PubMed Health⌕ Search

Biomedical subjects

T Bistritzer

Publications and source records attributed to T Bistritzer.

At least 37 records · Page 2Linked to original sources

Prevention of autoimmune diabetes by linomide in nonobese diabetic (NOD) mice is associated with up-regulation of the TCR-mediated activation of p21(ras).

Oral therapy with linomide protects prediabetic nonobese diabetic (NOD) mice from insulin-dependent diabetes mellitus. The mechanisms by which linomide exerts its protective effect are not fully understood. A decreased TCR-mediated activity of the GTP-GDP binding p21(ras) proto-oncogene is associated with prediabetes in NOD mice. However, the role of this signal transduction defect in the pathogenesis of autoimmune diabetes is not known. The TCR-mediated and protein kinase C-induced activations of p21(ras) were determined in mononuclear cells from lymph nodes of linomide-treated and untreated prediabetic NOD mice. TCR cross-linking by Con A induced an increase of 13 +/- 6.8% and a decrease of 0.8 +/- 1.8% in p21(ras) activity in the linomide-treated group and the untreated controls, respectively. Cell stimulation with PMA resulted in a 15 +/- 2% increase in p21(ras) activity in the linomide-treated mice and a 10 +/- 11.4% decrease in the untreated mice. Protein levels of p21(ras) and its regulatory elements, the GTPase-activating protein and the guanine nucleotide-releasing factor, mSOS, were comparable in both groups. We, therefore, conclude that prevention of autoimmune diabetes by linomide is associated with up-regulation of the p21(ras) T cell signal transduction defect in NOD mice.

Adjuvants, Immunologic↗

Severe pseudohypoaldosteronism in a pair of twins not associated with hydramnios.

A pair of non-identical twins with severe pseudohypoaldosteronism (PHA) were followed over a period of 4 years. The diagnosis was based on dehydration, hyponatremia, hyperkalemia, high urine sodium/potassium ratios, and high serum concentrations of aldosterone and renin. Sweat and saliva electrolyte concentrations were high, suggesting multifocal target-organ unresponsiveness to mineralocorticoids. No hydramnios was observed during pregnancy. Despite continuous treatment with sodium chloride and sodium bicarbonate (< or = 20 g/day) and cation exchange resin (Kayexalate, sodium polystyrene sulfonate, < or = 4 g/kg per day), the children had repeated episodes of dehydration, hyponatremia, and hyperkalemia. Growth velocity was normal in both twins. Catch-up growth was observed following infancy in the first twin. Normalization of plasma aldosterone, electrolytes, and renin concentrations was achieved at the age of 9 months.

Body Height↗

Dumping syndrome following Nissen fundoplication, diagnosis, and treatment.

We evaluated the prevalence, diagnosis, and treatment of dumping syndrome (DS) following Nissen fundoplication in 50 consecutive infants and children who underwent the operation for gastroesophageal reflux. Examination included a preoperative dietary assessment with emphasis on specific postprandial clinical symptoms and technetium scintigraphy to evaluate gastric emptying. In the immediate postoperative period, postprandial glucose levels were examined in all patients with symptoms clinically suggestive of DS. In the late postoperative period (6 months to 5.5 years), all patients with more than one specific clinical symptom of DS were further evaluated by glucose tolerance test (GTT), HbA1C levels, and gastric technetium scintigraphy. DS was diagnosed in 15 patients (30%). Five patients had immediate severe DS (SDS), and 10 in the late postoperative course had latent postoperative DS (LDS). In all patients with DS, preoperative and postoperative gastric emptying scan T1/2 did not show any statistical significance. High levels of HbA1C ranging from 7.9 to 9% (mean, 8.25 +/- 0.5) were found in only three patients. Treatment included parenteral nutrition in one patient. All the others were successfully managed with nutritional manipulation alone, using a combination of lactose-free formula and fat emulsion. In patients whose postprandial symptoms persisted, pectin 5-15 g/day divided into six doses was added to the diet. Following 6 months of dietary treatment, the postprandial normoglycomic response was restored. Eleven patients experienced complete resolution of symptoms (78.5%), and three patients (21.4%) showed significant clinical improvement. This study indicates that DS is a common complication following Nissen fundoplication. The GTT is the most reliable examination for establishing the diagnosis. Treatment is simple and effective. The technetium gastric emptying scan and HbA1C level do not play a significant role in the diagnosis.

