus was sewn up in lay-ers. The weight of a delivered baby girl was 2850 grams. After a day spent in the Intensive Care Ward the patient was moved to Postnatal Ward and discharged 4 days later. As a result of congenital uterus anomaly the patient was under strict control of the obstetri-cians and was subjected to ultrasound and obstetric examinations and mandatory cervicometry (Figure 1).

DISCUSSION

Discussion on congenital anomalies with a particular reference to uterus unicornus cum cornu rudimentario, brings up several is-sues such as: outcome of pregnancy, uterus reactivity, and the issue of anomalies causing infertility. Unicornuate uterus is certainly the state of uterus with limited space, resulting in preterm birth and pathological and abnormal presentation of the fetus inside uterus, which in majority of cases ends in caesarian delivery. Number of au-thors have described unfavorable outcome of pregnancies in wom-en with congenital fetus anomalies (7, 8). Pregnancy in women with unicornuate uterus can be regularly controlled if timely diagnosed, even before the pregnancy. Regular obstetric controls and monitor-ing biometrics of the fetus and its presentation could result in full term pregnancy and a mature newborn delivery.

CONCLUSION

Uterus unicornis cum cornum rudimentarium is a rare uterus anomaly, and occurs in one out of 10,000 pregnant women. If preg-nancy happens, breech presentation delivery occurs in majority of cases. Unfortunately, the anomaly is detected during the surgical completion of delivery, in women giving birth for the first time, or during sterility treatment, when a radiology-diagnostic method is used.


REFERENCES

1. Kupešić S. Okrugli stol o prirođenim anomalijama maternice. Gynaecol Perinatol.

2002;11:42–4.

2. Fedele L, Zamberletti D, Vercellini P, Dorta M, Candiani B. Reproductive perfor-

mance of women with unicornuate uterus. Fertil Steril. 1987 Mar;47(3):416–9.

3. Goldenberg M, Sivian E, Sharabi Z, Mashiach S, Lipitz S, Seidman DS. Reproductive

outcome following hysteroscopic management of intrauterine septum and adhe-

sions. Hum Reprod. 1995 Oct;10(10):2663–5.

4. Williams Obstetrics. Cunningham FG, MacDonald PC, Gant NF, Leveno KJ, Gil-

strap LC (ur.). Stanford: Appleton & Lange, 1993.

5. Buttram VC Jr, Gibons WE. Müllerian anomalies: a proposed classification. Fertil

Steril. 1979 Jul;32(1):40–6.

6. Ivanišević M, Đelmiš J, Mayer D. Početak i napredovanje poroda. Gynaecol Perina-

tol. 2001;11:74–9.

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col Perinatol. 2001;11:129–37.

8. Radaković B. Urođene anomalije ženskih spolnih organa. U: Šimunić V. i sur. (ur.).

Ginekologija. Zagreb: Naklada Ljevak, 2001;91–100.

Reprint requests and correspondence:Lejla Imširija-Idrizbegović, MD, MSc Clinic of Obstetrics Clinical Center University of Sarajevo Patriotske lige 8171000 Sarajevo Bosnia and HerzegovinaPhone: +387 61 190 622Email: [email protected]

Uterine anomalies and pregnancy outcome 131

Figure 1 Uterus during caesarian section (typical example of uterus unicornis).

Hemorrhagic fever with renal syndrome and coexisting hantavirus pulmonary syndrome

Hemoragijska groznica sa bubrežnim sindromom udružena sa hantavirusnim plućnim sindromomDuško Anić*, Emina Vukas, Almira Kadić

Pediatric Clinic, Clinical Centre University of Sarajevo, Patriotske lige 81, 71000 Sarajevo, Bosnia and Herzegovina


