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Biomedical subjects

R Stewart

Publications and source records attributed to R Stewart.

At least 37 records · Page 2Linked to original sources

Mapping of QTL influencing saccharin consumption in the selectively bred alcohol-preferring and -nonpreferring rat lines.

The inbred preferring (iP) and nonpreferring (iNP) rat strains were derived from the selectively bred alcohol-preferring (P) and alcohol-nonpreferring (NP) lines. Previously, 381 iP x iNP F2 progeny were generated to identify quantitative trait loci (QTLs) influencing alcohol consumption and preference. Saccharin consumption (ml/48 h) and saccharin intake (ml/kg/day) were also measured in the F2 sample and were significantly correlated with both alcohol consumption and preference (all r > or = .20, p < .0001), suggesting that there might be some QTLs influencing both saccharin and alcohol phenotypes. We have performed a genome screen using F2 animals with extreme saccharin or alcohol consumption to identify QTLs contributing to saccharin-related phenotypes. Lod scores greater than 2.0 were found on chromosomes 3, 16 and 18 in this sample. Additional genotyping was performed in these regions in the full sample of 381 F2 progeny to further characterize these putative QTLs. On chromosome 3, the maximum lod score in the full sample was 2.7 with saccharin consumption. This QTL appears to overlap with a QTL identified for alcohol consumption in the iP and iNP lines and has pleiotropic effects on both phenotypes. Interestingly, this region of rat chromosome 3 is syntenic with mouse chromosome 2, where a QTL influencing alcohol preference has been previously reported. The QTL on chromosome 16 has a maximum lod score of 4.0 with saccharin intake and 2.6 with saccharin consumption. The QTL on chromosome 18 has a maximum lod score of 2.7 with saccharin consumption. Taken together, these data provide the first results of a genome screen for QTLs contributing to saccharin phenotypes in the rat.

Alcohol Drinking↗

Dexamethasone reduces pain after tonsillectomy in adults.

The aim of this study was to assess the effect of a course of dexamethasone on postoperative pain and morbidity after adult tonsillectomy. We report the results of a double-blind, randomized, placebo-controlled trial of 200 adult patients undergoing elective tonsillectomy. Patients were randomized to three groups: one group received the non-steroidal anti-inflammatory drug piroxicam for 8 days postoperatively, one group received dexamethasone for the same period and the third group received both drugs. Patients recorded their pain scores and analgesic requirements daily for 10 days. Patients treated with a combination of piroxicam and dexamethasone recorded consistently lower pain scores than those treated with either drug alone. This difference was statistically significant (P < 0.05) on all days except the day of surgery and the second postoperative day. Patients treated with piroxicam alone had significantly higher analgesic requirements than in either of the other groups. Dexamethasone given in this regime reduces postoperative pain and analgesic requirements after adult tonsillectomy.

Analgesics↗

Purification of human immunoglobulin G: a new approach to plasma fractionation.

BACKGROUND AND OBJECTIVES: Currently, plasma fractionation involves multiple processing steps using established methods such as ethanol precipitation and column chromatography. The known limitations associated with conventional purification techniques, combined with strict regulations on safety and high demand for particular plasma proteins, have resulted in a shortage of plasma-derived therapeutics such as intravenous immunoglobulin G (IgG). MATERIALS AND METHODS: In this study, IgG was purified from human plasma using Gradiflow technology, an electrophoresis-based separation technology. RESULTS: IgG was isolated from plasma to high purity, with 94 +/- 5% recovery in a short processing time. CONCLUSIONS: The technology has been shown to be linearly scalable and has the capacity to contribute to increased production of important plasma fraction therapeutics.

Chemical Fractionation↗

The effects of hemodilution with Hemolink upon hemodynamics and blood flow distribution in anesthetized dogs.

