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Biomedical subjects

E Carter

Publications and source records attributed to E Carter.

At least 19 recordsLinked to original sources

Alosetron controls bowel urgency and provides global symptom improvement in women with diarrhea-predominant irritable bowel syndrome.

OBJECTIVES: Bowel urgency is one of the most bothersome symptoms for nonconstipated IBS patients. The efficacy of alosetron in control of bowel urgency and Global Improvement of IBS symptoms were evaluated in a multicenter double-blind, randomized, placebo-controlled study. METHODS: Female IBS patients with lack of satisfactory control of bowel urgency were randomized 2:1 to alosetron 1 mg twice daily or placebo treatment groups. The primary endpoint was the proportion of days with satisfactory control of bowel urgency during the 12-wk treatment period and 2-wk follow-up period. Secondary endpoints included IBS Global Improvement (responder defined as patient-reported moderate or substantial improvement in IBS symptoms) and improvements in bowel function (stool frequency, consistency, and sensation of incomplete evacuation). RESULTS: A total of 801 women were randomized to the alosetron (n = 532) or placebo groups (n = 269). Physicians classified 98% of patients with diarrhea-predominant IBS. Patients treated with alosetron had a significantly greater proportion of days with satisfactory control of urgency compared to placebo for the treatment period (73% vs 57%, p < 0.001). A significantly greater number of patients treated with alosetron were IBS Global Improvement responders compared to placebo at week 12 (76% vs 44%, p < 0.001). IBS Global Improvement responders had more days with satisfactory control of urgency at week 12 (88% vs 48%) as well as firmer stools, fewer stools/day, and fewer days with incomplete evacuation compared with nonresponders. Alosetron-treated patients showed improvements in bowel functions compared to placebo-treated patients. Constipation was the most commonly reported adverse event.

Carbolines↗

New approaches to therapy for mastocytosis. A case for treatment with kit kinase inhibitors.

Some forms of mastocytosis are caused by c-kit mutations which cause constitutive activation of kit kinase. Compounds that inhibit kit kinase, such as indolinones, are therefore attractive as potential therapeutic agents. A hierarchy exists in the ability of compounds to inhibit kit kinase effectively. Some compounds can inhibit ligand-induced activation of wild-type receptor but are ineffective against constitutively activated mutants. Other compounds can inhibit ligand-induced activation of wild-type kit and ligand-independent activation by juxtamembrane domain mutations but not activation by activation loop mutations. Still others effectively inhibit wild-type kit and constitutively activated kit bearing either juxtamembrane or kinase domain mutations and kill the neoplastic mast cells expressing these mutants. No therapy currently exists that specifically targets a cause of mastocytosis, but there are good reasons to believe that kit kinase inhibitors may fulfill that role someday.

Amino Acid Substitution↗

Indolinone derivatives inhibit constitutively activated KIT mutants and kill neoplastic mast cells.

Mastocytosis is a neoplastic disease caused at least in part by somatic mutations of the c-KIT proto-oncogene resulting in constitutive activation of its protein product, KIT, the receptor tyrosine kinase for stem cell factor. KIT stimulates mast cell proliferation and prevents apoptosis of neoplastic mast cells. To develop potential therapies for mastocytosis we used indolinones, small molecules that inhibit tyrosine kinases. Four indolinone derivatives (SU4984, SU6663, SU6577, and SU5614) inhibited wild-type KIT, but variably inhibited constitutively activated KIT mutants. SU4984, SU6577, and SU5614 were effective against KIT with juxtamembrane activating mutations, whereas only SU6577 could suppress KIT containing either juxtamembrane or kinase domain activating mutations. Furthermore, SU4984, SU6577, and SU5614 killed neoplastic mast cells expressing a juxtamembrane-mutated KIT, whereas SU4984 and SU6577 killed neoplastic mast cells expressing KIT bearing a kinase domain mutation. These data show a direct correlation between inhibition of constitutively activated KIT and the death of neoplastic mast cells, and point to specific tyrosine kinase inhibitors as a potential therapy aimed directly at a cause of mastocytosis.

Gene Expression Regulation↗

Perspectives of those impacted: flight attendant's perspective.

New regulations regarding radiation exposure to flight attendants are compared to regulations regarding airlines' "no smoking" policies. The new regulations will not be accepted as wholeheartedly by the industry because the ill effects of radiation are not as tangible as those of cigarettes, and there is a risk of a loss of wages due to restrictions during pregnancy. Nevertheless, the carrier's unions would like to act responsibly to ensure the safety of all flight attendants.

Aircraft↗

A multicentre evaluation of the laser assisted ratio analyser (LARA): a novel device for measurement of 13CO2 in the 13C-urea breath test for the detection of Helicobacter pylori infection.

