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Urinary excretion of endothelin-1 (ET-1) and plasma ET-1 were measured in 21 children with absorptive idiopathic hypercalciuria (AIH) and 22 controls. The absorptive type of idiopathic hypercalciuria was determined by a calcium loading test. Daily urinary excretion of ET-1 and urinary ET-1/creatinine ratio were significantly increased ( P=0.005 and P=0.007, respectively) in patients with AIH (9274+/-6444 pg/24 h and 14.04+/-9.52 pg/mg, respectively) compared with controls (4699+/-2120 pg/24 h and 7.36+/-4.71 pg/mg, respectively). Plasma ET-1 levels were significantly lower in patients with AIH (0.84+/-0.64 pg/ml) than in controls (1.54+/-0.54 pg/ml, P=0.0001). In conclusion, patients with AIH had increased urinary ET-1 excretion and decreased plasma ET-1 levels. This is most likely due to the decreased reabsorption of ET-1 in the renal tubule and increased renal production.

We investigated whether mesenteric lymphadenopathy could be a cause of abdominal pain in children with lobar or segmental pneumonia. The study population consisted of 1)119 consecutive children with lobar pneumonia, older than 4 years of age, and 2) 31 healthy controls. Demographic, clinical, inflammatory, and radiographic data were recorded in all patients. All study subjects underwent abdominal ultrasound, focusing on the identification of mesenteric lymphadenopathy. One month later, a follow-up ultrasound was performed in patients with enlarged mesenteric lymph nodes at the initial examination. Forty patients complaining of abdominal pain were included in group 1, while the remaining 79 were in group 2. The two groups of patients did not significantly differ regarding their demographic, clinical (other than abdominal pain), and radiographic indices. In contrast, enlarged mesenteric lymph nodes with a sagittal diameter of at least 10 mm were identified significantly more commonly in the children of group 1 (P = 0.001). The association of enlarged lymph nodes with the presence of abdominal pain remained significant when the data were analyzed through multiple regression analysis (odds raio, 1.47; 95% confidence interval, 3-44). Enlarged mesenteric lymph nodes were found in a significantly lower ratio of healthy controls (3/31) compared to that observed in group 1 (P = 0.003). In all patients who were followed up, mesenteric lymph nodes had either decreased or were not detectable. Our findings indicate that mesenteric lymphadenopathy might be considered as a mechanism responsible for the development of abdominal pain in a relatively high percentage of children with pneumonia., (Copyright 2003 Wiley-Liss, Inc.)

Methylprednisolone produced a dose dependant significant increase in glomerular filtration rate, a significant decrease in sodium excretion, and a significant increase in urinary alkaline phosphatase activity in guinea pigs. The renal histology in groups with 4, 5 and 6 doses revealed mild degenerative changes in the tubular epithelial cells. The results suggest the beneficial effects of methylprednisolone pulse therapy on renal function mainly by increasing glomerular filtration rate with only minimal side effects.

This study aimed to investigate whether carbamazepine, sodium valproate or phenobarbital as monotherapy in ambulatory epileptic children with adequate sun exposure have some effect on their bone metabolism based on the determination of total serum alkaline phosphatase (AP) levels and its bone isoenzyme activity. Blood samples were obtained from 118 epileptic children (37 on carbamazepine, 47 on sodium valproate and 34 on phenobarbital) and from corresponding healthy controls matched for age, gender and anthropometric parameters. AP and its liver, bone and intestinal isoenzyme levels, other common biochemical markers of bone and liver metabolism and drug levels were measured in the study participants. Patients on carbamazepine or phenobarbital had significantly elevated AP levels accompanied by increased bone and liver isoenzyme activity compared to controls. An increase of bone AP isoenzyme values, correlated with the duration of treatment ( r= 0.49, P= 0.002), was found in children on sodium valproate without, however, a concomitant significant elevation of total AP values. We conclude that children who receive antiepileptic drugs as monotherapy, even when residing in a Mediterranean country with adequate sunlight, may have their bone metabolism affected as indicated by the elevated levels of bone AP isoenzyme. This isoenzyme, but not total AP values, could therefore be used as a marker for the selection of patients who would be benefited by a thorough evaluation of their bone metabolism profile.

