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Biomedical subjects

D J Becker

Publications and source records attributed to D J Becker.

At least 109 records · Page 6Linked to original sources
PubMed1986

Glucose tolerance in siblings of type 1 diabetic patients: relationship to HLA status.

In this report, we present an analysis of glucose and insulin responses during oral glucose tolerance tests in 369 siblings of Type 1 diabetic patients. All have been HLA typed at the A, B and C loci. Though most had normal glucose tolerance by National Diabetes Data Group criteria (92% of the males and 95% of the females), siblings who shared both HLA haplotypes with the diabetic patient in the family had higher mean 3-hour glucose areas than those who shared one or neither HLA haplotype (p less than 0.01). This difference was more marked in males and older siblings. Insulin concentrations did not differ significantly between the two groups except that, for those aged less than 16 years, the group sharing both haplotypes had lower fasting insulin concentrations (p = 0.05); for 16-29 year olds, the corresponding group had marginally higher 3-hour insulin areas than the remainder of siblings (p = 0.17). Little association with specific haplotypes (A1B8 or A2B15) was seen. Multivariate analyses, adjusting for age and obesity, eliminated the 3-h glucose difference in females by HLA sharing status (p = 0.37) although in males it remained significant (p less than 0.001). Failure to account for age, sex and obesity may explain some of the conflicts in the reported literature. The glucose tolerance differences seen by HLA haplotype sharing status did not correlate with the presence of anti-islet cell antibodies. These results are consistent with the hypothesis that the HLA identical siblings, particularly males, have different (i.e. worse) glucose tolerance than their haploidentical and non-HLA identical siblings.

Adolescent↗
PubMed1986

Differences between blacks and whites in the epidemiology of insulin-dependent diabetes mellitus in Allegheny County, Pennsylvania.

Racial differences in the incidence and natural history of insulin-dependent diabetes mellitus were evaluated in Allegheny County, Pennsylvania. The yearly incidence rate for whites was approximately 1.5 times that for blacks. The cumulative risk of developing insulin-dependent diabetes prior to age 20 was greater for whites (3.1/1,000, males; 2.8/1,000, females) than for blacks (1.7/1,000, males; 2.0/1,000, females). There was a slight excess risk for white males versus white females (relative risk = 1.09, p = 0.04), while no sex differential in risk was noted for blacks. The temporal trends and seasonal patterns were similar. Blacks more frequently possessed human lymphocyte antigen (HLA)-DR3/X and whites DR4/X; however, the risks associated with these antigens were similar by race. At onset, blacks had evidence of greater immunologic disturbance and less frequently reported infection than whites, although blacks more often had evidence of previous coxsackie viral infections. Evaluation of mortality patterns by race revealed that blacks had a higher mortality rate than whites. By 20 years duration of diabetes, blacks had a 2.4-fold increase in the risk of mortality compared with whites.

Adolescent↗
PubMed1986

Growth hormone therapy for patients with Turner's syndrome.

The linear growth of 8 patients with Turner's syndrome during human growth hormone (GH) administration was documented. Mean growth velocity was significantly greater during GH treatment (4.9 +/- 0.8 cm/year) than before treatment (3.3 +/- 0.8 cm/year, p less than 0.001). Growth velocity was related to dosage but not correlated with chronologic age, skeletal age or weight.

Adolescent↗
PubMed1986

Pittsburgh Insulin-Dependent Diabetes Mellitus Morbidity and Mortality Study: physical activity and diabetic complications.

The long-term health consequences of chronic physical activity for patients with type I diabetes are unknown. In the current study, the association of physical activity to diabetic complications was assessed in 696 type I diabetic individuals diagnosed between 1950 and 1964. Participation in team sports in high school or college was not associated with a decreased prevalence of severe retinopathy or blindness later in life. There was, however, a suggestion of a negative association between physical activity and both cardiovascular disease and overall mortality, ie, individuals who participated in team sports were somewhat less likely to report macrovascular disease at follow-up or to have died than nonparticipants. The relationship between physical activity and diabetic complications only appeared in male subjects. The results suggest that activity early in life by patients with type I diabetes does not appear to be associated with an adverse health effect and may, in fact, be beneficial.

Actuarial Analysis↗
PubMed1985

Growth hormone therapy and tumor recurrence. Findings in children with brain neoplasms and hypopituitarism.

