Search PubMed⌕ Search

Biomedical subjects

M Stewart

Publications and source records attributed to M Stewart.

At least 433 records · Page 24Linked to original sources

Paradoxical response of malignant melanoma to methotrexate in vivo and in vitro.

Methotrexate (MTX) shows consistent cytotoxicity for melanoma cells in vitro but it is ineffective in clinical use at equivalent concentrations in vivo. This apparent paradox has been investigated by cell culture techniques and results quantified by cell number. In an in vitro model of high dose MTX therapy followed by leucovorin rescue (HD-MTX-LCR) there was survival of both melanoma and choriocarcinoma cell lines but not of an acute lymphocytic leukaemia cell line. The 70H metabolite of MTX was identified by HPLC in plasma samples of melanoma patients treated by HD-MTX-LCR, in which MTX concentrations approximately 10(-5) M were maintained for 24 h. However, metabolism per se is unlikely to account for the lack of response to MTX clinically. In vitro 70H MTX (10(-7) - 10(-6) M) was two orders of magnitude less cytotoxic for melanoma than MTX (10(-9) - 10(-8) M). The cellular accumulation of [3H]-MTX, using a rapid gradient centrifuge technique for separation of melanoma cells from medium, was reduced in the presence of 70H-MTX. The results suggest that reduced cellular uptake of MTX combined with biochemical rescue of tumour cells may partially explain the paradoxical lack of clinical response of melanoma to the drug.

Animals↗

Frog skeletal muscle thick filaments are three-stranded.

A procedure has been developed for isolating and negatively staining vertebrate skeletal muscle thick filaments that preserves the arrangement of the myosin crossbridges. Electron micrographs of these filaments showed a clear periodicity associated with crossbridges with an axial repeat of 42.9 nm. Optical diffraction patterns of these images showed clear layer lines and were qualitatively similar to published x-ray diffraction patterns, except that the 1/14.3-nm meridional reflection was somewhat weaker. Computer image analysis of negatively stained images of these filaments has enabled the number of strands to be established unequivocally. Both reconstructed images from layer line data and analysis of the phases of the inner maxima of the first layer line are consistent only with a three-stranded structure and cannot be reconciled with either two- or four-stranded models.

Animals↗

The urinary bacterial flora in patients with three types of urinary tract diversion.

There is known to be a high risk of malignancy at uretero-colic anastomoses and it has been postulated that bacteria catalyse both the local formation and the activation of carcinogens such as N-nitrosamines. If this theory is correct, then the risk of malignancy should be greatest when the prevalence of mixed urinary tract infection is greatest. Bacterial culture was performed on samples of urine obtained from 56 patients with three forms of urinary tract diversion: ureterosigmoidostomy, isolated ileal and colon conduits. As expected, the rectal urine of all patients with a ureterosigmoidostomy had a rich bacterial flora. However, 11 of the 15 patients with ileal conduits (73%) had significant mixed growths of bacteria in the loop urine, whereas only six out of 16 colon loop urines (37.5%) were infected, all being monobacterial infections. The implications of these bacteriological findings for carcinogenesis associated with urinary diversion are discussed.

Bacteria↗

Lung structure as a risk factor in adverse pulmonary responses to asbestos exposure. A case-referent study in Quebec chrysotile miners and millers.

To investigate the hypothesis that lung structure may predispose to the development of asbestos-related pulmonary fibrosis, we carried out a case-referent study using data gathered in a cross-sectional study of Quebec chrysotile asbestos miners and millers. Tracheal and thoracic measurements were derived from the routine chest radiographs of 44 men with established radiologic fibrosis and compared with similar measurements for 88 men matched for age and cumulative exposure in the same industry who had not developed pulmonary fibrosis. Intrathoracic tracheal lengths were, on the average, shorter, and transthoracic diameters narrower in cases compared with those in referents. In addition, cases were shorter than the referents, suggesting that height might be an indirect measure of the structural characteristics relevant to the response to inhaled asbestos particles. Our findings are thus consistent with the hypothesis outlined, and they suggest a line of investigation that might be useful in relation to other inhaled pollutants.

Adult↗

Supportive group action for women: a self-help strategy.

A major goal of the demonstration project described was to test a model of self-help and voluntary support in developing groups for female single parents. Community meetings, study programs, and related experiential strategies were used to promote coping skills and strategies; access to resources; decision-making learning and responsibility; social contacts and networking; work skills and employment opportunities. The effectiveness of the model, which emphasized self-help, consumer power, and accessibility, was reflected in increased membership, self-awareness and confidence, leadership, employment and development of community resources. Initial individual contact, informal contracting, and community support were seen as important factors in the project's success.

Female↗

Neoplasia and ureterosigmoidostomy: a colonoscopy survey.

