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Biomedical subjects

S Marshall

Publications and source records attributed to S Marshall.

At least 37 records · Page 2Linked to original sources

Identification of ICAM-1 polymorphism that is associated with protection from transplant associated vasculopathy after cardiac transplantation.

Transplant associated coronary disease (TxCAD) is the main cause of late graft loss following cardiac transplantation. It is a multifactorial disease with immunologic and nonimmunologic components involved. This study was undertaken to analyze the gene polymorphism in adhesion molecules in donors and recipients and to investigate its potential association with the development of TxCAD. A total of 82 cardiac transplant patients, 96 donors and 101 UK controls, were genotyped retrospectively. Nine nucleotide polymorphisms in L-selectin, E-selectin, ICAM-1, and PECAM were analyzed using allele-specific PCR-SSP assay. Recipients were selected on the basis of the development of TxCAD: patients who had developed TxCAD within 2 years after transplantation, and patients who did not have TxCAD within 4.5-5 years after transplantation. All recipients received CyA and azathioprine as a primary immunosuppression. Associations were assessed by using Fisher's exact test. No association was found between E-selectin, L-selectin, and PECAM allele or genotype frequencies and TxCAD. However, the donors whose recipients did not develop TxCAD at first 2 years had a significant increase of ICAM-1 E-469 allele compared with donors, whose recipients developed TxCAD (63.8% vs 46.4%, p = 0.042) and to UK controls (63.8% vs 47%, p = 0.04). Moreover, we found that the decreased frequency of ICAM E469 allele was associated with the increased number of rejection episodes. The 469 E/K polymorphism is in exon 6 and results in a change from glutamic acid to lysine in Ig-like domain 5 of ICAM-1, which is thought to affect interactions with LFA-1 and adhesion of B-cells. Our data suggest the presence of allele E469 ICAM-1 in either donor or recipient is protective against allograft rejection in a transplant setting.

Coronary Disease↗

A new verbal learning and memory test for English- and Spanish-speaking older people.

Word-list verbal learning and memory tests with appropriate normative data can be highly sensitive to cognitive decline, but there are significant limitations of such tests available for use with older Hispanic and non-Hispanic people living in the US. The purpose of this study was to (1) create a new word-list learning and memory test in both English and Spanish and, (2) validate it with respect to sensitivity to cognitive impairment, and (3) develop statistical corrections for the effects of significant demographic variables, including ethnicity, language of administration, age, education, and gender. A community dwelling sample of 801 English- and Spanish-speaking older people was employed. Recall on learning trials and the delayed recall trial of the word-list learning test were strongly related to the Mini-Mental State Examination (MMSE). moderately related to age, and weakly related to gender and education. The relationship of word-list variables and the MMSE did not significantly differ across ethnicity/language groups. Regression coefficients for demographic variables were used in a statistical correction formula to adjust raw word-list scores, and then to develop specific percentile cut-off values.

Aged↗

Factors that influence the cost of caring for patients with severe psychotic illness: report from the UK 700 trial.

BACKGROUND: Many factors influence the type and quantity of services received by patients and, thus, the total cost of care. Knowledge of these factors can aid budgetary and service-planning decisions. AIMS: To investigate factors that influence the cost of caring for patients with severe psychotic illness. METHOD: Univariate and multivariate analyses were used to examine associations between baseline characteristics and subsequent 2-year total direct costs in 667 patients from the UK 700 case management trial. RESULTS: Significantly more money was spent on younger patients, those with longer duration of illness, those who had spent less time living independently and those who had spent longer in hospital for psychiatric reasons. CONCLUSIONS: Total costs of caring for patients with severe psychotic illness appear to be influenced to a large extent by age, duration of illness and past levels of dependence on statutory services. The strength of these relationships is greater than the impact of illness severity.

Adolescent↗

Effects and risk assessment of linear alkylbenzene sulfonates in agricultural soil. 4. The influence of salt speciation, soil type, and sewage sludge on toxicity using the collembolan Folsomia fimetaria and the earthworm Aporrectodea caliginosa as test organisms.

