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Biomedical subjects

A Thompson

Publications and source records attributed to A Thompson.

At least 181 records · Page 10Linked to original sources

A placebo controlled comparison of the effects of metoprolol and celiprolol on echo-Doppler measurements of cardiovascular function in normal volunteers.

1. This study used a continuous-wave echo-Doppler method (Exerdrop) to investigate the effects of beta-adrenoceptor antagonism and partial agonism on cardiovascular responses at rest and during dynamic exercise. 2. A double-blind, randomised, placebo controlled comparison of metoprolol (50 mg) and celiprolol (200 mg) was undertaken in nine normal volunteers; single oral doses of medication were administered at weekly intervals. Rest and exercise (supine bicycle) haemodynamics were assessed at 0, 2, 4, 6 and 8 h following dosing. 3. Before dosing and after placebo, the aortic flow velocity, acceleration and velocity integral increased progressively during exercise, as did heart rate, blood pressure and cardiac output. 4. Following metoprolol 50 mg, heart rate was significantly reduced without change in systolic or diastolic blood pressure. Echo-Doppler peak acceleration and velocity decreased at rest. On exercise, heart rate and systolic blood pressure fell significantly; the increase in acceleration was significantly blunted compared with placebo (a decrease of 15.2% at rest and 22.9% at 75 watts; P < 0.01 vs placebo). Peak velocity fell significantly by 75 watts exercise. 5. Celiprolol 200 mg at rest significantly increased systolic blood pressure, peak acceleration and velocity. On exercise celiprolol, in contrast to metoprolol, did not reduce peak acceleration or peak velocity; however exercise heart rate and systolic blood pressure were significantly reduced. The difference between celiprolol and metoprolol in respect of peak acceleration persisted over the 8 h of the study. 6. These differences between metoprolol and celiprolol are compatible with the partial agonism of celiprolol.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Khat chewing and bladder neck dysfunction. A randomized controlled trial of alpha 1-adrenergic blockade.

OBJECTIVE: To assess whether the effect of chewing khat leaves (Catha edulis) on the urodynamics of healthy males is altered by the selective alpha 1-adrenergic blocking agent indoramin in a prospective randomized double-blind controlled trial. SUBJECTS AND METHODS: The urodynamics of 11 healthy males were studied before and during a khat chewing session preceded by indoramin or placebo. RESULTS: Khat chewing produced a fall in average and maximum urine flow rate. This effect was inhibited by indoramin. CONCLUSIONS: The urinary side-effects of khat chewing are probably mediated through stimulation of alpha 1-adrenergic receptors.

Adult↗

Endothelin receptor A blockade alters hemodynamic response to nitric oxide inhibition in rats.

We examined the extent to which the systemic and renal vasoconstriction induced by nitric oxide (NO) inhibition in vivo is mediated by endothelin (ET). We examined the effects of BQ-610, a specific ETA-receptor antagonist, after NO inhibition with N omega-nitro-L-arginine methyl ester (L-NAME) in the anesthetized rat. Mean arterial pressure (MAP) increased after L-NAME infusion from 107 +/- 2 to 133 +/- 3 mmHg (P < 0.05 vs. baseline period) then fell to 115 +/- 3 mmHg after administration of BQ-610 (P < 0.05 vs. L-NAME and baseline periods). Systemic vascular resistance (SVR) increased from 1.26 +/- 0.06 to 2.17 +/- 0.18 mmHg.ml-1.min.300 g after L-NAME (P < 0.05 vs. baseline period) then fell to 1.69 +/- 0.12 mmHg.ml-1.min.300 g after BQ-610 (P < 0.05 vs. L-NAME and baseline periods). The increase in renal vascular resistance (RVR) from 6.4 +/- 0.4 to 13.7 +/- 1.4 mmHg.ml-1.min.300 g induced by L-NAME (P < 0.05 vs. baseline period) was reduced to 11.1 +/- 1.0 mmHg.ml-1.min.300 g by BQ-610 (P < 0.05 vs. L-NAME and baseline periods). The extent to which BQ-610 reversed the L-NAME-induced increases in RVR and SVR was comparable (RVR by 40 +/- 9%; SVR by 52 +/- 7%). Glomerular filtration rate and renal blood flow were both reduced by L-NAME, but neither value increased after BQ-610, possibly because the renal vasodilation induced by ETA blockade was offset by the concomitant reduction in MAP and renal perfusion pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Metabolic end products inhibit sarcoplasmic reticulum Ca2+ release and [3H]ryanodine binding.

