Israel Medical Association Journal

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.

Background: Seroepidemeliogic surveys have provided valuable information on the prevalence and incidence of herpes simplex virus-2 infection in general and in selected populations.

Objective: To review the reliability of traditional diagnostic approaches in herpes simplex virus-2 infection.

Methods: In this cross-sectional study, 472 patients attending a clinic for sexually transmitted disease in 1998-1999 were evaluated for HSV-2 infection through collection of epidemiologic and clinical data.

HSV-2 infection was confirmed by the presence of specific Viral glycoprotein, gG-2, antibody in sera.

Results: The seroprevalence of HSV-2 among clinic attendees was 9.33%. Of these attendees only 22% presented with or reported a history of typical vesicular lesions in the genital area. Infection rate was  higher in patients with multiple sex partners (20.8% vs. 8.7%, P< ( 0.0023 in individuals aged 30 or older (12.6 vs. 6.4%, P = 0.03) and  in the Israeli Jewish population as compared to the Israeli Arab population (11.1% vs. 2.4%, P ~ 0.01). Females with multiple sex partners exhibited higher rates of infection than did their male counterparts (50 vs. 16.1%, P < 0.0275(.

Conclusion: The findings support the need for HSV-2 serologi  testing in patients presenting to STD clinics even when typical genital  lesions are not evident but where risk factors for HSV-2 infection are  identified.
 

Background: The beneficial effect of 3-hydroxy-3-methylglutyaryl co-enzyme A reductase inhibitors on cardiovascular risk reduction has been clearly established. Concerns have been raised that lowering blood cholesterol by other hypolipidemic drugs or by a non-pharmacologic approach may have deleterious effects on psychopathologic parameters. Garlic is one of the most commonly used herbal remedies and is considered to have hypocholesterolemic as well as other cardio-protective properties. Its effect on psychopathologic parameters has never been reported.

Objectives: To evaluate the effect of garlic on lipid parameters and depression, impulsivity, hostility and temperament in patients with primary type 2 hyperlipidemia.

Methods: In a 16 week prospective double-blind placebo-controlled study, 33 patients with primary hypercholesterolemia and no evidence of cardiovascular disease were randomly assigned to receive either garlic or placebo. Garlic in the form of alliin 22.4 mg/day was given to 13 patients, and placebo to 20. Both groups received individual dietary counseling. The changes in lipid profile and the various psychopathologic parameters were determined at the beginning and end of the trial. The differences in lipid parameters were evaluated by Student’s t-test. The psychological data were analyzed by one-way analysis of variance (ANOVA) with repeated measures and Neuman-Keuls test.

Results: No significant changes were observed in levels of total cholesterol, low density lipoprotein-cholesterol, high density lipoprotein-cholesterol and triglycerides, or in the psychopathologic parameters evaluated.

Conclusion: Short-term garlic therapy in adults with mild to moderate hypercholesterolemia does not affect either lipid levels or various psychopathologic parameters.

Background: Drains are inserted in the dissected axilla of most patients during surgery for breast cancer.

Objective: To evaluate the presence and prognostic value of MUC1 and Met-HGF/SF in the axillary drainage of these patients.

Methods: The study group included 40 consecutive patients with invasive ductal carcinoma of the breast who were suitable for breast-conserving treatment; 20 malignant melanoma patients found to have negative axillary sentinel lymph node served as the control group. The output of the drains, which had been placed in the axilla during operation, was collected, and the presence of MUC1, Met-hepatocyte growth factor/scatter factor and b-actin were assessed in the lymphatic fluid by reverse transcription-polymerase chain reaction assays. The data were compared to the pathologic features of the tumor and the axillary lymph nodes, and to the estrogen and progesterone receptors status.

Results: RT-PCR[1] assays of the axillary lymphatic drainage were positive for MUC1 and Met-HGF/SF[2] in 15 (37.5%) and 26 (65%) of the patients, respectively. Patients in whom MUC1 and Met-HGF/SF were not found in the axillary fluid had smaller tumors and less capillary and lymphatic invasion, compared to patients with positive assays (P < 0.02 for all these comparisons). The lymph nodes were negative for metastases in all patients with negative assays (P < 0.001). The presence of MUC1 and Met-HGF/SF showed negative correlations with the estrogen and progesterone receptors (P < 0.05).

Conclusion: MUC1 and Met-HGF/SF can be detected in the axillary fluids of patients with breast cancer. The expression of both tumor markers in the axillary drainage is strongly associated with unfavorable tumor features and can be used as a prognostic factor.

Background: There are radiobiologic and technical advantages to the use of interstitial brachytherapy alone or as an adjunct to external beam radiotherapy in the postoperative treatment of soft tissue sarcomas.

Objectives: To review the experience of the Rambam Medical Center in implementing interstitial brachytherapy in the treatment of 32 patients with soft tissue sarcomas.

Methods: Thirty-two patients with variously located soft tissue sarcomas were managed with a combination of surgery and brachytherapy of the tumor bed, with or without EBRT[1]. In 27 of 32 patients, brachytherapy catheters were placed intraoperatively, while in 5 patients the implant was performed as a separate postoperative procedure. Twenty-seven patients received low dose-rate brachytherapy with iridium-192 seeds. Five patients received fractionated high dose-rate brachytherapy using the microSelectron machine.

Results: With a median follow-up of 36 months, the overall local control rate was 87.5%. Four of 32 patients (13%) failed locally at the implant site, and 6 (19%) developed lung metastasis. Two of the five patients with lung metastasis had a local recurrence as well. At the time of analysis, eight patients had died of sarcoma (disease-specific mortality rate was 25%), while three had died of intercurrent causes. The 5 year actuarial disease-free survival rate was 56%, and the 5 year actuarial overall survival was 70%. Five patients (16%) developed severe wound complications following surgery/brachytherapy, and six patients (19%) developed late local toxicity (fibrosis and telangiectasia).

Conclusions: Wide local excision followed by interstitial brachytherapy has resulted in an 87.5% local control rate with a 17% local complication rate.

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