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Biomedical subjects

S Harris

Publications and source records attributed to S Harris.

At least 37 records · Page 2Linked to original sources
PubMed2004

Effects of the European Working Time Directive on anaesthetic training in the United Kingdom.

Decreases in the hours worked by trainee anaesthetists are being brought about by both the New Deal for Trainees and the European Working Time Directive. Anticipated improvements in health and safety achieved by a decrease in hours will be at the expense of training time if the amount of night-time work remains constant. This audit examined the effects of a change from a partial to a full shift system on a cohort of trainee anaesthetists working in a large district general hospital in the South-west of England. Logbook and list analyses were performed for two 10-week periods: one before and one after the decrease in hours. An 18% decrease in the number of cases done and an 11% decrease in the number of weekly training lists were found for specialist registrars. A 22% decrease in the number of cases done and a 14% decrease in the number of weekly training lists were found for senior house officers. Furthermore, a decrease of one service list per specialist registrar per week was seen, which will have implications for consultant manpower requirements.

Anesthesiology↗
PubMed2004

Multiple congenital melanocytic naevi presenting with neurofibroma-like lesions complicated by malignant melanoma.

Giant congenital pigmented naevi and neurofibromatosis (NF-1) may rarely occur together. We report an unusual case where extensive congenital melanocytic naevi were associated with neurofibroma-like lesions that were clinically and histologically confused with neurofibromatosis. The development of malignant melanomas within the pigmented and pendulous lesions representing multiple congenital melanocytic naevi highlights the importance of an accurate diagnosis and a close follow-up of such patients.

Diagnosis, Differential↗
PubMed2004

Risk of disease from wildlife reservoirs: badgers, cattle, and bovine tuberculosis.

Livestock face complex foraging options associated with optimizing nutrient intake while being able to avoid areas posing risk of parasites or disease. Areas of tall nutrient-rich swards around fecal deposits may be attractive for grazing, but might incur fitness costs from parasites. We use the example of dairy cattle and the risks of tuberculosis transmission posed to them by pastures contaminated with badger excreta to examine this trade-off. A risk may be posed either by aerosolized inhalation through investigation or by ingestion via grazing contaminated swards. We quantified the levels of investigation and grazing of 150 dairy cows at badger latrines (accumulations of feces and urine) and crossing points (urination-only sites). Grazing behavior was compared between strip-grazed and rotation-grazed fields. Strip grazing had fields subdivided for grazing periods of <24 h, whereas rotational grazing involved access to whole fields for 1 to 7 d each. A higher proportion of the herd investigated badger latrines than crossing points or controls. Cattle initially avoided swards around badger latrines but not around crossing points. Avoidance periods were shorter in strip-compared with rotation-grazing systems. In rotation-grazing management, latrines were avoided for longer times, but there were more investigative contacts than with strip-grazing management. If investigation is a major route of tuberculosis transmission, the risk to cattle is greatest in extensive rotation-grazing systems. However, if ingestion of fresh urine is the primary method of transmission, strip-grazing management may pose a greater threat. Farming systems affect the level and type of contact between livestock and wildlife excreta and thus the risks of disease.

Agriculture↗
PubMed2003

Adjuvant interferon in high-risk melanoma: the AIM HIGH Study--United Kingdom Coordinating Committee on Cancer Research randomized study of adjuvant low-dose extended-duration interferon Alfa-2a in high-risk resected malignant melanoma.

