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Biomedical subjects

Peter Smith

Publications and source records attributed to Peter Smith.

At least 37 records · Page 2Linked to original sources
PubMed2005

Age-related differences in work injuries: a multivariate, population-based study.

BACKGROUND: Many population-based studies find that the rate of work injuries is higher among adolescent and young adult workers compared to older adults. The present study examines age-related differences in work injuries, with an emphasis on adjusting for the potential confounding effects of job characteristics. METHODS: Age-related differences in work injuries were examined in a representative sample of 56,510 working Canadians aged 15 years and over. Respondents reported work-related injuries and job characteristics (e.g., occupation) in the past 12 months. Total hours worked in the past year were computed for each worker and accounted for in the logistic regressions. Analyses were stratified by gender. RESULTS: For men, adjusting for job characteristics substantially reduced, but did not eliminate the elevated risk status of adolescent and young adult workers. For women, only young adult women showed an elevated risk of work injury with job characteristics controlled. CONCLUSIONS: This is one of the few multivariate studies specifically examining contributors to age-related differences in work injuries in a population-based sample of workers. The substantial reduction in age-work injury association in the fully adjusted model suggests that differences in the types of jobs young workers hold play a critical role in their high-risk status.

Accidents, Occupational↗
PubMed2005

Qualitatively distinct patterns of cytokines are released by human dendritic cells in response to different pathogens.

Dendritic cells produce cytokines that regulate the class of the adaptive immune response. Microbial recognition is mediated, at least in part, by pattern recognition receptors such as Toll-like receptors, which influence dendritic cell maturation. In humans it is not yet clear how intact pathogens modulate the developing immune response. To address the effects of intact pathogens on the maturation and effector functions of human dendritic cells, we investigated their responses to a number of microbial pathogens. We studied a range of micro-organisms including Gram-negative bacteria (Escherichia coli and Salmonella enterica sv. typhimurium), Gram-positive cocci (Staphylococcus aureus) and atypical bacteria (Mycobacterium tuberculosis and Mycoplasma hominis) as well as the human protozoal parasite Trichomonas vaginalis. The micro-organisms were fixed in formaldehyde to prevent replication whilst preserving surface morphology. All the pathogens induced similar up-regulation of dendritic cell activation-associated cell surface markers but there was a profound difference in the patterns of cytokines produced by the stimulated dendritic cells. Some pathogens (E. coli, Salmonella enterica sv. typhimurium and S. aureus) induced interleukin-12 (IL-12), IL-10 and interferon-alpha whereas others (M. tuberculosis, Mycoplasma hominis and T. vaginalis) induced only IL-10. This differential effect was not altered by costimulation of the dendritic cells through CD40. These results support the notion that human dendritic cells are plastic in their response to microbial stimuli and that the nature of the pathogen dictates the response of the dendritic cell.

Animals↗
PubMed2005

Crystalloid deposits in the kidney.

Light chain-producing lymphoproliferative disorders such as multiple myeloma are frequently complicated by renal impairment. Typically, the renal biopsy of a patient with renal failure caused by multiple myeloma shows cast nephropathy, but occasionally crystals may be seen. We describe the case of a patient with acute renal failure caused by multiple myeloma in which, on renal and bone marrow biopsy, there were widespread crystalloid deposits. Crystalloid nephropathy is a very rare condition associated with multiple myeloma and other light chain-secreting disorders. An underlying lymphoproliferative disorder should be considered in the differential diagnosis if crystalloid deposits are seen on a renal or other tissue biopsy.

Acute Kidney Injury↗
PubMed2005

Fresh frozen plasma prepared with amotosalen HCl (S-59) photochemical pathogen inactivation: transfusion of patients with congenital coagulation factor deficiencies.

