Israel Medical Association Journal

Background: Hepatitis C virus is the major cause of acute and chronic hepatitis in patients with end-stage renal disease receiving replacement therapy.

Objectives: To define the prevalence of HCV RNA in a population of patients on dialysis in Israel, to determine the relative risk of acquiring HCV infection while treated by hemodialysis or chronic ambulatory peritoneal dialysis, and to define the HCV genotypes in this population.

Methods: During 1995 we studied 162 dialysis patients. Information was obtained regarding the mode of dialysis, years of treatment, number of blood transfusions, and results of serological testing for HCV, hepatitis B virus, and human immunodeficiency virus. Anti-HCV antibodies were tested by a third-generation microparticle enzyme immunoassay. HCV RNA was determined by polymerase chain reaction. HCV genotyping was performed by a hybridization assay.

Results: HCV RNA was detected in 18% of the HD group and 7% of the CAPD group. The number of HCV RNA-positive patients was significantly higher in the HD than the CAPD group (P < 0.05). HCV RNA-positive HD patients were treated longer than the HCV RNA-negative patients (P < 0.02).

Conclusions: Third-generation immunoassay proved to be highly sensitive (94%) and specific (91%) in identifying HCV RNA positivity. Several HCV subtypes were detected, lb being the most frequent. Identification and isolation of infected HCV patients may minimize its spread in dialysis units and prevent cross-infection.

Cancer is a multi-step disease involving a series of genetic alterations that result in the loss of control of cell proliferation and differentiation. Such genetic alterations could emerge from the activation of oncogenes and the loss or malfunctioning of tumor suppressor gene activity. Our understanding of cancer has greatly increased through the use of DNA tumor viruses and their transforming proteins as a biological tool to decipher a cascade of events that lead to deregulation of cell proliferation and subsequent tumor formation. For the past ten years our laboratory has focused on the molecular biology of the human neurotropic papovavirus, JCV. This virus causes progressive multifocal Ieukoencephalopathy, a fatal neuro­degenerative disease of the central nervous system in immunocompromised patients. JCV is a common human virus that infects more than 80% of humans but does not induce any obvious clinical symptoms. The increased incidence of acquired immune deficiency syndrome and the use of immunosuppressive chemotherapy have dramatically raised the incidence of PML. The coincidental occurrence of malignant astrocytes and oligodendrocytes in PML patients, coupled with the induction of glioblastoma in JCV-intected non­human primates, provides intriguing speculation on the association between JCV and CNS malignancies. In this report we discuss clinical data and laboratory observations pointing to the direct involvement of JCV in cancer.

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: 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.

Background: inflammation is an important feature of atherosclerotic lesions and increased production of the actuephase reactant. The contribution of coagulation factor to the development of coronary artery disease has not yet been clearly established.

Objective: To test whether C-reactive protein, fibrinogen and antithrombin-III are associated with angiograpic CAD, history of myocardial infarction and extensive atherosclerotic involvement.

Methods: Blood samples were tested for CRP, fibrinogen and AT-III levels from 219 individuals undergoing coronary angiography.

Results: CRP was higher in patients with CAD (0.95 + 1.31, n=180, vs. 0.39 + 0.61 mg/dl, n=39, P<0.0001) and in those with a history of MI (1.07 + 1.64, n=96, vs. 0.65 + 0.72 mg/dl, n=84, P<0.05) than in control subjects. The patients who developed unstable angina had higher CRP levels than the patients with stable CAD (2.07 + 2/38, n=7, vs. 0.80 + 1.13 mg/dl, n=173, P<0.001).

Fibrinogen was significantly higher in patients with CAD (298 + 108 vs. 258 + 63 mg/dl, P<0.01). In patients with CAD, mean AT-III value was less than in patients without CAD, but this difference was found in CRP, fibrinogen and AT-III values among the patients with single, double or triple vessel disease.

Conclusion: CRP is elevated in patients with CAD and a history of MI. Elevated levels of CRP at the time of hospital admission is a predictive value for future ischemic events.

There is an association between higher levels of fibrinogen and CAD. The association of AT-III levels with CAD needs testing in further studies.
 

Background: Narcotic abuse has steadily become more prevalent in Israel and may result in an increasing number of children exposed prenatally to narcotics, with a consequent increase in the number of infants born with neonatal abstinence syndrome.

Objective: To report our experience with infants born to narcotic-addicted women between the years 1995 and 1998 at the Soroka University Medical Center.

Methods: The medical records of 24 newborns and their drug-addicted mothers admitted to our Medical Center for parturition were analyzed retrospectively. A diagnosis of NAS was established on the basis of the clinical presentation and anamnesis. The Finnegan Neonatal Abstinence Scoring System was used to assess drug withdrawal. Urine toxicological analysis for narcotics was done only for year 1998.

Results: Of the 24 newborn infants exposed prenatally to narcotics 23 (96%) developed NAS, and 78% (18 of the 23) had a Finnegan score of 8 or more. These 18 infants were treated pharmacologically (tincture of opium and/or Phenobarbital) until the score was reduced to less than 8, after which they received supportive treatment. In one child who became lethargic after the first dose of tincture of opium, the medication was stopped and supportive treatment alone was given. Four of the five neonates with scores of 7 and less were given supportive treatment. One of five infants who had a low Finnegan score at birth nevertheless received pharmacological therapy to prevent further deterioration of his physical state since he was born with severe dyspnea. Ten of the 24 children (42%) were followed for lengths of time ranging from 6 to 22 months after discharge, all of whom showed normal development.

Conclusion: About three-quarters of newborns exhibiting withdrawal syndrome required pharmacological therapy. Previous information on maternal drug abuse is a crucial criterion for early detection and treatment.
 

In recent years liver transplantation was shown to be the only clinically effective method of treating acute or chronic hepatic failure due to various causes. However, this ultimate therapeutic approach is limited by the growing disparity between organ donation and the number of patient on the waiting list.

Factors such as high cost, morbidity, and the need for lifelong immunosuppression accelerated the research on alternative methods to support the failing liver. Recently, new technologies incorporating hepatocytes and extracorporal circulation devices were introduced for liver support systems and their role in the treatment of acute liver failure.