Biomedical subjects
Publications and source records attributed to P M Villiger.
Cogan's syndrome is characterized by noninfectious, interstitial keratitis combined with a vestibulo-auditory deficit. Despite therapy with corticosteroids in combination with immunosuppressive agents, relapses occurred in two subjects and the clinical course suggested a progression of the disease. Treatment with anti-TNF-alpha was started leading to a rapid and sustained clinical remission for over 2 respectively 3 years.
OBJECTIVE: To examine whether the G-to-A polymorphism at position -308 in the promoter of the tumour necrosis factor-alpha (TNFalpha) gene influences the therapeutic response to TNFalpha-blockers in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS). METHODS: A total of 54 patients with RA, 10 with PsA and 22 with AS were genotyped by polymerase chain reaction for the -308 TNFalpha promoter polymorphism. They were treated with infliximab (n = 63), adalimumab (n = 10) or etanercept (n = 13). Clinical response was assessed after 24 weeks by the Disease Activity Score in 28 joints (DAS28) for RA and PsA, and the Bath Ankylosing Spondylitis Activity Index (BASDAI) for AS patients. RESULTS: All patients with the A/A genotype (n = 3, all RA) and two patients with the A/G genotype (AS) failed to respond to anti-TNF treatment. Irrespective of the underlying disease, moderate response (n = 44) was predominantly associated with the A/G genotype (A/G 18/22, G/G 4/22), whereas good response (n = 59) was exclusively seen in patients with the G/G genotype. The average improvement in the DAS28 score was 0.83 in the A/A, 1.50 in the A/G and 2.64 in the G/G group of RA and PsA patients (P < 0.0001). The BASDAI score in AS improved on average by 1.21 in the A/G and by 3.30 in the G/G group (P < 0.005). CONCLUSIONS: The data suggest that humans with a TNFalpha -308 G/G genotype are better responders to anti-TNFalpha treatment than those with A/A or A/G genotypes independent of the treated rheumatic disease (RA, PsA or AS).
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OBJECTIVE: To gain insight into patient experience of the disease course and health related quality of life during and after pregnancy in women with rheumatoid arthritis and ankylosing spondylitis. METHODS: 10 patients with rheumatoid arthritis, 10 patients with ankylosing spondylitis, and 29 age matched healthy pregnant controls were evaluated by the medical outcomes study short form 36 (SF-36) health survey once at each trimester and at 6, 12, and 24 weeks postpartum. A group of non-pregnant age matched female patients (40 rheumatoid arthritis, 16 ankylosing spondylitis) was studied for comparison. RESULTS: Impaired physical dimensions as well as increased bodily pain was observed in healthy women in late pregnancy. Patients with rheumatoid arthritis showed improved physical functioning scores in the second trimester and reduced pain in the third trimester. Among pregnant patients, those with ankylosing spondylitis suffered the greatest impairment of health related quality of life during pregnancy. In all patient groups the physical impairment in the third trimester was less pronounced than in healthy controls. Mental health scores remained stable even with persisting active disease during pregnancy, or with a postpartum flare. CONCLUSIONS: Pregnancy reduced physical functioning in healthy women and patients, but had no impact on mental and emotional health, even at times of disease aggravation. The pregnancy experience documented in our patients may be helpful when counselling patients contemplating pregnancy.
OBJECTIVE: To study the putative shift of a Th1 to a Th2 immune response in pregnancy and its reversal post partum in healthy women and patients with rheumatoid arthritis (RA). METHODS: Peripheral blood mononuclear cells (PBMC) were examined by FACS analysis for the expression of activation markers CD25 and HLA-DR and chemokine receptors CXCR3 and CCR4 on CD4+ and CD8+ T cells in four healthy women and four patients with RA. Samples were analysed once in the third trimester and six and 12 weeks post partum. Eight healthy non-pregnant women served as controls. RESULTS: No reduction of CD25 and HLA-DR+ T cells occurred in the third trimester, but a significant increase was observed post partum in healthy women and an even greater increase in patients. Proportions of T cells expressing the CXCR3 or CCR4 marker were similar in patients and controls during pregnancy, whereas a significant increase occurred post partum. The ratio of CXCR3+ to CCR4+ cells remained unchanged during the observation period and did not differ significantly from that in non-pregnant controls. CONCLUSION: A shift from a Th1 to a Th2 immune response was not detected in the circulation of healthy pregnant women or pregnant patients. The significant increase of T cell activation after pregnancy warrants further investigation into the mechanisms of adjustment of the immune system post partum and its clinical correlates in rheumatic patients.
