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Biomedical subjects

David Watson

Publications and source records attributed to David Watson.

At least 37 records · Page 2Linked to original sources

Health care resource use after acute stroke in the Glycine Antagonist in Neuroprotection (GAIN) Americas trial.

BACKGROUND AND PURPOSE: To compare 3-month stroke outcomes and stroke-related health care resource use between the US and Canada in the Glycine Antagonist in Neuroprotection (GAIN) Americas study. Delivery of medical care for stroke patients, often driven by efforts to curb costs, varies substantially between countries. Data on the potential impact of these variations on clinical outcomes are sparse. METHODS: The analysis of health care resource included total length of stay (LOS) in hospital, intensive care unit (ICU), and acute-care ward or rehabilitation unit, or both; number of outpatient rehabilitation sessions and visits to a physician; place of residence after discharge; and employment status. Cox proportional hazards models and logistic regression were used to calculate survival hazards and predictors of favorable functional outcome (Barthel Index of 95 to 100). RESULTS: One thousand six hundred four patients who were independent before stroke (mean age: 69.9+/-12.7 years, 53% men, 85% ischemic stroke, 69% in the US) were included. Three-month survival and functional outcome did not differ between the US and Canada. Survival rate was 80% in both countries. Favorable functional outcome was achieved in 43% of Canadian and 47% of US patients. Fewer Canadian patients received treatment in ICU (19% versus 63% in the US), and Canadians had longer stays in hospital or rehabilitation facility (median: 33 days versus 16 days in the US). CONCLUSIONS: Despite similar 3-month survival and functional outcome, patterns of health care resource varied substantially between the US and Canada. US patients had more intensive early care; Canadian patients had longer hospitalizations and rehabilitation care. Further research is required to determine the most cost-effective treatment and rehabilitation plan for people who have a stroke.

Acute Disease↗

The phobic stimuli response scales: a new self-report measure of fear.

Data from two large undergraduate samples were used to develop the phobic stimuli response scales (PSRS). Factor analyses of data from the first sample (N = 380) led to the creation of several scales, two of which (Social and Blood-Injection Fears) demonstrated good reliability and convergent validity. Analyses of data from a second sample (N = 330) were used to modify the three remaining scales (Animal, Bodily Harm, and Physical Confinement Fears), which also showed sound psychometric properties. As predicted, the PSRS were differentially correlated with neuroticism and extraversion, which may represent predisposing factors for these phobic responses. These new scales improve our understanding of the individual differences that are associated with various fears.

Adolescent↗

Symptom subtypes of obsessive-compulsive disorder and their relation to dissociation.

We examined relations between obsessive-compulsive disorder (OCD) symptoms and dissociation in three studies. Studies 1 and 2 established a strong level of convergence between our two OCD symptom measures. Specific types of symptoms showed a clear convergent/discriminant pattern, indicating that they can be meaningfully distinguished from one another. In both studies, dissociation correlated more strongly with checking and obsessive intrusions than with cleaning, ordering, and hoarding. Moreover, these associations remained substantial even after controlling for neuroticism (Study 1) and other types of anxiety (Study 2). In Study 3, we replicated our key findings in a psychiatric outpatient sample, indicating that they are generalizable to clinical participants. Taken together, our results (a) establish a strong link between dissociation and OCD, and (b) illustrate the importance of analyzing different types of OCD symptoms separately.

Adult↗

The role of person versus situation in life satisfaction: a critical examination.

Two main theoretical approaches have been put forward to explain individual differences in life satisfaction: top-down (i.e., personological) and bottom-up (i.e., situational). The authors examine the relative merit of these 2 approaches and the psychological processes underlying top-down models. Consistent with a top-down approach, meta-analytic findings indicate that Neuroticism, Extraversion, Agreeableness, and Conscientiousness are related to both various domain satisfactions and life satisfaction; however, consistent with a bottom-up approach, domain satisfactions are strongly linked to life satisfaction but only weakly linked to each other. Path analyses based on meta-analytic estimates did not support a simple "direct-effects" top-down model but supported both (a) a temperament-based top-down model and (b) an integrative model that incorporates the direct influence of domain satisfactions on life satisfaction.