Sewage sludge applied to agricultural soils often contains linear alkylbenzene sulfonates (LAS) in the range of 1 to 10 g/kg dry weight, and their toxicity to relevant soil organisms should, therefore, be assessed to ensure safe use of sewage sludge as a fertilizer. Studies of LAS toxicity to soil organisms are few, and to our knowledge, factors that may influence the toxicity in the field have not been studied in detail. In this paper, we report on the influence of speciation of LAS in the test solution added to soil (soluble Na-LAS vs poorly soluble Ca-LAS or Mg-LAS), the influence of soil type, and the modifying effects of sludge amendment on the toxicity of LAS. These issues were investigated using reproduction of Collembola and growth of juvenile earthworms as test parameters. Speciation of the LAS added to test soil did not have any influence on toxicity for any of the test species. Likewise, in three different agricultural soils (sand, loam, and clay), we found almost equal toxicities. The LAS added to test soil in a sludge-water suspension was equally toxic as when it was added in an aqueous solution. However, anaerobic incubation for 7 and 14 d of the LAS-sludge suspension (with no decay of LAS) caused the toxicity to increase almost threefold in both collembolan and earthworm. The relationships between soil constituents, bioavailability, and toxicity are also discussed.

Agriculture↗

The role of ITAM- and ITIM-coupled receptors in platelet activation by collagen.

The major activation-inducing collagen receptor glycoprotein VI (GPVI) has been cloned within the last two years. It is a member of the Ig superfamily of proteins and is constitutively associated with the ITAM-bearing Fc receptor gamma-chain (FcR gamma-chain). GPVI signals through a pathway that involves several of the proteins used by Fc, B- and T-lymphocyte receptors and which takes place in glycolipid-enriched membrane domains in the plasma membrane known as GEMs. Responses to GPVI are regulated by PECAM-1 (CD31) and possibly other ITIM-bearing receptors. Despite a pivotal role for GPVI, there are important differences between signalling events to collagen and GPVI-specific ligands. This may reflect a role for co-receptors in the response to collagen.

Amino Acid Motifs↗

Selection of controls in injury case-control studies.

PURPOSE: To assist in elucidating principles underlying the design of injury case-control studies.APPROACH: We begin by defining "event" as the sequence of circumstances that place a person at risk of injury (e.g. bicycle crash) and "injury given the event" as the resultant physical damage (e.g. head injury in bicycle crash). We then identify two broad classes of research question: 1) Studies of risk factors for the event, and, 2) Studies of risk factors for injury given the event. The study base for the first type of research question is all persons at risk of the event, while the study base for the second type is all persons who experience the event, and are therefore at risk of injury. It follows that in studies of risk factors for injury given the event, the controls should be a sample of all persons who experience the event. For example, in a study of bicycle helmets and head injuries, a suitable case group would be cyclists treated for head injury following a bicycle crash. The appropriate control group is drawn from the base population of all cyclists who crashed, including those who had no injuries. The control group may be restricted to cyclists who crashed and sought treatment for non-head injury under the assumption that the exposure distribution (prevalence of cycle helmet use) in the crash/no injury group is identical to the exposure distribution in the crash/non-head injury group.CONCLUSIONS: It is over ten years since innovative researchers in Seattle first applied the case-control design to the problem of bicycle crashes. Since then, successive bicycle injury studies at other centers have largely failed to extend and refine the Seattle methodology. A more critical approach to the design of case-control studies is required if we are to continue to advance the field of injury epidemiology.

Journal Article↗

Monitoring Piscirickettsia salmonis by denaturant gel electrophoresis and competitive PCR.

