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Biomedical subjects

W Perkins

Publications and source records attributed to W Perkins.

At least 19 recordsLinked to original sources
PubMed1996

Susceptibility to multiple cutaneous basal cell carcinomas: significant interactions between glutathione S-transferase GSTM1 genotypes, skin type and male gender.

The factors that determine development of single and multiple primary cutaneous basal cell carcinomas (BCCs) are unclear. We describe a case-control study firstly, to examine the influence of allelism at the glutathione S-transferase GSTM1 and GSTT1 and cytochrome P450 CYP2D6 loci on susceptibility to these tumours and, secondly, to identify interactions between genotypes and relevant individual characteristics, such as skin type and gender. Frequency distributions for GSTM1 genotypes in cases and controls were not different, although the frequency of GSTM1 A/B was significantly lower (P = 0.048) in the multiple BCCs than in controls. We found no significant differences in the frequencies of GSTT1 and CYP2D6 genotypes in cases and controls. Interactions between genotypes were studied by comparing multinomial frequency distributions in mutually exclusive groups. These identified no differences between cases and controls for combinations of the putatively high risk GSTM1 null, GSTT1 null, CYP2D6 EM genotypes. Interactions between GSTM1 A/B and the CYP2D6 PM and GSTT1-positive genotypes were also not different. Frequency distributions of GSTM1 A/B with CYP2D6 EM in controls and multiple BCCs were significantly different (P = 0.033). The proportion of males in the multiple BCC group (61.3%) was greater than in controls (47.0%) and single BCC (52.2%), and the frequency of the combination GSTM1 null/male gender was significantly greater in patients with multiple tumours (P = 0.002). Frequency distributions of GSTM1 null/skin type 1 were also significantly different (P = 0.029) and the proportion of subjects who were GSTM1 null with skin type 1 was greater (P = 0.009) in the multiple BCC group. We examined the data for interactions between GSTM1 null/skin type 1/male gender by comparing frequency distributions of these factors in the single and multiple BCC groups. The distributions were almost significantly different (exact P = 0.051). No significant interactions between GSTT1 null or CYP2D6 EM and skin type 1 were identified. Comparisons of frequency distributions of smoking with the GSTM1 null, GSTT1 null and CYP2D6 EM genotypes identified no differences between patients with single and multiple tumours.

Aged↗
PubMed1995

Mediation of inflammation by cyclooxygenase-2.

Non-steroidal antiinflammatory drugs (NSAIDs) are commonly used for the treatment of inflammation, pain, and fever. Mechanistically, these compounds are believed to act via inhibition of the enzyme cyclooxygenase (COX), which catalyzes the conversion of arachidonic acid to the prostaglandins (PGs). Although commercially available NSAIDS are efficacious antiinflammatory agents, significant side effects limit their use. Recently two forms of COX were identified- a constitutively expressed COX-1 and a cytokine-inducible COX-2. Commercially available NSAIDs like indomethacin inhibit both COX-1 and COX-2 suggesting the hypothesis that toxicities associated with NSAID therapy are due to inhibition of the non-regulated or constitutive form of COX (COX-1) in normal tissues, whereas therapeutic benefit derives from inhibition of the inducible enzyme, COX-2, at the site of inflammation. Therefore, a selective inhibitor of COX-2 may be anti-inflammatory without GI toxicity-providing a significant improvement over currently available NSAIDs.

Animals↗
PubMed1995

Follicular atrophoderma in association with congenital pseudarthrosis of the tibia.

Follicular atrophoderma has always been associated with other congenital malformations including, Conradi-Hünermann syndrome, Bazex's syndrome and keratosis palmaris et plantaris dissipata. Congenital pseudarthrosis of the tibia has usually been associated with neurofibromatosis. We report a case of follicular atrophoderma in association with congenital pseudarthrosis of the tibia: a previously unreported association with, in our case, a good outcome for the pseudarthrosis.

Adolescent↗
PubMed1995

Cutaneous necrosis in pregnancy secondary to activated protein C resistance in hereditary angioedema.

A 26-year-old woman with hereditary angineurotic oedema (HAE) presented at 22 weeks gestation with severe cutaneous necrosis similar to that seen in coumarin skin necrosis. Protein S deficiency secondary to HAE and pregnancy was postulated. Treatment with heparin, C1-inhibitor concentrates, systemic steroids and surgical debridement resulted in a successful outcome for both mother and child. Subsequent investigations revealed normal levels of protein C, antithrombin III, total protein S, free protein S but reduced function protein S activity with evidence of activated protein C resistance. Cutaneous necrosis has not been reported in associated with activated protein C resistance previously and the possible mechanisms are discussed.

Adult↗
PubMed1994

Pharmacological and biochemical demonstration of the role of cyclooxygenase 2 in inflammation and pain.