Hemoglobin based oxygen-carrying solutions (HBOCs) as hemoglobin replacement therapeutics are being tested for clinical use. Some of these products are associated with elevations in both systemic and pulmonary vascular resistances but their effect on the distribution of blood flow to major organs in larger animals have not been extensively described. We tested two formulations of o-raffinose cross-linked human hemoglobin, Hemolink (frozen-Hemolink-1 and refrigerated Hemolink-2) and compared them to Pentaspan, a colloid volume expander in extensive clinical use. Cardiovascular measurements and the distribution of blood flow (radionuclide-labeled microspheres) to the major organs were determined in Beagle dogs (n = 5 per group). After baseline measurements, either Hemolink-1, Hemolink-2, or Pentaspan was exchange transfused in an isovolemic manner (resulting in hematocrit reduction to approximately 20-25%); measurements were made 30, 60, 120 and 180 min post-exchange. There was no significant difference in cardiac output, mean arterial pressures and systemic or pulmonary vascular resistances after exchange in any of the three groups. Myocardial blood flow increased in all three groups post-exchange but the increase was more sustained in the Hemolink groups. Endocardial/epicardial flow ratios were also maintained after exchange in all groups. Thus, Hemolink is ideally suited for volume replacement when used in conjunction with acute normovolemic hemodilution because under these circumstances, the adverse hemodynamic effects are alleviated while extra hemoglobin is added to the blood.

Anesthesia↗

Low cholesterol, cognitive function and Alzheimer s disease in a community population with cognitive impairment.

BACKGROUND: The association between cholesterol levels, cognitive impairment and dementia is controversial. OBJECTIVES: To investigate differences in serum total cholesterol levels between mild and moderate cognitive impairment and between dementia syndromes. To investigate the association between cholesterol level and progression of Alzheimer s disease (AD). DESIGN: Non-fasting cholesterol levels were measured in two groups: a) 291 participants in a community study in South Korea, aged 65 or over, and scoring below 25 on the Mini-Mental State Examination (Korean version: MMSE-K); and b) 79 patients with AD attending a local hospital. In the community sample, associations were investigated between cholesterol level and both cognitive function and dementia (DSM-IV). For the hospital sample, associations were investigated between cholesterol level and decline in cognitive function (MMSE-K) and/or functional activities of daily living (ADL, Blessed Dementia Scale) over one year. RESULTS: Lower serum cholesterol level was associated with worse cognitive function in the community sample. Associations with dementia were specific to AD rather than other subtypes. No cross-sectional association was found between cholesterol levels and cognitive function in AD groups from either sample. No prospective associations were found between cholesterol level and decline of cognitive function or functional ADL in hospital attenders with AD. Adjustment for age, gender, education, past occupation, disablement, duration of dementia, and the presence of APOE e4 made little difference to the associations in the hospital sample. CONCLUSION: Lower serum cholesterol level may be a state marker of AD but does not appear to influence its rate of progression.

Journal Article↗

Impact of solubility on laser tissue-welding with albumin solid solders.

BACKGROUND AND OBJECTIVE: The correlation between the solubility of solid albumin solders and their laser weld strength was investigated. STUDY DESIGN/MATERIALS AND METHODS: Sections of dog intestine were laser welded with soluble or insoluble solid strips of solder. Two different treatments were followed for tissue soldering: "wet weld" and "dry weld." These treatments were chosen to assess the impact of solubility on the repair strength. The laser power and radiation dose were 0.14 W and 14 J/mg, respectively. Calorimetric measures of solders were also performed. RESULTS: The moisture on the tissue partially dissolved the soluble strips at the tissue interface. Hence, the repair strength of the soluble solder was significantly stronger than the repair strength of the insoluble solder (0.22 N and 0.06 N, P < 0.0001). Temperature (approximately 70 degrees C) and enthalpy variation (approximately 1.4 J/g) for denaturing the soluble and insoluble solders were not significantly different (P > 0.05). CONCLUSION: The soluble solid solder behaved like dense liquid solder at the tissue interface. Hence, the interface strength of these two forms of solder should be similar. This correlation made it possible to identify an intrinsic limit for the weld strength of albumin solders.

Animals↗

Cognitive function in UK community-dwelling African Caribbean elders: normative data for a test battery.

