PubMed Health⌕ Search

Biomedical subjects

M Stephens

Publications and source records attributed to M Stephens.

At least 37 records · Page 2Linked to original sources

Times on trees, and the age of an allele.

In this paper we consider the genealogy of a random sample of n chromosomes from a panmictic population which has evolved with constant size N over many generations. We address two related problems. First we describe how genealogical information may be usefully partitioned into information on the events (mutations and coalescences) which occur in the genealogy, and the times between these events. We show that the distribution of the times given information on the events is particularly simple and describe how this can considerably reduce the computational burden when performing inference for these times. Second we investigate the effect on the genealogy of conditioning on a single mutation having occurred during the ancestry of the sample. In particular we use results from the first part of the paper to derive explicit formulae for the density of the age of a mutant allele, conditional on its frequency in either a sample or the population.

Aging↗

Inference of population structure using multilocus genotype data.

We describe a model-based clustering method for using multilocus genotype data to infer population structure and assign individuals to populations. We assume a model in which there are K populations (where K may be unknown), each of which is characterized by a set of allele frequencies at each locus. Individuals in the sample are assigned (probabilistically) to populations, or jointly to two or more populations if their genotypes indicate that they are admixed. Our model does not assume a particular mutation process, and it can be applied to most of the commonly used genetic markers, provided that they are not closely linked. Applications of our method include demonstrating the presence of population structure, assigning individuals to populations, studying hybrid zones, and identifying migrants and admixed individuals. We show that the method can produce highly accurate assignments using modest numbers of loci-e.g. , seven microsatellite loci in an example using genotype data from an endangered bird species. The software used for this article is available from http://www.stats.ox.ac.uk/ approximately pritch/home. html.

Algorithms↗

Malignant vascular tumours of the pleura in "asbestos" workers and endothelial differentiation in malignant mesothelioma.

BACKGROUND: Three cases of diffuse malignant vascular tumours of the pleura are described which mimicked malignant mesothelioma clinically and pathologically (so called "pseudomesothelioma"). All had occupational histories of exposure to asbestos. The relationship of these tumours to mesothelioma and asbestos exposure is discussed. METHODS: To examine the histogenetic relationship between mesothelioma and these three tumours an immunohistochemical analysis of vascular marker (CD31, CD34, and Von Willebrand factor) expression was undertaken in 92 cases of pleural mesothelioma, in addition to these three tumours. Electron microscopic fibre analysis of lung tissue was performed on each of the three cases to assess asbestos fibre content. RESULTS: Diffuse pleural epithelioid haemangioendotheliomas may closely resemble malignant mesothelioma clinically and pathologically but, of the 92 pleural mesotheliomas tested, none showed expression of CD31, CD34, and Von Willebrand factor. Although all three cases had claimed exposure to asbestos, ferruginous bodies typical of asbestos were only seen by light microscopy in case 2, and only in this subject was the asbestos fibre content raised in comparison with the range seen in a non-exposed background population. The latent period in the pleural epithelioid haemangioendotheliomas ranged from 18 to 60 years. CONCLUSIONS: Endothelial differentiation does not appear to occur in mesothelioma and therefore should be clearly separated from it. No definite association between pleural epithelioid haemangioendothelioma and exposure to asbestos can be made from this small series but further investigation is warranted.

Adult↗

Prospective study of a laparoscopically placed, adjustable gastric band in the treatment of morbid obesity.

BACKGROUND: Surgical control of morbid obesity should benefit from a minimally invasive approach and the ability to adjust the degree of gastric restriction. METHODS: The Lap-Band adjustable gastric banding system was evaluated prospectively in a consecutive series of 302 patients, and data on perioperative outcome and weight loss pattern at up to 4 years of follow-up are presented. Some 302 patients (89 per cent women; mean age 39 years, mean weight 124 kg) were entered into the study. Laparoscopic placement was used in 277 patients. Previous gastric stapling surgery was the principal reason for an elective open approach. RESULTS: The incidence of significant early complications was 4 per cent and included two perforations of the stomach after open placement. The mean length of stay after laparoscopic placement was 3.9 days and only one complication (infected reservoir site) occurred in these patients. The principal late complication of prolapse of the stomach through the band occurred in 27 patients (9 per cent). Significant modification of technique and patient care has enabled reduction of this complication in the latter part of the series. Mean(s.d.) excess weight loss was 51.0(17) per cent at 12 months (n = 120), 58.3(20) per cent at 24 months (n = 43), 61.6(2) per cent at 36 months (n = 25) and 682(21) per cent at 48 months (n = 12). CONCLUSION: The Lap-Band is an effective method for achieving good weight loss in the morbidly obese at up to 4 years of follow-up. Laparoscopic placement has been associated with a short length of stay and a low frequency of complications. The ability to adjust the setting of the device to achieve different degrees of gastric restriction has enabled progressive weight loss throughout the period of study.

