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Biomedical subjects

J T Lear

Publications and source records attributed to J T Lear.

At least 73 records · Page 4Linked to original sources
PubMed1997

Azathioprine in dermatology: a survey of current practice in the U.K.

Azathioprine has an important role in treatment of many inflammatory dermatoses. In view of the current emphasis on evidence-based medicine, we performed a questionnaire-based survey to establish current practice in the use of azathioprine by consultant dermatologists and associate specialists in the U.K. The response rate was 68%. In contrast with the manufacturer's recommendation, our data provide evidence that azathioprine is useful in the treatment of a wide variety of dermatological diseases. However, there is still a need for controlled trials in some conditions. The most common conditions treated were pemphigoid, pemphigus and atopic eczema. In addition, we found that only 13% of dermatologists prescribe azathioprine according to body weight. Most dermatologists felt that azathioprine was well tolerated. No one tested for thiopurine methyltransferase (TPMT) activity, which is thought to be a predictor of severe myelosuppression. The combination of prescribing azathioprine according to body weight and measuring TPMT activity would optimize efficacy and minimize potential severe myelotoxicity.

Azathioprine↗
PubMed1996

Polymorphism at the glutathione S-transferase locus GSTM3: interactions with cytochrome P450 and glutathione S-transferase genotypes as risk factors for multiple cutaneous basal cell carcinoma.

The influence of polymorphism in the glutathione S-transferase, GSTM3 gene on susceptibility to cutaneous basal cell carcinoma (BCC) has been investigated. We have reported previously two GSTM3 alleles, GSTM3*A and GSTM3*B, distinguished by a recognition motif for the YY1 transcription factor in GSTM3*B. In this study, immunohistochemistry was used to identify GSTM3 expression in the epidermis of skin samples from 11 controls and 9 patients with BCC. A PCR method was used to identify GSTM3*A and GSTM3*B and thereby the GSTM3 AA, GSTM3 AB, and GSTM3 BB genotypes in 300 controls and 286 Caucasians with 1-35 primary BCCs. Genotypes at GSTM1, GSTT1, and the cytochrome P450 CYP1A1 and CYP2D6 loci were also determined. Frequencies of GSTM3, GSTM1, GSTT1, CYP2D6, and CYP1A1 genotypes in the cases and controls were not different. Dividing the BCC cases into groups of 92 patients with 1 lesion and 194 patients with 2-35 lesions showed that the frequencies of GSTM3 BB (2.6%) and GSTM1 A/B (1.3%) in the group with 2-35 tumors were almost significantly lower than in the group with 1 lesion (7.6%, exact P = 0.0601, chi 2(1) = 3.390; 6.5%, exact P = 0.055, chi 2(1) = 4.946, respectively). Within the cases with 2-35 tumors, a Poisson regression model was used to identify genotypes, characteristics such as skin type, and interactions between genotypes and characteristics associated with increasing numbers of tumors. This showed, after correction for male gender and age, that GSTM3 AA was not associated with risk of increased numbers of tumors, although in combination with skin type 1, GSTM1 null, and CYP1A1 m1m1, the genotype did confer increased risk (P < 0.001, rate ratio, 2.058; P < 0.001, rate ratio, 1.606; P < 0.001, rate ratio, 1.470 respectively). The data suggest that, like other allelic GST, GSTM3 influences cancer risk. As GSTM3 AA was associated with increased tumor numbers, it appears that YY1 acts as an activator of the recognition motif in GSTM3*B.

Aged↗
PubMed1996

Prevalence of diabetes in elderly patients requiring permanent cardiac pacemaker insertion.

Diabetes mellitus increases the rate of atrioventricular block after a myocardial infarction; right bundle branch block is more common than expected in the diabetic outpatient population. We decided to assess whether diabetic subjects were more likely to need permanent cardiac pacemaker insertion. Data from patients in Leicestershire who had undergone permanent cardiac pacemaker insertion during a 4-year period were analysed. The capture recapture technique was used: Hospital Activity Analysis data as capture, ward admission book and case note confirmation as recapture. Diabetes coding accuracy was confirmed from the central register and from an analysis of 100 sets of case notes. The number of these patients with diabetes was then recorded. Data for the reference population was obtained using a survey of a market town in Leicestershire. There were 688 patients, most (79%) aged over 65 years. Our analysis was performed on this group. Of this age group undergoing pacemaker insertion. 11.1% was diabetic. In the same age group, 8.3% of the controls were diabetic: a relative risk of 1.34 (P < 0.01, 95% confidence interval 1.25-1.44). This relative risk is likely to be an underestimate. The aetiology of this excess risk is uncertain: it is most likely due to ischaemic heart disease, but microangiopathy or increased cholinergic sensitivity may play a role.

