Zeev Josefsberg

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.

Relationship between changes in thyroid hormone level and severity of the postoperative course in neonates undergoing open-heart surgery.

Background:  Our aim was to determine whether the changes in thyroid function after open‐heart surgery in neonates depend on the postoperative course.

PENILE SIZE AND GROWTH IN CHILDREN AND ADOLESCENTS WITH ISOLATED GONADOTROPHIN DEFIENCY (IGnD)

Penile length and circumference were measured in twenty boys with isolated gonadotrophin deficiency, before and during the administration of androgen therapy. Their age ranged between 3 and 20 years. Considering as normal, measurements above the tenth centile, in all the patients but four the penile length was below normal, and in two it was borderline. Penis circumference was normal in two, borderline in four and subnormal in sixteen. Regular administration of androgen therapy increased penile length in eleven out of fourteen patients with achievement of normal length in four.

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] > 140 mmHg and/or diastolic blood pressure [dBP] >90 mmHg) NIDDM patients with albuminuria (15-200 μg/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.

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.

Bedside Scoring Procedure for the Diagnosis of Diabetic Peripheral Neuropathy in Young Patients with Type 1 Diabetes Mellitus

OBJECTIVE To test the applicability of a bedside scoring method for screening for diabetic peripheral neuropathy (DPN) in patients with type 1 diabetes mellitus (DM) in an ambulatory clinic. The prevalence of DPN was estimated and its risk factors identified. METHODS A total of 217 patients (102 males) with type 1 DM, median age 23.4 years (7.5-49 years) and median duration of DM 13.2 years (1-34 years) were evaluated for DPN using the bedside Neuropathy Disability Score (NDS). A score of 3-5 indicated mild DPN, 6-8 moderate DPN and 9-10 severe DPN. The presence of DPN was correlated with possible predictive factors. RESULTS The NDS was reliable and highly reproducible. The overall prevalence of DPN was 17.1%: mild in 14.3%, moderate in 2.3%, and severe in 0.5% of patients. The prevalence and severity of DPN were significantly related to long-term glycemic control (p < 0.001), DM duration (p < 0.005), age (p = 0.005), and duration of pubertal DM duration (p = 0.03). The prevalence of DPN was significantly associated with the presence of retinopathy (p < 0.002) and overt proteinuria (p < 0.005). CONCLUSIONS The NDS is a simple, reliable and reproducible screening method for use in the ambulatory clinic to identify the early signs of DPN, leading to early institution of intensive diabetes control measures and preventive foot care.

Acute Painful Neuropathic Cachexia in a Young Type I Diabetic Woman: A case report

Diabetic neuropathic cachexia is a rare syndrome of acute neuropathic pain and profound weight loss. It affects mainly middle-aged men with insulin or non-insulin treated diabetes (1,2) and resolves spontaneously within 10 months. Insulin-induced edema is an infrequent, usually mild and self-limiting complication of initiating or intensifying insulin therapy (3,4). We present a young female patient with long-standing type I diabetes and severe recurrent insulin-induced edema, in whom acute painful diabetic neuropathic cachexia developed following the institution of both tight glycemic control and ephedrine therapy for the insulininduced edema. This is, to the best of our knowledge, the first description of a young woman with diabetic neuropathic cachexia.

Greater Efficiency of Human Growth Hormone Therapy in Children below Five Years of Age with Growth Hormone Deficiency

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.

The influence of oral glucose loading on the insulin response to i.v. glucagon in children and adolescents

Abstract Fourteen children and adolescents with slight constitutional growth retardation (12 males and two females) aged from 7 1 2 to 18 1 2 , yr underwent an oral glucose tolerance test (OGTT 1.75 g/Kg followed at 180 min by an i.v. glucagon injection (0.03 mg/Kg). On a separate occasion these children underwent a simple i.v. glucagon test. Comparing the glucose and insulin response in the two glucagon tests for each child we found that whereas in the single test the blood glucose rose slowly with a peak at 30 min, in the combined test the peak was at 5 min. The mean peak values were similar ( 129 and 121 mg 100 ml ). The mean peak insulin response in the single test was 70 μU/ml (at 2 min) as compared to 253 μU/ml (at 2 min) in the combined test. Our studies provide further evidence for a direct effect of glucagon on insulin release and that glucose preloading augments this effect, without relation to the concomitant blood glucose concentrations.

LONG‐TERM ADMINISTRATION OF MEDROXY‐PROGESTERONE ACETATE (MPA) TO ACROMEGALIC PATIENTS

The long‐term administration of medroxyprogesterone acetate (MPA), 40 mg/day, has not proved to be an effective treatment of acromegaly. It neither stops the growth of the tumour nor adequately suppresses growth hormone secretion and it brings no change in the glucose intolerance and hyperinsulinism.