Israel Medical Association Journal

Since both major forms of diabetes involve inadequate function of pancreatic beta cells, intensive research is ongoing to better understand how beta cells perform their complex role of secreting the hormone insulin in response to physiologic needs. Identification and characterization of pancreatic transcription factors has revealed that they play a crucial role not only in maintenance of mature beta-cell function but also at multiple stages in pancreatic development. Furthermore, recent reports have revealed their potential to convert non-beta cells into insulin-producing cells, which in some cases can function to ameliorate diabetes in experimental animals. The ability to translate these successes to the clinic will require a detailed mechanistic understanding of the molecular basis of action of these proteins. Specific gene regulation in beta cells involves the action of multiple transcription factors recruited to the promoter and functioning synergistically to activate transcription, in part through recruitment of co-activator proteins and components of the basal transcriptional machinery. In addition, the process involves modification of chromatin structure, the details of which are beginning to be elucidated. Our ability to modulate gene expression patterns may lead to developing ways to provide an unlimited supply of functional beta cells for transplantation, permitting a dramatic improvement in therapeutic options for diabetes.

Background: Hypertrophic pyloric stenosis classically presents as projectile vomiting during the third to fourth week of life associated with good appetite. Additional classical presenting findings include palpation of the pyloric tumor, described as olive-shaped, a visible gastric peristaltic wave after feeding, and hypochloremic, hypokalemic metabolic alkalosis. It was recently claimed that this presentation has changed due to the easier access to gastrointestinal imaging.

Objective: To validate this contention and discuss possible reasons.

Methods: We conducted a retrospective chart review of all patients who underwent pyloromyotomy for HPS[1] between 1990 and 2000. Only patients with confirmed HPS at the time of surgery were included. We also performed a comprehensive review of older studies for comparison.

Results: Seventy patients underwent pyloromyotomy over the 10 year period. Overall, 81% of patients were male infants and the mean age at diagnosis was 40 days. The mean duration of symptoms was 8 days. A firstborn child was noted in 43% of the cases. The classical symptom of projectile vomiting was absent in one-third of the patients, a pyloric tumor was not palpated in one-half of the cases, bicarbonate was higher than 28 mEq/L in 20% and a pH of above 7.45 was present in 25% of patients. Hypochloremia was noted in about one-third. We found a good correlation between ultrasonographic width and length of the pylorus and the intraoperative findings. Pylorus length ≥ 24 mm correlated with significantly longer duration of symptoms. When compared with previous studies, the main findings were not significantly different; namely, mean age at diagnosis, percentage of male gender and duration to diagnosis. The decrease in the number of pyloric tumors palpated paralleled the increase in the use of upper gastrointestinal series and ultrasonography in particular.

Conclusions: The clinical presentation of HPS has not actually changed despite the easier accessibility of GI imaging studies. However, the one significant change is the low percentage of pyloric tumors palpated, probably due to declining clinical skills, accompanied by earlier utilization of imaging studies. The use of imaging and laboratory studies did not change the age at diagnosis but may have shortened the time for diagnosis and reduced the postoperative stay. Imaging and laboratory studies may be helpful for the subgroup with a non-classical clinical presentation.

Background: Intravenous recombinant tissue plasminogen activator therapy within 3 hours of stroke onset is a proven effective treatment for acute ischemic stroke.

Objectives: To assess the feasibility and safety of rt-PA[1] therapy for reperfusion in routine clinical practice in Israel, in a setting of a dedicated stroke unit.

Methods: Consecutive patients presenting within less than 3 hours of stroke onset were evaluated by an emergency physician and the neurology stroke team. After brain computerized tomography eligible patients were treated with intravenous rt-PA (0.9 mg/kg; maximum dose 90 mg) according to an in-hospital protocol corresponding to recommended criteria. Patients were admitted to the acute stroke unit. Safety and clinical outcome were routinely assessed. Re-canalization was assessed by serial transcranial Doppler.