Reported strains of Piscirickettsia salmonis, a pathogen of salmonid fishes, were analyzed by amplifying part of the internal transcribed spacer (ITS) of the ribosomal RNA (rRNA) operon followed by denaturing gradient gel electrophoresis (DGGE) of the amplicons. All amplified fragments differing in sequence were distinguished by migration during DGGE. A simpler format, constant denaturant gel electrophoresis (CDGE), allowed the same diagnostic distinctions among strains. Sampling during 1997 and 1998 of salmonids from 5 different sites on and near Chiloé Island in southern Chile displaying piscirickettsiosis revealed only P. salmonis resembling LF-89, the type strain first isolated in 1989. These observations are encouraging for control strategies, which might otherwise be compromised by unpredictable shifts of P. salmonis types in salmon farms. A competitive PCR assay offered insight about the power of PCR for quantification and about specific tissue invasiveness by this intracellular pathogen. This approach revealed that the PCR could amplify approximately 1 to 10 P. salmonis genome equivalents against a background of > 99.9% salmonid DNA. It also raised the possibility that the salmonid brain is an important site for P. salmonis survival, with its bacterial load in 1 individual having been about 100 times the loads observed in liver and kidney. Pathogen detection by competitive PCR in a surface seawater sample from a netpen in use indicated a density of about 3000 to 4000 P. salmonis cells (or their DNA remnants) 1(-1). Such quantitative estimates should aid decisions about disease prevention and management as, for example, choice of netpen sites following fallow periods and certification of ova, which are known conduits of infection.

Animals↗

Autoreactive B cells escape clonal deletion by expressing multiple antigen receptors.

IgH and L chain transgenes encoding a phosphocholine (PC)-specific Ig receptor were introduced into recombinase-activating gene (Rag-2-/-) knockout mice. The PC-specific B cells that developed behaved like known autoreactive lymphocytes. They were 1) developmentally arrested in the bone marrow, 2) unable to secrete Ab, 3) able to escape clonal deletion and develop into B1 B cells in the peritoneal cavity, and 4) rescued by overexpression of bcl-2. A second IgL chain was genetically introduced into Rag-2-/- knockout mice expressing the autoreactive PC-specific Ig receptor. These dual L chain-expressing mice had B cells in peripheral lymphoid organs that coexpressed both anti-PC Ab as well as Ab employing the second available L chain that does not generate an autoreactive PC-specific receptor. Coexpression of the additional Ig molecules rescued the autoreactive anti-PC B cells and relieved the functional anergy of the anti-PC-specific B cells, as demonstrated by detection of circulating autoreactive anti-PC-Abs. We call this novel mechanism by which autoreactive B cells can persist by compromising allelic exclusion receptor dilution. Rescue of autoreactive PC-specific B cells would be beneficial to the host because these Abs are vital for protection against pathogens such as Streptococcus pneumoniae.

Animals↗

Prompt Optical Observations of Gamma-Ray Bursts.

The Robotic Optical Transient Search Experiment (ROTSE) seeks to measure simultaneous and early afterglow optical emission from gamma-ray bursts (GRBs). A search for optical counterparts to six GRBs with localization errors of 1 deg2 or better produced no detections. The earliest limiting sensitivity is mROTSE>13.1 at 10.85 s (5 s exposure) after the gamma-ray rise, and the best limit is mROTSE>16.0 at 62 minutes (897 s exposure). These are the most stringent limits obtained for the GRB optical counterpart brightness in the first hour after the burst. Consideration of the gamma-ray fluence and peak flux for these bursts and for GRB 990123 indicates that there is not a strong positive correlation between optical flux and gamma-ray emission.

Journal Article↗

Local corticosteroid injection for carpal tunnel syndrome.

