Israel Medical Association Journal

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.

Tremor is extremely common and often functionally disabling. When tremor becomes medically intractable, surgery is a good and safe option for appropriate candidates. Both stereotactic thalamotomy and thalamic deep brain stimulation by means of an implanted electrode offer very high rates of success with an acceptably low complication rate.

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: About 40% of patients with infective endocarditis will require surgical treatment. The guidelines for such treatment were formulated by the American College of Cardiology and American Heart Association in 1998.

Objectives: To examine our experience with surgical treatment of infective endocarditis in light of these guidelines.

Methods: Surgery was performed in 59 patients with infective endocarditis between 1990 and 1999. The patients' mean age was 48 years (range 13–80). The indications for surgery were hemodynamic instability, uncontrolled infection, and peripheral embolic events. The surgical treatment was based on elimination of infection foci and correction of the hemodynamic derangement. These objectives were met with valve replacement in the majority of patients. Whenever conservative surgery was possible, resection of vegetation and subsequent valve repair were performed and the native valve was preserved.

Results: Six patients (10%) died perioperatively from overwhelming sepsis (n=3), low cardiac output (n=2) and multiorgan failure (n=1). The mean hospital stay was 15.6 days. Of 59 patients, 47 (80%) underwent valve replacement and in 11 (19%) the surgical treatment was based on valve repair. After 1 year of follow up, there was no re-infection.

Conclusion: The new guidelines for surgical treatment of infective endocarditis allow better selection of patients and timing of surgery for this aggressive disease, which consequently decreases the mortality rate. Valve repair is feasible and is preferred whenever possible. According to the new guidelines, patients with neurologic deficit in our series would not have been operated upon, potentially decreasing the operative mortality to 7%.

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: The Arterial Revascularization Therapies Study was a multicenter, randomized trial designed to compare percutaneous coronary intervention with stenting versus coronary artery bypass graft surgery in 1,205 patients with multivessel coronary artery disease. The most appropriate type of treatment for these patients is still a matter of considerable debate.

Objectives: To evaluate the clinical characteristics of patients enrolled in the ARTS[1] trial in Israel in comparison to those worldwide, and to assess the 1 year outcome in these patients.

Methods: Between April 1997 and June 1998, a total of 1,205 patients with multivessel coronary artery disease, who were considered to be equally treatable with both modalities, were randomized to either stenting (n=600) or CABG[2] (n=605) at 67 centers around the world. In Israel, 53 patients at four participating medical centers underwent randomization to either PCI[3] with stents (n=27) or CABG (n=26).

Results: Clinical and angiographic characteristics were similar in the two groups, except for a significantly higher incidence of diabetic patients in Israel who were randomized to CABG, compared to those worldwide (35% vs. 16%, P = 0.01). Also, there were more patients with unstable angina in Israel (63 vs. 37%, P = 0.006). At 1 year follow-up, overall mortality and cerebrovascular accident rates were similar between the two groups and equivalent to results obtained around the world. There was a significantly higher incidence of myocardial infarction rates in patients randomized to stenting in Israel compared to patients worldwide (7.4 vs. 5.3%, P = 0.01) or to patients randomized to CABG in Israel (7.4 vs. 0%, P = 0.006). Similar to the overall ARTS results, there was a higher incidence of repeat revascularization procedures in patients assigned to the PCI with stenting arm (22.2 vs. 3.8%, P = 0.004) compared to those randomized to CABG, respectively.

Conclusions: The results of this analysis of the Israeli ARTS population indicate that coronary stenting and bypass surgery yield similar findings with regard to mortality and stroke and are comparable to those obtained in the whole study group. Likewise, coronary stenting was associated with an increased incidence of repeat revascularization procedures as compared to CABG. However, patients in Israel randomized to stenting had a higher rate of myocardial infarctions as compared to the overall results and to patients who underwent CABG in Israel. The present analysis provides important data for the safety and efficacy of either stenting or bypass surgery in treating patients with multivessel disease in Israel.

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Background: Spasticity is a common neurologic disorder with adverse effects on the patient's function. Conservative management is unsuccessful in a significant proportion of patients and neurosurgical intervention should be considered. The mainstay of surgical treatment of spasticity is selective posterior rhizotomy, i.e., section of sensory nerve roots of the cauda equina.

Objective: To report our experience with selective posterior rhizotomy in the treatment of spasticity.

Methods: We retrospectively reviewed our experience in 154 patients who underwent SPR during 30 years. The indication for surgery was spasticity that significantly hindered the patient's function or care and was resistant to conservative treatment. All patients were evaluated for spasticity in the lower and upper limbs, the presence or absence of painful spasms, and sphincter disturbances. The decision

as to which roots to be sectioned, and to what extent, was based mainly on clinical muscle testing.

Results: Reduction of spasticity in the lower limbs was obtained in every case, with improvement in movements in 86% of cases. Painful spasms were alleviated in 80% of cases. Amelioration of neurogenic bladder was observed in 42%. A minority of the patients also showed improvement in speech and cognitive performance. There was no perioperative mortality or major complications.

Conclusion: SPR is a safe and effective method for the treatment of spasticity with long-lasting beneficial effects. We suggest that this method be considered more frequently for patients with spasticity that interferes with their quality of life.

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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Background: Understanding discharge instructions is crucial to optimal healing but may be compromised in the hectic environment of the emergency department.

Objectives: To determine parents’ understanding of ED[1] discharge instructions and factors that may affect it.

Methods: A convenience sample of parents of children discharged home from the ED of an urban tertiary care pediatric facility (n=287) and a suburban level II general hospital (n=195) completed a 13-item questionnaire covering demographics, level of anxiety, and quality of physician’s explanation. Parents also described their child’s diagnosis and treatment instructions and indicated preferred auxiliary methods of delivery of information. Data were analyzed using the BMPD statistical package.

Results: Full understanding was found in 72% and 78% of the parents at the respective centers for the diagnosis, and in 82% and 87% for the treatment instructions (P  = NS between centers). There was no statistical correlation between level of understanding and parental age, gender, education, level of anxiety before or after the ED visit, or time of day. The most contributory factor to lack of understanding was staff use of medical terminology. Parents suggested further explanations by a special discharge nurse and written information as auxiliary methods.

Conclusions: Overall, parental understanding of ED discharge instructions is good. However, there remains a considerable number (about 20%) who fail to fully comprehend the diagnosis or treatment directives. This subset might benefit from the use of lay terminology by the staff, institution of a special discharge nurse, or use of diagnosis-specific information sheets.