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Biomedical subjects

F Ginsberg-Fellner

Publications and source records attributed to F Ginsberg-Fellner.

At least 55 records · Page 3Linked to original sources

Measurement of thyroid-stimulating hormone in human amniotic fluid.

TSH was measured in human amniotic fluid after 3- to 8-fold concentration of the fluids. Amniotic fluid TSH was identical to standard pituitary TSH by immunological and gel chromatographic criteria. In 201 samples of normal second trimester amniotic fluid (16-19 weeks of pregnancy), amniotic fluid TSH concentrations had a mean value of 0.4 microunits/ml (range, less than 0.15 to 1.7 microunits/ml). In 21 samples of third trimester amniotic fluid (obtained to check fetal lung maturity), amniotic fluid TSH concentrations had a mean value of 0.25 microunits/ml (range, less than 0.15 to 0.55 microunits/ml). The capability of measuring TSH in amniotic fluid and the relative constancy of these values between the second and third trimesters of pregnancy suggest that the determination of TSH levels in amniotic fluid may be useful in the diagnosis of fetal hypothyroidism in utero.

Amniotic Fluid↗

HLA antigens, cytoplasmic islet cell antibodies, and carbohydrate tolerance in families of children with insulin-dependent diabetes mellitus.

Cytoplasmic pancreatic islet cell antibodies were found in 21% of 244 unaffected first degree relatives of type I diabetic patients. Twenty-five percent of HLA-identical, 35% of HLA-haploidentical, 16% of HLA-nonidentical siblings, and 14% of parents were ICA-positive. In the HLA-identical sibs, irrespective of ICA, and in the 18 ICA-positive parents but not the other groups, increased plasma glucose levels were observed after the administration of glucose. In most children, these were associated with reduced insulin levels, while in the adults elevated insulin responses were noted. In 48% of the ICA-positive children and 84% of the ICA-positive parents, other evidence of "autoimmunity" was obtained either by history or by testing for specific autoantibodies. Two of the originally unaffected HLA-identical and ICA-positive siblings developed diabetes during the course of the study. These findings, plus previously reported data in families with two diabetic sibs demonstrating that the empiric risk for developing IDDM is of the order of 30% for HLA-identical sibs but less than 5% for those that are HLA-haploidentical, suggest that HLA-identity may be a useful predictor of potential type I diabetes. The presence of ICA may, at times, portend the need for future antidiabetic therapy but prospective studies must be continued to fully elucidate this relationship.

Adolescent↗

The HLA system in congenital rubella patients with and without diabetes.

The HLA antigens of 173 patients with the congenital rubella syndrome (CR) are reported. Twenty-one of these patients are also clinically diabetic, and among them the frequencies of the HLA antigens DR2 and DR3 are significantly lower and higher, respectively, than in CR patients without diabetes or in controls. These data suggest that the genes that control susceptibility to type I or insulin-dependent diabetes mellitus are necessary for the development of glucose intolerance in CR patients.

Adolescent↗

Abnormalities of immunoregulatory T cell subsets in patients with insulin-dependent diabetes mellitus.

Patients with insulin-dependent diabetes mellitus (IDDM) have autoantibodies that react with cells in the islets of Langerhans. To determine whether these patients suffer from a more generalized immunoregulatory disorder, the ratio of phenotypic helper to suppressor cells was evaluated by specific monoclonal antibodies. Our experiments showed that the helper/suppressor cell ratio was significantly increased in patients with IDDM of less of 2 mo duration and then gradually returned to normal. Despite the alteration in the helper/suppressor cell ratio, there was no evidence for polyclonal activation as measured by the number of immunoglobulin-secreting plaque-forming cells in the peripheral blood. There was, however, a significant increase in the number of spontaneous plaque-forming cells in patients suffering from both IDDM and Hashimoto's thyroiditis (HT). Nonetheless, immunoglobulin production after stimulation with pokeweed mitogen was not different in diabetics with or without HT when compared to normal controls. These findings suggest that subtle changes in the immunoregulatory system occur during the early stages of IDDM.

Adolescent↗

Cerebral edema and ophthalmoplegia reversed by mannitol in a new case of insulin-dependent diabetes mellitus.

Cerebral edema is a sometimes fatal complication of diabetic ketoacidosis which occurs unpredictably and when biochemical parameters show improvement. A case of a young, newly diagnosed insulin-dependent diabetic boy who developed this complication while receiving a low-dose continuous insulin infusion is reported. Two hours after treatment signs of headache, ophthalmoplegia, and blurred disc margins suggested early cerebral edema. Despite fluid restriction, avoidance of alkali, and phosphate supplementation, cerebral edema ensued three hours later. This complication was then reversed by administration of mannitol. Our patient's ophthalmoplegia, unlike typical diabetic ophthalmoplegia, improved immediately and completely resolved within two weeks after this episode. It is concluded that the use of mannitol in the cerebral edema of diabetic ketoacidosis is beneficial if it is instituted promptly.