Adolescent↗

Effect of caffeine consumption on tissue oxygen levels during hyperbaric oxygen treatment.

Ten men were exposed to hyperbaric oxygen (HBO2), and their tissue oxygen levels were monitored after they drank either placebo or caffeine beverages. Transcutaneous tissue oxygen (PtcO2) monitor measurements in a normobaric air environment were initially obtained from transducers on the subject's chest and foot. The subjects then consumed either the caffeine (3 mg.kg-1) or the placebo beverage, and after 20 min the subjects were pressurized in a hyperbaric chamber to 2.36 atm abs (1 atm = 101.3250 kPa). The test subjects began breathing 100% oxygen at 2.36 atm abs, 30 min after administration of the experimental beverage, and continued for 30 min, after which the final chest and foot PtcO2 measurements were recorded (1 h after ingestion of the test drink). Each subject underwent a second hyperbaric exposure during which the alternate drink was administered (either the placebo or the caffeine), and PtcO2 measurements were again obtained. The increase in right foot PtcO2 values during HBO2 exposure was significantly smaller after caffeine consumption than after placebo (P = 0.0018).

Adult↗

Molecular characterisation of tumour infiltrating lymphocytes in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is often associated with a lymphocytic infiltrate that is believed to represent an in vivo immune reaction to the tumour cells. In this study, the tumour-infiltrating lymphocytes (TIL) associated with primary OSCC were characterised molecularly in six newly-diagnosed patients to determine the nature of the immune response to the primary tumour. The primary tumours in three of the six patients were associated with a moderate to dense CD8+ T cell infiltrate whilst the cellular infiltrate in the other primary tumours was sparse. The CD3+ T cells were also HLA-DR+. In all cases, there were few CD56+ cells, suggesting that TIL were predominantly T cells bearing the alpha/beta T cell receptors (TCR). The TCR Vbeta repertoire of TIL in these six cases was analysed. TCR Vbeta gene usage by TIL was heterogeneous. A restricted usage of TCR Vbeta genes by TIL was evident in two tumours associated with a dense CD3+ T cell infiltrate. In one of these, there was histological evidence of tumour cell destruction by TIL. Further analysis of the predominant TCR Vbeta gene family used by TIL in this individual showed a unique in-frame nucleotide sequence in 100% of the transcripts. This recurrent transcript was not detected in the peripheral blood of this patient, indicating a local T cell clonal expansion in the vicinity of the tumour. Overall, these results suggest that activation and clonal expansion of T cells occurs and may play a role in local tumour destruction in OSCC.

Adult↗

Smoking prevalence, quit attempts and successes.

OBJECTIVES: This article provides a brief overview and update of Canadian smoking trends since 1966. It presents the characteristics of daily smokers who have successfully quit as well as those who have tried to quit but continue to smoke daily. DATA SOURCES: The time series smoking data are from a variety of surveys. The analyses pertaining to individuals who tried to quit smoking and those who successfully quit are based on a Health Canada-sponsored supplement to the 1994/95 National Population Health Survey (NPHS). MAIN RESULTS: In contrast to the overall trend, smoking rates among teens have been rising in the 1990s. Approximately 16% of daily smokers reported that they had recently stopped smoking. The majority of former daily smokers indicated that their main reason for quitting was concern about their future health. The vast majority reported that they had gone cold turkey. About four in ten daily smokers reported that they had tried, unsuccessfully to quit smoking in the 12 months before their NPHS interview.

Adolescent↗

Progression of borderline increases in albuminuria in adolescents with insulin-dependent diabetes mellitus.