PURPOSE: To evaluate low-dose extended duration interferon alfa-2a as adjuvant therapy in patients with thick (> or = 4 mm) primary cutaneous melanoma and/or locoregional metastases. PATIENTS AND METHODS: In this randomized controlled trial involving 674 patients, the effect of interferon alfa-2a (3 megaunits three times per week for 2 years or until recurrence) on overall survival (OS) and recurrence-free survival (RFS) was compared with that of no further treatment in radically resected stage IIB and stage III cutaneous malignant melanoma. RESULTS: The OS and RFS rates at 5 years were 44% (SE, 2.6) and 32% (SE, 2.1), respectively. There was no significant difference in OS or RFS between the interferon-treated and control arms (odds ratio [OR], 0.94; 95% CI, 0.75 to 1.18; P =.6; and OR, 0.91; 95% CI, 0.75 to 1.10; P =.3; respectively). Male sex (P =.003) and regional lymph node involvement (P =.0009), but not age (P =.7), were statistically significant adverse features for OS. Subgroup analysis by disease stage, age, and sex did not show any clear differences between interferon-treated and control groups in either OS or RFS. Interferon-related toxicities were modest: grade 3 (and in only one case, grade 4) fatigue or mood disturbance was seen in 7% and 4% respectively, of patients. However, there were 50 withdrawals (15%) from interferon treatment due to toxicity. CONCLUSION: The results from this study, taken in isolation, do not indicate that extended-duration low-dose interferon is significantly better than observation alone in the initial treatment of completely resected high-risk malignant melanoma.

Adolescent↗
PubMed2003

Traveling waves with dispersive variability and time delay.

We first determine an approximate traveling wave profile for the Cook model [J. Murray, Mathematical Biology I: An Introduction (Springer, New York, 2002), pp. 471-478] for the case in which the number of dispersers is small relative to the number of nondispersers. The results are consistent with the previous linearized wavefront analysis that predicts, counterintuitively, that relatively few dispersers can drive the population expansion wave with a wavespeed not too different from that for the case of a single dispersing population as described by the Fisher equation. The method of solution differs from that used in the latter case since here the dimensionless wavespeed is close to unity. We next generalize the Cook model to include time-delay effects. While the Cook model, like the Fisher equation, does not adequately describe the wave of advance during the Neolithic transition in Europe, we show that the generalized Cook model provides a close agreement with the historical record.

Journal Article↗
PubMed2003

Comparison of the incidence rates of selected gastrointestinal events reported for patients prescribed celecoxib and meloxicam in general practice in England using prescription-event monitoring (PEM) data.

BACKGROUND: Celecoxib and meloxicam are classified as cyclo-oxygenase (COX)-2 selective inhibitors, and were developed to minimize the risk of gastrointestinal (GI) toxicity commonly associated with non-steroidal anti-inflammatory drugs (NSAIDs). The Drug Safety Research Unit (DSRU) monitored the safety of these drugs immediately after launch in England using the non-interventional observational cohort technique of prescription-event monitoring (PEM). Our objective was to investigate whether there is a clinically relevant difference in incidence of reported symptomatic (acid/peptic) and complicated upper GI conditions (perforations/bleeding) between celecoxib and meloxicam during use in general practice. METHODS: Patients were identified from dispensed prescriptions written by general practitioners (GPs) for meloxicam (December 1996 to March 1997) and celecoxib (May to December 2000). Simple questionnaires requesting details of events occurring during/after treatment and potential risk factors (including age, sex, history of upper GI problems, and NSAIDS prescribed within 3 months of treatment) were posted to prescribing GPs at least 6 months after the first prescription for each patient. Incidence rates of the first event were calculated; crude and adjusted rate ratios (RR) obtained using regression modelling. RESULTS: For celecoxib and meloxicam, respectively, 1054 (6.0%) and 1376 (7.2%) patients had symptomatic (acid/peptic) upper GI events whereas 42 (0.2%) and 67 (0.4%) had complicated upper GI conditions (perforations/bleeding). A higher proportion of the celecoxib cohort had an indication for osteoarthritis (28.1 vs 23.2%), were female (68.3 vs 67.1%), were aged 60 yr or more (59.5 vs 55.0%), were prescribed NSAIDs within 3 months of starting treatment (49.4 vs 47.9%), and had a past medical history of upper GI conditions (54.7 vs 29.2%) than those prescribed meloxicam. This suggests differential channelling of groups at higher risk of such events on to celecoxib compared with meloxicam. There was no difference between the two drugs in the time to occurrence of either group of event. The RR over the 270-day study period for celecoxib compared with meloxicam were 0.77 (95% CI 0.69, 0.85) and 0.56 (95% CI 0.32, 0.96) for symptomatic (acid/peptic) upper GI events and complicated upper GI conditions (perforations/bleeding), respectively, adjusted for age, age2, sex, indication, medical history of upper GI problems and whether NSAIDs were prescribed within 3 months prior to starting treatment. CONCLUSIONS: This study reports a relative reduction (23%) in the incidence of symptomatic (acid/peptic) GI events, and a relative reduction (44%) in the incidence rate of complicated upper GI conditions (perforations/bleeding) for celecoxib compared with meloxicam.

