BM JOURNAL

Albumin. Its place in critical carepractice

Mariam A. Al-Ansari, MD, FRCSI.

ost critically ill patients have a commonpathophysiological process. Infection, trauma,

or major surgery initiates an inflammatory cascadeleading to the release of various inflammatorymediators (for example, cytokines) and activation ofleukocytes. This is a self-perpetuating cascade,which results in damaged endothelial integrity,increasing microvascular permeability and promotesextravasations of fluids (including albumin) into thetissue. Moreover, there are several reasons whyalbumin supplementation might make things worsefor critically ill patients.1 Cost containment isbecoming an increasingly important factor inmedical decision making. Human albumin solutionsare more expensive than other colloids andcrystalloids. An acceptable alternative to albuminwould be favorable. The impact of albumin infusionon survival has long been a subject of debate andseveral investigations. It is very difficult tocomment on the rational of use of albumin inclinical practice. Variations in patients, targets,additive therapy, and other factors makeinterpretation of the literature difficult. Interestingly,despite advice not to use albumin, use of thisproduct continues. There is no convincing datajustifying administration of albumin either fortreating hypovolemia or for correcting hypo-albuminemia. In this report, we will summarizewhat the literature states on the use of albumin forthe critically ill patient.

Despite a growing body of systematic reviewsand evidence based medicine analyses, the safetyprofile of albumin is still under dispute. Two meta-analysis of randomized trials have broadly assessedthe effects of albumin on survival.2,3 None showed asignificant overall survival benefit. Indeed, theCochrane Injuries Group Albumin Reviewers meta-analyses even indicated increased mortality amongstalbumin recipients (6.8%). A major limitation ofboth meta-analyses is the reliance on survival as theend point. More than half of the includedrandomized trials were not designed to assess thisend point. Another meta-analysis included onlystudies using purified albumin and a wide spectrumof patients. It included 55 trials involving 3,504patients. Overall, this analysis detected nodifference in mortality between patients treated withalbumin and other fluids.4 A more recent systematicreview included 79 randomized trials with a total of4,755 patients.5 It showed definite beneficial effectsof albumin in both cardiac and non cardiac surgery.

M

Brief Communication

They analyzed the use of albumin administration indiverse clinical settings, such as hypoalbuminemia,ascites, sepsis, burn patients and outcomes afterbrain injury. They concluded that albumin doesbestow benefit in terms of decreased morbidity in awide array of clinical settings. However, the optimaldose and administration schedule for albuminremain to be delineated. Further investigations arewarranted to address these issues.

The Saline versus Albumin Fluid Evaluation(SAFE) study is the largest ever multicentric,double blind, randomized controlled trial of SAFEfor fluid resuscitation of critically ill patients inintensive care from 16 intensive care units inAustralia and New Zealand over an 18 monthperiod. Of the 6,997 patients who underwentrandomization, 3,497 were assigned to receive 4%albumin and 3,500 to receive saline.6 There were726 deaths in the albumin group compared to 729deaths in the saline group (relative risk of death,0.99; 95% confidence interval: 0.91-1.09; p=0.87).The 2 groups of patients had a similar proportion ofnew single-organ and multiple-organ failure(p=0.85). There were no significant differencesbetween the groups in the mean numbers of daysspent in the ICU, days spent in the hospital, days ofmechanical ventilation, or days of renal-replacementtherapy. Subgroup analysis of the albumin-treatedgroup revealed a trend towards decreased mortalityin patients with septic shock, and a trend towardsincreased mortality in trauma patients, especiallythose with traumatic brain injury. This study hadconclusive evidence that 4% albumin is as safe assaline for resuscitation, although no overall benefitof albumin use was seen. The commonly usedhigher albumin concentrations require rigorousevaluation in clinical trials.

The Cochrane Injuries Group Albumin Reviewerscontinuously publishes an update of the originalmeta-analysis. Their last search was updated inAugust 2004.7 The conclusion was that there is noevidence that albumin reduces mortality whencompared with cheaper alternatives such as saline incritically ill patients with burns and hypoalbuminemiaor hypovolemia (Table 1). Very recently, Vincent etal8 looked at the effect of albumin administration onmorbidity (including death) in acutely illhospitalized patients. In their meta-analysis, theyanalyzed a nonselective, transparent large datasampling of 71 trials. They concluded that albuminreduces morbidity in a broad category of acutely illhospitalized patients. To make a recommendationfrom this study, one needs to study the datacarefully, as the median duration of follow-up for allincluded trials was only 4 days. Also, the numberneeded to treat to avoid one complication was 44patients. Using such costly therapy in this meta-analysis, there was no evidence that this was

www.smj.org.saSaudi Med J 2005; Vol. 26 (11) 1823

Ann Intern Med 2001; 135: 149-164. 4. Astiz ME, Rackow EC. Crystalloid-colloid controversy

revisited. Crit Care Med 1999; 27: 34-35. 5. Haynes GR, Navickis RJ, Wilkes MM. Albumin

administration what is the evidence of clinical benefit? Asystematic review of randomized controlled trials. Eur J

Anaesthesiol 2003; 20: 771-793. 6. Finfer S, Bellomo R, Boyce N, French J, Myburgh J,

Norton R. SAFE Study Investigators. A comparison ofalbumin and saline for fluid resuscitation in the intensivecare unit. N Engl J Med 2004; 350: 2247-2256.

7. The Albumin Reviewers. Human albumin solution forresuscitation and volume expansion in critically ill patients.The Cochrane Database Systematic Reviews 2004.Available from: http://www.cochrane.org/cochrane/revabstr/AB001208.htm

8.Vincent JL, Navickis RJ, Wilkes MM. Morbidity inhospitalized patients receiving human albumin: a meta-analysis of randomized, controlled trials. Crit Care Med2004; 32: 2029-2038.

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Use of adrenaline as an adjunct tolocal anesthetic agent. A cause ofconcern for the anesthesiologist

Mobarak H. Ansari, MD, Annamma Abraham, DA.

drenaline is an endogenous catecholamine. It isa sympathomimetic agent that has both a and b

adrenergic effects. Physicians mainly use it as abronchodilator, during cardiopulmonary resuscitationand in the treatment of acute anaphylactic reactions.We often use adrenaline in a concentration of 5gm/ml (1:200,000) to reduce blood flow and slowthe rate of absorption of the local anesthetic agent,thus reducing the plasma concentration andprolonging the duration of action.1 It has beenrecognized for a long time that halothane and, to alesser extent, other volatile anesthetics sensitizemyocardium to the arrhythmogenic effects ofadrenaline. Sensitization is the interaction betweenvolatile anesthetics and catecholamines that leads toreductions in the threshold for both atrial andventricular arrhythmias. Sequentially escalatingdoses of adrenaline produce premature ventricularcontractions and sustained ventricular tachyarrhythmiasduring halothane anesthesia. Pretreatment withthiopentone attenuates halothane-adrenaline inducedarrhythmias, presumably via effects on theatrioventricular node or the upper bundle of His.The doses of adrenaline required to produceventricular arrhythmias during desflurane orsevoflurane anesthesia are similar to, butsignificantly less than those observed duringadministration of isoflurane and halothane.2However, Katz and Katz3 made 3 suggestions for

translated to a better outcome in terms of shorterICU/hospital stay or hospital discharge.Furthermore, the albumin used by the trials includedvaried from 2-25% albumin concentration.Although they calculated the total amount ofalbumin received in grams, the question remainswhether it is the concentration of albuminpreparation used, the target serum albumin level orthe total grams of albumin received, that matters?Albumin has been used for over 50 years for fluidresuscitation in the ICU, despite the lack of anyadequately powered randomized clinical trials. Asyet, there is no evidence to support the widespreaduse of albumin. There is no convincing datajustifying administration of albumin either fortreating hypovolemia or for correctinghypoalbuminemia. Until convincing data proalbumin is presented, injudicious use of albumin isnot to be recommended. Further trials are requiredto form optimal fluid regimens, and indications.That use of albumin in critically ill patients shouldurgently be reviewed by the critical carepractitioner. It should not be used outside thecontext of rigorously conducted randomizedcontrolled trials.

Acknowledgment. We thank all authors of the references usedfor allowing us to comment on their original work.

Received 25th June 2005. Accepted for publication in final form 16thAugust 2005.

