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Biomedical subjects

P M Villiger

Publications and source records attributed to P M Villiger.

At least 19 recordsLinked to original sources

[Chlamydia pneumoniae: an cause of reactive arthritis?].

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.

Acute Disease↗

Pulmonary rehabilitation in outpatients with asthma or chronic obstructive lung disease. A pilot study of a "modular" rehabilitation programme.

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.

Adult↗

[Vasculitis].

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.

Diagnosis, Differential↗

Prediction of depression in systemic lupus erythematosus patients using SF-36 Mental Health scores.

OBJECTIVE: As depression is common in systemic lupus erythematosus (SLE) patients, we investigated whether and how the Medical Outcome Survey Short Form 36 (SF-36) scores, routinely used in the assessment of SLE patients, would indicate the absence or presence of depression. METHODS: The Depression subscale of the Hospital Anxiety and Depression Scale (HADS-D) and the SF-36 were applied in a cross-sectional cohort of 60 SLE patients [mean age 45 (S.D. 15) yr, disease duration 11 (9) yr, 90% female, 100% Caucasians]. The SF-36 domain score with the closest association with HADS-D was used for further analysis. On the basis of HADS-D scores, the patients were split into two groups: one without depression (score<8) and the other with possible depression (score > or =8). RESULTS: The SF-36 Mental Health score was most closely correlated to the depression score (rho=-0.69, P<0.0005). The calculated Mental Health score cut-off value which significantly differentiated possibly depressed from non-depressed SLE patients was 61. Its sensitivity for the detection of possible depression was 89%, its specificity 77% and its negative predictive value 97%. CONCLUSIONS: The present study contributes to knowledge of means of excluding depression and the prevention of underdiagnosis and undertreatment of depression in SLE patients.

Adult↗

Nonsteroidal anti-inflammatory drugs in systemic lupus erythematosus.

Up to 80% of patients with systemic lupus erythematosus (SLE) are treated with nonsteroidal anti-inflammatory drugs (NSAID) for musculoskeletal symptoms, serositis and headache. This survey reviews the literature on non-selective and selective inhibitors of cyclooxygenases with an emphasis on the efficacy and safety profile reported in SLE patients. No lupus-specific data on gastro-intestinal side effects of NSAID exist. Both non-selective Cox-inhibitors and selective Cox-2 inhibitors induce renal side effects including sodium retention and reduction of the glomerular filtration rate. Lupus nephritis is a risk factor for NSAID-induced acute renal failure, but not for rare idiosyncratic toxic renal reactions to NSAID. In refractory nephrotic syndrome, NSAID have been used successfully. Cutaneous and allergic reactions to NSAID are increased in SLE patients as well as hepatotoxic effects, particularly with high dose aspirin. Whereas a variety of central nervous system side effects of NSAID are probably no more common in SLE patients than in others, aseptic meningitis has been reported more frequently. Ovulation and pregnancy can be adversely affected by Cox-inhibitors. The antiplatelet effect of aspirin and non-selective Cox-inhibitors has a therapeutic potential in patients with the antiphospholipid syndrome (APS). In summary, treatment of SLE with NSAID requires awareness for the increased frequency of some side effects and close monitoring of toxicity.

Anti-Inflammatory Agents, Non-Steroidal↗

[Whipple's disease with normal intestinal histology: rarity or reality?].

Whipple's disease has been diagnosed more frequently in recent years as a consequence of better awareness and of improved diagnostic tools. The number of case reports of Whipple's disease without gastrointestinal symptoms and without histological lesions of the intestinal mucosa is increasing. Therefore, the traditional perception of this disease as well as the methods for its diagnosis need to be revised. We report on 2 patients with Whipple's disease who had systemic inflammatory reactions but neither gastrointestinal symptoms nor an abnormal duodenal histology. Whipple's disease was diagnosed on the basis of extraintestinal tissue histology (lymph node, vertebral body) and by polymerase chain reaction, and was treated successfully with antibiotics. Recommendations for diagnostic procedure in Whipple's disease with both typical and atypical clinical presentation are discussed.

Anti-Bacterial Agents↗

Nonsteroidal anti-inflammatory drugs in systemic lupus erythematosus.

Up to 80% of patients with systemic lupus erythematosus (SLE) are treated with nonsteroidal anti-inflammatory drugs (NSAID) for musculoskeletal symptoms, serositis and headache. This survey reviews the literature on non-selective and selective inhibitors of cyclooxygenases, with an emphasis on the efficacy and safety profile reported in SLE patients. No lupus-specific data on gastro-intestinal side effects of NSAID exist. Both non-selective Cox inhibitors and selective Cox-2 inhibitors induce renal side effects, including sodium retention and reduction of the glomerular filtration rate. Lupus nephritis is a risk factor for NSAID-induced acute renal failure, but not for rare idiosyncratic toxic renal reactions to NSAID. In refractory nephrotic syndrome, NSAID have been used successfully. Cutaneous and allergic reactions to NSAID are increased in SLE patients as well as hepatotoxic effects, particularly with high dose aspirin. Whereas a variety of central nervous system side effects of NSAID are probably no more common in SLE patients than others, aseptic meningitis has been reported more frequently. Ovulation and pregnancy can be adversely affected by Cox inhibitors. The antiplatelet effect of aspirin and non-selective Cox inhibitors has a therapeutic potential in patients with antiphospholipid syndrome (APS). In summary, treatment of SLE with NSAID requires awareness for the increased frequency of some side effects and close monitoring of toxicity.

