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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
PubMed2006

The unexpected sites of melanoma regional recurrences.

UNLABELLED: Sentinel node biopsy is a means of identifying nodal involvement in melanoma and lymphoscintigraphy identifies unpredictable sites of melanoma sentinel nodes in up to 25% of cases. Whilst there is a dearth of recent publications in this area, it nevertheless remains an interesting observation that unpredictable sites of sentinel nodes are so common as to be accepted as normal. This study was performed to determine if this high rate of unpredictable lymphatic drainage was reflected in clinical practice, where therapeutic lymph node dissections were performed for pathologically confirmed regional disease. METHODS: Patients undergoing regional lymph node dissections for histologically proven malignant melanoma were identified from a computer database. Patient details were analysed from case records. RESULTS: Two hundred and forty-three case records were examined and 237 were suitable for analysis. The site of the primary was the head and neck in 50 (21%), trunk in 73 (31%), upper limb in 27 (11%) and lower limb in 87 (37%). In 15 cases (6%), the first site of regional disease was unpredictable. In these 15 cases, the site of the primary was the head and neck in two, trunk in 11, upper limb in one and lower limb in one. In 37 cases (16%), a subsequent site of nodal recurrence was unpredictable. Clinicians should be aware that patients with melanomas, particularly of the trunk, especially those in whom a therapeutic nodal dissection has been performed, may have nodal disease at unpredictable sites. However, unexpected sites of regional disease are not as common as sentinel node biopsy would suggest. Guidelines for lymph node examination in cutaneous melanoma are suggested based on these findings.

Female↗
PubMed2004

Ground-level solar spectral irradiance in Glasgow: an inter-comparison of two sites.

BACKGROUND: Solar spectral radiometry presents significant challenges to produce accurate and reproducible data. To investigate the reliability of the measurements, several inter-comparisons have been set up. Although these are useful, their main drawback is that equipment must be dismantled and transported to a common site and re-calibrated. METHODS: In this study, an inter-comparison has been performed of two spectroradiometers that are located 3 miles apart some 30 m above sea level. These two systems have operated using different calibration techniques. Data were compared on clear days, to minimise actual differences in ultraviolet irradiation. RESULTS: There were substantial differences at some individual wavelength points, but overall the mean difference of results at 5 nm intervals on an individual scan from the two systems agreed to within 11%. If the data were used to compute the erythemal irradiance, the differences were reduced to 4%. CONCLUSION: This study demonstrates both the limitations and the level of reliability that might be expected from these systems operating under careful scientific supervision.

Geography↗
PubMed2001

Adjuvant interferon alpha 2b in high risk melanoma - the Scottish study.

In 1989, the Scottish melanoma group initiated a randomized trial, comparing observation alone with 6 months' therapy with low dose interferon (given subcutaneously 3 MU day-1, twice weekly), for patients with primary melanomas of at least 3 mm Breslow thickness, or with evidence of regional node involvement. The trial was closed in 1993 with only 95 eligible patients randomized. There were no toxic deaths, and no patient failed to complete the treatment for reasons of toxicity. 6 months' treatment with low-dose interferon- resulted in a statistically significant improved disease-free survival for up to 24 months after randomization (P< 0.05). However, at a median follow-up of over 6 years, although there was an apparent improvement in disease-free survival (from 9 to 22 months), and overall survival (from 27 to 39 months), consistent with larger studies powered to detect such differences, these differences were not statistically significant. The data therefore suggest that 6 months of low-dose interferon is active, and confirm the importance of the large randomized studies, such as the UKCCCR AIM-High and EORTC trials, that seek to confirm a possible survival advantage for low or intermediate dose interferon.

Adult↗
PubMed2000

The spectrum of mutations in erythrokeratodermias--novel and de novo mutations in GJB3.

Intercellular channels in skin are a complex and functionally diverse system formed by at least eight connexins (Cx). Our recent molecular studies implicating Cx defects in inherited skin disorders emphasize the critical role of this signaling pathway in epidermal differentiation. Erythrokeratodermia variabilis (EKV) is an autosomal dominant genodermatosis with a striking phenotype characterized by the independent occurrence of transient localized erythema and hyperkeratosis. The disease maps to 1p34-p35, and recently we identified the causative gene GJB3 encoding Cx31. We have now investigated GJB3 in two families and three sporadic cases with EKV, and report three new heterozygous mutations. In a sporadic case, we detected a mutation leading to substitution of a conserved phenylalanine (F137L) in the third transmembrane domain, which likely interferes with the proper assembly or gating properties of connexons. In another family, all three affected individuals carried two distinct mutations on the same GJB3 allele. However, only a de novo heterozygous missense mutation replacing arginine 42 with proline (R42P) co-segregated with the disease, while a 12 bp deletion predicted to eliminate four amino acid residues in the variable carboxy terminal domain of Cx31 was also found in clinically unaffected relatives but not in 90 unaffected controls. Including the previously published mutations, in toto, five different missense mutations have now been detected in 6 out of 17 families investigated by our laboratory, all of which presumably affect the cytoplasmic amino terminal and transmembrane domains of Cx31. In contrast, two mutations linked to progressive high-tone hearing impairment were located in the second extracellular domain, suggesting that the character and position of Cx mutations determine their phenotypic expression in different tissues. However, the phenotypic spectrum of GJB3 mutations seems not to include progressive symmetric erythrokeratodermia, another dominant genodermatosis with overlapping features, since no mutations were found in six unrelated families tested.

