Israel Medical Association Journal

Background: Primary idiopathic pulmonary hypertension is a rapidly progressive disease with a median survival of less than 3 years. Recently its prognosis was shown to dramatically improve with the use of epoprostenol, an arachidonic acid metabolite produced by the vascular endothelium, which increases the cardiac output and decreases the pulmonary vascular resistance and pulmonary arterial pressure. This drug enhances the quality of life, increases survival and delays or eliminates the need for transplantation.

Objective: To review the experience of Israel hospitals with the use of epoprostenol.

Methods: The study group comprised 13 patients, 5 men and 8 women, with an age range of 3–53 years. All patients suffered from arterial pulmonary hypertension. Epoprostenol was administered through a central line in an increased dose during the first 3 months, after which the dose was adjusted according to the clinical syndrome and the hemodynamic parameters.

Results: After 3 months the mean dose was 10 ng/kg/min and the pulmonary artery pressure decreased from 7 to 38%. After one year, the PAP decreased at a slower rate. Two cases required transplantation, three patients died, and seven continued taking the drug (one of whom discontinued). Four episodes of septicemia were observed. Today 10 patients are alive and well and 7 continue to take epoprostenol.

Conclusion: We found that epoprostenol improves survival, quality of life and hemodynamic parameters, with minimum side effects.

Background: Familial Mediterranean fever is an autosomal recessive disease characterized by sporadic attacks of inflammation affecting the serosal spaces. The gene associated with FMF[1] (MEFV), mainly expressed in neutrophils, was recently found to be expressed also in primary cultures of serosal origin (peritoneal and synovial fibroblasts). A C5a inhibitor, previously detected in normal serosal fluids, was recently identified in serosal cultures as well, and was found to be deficient in serosal fluids and cultures obtained from FMF patients.

Objective: To investigate the effect of colchicine (the main therapeutic agent for FMF patients) and certain inflammatory cytokines (IL-1b, TNF-a, IFN-a, IFN-g) on MEFV expression and C5a inhibitor activity in neutrophils and primary peritoneal fibroblast cultures.

Methods: Human primary peritoneal fibroblast cultures and neutrophils were studied for MEFV expression and C5a inhibitor activity, using reverse transcription-polymerase chain reaction and C5a-induced myeloperoxidase assay, respectively, in the presence and absence of colchicine and cytokines.

Results: MEFV expression in neutrophils was high and could not be induced further. Its expression in the peritoneal fibroblasts was lower than in neutrophils and could be induced using colchicine and cytokines parallel with induction of C5a inhibitor activity. Semi-quantitative RT-PCR[2] assays enabled estimation of MEFV induction by the cytokines at 10–100-fold and could not be further increased by concomitant addition of colchicine.

Conclusion: Serosal tissues, which are afflicted in FMF, express colchicine and cytokine-inducible MEFV and contain inducible C5a inhibitor activity. The relation between colchicine ability to induce MEFV and C5a inhibitor activity, and its efficacy in FMF treatment, require further investigation.

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[1] RT-PCR = reverse transcription-polymerase chain reaction

[2] FMF = familial Mediterranean fever

Background: The rapidly increasing costs of healthcare pose a major challenge to many governments, particularly those of developed countries. Health policy makers in some Western European countries have adopted the policy of a strong primary healthcare system, partly due to their recognition of the value of primary care medicine as a means to restrain costs while maintaining the quality and equity of healthcare services. In these countries there is a growing comprehension that the role of the family physician should be central, with responsibility for assessing the overall health needs of the individual, for coordination of medical care and, as the primary caregiver, for most of the individual’s medical problems in the framework of the family and the community.

Objectives: To describe primary care physicians in Israel from their own perception, health policy makers' opinion on the role PCPs should play, and patients' view on their role as gatekeepers.

Methods: The study was based on three research tools: a) a questionnaire mailed to a representative sample of all PCPs employed by the four sick funds in Israel in 1997, b) in-depth semi-structured interviews with key professionals and policy makers in the healthcare system, and c) a national telephone survey of a random representative sample of patients conducted in 1997.