From Intensive Care Unit, Salmaniya Medical Complex, Ministry ofHealth, Kingdom of Bahrain. Address correspondence and reprintrequests to Dr. Mariam A. Al-Ansari, Consultant Intensivist, IntensiveCare Unit, Salmaniya Medical Complex, Manama, PO Box 12,Kingdom of Bahrain. Tel. +973 17255555 Ext. 4205/5205. Fax. +97317289295. E-mail: [email protected]

References

1. Offringa M. Excess mortality after human albuminadministration in critically ill patients. BMJ 1998; 317:223-224.

2. Cochrane Injuries Group Albumin Reviewers. Humanalbumin administration in critically ill patients: systematicreview of randomized controlled trials. BMJ 1998; 317:235-240.

1824 Saudi Med J 2005; Vol. 26 (11)www.smj.org.sa

Table 1 - Cochrane Database Systematic Review result on albuminuse in critically ill patients from 32 trials (updated August2004)*:

Patients category

HypovolemiaBurnsHypoalbuminemia

Relative risk of death

1.012.4 1.38

95% Confidence interval

0.92 - 1.1 1.11 - 5.190.94 - 2.03

*The pooled relative risk of death with albumin administration was 1.04.

A

Albumin

adrenaline. However, clinical acumen and awarenessof the committed anesthesiologists will be the key inprevention and finding an apt solution to thisseemingly insignificant yet, potentially hazardousproblem.

Received 30th April 2005. Accepted for publication in final form 31stJuly 2005.

From the Anesthesiology, Prince Saud Bin Jalawi Hospital, Al-Hasa,Kingdom of Saudi Arabia. Address correspondence and reprint requeststo Dr. Mobarak H. Ansari, Prince Saud Bin Jalawi Hospital, Al-Hasa31982, Eastern Province, Kingdom of Saudi Arabia. Tel. +966 (3)5305094. Fax. +966 (3) 5300070. E-mail: [email protected]

References

1.Scott B. Adrenaline in local anesthetic solutions. ActaAnaesthesiol Belg 1988; 39: 159-161. 2.Hayashi Y, Sumikawa K, Tashiro C, Yamatodani A,

Yoshiya I. Arrhythmogenic threshold of epinephrine duringsevoflurane, enflurane and isoflurane anesthesia in dogs.

Anesthesiology 1988; 69: 145-147. 3.Katz RL, Katz GJ. Surgical infiltration of pressor drugs and

their interactions with volatile anesthetics. Br J Anaesth1966; 38: 712-718.

4.Pasternak JJ, Atkinson JL, Kasperbauer JL, Lanier WL.Hemodynamic responses to epinephrine-containing localanesthetic injection and to emergence from generalanesthesia in trans-sphenoidal hypophysectomy patients. J

Neurosurg Anesthesiol 2004; 16: 189-195. 5.Murthy HS, Rao GS. Cardiovascular responses to scalp

infiltration with different concentrations of epinephrinewith or without lidocaine during craniotomy. Anesth Analg2001; 92: 1516-1519.

6.Phillips S, Hutchinson SE, Bayly P, Hollway TE.Adrenaline-induced hypotension in neurosurgery. Br J

Anaesth 1993; 70: 687-688. 7.Muralidhar K, Bhanumurthy S. Attenuation of

cardiovascular responses to subcutaneous adrenaline inneurosurgical patients. Br J Anaesth 1992; 68: 264-267.

clinical precautions that have stood the test of time.1. We should only use solutions of adrenaline of1:100,000-1:200,000. 2. The dose in adults shouldnot exceed 10 ml of 1:100,000 adrenaline in any10-minute period. 3. The dose in adults should notexceed 30 ml of 1:100,000 adrenaline in any given60-minute period. The Ear Nose and Throat, Plastic,Dental and Neurosurgeons mainly use adrenalinemixed with lidocaine. Different studies haverevealed that ranges of hemodynamic changes occurby the addition of adrenaline to either lidocaine ornormal saline (Table 1).4-6

In a study conducted by Murthy and Rao5 among5 groups, 4 groups of patients developed significanthemodynamic changes irrespective of mixtures andthe concentrations of adrenaline used. Likewise, inanother study conducted by Phillips et al,6 amongthe 4 groups, 2 of the study groups of patientsdeveloped significant hypotension, unlike thecontrol groups when they mixed adrenaline withlidocaine and normal saline. Moreover, in tumescentanesthesia where the volume of the local anestheticmixed with adrenaline is relatively more, it poses agreater threat to the development of potentially fatalcardiovascular responses, as the likelihood ofexceeding the maximum dose of adrenalineincreases further.

These hemodynamic changes are typicallytransient, and pretreatment with metoprolol (1 mg,IV) has been effectively used to alleviate theadverse cardiovascular responses to adrenalineinfiltration.7 Nonetheless, they may often be lifethreatening.4-6 Currently in the literature, there is alack of reliable information on measures to preventor effectively counteract these adverse effects of

Table 1 - Studies showing potentially serious hemodynamic side effects of ADR when used as an adjuvant to LDC among patients undergoingvarious surgical procedures.

Pasternak et al4Murthy and Rao5

Phillips et al6

20042001

1993

LDC + ADR5 Groups

LDC LDC + ADR LDC + ADR

N. saline + ADR N. saline + ADR

4 GroupsLDC

LDC + ADRN.Saline

N. Saline + ADR

--

LDC-0.5% (Control)LDC-0.5%, ADR 1:200,000LDC-0.5%, ADR 1:100,000NaCl-0.9%, ADR 1:200,000NaCl-0.9%, ADR 1:100,000

LDC-0.5% (Control)LDC-0.5%, ADR 1:200,000

NaCl-0.9% (Control)NaCl-0.9%, ADR 1:200,000

100112 20 23 24 23 22 80----

Arterial hypertension (58%)

No significant hemodynamic changesBiphasic hypotensionBiphasic hypotensionDiastolic hypertension

Severe tachycardia

No significant hemodynamic changesHypotension (55%)

No significant hemodynamic changesHypotension (40%)

Author and referenceYear Drug combination Composition No. of patients Side effects (%)

LDC - Lidocain, ADR - adrenaline, N. saline - normal saline, NaCl - sodium chloride

Adrenaline with local anesthetic


course was uneventful, she was discharged home onthe 4th day of admission.

Hemorrhage from ruptured ovarian vessels is arare but life-threatening complication duringpregnancy.1 Mojab and Rodriguez,2 and Ginsburg etal3 discussed postpartum ovarian artery rupture withretroperitoneal hemorrhage and post-partumspontaneous rupture of a branch of the ovarianartery. The clinical manifestation is mostlyabdominal pain with hemodynamic collapse.Laboratory findings show a decrease of hemoglobinand hematocrit levels. Ultrasound examinationdemonstrates free fluid in the abdomen. At thebeginning after delivery she had no signs ofhemodynamic instability. The blood loss developedslowly and the level of hemoglobin decreasedgradually; the young patient could adjust to thedecreasing circulating volume of blood. Finally, shebegan to show signs of hemodynamic instability.The treatment consists of preoperative hemodynamicstabilization of the patient and urgent laparotomy.Rupture of uterus, uterine artery, utero-ovarianvessels, adrenal-gland vein, splenic vein, renalarterial aneurysm, kidney, liver or spleen shouldremain in differential diagnosis.3 Cardiac output,heart rate, blood volume increases, and hormonalfactors may impair the arterial wall and additionalstress such as delivery may result in the spontaneousrupture of ovarian artery.4 Structural changes inintima and media of the arterial wall aredemonstrated during pregnancy. The observedhyperplastic intimal changes are histologicallyequivalent with the changes that appear withhypertension and oral contraceptive use.5 All thesechanges during pregnancy may contribute to theetiology of spontaneous ovarian artery rupturefollowing spontaneous vaginal birth. It is stillcontroversial whether the arterial wall weakensduring pregnancy and additional stress such asdelivery or previous cesarean section may causespontaneous rupture of ovarian artery.

Spontaneous rupture of an ovarian artery afterdelivery is an extremely rare complication. Onemust think about it in cases of diffuse abdominalpain and hemodynamic collapse. The treatmentconsists of performing a laparotomy with suturingof the ruptured ovarian artery. Received 14th May 2005. Accepted for publication in final form 15thAugust 2005.

