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Biomedical subjects

J H Silverstein

Publications and source records attributed to J H Silverstein.

At least 55 records · Page 3Linked to original sources
PubMed1990

A prospective study of the development of diabetes in relatives of patients with insulin-dependent diabetes.

BACKGROUND: The presence of cytoplasmic islet-cell autoantibodies has been recognized as a risk factor for the development of diabetes mellitus in relatives of patients with insulin-dependent diabetes mellitus (IDDM), but the magnitude of the risk is unknown, as is the influence of other factors, such as age, sex, and race. METHODS: From 1979 through 1989, we studied 4015 initially nondiabetic relatives of 1590 probands with IDDM to determine the risk of IDDM according to the presence and titer of autoantibodies, as well as other factors. RESULTS: Of the 4015 nondiabetic relatives, 125 (3.1 percent) had islet-cell antibodies in their initial serum samples, and 40 contracted IDDM. Islet-cell antibodies were most frequent (4.3 percent) in relatives who were under 20 years of age (P = 0.001) and in those (4.8 percent) from families with more than one affected member (a multiplex pedigree) (P = 0.003). Independent risk factors for the development of diabetes in the relatives included age of less than 10 years at the time of the initial study (P = 0.001), membership in a multiplex pedigree (P = 0.02), and a positive test for islet-cell antibodies in the initial serum sample (P = 0.0001). Twenty-seven of the relatives in whom diabetes developed (67.5 percent) had positive tests for islet-cell antibodies before the diagnosis of IDDM, giving a relative risk of IDDM of 68 (95 percent confidence interval, 34 to 134) for antibody-positive relatives. Islet-cell-antibody titers of 20 Juvenile Diabetes Foundation units or higher were associated with an increasing risk of diabetes. CONCLUSIONS: Nondiabetic relatives of probands with IDDM who are in the first two decades of life, are members of multiplex pedigrees, and have increased titers of islet-cell antibodies are the most likely to contract IDDM themselves.

Adolescent↗
PubMed1989

Insulinlike growth factors in patients with active nephrotic syndrome.

The serum concentrations of insulinlike growth factors 1 and 2 (IGF-1 and IGF-2) were measured by specific radioimmunoassays in 25 nephrotic patients. The serum concentration of IGF-1 in nephrotic patients (mean +/- SEM, 169 +/- 17 ng/mL) was significantly lower than that observed in 20 control subjects matched for sex and age (338 +/- 36 ng/mL). The IGF-2 serum concentration was significantly lower in nephrotic patients (343 +/- 22 ng/mL) than in control subjects (898 +/- 80 ng/mL). The IGF-1 and IGF-2 150-kd and 45-kd carrier protein complexes were found in the urine of nephrotic patients, whereas there was no binding of radiolabeled IGF-1 or IGF-2 to IGF carrier proteins in the urine of control subjects. The low serum IGF-1 and IGF-2 levels observed in nephrotic patients could be partially due to the increased urinary losses of the IGF carrier proteins.

Adolescent↗
PubMed1989

Long-term immunoregulatory effects of therapy with corticosteroids and anti-thymocyte globulin.