Sarcoplasmic reticulum (SR) Ca2+ release channel function is modified by ligands (Mg2+, Ca2+, ATP, and H+) that are generated during a bout of exercise. We have examined the effects of changing intracellular metabolites on Ca2+ release, [3H]ryanodine binding, and single-Ca2+ release channel activity of SR isolated from white rabbit skeletal muscle. Increasing Mg2+ (from 0 to 4 mM) and decreasing pH (7.1-6.5) inhibited SR Ca2+ release and [3H]-ryanodine binding. In addition, increasing lactate concentrations from 2 to 20 mM inhibited [3H]ryanodine binding to SR vesicles, inhibited SR Ca2+ release, and decreased the single-channel open probability. These findings suggest that intracellular modifications that disrupt excitation-contraction coupling and decrease Ca2+ transients will promote a decline in tension development and contribute to muscle fatigue. In addition, we show that hydrogen peroxide induces Ca2+ release and increases [3H]ryanodine binding to its receptor, suggesting that reactive oxygen species produced during exercise may compromise muscle function by altering the normal gating of the SR Ca2+ release channel.

Adenosine Triphosphate↗

A scale for identifying "Stockholm syndrome" reactions in young dating women: factor structure, reliability, and validity.

The factor structure, reliability, and validity of a 49-item scale designed to measure Stockholm Syndrome (also referred to as "traumatic bonding" and "terror bonding"), that is, bonding with an abusive partner, were assessed for college women in heterosexual dating relationships. Factor analysis identified three major factors: Core Stockholm Syndrome, characterized by cognitive distortions and other strategies for coping with abuse; Psychological Damage, marked by depression, low self-esteem, and loss of sense of self; and Love-Dependence, typified by the feeling that one cannot survive without one's partner's love. The scale and factors had excellent internal consistency and good test-retest reliabilities. They correlated negatively with the Marlowe-Crowne Social Desirability scale and positively with Horowitz, Wilner, & Alvarez' (1979) Impact of Event Scale, Hyler and Rieder's (1987) Borderline Personality Disorder Scale, Hatfield and Sprecher's (1986) Passionate Love Scale, and Straus' (1979) Verbal Aggression and Violence scales of the Conflict Tactics Scales.

Adaptation, Psychological↗

A PCR-based genetic linkage map of human chromosome 16.

A high-resolution cytogenetic-based physical map and a genetic linkage map of human chromosome 16 have been developed based on 79 PCR-typable genetic markers and 2 Southern-based RFLP markers. The PCR-based markers were previously characterized polymorphic (AC)n repeats. Two approaches have led to the characterization of 47 highly informative genetic markers spread along chromosome 16, some of which are closely linked to disease loci. In addition, 22 markers (D16S401-423) previously genetically mapped were also physically mapped. Ten markers characterized by other laboratories were physically mapped and genotyped on the CEPH families. These 32 markers were incorporated into the PCR-based map. Seventy-two markers have heterozygosities > 0.50 and 51 of these markers > 0.70. By multipoint linkage analysis a framework genetic map and a comprehensive genetic map were constructed. The length of the sex-averaged framework genetic map is 152.1 cM. The average distance and the median distance between markers on this map are 3.2 and 2.7 cM, respectively, and the largest gap is 15.9 cM. These maps were anchored to the high-resolution cytogenetic map (on average 1.5 Mb per interval). Together these integrated genetic and physical maps of human chromosome 16 provide the basis for the localization and ultimately the isolation of disease genes that map to this chromosome.

Animals↗

Rat heart fatty acid-binding protein content is increased in experimental diabetes.