Humans↗

Cardiovascular effects of the nitric oxide synthase inhibitor NG-methyl-L-arginine hydrochloride (546C88) in patients with septic shock: results of a randomized, double-blind, placebo-controlled multicenter study (study no. 144-002).

OBJECTIVE: To assess the hemodynamic effects of the nitric oxide synthase inhibitor 546C88 in patients with septic shock, although this was not a stated aim of the protocol. The predefined primary efficacy objective of the protocol was resolution of shock determined at the end of a 72-hr treatment period. DESIGN: Multicentered, randomized, placebo-controlled, safety and efficacy study. SETTING: Forty-eight intensive care units in Europe, North America, and Australia. PATIENTS: A total of 312 patients with septic shock diagnosed within 24 hr before randomization. INTERVENTIONS: Patients were randomly allocated to receive either 546C88 or placebo (5% dextrose) by intravenous infusion for up to 72 hrs. Conventional vasoactive therapy was restricted to norepinephrine, dopamine, and dobutamine. Study drug was initiated at 0.1 mL/kg/hr (5 mg/kg/hr 546C88) and titrated according to response up to a maximum rate of 0.4 mL/kg/hr with the objective to maintain mean arterial pressure at 70 mm Hg while attempting to withdraw any concurrent vasopressor(s). MEASUREMENTS AND MAIN RESULTS: Requirement for vasopressors, systemic and pulmonary hemodynamics, indices of oxygen transport, and plasma concentrations of arginine and nitrate were assessed over time. The median mean arterial pressure for both groups was maintained > or =70 mm Hg. There was an early increase in systemic and pulmonary vascular tone and oxygen extraction, whereas both cardiac index and oxygen delivery decreased for patients in the 546C88 cohort. Although these parameters subsequently returned toward baseline values, the observed differences between the treatment groups, except for pulmonary vascular resistance and oxygen extraction, persisted throughout the treatment period, despite a reduced requirement for vasopressors in the 546C88 cohort. These changes were associated with a reduction in plasma nitrate concentrations, which were elevated in both groups before the start of therapy. CONCLUSIONS: The nitric oxide synthase inhibitor 546C88 can reduce the elevated plasma nitrate concentrations observed in patients with septic shock. In this study, treatment with 546C88 for up to 72 hrs was associated with an increase in vascular tone and a reduction in both cardiac index and oxygen delivery. The successful maintenance of a target mean arterial blood pressure > or =70 mm Hg was achieved with a reduction in the requirement for, or withdrawal of, conventional inotropic vasoconstrictor agents (i.e., dopamine and norepinephrine). There were no substantive untoward consequences accompanying these hemodynamic effects. An international, randomized, double-blind, placebo-controlled phase III study has since been conducted in patients with septic shock. Recruitment into the study was discontinued due to the emergence of increased mortality in the 546C88-treated group.

Adult↗

Administration of the nitric oxide synthase inhibitor NG-methyl-L-arginine hydrochloride (546C88) by intravenous infusion for up to 72 hours can promote the resolution of shock in patients with severe sepsis: results of a randomized, double-blind, placebo-controlled multicenter study (study no. 144-002).

