Israel Medical Association Journal

Background: Repaglinide, a new insulin secretagogue, is purported to be as effective as sulphonylurea but is less hypoglycemic-prone.

Objectives: To assess the efficacy of repaglinide and its proclivity for hypoglycemia in a post-marketing study.

Methods: The study group comprised 688 patients, aged 26–95 years, clinically diagnosed with non-insulin-dependent type 2 diabetes. The patients were divided into three groups based on previous therapy: a) sulphonylurea-treated (group 1, n=132); b) metformin with or without sulphonylurea where sulphonylurea was replaced with repaglinide. (group 2, n=302); and c) lifestyle modification alone (drug-naïve) (group 3, n=254). At initiation of the study, all patients were transferred from their current treatment to repaglinide. Only patients in group 2, with combined sulphonylurea plus metformin, continued with metformin plus repaglinide. Fasting blood sugar, hemoglobin A1c and weight were measured at study entry and 4–8 weeks following repaglinide therapy. A questionnaire documented the number of meals daily and the presence of eating from fear of hypoglycemia.

Results: The fasting blood sugar level of the entire cohort dropped from 191 ± 2.4 to 155 ± 2.0 mg/dl (P < 0.0001); HbA1c from 8.8 ± 0.1 to 7.7 ± 0.1% (P < 0.0001). The drop of HbA1c in groups 1, 2 and 3 respectively were: 1.04 ± 0.22% (P < 0.0001), 1.14 ± 0.24% (P < 0.0001), and 1.51 ± 0.31% (P = 0.0137). Weight dropped from 81 ± 0.7 to 80.2 ± 0.7 kg (P < 0.0001), and eating from fear of hypoglycemia from 157 to 97 (P < 0.001). The daily number of meals decreased from 2.9 ± 0.4 to 2.4 ± 0.4 (P < 0.001). No serious adverse reactions occurred during the study.

Conclusions: Repaglinide is an effective oral hypoglycemic agent taken either as monotherapy or combination therapy. There is less eating to avoid hypoglycemia, fewer meals consumed, and weight loss.
 

Background: Alteration of innate and acquired immunity can play a role in the mechanism involved in the development of dementia. Epidemiologic studies indicate that the use of non-steroidal anti-inflammatory drugs can delay the onset or slow progression of Alzheimer disease.

Objectives: To determine whether the use of NSAIDs[1] is associated with natural killer activity alteration in AD[2] and multi-infarct vascular dementia patients, as compared with non-demented elderly and healthy young people.

Methods: In this prospective open study four groups of subjects (AD, VD[3], non-demented elderly, and healthy young people) were treated with an NSAID drug (rofecoxib 12.5 mg/day or ibuprofen 400 mg twice daily) for 7 days. Natural killer cell cytotoxicity was measured after flow cytometry analysis before and after treatment.

Results: Of the 49 subjects studied, 15 had a diagnosis of AD (3 men, 12 women; mean age 83.5 ± 8.1 years), 15 had a diagnosis of multi-infarct VD (7 men, 8 women; mean age 75.5 ± 8.4), 13 were non-demented elderly (1 man, 12 women; mean age 80.2 ± 7.2), and 6 were healthy young volunteers (3 men, 3 women; mean age 36.8 ± 4.4). While all examined subjects showed decreased NK[4] cell cytotoxicity after treatment, this decrease was most prominent and statistically significant in elderly patients suffering from vascular dementia –  from an average of 30.5 ± 11.8% before treatment to 22.5 ± 16% after treatment (P = 0.04). The decrease in NK cell cytotoxicity was only moderate and not statistically significant in all other elderly and young subjects. Young healthy volunteers exhibited a significantly higher total NK cytotoxicity before and after treatment compared to all age groups (P < 0.001).

Conclusion: These findings suggest that NSAIDs decrease NK activity in vascular dementia patients. Our findings also suggest that natural killer activity alteration cannot explain the ability of anti-inflammatory drugs to delay the onset or slow the progression of AD.

Objectives: To evaluate operative procedures, complications, early and late results and long-term functional outcome in FAP[1] patients operated in our department.

Methods: The study group included all patients with FAP who were operated between 1988 and 2003. Demographic data, length of follow‑up, complications, colorectal cancer, pouch function and extracolonic manifestations were recorded.

Results: Median age at surgery was 33 years (range 13–61 years). The final operative breakdown was: 48 proctocolectomies, 41 ileal pouch-anal anastomoses, 2 Kock’s pouch, 5 permanent ileostomies, and 2 colectomies with ileorectal anastomosis. There was no perioperative mortality. Early and late complications occurred in 20 and 9 patients, respectively. Twelve patients required re‑operation. Colorectal carcinoma was diagnosed in eight patients, three of whom were in an advanced stage. The mean follow‑up was 74 months (range 3–288 months). Four patients were lost to follow‑up. Extracolonic manifestations developed in 38 patients, including desmoid tumors (in 12), duodenal adenomas (in 9), pouch adenomas (in 5), and rectal stump adenomas (in 3). Two patients died (4%) because of desmoid tumor and malignant fibrous histiocytoma. At last follow‑up, 37 IPAA[2] patients have (median) six bowel movements/24 hours and good fecal control.