Cell adhesion molecules play a rather important role in the development of atherosclerosis mediating the attachment of monocytes to the endothelium. It has also been well established that hyperlipidemia is a risk factor for atherosclerosis from childhood. The aim of this study was to investigate whether the soluble adhesion molecules correlate with the circulating lipid levels in children. The study population consisted of 107 children (64 boys, 43 girls) aged 6-13 y. Parental history of cardiovascular disease, age, gender, and anthropometric parameters were recorded in all children. Blood samples were obtained from every child following a 12-hour fasting period. Serum triglycerides, total cholesterol, and its fractions as well as plasma levels of P and E selectins and adhesion molecules sVCAM-1 and sICAM-1 were determined. After controlling for age and body mass index, both sVCAM-1 and sP-selectin levels were inversely associated with HDL values (r = -0.33, p = 0.005 and r = -0.39, p = 0.001, respectively). A significant positive correlation was found between sVCAM-1 and triglycerides (r = 0.48, p < 0.001). An increment of 10 mg/dL of HDL corresponds to about 50% reduction of the odds for endothelial dysfunction whereas an increment of 10 mg/dL of triglyceride levels indicates a more than 3-fold excess risk, using either sP-selectin or sVCAM-1 levels as a surrogate for the determination of endothelial dysfunction. We suggest that HDL-C and triglycerides correlate in a biologically plausible way with soluble adhesion molecules, which therefore could be considered as useful indicators of the process of preclinical atherosclerosis even from childhood.

Catenins (alpha-, beta-, gamma-catenin, p120(ctn)) are cytoplasmic proteins initially identified in a complex with E-cadherin (ECD). The latter belongs to a superfamily of transmembrane glycoproteins important for cell adhesion in normal and disease states. Catenins and p120(ctn), in particular, are substrates for growth factor receptor tyrosine kinases. Cell adhesive mechanisms have an impact on cell migration and proliferation and thus are potentially involved in the pathogenesis of glomerulonephritides (GNs). Using appropriate monoclonal antibodies, we investigated the immunohistochemical expression of ECD, alpha-catenin, beta-catenin, gamma-catenin, and p120(ctn) in renal biopsy specimens from 95 patients with primary GN (n = 51) and secondary lupus-associated GN (n = 44). Examined cases were divided into two groups (proliferative [n = 35] and nonproliferative [n = 60] GNs). Among examined molecules, p120(ctn), beta-catenin, and gamma-catenin were expressed more frequently in glomerular epithelial cells, mainly in parietal epithelium (76%, 48%, and 40%, respectively). p120(ctn) and gamma-catenin epithelial expression appeared to be linked closely with proliferative lupus-associated GNs (P = 0.050 and P = 0.029, respectively). Mainly in lupus GNs, with regard to cellular crescents and epithelial cells around microadhesions to Bowman's capsule, p120(ctn) (63% and 73%, respectively), beta-catenin (72% and 75%), and gamma-catenin (75% and 64%) showed the greatest frequencies of positive detection. Mesangial cells were positive only occasionally for the examined molecules. In proliferative lupus GNs, expression of beta-catenin in mesangial cells tended to be prominent (P = 0.066). ECD and alpha-catenin were not expressed in cellular crescents or microadhesions, whereas only ECD was barely detectable in glomerular epithelial cells. In conclusion, expression of beta-catenin, gamma-catenin, and p120(ctn) is focused on glomerular epithelium, as well as on such lesions deriving from it as cellular crescents. This expression probably is linked with epithelial cells' responses to various mitogens, such as growth factors., (Copyright 2002 by the National Kidney Foundation, Inc.)

