Transcript
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Methods: The study was conducted intwo parts: an experimental section andclinical research. In the experimentalsection four series of tests were carriedout on young Chinchilla rabbits (72experiments). The first two series oftests were devoted to the study of gen-tamicin concentration in renal parenchy-ma and urine with different methods ofantibiotic administration. The secondexperiment on animals studied the con-centration ability of diadynamophoresisof antibiotics. The clinical research con-sisted of studying 125 children with con-genital hydronephrosis caused byobstructive anomalies of pelviureteralsegment and complicated by secondarypyelonephritis. The children were alsodivided into two groups. The first group(control, n=50) received a standard regi-men of post-operative antibacterial ther-apy while the second group (main, n=75)underwent intratissue diadynamophore-sis.

Application of IntratissueDiadynamophoresis of Antibioticsand Ozonized Saline Solution inMultimodality Treatment ofCongenital Hydronephrosis inChildrenMaher Yousef, MD, PhD*

Vyacheslav Davidenko, MD, PhD*

Syed Hasan, MD, FABHP†

Mahmoud Yousef, PhD‡

*Kharkov State Medical University, Kharkiv, Ukraine †Western Missouri Medical Center, Warrensburg, Missouri‡Central Missouri State University, Warrensburg, Missouri

KEY WORDS: diadynamophoresis, con-genital hydronephrosis, pyelonephritis,Andersen-Hynes operation

ABSTRACTObjective: Malformations of the urinarysystem (US) are among the most wide-spread anomalies of development.Congenital hydronephrosis, typicallycaused by pyeloureteral segmentobstruction, is a frequent pathology inchildren and is often complicated bypyelonephritis. The purpose of this studyis to improve the results of treatment ofcongenital hydronephrosis complicatedby obstructive pyelonephritis in childrenby means of early surgical correction ofthe malformation that causeshydronephrosis and to increase the effi-ciency of antibacterial therapy throughapplying intratissue diadynamophoresisof antibiotics and urine sanitation withozonized solutions.

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Results: Our study shows the advantageof early surgical correction of congenitalhydronephrosis for preventing renalparenchyma atrophy, nephrosclerosisdevelopment, and urinary tract infec-tion. For treating the secondarypyelonephritis, the application ofintratissue diadynamophoresis of antibi-otics with a novel device showed statisti-cally significant improvement in patientrecovery. For the first time this researchuses renal excretory system and urinesanitation with ozonized saline solution.

Conclusion: Early surgical correction ofmalformations and anomalies of urinarysystem development enables timelyrestoration of normal urodynamics andprevention of further hydronephrotictransformation of kidney, as well asdevelopment of secondary pyelonephri-tis. The developed methods of integratedtreatment of secondary pyelonephritisare highly effective, economical andaccessible.

INTRODUCTIONIn recent years, the range of options forthe surgical treatment of hydronephrosisin children has been greatly expanded.Among those aimed at the restorationof urodynamics, the most frequentlyused is the Anderson-Hynes operationwhich involves the resection of patho-logically formed pyeloureteral segmentand creation of anastomosis between thepelvis and ureter. However, the resultsof therapy for this pathology depend notonly on the method of operation, butalso on such important aspects as theinitial state of the kidney and theabsence or presence of inflammation inthe parenchyma and urinary tract.

The main cause of pyelonephritisdevelopment in children is congenitalanomalies and malformations in theform of urinary system obstructionsresulting in impairment of urodynamics,urine stagnation, and infections.1

Contemporary microflora, causing sec-ondary pyelonephritis, is characterizedwith considerable variety, high virulence,and resistance.

Long-term existence of hydro-nephrosis, complicated with secondarypyelonephritis, leads to the developmentof nephrosclerosis, secondary renal scar-ring, and renal insufficiency. The pres-ence of infection in the urinary systemcan result in scarring in the area of anas-tomosis and stricture formation. In addi-tion, hydronephrotic transformationaccompanied with pyelonephritis andcicatricosclerotic changes in the renalparenchyma cause serious disturbancesof blood circulation in the kidney. Thiscomplicates the penetration of antibac-terial agents into all renal sections andsignificantly reduces the efficacy ofpyelonephritis treatment.2

The given peculiarities of hydro-nephrosis complicated with secondarypyelonephritis in children have ledresearchers to look for new methods ofeffective therapy. Despite much success,current treatment protocols forhydronephrosis in children are far fromperfect, and further research in this fieldis needed.