From the Department of Obstetrics and Gynecology, Dicle UniversityFaculty of Medicine, Diyarbakir, Turkey. Address correspondence andreprint requests to Dr. Ahmet Kale, Department of Obstetrics andGynecology, Dicle University School of Medicine, Diyarbakir 21280,Turkey. Tel. +90 (412) 2488001-16 Ext. 4746. Fax. +90 (412) 2488520.E-mail: [email protected]

Spontaneous rupture of the ovarianartery following spontaneous vaginalbirth

Ahmet Kale, MD, Nurten Akdeniz, MD, Mahmut Erdemoglu, MD, Yilmaz Ozcan, MD,

Ahmet Yalinkaya, MD.

emorrhage from ruptured ovarian vessels is anextremely rare but life-threatening complication

during pregnancy.1 These are very few earlierreported cases on postpartum ovarian artery ruptureafter delivery.2-3 We describe a patient withspontaneous ovarian artery rupture 5 hours afterdelivery.

A 30-year-old woman, gravida 5 para 5 (G5P5)was referred to the Obstetrics Department with thecomplaint of diffuse abdominal pain and minimallyvaginal bleeding 5 hours after delivery. The painwas associated with nausea and vomiting. Herantenatal course was uneventful, and past obstetrichistory included a previous cesarean sectionfollowed by 3 normal vaginal births no systemicillness. On physical examination, she seemed to bein moderate distress secondary to abdominal pain.The body temperature was 37C, heart rate was 110beats/min, respiratory rate was 20 breaths/min, andblood pressure was 90/60 mm Hg. Abdominalexamination revealed diffuse and rebound tenderness.Pelvic examination revealed a tender uterus with apost delivery open cervix and minimal vaginalbleeding. The attending radiologist performedultrasonographic examination, which revealed anormal liver and spleen. Perihepatic and perisplenic,an amount of free fluid was visible in the abdomen.Her hematologic workup demonstrated hemoglobin=8.38 g/dl (normal range [NR]: 12.3-15.3 g/dl),hematocrit=4.1% (NR: 37.7-53.7%), white bloodcell=1300 (NR: 4.4-11.3 uL), platelet counts=385,000x 103/ul (NR: 142-424 uL). Hemoglobin levelgradually decreased and she seemed to enter a stateof shock. We performed emergency exploitivelaparotomy with a suspicion of uterine rupture.After opening the peritoneum approximately 1500ml blood was aspirated. There was no retroplacentalhematoma. Further inspection of uterus, tubes, andovaries were normal. The liver, spleen, stomach,gallbladder, and intestines showed no signs ofbleeding. Closer inspection showed the spontaneousrupture of left ovarian artery, which was bleeding.Left ovarian artery was sutured primarily and weobserved no further bleeding. After operation shewas referred to their intensive care unit in a stablecondition. She was transfused with 5 units of bloodintra- and postoperatively, and as the postoperative

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Spontaneous ovarian rupture


humerus, both nerve and artery pass through theantecubital fossa underneath a fibrous sheath andthe bicipital aponeurosis, which takes origin fromthe biceps tendon and the fascia of the flexor-pronator mass. It then passes between the 2 heads ofthe pronator teres. In this muscle, the largest branchcan be found, the anterior interosseus nerve. Thenerve continues in the forearm between the flexordigitorum profundus and flexor digitorumsuperficialis.2

We encountered 2 anatomic variations that cancause entrapment neuropathy of the median nerveduring our routine student dissections. In one of ourdissections, we encountered a variation of themedian nerve at the level of the Br. The cadaver wasa 47-year-old male and has no visible scars orwounds on both upper extremities. Normally, themedian nerve courses in the groove between thebiceps brachii (BB) and Br.2 The median nerve canbe compressed above the elbow due to an accessorytendon, which arises form the Br in 10% of thecases. According to some authors, the muscle fibersarise form the Br connect to some of the fibers ofBB and end in bicipital aponeurosis and compress.In this case, which is located in the arm, at 9 cmproximal to the medial epicondyle, the nerve leavesthe brachial artery and passed through theantecubital fossa piercing the Br (Figure 1a). Thecourse of the median nerve on the other arm wasnormal. In another dissection, we encountered anabnormal pattern of the accessory head of flexorpollicis longus (FPL) (Gantzers muscle). Thecadaver was a male with unknown age with novisible scars or wounds on both upper extremities.

Gantzers muscle is the accessory head of theFPL, which usually originates from medialepicondyle or processus coronoideus and lies on theulnar side of the FPL. It has been implicated as oneof the causes of the anterior interosseous nerve(AIN) compression in the proximal forearm.1,3-5 Theanterior interosseous nerve is the largest branch ofthe median nerve is the forearm and has no sensoryfibers.2 The incidence of the Gantzers muscle wasreported between 45-74%.3-5 The difference of theseratios might be due to the fact that the muscle can befused with some of the superficial flexor group andcan be overlooked during dissection. The muscleusually passes between the superficial branch of themedian nerve and the anterior interosseous nerve;but rarely passes superficially to both of the nerves.2

References

1.Banas T, Boryczko M, Durzynska-Urbaniec J.Intraperitoneal hemorrhage due to the rupture of rightovarian artery in the second day of puerperium. Ginekol

Pol 2004; 75: 729-732. 2.Mojab K, Rodriguez J. Postpartum ovarian artery rupture

with retroperitoneal hemorrhage. AJR Am J Roentgenol1977; 128: 695-696.

3.Ginsburg KA, Valdes C, Schnider G. Spontaneusutero-ovarain vessel rupture during pregnancy: three casereports and a review of the literature. Obstet Gynecol 1987;69: 474-476.

4.Swaegers MC, Hauspy JJ, Buytaert PM, De MaeseneerMG. Spontaneous rupture of the uterine artery inpregnancy. Eur J Obstet Gynecol Reprod Biol 1997; 75:145-146.

5.Nolta JE, Rutherford RB, Nawaz S, Rosenberger A, SpeersWC, Krupski WC. Arterial dissections associated withpregnancy. J Vasc Surg 1995; 21: 515-520.

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Two anatomic variations in the armrelated to the median nerve

Burak Bilecenoglu, MD, Aysun Uz, MDNazim Karalezli, MD, Sinan Issi, MD.

isorders of the peripheral nervous system arequite common; of these disorders entrapment

neuropathies are frequently encountered by theclinician. The term entrapment neuropathy impliesthat the nerve is compressed by adjacent anatomicstructures.1-2 Distribution of the median nerve in thearm is rarely subjected to variation, but there arenumerous report regarding median nervecompression. Variations of the nerve and theadjacent structures may be seen clinically orobserved during surgery, autopsy or cadavericdissection. We recently encountered 2 anatomicvariations that can possibly cause entrapmentneuropathy of the median nerve during our routinecadaver dissections. Typically, the median nervereceives fibers from C6, C7, C8 and T1 spinalnerves and supplies motor, sensory and sympatheticnerve fibers to the upper limb. In the arm, its courseis closely related to the brachial artery. Along withthe brachial artery, it travels between the brachialis(Br) and the medial intermuscular septum in the armuntil it reaches the nerve and the cubital fossa,which has no branches. Sometimes a small branchto the brachial artery can be seen. At the distal

D

Spontaneous ovarian rupture


mind by orthopaedic surgeons dealing with thesurgical interventions and release operations relatedto the entrapment neuropathies of the upperextremity.

Received 30th January 2005. Accepted for publication in final form17th April 2005.

From the Department of Anatomy (Bilecenoglu, Uz), Ankara UniversitySchool of Medicine, Department of Orthopedic Surgery (Karalezli),Municipality of Health, Ankara Training and Research Hospital,Ankara, and the Department of Anatomy (Issi), Kirikkale UniversitySchool of Medicine, Kirikkale, Turkey. Address correspondence andreprint requests to Dr. Burak Bilecenoglu, Research Assistant, AnkaraUniversity, School of Medicine, Sihhiye 06100 Ankara, Turkey. Tel. +90(312) 3105001. Fax. +90 (312) 3105001. E-mail: [email protected]

References

1.Al-Qattan MM. Gantzers muscle: An anatomical study ofthe accessory head of the flexor pollicis longus muscle. J

Hand Surg 1996; 21B: 269-270. 2.Bilecenoglu B, Uz A, Karalezli N. Possible Anatomic

structure causing entrapment neuropathies of the mediannerve: An anatomic study. Acta Orthop Belg 2005; 71:169-176.

3.Dykes J, Anson BJ. The accessory tendon of the flexorpollicis longus muscle. Anat Rec 1944; 90: 83-89.

4.Hemmady MV, Subramanya AV, Mehta IM. Occasionalhead of flexor pollicis longus muscle: A study of itsmorphology and clinical significance. J Postgrad Med1993; 39: 14-16.

