Biomedical subjects

André Kahan

Publications and source records attributed to André Kahan.

At least 19 recordsLinked to original sources

PubMed2006

Cardiovascular disease in rheumatoid arthritis: single-center hospital-based cohort study in France.

INTRODUCTION: Rheumatoid arthritis (RA) was independently associated with cardiovascular events in several studies, most of which were conducted in the US. OBJECTIVES: To estimate the risk of cardiovascular events in a cohort of RA patients recruited at a hospital in France, to identify cardiovascular risk factors, and to measure the severity of cardiovascular events. METHODS: Two hundred and thirty-nine patients admitted between January 1, 1998, and March 31, 1999, for RA meeting American College of Rheumatology criteria, with a negative history for cardiovascular events, were sent a questionnaire in 2004 to evaluate the occurrence of myocardial infarction, stroke, or cardiovascular death. RESULTS: During the mean follow-up of 5.4+/-1.8 years, there were 10 cases of myocardial infarction (0.8%/year), 3 cases of stroke (0.2%/year), and 9 cardiovascular deaths (0.7%/year). Of the 10 patients who experienced myocardial infarction, 5 had clinical symptoms of heart failure and 4 died from cardiovascular causes. Independent risk factors for cardiovascular events were older age (relative risk [RR], 2.5/10 years; 95% confidence interval [95%CI], 1.4-4.2), male gender (RR, 5.1; 95%CI, 1.8-14.6), treated hypertension (RR, 4.3; 95%CI, 1.4-13.2), and treated hypercholesterolemia (RR, 6.0; 95%CI, 1.8-20.7). CONCLUSION: Our data suggest a higher risk of cardiovascular events in patients with RA compared to the general population in France (0.1-0.5%/year for myocardial infarction and 0.07%/year for stroke in the age group covered by our cohort). Cardiovascular events in the patients with RA seemed unusually severe. Patients with RA should be carefully screened for conventional cardiovascular risk factors.

Age Distribution↗

PubMed2006

IL13RA2 gene polymorphisms are associated with systemic sclerosis.

OBJECTIVE: To investigate the influence of genetic variability on the phenotypic expression of systemic sclerosis (SSc), by testing possible associations between single nucleotide polymorphisms (SNP) in IL13RA1 and IL13RA2 genes and SSc in a Caucasian population. METHODS: As IL13RA1 and IL13RA2 are located on the X chromosome and SSc occurs far more frequently in women than in men, only women were genotyped. The study group comprised 97 women with SSc, 36 with diffuse (dcSSc) and 61 with limited (lcSSc) cutaneous forms of disease, and 109 healthy controls. Patients and controls were Caucasian. We investigated 4 SNP in IL13RA1 and 3 in IL13RA2 by polymerase chain reaction amplifications and enzymatic digestion or primer extension reactions and denaturing high-performance liquid chromatography. RESULTS: We detected an association between IL13RA2 rs638376 and patients with SSc [p = 0.004, odds ratio (OR) = 1.85, confidence interval (CI) 1.22-2.74, p corr = 0.02], as well as with dcSSc in that subgroup of patients (p = 0.01, OR 2.22, 95% CI 1.27-3.89, p corr = 0.05). The IL13RA2 rs638376G allele frequency was higher in patients with SSc (51.6%) than in controls (36.4%, p = 0.003, OR 1.86, 95% CI 1.24-2.79, p corr = 0.015) and in the subgroup with dcSSc (57.6%) than in controls (36.4%, p = 0.003, OR 2.37, 95% CI 1.35-4.15, p corr = 0.015). One other IL13RA2 SNP was only associated with the dcSSc subgroup: the IL13RA2 rs5946040G allele was more common in patients with dcSSc (33.8%) than in controls (17%, p = 0.004, OR 2.5, 95% CI 1.36-4.60, p corr = 0.02). CONCLUSION: Our data suggest that IL13RA2 gene polymorphisms may be involved in susceptibility to SSc. Further studies are under way to show that they contribute to disease.

Adult↗

PubMed2006

Evaluation of interleukin 13 polymorphisms in systemic sclerosis.