The important aspect of antibacterialtherapy is the concentration of antibi-otics in the kidney and urinary tract.One effective method designed to pro-vide high concentration of antibacterialagents in the inflamed area in spite ofmicrocirculation impairments is intratis-sue diadynamophoresis (DDP) of antibi-otics.3 In the available literature,however, we could not find any informa-tion about the efficacy of intratissueDDP of antibiotics for treatment ofhydronephrosis against a background ofsecondary pyelonephritis in children.Therefore, we decided to undertake thisstudy.

One important factor in suppressingurine excretory system infection is directurine sanitation. Recent data show high

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hydronephrosis complicated with sec-ondary pyelonephritis by studyingimmediate and long-term results.

MATERIALS AND METHODSAnimal ExperimentsThe study consisted of two parts: anexperimental section and clinicalresearch. The experimental part of thisresearch was devoted to the study of theconcentration ability of DDP of antibi-otics. For this purpose, four series oftests on young Chinchilla rabbits (72experiments) were carried out.The first two series of tests were devot-ed to the comparative study of gentam-icin concentration in renal parenchymaand urine with different methods ofantibiotic administration. For this, theear edge vein and urinary bladder werecatheterized in animals of series one(control, 20 animals) and gentamicin, 5mg/kg, was administered by intravenous(IV) drops within 30 minutes.

To determine the gentamicin con-centration in renal parenchyma, 500 mgof renal tissue were obtained. Studymaterials were obtained at 2-hour inter-

bactericidal activity of ozonized solu-tions in relation to the majority of gram-positive, gram-negative, and anaerobicmicroorganisms.4 Direct studies of theuse of ozonized solutions for sanitationof children’s urinary system and urinewere not found. Studies of this methodof treatment of secondary pyelonephri-tis, in our opinion, are quite relevant andpromising.

STUDY OBJECTIVESThe objective of this study was to exam-ine the incidence of secondary pyelo-nephritis in children with hydronephrosisin different age groups. Specifically, weplanned to study species composition ofchildren’s secondary pyelonephritismicroflora and its sensitivity to antibi-otics and to develop experimentally andintroduce to medical practice themethod and device for DDP of antibi-otics at secondary pyelonephritis in chil-dren. We also planned to study theefficiency of renal excretory system andurine sanitation with ozonized salinesolution, and assess the efficiency oftreatment of children with congenital

Figure 1. Dynamics of hourly difference of gentamicin concentrations in renal parenchyma.

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vals beginning at hour 2 and ending athour 16. Urine was taken at the sametime. Determination of gentamicin con-centration in biological substrates wascarried out by the method of agar diffu-sion effected in two layers of medium onPetri dish.

The second experiment on animals(main, 32 animals) was carried out usingthe following methods: after removingall of the hair from the abdomen andback under IV hexenalum anesthesia,lumbotomy was performed, the kidneywas mobilized from the surrounding tis-sues, the pelvis was opened, and amicroirrigator with numerous openingswas introduced to the ureter through therenal parenchyma. A flexible wire elec-trode was inserted in the lumen withoutput to the back skin.

The next day a gentamicin solution(5 mg/kg) was administered to the earedge vein using the drop method.External electrodes were fixed on theanterior abdominal wall and back. Allelectrodes were connected to a Tonusdevice (Apparatus machine for treat-ment by Dynomic Electric stream,TONUS_1 DT-50-3, OOO Neva-Treid,

St. Petersburg, Russia). The kidney wastreated with two-semiperiodic continu-ous diadynamic current 0.5 amp for 15minutes at the time of IV administrationof antibiotic, and continued for 15 min-utes after stopping the infusion.

With the aim of comparative analy-sis of the efficiency of intratissue DDPof antibiotics in conditions of experi-mental pyelonephritis, two more seriesof experiments were performed. In theseexperiments, pyelonephritis in rabbits(20 chinchilla rabbits) was induced byIV administration of day culture of plas-macoagulating staphylococcus (ATCC-25923) containing 800 million microbialbodies.

Development of inflammatoryprocess and confirmation of pyelo-nephritis were seen in the course of theexamination of the renal preparationstaken on the third and sixth day afterinfection. The experimental methods ofthe third series (10 animals) correspond-ed to the first series and the methods ofthe fourth series (10 animals) corre-sponded to the second series. Therapyand study of its efficacy took 10 days.Urine tests for determining the bac-

Figure 2. Dynamics of hourly difference of gentamicin concentrations in the urine.