Adolescent↗

Increased prevalence of diabetes-related autoantibodies in celiac disease.

Forty-four nondiabetic patients with celiac disease (CD) were examined for the presence of insulin-dependent diabetes mellitus (IDDM)-related autoantibodies. Islet cell antibodies (ICA) were detected in 2 of 44 (4.5%). None of the 200 age- and sex-matched healthy controls was ICA positive (p < 0.05). Competitive anti-insulin antibodies (CIAA) were detected in 1 of 44 (2.5%) patients. First-phase insulin reserve (FPIR), stimulated insulin reserve (SIR), and glycosylated hemoglobin (GHB) levels were normal in the autoantibody-positive patients. Our data suggest that, like first-degree relatives of IDDM patients, CD patients are characterized by an increased prevalence of diabetes-related autoantibodies. Further follow-up is needed to determine whether the presence of these autoantibodies in nondiabetic CD patients predicts future IDDM.

Adolescent↗

Peritoneal ventilation in rabbits: augmentation of gas exchange with cisapride.

BACKGROUND: Peritoneal ventilation has been shown to be effective in achieving extrapulmonary oxygenation and carbon dioxide elimination in an animal model of severe adult respiratory distress syndrome (ARDS). Cisapride is a "prokinetic" agent (increases gastric emptying), that may increase the splanchnic circulation and thus favourably affect gas exchange in peritoneal ventilation. METHODS: Using Doppler ultrasound the effect of cisapride on the portal venous circulation was examined in eight spontaneously breathing rabbits and the effect of cisapride on gas exchange in five rabbits spontaneously breathing room air was compared with that of a control group who did not receive cisapride. Its effect on gas exchange in five rabbits with ARDS being treated with mechanical lung and peritoneal ventilation was compared with that of a control group, and its effect on gas exchange in five rabbits with ARDS treated with conventional ventilation was also compared with that of a control group. RESULTS: Enteral administration of cisapride increased portal venous blood velocity, as measured ultrasonographically, by a mean of 188% one hour after receiving the drug. In rabbits with ARDS being treated with both peritoneal ventilation and mechanical ventilation to the lungs, those receiving cisapride had arterial oxygen tensions 1.5-3 times that of controls. Cisapride had no effect on arterial blood gas tensions in rabbits who were spontaneously breathing room air, nor in rabbits with ARDS who received only conventional mechanical lung ventilation. CONCLUSIONS: Cisapride increases arterial oxygenation in rabbits with severe ARDS treated with peritoneal ventilation, probably due to its ability to increase splanchnic circulation. It should be considered as an adjuvant medication to peritoneal ventilation.

Animals↗

Renal and absorptive hypercalciuria: a metabolic disturbance with varying and interchanging modes of expression.