5.Oh CS, Chung IH, Koh KS. Anatomical Study of theaccessory head of the flexor pollicis longus and the anteriorinterosseous nerve in the Asians. Clin Anat 2000; 13: 434-438.

The most frequent site of origin of the muscle hasbeen reported to be the medial epicondyle ofhumerus, a well-developed connecting fascia madeup of the intermuscular septa among the pronatorteres and flexor muscles in the proximal forearm,flexor digitorum superficialis and both the medialepicondyle and coronoid process.3-5 However, themost frequent site of the origin of the muscle hasalso been reported to be the coronoid process in87.5%. In the forearm the muscle ends in the ulnarpart of the FPL or ends in 2 tendinous slips, one ofwhich connects to FPL, whereas the other coursedto join the tendon of the flexor digitorum profundus(FDP) to the index finger.3-5 Although the accessoryhead of the FPL is not a rare variation,3-5 in ourdissection the accessory head was seen as 2tendinous slips clearly different that have beenreported and course of these slips were extremelydifferent from the cases in the literature. It turns tothe radial side and fuses to the FPL immediatelyafter its origin, and it seemed to compress theanterior interosseous nerve strongly especially whenthe forearm is in supination (Figure 1b). When theforearm is in pronation there is no significant effecton the nerve (Figure 1c).

In this study, we report 2 anatomic variationsthat are responsible for entrapment neuropathies ofthe median nerve. These variations must be kept in

Figure 1 - Photograph showing: (a) Right arm, elbow. BB - bicepsbrachii, Br - brachialis, M - median nerve. The figureshows the median nerve piercing the brachialis muscle.(b) Left arm, distal of the elbow joint deep compartment,supination. FD -flexor digitorum profundus, FLP - flexorpollicis longus, AIN - anterior interosseal nerve, Blackarrowhead: Gantzers muscle seen as 2 tendinous slips.The figure shows the accessory head of the flexorpollicis longus in supination. (c) Left arm, distal of theelbow joint deep compartment, pronation. FDP - flexordigitorum profundus, FLP - flexor pollicis longus, AIN -anterior interosseal nerve, Black arrowhead: Gantzersmuscle seen as 2 tendinous slips. The figure shows theaccessory head of the flexor pollicis longus in pronation.

a c

b

Variations of the median nerve


visualized by exposure to ultraviolet light afterethidium bromide staining. A female staff memberperformed all procedures including blood specimencollection and preparation, DNA extraction and PCRamplification. To determine the specificity of malegenomic DNA in a single PCR using SRY forward /SRY 3-nested primers; we examined 15 malegenomic DNA and 15 female genomic DNAsamples. All the male samples were positive andproduced a 173 bp fragment while the 173 bpfragment was not detectable in the female samples(Figure 1). We amplified all female samples givingnegative results for the Factor VIII gene, as apositive control (data not shown). To evaluate thesensitivity of the developed assay, we applied thesingle PCR, using SRY forward/SRY 3-nestedprimers, to serial dilutions of 220 ng of malegenomic DNA in female genomic DNA. Positivesignals were detected up to the 1/10000 dilution,which is almost at the 3 cells level (data not shown).

We developed a new single PCR of a nested PCRfor sex determination, which is able to identify Y-specific signals with no false-positives and false-negatives. Honda et al5 developed a single PCR byuse of the internal pair of primers used in the nestedPCR devised by Lo et al.3 This study is an attemptto cross-use one primer from the external pair ofprimers and another from the internal pair ofprimers of a nested PCR to develop a single PCR.Although this method is incomparable to real timequantitative PCR, it has overcome the difficulties ofnested PCR and provided a feasible methodologywith an acceptable specificity and sensitivity.However, the sensitive nature of this assay, whichcan detect copies at the 3 cells level, implies thatgreat care must be taken to avoid contamination.

Sex determination using sexdetermining region Y primers bysingle conventional polymerase chainreaction

Nafisseh Pakravan, Ms, PhD, Fereydoun A. Ala, MD, FRCPath

Ghassem Rastegar Lari, Ms, PhD.

he development of the polymerase chainreaction (PCR) as a means of amplifying known

sequences of DNA allows determination of genderby amplification of sequences unique to the Ychromosome. Detection of Y-specific sequences hasclinical importance as it would be useful in fetalgender identification in mothers who are carriers forX-linked disorders and in forensic medicine.1 Therewere reports dealing with sex determination todetect Y-specific sequences by PCR. EstablishedPCR-based on sex determination methods using theXY homologous region of the amelogenin gene,2the Y chromosome specific sequences include theY-specific repeat sequences, DYS14,3 and the sexdetermining region Y (SRY).4 One study used anested PCR using SRY forward/reverse as externalprimers and SRY-5netsed/3-nested as internalprimers5 for detection of Y-specific sequences. Thedifficulties with the nested PCR prompted us todevelop a single conventional PCR by cross-usingthe SRY forward/SRY 3-nested primers.

We prepared genomic DNA from the peripheralblood samples collected from adult males andfemales in EDTA-containing tubes. Cell-free DNAfrom plasma to plasma by using QIAamp DNAblood Mini Kits (Qiagen, UK) according to theblood and body fluid protocol with minormodifications. Primers for amplification of 173 bpsequence are as follows:

SRY forward: 5GTG TCC TCT CGT TTT GTGAC 3,

SRY 3-nested: 5CTA GTA CCC TGA CAA TGTATT C 3.

We performed PCR amplification in a total volumeof 25 l containing extracted DNA, 200 M dNTPs,20 pmol of each primer, 1 x Taq polymerase buffer(containing 1.5 mM MgCl2), and 1 U of Taqpolymerase (Roche Biochemicals). The thermalcycling began with denaturation at 94C for 7minutes, followed by 40 cycles of 94C for 30seconds, 55C for 30 seconds, and 72C for oneminute, with final incubation at 72C for 12minutes. The PCR amplification products wereseparated by 8% acrylamide gel electrophoresis and

TFigure 1 - Photograph of electrophoresed polymerase chain reaction

products of 4 males and 3 females genomic DNA. Lane 1represent molecular weight marker VIII (pUCBM21 DNAcleaved by Hpa II, Dra I and Hind III). Lane 2, 3, 4 and 5represent male DNA. Lane 6, 7 and 8 represent femaleDNA.

Sex determination


magnesium between cases who died fromcardiovascular diseases and controls.2

Jorde et al3 shows that total serum calcium is apredictor of cardiovascular disease in men. Weperformed this cross-sectional study in order tocompare the status of total serum calcium andphosphorus levels in patients with coronary arterydisease (CAD) with normal controls. We used aquestionnaire for demographic data and weexcluded patients with malignancy, renal failure(creatinine >1.5 mg/dl), liver diseases, digestivedisorders, hyperthyroidism, and those undergoingtreatment with thiazide diuretics. We collectedblood samples for measurement of serum totalcalcium, phosphorus, urea, creatinine, triglyceride,uric acid, cholesterol and fasting blood sugar afterovernight fasting, and we determined biochemicalparameters with ordinary kits using RA 1000apparatus.

The patients underwent routine coronary angiographyusing optimus-M 200 Philips angiography system.The number of the vessels with significant stenosis(>50%) was detected by a cardiologist who was notaware of the investigation. Stenosis less than 50%was known as non-significant lesions and wereexcluded. We analyzed all data through EPI info2000 and p values

provides information not only regarding changes inglycolysis, but also on anaerobic work capacity.Blood sampling involves blood loss, emotionalstress and discomfort, whereas saliva is easy tocollect and non-invasive. Several authors havedescribed the possibility of evaluating the changesproduced in the composition of saliva in response toexercise as a non-invasive method of determininglactate threshold.1,2 There is some research, whichshows parallelism between the saliva and bloodlactate response during incremental exercise.2 Theaim of this study is to investigate whether there is arelation between lactate increase of blood andsaliva, during seated recovery after supramaximalexercise.

