Search PubMed⌕ Search

Biomedical subjects

A L Rosenbloom

Publications and source records attributed to A L Rosenbloom.

At least 19 recordsLinked to original sources
PubMed2001

Positional dissociation between the genetic mutation responsible for pseudohypoparathyroidism type Ib and the associated methylation defect at exon A/B: evidence for a long-range regulatory element within the imprinted GNAS1 locus.

Pseudohypoparathyroidism type Ib (PHP-Ib) is a paternally imprinted disorder which maps to a region on chromosome 20q13.3 that comprises GNAS1 at its telomeric boundary. Exon A/B of this gene was recently shown to display a loss of methylation in several PHP-Ib patients. In nine unrelated PHP-Ib kindreds, in whom haplotype analysis and mode of inheritance provided no evidence against linkage to this chromosomal region, we confirmed lack of exon A/B methylation for affected individuals, while unaffected carriers showed no epigenetic abnormality at this locus. However, affected individuals in one kindred (Y2) displayed additional methylation defects involving exons NESP55, AS and XL, and unaffected carriers in this family showed an abnormal methylation at exon NESP55, but not at other exons. Taken together, current evidence thus suggests that distinct mutations within or close to GNAS1 can lead to PHP-Ib and the associated epigenetic changes. To further delineate the telomeric boundary of the PHP-Ib locus, the previously reported kindred F, in which patient F-V/51 is recombinant within GNAS1, was investigated with several new markers and direct nucleotide sequence analysis. These studies revealed that F-V/51 remains recombinant at a single nucleotide polymorphism (SNP) located 1.2 kb upstream of XL. No heterozygous mutation was identified between exon XL and an SNP approximately 8 kb upstream of NESP55, where this affected individual becomes linked, suggesting that the genetic defect responsible for parathyroid hormone resistance in kindred F, and probably other PHP-Ib patients, is located >or=56 kb centromeric of the abnormally methylated exon A/B. A region upstream of the known coding exons of GNAS1 is therefore predicted to exert, presumably through imprinting of exon A/B, long-range effects on G(s)alpha expression.

Chromosome Mapping↗
PubMed2001

Type 2 diabetes in children.

The emerging epidemic of type 2 diabetes (T2DM) in young people reflects increasing rates of obesity and parallels the increasing frequency of T2DM in adults. As in adults, T2DM in children is part of the insulin resistance syndrome that includes hyperandrogenism seen as premature adrenarche and polycystic ovary syndrome, hypertension, dyslipidemia, and other atherosclerosis risk factors. Recent studies in children document risk factors for T2DM, and associated cardiovascular risk factors, including obesity, family history, diabetic gestation, and underweight or overweight for gestational age. Genetically determined insulin resistance or limited beta-cell reserve has been demonstrated in high-risk individuals, including first-degree relatives of girls with premature adrenarche. This genetic background, considered advantageous in a feast-and-famine existence (the thrifty genotype), is rendered detrimental with abundant food and physical inactivity, a lifestyle demonstrated to be typical of families of children with T2DM. The increasing incidence of T2DM in children and adolescents threatens to become a major public health problem. Risk factors for cardiovascular disease, hypertension, hyperlipidemia, and microalbuminuria are present at diagnosis of T2DM in Native American adolescents, indicating that insulin resistance has been present for some time before the diagnosis of diabetes was made. Case finding is likely to be beneficial in high-risk youths. Treatment is the same as that of adults. The only data on use of oral hypoglycemic agents in children have been with metformin. Community and governmental efforts to educate all children and their parents about the need for physical activity and dietary modification are essential to control this epidemic.

Child↗
PubMed2001

Changes in frequency and severity of limited joint mobility in children with type 1 diabetes mellitus between 1976-78 and 1998.