BACKGROUND: The laser assisted ratio analyser (LARA) was developed as a novel device to measure 13CO2 in the urea breath test for the detection of H. pylori infection. The analyser was tested in a prospective multicentre study in 444 patients in North America (Phase 1) followed by second study involving 160 patients (Phase 2). METHODS: Patients undergoing endoscopy for clinical indications had antral and gastric biopsies taken for histological examination, culture and CLO test. One hour after endoscopy, a baseline breath sample was obtained, 100 mg of 13C-urea were ingested and breath samples were obtained at 30 and 60 min post ingestion. Data obtained with the LARA were compared with the results of culture, rapid urease testing and central pathology in two different combinations {reference standards}. The study was conducted in two phases: in Phase 2, a modification was made to the LARA that improved the removal of water vapour from the breath sample. RESULTS: In Phase I, data from 331 patients were analysed using a cut off of (delta) 7.8 +/- 0.8, the sensitivity of the method was 91.7% and the specificity was 86.5%, using the reference standard of 2 of 3 tests (CLO, culture or histology) being positive. Positive and negative predictive values were, respectively, 85.2% and 92.5%. In Phase 2 of the study, 160 patients were enrolled and 141 patients were analysed using the same standards. We used the same reference standards but with a cut off of (delta) 6.1 +/- 0.6. The sensitivity and specificity increased to 96.8% and 98.6%, respectively. Positive and negative predictive values were, respectively, 98.4% and 97.3%. The detection rates for H. pylori were similar in patients with peptic ulcer or H. pylori associated gastritis. CONCLUSIONS: The LARA provides an accurate non-invasive means of detecting 13CO2 in the 13C-urea breath test for H. pylori in a multicentre clinical environment that compares well with invasive 'gold standard' methods.

Adolescent↗

Human immunodeficiency virus neurotropism: an analysis of viral replication and cytopathicity for divergent strains in monocytes and microglia.

Productive replication of human immunodeficiency virus type 1 (HIV-1) in brain macrophages and microglia is a critical component of viral neuropathogenesis. However, how virus-macrophage interactions lead to neurological disease remains incompletely understood. Possibly, a differential ability of virus to replicate in brain tissue macrophages versus macrophages in other tissues underlies HIV-1 neurovirulence. To these ends, we established systems for the isolation and propagation of pure populations of human microglia and then analyzed the viral life cycles of divergent HIV-1 strains in these cells and in cultured monocytes by using identical viral inocula and indicator systems. The HIV-1 isolates included those isolated from blood, lung tissue, cerebrospinal fluids (CSF), and brain tissues of infected subjects: HIV-1(ADA) and HIV-1(89.6) (from peripheral blood mononuclear cells), HIV-1(DJV) and HIV-1(JR-FL) (from brain tissue), HIV-1(SF162) (from CSF), and HIV-1(BAL) (from lung tissue). The synthesis of viral nucleic acids and viral mRNA, cytopathicity, and release of progeny virions were assessed. A significant heterogeneity among macrophage-tropic isolates for infection of monocytes and microglia was demonstrated. Importantly, a complete analysis of the viral life cycle revealed no preferential differences in the abilities of the HIV-1 strains tested to replicate in microglia and/or monocytes. Macrophage tropism likely dictates the abilities of HIV-1 to invade, replicate, and incite disease within its microglial target cells.

Cells, Cultured↗

A review of nursing research on the use of unlicensed assistive personnel (UAP).

The increased use of unlicensed assistive personnel (UAP) has raised the question: "What nursing research has been conducted to evaluate the effectiveness of the UAP in relation to patient outcomes?" To answer this question, the New York State Nurses Association Council on Nursing Research conducted a literature review on the issue of UAP. The specific purposes of this article are to: (a) present an overview of the health care climate and consumer and RN reaction in relation to the UAP movement, (b) summarize reported reviews of UAP research conducted between 1988 and 1994, (c) critique and synthesize the most recent UAP nursing research conducted between 1994 and 1997, and (d) make recommendations for education, practice, and research.

Attitude of Health Personnel↗

Myocardial adaptation during and after sustained, demand-induced ischemia. Observations in closed-chest, domestic swine.

BACKGROUND: We tested the hypotheses that prolonged, demand-induced myocardial ischemia plateaus and that on relief of stress, myocardial function remains depressed, with proportionate reductions in blood flow and oxygen consumption indicative of hibernation. METHODS AND RESULTS: Closed-chest swine (n = 20) were prepared with an 80% coronary stenosis. Hemodynamics, myocardial blood flow, oxygen, and lactate metabolism were measured in group 1 (n = 9) (1) at baseline, (2) at 10 and 30 minutes of atrial pacing plus intravenous norepinephrine infusion, and (3) in 5 of 9 (group 1a) at approximately 50 minutes after stress. Group 1a had ischemia assessed with 99mTc-labeled BMS 181321. In group 2 (n = 11), myocardial function was determined with radionuclide ventriculography (n = 8), and myocardial necrosis was looked for with trichlorotetrazolium chloride staining (n = 7), histology (n = 10), and myocardial creatine kinase concentration (n = 4). Baseline stenotic-zone endocardial blood flow was reduced versus the normal zone (0.94 +/- 0.33 versus 1.38 +/- 0.27 mL.min-1.g-1, mean +/- SD; P < .05), whereas epicardial flows were comparable (1.15 +/- 0.36 versus 1.16 +/- 0.26 mL.min-1.g-1). Stenotic-zone endocardial flow was unchanged versus baseline at 10 and 30 minutes of stress, whereas epicardial flow increased (1.62 +/- 0.53 mL.min-1.g-1 at 10 minutes and 1.44 +/- 0.51 mL.min-1.g-1 at 30 minutes, both P < .05). Myocardial oxygen consumption increased versus baseline (10.8 +/- 2.9 mL.min-1.100 g-1) at 10 and 30 minutes of stress (14.9 +/- 5.2 and 13.9 +/- 4.5 mL.min-1.100 g-1, both P < .05). After stress, stenotic-zone blood flow and oxygen consumption were reduced approximately 30% (P < .01) versus baseline. In group 2, stenotic-zone contraction with stress declined versus baseline and remained depressed throughout recovery. Histological and biochemical evidence of myocardial necrosis was absent in group 2. CONCLUSIONS: Myocardial ischemia induced by a sustained increase in oxygen demand may not progress to necrosis but may instead plateau. After relief of stress, myocardial function remains depressed, with a proportionate reduction in blood flow and oxygen consumption consistent with myocardial hibernation.

