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Biomedical subjects

W Shannon

Publications and source records attributed to W Shannon.

At least 19 recordsLinked to original sources

A rapid assay for the detection of circulating D-dimer is associated with clinical outcomes among critically ill patients.

OBJECTIVE: To determine whether the results of a rapid, semiquantitative assay for the detection of circulating D-dimer in whole blood (SRDD assay) are associated with the occurrence of clinical outcomes among critically ill patients. DESIGN: Prospective, blinded, single-center study. SETTING: Medical intensive care unit (ICU) of Barnes-Jewish Hospital, St. Louis, MO, a university-affiliated teaching hospital. PATIENTS: Three hundred twenty-three adult patients admitted to a medical ICU. INTERVENTIONS: Collection of blood samples within 24 hrs of ICU admission. MEASUREMENTS AND MAIN RESULTS: The main outcome measures evaluated included vascular thrombosis, hospital mortality, and the development of multiorgan dysfunction. Fifty (15.5%) patients were found to have increased concentrations of D-dimer as detected by the SRDD assay within 24 hrs of ICU admission. The concentrations of plasma D-dimer simultaneously measured by an enzyme immunoassay based on the same antibody were significantly greater among patients with a positive SRDD assay compared with patients with a negative SRDD assay (1214+/-483 vs. 405+/-407 ng/mL; p< .001). The hospital mortality rate was significantly greater among SRDD-positive patients compared with SRDD-negative patients (32.0% vs. 15.0%; p=.004). SRDD-positive patients also had significantly greater frequencies of acquired multiorgan dysfunction (48.0% vs. 17.6%; p < .001), severe sepsis or septic shock (56.0% vs. 20.9%; p< .001), and vascular thrombosis (14.0% vs. 4.0%; p=.005) compared with SRDD-negative patients. Multiple logistic regression analysis identified the presence of increased concentrations of D-dimer, detected by a positive SRDD assay, as being independently associated with vascular thrombosis (adjusted odds ratio 5.06; 95% confidence interval 2.96 to 8.65; p=.003) and the development of multiorgan dysfunction (adjusted odds ratio 1.51; 95% confidence interval 1.28 to 1.78; p=.012). CONCLUSIONS: Our preliminary investigation suggests that the results from a rapid whole blood assay for the semiquantitative detection of circulating D-dimer are associated with clinical outcomes among patients admitted to a medical ICU. In addition, the use of D-dimer to identify the presence of active intravascular thrombosis may identify patients likely to benefit from antithrombotic therapies in the ICU setting.

APACHE

A randomized, controlled trial of protocol-directed versus physician-directed weaning from mechanical ventilation.

OBJECTIVE: To compare a practice of protocol-directed weaning from mechanical ventilation implemented by nurses and respiratory therapists with traditional physician-directed weaning. DESIGN: Randomized, controlled trial. SETTING: Medical and surgical intensive care units in two university-affiliated teaching hospitals. PATIENTS: Patients requiring mechanical ventilation (n = 357). INTERVENTIONS: Patients were randomly assigned to receive either protocol-directed (n = 179) or physician-directed (n = 178) weaning from mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: The primary outcome measure was the duration of mechanical ventilation from tracheal intubation until discontinuation of mechanical ventilation. Other outcome measures included need for reintubation, length of hospital stay, hospital mortality rate, and hospital costs. The median duration of mechanical ventilation was 35 hrs for the protocol-directed group (first quartile 15 hrs; third quartile 114 hrs) compared with 44 hrs for the physician-directed group (first quartile 21 hrs; third quartile 209 hrs). Kaplan-Meier analysis demonstrated that patients randomized to protocol-directed weaning had significantly shorter durations of mechanical ventilation compared with patients randomized to physician-directed weaning (chi 2 = 3.62, p = .057, log-rank test; chi 2 = 5.12, p = .024, Wilcoxon test). Cox proportional-hazards regression analysis, adjusting for other covariates, showed that the rate of successful weaning was significantly greater for patients receiving protocol-directed weaning compared with patients receiving physician-directed weaning (risk ratio 1.31; 95% confidence interval 1.15 to 1.50; p = .039). The hospital mortality rates for the two treatment groups were similar (protocol-directed 22.3% vs. physician-directed 23.6%; p = .779). Hospital cost savings for patients in the protocol-directed group were $42,960 compared with hospital costs for patients in the physician-directed group. CONCLUSION: Protocol-guided weaning of mechanical ventilation, as performed by nurses and respiratory therapists, is safe and led to extubation more rapidly than physician-directed weaning.

