Long-term follow-up of patients with persistent/recurrent,isolated haematuria: A Hungarian multicentre study

A retrospective multicentre study of 341 children with persistent/recurrent, isolated haematuria is described. The haematuria was isolated for at least 6 months at the beginning of observation. The duration of follow-up was 2–5 years in 201, 5–10 years in 119, 10–15 years in 19, and over 15 years in 2 cases. Of these patients 47.8% became symptom-free. In 18.4% the haematuria remained isolated; in 13.8% it was combined with proteinuria over 250 mg/day more than 2 years later. The occurrence of associated proteinuria increased progressively with time. It was 8.6% between the 3rd and 5th years, and 37.0% after the 5th year. Renal biopsy was performed because of the symptoms of glomerular disease in 47 cases at an average time of 12 months following the appearance of proteinuria. Proteinuria appeared after a 2–5, 5–10, 10–15 and more than 15 years follow-up period in 16, 23, 6, and 2 patients respectively; 14 of them had Alport's nephropathy. The percentage of more serious azotaemia was 1.7 (creatinine clearance: 10–50 ml/min per 1.73 m²) and 0.3 (creatinine clearance: < 10 ml/min per 1.73 m²). Mortality was 0.58%. Most of the patients who developed severe azotaemia had persistent microscopic haematuria at the beginning. The prevalence of hypertension was only 1.2%. The time of its appearance was above 5 years in 2 and below 5 years in 2 cases. All these patients had chronic glomerulonephritis. The haematuria was associated with hypercalciuria in 19.9%. In 14.3% of the overall group of patients urolithiasis developed 2–15 years after onset. All of these had hypercalciuria. Our findings suggest that symptoms of isolated haematuria may last for a longterm period and need systematic control. When proteinuria and/or hypertension is associated with haematuria a worse prognosis can be expected.Participating paediatric hospitals and university departments: Second Department of Paediatrics, I. Semmelweis Medical University of Budapest (M. Visy); Department of Paediatrics, University Medical School of Pécs (V. Jászai); Department of Paediatrics, A. Szent-Györgyi Medical University of Szeged (I. Haszon, S. Túri); County Children's Hospital, Miskolc (Á. Vissy); P. Heim Children's Hospital, Budapest (Z. Czirbesz); County Children's Hospital, Györ (Zs. Szelid); Buda-Children's Hospital, Budapest (I. Ferkis); I. Apáthy Hospital, Budapest (J. Kisbán); János Hospital, Budapest (I. Marosváry); Hospital of Hungarian State Railway, Budapest (J. Fehér); L. Madarász Hospital, Budapest (F. Kalmár); South Pest Hospital, Budapest (G. Halász); County Children's Hospital, Pécs (E. Kolman); County Children's Hospital, Gyula (P. Sipos); County Children's Hospital, Szolnok (I. Jaksics); County Children's Hospital, Debrecen (Á. Miskolczi); County Children's Hospital, Tatabánya (I. Kiss); County Children's Hospital, Eger (M. Frank, E. Ladányi); County Children's Hospital, Nyíregyháza (E. Bujdosó); County Children's Hospital, Szombathely (M. Andics); Kerepestarcsa Hospital, Budapest (M. Marcell); Komárom Hospital, Komárom (J. Kecskés)     

Differential sensitivity to Arg side chain modification of IL-1β binding to type I and type II receptors

The central role of interleukin-1 (IL-1) in several disease processes, including fever and inflammation, makes the characterization of ligand-receptor interaction of prime importance.The role of arginine (Arg) side chains of hr-IL-1 in receptor recognition was studied by the modification of Arg residues with the specific reagent 1,2-cyclohexanedione. It was found that chemical modification of Arg residues decreased the binding potential of IL-1 to type I receptor dramatically (by 230-fold) while the affinity to type II receptor was reduced only moderately (by 10-fold), with an insignificant reduction of the dissociation rate.These studies suggest that intact Arg side chains of IL-1 may be necessary for high affinity binding to type I IL-1 receptor, but have less importance for the interaction of IL-1 with type II IL-1 receptor.This observation may be useful in the study of type II IL-1 receptor-mediated biological responses and design of receptor-subtype specific ligands as well.     