Adult↗
PubMed2003

Clines: a reductionist model.

A piecewise linear model is used to provide a caricature of the nonlinear equation describing genetic variation due to migration and local natural selection in an inhomogeneous bounded habitat. The conditions for which nontrivial spatially-dependent steady state solutions exist are analytically determined together with these solutions for three distinct scenarios. For the usual case of no flux (Neumann) boundary conditions, explicit solutions require additional information to fix the genetic frequency within the habitat. This difficulty can be bypassed in two of the scenarios considered (this is an artifact of the model), but in the remaining scenario it is necessary to take into account the connection with the initial data to explicitly determine the steady state frequency. Some numerical examples are considered for each of the scenarios to illustrate the analytical results that are the primary focus of the work presented here.

Gene Frequency↗
PubMed2002

Addendum to "Random population dispersal in a linear hostile environment".

We extend the previous results, describing the population dispersal that occurs in some insects and small animal populations when this process is not strictly random, by including both the downgradient diffusion and the full Pearl-Verhulst logistic growth term in the equation of evolution. Motivated by the increasing fragmentation of natural habitats that is the result of human activities, we consider a finite habitat surrounded by a hostile environment. Previous work [Phys Rev. E 62, 4032 (2000)] considered only the case of an unbounded habitat, obviating issues concerned with the critical habitat size and the adoption of strategies best suited to achieve lower densities by dispersal through downgradient diffusion.

Journal Article↗
PubMed2002

Recall of early menstrual history and menarcheal body size: after 30 years, how well do women remember?

The validity of recall of early menstrual characteristics is of interest because of their putative role in the etiology of breast cancer and other diseases. A retrospective follow-up of the Newton Girls Study (1965-1975) provided an opportunity to assess the accuracy and precision of recall of several early menstrual characteristics. In 1998-1999, 57 percent of the original 793 Newton Girls Study participants completed a mailed questionnaire to assess the accuracy of recall for age and body size at menarche, usual cycle length during the first 2 years, and age at regularity. Recalled and original age at menarche were highly correlated (r = 0.79, p < 0.001). The body mass index percentile at menarche was well correlated with recalled body size at menarche (r = 0.61, p < 0.001), but with some evidence of systematic bias. Overall, a woman's recall of menarcheal age and body size was better than recall of cycle length and occurrence of regularity. The failure to identify certain menstrual characteristics as exposures for subsequent disease may reflect limitations in the accuracy and precision of the recalled measures.

Adult↗
PubMed2002

Niemann-Pick disease type C in adults.

Although it is often perceived as a paediatric disorder, significant numbers of patients with Niemann-Pick disease type C present for the first time in adult life or survive into adult life. The presentation in these patients differs from that seen in the classical juvenile form of the disease. Adult patients are often referred to clinicians with psychosis or other major psychiatric problems. The dystonia with preserved intellectual functioning can be mistaken for other basal ganglia disorders such as Wilson disease. The presence of vertical gaze palsy is an important clinical clue and, in the presence of a modest increase in plasma chitotriosidase activity, can be very helpful in the differential diagnosis. The diagnosis should be confirmed in suspected cases by filipin staining of cultured fibroblasts, as well as cholesterol esterification studies and DNA mutation analysis.

Adolescent↗
PubMed2002

Computerized information-gathering in specialist rheumatology clinics: an initial evaluation of an electronic version of the Short Form 36.