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teruria and leukocyturia was performeddaily. A histological study of morpholog-ical changes in kidneys was carried outon the third, sixth, and tenth day of theexperiment.

Clinical StudiesAll clinical studies were performed atthe Child Surgical Clinic of KharkivRegional Child Clinical Hospital No.1,Ukraine. Consents were obtained fromthe parents of patients prior to study.

Clinical observations consisted ofstudying 125 children with congenitalhydronephrosis caused by obstructiveanomalies of pelviureteral segment andcomplicated by secondary pyelonephritis(84 boys and 41 girls). The ages of chil-dren were from birth to 14 years.

All children with congenitalhydronephrosis complicated withpyelonephritis underwent complex ther-apy consisting of pre-operative prepara-tion, operation, and post-operativeconservative treatment. They underwentsimilar operations: resection ofpyeloureteral segment according toAnderson-Hynes.

In order to compare the efficacy oftreatment of secondary pyelonephritis,the patients were divided into twogroups. The first group (controls, n=50)underwent a standard regimen of post-operative antibacterial therapy. In thesecond group (main, n=75) administra-tion of antibiotic was performed usingour methods, and pelvis and ureter weresanitized using drop-by-drop administra-tion of ozonized saline solution (6-8mg/L).

To perform intratissue DDP ofantibiotics in clinical conditions a devicecomposed of two electrodes, one ofwhich was designed as a flexible plasticprobe with several openings with a wireelectrode of stainless steel 20 cm inlength, cross-section 0.0002 m2 in thelumen was made. The second electrodewas cutaneous in the form of two stan-dard plates. The electrodes were placedas follows: a wire electrode was placedusing a nephrostome into the pelvis andureter and was fixed to the renal capsuleduring operation, and its other end wasled to the skin. Another electrode wasplaced on the skin on both sides of the

Figure 3. Dynamics of bacteriuria parameter logarithm in animals of the third and fourth series ofexperiment.

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kidney projection. A Tonus device(Apparatus machine of Microwavephysiotherapy, Amplipuls-5, OOO Neva-Treid, St. Petersburg, Russia) designedfor young children, Amplipuls-5, wasused.

Ozonizing of saline solution waseffected just before application using theuniversal medical device for ozonothera-py, Ozon UM-80 (Institute of OzoneTherapy, Kharkov, Ukraine). Admini-stration of ozonized saline solution intothe microirrigator that had been placedin the pelvis and ureter was performedby the infusion machine Ascor (AscorSEP 21s, Poland) at the rate 5-40 mL ofsolution per hour within 30 minutesdepending on the child’s age. Sessions ofDDP and ozonizing were initiated onthe first post-operative day and lasted 5-6 days. The criteria to stop the treatmentwas based on significant decrease in bac-teriuria and leukocyturia.

In this study the following researchmethods were applied: clinical, laborato-ry, x-ray (excretory and infusion dripurography), and echosonography (pre-natal, diuretic).

Aspects such as complaints, presenceor absence of fever, history of disease,and the general state of children were

considered when examining the patients.Laboratory studies included clinicalblood tests, levels of medium mass mole-cules, leukocyte toxicity index, clinicalurine test, and determination the degreeof bacteriuria according to Kass et al.5

Microbiological study of urine (iden-tification, microbial count, sensitivitydegree to antibacterial preparations)was carried out by the bacteriologicallaboratory of Regional Child ClinicalHospital No. 1 (Kharkiv).

Echosonographic studies were car-ried out using ultrasound deviceSonolane SL-1 (Sonobane SL-1, SiemensCompany, St. Petersburg, Russia) withlinear and sector 3.5 MHz transducers.

With the aim to make differentialdiagnoses of congenital hydronephrosisand functional pyeloectasia in newbornsand children of early age, diuretic sonog-raphy according to Krasovska et al6 wasperformed looking into the followingfeatures: moderate hydration (10 mL/kgbody weight) 30-40 minutes before thestudy, assessment of output degree ofwidening of the renal excretory system,determination of linear size of pelvis in2 dimensions in transversal projection,IV introduction of 0.5 mg/kg of lasix,sonographic observation of the process

Figure 4. Dynamics of leukocyturia level in animals of the third and fourth series of experiment.

