Israel Medical Association Journal

Objectives: To evaluate immunologic parameters in B-CLL[1] associated with autoimmune disorders. As a hypothesis we postulated that in those cases, the malignant B cells might disclose an activated phenotype pattern leading to the production of autoantibodies.

Methods: In the Registry of the Israel Study Group on CLL that includes 964 patients, we found 115 cases showing a single or a complex of autoimmune disorders. We evaluated the lymphocyte morphology, immunoglobulin G and beta-2-microglobulin serum levels and positivity of the CD38 and FMC7 markers, and compared these values with those of a matched CLL population without autoimmune disorder. 

Results: The main autoimmune disorders encountered were autoimmune hemolytic anemia (55 patients), Evan's syndrome (n=7), Hashimoto's thyroiditis (n=15), vasculitis (n=5) and rheumatoid arthritis (n=4). We found atypical prolymphocytic morphology in 22%, high expression of the activation antigens CD38 and/or FMC7 in 30%, and high level of immunoglobulin G (> 1000 mg/dl) and beta-2-microglobulin in 57% and 78% respectively. When compared with a matched CLL population without an autoimmune disorder, these values were statistically significant.

Conclusions: Our data, which show activated lymphocyte morphology, high levels of IgG[2] and beta-2-microglobulin, and increased expression of CD38 and/or FMC7 in a significant number of cases, suggest that some degree of activation of B cells may lead to the occurrence of an autoimmune disorder in CLL.

Objectives: To determine whether drug studies in the pulmonary/allergy literature also demonstrate a publication bias towards more favorable results when a pharmaceutical company funds the study.

Methods: We reviewed all original articles published in seven pulmonary and allergy journals between October 2002 and September 2003. Included in the review were studies of inhaled corticosteroids (oral or nasal), long- or short-acting bronchodilators, or leukotriene receptor antagonists. Articles with funding from a pharmaceutical company and/or one or more authors employed by a pharmaceutical company were considered pharmaceutical company-sponsored studies. The remaining studies were considered not sponsored by a pharmaceutical company. Results were compared to ascertain whether positive results were obtained more frequently in the company-sponsored studies.

Results: Of the 100 articles included in this review 63 were considered pharmaceutical company-sponsored research. Results favorable for the drugs studies were significantly more common in those funded by a pharmaceutical company (98% vs. 32%).

Conclusions: In the pulmonary and allergy literature, as in other fields, there is a publication bias towards positive results in pharmaceutical company-sponsored research.

Background: Q fever is endemic in Israel, yet a large series describing the clinical spectrum of inpatients with acute Q fever in Israel is lacking. 

Objectives: To report on the clinical characteristics and outcome of hospitalized patients with acute Q fever in Israel. 

Methods: We conducted a retrospective study of 100 patients hospitalized in six medical centers, in whom acute Q fever was diagnosed by the presence of immunoglobulin G and M antibodies to phase II Coxiella burnetti antigens. 

Results: The mean age of the patients was 42.7 ± 17.3 years with a male to female ratio of 1.6:1. Acute Q fever occurred throughout the year but was more common during the warm season. The most common clinical presentation was acute febrile disease (98%, mean length of fever 15.5 ± 8.6 days), followed by hepatitis (67%) and pneumonia (32%). The prominent laboratory findings included: accelerated erythrocyte sedimentation rate, normal or low white blood count with many band forms, thrombocytopenia, and abnormal urinalysis. Although the diagnosis of acute Q fever was not known during the hospitalization in the majority of patients, about 80% of our patients received appropriate antibiotic therapy and all patients recovered. 

Conclusions: Patients with acute Q fever present with a typical clinical picture that enables clinical diagnosis and empiric therapy in most cases. The prognosis of hospitalized patients with acute Q fever is excellent.

Background: The current methods for pre‑ and post‑chemotherapy examination of the extent of disease in the breast and lymph nodes do not provide sufficiently accurate information and, not infrequently, the surgeon has to re‑operate.

Objectives: To correlate the findings between three methods of examination (physical examination, ultrasonography, mammography), all performed by the same oncologic and radiologic team, in patients with locally advanced breast cancer or a tumor/breast tissue ratio that precludes breast-conserving surgery.

Methods: Forty patients (median age 48 years, range 24–73) with locally advanced breast cancer or with a tumor/breast ratio that precluded breast‑conserving surgery were evaluated by the same medical team and received neoadjuvant chemotherapy. Surgery was performed in all, and the pathologic specimen was correlated with the results of the other examinations.

