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)     

Human herpesvirus 6 variant a infects human term syncytiotrophoblasts in vitro and induces replication of human immunodeficiency virus type 1 in dually infected cells

Human herpesvirus 6 (HHV-6) and human immunodeficiency virus type 1 (HIV-1) may interact during transplacental transmission of HIV-1. The placental syncytiotrophoblast layer serves as the first line of defense of the fetus against viruses. Patterns of replication of HHV-6 variant A (HHV-6A) and HIV-1 were analyzed in singly and dually infected human term syncytiotrophoblast cells cultured in vitro. For this purpose, the GS strain of HHV-6A and the Ba-L and IIIB strains of HIV-1 were used. HHV-6A replication was restricted at the level of early gene products in singly infected syncytiotrophoblasts, whereas no viral protein expression was found in cells infected with HIV-1 alone. Coinfection of syncytiotrophoblast cells with HHV-6A and HIV-1 resulted in production of infectious HIV-1. In contrast, no enhancement of HHV-6A expression was observed in cell cultures infected with both viruses. Uninfected syncytiotrophoblast cells were found to express CXCR4 and CCR3 but not CD4 or CCR5 receptors. Infection of syncytiotrophoblasts with HHV-6A did not induce CD4 expression and had no influence on chemokine receptor expression. Activation of HIV-1 from latency in coinfected cells was mediated by the immediate-early (IE)-A and IE-B gene products of HHV-6A. Open reading frames U86 and U89 of the IE-A region were able to activate HIV-1 replication in a synergistic manner. The data suggest that in vivo double infection of syncytiotrophoblast cells with HHV-6A and HIV-1 could contribute to the transplacental transmission of HIV-1 but not HHV-6A.     

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.     

Prevalence of human papillomaviruses in the healthy oral mucosa of women with high‐grade squamous intra‐epithelial lesion and of their partners as compared to healthy controls

Oral human papillomavirus (HPV) carriage rates were investigated in relation to genital HPV carriage in women with HPV‐associated cervical lesions and male partner of such women, including several couples, in comparison with healthy individuals. Buccal and lingual mucosa of 60 males and 149 females with healthy oral mucosa and without known genital lesion, genital and oral mucosa of further 40 females with cervical high‐grade squamous intraepithelial lesion (HSIL) and 34 male sexual partners of women with HSIL (including 20 couples) were sampled. HPV DNA was detected using MY/GP PCR. Genotype was determined by sequencing or restriction fragment length polymorphism. Virus copy numbers were determined by real‐time PCR. Overall, oral HPV carriage rate was 5.7% (12/209) in healthy individuals; average copy number was 5.8 × 10² copies/1 μg DNA; male and female rates were comparable. Oral carriage in women with HSIL was significantly higher, 20.0% (8/40, P = 0.003); males with partners with HSIL showed a carriage rate of 17.6% (6/34), copy numbers were similar to the healthy controls. In contrast, genital carriage rate (52.9%, 18/34 vs. 82.5%, 33/40; P = 0.006) and average copy number were lower in males (5.0 × 10⁵ vs. 7.8 × 10⁵ copies/1 μg DNA; P = 0.01). Oral copy numbers in these groups and in healthy individuals were comparable. High‐risk genotypes were dominant; couples usually had the same genotype in the genital sample. In conclusion, genital HPV carriage is a risk factor of oral carriage for the individual or for the sexual partner, but alone is not sufficient to produce an oral HPV infection in most cases.