We report the outcome of growth hormone (GH) therapy in 34 children (17 boys and 17 girls) with brain tumors in whom hypopituitarism developed. The types of tumors included the following: craniopharyngiomas (18); germinomas (four); astrocytomas (three); chromophobe adenomas (three); medulloblastomas (two); glioma (one); dermoid (one); retinoblastoma (one); and metastatic rhabdomyosarcoma from the pelvis (one). Ninety-four percent of the patients were GH deficient post-tumor therapy, which consisted of surgery with and without radiotherapy. Twenty-four of 34 patients received GH. Eight of 24 patients receiving GH had recurrence of tumor; 16 were tumor free eight to 72 months after initial therapy. Eleven patients had 12 recurrences. Patients with tumor recurrence had a considerably lower growth rate during the first year of GH therapy than those without recurrence (mean, 3.5 +/- 1.3 cm/yr v 6.2 +/- 2.5 cm/yr). Three of 11 patients with recurrence had not received GH therapy; however, one was receiving testosterone intramuscularly monthly at the time of a second recurrence. Thus, 24 of 34 patients with brain tumors and hypopituitarism received GH therapy. Eight (33%) of 24 had tumor recurrence, compared with three (30%) of ten who did not receive GH. The data suggest that GH therapy is probably not associated with increased rate of tumor recurrence.

Adolescent↗
PubMed1985

HLA heterogeneity of insulin-dependent diabetes mellitus at diagnosis. The Pittsburgh IDDM study.

Although some previous studies have suggested that insulin-dependent diabetes mellitus (IDDM) is a heterogeneous condition with variant forms being associated with HLA-DR types, the evidence, thus far, is conflicting. To address this issue, we have examined the presenting characteristics of a consecutive admission series of 200 newly diagnosed cases of IDDM from the Children's Hospital of Pittsburgh. Because HLA-DR frequencies vary by race, data are presented only for the 172 white cases with complete HLA-DR typing. HLA-DR3 was found more frequently among male cases and DR4 among female cases (P less than 0.005). Generally, patients with DR4 presented with a severer clinical picture, being more likely to have impaired consciousness and significant dehydration. In addition, patients with DR4 were more likely to be acidotic, ketotic, and to more frequently report a recent viral infection. This latter finding was supported by a greater frequency of antibodies to Coxsackie-B viruses in the DR4 cases at presentation. These results therefore suggest that there is considerable heterogeneity in IDDM, at least in presenting characteristics, according to HLA-DR type.

Adolescent↗
PubMed1985

Correlates of insulin antibodies in newly diagnosed children with insulin-dependent diabetes before insulin therapy.

Insulin antibodies, as measured by plasma radiolabeled insulin-binding capacity, were determined in 124 newly diagnosed insulin-dependent diabetic (IDDM) children before and after 1, 3, and 5 days of insulin therapy. Controls were 35 nondiabetic children with plasma insulin binding capacity of 1.0 +/- 0.7%. The patients were divided into three groups according to their plasma insulin-binding capacity. Group 1 (N = 79) had binding within two standard deviations (SD) of the control mean, group 2 (N = 20) had insulin binding 2-6 SD above controls, and group 3 (N = 25) showed insulin-binding capacity of more than 6 SD above the control mean. After exogenous insulin therapy, plasma 125I-insulin-binding capacity dropped significantly in both groups 2 and 3, concurrent with significant increases in plasma insulin levels. The three groups differed from each other in that patients in group 3 were significantly younger than in the other groups and clinically seemed to be more severely dehydrated, as reflected in their higher levels of serum urea nitrogen, plasma glucose, potassium, and elevated pulse rate. The three groups did not differ in respect to sex, HLA-DR antigens, Coxsackie-B antibody titers, islet cell cytoplasmic antibodies, immunoglobulin level, and C-peptide levels. Only two of 446 siblings of IDDM children showed elevated insulin binding, one of whom developed IDDM 6 wk later. The presence of an insulin-binding substance probably representing insulin antibodies in some cases of newly diagnosed IDDM suggests that autoimmunity in this disorder is not limited to the B-cell membrane and cytoplasm and lends further support to the heterogeneity of IDDM.

Adolescent↗
PubMed1985

A computer-aided system for planning acute care bed need in Michigan.

As part of an effort within Michigan to promote cost containment and equitably distribute hospital resources, the Acute Care Bed Need Methodology (ACBNM), a model for determining bed need based on normative use rates, was created. We describe herein the ACBNM, the associated interactive computer system, and the data base requirements, and make suggestions for improving the methodology. We also discuss the functions the ACBNM has served in Michigan and the role it could serve in future health planning efforts.

Age Factors↗
PubMed1984

Comparison of physiologic and pharmacologic assessment of growth hormone secretion.

To determine if pharmacologic and physiologic tests are equally effective in the assessment of growth hormone (GH) secretory status, serum GH levels were measured during sequential tests with intravenous arginine infusion and insulin-induced hypoglycemia (arginine-insulin tolerance test [ AITT ] ) and during sleep in 62 children, aged 2.1 to 17.3 years. Responses during AITT and sleep were concordant in 53 patients and discordant in nine patients. Arginine-insulin tolerance test results were consistent with the subsequent clinical course in 80% of the patients while nocturnal sampling was consistent with the subsequent clinical course in 93% of the patients. Thus, the failure of a normal serum GH response to pharmacologic stimuli is not always a diagnostic indicator of GH deficiency. Additional investigation of discordant GH responses to pharmacologic and physiologic stimuli may lead to a further understanding of the control mechanisms of GH secretion.

