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Biomedical subjects

R M MacKie

Publications and source records attributed to R M MacKie.

At least 19 recordsLinked to original sources
PubMed1992

Effect of maintenance chemotherapy in childhood on numbers of melanocytic naevi.

OBJECTIVE: (a) To determine whether children given chemotherapy for haematological malignancy have significantly more melanocytic naevi than age matched children in the local population; (b) to establish whether any observed variation in naevus counts from normal is seen at the start of maintenance chemotherapy. DESIGN: Follow up of 29 consecutive children starting maintenance chemotherapy, with parental interview and count of all melanocytic naevi > or = 2 mm on the child's skin. Assessment repeated three years later after completion of maintenance chemotherapy. Other dermatological problems identified at either visit were also recorded. SETTING: Royal Hospital for Sick Children, Glasgow. RESULTS: At the start of maintenance chemotherapy all children had total body counts of melanocytic naevi within the normal range established for age matched children in the local population. Three years later total body naevus counts were significantly increased, the median increase being 66 naevi per child (95% confidence interval 57 to 94). The only other problem noted in these children was relatively poor regrowth of scalp hair. CONCLUSION: Children on maintenance chemotherapy for haematological malignancies develop an excessive number of melanocytic naevi. Excessive numbers of melanocytic naevi are the most important risk factor for melanoma in the general population. These children should have periodic skin examinations at their follow up visits, and both child and parent should be educated about clinical features of early melanoma.

Adolescent↗
PubMed1992

Audit of public education campaign to encourage earlier detection of malignant melanoma.

OBJECTIVES: To evaluate a public campaign to encourage earlier referral and treatment of primary cutaneous malignant melanoma and thus reduce mortality related to melanoma. DESIGN: Production and distribution of educational material aimed at adults. Update information sent to general practitioners before campaign. Analysis of data on melanoma before and after campaign in June 1985. SETTING: West of Scotland, population 2.7 million. MAIN OUTCOME MEASURES: Total numbers of referrals per month to melanoma clinic, numbers of melanomas diagnosed, change in distribution of thickness, and mortality before and after introducing the campaign. RESULTS: Referrals to the pigmented lesion clinic increased by 278%, from five a week in June-July 1984 to 19 a week in June-July 1985. Twice as many women as men were referred to the clinic (49% of referrals were of women aged under 65). The numbers of newly diagnosed primary cutaneous melanoma were 63 (12/month) in January-May 1985 and 146 (21/month) in June-December 1985, an increase of 131%. The percentage of tumours detected that were less than 1.5 mm thick rose significantly by 16% (95% confidence interval 11% to 19%), from 38% (328) in 1979-84 to 54% (592) in 1985-9. Mortality began to fall in women from 1988. CONCLUSIONS: The public education campaign succeeded in reducing the absolute number of thick tumours and melanoma related mortality in women.

Adult↗
PubMed1992

Melanoma in people aged 65 and over in Scotland, 1979-89.

OBJECTIVE: Detailed analysis of primary cutaneous melanoma first diagnosed in Scotland in patients aged 65 and over. DESIGN: Comparison of changing incidence, sex distribution, site, histogenetic type, tumour thickness, and prognosis of all primary cutaneous melanomas in patients aged 65 and over diagnosed in Scotland in the 11 years 1979-89 with similar data for patients aged under 65. SETTING: Data were obtained from the Scottish Melanoma Group's database, established in 1979, which aims to record detailed clinical, pathological, and surgical follow up details of all primary cutaneous melanomas registered in Scotland. PATIENTS: 1430 patients (954 women, 476 men) aged 65 and over; comprising over a third of the 3903 patients with primary melanoma recorded for all age groups in Scotland during this period. RESULTS: The overall incidence of melanoma in patients aged 65 and over increased from 12.2/100,000 in 1979 to 20.7/100,000 in 1989, with the greatest increase seen in older men, from 7.8/100,000 in 1979 to 18.0/100,000 in 1989. The site most commonly affected was the face in both men and women (33% of all tumours). The most common histogenetic type was superficial spreading melanoma. 526 patients (37%) had melanomas with a tumour thickness of 3.5 mm or greater in the older age group, compared with 453 patients (18%) in those aged under 65. The highest proportion of thick tumours was seen in older men. Five year survival figures for 616 patients diagnosed between 1979 and 1984 were 88%, 66%, and 47% for thin, intermediate, and thick tumours respectively. Overall five year survival for the older age group was 64% compared with 78% for the younger age group. CONCLUSION: The increase in melanoma in the elderly and the high proportion of thick tumours, especially in men, require a specific educational programme for both primary and secondary prevention directed towards the older population.

