Slobodan Ilić

Kidney Ectopeptidases in Gentamicin and Mercuric Chloride-Induced Acute Renal Failure

The clinical use of gentamicin is associated by nephrotoxicity in over 10% of patients. However, the biochemical events responsible for proximal tubular injury and acute renal failure (ARF) are still unclear. In the present study, effects of gentamicin and, comparatively, of mercuric chloride upon rat kidney cortex ectopeptidases were studied. Gentamicin was given i.p., 100 mg/kg daily for up to 6 days, mercuric chloride i.p. once 2.5 mg/kg to rats studied after 3 days. Kidney cortex aminopeptidase N decreased significantly after 3 and 6 days’ treatment (p < 0.01), however, angiotensinase A significantly decreased after 3 (p < 0.01), and much more after 6 days of gentamicin treatment (p < 0.001). Dipeptidylpeptidase IV activity was significantly decreased only after 6 days of treatment with gentamicin. In mercuric chloride-induced ARF all three peptidase activities were markedly decreased (p < 0.001). These results suggest that gentamicin-induced decrease in ectopeptidase activities could compromise vasoactive and other biologically active peptides handling, with important consequences upon renal function and metabolism.

THE PREDICTIVE VALUE OF 131I-HIPPURATE CLEARANCE IN THE PROGNOSIS OF ACUTE RENAL FAILURE

The aim of this investigation was to study the validity ofthe radionuclide methods in the estimation of kidney function, for prognosisand follow-up of acute renal failure (ARF). In thirty-one ARF patients, theevaluation of glomerular filtration rate (GFR) by 99mTc-DTPAclearance and effective renal plasma flow (ERPF) by 131I-ortoiodohippurate(131I-OIH) clearance was performed within 7 daysand after 6 months from ARF onset. All patients were divided in three groupsaccording to 131I-OIH clearance values obtainedwithin 7 days: group 1, under 150 mL/min; group 2, 150–250 mL/min; andgroup 3, over 250 mL/min. Seven days clearance values of both radiopharmaceuticalswere found to be very low, however, GFR was found more severely impaired thanERPF. Clearance values obtained after 6 months demonstrated no recovery ofrenal function in the first group, partial recovery in the second and almostcomplete recovery in the third group. Patients with the lowest 131I-OIHclearance values at the ARF onset had no recovery of renal function, whilein the other two groups recovery corresponded to initial 131I-OIHclearance values. In patients with ARF both, 99mTc-DTPAand 131I-OIH clearances were shown suitable forthe follow up of renal function, however, only 131I-OIHclearance had a strong predictive prognostic value for renal function recoveryin ARF.

Thyroid hormone profiles in experimental acute renal failure.

Thyroid hormone profiles were determined in two groups of dogs made uremic, either by i.v. uranyl nitrate 10 mg/kg BW injection or by bilateral ureteral ligation, and in one group of sham-operated animals. Each group consisted of 6 dogs and served as its own control. From blood samples taken in 12-h intervals up to 144 h for uranyl nitrate-injected dogs and 96 h for operated dogs, serum levels of T4, T3, fT4, fT3, rT3, and cortisol were measured by radioimmunoassays. The results obtained in both groups of uremic dogs showed an initial sharp fall of T4, T3, fT4, and fT3 followed by a plateau or retarded decrease. In sham-operated dogs the fall of these hormones was slight and of short duration. Reverse T3 had a tendency to increase in all groups examined, but a significant elevation was recorded only after bilateral ureteral ligation. In this group cortisol serum levels were found the highest, being also significantly increased in the other two groups. The temporal coincidence of the most marked alterations in T3, rT3, and cortisol serum concentrations indicates a significant role of stress in thyroid dysfunction. Although serum creatinine rise and weight loss were not parallel with thyroid hormone alterations, the involvement of uremic compounds and malnutrition in this process is also quite clear. Thus, the data presented suggest simultaneous influences of uremic toxins, stress, and malnutrition on the induction of thyroid dysfunction in dogs made uremic by uranyl nitrate injection or bilateral ureteral ligation.(ABSTRACT TRUNCATED AT 250 WORDS)

