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Biomedical subjects

B R Allen

Publications and source records attributed to B R Allen.

At least 19 recordsLinked to original sources
PubMed2006

Low systemic exposure in infants with atopic dermatitis in a 1-year pharmacokinetic study with pimecrolimus cream 1%*.

Systemic drug exposure following the application of topical agents is a very important safety consideration, particularly in infants, who have a significantly higher ratio of body surface area to body mass than older children and adults. Here, we report on drug exposure in five infants aged 5.7-11.9 months at baseline, with extensive, moderate-to-severe atopic dermatitis (AD). Patients were treated bid for 1 year, as needed, with pimecrolimus cream 1% in an open-label, non-controlled study. No indication of drug accumulation was found; pimecrolimus blood concentrations were consistently low, ranging from below the limit of quantitation (0.1 ng/ml) to 1.94 ng/ml. Treatment over this prolonged period was well tolerated, with no evidence of any treatment-related adverse events. The results of this 1-year study indicate that long-term management of AD with pimecrolimus cream 1% is associated with consistently very low systemic absorption, even in the youngest patients with extensive disease.

Administration, Cutaneous↗
PubMed2003

Systemic exposure, tolerability, and efficacy of pimecrolimus cream 1% in atopic dermatitis patients.

AIMS: To measure pimecrolimus blood concentrations and to evaluate tolerability and efficacy in children and infants treated topically for atopic dermatitis with pimecrolimus cream 1% for three weeks. METHODS: Three open label, non-controlled, multiple topical dose studies were conducted in children aged 8-14 years (study A, ten patients), and in infants aged 8-30 months (study B, eight patients) and 4-11 months (study C, eight patients). Pimecrolimus blood concentrations were determined on days 4 and 22 of treatment, and at end of study. Efficacy was assessed using the Eczema Area and Severity Index (EASI). RESULTS: Pimecrolimus blood concentrations were consistently low, typically (81%) below 1 ng/ml, with more than half of the measurements below the assay limit of quantitation (0.5 ng/ml) in studies A and B. The highest blood concentration measured throughout the three studies was 2.6 ng/ml. The cream was well tolerated, locally and systemically. The most common adverse event suspected to be related to study medication was a transient mild to moderate stinging sensation at the application site in 5/26 patients. There was no indication of any systemic adverse effect. The patients responded well to therapy with a rapid onset of action, usually within four days. Median reductions of EASI from baseline at day 22 were 55% (study A), 63% (study B), and 83% (study C). CONCLUSION: Three weeks treatment of children and infants with extensive atopic dermatitis, using pimecrolimus cream 1% twice daily, is well tolerated and results in minimal systemic exposure, at which no systemic effect is expected.

Adolescent↗
PubMed2003

Atopic dermatitis management with tacrolimus ointment (Protopic).

Tacrolimus ointment is the first of a new class of non-steroidal topical immunomodulators indicated for the treatment of atopic dermatitis. Topical tacrolimus has been subject to an extensive clinical development program involving more than 16,000 patients. A clinical trial program, including vehicle-controlled studies, short- and long-term comparative studies and long-term safety studies, has investigated tacrolimus 0.1% and 0.03% ointment for the treatment of atopic dermatitis in adults and children aged 24 months and older. Tacrolimus monotherapy is rapidly effective, resulting in clinical improvements within three days of starting therapy, and produces a progressive increase in efficacy that is sustained during long-term treatment. Tacrolimus treats the signs and symptoms of atopic dermatitis, reduces the incidence of flares, and offers the potential for long-term disease control. No major safety concerns have been reported to date. Tacrolimus ointment is generally well tolerated, the primary adverse events being mild to moderate and transient application-site reactions: skin burning, pruritus and erythema. Tacrolimus ointment is a significant advance in dermatology and provides physicians with an alternative to conventional topical corticosteroid therapy.

Adolescent↗
PubMed2002

Interactions of platelets with Synthocytes, a novel platelet substitute.

