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Biomedical subjects

M Stephens

Publications and source records attributed to M Stephens.

At least 19 recordsLinked to original sources

Association mapping in structured populations.

The use, in association studies, of the forthcoming dense genomewide collection of single-nucleotide polymorphisms (SNPs) has been heralded as a potential breakthrough in the study of the genetic basis of common complex disorders. A serious problem with association mapping is that population structure can lead to spurious associations between a candidate marker and a phenotype. One common solution has been to abandon case-control studies in favor of family-based tests of association, such as the transmission/disequilibrium test (TDT), but this comes at a considerable cost in the need to collect DNA from close relatives of affected individuals. In this article we describe a novel, statistically valid, method for case-control association studies in structured populations. Our method uses a set of unlinked genetic markers to infer details of population structure, and to estimate the ancestry of sampled individuals, before using this information to test for associations within subpopulations. It provides power comparable with the TDT in many settings and may substantially outperform it if there are conflicting associations in different subpopulations.

Alleles

Cheilectomy for hallux rigidus.

Cheilectomy is the excision of an irregular osseous rim that interferes with joint motion. Twenty cases of hallux rigidus/limitus treated by cheilectomy have been reviewed 18 months after surgery. A satisfactory outcome was achieved in all but 2 cases, which were failures. Range of joint motion, in particular dorsi flexion, improved in all but 6 cases. Cheilectomy is a simple and effective alternative to arthrodesis in the treatment of hallux rigidus.

Adult

Combined high grade sarcoma and serous ovarian neoplasm.

A case of an ovarian serous epithelial neoplasm of borderline type admixed with sarcomatous elements is reported. This combination seems to be extremely rare with only four cases previously reported. It may represent a type of collision tumour or the development of a sarcoma in a growth with borderline differentiation.

Adenofibroma

Human articular surface chondrocytes initiate alkaline phosphatase and type X collagen synthesis in suspension culture.

The type X collagen is a short chain collagen associated with calcific cartilage and/or the expression of the hypertrophic chondrocyte phenotype. In articular cartilage, type X collagen is restricted to the basal zone of calcified cartilage adjacent to the subchondral bone. However, during pathological change such as in osteoarthritis, the synthesis of type X collagen becomes more widespread but never extends to the articular surface. Using immunocytochemistry and fluorography of newly synthesised collagens, we report that surface articular chondrocytes (which occupy the uppermost 10-15% of the tissue depth) from normal human cartilage initiate de novo synthesis of both type X collagen and alkaline phosphatase when maintained in suspension culture.

Alkaline Phosphatase

Fibre distribution in the lungs and pleura of subjects with asbestos related diffuse pleural fibrosis.

The lungs from 13 cases of diffuse pleural fibrosis associated with a history of exposure to asbestos were examined. Samples were taken from the visceral pleura and central and subpleural zones of the lungs for histopathological and mineralogical studies. The fibre type, size, and number were estimated for each of these regions by transmission electron microscopy and energy dispersive x ray analysis. Amphibole fibre counts were raised when compared with a non-occupationally exposed group and matched those seen in cases of pleural plaques, mild asbestosis, and mesothelioma. A wide case to case variation of distribution was seen. No significant difference was apparent between central and subpleural zones, whereas low asbestos counts were found in the pleura; these were mainly short chrysotile fibres. Within the lungs more (45%) of the longer (greater than 4 microns) and thinner (less than 0.25 micron) amphibole fibres were retained in keeping with other studies implicating such fibre profiles in the pathogenesis of asbestos related disease.

Aged

A computer-assisted health care cost management system.

To our knowledge, First Chicago has developed and implemented the first operational integrated health data computer system that includes the traditional occupational medicine data base together with medical claims and health risk appraisal data. OMNIS has combined medical claims, personnel, disability, employee assistance program, wellness program participation, administrative functions, laboratory, periodic health evaluation data, and health risk appraisal data in a single system. OMNIS provides data that are being used to more accurately predict health care and disability costs and design intervention strategies. Clearly, the integrated health data computer system provides information to manage increasingly complex issues of health care quality and cost. For companies concerned about the quality as well as the cost of health care, an integrated health data computer system (OMNIS) may be a valuable tool to objectively assess quality of care. For example, a company could evaluate how effectively various providers (eg, health maintenance organizations, preferred provider organizations, indemnity plan) control medical conditions such as hypertension. Integrated health data management systems have the potential to assist in the selection of the highest quality and most cost-effective health care plans.

Chicago

Radiosensitizing and cytotoxic effects of nitroimidazoles in CHO cells expressing elevated levels of glutathione-S-transferase.

A cell line, CHO-Chlr, which has elevated levels of glutathione-S-transferase (GST), is resistant to damage caused by bi-functional nitrogen mustards. This cell line has a similar radiation sensitivity to and value of oxygen enhancement ratio as the wild type cells, CHO-K1, from which the mutant line was derived. Hypoxic cell radiosensitizing efficiencies for misonidazole, etanidazole (SR2508), and pimonidazole (R0 03-8799) are similar in both cell lines with values for C1.6 of 0.5, 0.75, and 0.08 mmol dm-3 for each drug respectively. In contrast, for RSU 1069 the sensitizing efficiency is lower in the cell line showing elevated levels of GST. The hypoxic toxicity of RSU 1069 and misonidazole is similar in each cell line, whereas in air, toxicity is 2 fold less in the CHO-Chlr cells. These results suggest that reaction of the alkylating aziridine part of RSU 1069 contributes to the high sensitizing efficiency of this drug. This is likely to be a consequence of either binding of the sensitizing moiety at the target site (ie, increased local concentration or induction of sub-lethal damage that is only expressed on subsequent irradiation.

Animals

The sensitivity of gentamicin-resistant gram-negative bacilli to cefotaxime, other cephalosporins and aminoglycosides.

The sensitivities of 80 gentamicin-resistant gram-negative bacilli to cefotaxime, cefuroxime, cefoxitin, cefamandole, cefazolin, tobramycin, netilmicin and amikacin were determined. Amikacin was the most active amino-glycoside. However, the percentage sensitivity to cefotaxime of most of the species was higher than, or equal to any of the other antibiotics tested. Cefotaxime was particulary active against Providencia spp., Serratia spp., Klebsiella spp., and Pseudomonas maltophilia, being 16 to 256 times more active than the next best cephalosporin or cephamycin. Clinical trials of cefotaxime are now required.

Acinetobacter

A hospital epidemic caused by gentamicin-resistant Klebsiella aerogenes.

In the 15 months, February 1976 to April 1977, more than 241 patients became colonized with a strain of Klebsiella aerogenes, capsular serotype K2, resistant to most antibiotics. Urinary tract infection was the most common clinical manifestation but bacteraemia and, occasionally, infections of other sites were encountered. The main reservoir of the epidemic klebsiella was the gut, urine and skin of colonized patients. Gut carriage among staff was very uncommon. The most susceptible patients were elderly males, with debilitating illnesses and urinary tract abnormalities, especially if they were catheterized or receiving antibiotics. Likely vehicles for spread were the hands of staff, and contaminated bedpans and urinals. Control measures were directed at these factors. At the end of April 1977 no new cases had occurred for 3 months in the ward in which the outbreak began, and which had been the main focus of infection, and only 5 patients in the affected hospitals were known to be colonized by the epidemic klebsiella.

Cross Infection