Systemic sclerosis (SSc) is a multisystem disease of unknown etiology. It is characterized by excessive cutaneous and visceral fibrosis, damage to small blood vessels, and production of autoantibodies. Interleukin-13 (IL-13) has been shown to be involved in abnormal fibrosis in other diseases. Therefore, we have evaluated its possible involvement in SSc. We analyzed four IL13 gene polymorphisms, rs1800925 (IL13-1055), rs20541 (Arg130Gln), rs847, and rs2243204 in 107 unrelated SSc patients (40 patients having diffuse cutaneous form and 67 patients having limited cutaneous form) and in 170 controls. All subjects were Caucasians. In the total patient population and in the diffuse cutaneous subset, we observed an association between two IL13 polymorphisms, IL13 rs1800925 (IL13-1055), and IL13 rs2243204, and disease (p=0.03-0.04). The IL13 rs2243204T allele was more common in SSc patients (p=0.01, OR=2.3 CI 1.21-4.38) and in the diffuse cutaneous form (p=0.01, OR=2.95, CI 1.35-6.49) than in control subjects. Our result supports the suggestion that polymorphisms in IL13 are associated to SSc and skin fibrosis process. However, further studies on larger and independent population and functional analyses are needed to confirm these findings.

Aged↗

PubMed2006

Anti-endothelial cell antibodies from patients with limited cutaneous systemic sclerosis bind to centromeric protein B (CENP-B).

By using a quantitative immunoblotting technique on protein extracts of human macrovascular and microvascular endothelial cells, we have analyzed the self-reactive repertoires of IgG from 20 patients with limited cutaneous SSc, 40 patients with diffuse SSc and 60 age- and sex-matched healthy controls. Serum IgG from 15/20 patients with limited cutaneous SSc and anti-centromere antibodies bound to at least one of the two 75- and 85-kDa protein bands in the different endothelial cell extracts, whereas IgG from healthy controls or patients with diffuse SSc did not. N-terminal sequencing of the 75- and 85-kDa bands identified CENP-B as the sole antigen in both bands. Moreover, IgG from all of the SSc patients who recognized the 75- and/or 85-kDa bands bound to a full-length recombinant CENP-B protein as assessed by ELISA, whereas IgG from other SSc patients did not. The main target of anti-endothelial cell antibodies in patients with limited cutaneous SSc is the nuclear and ubiquitous protein CENP-B.

Antibody Specificity↗

PubMed2006

Osteosarcoma presenting as a solitary focus of osteolysis in the calvarium.

Osteolysis of the skull is fairly common. The clinical presentation and results of laboratory or imaging tests may suggest a benign or a malignant disease. However, histology is the only means of obtaining a definitive diagnosis and should therefore be performed at the slightest doubt. We report the case of a 58-year-old man who presented with a recent painless lump in the right temporoparietal region. Laboratory tests were normal. Brain imaging studies and total body radionuclide scanning showed no other lesions. However, the heterogeneous and aggressive appearance of the skull lesion prompted a surgical biopsy, which showed osteoblastic osteosarcoma. Chemotherapy and radiation therapy were given after complete excision of the tumor.

Diagnosis, Differential↗

PubMed2006

Evaluating vitamin D status. Implications for preventing and managing osteoporosis and other chronic diseases.

Recent studies have added new dimensions to the fund of knowledge on vitamin D. In addition to the classic role of vitamin D in preventing rickets and osteomalacia, a preventive effect against osteoporotic fractures has been convincingly established, and abundant evidence suggests a role in preventing malignancies and autoimmune diseases. Serum 25-OH-vitamin D assay is a simple test for evaluating vitamin D status. However, recent review articles indicate that current reference ranges for serum 25-OH-vitamin D are too low. An appropriate lower normal limit may be between 50-100 nmol/l (20-40 ng/ml). Standard supplement dosages may fail to provide concentrations above this range.

Fractures, Bone↗

PubMed2006

High redox thioredoxin but low thioredoxin reductase activities in the serum of patients with rheumatoid arthritis.