Many 'first generation' African Caribbean residents in the UK have now reached ages where risk of cognitive impairment and dementia starts to increase. In addition, conditions which may impair cognitive function, such as hypertension, diabetes and stroke, have high prevalence rates in African Caribbean populations. However, there is a lack of normative data for cognitive tests in this ethnic group. Cognitive assessment was carried out in a south London community population of 285 African Caribbean participants aged 55-75 years. Tests were drawn principally from the consortium to establish a registry for Alzheimer's disease (CERAD) battery (Boston Naming Test, verbal fluency, word list recall, and Trailmaking Tests A and B) and also included orientation items from the Mini-Mental State Examination (MMSE) and the Clock Drawing Test. Independent effects of age, sex, education and occupation were identified on scores for most but not all cognitive tests. Compared with normative data for African American populations, lower scores on verbal fluency and the Boston Naming Test were observed but scores on memory tests were comparable. Normative data for the tests are presented, stratified by level of education.

Aged↗

The construct validity of the Griffiths Scales of Mental Development.

The aim of this study was to contribute to our knowledge of the construct validity of the Griffiths Scales of Mental Development (Griffiths Scales) through an examination of the underlying dimensions tapped by the six subscales, using Common Factor Analysis. A sample of 430 South African children, from four ethnic groups (i. e. White, Mixed Race, Asian and Black) participated. The correlation coefficients obtained for the South African groups were compared to those Griffiths obtained in her work with the British standardization sample of the Griffiths Scales. The pattern of correlation for South African and British subjects was found to be similar. This suggests that the Scales are measuring a construct which is consistent across cultures and through time. A factor analysis was performed with the data for each South African ethnic group separately and the factor solutions were compared to determine whether the Griffiths Scales measure similar or different constructs for the groups. The results indicate that the Griffiths Scales tend to measure one factor, and including only common variables, the factor appears to be similar cross-culturally.

Child↗

How to validate clinically important change in health-related functional status. Is the magnitude of the effect size consistently related to magnitude of change as indicated by a global question rating?

Some clinical trials perform repeated measurement over time and estimate clinically relevant change in an instrument's score with global ratings of perceived change or so-called transition questions. The conceptual and methodological difficulties in estimating the magnitude of clinically relevant change over time in health-related functional status (HRFS) are discussed. This paper investigates the concordance between the amount of serially assessed change with effect size estimates (the researcher's perspective) and global ratings of perceived change (the patient's perspective). A total of 217 patients who were scheduled for diagnostic examination were included, and the Minnesota Living with Heart Failure Questionnaire, extended with MOS-20 items, was assessed before and after medical intervention (percutaneous transluminal coronary angioplasty, coronary artery bypass grafting or pharmaco-therapy). Global questions were applied to assess perceived change over time for every item from domains of physical and emotional functioning and used as the external criterion of relevant change in the analysis of items. Global questions corresponding with overall change in these domains were used in the comparison of change in physical and emotional functioning scales. Two effect size indices were used: (i) ES (mean change/SDpooled) and (ii) ES (mean change/SDchange). A method is described to calculate a value indicating the extent of discordance between the researcher's interpretation of magnitude of change and the external criterion (the patient's perspective). Findings suggest that effect size (ES) (mean change/SDpooled) was in keeping with the magnitude of change indicated by patients' judgements, or their category of subjective meaning, for all scales. Furthermore, in cases in which the magnitude of change estimated with the SRM (mean change/SDchange) was not confirmed empirically by the external criterion ratings, the discordance could be interpreted as a trivial discordance.

Activities of Daily Living↗

Self-reported photophobic symptoms in migraineurs and controls are reliable and predict diagnostic category accurately.