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of filling and ejection of pelvis within 60minutes with registration of changes ofinterrelation between studied valuesevery 5 minutes with computer process-ing.

RESULTSAnimal Experiment ResultsStability and mobility of gentamicin inthe electric field were studied in vitro.Identical spectra of absorption beforeand after the use of diadynamic currentwere obtained, which showed the preser-vation of the basic structure of thepreparation molecule. Also, no changeswere found in its antibacterial activityafter the use of diadynamic currents.

Study of the histological prepara-tions of renal parenchyma showed that 3days after IV infection with the cultureof plasmacoagulating Staphylococci therabbits had developed acute pyelo-nephritis.

During the analysis of the results ofthe first two series of tests, it was notedthat the highest concentrations of gentamicin in renal parenchyma (38.41 ± 0.38 in the control group and106.48 ± 0.74 in the main series) werefound 2 hours after the beginning of theexperiment, and the difference betweenthese concentrations (78.07 ± 0.12µg/cm3 ) was statistically significant(P<0.001).

Thereafter, within 8 hours of begin-ning the experiment, the concentrationof gentamicin in the control series wasreduced by 29.17 ± 0.31 µg/cm3, for an

average hourly reduction of 3.6 ± 0.05µg/cm3, whereas in main series, reductionof concentration at 8 hours was8.8 ± 0.01 µg/cm3, for an hourly reduc-

tion of 1.1 ± 0.07 µg/cm3.The final detectable concentration of

gentamicin in renal parenchyma in ani-mals in the control group was 5.33 ± 0.32 µg/cm3 in a 10-hour sample oftested material. In the main series oftests, gentamicin was detected within 16hours of observation with the final con-centration of 9.38 ± 0.09 µg/cm3 (Figure1).

The results obtained showed a statis-tically significant difference in the levelof gentamicin concentration in the kid-ney undergoing DDP administration ofantibiotic (P<0.01). There is a significantdifference in the summarized determina-tion of antibiotics in the kidney in thetemporal aspect which was noted within6 hours. A significant reduction in theconcentration rate was also noted withinthe first 8 hours of the experiment. Theantibiotic concentration reduction ratein the main series was 2.5 times less thanin the control series. A significant levelof probability of concentrations betweenthe control and the main series of testsin all temporal samples (P<0.001-0.01)was reached.

Using normal IV administration,gentamicin was detected in the urineafter 6 hours with an increase of concen-tration within 2 hours by 10.83 ± 0.08µg/mL, and then the concentrationtapered until the end of observation. In

Table 1. Etiology of Congenital Hydronephrosis Development in Children (n=125)

Etiology of Hydronephrosis Absolute Number %%Congenital dysgenesis of PUS 92 73.6Embryonic bands strangulating PUS 6 4.8Aberrant vessels strangulating PUS 11 8.8High exit of ureter 9 7.2Deformation of ureter in PUS section 7 5.6

PUS=pyeloureteral segment

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total, the antibiotic in the urine wasfound within 8 hours with an averageconcentration of 18.1 ± 0.15 µg/mL. Intests where the antibiotic was adminis-tered using DDP, it was found in theurine 4 hours after beginning the experi-ment with an increase of concentrationwithin the next 6 hours. In total, antibi-otic in urine was detected within 12hours with the average concentration of42.2 ± 0.12 µg/mL (Figure 2).

Thus, average concentration of gen-tamicin in the urine of the main seriesanimals was 2.3 times higher than in thecontrols. The time of discharging theantibiotic with the urine in the mainseries was 4 hours longer.

The level of bacteriuria in animals ofthe control series gradually reducedfrom the sixth day of observation, andon the tenth day it was two orders ofmagnitude less. In the main series reduc-tion was detected starting from the fifthday with a four-order difference.Beginning from the sixth day significantdifference in bacteriuria level (P<0.01),which progressively increased until thetenth day (P<0.001), was detected

(Figure 3).Another parameter used to deter-

mine the efficiency of treatment ofpyelonephritis is leukocyturia.Leukocyturia in both test seriesoccurred 3 days after infection and was4.0-4.6 x 106. Before the fifth day in bothseries, leukocyturia increased equallyand reached the level of 7.8-8.0 x 106. Anincrease of leukocyturia in animals inthe control group was found up to theseventh day (9.1 x 106). At the sametime, in the test group, the reduction ofleukocyturia down to 7.5 x 106 wasdetected (Figure 4).

