Israel Medical Association Journal

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.

Background: The number of child adoptions from abroad is increasing, but the adverse living conditions of these children prior to the adoption raise questions on their medical and neurodevelopmental status, particularly since there are no guidelines for pre- or post-adoption medical evaluation.

Objectives: To describe the condition of a cohort of young children who were candidates for adoption in East European orphanages and foster homes, and to determine those attributes associated with a family's decision to adopt or refuse a particular child.

Methods: Eighty-two young children, median age 11 months, were evaluated by Israeli pediatricians in Eastern Europe between 3 weeks and 6 months prior to their adoption. The evaluation consisted of comprehensive medical and neurodevelopmental testing on site using a battery of standardized assessment tools, and observation of free play and social interactive behaviors recorded on videotape. Laboratory tests included complete blood count, chemistries, serology screening, and metabolic and genetic testing.

Results: The children were growth-retarded. Medical problems were classified as resolved (pneumonia and diarrhea) in 32.8%; or ongoing, such as hepatitis B and (3, failure to thrive, organomegaly, and visual and hearing disorders, in 14.8%. Neuromotor status was grossly abnormal in 13.4%. Twenty-two percent of the children were rejected for adoption by families in Israel. Factors associated with the adoption decision were performance skills on developmental testing (P = 0.0001), present medical status (P = 0.002), and weight )P = 0.016(.

Conclusions: Pre-placement comprehensive screening of children eligible for foreign adoption, which includes developmental screening, helps to identify a wide variety of strengths and impairments in a child's background before the adoption procedure is finalized. A family's decision to adopt or not was associated with the child's performance on Bayley Scales, weight, and current medical status, but not with language delays, serious past medical history or suspect family background.
 

Background: Leukotriene antagonist therapy in asthmatic patients alleviates symptoms and improves exercise tolerance, however the effect of these drugs on bronchial provocation tests and exhaled nitric oxide levels are less clearly established.

Objective: To determine the effect of montelukast treatment on airway hyperresponsiveness to exercise, methacholine and adenosine-5’-monophosphate and on exhaled nitric oxide levels in steroid-naive asthmatics.

Methods: Following a 2 week run-in period, 20 mild to moderate asthmatics were enrolled in an open label 6 week trial of oral montelukast-sodium therapy. Bronchial hyperreactivity (exercise, methacholine and adenosine-5’-monophosphate challenges) and exhaled nitric oxide levels were measured before and after the 6 week period.

Results: Montelukast treatment resulted in a significant improvement in exercise tolerance: median DFEV₁ 20.0% (range 0–50) prior to treatment vs. 15.0% (range 0–50) post-treatment (P = 0.029). A significant difference was also observed for exhaled NO[1] following therapy: median NO 16.0 ppb (range 7–41) vs. 13.0 (range 4.8–26) (P = 0.016). No change was seen in baseline lung function tests (FEV₁, MEF₅₀) or in the bronchial responsiveness (PC₂₀) for methacholine and adenosine-5’-monophosphate.

Conclusions: This study demonstrates that the leukotriene antagonist, montelukast-sodium, reduces bronchial hyperreactivity in response to exercise and reduces exhaled nitric oxide levels but has little effect on bronchial responsiveness to methacholine and adenosine challenges.

Background: Sulfur mustard and VX are potent chemical warfare agents that penetrate rapidly through the skin, causing severe prolonged injuries and sometimes death.

Objectives: To develop a topically applied pretreatment that will act as a barrier and prevent the absorption of these agents through the skin, reducing morbidity and saving life.

Methods: Several formulations were developed and tested in preclinical animal studies in pigs. The protecting cream was applied as a single application (0.5–1 ml/100 cm²) prior to exposure (10 minutes to 12 hours) to sulfur mustard or VX. Assessment of sulfur mustard-induced skin damage was based on clinical and histologic evaluations. When tested against VX, clinical signs and blood cholinesterase activity were monitored. At the final stage of development, safety studies were conducted in animals and in human volunteers.

Results: The formulation that gave the best results, coded IB1 (under patent application), provided significant protection against a 1 hour exposure to sulfur mustard (droplets or vapor). All the pigs pretreated with IB1 cream survived a 1–4 hour challenge of 2xLD₅₀ VX and did not exhibit any overt clinical signs. Protection was exhibited even when the cream was applied 12 hours (single application) prior to exposure. IB1 was found to be non-irritating in animals and humans. No adverse effects were found in a Phase I clinical study in young healthy volunteers when the cream was applied to around 20% of the skin surface (results presented elsewhere).

Conclusions: IB1 cream has been shown to be a safe and effective topical skin protectant against the chemical warfare agents sulfur mustard and VX.

Background: Recent advances in immunosuppressive therapy have led to a substantial improvement in the outcome of kidney transplantation. Living unrelated donors may become a source of additional organs for patients on the kidney waiting list.

Objectives: To study the impact of combination of calcineurin inhibitors and mycophenolate-mofetile, together with steroids, on outcomes of living related and unrelated transplants. 

Methods: Between September 1997 and January 2000, 129 patients underwent living related (n=80) or unrelated (n=49) kidney transplant. The mean follow-up was 28.2 months. Immunosuppressive protocols consisted of MMF[1] with cyclosporine (41%) or tacrolimus (59%), plus steroids. Patient and graft survival data, rejection rate, and graft functional parameters were compared between the groups.

Results: LUD[2] recipients were older (47.8 vs. 33.6 years) with higher number of re-transplants (24.5% vs. 11.2% in LRD[3] recipients, P < 0.05). Human leukocyte antigen matching was higher in LRD recipients (P < 0.001). Acute rejection developed in 28.6% of LUD and 27.5% of LRD transplants (P = NS). Creatinine levels at 1, 2 and 3 years post-transplant were 1.6, 1.7 and 1.7 mg/dl for LRD patients and 1.5, 1.5 and 1.3 mg/dl for LUD recipients (P = NS). There was no difference in patient survival rates between the groups. One, 2 and 3 year graft survival rates were similar in LRD (91.3%, 90% and 87.5%) and LUD (89.8%, 87.8% and 87.8%) recipients.

Conclusions: Despite HLA[4] disparity, rejection and survival rates of living unrelated transplants under current immunosuppressive protocols are comparable to those of living related transplants.