Israel Medical Association Journal

Type 1 diabetes mellitus is caused by an autoimmune destruction of pancreatic islet beta cells, leading to insulin deficiency. Beta-cell replacement is considered the optimal treatment for type 1 diabetes, however it is severely limited by the shortage of human organ donors. An effective cell replacement strategy depends on the development of an abundant supply of beta cells and their protection from recurring immune destruction. Stem/progenitor cells, which can be expanded in tissue culture and induced to differentiate into multiple cell types, represent an attractive source for generation of cells with beta-cell properties: insulin biosynthesis, storage, and regulated secretion in response to physiologic signals. Embryonic stem cells have been shown to spontaneously differentiate into insulin-producing cells at a low frequency, and this capacity could be further enhanced by tissue culture conditions, soluble agents, and expression of dominant transcription factor genes. Progenitor cells from fetal and adult tissues, such as liver and bone marrow, have also been shown capable of differentiation towards the beta-cell phenotype in vivo, or following expression of dominant transcription factors in vitro. These approaches offer novel ways for generation of cells for transplantation into patients with type 1 diabetes.

Background: Idiopathic left ventricular tachycardia with a right bundle branch block configuration and left axis deviation, first described by Belhassen et al., is a rare electrocardiographic-electrophysiologic entity. Radiofrequency catheter ablation has been proposed as a good therapeutic option, but the best criteria for determining the optimal site of ablation are still under debate.

Objectives: To report the clinical features, electrophysiologic characteristics, results of RFA[1], and long-term outcome in 18 patients with "Belhassen's VT” treated in our laboratory during the last 10 years, stressing the best electrophysiologic criteria for determining the optimal site of ablation.

Methods: Eighteen consecutive patients with this specific VT[2] underwent RFA in our laboratory during the last 10 years. RFA was acutely successful in 17 patients after one or two procedures (15 and 2 patients, respectively) using 4.1 ± 2.2 RF pulses. The putative ablation sites were defined by good pace-mapping (3 patients), earliest recorded Purkinje spike prior to the QRS onset during VT or sinus rhythm (6 patients), earliest endocardial activation during VT (1 patient), and diastolic potential preceding the Purkinje spike during VT and/or late diastolic potential in sinus rhythm (7 patients). In the patients with a definite successful ablation, the ratio of successful to unsuccessful radiofrequency pulse delivery to the diastolic potential site was compared to that of other methods. The ratio of successful RFA at the diastolic potential site (5:8) was higher than in the other methods (8:31), and the difference was statistically significant (P = 0.05). Successful ablation sites were more basal when the diastolic potential site was chosen.

Conclusion: The results of the present study confirm the high success rate and safety of RFA using conventional techniques in the management of “Belhassen VT,” suggesting that this procedure can be proposed as a first-line therapy. Ablating at a site demonstrating a late diastolic potential is at least as effective as ablating at a ventricular exit site, although the use of combined electrophysiologic criteria may be the optimal approach.

Background: Atopic dermatitis is a common disease in infants and children and the incidence appears to be rising.

Objectives: To determine the presentation, allergies, and outcome among Israeli infants and children.

Methods: Children with atopic dermatitis referred to the allergy clinic at a regional pediatric center were evaluated for their medical history and their allergy. The allergic assessment was determined by utilizing skin prick tests and/or serum specific immunoglobulin E concentrations. The children were reexamined again for all parameters at the end of the follow-up period.

Results: Forty-six children with atopic dermatitis were studied, 27 males (58.7%) and 19 females (41.3%). A family history of allergy was found in 19 (41.3%). The median age at presentation was 17 months. Of the 46 children 33 (71.7%) revealed an allergy to one or more of the allergens. The most common combination was allergy to food and house-dust mites. The mean follow-up time was 64 months. By the age of 8 years full recovery was seen in 16 patients, half of whom recovered within 3.3 years from the date of presentation. The probability of complete remission was 58%, and for either complete or partial remission 76%. Upon reevaluation at the end of the follow-up period some patients lost their sensitivities, while others, who had been allergic to foods, became sensitive to house-dust mites and/or pollens.

Conclusions: Atopic dermatitis is an allergic problem in the northern region of Israel, as it is in other parts of the world. Food allergy and house-dust mites are major contributors to the evolution of eczema.

Background: Hyperhomocysteinemia is a well-recognized risk factor for accelerated atherosclerosis in hemodialysis patients.

Objectives: To examine the effects of two doses of vitamins B6 and B12 and folic acid on homocysteine levels in hemodialysis patients and assess the functional impact of the methylenetetrahydrofolate reductase genotype on the response to treatment.

Methods: In a randomized prospective study, we assessed the effects of folic acid and two doses of B-vitamins in 50 hemodialysis patients with hyperhomocysteinemia. Patients were divided into two groups: 26 patients (group A) who received 25 mg of vitamin B₆ daily and one monthly injection of 200 µg vitamin B12, and 24 patients (group B) who received 100 mg of vitamin B6 daily and one monthly injection of 1,000 µg vitamin B12. In addition, both groups received 15 mg folic acid daily. Patients were evaluated for homocysteine levels as well as for coagulation and a thorough lipid profile. Baseline Hcy[1] levels were determined after at least 4 weeks washout from all folic acid and B-vitamins that were given. MFTHR[2] alleles were analyzed, as were activated protein C resistance, von Willebrand factor and lupus anticoagulant.

Results: Basal plasma Hcy levels were significantly elevated in hemodialysis patients compared with normal subjects (33.8 ± 4.3 vs. 4.5 to 14.0 mmol/L). Following treatment, Hcy levels were significantly reduced to 21.2 ± 1.6 in group A and 18.6 ± 1.4 mmol/L in group B (P < 0.01). There was no difference in Hcy reduction following the administration of either high or low dosage of vitamins B6 and B12 utilized in the present study. There was no correlation between Hcy levels or thrombophilia and high incidence of thrombotic episodes in hemodialysis patients. Genotypic evaluation of MTHFR revealed that the presence of homozygous thermolabile MTHFR (n = 5) was associated with higher Hcy levels and better response to treatment (Hcy levels decreased by 58%, from 46.2 ± 14.6 to 19.48 ± 4.1 mmol/L following treatment). In patients with heterozygous thermolabile MTHFR (n = 25), Hcy levels decreased by 34%, from 31.2 ± 3.7 to 18.1 ± 1.1 mmol/L following treatment. The efficacy of high and low doses of B-vitamins on the reduction of homocysteine levels was comparable.

Conclusions: Treatment with B-vitamins in combination with folic acid significantly decreased homocysteine levels in hemodialysis patients, independently of the tested doses. In addition, mutations in MTHFR were associated with elevated plasma levels of Hcy. Neither vascular access nor.