Results: PCPs were asked to rank the importance of 12 primary functions. A total of 95% considered coordination of all patient care to be a very important function, but only 43% thought that weighing economic considerations in patient management is important, and 30.6% thought that 24 hour responsibility for patients is important. Also, 60% of PCPs have undergone specialty training and 94% thought that this training is essential. With regard to the policy makers, most preferred highly trained PCPs (board-certified family physicians, pediatricians and internists) and believed they should play a central role in the healthcare system, acting as coordinators, highly accessible and able to weigh cost considerations. Yet, half opposed a full gatekeeper model. They also felt that the general population has lost faith in PCPs, and that most have a low status and do not have adequate training. Regarding the patients’ viewpoint, 40% preferred that the PCP function as their “personal physician” coordinating all aspects of their care and fully in charge of their referrals; 30% preferred self-referral to sub-specialists, and 19% preferred their PCP to coordinate their care but wanted to be able to refer themselves to specialists.

Conclusions: In order to maintain high quality primary care, it is important that all PCPs have board certification. In addition, PCP training systems should emphasize preventive medicine, health promotion, health economy, and cost-effectiveness issues. Efforts should be make to render PCPs a central role in the healthcare system by gradually implementing the elements of the gatekeeper model through incentives rather than regulations.
 

Background: Domestic violence is a prevalent problem with serious consequences, including a 30% risk of death. The lifetime prevalence ranges from 21 to 34%, with 8–14% of them reporting abuse in the previous year. The incidence seen in primary care practice is about 8%. Despite this high rate, domestic violence is under-diagnosed in primary care.

Objectives: To estimate the prevalence of domestic violence among women visiting a primary care center, to characterize them and to evaluate a screening tool.

Methods: A brief anonymous questionnaire (in Hebrew and Russian) for self-completion was used as a screening tool. During October 1998 we distributed the questionnaires in a primary care clinic in Beer Sheva to all women aged 18–60 years whose health permitted their participation. A woman was considered at high risk for domestic violence when she gave a positive answer to at least one of the three questions related to violence. The risk factors for domestic violence were calculated by odds ratio with 95% confidence intervals.

Results: The response rate was 95.7%. We found 41 women (30.8%) at high risk for violence. Women preferred talking about this issue with their family physician. Women at highest risk were older than 40 years, had emigrated from the former Soviet Union during the last 10 years, were living alone, and were unemployed. None of the women visited the Domestic Violence Center during the study period and 2 months thereafter. Only three women tore off the address and phone number of the center that were attached to the questionnaire.

Conclusions: The anonymous questionnaire was well accepted and had a high compliance rate. Its disadvantages are that respondents must be literate and that it permits the woman to continue with her “secret-keeping” behavior. A high prevalence of domestic violence among women visiting a primary care clinic should convince family physicians to be more active in diagnosing the problem accurately among their patients, providing treatment and preventing further deterioration and possible danger. Further effort should be directed at improving the clinic staff's ability to detect domestic violence among patients, and in developing management programs in the health system to help combat domestic violence.

Background: The prevalence of attention deficit-hyperactivity disorder and its pharmacologic treatment have increased dramatically in the past decade in the United States and Britain. We examined the use of methylphenidate hydrochloride for the treatment of ADHD in children in northern Israel.

Methods: We evaluated all prescriptions for methylphenidate filled in 1999 for children aged 5–18 years residing in northern Israel who were insured by Clalit Health Services, a health maintenance organization that covers approximately 70% of the population.

Results: Methylphenidate was prescribed to 1.45% of the children in northern Israel in 1999, an increase of 20% in the overall prevalence of methylphenidate use since 1992. Eighty-two percent were boys. The rate of prescription varied widely by type of settlement, from 0.2% in Arab cities and towns to 5.7% in kibbutzim. Primary care physicians wrote 78% of all the prescriptions.

Conclusions: The increase in methylphenidate use was much smaller in northern Israel than in most other developed regions and countries. More efforts at diagnosis and treatment of attention deficit disorders may need to be directed at Arab populations and those with inadequate medical services.

One of the most important issuesfor a country, its population and doctors is the effective use of its health system. The tremendous waste of resources. To combat this, and at the same time ensure that medical quality plays a role when making decisions on interventions, it is essential to equip doctors and clinic directors with information on the quality of the medical care they are providing. In order to assist clinic directors in maitaining medical quality, Clalit Health Services has developed comparative medical indices enabling doctors to compare their performance to that of their colleagues, as well as to the standard and their performance over time. The development of an index to evaluate the quality of medical treatment offered in clinics provides doctors and the health system with an essential tool to lessen the existing variation among doctors and to enhance and evaluate performance.

