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Biomedical subjects

J A Hunter

Publications and source records attributed to J A Hunter.

At least 55 records · Page 3Linked to original sources
PubMed1997

Cutaneous malignant melanoma in Scotland: incidence, survival, and mortality, 1979-94. The Scottish Melanoma Group.

OBJECTIVE: To determine the changing incidence of and mortality from cutaneous malignant melanoma in Scotland from 1979 to 1994. DESIGN: Detailed registration of clinical and pathological features, surgical and other treatment, and follow up of all cases of cutaneous malignant melanoma diagnosed from 1979 to 1994 and registered with specialist database for Scotland. SETTING: Scotland. SUBJECTS: 6288 patients with invasive primary cutaneous malignant melanoma diagnosed between 1 January 1979 and 31 December 1994. RESULTS: The annual age standardised incidence of cutaneous malignant melanoma rose significantly from 3.5 to 7.8 per 100,000 per year in men and from 6.8 to 12.3 per 100,000 per year in women (P < 0.001 for both). World standardised rates increased from 2.7 to 6.0 per 100,000 per year in men and 4.6 to 8.50 per 100,000 in women. The incidence of melanoma continued to increase significantly in men of all ages during the study, but the rate stabilised in women after 1986. Mortality from cutaneous malignant melanoma was 1.3 per million per annum in men in 1979, rising to 2.3 per million per annum in 1994 (P < 0.01); it was 2.4 per million per annum in women in 1979, falling to 1.9 per million per annum in 1994 (P = 0.09). The underlying mortality trends showed a continuing rise for men but a downward trend for women that was not significant (P = 0.09). In men, melanoma free survival was 69% at 5 years and 61% at 10 years; in women the corresponding rates were 82% and 75%. Younger patients had higher survival rates, which were not entirely explained by thinner tumours. Over the 15 year period, survival rates improved by 12% overall, only partly owing to thinner tumours. CONCLUSIONS: In Scotland the incidence of melanoma in women has stabilised, while mortality associated with melanoma in women shows a downward trend.

Adolescent↗
PubMed1997

Renal allograft recipients with high susceptibility to cutaneous malignancy have an increased prevalence of human papillomavirus DNA in skin tumours and a greater risk of anogenital malignancy.

Renal allograft recipients (RARs) have a well-documented increased incidence of viral warts and cutaneous neoplasia, particularly those with long graft life and high sun exposure. A clinicopathological survey of 69 RARs in south-east Scotland, with follow-up periods of up to 28 years after transplantation, revealed marked variation in patient susceptibility to cutaneous malignancy with concomitant variation in HPV prevalence. Skin cancers were found in 34 patients. Eight patients showed high susceptibility [defined as more than four intraepidermal carcinomas (IECs) or invasive squamous cell carcinomas (SCCs)] 42 had intermediate susceptibility (1-3 IECs or SCCs, or >3 keratoses) and 18 had low susceptibility (< or = 3 keratoses and no cancers). SCCs, IECs and keratoses from the high-susceptibility group were found to have greater prevalences of human papillomavirus (HPV) DNA (56%, 45% and 50% respectively), than SCCs (0%) and IECs (33%) from intermediate-susceptibility RARs and keratoses (36%) from the combined intermediate- and low-susceptibility groups and compared with a group of immunocompetent controls (27%, 20% and 15% respectively). No differences in p53 protein accumulation, determined immunohistochemically, were observed in tumours from the three groups. Categorization of RARs by susceptibility to cutaneous malignancy provides clinically useful information, as significantly more high-susceptibility patients (38%) developed aggressive, potentially lethal anogenital or cutaneous squamous cell cancers than did patients in the intermediate group (5%, P=0.005) or the low-susceptibility group (0%).

Adult↗
PubMed1997

Atopic and non-atopic individuals react to nickel challenge in a similar way. A study of the cytokine profile in nickel-induced contact dermatitis.

The influence of atopy on delayed-type hypersensitivity remains unclear. The expression of cytokine mRNA was assessed by reverse transcription-polymerase chain reaction (RT-PCR) in biopsy skin taken 24 h after the application of a 5% NiSO4 patch to five patients with atopic dermatitis and seven non-atopic subjects with previously proven contact allergy to nickel. Control specimens were obtained from untested and vehicle-tested skin from the same individuals. There was a significant increase in the mRNA expression for interferon-gamma (IFN-gamma), interleukin (IL)-2 and IL-4 together after nickel challenge in both patients (analysis of variance P = 0.007) and non-atopic-individuals (P = 0.005). In contrast, IL-10 mRNA increased in the non-atopic group only. These results show that atopic patients and normal subjects have a similar immunological reaction to nickel challenge. Moreover, it is suggested that both Th1- and Th2-type cytokines are involved in the immunopathogenesis of contact dermatitis.