Adult

BLEED: a classification tool to predict outcomes in patients with acute upper and lower gastrointestinal hemorrhage.

OBJECTIVE: To develop an outcome prediction tool (BLEED: ongoing bleeding, low systolic blood pressure, elevated prothrombin time, erratic mental status, unstable comorbid disease) for clinical use in patients with either acute upper or acute lower gastrointestinal (GI) hemorrhage. DESIGN: A cohort study. SETTING: Barnes Hospital and Jewish Hospital, two private university-affiliated teaching hospitals in St. Louis, MO. PATIENTS: Four hundred sixty-five patients with either acute upper or acute lower GI hemorrhage admitted from the emergency department. INTERVENTIONS: Admission of patients to the intensive care unit or hospital ward was determined by emergency department physicians, without use or knowledge of BLEED criteria. Patients meeting any BLEED criteria at their initial assessment in the emergency department were classified as "high-risk." All other patients were classified as "low-risk." MEASUREMENTS AND MAIN RESULTS: The main outcome measure was the occurrence of an inhospital complication, defined as recurrent GI hemorrhage, surgery to control the source of hemorrhage, and hospital mortality. Patients classified as high-risk had significantly greater rates of inhospital complications at both Barnes Hospital (relative risk, 2.47; 95% confidence interval, 1.38 to 4.44; p < .001) and Jewish Hospital (relative risk, 8.94; 95% confidence interval, 3.92 to 20.41; p < .001) compared with patients classified as low-risk. Patients classified as high-risk at either hospital were significantly more likely to develop additional organ system derangements, require a greater number of transfused units of packed red blood cells, and have longer hospital stays compared with patients classified as low-risk (p < .006). The BLEED classification also identified a greater frequency of intensive care admission for both low-risk (RR, 4.21; 95% Cl, 2.24 to 7.89) and high-risk (relative risk, 1.58; 95% confidence interval, 1.23 to 2.02) patients at Barnes Hospital compared with those patients at Jewish Hospital, although no beneficial effects on patient outcome were reported. CONCLUSIONS: The BLEED classification, applied at initial emergency department evaluation and before admission, predicts hospital outcomes for patients with acute upper or lower GI hemorrhage. This outcome prediction tool also identified variations in intensive care utilization between two hospitals.

APACHE

A new short form individual quality of life measure (SEIQoL-DW): application in a cohort of individuals with HIV/AIDS.

Quality of life is an increasingly important outcome measure in medicine and health care. Many measures of quality of life present patients with predetermined lists of questions that may or may not be relevant to the individual patient. This paper describes a brief measure, the SEIQoL-DW, which is derived from the schedule for evaluation of individual quality of life (SEIQoL). The measure allows respondents to nominate the areas of life which are most important, rate their level of functioning or satisfaction with each, and indicate the relative importance of each to their overall quality of life. Given its practicality and brevity, the measure should prove particularly useful in clinical situations where patient generated data on quality of life is important. This article describes the first clinical application of the measure, assessing the quality of life of a cohort of patients with HIV/AIDS managed in general practice.

Acquired Immunodeficiency Syndrome

Clinical guidelines: their implementation in general practice.

In recent years the development of clinical guidelines has received increasing attention from medical educators and those involved in standard setting, and has been initiated at both central and local levels. This review article outlines the current state of knowledge with regard to clinical guideline implementation in medical practice. It deals with the main aspects of the current guideline debate, such as, clinical freedom and doctor autonomy, the importance of ownership in guideline implementation, the effectiveness of guidelines in changing practice and, in particular, the strategies needed to implement clinical guidelines in general practice. Mechanisms of behavioural change that have been recognized as being important for implementation are also discussed. If implementation strategies are not treated as an integral part of the development process then clinical guidelines may fail to achieve their potential in changing clinical practice.

