Biomedical subjects

Anita Akesson

Publications and source records attributed to Anita Akesson.

5 recordsLinked to original sources

PubMed2007

Recombinant human anti-transforming growth factor beta1 antibody therapy in systemic sclerosis: a multicenter, randomized, placebo-controlled phase I/II trial of CAT-192.

OBJECTIVE: To evaluate CAT-192, a recombinant human antibody that neutralizes transforming growth factor beta1 (TGFbeta1), in the treatment of early-stage diffuse cutaneous systemic sclerosis (dcSSc). METHODS: Patients with SSc duration of <18 months were randomly assigned to the placebo group or to 1 of 3 CAT-192 treatment groups: 10 mg/kg, 5 mg/kg, 0.5 mg/kg. Infusions were given on day 0 and weeks 6, 12, and 18. The primary objective of this study was to evaluate the safety, tolerability, and pharmacokinetics of CAT-192. Secondary outcomes included the modified Rodnan skin thickness score (MRSS), the Scleroderma Health Assessment Questionnaire, assessment of organ-based disease, serum levels of soluble interleukin-2 receptor, collagen propeptides (N propeptide of type I [PINP] and type III collagen), and tissue levels of messenger RNA for procollagens I and III and for TGFbeta1 and TGFbeta2. RESULTS: Forty-five patients were enrolled. There was significant morbidity and mortality, including 1 death in the group receiving 0.5 mg/kg of CAT-192 and 3 deaths in the group receiving 5 mg/kg of CAT-192. There were more adverse events and more serious adverse events in patients receiving CAT-192 than in those receiving placebo, although these events were not more frequent in the high-dose treatment group. The MRSS improved in all groups during the study, but there was no evidence of a treatment effect for CAT-192. Improvement in the MRSS correlated with the disease duration (r = -0.54, P = 0.0008). Changes in the PINP level from baseline correlated with changes in the MRSS (r = 0.37, P = 0.027). CONCLUSION: We report the first evaluation of a systemically administered and repeatedly dosed anti-TGFbeta1 drug. In this pilot study, CAT-192, in doses up to 10 mg/kg, showed no evidence of efficacy. The utility of clinical and biochemical outcome measures and the feasibility of multicenter trials of early dcSSc were confirmed.

Adult↗

PubMed2005

Small intestinal manometry in patients with systemic sclerosis.

OBJECTIVES: The study explores, by the use of manometry, the frequency and severity of small intestinal involvement in patients with systemic sclerosis, and relates the manometric findings to clinical symptoms, radiology, and some intestinal regulatory peptides. METHODS: Stationary antroduodeno-jejunal manometry was used to study small bowel involvement in 10 patients with systemic sclerosis and dysmotility of the oesophagus or signs of malabsorption. Measurements were made during fasting, after a meal, and after octreotide administration and were then compared with a sex-matched control group of healthy individuals. Plasma samples were taken in order to analyse levels of motilin, peptide YY, cholecystokinin, and somatostatin. RESULTS: Manometry was abnormal, with signs of intestinal pseudo-obstruction in eight out of 10 patients. In the control group, one individual had an abnormal manometry, as a result of burst activity. The mean contractile amplitudes during fasting and periods after food, spontaneous phase III periods, and octreotide-induced activity complexes were significantly reduced in the systemic sclerosis group when compared with controls. None of the patients, including two with advanced manometric intestinal disturbances, had small intestinal dilatation when examined by radiography. The plasma peptide levels did not differ significantly between the two groups. CONCLUSIONS: In eight out of 10 patients the manometric criteria for intestinal pseudo-obstruction were fulfilled, with a motility pattern consistent with both neuropathy and myopathy. The release of motility-regulating peptides was unaffected.

Adult↗

PubMed2004

Evaluation of paraffin bath treatment in patients with systemic sclerosis.

