Basic research on the cellular mechanisms that control the expression of the gene encoding glucagon has led to the discovery of proglucagon. This precursor is processed by tissue-specific proteolysis to produce glucagon in pancreatic alpha-cells and a glucagon-like peptide-1 (GLP-1) in the intestine. GLP-1 is a hormone that is released by intestinal cells into the circulation in response to food intake. GLP-1 and gastric inhibitory peptide (GIP) which has also been termed glucose-dependent insulinotropic peptide appear to account for most of the incretin effect in the augmentation of glucose-stimulated insulin secretion. These two hormones have specific beta-cell receptors that are coupled to GTP binding proteins to induce production of cyclic AMP and activation of cyclic AMP-dependent protein kinase. It is proposed that at least one factor contributing to the pathogenesis of non-insulin-dependent diabetes mellitus (NIDDM) is desensitization of the GLP-1 receptor on beta-cells. At pharmacological doses, infusion of GLP-1, but not of GLP, can improve and enhance postprandial insulin response in NIDDM patients. Agonists of GLP-1 receptor have been proposed as new potential therapeutic agents in NIDDM patients. The observations that GLP-1 induces both secretion and production of insulin, and that its activities are mainly glucose-dependent, led to the suggestion that GLP-1 may present a unique advantage over sulfonylurea drugs in the treatment of NIDDM.
The rate of sudden infant death syndrome (SIDS) In Israel is relatively low (0.5-0.9:1,000). Home cardiorespiratory monitoring (HM) is an accepted practice in infants at high risk for SIDS. We report our experience with 261 infants who were referred to our SIDS prevention program. They included: 52 preterm infants with apneas and bradycardias, 83 SIDS siblings (3 twins), 22 infants of drug-addicted mothers, and 104 infants after an idiopathic apparent life-threatening event (ALTE). HM was performed in 40 of 52 preterms, 38 of 83 SIDS siblings, all 22 infants of addicted mothers and 67 of 104 post-ALTE. All received 24 h/day medical and technical backup as well as emotional support, and were closely followed until 15 months of age. None of the 261 infants died. Five infants experienced six ALTEs that required resuscitative measures; another 28 infants had monitor alarms judged as real by the caregivers. The average duration of HM was 3.2 months (range 1-7). In 8 of 167 cases the parents stopped HM earlier than recommended, and in 34 of 167 cases (20%), parents continued HM beyond the time when discontinuation was recommended by the medical personnel. Among the caregivers, 85% found HM to be reassuring and stated that it helped them to conduct a normal life. We suggest that in our population, HM may have a favorable effect on family life. With close backup and support, most families will benefit from HM and will gain reassurance that will enable them to conduct normal life.
The relationship between height and social class, independent of the effect of ethnic background was examined. This is a population-based study of 17-year-old israeli-born Jewish males born between 1966-1969 who underwent routine physical examination prior to army recruitment. Inductees descending from 9 ethnic backgrounds-Germany, Hungary, India, Morocco, Poland, Romania, Russia, Yemen and at least 3rd-generation israeli-born were used for this analysis. Anthropometric data was abstracted from the computerized induction examination; socioeconomic status (SES) was assigned according to the residence of each recruit. Statistical analysis included analysis of variance and chi square test for linear trend. Mean height of the total (reference) group was 173.7 cm, ranging from 172.0 cm in the lowest SES level to 175.1 cm in the highest level. The proportion of individuals above the 85th percentile of height of the reference group, increased linearly from 8.7% (lowest SES) to 18.5% (highest SES) (p < 0.01). The mean height of recruits differed considerably among ethnic groups in each SES level and ranged from 170.8 cm (Yemenites) to 175.4 cm (Russian and Romanian) in the total group. In each ethnic group, height differences between extreme levels of SES were observed ranging from 2.3 cm (Morocco) to 4.3 cm (Russia). We conclude that height among 17-year old israeli-born males is positively associated with SES after controlling for ethnicity.