Adolescent↗

HLA antigens and islet cell antibodies in gestational diabetes.

The HLA antigens of 136 patients with gestational diabetes are compared with control populations. No significant variations are observed in their frequencies, particularly for those antigens associated with Type 1 diabetes mellitus. Islet cell antibodies have also been studied in the serum of 52 of these patients and 20 of them were positive, whereas only one of 37 pregnant nondiabetic women had such antibodies (chi 2 = 15.2). A very high association between ICA and DR3 and DR4 was encountered (chi 2 = 17, with two df); half of the patients positive for either one of these antigens were ICA positive. These results indicate that ICA associates equally with DR3 and DR4, against the hypothesis that this expression of autoimmunity is more a characteristic of DR3- than of DR4-associated genetic susceptibility. These patients will be followed to determine if the ICA+ individuals are at increased risk for the development of insulin-dependent diabetes.

Adult↗

Overweight and obesity in preschool children in New York City.

In an effort to ascertain the prevalence of obesity in young children, 48 nursery schools in Manhattan and Queens, New York City were surveyed. The weights and heights of 2606 children, ages 3 to 6 yr, were obtained. Three-hundred seventeen children (12.2%) were above 120% of ideal body weight and 122 (4.7%) were above 130% of ideal weight. Twenty percent of the children from schools attended by youngsters from low income families, 12% from schools attended by pupils from middle income families, and 5% from schools with pupils from families with a high income were classified as obese. Of the obese children's actual body weights 90% were at or greater than the 75th percentile for age while mean higher percentiles of the obese and nonobese children were not significantly different. Sex specific prevalence rates were similar for boys and girls. These data indicate that obesity is already prevalent in the nursery school population and that such obese children can be easily identified from weight and height measurements at a time when programs for successful permanent weight reduction and maintenance may be feasible.

Body Height↗

Weight reduction in young obese children. I. Effects on adipose tissue cellularity and metabolism.

A 10-year longitudinal study was conducted on 16 prepubescent youngsters who had undergone successful weight reduction. Their ages ranged from 2 to 10 years when the study began. In all subjects, weight reduction proceeded only by a decrease in adipose cell size (from 0.62 +/- 0.02 to 0.46 +/- 0.02 micrograms lipid per cell) and resulted in a corresponding 33% decrease (from 177 +/- 6 to 144 +/- 5%) in percent ideal body weights. Cell numbers did not change appreciably during the period of weight loss (29.4 +/- 2.6 versus 28.7 +/- 2.3 x 10(9) total adipocytes). Three years after the start of the study, 14 of 20 youngsters had maintained their reduced percent ideal body weights, including eight who remained below 130% ideal body weight. Ten years later, only four remained below 130% ideal body weight. All four children had total adipose cell numbers below 20 x 10(9) total adipocytes at the start of the weight reduction program, a value below the lower limit for adult normal weight subjects. Thirteen other children have maintained or decreased their initial percent ideal weights. The remaining nine youngsters have further increased their percent ideal body weights. In vitro metabolic studies of the patient's adipocytes revealed a greater than 50% depression of epinephrine-stimulated lipolysis pre- and immediately postweight reduction; this decrease persisted for the entire period of study, irrespective of the maintenance of a normal percent ideal body weight. At the same time, normal 150% increases in the in vitro production of 14CO2 from [1-14C]glucose in the presence of insulin occurred.

Adipose Tissue↗

Genetics of Type I diabetes mellitus: a single, recessive predisposition gene mapping between HLA-B and GLO. With an appendix on the estimation of selection bias.

Three different published sets of HLA-typed families of juvenile diabetes mellitus (JDM) patients have been analyzed. There was no significant genetic heterogeneity between them according to the criterion of Morton, and the total material was analyzed on the assumption of a single recessive (JDM-P) gene with incomplete penetrance. The analysis, carried out with the NYLIP program modified to account for penetrance less than 1 and for selection bias, yields highly significant lod scores for linkage between HLA and JDM-P, with a maximum value of 7.40 at theta = .05 +/- .03. The segregation of HLA and GLO in five affected sib pairs, in which one of the sibs carries an HLA/GLO recombinant, places JDM-P closer to HLA than the GLO locus: four of these five pairs are HLA-identical and GLO-different, in agreement with the conclusions of the formal linkage analysis. The data from these three independent sets of families are therefore consistent with our earlier claim that JDM is inherited as a recessive trait closely linked to HLA with reduced penetrance, and its analysis does not require more complicated genetic models.

Chromosome Mapping↗

Growth of adipose tissue in infants, children and adolescents: variations in growth disorders.