BACKGROUND: Carpal tunnel syndrome (CTS) is a clinical syndrome manifested by signs and symptoms of irritation of the median nerve at the level of the carpal tunnel in the wrist. Treatment of CTS can be surgical or non-surgical. Local corticosteroid injection for CTS has been previously studied but most studies have been either retrospective or uncontrolled. The effectiveness and duration of benefit of local corticosteroid injection for CTS remain unknown. OBJECTIVES: To evaluate the effectiveness of local steroid injection for carpal tunnel syndrome versus placebo injection or other non-surgical interventions in improving clinical outcome and to determine the length of symptom relief post injection. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group register, MEDLINE, EMBASE and CINAHL. SELECTION CRITERIA: Studies using either a randomized or quasi-randomized methodology were eligible for inclusion. The studies included participants with the diagnosis of carpal tunnel syndrome and the treatment intervention was local corticosteroid injection. The primary outcome measure was clinical improvement after injection. DATA COLLECTION AND ANALYSIS: Three reviewers independently selected the trials to be included in the study. Studies were rated for their overall quality independently by the reviewers. Studies were compared for heterogeneity using the chi square statistic. Relative risks and 95% confidence intervals were calculated for each trial and summary relative risks and 95% confidence intervals (CI) were also calculated. MAIN RESULTS: We identified four randomized controlled trials studying local corticosteroid injection for the treatment of CTS. Two trials were excluded. One did not include clinical assessment as an outcome and the other did not provide patient outcomes, but only statistical values. Each of the remaining two trials had demonstrated clinical improvement of CTS at one month following local corticosteroid injection compared to placebo injection. The pooled relative risk (RR) favouring treatment was 3.62 (95% CI 1.94 to 6.73). REVIEWER'S CONCLUSIONS: Local corticosteroid injection for CTS provides greater clinical improvement in symptoms one month after injection compared to placebo. Symptom relief beyond one month compared to placebo has not been demonstrated. The effectiveness of local corticosteroid injection has not been compared to other non-surgical or surgical interventions for CTS in randomized controlled trials.

Adrenal Cortex Hormones↗

Intraoperative vs postoperative morphine improves analgesia without increasing PONV on emergence from ambulatory surgery.

PURPOSE: To compare the timing of administration of morphine in patients undergoing painful ambulatory surgical procedures to determine whether there was a difference in postoperative nausea or vomiting (PONV), quality of analgesia, and recovery profile. METHODS: In a double-blinded, placebo-controlled, prospective study, 70 ASA I-II patients were randomized to receive 0.1 mg x kg(-1) morphine intraoperatively (lop) (n=35), or postoperatively (Pop) (n=35). The severity of nausea and pain were measured using visual analog scales (VAS). RESULTS: There was no difference between the groups in postoperative nausea scores or the incidence of PONV. Upon awakening, patients who received Pop morphine had higher pain VAS scores with movement (7.6 +/- 2 vs 5.4 +/- 3, P < 0.003) and at rest (6.9 +/- 3 vs 5.1 +/- 3, P < 0.013) than the lop morphine group. The total number of PCA attempts and analgesic requirements were similar. Patients who received Pop morphine were able to drink sooner than the lop group (90 +/- 34 vs 111 +/- 38 min, P < 0.05). All other recovery milestones were similar. Times to discharge from hospital were similar. CONCLUSIONS: Administration of 0.1 mg x kg(-1) morphine iv intraoperatively improves postoperative analgesia upon emergence from painful ambulatory surgical procedures without increasing the incidence of PONV There was no increase in PONV when morphine was administered intraoperatively rather than postoperatively.

Adolescent↗

Mannose-binding lectin promoter and structural gene variants in sarcoidosis.

BACKGROUND: Sarcoidosis is a chronic granulomatous disease of unknown aetiology. Studies have suggested that the causative agent may be an infectious micro-organism. The mannose binding lectin (MBL) is involved in innate immunity to a wide range of micro-organisms. Mutations in the promoter region and exon 1 of the MBL gene occur with high frequency and are associated with reduced serum levels of MBL and increased susceptibility to microbial diseases. This study investigated whether MBL variants predispose to sarcoidosis by increasing their susceptibility to micro-organisms. METHODS: MBL gene promoter and exon 1 variants were detected by sequence specific primer polymerase chain reaction (SSP-PCR) in 167 UK Caucasian sarcoidosis patients and 164 control subjects. Severity of pulmonary disease outcome among patients was assessed by radiography after a minimum of 4 years from disease onset and classified as mild, moderate, and severe disease categories, accordingly. RESULTS: MBL variant frequencies were similar in patients and controls studied. Among sarcoidosis patients, the frequencies of variants were similar regardless of severity of disease outcome. The average patient ages at time of diagnosis were similar for all MBL genotypes. CONCLUSIONS: MBL gene variants do not appear to influence susceptibility to sarcoidosis, age of disease onset, or severity of disease.