OBJECTIVES: Longitudinal outcome data are important for research and are becoming part of routine clinical practice. We assessed an initial version of an electronic Short Form 36 (SF-36), a well-established health assessment questionnaire, in comparison with standard paper forms, in two specialist rheumatology clinics. METHODS: Out-patients (20 with systemic lupus erythematosus and 31 with vasculitis) were randomly selected to complete either paper (n=29) or electronic and paper SF-36 versions (n=51) before and after consultation (paper vs paper comparison). Data were evaluated as the response correlation, internal consistency, missing data, patient satisfaction and preference. RESULTS: There were very good correlations in SF-36 responses (P<0.001) between the paper and electronic forms and the paper and paper forms. Internal reliability coefficients (Cronbach's alpha) showed good internal consistency for all reported responses in either computer or paper forms. There were no missing data in the computerized version but 24% of patients failed to answer all of the paper form questions. Ease of use of the computer version was rated highly by 71% of all the respondents, and 69% would prefer to use the computer version in future. DISCUSSION: Computerized data collection is acceptable to patients and feasible in clinical settings. It provides responses that are at least comparable to those to the paper form, improves data capture and is available immediately.

Ambulatory Care↗
PubMed2002

MLO-Y4 osteocyte-like cells support osteoclast formation and activation.

Osteocytes are terminally differentiated cells of the osteoblast lineage that have become embedded in mineralized matrix and may send signals that regulate bone modeling and remodeling. The hypothesis to be tested in this study is that osteocytes can stimulate and support osteoclast formation and activation. To test this hypothesis, an osteocyte-like cell line called MLO-Y4 and primary murine osteocytes were used in coculture with spleen or marrow cells. MLO-Y4 cells support osteoclast formation in the absence of 1,25-dihydroxyvitamin D3 [1,25(OD)2D3] or any other exogenous osteotropic factor. These cells alone stimulate osteoclast formation to the same extent or greater than adding 1,25(OH)2D3. Coaddition of 1,25(OH)2D3 with MLO-Y4 cells synergistically increased osteoclast formation. Optimal osteoclast formation and pit formation on dentine was observed with 200-1,000 MLO-Y4 cells per 0.75-cm2 well. No osteoclast formation was observed with 2T3, OCT-1, or MC3T3-E1 osteoblast cells (1,000 cells/well). Conditioned media from the MLO-Y4 cells had no effect on osteoclast formation, indicating that cell contact is necessary. Serial digestions of 2-week-old mouse calvaria yielded populations of cells that support osteoclast formation when cocultured with 1,25(OH)2D3 and marrow, but the population that remained in the bone particles supported the greatest number of osteoclasts with or without 1,25(OH)2D3. To examine the mechanism whereby these cells support osteoclast formation, the MLO-Y4 cells were compared with a series of osteoblast and stromal cells for expression of macrophage colony-stimulating factor (M-CSF), RANKL, and osteoprotegerin (OPG). MLO-Y4 cells express and secrete large amounts of M-CSF. MLO-Y4 cells express RANKL on their surface and their dendritic processes. The ratio of RANKL to OPG mRNA is greatest in the MLO-Y4 cells compared with the other cell types. RANK-Fc and OPG-Fc blocked the formation of osteoclasts by MLO-Y4 cells. These studies suggest that both RANKL and OPG may play a role in osteocyte signaling, OPG and M-CSF as soluble factors and RANKL as a surface molecule that is functional in osteocytes or along their exposed dendritic processes.

Animals↗
PubMed2001

Transgenic knockouts as part of high-throughput, evidence-based target selection and validation strategies.

The worldwide genome sequencing projects are helping to define the size and complexity of the expressed genome and are thereby identifying an unprecedented number of genes of uncertain disease alignment and unknown function. It is widely recognized that, within the pharmaceutical industry, a significant commercial advantage will accrue to those companies that most effectively gather and integrate additional biological information into their therapeutic target selection and drug progression strategies. This article presents the rationale for including comparative phenotypic information obtained from transgenic gene knockouts as an integral part of any future therapeutic target selection strategy.

Journal Article↗
PubMed2001

Lifestyles, diets, and Native American exposure factors related to possible lead exposures and toxicity.