Adolescent↗
PubMed1984

The Pittsburgh Insulin-Dependent Diabetes Mellitus (IDDM) study. HLA antigens and haplotypes as risk factors for the development of IDDM in IDDM patients and their siblings.

The relationships between HLA antigens, sex, age at diagnosis, season of onset and insulin-dependent diabetes mellitus (IDDM) were studied in a consecutive admissions series of newly-diagnosed IDDM patients at Children's Hospital of Pittsburgh. In agreement with the findings of others, the strongest positive associations between IDDM and HLA antigens were seen with DR3 and DR4 (odds ratios (OR) of 3.5 and 4.4, respectively), while a very strong negative association was observed with DR2 (OR of 0.1). Male patients were significantly more likely than female patients to possess DR3 while female patients were significantly more likely to be DR4+. No consistent relationships were found between HLA antigens and either age at diagnosis or season of onset. Using a life table approach, the cumulative risk of IDDM by age 24 in HLA-identical siblings of IDDM patients was estimated to be 10.3%. This risk was significantly greater than the risks to either HLA-haploidentical siblings (2.2%) or to HLA-nonidentical siblings (1.0%), whose risks were not significantly different. B7 + HLA-identical siblings of patients appeared to be protected from the effects of HLA-identicality--their cumulative risk by age 24 was estimated to be only 2.3%.

Actuarial Analysis↗
PubMed1984

Multivariate analyses of the risk of insulin-dependent diabetes mellitus for siblings of insulin-dependent diabetic patients.

Multivariate models for the risk of insulin-dependent diabetes mellitus for siblings of patients with insulin-dependent diabetes were developed using logistic regression analysis. The individuals studied in this report are full siblings of the insulin-dependent diabetic patients diagnosed at Children's Hospital of Pittsburgh between 1964 and 1982. For all siblings considered together, the sharing of two (but not one) HLA haplotypes, the presence of insulin-dependent diabetes in a parent, and being relatively young at the time the proband in the family was diagnosed were significantly associated with increased risk. On the other hand, B7 + siblings had a significantly decreased risk compared to B7--siblings, indicating the presence of an HLA-linked protective gene for the development of the disease. There was a significant interaction between sharing two HLA haplotypes and maternal age at the time of birth; for non-HLA-identical siblings, risk increased with increased maternal age, but maternal age had little or no effect on the risk for HLA-identical siblings. When non-HLA-identical siblings (0 or 1 HLA haplotypes shared) were analyzed separately, only the presence of insulin-dependent diabetes in one of the parents and increased maternal age at the time of birth of the sibling were found to be significantly associated with increased risk. Both of the totally non-HLA-identical diabetic siblings (neither HLA haplotype shared) in this data set had a parent with insulin-dependent diabetes, indicating that at least one HLA haplotype must be inherited in common with an affected family member for diabetes to develop. For HLA-identical siblings, the significant variables were the age of the sibling when the proband was diagnosed, the possession of B7, and maternal age at the time of birth of the sibling, and all three were negatively associated with risk.

Adult↗
PubMed1984

Characterization of somatostatin specific binding in plasma cell membranes of human placenta.

Somatostatin is a known inhibitor of hormone secretion and of nutrient transport. Because somatostatin-like immunoreactivity has been detected in amniotic fluid and the placenta has both hormone secretory and nutrient transport functions, we investigated the possible existence of somatostatin receptors on placenta cell membranes. Binding of 125I-Tyr1- and 125I-Tyr11-somatostatin (5-21%) to solubilized placenta cell membranes was observed. Binding was time-, temperature-, and pH-dependent and occurred maximally with incubation at concentrations of 25 micrograms of membrane protein. Displacement of binding of 125I-Tyr1 and Tyr11 somatostatin by cold cyclic and linear somatostatin and somatostatin analogs Ala-5, Ala-8, and Ala-11 was observed. Scatchard analysis of data revealed high capacity of (Ro 0.44 mol/micrograms X 10(-12) but low affinity (Kd 1.8 M X 10(-7) binding sites similar to that reported in other tissues. Binding was not reversible under our experimental conditions. The significance of this low affinity binding of somatostatin to placenta cell membranes remains to be determined.

Binding, Competitive↗
PubMed1984

Hormonal, metabolic, and neuroradiologic abnormalities associated with septo-optic dysplasia.

