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Biomedical subjects

F A Wollheim

Publications and source records attributed to F A Wollheim.

At least 19 recordsLinked to original sources
PubMed2002

Long term efficacy and safety of cyclosporin versus parenteral gold in early rheumatoid arthritis: a three year study of radiographic progression, renal function, and arterial hypertension.

OBJECTIVE: To compare the three year safety and efficacy of cyclosporin and parenteral gold in the treatment of early, active, severe rheumatoid arthritis (RA), and to study the reversibility of cyclosporin associated renal dysfunction in patients who discontinued cyclosporin treatment. METHODS: The patients continued to receive cyclosporin or parenteral gold in an 18 month open extension to an 18 month randomised, parallel group study. The main efficacy variable was blinded evaluation of radiographic progression of joint damage. Safety variables included serum creatinine, calculated creatinine clearance, and blood pressure. RESULTS: Radiographic progression during follow up was similar in both groups. About 60% of the patients in the intention to treat groups (n=272) and about half of the patients in the completer groups (n=114) had definite radiographic progression in joint damage (increases >6 in the Larsen-Dale score), and about one in three also had substantial progression (>18 increase in Larsen-Dale score). Both systolic and diastolic blood pressure were significantly increased in the cyclosporin group compared with the gold group, and 12/139 (9%) versus 3/139 (2%) (p=0.03) had notably raised blood pressure. The mean serum creatinine increased by 28% at the treatment end point in the cyclosporin group as compared with 7% in the gold group. The mean calculated creatinine clearance was reduced by 16% and increased by 1% in the cyclosporin and gold groups, respectively, at the end of the study. At the final follow up visit after discontinuation of cyclosporin (at least three months after treatment was stopped) the mean serum creatinine was increased by 15% and creatinine clearance reduced by 16%. Sustained increases in serum creatinine at this post-treatment end point were mostly seen in patients with a raised serum creatinine during treatment of at least 50%. CONCLUSION: Three year changes in radiographic damage during cyclosporin and parenteral gold were similar in patients with early, active RA. Abnormal renal function and raised blood pressure were often seen in the cyclosporin treated patients.

Activities of Daily Living↗
PubMed2001

[Meager support for herbal therapy of rheumatoid arthritis].

The Cochrane collaboration has recently published a systematic review of placebo controlled randomized trials of herbal therapies for rheumatoid arthritis. An extensive search including all languages screened 2500 hits, identified 47 trials and accepted 11 as meeting set quality criteria. Modest efficacy of gamma linolenic acid containing products was supported by 7 trials, 4 trials dealt with 4 different products, and no conclusions could be derived from these. Although it was stated in the review that safety was probably good, this is not apparent from the presented material.

Arthritis, Rheumatoid↗
PubMed2001

Von Willebrand factor propeptide as a marker of disease activity in systemic sclerosis (scleroderma).

In 44 consecutive patients with systemic sclerosis (SSc), plasma concentrations of von Willebrand factor (vWf) were higher than those of the vWf propeptide, but the propeptide showed less variability within patient subgroups. Higher values of the propeptide were observed in patients with early pulmonary involvement. A closer correlation of the propeptide than of vWf to biochemical markers of activity was also evident. Our results suggest that the propeptide, despite a shorter circulating half-time and lower plasma concentrations than vWf, is more useful in the assessment of disease activity in SSc.

Adult↗
PubMed2001

Cytokines, metalloproteinases, their inhibitors and cartilage oligomeric matrix protein: relationship to radiological progression and inflammation in early rheumatoid arthritis. A prospective 5-year study.

OBJECTIVE: To assess how serum concentrations of some cytokines, proteases and their inhibitors and cartilage oligomeric matrix protein (COMP) relate to the evolution of clinical disease and joint damage in early rheumatoid arthritis (RA). METHODS: Annual assessment was performed in 24 RA patients subdivided into three groups according to disease severity as determined by the radiological progression rate. All patients were followed for 5 yr after inclusion. Functional status, Larsen's radiographic index in hands and feet (joint damage score, JDS) and C-reactive protein (CRP) were assessed annually and compared with interleukin (IL)-6, IL-10, the IL-1 receptor antagonist (IL-1Ra), promatrix metalloproteinase 3 (proMMP-3), tissue inhibitor of metalloproteinases 1 (TIMP-1) and COMP, which were determined by specific immunological tests. RESULTS: The median JDS was initially between 4.5 and 7. During the study time the progression of JDS was 1 (median) for patients with slow progression, 33 for patients with intermediate progression and 62 for patients with rapid progression. Changes in CRP and proMMP-3 concentrations over time differed significantly between the groups, but no significant difference was observed for IL-1Ra, TIMP-1 or COMP. ProMMP-3 was closely related to CRP at each time point. IL-6 correlated significantly with CRP at the last four annual follow-up examinations. CRP and proMMP-3 correlated with JDS at the last two or three examinations and the combined levels of these markers over 5 yr correlated significantly with joint damage progression (Spearman rank correlation 0.73 and 0.74 respectively). IL-1Ra showed a weak negative correlation with JDS, and COMP tended to correlate with JDS only at the start. The initial proMMP-3 concentration was the only significant variable predicting rapidly developing joint damage, but the predictive value was low. CONCLUSIONS: ProMMP-3 correlated closely at all time points with CRP, but gave little or no additional clinical information regarding inflammation or radiographic progression. IL-1Ra and TIMP-1 showed weaker, acute-phase-like variation, which may reflect pathogenic agonist/inhibitor imbalance in the evolution of RA. COMP, in contrast, did not reflect the inflammatory CRP-related component of the disease or the destructive aspect in this study.