Lead exposure is still a national concern, and it is possible that Native Americans who live on reservations and pursue traditional lifestyles may be at higher risk through both their unique exposure profiles and their potentially greater sensitivity. A major component of the exposure assessment is the diet. For tribal members, traditional lifestyles that include native foods, medicines, and traditional practices have evolved and proven to be the most healthful over many thousands of years of coexistence with the environment. However, a completely traditional diet may not be fully available for a variety of reasons; so, one must also consider the adverse health consequences caused by the loss of healthy native foods and medicines, the contamination of remaining native foods, the inability to practice one's religion, and the possibly lower quality of the substitute diet. Health evaluations of lead exposure on reservations should therefore consider at least two types of diets in addition to the typical suburban diet: (a) traditional diets composed of native foods and medicines that would result in increased exposure if the plants and animals are contaminated and (b) disadvantaged or commodity food diets that result in widespread vitamin and mineral deficits of the sort known to increase absorption of and response to lead. Additional exposure to lead might come from reservation housing which is often older, although the prevalence of lead-based paint on reservations is unknown. The degree of physiological response could also be affected by widespread exposures to other neurotoxins (such as mercury and PCBs in fish), underlying disease patterns, and genetics. Although each of these factors is plausible, their prevalence singly or in combination is unknown. Any correlation between these risk factors and blood lead levels on reservations is also unknown. This paper begins to address these gaps by discussing the range of traditional and current diets that may exist among tribes and methods for developing a whole-lifestyle exposure scenario that is appropriate for an individual tribe. Some of the factors discussed in this paper may not apply to the large population of Native Americans who live in urban situations.

Adult↗
PubMed2001

Fine mapping of Ath6, a quantitative trait locus for atherosclerosis in mice.

Ath6 is a novel quantitative trait locus associated with differences in susceptibility to atherosclerosis between C57BL/6J (B6) and C57BLKS/J (BKS) inbred mouse strains. Combining data from an intercross and a backcross (1593 meioses) between mice from B6 and BKS strains and from The Jackson Laboratory interspecific backcross panels, (C57BL/6J x Mus spretus) F1 x C57BL/6J and (C57BL/6J x SPRET/Ei) F1 x SPRET/Ei, we constructed a consensus genetic map and narrowed Ath6 to a 1.07 +/- 0.26 cM interval between the anonymous DNA marker D12Pgn4 and the gene Nmyc1. This region is near the proximal end of murine Chromosome (Chr) 12, which is homologous to the human chromosomal region 2p24-p25. Marker order in the Ath6 region was concordant among the two crosses and The Jackson Laboratory interspecific backcross panels. This high resolution map rules out candidate genes encoding apolipoprotein B, syndecan 1, and Adam17. The two Ath6 crosses have a combined potential resolution of 0.06 cM.

Alleles↗
PubMed2001

Dietary habits and dental health over the first 18 months of life.

OBJECTIVES: The main objective of this study was to describe the dental health of infants and toddlers with special reference to their dietary habits and oral hygiene behaviour over the first 18 months of life. METHODS: The longitudinal dietary data were obtained at 6, 12 and 18 months of age by using a 3-day weighed diet diary. Dental examinations were carried out at 12, and again at 18 months of age. The information on demographic factors and oral hygiene behaviours over the first 18 months of life was gathered by using a structured questionnaire at 12 and 18 months. RESULTS: 163 children were studied. Visible dental plaque was present in 18% and 25% of children at 12 and 18 months of age, respectively. No child had dental caries at either 12 or 18 months of age. There was a statistically significant correlation between visible plaque measured as plaque index at 12 months and the mean daily eating/drinking episodes at 6 months (r=0.25, P=0.001) and 12 months (r=0.15, P=0.05). The correlations between plaque index at 18 months and the mean eating/drinking episodes at both 12 months (r=0.2, P=0.04) and 18 months (r=0.2, P=0.02) were low but statistically significant. Nevertheless, there was no significant correlation between accumulation of plaque at either 12 or 18 months and the mean daily frequency consumption of food and drink containing non-milk extrinsic sugars (NMES) at any age. Children who brushed their teeth themselves were more likely to have visible plaque compared with children whose teeth were cleaned by their parents. The partial correlation showed that positive relation between mean daily eating/drinking episodes and plaque was not influenced by tooth brushing.

Analysis of Variance↗