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Biomedical subjects

N Edwards

Publications and source records attributed to N Edwards.

At least 37 records · Page 2Linked to original sources
PubMed2001

SCOPE: a probabilistic model for scoring tandem mass spectra against a peptide database.

Proteomics, or the direct analysis of the expressed protein components of a cell, is critical to our understanding of cellular biological processes in normal and diseased tissue. A key requirement for its success is the ability to identify proteins in complex mixtures. Recent technological advances in tandem mass spectrometry has made it the method of choice for high-throughput identification of proteins. Unfortunately, the software for unambiguously identifying peptide sequences has not kept pace with the recent hardware improvements in mass spectrometry instruments. Critical for reliable high-throughput protein identification, scoring functions evaluate the quality of a match between experimental spectra and a database peptide. Current scoring function technology relies heavily on ad-hoc parameterization and manual curation by experienced mass spectrometrists. In this work, we propose a two-stage stochastic model for the observed MS/MS spectrum, given a peptide. Our model explicitly incorporates fragment ion probabilities, noisy spectra, and instrument measurement error. We describe how to compute this probability based score efficiently, using a dynamic programming technique. A prototype implementation demonstrates the effectiveness of the model.

Amino Acid Sequence↗
PubMed2001

Delayed gastric emptying in ventilated critically ill patients: measurement by 13 C-octanoic acid breath test.

OBJECTIVE: To measure gastric emptying in ventilated critically ill patients with a new noninvasive breath test. DESIGN: Single-center, open study. SETTING: Combined medical and surgical intensive care unit of a university hospital. SUBJECTS: Thirty unselected mechanically ventilated critically ill patients receiving gastric feeding and 22 healthy volunteers. INTERVENTIONS: None. PATIENTS: After 4 hrs without feeding, intragastric infusion of 100 mL of a liquid meal (Ensure) labeled with 100 microL 13C-octanoic acid. End-expiratory breath samples were collected into evacuated tubes from the respirator circuit every 5 mins for the first hour, then every 15 mins for 3 hrs. End-expiratory breath samples were also collected from volunteers studied supine after an overnight fast following an identical infusion via a nasogastric tube. Breath 13CO2 was measured with an isotope ratio mass spectrometer. MEASUREMENTS AND MAIN RESULTS: Performance of the breath test posed no difficulty or interference with patient care. The CO2 level was >1% in 1297/1300 breath samples, indicating satisfactory end-expiratory timing. Data are median and interquartile range. Gastric emptying was slower in patients compared with volunteers: gastric emptying coefficient 2.93 (2.17-3.39) vs. 3.58 (3.18-3.79), p <.001 and gastric half emptying time, derived from the area under the 13CO2 curve, 155 min (130-220) vs. 133 min (120-145), p <.008. Fourteen of the 30 patients had a gastric emptying coefficient <95% of all volunteers and 11 had a gastric half emptying time longer than 95% of all volunteers. The Acute Physiology and Chronic Health Evaluation (APACHE II) score (median 22, range 13-43) either at admission or on the day of the study did not correlate with gastric emptying coefficient. CONCLUSION: Gastric emptying of a calorie-dense liquid meal is slow in 40% to 45% of unselected mechanically ventilated patients in a combined medical and surgical intensive care unit. The 13C-octanoic acid breath test is a novel and useful bedside technique to measure gastric emptying in these patients.

APACHE↗
PubMed2001

Planning and policy for emergency services: four fallacies, two problems and some possible solutions.

This paper examines some of the misapprehensions that have often underpinned the planning of accident and emergency services in the UK. Accident and emergency (A&E) is not a homogenous group of activities and the different components that make up the service should be planned separately. This planning needs to be accompanied by some significant redesign to meet growing patient expectations. In particular, there is a major challenge for services to offer local access in an environment in which acute care is increasingly centralized.

Emergency Medical Services↗
PubMed2001

Disruption of poly (ADP-ribose) polymerase (PARP) protects against stress-evoked immunocompromise.

BACKGROUND: Chronic stress, mediated by adrenal hormones, is a major risk factor in the progression and outcome of human disease. While the secretion of adrenal hormones is known to be the primary endocrine mediator of stress-induced immunocompromise, the molecular mechanisms underlying the immunocompromise remain unspecified. Overproduction of the nuclear enzyme, poly (ADP-ribose) polymerase (PARP) has been implicated in the molecular pathway that leads to cell death by energy depletion following stress. MATERIALS AND METHODS: Wild-type (WT) mice and mice with targeted disruption of the gene encoding PARP-1 (PARP-1 -/-) were subjected to 2 wk daily cold-water swim; splenocyte proliferation, anti-KLH IgG, and serum corticosterone concentrations were assessed. Additional mice of each genotype received daily i.p. injections of dexamethasone (DEX) (0.75 mg/kg) for 2 wk, and splenocyte proliferation and anti-KLH IgG were assessed. RESULTS: Splenocyte proliferation and specific antibody concentrations of stressed WT mice were reduced by ~20% of their pre-stress levels. In contrast, PARP-1 -/- mice maintained normal cell-mediated and humoral immune function following enforced cold-water swim stress. PARP-1 -/- mice also failed to compromise immune function following DEX treatment, whereas WT mice displayed significant reductions of immune function following this treatment. CONCLUSIONS: These results provide support for the involvement of PARP activation in immunological damage following physical stress. These results suggest that glucocorticoid-induced immunosuppression may require the activation of PARP in order for apoptosis of immune cells to take place. Taken together, these results suggest that therapies designed to inhibit PARP may prove valuable in the treatment of stress-related diseases.

