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Biomedical subjects

G M Anderson

Publications and source records attributed to G M Anderson.

At least 73 records · Page 4Linked to original sources
PubMed1997

Assessment of diurnal variation of cerebrospinal fluid tryptophan and 5-hydroxyindoleacetic acid in healthy human females.

The role of serotonin (5-HT) in the pathogenesis and treatment of major neuropsychiatric disorders, including mood and anxiety disorders, continues to be the subject of extensive research. Previous studies examining central 5-HT functioning measured cerebrospinal fluid (CSF) levels of 5-hydroxyindoleacetic acid (5-HIAA) by using single or multiple lumbar punctures. A number of investigators have demonstrated the feasibility of continuous CSF sampling via an indwelling lumbar catheter to study CSF neurochemistry in healthy subjects and patients with neuropsychiatric illness. Four healthy female volunteers, aged 21-34 years, underwent continuous CSF sampling. CSF was collected at a constant rate of 1 ml every 10 minutes over a 30-hour period, with levels of tryptophan (TRP) and 5-HIAA measured every hour. Plasma was also obtained hourly for TRP determination. The results of this study indicate that CSF 5-HIAA, CSF TRP, and plasma TRP levels showed variation over time, but failed to show diurnal fluctuation. Intra-individual coefficients of variation determined for CSF 5-HIAA, CSF TRP, and plasma TRP ranged from 9.2 to 14.9%, 8.8 to 14.6%, and 14.7 to 19.0%, respectively. Continuous CSF sampling is safe and feasible in humans, and may prove useful for studies of central 5-HT neurotransmission in neuropsychiatric illness.

Adult↗
PubMed1997

Auditing prescription practice using explicit criteria and computerized drug benefit claims data.

Bringing information on patterns of existing practice together with information on appropriate practice is an essential component of efforts to improve health care. In this study, computerized claims from a universal and comprehensive drug benefit plan for the elderly were brought together with explicit criteria for appropriate prescribing in the elderly in order to provide an estimate of the extent of potentially inappropriate prescribing in the covered population and the degree to which inappropriate prescribing was associated with defined physician characteristics. The analysis showed that 38% of elderly people who received antidepressants, 19% of those who received oral hypoglycemics, 18% of those who received sedative hypnotics and 13% of those who received non-steroidal anti-inflammatory drugs were defined as having received a potentially inappropriate drug. Older physicians and physicians without speciality certification were more likely to prescribe potentially inappropriate drugs. This analysis shows that criteria-based audits of drug claims databases can be used to provide an overview of prescribing problems at a population level and can reveal physician characteristics that may predict poor prescription practice. However, since neither explicit criteria nor claims databases can accurately capture the clinical details that ultimately define the appropriateness of care, audits of claims data should be linked to a more definitive measure of appropriateness and strategies designed to improve care.

Administration, Oral↗
PubMed1997

Risperidone treatment of children and adolescents with pervasive developmental disorders: a prospective open-label study.

OBJECTIVE: To investigate the short-term safety and efficacy of risperidone in the treatment of children and adolescents with pervasive developmental disorders. METHOD: This was a 12-week, prospective, systematic, open-label trial that included 18 subjects (15 boys and 3 girls) with a mean age of 10.2 +/- 3.7 years. The sample included 11 subjects with autistic disorder, 3 with Asperger's disorder, 1 with childhood disintegrative disorder, and 3 with pervasive developmental disorder not otherwise specified. Fourteen subjects had comorbid mental retardation. Behavioral ratings were obtained during two baseline visits and again after 12 weeks of risperidone treatment. RESULTS: The optimal dose of risperidone for the 18 subjects was 1.8 +/- 1.0 mg/day. On the basis of the global improvement item of the Clinical Global Impression Scale, 12 of 18 subjects were considered responders. Significant improvement was seen in measures of interfering repetitive behavior, aggression and impulsivity, and some elements of impaired social relatedness. The most common side effect was weight gain (range 10 to 35 lb). CONCLUSIONS: These preliminary results suggest that risperidone may be effective for improving interfering behavioral symptoms in some children and adolescents with pervasive developmental disorders. Double-blind, placebo-controlled studies are needed before definitive statements of safety and efficacy can be made.

Adolescent↗
PubMed1997

On becoming 65 in Ontario. Effects of drug plan eligibility on use of prescription medicines.