The association of leptin with body fat concentration is well established. There is also experimental evidence of a direct effect of leptin on lipid metabolism. The aim of this study was to evaluate whether leptin levels are related to the corresponding serum lipid levels independently of body fat mass. The study population consisted of 294 phenotypically healthy school children aged 6 to 12 years. Age, sex, body weight, height, Tanner stage, and triceps skinfold thickness were recorded for all participating subjects. A blood sample was drawn in the morning after a 12-hour fast, and serum total, high-density lipoprotein (HDL), and low-density lipoprotein cholesterol; triglyceride; and leptin levels were determined. Multiple regression analysis showed that triglyceride values were positively correlated with the ln(log(e))-transformed leptin levels (beta =.01, P <.001), whereas HDL levels were inversely associated with lnleptin values (beta = -.06, P =.05) after controlling for age, sex, Tanner stage, and body mass index when each of the lipid parameters was tested separately in the regression model. However, the introduction of both triglycerides and HDL values in the same model eliminated the significance of association of HDL with lnleptin, and the positive relationship of triglycerides with lnleptin remained significant. Our results indicate that triglycerides are independently associated with leptin levels after controlling for any known confounder., (Copyright 2001 by W.B. Saunders Company)

Background: The aim of the present study was to investigate to what extent IgM nephropathy in children with minimal change nephrotic syndrome (MCNS) and diffuse mesangial hypercellularity (DMH) evolves to focal segmental glomerulosclerosis (FSGS)., Methods: Tissues from renal biopsies were examined by light microscopy (LM), immunofluorescence (IF) and, in four cases, by electron microscopy (EM). From a total of 352 nephrotic children, 121 had renal biopsy results as steroid dependent or resistant. A diagnostic renal biopsy was also performed in 331 children with non-nephrotic proteinuria and/or hematuria. A second renal biopsy was performed in 16 children whose renal function was impaired during the follow up. The clinical course of IgM-positive children was compared with that of IgM-negative children., Results: Of the 121 nephrotic children with renal biopsy, 85 were MCNS. Twenty were IF positive mainly for IgM, six of whom (30%) presented evolution to FSGS, while of the remaining 65 IF-negative children, only three (4.6%) presented evolution to FSGS. Of the total 331 children with non-nephrotic proteinuria and/or hematuria, 139 were diagnosed as IgA--IgG nephropathy, 44 had positive IF for IgM and 148 were IF negative. Of the 44 children IF positive for IgM, seven (15.9%) presented evolution to FSGS, while none of the 148 IF-negative children presented evolution to FSGS. The follow-up time for all children ranged from 1 to 14 years., Conclusions: Of IgM nephropathy patients with MCNS and DMH, a significant percentage develop impaired renal function, due to the evolution of FSGS, as revealed by repeat biopsy during long-term follow up.

Poly(inosinic) and poly(cytidylic) acids (Poly I:Poly C) have been used to induce the production of endogenous interferon or release preformed interferon in mammals. Interferon increases the resistance of the cells. Sixty guinea pigs were used to investigate whether Poly I:Poly C gave protection from gentamicin nephrotoxicity. The animals were divided into six equal groups. Group 1 were controls; group 2 received gentamicin intramuscularly; group 3 received gentamicin and 12 h later frusemide; group 4 received gentamicin and 12 h later 1-deamino-8-D-argine vasopressin (DDAVP) intramuscularly; group 5 received subcutaneously Poly I:Poly C; group 6 received Poly I:Poly C and 24 h later gentamicin. Frusemide in group 3 potentiated gentamicin nephrotoxicity while DDAVP in group 4 ameliorated gentamicin nephrotoxicity. Poly I:Poly C itself had no toxic effect on renal tissue, while Poly I:Poly C followed 24 h later by gentamicin indicated a protective effect from the gentamicin nephrotoxicity as the functional and histological investigations indicated.

Acute necrotizing encephalopathy following influenza A is frequently reported from Japan and Taiwan but is very rarely seen in Western countries. We describe a 10-year-old boy with acute necrotizing encephalopathy, who developed symmetrical thalamic and brain stem lesions seen on magnetic resonance imaging (MRI). Serological confirmation of influenza A was made 2 weeks after the onset of symptoms. The child made a full recovery. This case is interesting because of its rarity in European countries, the striking brain MRI findings and the good neurological outcome.