Adult↗
PubMed1996

Multiple cutaneous basal cell carcinomas: glutathione S-transferase (GSTM1, GSTT1) and cytochrome P450 (CYP2D6, CYP1A1) polymorphisms influence tumour numbers and accrual.

The genetic factors that mediate the pathogenesis of multiple primary cutaneous basal cell carcinomas (BCC) are largely unclear. Thus, some patients suffer many BCC (>30) and/or rapid accrual (number of tumours/year from first presentation) of further lesions. We have studied, in 827 English Caucasians, the influence of polymorphism in carcinogen-metabolizing enzymes on susceptibility to this cancer. Accordingly, we describe, first, a cross-sectional analysis of the influence of GSTM1, GSTT1, CYP2D6 and CYP1A1 genotypes on tumour numbers, and secondly, a longitudinal analysis, in 169 of these cases, of the effect of these genes on tumour accrual. We have confirmed the expected importance of age and number of lesions at presentation, and male gender and skin type as risk factors. Furthermore, the cross-sectional analysis showed CYP1A1 m1m1 (P = 0.004; rate ratio 1.242) and CYP2D6 EM (P < 0.001, rate ratio 1.266) are associated with increased numbers of BCC. The longitudinal study showed, after adjustment for age and tumour number at presentation, that GSTT1 null (P < 0.001, rate ratio 2.677) and CYP2D6 EM (P < 0.001, rate ratio 2.154) were significant determinants of accrual while CYP1A1 Ile/Ile was associated with slower accrual than the Ile/Val and Val/Val genotypes (P = 0.008, rate ratio 0.690). We believe these are the first genetic factors to be associated with tumour accrual. No significant interactions between genotypes were identified, though the combinations GSTM1 null/skin type 1 (P < 0.001, rate ratio 2.702), CYP2D6 EM/male gender (P = 0.049, rate ratio 1.279) and CYP2D6 EM/blue+green eyes (P = 0.046, rate ratio 1.388) influenced tumour numbers. Previous studies indicate the importance of effective repair of UV-damaged DNA in the pathogenesis of multiple BCC; indeed the influence of GSTM1 may result from its ability to utilize 5'-hydroxymethyluracil. However, the finding that CYP2D6 and CYP1A1 influence tumour numbers and accrual indicates detoxification of unknown molecules is important and supports the view that factors other than UV are important in the pathogenesis BCC.

Adult↗
PubMed1996

Transient re-emergence of oil of turpentine allergy in the pottery industry.

Allergy to oil of turpentine has diminished largely due to the use of cheaper substitutes in many occupations. However, 2 particular areas still reliant on real oil of turpentine are those of the perfume industry and ceramic decoration. We report 24 cases of hand dermatitis in pottery workers involved in ceramic decoration, paintresses, liners, gilders, enamellers and a fine china painter, seen in a 6-month period following a change from Portuguese to Indonesian turpentine, of whom 14 were sensitive to Indonesian turpentine, 8 to alpha-pinene, 4 to delta-3-carene and 2 positive to turpentine peroxides. Previous reports suggest that delta-3-carene is the main allergen and reports of sensitivity to alpha-pinene in the absence of sensitivity to turpentine peroxide, in particular to the hydroperoxide of delta-3-carene, are few. Turpentine allergy continues to be a problem in the pottery industry and is more common than allergy to the heavy metals of the colours used in ceramic decoration. alpha-Pinene, an unusual allergen, appears to be the most common in our area. Reversion to Portuguese turpentine seems to have alleviated the problem.

Allergens↗
PubMed1996

Erosive and generalized lichen planus responsive to azathioprine.

Systemic corticosteroids are of value in severe lichen planus which interferes with the patient's life or is ulcerative or where there is nail destruction. Azathioprine has been shown to be effective steroid sparing treatment for generalized lichen planus. We report two patients with severe lichen planus who responded to azathioprine alone and suggest it may be an alternative therapy, especially when there are risk factors against corticosteroid use. Lichen planus accounts for approximately 1% of new presentations to a dermatology unit. It can affect all body areas and markedly interfere with a patient's life. Mucous membrane lesions are common (30-70%) but ulcerative lesions in the mouth are uncommon. Lichen planus seems to be immunologically mediated with evidence favouring a lymphocytotoxic process described in the literature. Treatment is mainly symptomatic and can be difficult. Systemic corticosteroids are of value in treating severe cases where the disease is interfering with a patient's life or when ulcerative mucous membrane lesions have occurred or if there is severe nail destruction. Relapse can occur on cessation of steroids. Azathioprine has been shown to be effective steroid sparing therapy for generalized lichen planus. However, the use of azathioprine alone has not been described. We report two cases of generalized, erosive lichen planus that responded well to azathioprine alone.

Aged↗