Age Factors↗
PubMed1992

Melphalan concentration and distribution in the tissues of tumour-bearing limbs treated by isolated limb perfusion.

Levels of melphalan (L-phenylalanine mustard) were measured in the tissues of tumour-bearing limbs treated by isolated limb perfusion (ILP). 41 samples of melanoma tissue, normal fat and skin were excised from 15 patients during ILP. A high performance liquid chromatography assay was used to measure melphalan concentrations. Levels of melphalan were higher in tumour than in fat (P < 0.01, Wilcoxon signed-ranks test), and not significantly different from levels in adjacent skin. In 2 cases there was significant regional toxicity in the treated limb, but this was not related to the levels of melphalan measured in the tissues of the limb. It is encouraging that the concentrations of melphalan which were achieved in large necrotic nodules by ILP were similar to those in well-perfused normal skin.

Adipose Tissue↗
PubMed1992

The pharmacokinetic advantages of isolated limb perfusion with melphalan for malignant melanoma.

We describe melphalan pharmacokinetics in 26 patients treated by isolated limb perfusion (ILP). Group A (n = 11) were treated with a bolus of melphalan (1.5 mg kg-1), and in a phase I study the dose was increased to 1.75 mg kg-1. The higher dose was given as a bolus to Group B (n = 9), and by divided dose to Group C (n = 6). Using high performance liquid chromatography (HPLC) the concentrations of melphalan in the arterial and venous perfusate (during ILP) and in the systemic circulation (during and after ILP) were measured. Areas under the concentration time curves for perfusate (AUCa, AUCv) and systemic (AUCs) data were calculated. In all three groups the peak concentrations of melphalan were much higher in the perfusate than in the systemic circulation. The pharmacokinetic advantages of ILP can be quantified by the ratio of AUCa/AUCs, median value 37.8 (2.1-131). AUCa and AUCv were both significantly greater in Group B than in Group A (P values less than 0.01, Mann-Whitney). In Groups B and C acceptable 'toxic' reactions occurred but were not simply related to melphalan levels. Our phase I study has allowed us to increase the dose of melphalan to 1.75 mg kg-1, but we found no pharmacokinetic advantage from divided dose administration.

Arteries↗
PubMed1992

Tamoxifen as a single agent for advanced melanoma in postmenopausal women. A phase II study of the EORTC Malignant Melanoma Cooperative Group.

Between 1983 and 1989 a phase II study was carried out by the EORTC Malignant Melanoma Cooperative Group in which postmenopausal women with advanced melanoma but a good performance status received tamoxifen, 40 mg per day, as a single agent. From 12 centres, 114 patients were registered of whom 107 appeared to be eligible and 102 evaluable. Seven died of progressive disease within 4 weeks, eight others had early progressive disease (of whom seven died within 7 weeks). The response rate was 4.9%, the complete response rate 1%. Without prior chemotherapy three of 58 responded, with prior chemotherapy two of 44. Except for one of 46 patients with lung metastases who experienced a PR of these metastases, all responders were patients with slowly growing small soft tissue metastases. We conclude that, because of the few side effects, tamoxifen can be recommended for (postmenopausal) patients who have only a small number of slowly growing metastases and who are not yet candidates for treatment with toxic drugs.

Adult↗
PubMed1992

Nine years' experience of BELD combination chemotherapy (bleomycin, vindesine, CCNU and DTIC) for metastatic melanoma.

During the 9-year period from 1982 to 1991, 72 patients with melanoma were treated with a 5-day quadruple drug chemotherapy regime (BELD) comprising bleomycin, vindesine (Eldesine), CCNU (Lomustine) and DTIC. Forty-three patients had stage III melanoma, 34 of whom had evaluable disease. Of these 34, six (17.6%) achieved a complete response (CR), eight (23.5%) had a partial response (PR), five (14.7%) had stabilized disease (SD) and 15 (44.1%) had progressive disease (PD). Overall median survival of stage III melanoma patients was 38 weeks. Median survival of responders (CR + PR) was 47 weeks and 21 weeks for non-responders (SD + PD) (P < 0.005). Median follow-up time was 38 weeks. Following these encouraging results, 30 patients with stage II melanoma received BELD chemotherapy as adjuvant therapy after regional node dissection and clearance. Adjuvant BELD chemotherapy did not alter survival in these patients. BELD combination chemotherapy is well-tolerated, the main problems being nausea, vomiting, and leucopenia. We have maintained a combined response rate (CR + PR) of 41.1% for stage III disease. This is comparable with other combination chemotherapy regimes, which have as yet not been superseded by the newer biological therapies.