Radionuclide voiding patterns in children with vesicoureteral reflux

The purpose of this study was to evaluate bladder function in children with vesicoureteral reflux (VUR) by means of indirect radionuclide cystography (IRNC), and to investigate whether IRNC can identify those children with voiding dysfunction. The study enrolled 74 neurologically intact children, 14 boys and 60 girls aged 2–14 years, with VUR documented using contrast micturating cystourethrography as the initial method. In all patients, IRNC was performed using technetium-99m diethylene triamine penta-acetate (DTPA). Based on the urodynamic findings, three groups were distinguished: a group with VUR and normal urodynamic findings (n=27), a group with VUR and detrusor hyper-reflexia (n=43) and a group with VUR and detrusor-sphincter dyssynergia (n=4). A control group comprised 64 healthy children, aged 2–13 years, without any symptoms of lower urinary tract dysfunction. The dynamics of bladder emptying were studied in the posterior view after intravenous injection of 37xa0MBq/10xa0kg b.w. DTPA, with acquisition of 90 2-s frames during voiding. The parameters evaluated were: voided urine volume (VV), bladder capacity, functional bladder capacity (FBC), residual urine, voiding time, average flow rate, peak flow rate (PFR) and ejection fraction (EF). With regard to the final urodynamic diagnosis, FBC, PFR and EF were found to be significant IRNC predictor variables using the logistic regression method. If abnormality on at least two of the three significant predictor variables was taken as the criterion of voiding dysfunction, the overall sensitivity, specificity and accuracy of IRNC in the detection of voiding dysfunction were 81%, 78% and 80%, respectively. Three radionuclide voiding patterns were detected in children with VUR: (1) a normal voiding pattern characterised by normal FBC with near-normal PFR and EF values, (2) a markedly reduced FBC with significantly reduced VV, PFR and EF values (in children with bladder instability), and (3) a higher bladder volume with a near-normal value for PFR and a slightly reduced or near-normal EF (in children with detrusor-sphincter dyssynergia). This study confirmed the association between lower urinary tract dysfunction and congenital VUR. IRNC was found to be a simple, non-invasive method which allows reliable differentiation of voiding patterns in patients with VUR. IRNC can be used as a first-line method for screening in children with VUR to identify those with abnormal voiding patterns.

Radionuclide Staging of Renal Function in Type 1 Diabetes Mellitus

Aim. The aim of this study was to assess renal function in different stages of type 1 diabetes mellitus by radionuclide methods. Additionally, glomerular and tubular functions were correlated with urinary albumin (UAER) and N-acetyl-β-D-glucosaminidase (NAGA) excretion rates. Patients and methods. Fifty-three patients with diabetes mellitus were classified into four groups: normoalbuminuric (NA, 18 patients), microalbuminuric (MiA, 12 patients), macroalbuminuric (MaA, 13 patients), and chronic renal failure group (CRF, 10 patients). Glomerular filtration rate (GFR) was estimated by diethylenetriamine pentaacetic acid-technetium 99m (99mTc-DTPA) clearance rate while tubular function was calculated as a percentage of net injected activity fixed in both kidneys, 4 h after intravenous injection of dimercaptosuccinate acid-technetium 99m (99mTc-DMSA). Additionally, 99mTc-DTPA clearance was correlated with estimated GFR (eGFR) by using modified Modification of Diet in Renal Disease (MDRD) Study Group formula. Results. 99mTc-DTPA clearance and 99mTc-DMSA fixation were found significantly higher in normoalbuminuric group (p < 0.05 and p < 0.02, respectively), unchanged in microalbuminuric group (p > 0.05, p > 0.05), and decreased in both macroalbuminuric (p < 0.0001, p < 0.00001) and chronic renal failure group (p < 0.0001, p < 0.00001). Renal function was denoted as normal, increased (hyperfunction), or decreased (hypofunction). It was found normal in a high percentage of patients with normalbuminuria (filtration 44.4%, fixation 72.2% pts) and microalbuminuria (66.7% and 66.7%). Renal hyperfunction was not only found frequent in normalbuminuric group (55.6% and 27.8%), but was also recorded in microalbuminuric group (8.3% and 8.3%). Renal hypofunction was present in all macroalbuminuric patients and in one-quarter of those with microalbuminuria as well. Such distribution of renal function conditions indicated normalbuminuric and microalbuminiric groups functionally heterogeneous. Regression analysis showed a significant correlation between 99mTc-DTPA clearance and eGFR in MaA and CRF groups only. Although urinary NAGA excretion rate was shown as a less sensitive staging parameter, being significantly increased when compared to control group only in MaA and CRF groups (p < 0.05), it significantly correlated with 99mTc-DTPA clearance rate (r = −0.485, p = 0.0004) and 99mTc-DMSA tubular fixation (r = −0.526, p = 0.0002). Conclusions. The results of this study favor the performance of radionuclide studies together with the determination of urinary albumin excretion rate in patients with type 1 diabetes mellitus in order to achieve more reliable staging of diabetic kidney disease. The demonstration of glomerular hyperfiltration and tubular hyperfunction by radiopharmaceuticals contributes to the early detection of diabetic kidney disease, while the quantification of renal function enables the follow-up of the progressive function loss in the later course of the disease.