Comparison of the obtained resultsdemonstrates that in the main series,leukocyturia in animals was reducedfrom 8.0 x 106 to 4.5 x 106 on the tenthday of observation, and in the controlseries it was reduced to 8.2 x 106.

Clinical Study ResultsStatistical analysis showed that in 73.6%of the cases, hydronephrosis was causedby congenital dysgenesis of the uretericmuscular layer in the area of thepyeloureteral segment (PUS). In other

Figure 5. The content of pathogenic microflora identified in children with secondarypyelonephritis.

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children, hydronephrosis was caused byaberrant vessel (8.8%), high exit of theureter (7.2%), ureter angulation (5.6%),or embryonic bands (4.8%) (Table 1).

Secondary pyelonephritis complicat-ed the course of hydronephrosis in anaverage of 56.8% of the observations.The incidence of pyelonephritis in chil-dren of various age groups was different.Children in the first year of life showedan incidence of 33 ± 8%, and in childrenin the first half-year period it was 18 ±10%. At the age of 1 through 5 years,pyelonephritis was found in 45 ± 11% ofthe observations, and in children above10 years, it was found in 96 ± 4%.

We studied the microbiological struc-ture of pyelonephritis (121 urine inocu-lations). The dominating microorganismwas Enterococcus (26.4%). Othermicroorganisms present were E. coli(20.5%), S. saprophyticus (11.2%), andS. epidermidis (10.3%). Other microor-ganisms were found much less often(Figure 5).

Analysis of microflora sensitivity toantibiotics found that almost allpathogens showed low sensitivity toantibiotics of penicillin group, and wererather sensitive to gentamicin and

cephalosporins. Thus, the isolatedmicroflora displayed high resistance toantibiotics. In more than half of thestudied antibiotics, sensitivity did notexceed 50%. The most efficient antibi-otics were imipinem, 80.3% sensitivity;ceftazadime, 83.4% sensitivity; cefo-taxime, 86.9% sensitivity; and aztreon-am, 89.3% sensitivity.

Analyzing the results of the treat-ment of children in both groups, it isworth noting that secondary pyelo-nephritis is the most frequent and con-stant complication of congenitalhydronephrosis in children. Pyelo-nephritis incidence sharply differs invarious age categories. Thus, in childrenabove 10 years of age pyelonephritis waspresent in nearly all (96%) of the obser-vations; in children below 6 months ofage pyelonephritis was found only in18%. A distinct dependence of second-ary pyelonephritis incidence from thestage of hydronephrotic transformationof kidney is evident. The first-stagehydronephrosis was accompanied bypyelonephritis in 44 ± 15% of the obser-vations, and in the third-stage,hydronephrosis was complicated withpyelonephritis in 100% of the observa-

Table 2. Incidence and severity of secondary pyelonephritis depending on the stage ofhydronephrosis

SecondaryPyelonephritis Leukocyturia

State of Absolute Hydronephrosis Number % number % Insignificant Moderate Pyuria Control group (n=50)

Stage I - initial 16 32+7 7 44+13 3 (43+20) 4 (57+20) —Stage II – marked 25 50+7 15 60+10 2 (13+9) 8 (53+13) 5 (33+13)Stage III – terminal 9 18+5 9 100 — 2 (22+15) 7 (78+15)Total 50 100 31 62+12 5 (16+7) 14 (45+9) 12 (39+9)

Main group (n=75)Stage I - initial 32 43+6 14 44+9 6 (43+14) 8 (57+14) —Stage II – marked 37 49+6 20 54+8 5 (25+10) 11 (55+11) 4 (20+9)Stage III – terminal 6 8+3 6 100 — 1 (17+17) 5 (83+17)Total 75 100 40 53+8 11 (28+7) 20 (50+8) 9 (22+7)

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tions (Table 2).Comparing the two groups of obser-

vations, it is necessary to emphasize thatin the main group, the number of chil-dren under the age of 1 year was consid-erably higher when compared with thecontrol group (14 ± 5%). In the maingroup, children aged 6 months andyounger make up 61 ± 9% of the chil-dren under the age of 1, and in the con-trol group there were no children underthe age of 6 months.

Overall, the comparative analysis ofthe clinical and laboratory findings forchildren in both groups showed that thedisease dynamics in children of the maingroup were better than those of the con-trol group.

