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N Weintrob

Publications and source records attributed to N Weintrob.

10 recordsLinked to original sources
PubMed2000

Combined clonidine-short-ACTH test for the simultaneous assessment of growth hormone reserve and hypothalamic-pituitary-adrenal axis integrity in children.

OBJECTIVE: To determine the feasibility of using the combined oral clonidine and the short-ACTH test instead of the sometimes dangerous insulin-induced hypoglycemia test as a screening procedure, for the simultaneous assessment of growth hormone reserve and hypothalamic-pituitary-adrenal axis integrity in children with growth retardation. DESIGN: Evaluative study. METHOD: Seventy-three children (52 males) aged 11+/-3 years with attenuated growth (group 1) were tested by combined clonidine (150 microg/m(2)) and short-ACTH test (either the standard 250 microg or the low-dose 1 microg/1. 73 m(2)). Thirty-one children received no pretreatment (nonprimed) (subgroup 1NP), and 42 were primed with ethynylestradiol 40 microg/m(2)/day two days before testing (subgroup 1P). The control group for the short-ACTH test (group 2) consisted of 42 children and adolescents (13 males) aged 12+/-3 years with early or accelerated puberty or premature closure of epiphyses, who received ACTH only (21 standard, 21 low-dose) with no evidence of adrenal or pituitary pathology. The peak GH response was compared between the primed and the nonprimed group 1 subjects, and the cortisol levels were compared between the combined test subgroups and the controls. The peak pass level for growth hormone was 10 ng/ml; the peak pass level for cortisol was 520 nmol/l. RESULTS: Sixty-four of the 73 children in group 1 (87.7%) showed a growth hormone level of >/=10 ng/ml on the first stimulation test, including 26/31 (84%) nonprimed and 38/42 (90.5%) primed. Of the 9 patients who failed the first clonidine test, 4 also failed the second, primed test, including 1/5 nonprimed patients (20%) and 3/4 primed patients (75%). This yielded a GH deficiency/insufficiency rate of 5.5% and a rather low false-positive rate of 13.3% (4/30) for the nonprimed subjects and 2. 6% (1/39) for the primed subjects. Peak 30-min cortisol in response to ACTH stimulation was similar in the patients who underwent the 250 microg or the 1 microg test within each group (subgroup 1NP, subgroup 1P and group 2); therefore, the results for the two tests were considered together. Compared with group 2, subgroup 1NP patients had a similar 30-min cortisol response (P=NS), and subgroup 1P patients had a much higher response (P<0.05) (group 2=690+/-145 nmol/l, subgroup 1NP=772+/-195 nmol/l, subgroup 1P=934+/-209 nmol/l). However, there was no significant difference in the increment in cortisol response between the three groups. CONCLUSIONS: Our results suggest that the combined clonidine-short-ACTH test is a reliable and safe tool for the simultaneous assessment of growth hormone reserve and hypothalamic-pituitary-adrenal axis integrity in children.

Adolescent↗
PubMed1999

Gastric emptying in patients with type I diabetes mellitus.

Diabetic autonomic neuropathy is a known complication of long-standing diabetes. The present study was designed to study the prevalence of asymptomatic prolonged gastric emptying (GE) in young patients with IDDM and its correlations with disease duration and autonomic nerve function. The study population included 40 poorly controlled patients, mean age 17.6 +/- 4.6 years, with a disease duration of 1-17.5 years, and 20 age- and sex-matched controls. Autonomic nerve functions were assessed by standard cardiovascular reflexes, and gastrointestinal (GI) symptoms were assessed by a detailed questionnaire. GE was assessed by electrical impedance tomography (EIT), at 2 hours after a standard semisolid meal. Mean half-time gastric emptying was significantly prolonged in diabetic patients, 54.80 +/- 26.63 versus 40.37 +/- 8.62 min (p < 0.05), with a higher prevalence in the first 3 years and after 10 years of disease duration. No differences were found between diabetics and controls regarding cardiovascular tests. No correlations were found between age, GI scores, cardiovascular tests, and GE. Patients with IDDM may suffer from prolonged GE. This is not always accompanied by autonomic impairments. As impaired gastric emptying may involve poor glycemic control and early satiety, patients with difficulties in metabolic control or poor caloric intake should be studied for the possibility of delayed gastric emptying.

Adolescent↗
PubMed1999

Neonatal pig islets induce a lower T-cell response than adult pig islets in IDDM patients.