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OBJECTIVE: To investigate changes in the levels of circulating cytokines with a focus on the Th1/Th2 balance during and after pregnancy in patients with rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), and ankylosing spondylitis (AS). METHODS: Plasma and serum samples of 34 pregnant patients, 19 with RA, 6 with JIA, and 9 with AS, and of 30 healthy pregnant women, 20 non-pregnant patients, and 10 non-pregnant healthy women were analysed for levels of interferon gamma (IFNgamma), interleukin (IL) 1beta, IL10, IL1 receptor antagonist (IL1Ra), soluble tumour necrosis factor receptor (sTNFR), and soluble CD30 (sCD30) by ELISA. Clinical assessment and blood sampling in pregnant women was done once in each trimester and 6, 12, and 24 weeks post partum. Disease activity in the patients was evaluated by validated clinical instruments and correlated with circulating levels of cytokines. RESULTS: Low levels of IL10 were found sporadically, whereas IFNgamma and IL1beta were below detection level in the samples tested. Significantly higher concentrations of sTNFR and IL1Ra were measured in pregnant than in non-pregnant subjects. An increase of IL1Ra from the second to the third trimester correlated with improvement of disease activity in patients with RA and AS. Compared with non-pregnant patients and the other pregnant women, patients with RA showed markedly raised levels of sCD30 during pregnancy. CONCLUSIONS: IFNgamma and IL10, markers of a Th1 and Th2 response, respectively, were either low or undetectable in the cohorts analysed. The increase of cytokine inhibitors IL1Ra and sTNFR was related to pregnancy and was independent of an underlying disease. These anti-inflammatory mediators seem to affect disease activity.
OBJECTIVE: To explore the regulation of factors involved in lymphocyte trafficking in patients with rheumatoid arthritis (RA) undergoing treatment with tumour necrosis factor alpha (TNF-alpha) inhibitors. METHODS: We examined 14 consecutive patients with RA according to ACR criteria prior to and during treatment with TNF-alpha inhibitors (seven etanercept, seven infliximab) and determined disease activity using the Disease Activity Score (DAS-28). Peripheral blood mononuclear cells were isolated before and after 6 and 14 weeks of treatment and analysed immediately for CD3, CD4 and CD8, expression of chemokine receptors CXCR3 and CCR4, CD45RO phenotype and for expression of interferon gamma (IFN-gamma) and interleukin 4 (IL-4) using four-colour flow cytometry. RESULTS: We found significant increases in CD4 and CD8 T lymphocytes expressing CXCR3 after 6 and 14 weeks. The overall proportion of T lymphocytes expressing CCR4 appeared unchanged. More than half of peripheral CD4 T lymphocytes showed a memory phenotype (CD45RO), with a non-significant increase under TNF-alpha inhibition. Upon activation, up to 30% of CXCR3(+)/CD4 T cells expressed IFN-gamma, while IL-4-expressing cells were rare. There was a robust negative correlation between CXCR3(+)/CD4 T lymphocytes and DAS-28. CONCLUSIONS: TNF-alpha inhibition with infliximab and etanercept results in sustained accumulation of CXCR3 positive T lymphocytes in the peripheral blood of RA patients. This suggests altered lymphocyte trafficking during TNF-alpha inhibition.
