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Biomedical subjects

Reuven Mader

Publications and source records attributed to Reuven Mader.

14 recordsLinked to original sources

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↗

Wegener granulomatosis with back pain, periaortitis, and dural inflammation developing while receiving monthly cyclophosphamide.

A 61-year-old white man was admitted to our department because of severe back and upper abdominal pain of 1 month's duration. The patient was diagnosed with Wegener granulomatosis 10 months before the presentation based on chronic otitis media, hoarseness, and hemoptysis; positive c-ANCA; and laryngeal and lung biopsies showing multinucleated giant cells. The patient was treated with monthly injections of cyclophosphamide (1-1.5 g per month) and 80 mg prednisone daily with rapid improvement. Prednisone dose was tapered off and 1 month before the present admission, the patient developed severe low back pain. Extensive workup, including abdominal computed axial tomography scan, computed tomography angiography, magnetic resonance image of the spinal cord, and fluorodeoxyglucose-positron emission tomography (FDG-PET) scan, revealed 2 periaortic soft tissue structures seen at the level of L3 and at the level of the celiac trunk and linear meningeal thickening of the spinal cord at the level of D4-8. All these structures showed strong signal on FDG-PET scan. Treatment with methylprednisolone (1000 mg/d) for 3 consecutive days followed by 80 mg prednisone per day and 100 mg cyclophosphamide per day was started with rapid attenuation of the patient's symptoms. This case describes the clinical course of the rare complication of Wegener granulomatosis, periaortitis, and dural inflammation despite monthly cyclophosphamide and demonstrates the role of magnetic resonance imaging and FDG-PET in their diagnosis.

Back Pain↗

Methotrexate enhances the anti-inflammatory effect of CF101 via up-regulation of the A3 adenosine receptor expression.

Methotrexate (MTX) exerts an anti-inflammatory effect via its metabolite adenosine, which activates adenosine receptors. The A3 adenosine receptor (A3AR) was found to be highly expressed in inflammatory tissues and peripheral blood mononuclear cells (PBMCs) of rats with adjuvant-induced arthritis (AIA). CF101 (IB-MECA), an A3AR agonist, was previously found to inhibit the clinical and pathological manifestations of AIA. The aim of the present study was to examine the effect of MTX on A3AR expression level and the efficacy of combined treatment with CF101 and MTX in AIA rats. AIA rats were treated with MTX, CF101, or both agents combined. A3AR mRNA, protein expression and exhibition were tested in paw and PBMC extracts from AIA rats utilizing immunohistochemistry staining, RT-PCR and Western blot analysis. A3AR level was tested in PBMC extracts from patients chronically treated with MTX and healthy individuals. The effect of CF101, MTX and combined treatment on A3AR expression level was also tested in PHA-stimulated PBMCs from healthy individuals and from MTX-treated patients with rheumatoid arthritis (RA). Combined treatment with CF101 and MTX resulted in an additive anti-inflammatory effect in AIA rats. MTX induced A2AAR and A3AR over-expression in paw cells from treated animals. Moreover, increased A3AR expression level was detected in PBMCs from MTX-treated RA patients compared with cells from healthy individuals. MTX also increased the protein expression level of PHA-stimulated PBMCs from healthy individuals. The increase in A3AR level was counteracted in vitro by adenosine deaminase and mimicked in vivo by dipyridamole, demonstrating that receptor over-expression was mediated by adenosine. In conclusion, the data presented here indicate that MTX induces increased A3AR expression and exhibition, thereby potentiating the inhibitory effect of CF101 and supporting combined use of these drugs to treat RA.

Adenosine↗

The involvement of NK cells in ankylosing spondylitis.

A role for NK cells in the regulation of autoimmunity has been demonstrated. Since there is a strong association between Ankylosing Spondylitis (AS) and HLA-B27, which is specifically recognized by the NK-inhibitory receptor KIR3DL1, this study evaluated the potential involvement of NK cells in AS. We studied 19 AS patients and 22 healthy volunteer donors and assessed the percentage, activity and receptor expression of peripheral blood NK cells. We also evaluated candidate-inflammatory mediators in sera. We found that AS patients have significantly higher percentages of NK cells. However, we found no differences between the ability of NK cells derived from AS and healthy controls to recognize target cells expressing HLA-B27. Remarkably, we observed that the NK-inhibitory receptor CEACAM1 (carcino-embryonic antigen-cell adhesion molecule) is highly expressed among AS-derived NK cells. Furthermore, engagement of CEACAM1 inhibited NK activity in these patients. Finally, we demonstrated that CEACAM1 expression is induced by IL-8 and SDF-1 (stromal cell derived factor), both of which are present in high levels in the sera of AS patients. These results may indicate that NK cells and CEACAM1 play a role in AS pathogenesis and implicate chemokines in the mechanism of CEACAM1 expression.