OBJECTIVES: The authors assess (1) the effects of first-dollar prescription drug insurance coverage provided by the Ontario Drug Benefit plan at age 65 on prescription drug use by seniors, and (2) the differential effects of this coverage on prescription drug use by seniors with varying levels of health status. METHODS: The authors modeled self-reported prescription drug use contained in the 1990 Ontario Health Survey as a function of eligibility for coverage, controlling for health status and other factors. The two-part model was used and was estimated by maximum likelihood. RESULTS: The provision of first-dollar prescription drug insurance coverage at age 65 is associated with an increase in drug use. Increases in drug use are, however, concentrated primarily among individuals with lower levels of health status. Most of the increased use occurs among individuals already under physician supervision, ie, an increase in the level of use among drug users rather than an increase in the probability of use. CONCLUSIONS: As Ontarians turn age 65 and become eligible for publicly subsidized prescription drugs, their use increases but the effect appears to be restricted mainly to persons with lower levels of health status. Given a growing trend toward reduction of public subsidy and increased reliance on patient cost sharing, more research is needed to quantify the use and health effects of such initiatives.

Age Factors↗
PubMed1997

Hospital restructuring and the epidemiology of hospital utilization: recent experience in Ontario.

OBJECTIVES: The author highlights changes in hospital utilization that have occurred in association with restructuring of Ontario hospitals. The basic features of the epidemiology of hospital utilization described link the analysis of the organizational and structural components of hospitals with a more comprehensive evaluation of the impacts of their restructuring and have implications for international comparative studies. METHODS: Data from the Canadian Institute for Health Information and the Canadian census were analyzed to provide a population-based description of hospital utilization and care. These hospital data provided information on changes in the patterns of care that occurred during restructuring, based on hospital separations for the fiscal years 1991-1992 through 1995-1996. RESULTS: Analysis of hospital utilization patterns revealed a 30% decrease in the days of care provided per 1,000 population during the period, the result of declines in both the age-adjusted inpatient separation rates and average length of hospital stay. The shift of surgical treatment to outpatient settings contributed to the reduction in inpatient days of care. The decline in utilization was experienced unevenly across age groups, with the elderly experiencing less of the decline than did younger age groups. Individuals living in the poorest areas used more inpatient care than did those living in the richest areas, although the gap in utilization narrowed over the period. CONCLUSIONS: International comparisons of the epidemiology of hospital utilization and the impact of hospital restructuring will require the use of multiple data sources and the development of shared evaluative frameworks. Health data systems in Canada support the assessment of the broader impacts of hospital restructuring and offer a framework for developing research projects that can provide useful information on these important changes in health-care policy.

Adolescent↗
PubMed1997

Pathogenesis of Tourette's syndrome.

This review presents a models of disease pathogenesis in the context of CNS development. It begins with an exploration of the clinical features and natural history of Tourette's syndrome. This is followed by a consideration of the role of genetic and nongenetic factors. An effort is then made to review the anatomical organization of the basal ganglia and related cortical sites. These circuits are intimately involved in the normal processing of sensorimotor, cognitive, and emotionally laden information. Evidence implicating these circuits in the pathobiology of Tourette's syndrome is then considered. The review closes with the prospects for advances in interdisciplinary research and therapeutics using this model as a guide.

Basal Ganglia↗
PubMed1997

Plasma beta-endorphin, adrenocorticotropin hormone, and cortisol in autism.

Plasma levels of the hypothalamo-pituitary-adrenal axis hormones beta-endorphin (BE), adrenocorticotropin hormone (ACTH), and cortisol were measured in autistic (N = 48), mentally retarded/cognitively impaired (MR/CI, N = 16), and normal control (N = 26) individuals. Comparison of log transformed data from the three groups revealed that levels of BE and ACTH were significantly higher (p < .05) in the autistic individuals than in normal controls. The higher means in the autistic group were due to significantly higher plasma levels of BE and ACTH, indices of acute stress response, in the more severely affected individuals. The data support the idea that individuals with severe autism have a heightened response to acute stressors rather than chronic hyperarousal or elevated basal stress response system functioning.

Adolescent↗
PubMed1997

Reperfusion nerve injury: pathology due to reflow and prolonged ischaemia.

