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Biomedical subjects

J A Hunter

Publications and source records attributed to J A Hunter.

At least 19 recordsLinked to original sources

Excision biopsy of malignant melanoma by general practitioners in south east Scotland 1982-91.

OBJECTIVE: To examine the management of patients who had a malignant melanoma excised initially by general practitioners in south east Scotland over the past 10 years and to assess the impact of the April 1990 contract on this. DESIGN: A retrospective case-control study. SETTING: South east Scotland. SUBJECTS: All patients in south east Scotland who had malignant melanomas excised by general practitioners in 1982-91. OUTCOME MEASURES: Demographic details of patients; Breslow thickness, clearance of excision. RESULTS: 42 patients had malignant melanomas excised by general practitioners in 1982-91: 15 in 1982-9 and 27 in 1990-1. These patients were significantly younger than those who had their tumours excised initially in hospital. Although the longest diameter of melanomas excised by general practitioners was significantly less than of those excised in hospital, the Breslow thicknesses were similar. Completeness of initial excision was doubtful or incomplete in nine (23%) general practitioner excisions compared with 4% of hospital excisions, but the time interval between excision biopsy and wide excision was similar. Pathology requests accompanying excision biopsies mentioned melanoma as a possible diagnosis in 15% (6/40) of general practitioner cases compared with 79% of hospital cases. Thirty nine general practitioners responded to a questionnaire and only 12 had considered melanoma in the differential diagnosis. CONCLUSIONS: General practitioners need to think more often of malignant melanoma when they excise pigmented lesions and when they consider this tumour a possibility should perform an excision biopsy with a lateral clearance of at least 2 mm.

Adult

Cutaneous malignant melanoma, Scotland, 1979-89. The Scottish Melanoma Group.

The Scottish Melanoma Group (SMG) was established in 1979 to assess mortality from and incidence, features, pathological data, and management of cutaneous malignant melanoma in Scotland. Incidence during the first five years and five-year survival have already been reported. We now have data about incidence and mortality over eleven years in relation to anatomical site and pathological types. From 1979 to 1989, 1354 male and 2459 female patients with primary cutaneous malignant melanomas were first diagnosed in Scottish residents. The incidence rate per 100,000 population per year has increased from 3.4 in 1979 to 7.1 in 1989 for men, and from 6.6 to 10.4 for women. The overall increase over eleven years is 82% (7.4% per year). The greatest rates of increase are seen in lesions of the superficial spreading histogenetic type, arising on the female leg and the male trunk. Following public education programmes started in 1985, the proportion of all melanomas less than 1.5 mm thick has shown a sustained and significant increase. Mortality data for 1661 patients for whom a minimum of five-year follow-up is available shows five-year survival of 71.6% overall (77.6% for women, 58.7% for men). The survival advantage for women persists when appropriate statistical adjustment is made for thickness, ulceration, and histogenetic type. These data are useful in designing public education programmes aimed at both primary and secondary prevention of melanoma and in auditing changes in trends that might result from such education.

Adolescent

Lymphoproliferative responses to human papillomaviruses in patients with cutaneous warts.

In vitro lymphoproliferative responses of peripheral blood mononuclear cells (PBMC) from patients with cutaneous warts, caused by infection with human papillomavirus type 1 (HPV-1) or type 2 (HPV-2), were assayed during the course of treatment. Purified HPV-1 and HPV-2 were used as antigens, as well as herpes simplex virus (HSV) and concanavalin A (Con A). All patients had normal percentages of subsets within the PBMC population and normal lymphoproliferative responses to Con A, and those with a clinical history of HSV infections had positive lymphoproliferative responses to HSV. Responses to both HPV antigens were poor. Only 10 of 100 assays of PBMC from 26 patients showed a stimulation index greater than 2. Addition of interleukin 2 made little difference in most cases. No correlation of clinical status of warts, i.e. improving, unchanged or resolved, with lymphoproliferation was found. When the PBMC were depleted of plastic-adherent cells and enriched for T cells, some samples which had not shown a lymphoproliferative response to HPV-1 or HPV-2 became positive; this response was abolished when the adherent cells were re-added. Thus it is possible that the adherent cell population from a proportion of patients contains cells which suppress lymphoproliferation, or that an immunoregulatory network is present so that lymphoproliferation does not take place in vitro without prior activation and cloning of T cells.

Adolescent

Prospective trial comparing the use of sulphasalazine and auranofin as second line drugs in patients with rheumatoid arthritis.