OBJECTIVES: To assess the reliability of self-reported photophobia across different patient populations and to examine how visual stress thresholds and photophobic symptoms may be predictive of diagnosis. BACKGROUND: Relatively little is known about interictal photophobia in migraine. In particular, the variability of photophobia across different patient groups has not previously been studied, and a pathophysiological hypothesis to account for the symptoms is not agreed upon. METHODS AND RESULTS: Study 1 compared 99 self-selected Dutch patients and 101 headache-free controls using survey methods. Patients both with and without aura were significantly more likely to report symptoms, such as the wearing of sunglasses in normal daylight, consistent with interictal photophobia. Study 2 replicated these findings in a series of consecutive referrals to a headache clinic in the United States. Study 3 used a specially designed laboratory test to examine the threshold for visual stress in those patients who had participated in study 2. Visual stress thresholds were significantly lower in patients than in controls. A discriminant function analysis of data from both studies 2 and 3 showed that diagnostic category (migraine; control) could be predicted from photophobic symptoms and visual stress thresholds at a level significantly better than chance. CONCLUSIONS: We suggest that interictal photophobia is common in migraine and similar across different patient populations. One pathophysiological hypothesis is that interictal photophobia is associated with cortical hypersensitivity to stimulation. The predictive validity of interictal photophobic symptoms suggests that clinical diagnosis may be aided by questioning the patient about light sensitivity in the period between attacks.

Humans↗

Vascular risk and cognitive impairment in an older, British, African-Caribbean population.

OBJECTIVES: In an older, British, African-Caribbean population with high prevalence rates of hypertension and diabetes mellitus, we ascertained clinical vascular disease (stroke or ischemic heart disease) and vascular risk (including hypertension, diabetes, and lipid profile) and investigated their associations with cognitive impairment. DESIGN: Cross-sectional community-based study. SETTING: The sample was drawn from registration lists for seven primary care services in south London, United Kingdom. PARTICIPANTS: 278 individuals, age 55 to 75, who were born in a Caribbean nation. MEASUREMENTS: Participants were interviewed and examined for cardiovascular risk factors, including a blood test for lipid profile and fibrinogen. A battery of 11 psychometric tests was administered blind to medical status. Cognitive impairment was defined on the basis of a composite measure derived from individual test scores. RESULTS: Seventy-nine (28%) subjects were classified as having relative cognitive impairment and were compared with the remainder of the sample. Marked differences were seen between low and normal/high educational levels in the strength of associations between measures of vascular risk and cognitive impairment. Hypertension, diabetes, and raised triglycerides were significant factors in those with lower levels of education. Low fibrinogen (negatively associated), high cholesterol, and manual occupation were significant factors in those with normal/high levels of education. Physical exercise was negatively associated with cognitive impairment: an association that persisted after adjustment for age, occupation, depression, and physical disability and after excluding subjects with the most severe imipairment. CONCLUSION: Measures of vascular risk were associated with relative cognitive impairment in this population. These associations were modified by previous educational attainment. Physical activity was negatively associated with cognitive impairment.

Black or African American↗

The effects of hemodilution with Hemolink upon hemodynamics and blood flow distribution in anesthetized dogs.

Hemoglobin based oxygen-carrying solutions (HBOCs) as hemoglobin replacement therapeutics are being tested for clinical use. Some of these products are associated with elevations in both systemic and pulmonary vascular resistances but their effect on the distribution of blood flow to major organs in larger animals have not been extensively described. We tested two formulations of o-raffinose cross-linked human hemoglobin, Hemolink (frozen Hemolink-1 and refrigerated Hemolink-2) and compared them to Pentaspan, a colloid volume expander in extensive clinical use. Cardiovascular measurements and the distribution of blood flow (radionuclide-labeled microspheres) to the major organs were determined in Beagle dogs (n=5 per group). After baseline measurements, either Hemolink-1, or Hemolink-2, or Pentaspan was exchange transfused in an isovolemic manner (resulting in hematocrit reduction to approximately 20-25%); measurements were made 30, 60, 120 and 180 min post-exchange. There was no significant difference in cardiac output, mean arterial pressures and systemic or pulmonary vascular resistance after exchange in any of the three groups. Myocardial blood flow increased in all three groups post-exchange but the increase was more sustained in the Hemolink groups. Endocardial/epicardial flow ratios were also maintained after exchange in all groups. Thus, Hemolink is ideally suited for volume replacement when used in conjunction with acute normovolemic hemodilution because under these circumstances, the adverse hemodynamic effects are alleviated while extra hemoglobin is added to the blood.