A platelet substitute, Synthocytes, is being developed for the prevention and treatment of thrombocytopenia. Synthocytes are composed of fibrinogen adsorbed on heat stabilised albumin microcapsules of defined size. The purpose of this study was to perform experiments in vitro to investigate the capacity of Synthocytes to interact with platelets, one of the means through which Synthocytes may contribute to haemostatic plug formation in vivo. Synthocytes were found to interact with platelets as shown by platelet aggregation assays and measurements of [(14)C]5HT release from platelets in whole blood and platelet-rich plasma. Platelet-Synthocytes co-aggregate formation was demonstrated directly using flow cytometry and the presence of activated platelets in these co-aggregates was demonstrated using an antibody to P-selectin. Synthocytes enhanced platelet responsiveness to conventional aggregating agents such as ADP. Indeed, antagonists of the action of ADP on platelets inhibited the direct effects of Synthocytes on platelets in whole blood, as did a GPIIb/IIIa antagonist. Enhancement of annexin V binding was also observed, indicative of increased pro-coagulant activity. Experiments performed with control microcapsules (lacking fibrinogen) confirmed the importance of fibrinogen in the interactions that occurred. The results suggest that fibrinogen on the surface of Synthocytes can interact with GPIIb/IIIa on platelets to induce platelet activation, secretory activity and aggregation, and that ADP contributes to this process. This initial interaction renders platelets more susceptible to the stimulatory effects of other platelet-activating agents. It is considered likely that in the clinical setting of thrombocytopenia any interaction between Synthocytes and residual platelets that are present may contribute to primary haemostasis.

Adenosine Diphosphate↗
PubMed2001

What is the cost of atopic dermatitis in preschool children?

BACKGROUND: Atopic dermatitis (AD) is the most common inflammatory skin disorder and an important cause of morbidity in young children in the U.K. Such disability produces significant economic burden reflected in direct medical costs associated with health service utilization, direct family care costs such as transport costs, indirect costs associated with loss of productivity of carers, and intangible costs associated with the psychological effects of the disease. OBJECTIVES: In order to evaluate this economic burden we conducted a cross-sectional survey of children aged 1-5 years in the Nottingham area in 1995-96. METHODS: We sent a postal questionnaire to parents of all children aged 1-5 years with questions to identify those with AD; a second questionnaire was sent to parents of identified children regarding costs and utilization of medical services. Intangible costs were not evaluated. RESULTS: The 12-month period prevalence of AD according to a dermatologist's diagnosis in 1761 children was 16.5% (95% confidence interval 14.7-18.2%). Total mean disease costs were estimated to be pound79.59 per child over the 12-month period of the study. The most significant costs were due to costs to the state for National Health Service (NHS) consultations ( pound28.62 mean annual cost) and prescriptions ( pound22.03). Consultations with general practitioners accounted for the significant bulk of consultation costs, with only 6% of children being seen in secondary care (17 of 290). Most prescribing costs (76%) were due to emollients and bath preparations. Family care costs ( pound28.94 mean annual cost) accounted for 36% of total disease costs and were associated with changes to the home environment, purchase of over-the-counter medicines, transport costs, visits to homoeopaths and salary loss. CONCLUSIONS: The results signify that AD is an important cause of economic burden both to the NHS and to the families of affected children. Using population census data and the results in this study, we estimated that the annual U.K. cost of AD in children aged 1-5 years in 1995-96 was pound47 million.

Age Distribution↗
PubMed2001

Thalidomide.

Explore the source record for details and available documents.

Dermatologic Agents↗
PubMed1999

Combination treatment with methotrexate and cyclosporin for severe recalcitrant psoriasis.

An increasingly important approach to the management of patients with severe psoriasis is the concurrent use of two systemic treatments. Previous guidelines have advised against the use of methotrexate and cyclosporin in combination. We report the successful use of a combination of methotrexate and cyclosporin in the treatment of 19 patients with severe, recalcitrant psoriasis, 15 of whom had psoriatic arthropathy. Most patients had previously received two or more systemic treatments. Before combination treatment was started nine of the patients were taking methotrexate and 10 were taking cyclosporin at the maximum tolerated doses. The duration of combination treatment was bimodally distributed, with seven patients having short-term treatment (mean +/- SD duration 18. 9 +/- 15.7 weeks) and 12 patients having long-term treatment (mean +/- SD duration 193.2 +/- 160.6 weeks). Those patients who received short-term treatment did not develop any evidence of toxicity from either agent. Of those patients on long-term treatment, three developed mild impairment of renal function that returned to normal following a reduction in dose of cyclosporin, and three had impairment of renal function (following long-term cyclosporin monotherapy) that improved, but did not normalize, following a reduction in dose of cyclosporin. In each case, combination treatment for psoriasis resulted in good control of both skin and joint problems using lower doses of each agent than would have been used for monotherapy. We conclude that the combination of methotrexate and cyclosporin is an effective treatment for this group of patients.

