Israel Medical Association Journal

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.

Objective: To identify correlates for under-utilization of influenza immunization among the elderly.

Methods: A telephone survey was conducted among a random sample of patients aged 65 and over registered at a Jerusalem primary care community clinic. The 626 questionnaires were analyzed for associations of immunization receipt for the latest influenza season. Multivariate logistic regression was performed to identify independent correlates. Respondents were also asked what factors had influenced their decision about immunization.

Results: The most frequently reported influence on getting immunized was a physician's recommendation. Immunization was independently associated with the identity of the primary care physician (P0.0001) and with having visited the physician during the previous 3 months (P=0.0006). Immunization was more likely among persons who believed that it provides complete protection from influenza (P0.0001) and less likely among those who believed immunization can cause influenza (P0.0001). Higher immunization rates were also associated with being married (P=0.0031).

Conclusion: Through their influence on patient knowledge and the effect of their recommendation, primary care physicians play a pivotal role in determining immunization rates. Physicians should routinely discuss the effects of immunization and recommend it to the elderly.

Background: Although influenza is usually a mild self-limiting disease it can cause serious complications in high risk groups. The economic costs of influenza are large due to the burden on the health system and absenteeism from work. There is evidence that the vaccine is underused in groups targeted for vaccination.

Objectives: To estimate: a) the compliance rate with the influenza vaccination in Israel during the winter seasons of 1998/1999 and 1999/2000, b) the role of health care personnel and the media in influencing compliance, and c) the reasons for lack of compliance in the elderly.      

Methods: Two national population-based random telephone surveys of 1,500 households were performed during October 1999 and January 2000 to survey influenza vaccination compliance prior to the winters of 1998/1999 and 1999/2000 respectively. Each survey was performed during four successive evenings. The response rate was 78.1% for the first survey and 79.1% for the second.

Results: Vaccination compliance was similar in both surveys. The average rate of vaccination was 6% for the population under 65 years and 50% for the population of 65 years and above. The overall vaccination rate was around 10%. The family physician was the main authority to recommend the vaccination, followed by the community nurse. Absence of recommendation and lack of faith in the efficacy of the vaccine were the main reasons for non-compliance.

Conclusion: Compliance rates with influenza vaccine in targeted groups in Israel remain relatively low. Health care personnel should be more involved in promoting the vaccine.
 

Background: Previous studies have suggested that prolactin may serve as an indicator of disease progression in breast cancer.

Objectives: To evaluate the use of PRL as a serum tumor marker in patients with breast cancer.

Methods: PRL serum level was determined in 99 breast cancer patients and compared with CA 15-3 serum level.

Results: Elevated serum level of PRL (>20 ng/ml) was found in 8 of 99 patients (8.1%). A stratified analysis of prolactin levels according to therapy revealed that PRL levels was increased in 8 of 55 untreated patients (14.5%), but not in patients who received hormonal or chemotherapy in the 3 months preceding the test (0/42 patients, P=0.009). However, mean PRL level was similar in patients with no evidence of disease activity and in patients with active disease (10.2 vs. 8.2 ng/ml, NS). In comparison, CA 15-3 mean level was significantly lower in patients with no evidence of disease as compared to patients with active disease (18.2 vs. 144.7 units/ml, P<0.001). PRL level was increased in 6 of 60 patients (10%) with no evidence of disease and in 2 of 39 (5.2%) with active disease (NS). In comparison, CA 15-3 level was increased in 3 of 60 patients (5%) with no evidence of disease and in 24 of 39 (61.5%) with active disease (P<0.001).

Conclusions: PRL levels are decreased following hormonal or chemotherapy in patients with breast cancer and there is no correlation between PRL serum level and the state of disease. Further studies are needed to clarify a possible clinical significance of hyperprolactinemia in a subset of patients with breast cancer.

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PRL = prolactin

Background: Articular cartilage is incapable of undergoing self-repair since chondrocytes lose their mitotic ability as early as the first year of life. Defects in articular cartilage, especially in weight-bearing joints, will predictably deteriorate toward osteoarthritis.  No method has been found to prevent this deterioration. Drilling of the subchondral bone can lead to fibrocartilage formation and temporary repair that slowly degrades. Animal experiments indicate that introducing proliferating chondrocytes such as cultured articular chondrocytes can reliably reconstruct joint defects.