Solitary congenital pelvic kidney: An extremely rare developmental aberration

&NA; An ectopic pelvic kidney contralateral to an agenetic one is an extremely rare congenital malformation that is usually discovered incidentally on abdominal ultrasound or computed tomography. The authors describe a 40‐yearold woman with right renal agenesis and a contralateral pelvic kidney who had a history of symptomatic recurrent urinary tract infections. She underwent Tc‐99m DTPA dynamic scintigraphy and clearance measurement to assess renal function and the patency of the urinary tract. She had bacteruria and proteinuria at the time of the study but normal blood urea (4.6 mmol/l) and serum creatinine (91 μmol/l) levels. An ultrasound scan did not show renal pelvis dilatation. Dynamic scintigraphy and the clearance value of Tc‐99m DTPA showed a compensatory elevated glomerular filtration rate and normal urine outflow despite the presence of a urinary tract infection and short ureter, which is commonly associated with an ectopic kidney.

Cigarette Smoking Has no Impact on the Effect of Radioiodine Therapy in Patients with Graves Disease / Pušenje cigareta nema uticaj na ishod radiojodne terapije kod bolesnika sa Grejvsovom bolešću

Summary Presently, there is very little data on the impact of nicotine and other components of tobacco smoking on the outcome of radioiodine therapy (RIT) in Graves’ disease (GD). Thus, this study was aimed to analyze a possible impact of cigarette smoking on the effect of radioiodine therapy in the patients with Graves’ disease. The study included 31 patients (16 smokers and 15 non-smokers) with GD, aged from 22 to 73 years, who were treated with a single dose of iodine-131 sodium iodide (131I-NaI) and subjected to a 12-month follow-up, thereafter. Patients were treated with antithyroid drugs (ATDs) before RIT and described very intense stressful events occurring prior to diagnosing Graves’ hyperthyroidism. A successful response to RIT was defined as euthyroidism and subclinical or clinical hypothyroidism, while an unsuccessful response was defined as persistent hyperthyroidism. Comparison of age (47.4±9.41 vs. 49.5±13.8 years, p=0.628) at the time of RIT, applied activity of 131I-NaI (372±78.4 vs. 363±43.7 MBq, p=0.675), and duration of ATDs therapy (3.47±3.33 vs. 4.94±5.62 years, p=0.387) between smokers and non-smokers showed no significant difference. The cumulative incidence of successful response to therapy in smokers and non-smokers was 31.2 vs. 46.7% (p<0.05), 50.0 vs. 60.0% (p>0.05), 56.2 vs. 60.0% (p>0.05), and 56.2 vs. 66.7% (p>0.05) after 3, 6, 9 and 12 months, respectively. The results showed that cigarette smoking has no impact on the effect of radioiodine therapy after twelve-month period in patients who had experienced stressful events before the occurrence of Graves’ disease. However, patients with smoking habits achieved successful response later than non-smokers. Sažetak Za sada ima veoma malo podataka u literaturi o uticaju nikotina i drugih komponenti duvanskog dima na ishod radiojodne terapije (RIT) kod Grejvsove bolesti (GB). U skladu sa tim, cilj ove studije bio je da se analizira mogući uticaj pušenja cigareta na efekat RIT kod bolesnika sa Grejvsovom bolešću. Efekat terapije jednom dozom radiojoda (131I-NaI) procenjen je nakon 12 meseci kod 31 bolesnika sa GB (16 pušača i 15 nepušača), od 22 do 73 godine. Bolesnici su lečeni antitiroidnim lekovima (ATL) pre RIT. Stresni događaji bili su prisutni kod svih ispitanika pre postavljanja dijagnoze Grejvsovog hipertiroidizma. Uspešan odgovor na RIT je definisan kao eutiroidizam i klinički ili subklinički hipotiroidizam, a neuspešan odgovor kao perzistentni hipertiroidizam. Komparacijom starosnog doba (47,4±9,41 vs. 49,5±13,8 godina; p=0,628) u vreme RIT, aplikovane aktivnosti 131I-NaI (372±78,4 vs. 363±43,7 MBq, p=0,675) i trajanja kontinuirane terapije ATL pre RIT (3,47±3,33 vs. 4,94±5,62 godina; p=0,387) nisu uočene statistički značajne razlike između pušača i nepušača. Kumulativna incidencija uspešnog odgovora na RIT kod pušača i nepušača nakon 3, 6, 9 i 12 meseci bila je: 31,2 vs. 46,7% (p<0,05), 50,0 vs. 60,0% (p>0,05), 56,2 vs. 60,0% (p>0,05) i 56,2 vs. 66,7% (p>0,05). Rezultati su pokazali da pušenje cigareta nije uticalo na efekat radiojodne terapije nakon 12 meseci kod bolesnika koji su naveli stresni događaj pre pojave Grejvsove bolesti. Međutim, uočeno je da se kod pušača kasnije postiže uspešan odgovor na RIT nego kod nepušača