Arthritis, Rheumatoid↗
PubMed2001

Approaches to rheumatoid arthritis in 2000.

The year 2000 was characterized by euphoria among clinicians based on the continued and consolidated success of tumor necrosis factor (TNF) inhibition but also by problems caused by the high cost of this therapy. Looking at the risks and adverse effects has only begun, and there is so far a remarkable lack of publications dealing with this topic. Leflunomide also emerges as an established disease-modifying antirheumatic drug (DMARD). Other therapies include the cyclooxygenase-2 (Cox-2) inhibitors, which are tolerated better by the gastrointestinal system but raise concerns regarding thromboembolism in patients at risk. The enthusiasm regarding Cox-2 inhibitors is somewhat tempered by recent reports of thromboembolic complications, although those have been rare. The advances in research regarding mechanisms of inflammation and pathogenesis continue to generate new therapeutic approaches, which, however, remain mostly experimental. The complexity of genetics has been emphasized by reports on susceptibility and severity relation to TNF, mannose-binding lectin, and gamma-interferon polymorphism. Epidemiologic studies focusing on prevalence, incidence and outcome continue to deliver conflicting messages. One major worry relates to chronic inflammation in RA and other rheumatic diseases as putative cause of accelerated atherosclerosis.

Antirheumatic Agents↗
PubMed2001

Enteropathic arthritis: how do the joints talk with the gut?

Enteropathic arthritis is a label for conditions in which gut pathology is believed to be of pathogenic importance for the developing joint disease. Impaired barrier function, as well as immunogenetic mechanism, are implicated. Recent publications have highlighted strong new support for the homing of lymphocytes from the gut mucosa to joint tissue, persistence of antigen- and cytokine-based immune deficiency. A convincing argument was made for the interesting observation that two distinct types of joint involvement with different class II HLA backgrounds occur in patients with inflammatory bowel disease. A new mechanism implicating dimeric HLA-B27 heavy chains in the pathogenesis of enteropathic arthritis is also presented. Despite evidence for persisting antigen presence, antimicrobial therapy seems ineffective in reactive arthritis.

Arthritis↗
PubMed2001

Disease severity of 100 patients with systemic sclerosis over a period of 14 years: using a modified Medsger scale.

OBJECTIVE: To assess organ involvement according to a modified Medsger severity scale and its relation to outcome and prognosis in patients with systemic sclerosis. METHODS: One hundred consecutive patients observed in Lund with systemic sclerosis were followed up for a period of 14 years. The mean follow up time was 7.7 years. Initial assessment and an annual evaluation was performed for each patient, with a mean visit frequency of 5.6 per patient. RESULTS: Age at referral, high total skin score, truncal skin involvement, low vital capacity, low static lung compliance, low Cr-EDTA clearance, and ECG abnormalities at the initial assessment predict poor outcome. A severity scoring system for five organ systems indicates a slow progression of organ dysfunction after recruitment into the study. The female: male ratio was 2:1, the mean age at onset of symptoms was 42.3 (range 3-82), and the mean age at recruitment was 47.2 years (range 17-82). Thirty patients died during the follow up period at the mean age of 61.3 years (range 33-85). The causes of death were directly related to systemic sclerosis in at least 10 patients, infections in six, cancers in nine, and other causes in four patients. The standardised mortality ratio was 3.5 and 3.7 for men and women, respectively. CONCLUSION: A high severity score for function of vital organs was shown to predict shortened survival. In this study a severity score based on simple clinical assessment variables was able to predict poor outcome from extensive skin changes, ECG changes, and compromised lung and renal function. Organ dysfunction mainly became manifest during the first five years of the disease, whereafter organ function remained largely stable.

