Israel Medical Association Journal

Background: Targeted anti-tumor necrosis factor-alpha (TNFα) therapy in patients with rheumatoid arthritis (RA) has resulted in dramatic improvement in the course of the disease and prognosis. One of the features of RA is hyperplasia of synovial cells, particularly RA synovial fibroblasts (RA-SF), caused partially by impaired apoptosis of RA-SF cells. It has been shown that TNFα may inhibit apoptosis in RA-SF cells and this process may be reversed by the use of TNFα antagonists.

Objectives: To determine the influence of etanercept, an anti-TNFα agent, on sFas (CD 95) receptor.

Methods: We analyzed serum levels of sFaS and TNFα in a group of 26 patients with high RA disease activity who were selected to start treatment with etanercept. Assessment of sFas receptor and TNFα levels was performed before and 6 months after treatment with etanercept.

Results: Treatment with etanercept resulted in increased TNFα levels (log TNFα 0.602 vs. 1.17, P < 0.05) but no change in sFas levels (log sFas 3.17 vs. 3.11, P = 0.37). As expected, treatment resulted in significant reduction in both disease activity and levels of inflammatory markers.

Conclusions: Etanercept may increase TNFα levels in patients with RA. We also speculate that the Fas pathway is not the main apoptotic pathway in patients with RA treated with etenercept, since sFas, a marker of apoptotic activity, remained unchanged and was not influenced by disease activity and concomitant treatment. 

Objectives: To investigate the association between CAD and H. pylori infection using MPI.

Methods: This prospective study evaluated CAD positivity among consecutive patients referred to a tertiary medical center for a stress/rest MPI. All patients were tested for serum anti-H. pylori and CagA protein immunoglobulin G antibodies. The CAD-positive group included patients with ischemia and/or myocardial infarctions (MI) on a stress MPI, coronary artery bypass graft surgery (CABG) or percutaneous coronary interventions (PCI). CAD-negative subjects were defined as participants with a normal MPI, no pathological Q waves in resting ECG tracing, and no history of CAD. Both groups were compared for H. pylori and CagA seropositivity. Patients’ demographic data, risk factors for CAD, and childhood socioeconomic status were recorded.

Results: The study group consisted of 300 consecutive patients, 170 men and 130 women; 64% (110/173) CAD-positive patients and 47% (60/127) CAD-negative participants were found seropositive for H. pylori infection (P = 0.005). In the adjusted analysis, H. pylori infection was found to be associated with CAD- positive (odds ratio 1.83, 95% confidence interval 1.06–3.17, P = 0.031), and MI (fixed perfusion defects on MPI) (OR 3.36, 95%CI 1.44–7.84, P = 0.005). No association was noted with CagA positivity.

Conclusions: In patients undergoing a stress MPI, serum anti-H. pylori antibodies positivity was found to be associated with CAD, independent of traditional cardiovascular risk factors. 

Objectives: To report the first results from the Serbian National Cohort study, which was started in January 2000.

Methods: Our study included 374 patients: 260 primary APS patients and 114 SLE patients with secondary APS. Antiphospholipid antibody (aPL) analysis included detection of anticardiolipin antibodies (aCL) (immunoglobulin G and M), ß₂-glycoprotein 1, and lupus anticoagulant. Echocardiography was performed in all patients, and data on myocardial infarction, unstable angina, chronic cardiomyopathy and acute heart failure were collected.

Results: There were 30.7% secondary APS patients and 9.2% primary APS patients with pseudo-infective endocarditis (P = 0.0001). Cardiac manifestations were observed in 28.7% of patients who had more than one type of antibody (category I), in 24.1% with category IIa, in 23.1% with category IIb, and in 27.8% with category IIc (P = 0.78). Age was confirmed as a significant factor for cardiac manifestations in APS patients (52.3 and 43.3 years, respectively, P = 0.001). aCL IgG and IgM positivity was related to valvular changes in all APS patients and high levels of those antibodies increased the risk of these manifestations.