ABSTRACT

Introduction: hantavirus causes hemorrhagic fever with renal syndrome (HFRS) or hantavirus pulmonary syndrome (HPS). HPS progression to a life-threatening pulmonary disease and has mor-tality rate of approximately 40-50%. To the best of our knowledge, there has no published pediatric case of HFRS with coexisting HPS in Bosnia and Herzegovina. Aims: objective of this paper is to describe the treatment and outcome of treatment of HFRS with coexisting HPS. Method: a 11 year old boy presenting with an abrupt respiratory distress, pulmonary edema and renal failure. After admission cardio-pulmonary resuscitation lasted for two hours. Received six doses of adrenaline. Introduced in therapeutic hypothermia and hemodialysis. Hantavirus infection was proven by serology: ELISA positive IgM and IgG titers. Results: the boy was discharged home completely recov-ered without complications except mild neurological deficit for which neuropediatricians was not sure that is a consequence of the disease. Conclusion: the primary resuscitation was a key for good outcome in case of renal failure with occurrence severe respiratory failure must alert clinician for possible HPS, especially in endemic areas.

Key words: hantavirus, resuscitation, pulmonary syndrome, renal syndrome

SAŽETAK

Uvod: hantavirus uzrokuje hemoragijsku groznicu sa bubrežnim sindromom (HVBS) ili hantavirus plućni sindrom (HPS). HPS dovodi do teškog oblika plućne bolesti sa mortalitetom od oko 40 -50%. Prema našim saznanjima nema objavljenih pedijatrijskih slučajeva HVBS udruženog sa HPS u Bosni i Hercegovini. Cilj: cilj ovog rada je da opiše tretman i ishod HVBS udruženog sa HPS. Metoda: 11–godišnji dječak je primljen sa naglo nastalim respiratornim distresom, plućnim edemom i bubrežnim zatajenjem. Po prijemu, kardiopulmonalna reanimacija je trajala dva sata. Primio je šest doza adrenalina. Uveden u terapijsku hipotermiju i rađena je hemodijaliza. Hantavirus infekcija je dokazana serologijom: ELISA IgG i IgM pozitivan titar antitjela. Rezultati: dječak je otpušten kući potpuno oporavljen, bez komplikacija osim blagog neurološkog deficita za koji neuropedijatri nisu sigurni da je povezan sa bolešću. Zaključak: primarna reanimacija je bila ključna za pozitivan ishod. U slučajevima akutnog bubrežnog zatajenja pojava teškog respiratornog zatajenja treba navesti ljekare da misle na hantavirusni plućni sindrom.

Ključne riječi: hantavirus, reanimacija, plućni sidrom i renalni sin-drom

INTRODUCTION

Since the first hantavirus was isolated in 1976, at least 22 new hantaviruses that are pathogenic to humans (1) were isolated, and have the potential to cause two different types of illnesses: hemor-rhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). Hantavirus pulmonary syndrome (HPS) was first described in the southwestern region of the United States in 1993 (2). HPS is a more serious disease than HFRS with a mortality rate of about 40-50% (3). Although, hantavirus infection was known to be endemic to Bosnia and Herzegovina for over 50 years (4), to our best knowledge there are no published pediatric cases of HFRS associated with HPS. The aim of this paper is to describe the treatment and outcome of HFRS associated with an HPS infection of an eleven-year-old boy.

CASE REPORT

Eleven-year old boy was admitted to the Local Hospital due to an illness that suddenly began five days earlier. The symptoms were

a weakness in the legs, difficulty in walking, vomiting, diarrhea, and hemorrhagic rash. He had no fever. On the day of admission his symptoms also included tachypnea, tachycardia, no urine output despite bolus fluids and diuretics, while having a normal blood pres-sure. Laboratory findings demonstrated markedly elevated levels of creatinine, N-urea, and metabolic acidosis. The lung X rays pointed to a significant homogeneous shadowing of the lower two thirds of the right lung in addition to a blurry cranial contour in a form of an infiltrating shadow that extended back all the way to the right-hand clavicle. Left paracardially nonhomogeneous shadow demonstrated an infiltrative nature. Because of the need for ventilatory support, the patient was sent to the Pediatric Clinic in Sarajevo. On admission he was conscious, communicative, disoriented, while having tachy-pnea (40/min), tachycardia (140/min), cold limbs, BP 132/76 (98) mmHg, no fever, bloody urine, hematoma on the left lower leg and a single petechial rush. Laboratory findings on admission: WBC 18.4 x 109/L, PLT 223 x 109/L, RBC 5.1 x 1012/L, Hb 144 g/L, Hct 0.42 AST 67 U / L, ALT 52 U/L, LDH 453 U/ L, N- urea 35.5 mmol/L, creatinine 899 nmol/L, sodium 115, Ca 1.96, albumin 29 g/L, APTT 34.6, INR 1.42 CRP 12.2. X-ray showed pulmonary ede-