Animals↗
PubMed2000

Pre-eclampsia is associated with marked alterations in sleep architecture.

STUDY OBJECTIVES: Pre-eclampsia is currently the predominant cause of maternal and fetal morbidity and mortality. Diurnal blood pressure variation is flattened or reversed in pre-eclampsia; however, sleep has not been extensively investigated in this disease. Our objective was therefore to study sleep architecture in this group of patients. STUDY DESIGN: Full polysomnography using the Compumedics Sleepwatch System or Compumedics p-series. SETTING: NA. PATIENTS: 25 pre-eclamptic patients and 17 primigravidas with normal pregnancies and no history of cardiovascular disease or sleep disorder. With the exception of one subject, all pre-eclamptics were taking clonidine (a known suppressant of rapid eye movement-REM-sleep) for control of their hypertension. INTERVENTIONS: NA. RESULTS: Pre-eclamptic subjects had markedly altered sleep architecture, with a markedly increased percentage of time spent in slow-wave sleep (SWS) (21 * 2% versus 43 * 3%, p<0.001). There was a longer latency to rapid eye movement (REM) sleep (92 * 11 mins vs. 205 * 23 mins in control and pre-eclamptic subjects, respectively, p<0.001) and reduced time spent in REM (18 * 1% and 10 * 2% in control and pre-eclamptic subjects, respectively, p<0.001). CONCLUSIONS: While the increased REM latency and decreased REM time are most likely due to clonidine, this is unlikely to also account for the increased SWS. Two possible explanations for this include cerebral edema and release of cytokines, which are known to alter sleep structure.

Adult↗
PubMed2000

Age-related brain volume reductions in amphetamine and cocaine addicts and normal controls: implications for addiction research.

The study evaluated the relationship between age and frontal and temporal lobe volumes in young cohorts of cocaine-dependent (CD), amphetamine-dependent (Am), and normal control subjects. Ten CD, nine Am, and 16 age- and gender-matched control subjects underwent magnetic resonance imaging (MRI). The volume of the frontal and temporal lobes was measured from an identically positioned slab of seven contiguous 3-mm-thick coronal images. Follow-up measures of the gray and white matter subcomponents of these volumes were also obtained. Both CD and Am groups had a significantly smaller temporal lobe volumes, but only the CD group demonstrated a significantly greater decline in temporal lobe volume with age (intracranial volume, education, and race were controlled for in all statistical analyses). Segmenting the brain regions into gray and white matter revealed that the negative correlation between age and temporal lobe volume of CD patients was mostly due to a significant age-related decline in the gray matter subcomponent. Negative trends between age and gray matter volumes were also observed in the Am and normal groups. In the frontal lobes, age was negatively correlated with gray matter volume in the control, CD, and Am groups. Unlike the consistent decreases in gray matter volumes, white matter showed non-significant increases in volume with age. The data suggest that CD patients may have an accelerated age-related decline in temporal lobe gray matter volume and a smaller temporal lobe volume compared to normal controls. In the frontal lobe, age-related gray matter volume reductions occur in all three groups. These age-related cortical gray matter volume reductions may be a biological marker for the risk of addictive behavior, which also decreases with age.

Adult↗
PubMed2000

Primary care trusts. Barrier grief.

Primary care trusts that want to shift resources from hospitals will face many of the barriers that have frustrated others before them. Part of the difficulty lies in hospitals' fixed overhead costs, which cannot be saved if patients are transferred. Incentives in the system tend towards preserving the status quo. PCTs will have to make full use of the relationship between GPs and consultants to effect change.

Cost Savings↗
PubMed2000

Prevention of rejection in cardiac transplantation by blockade of the interleukin-2 receptor with a monoclonal antibody.

BACKGROUND: Alloantigen-activated T cells express the high-affinity interleukin-2 receptor. Specific blockade of this receptor with the human IgG1 monoclonal antibody daclizumab may prevent rejection of allografts after cardiac transplantation without inducing global immunosuppression. METHODS: We randomly assigned 55 nonsensitized patients undergoing a first cardiac transplantation to receive either induction therapy with daclizumab (1.0 mg per kilogram of body weight), given intravenously within 24 hours after cardiac-transplantation surgery and every two weeks thereafter, for a total of five doses, or generalized immunosuppressive therapy. Concomitant immunosuppression was achieved in both groups with cyclosporine, mycophenolate mofetil, and prednisone. The primary end points were the incidence and severity of acute rejection, and the length of time to a first episode of biopsy-confirmed rejection. RESULTS: Of the 55 patients in the study, 28 were randomly assigned to receive daclizumab and 27 served as the control group. During induction therapy, the mean frequency of acute rejection episodes (defined as a histologic grade of 2 or higher according to the classification of the International Society of Heart and Lung Transplants) was 0.64 per patient in the control group and 0.19 per patient in the daclizumab group (P=0.02). Acute rejection developed in 17 of 27 patients in the control group (63 percent), as compared with 5 of 28 patients in the daclizumab group (18 percent; relative risk, 2.8; 95 percent confidence interval, 1.1 to 7.4; P=0.04). Throughout follow-up, there were nine patients with episodes of acute rejection of histologic grade 3 in the control group, as compared with two in the daclizumab group (P= 0.03), and the time to a first episode of rejection was significantly longer in the daclizumab group (P=0.04). There were no adverse reactions to daclizumab and no significant differences between the groups in the incidence of infection or cancer during follow-up. CONCLUSIONS: Induction therapy with daclizumab safely reduces the frequency and severity of cardiac-allograft rejection during the induction period.

Acute Disease↗