The current gold standard test for diagnosis of Helicobacter pylori involves histological staining and/or urease testing of antral biopsy specimens. However, these methods are invasive, and alternative non-invasive methods, i.e. the urease breath test and serological tests, are available. The test for H. pylori-specific serum immunoglobulin G (IgG) is now available commercially. The aim of this study was to compare the gold standard tests for diagnosis of H. pylori to the non-invasive method of detecting IgG antibody in the serum. Two hundred and twenty-five (225) subjects were tested for H. pylori by histological staining, urease testing, direct microscopy of antral biopsy specimens and quantification of serum IgG antibody. The population examined was divided into 2 groups--a group of 52 patients with no gastrointestinal symptoms and a group of 173 patients with dyspepsia. Out of 173 dyspeptic patients, 22 (12.7%) were false-positive to H. pylori. Out of 52 non-dyspeptic subjects, 30 (57.7%) were false-positive (p < 0.0001). The sensitivity and specificity were 91.6% and 51.7%, respectively. The specificity and positive predictive value increased by approximately 30% when the subjects examined were in the younger age group (< 30 years), while the sensitivity and the negative predictive value did not change significantly. This study indicates that serological testing is not recommended for diagnosis nor is it recommended for follow-up treatment, especially among the older age group (> 30 years).
Hypertension is often associated with impaired glucose tolerance and high insulin levels, factors that contribute to insulin resistance. The present study evaluates the effect of acarbose, a hypoglycemic drug that inhibits carbohydrate digestion in sucrose-induced hypertension in rats. The effects of diets fed to 3 groups of rats for a 16-week period were studied: sucrose + NaCl (1% wet volume [w/v]) with acarbose (0.04% wet weight [w/w]), sucrose + NaCl (1% w/v) without acarbose, and a third diet of complex carbohydrates. There was no statistical difference in the body weight between rats fed with or without acarbose. Fasting glucose levels were significantly lowered when treated with acarbose. Postprandial blood glucose and insulin levels were attenuated in rats fed sucrose + acarbose. Systolic blood pressure increased significantly (p < 0.001) in rats fed sucrose + NaCl for 3 months, whereas systolic blood pressure of acarbose-fed rats remained at the initial level. Blood pressure changes in the complex carbohydrate-fed group were lower than in rats fed sucrose. The urinary volume, Na+, and K+ of rats fed acarbose tended to increase compared to the acarbose-free diet (p < 0.05). We conclude that high insulin levels, impaired glucose tolerance and Na+ retention may contribute to the development of sucrose-induced hypertension. Acarbose prevents sucrose-induced increases in plasma glucose and insulin levels. Increases in urinary Na + may contribute indirectly to this effect with resultant normal systolic blood pressures.
Under conditions of beta-adrenergic receptor stimulation, cardiac performance is enhanced. cAMP-dependent phosphorylation of proteins located in the sarcolemma, in the membrane of the sarcoplasmic reticulum (SR), and in the myofibrils of the cardiomyocytes, mediates the effects of catecholamines on the heart. Altered Ca2+ handling leads to increased levels of intracellular free Ca2+. This is mainly responsible for the enhanced contractility of the myocardium that can be observed following beta-adrenergic receptor stimulation. Phosphorylation of the thin filament regulatory protein troponin I (TnI), on the other hand, decreases the Ca2+ sensitivity of the myofilaments, which means that the Ca2+ concentration necessary for the development of half-maximal force is increased. Cardiac TnI has a 26-33 amino acid N-terminal extension that is not present in fast and slow skeletal muscle TnI isoforms. Within this segment, two adjacent serine residues can be phosphorylated by a cAMP-dependent protein kinase. Replacement of endogenous TnI by different mutants obtained using site-directed mutagenesis of one or both of the serine residues has shown that only the bis-phosphorylated form decreases the Ca2+ sensitivity. This Ca2+ desensitizing effect, together with an increased rate of Ca2+ uptake into the SR due to phosphorylation of the SR membrane protein phospholamban, is responsible for the relaxation-enhancing effect (lusitropic action) of catecholamines. The latter is an important determinant of coronary perfusion and rapid diastolic filling of the ventricles, and is also a prerequisite for the elevation of heart rate that accompanies beta-adrenergic receptor stimulation.
