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Biomedical subjects

Michael Rozenbaum

Publications and source records attributed to Michael Rozenbaum.

At least 19 recordsLinked to original sources
PubMed2006

Prevalence and clinical aspects of Behcet's disease in the north of Israel.

Behcet's disease (BD) has a higher prevalence in countries along the ancient silk route, but the actual prevalence in Israel is unknown. We evaluated the occurrence and clinical expression of BD in the northern region of Israel: in the whole population and by ethnic groups. The sample included all adult patients with BD (International Study Group criteria) treated at three medical centers in northern Israel. Patient data were collected by file review and physician survey. Relevant demographic data for the population served by the medical centers were obtained from the official Israeli authorities. A total of 112 patients were identified. The overall prevalence of BD was 15.2/100,000 and was similar in men and women. The prevalence rates among the Jewish, Arab, and Druze populations were 8.6, 26.2, and 146.4 per 100,000, respectively. Age at disease onset was similar in all ethnic groups and significantly lower in males (28.6+/-9.7 vs 32.9+/-11.3, p=0.03). There were no differences in disease manifestations by sex or ethnicity. All Druze patients were HLA-B5 positive, compared to 80.8% of the Arab patients and 72.0% of the Jewish patients. Recurrent oral ulcers in family members were more common in Arab patients (p=0.004). The BD severity index was significantly lower in Druze patients (p=0.05), mainly in males (p=0.03). This study confirms the high prevalence of BD in Israel and the variability in disease rates and expression by ethnic origin. Our findings, particularly regarding the Druze population, call for further field surveys and genetic studies.

Adult↗
PubMed2006

LPS-stimulated production of TNF-alpha by peripheral blood monocytes in patients with Behcet's disease.

Tumor necrosis factor alpha (TNF-alpha) is believed to play a significant role in disease pathogenesis of Behcet's disease (BD). High serum levels of TNF-alpha were repeatedly reported in patients with active BD and anti-TNF agents are effective in its treatment. The pathophysiology of TNF-alpha in BD is still unknown and conflicting results regarding TNF-alpha overproduction by peripheral blood monocytes (PBM) from patients with BD were reported. The aim of the study is to compare stimulated production of TNF-alpha by PBM of BD patients with that of healthy volunteers (HV) and to examine correlations between the ability of PBM to produce TNF-alpha and organ/system involvement in patients with BD. Eighteen patients with BD (mean age 38.4+/-12.4 years, 12 males) gave informed consent and completed the European BD Current Activity Form. The PBM were separated and treated with lipopolysaccharide (LPS) overnight. TNF-alpha levels in the supernatants were assayed by ELISA and values were expressed in terms of cell protein contents. The control group included 15 HV (mean age 34.2+/-9.9 years, seven males). The mean production of TNF-alpha/cell protein (ng/mg) and in-group dispersion were similar in both groups (p=0.98). In the subgroup analysis, TNF-alpha production by PBM in BD patients who reported "bad" or "very bad" global well-being over the last month (n=4) was higher compared to other patients with better self-rating (p=0.03). PBM of BD patients in the present study did not overproduce TNF-alpha upon stimulation with LPS. However, BD patients with a higher TNF-alpha-producing capacity had worse sense of well-being.

Adult↗
PubMed2006

Polyarthritis flare complicating rheumatoid arthritis infliximab therapy: a paradoxic adverse reaction.

BACKGROUND: The treatment of rheumatoid arthritis (RA) has changed dramatically over the past decade with the introduction of antitumor necrosis factor (anti-TNF) agents. Although subsets of patients may have only partial or no response, there is no report yet on possible worsening of RA with this therapy. OBJECTIVE: The objective of this study was to determine whether infliximab may paradoxically exacerbate RA. METHODS: One hundred seven patients with RA refractory to 3 disease-modifying antirheumatic drugs were treated with 3 mg/kg infliximab and methotrexate for at least 6 months. RESULTS: In 3 patients, there was an exacerbation of RA associated with the use of infliximab. The flare occurred during the first 6 to 12 months of treatment with polyarthritis, fever, and elevated acute phase reactants. Increase of infliximab dose resulted in further deterioration. CONCLUSION: We describe a paradoxic reaction, an exacerbation of RA, with infliximab. The mechanism of this side effect is unclear but may be related to altered immunity induced by the inhibition of TNF activity in predisposed patients.