Adolescent↗
PubMed2001

Tumour necrosis factor microsatellites and HLA-DRB1*, HLA-DQA1*, and HLA-DQB1* alleles in Peruvian patients with rheumatoid arthritis.

OBJECTIVE: To study the association between rheumatoid arthritis (RA) and HLA and tumour necrosis factor (TNF) polymorphism in Peruvian mestizo patients in comparison with ethnically similar controls. METHODS: Seventy nine patients with RA and 65 ethnically matched healthy controls were genotyped for HLA-DRB1, HLA-DQA1, HLA-DQB1, and TNFalpha and TNFbeta alleles using PCR amplification. Clinical severity was assessed as mild, moderate, or severe in 35 of the patients. RESULTS: TNFalpha6 showed the strongest association with disease susceptibility. The TNFalpha6 allele was more common in patients than in controls (p<0.0076) and the proportion of patients with at least one copy of this allele was greater (p<0.015, relative risk 2.35). Among the HLA-DRB1* alleles with the shared epitope sequence, only the DRB1*1402 allele was significantly increased in patients compared with controls (p<0.0311), as was the proportion of patients with at least one copy of this allele (p<0.0232, relative risk 2.74). In contrast, the overall frequency of alleles with the shared epitope was not different in patients and controls. The haplotype HLA-DRB1*1402-DQB1*0301-DQA1*0401 was significantly more common in patients. TNFalpha6 was more common in patients whether or not they had this haplotype. None of the 11 patients lacking the TNFalpha6 allele had severe disease. CONCLUSIONS: This study shows for the first time that TNF gene polymorphism is associated with susceptibility to RA in a non-white population. TNFalpha6 and HLA-DRB1*1402 independently conferred significantly increased risk in Peruvian mestizo patients.

Alleles↗
PubMed2000

[Interleukin-18 and new drugs. Protective effect against tumor growth and infections].

IL-18, originally identified as interferon-gamma inducing factor (IGIF), is related to the IL-1 family in terms of its structure as well as its processing, receptor, signal transduction pathway and pro-inflammatory properties. IL-18 is also functionally related to IL-12, as it induces the production of Th1 cytokines and participates in cell-mediated immune cytotoxicity. A summary is made of recent advances in the understanding of IL-18 structure, processing, receptor expression and immunoregulatory functions. It focuses on the role of IL-18 modulation in tumours, infections and autoimmune and inflammatory diseases.

Animals↗
PubMed2000

Circulating collagen metabolites in systemic sclerosis. Differences between limited and diffuse form and relationship with pulmonary involvement.

OBJECTIVE: To study collagen metabolites in systemic sclerosis (SSc) and their relationship with clinical manifestations of the disease. METHODS: Forty-eight SSc patients, 13 with a diffuse form (dcSSc), 23 with a limited form (lcSSc) and 12 with suspected SSc not fulfilling the ACR criteria, and 31 healthy controls were examined. Serum concentrations of aminoterminal type III procollagen peptide (PIIINP), aminoterminal and carboxyterminal type I procollagen peptides (PINP and PICP) and cross-linked carboxyterminal telopeptide of collagen I (ICTP) were determined by radioimmunoassay. RESULTS: Increased serum concentrations of ICTP were found in SSc patients compared with controls. Distinctly higher levels of ICTP were observed in dcSSc than in lcSSc. High serum ICTP was correlated with skin score and acute phase reactants, and with reduced pulmonary function. Serum PIIINP concentration was elevated in both lcSSc and dcSSc. CONCLUSION: Augmented collagen catabolism accompanies the increased collagen synthesis in SSc. Serum ICTP concentration is a marker of this feature and also reflects clinical severity.

Adult↗
PubMed2000

Markers of disease in rheumatoid arthritis.

Substantial progress can be noted in the efforts to demonstrate the usefulness of tissue-related markers of disease in rheumatoid arthritis and other joint diseases. The most informative studies use longitudinal analyses of well-characterized patient groups. Emphasis should be on searching for markers which can be of prognostic significance. New markers need to be assessed in relation to existing ones, such as C-polysaccharide reacting protein and erythrocyte sedimentation rate, which, although not specific, are hard to beat as measures of inflammation. A newly identified matrix component, cartilage intermediate layer protein, has features which make it attractive as a potential cartilage specific marker. Many markers may not in the end prove clinically useful. They will, however, give important insight into pathogenic processes, and may help in evaluating new therapy. Finally, markers originally identified in humans have now proven their value in experimental arthritis.

Arthritis, Rheumatoid↗