Patients with chronic pain after whiplash injury and fibromyalgia patients display exaggerated pain after sensory stimulation. Because evident tissue damage is usually lacking, this exaggerated pain perception could be explained by hyperexcitability of the central nervous system. The nociceptive withdrawal reflex (a spinal reflex) may be used to study the excitability state of spinal cord neurons. We tested the hypothesis that patients with chronic whiplash pain and fibromyalgia display facilitated withdrawal reflex and therefore spinal cord hypersensitivity. Three groups were studied: whiplash (n=27), fibromyalgia (n=22) and healthy controls (n=29). Two types of transcutaneous electrical stimulation of the sural nerve were applied: single stimulus and five repeated stimuli at 2 Hz. Electromyography was recorded from the biceps femoris muscle. The main outcome measurement was the minimum current intensity eliciting a spinal reflex (reflex threshold). Reflex thresholds were significantly lower in the whiplash compared with the control group, after both single (P=0.024) and repeated (P=0.035) stimulation. The same was observed for the fibromyalgia group, after both stimulation modalities (P=0.001 and 0.046, respectively). We provide evidence for spinal cord hyperexcitability in patients with chronic pain after whiplash injury and in fibromyalgia patients. This can cause exaggerated pain following low intensity nociceptive or innocuous peripheral stimulation. Spinal hypersensitivity may explain, at least in part, pain in the absence of detectable tissue damage.
Arthritis urica is one of the most frequent forms of arthritis in Switzerland. On one hand it can mimic septic arthritis, on the other hand it may progress into chronic polyarticular disease. Age, sex and initial clinical presentation lead to the suspicion of crystal arthropathy. The diagnosis, however, has to be proven by microscopic analysis of synovial fluid. Functional ultrasound may be extremely helpful in collecting minute amounts of liquid in small joints. This approach enables definite diagnosis and at the same time crystalline glucocorticoids together with local anesthetics can be injected intra-articularly in order to interrupt the inflammatory process and to kill pain. Other conventional treatment modalities include non-steroidal anti-inflammatory drugs (including Cox-2 inhibitors) which should be started immediately and at maximal doses as well as glucocorticoids at moderate doses for a few days. Serum uric acid levels should be normalized in order to prevent recurrence of arthritis.
OBJECTIVES: To assess the appreciation of self assessment (SA) by multiple choice question (MCQ) tests during continuous professional development (CPD) meetings and to evaluate the attitude towards the option of recertification. METHODS: A questionnaire was completed at a meeting of the Swiss Societies of Rheumatology and Physical Medicine and Rehabilitation in 2003 (response rate 94.9% (223/235)). RESULTS: 60.9% of members found SA useful to assess rheumatological knowledge by MCQ tests; 71.3% thought it motivating to receive an anonymous feedback; 47.2% wanted an additional individualised feedback; 70.8% asked for SA to be continued every 2 years during CPD sessions; 26.3% favoured the option of recertification with identical standards to the Swiss certifying examination in rheumatology. Physicians in private practice less often chose the option of recertification than physicians employed by hospitals (OR = 2.09, 95% CI 1.03 to 4.18). No correlations between the type and duration of specialisation, personal reading time, frequency of attendance at CPD meetings, sex of the members, and the choices made were found. CONCLUSIONS: SA by MCQ tests during CPD meetings is highly accepted by Swiss rheumatologists. This reliable, valid, and economic method of learning needs assessment enables individual physicians and scientific societies to plan educational with specific goals in mind.
OBJECTIVE: : To analyse the disease course of patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) during and after pregnancy by validated clinical instruments for measurement of disease activity, and assess their usefulness in pregnant patients. METHODS: Included were 10 patients with RA and 9 with AS (10 pregnancies). Clinical examination and blood/urine sampling was performed before conception, at each trimester, and weeks 6, 12, and 24 post partum. Assessment of RA was by the RA Disease Activity Index (RADAI), the 44 joint count, and the Health Assessment Questionnaire; assessment of AS by the Bath Ankylosing Spondylitis Activity Index (BASDAI), the Dougados Functional and Articular Index, and a night pain index. Common for all patients were the patient's and physician's global assessment. RESULTS: : Most patients with RA showed sustained or increased improvement of disease activity during pregnancy. Higher disease activity scores were found in the patients with AS with a frequent increase of disease activity in the second trimester and mitigation of symptoms in the third trimester. Analysis specifically for the patient's assessment of pain showed continuously higher pain scores in the patients with AS than in those with RA. Rank correlation showed good to moderate correlation between most clinical measurements and RADAI or BASDAI, respectively. Functional indices were confounded by physiological changes of late pregnancy. CONCLUSION: RA can be monitored during and after pregnancy by the swollen joint count and RADAI without interference from pregnancy related symptoms, whereas usual measures of disease activity are not always applicable in pregnant patients with AS.