Family Practice

Employing a practice nurse--role and training implications in an Irish context.

All 102 nurses known to be practising as practice nurses in the Republic of Ireland were sent a questionnaire for completion anonymously. A response rate of 56% was obtained. Over half the respondents had commenced practice nursing since the new General Medical Services contract in 1989 following a career break, the median duration of which was 5.5 years. Two thirds had completed midwifery training but only one was a qualified Public Health Nurse. An examination of the tasks performed by the respondents suggests that Irish practice nurses are already filling an extended role beyond their treatment room duties with 46% involved in smoking counselling, 74% in counselling on cholesterol and 37% involved in asthma care. Nurses providing antenatal care or taking cervical smears were not, however, more likely to have completed midwifery training.

Education, Nursing

Temporal regulation of light-induced Fos and Fos-like protein expression in the ventrolateral subdivision of the rat suprachiasmatic nucleus.

We measured c-fos messenger RNA levels and Fos protein immunoreactivity in the suprachiasmatic nucleus of rats as a function of light and time of day. Immunohistochemistry demonstrated a daily rhythm of immunoreactive Fos in the ventrolateral subdivision of the suprachiasmatic nucleus of animals entrained to a 12 h/12 h light-dark cycle; expression was low during the dark phase, peaked about 2 h after light onset at dawn, and remained elevated at an intermediate level for the remainder of the light phase. Immunoblots of nuclear extracts showed a 54,000 mol. wt band that increased in density from the dark phase to the early light phase and decreased again during the late light phase. In situ hybridization using a radiolabeled cDNA probe revealed a c-fos messenger RNA signal that was detected as early as 15 min after dawn, prominent at 30 min, and absent by 2 h. The expression of c-fos messenger RNA and Fos immunoreactivity in the suprachiasmatic nucleus depended on the presence of ambient light. In rats entrained to two daily 1-h light pulses corresponding to dawn and dusk ("skeleton" photoperiod) instead of the complete light-dark cycle, immunoreactive Fos was elicited by the dawn pulse alone and was less persistent than during the complete photoperiod. In rats free-running in constant darkness, c-fos messenger RNA and Fos immunoreactivity were stimulated by 2-h light pulses administered only during the subjective night and early subjective day, but not by light pulses during the middle or late subjective day or in the absence of light pulses.

Animals

In vitro cytokine production by normal human peripheral blood mononuclear cells as a measure of immunocompetence or the state of activation.

Measurements of cytokine levels in serum may not adequately reflect the cytokine-producing potential of immune cells because of the short half-lives of cytokines and the presence of various inhibitors in human sera. In vitro cytokine production by peripheral blood mononuclear cells (PBMCs) can be an important and reliable measure of immunocompetence. Also, spontaneous in vitro release of cytokines by PBMCs may serve as a measure of their activation in vivo. In the present study, normal ranges for the in vitro production by PBMCs of interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF-alpha), IL-2, and gamma interferon (IFN-gamma) were established; the feasibility of using cryopreserved PBMCs for assays of in vitro cytokine production was evaluated; and spontaneous (unstimulated) versus induced production of cytokines by fresh and cryopreserved PBMCs from healthy donors was compared. Supernatants obtained from paired fresh and frozen PBMCs were quantitated for IL-1 beta, TNF-alpha, IL-2, and IFN-gamma by using enzyme-linked immunosorbent assay or a radioimmunoassay standardized against World Health Organization cytokine standards. Fresh or cryopreserved PBMCs activated with lipopolysaccharide produced comparable levels of IL-1 beta. However, the mean levels of stimulated production of TNF-alpha, IFN-gamma, and IL-2 were significantly higher in cryopreserved versus fresh PBMCs (P < or = 0.0004). Correlations between the level of production of each cytokine by fresh versus cryopreserved in vitro-stimulated PBMCs were statistically significant, although of moderate magnitude. Spontaneous cytokine release by fresh versus cryopreserved cells was not significantly different.

