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Biomedical subjects

M Rustin

Publications and source records attributed to M Rustin.

15 recordsLinked to original sources

Safety and efficacy of 1 year of tacrolimus ointment monotherapy in adults with atopic dermatitis. The European Tacrolimus Ointment Study Group.

OBJECTIVE: To investigate the safety and efficacy of using 0.1% tacrolimus ointment for long-term treatment of atopic dermatitis. DESIGN: Open-label, noncomparative study with 6 to 12 months of follow-up. SETTINGS: Outpatient departments in 30 study centers in 11 European countries. PATIENTS: We enrolled 316 patients aged 18 years and older with moderate to severe atopic dermatitis, 200 for 6 months and 116 for 12 months; 77.5% of patients completed the study. INTERVENTION: Twice-daily application of 0.1% tacrolimus ointment on all affected skin. Visits were scheduled on day 1; after 1, 2, and 4 weeks of treatment; and monthly thereafter. MAIN OUTCOME MEASURES: Safety assessments included monitoring of adverse events, clinical laboratory values, and tacrolimus blood concentrations. Efficacy end points included a combined score (modified Eczema Area and Severity Index) and an investigator's global assessment. RESULTS: Local irritation, adverse events such as burning sensation (47% of patients), pruritus (24% of patients), and erythema (12% of patients) were common but tended to occur only when initiating treatment. Laboratory values showed no marked changes over time. Systemic absorption was minimal, with the maximum tacrolimus blood concentration being less than 1 ng/mL in 76% of patients. All efficacy end points showed improvement. The mean (SD) modified Eczema Area and Severity Index score was 23.7 (12.6) at day 1, 13.5 (11.3) at week 1, 6.1 (9.2) at month 6, and 6.1 (8.1) at month 12. Marked or excellent improvement or clearance of disease was reported in 54%, 81%, and 86% of patients at week 1, month 6, and month 12, respectively. CONCLUSION: Up to 1 year of tacrolimus ointment use was safe and effective in patients with atopic dermatitis. Arch Dermatol. 2000;136:999-1006

Administration, Topical↗

The treatment of atopic dermatitis with adjunctive high-dose intravenous immunoglobulin: a report of three patients and review of the literature.

There are few reports of the use of high-dose intravenous immunoglobulin (hdIVIg) in the treatment of atopic dermatitis (AD). We describe our experience using this therapy in three patients with severe AD, all of whom had steroid-related side-effects. These patients received either Alphaglobin(R) or Sandoglobulin(R) 2 g/kg monthly: all had improved skin scores, allowing reduction of their steroid dose. Total IgE fell in one of three patients. We discuss the side-effects of hdIVIg and their management, and detail the differences between the available immunoglobulin products available in the U.K. There are several proposed mechanisms of action of this therapy which may be operative, and those most important in AD are discussed. In view of the time and expense involved in the treatment of patients with hdIVIg, careful patient assessment is vital. We describe dose reduction strategies and methods for cost containment. In addition, one of the patients has embarked on IVIg home therapy training. This will be the first time this has been attempted for a dermatological indication. Training of this type may be available through an immunotherapy service such as exists for patients with primary immunodeficiencies.

Adult↗

Association of immunological changes with clinical efficacy in atopic eczema patients treated with traditional Chinese herbal therapy (Zemaphyte).

The efficacy of the Chinese herbal therapy (Zemaphyte) has been well established as a treatment for atopic eczema (AE) in clinical trials. The purpose of this study was to probe the immunological changes that occurred when patients were treated with the herbs for a period of 8 weeks. This treatment decreased serum IgE complexes (p less than 0.05) but did not affect total serum IgE or CD23 expression on peripheral blood monocytes. Peripheral blood mononuclear cells from patients before and after treatment were cultured overnight with interleukin 4 and the ability of this cytokine to induce CD23 on monocytes from treated patients was found to be significantly diminished (p less than 0.01). Soluble interleukin 2 receptor and soluble vascular cell adhesion molecule were both raised in the serum of AE patients compared to control individuals. Both these parameters were decreased following treatment (p less than 0.05). All these changes coincided with improvement in erythema and surface damage scores. There was no alteration in soluble intracellular adhesion molecule or soluble CD23. The results of these investigations would suggest that this herbal treatment has the ability to target various immunological parameters which may be involved in the pathogenesis of AE.

Administration, Oral↗

Comparative effects of calcipotriol (MC903) solution and placebo (vehicle of MC903) in the treatment of psoriasis of the scalp.

The efficacy and safety of calcipotriol solution in the treatment of scalp psoriasis was compared with placebo (vehicle solution), in a multicentre double-blind, randomized, parallel-group study of 49 adult patients. Calcipotriol solution (50 micrograms/ml), or placebo, was applied twice daily over a 4-week period. At the end of the study period 60% of patients on calcipotriol showed clearance or marked improvement of their psoriasis compared with 17% on placebo. Overall assessment of treatment response showed that calcipotriol was superior to placebo in both investigator (P < 0.001; 95% confidence interval for difference 19.0-67.6) and patient (P < 0.001; 95% confidence interval for difference 18.3-68.0) assessments. Total sign score for psoriasis (i.e. the sum of the scores for redness, thickness and scaliness) decreased by 48.9% in the calcipotriol group, and by 18.6% in the placebo group (P = 0.005). Calcipotriol was significantly superior to placebo in reducing redness, thickness, scaliness and extent of psoriasis, and in the patients' assessment in reducing scalp flaking and itching. No statistically significant changes in blood biochemistry were detected during the study, and the solution was generally well tolerated.