OBJECTIVE: To assess the safety and efficacy of the nitric oxide synthase inhibitor 546C88 in patients with septic shock. The predefined primary efficacy objective was resolution of shock, defined as a mean arterial pressure > or =70 mm Hg in the absence of both conventional vasopressors and study drug, determined at the end of the 72-hr treatment period. DESIGN: Multicentered, randomized, placebo-controlled, safety and efficacy study. SETTING: Forty-eight intensive care units in Europe, North America, and Australia. PATIENTS: A total of 312 patients with septic shock diagnosed within 24 hr before randomization. INTERVENTIONS: Patients were randomly allocated to receive either 546C88 or placebo (5% dextrose) by intravenous infusion for up to 72 hrs. Conventional vasoactive therapy was restricted to norepinephrine, dopamine, and dobutamine. Study drug was initiated at 0.1 mL/kg/hr (5 mg/kg/hr 546C88) and titrated according to response up to a maximum rate of 0.4 mL/kg/hr with the objective to maintain mean arterial pressure at 70 mm Hg while attempting to withdraw any concurrent vasopressor(s). MEASUREMENTS AND MAIN RESULTS: Requirement for vasopressors, systemic hemodynamics, indices of organ function and safety (including survival up to day 28) were assessed. The median mean arterial pressure for both groups was maintained >70 mm Hg. Administration of 546C88 was associated with a decrease in cardiac index while stroke index was maintained. Resolution of shock at 72 hr was achieved by 40% and 24% of the patients in the 546C88 and placebo cohorts, respectively (p =.004). There was no evidence that treatment with 546C88 had any major adverse effect on pulmonary, hepatic, or renal function. Day 28 survival was similar for both groups. CONCLUSIONS: In this study, treatment with the nitric oxide synthase inhibitor 546C88 promoted the resolution of shock in patients with severe sepsis. This was associated with an acceptable overall safety profile.

Adult↗

Match makers and deal breakers: analyses of assortative mating in newlywed couples.

We conducted a comprehensive analysis of assortative mating (i.e., the similarity between wives and husbands on a given characteristic) in a newlywed sample. These newlyweds showed (a) strong similarity in age, religiousness, and political orientation; (b) moderate similarity in education and verbal intelligence; (c) modest similarity in values; and (d) little similarity in matrix reasoning, self- and spouse-rated personality, emotional experience and expression, and attachment. Further analyses established that similarity was not simply due to background variables such as age and education and reflected initial assortment (i.e., similarity at the time of marriage) rather than convergence (i.e., increasing similarity with time). Finally, marital satisfaction primarily was a function of the rater's own traits and showed little relation to spousal similarity.

Adult↗

A comparative developmental study of impulsivity in rats and humans: the role of reward sensitivity.

The present study was conducted to test the hypothesis that differences in reward sensitivity between adolescents and adults account for differences in impulsivity. In a comparative study, we examined preferences for various concentrations of sucrose solutions as an operational measure of reward sensitivity in adolescent and adult rats and humans. Humans also completed self-report measures of impulsivity and reward sensitivity. There was some indication that adolescents preferred sweeter solutions compared to adults. Also, adolescents scored substantially higher on impulsivity. However, adolescents and adults did not differ in self-ratings of reward sensitivity and personality scores were not consistently related to sucrose preferences. The data highlight some of the benefits and issues that arise with developing comparative measures in humans and animals. Future comparative research using alternative behavioral paradigms is necessary to determine if and how changes in reward sensitivity influence developmental shifts in impulsivity.

Adolescent↗

Towards more chemically robust polymer-supported chiral catalysts: alpha,alpha-diphenyl-L-prolinol based catalysts for the reduction of prochiral ketones with borane.

alpha,alpha-Diphenyl-L-prolinol derivatives with para-bromo substituents in either one or both of the phenyl rings are easily bound to crosslinked polystyrene beads containing phenylboronic acid residues by Suzuki couplings. By using extended reaction periods boronic acid residues that do not take part in the couplings are simply lost by hydrolysis. The polymer-supported (PS) alpha,alpha-diphenyl-L-prolinols were used to catalyse reductions of several prochiral ketones with borane in tetrahydrofuran at 22 degrees C. The expected secondary alcohols were obtained in high chemical yields and ees were generally in the range 79-97%. One PS catalyst was recycled 14 times without loss of stereochemical performance.

Boranes↗

Direct detection of deletion mutations in the yeast DEL assay using quantitative PCR (TaqMan).