Two hundred patients with rheumatoid arthritis were studied in a prospective open trial comparing treatment with sulphasalazine and auranofin in patients with active disease over 12 months. The two drugs improved many parameters of disease activity at 12, 24, and 48 weeks. At 12 weeks, the group treated with sulphasalazine had a lower platelet count (Mann-Whitney U test), erythrocyte sedimentation rate, and articular index, with a greater decrease in erythrocyte sedimentation rate (Students t test) and C reactive protein between 0 and 12 weeks. There were no significant differences between sulphasalazine and auranofin treatment after 24 and 48 weeks. Life table analysis showed no significant differences in the rate of side effects which caused treatment to be stopped. Sulphasalazine works more rapidly, may be a more effective disease modifying antirheumatic drug, and is as well tolerated as auranofin.

Adult

Double blind, placebo controlled study of metronidazole as a disease modifying agent in the treatment of rheumatoid arthritis.

Anecdotal reports suggest that metronidazole may have disease modifying activity in the treatment of rheumatoid arthritis. To assess possible beneficial effects a double blind, comparative trial of metronidazole and placebo was performed. Fifty patients with active rheumatoid arthritis were randomly allocated to receive active drug (n = 24) or placebo (n = 26) and reviewed at weeks 0, 1, 4, 8, 12, 16, and 24. Detailed assessment of drug safety, biochemical and haematological parameters, and efficacy was made at these dates. Dose regimen was 400 mg twice daily from weeks 0 to eight, increasing to 400 mg three times a day from weeks nine to 24 provided that no adverse effects were recorded. Most patients were unable to tolerate metronidazole because of side effects or lack of efficacy, with only five (21%) continuing to take the drug at 24 weeks. For those patients attaining 12 weeks of treatment an overall improvement in articular index and morning stiffness was found. No improvement in laboratory indices of disease activity was seen, however. In this study metronidazole did not have disease modifying properties and was unacceptably toxic.

Adult

Antibodies to neutrophil cytoplasmic antigens: serologic marker for Sweet's syndrome.

Seven patients with a clinical and histologic diagnosis of Sweet's syndrome were tested for the presence of circulating antibodies to neutrophil cytoplasmic antibodies. Six of the seven patients had detectable antibodies to neutrophil cytoplasmic antibodies at a serum dilution of at least 1:20. Antibodies to neutrophil cytoplasmic antibodies were not found in serum from patients with a range of cutaneous diseases, some known to cause clinical or histologic confusion with Sweet's syndrome. The detection of circulating antibodies to the neutrophil cytoplasm may be of possible diagnostic value in Sweet's syndrome.

Adult

Morphological evidence for calcium-dependent association of calgranulin with the epidermal cytoskeleton in inflammatory dermatoses.

The association of calgranulins, intracellular calcium-binding proteins, with the keratinocyte cytoskeleton has been studied. These molecules are expressed in various inflammatory dermatoses and in organ-culture explants. Triton X-100 extraction in the presence of calcium or EDTA suggested that calgranulins are detergent insoluble in the presence of calcium. The molecules were localized in a plaque-like structure at the cell periphery in lesional skin and in organ-culture explants. Following induction of calgranulins in vitro there was a redistribution of the intermediate filament cytoskeleton into a perinuclear halo, although desmosomes remained intact. These various features suggest that these members of the S-100 protein family have a role in cytoskeletal changes seen in various skin diseases.

Blotting, Western

The effects of astemizole, cetirizine and loratadine on the time course of weal and flare reactions to histamine, codeine and antigen.

An open cross-over study was performed to assess the effects of astemizole, cetirizine and loratadine on weal and flare reactions to intradermal histamine, codeine and house dust mite antigen. Percentage inhibition of weal area, flare area and weal volume was greatest for cetirizine, then astemizole and smallest for loratadine. Wealing due to mast-cell degranulation with either codeine or antigen was less inhibited by all three antihistamines than that due to histamine itself. Time-course studies revealed similarities between wealing provoked by codeine and histamine but different characteristics to that induced by antigen.

Adult

Lymphocyte transformation and thiuram sensitization.