Adult↗
PubMed1997

Leukaemia inhibitory factor: induction in the early phase of allergic contact dermatitis.

It has been suggested that leukaemia inhibitory factor (LIF), may be involved in the pathogenesis of cutaneous inflammation. In 5 patients with previously proven contact allergy to nickel, LIF mRNA and protein expression were assessed by reverse transcription-polymerase chain reaction and immunohistochemistry in 5% nickel sulfate patch test biopsies 24 h after application of the patch. Control specimens were obtained from non-tested and vehicle-tested skin from the same individuals. LIF mRNA expression was significantly increased in nickel-tested skin compared with both vehicle-tested (p = 0.045) and non-tested skin (p = 0.041). All biopsies showed similar patterns of LIF immunoreactivity, with no significant differences between nickel-tested, vehicle-tested and non-tested skin. Immunostaining was cytoplasmic and was present in the epidermis and hair follicles. No dermal staining was observed. This study suggests that LIF may play a role in the early phase of allergic contact dermatitis.

Adult↗
PubMed1997

Intergroup bias and self-evaluation: domain-specific self-esteem, threats to identity and dimensional importance.

Recent theoretical statements argue that two predictions about self-esteem and intergroup bias may be derived from social identity theory. The first suggests that in-group bias enhances self-esteem. The second suggests that threats to self-esteem enhance in-group bias. Previous research has provided little firm evidence for either prediction. Much of this work has, however, tended to ignore realistic groups, domain-specific self-esteem, the assessment of self-esteem prior to and following the display of in-group bias and the importance attached to evaluative dimensions. The current investigation sought to redress these issues. In separate experiments, men and women presented with positive and negative feedback, evaluated in-group and out-group success and failure on dimensions important and unimportant to the in-group. Women displayed out-group bias on dimensions unimportant to their in-group (i.e. physical ability) with respect to evaluations of failure. Women subsequently manifested a decrease in physical self-esteem. Men displayed in-group bias on dimensions unimportant to their in-group (i.e. verbal ability) and, following positive feedback, on dimensions important to the in-group (i.e. physical ability). Men subsequently manifested an increase in verbal and physical self-esteem. Global self-esteem was unaffected in each study. These findings suggest that the relative display of bias can affect domain-specific self-esteem. No support was found for the postulate that low or threatened self-esteem can enhance bias on evaluative dimensions important to the in-group.

Ego↗
PubMed1997

Effect of disease modifying agents on the lipid profiles of patients with rheumatoid arthritis.

OBJECTIVE: To determine the effect of intramuscular gold and oral hydroxychloroquine (HCQ) on the lipid profile of patients with rheumatoid arthritis (RA). METHOD: A prospective randomised clinical trial of 12 months' duration was performed in 100 RA patients. Data on clinical and laboratory parameters of disease activity, and fasting serum lipid samples was collected at baseline and at three monthly intervals over one year. RESULTS: The expected second line response was seen with no significant difference in efficacy between the groups at 12 months. The HCQ group had a significant overall improvement in their lipid profile while there was a trend for lipid profiles in the gold group to worsen. CONCLUSIONS: HCQ is an effective second line agent that has beneficial effects on serum lipids. This should be taken into account when choosing a disease modifying anti-rheumatic drug in patients who suffer from RA and who have significant cardiovascular risk factors.

Adult↗
PubMed1997

Measurement of quality of life in atopic dermatitis: correlation and validation of two different methods.

Atopic dermatitis is a chronic relapsing condition that can have considerable effects on the lives of sufferers. It is apparent that good, valid measures of life quality are necessary for quantifying the patients' perspective of the severity of their disease and the Dermatology Life Quality Index is often employed in clinical research. In a community study of atopic dermatitis we have assessed disability using the Dermatology Life Quality Index and the Patient Generated Index and compared the results from both indices. The results were significantly correlated and reflected the range of disability in patients in the community. Some items of the Dermatology Life Quality Index were not relevant for atopic dermatitis patients in the community and others, including swimming and sleep loss, were often cited in the Patient Generated Index but are not included in the Dermatology Life Quality Index. The Patient Generated Index is a novel, flexible approach to quality of life measurement that may be suitable for reflecting the wide variety of disability that is experienced by dermatological patients.

Activities of Daily Living↗
PubMed1996

Aceclofenac in rheumatoid arthritis: a useful and novel anti-inflammatory.