BACKGROUND: Photochemical treatment (PCT) with amotosalen HCl (S-59) was developed to inactivate pathogens and white blood cells in plasma (PCT-FFP) used for transfusion support. STUDY DESIGN AND METHODS: An open-label, multicenter trial was conducted in patients with congenital coagulation factor deficiencies (factors [F]I, FII, FV, FVII, FX, FXI, and FXIII and protein C) to measure the kinetics of specific coagulation factors, hemostatic efficacy, and safety of PCT-FFP. Posttransfusion prothrombin time (PT), partial thromboplastin time (PTT), and clinical hemostasis were evaluated before and after PCT-FFP transfusions. RESULTS: Thirty-four patients received 107 transfusions of PCT-FFP for kinetic studies or therapeutic indications (mean dose, 12.8 +/- 8.5 mL/kg). Incremental factor recoveries ranged from 0.9 to 2.4 IU per dL per IU per kg (FII, FV, FVII, FX, FXI, and protein C). Mean pretransfusion PT (20.7 +/- 22.2 sec) corrected after PCT-FFP (13.8 +/- 2.4 sec, p < 0.001). Mean pretransfusion PTT (51.2 +/- 29.3 sec) corrected after PCT-FFP (32.0 +/- 5.1 sec, p < 0.001). Thirteen patients required 77 transfusions for therapeutic indications. PCT-FFP provided effective hemostasis and was well tolerated. CONCLUSIONS: Replacement coagulation factors in PCT-FFP exhibited kinetics and therapeutic efficacy consistent with conventional FFP.

Adolescent↗
PubMed2005

Population pharmacokinetics of rifapentine and its primary desacetyl metabolite in South African tuberculosis patients.

This study was designed to describe the population pharmacokinetics of rifapentine (RFP) and 25-desacetyl RFP in a South African pulmonary tuberculosis patient population. Special reference was made to studying the influence of previous exposure to rifampin (RIF) and the variability in pharmacokinetic parameters between patients and between occasions and the influence of different covariates. Patients were included in the study if they had been receiving first-line antimycobacterial therapy (rifampin, isoniazid, pyrazinamide, and ethambutol) for not less than 4 weeks and not more than 6 weeks and were divided into three RFP dosage groups based on weight: 600 mg, <45 kg; 750 mg, 46 to 55 kg; and 900 mg, >55 kg. Participants received a single oral dose of RFP together with concomitant antimycobacterial agents, excluding RIF, on study days 1 and 5 after they ingested a soup-based meal. The RFP and 25-desacetyl RFP concentration-time data were analyzed by nonlinear mixed-effect modeling using NONMEM. The pharmacokinetics of the parent drug were modeled separately, and the individual pharmacokinetic parameters were used as inputs for the 25-desacetyl RFP pharmacokinetic model. A one-compartment disposition model was found to best describe the data for both the parent and the metabolite, and the metabolite was assumed to be formed only from the central compartment of the parent drug. Prior treatment with RIF did not alter the pharmacokinetics of RFP but appeared to increase the excretion of 25-desacetyl RFP in a nonlinear fashion. The RFP oral clearance and volume of distribution were found to increase by 0.049 liter/h and 0.691 liter, respectively, with a 1-kg increase from the median weight of 50 kg. The oral clearance of 25-desacetyl RFP was found to be 35% lower in female patients. The model developed here describes the population pharmacokinetics of RFP and its primary metabolite in tuberculosis patients and includes the effects of prior administration with RIF and covariate factors.

Adult↗
PubMed2005

Novel caprine adeno-associated virus (AAV) capsid (AAV-Go.1) is closely related to the primate AAV-5 and has unique tropism and neutralization properties.