Previous investigators agree on the increased DNA synthesis and destruction of tissues caused by folic acid (FA) administered parenterally. This study aims to clarify whether DNA degradation due to the destruction of cells and nuclei precedes DNA synthesis following FA administration. Forty guinea pigs were divided into four groups: group 1, contained 10 controls; in group 2, ten animals received intraperitoneally 300 mg/kg of body wt FA; in group 3, ten animals received FA and 12 h later frusemide intramuscularly in a dose of 7 mg/kg body wt; and finally in group 4, ten animals received frusemide as in group 3. FA produced necrosis of the epithelial cells of the convoluted tubules as the detection of the beta-aminoisobutyric acid end product of DNA and thymine catabolism indicated. Frusemide administered in group 3 had a favourable effect on the acute renal failure induced by FA.

The cases of 2 siblings with cat scratch disease are described who presented with symptoms suggestive of acute febrile gastroenteritis. The first patient, a 7.5-y-old girl, developed mesenteric lymphadenitis, hepatosplenic granulomas and osteolytic bone lesions only late in the course of her protracted illness. Her 3-y-old brother had a shorter, self-limited illness without complications. Cat scratch disease is often unrecognized and the full spectrum of its clinical manifestations remains to be investigated.

A case of congenital nephrotic syndrome with diffuse mesangial sclerosis and bilateral cataract without other ocular anomalies is presented. This association, to our knowledge, has not been reported before.

Background: Bcl-2 oncogene was identified as a transcript associated with the t (14;18) and exhibits the unique functional role of blocking apoptosis. Apoptosis as a remodelling mechanism has been reported to embryonic and adult kidney. The aim of this study was to investigate the expression of bcl-2 protein in normal and diseased renal tissue and to define any correlation with the type of renal injury., Materials and Methods: Our material comprised of 10 normal adult kidneys, 31 renal allografts with acute (22) and chronic (9) rejection, and 70 renal biopsies with various types of primary (49) (31 proliferative and 18 non-proliferative) and secondary (21) glomerulonephritis. The immunohistochemical strept.ABC method was performed on paraffin sections for the detection of bcl-2 protein with a monoclonal antibody after microwave pretreatment., Results: Bcl-2 protein was detected in all the cases of normal and diseased renal tissue, showing an analogous expression. The antigen was expressed in a few parietal epithelial cells, and in the majority of distal and collecting tubular epithelial cells, but not in the glomerular capillary tuft. No difference was found in bcl-2 expression between cases of proliferative and non-proliferative glomerulonephritis as a whole, or between primary and secondary glomerulonephritis. Bcl-2 expression in acute and chronic rejection demonstrated a similar cytoarchitectural expression to the one observed in normal kidneys and glomerulonephritis. Bcl-2 was detected in podocytes near intraglomerular fibrotic lesions and in epithelial cells of early adhesions and cellular crescents, wherever observed in cases of glomerulonephritis. However, bcl-2 expression in proximal tubular epithelial cells was significantly higher in cases of proliferative glomerulonephritis than in non-proliferative glomerulonephritis (P<0.01), while bcl-2 expression in parietal epithelial cells in cases of chronic rejection was higher than in cases of acute rejection (P<0.08)., Conclusions: The absence of bcl-2 expression in normal and diseased glomeruli suggests and supports the reported notion that the mechanism of apoptosis may be available in the injured glomerulus. Moreover, bcl-2 expression in podocytes near intraglomerular fibrotic lesions and in epithelial cells of early adhesions and cellular crescents indicates the deregulation of apoptosis and its possible role in the progression of glomerular scarring. Key words: apoptosis; bcl-2 oncoprotein; glomerulonephritis; immunohistochemical; renal rejection.