A group of 10 male athletes, practicing anaverage of 6 hours of sports activities per week, andwith an acceptable level of physical fitness, agreedto participate in the study after the objectives of theinvestigation and the protocol to be followed wasexplained to them. The characteristics of theparticipants were as follows: average age 21.4 1.50 years (range 21-26.5 years), height 179 4.01cm (range 174-189 cm), weight 81.7 13.30 kg(range 65 - 100 kg), and body mass index 25.4 4.40 kg/m2 (19.4-30.3 kg/m2). No athlete has asmoking habit. All participants followed theircustomary diets and performed their habitualprofessional and recreational activities. The time ofexperiment (10:00-12:00 am) was chosen tominimize the influence of circadian variations insalivary flow and composition. The test wasperformed at a minimum of 3 hours after breakfastand conducted in a well-ventilated room with anambient temperature of 20-24OC, and relativehumidity ranging between 40-55%. The subjectsperformed a Wingate anaerobic power test (WAPT)on Monark 814 E (Monark Exercise AB, Vansbro,Sweden). They warmed-up for 5 minutes at apedaling rate of 60-70 RPM against a resistanceequal to 20% of that was calculated for thesubsequent WAPT. Two unloaded 5-second sprintswere performed at the end of the 3rd and 5th minuteof the warm-up period. The maximal pedaling rate(RPMmax) attained during the sprints was recorded.Following a 5 minute rest to eliminate any fatigueassociated with the warm-up, they performed theWAPT against a resistance of 0.75 kg/kg bodymass. They were instructed to pedal as fast aspossible from the onset of the test. The resistancewas applied when 70% of the previously recordedRPMmax was attained. They were verballyencouraged to maintain as high a pedaling rate aspossible throughout the 30 second test duration.Heart rate was monitored throughout the warm-up,the test and the recovery method using a sport-

CAD, and serum calcium and phosphorus had nosignificant association with the angiographicseverity of CAD.

Narang et al,6 showed that serum phosphorus hadan independent positive association with theangiographic severity of CAD. In this study, wecould not measure the amount of calcium depositionin atherosclerotic plaques of patients with CAD, butregarding the unique concentrations of the totalserum calcium and phosphorus between 2 groups ofpatients with and without CAD, our data suggeststhat the total serum calcium and phosphorus had norelation with IHD.

Received 15th January 2005. Accepted for publication in final form13th July 2005.

From the Department of Cardiology and Physiology Research Center,Kerman University of Medical Sciences, Kerman, Iran. Addresscorrespondence and reprint requests to Dr. Mohammad Masoomi,Department of Cardiology, Shafa Hospital, Farabi St, Kerman, Iran.Tel. +98 (341) 3210169. Fax. +98 (341) 2115803. E-mail:[email protected]

References

1.Murray CJL, Lopez AD. Alternative projections ofmortality by cause 1990-2020. Global Burden of Diseasestudy. Lancet 1997; 349: 1498-1504.

2.Reunanen A, Knekt P, Marniemi J, Maki J, Maatela J,Aromaa A. Serum calcium, magnesium, copper and zincand risk of cardiovascular death. Eur J Clin Nutr 1996; 50:431-437.

3.Jorde R, Sundsfjord J, Fitzgerald P, Bonaa KH. Serumcalcium and cardiovascular risk factors and diseases. TheTromso study. Hypertension 1999; 34: 484-490.

4.Lind L, Jakobsson S, Lithell H, Wengle B, Ljunghall S.Relation of serum calcium concentration to metabolic riskfactors for cardiovascular disease. BMJ 1988; 297:960-963.

5.Lind L, Skarfors E, Berglund L, Lithell H, Ljunghall S.Serum calcium: a new, independent, prospective risk factorfor myocardial in farction in middle-aged men followed for18 years. J Clin Epidemiol 1997; 50: 967-973.

6.Narang R, Ridout D, Nonis C, Kooner JS. Serum calcium,phosphorus and albumin levels in relation to theangiographic severity of coronary artery disease. Int J

Cardiol 1997; 60: 73-90.

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Blood and saliva lactate levels duringrecovery from supramaximal exercise

Hilmi Karatosun, MD, PhD, Cem Cetin, MD, PhD,Metin L. Baydar, MD, PhD.

actate is now recognized to be an importantsource of energy for skeletal muscle metabolism,

measuring blood lactate concentration (samples)L

Blood and saliva lactate


taken during rest and recovery (Friedman p

Target level controlled sedation. Analternative to general anesthesia inendovascular treatment of intracranialaneurysms

Ahmet C. Senel, MD, Ahmet Akyol, MD, Halil Uzunlar, MD, Ahmet Eroglu, MD.

ontrolled sedation, commonly used to describethe process of administering sedatives or

dissociative agents with or without analgesics toinduce a state that allows the patient to tolerateunpleasant procedures by relieving anxiety,discomfort, or pain; while maintaining independentcardio-respiratory function is a term we refer to astarget level controlled sedation (TLCS).1Endovascular therapy as interventional neuro-radiology (INR) is now an established therapeuticalternative to surgical clipping of some cerebralaneurysms.2 In most institutions, an anesthesiologistis involved in the care of the patient during INRtreatment.3 The roles of the anesthesiologist in theINR suite are to monitor the patient, to provideappropriate anesthesia to facilitate the procedure,and to manage any complication that may arise.Embolization is usually performed under generalanesthesia (GA) but in our study, we evaluate TLCSusing 2 different agents in the anestheticmanagement of patients during the treatment of theircerebral aneurysm in the neuroradiology suite.

After approval of the Institutional EthicsCommittee, and obtaining informed consent; 63American Society of Anesthesiologists (ASA) I-IIIpatients (37-68 years old, at least one week laterthan their subarachnoid hemorrhage) undergoingtreatment for intracranial aneurysms by Guglielmidetachable coils (GDC) embolization were enrolledfor our study. Patient demographic data, and currentevents prior to treatment, including the neurologicalstatus of the patient and duration of the procedurewere documented. We established the intravenousaccess in the left hand. Patients were premedicatedwith midazolam 0.05 mg/kg and fentanyl one mg/kgintravenously (IV), and oxygen supplementationwas stated at 2 L/min via nasal cannulae. Afterrandomization, patients received an initial dose ofpropofol (10 mg/ml Fresenius-Kabi GmbH, Austria)0.5 mg/kg (group P) or midazolam (one mg/ml,Dormicum, Roche, Basel, Switzerland) 0.05 mg/kg(group M), followed by an infusion of eitherpropofol or midazolam as a sedative agent. Theinfusion rate was adjusted to maintain a sedationlevel of "5" by Ramsey Sedation Scale. If there wasmovement during the procedure, patients received

an increase of 14% at R0 and 29% at R5, plasmalactate was eliminated by 26% at R15, while salivalactate increased by 104% at R15, compared to theresting values (Table 2). As can be seen, plasma andsaliva lactate show different types of dynamics andthere is not a linear relation between the 2. Whenthe percentage increase of saliva lactate is comparedwith that of plasma lactate in our previous study aswell as in present study, no relation between them isobserved. However, following WAPT, saliva lactatelevels at the post-exercise 15th minute in theprevious and current studies were the same (0.43mmol/l). Our results do not indicate the presence ofany significant relationship between saliva andblood lactate values.5It is expected that salivary lactate levels are parallelwith plasma lactate levels with increasingworkloads. Some studies suggest that determinationof lactate in saliva may be an alternative to bloodlactate investigation.2 In both studies our plasmalactate and saliva lactate showed increases withsupramaximal loading. There was no significantcorrelation between the peak lactate of saliva andblood increase, also percentile of lactate increases inblood and saliva, after supramaximal exercise.

In conclusion, it seems doubtful to estimateplasma lactate level by using saliva lactate levelafter supramaximal exercise.

Received 16th March 2005. Accepted for publication in final form 29thMay 2005.

From the Department of Sports Medicine, Suleyman DemirelUniversity, Isparta, Turkey. Address correspondence and reprintrequests to Dr. Hilmi Karatosun, Assistant Professor, 126 Cad. 5/1,Isparta, Turkey. Tel. +90 (246) 2112317. Fax. +90 (246) 2326060. E-mail: [email protected]

References

1.Ohkuwa T, Itoh H, Yamazaki Y, Sato Y. Salivary andblood lactate after supramaximal exercise in sprinters andlong-distance runners. Scand J Med Sci Sports 1995; 5:285-290.

2.Segura R, Javierre C, Ventura JL, Lizarraga MA, CamposB, Garrido E. A new approach to the assessment ofanaerobic metabolism: measurement of lactate in saliva. Br

J Sports Med 1996; 30: 305-309. 3.Weinstein Y, Bediz C, Dotan R, Bareket F. Reliability of

peak-lactate, heart rate and plasma volume following theWingate test. Med Sci Sports Exerc 1998; 30: 1456-1460.