Analysis of laboratory findingsshowed that leukocytosis in children ofthe main group significantly reducedfrom the second day, and in the controlsfrom the tenth day. The dynamics of thewhite blood cell (WBC) formula was thesame. The erythrocyte sedimentationrate (ESR) in the control group showedno changes before the tenth day, and inthe main group demonstrated significant

changes on the fifth day of observation.The level of medium-mass molecules inchildren of the main group differed sig-nificantly from the initial level on thesecond day, and in the control group, thisdifference in this parameter did notreach statistical significance until thetenth day.

Leukocyte toxicity index (LTI) inchildren of the main group was signifi-cantly reduced on the fifth day, and inthe control group at that time it showedno considerable changes (Figure 6).Analysis of bacteriuria dynamics in chil-dren ages 1-5 in the main group showedthat after the first session of pelvis andureter treatment with ozonized salinesolution, the level fell considerably,almost down to the normal level froman initially high parameter (up to 108).Only on the second and third day thelevel of bacteriuria partially recoveredto 108-106, although in the prevailingmajority of observations it neverexceeded 105-103. This shows efficiencyof the administered therapy. In themajority of cases, the urine was sterileby the fourth or fifth day (Figure 7).

Figure 6. Level of leukocyte toxicity index (LTI) in children with secondary pyelonephritis.

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In older children, urine sanitationwas much slower than in younger chil-dren. This may be due to the increasedresistance of microflora. Thus, after thefirst sanitation, no considerable changesof bacteriuria level were detected, buton the second day after the second san-itation, in several children the parame-ter was normal, although initialbacteriuria on the third day slightlyincreased. Efficient reduction of bac-teriuria level in these children wasfound after the fourth or fifth sanita-tion (P<0.001).

All children in the main groupunderwent organ-preserving plasticoperations, and in the control group theresearchers had to perform nephrecto-my in 3 (6 ± 3.4%) patients.

According to the histological studiesconducted using the original technique,antibacterial therapy limited the area ofspreading infection to the cortical layer ofthe renal tissue. Moderate intensity andthe spread of inflammatory infiltration ofthe tissue, an almost complete absence ofleukocytic component of cellular reaction,and an early termination of the inflamma-tory process in the kidneys resulted in fullrestitution of the tissue.

DISCUSSIONMethods of combined application ofintratissue DDP of antibiotics andozonized solutions in treating secondarypyelonephritis, complicating congenitalhydronephrosis in children was workedout. These methods significantlyimproved immediate and late results oftherapy.

Recommendations regarding usageof intratissue DDP of antibiotics andozonized solutions in the therapy of sec-ondary pyelonephritis in children, basedon research results, have been imple-mented in practice in the surgical clinicof Kharkiv Regional Child ClinicalHospital No. 1, Kremenchuk ChildHospital and Regional Child Hospital inSumy.7

Our experimental studies showedthat antibacterial therapy of pyelo-nephritis in animals, treated usingintratissue diadynamophoresis of antibi-otics, considerably differs in efficiencyfrom the standard protocol of antibiotictherapy. Early elimination of the inflam-matory process in the kidneys facilitatesminimum morphological changes in theparenchyma and rapid renovation of allstructural and functional impairments.

Figure 7. Dynamics of general microbial contamination of the urine in children of main group (1-5 years old) when performing treatment of the pelvis and ureter with ozonized saline solution.

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The positive experimental resultsenabled us to introduce our methods ofantibacterial therapy into clinical prac-tice.

Pyeloureteroplasty in hydronephro-sis in children of an early age is a micro-surgical procedure that can beperformed only with optical magnifica-tion and use of microsurgical equip-ment. Therefore, we developed andintroduced into practice the techniqueof video-assistance in which a laparo-scope tubus with video camera is intro-duced into the surgical wound. Theoperative area is projected on the moni-tor, enabling us to magnify considerablythe anatomic structure subjected toanastomosis and providing an adequateview of the operation field for the sur-geon and assistants.

We performed 10 operations withvideo-assistance for newborn childrenand two 3-month-old children. The earli-est successful operation was for a 3-week-old child with bilateralhydronephrosis. The second kidney wasoperated on when the child was 1.5months old.

While studying the results at each 3-month period following the initiation ofthe study it was found that during thefirst year of observation, relapses ofpyelonephritis in hydronephrosis ofthird-degree of severity were recordedin both groups, but during the secondyear a significant difference was detect-ed. In the control group, relapses ofpyelonephritis were recorded in 67 ±17% of children, and in the main group,only in 33 ± 21% of patients. After 3years of observation, in the main grouprelapses were recorded in 17 ± 17% ofchildren, and in the control group, in 44± 18% of patients.