BACKGROUND: Thioredoxin (Trx)/thioredoxin reductase (TrxR) is a redox-active system induced by oxidative stress. We investigated its status as a function of RA disease activity. METHODS: 64 consecutive RA patients and 27 healthy subjects were enrolled in the study. Serum Trx protein levels were evaluated using an immunoassay and immunoblot, while redox Trx and TrxR activities and oxidative stress markers (carbonyl groups, thiols), were determined using spectrophotometric methods. RESULTS: Redox Trx activity and Trx protein concentrations were significantly higher in RA patients than in controls (redox Trx activity: 37.7+/-22.6 versus 21.1+/-7.9 ng/mL, p<0.01; Trx protein: 25.5+/-12.0 versus 12.3+/-5.1 ng/mL, p<0.0001). Redox Trx activity correlated with the DAS score (r=0.45, p=0.004) and with the tender joint count (r=0.49, p=0.002) whereas there was no correlation with Trx protein concentrations. Immunoblot analysis showed that circulating Trx was partially aggregated. TrxR activity was lower in the serum of RA patients than in healthy subjects (197+/-70 versus 263+/-56 U/L, p=0.002). TrxR activity was correlated with the DAS score (r=0.53, p<0.001) and with the tender joint count (r=0.36, p<0.01). There were no correlations between oxidative stress marker levels and redox Trx activity, Trx protein concentrations or TrxR activity. CONCLUSION: Redox Trx and TrxR activities correlated with the disease activity of RA patients consistent with the hypothesis that Trx/TrxR activities may contribute to disease activity in RA.

Adult↗

PubMed2006

Treatment of systemic sclerosis.

Systemic sclerosis is the most severe of all connective tissue diseases. The distinctive pathogenic process involves sequential or concomitant abnormalities in blood vessel function, immunity and, ultimately, fibroblast function. These specific characteristics may explain the results of treatment evaluations. The decrease in excess mortality shown in recent studies seems chiefly ascribable to the use of cardiovascular drugs. Angiotensin-converting enzyme (ACE) inhibitors are effective in resolving renal crisis, prostacyclins and endothelin antagonists improve pulmonary hypertension, and calcium antagonists and ACE inhibitors benefit patients with myocardial involvement. On the other hand, immunomodulatory drugs and other agents investigated for their disease-modifying potential failed to influence skin fibrosis in controlled trials. Trials of immunosuppressants are ongoing. Available results indicate that emphasis should be put on cardiovascular drugs. The development of criteria for disease activity and severity would facilitate future research on the treatment of systemic sclerosis.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2006

Variations of neuronal nitric oxide synthase in systemic sclerosis skin.

OBJECTIVE: In systemic sclerosis (SSc), derangement of the peripheral nervous system is linked to vascular tone dysfunction. Nitric oxide (NO) produced by neuronal nitric oxide synthase (nNOS, NOS-I) might play a dynamic role in the control of vascular tone. This study was performed to verify, by immunohistochemical and biochemical analyses, the presence and expression of nNOS and protein gene product 9.5 (PGP 9.5) in SSc skin, in different subsets and various phases of the disease. METHODS: Biopsy samples of clinically involved skin from 32 SSc patients (12 with limited cutaneous SSc [lcSSc] and 20 with the diffuse form [dcSSc]) and skin samples from 6 healthy controls were either immunostained with anti-PGP 9.5 and anti-nNOS antibodies or analyzed by semiquantitative reverse transcription-polymerase chain reaction and Western blotting. RESULTS: Immunohistochemical and biochemical data showed a decrease in PGP 9.5 and nNOS innervation and in their messenger RNA (mRNA) levels in lcSSc and dcSSc skin. In the edematous phase of SSc, a light alteration in cutaneous innervation was initiated and slowly progressed into the sclerotic phase, becoming most evident in the atrophic phase. Levels of nNOS mRNA were significantly lower between the edematous phase and the sclerotic phase in both dcSSc and lcSSc skin, which was attributable to the earlier occurrence of more severe pathologic alterations. CONCLUSION: Total cutaneous innervation and nNOS innervation slowly disappear in the skin of SSc patients. Expression of nNOS depends on the severity of tissue damage in SSc, and increased synthesis of NO also contributes to this process. It remains to be determined whether the changes in cutaneous innervation are due to the disease itself or whether these changes contribute to the pathogenesis and evolution of SSc.