The clinical, neuroradiologic, and endocrine features in 16 patients with septo-optic dysplasia are reviewed. All of the patients had clinical optic nerve hypoplasia with varying degrees of nystagmus and visual impairment. Only one-half of the patients had absence of the septum pellucidum. Fourteen children were growth hormone deficient, 9 were adrenocorticotrophic hormone deficient, 3 were thyroid-stimulating hormone deficient, and 4 had diabetes insipidus. In most instances, the diagnosis of septo-optic dysplasia can be established by physical examination and neuroradiologic findings, at which point a thorough evaluation of the hypothalamic-pituitary endocrine function is indicated because of the high incidence of hypopituitarism with this syndrome.

Abnormalities, Multiple↗
PubMed1984

The Pittsburgh insulin-dependent diabetes mellitus (IDDM) morbidity and mortality study. Mortality results.

A follow-up study of 1966 patients with insulin-dependent diabetes mellitus (IDDM) who were diagnosed at Children's Hospital of Pittsburgh (CHP) between 1950 and 1981 has been completed. The mean age of the population at follow-up was 21.2 yr with a mean duration of IDDM of 12.9 yr. Nine percent of the patients were deceased, a sevenfold excess in mortality compared with the U.S. population. The relative increase in mortality was greater for females than males and greater for blacks than whites. Before age 20, the primary excess in mortality was at onset of IDDM, or within 6 mo after onset, and was due to acute diabetic complications. After age 20, the annual mortality risk was approximately 2%, which was more than 20 times greater than for the U.S. population. Renal disease was responsible for the majority of these deaths. There was a reduced risk of dying for diabetic patients who were diagnosed between 1966 and 1971 compared with patients diagnosed during earlier years.

Adolescent↗
PubMed1983

Phosphate replacement during treatment of diabetic ketosis. Effects on calcium and phosphorus homeostasis.

Thirty-five patients with diabetic ketosis were given initial intravenous (IV) potassium replacement as phosphate (N = 13) or chloride (N = 13), or received no potassium replacement other than that contained in a normal diet (N = 9). All patients experienced a slight decrease in serum calcium level by 12 hours after the start of insulin therapy, but there was no statistically significant change in serum ionized calcium values. The phosphorus-supplemented group had significantly lower serum phosphorus concentrations at 24 and 36 hours when compared with patients receiving no IV hydration and excreted significantly more phosphorus during the first 12 hours of the study than either of the other two groups of patients. Our use of phosphorus supplements (4.7 to 28.5 mg/kg) did not cause abnormalities in calcium metabolism but did not prevent late hypophosphatemia.

Adolescent↗
PubMed1983

The development of Type 1 (insulin-dependent) diabetes mellitus: two contrasting presentations.

Genetic, immunological and viral factors have been implicated in pathogenesis of Type 1 diabetes mellitus. The development of Type 1 diabetes in two siblings of patients with Type 1 diabetes studied as part of a large epidemiological study, is described. One case, a 13-year-old male not sharing either HLA haplotype with his diabetic sister, had virtually normal glucose tolerance 80 days before symptomatic presentation. He showed serological evidence of infection by Coxsackie CB4 (at diagnosis) and influenza A virus (soon after diagnosis). The other case, a 15-year-old male, had impaired glucose tolerance for over 500 days (i.e., since the diagnosis of diabetes in his HLA-identical brother) before symptomatic presentation which was not associated with serological evidence of acute viral infection. The former case was negative for islet cell antibody (cytoplasmic) when first seen though positive at diagnosis, while the latter was positive throughout. These two cases suggest contrasting interactions of the main pathogenetic factors associated with Type 1 diabetes.

Adolescent↗
PubMed1983

Proteinuria in children with insulin-dependent diabetes: relationship to duration of disease, metabolic control, and retinal changes.

The relationship of early retinal changes and subclinical proteinuria to duration and metabolic regulation of insulin-dependent diabetes was studied in 67 children. Retinopathy was found in 25 patients and occurred almost exclusively (96%) in those with duration of disease longer than five years. Glomerular filtration rate was normal or increased in all patients. Urinary excretion of beta 2-microglobulin, albumin, transferrin, and IgG was significantly increased in patients, as compared with controls, whereas serum concentrations of these proteins were generally normal. The mechanisms responsible for the hyperexcretion of both large and small proteins are unclear but probably involve both glomerular and tubular dysfunction. Increased urinary protein excretion occurred independently of duration of disease. Retinopathy but not microproteinuria was more common in patients with glycosylated hemoglobin greater than 11% and in those with duration of disease longer than five years. Although a significant association was found between retinopathy and the hyperexcretion of one or more of the large molecular weight proteins, the weight of the evidence suggests that these two sequelae of diabetes differ in their pathogenesis. Long-term follow-up of these patients may provide insight as to their risk of developing more serious retinopathy or nephropathy, and whether good glycemic control may protect against these complications of insulin-dependent diabetes.

Adolescent↗