Israel Medical Association Journal

Background: Recent years have brought significant progress to the development of hormonal therapies for the treatment of breast cancer. Several new agents have been approved for the treatment of breast cancer in the metastatic setting, among which is the new non-steroidal aromatase inhibitor, anastrozole, introduced for clinical use in Israel in March 1997.

Objectives: To evaluate the response rate and survival duration of patients treated with anastrozole for metastatic breast cancer, who had previously received at least one line of hormonal therapy.

Methods: Anastrozole was administered to 37 patients with metastatic breast cancer. The median age was 64 years. Estrogen receptor was positive in 20 patients, negative in 10 and unknown in 7. All patients were previously treated with tamoxifen in the adjuvant setting or as first-line hormonal therapy for metastatic disease. Anastrozole was given orally, 1 mg/day. Response was evaluated 2 months after the initiation of treatment and reevaluated every 2 months. Therapy was given until disease progression. Ten ER[1]-negative patients were excluded from the final analysis.

Results: Twenty-seven patients were eligible for response and toxicity analysis. The median follow-up was 20 months. One patient (3.7%) achieved complete response and remains free of disease 28 months after start of therapy. No partial responses were seen. Twenty patients (74%) had stable disease. Two year actuarial survival was 57%. Median survival was 26.5 months after starting therapy and median progression free survival was 11 months. The toxicity was mild: one patient (3.7%) complained of weight gain and one patient (3.7%) had mild fatigue.

Conclusion: Although the response rate was low, hormonal therapy with anastrozole seems to be beneficial in terms of disease stabilization, freedom from progression, and overall survival without serious toxicity.  

Background: Nitrofurantoin is a commonly prescribed urinary antiseptic. Hepatic injury has been associated with its use.

Objectives: To present three patients in whom long-term exposure to the drug resulted in chronic active hepatitis, and review the epidemiology, clinical immunology, histopathology, pathogenetic features and treatment of previously reported cases.

Findings: Withdrawing nitrofurantoin once the diagnosis was suspected did not lead to remission of the liver disease and glucocorticoids had to be administered. One patient died of liver failure.

Conclusions: Awareness of this unusual side effect of nitrofurantoin is important and caution should be exerted before prescribing it. Over the past years new insight into the immune nature of this drug has emerged.
 

Background: Patients’ consent to being part of medical education is often taken for granted, both in primary and secondary care. Formal consent procedures are not used routinely during teaching and patients are not always aware of teaching activities.

Objective: To investigate patients’ attitudes and expectations on issues of consent regarding participation in teaching in general practice, and the influence of a student’s presence on the consultation.

Methods: The study took place in 46 teaching practices during the sixth year clinical internship in family medicine. Patients completed questionnaires at the end of 10 consecutive eligible consultations. The questionnaire contained data on the willingness to participate in teaching, the preferred consent procedure and the effects of the student’s presence. The doctors were asked to estimate the sociodemographic level in their clinic area.

Results: A total of 375 questionnaires were returned; the response rate was not affected by the clinic’s sociodemographic level. Overall, 67% of the patients had come into contact with students in the past; 3.2% of the participants objected to the presence of a student during the consultation; 15% would insist on advance notification of the presence of a student, and another 13.9% would request it; 4% stated that the presence of students had a detrimental influence on the physical examination and history; and 33.6% would refuse to be examined by a student without the doctor’s presence.

Conclusion: Most patients agreed to have a student present during the consultation; some would like prior notification; a minority refused the student’s presence. A large minority would refuse to be examined without the tutor’s presence. Our findings need to be taken into account when planning clinical clerkships.

Background: Leiomyoma is the common benign tumor of the female genital tract. The traditional treatment is hysterectomy, myomectomy or medical therapy by hormonal manipulation. Uterine arterial embolization, a recognized treatment for acute pelvic hemorrhage, has recently been applied to the management of non-acute uterine hemorrhage due to leiomyoma.

Objective: To describe our experience with uterine arterial embolization for the management of uterine fibroid.

Methods: Uterine arterial embolization was performed in nine patients with leiomyomas in whom medical therapy failed and who sought to avoid surgery.

Results: Follow-up ultrasound examination after 2 months revealed an average reduction in fibroid volume of 38%. There were no early or long-term complications.

Cunclusions: Uterine arterial embolization appears to be effective and safe in the management of symptomatic leiomyomas. It is a promising alternative to myomectomy or hysterectomy and warrants further investigation in this setting.
 