Adult↗
PubMed1998

Severity distribution of atopic dermatitis in the community and its relationship to secondary referral.

Although atopic dermatitis is the most common inflammatory dermatosis affecting children, no previous studies have evaluated the relationship between disease severity and the referral pattern to secondary health care services. We carried out a cross-sectional survey of 1760 children aged 1-5 years selected from the age-sex registers of four urban and semiurban general practices in Nottingham. Atopic dermatitis was diagnosed by a dermatologist on the basis of symptoms and signs of a flexural itchy rash that had been present in the previous 12 months. The severity of atopic dermatitis was assessed clinically by the same dermatologist on the basis of reported symptoms over the previous 12 months and clinical signs, and was graded on a three-point scale as mild, moderate or severe. Information on the use of primary and secondary health care services was recorded at the time of the interview. The 1-year period prevalence of atopic dermatitis was 16.5% (95% confidence interval 14.7-18.2%). The severity distribution of atopic dermatitis was: mild 84% (n = 242), moderate 14% (n = 41) and severe 2% (n = 7). Of those children with atopic dermatitis, 96% (n = 278) had consulted their general practitioner in the previous 12 months and 6% (n = 17) had been seen in secondary care. Overall, 4% (n = 11) of those children with atopic dermatitis had a consultation with a dermatologist. Other sources of secondary care referral included the paediatric department (n = 2) and accident and emergency department (n = 6). Referral to secondary care was found to be positively related to disease severity, with referral occurring in 3% of mild cases, 15% of moderate cases and 43% of severe cases. Although the relative referral rate of mild and moderately severe disease was low, these cases were found to represent a significant proportion (82%) of the total numbers of children seen in secondary care. This study has shown that: (i) most cases of atopic dermatitis in the community are mild in severity; (ii) referral to secondary health care services by general practitioners is infrequent; (iii) disease severity is an important determinant of referral to secondary care; and (iv) any potential change in the referral pattern of mild/moderate cases of atopic dermatitis to secondary care is likely to produce a significant increase in workload for dermatology departments.

Child, Preschool↗
PubMed1997

Long-term efficacy and safety of cyclosporin in severe adult atopic dermatitis.

A prospective, open, multicentre study was performed to investigate the efficacy and safety of long-term treatment with cyclosporin in adults with severe atopic dermatitis. Subjects were treated for a maximum of 48 weeks. For the first 8 weeks, cyclosporin was administered at 2.5 mg/kg per day. The dose was then adjusted according to response. Disease activity was monitored using the six-area, six-sign score and the proportion of skin involved. Pruritus and sleep disturbance were assessed using four-point scales. Response was further evaluated on a five-point scale. Adverse events, blood pressure and serum biochemistry were monitored. Tolerability was assessed on a five-point scale. One hundred subjects were enrolled and 65 completed 48 weeks of treatment. Withdrawals occurred due to remission (three), inadequate response (seven), protocol violations (11) and adverse events (14, of which seven were probably treatment related). Cyclosporin produced rapid and highly significant improvements in all indices of disease activity. Sixty-five subjects considered that they had shown a considerable improvement or complete clearance of disease. Most patients relapsed after cessation of treatment, but neither signs nor symptoms had returned to baseline severity 8 weeks later. Blood pressure and serum creatinine levels increased slightly, and in one subject renal impairment was a major factor contributing to withdrawal of the drug. Overall, 85 subjects rated the tolerability of cyclosporin as good or very good. The results indicate that cyclosporin has a place in the long-term treatment of severe atopic dermatitis provided that appropriate patients are selected and careful monitoring is performed.

Adolescent↗
PubMed1997

Graft-versus-host disease-like eruption in a patient with non-Hodgkin's lymphoma.

Graft-versus-host disease (GVHD) is most commonly seen as a complication of bone marrow transplantation, although it can occur whenever tissue or blood products are given whereby immunologically competent donor lymphocytes react against host tissues. A 65-year-old man with non-Hodgkin's lymphoma developed a severe widespread erosive eruption of the skin and mucosal surfaces. Clinically and histologically it was identical to cutaneous GVHD even though the patient had never received tissue or blood products. He failed to respond to conventional therapy for GVHD, but his skin improved significantly on treating his underlying lymphoma, which eventually proved fatal. There are two previous reports of GVHD associated with malignancy but we believe this to be the first case secondary to a lymphoma.

Aged↗
PubMed1996

Cyclosporine in severe childhood atopic dermatitis: a multicenter study.