The efficacy and safety of 100 mg aceclofenac twice daily was investigated in 73 patients with active rheumatoid arthritis in a multi-centre, double blind, randomised, parallel group, placebo controlled study over a period of 4 weeks. Treatment with aceclofenac was effective in improving the Ritchie articular index (predetermined primary end point), duration of morning stiffness, joint swelling, ARA functional class, patient's and physician's global assessments, and pain. All these improved to a significantly (P < 0.05) greater extent than in placebo-treated patients. Grip strength showed a significant improvement from baseline in the aceclofenac-treated group and this was greater than the improvement measured in placebo treated patients. No significant difference was detected between the treatment groups for the number of subjects reporting an adverse event. Aceclofenac administered orally at 100 mg twice daily for four weeks thus produced significant improvements in patients with active rheumatoid arthritis. This treatment was well tolerated with an adverse event profile similar to that of placebo.

Administration, Oral↗
PubMed1996

Cytokine mRNA expression in cutaneous warts: induction of interleukin-1 alpha.

The persistence of human papillomavirus at cutaneous sites may be due to impaired trafficking of immune effector cells to the epidermis. We investigated whether HPV infection modulates cytokine mRNA expression in skin, thereby influencing local immunity. The mRNA expression of tumour necrosis factor-alpha, interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-1 receptor antagonist (IL-1ra), IL-4, IL-8, IL-10, IL-12, granulocyte macrophage colony-stimulating factor, transforming growth factor-beta, interferon-gamma and amphiregulin were assayed in cutaneous warts and normal skin by semiquantitative reverse transcriptase-polymerase chain reaction. The expression of the cytokines was heterogeneous in the specimens but, of the 12 mRNA species investigated, only IL-10 mRNA was significantly downregulated in warts compared with normal skin (P = 0.002). IL-1 alpha mRNA expression was significantly upregulated in common warts (P = 0.019) and plantar warts (P = 0.003) compared with normal skin. The expression of IL-1 alpha and IL-1ra mRNAs were significantly correlated in plantar warts (P < 0.05). Warts expressing IL-1 alpha also expressed amphiregulin, and there was a significant correlation between the expression of these two genes (P < 0.05). It is possible that IL-1 alpha expression in cutaneous warts may modulate the growth of papillomavirus-infected keratinocytes, mediated by amphiregulin, thus ensuring viral persistence.

Adolescent↗
PubMed1996

The chemoattractant activity of rheumatoid synovial fluid for human lymphocytes is due to multiple cytokines.

The majority of synovial fluids from 29 rheumatoid arthritis patients were strongly attractive for normal blood lymphocytes judged by assays of polarization and collagen gel invasion. While rheumatoid synovial fluids contained IL-15, IL-8, monocyte chemotactic protein-1 (MCP-1) and macrophage inflammatory protein-1 alpha (MIP-1 alpha) at levels sufficient to attract lymphocytes, inhibition of the activity of any single cytokine using specific antibody did not abolish the activity of the fluid. However combinations of anti-cytokine antibodies used together (anti-IL-15+anti-MCP-1; anti-IL-8+anti-MCP-1 or +anti-MIP-1 alpha) inhibited most of the activity, suggesting that attraction of lymphocytes by the fluids is due to a combination of attractants. Blood lymphocytes required activation by overnight culture to respond optimally, while rheumatoid synovial tissue lymphocytes responded to synovial fluids without a requirement for a period of culture. Lymphocytes derived from rheumatoid synovial fluids were poorly responsive to locomotor stimulants. Most of the responding cells from blood mononuclear cell fractions were T lymphocytes of the CD45RO isotype. Incubation in the presence of cyclosporin A or corticosteroids inhibited the response of lymphocytes to the fluids, but the presence of non-steroidal anti-inflammatory drugs (NSAIDs) and other agents used in therapy of the patients from whom the fluids were taken had no inhibitory effect.

Adult↗
PubMed1996

Is rheumatoid arthritis becoming a milder disease? Or are we starting second-line therapy in patients with milder disease?

The aim of the study was to see whether rheumatoid arthritis (RA) is becoming a milder disease. Information on the initial disease activity and patient function (modified Health Assessment Questionnaire-HAQ) was collected in all RA patients enrolled into studies of sulphasalazine since 1980 in two Glasgow teaching hospitals. Patients (352) were enrolled in trials in the decade 1980-1989, and were compared to 374 patients enrolled in 1990-1994. Patients recruited in the 1980s were significantly younger, but had a similar disease duration to the 1990s patients. The 1980s patients had more active disease as measured by erythrocyte sedimentation rate (61 vs 44, P < 0.0001) and C-reactive protein (40 vs 26, P < 0.0001), and significantly worse function (HAQ 2.3 vs 1.9, P < 0.001). The response to sulphasalazine was very similar in the two cohorts, in terms of the percentage of patients remaining on therapy for 6 months, and the percentage improvement in measures of disease activity. Patients with milder disease were enrolled into the more recent trials of sulphasalazine. This may be because RA is becoming a milder disease, but other possible explanations are discussed.