Adult↗

Evaluation of the pituitary-adrenal axis function following single intraarticular injection of methylprednisolone.

OBJECTIVE: To determine the effects of a single session of intraarticular methylprednisolone (IA-MP) injections on the function of the pituitary-adrenal axis. METHODS: Twenty-five patients with rheumatic diseases were treated with a single IA-MP injection. The dose varied between 20 and 160 mg. The basal cortisol level and the response to 1 microg adrenocorticotropic hormone (ACTH) stimulation were determined before treatment, at 1 day, and at 1 week after IA-MP injections. Further tests were carried out for up to 6 weeks in patients with blunted cortisol response. Results were compared with those obtained in a group of 22 healthy subjects. RESULTS: Before treatment, all patients had normal basal and peak cortisol responses to ACTH (>396 nmoles/liter at 30 minutes). Reduced fasting cortisol levels (<147 nmoles/liter) were detected in 12 of 25 patients (48%) after 1 day, in 1 of 25 patients (4%) after 1 week, and in 1 of 25 patients (4%) 2 weeks after IA-MP injections. Blunted peak cortisol response (<396 nmoles/liter at 30 minutes) was observed in 1 of 25 patients (4%) after 1 day, in 3 of 25 patients (12%) after 1 week, and in 1 of 25 patients (4%) 2 weeks after IA-MP injections. Decreased fasting levels and peak cortisol responses to ACTH stimulation were more common in patients with inflammatory diseases and in those injected with 80-160 mg MP. CONCLUSION: Single-session IA-MP injection(s) are associated with systemic absorption of MP, causing impaired adrenocortical reserve. Recovery is expected in most patients after 1-2 weeks. Only a few patients exhibited suppression for up to 2 weeks. The magnitude of this suppression depends on the dose injected, and is more common in patients with inflammatory joint diseases. Caution is required if repeated large doses of IA-MP are considered in these patients.

Adrenocorticotropic Hormone↗

Current therapeutic options in the management of diffuse idiopathic skeletal hyperostosis.

Diffuse idiopathic skeletal hyperostosis (DISH) is a condition characterised by calcification and ossification of soft tissues, mainly ligaments and enthesis. Although DISH often coexists with osteoarthritis, this disorder differs from primary osteoarthritis by a dissimilar prevalence within the general population, gender distribution, anatomical site of primary involvement and magnitude and distribution in the spine and the peripheral joints. Little is known about the pathogenesis of the disease and possible therapeutic interventions. Treatment should be aimed at the symptomatic relief of pain and stiffness; the prevention, retardation or arrest of progression; the treatment of associated metabolic disorders and the prevention of spontaneous or induced complications. Change of lifestyle, nutrition and therapeutic options to alleviate pain and stiffness are measures that might improve quality of life in patients affected by DISH. Control of associated metabolic disorders such as hypertension, hyperinsulinaemia with or without hyperglycaemia, hyperlipidaemia and hyperuricaemia may reduce the morbidities associated with these disorders and prevent further progression of the condition. Recent developments in our understanding of the molecular basis of the ligamentous and entheseal changes that lead to the development of DISH might pave the way to future, more targeted and effective therapies.

Anti-Inflammatory Agents, Non-Steroidal↗

Arthritis or vasculitis as presenting symptoms of Crohn's disease.

OBJECTIVE: The aim of this study was to describe arthritis or vasculitis as initial manifestations of Crohn's disease (CD). METHODS: We describe three cases in which the rheumatological manifestations preceded the bowel disease and one with rheumatological manifestation and asymptomatic gut inflammation. The information on clinical manifestations, laboratory examination results, imaging procedures, and histological data were gathered from the patients' medical charts. A MEDLINE search for the associations of extraintestinal manifestations of inflammatory bowel disease was performed. RESULTS: Arthritis or vasculitis preceded the bowel disease by 3 to 15 months. In one case, the bowel disease remained asymptomatic throughout the follow-up period. CONCLUSION: Rheumatological presentations of CD such as arthritis and vasculitis are uncommon. The diagnosis of CD without evident bowel symptoms might offer explanations and treatment options for puzzling symptoms and signs. Recognition, early diagnosis, and treatment of the underlying gut disease might prove useful for both the bowel disease and the rheumatological manifestations.