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The most important diagnostic steps in the initial, non-specialist evaluation of joint pains are the careful anamnesis, clinical examination and laboratory tests for inflammations parameters and for infectious and autoimmune serologies. The arthrocentesis and consecutive analysis of synovial fluid, the interpretation of which, due to their complexity, lie in the hands of rheumatologists and most often allow the clear differentiation of non-inflammatory versus inflammatory causes. Conventional radiology is seldom diagnostic but a prerequisite for monitoring the course of the joint disease. Arthrosonography is cost-effective and often provides additional information besides clinical examination. More expensive diagnostic procedures such as arthroscopy, magnetic resonance imaging, scintigraphy and CT are reserved for more specific clinical situations.
Chlamydia pneumoniae is a common cause of acute infections within the upper respiratory tract. It is less well known that chlamydia pneumoniae, just like chlamydia trachomatis, may also trigger reactive arthritis. We describe three patients with arthritis possibly triggered by chlamydia pneumoniae. The patients showed the typical symptoms of reactive arthritis like asymmetric oligo- or polyarthritis, dactylitis, enthesiopathies and tendovaginitis. The course of the disease was quite different. The first patient developed persistent polyarthritis which required longterm treatment with a rheumatic disease modifying drug; the second patient improved after several weeks and the third patient experienced a full remission within a few days.
STUDY/PRINCIPLES: Pulmonary rehabilitation programmes are often costly and dependent on the infrastructure of specialised centres. We developed a modular, outpatient-based rehabilitation programme, which is inexpensive and can be implemented in a variety of settings. The aim of this study was to determine the effects and feasibility of this programme. METHODS: Thirteen patients with COPD and 7 patients with asthma were enrolled by their primary care physician because of dyspnoea. Initial assessment included cardiopulmonary exercise testing, six-minute walking distance, lung function testing and multiple questionnaires addressing dyspnoea, depression and quality of life issues. The training consisted of 36 sessions of high intensity training of 2 hours duration to improve exercise tolerance, including 30 minutes of stationary cycling at the anaerobic threshold. Another complete assessment was done on completion of the study at 3 months. RESULTS: The six-minute walking distance improved significantly from 401 to 551 m (p < 0.0001). The maximal exercise capacity increased significantly from 85 W to 99 W (p < 0.001). The anaerobic threshold remained unchanged despite the high intensity training. There was a reduction of dyspnoea and an improvement of quality of life. CONCLUSION: This study shows that our outpatient rehabilitation programme leads to a benefit in exercise tolerance and health related quality of life comparable to other programmes published in the literature. The rehabilitation programme was very well accepted among patients, primary care physicians and health insurers.
Systemic vasculitis is a rare condition that usually takes a chronic and often unpredictable course. Long-term outcome is crucially dependent on a close cooperation between the primary caregiver and the specialist. The tentative diagnosis is based on the medical history and clinical examination and verified by laboratory diagnostics, high-resolution imaging and histological assessment. The primary aim of therapy is to induce remission and provide emergency treatment of any vital organs that may be in jeopardy. Later on, remission maintenance and glucocorticoid sparing are important targets. During this phase, it is important to differentiate between disease activity and disease damage when optimizing the drug regimen. In addition to the basic treatment, arterial blood pressure should be controlled, screening for cardiovascular risk factors conducted and infections identified early. Nowadays, good outcomes can be achieved thanks to improved diagnostic tests, a broader therapeutic spectrum and more effective monitoring.