Aged↗
PubMed2005

Rheumatoid lung nodulosis and osteopathy associated with leflunomide therapy.

BACKGROUND: Leflunomide (LEF) is indicated in adults for the treatment of active rheumatoid arthritis (RA). LEF inhibits dehydroorotate dehydrogenase, a key enzyme of the pyrimidine synthesis in activated lymphocytes. Among rare adverse effects, fatal interstitial lung disease has been recently reported during treatment of RA with LEF in Japan. Clinical trials outside Japan do not suggest that LEF causes an excess of pulmonary adverse effects. Development and increase of peripheral rheumatoid nodules in typical sites of RA patients following LEF therapy has been recently reported. OBJECTIVES: Two cases with new and accelerated development of rheumatoid lung nodulosis during LEF therapy were described in this study. METHODS: LEF treatment was administered to two male patients (77 and 66 years old) with long-standing active seropositive nodular RA with failure of multiple second line drugs and without lung involvement. Clinical and laboratory assessment using the American College of Rheumatology response criteria, chest computed tomography (CT), quantification of serum rheumatoid factor (RF), and monocyte count of peripheral blood along with routine laboratory follow up were performed on both patients before and during therapy. In case 1, a bone scan was performed due to sustained limbs pain. Open lung biopsy was performed in case 1 and core lung biopsy in case 2. RESULTS: Both patients achieved full clinical remission during 2 months of LEF therapy. In case 1, the first complaints were limbs pain after 10 months of treatment associated with intensive bone uptake on a bone scan consistent with hypertrophic pulmonary osteopathy. Productive cough developed after 3 months of the therapy in case 2. Initially, these complaints were not attributed to therapy. New lung disease was present on CT with cherry-like progressive cavitary nodules, predominantly involving the basal segments of the right lung. The first lung lesions were found by CT 13 months (case 1) and 7 months (case 2) after the beginning of therapy and were erroneously related to bronchiectasia in case 2. In both cases, the lung biopsy showed necrosis surrounded by epithelioid mononuclear inflammation with giant cells, consistent with rheumatoid lung node. The time that elapsed between the beginning of the first symptoms to LEF discontinuation was very long: 13 months in case 1 and 24 months in case 2. Discontinuation of LEF therapy was followed by an arrest in growth of lung nodules, resolution of limb pain, and gradual improvement of bone scan. A significant decrease of monocyte count and RF level in peripheral blood was observed during LEF therapy in both cases. CONCLUSION: For the first time, we described rheumatoid lung nodulosis as complication of successful LEF therapy for RA. Hypertrophic pulmonary osteopathy with severe limbs pain and dry cough were the first manifestations of the lung nodulosis. Monocytopenia during LEF therapy is proposed to be involved in pathogenesis of this rare complication of LEF therapy.

Aged↗
PubMed2005

Sjögren's syndrome in the community: can serology replace salivary gland biopsy?

BACKGROUND: It is relatively difficult in a community setting to perform salivary gland biopsy or reliable diagnostic tests for salivary gland involvement in a patient suspected to suffer from Sjögren's syndrome (SS). OBJECTIVE: To investigate whether anti-Ro/La antibodies are a good substitute for salivary gland biopsy in community patients suspected to suffer from SS. METHODS: Forty-one patients suspected as having SS due to dry eyes and mouth, articular complaints, and/or serological findings were examined for the presence of anti-Ro/La, and underwent minor salivary gland biopsy. RESULTS: Sixteen patients (39%) were classified as primary SS by the American-European Consensus Group criteria. Twelve subjects had anti-Ro/La antibodies and 11 subjects in this group had positive biopsy findings. Of 29 patients without anti-Ro/La antibodies, only four manifested positive biopsy findings. A significant association was found between the presence of anti-Ro/La antibodies and positive salivary gland findings characteristic for SS (p<0.0001, Fisher's exact test). CONCLUSION: These findings tend to support the suggestion that a patient suspected to suffer from SS in a community setting may be first tested for the presence of anti-Ro/La antibodies to confirm the diagnosis. Only those with a negative result for the presence of anti-Ro/La antibodies need to be referred for salivary gland biopsy.