In countries in which a primary care-oriented system has developed, general practitioners, family physicians, and other primary care doctors are the keystone of an approach that aims to achieve high quality and satisfaction with relatively low costs. Despite this new trend, medical schools still produce excessive numbers of sub-specialists rather than prinary care physicians. Among multiple reasons influencing a career choice either towards or away from primary care (institutional, legislative, and market pressures), the present article discusses ways in which medical school curricula may affect students in their perceptions of the role of primary care physicians. Since students are greatly influenced by the cultures of the institutions in which they train, the negative attitude of university towards family medicine may negatively affect the number of students going into this specialty. Examples from Israeli faculties are presented.

Background: The time to recurrence after surgical removal of primary pterygium (pterygium) and the association between the rate of recurrence and the postoperative interval remain unclear.

Objective: To determine the amount of follow-up time needed to identify recurrence in patients after surgical removal of pterygium.

Methods: We rviewed the files of 143 patients (143 eyes) with recurrent pterygium to determine the interval from surgery to recurrence.

Results: Almost all (91.6%) of the recurrences appeared by 360 days after surgery.

Conclusions: One year is the optimal follow-up time to identify recurrence of pterygium.

Sjogren’s syndrome is a chronic inflammatory process invol­ving primarily the exocrine glands. Its association with lymphoma is well documented. A low grade marginal-zone lymphoma related to mucosa-associated lymphoid tissue is the commonest lymphoid neoplasia in Sjogren’s syndrome. We review the literature and comment on the molecular, clinical, histopathologic and therapeutic aspects of these tumors in Sjogrens syndrome.

Background: The neurosteroids dehydroepiandrosterone (DHEA) and its sulfated metabolite (DHEAS) have been reported to possess neuroprotective as well as anti-tumoral activity in vitro and in vivo.

Objectives: To compare the effect of the two neurohor­mones on cell viability in primary whole-brain fetal mouse culture and isolated neuronal culture, as well as in a human neuroblastoma cell line (SK-N-SH).

Methods: Cell viability and cell proliferation were deter­mined with the neutral red and ³H-thymidine uptake methods, Apoptosis in propidium iodide-stained neuroblastoma cells was determined using flow cytometry.

Results: DHEA (1 nM-10 ìM) decreased the viability of selected primary neuronal cells (33-95% after 24 and 72 hours) but not of whole-brain cultured cells (neuron+glia). DHEAS did not significantly modify cell viability in either primary culture. In a human neuroblastoma cell line, DHEA (1 nM- 1 ìM) decreased ³H-thymidine uptake (30-60%) and cell viability (23-52%) after 24 hours. DHEAS did not significantly modify, or only slightly stimulated, cell viability and uptake of  ³H-thymidine (132% of controls). The combination of DHEA and DHEAS neutralized the toxic effect of DHEA in both primary neuronal culture and neuroblastoma cell line. Flow cytometric analysis of DNA fragmentation in neuroblastoma cells treated with 100 nM DHEA/DHEAS for 24 hours showed an increase in apoptotic events (31.9% and 26.3%. respec­tively, vs. control 2.54%).

Conclusions: Our results do not confirm a neuroprotective role for DHEA and suggest that DHEA and DHEAS have a differential role: DHEA possesses a neurotoxic (expressed only in isolated neurons) and anti-proliferative effect DHEAS demonstrates only a slight neuroprotective effect.
 

Background: Urinary incontinence in older women is common. Its characteristics and impact on quality of life is not well established since these women are usually reluctant to tell their healthcare providers about the problem.

Objective: To determine the characteristics of urinary incontinence in women and the manner in which it affects patients quality of life.

Methods: Twenty family physicians were requested to distribute a questionnaire to the first 25 consecutive women aged 30 to 75 years who visited their clinic for any reason. The questionnaire covered general health issues, symptoms of urinary incontinence, and quality of life.

Results: A total of 418 women, mean age 50.0 ± 11.8 years, completed the questionnaire (84% response rate). Of these, 148 (36%) reported having episodes of urinary incontinence. Urinary incontinence was found to be associated with older age, menopause, obesity and coexisting chronic disorders. Sixty percent of the women with urinary incon­tinence found it to be a disturbing symptom, and 44% reported that it had a detrimental effect on their quality of life. Only 32% of the affected women had sought medical advice, half of them from their family physician. Treatment was recommended to 66% of those who sought help, and in about two-thirds of these it brought some measure of relief.

Conclusions: Urinary incontinence is a common com­plaint among women attending primary care clinics, but it does not receive appropriate attention, Though it often adversely affects quality of life, only a small proportion of women seek medical advice. Family physicians should raise the issue as a part of the routine general health check-up.