Israel Medical Association Journal

Background: Pulmonary disease is the most frequent cause of morbidity and mortality in cystc fibrosis patients. New techniques such as non-invasive positive pressure ventilation have resulted in prolongation of life expectancy in CF[1] patients with end-stage lung disease.

Objectives: To determine the role of NIPPV[2] in CF patients awaiting lung transplantation.

Methods: Between 1996 and 2001 nine CF patients (5 females) with end-stage lung disease were treated with bi-level positive airway pressure ventilation in the "spontaneous" mode.

Results: The patients' mean age at initiation of BiPAP[3] was 15 years (range 13–40 years) and the mean duration of BiPAP usage was 8 months (range 3–16 months). Four patients underwent successful lung transplantation, three patients died while awaiting transplantation, and the remaining two are still on NIPPV while waiting for transplantation. Patients' body mass index increased significantly (P < 0.05) during BiPAP therapy (from 16.1 to 17.2 kg/m²). Blood pH, p_aCO₂, and bicarbonate improved significantly (from 7.31 to 7.38, 90.8 to 67.2 mmHg, and 48.9 to 40.3 mEq/L, respectively). Pulmonary function tests were not affected by BiPAP usage. The patients experienced a significant alleviation in morning headaches and improvement in quality of sleep (P < 0.003). There were no major complications during BiPAP usage.

Conclusions: We demonstrated that long-term NIPPV can stabilize and improve physiologic parameters such as ventilation, arterial blood gases and body mass index, as well as subjective symptoms such as sleep pattern, daily activity level, and morning headaches in CF patients with end-stage lung disease. Further prospectively controlled studies are needed to evaluate the potential of BiPAP therapy and its influence on morbidity and mortality in the post-lung transplantation period.

Background: Transmission of Pseudomonas aeruginosa among cystic fibrosis patients attending health camps has been reported previously.

Objectives: To determine the transmission of P. aeruginosa among CF[1] patients during three winter camps in the Dead Sea region in southern Israel.

Methods: Three consecutive CF patient groups were studied, each of which spent 3 weeks at the camp. The patients were segragated prior to camp attendance: patients who were not colonized with P. aeruginosa constituted the first group and colonized patients made up the two additional groups. Sputum cultures were obtained upon arrival, at mid-camp and on the last day. Environmental cultures were also obtained. Patients were separated during social activities and were requested to avoid social mingling. Isolates were analyzed by antibiotics susceptibility profile and by pulsed field gel electrophoresis.

Results: Ninety isolates from 19 patients produced 28 different fingerprint patterns by PFGE[2]. Isolates from two siblings and two patients from the same clinic displayed the same fingerprint pattern. These patients were already colonized with these organisms upon arrival. Two couples were formed during the camp, but PFGE showed no transmission of organisms. All other patients' isolates displayed unique fingerprint patterns and were distinguishable from those of other attendees, and none of the P. aeruginosa-negative patients acquired P. aeruginosa during camp attendance. Environmental cultures were negative for P. aeruginosa.

Conclusions: We were unable to demonstrate cross-infection of P. aeruginosa among CF patients participating in health camps at the Dead Sea who were meticulously segregated.

Background: Prenatal care in Israel is established as a universal service, but the degree of compliance with care recommendations may vary with the healthcare provider or the characteristics of the population.

Objectives: To study referral to and compliance with the performance of ultrasound, alpha-fetoprotein and amniocentesis and the factors associated with them in a national sample. 

Methods: The sampling frame consisted of women who gave birth during March 2000. The sample included 1,100 Israeli Jewish and Arab women who resided in localities with over 50,000 and 20,000 inhabitants respectively. They were interviewed by phone 3 months after delivery. 

Results: In both population groups 30% reported having seven or more ultrasounds during pregnancy. The performance of fetal body scans was relatively low. Factors associated with non-performance among Jewish women were: lower education, religiousness, and attending Mother and Child Health services as compared to all other services. Seventy-seven percent of Jewish women and 84% of Arab women reported that they had been referred for alpha-protein tests. For women aged 35 and over, 55% of Jewish women were referred and 63% complied, whereas 39% of Arab women were referred but none complied.

Conclusions: Ultrasound is almost universally performed among Jewish and Arab women; however fetal body scans, alpha-fetoprotein and amniocentesis (for women over the age of 35) are not. The reasons for the lower coverage may be due to under-referral and/or lack of compliance of the women, perhaps due to sociocultural barriers. In both population groups considerable out-of-pocket money is paid for the tests.

Background: Hyperthermia combined with radiation therapy was shown to be more effective in local recurrent breast cancer than radiotherapy alone, but it use is limited due to technical difficulties, stringent reimbursement policies and because it is time consuming.

Objectives: To report our experience with a simple and convenient XRT+HT[1] delivery system.

Methods: XRT was delivered through either electron or photon beams (total dose 30–40 Gy in previously irradiated fields or 50–70 Gy in non-irradiated fields). Hyperthermia was delivered by a dedicated HT device operating at 915 MHz. The heating session lasted 45 minutes. The maximal tumor surface temperature was set at 45°C and modified according to patient comfort. No intratumoral (invasive) thermometry was used. At least two HT sessions were scheduled to each HT field during the entire XRT treatment period. Tumor response was evaluated every 3 months after completion of treatment. The overall survival was measured from XRT+HT initiation until the last follow‑up.

