Davor Ivanković

Ultrasonic assessment of fetal kidney function in normal and complicated pregnancies

Fetal renal function was evaluated in 255 normal singleton pregnancies between 22 and 41 weeks of gestation and in 133 complicated pregnancies. Hourly fetal urinary production rate (HFUPR), fetal glomerular filtration rate (GFR), fetal tubular water reabsorption (TWR), and the effect of furosemide on fetal micturition was evaluated by ultrasound and a combination of ultrasound and biochemical tests. In normal pregnancies, the HFUPR increased from 2.2 ml/hr at 22 weeks of gestation to 26.3 ml/hr at 40 weeks of gestation. The fetal GFR was 2.66 ml/min at term, and the percentage of TWR was 78%. In complicated pregnancies, the HFUPR was above normal in 5.7% of the growth-retarded fetuses and below the tenth percentile in 58.6%. The GFR was below normal in 68.2% of the group of complicated pregnancies, but TWR did not significantly differ from that in the normal pregnancies. The effect of furosemide was the same in both growth-retarded and normal fetuses. In diabetic pregnancies, HFUPR values varied considerably and correlated with the fetal size. The HFUPR was normal in anencephalic fetuses and in 90.0% of the pregnancies with hydramnios.

Ultrasound Assessment of Detrusor Muscle Thickness in Children with Non-Neuropathic Bladder/Sphincter Dysfunction

OBJECTIVE To measure detrusor muscle thickness in children with non-neuropathic bladder/sphincter dysfunction (NNBSD), and to evaluate the difference between children with various bladder dysfunctions and those with normal urodynamics. MATERIALS AND METHODS In 139 children the urodynamic study was performed, and the detrusor of the anterior bladder wall was measured using high-frequency ultrasonography (US). Children were categorized into five groups, according to urodynamic findings. Differences in detrusor thickness between groups were tested by one-way ANOVA with post hoc Scheffé test. RESULTS Forty-six children (33.1%) had normal urodynamics, and mean (+/-S.D.) detrusor thickness 1.3 +/- 0.5 mm (range 0.5-3.0). Fifty-two (37.4%) had urge syndrome, with detrusor thickness of 2 +/- 0.7 mm (1.0-3.6). Thirty-three (23.7%) had dysfunctional voiding, with detrusor thickness of 2.6 +/- 0.5 mm (1.5-3.6). Four (2.9%) had lazy bladder, with detrusor thickness of 0.9 +/- 0.1 mm (0.8-1.0), and four had anatomical infravesical obstruction, with detrusor thickness of 4.4 +/- 0.3 mm (4-4.6). The mean detrusor thickness in all children with NNBSD was 2.2 +/- 0.7 mm (range 0.8-3.6). Multiple comparisons showed significant difference between all groups, except between children with normal urodynamics and children with lazy bladder. CONCLUSION There is statistically significant difference in mean detrusor thickness between children with normal urodynamics and children with NNBSD. However, due to the overlap of measured values, it is not possible to determine the cut-off value that could be used to distinguish children with and without NNBSD.

The comparison of fetal behavior in high risk and normal pregnancies assessed by four dimensional ultrasound.

Objective. We compared fetal behavior (FB) in high risk and normal pregnancies using four dimensional ultrasound (4DUS). Methods. For assessment of FB in high risk and normal pregnancies, we used a scoring system of Kurjaks antenatal neurological test (KANET). The newborns were assessed by a postnatal neurological test, Amiel-Tison neurological assessment at term (ATNAT). The scores of KANET in high risk (N = 116) and in normal pregnancies (N = 110) were compared. After delivery, the results of KANET from both groups were compared with ATNAT test. Results. There was a statistically significant difference between group of high risk and normal pregnancies, for 8 out of 10 parameters in KANET: isolated anteflection of the head, eye blinking, facial expressions, mouth movements, isolated hand movement, hand to face movement, fist and finger movements, general movements. There was no difference for cranial sutures and isolated leg movements. Comparison of KANET and ATNAT showed statistically significant, moderate correlation between the two tests, which means that the neuropediatric exam (ATNAT) confirmed the prenatal 4DUS finding (KANET). Conclusion. The difference of FB between the high risk and normal pregnancies was evident. These preliminary results are promising but further studies have to be done before the test could be recommended for wider clinical practice.

Doppler sonographic renal resistance index in healthy children.