In order to identify factors important in the growth of adipose tissue, four groups of children were studied. Infants of gestational diabetic mothers demonstrated increased fat cell numbers as early as age two months, a finding which accelerated with increasing age, and which was associated with persistent hyperinsulinemia and increasing obesity. Children with growth hormone deficiency increased their adipose cell number following treatment with exogenous hormone. Patients with the Prader-Willi syndrome, who developed obesity after the age of two, did so primarily via increases in fat cell size. Identical twins who were concordant for birthweight continued to have similar weights and total adipocyte numbers, while in those with discordant birthweights the smaller twin displays lower body weight and adipose cell number. The data indicate that growth hormone and insulin, as well as genetic factors, which may be modified by the in-utero environment, are important determinants of human adipose tissue mass.

Adipose Tissue↗

Cytotoxic autoantibodies to beta cells in the serum of patients with insulin-dependent diabetes mellitus.

We studied serum from 36 patients with insulin-dependent diabetes mellitus (IDDM) for the capacity to lyse beta cells. Immunofluorescence revealed an islet-cell cytoplasmic antibody (ICA) in 20 patients with IDDM and an islet-cell-surface antibody (ICSA) in 23. Neither ICA nor ICSA was found in any of 21 normal controls or 15 patients with non-insulin-dependent diabetes. In the presence of complement. ICSA-positive serum caused significant lysis as measured by release of 51Cr (50.1 +/- 8.8 per cent) from cultured rat islet cells, but ICSA-negative serum did not (17.7 +/- 7.3 per cent) (P < 0.001). Proof that ICSA-positive serum was lytic for beta cells was obtained by a double-fluorescence technique that identified lysed cells by their capacity to take up ethidium bromide and beta cells by their staining with fluorescein-conjugated antibody to insulin. These findings suggest that cytotoxic ICSA contributes to the pathogenesis of IDDM, but the mere presence of ICSA does not appear to be sufficient to produce diabetes; family studies showed that one fourth of the serum samples from nondiabetic first-degree relatives of diabetic probands were ICSA-positive and cytotoxic for beta cells.

Adolescent↗

Metabolic studies in a child with a pancreatic insulinoma.

An 8-year-old boy with a convulsive disorder for 3 1/2 years remined seizure free for 20 months while being treated with phenytoin (diphenylhydantoin) sodium, and then he had a relapse. He first demonstrated hypoglycemia when he fasted prior to being placed on a ketogenic diet. An oral glucose tolerance test indicated fasting and postglucose hypoglycemia and substantial hyperinsulinemia. Somatostatin infusion resulted in a modest increase in plasma glucose levels and a decrease in serum insulin concentrations. A discrete pancreatic mass was demonstrated preoperatively by celiac angiography that on surgical extirpation, proved to be a benign intrapancreatic insulinoma. Evaluation for islet cell tumors is of importance in children with seizure disorders unresponsive to anticonvulsant medication. Furthermore, somatostatin may be useful preoperatively in maintaining normal blood glucose concentrations in patients with islet cell adenomas.

Adenoma, Islet Cell↗

C-Peptide reserve in insulin-dependent diabetes. Comparative responses to glucose, glucagon and tolbutamide.

Residual beta cell secretory capacity was assessed in short term (2 months to 2 years) and long term (5 to 8 years) insulin-dependent diabetics by measurement of serum C-peptide immunoreactivity during three provocative tests: glucose, tolbutamide, and glucagon. Minimal C-peptide secretion could be detected in only one out of seven long term diabetics by the stimulatory tests. All seven short-term diabetics responded to at least one provocative test of beta cell reserve, although these responses were blunted. The greatest C-peptide responses occurred after glucagon administration (mean increase 0.62 pmol/ml) in short-term responders. Patients who responded to one test did not necessarily respond to another stimulus. There was no correlation between basal C-peptide levels and the ability to provoke further C-peptide secretion by any of the three tests. C-peptide responses did not correlate with % Haemoglobin A1c, mean fasting blood glucose levels, or mean blood glucose concentrations during an oral glucose tolerance test. The data indicate that stimulation tests are only useful in assessing endogenous beta cell reserve in patients with diabetes of less than 5 years duration. In diabetics of longer duration there is little insulin reserve above basal levels.

Adolescent↗

Prader-Willi syndrome and a bisatellited derivative of chromosome 15.

A de nova bistaellited derivative of chromosome 15, inv dup (15) (pter leads to q11 or 12::p11 or q11 or 12 leads to pter), was identified by multiple banding techniques in a patient with Prader-Willi syndrome. A comparison of familial no. 15 short arm polymorphisms indicated that the extra chromosome was the result of a non-sister chromatid exchange between the paternal no. 15 homologs prior to or during meiosis.

Adolescent↗