Patients who have undergone implantation of ureters into the sigmoid colon (ureterosigmoidostomy) are known to be at high risk of developing cancer of the colon many years later. The operation is often performed in infancy for congenital abnormalities of the bladder, thus creating a long term surveillance problem. Six of 34 patients (17.6 per cent) who had undergone ureterosigmoidostomy were found at a screening fibresigmoidoscopy to have adenomas of the left colon or severe dysplasia of the stoma, a mean interval of 22 years after their urinary diversion. Four other patients had previously had a sigmoid adenoma or cancer; thus, 29 per cent overall had developed colonic neoplasms, almost all closely related to their stomas. Another patient who, by error, was excluded from the surveillance, died of metastatic cancer of the sigmoid colon within the study period. Regular surveillance by fibresigmoidoscopy of patients who have had urinary diversion affords the opportunity to detect and remove potentially malignant sigmoid lesions. In addition to its clinical importance, it allows a closer study of this unique model of colon carcinogenesis.

Adenoma↗

Psychiatric interface with neurology: conflicts and cooperation.

The recent interest in biologically oriented psychiatry has opened up new opportunities for collaboration between psychiatry and neurology. Traditionally neurologists emphasized neuronal pathways and lateralizing signs, while psychiatrists' main interest was feeling states and emotions. Increasingly, both specialties are becoming aware of the complexity of the nervous system and the frequency with which neuronal disturbances and psychological conflict interact and influence treatment and outcome. The most important factor in facilitating an increased number of consultations and generating research protocols involves achieving a certain mutuality and complementary role between two disciplines. Traditionally there has been a fair amount of antagonism, primarily because of each specialty's insistence that its vantage point of view was correct. The consultation-liaison psychiatrist is in the ideal position to bring about a rapprochement. To achieve this, it is paramount that the psychiatrist understand and be conversant in the neurologist's language.

Conflict, Psychological↗

Longitudinal study of growth and development of young Jamaican children recovering from severe protein-energy malnutrition.

The developmental level and nutritional status of a group of 17 children aged between six and 24 months who were admitted to hospital with severe protein-energy malnutrition were studied from admission to hospital until 36 months after returning home. They were compared with a group of 14 adequately nourished children of similar age who had been admitted to hospital for other reasons. Initially the malnourished group were markedly behind the controls in developmental level, and they failed to reduce their deficit in hospital. Over the following 36 months they showed a gradual improvement relative to the controls in developmental level, height and head circumference, but were still significantly behind at the end of the study. In contrast, they caught up in weight for height by one month after returning home. When length of stay in hospital, age at admission, birthweight, mother's IQ and home background measures were taken into account, the direction of the differences between the two groups and significance levels were unchanged.

Body Height↗

Structure of the regular surface layer of Aquaspirillum serpens MW5.

The structure of the regular surface layer of Aquaspirillum serpens MW5 has been investigated by electon microscopy supplemented by computer image processing and least-squares analysis. The layer has a ribbed appearance, both on the bacterium and in isolated, negatively stained fragments. However, detailed analysis indicated that the layer was composed of two hexagonal sheets having p6mm symmetry and a = 16 nm. One sheet was staggered by one half repeat along a (1,0) line of the p6nm lattice relative to the second so that, in projection, the pattern of the composite layer was a translational moiré, characterized by a series of ribs spaced 16 nm apart. The ribbed layer had cmm symmetry with a = 32 nm and b = 18.5 nm. Analysis of this pattern indicated that the two p6nm hexagonal sheets were unevenly stained, and this was confirmed by using least-squares methods to simulate the observed pattern by combining two hexagonal patterns. The general structure of the layer was consistent with a role as a selective and protective barrier on the cell surface.

Cell Membrane↗

Advanced extragonadal germ-cell tumors. Successful treatment with combination chemotherapy.

Thirty-two patients with primary extragonadal germ-cell tumors were treated at Vanderbilt and Indiana University Hospitals during the period from 1967 to 1981. Thirty-one patients had far-advanced disease when treatment was begun. All patients received intensive cisplatin-containing combination chemotherapy regimens. Tumors remaining after chemotherapy were surgically removed when feasible. Of the 31 evaluable patients, 18 have been continuously disease-free after therapy, 21 patients had a complete remission; the remaining 10 had partial response. Eighty-nine percent of patients with complete remission remain free of disease after median follow-up of 30 months. No relapses occurred after 12 months of complete remission. Patients with partial response had a median survival of 9 months with no long-term survivors. Response rates and survival are similar to patients with advanced-stage testicular germ-cell tumors. Extragonadal germ-cell tumors are as curable as testicular germ-cell tumors when treated with intensive cisplatin-containing combination chemotherapy regimens, and surgical resection when necessary.

Adolescent↗