BACKGROUND: Pancreatic pig islets may provide a substitute in the future for difficult to obtain human islets for transplantation in insulin-dependent diabetes millitus (IDDM) patients. However, the immune response to xenografts may significantly hamper this approach. Because neonatal tissue is believed to be less immunogenic, we examined whether the T-cell response to neonatal pig islets differs from the response to adult islets. METHODS: The T-cell proliferative response to different concentrations of sonicated neonatal and adult pig islets, as well as to insulin and mitogens, was tested in 21 recent onset IDDM patients and 21 healthy controls. We determined the presence of various circulating islet autoantibodies and their association with the T-cell response in IDDM patients. RESULTS: In the IDDM patients, sonicated adult pig islets (at 1 microg protein/ml) induced a significantly higher frequency (12 of 21 vs. 1 of 21, p<0.001) and magnitude (2.58+/-0.44 vs. 1.38+/-0.13, p<0.02) of positive T-cell responses than neonatal islets at the same concentration. Similar results were obtained with a 10-fold higher concentration of islet sonicate. There was no significant association between the individual T-cell responses and the presence of circulating autoantibodies in IDDM patients. CONCLUSION: These results indicate that neonatal pig islets induce a lower T-cell reactivity than adult islets, suggesting that the neonatal tissue may be immunologically more suitable for future islet xenotransplantation.

Adolescent↗
PubMed1998

[Islet autoantibody assays in type I diabetes: superiority of passage from use of ICA to traditional tests].

Islet cell antibodies (ICA) continue to serve as the basis of the principal serological test for definition of active autoimmunity of beta-cells. Its disadvantages are the need for human pancreatic tissue and difficulty in obtaining quantitative results. In the past decade biochemically-defined beta-cell antigens were described, leading to the development of sensitive and specific autoantibody assays, to predict insulin-dependent diabetes mellitus (IDDM). We examined the value of combined biochemically-based serological assays, such as autoantibodies to insulin (IAA), glutamic acid decarboxylase (GADA) and ICA512 (ICA512A) to replace the traditional ICA assay. Blood samples of 114 newly diagnosed IDDM patients, aged 12 +/- 5 yrs (range 2 months-29 years) were tested for ICA (indirect immunofluorescence), IAA, GADA and ICA512A (radiobinding assay). The latter 2 assays were performed using recombinant human [35S]-labeled antigen produced by in vitro transcription/translation. We found that fewer sera scored positive for ICA and/or IAA (80.7%, 92/114) than for 1 or more of IAA, GAD, or ICA512 (88.6%, 101/114). We conclude that combined testing for IAA, GAD and ICA512 can replace the traditional ICA/IAA test to predict IDDM and is helpful in the differential diagnosis of insulin-dependent and noninsulin-dependent diabetes.

Adolescent↗
PubMed1998

HLA class II immunogenetics of IDDM in Yemenite Jews.

The association between HLA-DR and DQ and insulin dependent diabetes mellitus (IDDM) was analyzed in 47 patients and 76 controls of Yemenite Jewish origin. The IDDM susceptibility alleles DRB1*03011, DQA1*0501, DQB1*02 and DRB1*0402, DQA1*0301, DQB1*0302 found in Caucasians had a very strong predisposing effect also in the Yemenite IDDM group. The DRB1*07, DQA1*0201 and DQB1*02 alleles were found to have a strong negative association with IDDM. None of the patients carried DRB1*07 and DQA1*0201 compared with healthy controls (43.7%). Our analysis revealed that the DRB1*03011 DQA1*0501 DQB1*02/DRB1*04 DQA1*03 DQB1*0302 heterozygous genotype confers the highest susceptibility (59.6% in patients vs. 0% in controls). The homozygous DRB1*03 and DRB1*04 genotypes were also found to be positively associated with the disease. 81% of the patients compared to 1.3% of controls carried the susceptibility alleles on both haplotypes. In conclusion, the development of IDDM in Yemenite Jews is strongly dependent on the presence of the susceptibility HLA alleles and on the absence of the DRB1*07 haplotype. The Yemenite Jewish group is uniquely homogenous with regard to genetic susceptibility factors involved in the process of IDDM, and may thus be an ideal model for further genetic studies.

Alleles↗
PubMed1998

Standard and low-dose short adrenocorticotropin test compared with insulin-induced hypoglycemia for assessment of the hypothalamic-pituitary-adrenal axis in children with idiopathic multiple pituitary hormone deficiencies.