Medical Journal (2014) Vol. 20, No. 2, 132 - 133 Case report

ma and hemorrhage on both sides (Figure 1). Ultrasound (US) also demonstrated pleural effusion on both sides. The content of the thoracic drain tube placed on the right hand side was bright while blood-stained. Fresh blood was observed coming from his mouth and nose. Due to the continuing respiratory distress, a child was in-tubated. In the endotracheal tube there was a significant amount of foam and bloody content. Immediately after intubation, the boy ex-periences a 40/min bradycardia and, cardiopulmonary resuscitation was initiated. The resuscitation lasted for two hours, during which he received six doses of adrenaline. The chest compressions were performed during 1.5 hours. In addition to resuscitation, left tho-racic drain and central venous catheter were placed. At one point a ventricular fibrillation (VF) occurs but without a need for defibrilla-tion. After establishing a normal hearth rhythm, the patient requires a continued inotropic support due to hypotension. Therapeutic hy-pothermia and hemodialysis were initiated. Control laboratory find-ings: WBC 17 x 109/L, neutrophils 90.3% with toxic granulation, PLT 285 x 109/L, the content of the thoracic drain WBC 0.190 x 109/L, with 70% lymphocytes, N - urea 35.4 mmol/L, creatinine 850 nmol/L, AST 165 U/L, ALT 79 U/L, CK 264 U/l LDH 654U/l, albumin 20 g/L, APTT not measurable, INR 1.69, lactates 3.1, tro-ponin 1.996 ng/mL, Buny viridae (Hantavirus) antibody WB IgG and IgM positive, Hantavirus IgG / IgM (ELISA) IgG (8.23) and IgM (7.02) positive index values, urine protein 3 +, mass of RBC and WBC 20-25. Starting with the third day, the urine output improved, although the serum creatinine and urea N – continued to be elevated. Ino-tropic drugs are excluded and the antihypertensives are introduced due to elevated blood pressure. On the sixth day the patient was extubated. Nevertheless, on the same evening, he was again intu-bated with signs of pulmonary hemorrhage. On 11th day the boy was again extubated, having spontaneous breathing. He continued a gradual recovery. The neuropediatrician observed a very discreet left-sided hemiparesis, for which he was not certain that it was as-sociated with the underlying disease and there was no other neuro-logical defects. He was discharged home, fully recovered, with the recommendations that the antihypertensives be gradually phased out and an MRI of the CNS be performed.

DISCUSSION

Hantaviruses, which cause HFRS and HPS, are widely spread in Evroasia and North America. Hantavirus is transmitted by rodents to humans in direct contact with infected animals or their secretions, such as urine, droppings and saliva. Increased vascular permeability plays a major role in the pathogenesis of severe hantavirus infec-tions. Clinical course is highly variable, and some infected patients are asymptomatic. Clinical manifestations and local distribution of the disease depend on the strain of the virus (6,7). HFRS occurs upon infection with Dobrava and Hantaan viruses, while Sin Nom-bre and Andes viruses primarily cause HPS (1,8). HFRS and HPS share some clinical manifestations. Bleeding and kidney failure are the characteristics of HFRS, while pulmonary problems are typical in patients with HPS. With advanced supportive care the mortality rate for patients with severe HFRS is reduced to 0.5%. However, HPS leads to life-threatening conditions more frequently than HFRS. After a prodromal phase similar to HFRS, patients with HPS may rapidly develop pulmonary edema and shock, which often requires

mechanical ventilation and/or extracorporeal membrane oxygen-ation. Mortality rate is approximately 40-50% (9, 10). HPS is rarely seen in pediatric population, particularly in Europe (11). According to the literature data, 95% of HPS cases affect adult patients (12).The presented case is the first to be published atypical HFRS case without fever in a pediatric patient in Bosnia and Herzegovina, com-bined with clinical presentation of the pulmonary syndrome, and satisfying most of the criteria of the Center for Disease Control and Prevention of Infection Diseases concerning HPS (13).

