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Biomedical subjects

R Mackie

Publications and source records attributed to R Mackie.

At least 19 recordsLinked to original sources

Diagnostic and neural analysis of skin cancer (DANAOS). A multicentre study for collection and computer-aided analysis of data from pigmented skin lesions using digital dermoscopy.

BACKGROUND: Early detection of melanomas by means of diverse screening campaigns is an important step towards a reduction in mortality. Computer-aided analysis of digital images obtained by dermoscopy has been reported to be an accurate, practical and time-saving tool for the evaluation of pigmented skin lesions (PSLs). A prototype for the computer-aided diagnosis of PSLs using artificial neural networks (NNs) has recently been developed: diagnostic and neural analysis of skin cancer (DANAOS). OBJECTIVES: To demonstrate the accuracy of PSL diagnosis by the DANAOS expert system, a multicentre study on a diverse multinational population was conducted. METHODS: A calibrated camera system was developed and used to collect images of PSLs in a multicentre study in 13 dermatology centres in nine European countries. The dataset was used to train an NN expert system for the computer-aided diagnosis of melanoma. We analysed different aspects of the data collection and its influence on the performance of the expert system. The NN expert system was trained with a dataset of 2218 dermoscopic images of PSLs. RESULTS: The resulting expert system showed a performance similar to that of dermatologists as published in the literature. The performance depended on the size and quality of the database and its selection. CONCLUSIONS: The need for a large database, the usefulness of multicentre data collection, as well as the benefit of a representative collection of cases from clinical practice, were demonstrated in this trial. Images that were difficult to classify using the NN expert system were not identical to those found difficult to classify by clinicians. We suggest therefore that the combination of clinician and computer may potentially increase the accuracy of PSL diagnosis. This may result in improved detection of melanoma and a reduction in unnecessary excisions.

Adult↗

A new approach to dose escalation in non-small-cell lung cancer.

PURPOSE: To describe the radiobiological rationale for dose-per-fraction escalation in non-small-cell lung cancer (NSCLC) and to devise a novel Phase I scheme to implement this strategy using advanced radiotherapy delivery technologies. METHODS AND MATERIALS: The data from previous dose escalation trials in NSCLC are reanalyzed to establish a dose-response relationship in this disease. We also use data relating prolongation in treatment time to survival to compute the potential doubling time for lung tumors. On the basis of these results, and using a Bayesian model to determine the probability of pneumonitis as a function of mean normalized lung dose, a dose-per-fraction escalation strategy is developed. RESULTS: Standard approaches to dose escalation using 2 Gy per fraction, five fractions per week, require doses in excess of 85 Gy to achieve 50% long-term control rate. This is partly because NSCLCs repopulate rapidly, with a 1.6% per day loss in survival from prolongation in overall treatment time beyond 6 weeks, and a cell doubling time of only 2.5 to 3.3 days. A dose-per-fraction escalation strategy, with a constant number of fractions, 25, and overall time, 5 weeks, is projected to produce tumor control rates predicted to be 10%-15% better than 2 Gy per fraction dose escalation, with equivalent late effects. This Phase I clinical study is divided into three parts. Step 1 examines the feasibility of the maximum breath-holding technique and junctioning of tomotherapy slices. Step 2 treats 10 patients with 30 fractions of 2 Gy over 6 weeks and then reduces duration to 5 weeks using fewer but larger fractions in 10 patients. Step 3 will consist of a dose-per-fraction escalation study on roughly 50 patients, maintaining 25 fractions in 5 weeks. Bayesian methodology (a modification of the Continual Reassessment Method) will be used in Step 3 to allow consistent and efficient escalation within five volume bins. CONCLUSION: A dose-per-fraction escalation approach in NSCLC should yield superior outcomes, compared to standard dose escalation approaches using a fixed dose per fraction, for a given level of pneumonitis and late toxicity. Highly conformal radiotherapy techniques, such as intensity modulated radiotherapy (IMRT) and helical tomotherapy with its adaptive capabilities, will be necessary to achieve significant dose-per-fraction escalation without unacceptable lung and esophageal morbidity.

Carcinoma, Non-Small-Cell Lung↗

Reduced accommodative function in dyskinetic cerebral palsy: a novel management strategy.