The use of a lymphocyte transformation test (LTT) to confirm allergic contact dermatitis from thiurams has been investigated. The responses of peripheral blood mononuclear cells (PBMC) from thiuram-sensitive and non-sensitive individuals following culture with dimethylcarbamoyl-protein (human serum albumin; HSA) and dimethylthiocarbamoyl-HSA conjugates has been compared. Only PBMC from those patients who were patch-test-positive with thiuram-mix and sensitized to tetramethylthiuram monosulphide (TMTM) or TMTM and tetramethylthiuram disulphide (TMTD) exhibited significant proliferative responses to these conjugates. Thiuram-patch-test-negative patients and control donors with no history of allergic contact dermatitis failed to mount a significant response to any concentration of either conjugate. Two of the thiuram-sensitive patients were also nickel-patch-test-positive, and PBMC isolated from these donors, but not from nickel-patch-test-negative patients, proved positive in a nickel LTT. The data reveal that relevant hapten-protein conjugates are capable of provoking specific human lymphocyte proliferative responses in vitro, and that, using this technique, the LTT can, in principle, be used for the investigation and/or diagnosis of skin sensitization to lipophilic contact allergens.

Cell Division

Intergroup violence and intergroup attributions.

Pettigrew's (1979) prediction that relative to in-group behaviour, negative out-group behaviour would be attributed to internal characteristics, was tested in the context of Northern Ireland's continued conflict. Catholic and Protestant respondents were presented with newsreel footage depicting scenes of in- and out-group violence. One showed a Protestant attack on mourners at a Catholic funeral. The other showed a Catholic attack on a car containing two plain clothes soldiers at a Catholic funeral. Using a free response format, subjects' explanations were classified into internal and external attributions. The results showed strong support for Pettigrew's hypothesis. The implications of these findings with regard to the maintenance of intergroup conflict are discussed.

Adult

Deep venous thrombosis. Implications after open heart surgery.

We reviewed the cases of 10,638 cardiac surgical patients to determine the incidence of deep vein thrombosis (DVT) after open heart surgery (OHS). Seventy-seven patients (0.7 percent) had DVT. Group 1 included 36 patients who had DVT without pulmonary embolism (PE). Occurrence was equal in either leg. Anticoagulation with heparin and warfarin sodium (Coumadin) was employed as treatment. Extension of hospital stay was 10.8 days. Group 2 consisted of 41 patients who experienced PE 9.9 days after OHS. Sixteen patients had known DVT and were receiving heparin. In 25 patients, PE was the first event. Risk factors for PE included perioperative myocardial infarction (16 percent), atrial fibrillation (41 percent); blood type A (70 percent) (p less than 0.05), and coronary artery bypass graft (CABG) (98 percent). Twenty-four patients were treated with anti-coagulation alone. Six died of recurrent PE; mortality was 25 percent. Seventeen patients received anticoagulation plus inferior vena cava (IVC) interruption using a Hunter balloon. There were no recurrent PEs and there was one death from myocardial infarction (6 percent). Deep vein thrombosis and PE are rare complications of OHS. Routine prophylaxis with either heparin or warfarin is unnecessary. Patients with DVT, atrial fibrillation (AF), and perioperative myocardial infarction are at high risk of PE. Aggressive diagnosis to identify major venous thrombi along with anticoagulation and early consideration of IVC interruption are recommended for these patients. Patients who have undergone OHS and who have PE are at an unusually high risk for recurrent PE with death and are more safely treated with IVC interruption and anticoagulation than anticoagulation alone.

Atrial Fibrillation

Rheumatoid arthritis: workload and outcome over 10 years.

Rheumatoid arthritis remains a chronic disabling disorder in which medical and surgical intervention may provide amelioration but not cure. In this study a cohort of 123 rheumatoid patients were followed for a period of 10 years from the time of prescription of their initial second-line agent. The workload involved in managing articular, extra-articular and intercurrent disease in these patients has been documented and outcome in relation to continued use of 'disease modifying' therapy evaluated. At 10 years 24 patients (20 per cent) had died and 7 (5 per cent) were not traced; of the 92 (75 per cent) who were assessed, three had become wheelchairbound, two for reasons other than rheumatoid arthritis. Seventy-one per cent of patients required joint surgery, 36 per cent management of peptic ulcer and 45 per cent experienced major episodes of sepsis. Analysis of the results in the 92 patients who were evaluated at 10 years showed significant improvement in Ritchie articular index, pain score, morning stiffness, haemoglobin, platelets, ESR, total globulins, IgG and IgM. Grip strength and Lee functional index showed a trend towards deterioration which did not reach significance. Sixty-seven (73 per cent) of the 92 patients remained on a second- or third-line agent at 10 years (median duration of treatment 107 months); 25 (27 per cent) were not receiving such therapy (median duration of second- and third-line therapy 13 months). The group remaining on treatment showed significant improvement similar to that of the total study group. Those not on treatment improved only for articular index; Lee functional index deteriorated significantly. There was a correlation between area under the curve for ESR over 10 years and radiological progression of disease in hands (r = 0.29, p = 0.026) and in knees and hips (r = 0.3748, p = 0.012) over the 10 year period. Radiographic score correlated well with Lee functional index at the outset and at 10 years and also with the change in the radiographic score over the 10-year period. Unlike the results of previous studies, there was no morbidity from vertebral collapse; this may be related to the low dose of corticosteroids in this cohort (seven patients received systemic corticosteroids). Thus while the aim of treating patients for prolonged periods with second- or third-line therapy was achieved in the majority with no overt evidence of cumulative toxicity, sustained medical and surgical intervention was and will be needed in order to minimize disability in these and other patients with rheumatoid arthritis.

