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Z Josefsberg

Publications and source records attributed to Z Josefsberg.

At least 19 recordsLinked to original sources
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↗
PubMed1999

Parenteral selenium supplementation in extremely low birth weight infants: inadequate dosage but no correlation with hypothyroidism.

OBJECTIVE: Selenium is an essential trace element, known to be important in thyroid metabolism. We speculated that parenteral selenium supplementation is inadequate in preterm infants and may contribute to the development of hypothyroidism. STUDY DESIGN: Serum selenium and thyroid function were evaluated on day 10 of life in extremely low birth weight infants. Selenium intake provided by parenteral nutrition was prospectively evaluated. RESULTS: Selenium intake was close to the recommended 2 micrograms/kg per day. Serum selenium values were 0.54 +/- 0.13 microM (mean +/- SD, n = 29). Selenium serum levels were low in 26 of 29 infants. In infants with subnormal serum selenium levels, free T4 was transiently low in 10 of 26 infants but was normal in 16 of 26 infants. No significant correlation was found between serum selenium levels and hypothyroidism. CONCLUSION: Current selenium supplementation guidelines may be inadequate in extremely low birth weight infants. However, selenium deficiency does not seem to play a major role in neonatal hypothyroidism.

Birth Weight↗
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

MR findings in hereditary isolated growth hormone deficiency.

PURPOSE: To describe the MR characteristics by which patients with hereditary isolated growth hormone deficiency (GHD) can be distinguished from patients with other types of GHD. METHODS: A total of 51 patients with GHD were examined prospectively with MR imaging. On the basis of familial occurrence of GHD and genetic analysis, 10 patients met the criteria for hereditary deficiency. In each case, the height of the pituitary gland, the presence and location of the posterior neurohypophysis, and the completeness of the stalk were recorded. The findings in the hereditary group were compared with those in the rest of the patients. RESULTS: In all 10 patients with hereditary GHD, the adenohypophysis, the neurohypophysis, and the stalk were normal. Of the other 41 patients, the height of the gland was normal in three (7%), the neurohypophysis was abnormal in all, and the stalk was truncated in all but two patients (95%). CONCLUSIONS: The subgroup of patients with hereditary GHD exhibited an anatomically normal pituitary-hypothalamic region. This is in contrast to the majority of patients with idiopathic GHD. MR imaging can contribute to the classification of patients with GHD.

Adolescent↗
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↗
PubMed1995

Effects of enalapril and nitrendipine on the excretion of epidermal growth factor and albumin in hypertensive NIDDM patients.

OBJECTIVE: To compare the effect of the antihypertensive drugs nitrendipine and enalapril on the excretion of epidermal growth factor (EGF) and albumin in hypertensive non-insulin-dependent diabetes mellitus (NIDDM) subjects. RESEARCH DESIGN AND METHODS: After a 4-week washout period, mildly hypertensive (systolic blood pressure [sBP] > or = 140 mmHg and/or diastolic blood pressure [dBP] > or = 90 mmHg) NIDDM patients with albuminuria (15-200 micrograms/min) were randomized into an 8-month-long therapy with either nitrendipine (n = 11) or enalapril (n = 10). Blood pressure, EGF, and microalbumin excretion were measured at baseline and throughout the treatment period. RESULTS: A significant fall in sBP was noticed in the enalapril group and in dBP in the nitrendipine group. In the enalapril group, EGF excretion progressively increased from 188 to 214 nmol/mmol creatinine after 6 weeks and to 274 after 8 months of therapy (P = 0.03). There was a significant fall in albumin excretion while patients were on enalapril, but in the nitrendipine group, neither albuminuria nor EGF excretion changed significantly. There was no correlation of improved EGF excretion with a decrease in albuminuria or BP. CONCLUSIONS: The angiotensin-converting enzyme inhibitor enalapril has been effective in decreasing albumin and increasing EGF excretion. Measurement of urinary EGF may provide a new valuable index of renal function.

Adult↗
PubMed1990

Excretion of epidermal growth factor (EGF) in diabetes.