Adolescent↗

Diffuse idiopathic skeletal hyperostosis: a distinct clinical entity.

Diffuse idiopathic skeletal hyperostosis is often incorporated into osteoarthritis. Although DISH often coexists with OA, patients affected by this disorder differ from patients with primary OA in several aspects: prevalence in the general population, gender distribution, anatomic site of primary involvement, magnitude and distribution in the spine and the peripheral joints. DISH is a distinct clinical entity. Its recognition as such should stimulate clinicians and researchers to focus on its pathogenesis, treatment and prevention.

Age Factors↗

CD66a interactions between human melanoma and NK cells: a novel class I MHC-independent inhibitory mechanism of cytotoxicity.

NK cells are able to kill virus-infected and tumor cells via a panel of lysis receptors. Cells expressing class I MHC proteins are protected from lysis primarily due to the interactions of several families of NK receptors with both classical and nonclassical class I MHC proteins. In this study we show that a class I MHC-deficient melanoma cell line (1106mel) is stained with several Ig-fused lysis receptors, suggesting the expression of the appropriate lysis ligands. Surprisingly, however, this melanoma line was not killed by CD16-negative NK clones. The lack of killing is shown to be the result of homotypic CD66a interactions between the melanoma line and the NK cells. Furthermore, 721.221 cells expressing the CD66a protein were protected from lysis by YTS cells and by NK cells expressing the CD66a protein. Redirected lysis experiments demonstrated that the strength of the inhibitory effect is correlated with the levels of CD66a expression. Finally, the expression of CD66a protein was observed on NK cells derived from patients with malignant melanoma. These findings suggest the existence of a novel class I MHC-independent inhibitory mechanism of human NK cell cytotoxicity. This may be a mechanism that is used by some of the class I MHC-negative melanoma cells to evade attack by CD66a-positive NK cells.

Antigens, CD↗

Clinical manifestations of diffuse idiopathic skeletal hyperostosis of the cervical spine.

OBJECTIVES: To describe the clinical manifestations and the complications of cervical spine (C-spine) involvement in diffuse idiopathic skeletal hyperostosis (DISH). METHODS: Two patients, who presented with dysphagia resulting from large anterior osteophytes of the C-spine, were diagnosed as having DISH. A Medline search from 1964 to present, using the terms "diffuse idiopathic skeletal hyperostosis" and "cervical spine," identified several clinical manifestations associated with DISH. RESULTS: Two groups of conditions associated with DISH were found. 1. Spontaneous complications such as: dysphagia, being the commonest, dyspnea, stridor, myelopathy associated with ossification of the posterior longitudinal ligament (OPLL) or with atlanto-axial pseudoarthrosis or subluxation. Other rare events were aspiration pneumonia, sleep apnea and thoracic outlet syndrome. 2. Provoked complications such as endoscopic and intubation difficulties and fractures of the C-spine with frequent transverse shift of the fractured segment and resultant myelopathy. CONCLUSIONS: C-spine involvement in DISH is a recognized cause of various clinical manifestations involving the pharynx, larynx and the esophagus. Prior knowledge of the existence of cervical DISH should alert the clinicians for possible complications, at times severe, during invasive procedures in the neck region and as a consequence of trauma.

Aged↗

[Plasma anti-oxidants and rheumatoid arthritis].

We present a clinical study aimed to compare plasma antioxidant vitamins, vitamin E, beta-carotene and vitamin A. The study consisted of a group (15 patients) with rheumatoid arthritis (RA) compared to a healthy control group. There was a significant decrease in plasma vitamin E, beta-carotene and vitamin A (vitamin E 30.4 +/- 4.9 VS 43.6 +/- 8.2 micrograms/ml, beta-carotene 0.73 +/- 0.26 VS 1.02 +/- 0.22 micrograms/ml and vitamin A 0.22 +/- 0.07 VS 0.46 +/- 0.15 microgram/ml, P < 0.01 patients VS control, respectively). Supplementation of Dunaliella (natural)--beta-carotene to the RA patients for 3 weeks, resulted in a significant increase in plasma vitamin E (47.9 +/- 5.5 micrograms/ml) beta-carotene (0.87 +/- 0.21 microgram/ml) and vitamin A (0.55 +/- 0.15 microgram/ml). There were no changes in the activity indexes of RA. Low plasma antioxidant vitamins in patients with RA are consistent with the observation that oxidative processes occur in the inflammed joints. The validity of antioxidant vitamins as supplementary therapy for RA is not clear.

Antioxidants↗