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Biomedical subjects

M Graeber

Publications and source records attributed to M Graeber.

16 recordsLinked to original sources
PubMed2001

The eczema area and severity index (EASI): assessment of reliability in atopic dermatitis. EASI Evaluator Group.

OBJECTIVE: To test the reliability of the eczema area and severity index (EASI) scoring system by assessing inter- and intra-observer consistency. DESIGN: Training of evaluators, application, and assessment over 2 consecutive days. SETTING: An academic center. PATIENTS: Twenty adults and children with atopic dermatitis (AD); cohort 1 (10 patients > or = 8 years) and cohort 2 (10 patients < 8 years). INTERVENTIONS: None. MAIN OUTCOME MEASURE: The EASI was used by 15 dermatologist evaluators to assess atopic dermatitis in cohort 1 and cohort 2 on 2 consecutive days. Inter- and intraobserver reliability were analyzed. RESULTS: Overall intra-evaluator reliability of the EASI was in the fair-to-good range. Inter-evaluator reliability analyses indicated that the evaluators assessed the patients consistently across both study days. CONCLUSIONS: This study demonstrated that the EASI can be learned quickly and utilized reliably in the assessment of severity and extent of AD. There was consistency among the evaluators between consecutive days of evaluation. These results support the use of the EASI in clinical trials of therapeutic agents for AD.

Adolescent↗
PubMed2001

SDZ ASM 981: an emerging safe and effective treatment for atopic dermatitis.

BACKGROUND: SDZ ASM 981 is a selective inhibitor of the production of pro-inflammatory cytokines from T cells and mast cells in vitro. It is the first ascomycin macrolactam derivative under development for the treatment of inflammatory skin diseases. OBJECTIVES: This study was designed to determine the safety and efficacy of SDZ ASM 981 cream at concentrations of 0.05%, 0.2%, 0.6% and 1.0% in the treatment of patients with atopic dermatitis and to select the concentration to be used in phase III studies. METHODS: This was a double-blind, randomized, parallel-group, multicentre dose-finding study. A total of 260 patients were randomly assigned to treatment with SDZ ASM 981 cream at concentrations of 0.05%, 0.2%, 0.6%, or 1.0%, matching vehicle cream, or the internal control 0.1% betamethasone-17-valerate cream (BMV). Treatment was given twice daily for up to 3 weeks. RESULTS: A clear dose-response relationship for SDZ ASM 981 was evident, with 0.2%, 0.6% and 1.0% SDZ ASM 981 creams all being significantly more effective than vehicle (P = 0.041, 0.001 and 0.008, respectively) in terms of baseline to end-point changes in the Eczema Area Severity Index (EASI) and pruritus score. The 1.0% cream was the most effective SDZ ASM 981 concentration. BMV was more effective than the SDZ ASM 981 creams tested in this study. It appears that the efficacy plateau was not reached with the SDZ ASM 981 creams within 3 weeks treatment. SDZ ASM 981 was well tolerated. Burning or a feeling of warmth were the only adverse events reported more frequently in the 0.6% and 1.0% SDZ ASM 981 treatment groups than in the vehicle treatment group (42.9%, 48.9% and 34.9%, respectively). Few systemic adverse events were reported during the study (headache was the most frequent systemic event reported by 15 of 252 patients) and none was considered to be related to treatment. The local tolerability profile of the 1.0% cream was similar to that of the lower concentrations. CONCLUSIONS: 1.0% SDZ ASM 981 cream, which was shown to be safe, well tolerated and the most effective concentration in this study, was selected as the concentration to be further developed in phase III studies.

Adolescent↗
PubMed2000

Ascomycins: promising agents for the treatment of inflammatory skin diseases.