Results: In the pre‑chemotherapy evaluation, the imaging findings of the breast correlated with the physical findings in 78% of the patients and with the axilla examination in 66.7%. In the post‑chemotherapy analysis, imaging agreed with the physical findings of the breast in 62.2% and in 76.3% of the axilla. Sonography best detected occult breast disease and axillary lymph nodes but correlated with pathology in only 58% of the patients in diagnosing breast tumor and in 65.8% in diagnosing axillary lymph nodes. Mammography correlated with breast and lymph node pathology in half the patients.

Conclusions: None of the classical methods of post‑neoadjuvant chemotherapy evaluations could adequately delineate the actual extent of the disease in the breast and axillary lymph nodes. More exacting techniques of imaging combined with the classical methods are required.

Background: Metastatic melanoma is an aggressive and highly malignant cancer. The 5 year survival rate of patients with metastatic disease is less than 5% with a median survival of only 6–10 months. Drugs like dacarbazin (DTIC) as a single agent or in combination with other chemotherapy agents have a response rate of 15–30%, but the duration of response is usually short with no impact on survival. Interleukin-2-based immunotherapy has shown more promising results. The National Institutes of Health recently reported that lymphodepleting chemotherapy, followed by an adoptive transfer of large numbers of anti-tumor specific tumor-infiltrating lymphocytes, resulted in an objective regression in 51% of patients.

Objectives: To introduce the TIL[1] technology to advanced metastatic melanoma patients in Israel.

Methods: We generated TIL cultures from tumor tissue, choosing those with specific activity against melanoma and expanding them to large numbers.

Results: TIL cultures from nine patients were established and examined for their specific activity against the patients' autologous tumor cells. Twelve TIL cultures derived from 5 different patients showed the desired anti-tumor activity, making those 5 patients potential candidates for the therapy.

Conclusions: Pre-clinical studies of the TIL technology in a clinical laboratory set-up were performed successfully and this modality is ready for treating metastatic melanoma patients at the Sheba Medical Center's Ella Institute.

Background: Magnetic resonance imaging is a diagnostic tool of growing importance. Since its introduction, certain medical implants, e.g., pacemakers, were considered an absolute contraindication, mainly due to the presence of ferromagnetic components and the potential for electromagnetic interference. Patients with such implants were therefore prevented from entering MRI systems and not studied by this modality. These devices are now smaller and have improved electromechanical interference protection. Recently in vitro and in vivo data showed that these devices may be scanned safely in the MRI.

Objectives: To report our initial experience with three patients with pacemakers who underwent cerebral MRI studies.

Methods: The study included patients with clear clinical indications for MRI examination and who had implanted devices shown to be safe by in vitro and in vivo animal testing. In each patient the pacemaker was programmed to pacing-off. During the scan, continuous electrocardiographic telemetry, breathing rate, pulse oximetry and symptoms were monitored. Specific absorption rate was limited to 4.0 W/kg for all sequences. Device parameters were assessed before, immediately after MRI, and 1 week later.

Results: None of the patients was pacemaker dependent. During the MRI study, no device movement was felt by the patients and no episodes of inappropriate inhibition or rapid activation of pacing were observed during the scan. At device interrogation here were no significant differences in device parameters pre-, post-, and 1 week after MRI. Image quality was unremarkable in all imaging sequences used and was not influenced by the presence of the pacemaker.

Conclusion: Given appropriate precautions, MRI can be safely performed in patients with a selected permanent pacemaker. This may have significant implications for current MRI contraindications.  

Twenty years ago the Israeli Association of Allergy and Clinical Immunology was established, unifying these two fields into one speciality.

Objective: To assess the effect of establishing a new dedicated acute stroke unit within a department of neurology on indicators of process of care and outcome of acute stroke in a routine clinical setting in Israel.

Methods: Stroke patients admitted to the Sheba Medical Center during the period March 2001 to June 2002 were included in a prospective study according to selection criteria. Data on demographics, risk factors, co-morbidities and stroke severity were collected. Indicators of process of care and outcome were assessed at hospital discharge and 30 days follow-up. Comparison between outcome variables by hospitalization ward was conducted using logistic regression analysis adjusting for confounders.