Antibodies, Antinuclear↗
PubMed2005

Calcinosis in rheumatic diseases.

BACKGROUND: Calcinosis, or dystrophic soft-tissue calcification, occurs in damaged or devitalized tissues in the presence of normal calcium/phosphorus metabolism. It is often noted in the subcutaneous tissues of connective tissues diseases--primarily systemic lupus erythematosus, scleroderma, or dermatomyositis--and may involve a relatively localized area or be widespread. The calcinotic accumulations may lead secondarily to muscle atrophy, joint contractures, and skin ulceration complicated by recurrent episodes of local inflammation and infection. OBJECTIVES: To review the classification, pathogenesis, clinical features, and treatment of calcinosis in rheumatic diseases. METHOD: A MEDLINE search of articles from 1972 to 2004 was conducted utilizing the index word "calcinosis" with the coindexing terms "scleroderma," "lupus," "dermatomyositis," and "dystrophic calcification." RESULTS: Calcinosis may be the source of both pain and disability in connective tissue disease patients. Illustrative cases of patients with severe calcinosis are described. The literature available was critically reviewed. While warfarin, colchicine, probenecid, bisphosphonates, diltiazem, minocycline, aluminum hydroxide, salicylate, surgical extirpation, and carbon dioxide laser therapies have been used, no treatment has convincingly prevented or reduced calcinosis. CONCLUSIONS: Calcinosis is common in the conditions reviewed and a number of agents have been used for treatment. However, the approach to calcinosis management is disorganized, beginning with the lack of a generally accepted classification and continuing with a lack of systematic study and clinical therapeutic trials.

Adult↗
PubMed2005

Search for disease-specific cardiovascular reactivity patterns: developing the methodology.

Aberrations of CVR (cardiovascular reactivity), an expression of autonomic function, lack specificity for a particular disorder. Recently, a CVR pattern particular to chronic fatigue syndrome has been observed. In the present study, we aimed to develop methodologies for assessing disease-specific CVR patterns. As a prototype, a population of 50 consecutive patients with FMF (familial Mediterranean fever) was studied and compared with control populations. A 10 min supine/30 min head-up tilt test with recording of the heart rate and blood pressure or the pulse transit time was performed. Five studies were conducted applying different methods. In each study, statistical analysis identified independent predictors of CVR in FMF. Based on regression coefficients of these predictors, a linear DS (discriminant score) was computed for every subject. Each study established an equation to assess CVR, calculate DS for FMF and determine the sensitivity and specificity of the DS cut-off. In each of the five studies, abnormal CVR was observed in FMF patients. The best accuracy (88% sensitivity and 90.1% specificity for FMF) was obtained by a method based on beat-to-beat heart rate and pulse transit time recordings. Data was processed by fractal and recurrence quantitative analysis with recordings in FMF patients compared with a mixed control population. Identification of disease-specific CVR patterns was possible with the methodologies described in the present study. In FMF, disease-specific CVR may be explained by the interplay between neuroendocrine loops specific to FMF with cardiovascular homoeostatic mechanisms. Recognition of disease-specific CVR patterns may advance the understanding of homoeostatic mechanisms and have implications in clinical practice.

Adult↗
PubMed2005

Cardiovascular reactivity in fibromyalgia: evidence for pathogenic heterogeneity.