Connexins↗
PubMed1998

Clinical accuracy of the diagnosis of cutaneous malignant melanoma.

Diagnostic accuracy for melanoma was determined in a dedicated pigmented lesion clinic. We assessed the impact of duration of experience in dermatology and also the relationship between tumour thickness and accuracy of clinical diagnosis. We reviewed the histopathology request forms and reports for all biopsies generated by the Pigmented Lesion Clinic, Western Infirmary, Glasgow during 1992-94 inclusive. The clinic is staffed by two consultants, one senior registrar and one registrar. Diagnostic accuracy, index of suspicion, sensitivity, specificity and positive predictive value were calculated for the clinic overall, and for each grade of staff. One hundred and sixty-three lesions were diagnosed clinically as melanoma. A histopathological diagnosis of melanoma was made for 128 lesions during this period, 113 of which had been correctly diagnosed before surgery. The diagnostic accuracy for two dermatologists each with > 10 years experience in dermatology was 80%, with sensitivity of 91% and positive predictive value of 86%. Diagnostic accuracy rates for two senior registrars (each with 3-5 years experience) and six registrars (each with 1-2 years experience) were 62% and 56%, respectively. Thin and intermediate thickness melanomas generated the greatest inaccuracy irrespective of clinical experience, although registrars failed to recognize melanoma three times more often than the other groups. We report the diagnostic accuracy for melanoma by trained dermatologists to be higher than previously reported. In comparison with trainees, > 10 years experience in dermatology and exposure to more than 10 melanomas per year appears to be associated with greater diagnostic accuracy. Knowledge of the current clinical diagnostic accuracy at varying levels of experience is essential if the impact of training is to be evaluated. As pigmented lesions of virtually all types can be treated within dermatology departments, dermatologists are the appropriate first point of referral for suspected early melanoma.

Clinical Competence↗
PubMed1998

The prescription of isotretinoin to women: is every precaution taken?

A questionnaire survey of dermatologists practising in Scotland was carried out to assess strategies for the management of women prescribed isotretinoin for acne. The results of the study suggested that the prevention of pregnancy during treatment is of considerable concern to dermatologists: over 90% routinely asked women about sexual activity and 97% routinely gave both verbal and written advice on the need to avoid pregnancy during treatment. However, clinical practices which might place women at risk of pregnancy were identified: only 30% of trainees and 51% of consultants routinely carried out pregnancy tests before treatment, and when tests were carried out, there was a tendency to rely on potentially insensitive urine assays. Additionally, there was an apparent lack of recognition of the possibility of sexual activity in girls aged under 16 years. Suggestions for the management of women prescribed isotretinoin include taking a sexual history from all women; providing clear information on the need to avoid pregnancy during treatment; obtaining informed consent prior to treatment; recommending the use of effective contraceptive measures; and exclusion of pregnancy prior to treatment by means of a suitably timed blood or urine sample and sensitive assay technique.

Abortion, Therapeutic↗
PubMed1998

An immunohistochemical study of androgen, oestrogen and progesterone receptors in the vulva and vagina.

OBJECTIVE: To map potential sites of sex steroid action in the human vulva. METHODS: Monoclonal antibodies to androgen, oestrogen and progesterone receptors were used to stain frozen sections of vulval skin, vagina and suprapubic skin. A scoring system was devised to compare receptor distribution in the epidermis and dermis of skin with vaginal epithelium and stroma. RESULTS: Androgen receptors were seen in epidermal keratinocytes, sebaceous glands, sweat glands, hair follicles and dermal fibroblasts of skin, and epithelial cells and stromal fibroblasts of the vagina. Androgen receptor scores were significantly higher in the epidermis of labia majora and minora than in vaginal epithelium. Oestrogen receptors were seen in basal and suprabasal cells of vaginal epithelium and epidermis of labia minora but were restricted to basal keratinocytes in true skin. They were seen in stromal fibroblasts and vaginal smooth muscle, and dermal fibroblasts of the skin. Oestrogen receptors were highest in vaginal epithelium and stroma, and lowest in suprapubic skin. Progesterone receptors were seen in vaginal epithelium, fibroblasts and smooth muscle but not in the vulva. There was no evidence of significant differences in androgen or oestrogen receptor staining in the vulva of pre- or postmenopausal women. CONCLUSION: The transition from vagina to vulva is marked by an increase in androgen and a decrease in oestrogen and progesterone receptors. This distribution of receptors would indicate a limited role for oestrogen creams on the vulva.