Cytoplasmic fatty acid-binding protein (FABP) was assayed immunochemically in hearts from rats with insulin-dependent (IDDM) or non-insulin-dependent diabetes mellitus (NIDDM). FABP contents were 34% higher in IDDM and 103% higher in NIDDM hearts than in respective age-matched controls. FABP levels returned to control values when islets of Langerhans were transplanted into diabetic IDDM animals. In the diabetic hearts the activity of fructose-6-phosphate kinase decreased (IDDM and NIDDM animals), while that of 3-hydroxyacyl-CoA dehydrogenase increased (NIDDM animals only). These data indicate that experimental diabetes induces a marked increase of the FABP content of rat heart and suggests that this protein is involved in the enhanced fatty acid utilization by the diabetic heart.

Animals↗

Ethical issues in the pediatric intensive care unit.

Advanced technology and better scientific understanding of mechanisms of disease now permit intensive care personnel to extend life beyond what some patients and families consider reasonable, leading, in part, to the "patients' rights" movement and the articulation of legal and moral guidelines for foregoing life support. In the case of pediatrics, commentaries on a few of the topics that have arisen most frequently or have provided the greatest challenge in the authors' experience are provided.

Adolescent↗

Continuous quality improvement in an acute hospital: a report of an action research project in three hospital departments.

Describes an action research project to improve quality in three hospital departments including operating theatres, X-ray, and medical records. The approach combined quality assurance (QA) or audit methods with those of continuous quality improvement (CQI) or TQM. The intention was to bring about improved organizational performance through an emphasis on bottom-up rather than top-down methodology, and to assess the relative effectiveness of different quality strategies being used within the hospital. Baseline studies of organizational climate and of patient perceptions enabled evaluation of effectiveness. Provides a description of the background to various health-care quality strategies, and argues that several perspectives are required if all stakeholders (e.g. policy makers, professionals, patients, and managers) are to be satisfied. Describes the responses of staff, superiors and professionals and recommendations offered for more effective quality strategy implementation.

Attitude of Health Personnel↗

Stroma-free hemoglobin increases blood pressure and GFR in the hypotensive rat: role of nitric oxide.

The short-term systemic and renal hemodynamic effects of two stroma-free hemoglobin (SFH) solutions, one unmodified and the other modified by cross-linking, were examined in anesthetized rats after hemorrhagic hypotension. Both forms of SFH increased mean arterial pressure (MAP) and glomerular filtration rate (GFR) to baseline (prehemorrhage) values. The increase in MAP induced by unmodified SFH was greater than the increase in MAP caused by an albumin solution isoncotic to the unmodified SFH solution. Similarly, the increase in MAP caused by the modified SFH was also substantially greater than that induced by an albumin solution of comparable oncotic pressure to the modified SFH solution. Both unmodified and modified SFH increased GFR. As with MAP, the increase in GFR induced by both SFH solutions was greater than that associated with the oncotically matched albumin solutions. In separate experiments, the effects of nitric oxide (NO) inhibition with N omega-nitro-L-arginine methyl ester (L-NAME) on MAP after hemorrhagic hypotension and subsequent infusion of unmodified SFH or albumin were also examined. In the albumin-infused rats, L-NAME increased MAP. In marked contrast, NO inhibition with L-NAME had no further effect on MAP when infused after SFH. We conclude that both unmodified and modified SFH solutions acutely improve MAP and GFR by the combined effects of intravascular volume expansion resulting from the colloid effect of the protein and by inactivation of NO.

Animals↗

Extracorporeal membrane oxygenation for pediatric respiratory failure: five-year experience at the University of Pittsburgh.