Adult

Compositional changes of AP-1 DNA-binding proteins are regulated by light in a mammalian circadian clock.

Recent reports have shown that the nuclear phosphoprotein Fos is induced by light in a mammalian circadian clock, the suprachiasmatic nucleus. To learn how light and circadian phase affect the binding of Fos to DNA, we analyzed the photic and temporal regulation of immunoreactive Jun protein expression and AP-1 DNA-binding activity in the rat suprachiasmatic nucleus. Immunohistochemistry and gel mobility shift assays suggest that AP-1 activity during the night and after a light pulse consists of constant, as well as variable, protein components; JunD could be identified as a constituent of both dark- and light-activated binding complexes, whereas binding by JunB and Fos could be implicated only after photic stimulation. Since JunD or JunB could be colocalized with Fos in individual suprachiasmatic nucleus cell nuclei, light may be acting in at least some suprachiasmatic nucleus cells by altering AP-1 protein composition rather than binding site occupancy.

Animals

Preparation of viable tumour cell vaccine from human solid tumours: relationship between tumour mass and cell yield. The Tissue Bank, Pittsburgh Cancer Institute.

Active specific immunotherapy for cancer often requires the use of autologous or allogeneic tumour cells as immunizing antigen. Tumours were obtained for such a protocol. However, estimation of viable cell yield from pre-processed fresh tumour mass was difficult, and initially there did not appear to be a direct relationship between pre-processed tumour mass and viable cells obtained after processing. We therefore analysed all of 293 tumour specimens processed to attempt to discern such a relationship. Of these 137 were melanoma, 14 were sarcoma, 48 were adenocarcinoma, 59 were renal cell carcinoma and 35 were classified as other. A positive correlation was found between pre-processed tumour mass and viable cell yield, with Spearman correlation values varying from r = 0.49 (adenocarcinoma) to r = 0.84 (melanoma). For all tumours the Spearman correlation was r = 0.70 (p = 0.0001). Not surprisingly, the most frequent site of removal associated with bacterial contamination was bowel. In conclusion, this study provides useful curves for predicting viable tumour cell yield from pre-processed tumour mass of given histology.

Adenocarcinoma

Immunocytochemical localization of estrogen receptors within neurotensin cells in the rostral preoptic area of the rat hypothalamus.

In situ hybridization procedures indicate that estrogen selectively increases neurotensin and neuromedin (NT/N) mRNA levels in the rostral preoptic area of the rat hypothalamus (RPH). Using the co-localization procedures of Axelson and Van Leeuwen, J. Neuroendocrinol., 2 (1990) 209-216, the present study examined whether NT cells in the RPH contained estrogen receptors (ER). Vibratome sections of brains from adult ovariectomized, colchicine-treated rats were first incubated with estrogen receptor antibody and stained with diaminobenzidine (DAB)-Ni+ producing a blue-black nucleus. Subsequently, NT antisera were used to provide a brown reaction product with DAB as chromogen. Approximately 25% of the NT cells in the RPH contained ER. These data support the hypothesis that NT cells in the RPH that play a role in luteinizing hormone release from the pituitary are, in part, influenced directly by estrogen feedback via nuclear ER and may act as interneurons controlling luteinizing hormone releasing hormone turnover.

Animals

Communication skills training in undergraduate medicine: attitudes and attitude change.

The importance of communication skills training in undergraduate medical education is now widely accepted. However little is known about student attitudes towards their own communication skills and whether their attitudes changes as a result of participating in communication skills courses. The aim of the present study was to identify these attitudes prior to commencing such a course and to further evaluate changes in these attitudes on completion of the course. Results demonstrated an improvement in perceived confidence regarding a number of specific communication skills. The study provides further evidence of the value of such courses in undergraduate medical training.

Attitude