Effects of idebenone on the intracellular water and dry mass content as well as of the intracellular monovalent ion concentrations of brain cortical cells of SHRsp rats as revealed by X-ray microanalysis

The cerebral cortex of ten male SHRsp rats kept in conventional housing conditions were studied. Starting from the age of 3 months, five animals received placebo (5% gum arabic solution) and five other rats received 50 mg/kg idebenone suspended in the gum arabic, through a gastric tube for 4 weeks (except Sundays). During the last 2 weeks of treatment, 0.9% NaCl was added to the drinking water. Several completely untreated SHRsp rats of various ages were also involved in these studies. Blood pressure was measured weekly on the tail by means of an appropriate instrument. Serious hypertension was observed already by the end of the second week of treatment, displaying values of 250-260 mm Hg and increased further by about 20 mm Hg during the last 2 weeks of treatment. Intracellular water, dry mass and monovalent electrolyte concentrations were measured by means of a bulk specimen X-ray microanalytic method. The brain cells contained 77+/-1% water and 23% dry mass by weight in both placebo and verum-treated groups. The intracellular Na(+) content of all the male SHRsp rats was found to be significantly higher (180-200%) in the brain cells, whereas K(+) content increased only moderately, when expressed as percent of the intracellular dry mass. Idebenone treatment, however, lowered the intracellular Na(+) content of the brain cells to a significant extent (about 20%), i.e., it improved the Na(+) tolerance of the SHRsp rats, but did not alter the blood pressure.     

Total sleep deprivation decreases saliva ghrelin levels in adolescents

Ghrelin, a regulator of food intake and energy expenditure, has been shown to be associated with insufficient sleep. The goal of the present study was to investigate the effect of a single night of total sleep deprivation on fasting saliva ghrelin and on nocturnal variation of saliva ghrelin concentration. A further aim of the study was to investigate the influence of body mass index on changes in saliva ghrelin levels. Altogether 35 adolescents (18 boys; age: 13.8 ± 1.14 years) were studied on two subsequent days (sleep and total sleep deprivation). Saliva samples were collected during the two experimental nights at 21:00 hours, 01:00 hours and 06:00 hours. Total-ghrelin concentration showed a continuous increase from the evening until 06:00 hours. This increase was blunted significantly (p = 0.003) by total sleep deprivation. Total-ghrelin level was significantly lower (p = 0.02) during total sleep deprivation at 06:00 hours (median 403.6 pg ml⁻¹; 95% confidence interval: 343.1–468.9 pg ml⁻¹) as compared with values during the sleep condition (median 471.2 pg ml⁻¹; 95% confidence interval: 205.4–1578.7 pg ml⁻¹). Acyl-ghrelin levels did not present any change at the three time points, and were not affected by total sleep deprivation. Stratifying the study population according to body mass index (normal weight and overweight/obese groups), the blunting effect of total sleep deprivation was more pronounced in the obese/overweight group (sleep: median 428.2 pg ml⁻¹; 95% confidence interval: 331.3–606.9 pg ml⁻¹ versus total sleep deprivation: median 333.1 pg ml⁻¹; 95% confidence interval: 261.5–412.9 pg ml⁻¹; p = 0.0479). Saliva total-ghrelin concentrations gradually increased during the night, and total sleep deprivation significantly blunted this increase. This blunting effect was mainly observed in subjects with overweight/obesity. The physiological and clinical implications of the present observation are to be clarified by further studies.     

Experiences in the perinatal management of congenital diaphragmatic hernia during the last 15 years in a tertiary referral institute

OBJECTIVE: Review of cases of perinatally diagnosed congenital diaphragmatic hernias with special regard to time of diagnosis, organs herniated into the thorax, associated malformations, and outcomes. METHODS: We analyzed the data of 106 cases between July 1, 1990, and June 30, 2005. The observation period was analyzed in two parts. RESULTS: Prenatal ultrasound was performed in 89.6% (95/106) of the cases. 51.7% (46/89) of the pre- and postnatally verified congenital diaphragmatic hernia cases were diagnosed before the 24th week of gestation. 11% (11/100) of the hernias were identified postnatally. 71% (71/100) of the cases were associated with other malformations. The hernia was on the left side in 86% (86/100) and bilateral in 5% (5/100) of the cases. Between 1990 and 1997, the proportion of right-sided hernias was 4.3% (2/46), while during the second period it was 13% (7/54). 27.5% (14/51) of the newborns survived the perinatal period. The survival rate of the newborns delivered by caesarean section was three times higher than that of infants delivered vaginally. In the latter group, the rate of premature deliveries was considerably higher. The pregnancy was terminated in 45% (40/89) of the cases. 15% (6/40) of the terminated cases were isolated. Intrauterine or intrapartum deaths occurred in 5.6% (5/89) of the prenatally diagnosed cases. Simultaneous thoracic herniation of liver, spleen, or stomach decreased the survival rate. In these cases, the discharge rate was between 6 and 22%. CONCLUSIONS: According to the analysis of 15-year data, the herniated organs, multiple malformations, as well as the mode of delivery influence the survival in a large number of cases. Early diagnosis predicts a large hernia, a higher malformation rate, and a less favourable prognosis.     