Corticosteroids and anti-thymocyte globulin (ATG) have been extensively used in the treatment of autoimmune diseases, aplastic anemia and organ graft rejection; nonetheless, the precise mechanisms of action of these agents are unknown. Studies of their long term immunoregulatory effects, particularly in humans, have been limited. We examined the long term effects of therapy with ATG given for 2-4 weeks and prednisone for 2 months in 4 patients with newly diagnosed insulin dependent diabetes (IDD). Three matched newly-diagnosed untreated IDD patients and 17 healthy volunteers served as controls. No differences in total lymphocyte count, percentage of B cells, percentage of total T cells (CD3), helper-inducer T cells (CD4) or cytotoxic-suppressor cells (CD8), lymphocyte blastogenesis assays, or pokeweed mitogen-induced IgG secretion in T & B cell co-cultures were detected before therapy. A transient lymphopenia following ATG administration was the only immunological defect found in the first month of therapy. At 2 months, however, patients treated with ATG and prednisone had diminished immunoregulatory T cell function demonstrated by production of only 28 +/- 3% IgG expected in T & B co-culture, compared to 205 +/- 35% for untreated IDD patients and 107 +/- 13% for normals (p less than 0.01). This diminished IgG production resulted from excessive suppressor function, since co-cultures of T cells from treated patients with T and B cells from normal volunteers suppressed the latter's IgG production by 76 +/- 9%. This enhanced suppressor activity persisted for 3-6 months following therapy. Other immunological functions were not statistically different from those present at the inception of the study. Thus, treatment with corticosteroids and ATG produces long-term enhanced suppressor activity, a finding which suggests that treatment with combination ATG and Prednisone is a rational form of immunomodulation in conditions associated with decreased suppressor function.

Adolescent↗
PubMed1987

Is insulin-dependent diabetes mellitus a preventable disease?

Despite improvements in the ongoing care of individuals with insulin-dependent diabetes, the disease continues to produce significant morbidity and mortality, especially early in life, in individuals developing insulin-dependent diabetes in childhood or adolescence. In order to have a major impact on disease outcome, the best therapeutic approach is disease prevention. Because insulin-dependent diabetes results from autoimmune pancreatic beta cell destruction, the disease may be amenable to immunological intervention with immunotherapy. This is particularly exciting as we develop tools, such as islet cell autoantibody determinations, that allow diagnosis of individuals prior to clinical presentation. It is during this time-period when immune manipulation may be most efficacious in preventing further beta cell destruction, and otherwise eventual insulin dependence. As such trials are highly experimental, they must be conducted only in research centers staffed by physicians and scientists with expertise in diabetes, autoimmunity, and immunology.

Autoantibodies↗
PubMed1985

Correlates of biopsy-studied nephropathy in young patients with insulin-dependent diabetes mellitus.

We have correlated pathologic findings in kidney biopsies from 12 adolescents with proteinuria or hypertension with severity of limited joint mobility (LJM) and retinopathy. We compared mean glucosylated hemoglobin (GHB) and clinical findings in these patients with those in patients without proteinuria or hypertension. Severity of LJM correlated with basement membrane thickening. Protein excretion correlated with degree of mesangial matrix increase and basement membrane changes. Retinal changes were related to basement membrane thickness and duplication. Despite treatment, blood pressures were significantly higher in patients with nephropathy than in the comparison group. Glycemic control status was generally poor and did not correlate with pathologic changes. The narrow spectrum of control did not permit assessment of possible effects of milder metabolic derangement. However, the similarity of GHB values in the groups with and without nephropathy implicates other factors. The group with clinical nephropathy had more LJM than did the comparison group, reaffirming LJM as a risk factor for early microvascular disease. Biopsy changes of nephropathy may begin relatively early in the course of diabetes (less than 7 years in three of our patients) and is already advanced when proteinuria appears.

Adolescent↗
PubMed1984

Familial DiGeorge syndrome with tetralogy of Fallot and prolonged survival.

Two brothers with DiGeorge syndrome had tetralogy of Fallot with pulmonary valve atresia, illustrating similarity of the type of congenital heart disease (CHD) within affected families; the specific type of CHD differs between families. The late recognition of hypocalcemia in the older brother and his survival to age 21 years emphasizes the need to consider. DiGeorge syndrome in patients of all ages with hypocalcemia and congenital heart disease.

Adult↗
PubMed1984

Influence of vasopressin on renal hemodynamics in conscious Brattleboro rats.