Ascomycin derivatives represent a novel class of anti-inflammatory macrolactams currently under development for the treatment of skin diseases. The main biological effect of ascomycins is an inhibition of the synthesis of both Th1 and Th2-type cytokines in target cells. Several compounds are being developed with SDZ ASM 981 being at the most advanced stage. It has high anti-inflammatory activity in animal models of skin inflammation and does not induce skin atrophy. Topical application of SDZ ASM 981 was shown to be effective in atopic dermatitis (AD), allergic contact dermatitis and also in psoriasis under semi-occlusive conditions. In patients with AD, SDZ ASM 981 cream led to consistently low systemic exposure even when applied on large areas of skin. SDZ ASM 981 overcomes the drawbacks of current topical therapies of inflammatory skin diseases as its safety profile is better than that of topical corticosteroids. Studies continue to investigate its efficacy and safety in the treatment of inflammatory skin diseases.

Adult↗
PubMed1998

The novel ascomycin derivative SDZ ASM 981 is effective for psoriasis when used topically under occlusion.

Topical SDZ ASM 981 has been found to be highly effective in preclinical models of T-cell-mediated skin disease. T cell activation is crucial in the pathogenesis of psoriasis. It has been hypothesized that SDZ ASM 981 may prove to be an effective treatment for chronic plaque psoriasis. Therefore, the study objective was to determine the efficacy, tolerability and safety of the new topical macrolactam, SDZ ASM 981, for chronic plaque psoriasis. Ten patients with chronic plaque-type psoriasis were treated with SDZ ASM 981 (0.3% and 1.0%), the corresponding ointment base (placebo) and open-labelled clobetasol-17-propionate ointment (0.05%) in a randomized, double-blind, within-subject comparison for 2 weeks using the microplaque assay. Evaluation was performed by daily determination of clinical scores for erythema and induration. The results of the study showed that, after 2 weeks of treatment, total scores described by 92% for clobetasol, by 82% for 1 SDZ ASM 981, by 63% for 0.3% SDZ ASM 981 and by 18% for the ointment base (placebo). No adverse drug effects were seen in any patient throughout the study. We conclude from our results that the new macrolactam SDZ ASM 981 (1%) is similar to clobetasol-17-propionate (0.05%) in plaque-type psoriasis when applied topically under occlusion for 2 weeks using the microplaque assay.

Administration, Topical↗
PubMed1993

The role of cytokines in the generation of skin lesions in dermatitis herpetiformis.

The infiltration of polymorphonuclear neutrophils (PMN) into the upper dermis which characterizes the skin lesions of dermatitis herpetiformis (DH) has never been satisfactorily explained. This study has shown that lesional skin of patients with DH has increased expression of endothelial leucocyte adhesion molecules (ELAM) in the deep dermis, combined with a markedly increased staining for interleukin 8 (IL-8) in the basal epidermal layer. Dendritic cells which stained for granulocyte macrophage colony stimulating factor (GM-CSF) were also observed at the dermo-epidermal junction, and this phenomenon was more pronounced in lesional than in uninvolved DH skin. ELAM, IL-8 and GM-CSF are known to promote infiltration and activation of PMN, and it is suggested that these cytokines may play a key role in the generation of DH lesions.

Adult↗
PubMed1992

Prevention of adjuvant arthritis by cyclosporine in rats.

The effect of cyclosporine A during the development phase of adjuvant arthritis was studied in 40 female rats. Five groups of eight animals each received oral cyclosporine, 2.5, 5, 10, 20, or 30 mg/kg daily for 30 days. Also, eight normal and eight diseased rats served as placebo controls. At the time of inoculation of the adjuvant suspension on day 0, measurement of disease parameters (paw swelling and vertebral density) was started concomitantly with beginning of therapy. On completion of the study, the animals were killed, and after measurement of total skeletal and segmental (hind legs and caudal spine plus two caudal vertebrae) calcium, the two assessed vertebrae and both femoral condyles were removed for histomorphometric evaluation (vertebrae) and for estimation of glycosaminoglycan (GAG) content of cartilage. Blood for osteocalcin determinations also was taken at term from control and untreated arthritic rats and from animals that had received 10 mg/kg cyclosporine. Treatment with 2.5 mg/kg was ineffective, but doses between 5 and 20 mg/kg prevented the development of articular and osseous lesions. The 20 mg/kg dose showed no better effect than 10 mg/kg. This was shown by the absence of inflammation and the presence of normal condylar GAG and total mineral content in the areas screened. Untreated animals showed marked reductions in all of these parameters. The 30 mg/kg dose was effective in blocking the GAG loss, but significant reductions in bone density and trabecular volume were seen. There was a close correlation between GAG and bone density values, suggesting a common causal relationship. Circulating osteocalcin was significantly elevated in the untreated animals with adjuvant arthritis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Induction of swelling, synovial hyperplasia and cartilage proteoglycan loss upon intra-articular injection of transforming growth factor beta-2 in the rabbit.