Female↗

PubMed2006

[Heart involvement in systemic sclerosis].

Primary myocardial involvement is common in systemic sclerosis. Increasing evidence strongly suggests that this involvement is related to repeated focal ischemic injury causing irreversible myocardial fibrosis. The underlying mechanism appears to be microcirculatory impairment with abnormal vasoreactivity, with or without structural vascular abnormalities. Clinically evident cardiac involvement is recognized to be a poor prognostic factor. Pericardial involvement is frequent but usually asymptomatic. Conduction system abnormalities appear common but not serious, while arrhythmias may be life-threatening. No significant valvular involvement appears to be associated with systemic sclerosis. Treatment for myocardial involvement includes long-term systematic administration of calcium channel blockers and possibly angiotensin-converting enzyme inhibitors, frequently given at high dosage.

Angiography↗

PubMed2005

Effects of repeated infliximab therapy on serum lipid profile in patients with refractory rheumatoid arthritis.

BACKGROUND: Patients with rheumatoid arthritis (RA) frequently display an atherogenic lipid profile which has been linked with inflammation. Tumor necrosis factor-alpha (TNF-alpha), a pivotal pro-inflammatory cytokine in RA may be involved in the development of the disturbed lipid metabolism. We investigated whether infliximab, an anti-TNF-alpha therapy, may modify the lipid profile. METHODS: 56 consecutive RA patients were treated with infliximab (3 mg/kg at weeks 0, 2, 6, 14, 22, 30). Lipid profile and CRP were assayed at baseline and before infusion at weeks 6 and 30. Baseline values were compared with those in 56 healthy volunteers. RESULTS: At baseline, the concentrations of HDL-cholesterol were lower in RA patients than in the controls (1.3+/-0.4 vs. 1.5+/-0.2 mmol/L; p<0.01). The triglyceride concentrations (1.6+/-0.8 vs. 1.3+/-0.4 mmol/L, p<0.01), the ratio of total cholesterol/HDL-cholesterol (4.3+/-1.6 vs. 3.2+/-0.5, p<0.001) and LDL-cholesterol/HDL-cholesterol (2.6+/-1.2 vs. 1.7+/-0.5, p<0.001) were significantly higher in RA patients than in controls. After 6 weeks of infliximab therapy, the mean total cholesterol concentration increased by 25% (p<0.001), LDL-cholesterol by 24% (p<0.001) and HDL-cholesterol by 30% (p<0.001). The decrease in CRP levels to 30 week inversely correlated with the increase in HDL-cholesterol (r=-0.47, p=0.005). CONCLUSIONS: Infliximab administration is associated with important increases in cholesterol levels in all its forms but as no significant beneficial effect on the atherogenic ratio.

Aged↗

PubMed2005

Systemic sclerosis and gastric MALT lymphoma.

CASE-REPORT: A 76-year-old woman was admitted for evaluation of esophagitis complicating limited cutaneous systemic sclerosis. Endoscopy showed persistent grade III esophagitis and an erythematous antral lesion found upon biopsy to be a lymphoma of mucosa-associated lymphoid tissue (MALT). Tests were positive for Helicobacter pylori. Moderate mucosal infiltration by endoscopic ultrasonography was the only finding from staging investigations. Six months after treatment to eradicate H. pylori, a repeat endoscopy showed no evidence of the lesion. DISCUSSION: MALT lymphomas are usually confined to the gastric wall. Gastric MALT lymphomas have a well-established association with H. pylori infection. The clinical manifestations are nonspecific. Endoscopy usually shows a focus of erythema or, less often, erosion. The diagnosis rests on histological examination of a biopsy, which shows infiltration by monoclonal cells whose immunophenotype is characteristic of marginal-zone B cells. Eradication of H. pylori is the mainstay of treatment.

Aged↗

PubMed2005

[Ossification of the common posterior longitudinal ligament of the spine and spinal cord compression in a patient from Senegal].