Animals↗

Influencing health care policy: nursing research and the ANA social policy statement.

This paper describes policy formation and its relationship to nursing research, examining ways in which nursing's disciplinary research can have greater influence on American health care policy. The American Nurses Association's Social Policy Statement (1995) is discussed in its role as a guide for nursing research efforts in a health care reform environment where favorable patient outcomes are key.

American Nurses' Association↗

Detection of acute bacterial infection within soft tissue injuries using a 99mTc-labeled chemotactic peptide.

OBJECTIVE: Infection imaging with a 99mTc-labeled chemotactic peptide was evaluated in a rabbit model of Escherichia coli infections in burned tissue. MATERIALS AND METHODS: The peptide was radiolabeled with 99mTc via the hydrazino nicotinamide derivative. Three groups of six animals were studied: (group A) unilateral infected burns; (group B) bilateral burns with unilateral infection; and (group C) uninfected burns. Twenty-four hours after injury, groups A and B were infected, and 8 hours later, all animals were injected with approximately 0.50 mCi of 99mTc-peptide. MEASUREMENTS AND MAIN RESULTS: In groups A and B, excellent images of the infections were obtained at 3 to 4 and 16 to 18 hours after injection of the peptide. At 3 to 4 hours after injection, the target-to-background ratios (T/B) were 3.12 +/- 0.28 for group A and 4.33 +/- 0.61 for group B (p = n.s.). At 16 to 18 hours, the T/B ratios increased significantly (p < 0.01): group A = 8.10 +/- 1.03 and B = 7.70 +/- 1.25. The T/B ratio for group C was only slightly greater than unity. CONCLUSIONS: These results indicate that 99mTc-labeled chemotactic peptides are effective radiopharmaceuticals for the rapid detection of focal sites of infection within thermally injured tissues.

Animals↗

Effects of breathing a normoxic helium mixture on exercise tolerance of patients with cystic fibrosis.

Breathing helium-oxygen (He-O2) mixtures of 20.9% O2/79.1% He has been shown to increase exercise ventilation and peak oxygen uptake in healthy subjects. The improved exercise performance is thought to be due to the reduced density of He-O2 compared to air and the resulting increases in ventilation. Patients with cystic fibrosis (CF) frequently have abnormal pulmonary function test results, low exercise ventilations and diminished exercise tolerance. This led to the hypothesis that in CF the exercise tolerance of patients might improve when breathing He-O2. To test this hypothesis, 11 patients with CF or mild to severe airway obstruction performed spirometry and progressive maximal exercise tests while breathing air or He-O2. The He-O2 mixture significantly increased (P < 0.05) forced expiratory volume in 1 sec (FEV1) by 8.2%, peak expired flow by 39%, and maximal voluntary ventilation (MVV) by 17.9% compared to air, while forced vital capacity (FVC) and forced mid-expiratory flow rate (FEF25-75%) were unchanged by breathing He-O2. Ventilation and oxygen uptake at matched submaximal power outputs were not increased while breathing He-O2, nor were peak exercise ventilation (VEpeak) or peak exercise oxygen uptake (VO2peak). Estimated hemoglobin saturation and total exercise time were also unchanged during He-O2 breathing. However, there was a trend for the subjects with the better FEV1 to increase VO2peak. Increases in VO2peak when breathing He-O2 and air were correlated (r = 0.67, P < 0.05) with the percent of predicted FEV1 values. Still, in the 11 patients as a group, breathing He-O2 did not significantly improve VO2peak, VEpeak, or exercise tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Methodist's migration path to the future.

As a result of work through the Care Data consortium in cooperation with Iowa Methodist and University of Chicago Hospitals, Methodist has implemented: an open systems integration strategy, a clinical repository, and clinician-centric access and distribution of information. The Care Data consortium gave rise to a new breed of automation that meets the needs of both ends of the clinical automation spectrum: migrating an integrated, single-vendor solution to an open systems integrated repository to users of a distributed, best-of-breed approach.

Computer Communication Networks↗