In vitro studies on the OH* and O2(-*) free radical scavenger properties of idebenone in chemical systems

OH(*) free radicals were generated by Fenton reaction in the presence of bovine serum albumin (BSA). The decreasing water-solubility of BSA with increasing Fe(2+) concentrations of the system is a sensitive indicator of the cross-linking effects of the OH(*) free radicals. Idebenone (oxidized form) was solubilized for this experiment in DMSO and added to the system in final concentrations of 0.01 or 0.1%. Neither of these concentrations displayed any protective effect against the insolubilization of BSA. Therefore, oxidized idebenone has to be considered as a substance which reacts with OH(*) free radicals slower than the BSA itself, i.e., its oxidized form is not an efficient scavenger of this type of free radicals under the given circumstances. The ability of idebenone to scavenge superoxide radicals was tested in ( [Formula: see text] ) the pyrogallol system; and (ii) the xanthine-xanthine oxidase-nitro blue tetrazolium (XXO-NBT) system. Idebenone did not show any O(2)(-*) radical scavenging ability as revealed by these two in vitro methods, in the concentration ranges studied (up to 75 or 220 microg/ml, respectively). On the contrary, an increasing O(2)(-*) radical generation was observed with increasing concentrations of the drug in both test systems used. The possible biological significance of these observations is discussed in the light of other results like ESR spin trapping and measurements of superoxide dismutase (SOD) activity in various tissues.     

Effects of idebenone on the composition of brain synaptosomal membranes of rats

Male and female CFY rats of 21 months of age were treated per os by 50 mg idebenone per kg body weight/day for 5 weeks while the controls received only the solvent. Synaptosomal fractions of the brain cortex were prepared and tested as follows: (1) Labeling by 1,6-diphenyl-1,3,5-hexatriene (DPH) and the fluorescence anisotropy (r) of this label was measured at various optical densities. The average values of r extrapolated to zero optical density were 0.1831 +/- 0.0025 in the control group and 0.1854 +/- 0.0019 in the idebenone-treated animals; the difference is statistically not significant. (2) Labeling with 3 different spin labels (5-NS, N-oxyl-4', 4'-dimethyloxazolidine derivative of stearic acid with the doxyl groups in C-5; 16-NS, the same derivative of stearic acid with the doxyl groups in C-16 position; and MAL-SL, 3-maleimido-2,2,5,5-tetramethyl-1-pyrrolidinyloxy). Routine ESR spectroscopy was applied to characterize the molecular motion of these labels in their microenvironment. These spin labels did not display any significant change in their environment under the influence of idebenone treatment. (3) Protein contents of the samples were measured and samples of synaptosomes containing 3.5 mg protein were dissolved in 1% Na(Dod)SO4 + 1% beta-mercaptoethanol and boiled for 2 min, then elaborated by gel filtration chromatography on a column of sepharose 2B. The elution fluid was collected in separate fractions of 1 ml volume and their protein content was estimated by measuring the absorbance at 280 nm. Distribution histogram of the protein fractions revealed no difference between the placebo- and verum-treated animals. These studies demonstrate that in vivo application of idebenone does not alter the composition of synaptosomal membranes.     

Microfluorimetric and X-ray microanalytic studies on the DNA content and Na+:K+ ratios of the cell nucleic in various types of thyroid tumors

Summary Parallel studies were performed using microfluorimetric DNA determination and X-ray microanalysis on the same thyroid biopsy material to compare the intranuclear DNA and monovalent electrolyte contents (Na⁺, K⁺, Cl^–). Samples were taken from apparently healthy, adenomatous, and cancerous parts of human thyroid glands removed surgically. The time interval was less than 1 min. The tissues were classified by the pathologist into four main classes: 1) Normal thyroid tissue; 2) benign adenomas; 3) differentiated (follicular and papillary) carcinomas; and 4) anaplastic cancers. The results revealed that the level of aneuploidization showed an increase parallel with the malignancy of the studied tumor. At the same time, a similar tendency was found in the average values of the intranuclear Na⁺:K⁺ ratios. The results obtained in this way confirm the possibility that the electric properties of the cell membrane, that is the sustained membrane depolarization, may have a role in the regulation of DNA synthesis and in mitogenesis. These results may offer new diagnostic and/or therapeutic possibilities.