Nonsteroidal antiinflammatory drugs (NSAIDs) are widely used for the treatment of inflammatory diseases, but significant side effects such as gastrointestinal erosion and renal damage limit their use. NSAIDs inhibit the enzyme cyclooxygenase (COX), which catalyzes the conversion of arachidonic acid to prostaglandins (PGs) and thromboxane. Two forms of COX have been identified--COX-1, which is constitutively expressed in most tissues and organs, and the inducible enzyme, COX-2, which has been localized primarily to inflammatory cells and tissues. In an animal model of acute inflammation (injection of carrageenan into the footpad), edema was produced that was associated with marked accumulation of COX-2 mRNA and thromboxane. A selective inhibitor of COX-2 (SC-58125) inhibited edema at the inflammatory site and was analgesic but had no effect on PG production in the stomach and did not cause gastric toxicity. These data suggest that selective inhibition of COX-2 may produce superior antiinflammatory drugs with substantial safety advantages over existing NSAIDs.

Abscess↗
PubMed1994

Protein S deficiency in lupus erythematosus secondary to hereditary angio-oedema.

We report a child with lupus erythematosus secondary to type 2 hereditary angio-oedema (HAE). Reduced levels of free protein S were found. Total protein S, and C4 binding protein (C4bp) were normal, and there was no evidence of anticardiolipin antibodies or lupus anticoagulant. We postulate that reduced levels of C4, secondary to C1 inhibitor deficiency, resulted in increased binding of protein S to C4bp, leading to reduced levels of free protein S and thus functional deficiency of protein S.

Angioedema↗
PubMed1993

A multicentre 12-week open study of a lipid-soluble folate antagonist, piritrexim in severe psoriasis.

An open, 12-week, multicentre study was conducted to assess the efficacy of piritrexim isethionate in the treatment of severe psoriasis. Piritrexim isethionate is a lipid-soluble dihydrofolate reductase inhibitor which cannot form polyglutamates, and may be as effective as methotrexate in the treatment of psoriasis. If, as is suspected, but as yet unproven, methotrexate polyglutamates are responsible for the hepatotoxicity of methotrexate, piritrexim should be less hepatotoxic, and may offer an alternative to methotrexate therapy. Fifty-five patients were enrolled, of whom 41 completed the study. Patients were allocated to receive either 150, 225, 300, or 450 mg of piritrexim weekly, in divided doses over 72 h (low-dose groups, 150 and 225 mg), or over 36 h (300 and 450 mg groups). Twenty-four of the 41 patients who completed the study had a greater than 50% improvement in the severity of their psoriasis, as demonstrated by a reduction in the Psoriasis Severity Score, a measure analogous to the PASI scoring system. Adverse events were common, but mild, and were controlled by dose reduction. Piritrexim appears to be an effective therapy for severe psoriasis at doses of 300 and 450 mg weekly, in three divided doses over 36 h.

Drug Administration Schedule↗
PubMed1992

Staphylococcus aureus and intra-nasal mupirocin in patients receiving isotretinoin for acne.

Thirty patients commencing isotretinoin for acne were entered into a double-blind, randomized, placebo-controlled trial to investigate the effect of pulsed intra-nasal mupirocin ointment on Staphylococcus aureus colonization and isotretinoin-related side-effects. In both mupirocin and placebo groups there was an increase in isolation of S. aureus throughout the period of treatment with isotretinoin from the anterior nares, facial skin and lips. However, these increases were significantly less in the mupirocin-treated group. A high proportion of all patients suffered inflammatory side-effects of isotretinoin such as cheilitis and nasal vestibulitis, with their maximum severities being recorded 2 months after starting isotretinoin. In spite of the smaller increase in S. aureus colonization in the mupirocin-treated group no difference was demonstrated in either the incidence of specific S. aureus infections (e.g. furunculosis) or the prevalence of isotretinoin-related inflammatory side-effects. Furthermore, no relationship between the presence of S. aureus and the severity of inflammatory side-effects was shown. Streptococcus species were isolated on four separate occasions from four different patients during the study but their pathogenicity was unclear. These findings suggest that although pulsed intra-nasal mupirocin produces a significant reduction in isotretinoin-related staphylococcal colonization, its routine use cannot be justified on the basis of clinical benefit.

Acne Vulgaris↗
PubMed1992

Keratin expression in normal skin and epidermal neoplasms demonstrated by a panel of monoclonal antibodies.