4.Chicharro JL, Legido JC, Alvarez J, Serratosa L, BandreasF, Gamella C. Saliva electrolytes as a useful tool foranaerobic threshold determination. Eur J Appl Physiol1995; 68: 214-218.

5.Karatosun H, Muratli S, Erman A, Senturk UK.Comparison of blood and saliva lactates followinganaerobic loading. Turkish Journal Sports Medicine 2000;35: 65-70.

C

Blood and saliva lactate


sedation that was adequate for the completion of theprocedure.

Traditionally, the treatment of cerebral aneurysmsinvolved surgical intervention,4,5 but recentdevelopments in INR have resulted in more patientsundergoing endovascular coiling. There is littleinformation in the literature regarding the anestheticmanagement of patients with cerebral aneurysmsundergoing endovascular treatment. Our goal was tomanage GDC embolization of the patients in theINR suite with TLCS. Target level controlledsedation; the less invasive approach of INR may bea good alternative in the management ofembolization procedure. In addition, to reducing therisk associated with GA, performing GDCembolization under sedation permits regularneurological evaluation of the patient throughout theprocedure. In the event of a thromboemboliccomplication, early detection of neurologicaldeficits and their severity allows timely andappropriate use of thrombolytic therapies. Thetechnique of anesthesia used for INR proceduresvaries from light sedation to GA from hospital to thehospital, but often GA is the preference of theneuroradiologist.6 Another benefit of TLCS in GDCembolization of the aneurysms is; during TLCS, thepatient serves as an effective overall monitor ofneurological status. In INR, the ability to assess theneurological status of patients during the procedureor immediately at the end of the procedure isdesirable. The maintenance of optimal level ofblood pressure is also very important during theseprocedures. The sedative agents in TLCS also helpto maintain intended mean arterial pressure duringthe procedure. The level of mean arterial bloodpressure during the procedure in this study wassimilar in both propofol and midazolam groups, andwe did not have any problem with the maintenance

additional bolus doses of propofol 0.3 mg/kg ingroup P, and midazolam 0.03 mg/kg in group M.After the femoral artery puncture and the initialangiogram, a 6F (2-mm diameter) nontapered guidecatheter is placed in the internal carotid or vertebralartery. This guide catheter allows the passage of themicrocatheter for contrast injection to performangiograms and road mapping. Road mapping is acomputer substraction technique that allows theinterventional neuroradiologist to see in real timethe radio-opaque endovascular tools in super-imposition with a map of the intracranial arteries.

Anticoagulation is provided with 3000-5000 IUheparin IV, followed by 1000 IU per hour.

Heparinization is necessary due to the risk ofthromboembolic complications. In the embolizationprocedure, coils of decreasing sizes were deliveredinto the aneurysm cavity and electrolyticallydetached. We recorded all complications(desaturation, apnea, hypotension, hypertension,bradycardia, tachycardia) relevant to sedation andthe procedures. At the end of the procedure, theradiologist was asked to evaluate patient sedation interms of excellent (no movement), good (onemovement, no critical time), average (more than onemovement or one movement at critical time) or poor(failed sedation; unable to perform procedure). Datafor groups are presented as mean SD. Statisticalanalysis was performed with Chi-square and t-testswhere appropriate, a p-value

3.Young WL, Pile-Spellman J. Anesthetic considerations forinterventional neuroradiology. Anesthesiology 1994; 8:427456.

4.Dangor AA, Lam AM. Anesthesia for cerebral aneurysmsurgery. Neurosurg Clin N Am 1998; 9: 647659.

5.Zander JF. Subarachnoid hemorrhage. Cur OpinAnaesthesiol 1999; 12: 503509. 6.Manninen PH, Chan ASH, Papworth D. Conscious sedation

for interventional neuroradiology: a comparison ofmidazolam and propofol infusion. Can J Anaesth 1997; 44:2630.

7.Qureshi AI, Suri MF, Khan J, Kim SH, Fessler RD, RingerAJ, et al. Endovascular treatment of intracranial aneurysmsby using Guglielmi detachable coils in awake patients:safety and feasibility. J Neurosurg 2001; 94: 880-885.

8.Manninen PH. Anaesthesia outside the operating room.Can J Anaesth 1991; 38: R126129. 9.Practice Guidelines for Sedation and Analgesia by Non-

Anesthesiologists. Developed by the American Society ofAnesthesiologists Task Force on Sedation and Analgesia byNon-Anesthesiologists. Anesthesiology 2002; 96: 1004-1017.

10.Shaughnessy TE. Sedation services for the anesthesiologist.Anesthesiol Clin North America 1999; 17: 355-363.

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The frequency of skin diseases inobese children and adult Iraqipopulation

Khalifa E. Sharquie, MBChB, PhD, Jamal R. Al-Rawi, MSc, FICMS, Firas F. Al-Tamimi, MBChB.

besity is a major health problem that iscommonly associated with skin manifestations,

such as acanthosis nigricans and skin tags, butunfortunately, only limited studies exist concerningthis problem.1 The aim of the present work is toevaluate the frequency of skin diseases among obesechildren and adults.

This study consists of 2 parts.Part 1: We took across-sectional sample from Basrah primary schools(urban only). We carried out the study fromDecember 2003 to March 2004, and included 13primary schools; 8 for boys and 5 for girls. Thenumber of pupils in the sample was 4189; 2616boys and 1573 girls. We used body mass index [(BMI) = (weight [kg])/height [m]2] to select thenumber of overweight and obese subjectsconsidered for study. There were 52 obese; 34 boysand 18 girls, and 94 overweight; 56 boys and 38girls, their ages ranged from 7-13 years. Weconsidered 100 pupils; 60 boys and 40 girls ofnormal weight as the control group, comparable forage, sex and selected from the same class as theobese pupils. We carried out a full clinical anddermatological examination to establish the

of blood pressure or fluid management of thepatients in INR, and no patients required anypharmacological agents to control their bloodpressure during the procedure. Target levelcontrolled sedation is an alternative to GA in GDCembolization of intracranial aneurysms. Monitoringstandards (electrocardiogram, pulse oximetry, noninvasive blood pressure, capnography, centralvenous lines for volume status) for anesthesia in theINR suite, is not different from the operationroom.7,8

Published data suggest that oximetry effectivelydetects oxygen desaturation and hypoxemia inpatients who are administered sedatives/analgesics,and early detection of hypoxemia through the use ofoximetry during sedation decreases the likelihood ofadverse outcomes.9 The use of propofol ormidazolam in INR suite requires the presence of ananesthetist, as the primary complication of sedationis related to respiratory or cardiovasculardepression. Safety aspects such as the need forassisted ventilation in cases of apnea must beready.10 Our results suggest that the application ofsedatives in TLCS may yield even better levels ofsafety compared with the conventional infusion ofmidazolam and propofol. The weakness of thisstudy or the question of the readers may be "why theauthors have not compared TLCS with GA for GDCembolization procedure?" The brief answer is; thereis no information in the literature regarding thesedative management of patients with cerebralaneurysms undergoing endovascular treatment inthe INR suite. And the next step of this study will bethe comparison of GA versus TLCS.

In conclusion, the anesthetic management ofpatients with cerebral aneurysms performed usingGDC embolization under TLCS appears to befeasible, and allows intra-procedural evaluation ofthe patient. Potential advantages of TLCS includeearly detection of neurological complications,decreased cardiopulmonary morbidity rates, shorterhospital stay, and lower hospital costs.

Received 17th March 2005. Accepted for publication in final form 17thAugust 2005.

From the Department of Anesthesiology and Critical Care, MedicalFaculty of Karadeniz, Technical University, Trabzon, Turkey. Addresscorrespondence and reprint requests to Dr. Ahmet C. Senel,Department of Anesthesiology and Critical Care, Karadeniz TechnicalUniversity Medical School, Trabzon 61080, Turkey. E-mail:[email protected]

References

1.Miller RD. Anesthesia: use of sedative-analgesic drugsduring MAC. 5th ed. Pennsylvania (PA): ChurchillLivingstone; 2000. p. 1454-1460.

2.Viuela F, Duckwiler G, Mawad M. Guglielmi detachablecoil embolization of acute intracranial aneurysm:perioperative anatomical and clinical outcome in 403patients. J Neurosurg 1997; 86: 475482.

O

Endovascular treatment of intracranial aneurysms under sedation


alopecia areata, were no different in both obese andnormal BMI adult individuals.

The present study emphasizes the strongassociation of skin manifestations and obesity,which reflects the abnormal metabolism mainlyinsulin resistance, and we also found that thefrequency of skin diseases is parallel with thedegree of obesity, especially in children.

