Israel Medical Association Journal

Background: Cigarette smoking is a well-known risk factor for the development of endothelial dysfunction and the progression of atherosclerosis. Oxidative stress and inflammation have recently been implicated in endothelial dysfunction.

Objectives: To assess the concomitant contribution of polymorphonuclear leukocytes to systemic oxidative stress and inflammation in cigarette smokers.

Methods: The study group comprised 41 chronic cigarette-smoking, otherwise healthy males aged 45.0 ± 11.5 (range 31–67 years) and 41 male non-smokers aged 42.6 ± 11.3 (range 31–65) who served as the control group. The potential generation of oxidative stress was assessed by measuring the rate of superoxide release from separated, phorbol 12-myristate 13-acetate-stimulated PMNL[1] and by plasma levels of reduced (GSH) and oxidized (GSSG) glutathione. Inflammation was estimated indirectly by: a) determining the in vitro survival of PMNL, reflecting cell necrosis; b) in vivo peripheral PMNL counts, reflecting cell recruitment; and c) plasma alkaline phosphatase levels, indicating PMNL activation and degranulation.

Results: PMA[2]-stimulated PMNL from cigarette smokers released superoxide at a faster rate than PMNL from the controls. Smokers had decreased plasma GSH[3] and elevated GSSG[4] levels. In vitro incubation of control and smokers' PMNL in sera of smokers caused necrosis, while control sera improved smoker PMNL survival. Smokers' PMNL counts, although in the normal range, were significantly higher than those of controls. Plasma ALP[5] levels in smokers were significantly higher than in controls and correlated positively with superoxide release and PMNL counts.

Conclusions: Our study shows that PMNL in smokers are primed in vivo, contributing concomitantly to systemic oxidative stress and inflammation that predispose smokers to endothelial dysfunction, and explains in part the accelerated atherosclerosis found in smokers.

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[1] PMNL = polymorphonuclear leukocytes

[2] PMA = phorbol 12-myristate 13-acetate

[3] GSH = reduced glutathione

[4] GSSG = oxidized glutathione

[5] ALP = alkaline phosphatase

Background: The threat to the individual’s physical integrity and well-being as well as to those of significant others, the disruption of normal patterns of life, and property losses make wartime a highly stressful condition.

Objectives: To assess the level of psychological distress in primary care attenders in a district of Jerusalem (Gilo) that experienced long-term exposure to gunfire.

Methods: A self-administered questionnaire exploring emotional distress (anxiety and depression symptoms), fire exposure, patterns of help-seeking behavior, and prescription of sedative or hypnotic drugs was administered to a sample of 125 consecutive attenders to a general practitioner during a 10 week period in the autumn of 2001. Eighty-four attenders residing in Gilo were compared with 41 attenders residing in neighborhoods that had not been under fire. T-tests and Mann-Whitney two-sample tests were used to determine statistical significance of differences.

Results: The mean distress score was significantly higher among the Gilo residents than among their counterparts in other neighborhoods (1.1 ± 0.8 vs. 0.8 ± 0.5, t = 1.73, P <0.01); 15.5% of the former reported probable clinically significant distress. Emotional distress was associated with periods of intensive gunfire exposure, psychological care-seeking behavior, and the prescription of sedative or hypnotic drugs. No significant differences in distress levels were found between those living in zones of Gilo that were at differential gunfire risk, nor between those whose houses and cars were or were not damaged.

Conclusions: War-related life events would seem to be associated with elevated emotional distress. A motivated primary care physician could easily and reliably ascertain the attenders’ psychological status and identify those requiring psychological support. These identification and intervention stages are facilitated if the specialized services are community-based.

Background: The evaluation of hospitalized patients with chest pain and non-diagnostic electrocardiogram is problematic and the optimal cost-effective strategy for their management controversial.

Objectives: To determine the utility of myocardial perfusion imaging with thallium-201 for predicting outcome of hospitalized patients with chest pain and a normal or non-diagnostic ECG.

Methods: On pain cessation, 109 hospitalized patients, age 61+14 years (mean+SD), with chest pain and non-diagnostic ECG underwent stress myocardial perfusion SPECT imaging with thallium-201. Costs related to their management were calculated. The occurrence of non-fatal myocardial infarction or cardiac death was recorded at 12+5 months follow-up.

Results: A normal SPECT was found in 84 patients (77%). During one year follow-up, only 1 (1.2%) compared to 7 (28%) cardiac events (6 myocardial infarctions, 1 cardiac death) occurred in patients with normal versus abnormal scans respectively (P < 0.0001). Negative predictive value and accuracy of the method were 99% and 83% respectively. Multivariate regression analysis identified an abnormal SPECT as the only independent predictor of adverse cardiac event (P = 0.0016). Total cost from admission until discharge was 11,193 vs. 31,079 shekels (P < 0.0001) for normal and abnormal scan. Considering its high negative predictive value, shortening the hospital stay from admission until scan performance to 2 days would result in considerably reduced management costs (from NIS 11,193 to 7,243) per patient.

Conclusion: Stress SPECT applied to hospitalized patients with chest pain and a normal or non-diagnostic ECG is safe, highly accurate and potentially cost effective in distinguishing between Iow and high risk patients.
 

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.

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 our experience, secondary enuresis nocturna is a common complaint among children after a motor vehicle accident.  However, as these children are often brought for examination as part of an insurance compensation claim, this complaint is not always reliable.

Objective: To describe a series of children in whom secondary enuresis occurred after a motor vehicle accident.

Methods and Results: Five children were brought to our clinic for evaluation of secondary nocturnal enuresis. Review of past history revealed a car accident preceding the onset of the enuresis. All but one had additional behavioral symptoms typical of post-traumatic stress disorder. Four children had evidence of head trauma, and one had psychological but no physical trauma. 

Conclusions: Nocturnal enuresis can occur after a motor vehicle accident due either to purely psychological trauma or organic head trauma. While nocturnal enuresis is generally attributed to organic causes, psychological mechanisms also play a significant role.