OBJECTIVE: To investigate the effects of treatment with paraffin bath in patients with systemic sclerosis (scleroderma). METHODS: In 17 patients with scleroderma one hand was treated daily with paraffin bath in combination with hand exercise. The other hand was treated with exercise only and was considered a control. Hand function was estimated before treatment and after 1 month of treatment, concerning hand mobility and grip force, and perceived pain, stiffness and skin elasticity. RESULTS: At the follow-up, finger flexion and extension, thumb abduction, volar flexion in the wrist, and perceived stiffness and skin elasticity had improved significantly in the paraffin-treated hand compared with the baseline values. The improved hand function was independent of skin score and disease duration. Improvements in function were significantly greater in the hand which was treated with paraffin bath and exercise than in the hand treated with exercise only concerning extension deficit, perceived stiffness and skin elasticity. CONCLUSIONS: In this pilot study hand exercise in combination with paraffin bath seemed to improve mobility, perceived stiffness and skin elasticity. However, further studies with larger sample size are needed to attain more reliable results of the effect of paraffin bath treatment in patients with scleroderma.

Adult↗

PubMed2003

Systemic sclerosis Th2 cells inhibit collagen production by dermal fibroblasts via membrane-associated tumor necrosis factor alpha.

OBJECTIVE: In systemic sclerosis (SSc; scleroderma), T cells infiltrate organs undergoing fibrotic changes and may participate in dysregulated production of collagen by fibroblasts. The objective of this study was to functionally characterize T cells infiltrating skin lesions in early SSc and investigate their capacity to affect production of type I collagen and interstitial collagenase (matrix metalloproteinase 1 [MMP-1]) by dermal fibroblasts. METHODS: Four-color cytometric analysis was used to characterize subset distribution and production of interferon-gamma (IFN gamma) and interleukin-4 (IL-4) in T cell lines generated from the skin of patients with SSc. T cell clones were generated, and their capacity to modulate collagen and MMP-1 production by fibroblasts derived from patients with SSc and from normal individuals was assessed. Neutralizing reagents were used to identify T cell mediators involved in fibroblast modulation. RESULTS: The skin of individuals with early-stage SSc contained T cells preferentially producing high levels of IL-4. Cloned CD4+ Th2-like cells inhibited collagen production by normal fibroblasts. Th2 cell-dependent inhibition was, at least in part, contact-dependent, was essentially mediated by tumor necrosis factor alpha (TNF alpha), and was dominant over the enhancement induced by profibrotic IL-4 and transforming growth factor beta cytokines. The simultaneous induction of MMP-1 production confirmed the specificity of these observations. To be inhibitory, Th2 cells required activation by CD3 ligation. Th2 cells were less potent than were Th1 cells in inhibiting collagen production by normal fibroblasts via cell-to-cell interaction, and SSc fibroblasts were resistant to inhibition. CONCLUSION: These findings indicate that, despite their production of IL-4, Th2 cells reduce type I collagen synthesis by dermal fibroblasts because of the dominant effect of TNF alpha, and suggest that strategies based on TNF alpha blockade aimed at controlling fibrosis in SSc may be unwise.

Adult↗

PubMedDate not supplied

Daily occupations and well-being in women with limited cutaneous systemic sclerosis.

OBJECTIVE: This study investigated occupational performance, well-being (operationalized as general life satisfaction, domain-specific life satisfaction, and self-rated health), and perceived symptoms in women with limited scleroderma and healthy controls. METHODS: Interview-based and self-administered questionnaires were used with 36 women with limited scleroderma and 40 healthy women. RESULTS: In the scleroderma group, most of occupation problems were perceived in work and household chores. The women with scleroderma were mainly satisfied with self-care and least satisfied with household chores. Regarding domain-specific life satisfaction, the women were least satisfied with physical health and leisure. General life satisfaction showed the strongest relations to performance of self-defined occupations and satisfaction with leisure, whereas the strongest association with self-rated health was found for satisfaction with work. Fatigue was perceived as a dominant problem and was significantly associated with well-being. Furthermore, the women with scleroderma felt lower satisfaction with daily occupations and well-being than the healthy women. CONCLUSION: Loss of occupations, low satisfaction with leisure, perceived fatigue, shortness of breath, and pain indicated poorer well-being in women with scleroderma and need to be focused on in occupational therapy interventions.

Activities of Daily Living↗