Acanthosis nigricans (AN) is a major problemamong obese individuals, and has been reported in74%.1 The present work showed 59.6% amongchildren and 72% among adults, while it was absentin normal weight children, and only 1% in normalweight adults. It has been suggested thathyperinsulinemia is a cause of AN by stimulation ofinsulin like growth factor 1.2 Also in a recent Iraqistudy, AN has been reported in 68.75% of infertilefemales with polycystic ovarian syndrome (PCOS).3There is a definite association between skin tags andadult obesity.1 We found skin tags in 13.5% ofobese children, and 58% in obese adults, while itwas absent in normal weight children, and only 30%in normal weight adults. Obese individuals in boththe children and adult groups, showed increasedprevalence of planter hyperkeratosis; 48.1% inchildren and 47% in adult individuals in comparisonwith normal weight individuals 2% in children and9% in adults. Only one study has shown an increasein planter hyperkeratosis in obese adults.1 This studyshows a striking association between obesity andstriae distensae, both in children and adultindividuals compared to normal BMI children andadults. These findings are comparable to previous

diagnosis of skin diseases. Table 1 shows thefrequency of skin diseases found in the normal BMI,overweight and obese children, and we found nodifferences between the BMI groups for thefollowing skin diseases: palmar peeling, pityriasisalba, macular hypopigmentation, pityriasisversicolor, and perioral hyperpigmentation.

Part 2: A case series descriptive epidemiologicalstudy conducted at Baghdad, Teaching Hospital,Department of Dermatology and Venereology,Baghdad, Iraq from December 2003 to August2004. We included 100 obese cases; 60 males and40 females, with an age range of 18-54 years, and100 normal weight individuals attending the samedepartment; 60 males and 40 females, as the controlgroup with the same age range. The frequency ofskin diseases was significantly high (p-value0.78-0.05). Other diseasessuch as dermatitis, psoriasis, leukonychia, and

Table 1 - Frequency of skin diseases found in normal BMI, overweight and obese children includedin the study.

Acanthosis nigricansPlanter hyperkeratosisSkin tagsStriae distensaeIntertrigoDry skinHyperhidrosisDermatitisCommon wartsLeukonychiaAngular cheilitisSkin infections

ImpetigoBoilsTinea crurisTinea versicolor

020213031

10 11

2610 115 312 1 6 215 1 2

Normal BMI

(0)(2)(0)(2)(1)(3)(0)(3)(1)

(10) (1)(1)

Overweight

(27.65)(10.6)

(1.1) (15.95) (3.2) (12.8)

(1.1) (6.4) (2.1) (15.95) (1.1) (2.1)

3125 7181924 6 6 2 8 3 2

Obese

(59.6) (48) (13.5) (34.6) (36.5)

(46.15) (11.5) (11.5) (3.8)(15.4) (5.8) (3.8)

Skin diseases Number (%)

0.00000010.00000010.000016 0.0000003 0.00000010.00000010.0001 0.11 0.49 0.4 0.09 0.49

Part 1p values

4. Ive FA. The umbilical, perianal and genital regions. In:Champion RH, Burton DA, Burns SM, editors. Breathnach.Rook textbook of Dermatology. 6th ed. London: BlackwellScience Ltd.; 1998. p. 3167-3168.

5. Sato K, Kang WH, Saga K. Biology of sweat glands andtheir disorders. J Am Acad Dermatol 1989; 20: 537-563.

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Prescribing pattern of angiotensin-converting enzyme inhibitors and betablockers after acute myocardialinfarction

Waleed M. Sweileh, B. Pharm, PhD, Fatma M. Shkokani, B. Pharm, MSc, Ansam F. Sawalha, B. Pharm, PhD, Rowa J. Al-Ramahi, B. Pharm, MSc, Nidal A. Jaradat, B. Pharm, PhD,

Abed Al-Naser M. Zaid, B. Pharm, PhD, Ali S. Barakat, BSc, PhD.

n recent years, many clinical trials suggestedusing certain medications such as beta-blockers

(BB), angiotensin converting enzyme inhibitors(ACE-I), low dose aspirin, and statins to reducemorbidity and mortality after acute myocardialinfarction (AMI). Since the 1980s, we have knownthe clinical benefits of BB post AMI. Angiotensinconverting enzyme inhibitors are also useful inmanaging asymptomatic and symptomatic left-ventricular dysfunction (LVD), and thus preventingthe development of cardiac remodeling process afterAMI.1 Lipid lowering agents, in particular statinsdecrease the risk of coronary events and totalmortality in patients after myocardial infarction.2Previous randomized trials illustrate the significantreductions of mortality rate in patients receivingaspirin for secondary prevention after AMI.3 Toevaluate the impact of these clinical trials andevidence based medicine on physician practicepattern, we examined the trends in the use of BB,ACE-I and other medication therapy in patientsdischarged after AMI. We tried to identify clinicalfactors associated with ACE-I prescribing patterns.

The data were collected from Al-WataniGovernmental Hospital in Nablus, Palestine fromJanuary to December 2004. The medical files ofpatients admitted to the ICU and diagnosed withAMI were reviewed and analyzed. An ECG,enzymes, and symptoms confirmed the diagnosis ofAMI. Data obtained from medical files includedage, gender, medical history, blood pressure, heartrate, myocardial infarction (MI) type and leftventricular ejection fraction (LVEF). The use ofmedications at admission and discharge was also

reports in adults of 42.9%,1 however, there is norecord of striae distensae among obese children.Previous reports demonstrate intertrigo amongobese individuals,4 and we similarly observed this inthe present work, as we found intertrigo higher inobese versus normal adult individuals and children.Dry skin was a common problem found more in theobese individuals, mainly affecting cheeks, dorsa ofthe hands, feet, and legs. This observation was notnoticed before, and we could find no clearexplanation. We found hyperhidrosis high in obeseindividuals, when compared to overweight andnormal weight children, and similarly found in adultobese in comparison with normal weightindividuals. Previous reports confirm this.5 Previousstudies found skin infections, mainly in the form ofboils, wart, tinea cruris, and erythrasma increasedamong obese individuals.1 While in the presentwork although they did not reach statisticallysignificant levels, we found more in obeseindividuals than normal weight individuals, apartfrom erythrasma, which was significantly high inadult obese individuals. The association betweenhirsutism and obesity was not be clear the inliterature, and often hirsutism had been reported tobe high in obese females with PCOS.3 Similarly, inthe present work, although it did not reach astatistically significant level, we found more in adultobese females than normal weight females.

The excessive fat deposition that leads tothickening of the fatty layer all over the bodydeserves the term adipomegaly, rather than obesityas it is more scientific, academic, and more sociallyand publically accepted.

In conclusion, skin manifestations are a commonproblem, and important markers of obesityreflecting impaired metabolism, especiallyacanthosis nigricans, skin tags, and planterhyperkeratosis.

Received 30th April 2005. Accepted for publication in final form 13thJuly 2005.

From the Department of Dermatology and Venereology, College ofMedicine, University of Baghdad, Medical Collection Office, Baghdad,Iraq. Address correspondence and reprint requests to Prof. Khalifa E.Sharquie, Department of Dermatology and Venereology, College ofMedicine, University of Baghdad, Medical Collection Office, PO Box61261, Baghdad 12114, Iraq. Tel. +964 (1) 5560036. Fax. +964 (1)4250243. E-mail: [email protected]

References

1. Garcia HL. Dermatological complications of obesity. Am JClin Dermatol 2002; 3: 497-506. 2. Cruz PD Jr, Hud JA Jr. Excess insulin binding to insulin

like growth factor receptors; proposed Mech for AcanthosisNigricans. J Invest Dermatol 1992; 98: 82-85.

3. Sharquie KE, Al-Bayatti AA, Al-Zaidi QM, Al-Bahar AJ.Acanthosis nigricans as skin manifestation of polycysticovarian syndrome in primary infertile female. Middle East

Fertility Society Journal 2004; 9: 136-139.