BACKGROUND: Severe atopic dermatitis (AD) remains difficult to treat. Cyclosporine is effective in adults but has not previously been investigated in children with AD. OBJECTIVE: The aims were to investigate the efficacy, safety, and tolerability of cyclosporine in severe refractory childhood AD. METHODS: Subjects 2 to 16 years of age were treated for 6 weeks with cyclosporine, 5 mg/kg per day, in an open study. Disease activity was monitored every 2 weeks by means of sign scores, visual analogue scales for symptoms, and quality-of-life questionnaires. Adverse events were monitored. Efficacy and tolerability were assessed with five-point scales. RESULTS: Twenty-seven children were treated. Significant improvements were seen in all measures of disease activity. Twenty-two showed marked improvement or total clearing. Quality of life improved for both the children and their families. Tolerability was considered good or very good in 25 subjects. CONCLUSION: Cyclosporine may offer an effective, safe, and well-tolerated short-term treatment option for children with severe AD.

Administration, Oral↗
PubMed1996

Treatment of severe atopic dermatitis in childhood with cyclosporin.

Cyclosporin has been shown to be effective in the treatment of adult atopic dermatitis, but there are no clinical trials evaluating its use in childhood. Atopic dermatitis is more common in children and the severe form can be associated with considerable morbidity. We report on 18 children with severe refractory atopic dermatitis who have been treated with cyclosporin on an open basis. The drug was given at an initial daily dose of 5 or 6 mg/kg and in some patients the dose was reduced according to response. Sixteen patients showed a good or excellent response to treatment, one a moderate response and one patient failed to improve. The treatment was well tolerated and there were no significant changes in serum creatinine or blood pressure. Long remission after withdrawal of treatment was seen in some patients, although most relapsed within a few weeks. We suggest that cyclosporin is an effective and safe short-term treatment for severe atopic dermatitis in childhood.

Adolescent↗
PubMed1996

Dissecting cellulitis of the scalp: response to isotretinoin.

We report three patients with dissecting cellulitis of the scalp. Prolonged treatment with oral isotretinoin was highly effective in all three patients. Furthermore, long-term post-treatment follow-up in two of the patients has shown a sustained therapeutic benefit.

Adult↗
PubMed1994

Dermatomyositis associated with malignant melanoma--case report and review of the literature.

Dermatomyositis (DM) is a connective tissue disorder characterized by cutaneous and muscle involvement. It is a well recognized paraneoplastic syndrome and has been linked with malignancy in 15-34% of adult patients. The course of DM in such patients usually correlates closely with the activity of the underlying malignancy. We report a patient who developed DM 4 years after excision of a malignant melanoma (MM) from the back and 1 year before the diagnosis of metastatic disease. A literature review revealed that the association of dermatomyositis with MM is rare and consistent with a dismal prognosis.

Dermatomyositis↗
PubMed1993

Cyclosporin greatly improves the quality of life of adults with severe atopic dermatitis. A randomized, double-blind, placebo-controlled trial.

A multicentre, randomized, double-blind, controlled crossover clinical trial was conducted on 33 patients with severe refractory atopic dermatitis, to determine the effects of cyclosporin (5 mg/kg/day) on their health-related quality of life. Treatments were administered for 8-week periods. One group (n = 16) received placebo followed by cyclosporin, and the other (n = 17) received cyclosporin and then placebo. Health-related quality of life was assessed at 0, 8 and 16 weeks using a general measure, the United Kingdom Sickness Impact Profile (UKSIP), an eczema-specific measure, the Eczema Disability Index (EDI), and a global 5-point rating scale of overall health (very good to very poor). In addition, clinical assessments (i.e. extent and activity of disease) were made by the investigators. UKSIP and EDI scores indicated significant improvement in quality of life (P < 0.05-P < 0.01) of patients with atopic dermatitis after treatment with cyclosporin. Although no patient required withdrawal from the study, 20 patients receiving cyclosporin reported adverse events, compared with eight taking placebo. There was a close correlation (P < 0.05-P < 0.01) between the UKSIP and EDI scores. In contrast, there was either no correlation, or only a very poor correlation, between the quality of life parameters and clinical measures of extent and activity of eczema. When cyclosporin was stopped, relapse was rapid, but the mean scores for disease activity and extent of disease were less than their baseline values (i.e. an improvement of greater than 25% was maintained in 11 patients at week 4).(ABSTRACT TRUNCATED AT 250 WORDS)

Activities of Daily Living↗