A 9-year-old boy with dyskinetic cerebral palsy secondary to neonatal encephalopathy is described. He presented with blurring of near vision which had begun to impact on his school work. Objective assessment of accommodation showed that very little was present, although convergence was almost normal. The near-vision symptoms were completely removed and reading dramatically improved with the provision of varifocal spectacles. Varifocal lenses provide an optimal correction for far, intermediate (i.e. for computer screens), and near distances (i.e. for reading). Managing this type of patient with varifocal spectacles has not been previously reported. It is clearly very important to prescribe an optimal spectacle correction to provide clear vision to optimize learning.

Accommodation, Ocular↗

Enhanced Butanol Production by Clostridium beijerinckii BA101 Grown in Semidefined P2 Medium Containing 6 Percent Maltodextrin or Glucose.

Dramatically elevated levels of butanol and acetone resulted in higher butanol and total solvent yields for hyperamylolytic Clostridium beijerinckii BA101 relative to the NCIMB 8052 parent strain grown in semidefined P2 medium containing either 6% glucose or STAR-DRI 5 maltodextrin. C. beijerinckii BA101 consistently produced on the order of 19 g of butanol per liter in 20-liter batch fermentations. This represents a greater than 100% increase in butanol concentration by the BA101 strain compared to the parent NCIMB 8052 strain. The kinetics of butanol production over time also indicate a more rapid rate of butanol production by BA101 in semidefined P2 medium containing glucose or maltodextrin. The lower levels of butyric and acetic acids produced over the course of the fermentation carried out by BA101 are consistent with an enhanced capacity for uptake and recycling of these acids. C. beijerinckii BA101 appears to more completely utilize carbohydrate compared to the 8052 strain. Carbon balance following fermentation by C. beijerinckii 8052 and BA101 indicates that sufficient carbon is available for the twofold increase in butanol concentration observed during BA101 fermentations. C. beijerinckii BA101 also has superior solvent production capacity during continuous culture fermentation in P2 medium containing 6% glucose. Volumetric solvent yields of 0.78 and 1.74 g/liter/h for BA101 and 0.34 and 1.17 g/liter/h for NCIMB 8052 were obtained at dilution rates of 0.05 and 0.20 h(sup-1), respectively. No drift towards acid synthesis (strain degeneration) was observed for up to 200 h (d = 0.05 h(sup-1)) and 100 h (d = 0.20 h(sup-1)).

Journal Article↗

A study of the impact of Sun Awareness Week 1995.

We report a questionnaire-based survey of parents of schoolchildren to assess the impact of Sun Awareness Week, organized by the U.K. Skin Cancer Working Party, from 4 to 10 June 1995. A questionnaire was designed, pre-tested and modified. Nine hundred and eighty-nine patients of schoolchildren were approached before and after Sun Awareness Week at eight comprehensive primary schools and a children's clothes shop. Responses to the questionnaires were analysed in the following categories: total knowledge, sunscreen knowledge, melanoma risk factor knowledge, attitude, self-reported behaviour and awareness of the link between childhood sun exposure and cancer (link). A reasonable level of knowledge was demonstrated in the sample population. Significant improvements in attitude and behaviour scores were observed (P < 0.05). Three of the four link questions were significantly improved (P < 0.005). These results were not explained by differences in age, sex, or occupation between the before and after populations. Further national studies are needed to establish long-term benefits of such interventions.

Adolescent↗

Cortical visual dysfunction in children: a clinical study.

Damage to the cerebral cortex was responsible for impairment in vision in 90 of 130 consecutive children referred to the Vision Assessment Clinic in Glasgow. Cortical blindness was seen in 16 children. Only 2 were mobile, but both showed evidence of navigational blind-sight. Cortical visual impairment, in which it was possible to estimate visual acuity but generalised severe brain damage precluded estimation of cognitive visual function, was observed in 9 children. Complex disorders of cognitive vision were seen in 20 children. These could be divided into five categories and involved impairment of: (1) recognition, (2) orientation, (3) depth perception, (4) perception of movement and (5) simultaneous perception. These disorders were observed in a variety of combinations. The remaining children showed evidence of reduced visual acuity and/ or visual field loss, but without detectable disorders of congnitive visual function. Early recognition of disorders of cognitive vision is required if active training and remediation are to be implemented.