I

Skin diseases in obese children and adults


diabetic patients, in patients with history of heartfailure, and in patients with an LVEF less than 40%.Analyses of medications at discharge showed thatpatients prescribed calcium channel blockers ordigoxin were more likely to receive ACE-I therapyat discharge. In contrast, patients prescribed withBB were less likely to receive ACE-I therapy atdischarge. Of all the patients included, 129/151(85.4%) were prescribed with BB at discharge. Thepresence of diabetes mellitus (DM) and MI had nosignificant effect on prescribing BB. However, BBprescribing was significantly more common amongpatients with an LVEF >40%, in patients with noheart failure, in patients with high blood pressureand in patients prescribed with neither CCB norACE-I (Table 1). All patients included wereprescribed with low dose of 100 mg aspirin; nonewere prescribed anti-hyperlipidemic statin drugswhile 10/151 (6.6%) patients were prescribed CCB.Temporal analysis showed that the prescribing ofACE-I or BB did not change with time during 2004,suggesting that changes in prescribing pattern areusually slow throughout the year.

We undertook this study to determine if, inPalestine, we have practically adopted the establishedclinical recommendations and evidence-basedmedicine for treatment after MI. We usedphysicians prescribing patterns of ACE-I and BB atdischarge after MI as the main parameter ofassessment, and concluded that there is a low post-infarction prophylactic used of ACE-I while a highpost-infarction prophylactic used of BB. Unfortunately,there are no previous studies carried out in Palestineregarding postinfarction prophylactic drugs tocompare the current data. Although we found BB

obtained. The major dependent variable analyzed inthis study was whether ACE-I or BB was prescribedat hospital discharge or not. The clinical factorsassociated with ACE-I and BB prescribing werealso analyzed. The other 2 important factors in thisstudy considered were MI type and LVEF, due totheir important roles in determining appropriatetreatment. All data were analyzed using statisticalpackage for social sciences (SPSS) version 11. Forstatistical significance, chi-square test and crosstabulation were used.

We identified 174 patients with AMI. Twenty-three patients (13.2%) died during hospitalizationand were excluded. The mean age of patients was61.7 years, and the majority was male (72%).Analysis of risk factors predisposing the patients toAMI, among the studied sample, showed that morethan half of the patients were men above 60 yearsold and mostly smokers. Approximately one-third ofthe patients were hypertensive, and 40% werediabetics. Low dose aspirin and BB were the mostcommon medication prescribed at discharge. Onadmission, approximately 93% of patients weregiven both low dose aspirin and heparin as ananticoagulant. Calcium channel blockers were givenat a higher rate on admission than at discharge (datanot shown). Regarding BB, the rates of prescribingon admission were 79.5% while at discharge were85.4%, with no statistical difference. Of all thepatients included, only 22.4% were prescribedACE-I at discharge. Neither gender, nor hypertensionor the type of MI has a significant effect onprescribing ACE-I at discharge. However, ACE-Iprescribing was significantly more common among

BP - blood pressure, DM - diabetes mellitus, LVEF - left ventricular ejection fraction, CHF - congestive heart failure, ACE-I - angiotensinconverting enzyme inhibitors, BB - beta blockers.

Variable

Table 1 - Influence of various clinical factors on the rate of ACE-I and BB prescribing at discharge after acute myocardial infarction.

BP HighNormal

DM YesNo

LVEF < 40%> 40%

CHF YesNo

ACE-I prescribed atdischarge

(23.5)(23)

(37) (13.4)

(58.3)(16.5)

(4.3)(17.2)

ACE-I not prescribedat discharge

(76.4)(77)

(62.9) (86.5)

(41.6)(83.5)

(43.5)(82.8)

BB prescribed atdischarge

(86.3)(85)

(9.7)(82)

(6.7)(98.4)

(13) (98)

BB not prescribed atdischarge

(13.7)(15)

(90.3)(18)

(83.3) (1.6)

(87) (1.6)

12/51 23/100

23/62 12/89

14/24 21/127

13/23 22/128

39/51 77/100

39/62 77/89

10/24106/127

10/23106/128

44/51 85/100

6/62 73/89

4/24125/127

3/23

126/128

7/5115/100

56/62 16/89

20/24 2/127

20/23 2/128

ACE-I and BB after acute MI


recommendations of major clinical trials. However,the post MI prescribing of ACE-I and statins do notclosely follow the publications of major trials.Focus should be made on the recent updated trials inpharmacological intervention. Non-pharmacologicalcounseling for patients is also needed and should becarried out by clinical pharmacists.

Received 18th June 2005. Accepted for publication in final form 13thAugust 2005.

From the College of Pharmacy, An-Najah University, Nablus,Palestine. Address correspondence and reprint requests to Dr. WaleedM. Sweileh, Dean, College of Pharmacy, Chairman, Clinical PharmacyGraduate Program. College of Pharmacy, An-Najah University,Nablus, Palestine. Tel. +966 (02) 2940475. E-mail:[email protected]

References 1.Kober L, Torp-Pedersen C, Carlsen JE, Bagger H, Eliasen

P, Lyngborg K, et al. A clinical trial of the angiotensin-converting-enzyme inhibitor trandolapril in-patients withleft ventricular dysfunction after myocardial infarction.Trandolapril Cardiac Evaluation (TRACE) Study Group. N

Engl J Med 1995; 21: 1670-1676. 2.Heart Protection Study Collaborative Group. MRC/BHF

Heart Protection Study of antioxidant vitaminsupplementation in 20,536 high-risk individuals: a randomizedplacebo-controlled trial. Lancet 2002; 360: 23-33.

3.Antithrombotic Trialists' Collaboration. Collaborative meta-analysis of randomized trials of antiplatelet therapy forprevention of death, myocardial infarction, and stroke inhigh risk patients. BMJ 2002; 12: 71-86.

4.Brotons C, Permanyer G, Pacheco V, Moral I, Ribera A,Cascant P, et al. Prophylactic treatment after myocardialinfarction in primary care: how far can we go? Fam Pract2003; 20: 32-35.

5.Gunnar HG, Steen ZA, Jeppe NR, Soren R, Pernilie B, IdaG, Jens F, et al. Nationwide trends in the prescription ofbeta-blockers and angiotensin-converting enzyme inhibitorsafter myocardial infarction in Denmark, 1995-2002. Scand

Cardiovasc J 2005; 39; 42-49. 6.Barron HV, Michaels AD, Maynard C, Every NR. Use of

angiotensin-converting enzyme inhibitors at discharge inpatients with acute myocardial infarction in the UnitedStates: data from the National Registry of MyocardialInfarction 2. J Am Coll Cardiol 1998; 32: 360-367.

7.Luzier AB, Navsarikar A, Wilson MF, Ashai K, Forrest A.Patterns of prescribing ACE inhibitors after myocardialinfarction. Pharmacotherapy 1999; 19: 655-660.

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commonly prescribed after AMI in the studiedsample, generally, under prescription amongpatients with MI and heart failure still exists. It isnoteworthy that a high percentage of diabeticpatients received BB after AMI, agreeing with manystudies indicating that BB is more effective indiabetic patients than non-diabetic patients.1

We cannot explain the low rate of ACE-Iprescribed in the studied patients. It could be thatfear from renal functional problems or potassiumlevels, or fears of hypotension discouragephysicians from prescribing ACE-I. Analysis of theeffect of age of patients on ACE-I prescribingshowed that physicians prescribe this class of drugmore commonly to patients above 70 years oldcompared with younger ones. Again, this is puzzlinggiven the fact that the elderly tend to have highercontraindications to ACE-I than younger patientsdue to kidney function.

All patients in the study were prescribed low doseaspirin and none were prescribed any other anti-platelet. Statins were not prescribed despite severaltrials showing their effect in decreasing the risk ofcoronary events and total mortality in patients afteracute MI. The failure to prescribe statins may bedue to the unavailability of this class of drug in thehospital. The modern management of patientsfollowing MI rests on lifestyle modifications andaddressing risk factors such as hypertension,hyperlipidemia, diabetes, and specificallyintervening with medications such as ACE-I, BB,statins, and aspirin. We found a large percentage ofsmokers, and many had other co-morbid conditionsthat necessitated aggressive post MI prophylactictherapy. Similar studies have taken place in othercountries. One carried out in Denmark, found therate of BB prescribed at discharge after AMI was67.9%, while prescribing of ACE-I was 35.5%.5Another study carried out in the USA in 1998 foundthe rate of ACE-I prescribing nationwide were30.7% during the year 1996.6 Another study carriedout in the USA in the state of New York in 1999,found that the ACE-I prescribing rate at dischargeafter AMI were 34%.7 A study carried out in Spainin year 2002 found that the rate of prescribing postMI of ACE-I was 32.5% and BB was 50.2%.8

In conclusion, we observed that post MIprescribing of BB and low dose aspirin follows the

ACE-I and BB after acute MI


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