Adult

The relationship of sulfoxidation status to efficacy and toxicity of penicillamine in the treatment of rheumatoid arthritis.

Penicillamine shows some structural similarities to carbocysteine. The ability to oxidize carbocysteine, i.e., the sulfoxidation status, shows a bimodal distribution in the general population. In this study, sulfoxidation status was determined in 50 of 60 rheumatoid arthritis patients receiving penicillamine. We found that poor sulfoxidation status, compared with good sulfoxidation status, was associated with a 3.9 times higher incidence of toxicity.

Arthritis, Rheumatoid

Sweet's syndrome: a clinicopathologic review of twenty-nine cases.

Twenty-nine patients with Sweet's syndrome were studied. Not all of Sweet's original criteria were necessarily present and diagnosis was dependent on the recognition of the typical, acute, tender, erythematous plaques and the characteristic histologic features of a neutrophilic infiltrate with leukocytoclasis. Women are affected much more frequently than men. The origin of Sweet's syndrome is still unclear, but an underlying disease was found in more than 50% of our cases. A streptococcal infection was evident in six cases, inflammatory bowel disease in three cases, malignancy in four cases, and pregnancy in two others. Treatment with oral prednisolone for an average of 6 weeks was the usual treatment, although in four patients the disease cleared spontaneously. Resolution of the eruption is occasionally followed by milia and scarring. Recurrences are common and affect up to one third of patients.

Adult

The prevalence of skin disorders in renal allograft recipients receiving cyclosporin A compared with those receiving azathioprine.

Ninety-four renal allograft recipients receiving cyclosporin A (CsA) immunosuppression for up to 4 years were examined for the presence of viral warts, keratoses, and skin cancers. They were compared with a group of 68 recipients on azathioprine who had been matched for duration of immunosuppression and other factors that might influence the occurrence of these lesions. No difference in prevalence of these tumours was found. Viral, bacterial, and fungal infections and other disorders of the skin related to immunosuppression were also noted. Apart from hypertrichosis, which occurred more frequently in the CsA group, no differences were observed. In view of the importance of duration of immunosuppression, the relative effects on the skin of the two drugs will not become apparent until CsA has been in general use for a much longer period of time. In the early stages, however, there appear to be no differences in the dermatological side-effects between CsA- and azathioprine-treated patients.

Adolescent

The changing face of dermatology out-patient referrals in the south-east of Scotland.

A study of out-patient dermatological services (NHS and private) in the south-east of Scotland was carried out by medical staff in the Department of Dermatology in Edinburgh during the month of November 1988. The aim was to assess changes in referral patterns and workload compared with the findings of an identical investigation undertaken in November 1981. Of particular interest were the possible effects of recent publicity campaigns aimed at increasing public awareness about skin cancer. The medical complement of the dermatology department had changed minimally since 1981 and the population increase in the south-east of Scotland over the same period was 1.5%. During November 1988 1592 new patients and 2037 review patients were seen. This represented an increase of 29.2% and 28.3%, respectively, since 1981. The most striking changes in diagnostic groups were a 173% rise in new cases presenting with benign tumours (excluding viral warts) and a 106% increase in new patients with malignant tumours. Viral warts and eczema were, as in 1981, the second and third most common diagnostic categories amongst new patients. There was a 98% increase in the number of surgical procedures performed on new patients compared with 1981. We conclude that the substantial increase in numbers of both benign and malignant tumours and the consequent doubling in surgical treatments was due to increased public awareness and concern about skin cancer.

Dermatology