OBJECTIVE: To evaluate disease-specific cardiovascular reactivity patterns in patients with fibromyalgia (FM) using a recently described method called fractal and recurrence analysis score (FRAS). METHODS: The study group included 30 women with FM, average age 46.7 years (SD 7.03). An age matched group of 30 women with other rheumatic disorders or having a dysautonomic background [chronic fatigue syndrome (CFS), non-CFS fatigue, neurally mediated syncope, and psoriatic arthritis (PsA)] served as controls. Subjects were evaluated with a head-up tilt test with beat-to-beat recording of the heart rate (HR) and pulse transit time. A 10-minute supine phase was followed by 600 cardiac cycles recorded on tilt. Data were processed by recurrence plot and fractal analysis. Variables acting as independent predictors of the cardiovascular reactivity were identified in FM patients versus controls. RESULTS: No statistically significant differences were found between the groups by univariate analysis comparing 92 variables of cardiovascular reactivity in FM patients compared to controls. CONCLUSION: Study of cardiovascular reactivity utilizing a head-up tilt test and processing the data using the FRAS method did not reveal a specific FM-associated abnormality. Our data confirm studies that utilized other methodologies and reached similar conclusions. Patients with FM represent a heterogenous group with respect to their pattern of cardiovascular reactivity.

Arthritis, Psoriatic↗
PubMed2004

The case for hepatitis C arthritis.

OBJECTIVE: To present the data available supporting the existence of an arthropathy associated with hepatitis C infection. METHODS: The MEDLINE database was searched for "arthritis" intersecting with "hepatitis C" in addition to the authors' investigations and experience on this subject. RESULTS: Arthritis, not otherwise explained, has been noted in 2% to 20% of hepatitis C virus (HCV) patients. This arthritis is rheumatoid-like in two thirds of the cases and a waxing/waning oligoarthritis in the rest. Cryoglobulinemia alone does not explain the arthritis, and there is difficulty in differentiating it from rheumatoid arthritis. The arthropathy is nonerosive/nondeforming. Whereas nonsteroidal anti-inflammatory drugs, low-dose corticosteroids, and hydroxychloroquine may be helpful, conventional treatment of arthritis may be problematic in the context of viral hepatitic arthropathy. Antiviral therapy is most effective, even without viral clearance, but rheumatic complications may ensue. CONCLUSIONS: HCV arthropathy should be considered in the differential diagnosis of new-onset arthritis.

Algorithms↗
PubMed2004

Increased CD8+ T cell apoptosis in scleroderma is associated with low levels of NF-kappa B.

Our objectives were (1) to compare lymphocyte subpopulation apoptosis rates in SSc patients versus healthy controls and (2) to compare Bcl-2 and NF-kappa B expression in cultured CD8 lymphocytes of SSc patients versus controls. Peripheral blood samples were obtained from 27 SSc patients meeting the American College of Rheumatology criteria for SSc and 28 healthy individuals. Mononuclear cells were isolated by Ficoll-Hypaque density gradient separation and cultured for 48 hr. For determination of apoptosis within specific cell populations, samples were labeled with PE-conjugated monoclonal antibody to CD8, CD4, and a FITC-conjugated monoclonal antibody to Annexin V. Flow cytometry was carried out with a FACS operating with Cellquest software. CD8+ lymphocytes were positively selected with magnetic microbeads conjugated to antihuman CD8. CD8 T cells were separated, then incubated with activation for 48 hr, and NF-kappa B and Bcl-2 analysis was carried out using Western immunoblotting. The CD4:CD8 ratio was increased in SSc compared to controls (2.6 +/- 1.13 vs.1.87 +/- 0.76; P = 0.018). The spontaneous apoptosis rate of SSc CD8 lymphocytes was increased compared to that of controls of (21.9 +/- 13.7 vs. 13.3 +/- 9.9; P = 0.019). No difference was found in the rate of CD4 apoptosis of SSc patients versus controls (9.8 +/- 5.2 vs. 7.18 +/- 4.89%; P = ns). The expression of NF-kappa B in SSc CD8 lymphocytes was decreased compared with that of CD8 lymphocytes from healthy controls (144 +/- 13 vs. 188 +/- 11; P = 0.018). Whereas expression of Bcl-2 was similar in activated CD8+ T cells of SSc patients and healthy controls, CD8+ T cell apoptosis rate was found to be in reverse correlation with expression of NF-kappa B in these cells ( r = - 0.53, P = 0.029). The increased CD4:CD8 ratio in SSC may result from increased CD8+ T cell apoptosis. Increased SSc CD8 T cell apoptosis is associated with low levels of NF-kappa B.