Adolescent↗

Genetic analysis of the Drosophila 63F early puff. Characterization of mutations in E63-1 and maggie, a putative Tom22.

The 63F early puff in the larval salivary gland polytene chromosomes contains the divergently transcribed E63-1 and E63-2 ecdysone-inducible genes. E63-1 encodes a member of the EF-hand family of Ca(2+)-binding proteins, while E63-2 has no apparent open reading frame. To understand the functions of the E63 genes, we have determined the temporal and spatial patterns of E63-1 protein expression, as well as undertaken a genetic analysis of the 63F puff. We show that E63-1 is expressed in many embryonic and larval tissues, but the third-instar larval salivary gland is the only tissue where increases in protein levels correlate with increases in ecdysone titer. Furthermore, the subcellular distribution of E63-1 protein changes dynamically in the salivary glands at the onset of metamorphosis. E63-1 and E63-2 null mutations, however, have no effect on development or fertility. We have characterized 40 kb of the 63F region, defined as the interval between Ubi-p and E63-2, and have identified three lethal complementation groups that correspond to the dSc-2, ida, and mge genes. We show that mge mutations lead to first-instar larval lethality and that Mge protein is similar to the Tom22 mitochondrial import proteins of fungi, suggesting that it has a role in mitochondrial function.

Amino Acid Sequence↗

Effect of exercise intensity on bone density, strength, and calcium turnover in older women.

PURPOSE: This study examined the effects of 24 wk of high intensity strength training or low intensity walking on lumbar bone mineral density (BMD), muscular strength, and calcium turnover in Australian women either taking hormone replacement therapy (HRT) or not taking HRT. METHODS: A subject pool of 64 women between 45-65 yr and randomly allocated into weights (N = 21), walking (N = 20), weightsHRT (N = 14), and walkingHRT (N = 9) groups completed this study. All subjects trained twice weekly in either a 50-min walking or weight-training program (60-90% IRM). Measurements included maximal isometric knee strength, IRM bench press, IRM squat, isokinetic back strength, lumbar (L2-L4) BMD, serum osteocalcin, and urinary deoxypyridinoline crosslinks (Dpd). RESULTS: No significant group differences in BMD were evident at the completion of training. However, a significant (P < 0.05) within group change was apparent for the walking group since BMD decreased 1.3% below baseline testing. Osteocalcin levels increased significantly (P < 0.05) in the walking (22%) group. Maximal bench press and squat strength improved significantly (P < 0.05) in the weights (25.8% and 37.7%) and weightsHRT (25.4% and 35.7%) groups. The weights group also increased significantly (P < 0.05) in isokinetic back strength (22.2%). CONCLUSION: It was concluded that short-term high intensity resistance training provides an effective means for increasing muscular strength in women between 45 and 65 yr. The training effects on lumbar BMD were not apparent in the present study.

Aged↗

Epidemiologic typing of Salmonella enterica serotype enteritidis in a Canada-wide outbreak of gastroenteritis due to contaminated cheese.

A major Canada-wide outbreak of gastroenteritis due to Salmonella enterica serotype Enteritidis phage type (PT) 8 occurred in 1998, and this was traced to contaminated cheese in a commercial lunch pack product. Phage typing and pulsed-field gel electrophoresis linked the clinical and cheese isolates of serotype Enteritidis but failed to differentiate outbreak from nonoutbreak PT 8 strains. Further differentiation was made by biotyping based on melibiose fermentation.