The influence of vasopressin on renal hemodynamics was assessed by treating conscious Brattleboro homozygotes (DI rats) both acutely and chronically with physiologic doses of vasopressin. Intravenous infusions of vasopressin for 1 h, resulting in plasma vasopressin concentrations of less than 1.25, 2.3, and 8.0 pg/ml, respectively, failed to change glomerular filtration rate (GFR) or effective renal blood flow (ERBF) significantly, nor were there significant changes during 5 h of infusion. Body weight was not altered during these infusions. When synthetic vasopressin was given by osmotic minipumps for 10 days, with the rats gaining weight and thus changing the volume of their body fluids, GFR and ERBF increased significantly, by approximately 45 and 55%, respectively. Acute administration of volume alone, as well as acute vasopressin plus acute administration of volume, did not alter GFR or ERBF significantly. The data are compatible with the view that vasopressin, in physiologic plasma concentrations, exerts an influence on renal hemodynamics, that may be mediated through the long-term alteration of body fluid volumes. Alternatively or additionally, prolonged exposure of DI rats to vasopressin may increase their renal hemodynamics through tubuloglomerular feedback.

Animals↗
PubMed1984

Pulmonary function in insulin-dependent diabetes mellitus with limited joint mobility.

Patients with insulin dependent diabetes mellitus (IDDM) and limited joint mobility (LJM) were studied to determine if altered respiratory mechanics were another manifestation of a generalized disturbance in collagen metabolism. Lung volumes and maximal expiratory flow volume curves were measured in 23 patients with IDDM. Patients were divided into 2 groups: (1) 11 without LJM, and (2) 12 with severe LJM. The groups were matched for age, sex, and glycemic control but not for duration of IDDM. In patients with severe LJM, forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were significantly decreased (p less than 0.05). Total lung capacity (TLC), thoracic gas volume (TGV) at functional residual capacity (FRC) and residual volume (RV) were also significantly lower (p less than 0.05) in the severe LJM group. There was no evidence of air-flow obstruction in either group. Our results demonstrate an association between severe LJM and a significant decrease in lung volumes. This could be due to decreased lung compliance or restriction of chest wall expansion.

Adolescent↗
PubMed1983

Autosomal dominant hypoparathyroidism with variable, age-dependent severity.

Hypoparathyroidism (hypocalcemia, hyperphosphatemia, mild hypomagnesemia, and inappropriately low serum C-terminal parathyroid hormone concentration) was found in six members of a family representing three successive generations. No patient had aortic arch or conotruncal malformations, lymphopenia, or features of type I or type II autoimmune polyglandular syndromes. Two individuals had transient neonatal seizures without further difficulties despite persistent hypocalcemia. None of the four affected adults has had major complications of hypoparathyroidism (mental retardation, cataracts, or seizures). We believe that persistence of hypoparathyroidism after resolution of neonatal hypocalcemic seizures should prompt a survey of the family for hypoparathyroidism.

Adult↗
PubMed1982

Limited joint mobility in diabetes mellitus of childhood: natural history and relationship to growth impairment.

We report a prospective study of the recently recognized complication of limited joint mobility in childhood diabetes, summarizing data collected over the seven years after the initial description of this sign. Of 309 patients, ranging in age from 1 to 28 years, 30% had limited joint mobility. No race or sex influence on expression of limited joint mobility was found; its appearance was temporally more influenced by age than by duration of diabetes. Of 142 patients with diabetes onset before puberty and of longer than three years' duration, 74 had limited joint mobility. Disproportionate distribution of height percentiles for age characterized this entire group, but those with limited joint mobility had four times the skewing of those without (74 vs 37% below the twenty-fifth percentile). The presence or absence of thyroid microsome or islet cell antibodies did not relate significantly to limited joint mobility. Diabetes control, assessed subjectively by clinical estimation and objectively by hemoglobin A1 levels, was generally unrelated to the joint findings. For patients with diabetes duration less than five years, there was a significant association between hemoglobin A1 and limited joint mobility, but the variability in values explained by this association was small (11%).

Adolescent↗