Adult↗
PubMed2004

The feeling of fatigue--fatigue severity by unidimensional versus composite questionnaires.

The authors' purpose in this study was to compare the perception of fatigue severity as measured by different fatigue questionnaires. The authors evaluated 3 groups of patients in a cross-sectional study: chronic fatigue syndrome (CFS, n = 20), non-CFS fatigue (n = 20), and familial Mediterranean fever (FMF n = 25). In addition, the authors tracked 7 patients with CFS longitudinally for severity of fatigue. The severity of fatigue-related symptoms was assessed with 2 questionnaires: the unidimensional Chalder's Fatigue Severity Scale (CH) and the composite Fatigue Impact Scale (FI) which has 3 subscales--cognitive, physical, and social--and a total score. In the cross-sectional study, correlations between CH and FI cognitive scores were r = .78 (p < .0001), CH versus FI physical scores r = .603 (p < .0001), CH versus FI social scores r = .66 (p < .0001), and CH versus FI total scores r = .74 (p < .0001). In the longitudinal survey of CFS patients, the authors compared 30 questionnaires revealing correlations of CH versus FI cognitive scores r = .64 (p = .0004), CH versus FI physical r = .68 (p = .0001), CH versus FI social r = .87 (p < .0001), and CH versus FI total r = .90 (p < .0001). Fatigue severity as assessed by the unidimensional CH scale and the composite FI scale is comparable. The simple CH scale may be adequate for the assessment of the feeling of fatigue, in general, and for monitoring the severity of fatigue in CFS, in particular.

Cross-Sectional Studies↗
PubMed2003

Cardiovascular reactivity score for the assessment of dysautonomia in familial Mediterranean fever.

OBJECTIVE: The aim of this study was to assess the presence of dysautonomia, as manifested in abnormal cardiovascular reactivity, in patients with familial Mediterranean fever (FMF). METHODS: Fifty-five consecutive patients with FMF and 23 age- and sex-matched healthy controls were evaluated. Cardiovascular reactivity was studied: (1) using recordings of blood pressure (BP) and heart rate (HR) during 10 min of recumbence and 30 min of head-up tilt test to identify clinical endpoints and (2) during tilt-test, identifying parameters acting as independent predictors of FMF reactivity and enabling computation of a cardiovascular reactivity score (CVRS). RESULTS: Clinically, vasovagal reaction, postural tachycardia syndrome, and/or orthostatic hypotension were observed in ten patients (18.1%). Utilizing a derived equation, the group average CVRS in FMF was 5.83+/-1.78 (healthy group -7.60+/-5.41) ( P=<0.0001). A CVRS of >3.25 was associated with FMF, with 98% sensitivity and 100% specificity. CONCLUSION: A very high percentage of FMF patients exhibit abnormal cardiovascular reactivity which is clinically occult but can be detected on autonomic challenge and application of the CVRS.

Adult↗
PubMed2003

Severe livedo vasculitis treated with potassium iodide.

A young woman presenting severe livedo vasculitis (LV) was successfully treated with potassium iodide (KI). Previous attempts to cure her disorder with corticosteroids, low-dose aspirin, and azathioprine in various combinations had failed. To our knowledge, this is the first report of LV treated with KI.

Adult↗
PubMed2002

Systemic sclerosis sine scleroderma: is it always the same disease? Report of three patients and discussion.

The recent description of a large cohort of patients with the diagnosis of systemic sclerosis sine scleroderma (ssSSc) provided significant progress in our understanding of this entity. The prognosis of patients with ssSSc is, however, very variable, from benign in most cases to rapidly disabling in others. By reporting three new cases and analyzing previously published data, we discuss possible subsets and variants of the disease form.

Adolescent↗