Correlation between clinical prediction tests for coronary heart disease and findings on spect myocardial perfusion scintigraphy and coronary angiography

Sažetak: Uvod i cilj: Klinički predikcioni testovi su značajan dijagnostički alat u odreĎivanju grupa pacijenata koji treba da budu podvrgnuti daljim dijagnostičkim metodama u cilju detekcije koronarne bolesti. Cilj ovog rada je bio utvrĎivanje korelacije izmeĎu verovatnoće za postojanje koronarne bolesti (CHD) dobijene Djukovom kliničkom predikcijom za postojanje koronarne bolesti i rezultata dobijenih SPECT perfuzionom scintigrafijom miokarda i koronarnom angiografijom. Pacijenti i metode: U studiju je bilo uključeno 56 pacijenata, 35 muškaraca i 21 žena, starosti od 32 do 78 godina, sa izraženom simptomima AP. Svim pacijentima izračunavana je verovatnoća za postojanje koronarne bolesti, odnosno potreba za indikovanjem drugih dijagnostičkih metoda preko Djukove kliničke predikcije (DCS). Pacijentima je nakon toga uraĎena SPECT perfuziona scintigrafija miokarda sa testom fizičkog opterećenja (SPECT MPI) i izračunavanjem Djuke trejdmil skora (DTS), odnosno koronarna angiografija (CA). Rezultati su statistički obraĎeni SPSS statističkim alatom, neparametrijskim statističkim testovima. Rezultati: DCS je pokazao nisku verovatnoću za postojanje CHD kod 10 (17,9%), dok je kod 46 (82,1%) pacijenata pokazao umerenu verovatnoću. DTS je kod 8 (14,3%) pacijenata pokazao nisku verovatnoću, a kod 48 (85,7%) visoku verovatnoću za CHD. SPECT MPI je dao 22 (39,3%) normalnih i 34 (60,7%) patoloških rezultata. CA je bila negativna kod 21 (37,5%) pacijenta, dok je kod 35 (62,5%) pokazala postojanje značajne stenoze koronarne arterije. U grupama pacijenata sa niskom DCS i DTS verovatnoćom za postojanje CHD, nisu naĎeni perfuzioni defekti na SPECT MPI, ni stenoze koronarne arterije na CA. Zaključak: Prediktivni klinički testovi, DCS i DTS, kojima se uspostavlja ili odbacuje sumnja na postojanje CHD, predstavljaju značajne dijagnostičke alate kojima se izbegava nepotrebno izlaganje pacijenata daljim dijagnostičkim metodama koje podrazumevaju bilo invazivni dijagnostički pristup, bilo nepotrebnu ekspoziciju pacijenata jonizujućem zračenju. DCS i DTS imaju visoku negativnu prediktivnu vrednost za CHD i pouzdani su u izboru pacijenata sa AP za dalje dijagnostičke modalitete. Ključne reči: Djuke klinički skor, Djuke trejdmil skor, perfuziona scintigrafija miokarda, koronarna angiografija.