Bacterial Typing Techniques↗

Intermittent administration of inhaled tobramycin in patients with cystic fibrosis. Cystic Fibrosis Inhaled Tobramycin Study Group.

BACKGROUND AND METHODS: We conducted two multicenter, double-blind, placebo-controlled trials of intermittent administration of inhaled tobramycin in patients with cystic fibrosis and Pseudomonas aeruginosa infection. A total of 520 patients (mean age, 21 years) were randomly assigned to receive either 300 mg of inhaled tobramycin or placebo twice daily for four weeks, followed by four weeks with no study drug. Patients received treatment or placebo in three on-off cycles for a total of 24 weeks. The end points included pulmonary function, the density of P. aeruginosa in sputum, and hospitalization. RESULTS: The patients treated with inhaled tobramycin had an average increase in forced expiratory volume in one second (FEV1) of 10 percent at week 20 as compared with week 0, whereas the patients receiving placebo had a 2 percent decline in FEV1 (P<0.001). In the tobramycin group, the density of P. aeruginosa decreased by an average of 0.8 log10 colony-forming units (CFU) per gram of expectorated sputum from week 0 to week 20, as compared with an increase of 0.3 log10 CFU per gram in the placebo group (P<0.001). The patients in the tobramycin group were 26 percent (95 percent confidence interval, 2 to 43 percent) less likely to be hospitalized than those in the placebo group. Inhaled tobramycin was not associated with detectable ototoxic or nephrotoxic effects or with accumulation of the drug in serum. The proportion of patients with P. aeruginosa isolates for which the minimal inhibitory concentration of tobramycin was 8 microg per milliliter or higher increased from 25 percent at week 0 to 32 percent at week 24 in the tobramycin group, as compared with a decrease from 20 percent at week 0 to 17 percent at week 24 in the placebo group. CONCLUSIONS: In a 24-week study of patients with cystic fibrosis, intermittent administration of inhaled tobramycin was well tolerated and improved pulmonary function, decreased the density of P. aeruginosa in sputum, and decreased the risk of hospitalization.

Administration, Inhalation↗

The relationship between dynamic, isokinetic and isometric strength and bone mineral density in a population of 45 to 65 year old women.

This study investigated the relationship between age, lumbar spine bone mineral density (LS BMD) and muscular strength of peri and postmenopausal women between 45 and 65 years either taking or not taking hormone replacement therapy (HRT). Ninety six women were tested for LS BMD (L2-L4), one repetition maximum (1RM) bench press and squat, maximal voluntary isometric contraction (MVC) of the knee extensors and peak torque of back extensor muscles at a speed of 30 degrees s(-1). Bone and strength data were analysed to evaluate the relationships in incrementing five year age groups and based on groups either taking or not taking HRT. ANOVA revealed significant differences in LS BMD between the 45-49 and 55-59 (F[3,92]=2.6411, p<0.05; -8%) age groups amounting to an annual bone loss of 0.8% for this Australian based population. Non significant LS BMD results were evident after controlling for the influence of age and menopausal status on the groups either taking or not taking HRT. Significant differences between the 45-49 and 60-64 (F[3,92]=2.7463, p<0.05) age groups for 1RM bench press and the 45-49 and 60-64, 50-54 and 60-64, and, 55-59 and 60-64 (F[3,92]=4.2816, p<0.05) age groups for 1RM squat amounting to an 18.8% and 37.5% loss of dynamic upper and lower body strength, respectively. Group correlation coefficients ranged between (r=-0.20 and -0.34, p<0.05) for LS BMD, strength and age. The conclusions demonstrate a concomitant decline in maximal muscle strength and bone density between women 45 and 65 years irrespective of HRT. These results also demonstrate a 50% greater decline in lower body strength compared to upper body strength between women 45 and 65 years.

Absorptiometry, Photon↗