OBJECTIVE: Limited joint mobility (LJM), the earliest clinically apparent long-term complication of type 1 diabetes mellitus, is a risk indicator for microvascular complications, and its appearance is primarily affected by long-term metabolic control. We hypothesized that the prevalence of LJM had decreased during the past 20 years. STUDY DESIGN: We examined 312 subjects with type 1 diabetes mellitus, aged 7 to 18 years, using the same examination method and criteria as in studies of 515 subjects in this age group carried out between 1976 and 1978 for whom primary data were available, including age, duration of diabetes, and LJM stage. Statistical analyses included exact chi(2) tests, independent sample t tests, and unconditional logistic regression. RESULTS: There was a >4-fold reduction in frequency of LJM between 1976-78 and 1998 (31% vs 7%, P <.001), with a decrease in the proportion having moderate or severe LJM (35% vs 9%, P =.025). CONCLUSIONS: These findings confirm the hypothesis that the prevalence of LJM has decreased, most likely the result of improved blood glucose control during the past 2 decades.

Adolescent↗
PubMed2000

Is short stature a handicap? A comparison of the psychosocial functioning of referred and nonreferred children with normal short stature and children with normal stature.

OBJECTIVES: Normal short stature (NSS), defined as height below the 5th percentile for age and sex norms that is not due to illness, hormonal deficiency, or part of a dysmorphic syndrome, has been thought to have a deleterious effect on psychosocial functioning based on observations of referred populations. Recent studies of nonreferred children with NSS, however, have demonstrated normal function. This study directly compared the psychosocial functioning of referred children with NSS, nonreferred children with NSS, and children with normal stature. STUDY DESIGN: Participants, 90 children (46 boys, 44 girls) between 6 and 12 years of age (mean, 9. 6 years), were administered intelligence and achievement tests. Parents and teachers assessed adaptive and problem behaviors. Family adaptability and cohesiveness were measured. RESULTS: Intelligence and achievement for referred and nonreferred children with NSS were average. Referred children with NSS were reported to have more externalizing behavior problems and poorer social skills than nonreferred children with NSS and children in the control group. Family adaptability and cohesiveness were comparable across groups. CONCLUSIONS: Children with NSS have normal psychosocial function, and results suggest that externalizing behavior problems, attention problems, and poor social skills in children referred to clinics for NSS are inappropriately attributed to short stature.

Achievement↗
PubMed2000

New developments in type 1 (insulin-dependent) diabetes.

The Diabetes Control and Complications Trial has conclusively demonstrated that improved metabolic control leads to reduction in the rate of microvascular complications of diabetes. In order to allow patients to achieve improved metabolic control, much research has focused on improved methods of glucose monitoring and more physiologic ways of insulin delivery. The 2 most promising methods of minimally invasive blood glucose monitoring are the Glucowatch, using the technique of reverse iontophoresis to measure interstitial fluid glucose levels every twenty minutes and an implantable sensor, in which a catheter resembling that used for insulin delivery through a pump is impregnated with glucose oxidase at the tip. This device monitors blood sugars every few minutes, but like a holter monitor, must be downloaded in the physician's office. Still under development are (1) implantable subcutaneous sensors with a high and low blood glucose alarm and (2) sensors in which the patient will be able to download the data using a home PC. Advances in insulin delivery have included the availability of new insulin analogs which more closely simulate endogenous insulin release, with rapid acting analogs simulating the increase in insulin production that normally occurs after meals. Phase III clinical trials are in progress of a long-acting basal insulin without peak actions to simulate the low dose continuous production of the insulin which normally inhibits hepatic glucose production. In addition, use of the insulin pump has increased markedly since publication of the DCCT with the greatest increase being among adolescents. In addition to advances in treatment of diabetes, research has continued on curing the disease using islet cell transplantation and preventing the disease with agents such as insulin (DPT-1 Trial) and nicotinamide (ENDIT). This article provides an overview of recent advances in diabetes management and prevention.

Administration, Inhalation↗
PubMed2000

Physiology and disorders of the growth hormone receptor (GHR) and GH-GHR signal transduction.