The frequency of hepatitis B surface antigen (HBsAg) was studied in the sera of 622 patients with glomerulonephritis (GN). The prevalence of HBs-antigenemia was 2.8% (18/622; eleven adults and seven children); the difference from 2.6% in the general population of Central and Southern Greece was not statistically significant (chi 2 = 0.01; p > 0.50). Two of the 11 HBsAg-seropositive adult patients with GN suffered from IgA nephropathy, one from IgA and membranous glomerulonephritis (MGN), four from diffuse proliferative GN, two from membranous GN and one each from crescentic GN and focal segmental glomerulosclerosis. Five children out of 12 with membranous glomerulonephritis, one out of 24 with IgA nephropathy and one out of 16 with focal segmental glomerulosclerosis had HBs-antigenemia. The frequency of HBs-antigenemia in children with MGN was 41.7%, which is significantly higher than in children with other types of GN (0.9%). All seropositive patients were asymptomatic HBsAg carriers, while one seropositive HBsAg child with MGN suffered from chronic persistent hepatitis. HBsAg was detected by the immunoperoxidase-antiperoxidase (PAP) method in the glomeruli of only 3 children with MGN and HBs antigenemia, while HBcAg was not detected in any case. Our study suggests that in the Greek population there is no increased prevalence of HBs-antigenemia in patients with glomerulonephritis. Moreover, HBsAg was not found to contribute in the pathogenesis of GN in adults but it may be associated with the pathogenesis of membranous GN in children.

Epidermal growth factor (EGF), a polypeptide with a potent mitogen activity, and its receptor [EGFR] have been previously identified in the kidney, but their expression in normal and diseased kidneys has not been fully elucidated. In order to evaluate EGFR in various histological types of renal injury, EGFR expression was studied by the immunohistochemical avidin-biotin complex (ABC) method with a monoclonal antibody EGFR1 on paraffin sections from 10 normal kidneys, 56 renal biopsies with various types of glomerulonephritis (GN), and 20 renal grafts with rejection. EGFR expression was observed in (a) 3 of 10 (30%) normal kidneys, (b) 17 of 39 (43.6%) renal biopsies with various types of GN mainly in membranous GN (57%) and in focal segmental glomerulosclerosis (FSG) (62.5%), (c) 6 of 17 (35.3%) biopsies with various types of systemic lupus erythematosus GN, and (d) 12 of 20 (60%) renal grafts with acute (42.9%) and chronic (69.2%) rejection. EGFR was mainly localized to the epithelial cells of the distal and collecting tubules and extraglomelar vessels, while it was observed less frequently in parietal epithelial cells and along glomerular basement membranes. Notably EGFR was detected in the epithelial cells adjacent to adhesions with Bowman's capsule and in the connective tissue of fibrocellular crescents. In conclusion, EGFR expression was observed more frequently in diseased than in normal kidneys. The increased incidence of EGFR expression in FSG, in chronic rejection, in small adhesions with Bowman's capsule and fibrocellular crescents suggest that EGF/EGFR may be correlated with a disturbed extracellular matrix production resulting in formation of early sclerotic lesions.

Laminin (LAM) and fibronectin (FI) are regarded as major components of the glomerular extracellular matrix. The aim of this study was to define the distribution of LAM and FI in primary glomerulonephritis (GN) and GN of systemic lupus erythematosus (SLE) and to correlate the type of glomerular disorders with possible changes in the expression of these components. Normal portions of kidney tissue from 10 patients with renal tumors and sixty-six renal biopsies obtained from patients with GN were studied by the immunoperoxidase-antiperoxidase (PAP) method for the detection of LAM and FI. Twelve patients had membranous GN (MGN), 8 mesangiocapillary GN (MCGN), 21 mesangioproliferative GN (MPGN), including 11 cases of IgA nephropathy, 11 focal segmental glomerulosclerosis (FSGS) and 14 had SLE. In MGN, LAM was detected more intensely than FI along the glomerular basement membranes (GBM), in subepithelial GBM protrusions and in the newly-formed GBM. On the contrary, FI was intensely expressed in the mesangium. LAM and FI expression was pronounced in stages II and III of MGN. In MCGN, LAM and FI were diffusely expressed along the GBM and in the mesangium. The distribution of the two antigens in MPGN and FSGS was similar to that seen in normal glomeruli. However, the FI staining reaction was more intense in severe mesangioproliferative lesions, mainly observed in the cases of IgA-nephropathy. There were no differences in the distribution of LAM and FI between primary and SLE GN. The antigen staining pattern was pronounced in the membranous and mesangiocapillary lesions of SLE GN.(ABSTRACT TRUNCATED AT 250 WORDS)