OBJECTIVES: To describe the etiology, respiratory severity of illness, and outcome in patients with pediatric respiratory failure who were treated with extracorporeal membrane oxygenation (ECMO). To identify predictors of death, and to compare our morbidity and mortality rates with those rates of a previously reported series of patients with pediatric respiratory failure managed conventionally. DESIGN: Survey, case series. SETTING: Intensive care unit in a tertiary care pediatric hospital. PATIENTS: Twenty-eight pediatric patients (3 wks to 20 yrs of age) who underwent ECMO for pediatric respiratory failure between 1985 and 1991. MEASUREMENTS AND MAIN RESULTS: Thirteen (46%) of the 28 patients survived. The most common diagnoses were adult respiratory distress syndrome and nonspecific pneumonitis. Multiple organ system failure occurred in only four (14%) patients; most patients died of respiratory failure. The occurrence of persistent airleak during ECMO was significantly greater in nonsurvivors than in survivors. Furthermore, nonsurvivors had significantly less response to lung reexpansion maneuvers compared with survivors, as measured by a calculated compliance index (effective tidal volume/mean airway pressure x 100). The mortality rate was comparable with those rates of other published studies of conventionally managed and ECMO-treated patients with pediatric respiratory failure. Moreover, our patients appeared to exhibit more severe respiratory failure at the start of ECMO than those patients in other studies. CONCLUSIONS: ECMO appears to be a rational therapy for patients with pediatric respiratory failure who are likely to die with continued conventional management. Recovery of lung function by the end of the first week of ECMO may be a favorable prognostic indicator. Persistent airleak may be a nonfavorable prognostic indicator.

Adolescent↗

Crystallization and preliminary X-ray analysis of the di-haem cytochrome c peroxidase from Pseudomonas aeruginosa.

Cytochrome c551 peroxidase is a periplasmic enzyme expressed in Pseudomonas aeruginosa at low oxygen tensions. The glycosylated enzyme has been purified to homogeneity and crystallized by vapour diffusion techniques using polyethylene glycol 2000 as the precipitant in the presence of isopropanol. The crystals belong to the trigonal space group P3(1)21 or P3(2)21 with unit cell dimensions of a = b = 113.8 A, c = 72.0 A. They are suitable for X-ray analysis and diffract to dmin = 2.5 A. There is one peroxidase molecule in the crystallographic asymmetric unit.

Cytochrome-c Peroxidase↗

Characterization of the bovine brain cytosolic phosphatidylinositol 3-kinase complex.

Receptor-linked phosphatidylinositol (PtdIns) 3-kinase may generate a second-messenger signal. Here a large-scale purification of the bovine brain enzyme, based on methods developed by Morgan, Smith and Parker [(1990) Eur. J. Biochem. 191, 761-767] and Fry, Panayotou, Dhand, Ruiz-Larrea, Gout, Nguyen, Courtneidge and Waterfield [(1992) Biochem. J. 288, 383-393] is described. The purified enzyme is shown to be a heterodimer of 85 kDa and 110 kDa protein subunits (p85 and p110). Labelling with 5'-p-fluorosulphonylbenzoyladenosine shows that p110 contains an ATP-binding site and confers catalytic activity to the complex. The purified complex is known to be highly phosphorylated on both p85 alpha and p110 subunits, and dephosphorylation generates a deactivated complex, indicating that phosphorylation is an important covalent modification of the complex and may modulate PtdIns 3-kinase activity.

Adenosine↗

Low dose continuous infusion doxorubicin in children and young adults.

Ten patients (age range 3.2-26.3 yrs) with relapsed or resistant malignancies received a total of 20 courses of low dose continuous infusion doxorubicin (3 mg/m2/day for 28 days) delivered by portable Graseby infusion pumps via central venous catheters. Each patient received a median dose of 144 mg/m2 (range 87-261). Four patients responded to treatment (1 complete response (CR) and 3 partial response (PR)) and performance status improved in seven patients. Overall toxicity was minimal: WHO Grade 4 anaemia in 2/18 courses, Grade 4 neutropenia in 1/18, Grade 3-4 thrombocytopenia in 3/18, nausea and vomiting of Grades 2 and 4 in 4/20 and 1/20 respectively, and mucositis of Grades 2 and 4 in 2/20 courses each. Cardiac toxicity was assessed using echocardiography, and fractional shortening remained within normal limits in all patients. Low dose continuous infusion doxorubicin is a feasible, well tolerated, ambulatory therapy in children and may be an effective way of delivering doxorubicin with less toxicity, thus enabling the development of more dose intensive regimens.

Adolescent↗