INTRODUCTION: Ossification of the posterior longitudinal ligament of the spine is a rare cause medullar compression. OBSERVATION: A 50-year-old man from Senegal was referred with recent-onset mechanical lumbar pain with proximal motor deficiency of the lower limbs and somatosensory disorders. Magnetic resonance imaging revealed layered medullar compression, due to anterior cervical and mixed anterior and posterior thoracic ossification. Corticosteroid treatment led to regression of the pain and neurological disorders within a few days. DISCUSSION: This case report of ossification of the posterior longitudinal ligament of the spine appears to be an idiopathic form corresponding to the "Japanese disease" initially thought to be limited to that population.

Anti-Inflammatory Agents↗

PubMed2005

Myocardial contractility is early affected in systemic sclerosis: a tissue Doppler echocardiography study.

AIMS: Systemic sclerosis (SSc) is a connective tissue disorder characterized by frequent myocardial involvement. Alteration in left ventricular (LV) function is reported to be rare; however, it may be underestimated by conventional measurements. Our aim was to prospectively investigate LV function in SSc patients, using Tissue Doppler echocardiography (TDE), a modern and accurate method of assessing myocardial function. METHODS AND RESULTS: Seventeen consecutive SSc patients with normal cardiac examination, pulmonary artery pressure (PAP) and radionuclide LV ejection fraction (EF) were prospectively investigated. Myocardial perfusion was investigated using single-photon-emission computerized tomography (SPECT). Echocardiography (ECHO), systolic and diastolic strain-rate (SR) measured in the posterior wall by TDE were used to investigate myocardial function, and compared with results of 15 matched controls. All patients (53+/-8 years; 14 women; systolic PAP 33+/-6 mmHg; LVEF 67+/-8%) had myocardial SPECT perfusion abnormalities. Despite normal ECHO, they had lower systolic SR than controls (1.7+/-0.5 versus 3.8+/-1.7 cm-1, p<0.0001), and lower diastolic SR (3.7+/-1.5 versus 5.6+/-1.2 cm-1, p=0.0004). Ten SSc patients had reduced systolic SR<1.7 cm-1 and 11 reduced diastolic SR<3.5 cm-1. CONCLUSION: Frequent abnormal myocardial perfusion is confirmed in SSc patients. Reduced contractility is also frequent as detected by TDE, despite normal radionuclide LVEF.

Blood Flow Velocity↗

PubMed2005

Early detection of pulmonary arterial hypertension in systemic sclerosis: a French nationwide prospective multicenter study.

OBJECTIVE: Screening allows for early management of pulmonary arterial hypertension (PAH), a severe complication of systemic sclerosis (SSc). Since no consensus has been reached on the method and criteria for optimal screening, we sought to develop an algorithm based on symptoms, Doppler echocardiography, and right heart catheterization (RHC) for application to a nationwide multicenter SSc population in France. METHODS: This prospective study was conducted from September 2002 to July 2003 by experts at 21 SSc centers. At each center, SSc patients without severe pulmonary function abnormalities underwent Doppler echocardiography by an experienced cardiologist. Patients with a peak velocity of tricuspid regurgitation (VTR) of >3 meters/second or 2.5-3 meters/second with unexplained dyspnea were asked to undergo RHC to confirm PAH according to international guidelines. RESULTS: Of the 599 patients analyzed, 29 had known PAH and 33 had suspected PAH, based on Doppler echocardiography, and underwent RHC. Of these 33, 18 were found to have PAH, 3 had left ventricular dysfunction, and 12 had no PAH. Newly diagnosed cases of PAH were of mild severity (mean +/- SD pulmonary artery pressure [mPAP] 30 +/- 9 mm Hg, mean +/- SD total pulmonary resistance [TPR] 524 +/- 382 dynes x second/cm(5)). Hemodynamic findings in patients with known PAH were mPAP 49 +/- 17 mm Hg and TPR 1,007 +/- 615 dynes x second/cm(5). The estimate of PAH prevalence was 7.85% (95% confidence interval 5.70-10.00). CONCLUSION: This screening algorithm, based on dyspnea, Doppler echocardiographic evaluation of VTR, and RHC, enabled early detection of PAH at a mild stage. Whether mild PAH will evolve to severe PAH in reported cases and whether this early diagnosis translates into improved prognosis for patients with mild PAH will be evaluated in the ongoing 3-year followup of this cohort.