Abstract. The objective of the study was to determine the values of Doppler resistance indices (RIs) in intrarenal arteries in healthy children. Color duplex Doppler sonography of intrarenal arteries was performed in 163 children and 58 adult patients, with the absence of clinical or laboratory pathologic changes of the urinary tract. All patients were classified following results of exploratory data analysis into three age groups: (a) 51 children between 2 and < 6 years of age; (b) 112 children 6–16 years of age; and (c) adults. The RIs were compared between different age groups. The mean RI ± 1 SD values in group 1 were 0.705 ± 0.018 (range 0.67–0.75), in group 2 0.605 ± 0.029 (range 0.55–0.65), and in the adult group 0.604 ± 0.035 (range 0.54–0.68). In the group of the youngest children (group 1), the RIs were significantly higher (p < 0.01) in comparison with the other group of children and the adult group. No statistically significant difference was observed between the group of children 6–16 years of age and the adult group. RI < 0.70 was noted in all children above 6 years of age; however, in younger children, RI ≥ 0.70 was observed in 72.5 % (37 of 51) of children. Resistance index in early childhood was considerably higher as compared with older children and the adult population: Apparently the RI value drops to adult level at approximately 6 years of age. The utilization of a threshold RI value of 0.70 for the increased renal vascular resistance in adults can also be applied to children over 6 years of age.

Quantifying the increase in average human heterozygosity due to urbanisation

The human population is undergoing a major transition from a historical metapopulation structure of relatively isolated small communities to an outbred structure. This process is predicted to increase average individual genome-wide heterozygosity (h) and could have effects on health. We attempted to quantify this increase in mean h. We initially sampled 1001 examinees from a metapopulation of nine isolated villages on five Dalmatian islands (Croatia). Village populations had high levels of genetic differentiation, endogamy and consanguinity. We then selected 166 individuals with highly specific personal genetic histories to form six subsamples, which could be ranked a priori by their predicted level of outbreeding. The measure h was then estimated in the 166 examinees by genotyping 1184 STR/indel markers and using two different computation methods. Compared to the value of mean h in the least outbred sample, values of h in the remaining samples increased successively with predicted outbreeding by 0.023, 0.038, 0.058, 0.067 and 0.079 (P<0.0001), where these values are measured on the same scale as the inbreeding coefficient (but opposite sign). We have shown that urbanisation was associated with an average increase in h of up to 0.08–0.10 in this Croatian metapopulation, regardless of the method used. Similar levels of differentiation have been described in many populations. Therefore, changes in the level of heterozygosity across the genome of this magnitude may be common during isolate break-up in humans and could have significant health effects through the established genetic mechanism of hybrid vigour/heterosis.

Haematological malignancies in childhood in Croatia: Investigating the theories of depleted uranium, chemical plant damage and 'population mixing'

Some of potential causes proposed to explain the reported increase of haematological malignancies in childhood during or after the war period in several countries include depleted uranium, chemical pollution and population mixing theory. The aim of this study was to define the population of Croatian children aged 0–14 years who were potentially exposed to each of those risks during the war and to investigate any possible association between the exposure and the incidence of haematological malignancies. The authors analyzed the data reported by the Cancer Registry of Croatia during the pre-war period (1986–1990), war period (1991–1995) and post-war period (1996–1999). In the group of 10 counties potentially exposed to depleted uranium and two counties where chemical war damage occurred, no significant difference in incidence of the studied haematological malignancies was noted in comparison to pre-war period. The incidence of lymphatic leukaemia significantly increased in four counties where population mixing had occurred during the war period, supporting the ‘mixing theory’. In those counties, the incidence of Hodgkins lymphoma decreased during and after the war. In Croatia as a whole, decreases in incidence of myeloid leukaemias during war and non-Hodgkin lymphoma after the war were noted.

Immunohistochemical analysis of NOTCH1 and JAGGED1 expression in multiple myeloma and monoclonal gammopathy of undetermined significance.

Notch signaling is implicated in the pathogenesis of multiple myeloma expressing high level of active Notch proteins NOTCH1 and JAGGED1 in tumor plasma cells. We investigated expression of NOTCH1 and JAGGED1 in bone marrow trephine biopsies of 80 newly diagnosed multiple myeloma and 20 monoclonal gammopathy of undetermined significance patients using immunohistochemical methods. The number of positive tumor cells was counted per 1000 tumor cells and the intensity of staining was assessed semi quantitatively. Multiple myelomas expressed NOTCH1 in 92.31% (72/78) and JAGGED1 in 92.21% (71/77) cases. NOTCH1 staining was strong in the majority of cases (59.7%), whereas JAGGED1 was predominately weak (67.6% of cases). In contrast, both markers were negative in all monoclonal gammopathy of undetermined significance cases. However, upon progression of disease from monoclonal gammopathy of undetermined significance to multiple myeloma (seen in 4 patients), analysis of the subsequent bone marrow biopsy showed weak expression of both markers in tumorous plasma cells. Immunohistochemistry results were compared with the pattern of bone marrow infiltration, plasma cell differentiation, and the presence of t(11;14)(q13,q32), t(14;16)(q32;q23),and t(4;14)(p16.3;q23) and overall survival in multiple myeloma patients. A significant correlation was found between strong NOTCH1 staining in multiple myeloma plasma cells and the diffuse type of bone marrow infiltration (P = .002) and an immature morphologic type of plasma cells (P = .043). After a median follow-up of 20.3 months, in multiple myeloma patients no difference in overall survival between NOTCH1 (P = .484) and JAGGED1 (P = .822) positive and negative cases were found. In conclusion, our results indicate importance of NOTCH1 and JAGGED1 expression in plasma cell neoplasia and a possible diagnostic value of their immunohistochemical evaluation of bone marrow infiltrates for multiple myeloma.