The tissue labelling of a panel of monoclonal antikeratin antibodies (LL001, LL002, LL003, LP2K, BA17, LP34, CAM5.2, and LH1) recognising keratins 1, 5, 8, 10, 14, 18, and 19 were investigated in frozen and formalin-fixed normal skin. Antibodies LL001, LL003, BA17, LP34, CAM5.2, and LH1 were found to be reactive in formalin-fixed material and were used to study 23 basal cell carcinomas, 8 squamous cell carcinomas, 5 keratoacanthomas, 5 Bowen's disease, and 6 clear cell acanthomas. All these tumours demonstrated a loss of keratin 10 expression as demonstrated by loss of labelling with LH1. Keratin 14 expression, as demonstrated by LL001, was reduced but present in all the tumours except squamous cell carcinomas and keratoacanthomas where increased labelling was observed in the more differentiated areas of these tumours. Simple epithelial keratin expression was demonstrated by positive labelling with CAM5.2 and keratin 19 by BA17 in a third of basal cell carcinomas and squamous cell carcinomas. Three of the five keratoacanthomas labelled with BA17, indicating the presence of keratin 19 in these lesions. These results support the concept that keratin expression is a phenotypic marker of the state of differentiation or malignant transformation and that patterns of keratin expression are not specific to any particular premalignant or malignant disorder.

Antibodies, Monoclonal↗
PubMed1991

Use of protein A immunoadsorption as a treatment for thrombocytopenia in HIV-infected homosexual men: a retrospective evaluation of 37 cases.

Thirty-seven HIV-infected homosexual men with thrombocytopenia (less than 100 x 10(9)/l) received protein A immunoadsorption treatments to remove platelet-sensitizing immunoglobulin (Ig) G and circulating immune complexes (CIC) from plasma. Patients received an average of six treatments each, consisting of 250 ml plasma over a 3-week period. Clinical improvement in hemorrhagic symptoms associated with substantial increase in platelet counts was achieved in 18 patients. These responses were maintained over a median follow-up period of more than 7 months in 14 evaluable patients who were not lost to follow-up (three patients relapsed in 2 weeks and one received another therapy). Generally, moderate transient treatment-related side-effects included fever, musculoskeletal pain, chills and nausea. A transient serum sickness-like reaction was observed in seven patients, leading to termination of treatment in two. Clinical responses were associated with significant decreases in levels of platelet-sensitizing Ig, including CIC. Stimulation of broadly cross-reactive anti-antigen-binding fragment [F(ab)2], antibodies contributed to these responses. Protein A immunoadsorption is an effective alternative treatment for HIV-associated thrombocytopenia.

Adult↗
PubMed1991

The effect of treatment with 13-cis-retinoic acid on the metabolic burst of peripheral blood neutrophils from patients with acne.

The N-formylmethionyl-leucyl-phenylalanine (f-MLP)-induced metabolic burst activity of peripheral blood neutrophils isolated from acne patients undergoing treatment with 13-cis-retinoic acid at a dose of 1.0 mg/kg/day was investigated using a luminol-enhanced chemiluminescence assay. The mean and median chemiluminescence response were significantly greater (P less than 0.05) in patients receiving 13-cis-retinoic acid than in untreated acne patients or age-matched controls. Pre-incubation of neutrophils with 13-cis-retinoic acid (10 nmol/l) did not affect the chemiluminescence response to formyl peptide. A sequential study over 20 weeks in seven patients demonstrated that chemiluminescence peaked after 2-8 weeks of treatment. In three patients this was accompanied by a worsening of their acne. These studies suggest that, in the initial phase, treatment with 13-cis-retinoic acid may exacerbate, through pro-inflammatory priming of neutrophils, certain neutrophil-mediated inflammatory processes in acne.

Acne Vulgaris↗
PubMed1985

An analysis of thyrotrophin receptor binding and thyroid stimulating activities in a series of Graves' sera.

Improved receptor and bioassays have been used to compare TSH receptor binding and thyroid stimulating activities in unextracted sera from 110 patients with Graves' disease. The two parameters showed a significant correlation (r = 0.65; P less than 0.001) although there were some clear discrepancies. Dose-response studies in 17 sera showed that both receptor binding and thyroid stimulating responses always increased with increasing doses of serum. In patients who were in relapse or remission following antithyroid drug treatment, the results of both bio- and receptor assays correlated well with disease activity with only one clear discrepancy which could have been attributable to the coexistence of autoimmune stimulation and destruction of the thyroid.

Carbimazole↗
PubMed1976

Stuttering: discoordination of phonation with articulation and respiration.

Complexity of phonatory and respiratory adjustments was systematically simplified in 30 adult stutterers under three speaking conditions: voiced, whispered, and articulated without phonation. Stuttering was reduced considerably when whispering and was practically eliminated when articulating silently. The possibility that stuttering consistently results from complexity of phonatory coordinations with articulation and respiration was strongly supported. Increased speaking rates under conditions that decreased stuttering seemed to be evidence that efficient rhythmical flow of speech is facilitated by simplification of phonatory and respiratory adjustments.

Adolescent↗