We aimed to determine the natural history of borderline increases in albuminuria in adolescents with insulin-dependent (Type 1) diabetes mellitus (IDDM) and factors which are associated with progression to persistent microalbuminura. Fifty-five normotensive adolescents with IDDM and intermittent microalbuminura (overnight albumin excretion ratte of 20-200 micrograms min-1 on one of three consecutive timed collections, n = 29) or borderline albuminura (mean overnight albumin excretion rate of 7.2-20 micrograms min-1 on one of three consecutive timed collections, n = 30) were followed prospectively at 3 monthly intervals. The endpoint was persistent microalbuminuria defined as a minimum of three of four consecutive overnight albumin excretion rates of greater than 20 micrograms min-1. One hundred and forty-two adolescents with IDDM and normoalbuminura were also followed prospectively. Fifteen of the 59 patients (25.4%) with intermittent (9/29) or borderline (6/30) albuminura progressed to persistent microalbuminura (progressors) over 28 (15-50) months [median (range)] in comparison with two of the 142 patients with normoalbuminuria at entry (relative risk = 12.6; p = 0.001). Progressors to persistent microalbuminura were pubertal and had higher systolic (p = 0.02) and diastolic (p = 0.02) blood pressure, and HbA1c (p = 0.004) than non-progressors. All patients remained normotensive. Glomerular filtration rate, apolipoproteins, dietary phosphorus, protein and sodium intakes, and prevalence of smoking did not differ between progressors and non-progressors. Total renin was higher in the diabetic patients without a difference between progressors and non-progressors. In conclusion there is a relatively high rate of progression to persistent microalbuminuria in pubertal adolescents with borderline increases in albuminura and duration greater than 3 years. These patients require attention to minimize associated factors of poor metabolic control and higher blood pressure in the development of incipient nephropathy.

Adolescent↗

T-cell receptor V beta usage by lesional lymphocytes in oral lichen planus.

To determine whether the T-cell inflammatory infiltrate in oral lichen planus (OLP) represents a selective activation and expansion of a limited repertoire of T-cell receptor (TCR) specific T-cells, V beta gene expression was investigated in lesional T-lymphocytes in OLP. A reverse transcriptase-polymerase chain reaction (RT-PCR) technique was used to amplify the 24 major V beta gene sub-families of infiltrating mucosal lymphocytes and peripheral blood mononuclear cells (PMNC) in seven patients with reticular OLP and four healthy control patients. Specificity of amplified products was confirmed by Southern blotting with a C beta internal probe. TCR V beta usage by lesional T-cells in OLP was markedly heterogeneous 5-23 V beta sub-families). In 6/8 patients with OLP, V beta usage was restricted with < or = 20/25 sub-families detected; only one of the V beta sub-families (V beta 8) was present in all of the OLP patients demonstrating TCR V beta restriction. In contrast, TCR V beta usage was unrestricted in PMNC from OLP patients and controls (> or = 23/ 25 sub-families detected). In three patients, certain V beta sub-families (V beta 13, V beta 14 & V beta 15) were present in the lesional T-cell population but were under-represented in PMNC. These results suggest a selective V beta gene usage by lesional infiltrating T-cells in oral lichen planus. The non-uniformity of V beta restriction in lesional T-cells does not support the concept of a common superantigen in OLP and reflects the heterogeneity of the disease.

Adult↗

Tendon shift in hallux valgus: observations at MR imaging.

OBJECTIVE: This study was undertaken to demonstrate a shift in tendon alignment at the first metatarsophalangeal joint in patients with hallux valgus by means of magnetic resonance imaging. DESIGN: Ten normal feet and 20 feet with the hallux valgus deformity conforming to conventional clinical and radiographic criteria were prospectively studied using magnetic resonance imaging. Correlation was made between tendon position at the first metatarsophalangeal joint and the severity of the hallux valgus deformity. RESULTS: There is a significant shift in tendon position at the first metatarsophalangeal joint of patients with hallux valgus. The insertion of the abductor hallucis tendon is markedly plantarward and the flexor and extensor tendons bowstring at the first metatarsophalangeal joint compared with patients without the deformity. The severity of the tendon shift correlates with the hallux valgus angle and clinical severity of the hallux valgus deformity in each case. CONCLUSION: Patients with hallux valgus have a significant tendon shift at the first metatarsophalangeal joint which appears to contribute to development of the deformity.

Case-Control Studies↗

Scaphoid osteochondroma mimicking carpal coalition.

We present the case of a 10-year-old girl who presented with a block to wrist abduction. Plain radiographs of the wrist suggested a coalition between the carpal bones. A CT scan, however, revealed the presence of an osteocartilaginous lesion on the distal pole of the scaphoid. This was resected and histology showed it to be an osteochondroma.

Bone Neoplasms↗

Surgical correction of a simian foot.

Congenital varus deformity of the first metatarsal can be secondary to the abnormal insertion of abductor hallucis, a space-occupying lesion of the first web space, or hypoplasia of the metatarsal. We report a unique case where all three factors were present in one foot. This was combined with talipes equinovarus, which gave the appearance of a simian or hand-like foot.

Female↗