Insulin-induced hypoglycemia (IIH) is the gold standard test for assessment of the integrity of the hypothalamic-pituitary-adrenal (HPA) axis, but it may be hazardous. We sought to determine whether the standard (250 micrograms) or low-dose (1 microgram/1.73 m2) short ACTH test can replace IIH in patients with idiopathic multiple pituitary hormone deficiencies (MPHD). Three groups of subjects were studied: 1) control group, children with early or accelerated puberty and no other evidence of adrenal or pituitary pathology (n = 13, age 10.1 +/- 2.2 yr, 3 males); 2) patients with idiopathic hypothalamic pituitary insufficiency and either isolated GH deficiency or MPHD and preserved HPA function (n = 20, age 13.7 +/- 4.4 yr, 13 males); and 3) MPHD patients with impaired HPA axis function (n = 10, age 16.8 +/- 4.8 yr, 9 males). IIH and the 250 micrograms and 1 microgram/1.73 m2 ACTH tests were performed in groups 2 and 3; group 1 underwent only the ACTH tests. Pass peak cortisol level was defined as 520 nmol/L. No significant difference was noted between the standard and low-dose tests in the 30-min cortisol response to ACTH. Basal and peak cortisol levels attained on both ACTH tests were similar in groups 1 and 2 and significantly lower in group 3 (P < 0.0001). Both the 250 and 1 microgram ACTH tests were highly correlated with IIH (r = 0.71, P < 0.0001 for the 250 micrograms, r = 0.7, P < 0.0001 for the 1 microgram, n = 30), and both demonstrated high sensitivity (90% each) and specificity (100% and 90%, respectively) compared with IIH. We conclude that in idiopathic MPHD patients, both the standard and low-dose ACTH tests are equivalent to IIH in detecting HPA insufficiency. We suggest that they can replace IIH as a screening test for the integrity of the HPA axis in children with suspected MPHD.

Adolescent↗
PubMed1997

Non-classical 21-hydroxylase deficiency in infancy and childhood: the effect of time of initiation of therapy on puberty and final height.

OBJECTIVE: To review the characteristics of children with non-classical 21-hydroxylase deficiency (NC-21-OHD) diagnosed during infancy and childhood, and to evaluate the relationship of pubertal and bone age maturation at initiation of glucocorticoid therapy with the course of puberty and final height. DESIGN: We retrospectively compared the course of puberty, growth pattern and final height in two groups of patients: group A (two males, six females), hydrocortisone (HC) treatment 7.5-15 mg/m2 per 24 h, initiated > or = 1 year before onset of true puberty and group B (seven females), treatment started with the first signs of true puberty present. PARTICIPANTS: Thirteen girls and two boys with NC-21-OHD diagnosed at age range 0.5-10.6 years were followed-up for 9.0 +/- 3.8 years (mean +/- S.D). Therapy with HC was initiated because of signs of hyperandrogenism, accelerated growth and bone maturation, or true precocious puberty. The HC dose was adjusted according to linear growth and basal plasma androgen levels. RESULTS: Puberty and peak height velocity developed significantly earlier in the girls of group B: gonadarche at 7.9 +/- 1.4 years and peak height velocity at 9.2 +/- 1.4 years vs 10.2 +/- 0.4 years (P = 0.002) and 11.5 +/- 0.7 years (P = 0.006) in group A. Menarche, however, occurred only slightly earlier in group B (12.0 +/- 1.1 vs 12.8 +/- 0.5 years, P = 0.068). All eight children in group A achieved a final height within the range of their mean parental height standard deviation scores (SDS) in comparison with only 1/7 in group B (P = 0.0014). Seven of eight patients who started therapy before a bone age of 9 years achieved a final height within the parental height SDS range, compared with 2/7 who started therapy later (P = 0.041). The final height SDS was significantly better for group A (0.05 +/- 0.19, mean +/- S.E.M.) than group B (-1.63 +/- 0.23, P = 0.0007), even when adjusted for a significant effect of the mean parental height SDS (A. -0.63 +/- 0.28; B, -0.89 +/- 0.31, P = 0.0245, ANCOVA). CONCLUSION: Every child with signs of excess androgen activity or early puberty should be studied for the possibility of NC-21-OHD. Screening programs for populations with a high frequency of the gene for NC-21-OHD would facilitate early diagnosis and treatment. Pubertal stage and bone age at the introduction of therapy dictate height prognosis. Initiation of therapy before puberty with careful follow-up and HC dose adjustment can assure the achievement of genetic adult height.