Conclusions: Patients with secondary APS had a higher prevalence of valvular lesions, and some aPL types and high levels of aPL were risk factors for specific cardiac manifestations in APS patients.

Background: Delayed diagnosis of choroidal neovascularization (CNV) in age-related macular degeneration (AMD) adversely affects visual outcome.

Objectives: To identify factors associated with early detection of CNV in the clinic setting.

Methods: Demographic and clinical data and lesion characteristics were retrospectively collected from 76 consecutive AMD patients who had a history of CNV in one eye and presented with CNV in the second eye. These data were evaluated for association with visual acuity (VA) at the time of presentation.

Results: Better VA was associated with a history of CNV in the fellow eye (P < 0.0001), adherence to follow-up every 4 months (P = 0.015), younger age (P = 0.03), smaller lesion (P < 0.0001), and non-subfoveal location (P = 0.048). VA of the fellow eye did not correlate with VA at presentation with CNV.

Conclusions: These data suggest that patients’ experience of CNV, regardless of VA, facilitates early diagnosis in the fellow eye. Adherence to follow-up in the routine clinic setting also facilitates early detection of CNV.

Background: The Fibrotest-Actitest™ is a six-parameter scoring system that allows quantification of liver fibrosis and inflammation. This test has been validated by several studies in hepatitis B and C viruses and alcoholic liver disease, with a high correlation between the liver biopsy and the results of the FT-AT[1] (AUROC between 0.78 and 0.95).The FT-AT was introduced in Israel (Rambam Laboratory) in March 2005.

Objectives: To assess the results of HCV[2] patients who underwent the test during the period March 2005 to February 2006.

Methods: Serum was taken and brought to the central laboratory performing the tests within 4 hours. Six parameters were evaluated using commercial kits approved by the designer of the test (Biopredictive): total bilirubin, gamma-glutamyltransferase, alpha-2 macroglobulin, haptoglobin, alanine aminotransferase, and apolipoprotein-A1. The results were sent to the website of Biopredictive (France), which provided the FT-AT score online using a patented formula.

Results: Of the 325 patients tested, only 4 were not interpretable because of hemolysis. Patients' age ranged from 7 to 72 years (median 42); 54% were female. Liver biopsy was performed in 81 patients and was compared with the results of the Fibrotest. Findings were as follows: 27% of the patients were F0, 19% F1, 20% F2, 17% F3 and 17% F4; 18% were A0, 32% A1, 28% A2 and 22% A3. The AUROC curve comparing the Fibrotest with liver biopsy with a cutoff point at F2 and A2 for significant fibrosis and inflammation was 0.85 and 0.79 respectively.

Conclusion: Fibrotest is a simple and effective method to assess liver fibrosis and inflammation and can be considered an alternative to liver biopsy in most patients with HCV.

Background: Chlamydia pneumoniae has previously been associated with higher prevalence of valvular and cardiac calcifications.

Objectives: To investigate a possible association of seropositivity for C. pneumoniae and the presence of cardiac calcifications (mitral annular or aortic root calcification, and aortic valve sclerosis).

Methods: We retrospectively analyzed serological data (immunoglobulin G TWAR antibodies) from the AZACS trial (Azithromycin in Acute Coronary Syndromes), and correlated the serological findings according to titer levels with the presence of cardiac calcifications as detected by transthoracic echocardiography.

Results: In 271 patients, age 69 ± 13 years, who underwent both serological and echocardiographic evaluation, we found no significant association between the "calcification sum score" (on a scale of 0–3) in seropositive compared to seronegative patients (1.56 ± 1.15 vs.1.35 ± 1.15, respectively, P = 0.26). The median "calcification sum score" was 1 (interquartile range 0–3) for the seronegative group, and 2 (interquartile range 0–3) for the seropositive group (P = 0.2757). In addition, we did not find a significant correlation of any of the individual sites of cardiac calcification and Chlamydia pneumoniae seropositivity.

Conclusion: Our findings suggest that past C. pneumoniae infection may not be associated with the pathogenesis of valvular and cardiac calcifications.