Adult↗

PubMed2005

Evaluation of depression and anxiety in patients with systemic sclerosis.

OBJECTIVE: To determine the prevalence of depression and anxiety in patients receiving follow-up in France for systemic sclerosis. PATIENTS: We prospectively evaluated 42 patients admitted for a follow-up evaluation of systemic sclerosis, including 18 with diffuse cutaneous scleroderma and 24 with limited cutaneous scleroderma. Patients admitted for recent organ involvement were excluded. Mean age was 57 +/- 13 years, mean disease duration was 10.2 +/- 8 years, and the mean functional Health Assessment Questionnaire score was 0.682 +/- 0.649. Only four patients had a history of antidepressive drug therapy. We used the Montgomery-Asberg Depression Rating Scale (MADRS) and the Hamilton Anxiety Rating Scale to evaluate depression and anxiety, respectively. RESULTS: Eighteen (43%) patients met criteria for depression and 11 (26%) had scores above the cutoff usually taken to define moderate-to-severe depression. Twenty-seven (64%) patients met criteria for minor anxiety and eight (19%) for major anxiety. Depression and anxiety were strongly correlated with each other (r = 0.89; P < 0.0001). The MADRS score was significantly higher in the patients with pulmonary restrictive disease (P = 0.009) but was not associated with the extent of skin involvement, organ involvement, or disability. CONCLUSION: Systemic scleroderma is associated with a high prevalence of depression and anxiety. These disorders should be looked for routinely and the need for specific treatment evaluated.

Adult↗

PubMed2005

Autoantibody induction in patients with refractory spondyloarthropathy treated with infliximab and methotrexate.

OBJECTIVES: Induction of antinuclear antibodies (ANA) has been reported in patients taking infliximab to treat refractory spondyloarthropathy, without concomitant methotrexate therapy. We investigated antibody induction in patients with spondyloarthropathy treated with both infliximab and methotrexate. METHODS: In 33 patients meeting ESSG criteria for spondyloarthropathy, infliximab was given (infusions at weeks 0, 2, 6, 14, 22, and 30) in combination with methotrexate (10-25 mg/week). At baseline, 6 and 30 weeks after treatment initiation, the patients underwent indirect immunofluorescence testing for ANA and ELISAs for antibodies to double-stranded DNA, soluble nuclear antigens, and histones. RESULTS: As compared to baseline, significant increases were found at week 30 in the number of patients with ANA (4% vs. 29%, P = 0.02), IgG antihistone antibodies (7% vs. 29%, P = 0.04), and IgM antihistone antibodies (29% vs. 57%, P = 0.03). No significant increases were noted for antibodies to double-stranded DNA or to soluble nuclear antigens. No cases of clinical lupus syndrome were recorded. CONCLUSION: Autoantibody induction was far less common in our patients than in the population studied by De Rycke et al. [Arthritis Rheum. 48 (2003) 1015], who found ANA in 88.6% and antibodies to double-stranded DNA in 17.1% of 35 patients taking infliximab without methotrexate. Methotrexate may reduce the risk of autoantibody induction and disimmunity associated with infliximab therapy.

Adult↗

PubMed2005

Disseminated extrapulmonary tuberculosis revealed by humeral osteomyelitis with chronic unremarkable pain.

Disseminated extrapulmonary tuberculosis is uncommon, particularly among immunocompentent individuals. We report the case of a 38-year-old woman from the Ivory Coast who had osteomyelitis in the right humerus, a cold abscess in the pectoralis major muscle, T11 spondylitis, deep lymphadenopathies, peritoneal nodules, and hepatitis. She had no evidence of immune deficiency, and her only risk factor for tuberculosis was her origin from an endemic area. The outcome was favorable after treatment with antitubercular drugs. This case illustrates the recent changes in the epidemiology of tuberculosis in France, where the incidence among immigrants is rising. It also serves as a reminder that tuberculosis can run a chronic and extremely insidious course. At diagnosis, our patient had a 2-year history of chronic pain in her right shoulder and back, suggestive of a minor mechanical disorder.

Adult↗