Adolescent↗

Naevi in schoolchildren in Scotland and Australia.

To test the hypothesis that children living in subtropical and tropical environments have more naevi than those of similar ethnicity living in temperature countries, a comparative study of melanocytic naevi in 111 schoolchildren from Brisbane, Australia, and 222 from Glasgow, Scotland, was carried out. All children were aged 13-15 years, of European ancestry, and had spent most of their lives at latitudes of less than 30 degrees S (Australia) or greater than 30 degrees N (Scotland). Using an identical protocol, all naevi of 2 mm or more in diameter occurring on the right arm were counted by either a highly experienced research nurse in Brisbane, or a dermatologist in Glasgow. Hair and eye colour, and facial freckling, were assessed by the examiner, and axillary skin colour of children in both cities was measured using the same reflectance spectrophotometer. Children in Brisbane had significantly more naevi than those in Glasgow (P < 0.05), after adjusting for complexion variables. The difference in the geometric mean number of naevi on the arm was much greater among boys (7.7 vs. 4.4, in Brisbane and Glasgow, respectively) than among girls (7.3 vs. 6.7). This has parallels with the sex differences in melanoma at later ages in the two countries. Besides country of residence, freckles and innate skin colour were the most significant predictors of large numbers of naevi, whereas red hair had a significant protective effect. Overall, these data on prevalence of naevi in children from contrasting environments provide some evidence in support of the theory that naevus development is related to the level of sun exposure in childhood and adolescence.

Adolescent↗

Balloon cell metastatic melanoma: an important differential in the diagnosis of clear cell tumours.

Two cases of metastatic balloon cell melanoma are reported. Each tumour was composed of large clear cells which did not contain melanin, glycogen or fat, but showed positive staining for S-100 protein, NK/1-C3 and HMB-45. In each case the primary lesion was a cutaneous melanoma of typical morphology. It is essential to consider balloon cell melanoma in the differential diagnosis of clear cell tumours. These cases emphasize the need for an accurate clinical history.

Adult↗

Treatment of arteriovenous malformations with stereotactic radiosurgery employing both magnetic resonance angiography and standard angiography as a database.

Twenty-one arteriovenous malformations were prospectively evaluated using magnetic resonance angiography and compared with stereotactic angiography. The goals were to establish the feasibility of magnetic resonance angiography, compare it to stereotactic angiography, employ magnetic resonance angiography in follow-up, and semiquantify flow. A correlative evaluation between flow and response to stereotactic radiosurgery was carried out. Phase contrast angiograms were obtained at flow velocities of 400, 200, 100, 60, and 20 cm/sec. The fractionated velocities provided images that selectively demonstrated the arterial and venous components of the arteriovenous malformations. Qualitative assessment of the velocity within the arteriovenous malformations and the presence of fistulae were also determined by multiple velocity images. In addition, 3-dimensional time-of-flight magnetic resonance angiograms were obtained to define the exact size and shape of the nidus. This technique also permitted evaluation of the nidus and feeding arteries for the presence of low flow aneurysms. Correlation between the two imaging modalities was carried out by subjective and semiquantitative estimation of flow velocity and estimation of nidus size. The following velocity parameters were employed: fast, intermediate, slow, and none (arteriovenous malformation obliterated). In 19 of 21 (90.5%) arteriovenous malformations, magnetic resonance angiography was equal or superior to stereotactic angiography for flow quantification and visualization of the nidus. Only 2 of 21 arteriovenous malformations were better demonstrated by stereotactic angiography than by magnetic resonance angiography (failure rate of 9.5%). The nidus size in one case was clearly underestimated by stereotactic angiography and would have resulted in a geographic miss without magnetic resonance angiography. Seven post-radiosurgery arteriovenous malformations were evaluated for follow-up with both magnetic resonance angiography and stereotactic angiography. In 6 of 7 arteriovenous malformations, magnetic resonance angiography response matched stereotactic angiography response. Correlation of flow with outcome was carried out for 14 arteriovenous malformations using magnetic resonance angiography only. Interestingly, all nine arteriovenous malformations with intermediate or slow flow demonstrated partial or complete obliteration; whereas only 3 of 5 fast flow arteriovenous malformations achieved a response with a median follow-up of 10 months. This early analysis suggests that slower flowing arteriovenous malformations may obliterate faster after stereotactic radiosurgery and flow parameters could be employed to predict response. In conclusion, magnetic resonance angiography permits semiquantitative flow velocity assessment and may therefore be superior to stereotactic angiography. An additional advantage of magnetic resonance angiography is the generation of serial transverse images which can replace the conventional CT scan employed for stereotactic radiosurgery treatment planning.(ABSTRACT TRUNCATED AT 400 WORDS)

Cerebral Angiography↗

A new biomechanical approach to assessing the fragility of the internal elastic lamina of the arterial wall.