Transforming growth factor beta (TGF-beta) is a multifunctional homodimeric polypeptide with potent actions upon many target cells, including those of mesenchymal and haemopoietic lineage. The recent reports of high levels of the cytokine in rheumatoid synovium and synovial fluid, prompted this study into the effect of intra-articular injection of TGF beta-2 into rabbit knee-joints. Four daily injections of 1 microgram caused swelling, probably as a consequence of prostaglandin E2 production, synovial fibroblastic hyperplasia and a striking loss of femoral condyle proteoglycan. Using the polymerase chain reaction, no evidence could be obtained for the induction of interleukin-1 alpha gene expression in either synovial tissue or synovial fluid cells. These findings suggest that the TGF-beta present in the rheumatoid joint may contribute directly to the pathogenesis of rheumatoid arthritis.

Animals↗
PubMed1990

Regression of bone and cartilage loss in adjuvant arthritic rats after treatment with cyclosporin A.

To test the effect of cyclosporin A (CsA) on arthritis-related bone resorption, we studied 30 female rats with adjuvant-induced arthritis (AIA). The animals were randomly assigned to 5 groups of 6 animals each; they received daily oral doses of 3, 5, 10, or 15 mg/kg CsA or placebo for 10 days. The parameters studied were (a) caliper measurements of hindpaw swelling, (b) radiometric densitometry of caudal vertebrae, (c) quantitative histomorphometry of radiographed vertebrae, and (d) glycosaminoglycan measurements in femoral condyles. A significant dose-dependent regression of articular swelling occurred in rats given 5, 10, and 15 mg/kg CsA, and this was concomitant with improvement in bone density. These results correlated with those of quantitative bone morphometry. Thus, trabecular volume was significantly reduced in AIA rats, but restoration to virtually normal values occurred with CsA doses between 5 and 15 mg/kg. The protective effect of CsA on articular damage was supported by the dose-dependent progressive improvement in total femoral condyle glycosaminoglycan content. The favorable effect of CsA on AIA is likely due to a blockade of T cell activation via an inhibition of production of lymphokines such as interleukin-2 and gamma-interferon. The consequent cessation of the immune reaction would lead to a reduction in the release of cytokines, such as interleukin-1, that are likely to be the mediators of the pathologic bone and cartilage breakdown that is characteristic of arthritic disease.

Animals↗
PubMed1989

[Corrective osteotomies of the thigh after faulty healing of infected burn wounds].

The occurrence of burn injuries and fractures of the extremities often necessitates that vital precautions be taken first and the possibility of osseous defective healing be initially accepted. After the vital functions have been stabilized, late corrective procedures become necessary. Two cases of the treatment strategy for femur fractures which healed defectively are reported.

Adult↗
PubMed1989

Transcranial Doppler arteriography--a technical note.

Transcranial Doppler (TCD) evaluation of the intracranial vessels was performed in sixty-six patients, 51 of whom received conventional angiography either prior to or subsequent to the ultrasonic arteriogram. Of the 14 patients evaluated for arteriovenous malformations (AVMs), TCD indicated the existence of the AVM in 10 cases. Of those 10 cases, 9 correlated with angiography. Twenty-one patients with aneurysms were evaluated with TCD and only 2 were detected. Twenty-three patients suspected of having ischemic disease were evaluated with TCD, which indicated the presence of stenosis in 21 patients. Twenty of those patients received conventional angiography, with 18 demonstrating significant stenosis.

Blood Flow Velocity↗