Israel Medical Association Journal

Background: Inflammatory mediators, including cytokines and reactive oxygen species. are associated with the pathology of chronic liver disease. Hepatocytes are generally considered as targets but not producers of these important mediators.

Objectives: To investigate whether cells of hepatocellular lineage are a potential source of various cytokines we estimated the expression and secretion of tumor necrosis factor alpha, transforming growth factor beta 1 and interleukins I beta, 6 and 8 in the culture of well-differentiated human HepG2 cells treated for 24 hours with ethanol, acetaldehyde and lipopolysaccharide. Lipid peroxidation damage, glutathione content and glutathione perox­idase, catalase and superoxide dismutase activity were also determined.

Methods: HepG2 cells were treated for 24 hours with ethanol (50 mM), acetaldehyde (175 ìM) and LPS (1 ìg/ml). TNF-á, TGF­-â, L-1â, IL-6 and IL-8 mRNA were determined by reverse transcriptase polymerase chain reaction and secretion by en­zyme-linked immunoassay. Lipid peroxidation damage, glutathione content and antioxidant enzyme activities were determined spectrophotometrically.

Results: Exposure to ethanol for 24 hours induced the expression of TNF-á and TGF- â1. secretion of IL-1â and TGF-â₁ and decreased catalase activity. Acetaldehyde markedly increased TNF-á and IL-8 expression, stimulated IL-1â and IL-8 secretion, increased lipid peroxidation damage and decreased catalase activity, while LPS exposure induced the expression of TNF-á. TGF- â₁, IL-6 and IL-8, the secretion of TGF-â₁, IL-1â, IL-6 and IL-8, and a decrease in catalase activity. No change in GSH, GSHPx or SOD was found in any experimental condition.

Conclusions: The present studies confirm and extend the notion that hepatocytes respond to ethanol, acetaldehyde and LPS-producing cytokines. Oxidative stress produced by the toxic injury plays an important role in this response through up­regulation of inflammatory cytokines.

The novel neuropeptides hypocretin/orexin have recently been located on the lateral hypothalamus cells. This system has been linked to the regulation of both feeding and sleep, and recent studies have found an association between a defect in these neuropeptides and narcolepsy. We conducted a MED­LINE review of all the articles published since the discovery of hypocretin/orexin peptides, narrowing the field to the relation­ship between these neuropeptides and sleep. The finding of a deletion in the transcription of the hypocretin receptor 2 gene in narcoleptic Doberman pinschers and the development of a knockout of the hypocretin gene in mice pointed to the relevance of this system in the sleep-wake cycle. We provide further evidence of the role of the hypocretin/orexin system in narcolepsy and in sleep regulation and present an integrative model of the pathophysiology of narcolepsy. The discovery of the link between these peptides and narcolepsy opens new avenues to both the understanding of sleep mechanisms and therapeutic implications for sleep disorders.

Background: Balneotherapy has been successfully used to treat various rheumatic diseases, but has only recently been evaluated for the treatment of fibromyalgia. Since no effective treatment exists for this common rheumatic disease, comple­mentary methods of treatment have been attempted.

Objectives:To assess the effectiveness of batneotherapy at the Dead Sea area in the treatment of patients suffering from both fibromyalgia and psoriatic arthritis.

Methods: Twenty-eight patients with psoriatic arthritis and fibromyalgia were treated with various modalities of bat­neotherapy at the Dead Sea area. Clinical indices assessed were duration of morning stiffness, number of active joints, a point count of 18 fibrositic tender points, and determination of the threshold of tenderness in nine fibrositic and in four control points using a dolorimeter.

Results: The number of active joints was reduced from 18.4+10.9 to 9+8.2 (P< 0.001). The number of tender points was reduced from 12.6+2 to 7.1±5 in men (P<0.003) and from 13.1+2 to 7.5+3.7 in women (P<0.001). A significant improvement was found in dolorimetric threshold readings after the treatment period in women (P< 0.001). No correlation was observed between the reduction in the number of active joints and the reduction in the number of tender points in the same patients (r= 0.2).

Conclusions: Balneotherapy at the Dead Sea area appears to produce a statistically significant substantial improvement in the number of active joints and tender points in both male and female patients with fibromyalgia and psoriatic arthritis. Further research is needed to elucidate the distinction between the benefits of staying at the Dead Sea area without balneotherapy and the effects of balneotherapy in the study population.