BACKGROUND: In previous studies, the oral calcium loading and deprivation test has been used to distinguish between children with renal (fasting) hypercalciuria (RH) and absorptive hypercalciuria (AH). OBJECTIVE: We evaluated the long-term clinical course of 30 children with idiopathic hypercalciuria and investigated the influence of urinary sodium excretion, as a reflection of its intake, on urinary calcium excretion. METHODS: Thirty normocalcemic, normophosphatemic children (21 boys and 9 girls) with urinary calcium to creatinine ratios greater than 0.57 mmol/L/mmol/L ( > 0.21 mg/dL/mg/dL on the three consecutive examinations participated in this study. They were divided according to their responses to calcium deprivation and loading into AH (16 patients) and RH (14 patients). RESULTS: When restudied 3 to 7 years later, 6 of the 16 children with AH were normocalciuric and three demonstrated characteristics compatible with RH. The remaining seven patients maintained their initial AH pattern. Of the 14 children with RH, four were normocalciuric and four demonstrated AH. The remaining six children maintained their initial RH pattern. A significant positive correlation was observed between urine sodium and calcium excretion in children with AH or RH. Children who were normocalciuric at the second study had significantly lower values of urine sodium excretion when compared with those in whom hypercalciuria persisted. CONCLUSIONS: We suggest that AH and RH constitute a continuum. The change in characteristics observed during the second study suggests that any attempt to divide these patients into two physiologically distinct subtypes may be artificial. The main factor influencing urinary excretion of calcium in our patients seemed to be sodium intake.

Absorption↗

Routine childhood screening for hyperlipidemia in Israel.

Screening of children and adolescents for hyperlipidemia is controversial. We performed a cholesterol surveillance study of 806 children aged between 6 and 14 years. The initial cholesterol screening test was done by finger stick in the non-fasting state. Children with cholesterol values exceeding 4.55 mmol/l ("borderline" risk) and their parents had their lipid profiles measured following a 12 h fast by venipuncture. The incidence of coronary risk factors in the families of children with hypercholesterolemia was estimated. Of the initial group, 71 children had total capillary cholesterol levels > or = 4.55 mmol/l, and in 65 of these children serum lipid profile was reexamined after an overnight fast. Fifty-five children were found to have total venous cholesterol (TVC) levels < 4.55 mmol/l, and 27 of the 55 had a low density lipoprotein (LDL) cholesterol level > 3.4 mmol/l ("borderline" risk). A positive correlation was found between TVC and LDL-cholesterol levels. Of the hypercholesterolemic children 49% had a parent with hyperlipidemia and 13% had a family history of premature myocardial infarction (before 55 years of age). We conclude that screening of children based on the presence of hypercholesterolemia or its possible complications in other family members may fail to identify many of the children with hypercholesterolemia. Thus, if thorough identification of young children with hypercholesterolemia is desired, inclusive population screening would be the most effective approach.

Adolescent↗

Urinary tract infection following ritual Jewish circumcision.

Circumcision seems to reduce the overall incidence of urinary tract infections (UTI), although a few studies have suggested that ritual circumcision may be a predisposing factor for UTI within the first 2 weeks following the procedure. The aim of this study was to investigate a possible causal relationship between ritual circumcision and UTI. The study comprised 82 infants with UTI, 55 females and 27 males under the age of 1 year. All males were circumcised on the eighth day of life. The median age of infection was 0.75 and 7.0 months for males and females, respectively. Fifty-two percent (14/27) of UTI episodes were diagnosed within the 2 weeks following circumcision. A significantly lower incidence in Escherichia coli-induced UTI was observed in males compared to females, 67% and 93%, respectively. Similarly, the incidence of E. coli-induced UTI was also significantly lower in males presenting within 2 weeks following circumcision (57%) compared to infants presenting prior or more than 2 weeks following the procedure (92%). Positive blood cultures of an identical microorganism were observed in 6/27 males compared to 2/55 females. The incidence of urinary tract malformations and their severity were similar in both sexes. We conclude that the high incidence of UTI following a ritual Jewish circumcision, as well as the relatively high preponderance of bacteria other than E. coli, may suggest a causal relationship between circumcision and UTI.

Age Distribution↗

Focal epileptic episodes associated with hypoglycemia in children with diabetes.

Focal neurological deficits associated with hypoglycemia have been well described in adults with diabetes. We could find only one report of the association between focal epileptic episodes and hypoglycemia in children with diabetes. We describe 3 patients with seven focal epileptic episodes associated with hypoglycemia.

Blood Glucose↗

Lipid profile with paternal history of coronary heart disease before age 40.