Thus, analysis of the results of ourexperimental clinical research enables usto state that secondary pyelonephritisconstantly accompanies congenitalhydronephrosis in children. It consider-

ably complicates the course of this dis-ease and worsens treatment results.

Early prenatal diagnosis of the mal-formations of urinary system and high-level postnatal dynamic observationenable us to diagnose timely congenitalhydronephrosis and to perform earlycorrective operations before the devel-opment of pyelonephritis. This can con-siderably improve the short-term andlong-term results of treatment.

Therapy of secondary pyelonephritisis a complex clinical problem stipulatedwith high resistance of contemporarymicroflora and nephrosclerotic changesresulting from hydronephrosis andimpairment of microcirculation in thekidney.8

With the aim to improve efficiencyof antibacterial therapy when treatingsecondary pyelonephritis at all therapystages, it is possible to successfully usethe method of intratissue diadynamo-pherosis of antibiotics, which apart fromits principal application—formation ofhigh and continuous concentrations ofantibacterial agents in inflammationfoci—creates favorable conditions forthe course of reparative processes in theoperated organ area, and performs elec-tric stimulation of the pelvis and ureter,and thus facilitates adequate urodynam-ics.9

For direct sanitation of the urinarytract and urine it is possible to effective-ly use drop administration of ozonizedsaline solution into the pelvis and ureter.This technique does not require largevolumes of antiseptic and long-terminstallations. This is very important inthe conditions of small volumes of pelvisand ureter in children.

Complex application of the devel-oped scheme of therapy of congenitalhydronephritis, complicated withpyelonephritis, makes it possible to con-siderably improve results of therapy andto avoid organ-removing operations inchildren.10-13

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CONCLUSIONSecondary pyelonephritis is the mostfrequent complication of congenitalhydronephrosis in children. The inci-dence of secondary pyelonephritisdepends on the child’s age: in childrenunder six months, it is 18 ± 10%, and inchildren above 10 years old the inci-dence is 96 ± 4%. Microflora causingsecondary pyelonephritis is diverse. Themain factor is coccus flora (24.47%) inassociation with E coli (22.7). More thanhalf of the studied antibiotics showmicroflora sensitivity not exceeding50%. High sensitivity was demonstratedby imipinem, ceftazadime, cefotaxime,and aztreonam.

Application of intratissue diady-namopherosis of antibiotics enables usto increase the concentration of antibi-otic in renal parenchyma by eight timesand in urine by 3.6 times in comparisonwith standard antibiotic therapy, to cre-ate its continuous concentration during16 hours, and to carry out early electros-timulation of pelvis and ureter facilitat-ing quicker healing the anastomosis andearly recovery of urodynamics.14 Theoriginal technique of antibacterial thera-py limited the spread of inflammationaffection in the kidney only in the corti-cal layer. Moderate intensity and thespread of inflammatory infiltration oftissues, an almost complete absence ofleukocyte component of cellular reac-tion and an early elimination of inflam-matory process stipulating completerestitution of renal tissues were noted.

Application of ozonized saline solu-tion with ozone concentration of 6-8mg/L for washing the renal excretorysystem enables us to perform full andstable sanitation of urine, to increaseoxygenation of anastomosis area (facili-tating early healing) within 4-5 days.15

Early surgical correction of congenitalhydronephrosis in children and intensiveconservative therapy of secondarypyelonephritis enabled us to create

favorable conditions for performingorgan-preserving operations, gave earlyrecovery of functional renal impair-ments, produced uncomplicated courseof post-operative period, and reducedthe incidence of pyelonephritis from30.8% down to 19.6%.

For early diagnosis of congenitalhydronephrosis in children and timelytreatment of this disease it is necessaryto apply prenatal ultrasound diagnosisand postnatal dynamic observation andcomprehensive examination. For directsanitation of renal excretory system andurine it is possible to effectively useinstillations of ozonized saline solutioninto pelvis and ureter with ozone con-centration of 6-8 mg/L daily within 5-6days with exposition up to 30 minutes.For treating the congenital hydro-nephrosis it is recommended to performearly surgical correction which facilitatesthe recovery of adequate urodynamicsof upper urinary tract and preventsdevelopment of nephrosclerotic andmicrocirculatory changes in the kidneysand secondary pyelonephritis. Thisfavorably affects short- and long-termfunctional results.