Preexisting humoral immunity to adeno-associated virus (AAV) vectors may limit their clinical utility in gene delivery. We describe a novel caprine AAV (AAV-Go.1) capsid with unique biological properties. AAV-Go.1 capsid was cloned from goat-derived adenovirus preparations. Surprisingly, AAV-Go.1 capsid was 94% identical to the human AAV-5, with differences predicted to be largely on the surface and on or under the spike-like protrusions. In an in vitro neutralization assay using human immunoglobulin G (IgG) (intravenous immune globulin [IVIG]), AAV-Go.1 had higher resistance than AAV-5 (100-fold) and resistance similar to that of AAV-4 or AAV-8. In an in vivo model, SCID mice were pretreated with IVIG to generate normal human IgG plasma levels prior to the administration of AAV human factor IX vectors. Protein expression after intramuscular administration of AAV-Go.1 was unaffected in IVIG-pretreated mice, while it was reduced 5- and 10-fold after administration of AAV-1 and AAV-8, respectively. In contrast, protein expression after intravenous administration of AAV-Go.1 was reduced 7.1-fold, similar to the 3.8-fold reduction observed after AAV-8 administration in IVIG-pretreated mice, and protein expression was essentially extinguished after AAV-2 administration in mice pretreated with much less IVIG (15-fold). AAV-Go.1 vectors also demonstrated a marked tropism for lung when administered intravenously in SCID mice. The pulmonary tropism and high neutralization resistance to human preexisting antibodies suggest novel therapeutic uses for AAV-Go.1 vectors, including targeting diseases such as cystic fibrosis. Nonprimate sources of AAVs may be useful to identify additional capsids with distinct tropisms and high resistance to neutralization by human preexisting antibodies.

Amino Acid Sequence↗
PubMed2005

Physiological effects of major genes affecting ovulation rate in sheep.

Genetic mutations with major effects on ovulation rate in sheep were recently identified in two genes of the transforming growth factor (TGFbeta) superfamily and a TGFbeta receptor, namely bone morphogenetic protein 15 (BMP15), otherwise known as the growth differentiation factor 9b (GDF9b), GDF9 and activin-like kinase 6 (ALK6) otherwise known as the BMP receptor type IB (BMPRIB). Animals homozygous for the BMP15 or GDF9 mutations are anovulatory whereas animals heterozygous for BMP15 or GDF9 or heterozygous or homozygous for ALK6 have higher than normal ovulation rates. Immunisation of ewes against BMP15 or GDF9 shows that both are essential for normal follicular development and control of ovulation rate. Common features of fertile animals with the BMP15, ALK6 (and possibly GDF9) mutations are changes in oocyte development during early preantral follicular growth, earlier maturation of granulosa cells and ovulation of mature follicles at smaller diameters. In summary, these findings have led to a new paradigm in reproductive biology, namely that the oocyte plays a key role in regulating the ovulation rate.

Activins↗
PubMed2005

Discussing the COSTS of asthma: controlling outcomes, symptoms, and treatment strategies.

Asthma is a very common chronic disease characterized by clinically recurrent episodes of wheezing, dyspnea, chest tightness, and coughing. Both genetic and environmental factors appear to play major roles in the etiology of asthma. The economic and social costs of asthma are varied and far reaching. Patients suffer a significant decline in quality of life, and managed care organizations have become increasingly aware of its impact on health care expenditures. This article explores current treatment therapies for asthma, the challenges of managing asthma effectively, and strategies for improving outcomes in patients with asthma.

Asthma↗
PubMed2004

First Atmospheric Science Results from the Mars Exploration Rovers Mini-TES.

Thermal infrared spectra of the martian atmosphere taken by the Miniature Thermal Emission Spectrometer (Mini-TES) were used to determine the atmospheric temperatures in the planetary boundary layer and the column-integrated optical depth of aerosols. Mini-TES observations show the diurnal variation of the martian boundary layer thermal structure, including a near-surface superadiabatic layer during the afternoon and an inversion layer at night. Upward-looking Mini-TES observations show warm and cool parcels of air moving through the Mini-TES field of view on a time scale of 30 seconds. The retrieved dust optical depth shows a downward trend at both sites.

Algorithms↗
PubMed2004

Stages of embryonic development in the Atlantic cod Gadus morhua.

The early development of the Atlantic cod, Gadus morhua was studied from fertilization until first-feeding. Multiple families were reared at 7 degrees C and a developmental staging series was prepared using morphological landmarks visible with the light microscope. Stages were named rather than numbered to allow for future additions and broadly grouped into larger time intervals called periods. The most useful staging features were found to be initially cell number, and later in development, somite number. The mean cell cycle time for the first six cleavages was 135 min and the linear regression equation for development of somites(s) over time (t) was s = 0.29t - 18.14. The segmentation period began at 220 h postfertilization (hpf), and unlike some other teleosts, the addition of new somites continued throughout the majority of embryonic development, until just prior to hatching. Hatching occurred at 256 hpf, after which individuals remained motionless at the water's surface, undergoing negative phototaxis only after the first day posthatch. The first-feeding stage was reached at the end of the third day posthatch, subsequent to development of a functional jaw and hindgut. This staging series provides an essential baseline reference for future experiments involving developing cod embryos and for the aquaculture industry.