Serum lipids were measured in children and their parents from 40 families in which the father had a myocardial infarction or coronary heart disease (CHD) before age 40 years. The relationship between physical activity and serum lipid concentrations in the children was also evaluated. Twenty six men had one or more abnormal lipid value (in mmol/l): total venous cholesterol (TVC) > 6.24, triglycerides < 2.55, low density lipoprotein cholesterol (LDL-C) > 4.42, or high density lipoprotein cholesterol (HDL-C) < 0.91. There were 15 spouses with significant hyperlipidaemia (values above). In the 107 children examined, TVC mean (SD) was 4.68 (1.17), triglycerides 1.4 (0.8), LDL-C 3.0 (1.0), and HDL-C 1.18 (0.28). Altogether 42% of the children had significant hyperlipidaemia. No significant correlation was found between the degree of physical activity of the children and their LDL-C and TVC concentrations. However, a significant positive correlation was found between the degree of physical activity and HDL-C and a significant negative one with triglyceride concentrations. It is concluded that screening the progeny of young CHD patients is highly productive in identifying young people at excessive risk for future CHD. The data also suggest that promoting high degrees of activity among these children may have a positive influence on risk factors for adult onset CHD.

Adolescent↗

Growth failure with plasma GH that is normal by RIA but low by radioreceptor assay: responsiveness to exogenous GH.

We measured the ratio of GH by radioreceptor assay (RRA) using IM-9 cells to its radioimmunoassay (RIA) level in: (a) 25 children and young adults with normal growth (controls); (b) 7 poorly growing children with GH neurosecretory dysfunction (GHND) who had normal stimulated GH but subnormal integrated concentration of GH (IC-GH) who responded to GH therapy; (c) 4 poorly growing children who had both normal stimulated GH and IC-GH but did not respond to GH therapy (GHNR - GH responder), and (d) 7 poorly growing patients with normal stimulated, and IC-GH who responded to GH therapy (GHR - GH responder). The RRA/RIA ratio of the GHND group was 1.3 +/- 0.4 similar to that of the control group - 1.3 +/- 0.3. The mean RRA/RIA ratio of the 7 GHR patients was 0.6 +/- 0.5, significantly lower than the controls and the GHND patients (p < 0.05). The RRA/RIA ratios of the 4 GHNR patients was not different from the controls. We conclude that: (1) GH binding is normal in GHNR and GHND patients and (2) RRA/RIA ratio below the normal range as measured by IM-9 cell GH RRA in short, poorly growing children with normal GH secretion, was a predictor of the response to GH therapy.

Adolescent↗

Exclusion of the locus for autosomal recessive pseudohypoaldosteronism type 1 from the mineralocorticoid receptor gene region on human chromosome 4q by linkage analysis.

Pseudohypoaldosteronism type 1 (PHA1) is an uncommon inherited disorder characterized by salt-wasting in infancy arising from target organ unresponsiveness to mineralocorticoids. Clinical expression of the disease varies from severely affected infants who may die to apparently asymptomatic individuals. Inheritance is Mendelian and may be either autosomal dominant or autosomal recessive. A defect in the mineralocorticoid receptor has been implicated as a likely cause of PHA1. The gene for human mineralocorticoid receptor (MLR) has been cloned and physically mapped to human chromosome 4q31.1-31.2. The etiological role of MLR in autosomal recessive PHA1 was investigated by performing linkage analysis between PHA1 and three simple sequence length polymorphisms (D4S192, D4S1548, and D4S413) on chromosome 4q in 10 consanguineous families. Linkage analysis was carried out assuming autosomal recessive inheritance with full penetrance and zero phenocopy rate using the MLINK program for two-point analysis and the HOMOZ program for multipoint analysis. Lod scores of less than -2 were obtained over the whole region from D4S192 to D4S413 encompassing MLR. This provdes evidence against MLR as the site of mutations causing PHA1 in the majority of autosomal recessive families.