Patterns of tearing of the internal elastic lamina induced by controlled tensile extension of the arterial wall in the axial direction are similar morphologically to those induced in vivo in the anastomosed arteries of experimental arteriovenous fistulae. The mural response is modelled with a simple bi-layer analogue and it is shown that the internal elastic lamina exhibits a greater degree of strain-limiting deformation behavior in the axial direction than the medial and adventitial layers. Application of laminate theory indicates that the frequency of intimal tearing along the vessel length is directly related to the failure strength of the intimal layer.

Animals↗

Screening for skin cancer.

Holidays in sunny climates are taking their toll on British skins. Professor Rona Mackie warns that 'flash frying' attitudes to sun bathing can precipitate skin cancer.

Health Education↗

Use of external shock-wave lithotripsy and adjuvant ursodiol for treatment of radiolucent gallstones. A national multicenter study.

A prospective multicenter trial was performed to evaluate the use of external shockwave lithotripsy (ESL) and adjuvant medical therapy for the treatment of gallstones. A Medstone STS lithotripter was used together with ursodiol. Two hundred twenty-three patients were treated under general anesthesia (75%) or with intravenous analgesia (25%). Initial treatments were on an inpatient basis, but as centers gained experience, outpatient treatments became more common. Stone fragmentation and clearance were greatest in patients with solitary gallstones less than 2 cm in diameter. In this group of patients, stone fragmentation occurred in 97% of patients, and the cumulative stone-free rates at three and six months were 54% and 90%, respectively. These results indicate that fragmentation of gallstones can be achieved by a dry shock-wave lithotripter and that stone clearance is induced more rapidly by external shock-wave lithotripsy and adjuvant ursodiol therapy than by ursodiol therapy alone.

Adult↗

Phase II studies of mitozolomide in melanoma, lung and ovarian cancer.

Seventy-seven patients were treated with oral mitozolomide to assess the activity of this drug in melanoma, lung and ovarian cancer. Partial responses were seen in five of 18 evaluable patients with small cell lung cancer (SCLC) and three of 20 with melanoma. No activity was apparent in non small cell lung or epithelial ovarian cancer. The major toxicity was myelosuppression which necessitated reduction in the initial dosage from 115 to 90 mg/m2. However, even at this dose level, unpredictable WHO grade 4 toxicity occurred in non-pretreated patients. Thrombocytopenia was more common than leucopenia and eight patients required platelet transfusion for spontaneous or tumour-related haemorrhage. Myelotoxicity was considered responsible for two deaths and was a significant contributory factor in a further three. Non-haematological toxicity was minor. Thus, despite demonstrable activity in SCLC and melanoma, unpredictable myelosuppression is likely to preclude further assessment in combination chemotherapy regimes in these tumours.

Adult↗

Staphylococcal colonization in atopic dermatitis and the effect of topical mupirocin therapy.

Forty-nine patients with atopic dermatitis entered a double blind placebo controlled cross-over study of mupirocin, a new topical antistaphylococcal antibiotic. Forty-five patients were evaluable. Quantitative bacteriological assessment before treatment showed that heavy colonization of the skin with Staphylococcus aureus was present in nearly all patients even in the absence of overt infection. However, the bacterial count was significantly reduced by 2 weeks' treatment with topical mupirocin, but not by the placebo. Moreover, a significant reduction of clinical severity was also observed after treatment with mupirocin, which was maintained over the following 4 weeks, although recolonization occurred during this period, with bacterial counts rising to pre-treatment levels. Despite recolonization, clinical deterioration was not observed during the trial period. No serious side-effects were observed. Phage typing showed that 50% of patients carried more than one bacterial phage type. Recolonization in eight patients (17%) was with a 'new' strain that had not previously been isolated.

Administration, Topical↗