Correlation between the minimal cross-sectional area of the nasal cavity and body surface area: preliminary results in normal patients.

Nasal symptoms often are inconsistent with rhinoscopic findings. However, the proper diagnosis and treatment of nasal pathology requires an objective evaluation of the narrow segments of the anterior part of the nasal cavities (minimal cross-sectional area [MCSA]). The problem is that the value of MCSA is not a unique parameter for the entire population, but rather it is a distinctive value for particular subject (or smaller groups of subjects). Consequently, there is a need for MCSA values to be standardized in a simple way that facilitates the comparison of results and the selection of our treatment regimens. We examined a group of 157 healthy subjects with normal nasal function. A statistically significant correlation was found between the body surface area and MCSA at the level of the nasal isthmus and the head of the inferior turbinate. The age of subjects was not found a statistically significant predictor for the value of MCSA. The results show that the expected value of MCSA can be calculated for every subject based on anthropometric data of height and weight.

Haloperidol-stomach lesions attenuation by pentadecapeptide BPC 157, omeprazole, bromocriptine, but not atropine, lansoprazole, pantoprazole, ranitidine, cimetidine and misoprostol in mice.

The focus was on haloperidol (central dopamine antagonist)-stomach lesion, a longly described suitable counterpart of dopamine blocker cysteamine-duodenal lesion. In this, the contribution of blockade of central/peripheral dopamine receptors and prostaglandins synthesis, along with influence of antiulcer agents was evaluated in mice. Male NMRI Hannnover mice were sacrificed 24 h after haloperidol (25 mg/kg b.w. i.p., given alone or with saline (haloperidol+saline) (i) or in combination (ii,iii)). Supporting central dopamine predominance for haloperidol stomach lesion induction, co-administration of peripheral dopamine receptor antagonist domperidone (5 mg/kg i.p.) (haloperidol+ domperidone) (ii), or prostaglandin synthesis inhibitor indomethacin (10 mg/kg s.c.) (haloperidol+ indomethacin) (iii) did not aggravate this lesion. (i) In haloperidol+saline challenged mice the lesions were inhibited by co-administration (/kg i.p.) of a gastric pentadecapeptide BPC 157, GlyGluProProProGlyLysProAlaAspAspAlaGlyLeuVal, M.W. 1419 (10 microg, 10 ng, 10 pg, but not 1 pg, 100 fg, 10 fg), bromocriptine (10 mg), omeprazole (10 mg, 100 mg, but not 1 mg). Atropine (10, 100, 200 mg), pirenzepine (10, 100, 200 mg), misoprostol (10, 100, 200 microg), pantoprazole (1, 10, 100 mg), lansoprazole (0.1, 1, 10 mg), cimetidine (10, 100, 200 mg) and ranitidine (10, 100, 200 mg) were not effective. (ii) Dopamine peripheral blockade influence: in haloperidol+domperidone mice, previously effective bromocriptine, pentadecapeptide BPC 157 (10 microg) or omeprazole (10 mg) did not attenuate stomach lesions. (iii) Prostaglandins synthesis blockade effect: in haloperidol+indomethacin mice, previously effective agents, bromocriptine or omeprazole were not active, while BPC 157 effect was only lessened.

The protective effect of zinc sulphate pretreatment against duodenal ulcers in the rat.

Exogenously administered zinc compounds have been shown to possess antiulcer activity in the development of gastric lesions. The aim of this study was to investigate the effects of zinc sulphate pretreatment of rats on cysteamine-induced duodenal ulcers and to correlate them with changes in zinc serum and tissue levels. Atomic absorption spectrophotometry was used to determine zinc serum and tissue concentrations in all animal groups. Cysteamine produced marked duodenal ulceration in control animals 24 h after application, with an increase in endogenous zinc tissue concentrations and a marked decrease in serum concentrations. Zinc sulphate (20, 40 or 80 mg kg-1) applied per os one hour prior to cysteamine application inhibited the development of duodenal lesions in a dose-related manner. The application of zinc sulphate in a single intraperitoneal (i.p.) application (80 mg kg-1) did not, however, prevent the formation of duodenal lesions. In order to assess zinc absorption from the gastrointestinal tract, one group of rats received a single oral dose of zinc sulphate (80 mg kg) without cysteamine application. The observations of this study seem to indicate that zinc plays an important cytoprotective role in duodenal ulcer disease.