Objectives: To describe our clinical experience in culturing and transplanting autologous chondrocytes. 

Methods: Biopsies were obtained from 10 patients, aged 18–45, undergoing a routine arthroscopy in which a cartilage defect was identified with indications for cartilage transplantation. The biopsies were further processed to establish chondrocyte cultures. ACT was performed in 8 of the 10 patients because of persistent symptoms for at least 2 months post-arthroscopy. All patients (6 men and 2 women) had a grade IV cartilage defect in the medial or lateral femoral condyle, and three had a defect in the trochlear region as well. Biopsies were removed from the lateral rim of the superior aspect of the femur, and cells were cultured in a clean room. Following a 2 order of magnitude expansion, cells were implanted under a periosteal flap.

Results: The eight patients implanted with autologous cells were followed for 6 months to 5 years (average 1 year). Complaints of giving-way, effusion and joint locking resolved in all patients, and pain as assessed by the visual analogue score was reduced by an average of 50%. Follow-up magnetic resonance imaging studies in all patients revealed that the defects were filled with tissue having similar signal characteristics to cartilage.

Conclusions: Chondrocyte implantation is a procedure capable of restoring normal articular cartilage in cases with isolated joint defects. Pain can be predictably reduced, while joint locking and effusion are eliminated. The effect on osteoarthritis progression in humans has not yet been elucidated.

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ACT = autologous chondrocyte transplantation

Background: Spectral analysis of heart rate variability has been shown to be a reliable non-invasive test for quantitative assessment of cardiovascular autonomic regulatory responses, providing a window reflecting the interaction of sympathetic and parasympathetic tone. Alterations in autonomic function are associated with a variety of physiologic and pathophysiologic processes and may contribute substantially to morbidity and mortality. Our previous study shows that patients with post-traumatic stress disorder have significantly lower HRV compared to controls, reflecting a basal autonomic state characterized by increased sympathetic and decreased parasympathetic tone.

Objectives: To apply this tool to PTSD patients treated with selective serotonin re-uptake inhibitors in order to assess the impact of such treatment on the autonomic dysregulation characterizing these patients.

Methods: Standardized heart rate analysis was carried out in nine PTSD patients treated with SSRI agents and compared to that in a matched control group of nine healthy volunteers and in nine untreated PTSD patients, based on a 15 minute resting electrocardiogram.

Results: Our preliminary results show that the HRV parameters indicating autonomic dysregulation, which characterize PTSD patients at rest, are normalized in responding patients by use of SSRIs. Neither the clinical implications of these findings nor their physiological mechanisms are clear at present, although we presume that they reflect a central effect, since the peripheral autonomic effects of SSRIs are relatively negligible.   

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HRV = heart rate variability

PTSD = post-traumatic stress disorder

SSRI = selective serotonin re-uptake inhibitor

Background: In trials comparing different formulations of measles vaccine, excess non-specific mortality occurred in female children who received high titer vaccine. These findings suggest a gender-specific effect of measles vaccine.

Objectives: To determine whether gender differences exist in the rates of adverse reactions and morbidity in the month following immunization with measles-containing vaccine, and to evaluate whether there is a gender-specific association between the humoral immune response to measles vaccination and post-vaccination morbidity.

Methods: Parents completed questionnaires on the health status of 755 infants aged 15-20 months, during the month preceding and the month following the measles-mumps-rubella vaccination. Blood samples were tested for measles antibody titers in a subsample of 237 infants.

Results: After controlling background morbidity in the infants, the relative risk of fever and rash following vaccination was 2.35 in females and 1.36 in males. The geometric mean antibody titers against measles were similar in both sexes and there was no significant association between antibody titer and post-vaccination morbidity in either sex.

Conclusions: Our findings demonstrate higher rates of adverse effects in females following vaccination with MMR vaccine, irrespective of the humoral response. This study emphasizes the need to consider possible gender differences when evaluating new vaccines.

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MMR= measles-mumps-rubella