Anesthesia↗

In vivo magnetic resonance imaging of experimental thrombosis in a rabbit model.

The process of atherosclerotic plaque disruption has been difficult to monitor because of the lack of an animal model and the limited ability to directly visualize the plaque and overlying thrombus in vivo. Our aim was to validate in vivo magnetic resonance imaging (MRI) of the thrombus formation after pharmacological triggering of plaque disruption in the modified Constantinides animal model of plaque disruption. Atherosclerosis was induced in 9 New Zealand White male rabbits (3 kg) with aortic balloon endothelial injury followed by a high cholesterol (1%) diet for 8 weeks. After baseline (pretrigger) MRI, the rabbits underwent pharmacological triggering with Russell's viper venom and histamine, followed by another MRI 48 hours later. Contiguous cross-sectional T2-weighted fast spin echo images of the abdominal aorta were compared by histopathology. In all animals, aortic wall thickening was present on the pretrigger MRI. On MRIs performed 48 hours after triggering, a histologically confirmed intraluminal thrombus was visualized in 6 (67%) of the 9 animals. MRI data correlated with the histopathology regarding aortic wall thickness (R=0.77, P<0.0005), thrombus size (R=0.82, P<0.0001), thrombus length (R=0.86, P<0.005), and anatomic location (R=0.98, P<0.0001). In vivo, MRI reliably determines the presence, location, and size of the thrombus in this animal model of atherosclerosis and plaque disruption. The combination of in vivo MRI and the modified Constantinides animal model could be an important research tool for our understanding of the pathogenesis of acute coronary syndromes.

Anatomy, Cross-Sectional↗

Stroke, vascular risk factors and depression: Cross-sectional study in a UK Caribbean-born population.

BACKGROUND: Stroke, hypertension and diabetes are common in older Caribbean-born populations in the UK who may be at risk of depression secondary to vascular disease. AIMS: We examined the association between stroke, vascular risk factors and depression in a community-based Caribbean-born population aged 55-75 years. METHOD: Vascular risk factors were identified by interview, examination and blood tests. Depression was categorised using the Geriatric Depression Scale. Disablement was assessed as a potential mediating factor. RESULTS: Physical illness and disablement were strongly associated with depression, independent of disablement. Previous stroke was associated with depression, independent of disablement. No vascular risk factors were associated with depression. CONCLUSIONS: The risk of depression associated with stroke was not explained by disablement. However, the hypothesis that vascular risk factors are important in the genesis of depression was not supported.

Age Distribution↗

Increased first-contact rates for very-late-onset schizophrenia-like psychosis in African- and Caribbean-born elders.

BACKGROUND: Studies have consistently shown a higher incidence of schizophrenia with onset in early adult life in African and Caribbean migrants to the UK. AIMS: To establish the incidence (first-contact rates) of very-late-onset (>60 years) schizophrenia-like psychosis (SLP) in south London and to test the hypothesis that this is higher among African- and Caribbean-born than indigenous elders. METHOD: We identified all new referrals of SLP to the Maudsley Hospital between 1995 and 2000. Demographic details, including age, ethnicity and electoral ward (address), were obtained from case notes. Incidence was estimated using 1997 census data to determine the denominator population for each ethnic group. RESULTS: The incidence of SLP was significantly higher in African- and Caribbean-born than indigenous elders: 172.4 per 100,000 population (95% CI=57.9--286.8) in African- and Caribbean-born males and 323.5 per 100,000 population (95% CI 167.8--479.1) in African- and Caribbean-born females. Rates also were increased in elders from other immigrant groups, but the numbers involved were too small to reach accepted levels of significance. CONCLUSIONS: Large-scale epidemiological studies are needed to determine both the incidence of and the coexistent risk factors for SLP among all elderly migrants, who may constitute a group with high service needs.

Africa↗