Alleles↗

Pseudohypoaldosteronism with increased sweat and saliva electrolyte values and frequent lower respiratory tract infections mimicking cystic fibrosis.

Four patients with severe pseudohypoaldosteronism caused by multiple end-organ resistance to aldosterone had frequently recurring lower respiratory tract infections and persistently elevated sweat and saliva electrolyte values. The increased saliva electrolyte values in these patients probably affect normal mucociliary function in the respiratory tract and facilitate the occurrence of frequent lower respiratory tract involvement. Patients with pseudohypoaldosteronism may require treatment similar to that for cystic fibrosis to prevent long-term respiratory complications.

Aldosterone↗

Reduced Na+, K(+)-ATPase activity in patients with pseudohypoaldosteronism.

Pseudohypoaldosteronism is a hereditary salt-wasting syndrome usually seen in infancy with weight loss, dehydration, and failure to thrive. The pathophysiologic origin of pseudohypoaldosteronism is unknown. The defect could be related to the unresponsiveness of target organs to mineralocorticoids resulting in hyponatremia, hyperkalemia, and markedly elevated plasma aldosterone and renin levels. Red blood cell Na+, K(+)-ATPase activity was measured in a pair of twins with pseudohypoaldosteronism, in an unrelated child with hypoaldosteronism, and in an age-matched group of 50 healthy infants and young children. The enzyme was assayed by a method that couples ATP hydrolysis with NADH oxidation. Plasma renin and aldosterone levels were measured by RIA. Red blood cell Na+, K(+)-ATPase activity in the twins with pseudohypoaldosteronism was very low at the time of diagnosis (3 wk). In both twins a time-related gradual increase in enzyme activity was observed during the 1st mo of life, reaching control values between 6 and 8 mo of age. This increase was associated with both a reduction in salt requirement and clinical improvement. Plasma renin activity and aldosterone levels were very high at the time of diagnosis. Plasma renin activity reverted gradually to normal values, whereas aldosterone levels remained high throughout the follow-up period. The child with hypoaldosteronism had normal Na+, K(+)-ATPase activity at diagnosis and during follow-up.

Aldosterone↗

Renal artery stenosis secondary to neurofibromatosis in children: detection by Doppler ultrasound.

Renal artery stenosis was diagnosed in two adolescents with neurofibromatosis using Doppler ultrasound. The diagnosis was confirmed by angiography. The renal vascular lesion in neurofibromatosis usually affects the proximal segment of the artery, which is the part most optimally visualized by ultrasound. We suggest that Doppler ultrasound of the renal arteries may be a useful technique in the investigation of hypertensive children with neurofibromatosis.

Adolescent↗

Congenital contractural arachnodactyly in two double second cousins: possible homozygosity.

A Bedouin family with two girls affected by severe congenital contractural arachnodactyly (CCA) is described. The girls were double second cousins. One of the girls also had ambiguous genitalia, an anomaly not generally associated with this disorder. The two children were both the product of first-cousin Bedouin parents from the same family. It is possible that both sets of parents were heterozygous for CCA; thus the infants may have been homozygous for CCA, which is usually an autosomal dominant condition. No instance of homozygous CCA has previously been reported. This family suggests genetic heterogeneity in CCA and that, in some rare families, the mode of inheritance may be autosomal recessive.

Consanguinity↗

Inhibition of human red blood cell glutathione reductase by valproic acid.

Glutathione reductase (GR) one of the enzymes of the glutathione redox cycle, plays a salient role in maintaining appropriate cellular levels of reduced glutathione. The enzyme in human red blood cells is inhibited in vitro by the anticonvulsant drug valproic acid (VPA). The inhibition is dose-dependent, reversible, uncompetitive and does not depend on the redox state of the enzyme. VPA also inhibits red blood cell GR activity in children being treated with the drug. The level of serum VPA correlates significantly with the suppression of GR activity.

Adolescent↗