Background: Erysipelas is a skin infection generally caused by group A streptococci. Although penicillin is the drug of choice, some physicians tend to treat erysipelas with antibiotics other than penicillin.

Objectives: To define the pattern of antibiotic use, factors affecting antibiotic selection, and outcome of patients treated with penicillin versus those treated with other antimicrobial agents.

Methods: A retrospective review of charts of adult patients with discharge diagnosis of erysipelas was conducted for the years 1993-1996.

Results: The study group comprised 365 patients (median age 67 years). In 76% of the cases infection involved the leg/s. Predisposing condition/s were present in 82% of cases. Microorganisms were isolated from blood cultures in only 6 of 176 cases (3%), and Streptococcus spp. was recovered in four of these six patients. Cultures from skin specimens were positive in 3 of 23 cases. Penicillin alone was given to 164 patients (45%). Other antibiotics were more commonly used in the second half of the study period (P < 0.0001) in patients with underlying conditions (P = 0.06) and in those hospitalized in the dermatology ward (P< 0.0001). Hospitalization was significantly shorter in the penicillin group (P= 0.004). There were no in-hospital deaths.

Conclusions: We found no advantage in using antibiotics other than penicillin for treating erysipelas. The low yield of skin and blood cultures and their marginal impact on manage­ment, as well as the excellent outcome suggest that this infection can probably be treated empirically on an outpatient basis.
 

Fibromyalgia syndrome is a chronic, painful musculoske­letal disorder of unknown etiology and/or pathophysiology. During the last decade many studies have suggested autonomic nervous system involvement in this syndrome, although contradictory results have been reported. This review focuses on studies of the autonomic nervous system in fibromyalgia syndrome and related disorders, such as chronic fatigue syndrome and irritable bowel syndrome on the one hand and anxiety disorder on the other, and highlights techniques of dynamic assessment of heart rate variability, It raises the potentially important prognostic implications of protracted autonomic dysfunction in patient populations with fibromyalgia and related disorders, especially for cardiovas­cular morbidity and mortality.

Background: Fixed dose combination therapy varies among countries.

Objective: To compare the list of fixed-dose combination therapies used in the USA, UK and Israel.

Methods: The total list of drugs and FDC drugs were counted manually from a list of generic names. We also counted the number of drugs in four characteristic subgroups:

cardiovascular, anti-infective, gastrointestinal, and dermatolo­gical. Data for drugs in the USA, UK and Israel were taken from the Physician’s Desk Reference (PDR 1997), the British National Formulary (BNF March 1997) and the Monthly Ethical Drug Indexed Compilation (MEDIC July 1997) respectively.

Results: The global percentage of FDC drugs in the USA and UK was higher than in Israel (20%, 25% and 15% respectively). A similar trend was found in all subclasses of FDC drugs except for the anti-infective category in which the percentage of FDC drugs was low and similar in all countries.

Conclusion: The list of FDC drugs varies greatly between the USA, UK and Israel. reflecting the differences in the outcome of debate between the pharmaceutical companies and the regulatory authorities.

Background: When encountering complaints of pain in the area of the Achilles tendon, the clinician seldom reaches a correct and precise diagnosis based solely on the grounds of physical examination and standard X-rays.

Objectives: To assess the usefulness of ultrasound in diagnosing pathologies of the Achilles tendon.

Methods: We conducted a retrospective review of patients presenting at our orthopedic clinics.

Results: Sonography was used to evaluate 41 patients with achillodynia. This modality enabled the diagnoses of 19 abnormal tendons (46%), peritendinous and other lesions a complete rupture in two patients (5%) a partial rupture of the Achilles tendon in 3 (7%) various degrees of calcification of the tendon in 7 (17%) and peritendinous lesions discerned by the tendon’s hypoechoic regions with disorganized arrange­ment of collagen fibrils in 4 patients (10%). Other lesions included tendonitis (3 patients, 7%), retrocalcaneal bursitis (3 patients, 7%), lipoma (1 patient, 2%), and foreign bodies (2 patients, 5%). The mean diameter of the pathological tendons was 10.4 +2.7 mm, while normal tendons measured 5.2 +0.8 mm (P<0.001).

Conclusion: As in many other soft tissue lesions, ultrasonography is a useful tool in the evaluation of the underlying pathology in patients presenting with achillodynia.