CONCLUSION

We believe that the primary resuscitation was essential for the positive outcome. In the case of renal failure with occurrence of severe respiratory failure clinician should be alerted for a possible HPS, especially in endemic areas.


REFERENCES

1. Lee HW, Lee PW, Johnson KM. Isolation of the etiologic agent of Korean Hemor-

rhagic fever. J Infect Dis. 1978 Mar;137(3):298-308.

2. Duchin JS, Koster FT, Peters CJ, Simpson GL, Tempest B, Zaki SR, et al. Hantavirus

pulmonary syndrome: A clinical description of 17 patients with a newly recognized

disease. N Engl J Med. 1994 Apr 17;330(14):949-55.

3. Lednicky JA. Hantavirus: a short review. Arch Pathol Lab Med. 2003 Jan; 127(1): 30-5.

4. Hukić M, Muzaferović S, Tulumović D, Calkić L, Sabović S, Karakas S, et al. Puumala

and Dobrava viruses in the northeastern and central regions of Bosnia. Acta Med

Croatica. 2003;57(5):373-80

5. Bugert JJ, Welzel TM, Zeier M, Darai G. Hantavirus infectio hemorrhagic fever

in the Balkans - Potential nephrological hazards in the Kosovo war. Nephrol Dial

Transplant. 1999 Aug; 14(8):1843–4.

6. Clement J, Colson P, McKenna P. Hantavirus pulmonary syndrome in New England

and Europe. N Engl J Med. 1994 Aug 25;331(8):545-6.

7. Glass GE, Watson AJ, LeDuc JW, Childs JE. Domestic cases of hemorrhagic fever

with renal syndrome in the United States. Nephron. 1994;68(1):48–51.

8. Khan AS, Khabbaz RF, Armstrong LR, Holman RC, Bauer SP, Graber J, et al.

Hantavirus pulmonary syndrome: the first 100 US Cases. J Infect Dis. 1996

Jun;173(6):1297-303

9. Bi Z, Pierre Formenty PB, Roth CE. Hantavirus Infection: a review and global up-

date. J Infect Dev Ctries. 2008 Feb 1; 2(1):3-23.

10. Terajima M, Hayasaka D, Maeda K, Ennis FA. Immunopathogenesis of hantavirus

pulmonary syndrome and hemorrhagic fever with renal syndrome: Do CD+8+T

cells trigger capillary leakage in viral hemorrhagic fevers? Immunol Lett. 2007 Nov

15;113(2):117–20.

11. Lednicky JA. Hantavirus: a short review. Arch Pathol Lab Med. 2003 Jan; 127(1): 30-5

12. Schutt M, Meisel H, Kruger DH, Ulrich R, Dalhoff K, Dodt C. Life-threatening Do-

brava hantavirus infection with unusually extended pulmonary involvement. Clin

Nephrol. 2004 Jul; 62(1): 54-7.

13. www.cdc.gov/hantavirus/hps

Reprint requests and correspondence:Duško Anić, MDPediatric Clinic Clinical Centre University of Sarajevo Patriotske lige 8171000 Sarajevo Bosnia and HerzegovinaEmail: [email protected]

Hemorrhagic fever with renal syndrome and coexisting hantavirus pulmonary syndrome 133

Surgical treatment of traumatic flail chest

Hirurški tretman traumatskog pokretnog kapkaDušan Janičić¹*, Bojan Gulić¹, Zoran Roljić², Velibor Škrbić³ 1Clinic of Thoracic Surgery, Clinical Center Banja Luka, 12 beba 1, 78000 Banja Luka, Bosnia and Herzegovina, ²Clinic of Vascular Surgery, Clinical Center Banja Luka, 12 beba 1, 78000 Banja Luka, Bosnia and Herzegovina, ³Clinic of General and Abdominal Surgery, Clinical Center Banja Luka, 12 beba 1, 78000 Banja Luka, Bosnia and Herzegovina