The role of stimulated tireoglobulin in the management of patients with differentiated thyroid carcinoma

Sažetak: Cilj: Cilj ove studije je bio da ispita znaĉaj stimulisanog tireoglobulina (sTg) kod pacijenata sa diferentovanim karcinomom štitaste ţlezde nakon tireoidektomije u razliĉitim fazama praćenja tokom i nakon inicijalnog leĉenja, korelirajući nalaz sTg sa kliniĉkim nalazom, 131I-NaI dijagnostiĉkim (DxWBS) i postterapijskim skenom (TxWBS) celog tela. Ispitanici i metode: Retrospektivnom analizom je obuhvaćeno 164 DxWBS uraĊenih kod 93 pacijenta, od kojih je kod 40 uraĊen samo posthirurški sken, dok su kod ostalih uraĊeni i kontrolni skenovi. Nalaz je smatran pozitivnim ukoliko je u regionu vrata ili na drugom mestu bila vizualizovana fokalna akumulacija radiojoda, i negativnim, ukoliko je bila prisutna samo fiziološka akumulacija. Vrednosti sTg su smatrane pozitivnim ukoliko su bile iznad 2ng/ml. Rezultati: Negativna vrednost sTg je detektovana u 56 sluĉajeva negativnih DxWBS, dok je pozitivna vrednost sTg bila u skladu sa pozitivnim nalazom DxWBS u 78 sluĉajeva. Saglasni nalazi dva testa su bili prisutni u 82% sluĉajeva. Nesaglasni nalazi su detektovani u 30 sluĉajeva (18%), od kojih su kod 20 (12%) dobijeni pozitivni nalazi DxWBS i negativan nalaz sTg, a kod 10 (6%) sluĉajeva negativni nalazi DxWBS i pozitivne vrednosti sTg. Kod svih 30 pacijenata je uraĊena radiojodna ablacija/terapija. Nalaz na postterapijskom skenu je bio u skladu sa nalazom DxWBS kod 20 ispitanika sa pozitivnim DxWBS i negativnim sTg, i kod 3 ispitanika sa negativnim DxWBS i pozitivnim sTg. MeĊutim, kod 7 od 10 ispitanika sa negativnim DxWBS i pozitivnim sTg, nalaz TxWBS je ostao negativan. Zakljuĉak: Rezultati ovoga rada su pokazali da nizak nivo sTg ne moţe pojedinaĉno biti pouzdan dijagnostiĉki marker za praćenje toka bolesti kod nekih pacijenata sa diferentovanim tireoidnim karcinomom. Rezultati pokazuju da sken celog tela radiojodom uz vrednosti sTg ima izuzetno veliki znaĉaj u dijagnostiĉkom algoritmu kod pacijenata sa DTC tokom razliĉitih faza leĉenja . Ključne reči: scintigrafija celog tela, tireoglobulin, diferentovani tireoidni karcinom.

The influence of Ki-67 proliferation index on Tc-99m-EDDA-HYNIC-TOC somatostatin receptor scintigraphy in patients with carcinoids

Abstract The aim of this paper is to determine the influence of Ki-67 proliferation index on somatostatin receptor scintigraphy (SSRS) with Tc-99m-EDDA-HYNIC-TOC (Tc-99m-Tektrotyd) somatostatin analogue in patients with carcinoid tumors. Sixty-one patients (31 female, 30 male; age range: 33-76 years) were examined: 13 patients highly suspected of having a carcinoid, and 48 patients who had undergone the surgical removal of the tumor. Whole body SSRS at 4 h postinjection, spot scintigrams and SPECT of the selected regions were obtained for all patients. Tc-99m-Tektrotyd scintigraphy was classified as true positive in 26 out of 30 and true negative in 24 out of 28 patients. The sensitivity of Tc-99mTc-Tektrotyd scintigraphy was found to be as high as 94.74% in the group of patients with low mitotic index Ki67 (<2%), and it progressively decreased in patients with higher mitotic index (77.78% for Ki67 2-15% and 20% for Ki67% >20%). The likelihood of Tc-99m-Tektrotyd scan being positive when a carcinoid is present was found to be inversely proportional to the value of Ki67 proliferation index. The results showed that Tc-99m-Tektrotyd SSRS is a sensitive method for diagnosing and staging patients with well-differentiated carcinoid tumors. However, in poorly differentiated tumors with high Ki67 proliferation index, additional analyses are necessary for precise staging.