Established mutagenesis assays measure mutant frequencies at selectable loci. These assays work by encouraging the growth of mutants to form visible colonies while suppressing the growth of non-mutants. An alternative strategy is to detect DNA alterations directly. We present an example of this latter strategy using TaqMan to quantify deletion mutants in mixed cultures of Saccharomyces cerevisiae strain RS112. The RS112 strain contains two heteroallelic his3 sequences that share approximately 400bp homology and are separated by approximately 7 kb of plasmid DNA. Spontaneous and chemical-induced strand breaks that occur in this region are repaired by intrachromosomal recombination, resulting in the loss of the plasmid DNA and creation of a His prototroph. Ordinarily, these prototrophs are detected by growth on His- medium over 2-3 days. In this case, we used TaqMan to selectively detect the DNA of deletion mutants in the presence of a large excess of DNA from non-mutants. This was accomplished using primers whose annealing sites were outside the region of DNA lost due to recombination. Thus, the primers were too far apart to produce PCR products using DNA from non-mutants, but produced a robust TaqMan signal using DNA from deletion mutants. Spontaneous and chemical-induced recombination frequencies (RF) were measured in a series of time-course and dose-response experiments with direct-acting mutagens. Interestingly, chemical-induced increases in RF were observed within a few hours of initiation of exposure, demonstrating that deletion mutations in RS112 can be fixed soon after DNA damage occurs. The ability to measure RF at any time during treatment will be useful for additional mechanistic studies. Chemical-induced increases in RF were also observed in the absence of selective growth conditions. As such, detection of deletion mutations with TaqMan may be applicable to measurements of RFs at non-selectable loci in yeast and other species. Finally, chemical-induced RFs after 17 h exposure were similar to those observed after 3 days growth on selective medium. The TaqMan assay may therefore be used to screen compounds more quickly for their ability to cause deletion mutations than is currently done by plating on selective medium.

Base Sequence↗

Measuring fatigue severity in primary care patients.

OBJECTIVE: We developed a new instrument to measure fatigue that synthesized information from existing instruments. METHODS: 35 candidate items and 4 formats for a new fatigue scale were obtained from 15 previously developed instruments. A new scale was developed using factor analysis on a data set of 409 primary care patients and validated on a sample of 816 additional subjects. RESULTS: Different formats for obtaining information about a given fatigue item gave similar results. The new 11 item scale contained four subscales: cognitive, fatigue, energy and productivity. Correlations between the four subscales ranged from.49 to.66. Patients with a higher fatigue score were much more likely to have lower health status, greater depression and more somatic symptoms. CONCLUSION: This new instrument may be useful in primary care and epidemiological studies to screen and monitor patients for fatigue severity and type.

Adolescent↗

Further investigation of the obsessive-compulsive inventory: psychometric analysis in two non-clinical samples.

The obsessive-compulsive inventory [OCI; Psychol. Assessment 10 (1998) 206-214] is a self-report measure of obsessive-compulsive disorder (OCD) intended for use with both clinical and non-clinical samples (). Two reports support its convergence with established measures of OCD and its assessment of specific symptom subtypes (e.g., checking and washing). The current studies investigate the OCI factor structure in two non-clinical samples. Based on correlational analyses and complementary factor analyses, Study 1 results indicate that five subscales, rather than the seven rationally derived ones, best capture the structure of symptoms measured by the OCI. These findings were replicated in Study 2. Based on these analyses, we offer suggestions for revising the original subscales into these five empirically derived subscales that closely resemble structures proposed in the current OCD literature.

Adult↗

Investigating the construct validity of the dissociative taxon: stability analyses of normal and pathological dissociation.

Research has suggested the existence of a pathological dissociative taxon. However, relatively little is known about this taxon. This study examined the 2-month retest stability of this taxon--together with other measures of dissociation and the Big Five--in a sample of 465 undergraduates. Contrary to expectation, taxon scores were only modestly stable and were substantially less stable than the other measures, including continuous indicators of dissociation. Furthermore, most individuals who were identified as taxon members at one assessment were classified as nonmembers at the other. These results challenge the existence of a pathological dissociative taxon. More generally, these data demonstrate that statistically identified taxa need to be explicated through the normal process of construct validation.