Adult↗
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

Pentoxifylline enhances lung colonization and alters cell adhesion and glycosaminoglycan synthesis by metastatic B16 melanoma cells.

The effect of pentoxifylline on B16 melanoma cell lung colonization, synthesis and properties of glycosaminoglycans (GAGS), and adhesion to and degradation of subendothelial extracellular matrix was examined. Pentoxifylline inhibited cell growth, cell numbers being reduced by 50% following incubation for 4 days in the presence of 250 micrograms/ml pentoxifylline, while the treated cells appeared more flattened, possessed numerous but short dendritic processes, and exhibited greatly enhanced tyrosinase activity and melanin synthesis. Pentoxifylline treatment increased the cells' ability to colonize the lungs of syngeneic C57BL mice following tail-vein injection of 10(5) cells. The number of lung tumours increased from 16.7 +/- 6.1 to 52.2 +/- 17.8. In addition, pentoxifylline-treated cell GAG synthesis was reduced by 36%, and the charge density of chondroitin sulphate reduced, while tumour-cell aggregation and adhesion to subendothelial extracellular matrix was increased, as was the tumour-cell-mediated release of 35SO4 from radiolabelled subendothelial matrix. The observed changes in GAG synthesis may contribute toward the increased cell adhesiveness which, in addition to increased degradation of certain components of the subendothelial extracellular matrix, may account, at least in part, for the enhancement of lung colonization.

Animals↗
PubMed1991

Lack of effect of pregnancy on outcome of melanoma. For The World Health Organisation Melanoma Programme.

To determine the effect of pregnancy on prognosis in melanoma we investigated 388 women treated for stage 1 primary cutaneous disease during their childbearing years. 85 women had been treated before any pregnancy, 92 during pregnancy, 143 after they had completed all pregnancies, and 68 between pregnancies. Women who had received treatment while pregnant had primary tumours of significantly greater thickness than did those in the other three groups (p = 0.002). Other possible confounding factors (site, age, parity) did not differ between the groups. Once tumour thickness was controlled for, survival rate of women in whom melanoma was diagnosed and treated while they were pregnant did not differ from that in the other three groups. Cox regression analysis showed no differences between the three groups of women who were not pregnant at diagnosis. Women with melanoma should be advised about pregnancy on the basis of thickness and site of tumour and evidence of vascular spread, and not hormonal status.

Adult↗
PubMed1991

Histopathologic diagnosis of dysplastic nevi: concordance among pathologists convened by the World Health Organization Melanoma Programme.

Dysplastic nevi are an important indicator of risk of cutaneous malignant melanoma. The study of and, particularly, international communication regarding this group of lesions have been hindered by a lack of precision in diagnosis. In an effort to broaden understanding, a panel of pathologists agreed upon a set of criteria for the diagnosis of dysplastic melanocytic nevi. Two major and four minor criteria were defined. The major criteria are (1) basilar proliferation of atypical nevomelanocytes (extending at least three rete ridges or "pegs" beyond any dermal nevo-cellular component), and (2) organization of this proliferation in a lentiginous or epithelioid-cell pattern. Minor criteria are (1) the presence of lamellar fibrosis or concentric eosinophilic fibrosis, (2) neovascularization, (3) inflammatory response, and (4) fusion of rete ridges. Diagnosis required presence of both major criteria and at least two minor criteria. One hundred fourteen histologic specimens of benign acquired nevi, dysplastic nevi, and radial-growth-phase melanomas were examined by the members of this panel; their diagnoses were compared to determine degree of concordance. The established criteria yielded 92% mean concordance overall.

Diagnosis, Differential↗
PubMed1991

Stage II melanoma in the west of Scotland, 1976-1985: prognostic factors for survival.

The outcome of 142 patients undergoing therapeutic lymphadenectomy for clinical stage II malignant melanoma was retrospectively assessed. 5 year survival was 26%, and survival was not altered in the 25 patients who received two courses of adjuvant combination chemotherapy after lymphadenectomy. On univariate analysis, the most significant determinants of survival were the number of malignant nodes removed at lymphadenectomy (P = 0.00004), the age of the patient (P = 0.009) and the disease-free interval between primary and stage II disease (P = 0.01). The following features were not significantly related to survival: sex, site, histogenetic type of primary tumour, tumour thickness and level of invasion. The number of malignant lymph-nodes was confirmed on multivariate analysis as the single most useful and significant predictor of survival, with the patient's age providing an additional significant contribution. In future adjuvant trials in stage II melanoma after therapeutic lymphadenectomy, patients should be stratified for both age and number of malignant nodes.

Adolescent↗