Results: Of 616 acute stroke patients (mean age 70 years, 61% men, 84% ischemic stroke), 353 (57%) were admitted to general wards and 263 (43%) to the stroke unit. Diagnostic procedures were performed more often, and infection rate was lower in the setting of the stroke unit. Poor outcome (modified Rankin scale ≥3 or death) was present less often in patients managed in the stroke unit both at hospital discharge (adjusted odds ratio 0.5, 95% confidence interval 0.3–0.8) and at 30 day follow-up (adjusted OR[1] 0.6, 95%CI[2] 0.3–0.9). A Functional Independence Measure score ≤90 or death at 30 day follow-up was less frequent among patients managed in the stroke unit than in general wards (adjusted OR 0.5, 95%CI 0.2–0.8).

Conclusions: Improved outcomes and higher adherence to guidelines were observed in patients treated in a stroke unit within a department of neurology. The results suggest that patients with acute stroke should have access to treatment in a dedicated stroke unit.

Objectives: To establish the impact of breast MRI on women undergoing testing in our institution.

Methods: We analyzed 82 cases that underwent MRI between January 2001 and April 2003. Analysis appraised the clinical impact of MRI testing in cases where medical summaries were available.

Results: Studies were categorized into five indications: a) screening in high risk women (n=7), b) search for primary disease in the presence of disease (n=5), c) monitoring of chemotherapy (n=2), d) postoperative assessment of tumor bed (n=9), and e) diagnostic/characterization of primary or recurrent breast cancer (n=59). Results were defined as negative, positive or no impact on clinical management. MRI testing had a positive impact in 62 cases, affecting measurable change in 9 cases. Benefit was seen in screening, diagnosis and postoperative cases. In 15 cases, MRI stimulated investigations.

Conclusion: MRI is a valuable tool in breast imaging and affects management. Further trials are necessary to define clearly the role of MRI and to ascertain whether in cases where beneficial impact on management is noted, there is ultimate impact on outcome. 

Objectives: To assess user satisfaction and clinical short-term effectiveness of a computerized store and forward teledermatology service in urban and rural units.

Methods: A multi-center, prospective, uncontrolled, cohort pilot trial was conducted for a period of 6 months. Primary care physicians referred patients to a board-certified dermatologist using text email accompanied by digital photographs. Diagnosis, therapy and management were sent back to the referring PCP[1]. Patients were asked to evaluate the level of the CSAFTD[2] service, effect of the service on accessibility to dermatologists, respect for privacy, availability of drugs, health improvement and overall satisfaction. PCPs assessed the quality of the teledermatology consultations they received, the contribution to their knowledge, and their overall satisfaction.

Results: Tele-diagnosis alone was possible for 95% (n=413) of 435 CSAFTD referrals; 22% (n=95) of referrals also required face-to-face consultation. Satisfaction with CSAFTD was high among patients in both rural and urban clinics, with significantly higher scores in rural units. Rural patients rated the level of service, accessibility and overall satisfaction higher than did urban patients. PCPs were satisfied with the quality of the service and its contribution to their knowledge. Rural physicians rated level of service and overall satisfaction higher than the urban physicians. Tele-referrals were completed more efficiently than referral for face-to-face appointments.

Conclusions: CSAFTD provided efficient, high quality medical service to rural and urban military clinics in the IDF[3].

Objective: To investigate the effectiveness of preoperative chemoradiation in increasing the resectability rates of rectal cancer and increasing the anal sphincter preservation rate.

Methods: The study group included 66 patients aged 33–84 years with T₂–T₃ rectal carcinoma who were treated in our institute from 1997 to 2002 with preoperative chemoradiation followed by surgery 6 weeks later. All patients underwent preoperative transrectal endoscopic ultrasound for tumor staging and localization. The duration of follow-up was 25 months.

Results: Chemoradiation led to tumor downstaging in 61 patients (92.4%), all of whom underwent low anterior resection. Only 11.4% of this group needed a temporary (6 weeks) loop colostomy/ileostomy. None of the 16 patients with post-treatment T₀ tumors had evidence of malignant cells on pathologic study. Five patients (7.6%) failed to respond to chemoradiation and underwent APR[1]. There were no major complications, such as leakage, and no deaths.

Conclusions: Neoadjuvant chemoradiation is an effective modality to downstage advanced rectal cancer, improving patient quality of life by significantly reducing the need for a terminal permanent colostomy, or even a temporary one.