Anti-Inflammatory Agents, Non-Steroidal↗

Systemic levels of the T cell regulatory cytokines IL-10 and IL-12 in Bechçet's disease; soluble TNFR-75 as a biological marker of disease activity.

OBJECTIVE: To analyze the levels of the T cell regulatory cytokines interleukin 10 (IL-10) and IL-12 in plasma of patients with Behçet's disease (BD), and to assess the value of cytokines and cytokine antagonists as biological markers of disease activity. METHODS: Sera/plasma of 66 consecutive outpatients with established diagnosis of BD were analyzed for the presence of IL-2R, IL-6, tumor necrosis factor-alpha (TNF-alpha), soluble (s) TNF receptor (R)-55, sTNFR-75, IL-10, and IL-12 using immunological methods. Additional laboratory measurements included erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Data from the history and clinical examination were recorded to correlate cytokine levels with clinical markers of disease activity. RESULTS: 18 patients had inactive (Group I), 36 had mildly active (Group II), and 12 patients had active BD (Group III). IL-10 was elevated in 42 plasma samples (64%). The percentage of samples containing IL-10 and the median levels of IL-10 of the 3 patient groups did not differ significantly. IL-12 was detectable in plasma of 9 patients: One from Group I (5%), 3 from Group II (8%), and 5 from Group III (41%). IL-12 correlated with disease activity (difference between Groups I and III, p = 0.02, between Groups II and III, p = 0.008). ESR in patients with active disease and mildly active disease was significantly higher than values in patients with inactive disease (p = 0.03, p = 0.02, respectively), while median CRP levels were significantly different between Group I and Group III only (p = 0.006). sTNFR-75 levels were significantly different between Groups II and III (p = 0.003) and between Groups I and III (p = 0.008). CONCLUSION: The elevation of plasma IL-10 in the majority of patients and the correlation of IL-12 plasma levels with disease activity suggest a pathogenic role of a TH1-type immune response in active disease. In addition, the correlation of sTNFR-75 levels with disease activity indicates that sTNFR-75 may serve as a biological marker of disease activity in BD.

Adolescent↗

[Osteoporosis of the lumbar spine].

This brief review demonstrates a positive influence of the treatment modalities established today on postmenopausal, age-related or glucocorticoid-induced bone loss. Measures developing direct anabolic effects are, however, rare. In other words prevention of osteoporosis is more important than therapy. Prevention means above all to change life style, to prevent excessive post-menopausal mineral losses and to treat patients with long-term steroid regimens in higher doses (over 7.5 mg/day). Preventive measures include adequate intake of calcium, reduced intake of salt, encouraging physical activities as well as avoiding excessive alcohol- and nicotine-consumption. From the osteoporotic point of view estrogen substitution is indicated in post-menopausal women. However, an individual evaluation of the indication is mandatory in view of the above discussed aspects. A densitometry-guided follow-up may contribute by valuable data to this decision. Only if these measures fail may further therapeutic and secondary-preventive measures be taken into consideration. Such secondary-preventive measures comprise anti-resorption drugs (calcitonin, higher doses of vitamin D, bisphosphonates) as well as fluoride which stimulates bone remodeling.

Adult↗

[Therapy of rheumatoid arthritis (chronic polyarthritis)].

A continuous and systematic monitoring of disease activity provides the basis for the therapeutic management of rheumatoid arthritis patients. This helps to individually tailor medication and to correctly time physiotherapy, ergotherapy, surgery, and rehabilitative measures. NSAID are the drugs of choice for symptomatic therapy. The dosage is adjusted to the circadian rhythm of the patient's complaints. Systemic glucocorticoids are very efficacious to control inflammation; however, caution is required in their long-term usage. Preventive measures to limit bone loss are mandatory. Disease-modifying antirheumatic drugs (DMARD) are prescribed early, at the time of diagnosis. The choice of sulfasalazine, antimalaric drugs, methotrexate or parenteral gold is based on the clinical presentation, the degree of systemic inflammation and on prognostic parameters. Treatment with DMARD has to be continued for years. If complete remission is achieved, lasting for at least six months, the dosage can be gradually reduced and finally stopped. At late stages of disease, residual joint pain is often due to secondary osteoarthritis.

Anti-Inflammatory Agents↗

[Gonarthritis: diagnosis and therapy].

The patient presenting with an acutely swollen and tender knee joint is the most frequent rheumatologic emergency in clinical practice. Most important is the exclusion of an infectious arthritis, which requires immediate antibiotic treatment. Synovial fluid analysis for color, clarity, viscosity and cell count is the initial evaluation. In the presence of an opalescent or purulent fluid, cultures and stains with gram and acid-fast methods and polarizing microscopy for crystals should be performed. A noninflammatory, clear (reading test) and highly viscous ("Fadentest') fluid and a white blood cell count of < 2000/mm3 make an infectious arthritis extremely unlikely. The most frequent cause of a noninflammatory fluid is inflammatory osteoarthritis, which usually responds to NSAID treatment. Typical changes of the axial skeleton, tendons, skin and mucosa point to a spondylarthropathy.