Adult↗

The efficacy of traditional Chinese herbal therapy in atopic eczema.

A traditional Chinese herbal therapy (Zemaphyte) for the treatment of atopic eczema (AE) is currently being assessed. This review attempts to highlight its success in patients who are recalcitrant to Western forms of treatment and the rationale behind its use. The herbal preparation is a mixture of 10 herbs with some known pharmacological agents and actions. The concept of such a complex mixture in clinical treatment is anathema to Western medicine but acceptable in traditional Chinese medicine. As this formation has been shown to be effective in two double-blind crossover trials, investigative work on components from the mixture must be established in order to find the active constituent(s) and describe their mode of action. This research will also lead to a greater understanding of the complex immunopathology of AE.

Clinical Trials as Topic↗

HTLV-1-associated cutaneous disease: a clinicopathological and molecular study of patients from the U.K.

The clinicopathological features of eight patients with cutaneous disease associated with HTLV-1 infection are reviewed. All were U.K. residents of West Indian extraction, and two are currently alive. Disease remained confined to the skin in two patients. Five patients with a cutaneous prodromal phase developed leukaemia after a median duration of 124 months (3 months-21 years), and in one of these combination chemotherapy produced a sustained clinical remission for 20 months. Two patients developed cutaneous disease after remission of their leukaemia. Cutaneous lesions were heterogeneous and included localized papules, a generalized papulonodular eruption, diffuse and localized erythematous plaques, pompholyx-like lesions on the palms and soles, and tumours. The histology of the skin lesions was also variable, and consisted of a heavy dermal infiltrate with lymphocytes, histiocytes, plasma cells, eosinophils and cytologically atypical mononuclear cells. Epidermotropism was present in biopsies from five patients. Tumour cells with large, densely staining, pleomorphic nuclei, arranged in rows between collagen bundles, were present in the majority of cases. In one patient the infiltrate also consisted of epithelioid cells and multinucleated giant cells. Six cases were classified histologically as pleomorphic T-cell lymphoma, and two as cerebriform or mycosis fungoides type. Molecular studies revealed a clonal T-cell population associated with monoclonal integration of HTLV-1 provirus in tissue DNA from six patients. In two patients HTLV-1 integration was established retrospectively using enzymatic in vitro amplification of a specific HTLV-1 po1 gene sequence in DNA extracted from paraffin-embedded sections. This study indicates that the clinical and pathological features of HTLV-1-associated cutaneous disease are diverse. Patients may have disease confined to the skin for prolonged periods, either at presentation or following clinical relapse--cutaneous adult T-cell lymphoma. Molecular techniques allow distinction from other types of cutaneous T-cell lymphoma, and provide an opportunity for retrospective studies of archival material.

Adult↗

Immunohistochemical, morphological and functional changes in the peripheral sudomotor neuro-effector system in elderly people.

Age-related changes in the human peripheral sudomotor neuro-effector system have been investigated in six 80-year-olds and six young adults. Histochemical and immunohistochemical studies on forearm skin biopsies showed diminished vasoactive intestinal polypeptide (VIP) and calcitonin gene related peptide (CGRP)-like immunoreactivity and a virtual absence of acetylcholinesterase in the elderly sudomotor nerve endings compared to the young. Reduced size of nerve bundles and decreased density of sympathetic nerve endings adjacent to the sweat glands of old people were shown by the neuronal marker, protein gene product (PGP 9.5), and by electron microscopy. Image analysis techniques were also used to demonstrate a marked regression in secretory coil size with age. Functional decrements accompanying the neurochemical and morphological changes in the neuro-effector system were measured in ten 80-year-olds by local quantitative nicotine axon reflex responses and compared with 12 young adults. These studies demonstrate marked regressive changes in both the nerve endings and target cells in old age and appear to express a significant loss of vigour in trophic interactions.

Acetylcholinesterase↗

Successful treatment of Raynaud's syndrome with Iloprost, a chemically stable prostacyclin analogue.

Twelve female patients with severe secondary Raynaud's phenomenon were treated in a randomized order with both placebo and Iloprost infusions. Infusions were for 5 hours on 3 consecutive days and Iloprost was administered at variable dosage from 1.0 to 3.0 ng/kg/min. A 6-week follow-up period was used between the two sets of infusions. A significant number of patients reported Iloprost had improved Raynaud's symptomatology compared with placebo and this effect lasted for up to 6 weeks. The number of attacks of Raynaud's as recorded by patients in diary books was similarly reduced after Iloprost. Digital and nail-bed blood flows measured by laser-Doppler methods were increased for up to 6 weeks after Iloprost, but not after placebo infusions. Iloprost may be a useful therapeutic agent in the treatment of severe secondary Raynaud's syndrome.

Aged↗

Corticosteroids.

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Administration, Oral↗