Adult↗
PubMed1997

Intraoperative identification of sentinel lymph node in patients with malignant melanoma.

We report our experience with the technique of lymphatic mapping using patent blue V dye in patients with limb malignant melanoma. The technique is based on the hypothesis that embolic metastases occur along lymphatic channels to a 'sentinel' lymph node: the draining lymph node nearest the site of the primary malignant melanoma. Patent blue V dye (0.5-1.0 ml) is injected intradermally around the site of the melanoma. Immediately the groin or axilla is opened and the blue lymphatic channels followed to the sentinel node. The node is removed and examined by both haematoxylin and eosin (H&E) and immunohistochemical staining. We have carried out this technique in 35 patients, all of whom had 'clinically assessed' stage I disease. In all 35 patients, sentinel nodes were identified, and nine were found to contain unsuspected micrometastases. Our initial evaluation of intraoperative lymphatic mapping is very promising. The technique is practicable and easy to master. If 25% of patients with cutaneous malignant melanoma who are clinically stage I have nodal disease, this has great importance not only for staging and treatment but also for all future therapeutic trials.

Adult↗
PubMed1997

Ultraviolet B radiation was increased at ground level in scotland during a period of ozone depletion.

The potentially harmful effects associated with stratospheric ozone depletion are widely acknowledged. As the ozone layer principally absorbs ultraviolet (UV) radiation of wavelengths below 290 nm, reductions in stratospheric ozone levels are likely to result in increased UVB at the earth's surface, with the risk of increased incidence of skin cancer. Measuring the sun's spectrum at ground level requires sophisticated and reliable spectral instruments. Results are reported for this for the first time in the U.K. using spectral instruments, showing a significant increase in short wavelength UV radiation at a time of depleted stratospheric ozone. If this trend increases, future ozone depletion could contribute to known risks for cutaneous malignancies of all types.

Atmosphere↗
PubMed1997

The labial melanotic macule: a review of 79 cases.

Seventy-nine patients presented to the pigmented lesion clinic between 1983 and 1996 with labial melanotic macules. We have followed up these patients for up to 13 years and 3 months (mean 6 years, 3 months). We present evidence that this is a benign entity. The appropriate management is reassurance and discharge, with the advice to return only if the lesion grows or darkens. This did not occur in any of our patients during the time of their follow-up.

Adolescent↗
PubMed1997

An audit of the completeness of non-melanoma skin cancer registration in Greater Glasgow.

The incidence of basal cell carcinoma and squamous cell carcinoma (non-melanoma skin cancer) is increasing in the U.K., and the importance of this has been recognized in the 'Health of the Nation' target of halting the annual increase in the incidence of skin cancer by the year 2005. An accurate assessment of incidence is necessary both in meeting this target and in planning skin cancer services. We have examined the ways in which basal cell carcinoma and squamous cell carcinoma are diagnosed and treated in Greater Glasgow and have determined how many of these tumours are, recorded by the West of Scotland Cancer Registry. Our results show that there is under-registration of both basal cell carcinoma and squamous cell carcinoma. Overall, 39 of 127 basal cell carcinomas (31%; 95% confidence interval [CI] 23-39%) and 11 of 25 squamous cell carcinomas (44%; CI 26-63%) were not registered by the cancer registry. We also showed that dermatologists rarely treat clinically suspicious tumours without obtaining pathological proof of the diagnosis. Accurate data collection by selected representative cancer registries is suggested as a possible solution.

Basal Cell Carcinoma↗
PubMed1996

Systemic complement activation in psoriasis vulgaris.

Nineteen patients with psoriasis vulgaris and no other cause for systemic complement activation were studied for evidence of such activation. There was a marked elevation in serum C5b-9 complexes with no other significant complement abnormalities, and no correlation between C5b-9 levels and disease activity. This is the most detailed study of complement in psoriasis yet attempted and confirms that complement activation is a feature of psoriasis vulgaris.

Adolescent↗
PubMed1996

Comparison of photodynamic therapy with cryotherapy in the treatment of Bowen's disease.