Aged↗

[Questionable gonarthritis--assessment and therapy].

The differential diagnosis of gonarthritis is widespread due to the fact that the knee participates in diseases ranging from infections to autoimmunopathies and metabolic disorders. The analysis of the synovial fluid provides important information and has to be performed without delay, if septic arthritis is suspected. Characteristics, symptoms and signs of underlying diseases help in the diagnostic work-up. Whereas radiologic examination is primarily done to document the evolution of the process, ultrasonography may add substantial morphological information. Therapy is based on drug treatment and physical measures. The primary goals of physiotherapy are analgesia and rehabilitation.

Arthritis, Infectious↗

Cytokine regulation of chondrocyte functions.

Regulation of chondrocyte secretory functions and proliferation by cytokines and growth factors is central to cartilage development and maintenance of homeostasis in the mature organism. Depending on the type of extracellular stimulus, chondrocytes can be induced to enter a catabolic matrix degrading or anabolic matrix forming functional program. Interleukin I and transforming growth factor beta are the prototypic stimuli for the catabolic and anabolic program, respectively. Insight into the regulation of chondrocytes by cytokines and growth factors provides the basis for improved concepts of osteoarthritis pathogenesis and new perspectives for therapeutic interventions.

Cartilage↗

[Interactions between the nervous and the immune system].

The immune and nervous systems have the capacity to modulate inflammatory processes in an additive, synergistic or antagonistic way. In addition to direct effects, feed-back systems connecting immune and nervous systems exist which provide the basis for a better understanding of the modulation of inflammatory reactions by the central nervous system (nervous as well as neuropsychological influences). It is well established that immunocompetent cells, but also endothelial, epithelial and mesenchymal cells induce and regulate inflammation by production of cytokines. However, the expression, synthesis and secretion of neuropeptides by cells of the immune system or even connective tissue cells has only been recognized recently. These findings indicate that non-neuronal cells in the periphery can feedback to the nervous system by secretion of neuropeptides (e.g. modulation of an afferent signal by interaction of peripherally produced neuropeptides with nerve endings). Nitrogen monoxide has recently been shown to act as an important mediator of inflammatory phenomena and to play an important role in neurotransmission. The rapidly accumulating knowledge of the nature metabolism of this highly reactive substance indicate new therapeutic options in the area of neuroimmunology.

Central Nervous System↗

Increased interleukin-6 (IL-6) production in a young child with clinical and pathologic features of multicentric Castleman's disease.

A 21-month-old boy presented with a papular rash, lymphoadenopathy, and splenomegaly. He developed symmetric polyarthritis, fever, and progressive glomerulonephritis. Serologies for viral agents including HIV were negative. Antinuclear antibody was transiently positive, but no anti-DNA antibodies were present. CH50 and serum C3 values were low. Biopsies of skin, kidney, bone marrow, and lymph node were obtained. There was a perivascular and periadnexal lymphocytic infiltrate in the skin, with a normal epidermis. Renal biopsy showed proliferative mesangial glomerulonephritis. Bone marrow showed an increased number of plasma cells. Lymph node showed histologic changes described in multicentric Castleman's disease including marked follicular hyperplasia, vascular proliferation, and interfollicular expansion with numerous plasma cells. IL-6 mRNA was demonstrated in cells in the marginal zone and interfollicular regions of the node by in situ hybridization. Likewise, the serum IL-6 level was elevated during a clinical exacerbation of the patient's nephritis. These data suggest an underlying lymphoproliferative disorder, such as Castleman's disease, with overproduction of IL-6 resulting in systemic features of the disease, including glomerulonephritis.

Castleman Disease↗

Neuropeptide Y is an inducible gene in the human immune system.

This study reports on neuropeptide Y (NPY) mRNA expression in human peripheral blood mononuclear cells (PBMC) and lymphoid tissues. By reverse transcription polymerase chain reaction (RT-PCR) it is shown that activated human PBMC of normal blood donors expressed the NPY gene. The PCR products had the expected size and Northern blotting demonstrated the presence of the 0.8-kb NPY mRNA. To define the subpopulations of mononuclear cells expressing this neuropeptide, purified monocytes, B cells and T cells were stimulated with specific activators. Monocytes and in vitro matured macrophages expressed NPY mRNA in response to phorbol myristate acetate (PMA). B lymphocytes expressed NPY mRNA following stimulation with antibody to surface immunoglobulin and PMA. In order to analyze whether these cell types express NPY under physiological conditions in vivo, human bone marrow, tonsil and thymus were analyzed. In situ hybridization of bone marrow revealed a small number of cells containing high levels of NPY mRNA which was also detected in RNA extracts of human thymus and tonsil. In summary, NPY is an inducible gene in human lymphocytes and monocytes and it is expressed at sites where these cells are activated in vivo.

Animals↗