Background: Foreign bodies are sometimes overlooked in the initial evaluation of soft tissue wounds in the emergency room setting. The physical examination identifies foreign bodies that are superficial enough to be seen or palpated, while radiographs reveal those that are radio-opaque. If these two criteria are not met, however, the foreign body may remain undetected. These patients present later with long-standing pain in the area of penetration sometimes associated with localized tenderness.

Objectives: To assess the role of ultrasonography in the diagnosis and management of patients with a suspected retained foreign body.

Methods: Ultrasound was used in 21 patients with suspected retained foreign bodies and the diagnosis was positive in 19. Fifteen underwent a surgical exploration in which the ultrasound was used as an adjunctive modality either pre- or intraoperatively to assist in the localization of the foreign body.

Results: All procedures were successful. No postoperative complications were recorded at an average follow-up of 2 years. Three patients gradually became asymptomatic and were left untreated. One patient was lost to follow-up.

Conclusion: Sonography is an extremely effective tool for the late diagnosis of retained foreign bodies in the soft tissues. We suggest that its availability in the emergency room may decrease the rate of misdiagnosis and avoid these unfortunate cases, although this remains tc be proven.
 

Objectives: To compare risk behavior between subjects attending anonymous and confidential clinics for human immunodeficiency virus testing, and to assess whether anonymous testing results in a higher accrual of persons at risk for HIV.

Methods: An anonymous questionnaire that addressed sociodemographic and risk behavior aspects was administered to 140 subjects attending an anonymous clinic and 124 attending a confidential clinic in the Tel Aviv area. A logistic regression analysis was used to compare the effects of various behavioral factors on the probability of attending each clinic.

Results: Chronological age, age at first sexual intercourse and the percent of married subjects were similar in both clinics. However, there was a significant difference in the sex ratio and in educational attainment (85.0% versus 55.6% were males, P< 0.001 and 58% vs. 34% had over 12 years of education, P<0.001, in the anonymous and confidential clinics respectively).

There was a striking difference between the two clinics with regard to sexual experience characteristics: of the subjects reaching the anonymous clinic 21.4% were homosexual and 10.0% bisexual versus a total of 2.6% in the confidential clinic. A logistic regression analysis, comparing the effects of various behavioral factors on the probability of attending each clinic showed that gender (male), high education, homosexuality, number of partners and sexual encounter with sex workers were the strongest predictors for selecting anonymous HIV examination.

Conclusions: Individuals at high risk for HIV, such as homosexuals and bisexuals, prefer to attend an anonymous clinic.
 

Background: The transfer of therapeutic genes into malignant brain tumors has been the subject of intense pre­clinical and clinical research in recent years. Most approaches have used direct intratumoral placement of a variety of vectors and genes, such as retroviruses or adenoviruses carrying drug-susceptibility genes, modified replication-competent herpes virus, and several vectors carrying tumor suppressor genes such as the p53 gene. However, clinical results have so far been disappointing, mainly due to the limited ability to effectively distribute the genetic material into the target cell population. Accordingly, alternative delivery approaches into the central nervous system, e.g., intravascular, are under investigation. Genetic vectors administered intravascularly are unlikely to penetrate the blood-brain barrier and transfer a gene into brain or tumor parenchyma. However, intravascular delivery of vectors may target endothelial cells lining the blood vessels of the brain. Since endothetial cells participate in a variety of physiological and pathological processes in the brain, their modulation by gene transfer may be used for a variety of therapeutic purposes. Angiogenically stimulated endothelial cells within tumors replicate rapidly and hence may become targets for retroviral-mediated gene transfer.

Objective: To assess the anti-tumor effect of transferring a drug-susceptibility gene into endothelial cells of the tumor vasculature.

Methods: As a model for this approach we delivered concentrated retroviral vectors carrying a drug-susceptibility gene via the internal carotid artery of rats with malignant brain tumors. The safety and efficacy of this approach, without and with subsequent treatment with a pro-drug (ganciclovir). was evaluated.

Results: No acute or long-term toxicity was observed after intraarterial infusion of the vector. Treatment with ganciclovir resulted in variable hemorrhagic necrosis of tumors, indicating preferential transduction of the angiogenically stimulated tumor vasculature. This was accompanied by severe toxicity caused by subarachnoid hemorrhage and intracerebral hemorrhage in vascular territories shared by the tumor and adjacent brain.

Conclusion: The data indicate that endothelial cells can be targeted by intraarterial delivery of retroviral vectors and can be used for devising new gene therapy strategies for the treatment of brain tumors.