Objective: To study whether retinolpalmitate, beta-car­otene or lycopene could prevent liver cirrhosis induced by thioacetamide in rats.

Methods: In the control group liver cirrhosis was induced in male Wistar rats by intraperitoneal injections of TAA 200 mg/ kg for 12 weeks. The three study groups received in addition to TM either beta-carotene, lycopene or retinolpalmitate by gavage through an orogastric tube. Histopathological analysis and determination of the hydroxyproline contents of the livers were performed at the end of the protocol.

Results: Rats treated with beta-carotene and TAA had lower histopathologic scores and reduced levels of hepatic hydroxyproline (P= 0.02) than those treated by TAA alone. A trend of decreased fibrosis was observed in the rats treated with lycopene and TAA although this lacked statistical significance.

Conclusions: Beta-carotene attenuated liver cirrhosis induced by TAA in rats. The mechanism may be related to effects on hepatic stellate cells or to scavenging of free radicals by beta-carotene. Retinolpalmitate and lycopen had no significant beneficial effect.

Background: Familial Mediterranean fever is a genetic disorder manifested by recurrent attacks of peritonitis, pleuritis and arthritis, and characterized by clinical, histological and laboratory evidence for localized and systemic inflammation. Colchicine treatment usually prevents the attacks and the associated inflammation. Inflammation of atherosclerosis and ischemic heart disease.

Objective: To study the effect of inflammation and its prevention on occurrence of IHD, using FMF as a model.

Methods and Patients: We studied the presence of IHD and its risk factors in 290 FMF patients aged 40 years or more, and in two control groups – 233 spouses of the FMF patients’ and 126 patients with inflammatory diseases obtained from other outpatient clinics. FMF patients were also compared with age and gender-matched individuals from the population reference data of the Israel Ministry of Health.

Results: The prevalence of IHD in FMF patients was significantly lower than in the group of controls from other outpatient clinics (15.5% vs. 30.2% P< 0.05) and comparable with their spouses (11.2%) and with the matched general population in Israel (16%).

Conclusion: These findings suggest that despite the evidence of recurrent inflammation, colchicines-treated FMF patients are not more predisposed to IHD than the normal population.

Background: The aim of family medicine is to provide patients with comprehensive care within the biopsychosocial model. High job satisfaction is necessary to attract physicians to this specialty

Objective: To compare job satisfaction levels between primary physicians with training in family medicine and physicians without specialty training.

Methods: A self-report questionnaire, the "Task Profiles of General Practitioners in Europe," was mailed to a stratified random sample of 664 primary care physicians in Israel. The response rate was 77.6%. Bivariate and logistic regression procedures were used to analyze the data.

Results: Physicians with training in family medicine were less satisfied with the rewards for their work than general practitioners with no formal specialization in family medicine. Satisfaction with the intrinsic aspects of the work was found to be equal. Women and rural physicians were more satisfied than men and urban physicians.

Conclusion: Measures should be taken by health maintenance organizations to increase the level of job satisfaction of specialist-certified family physicians to avoid a crisis in the profession.
 

Background: Most corneal damage induced by contact lenses is due to interference with corneal oxygenation.

Objective: To investigate the effect on the rabbit cornea of a rigid gas-permeable contact lens with a newly designed periphery.

Method: We fitted New Zealand white rabbits (n=12) with RGP[1] contact lenses that were identical in all respects except for the design of the periphery. In each animal, one contact lens had an innovative periphery consisting of a microscopic diffractive relief lathed on the back surface; the other contact lens was of a conventional design. The lenses were worn continuously for 7 days. During this experimental period and for 1 additional week we assessed the corneal damage by daily testing lactic dehydrogenase activity in the tears.

Results: On the last day of the experimental week and the first 3 days of the healing period, mean tear LDH[2] activity was significantly lower in the eyes with the new contact lens design than in eyes with the conventional lenses.

Conclusions: The novel periphery design reduces corneal damage resulting from contact lens wear, as reflected by LDH levels in the tears. The new design probably facilitates the flow and exchange of tears under the contact lens, resulting in improved metabolism of the cornea. These findings may also prove applicable to soft contact lenses.

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.