ABSTRACT

Introduction: traumatic flail chest is movable segment of the chest wall, which is caused by multiple fractures or by separation of ribs rib bones (at least three sequential broken ribs or separated into two fracture lines). These injuries are mainly seen in polytrauma patients. Our goal is to show the therapeutic benefits of surgical treatment (operative stabilization) of the flail chest. Materials and methods: retrospective analysis of the treated patients who under-went surgery at the Clinic of Thoracic Surgery in Clinical Center Banja Luka in the period from 01.12.1997 - 31.12.2012. Results: thirty five middle age patients with average age of 47.42 years with traumatic flail chest were surgicaly treated in the fifteen year peri-od at the Clinic of Thoracic Surgery Center in Banja Luka. Survival rate in the operated group was 91.43%. Conclusion: if conservative measures such as internal stabilization, the use of analgesics, antibi-otics, oxygen therapy and airway toilet does not lead to stabilization of respiratory function, surgical stabilization of the chest wall is nec-essary.

Key words: flail chest, surgical stabilization

SAŽETAK

Uvod: traumatski pokretni kapak je segment grudnog zida, koji nastaje višestrukim prelomom ili separacijom koštanih struktura (najmanje tri rebra serijski prelomljena ili odvojena u dvije frakturne linije). Ovakva povreda se najčešće sreće u sklopu politraume. Cilj rada je prikazati terapijske prednosti hirurškog tretmana (operativna stabilizacija) pokretnog kapka. Materijal i metode: retrospektivnom analizom obrađeni su pacijenti operisani na Klinici za torakalnu hirurgiju KC Banja Luka u periodu od 01.12.1997. – 31.12.2012. Rezultati: u petnaestogodišnjem periodu na Klinici za torakalnu hirurgiju KC Banja Luka operativno su tretirana 35 pacijenata sa traumatskim pokretnim kapkom srednje životne dobi od 47.42 godine. Prosječno trajanje hospitalizacije je 15 dana. Preživljavanje u grupi operisanih je 91.43%. Zaključak: ukoliko konzervativne mjere kao što su untrašnja stabilizacija, primjena analgetika, antibiotika, oksigenoterapija i toaleta disajnih puteva ne dovedu do stabilizacije disajne funkcije operativno stabilizacija zida grudnog koša je neophodna.

Ključne riječi: pokretni kapak, operativna stabilizacija

INTRODUCTION

Flail chest is post-traumatic thoracic segment of the wall that does not have continuity with the remaining bony skeleton of the chest. It occurs with lost support of at least three ribs in two lines with the trauma (1). Pathophysiological disorder occurs due to the paradoxical movement: during inspiration flail chest moves toward the inside of the chest, while it moves outward during the expirium. This reduces the efficiency of breathing and the volume of inhaled air. This condition is followed by typical clinical triad intrabronhial- hemorrhage, ineffective cough and anoxia (1.2). Post-traumatic flail chest is a source of high mortality, especially in polytrauma patients. Early work on the moving flail chest record-ed a mortality of up to 80% (2). Standard treatment is focused on the treatment of lung parenchymal injury and pain control, often with the use of mechanical ventilation with positive pressure. Sev-eral previous studies have shown that there are multiple benefits of operative, surgical, stabilization of the flail chest (3). The aim of the work consists in the presentation of therapeutic benefits of surgical treatment (operative stabilization) of flail chest.


Hospital records were processed by using the retrospective analysis of data on patients treated at the Clinic of Thoracic Sur-gery, Clinical Center of Banja Luka with traumatic flail chest in the period from 01.01.1997 - 31.12.2012. Both methods described so far: osteosynthesis systems and intramedullary stabilization (kischner’s wire and wire stitches) were used for stabilization of the flail chest. CT scanning was performed preoperatively to assess the volume of the thoracic trauma. All surgical treatments were performed under general endo-tracheal anesthesia, used by double-lumen tube by Karlens. Posterolateral thoracotomy with exploration of the pleural cavity was used as an operational method for the treatment of pa-renchymal lung lesions, intrathoracic hemorrhage and intrapleural clot removal. In the case of laceration of the parenchyma and le-sions intrathoracic structures, two intrathoracic drainages were placed in the front and back line in the fifth and seventh intercostal space.