Ischaemia plays an important role in the development of pathological changes in various neuropathies. Nerve pathology in acute ischaemic injury has been delineated longitudinally in peripheral nerve and reperfusion injury could amplify ischaemic pathology. We examined ischaemia/reperfusion-induced pathological changes along the length of sciatic, tibial and peroneal nerves from pelvic to ankle levels. Pathological features were correlated with the degree of postischaemic nerve blood flow (NBF) restoration, measured by a laser Doppler flowmeter, and the blood-nerve barrier function by a horseradish peroxidase (HRP) technique. Major arteries which supply rat hindlimb were occluded for 3, 5, or 7 hours, and reperfusion was accomplished by the removal of vascular clips. Nerve pathology was assessed after 12, 24 and 48 hours, and 5 and 7 days of reperfusion. Pathological alterations at the thigh level included vascular swelling, endoneurial and intramyelinic oedema, demyelination, thrombosis, and red blood cell (RBC) extravasation. A paucity of axonal degeneration was also characteristic at this level. By contrast, the distal nerve from knee to ankle showed evidence of extensive axonal changes, occluded vessels, and panfascicular nerve fibre and vascular degeneration. Postischaemic NBF reflow was confirmed at the thigh level immediately, 24 and 48 hours after reperfusion, whereas NBF restoration at the knee to calf level was less than preischaemic values. HRP leakage was found in both proximal and distal nerve segments. In conclusion, we demonstrated different types of structural changes along the length of ischaemic/reperfused rat sciatic nerves. The present study suggests that pathological abnormalities at the thigh level are most likely due to reoxygenation of ischaemia-inflicted endothelial cells, and distal morphological changes could be induced by prolonged ischaemia resulting from occluded vessels.

Animals↗
PubMed1997

Case selection and appropriateness of coronary angiography and coronary artery bypass graft surgery in British Columbia and Ontario.

OBJECTIVES: To compare the types of patients selected for coronary angiography (CA) and coronary artery bypass graft (CABG) surgery, and the appropriateness of the procedures performed on these patients in a random sample of cases in British Columbia and Ontario. DESIGN: Retrospective randomized medical record review. SETTING: All hospitals performing CA and/or CABG in British Columbia and Ontario in fiscal year 1989/90. PATIENTS: For CA, 395 randomly selected patients in Ontario and 139 randomly selected patients in British Columbia; for CABG, 431 randomly selected patients in Ontario and 125 randomly selected patients in British Columbia. MAIN OUTCOME MEASURES: Case selection was measured in terms of the demographic and clinical characteristics of patients undergoing the procedures. Appropriateness was measured by comparing the clinical characteristics of patients undergoing the procedures with explicit criteria established by a panel of Canadian physicians. The yield from CA was measured as the proportion of patients who were found to have insignificant anatomical disease. RESULTS: Analysis of patients selected for CA showed that sample patients from Ontario were less likely than those from British Columbia to be female (25% versus 37%, respectively, P = 0.012) and less likely to have undergone a previous revascularization (12% versus 24%, respectively, P = 0.005). The distribution of main indications for CA differed between the two provinces (P = 0.002), with Ontario patients more likely to have chronic stable angina (45% versus 24%) and less likely to have unstable angina (16% versus 26%). For CABG, sample patients from Ontario were less likely to be 65 years of age or older (32% versus 45%, P = 0.016) and more likely to have an ejection fraction less than 35% (14% versus 5%, P = 0.006). The distribution of the main indications for CABG differed (P < 0.001), with Ontario patients more likely to have chronic stable angina (68% versus 38%) and less likely to have unstable angina (20% versus 43%). There was no statistically significant difference in CA cases rated as inappropriate (8.4% in Ontario versus 10.8% in British Columbia, P = 0.396) or CABG cases rated as inappropriate (3.9% in Ontario versus 2.4% in British Columbia, P = 0.393). There were no statistically significant differences in the proportion of CA that yielded insignificant anatomical disease (17.5% in Ontario versus 18.4% in British Columbia, P = 0.355). CONCLUSIONS: There were differences between Ontario and British Columbia in the demographic and clinical characteristics of patients selected for CA and CABG. This may indicate differences in the referral process in the two provinces. Despite these differences the rates of inappropriate procedures and the yield from CA were similar.

Aged↗
PubMed1997

Is colour flow imaging needed to exclude clinically significant valvular regurgitation in adult patients undergoing transthoracic echocardiography?