GH exerts its actions through binding with two receptor molecules at the cell surface and interaction with Janus kinase and signal transducers and activators of transcription, and other likely effectors to stimulate metabolic effects and IGF synthesis. The circulating GH binding protein is the proteolytic product of the cell surface receptor and serves as a marker of receptor number and function. Thirty-six distinct mutations of the receptor in the extracellular and transmembrane domains cause a clinical picture of severe GH/IGF-I deficiency, whereas two dominant negative mutations of the intracellular domain result in a milder clinical syndrome. These mutations have provided insight into the physiology of the GH receptor. A few patients have been described with what appears to be primary GH insensitivity due to defective signal transduction by the GH-GH-receptor complex. Clinical and biochemical features of primary GH insensitivity are not a function of genotype, with as much variability in a genetically homogeneous population as in a heterogeneous one. Except for those dominant negative mutations where co-transfection of the mutant GH receptor gene with wild-type receptor gene has been informative, evidence for an effect of a single mutant allele remains speculative. Treatment of GH receptor deficiency with recombinant human IGF-I suggests that the absence of a direct effect of GH limits growth response.

Animals↗
PubMed2000

Treatment of type 2 diabetes mellitus in children and adolescents.

The treatment of type 2 diabetes mellitus (DM) is directed at decreasing insulin resistance and increasing insulin secretion. alpha-Glucosidase inhibitors slow carbohydrate absorption, resulting in reduced postprandial hyperglycemia; thiazolidinediones increase insulin sensitivity, especially in muscle and adipocytes; metformin decreases hepatic gluconeogenesis; sulfonylureas result in prolonged increases in insulin secretion; and meglitinide causes rapid, short-lived increases in insulin secretion. A survey of 130 pediatric endocrinology practices in the USA and Canada indicated that 48% of children with type 2 DM were treated with insulin and 44% with one or more oral hypoglycemic agents (OHA). Of those treated with OHA, 71% received metformin, 46% sulfonylureas, 9% thiazolidinediones and 4% meglitinide. Similarly, in the three university-based diabetes centers in Florida, 50% of the children with type 2 DM were treated with OHA. Treatment is based on symptoms at presentation. Patients identified on routine testing are often treated with exercise and diet alone. Those who are mildly symptomatic at onset are often started on OHA. Patients with substantial ketosis, ketoacidosis or markedly elevated blood glucose levels are initially treated with insulin, followed by a tapering of the dose and the addition of an OHA after blood glucose control is established and symptoms subside. There are no studies of the efficacy or compliance with treatment for type 2 DM in adolescents. Treatment is currently based on the clinical experience with adults. Controlled clinical trials in children are essential.

Adolescent↗
PubMed2000

An initial investigation of validation of the Matrix Analogies Test-Expanded Form in Ecuador.

This is a first preliminary study of the validity and reliability of the Matrix Analogies Test--Expanded Form in South America. Participants were 104 Spanish-speaking children between the ages of 5 and 17 years living in Ecuador. Values of Cronbach alpha ranged from .87 to .92 for the 4 groups of items and was .95 for the total score. Raw scores on the MAT increased across ages. Scores of boys did not differ significantly from those of girls. Total test scores correlated significantly with scores on the Raven Standard Progressive Matrices (r = .62, p < .005; r = .82 before controlling for age). A principal factor analysis conducted to provide evidence of the test's construct validity indicated that all four sets of items loaded substantially on one unrotated factor, presumed to be g. In sum, these results suggest that the test is a valid and reliable nonverbal measure of general cognitive ability in this population.

Adolescent↗
PubMed1999

Natural history of growth hormone receptor deficiency.

This review discusses the natural history of growth hormone receptor deficiency (GHRD) in relation to epidemiology, mortality, growth, certain aspects of body composition, and intellectual development. The majority of affected individuals are of Semitic origin and 90% come from the Indian peninsula, the Middle East, or elsewhere in the Mediterranean. There is a twofold increased mortality before the age of 7 years for children with GHRD. Affected adults may have increased cardiovascular risk resulting from increased total cholesterol and low-density lipoprotein cholesterol, unrelated to adiposity or insulin resistance. Intrauterine growth is affected minimally, if at all. Within a genetically homogeneous population in Ecuador, postnatal growth effects are as variable as in a large genetically heterogeneous population. There is no influence of parental heights. Areal bone mineral density is reduced in adults with GHRD, but estimated volumetric bone density (bone mineral apparent density) is normal. Intellectual development is unaffected by GHRD.

Adult↗