Results: Fifteen women underwent 114 HT treatments delivered through 28 HT fields. Twenty-four HT fields (15 patients) were previously irradiated. There was complete infield response in 10 fields (6 patients), partial response in 8 fields (4 patients), no response or progressive disease in 4 fields (3 patients), and no parameters in 6 fields (5 patients). Eighteen (64%) fields had complete or partial response. Seven patients had outfield recurrence despite wide XRT+HT fields. Ulceration was the only major side effect (three patients, three fields).

Conclusions: The combined HT+XRT delivery system, with no invasive thermometry, is a simple and effective method for treating local recurrent breast cancer.

The ubiquitin-proteasome pathway has a central role in selective degradation of intracellular proteins. Among the key proteins degraded by the system are those involved in the control of inflammation, cell cycle regulation and gene expression. With numerous important cellular pathways affected, derangements in the ubiquitin system were shown to result in a variety of human diseases including malignancies, neurodegenerative diseases and hereditary syndromes, and proteasome inhibition was implicated as a potential treatment for cancer and inflammatory conditions. Two proteasome inhibitors are currently under clinical evaluation for multiple myeloma and acute ischemic stroke. The ubiquitin system also has an important function in the immune and inflammatory response. It is involved in antigen processing and presentation to cytotoxic T cells, and the activation of nuclear factor-kappa B – the central transcription factor of the immune system. Since the proteasome is the central source of antigenic peptides that are presented to the immune system, some viruses, such as the Epstein-Barr virus, developed escape mechanisms that manipulate the ubiquitin-proteasome system in order to persist in the infected host. Understanding the mechanisms underlying the production of viral antigens by the ubiquitin-proteasome system may have therapeutic applications such as future development of vaccines.

Background: Contralateral exploration of the groin has been common practice among pediatric surgeons for nearly 50 years, based on the high incidence of patent processus vaginalis on the contralateral side with the potential for the subsequent development of a hernia.

Objectives: To evaluate transinguinal laparoscopic examination of the contralateral side during repair of inguinal hernia in children in order to reach a decision regarding exploration of the contralateral side.

Methods: Over a of 21 month period 124 children with unilateral inguinal hernia underwent laparoscopic evaluation of the contralateral groin. The operations were performed under general anesthesia as ambulatory procedures.

Results: Transinguinal contralateral laparoscopic exploration was positive (patent processus vaginalis) in 26 children (21%) and negative (closed processus vaginalis) in 88 (71%). Failure to introduce the telescope occurred in 10 patients (8%) due to a friable or narrow hernia sac. Twenty-five children below 2 years of age were spared exploration of the contralateral side as a result of the negative laparoscopic examination. On the other hand, 15 children aged 2–17 had their contralateral groin explored because of a positive finding at laparoscopy.

Conclusions: Transinguinal laparoscopic examination of the contralateral side during repair of inguinal hernia in children is a simple, safe and quick method to avoid systematic bilateral explorations and should be part of every pediatric surgeon's experience.

Background: Pseudomembranous colitis is a well-recognized cause of diarrhea in patients receiving antibiotics and has significant consequences in terms of morbidity, mortality and cost. Clostridium difficile infection is the single most important infectious cause of PMC[1]. PMC is frequently nosocomial, with an increased risk of spread among institutionalized patients, both in hospitals and nursing homes.

Objective: To investigate the demographic, clinical and laboratory characteristics of PMC patients in an Israeli elderly population.

Methods: We studied 72 hospitalized patients with endoscopically proven PMC. The medical records of all patients including clinical history and laboratory data were reviewed, such as: age, pre-hospitalization status (dependency or not, in the community as compared to the nursing home), background medical history, presenting symptoms, antibiotic history, physical examination on admission, hematologic and biochemical parameters, treatment, duration of hospitalization, complications, mortality and recurrence of disease.

Results: Of the 72 patients (34 males and 38 females, mean age 77 years) 47% were nursing home residents. Pre-hospitalization antibiotic treatment was given to 91.4% for infections of the upper respiratory tract (45%) and urinary tract (45%). The most common antibiotics were cephalosporin (64%), penicillins (42%) and quinolones (28%). Sixty-four percent of the patients were treated with more than one antibiotic, 26% of patients received anti-acid therapy and 36% had been fed with a nasogastric tube. On admission, leukocytosis was found in 79% of patients, >20,000/mm³ in half of them; 60% were anemic, 60% had elevated erythrocyte sedimentation rate, and 78% had hypoalbuminemia. Treatment consisted of metronidazole (41%) or a combination of metronidazole and vancomycin (56%). Overall, 31% of patients recovered without complications, 29% died within 30 days of hospitalization, and 24% were re-hospitalized due to recurrence of PMC.

Conclusion: The most common antibiotics implicated in PMC are cephalosporin, penicillins and quinolones. The disease is associated with high mortality and recurrence rates.

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.