Medical Journal (2014) Vol. 20, No. 2, 134 - 135 Review article

RESULTS

Our study covers a fifteen year period from 01.12.1997 to 31.12.2012 during which the Clinic of Thoracic Surgery of CC Banja Luka surgically treated 35 patients with traumatic created flail chest. Surgery was performed on 28 men (80%) and 7 women (20%). Pa-tients’ average age was 47.42 years. In 51.42% (18 patients), the mechanism of injury was traffic traumatism. Postoperative mortal-ity rate was 8.57%. Causes of mortality associated comorbidity in the elderly and associated polytrauma (abdominal injury, locomo-tor system, craniocerebral injury). Survival in the operated group was 91.43%. The average length of hospitalization was 15 days. On twenty patients (57.14%), a suture lung parenchyma was performed with the thoracotomy and stabilization of flail chest due to its lac-eration. Four patients (11:42%) underwent an extensive resective surgery of lung parenchyma (lobectomy or bilobectomy type). Five patients (14:28%) underwent suture hemidiaphragm due to its lac-eration. Only two patients (5.71%) underwent a fenestration of pericardium. Three patients (8.57%) were registered with a chronic postoperative pain.

DISCUSSION

Prolonged artificial ventilation, is still the most commonly used method for the treatment of the unstable segment of the chest wall (2). The goal of surgical stabilization of the unstable chest wall, is to shorten the time of application of respirators and avoid complica-tions due to his prolonged applications (4). Most studies have shown that surgical stabilization leads to a reduction in mortality in thoracic trauma, shortens time in the inten-sive care unit, and reduces the length of application of mechanical ventilation (2,4,5). Indications for use of this surgical procedure are not yet stan-dardized, but the following are generally accepted by the thoracic surgeons:• unstablechestwallif thereisanindicationforthoracotomydue

to intrathoracic injury,• unstablechestwallwithoutcontusionof thelungparenchyma,• paradoxicalmovementof theunstablesegmentof thechestwall

in patients on a ventilator (PEEP insufficient stabilization),• extensivedeformityof thechestwall(4,5).Some authors suggest the following indications:• theexistenceof strongpostoperativepaindespitetheslightpar-

adoxical movement, which could lead to respiratory failure,• forassociatedabdominalinjuries,aftersplenectomyanddisposal

rifts diaphragm,• afterexploratorythoracotomyduetopenetratingwounds(5).Advantages of the surgical procedure are: • painreduction,• reductionof thetimethatapatientspendsonaventilator,

• earlyextubationof thepatient,• completereductionof thefracture,withperfectanatomicalcon-

solidation (2,3,4,5). Most of thoracic surgeons believe that the extensive postero-lateral thoracotomy is the optimal approach, without the need for additional thoractic incisions (6). Poor coalesced fractures of ribs in flail chest treated with artificial ventilation, as well as the consequent pain are additional arguments in favor of the rib fixation (6).

CONCLUSION

Flail chest is a serious therapeutic problem which, if not treated appropriately, leads to disturbances in ventilation and gas exchange and ultimately to respiratory failure. If conservative measures such as the inside stabilization, the use of analgesics, antibiotics, oxygen therapy and airway toilet does not lead to a stabilization of respi-ratory function, surgical stabilization of the chest wall is necessary. Such a relatively simple surgical procedure is far less risky compared to the all complications that can arise without it.


REFERENCES

1. Leenen I. Special Issue on rib fixation. Eur J Trauma Emerg Surg. 2010 Oct;36(5):405.

2. Bemelman M, Poeze M, Blokhuis TJ, Leenen LP. Historic overview of treat-

ment techniques for rib fractures and flail chest. Eur J Trauma Emerg Surg. 2010

Oct;36(5):407-415.