Adult↗
PubMed1996

Cardiac outcome after peripheral vascular surgery. Comparison of general and regional anesthesia.

BACKGROUND: Despite evidence that regional anesthesia may be associated with fewer perioperative complications than general anesthesia, most studies that have compared cardiac outcome after general or regional anesthesia alone have not shown major differences. This study examines the impact of anesthetic choice on cardiac outcome in patients undergoing peripheral vascular surgery who have a high likelihood of associated coronary artery disease. METHODS: Four hundred twenty-three patients, between 1988 and 1991, were randomly assigned to receive general (n = 138), epidural (n = 149), or spinal anesthesia (n = 136) for femoral to distal artery bypass surgery. All patients were monitored with radial artery and pulmonary artery catheters. Postoperatively, patients were in a monitored setting for 48-72 h and had daily electrocardiograms for 4-5 days and creatine phosphokinase/isoenzymes every 8 h x 3, then daily for 4 days. Cardiac outcomes recorded were myocardial infarction, angina, and congestive heart failure. RESULTS: Baseline clinical characteristics were not different between anesthetic groups. Overall, the patient population included 86% who were diabetic, 69% with hypertension, 36% with a history of a prior myocardial infarction, and 41% with a history of smoking. Cardiovascular morbidity and overall mortality were not significantly different between groups when analyzed by either intention to treat or type of anesthesia received. In the intention to treat analysis, incidences of cardiac event or death for general, spinal, and epidural groups were 16.7%, 21.3%, and 15.4%, respectively. The absolute risk difference observed between general and all regional anesthesia groups for cardiac event or death was -1.6% (95% confidence interval -9.2%, 6.1%) This reflected a nonsignificant trend for lower risk of postoperative events with general anesthesia. CONCLUSIONS: The choice of anesthesia, when delivered as described, does not significantly influence cardiac morbidity and overall mortality in patients undergoing peripheral vascular surgery.

Aged↗
PubMed1996

Epidermal keratinocyte production of interferon-gamma immunoreactive protein and mRNA is an early event in allergic contact dermatitis.

Previous work has indicated the importance of cytokine cascades in the induction of contact dermatitis, but there is little information on the cellular localization of cytokines in human skin, particularly during the early phases of the inflammatory response to contact allergens. Using in situ hybridization for mRNA and immunocytochemistry on biopsies from a series of 16 patients with known allergic contact dermatitis, we examined the kinetics of early cytokine production after challenge with relevant or irrelevant antigen. We show that epidermal keratinocytes from patients challenged in vivo with allergen, but not irrelevant antigen, rapidly synthesize (within 4 h) mRNA for interferon-gamma and produce immunoreactive interferon-gamma. Interleukin-1alpha and interleukin-8 mRNA were also detected but showed no correlation with relevant antigen challenge. This study demonstrates that keratinocytes can produce interferon-gamma and that this production is linked to challenge with relevant antigen in allergic contact dermatitis. These findings indicate that keratinocytes may amplify allergen-specific T-lymphocyte-triggered interferon-gamma dependent responses and might partially explain the speed of reaction in this common disease and other delayed hypersensitivity reactions involving the skin.

Adult↗
PubMed1996

Low dose desensitisation does not reduce the toxicity of sulphasalazine in rheumatoid arthritis.

OBJECTIVE: To examine the proposal that pretreatment low dose desensitisation may reduce the incidence of toxicity of sulphasalazine in the treatment of rheumatoid arthritis (RA). METHODS: A double blind, placebo controlled trial was performed with 422 patients satisfying the American College of Rheumatology criteria for RA who required sulphasalazine treatment because of increased disease activity. Patients received either sulphasalazine desensitisation, or placebo, for three weeks before commencement of sulphasalazine treatment. The frequency and nature of adverse effects and changes in clinical and laboratory parameters of disease activity were measured after three and six months. RESULTS: Improvement in the efficacy of sulphalasazine (measured by clinical and laboratory parameters) was significant and similar in magnitude in both groups. There was no significant difference between actively and placebo desensitised patients as regards the incidence or profile of adverse effects (toxicity). CONCLUSION: Pretreatment low dose desensitisation is unhelpful in reducing the toxicity associated with sulphasalazine treatment of RA.

Anorexia↗