The efficacy and suitability of photodynamic therapy (PDT) was compared with that of cryotherapy in the treatment of 40 lesions of Bowen's disease. Lesions were randomized to receive either cryotherapy with liquid nitrogen, or PDT using a portable desktop lamp incorporating a 300 W xenon short arc discharge source. A porphyrin precursor, 5-aminolaevulinic acid (5-ALA), was applied topically 4 h before irradiation in the PDT group. Each lesion received 125 J/cm2 at a fluence rate of 70 mW/cm2. All patients were reviewed at 2-monthly intervals and treatments repeated if required. Cryotherapy produced clearance in 10 of 20 lesions after one treatment, the remaining 10 lesions requiring two or three treatment applications. PDT resulted in clearance of 15 of 20 lesions after one treatment and of the remaining five lesions after a second treatment. The probability that a lesion cleared after one treatment was greater with PDT than cryotherapy (P < 0.01). Cryotherapy was associated with ulceration (five of 20), infection (two of 20) and recurrent disease (two of 20); no such complications occurred following PDT. PDT using a non-laser light source and topical 5-ALA appears to be at least as effective as cryotherapy in the treatment of Bowen's disease with fewer adverse effects.

Aged↗
PubMed1995

Single-centre prospective study of isolated limb perfusion with melphalan in the treatment of subungual malignant melanoma.

Subungual melanoma is rare and experience in treating this condition with isolated limb perfusion is limited. Between 1985 and 1990, 24 patients were treated by digital amputation and isolated limb perfusion with melphalan and mild hyperthermia. The disease was staged according to the M.D. Anderson classification: stage I (17 patients), stage IIIA (one), stage IIIB (two) and stage IIIAB (four). Thirteen lesions were on the foot and 11 on the hand. Seven patients have developed locoregional recurrence. The estimated overall 2- and 5-year probabilities of survival were 77 and 46 per cent respectively, while for disease-free survival the rates were 58 and 51 per cent. When these results were compared retrospectively with those in 111 patients treated by amputation alone, no significant difference in survival was demonstrated. This experience suggests that isolated limb perfusion with melphalan and mild hyperthermia confers no additional survival benefit over appropriate surgery.

Adult↗
PubMed1994

Localization of transforming growth factor-alpha RNA and protein in the skin of psoriatic patients receiving therapy.

Fourteen patients with chronic plaque psoriasis requiring in-patient therapy were treated with a variety of antipsoriatic agents. All had four skin biopsies taken: two prior to therapy, one from a psoriatic plaque and one from adjacent clinically normal skin, and two further biopsies, one 2-3 weeks after starting therapy, and one at clinical clearance, taken from an area where there was previously a psoriatic plaque. In addition, three biopsies were taken from clinically normal skin of non-psoriatics. Transforming growth factor-alpha (TGF-alpha) RNA and protein distributions were estimated in these biopsies, using in situ hybridization with a cRNA TGF-alpha probe, and an antibody to TGF-alpha polypeptide. Prior to therapy, grain counts showed elevated levels of TGF-alpha RNA in the subcorneal layers of the epidermis. These levels decreased during clearance of the psoriasis. In one patient whose plaques did not clear, there was no decrease of TGF-alpha mRNA. Antibody studies showed the presence of TGF-alpha polypeptide in the epidermis prior to therapy, with a relative concentration of immunoprotein in the upper epidermal layers, compared with a more uniform distribution of immunoprotein after treatment, and in uninvolved skin of the same psoriatic patient. These studies extend our knowledge of the relationship between TGF-alpha and psoriatic skin.

Anthralin↗
PubMed1994

Point mutations in the N-ras oncogene in malignant melanoma and congenital naevi.

DNA from formalin-fixed and paraffin-processed samples from 100 melanocytic lesions (39 malignant melanomas, 18 cases of dysplastic naevi, and 43 congenital naevi) was extracted, and the sequences around codons 12/13 and 61 of the N-ras oncogene were amplified using the polymerase chain reaction. The amplified product was then analysed both by dot-blotting and by direct sequencing for point mutations. By the dot-blotting technique, mutations were seen in 18 of 100 lesions. These were in one of five distant metastases (20%), in one of three nodal metastases (33%), in four of 31 (13%) primary melanomas, in none of 18 dysplastic naevi, and in 12 of 43 (28%) congenital naevi, all at codon 61. On direct sequencing, nine of 18 mutations were confirmed, in two of 31 (6%) primary tumours, one distant metastasis, and six of 43 (14%) congenital naevi. Of the 23 superficial spreading melanomas examined, eight were on sun-exposed skin. A superficial spreading melanoma, in which the N-ras mutation at codon 61 was confirmed, was on non-exposed skin, and an unconfirmed mutation was from an exposed site. One of three nodular melanomas with a confirmed mutation was on a light-exposed site, and the other two nodular melanomas were from non-exposed areas. All four lentigo maligna melanomas were from exposed sites, and one of these had an unconfirmed mutation. The only acral lentiginous melanoma, which had no mutation, was from a sun-exposed area.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