3. Bottlang M, Walleser S, Noll M, Honold S, Madey SM, Fitzpatrick D, et al. Biome-

chanical rationale and evaluation of an implant system for rib fracture fixation; Eur J

Trauma Emerg Surg. 2010 Oct;36(5):417-426.

4. Fitzpatrick DC, Denard PJ, Phelan D, Long WB, Madey SM, Bottlang M. Operative

stabilization of flail chest injuries: review of literature and fixation options. Eur J

Trauma Emerg Surg. 2010 Oct;36(5):427-433.

5. Gasparri MG, Tisol WB, Haasler, GB: Rib Stabilization: Lessons Learned. Eur J Trau-

ma Emerg Surg. 2010;36:435–440

6. Billè A, Okiror L, Karenovics W, Routledge T. Experience with titanium devices for

rib fixation and coverage of chest wall defects; Interac Cardiovasc Thorac Surg.

2012 Oct;15(4):588-95.

Reprint requests and correspondence:Dušan Janičić, MD, PhDClinic of Thoracic SurgeryClinical Center Banja Luka12 beba 178000 Banja Luka, RSBosnia and HerzegovinaEmail: [email protected]

Surgical treatment of traumatic flail chest 135

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136

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RESULTS

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Instructions to authors 137

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Instructions to authors 139

Risk factor Score

Congestive heart failure/LV dysfunction 1

Hypertension 1

Age >75 2

Diabetes mellitus 1

Stroke/TIA/thrombo-embolism 2

Vascular disease* 1

147–56 egA

1)xes elamef .e.i( yrogetac xeS

9erocs mumixaM

Risk factor-based point-based scoringsystem - CHA2DS2 -VASc

*Prior myocardial infarction, peripheral artery disease, aortic plaque. Actual rates of stroke in contemporary cohorts may vary from these estimates.

AF = atrial fibrilation; EF = ejection fraction (as documented by echocardiography, radio nuclide ventriculography, cardiac catheterization, cardiac magnetic resonance imaging, etc.); LV = left venticular; TIA = trasient ischaemic attack.

Risk factors for stroke andthrombo-embolism in non-valvular AF

CHF or moderate to severe LV systolicdysfunction [e.g. LV EF � 40%]

Hypertension

Clinically relevant non-majorrisk factors

Diabetes mellitus

Age 65-74 years

Female sex

Vascular disease

Major risk factors

Previous stroke

TIA or systemic embolism

Age �75 years

Atrial fibrilation

Yes

Yes

No (i.e. non-valvular AF)

No

<65 years and lone AF (including females)

Valvular AF*

Oral anticoagulant therapy

Assess bleeding risk (HA S-BLED score)Consider patient values and preferences

Choice ofAnti-coagulant

Includes rheumatic valvularAF, hypertrophiccardiomyopathy, etc.

Antiplatelet therapy withaspirin plus clopidogrel, or -less effectively - aspirin only,may be considered in patientswho refuse any OAC

**

*

Assess risk of stroke(CHA2DS2-VASc score)

0 1** �2

No antithrombotic therapy NOAC VKA

NOAC - Novel Oral Anticoagulants, VKA - Vitamin K Antagonists

CHA2DS2-VASc skor za procjenu rizika od tromboembolizma kod A Fib!

Novi Evropski vodič za prevenciju tromboembolizma kod A Fib

Major i non-major riziko fakori za procjenu tromboembolizma kod A Fib!

Algoritam antikoagulantne terapije nakon procjene CHA2DS2VASc i major risk faktora!

140

Prijedlog mreže Primarne Perkutane Koronarne Intervencijeza Bosnu i Hercegovinu!

Prijedlog mreže Primarne Perkutane Koronarne Intervencije za Federaciju Bosne i Hercegovine!

Documents

April/June 2014 - KCUS journal vol 20 no2.Final.pdf · 71 New ORs - Central Medical Building - Clinical Center University of Sarajevo Novi operacioni blok - Klinički Centar Univerziteta