Animals↗
PubMed2004

Pathways of the determinants of unfavourable birth outcomes in Kenya.

This paper explores the pathways of the determinants of unfavourable birth outcomes, such as premature birth, the size of the baby at birth, and Caesarean section deliveries, in Kenya using graphical log-linear chain models. The results show that a number of factors that do not have direct associations with unfavourable birth outcomes contribute to these outcomes indirectly through intermediate factors. Marital status, the desirability of a pregnancy, the use of family planning and access to health facilities have no direct associations with poor birth outcomes, such as premature births and the small size of the baby at birth, but are linked to these outcomes through antenatal care. Antenatal care is identified as a central link between various sociodemographic or reproductive factors and birth outcomes.

Adult↗
PubMed2004

Measuring service quality provision within an eating disorders context.

Traditionally, research concerning quality measurement and improvement has centred on manufacturing and industrial sectors. In the last decade, however, the focus has turned to the measurement of quality in services and more recently to healthcare. In today's progressively competitive health-care environment hospitals increasingly realise the need service quality as a means to improve their competitive position. The aim of this study is to assess the service quality provision of a leading UK-based eating disorder service provider, achieved through the development and application of the SERVQUAL research instrument for measuring service quality. Following thematic analysis of service user feedback, six dimensions of service quality were identified and mapped on to the P-C-P attributes model. The approach adopted for this case study research may usefully inform service assessment programmes for similarly positioned health-care service providers.

Benchmarking↗
PubMed2004

Is patient choice an effective mechanism to reduce waiting times?

In many countries, patient choice is a routine part of the normal healthcare system. However, many choice initiatives in secondary care are part of policies aimed at reducing waiting times. This article provides evidence on the effectiveness of patient choice as a mechanism to reduce waiting times within a metropolitan area. The London Patient Choice Project was a large-scale pilot offering patients on hospital waiting lists a choice of alternative hospitals with shorter waiting times. A total of 22 500 patients were offered choice and 15 000 accepted. The acceptance rate of 66% was very high by international standards. In this article we address two questions. First, did the introduction of choice significantly reduce waiting times in London relative to the rest of the country where there was no choice? Second, how were the waiting times of London patients not offered choice affected by the choice regime? We examine the evidence on these issues for one specialty, orthopaedics. A difference-in-difference analysis is used to compare waiting times for hospitals within London before and after the introduction of choice. Although there was a small but significant reduction in waiting times in London relative to other areas where there was no patient choice, the main effect of the choice regime was to produce convergence of mean waiting times within London. Convergence was achieved by bringing down waiting times at the hospitals with high waiting times to the levels that prevailed in hospitals with low waiting times. This represented a clear improvement in equity of access, an important objective of the English National Health Service.

Choice Behavior↗
PubMed2003

Synthesis of totarol amino alcohol derivatives and their antiplasmodial activity and cytotoxicity.

The previously unknown antiplasmodial activity of the plant derived natural product totarol is reported. Novel beta-amino alcohol derivatives based on this natural product were designed, synthesised and evaluated for in vitro antiplasmodial activity and cytotoxicity. These derivatives showed antiplasmodial IC50 values in the range of 0.6-3.0 microM and were equally active against a chloroquine-sensitive and resistant strain of Plasmodium falciparum, while showing little cytotoxicity against a mammalian cell line (CHO). In terms of lead development, two of the compounds based on substituted phenylpiperazine warrant further investigation as potential antiplasmodial leads. In addition to their selective antiplasmodial activity and lack of chloroquine cross-resistance, these compounds are structurally different to any of the available antimalarial drugs.

Abietanes↗