OBJECTIVE: To establish whether clinically significant aortic and mitral valvular regurgitation can be excluded in adult patients undergoing transthoracic echocardiography without using colour flow imaging. SETTING: Sunnybrook Health Science Centre, a tertiary referral centre with full cardiovascular services affiliated with the University of Toronto, Toronto, Ontario. DESIGN: Logistic regression models were developed from a retrospective review of 14,051 unselected consecutive echocardiograms from 1991 through 1994. The dependent variable was more than mild aortic or mitral valvular regurgitation. Independent variables included age, sex and various functional and structural measures obtained during routine two-dimensional echocardiography. The negative predictive values and sensitivity of the models were estimated. INTERVENTION: The number of patients correctly classified by these models, as well as the proportion for whom the colour flow imaging did not add to the baseline echocardiogram, was determined. Nonparametric bootsrapping was used to obtain confidence intervals for these statistics. MAIN RESULTS: Ten models were developed, with negative predictive values ranging from 96.2% to 100%. Incorporation of such decision aids into the software of echocardiographic machinery would help echocardiographers to rule out significant aortic or mitral regurgitant lesions. In practices where colour flow imaging is routinely employed, 40% fewer procedures could be performed. CONCLUSIONS: Models based on simple demographic and two-dimensional echocardiographic variables can reliably exclude significant valvular regurgitation and could potentially reduce the volumes and costs of colour flow imaging. Given the widespread diffusion of colour Doppler imaging, the models may also be helpful to avoid misinterpretation of flow imaging results, by defining subgroups in whom the prior probability of significant aortic or mitral regurgitation is extremely low.

Aged↗
PubMed1996

Adenosine diphosphate inhibits the serotonin transporter.

Adenosine 5'-diphosphate (ADP) caused rapid and significant reductions in the rates of [3H]serotonin uptake observed for human platelets, human platelet vesicles, and rat brain synaptic vesicles. Estimated Vmax values in platelets (N = 15). platelet vesicles (N = 3), and synaptic vesicles (N = 3) exposed to 100 microM ADP were 42.3 +/- 11.4%, 78.8 +/- 1.4%, and 56.8 +/- 9.9% of control values, respectively. The EC50 values observed for ADP in platelets and platelet vesicles were 10-24 microM. Exposure to 100 microM ADP had small, inconsistent effects on KM values observed for the platelet transporter. ADP (100 microM) caused only a slight competitive inhibition of the platelet membrane binding of [3H]citalopram, a ligand for the 5HT uptake site of the transporter (5.0% displacement of 1.0 nM [3H]citalopram, 13% increase in apparent KD). The ADP analogue 2-methylthioADP caused similar decreases in the rates of platelet [3H]serotonin uptake, while a number of other related compounds had little or no effect on rates of platelet uptake. The ADP-effect on uptake was rapid, occurring in less than 2.5 s. and was additive with reductions produced by protein kinase C (PKC) activation. The ADP-induced decreases in uptake did not appear to occur through the ADP receptor or known platelet second messenger systems. The exact mechanism of the ADP-effect and its functional significance remain to be determined.

Adenosine Diphosphate↗
PubMed1996

Delayed-type hypersensitivity in mast cell-deficient mice: dependence on platelets for expression of contact sensitivity.

Previous studies of cutaneous T cell-mediated responses in mice have obtained pharmacologic, morphologic, and immunologic evidence pointing to a critical role for local mast cells in release of the vasoactive amine serotonin (5-HT) to mediate early, initiating events that are required for elicitation of these responses. However, the role of mast cells in initiating these T cell-mediated cutaneous responses has been questioned due to the presence of relatively intact delayed-type hypersensitivity responses, such as contact sensitivity (CS), in mast cell-deficient mice whose skin contains only 1 % normal mast cell numbers. The contribution of other potential local sources of 5-HT, such as circulating platelets, at the site of a delayed-type hypersensitivity or CS response in these mast cell-deficient strains, has not been investigated. Therefore, we studied the effect of systemic platelet depletion, produced with an anti-platelet Ab, on blood and tissue levels of 5-HT, and on in vivo T cell-mediated cutaneous sensitivity responses, in W/Wv and Sl/Sld mast cell-deficient mice. The results showed that: 1) platelet depletion severely reduced whole blood 5-HT; 2) tissue levels of 5-HT, in mast cell-deficient mice, depended in large part on the presence of circulating platelets, and 3) specific depletion of platelets markedly suppressed CS responses in both W/Wv and Sl/Sld mast cell-deficient mice, and only moderately reduced CS in normal +/+ congenic mast cell-sufficient controls, but did not decrease CS in beige mice, with platelet granules that are defective in storage of 5-HT. We concluded that platelets may provide 5-HT crucial for the initiation of cutaneous T cell-mediated immune responses, such as CS.