Adult↗

Efficacy and safety of darbepoetin alfa in anaemic patients with lymphoproliferative malignancies: a randomized, double-blind, placebo-controlled study.

This phase 3, randomized, double-blind, placebo-controlled study was designed to evaluate the efficacy and safety of darbepoetin alfa in anaemic patients with lymphoproliferative malignancies. Patients (n = 344) with lymphoma or myeloma received darbepoetin alfa 2.25 microg/kg or placebo s.c., once weekly for 12 weeks. The percentage of patients achieving a haemoglobin response was significantly higher in the darbepoetin alfa group (60%) than in the placebo group (18%) (P < 0.001), regardless of baseline endogenous erythropoietin level. However, increased responsiveness was observed in patients with lower baseline erythropoietin levels. Darbepoetin alfa also resulted in higher mean changes in haemoglobin than placebo from baseline to the last value during the treatment phase (1.80 g/dl vs 0.19 g/dl) and after 12 weeks of treatment (2.66 g/dl vs 0.69 g/dl). A significantly lower percentage of patients in the darbepoetin alfa group received red blood cell transfusions than in the placebo group (P < 0.001). The efficacy of darbepoetin alfa was consistent for patients with lymphoma or myeloma. Improvements in quality of life were also observed with darbepoetin alfa. The overall safety profile of darbepoetin alfa was consistent with that expected for this patient population. Darbepoetin alfa significantly increased haemoglobin and reduced red blood cell transfusions in patients with lymphoproliferative malignancies receiving chemotherapy.

Aged↗

Towards more chemically robust polymer-supported chiral catalysts for the reactions of aldehydes with dialkylzincs.

N-Methyl-alpha,alpha-diphenyl-L-prolinol derivatives with para-bromo substituents in one or both of the phenyl rings are easily bound to crosslinked polystyrene beads containing phenylboronic acid residues using Suzuki reactions. When the products were used as catalysts for the reactions of aldehydes with diethylzinc in toluene at 20 degrees C, the alcohols were produced in chemical yields >90% and with ees of upto 94%. The better of the two supported catalysts gave ees only 0-9% lower than those obtained with the corresponding soluble catalyst. One of the supported catalysts was recycled successfully nine times.

Alcohols↗

Antenatal supplementation of antioxidant vitamins to reduce the oxidative stress at delivery--a pilot study.

BACKGROUND: Preterm infants are at increased risk of oxidative stress and free-radical mediated diseases partly related to deficient antioxidant state. The purpose of this study was to investigate if maternal supplementation of antioxidant vitamins prior to delivery would reduce the oxidative stress in the mothers and their infants. STUDY DESIGN: A pilot case-control study. PATIENTS AND METHODS: Five mothers at risk of preterm delivery between 30 and 36 weeks were given a daily oral dose of betacarotene 20 mg, vitamin E 167.8 mg and vitamin C 1000 mg until delivery. Plasma levels of MDA and vitamins A, E and beta-carotene were measured prior to treatment in mothers and at delivery in both mothers and neonates. Seven mother-infant pairs comparable in gestation and birthweight acted as controls. RESULTS: In the supplemented group, median maternal plasma MDA at delivery was significantly lower compared to the pretreatment level (1.9 vs. 3.2 micromol/l, p=0.04) and it was also lower than the control group (1.9 vs. 3.65 micromol/l, p<0.001). In the supplemented group, median maternal plasma vitamin E at delivery was significantly higher than the levels prior to treatment (46 vs. 31 micromol/l, p=0.007) in the same group and those at delivery in the control group (46 vs. 30 micromol/l, p=0.03). There was a trend of lower plasma MDA and higher vitamin E at birth in infants born to supplemented mothers, but it did not reach statistical significance. CONCLUSION: A short supplementation of multiple antioxidant vitamins to a small sample of preterm pregnant women reduced the oxidative stress at delivery in mothers and probably in their neonates. Larger studies probably using larger doses are needed to evaluate the efficacy of this strategy.

Administration, Oral↗