Adrenal Hyperplasia, Congenital↗
PubMed1996

Normal proinsulin processing despite beta-cell dysfunction in persistent hyperinsulinaemic hypoglycaemia of infancy (nesidioblastosis).

Persistent hyperinsulinaemic hypoglycaemia of infancy (PHHI) is a genetic disorder which causes severe hypoglycaemia in the neonate. The beta cells fail to respond to changes in blood glucose levels in all the stages of the disease, which often ends with NIDDM. Fasting insulin, intact proinsulin and des 31,32 split proinsulin levels were measured in PHHI patients with active disease, patients after partial pancreatectomy, and those in clinical remission. All but one of the pancreatectomized patients developed diabetes and were hyperglycaemic on evaluation. Fasting insulin was comparable in pancreatectomized and medically treated patients. Des 31,32 split proinsulin levels were much higher in pancreatectomized compared to non-pancreatectomized patients (10.7 +/- 2.5 vs 3.4 +/- 0.8 pmol/l, p = 0.001) and age-matched control subjects (3.8 +/- 1.4 pmol/l, p = 0.018). Also the ratio of des 31,32 split proinsulin to total insulin plus proinsulin-like peptides was higher in pancreatectomized patients (18.7 +/- 2.8 vs 7.2 +/- 0.8% in non-pancreatectomized patients, p = 0.001, and 6.8 +/- 2.1% in normal control subjects, p = 0.004). Furthermore, des 31,32 split proinsulin was the dominating species of proinsulin-like molecules in the pancreatectomized patients (62.7 +/- 1.6% vs 45.5 +/- 3.8%, and 49.0 +/- 3.2% in non-pancreatectomized patients and control subjects, respectively, p = 0.001 and p = 0.0002). Intact proinsulin levels, and the proinsulin percentage, tended to be higher in pancreatectomized patients; however, the differences did not reach statistical significance. All parameters were similar in non-pancreatectomized patients and age-matched control subjects. Subgroup analysis showed comparable proinsulin-like peptide levels in patients with active disease and those in apparent clinical remission. Fasting levels of insulin and proinsulin-like peptides were also measured in a larger group of healthy children and young adults. Insulin and des 31,32 split proinsulin increased with age, the differences being most prominent when the young age group (0-8 years) was compared to the older groups (8-16 and > 16 years). The fasting levels of plasma insulin were correlated with those of intact proinsulin and des 31,32 split proinsulin (r = 0.82 and 0.81, respectively). Fasting insulin, intact proinsulin and des 31,32 split proinsulin were correlated with BMI (r = 0.55, 0.56 and 0.53, respectively). In summary, relative hyperproinsulinaemia was noted only in PHHI patients with increased secretory demand following pancreatectomy, but not in patients with active disease or those in spontaneous clinical remission. These findings suggest that abnormal proinsulin processing is not an intrinsic feature of PHHI despite the severe beta-cell dysfunction.

Adolescent↗
PubMedDate not supplied

Short- and long-range complications in offspring of diabetic mothers.

The perinatal mortality rate of infants of diabetic mothers (IDMs) has declined dramatically from 250 per 1000 live births in the 1960s to a near-normal 20 per 1000 live births in the 1980s. Five to 8% of all IDMs suffer from major congenital malformations, and it is the latter that are responsible for 50% of these perinatal deaths. It has been shown that tight glycemic control prior to conception and during pregnancy can prevent an excess rate of congenital malformations, fetal macrosomia, birth trauma, and neonatal respiratory distress syndrome. We briefly review the short- and long-range complications that occur in offspring of diabetic mothers (ODMs) from gestation through young adulthood. Short-term neonatal complications, such as hypoglycemia, hypocalcemia, hypomagnesemia, hyperbilirubinemia, and polycythemia, are related mainly to fetal hyperinsulinemia, hypoxemia, and prematurity. They are readily controllable within the setup of modern neonatal intensive care units. Long-range complications include an increased rate of childhood and adolescent obesity, impaired glucose tolerance or diabetes mellitus, and subtle neuropsychological dysfunctions. These may be related to the severity of the maternal hyperglycemia during pregnancy, the consequent fetal hyperinsulinemia, and third trimester maternal lipid metabolism disturbances. Today we have at hand the knowledge and tools to properly treat both pregestational and gestational diabetes. Increased education of the general practitioner and the target population regarding early referral of pregestational diabetic mothers and the implementation of screening programs for gestational diabetes will further reduce diabetic pregnancy-related morbidity.

Adolescent↗