Results: The study group comprised 16 patients, mean age 61 years (range 47–80 years), male to female ratio 10:6, whose median baseline National Institutes of Health stroke scale was 13 (range 6–24). They were treated within a mean door-to-CT time of 39 minutes (range 17–62 min), door-to-drug time 101 minutes (range 72–150), and stroke onset-to-drug time 151 minutes (range 90–180). There was an early improvement within 24 hours (of ≥ 4 points in the NIHSS[2] score) in 7 patients (44%) and no early deteriorations. There were no protocol deviations, no symptomatic intracranial hemorrhages, and no major systemic hemorrhage within 36 hours of rt-PA treatment. Three asymptomatic hemorrhagic transformations of the infarct were noted on routine follow-up brain CT associated with neurologic improvement. Outcome data were comparable to the National Institute of Neurological Disorders and Stroke rt-PA Stroke Study.

Conclusion: Intravenous rt-PA treatment within 3 hours of stroke onset in routine clinical practice in Israel is feasible and appears safe in the setting of a neurology stroke unit and team. Careful implementation of rt-PA therapy for selected patients in Israel is encouraged.

Background: Leptospirosis is a zoonotic disease that occurs worldwide, found predominantly in agricultural workers, port workers and dairy workers.

Objective: To investigate the risk of disease transmission to dairy workers following an outbreak in 1999 of Leptospirosis hardjo in the dairy herds of two kibbutzim in southern Israel.

Methods:  A seroepidemiologic survey of all the dairy workers from these two kibbutzim was conducted, including individual interview and examination. Data were collected on the presence of clinical symptoms of leptospirosis during the previous month. One month later the medical personnel on the two kibbutzim were contacted in order to determine if any worker had subsequently developed clinical signs or symptoms of leptospirosis. All dairy workers had blood drawn for serology. Those workers whose initial serology had been borderline for leptospirosis had a repeated serology test between 2 and 4 weeks later. Doxycycline was given prophylactically to all dairy workers on one kibbutz only.

Results:  Either with or without chemoprophylaxis, no dairy workers exposed to herds infected with Leptospira hardjo showed evidence of seroconversion or disease. This indicated a low risk of transmission of this serovar from cows to dairy workers.

Conclusion: Since human illness with leptospirae can cause illness associated with significant morbidity we recommend that dairy workers exposed to an infected herd receive doxycycline prophylaxis.

Background: Vaginal symptoms are a leading reason for a patient to visit her gynecologist. Little is known about the prevalence of the different causes of vaginitis and the risk factors for this entity in Israel.

Objective: To determine the prevalence in a gynecologic practice in Israel of the main forms of vaginitis: vulvovaginal candidiasis, bacterial vaginosis, and trichomoniasis.

Methods: We evaluated 208 patients presenting with vaginal symptoms to a gynecologic clinic; 100 asymptomatic women who attended the clinic for routine check-up served as controls. Demographic, medical and gynecologic histories were obtained, and a pelvic examination was performed in all patients. Vaginal specimens were tested for pH and amine reaction, smeared for Gram-staining and cultured for yeasts and Trichomonas vaginalis. Bacterial vaginitis was diagnosed using the Nugent scoring system. candida infection was diagnosed by microscopic examination and by culture.

Results: Candida spp. was the most common pathogen, documented by microscopy and culture in 35.5% of symptomatic women and 15% of asymptomatic controls (P < 0.001). Detection by culture only (negative microscopy) was documented in 18.7% of symptomatic patients and 15% of controls (P = 0.5). Bacterial vaginosis (Nugent score ≥ 7) was diagnosed in 23.5% of patients and 13% of controls (P = 0.04). Trichomoniasis was present in 8.1% of symptomatic women and 4% of controls (P = 0.1). The main risk factors were antibiotic use for candidiasis and lack of use of oral contraception and condom use for trichomoniasis.

Conclusion: Candida was by far the most common pathogen detected in our population. A statistically significant difference between patients and controls was noted for the prevalence of microscopically diagnosed candidiasis and bacterial vaginosis.