Taking into account the diversity ofmicroflora causing secondarypyelonephritis and its manifested resist-ance to antibacterial agents, it isrequired to use highly efficient antibi-otics of wide spectrum of action such asimipinem, ceftazadime, cefotaxime, andaztreonam. With the aim to improveefficiency of antibacterial therapy it isrecommended to apply intratissue dia-dynamopherosis of antibiotics under theoriginal technique described in thisresearch. This enables us to form highand continuous concentrations of anti-bacterial agents in renal tissues andurine with simultaneous electric stimula-tion of pelvis and ureter in the earlypost-operative period. The research hassolved the urgent problems of improvingresults of treating the congenital

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hydronephrosis complicated withpyelonephritis in children with early sur-gical correction of malformation andimprovement of conservative methodsof therapy.

REFERENCES1. Lapshin VV, Davydenko VB, Vyun VV, et al.

Prophylaxis and treatment of postnatalpyelonephritis at surgical correction ofhydronephrosis in children. Medical Practice.2001;2:91-93.

2. Tsyganenko AY, Davydenko VB, VasylchenkoVN, et al. Development of efficient methodsof treating the purulent septic processes inchildren on the basis of integrated clinicaland microbiological studies. Exper Clin Med.2002;3:73-75.

3. Yousef MA. Experimental substantiation ofdiadynamopherotic antibacterial therapy ofpyelonephritis. Exper Clin Med. 2002;2:119-121.

4. Yousef MA. Contemporary approaches totreating the secondary pyelonephritis in chil-dren. Today Tomorrow Med. 2002;4:87-89.

5. Kass EH, Svanborg-Eden C. Host-parasiteinteractions in urinary tract infections.University of Chicago Press, Chicago, 1989,l94-197.

6. Krasovska IV, Rostovskaya VV, Babanin IL.Diagnostic sonography for obstructive disor-ders and urodynamics of the upper urinarysystem in hydronephrosis, Pedtr Surg.2002;2:21-26.

7. Yousef MA, Davydenko VB. New method oftreating secondary pyelonephritis inhydronephrosis in children. Dig ResearchKyiv Med Acad Postgrad Ed, Kyiv. 2001:314-315.

8. Yousef MA, Davydenko VB. Method of anti-bacterial therapy at treating pyelonephritis inchildren. Ped Obstet Gynecol. 2003;3:69.

9. Lapshin VV, Yousef MA, Davydenko VB.Declaration Patent of Ukraine for InventionNo. 52255A, MPK 7 A61P13/00. The methodof sanitation of urinary system at secondarypyelonephritis. Kharkiv State MedicalUniversity, Application No. 2002032497 dated29 March 2002; Published: December 16,2002. Bulletin No. 12.

10. Lapshin VV, Davydenko VB, Vyun VV, et al.Optimization of post-operative therapy forpyelonephritis in hydronephrosis in children.Surgery 2001. Achievements in contemporarysurgery: Materials of IIIrd Russian ScientificForum. Moscow. 2001:206-207.

11. Lapshin VV, Davydenko VB, Yousef MA.Facilitation of therapy of post-operationpyelonephritis in children. Proceedings of VIConference of Pediatric Urologists ofUkraine 25-26 October 2001: Theses ofReports. Zhytomyr. 2001:24-25.

12. Davydenko VB, Yousef MA. Improvement ofefficiency of antibacterial therapy of second-ary pyelonephritis in children. Materials of20th Congress of Surgeons of Ukraine.Ternopil. 2002:311.

13. Shtyker SY, Yousef MA, Davydenko VB.New trends in ozone therapy in pediatric sur-gery. New techniques of recovery using natu-ral and performed factors (physiotherapy,ozone therapy, resorts). Materials ofResearch and Practical Conference. Kharkiv.2002:194-197.

14. Yousef MA. Methods of improving the anti-bacterial therapy of pyelonephritis in chil-dren. 7th International Medical Congress ofStudents and Young Scientists: Proceedings ofCongress. Ternopil. 2003:62.

15. Shtyker SY, Yousef MA, Davydenko VB.Prospects of applying ozone in pediatric sur-gery. Third International Research andPractical Conference “Science and SocialProblems of Society: Medicine, Pharmacy,Biotechnology”: Proceedings of the confer-ence. Kharkiv. 2003:237.