It is well established that old people living in institutions are more susceptible to tuberculous reactivation and exogenic infection than the general population. Therefore, annual screening with a tuberculin (T) skin test is suggested. Unfortunately, the specificity and sensitivity of this test is limited because of cross-reactivity with non-tuberculous mycobacteria (NTM) and anergy. We therefore investigated the possibility that a simultaneous test with NTM antigen might be helpful in the interpretation of the T test in the elderly. We tested 220 inhabitants of a geriatric institution in Israel simultaneously with T and Mycobacterium scrofulaceum sensitin (S). Ninety-six subjects reacted to the T test, and 64 of them reacted to S as well. In this last group, 38 reacted more to T, 22 more to S, and 4 reacted equally to both antigens. Of the 124 subjects who did not react to T, 24 did react to S and 123 were retested with T. Twenty-two of the latter group had a positive booster effect, but 9 of the positive booster responders initially reacted to S. The difference between the proportions of the positive booster effect in the responders and the non-responders to S was significant. We conclude that in an area where infection with NTM is present a simultaneous S test may clarify the meanings of initial and booster-positive responses to T in the elderly, as well as exclude anergy when the T test is negative.
Transurethral thermal treatment has been used to relieve obstructive voiding symptoms in 10 patients with prostate cancer. All patients failed previous endocrine treatment for the relief of obstructing urinary symptoms. Temperature ranging from 46 degrees C to 47 degrees C was applied transurethrally using Thermex II thermal system. Treatment was given in a single session for a duration of 180 minutes on an outpatient basis without sedation. Mean duration of follow-up was 8.5 months (range 4-13 months). Maximal urine flow rate, post-voiding residual volumes and changes in subjective symptoms were used to assess treatment response. Removal of an indwelling catheter was possible in all 3 patients with chronic retention. Urinary infection (2 patients) and temporary retention (3 patients) were the only complications recorded. The preliminary results suggest that transurethral hyperthermia is a well-tolerated, safe and effective procedure for obstructive voiding symptoms in patients with hormone refractory prostate cancer. Longer follow-up and a larger group of patients is required to assess this alternative modality.
Anemia of chronic renal failure (CRF) prior to initiation of dialysis is an important cause of morbidity and requires early therapeutic intervention. The current study was designed to investigate the efficacy and tolerability of a therapeutic algorithm for anemia of CRF in pre-dialysis patients which is based on low dose once-a-week subcutaneous (s.c.) administration of recombinant human erythropoietin (r-HuEPO). Thirty-one patients participated in a prospective open-label multicenter study. At baseline, hemoglobin was 8.8+/-0.1 g/dl, transferrin saturation 27+/-2%, ferritin 207+/-28 ng/ml and serum creatinine 4.7+/-0.2 mg/dl. Treatment with r-HuEPO was started at a fixed s.c. dose of 4,000 units once weekly, irrespective of body weight, and titrated upwards or downwards according to a predetermined algorithm. Hemoglobin rose to levels >10 g/dl within 8 weeks and remained stable throughout the remaining period of the study. By week 24, most patients required less than or equal to 4,000 units/week as maintenance dose. Transferrin saturation and ferritin concentration tended to fall during the course of r-HuEPO treatment, despite iron supplementation. There was no change in white blood cell or platelet count. Eight patients required an increase in antihypertensive therapy, but blood pressure remained well-controlled. Twelve patients failed to complete the full length of the study, 7 of them because dialysis had to be initiated. The rate of decline in kidney function, however, was not altered by r-HuEPO. We conclude that the proposed therapeutic algorithm is practical, efficacious, safe, and cost-effective.
Ectopic atrial tachycardia (EAT) is an uncommon type of supraventricular tachycardia. It is usually chronic, incessant and resistant to pharmacologic therapy. Radiofrequency catheter ablation, which has become one of the treatments of choice for the more common types of supraventricular tachycardia, has recently also been shown to be effective in EAT. Radiofrequency catheter ablation was attempted in three patients with incessant EAT. Two of the patients, aged 7 and 13 years, had signs of left ventricular dysfunction, and the EAT originated in the left atrium. The remaining patient, aged 72 years, had a right EAT with normal left ventricular function. Radiofrequency ablation was guided by endocardial atrial mapping to locate the site of earliest atrial activation. Ablation was successful in all three patients, with complete cure of the tachycardia for a follow-up period of 12 to 19 months. Radiofrequency catheter ablation of EAT is highly successful and should be considered as one of the treatments of choice for this arrhythmia.