Excretion of epidermal growth factor (EGF) is decreased in renal failure. We assayed it in diabetes mellitus in an attempt to relate it to clinical parameters, esp. those of diabetic nephropathy. EGF excretion declined with age but in all age groups of diabetic patients was below the first percentile for controls. In 26 control and 34 prepubertal diabetic children excretion was correspondingly 1126 +/- 442 and 932 +/- 489 pmol/mmol creatinine (P = 0.087); in 26 control and 42 diabetic adolescents below age 18, 778 +/- 222 and 676 +/- 335 (P = 0.023) and in 81 control and 83 diabetic adults, 371 +/- 153 and 235 +/- 140 (P less than 0.0001). Decreased excretion of EGF was seen in some patients without any diabetic complications. Excretion of EGF was independently and inversely correlated with age and duration of diabetes but not with type of diabetes, treatment, body built, C-peptide, plasma glucose, glycohemoglobin or retinopathy. A positive correlation was seen with creatinine clearance and a negative correlation, with albuminuria, but the strongest and the only independent correlation found by stepwise multiple variable selection was with serum creatinine (r -0.711, P less than 0.0001). EGF excretion was not elevated in patients with hyperfiltration. We conclude that EGF excretion is abnormal in many patients with diabetes and that this abnormality reflects a kidney function different from glomerular filtration or glomerular permeability.

Adolescent↗
PubMed1990

Congenital hereditary hypothyroidism--prenatal diagnosis and treatment.

Intrauterine diagnosis of congenital hypothyroidism was established on the basis of TSH concentration in amniotic fluid in the 22nd week of gestation for the offspring of a couple both known to have an iodide organification defect. Prenatal treatment consisted of intramniotic injections of 500 mcg Na-1-thyroxine, which was administered from the first amniocentesis until one week before delivery. Following delivery, the diagnosis was confirmed by the elevated level of TSH, 60.5 uU/ml, and a gradual decrease of fT4 to 0.8 ng/ml. Regular substitution therapy was commenced on the third day of life. The normal shape and location of the thyroid gland was demonstrated by Technetium scintiscan. At 18 months the infant revealed no significant deviation from normalcy in growth or mental capacity. This experience indicates that testing of amniotic fluid for TSH in the 22nd week of gestation can be diagnostic for congenital primary hypothyroidism. Furthermore, it is suggested that the treatment approach described is warranted in all cases in which there is a high risk of congenital primary hypothyroidism.

Amniotic Fluid↗
PubMed1990

Effect of oral clonidine, insulin-induced hypoglycemia and exercise on plasma GHRH levels in short-stature children.

Human growth hormone release is affected by a variety of pharmacological and physiological stimuli. We have studied the effect of oral clonidine, insulin hypoglycemia, and exercise on plasma hGH and GHRH levels in 31 healthy short-stature children. Thirteen underwent an oral clonidine test (0.15 mg/m2), 12 an iv. insulin test (0.1 U/kg), and 6 performed exercise (running for 10 min in a defined route). GHRH-1-44 was extracted from plasma on silica columns and determined by RIA. Although all three stimuli induced a marked increase in plasma hGH levels, only clonidine induced a significant increase in plasma GHRH levels. Maximal increment in GHRH during clonidine was 6.82 +/- 1.05 pmol/l (mean +/- SEM) as compared with 0.51 +/- 0.28 and 0.53 +/- 0.62 during hypoglycemia and exercise (p less than 0.0005 and p less than 0.005), respectively. An additional 24 subjects received TRH 0.2 mg/kg iv: 8 TRH alone, 8 TRH and insulin, and 8 TRH and clonidine. Only insulin potentiated the TRH-induced TSH response with a peak of 22.0 +/- 3.2 vs 16.0 +/- 0.8 and 15.3 +/- 1.5 mU/l (p less than 0.025) for TRH alone and TRH and clonidine, respectively. It is suggested that clonidine stimulates hGH secretion mainly through an enhancement of GHRH release, whereas stress stimuli such as hypoglycemia and exercise achieve hGH release by a different mechanism, possibly inhibition of somatostatin.

Administration, Oral↗
PubMed1988

When should hydrocortisone therapy be instituted in children with hypopituitarism?