Animals↗
PubMed1996

Strategies for improving prescribing practice.

Drug therapy is an integral component of modern medical care, and practising physicians are faced with the difficult task of keeping up with rapid changes in pharmacologic treatments. Recent evidence indicates that prescribing practice is often inconsistent with criteria for safety and effectiveness. Surveys indicate that community-based physicians are not satisfied with current sources of information on prescription drugs. The dissemination of printed material alone does not lead to improved prescribing practice, but specific education and feedback strategies can. To improve prescribing practice in Canada we need to systematically evaluate strategies to change prescribing behaviour, to design quality assurance programs based on proven strategies and to develop collaboration and cooperation among providers, manufacturers, governments and the public.

Canada↗
PubMed1996

Appropriateness in health care delivery: definitions, measurement and policy implications.

A major focus of the current health care debate is the notion that a substantial proportion of the health care delivered in Canada is inappropriate. There are two types of appropriateness: appropriateness of a service and appropriateness of the setting in which care is provided (i.e., inpatient v. outpatient or home care). Measuring both types objectively requires the comparison of observed patterns of care with explicit criteria for appropriate care. The few studies of appropriateness conducted in Canada have shown that inappropriate services are provided and inappropriate settings are used. Reducing inappropriate health care delivery could involve active strategies for the implementation of guidelines and better cooperation and coordination within the health care system. However, lower rates of health care delivery or even inappropriate health care will not necessarily translate into higher quality care or lower costs overall.

Canada↗
PubMed1996

Recent findings on preventable hospitalizations.

Disparities in health outcomes for low-income populations as documented by rates of preventable hospital admission remains large in the United States, even with the moderate expansion of Medicaid and efforts at the state and local levels to improve primary care services that began in the mid-1980s. These differences in outcome for rich and poor are not an isolated phenomenon of a few old and decaying Northeast urban centers but are documented in a broad range of urban areas. Much smaller differences are found in urban areas in Ontario, where universal coverage may help to reduce barriers to care.

Ambulatory Care↗
PubMed1995

Regionalization of cardiac surgery in the United States and Canada. Geographic access, choice, and outcomes.

OBJECTIVE: To determine how regionalization of facilities for coronary artery bypass surgery (CABS) affects geographic access to CABS and surgical outcomes. DESIGN: Computerized hospital discharge records were used to measure hospital CABS volume and in-hospital post-CABS mortality rates. Relationships between surgical volume and age- and sex-adjusted mortality rates were compared using chi 2 tests. Small-area analysis of the association between CABS rates and distances to nearest CABS hospital was performed using multivariate linear regression methods. SETTING: All nonfederal hospitals in New York, California, Ontario, Manitoba, and British Columbia. PATIENTS: All adult residents of the five jurisdictions who underwent CABS in a hospital in their jurisdiction from 1987 through 1989. RESULTS: In New York and Canada, approximately 60% of all CABS operations took place in hospitals performing 500 or more CABS operations per year, compared with only 26% in California. The highest mortality rates were found among California hospitals performing fewer than 100 CABS operations per year (adjusted 14-day in-hospital mortality was 4.7% compared with 2.4% in high-volume California hospitals, P < .001). The percentage of the population residing within 25 miles of a CABS hospital was 91% in California, 82% in New York, and less than 60% in Canada. Eliminating very low-volume (< 100 cases per year) CABS hospitals in California would increase travel distances to a CABS hospital only slightly for a small number of residents. The Canadian degree of regionalization was not associated with lower CABS rates within provinces for populations living at more remote distances from the nearest CABS hospital. CONCLUSION: Regionalization of CABS facilities in New York and Canada largely avoids the problem of low-volume outlier hospitals with high postoperative mortality rates found in California. New York has avoided the redundancy of facilities that exists in California while still providing residents a geographically convenient selection of CABS hospitals. Stricter regionalization in Canada may leave residents with a more narrow choice of facilities, but does not disproportionately affect access to surgery for populations living at remote distances from CABS facilities.

Canada↗