Conclusions: Restorative proctocolectomy can be performed with low mortality, acceptable morbidity, and good functional results. Patients should be closely followed after surgery for development of other manifestations of the syndrome. Relatives of the affected patients should be referred to a specialist multidisciplinary clinic.

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[1] FAP = familial adenomatous polyposis

[2] IPAA = ileal pouch-anal anastomosis

Objective: To investigate the effect of the Dead Sea environment (climatotherapy) on the signs, symptoms and clinical course of chronic uveitis.

Methods: Fifty-five patients with chronic uveitis were examined at the beginning and end of a 3–4 week stay at the Dead Sea region and on repeat visits to the region. Study data included demographic information, medical history, etiology, diagnosis, medication, and a complete ophthalmic examination.

Results: Statistically significant improvements were seen between the two examinations within each visit in four parameters (negative values indicate improvement): a) visual acuity for near and far: Jaeger (‑1.18 ± 0.28, P < 0.0001) and best corrected visual acuity (‑0.08 ± 0.02, P < 0.0001); b) anterior chamber flare (-0.18 ± 0.06, P < 0.01); c) anterior chamber cells (-0.16 ± 0.05), P < 0.001); and d) vitreous cells (-0.15 ± 0.09, P < 0.05). There was a significant mean improvement during visits to the Dead Sea area and a slight dissipation of the effect during the intervals between visits. Sixty-four percent of the patients reported that they required less medication and had fewer and milder attacks of uveitis following the visits.

Conclusions: The results of this study provide evidence of short- and possibly long-term improvement in the signs and symptoms of uveitis following exposure to the Dead Sea environment.

Background: Salmonella species commonly produce acute gastroenteritis. The clinical course may be affected by factors such as age, immunosuppression, and underlying disorders.

Objectives: To investigate clinical and laboratory differences in the infected population and the risk of complications according to the different age groups.

Methods: The records of 295 patients with positive cultures for Salmonella were divided into six age groups and reviewed retrospectively for the years 1994–1997. Demographic, clinical and laboratory data, extraintestinal manifestations, underlying disorders, organism source, and susceptibilty to antibiotics were analyzed.

Results: We found that 88.5% were only stool positive, 9.2% had positive blood cultures, and 2.4% were positive in both blood and stool; 3.6% were found to have underlying disorders. Anemia, disturbed liver function tests and hypoalbuminemia were the most common pathologic laboratory findings. Salmonella serogroups B and D were isolated most frequently. The rate of positive blood cultures increased significantly during the years, as did resistance to ampicillin and trimethoprim-sulfamethoxazole. Salmonella infection has two peaks of incidence: at ages 1–5 and 15–65 years. Bacteremia was prominent in the extreme ages.

Conclusions: Salmonella infection has a different clinical presentation in different age groups. The significant increase in the rate of bacteremia in the extreme age groups necessitates a different attitude and management for these heterogeneous patient populations.

Objective: To describe the experience of our CF[1] center in the management of CF pregnant woman from 1977 to 2004.

Methods: We analyzed 27 years of records (1977–2004) of the national CF registry of all CF women who wished to conceive and became pregnant.

Results: Eight CF women (mean age 24 ± 4.5 years) who wished to conceive had 11 pregnancies and delivered 12 neonates. The pregestational results of forced expiratory volume per 1 second varied significantly among patients (59 ± 23%), yet most (10/11) stayed stable throughout the pregnancy course. Maternal deterioration in CF condition occurred in only one mother, necessitating cesarean section. In 9 of the 11 pregnancies the women were pancreatic-insufficient. Of the 11 pregnancies, 2 CF women had diabetes mellitus and 3 developed gestational diabetes. One pregnancy occurred in a mother with a transplanted lung. Of the 12 neonates, 3 were preterm and one was born with esophageal atresia. No miscarriages, terminations or neonatal mortalities occurred. Although most of the CF mothers had FEV_1[2] below 55% before pregnancy, the maternal and neonatal outcome was favorable and lung function tests generally remained stable.

Conclusions: We conclude that pregnancy in CF is feasible with a positive maternal and neonatal outcome. Early participation of the CF physician in the wish of the CF woman to reproduce is required. The integration of an intensive multidisciplinary approach during pregnancy, which includes close follow-up of maternal and fetal condition by the various specialists, should ensure an optimal outcome.

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[1] CF = cystic fibrosis

[2] FEV₁ = forced expiratory volume per 1 sec