A 5-year-old boy was found to have severe rickets in association with hyperpigmented, linear, verrucous, epidermal tumors, typical of the epidermal nevus syndrome. Normocalcemia (9.6 mg/dl), hypophosphatemia (2.0 mg/dl), elevated serum alkaline phosphatase concentration (313 IU), decreased renal tubular reabsorption of phosphorus (35%), radiologic evidence of rickets, and lack of response to usual therapeutic doses of vitamin D suggested hypophosphatemic vitamin D-resistant rickets. Therapy with vitamin D in doses to 750,000 IU and oral phosphate, 2.0 gm/day, failed to induce healing of the rickets. A subtotal parathyroidectomy performed when the patient was 9 years old was also without effect. When he was 12 years old several fibroangiomas on the face and left lower limb were excised. Within three months all biochemical abnormalities resolved and radiologic evidence of healing was observed. A portion of excised tissue was homogenized and injection of the supernate into a 6-week-old puppy induced excessive phosphaturia. The data suggest that the rickets was induced by a phosphaturic substance extractable from the tumors.

a 12 1/2-year-old boy with the rare autosomal recessive syndrome of osteoporosis with pseudoglioma is reported. Pertinent laboratory findings included osteoporotic lesions of the skeleton and calcification of the left lens. He was hypotonic and presented atrophic globes with opacities of the lenses. His psychomotor development was normal. Parental consanguinity is not excluded.

An 11-month-old boy had an episode of generalized convulsions followed by a right peripheral facial palsy, which resolved gradually within 3 weeks. Three months later he had another similar episode of convulsions followed by a left peripheral facial palsy. On both occasions it was found that he had polycythaemia. A careful physical examination discovered that the child had severe hypertension. Extensive laboratory investigations did not reveal a cause for his hypertension. Haematologic investigations showed that the polycythaemia was due to a contracted plasma volume as a result of the hypertension. The peripheral facial palsy most probably was due to a blood clot in the facial canal, below the origin of the nerve to m. stapedius, as audiograms were normal and lacrimation preserved. Control of the hypertension resulted in resolution of the facial palsy within 4 weeks and normal haematocrit readings within 6 weeks. It should be stressed that every patient with peripheral facial palsy should be examined for hypertension.

Two children presenting typical clinical features of the hemolytic-uremic syndrome had a positive direct Coombs test that remained positive throughout the illness. It is probable that an upper respiratory tract infection precipitated an antigen-antibody reaction that caused the autoimmune hemolytic anemia and immune-complex glomerulonephritis.

Fifteen patients, aged 8 to 17 years, were found to have hpertension and were studied from February 1974 to Decemober 1975. Hypertension was defined as supine diastolic blood pressure repeatedly above 90 mm Hg. Five patients had a family history of hypertension. Extensive diagnostic evaluation performed in all cases failed to show an underlying cause for the hypertension. Patients with target-organ involvement were treated with hydrochlorothiazide; five of them are currently normotensive. Of the remaining nine untreated patients, four became spontaneously normotensive within eight to 14 months of the initial evaluation. These results suggest that extensive studies in children with hypertension may not be necessary in every case if clinical findings meet the critiera for the diagnosis of essential hypertension. These studies might be desirable, however, if target-organ involvement is present.

The quantity of beta-aminoisobutyric acid (BAIB) excreted in the urine of patients with an intact spleen suffering from thalassaemia major appears to be proportional to the number of the circulating normoblasts and inversely proportional to the haemoglobin level. After splenectomy only minute amounts of BAIB are excreted. Transfusion constantly, but temporarily, reduces urinary excretion of beta-aminoisobutyric acid. Other anaemic but non-thalassaemic patients may excrete low levels.