The records of 72 pediatric and adolescent patients with multiple hypothalamic and/or pituitary hormone deficiencies of nontumoral origin who were followed up for years and receiving somatotropin, thyroxine, and sex hormones at the appropriate age have been reviewed. According to their corticotropin-releasing factor-corticotropin-cortisol (CAC) axis function as evaluated by basal plasma cortisol levels and the response of cortisol to insulin hypoglycemia and to corticotropin-releasing factor, the patients were divided into three groups: group 1 (n = 25), patients with multiple hypothalamic and/or pituitary hormone deficiencies with normal CAC axis; group 2 (n = 38), patients with partial CAC deficiency without cortisol replacement therapy (hydrocortisone); and group 3 (n = 9), patients with CAC deficiency receiving hydrocortisone therapy (5 to 10 mg/d). Repeated CAC axis evaluation in patients of group 2 over years revealed a progressive decrease in the basal and stimulated cortisol levels with age and pubertal advancement. Despite the low cortisol levels and the low cortisol response to insulin hypoglycemia, these patients did not have clinical symptoms until the end of puberty when nine of 24 patients complained of abdominal pain, weakness, or anorexia. Linear growth, which was followed up in all patients at regular intervals, showed a lower growth velocity and irregular growth in response to somatotropin treatment in the patients receiving low doses of hydrocortisone (group 3 patients when compared with group 2 patients not receiving hydrocortisone).

Adolescent↗
PubMed1987

Greater efficiency of human growth hormone therapy in children below five years of age with growth hormone deficiency. A 5-year follow-up study.

The effect of human growth hormone (hGH) therapy was studied in 39 prepubertal children with growth hormone deficiency (24 with isolated growth hormone deficiency; 15 with multiple pituitary hormone deficiencies) who had been treated for 2-5 years. They were divided into two groups according to age at the initiation of therapy: group A (n = 21), 0.7-4.8 years (mean chronological age, 2.9 +/- 1.4 years, and bone age, 1.2 +/- 0.9 years); group B (n = 18), 5.2-9.9 years (mean chronological age, 7.4 +/- 1.3 years, and bone age, 4.0 +/- 1.5 years). hGH was given at an initial dose of 2-4 IU 3 times/week, raised to 4-6 IU 3 times/week when growth velocity slowed. In the first year, the mean height SDS gain was 1.7 for group A and 0.8 for group B, and in the second year, 1.1 and 0.1, respectively. Subsequently this remained consistent. Bone age advancement was significantly slower in the younger group (3.8 vs. 5.8 years during 5 years) although this group had a greater catch-up response to therapy. It is concluded that hGH therapy is significantly more effective in achieving normalization of height when treatment is initiated at an early age.

Age Factors↗
PubMed1986

Responsiveness of pituitary hGH to GRH1-44 in juveniles with obesity.

The response of plasma hGH to an iv bolus injection of GRH1-44 (1 microgram/kg) was studied in 14 obese juveniles with a mean overweight of 4.7 +/- 0.05 standard deviation score (SDS). Two patterns of response were observed: in all 7 adolescents with 'simple' obesity not related to any particular disorder (group A) the response was good (a mean of 11.8 +/- 2.4 ng/ml) whereas in 6 of the 7 juveniles suffering from syndromes associated with obesity (group B) the response was poor (a mean of 3.2 +/- 1.4 ng/ml). This divergence in response could not be related to a difference in the degree of overweight. These results indicate that in group B with syndromes associated with obesity there may also be a pituitary impairment in addition to the hypothalamic defect.

Adolescent↗
PubMed1985

Some properties of the plasma hGH activity in patients with Laron-type dwarfism determined by a radioreceptor assay using human liver tissue.

A radioreceptor assay for human growth hormone (hGH) using the 100,000-g pellet of human liver tissue homogenates obtained from a 13-year-old male donor of a kidney transplantation is described. The dilution curves of the plasma hGH of 6 patients with Laron-type dwarfism (LTD) as well as those of the plasma hGH from 1 normal child and 2 acromegalic patients were all found to be parallel to the standard curve, suggesting that in the LTD syndrome the circulating hGH is biologically active.

Acromegaly↗