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Biomedical subjects

G M Anderson

Publications and source records attributed to G M Anderson.

At least 145 records · Page 8Linked to original sources

Human platelet dense granules: improved isolation and preliminary characterization of [3H]-serotonin uptake and tetrabenazine-displaceable [3H]-ketanserin binding.

An improved method for the isolation of human platelet dense granules was developed. A good yield (45%) of highly enriched (69-fold, based on serotonin content) dense granules was obtained after mild sonication and Percoll gradient centrifugation. The method has facilitated characterization of the granule, permitting the first report of Km and Vmax values for [3H]-serotonin uptake, as well as the first determination of Kd and Bmax values for tetrabenazine-displaceable [3H]-ketanserin binding, in the human platelet dense granule. The rates and affinities (Vmax 1.45 nmol/mg/min, Km 0.93 uM) of [3H]-serotonin uptake were similar to those previously reported for porcine dense granules. Tetrabenazine-displaceable [3H]-ketanserin binding was observed with a Kd (9.4 nM) similar to, and a Bmax (5.4 pmol/mg) approximately 10-fold lower than, that previously seen in bovine chromaffin granules.

Acid Phosphatase↗

Flat on your back or back to your flat? Sources of increased hospital services utilization among the elderly in British Columbia.

Between 1969 and 1985, the British Columbia hospital system allocated an increasing proportion of the province's total hospital days to elderly patients who stayed for 60 days or more. By 1985/86, long stay patients accounted for almost 50% of all days. In this paper, we explore the diagnoses which contributed the greatest number of patient days of increase among the elderly as a first step in evaluating the appropriateness of this response to the pressures of an aging population. Patient days of increase were not distributed smoothly across a large number of diagnoses, but could be explained by a small number of chronic conditions. Most important were conditions related to senility and senile dementia, the chronic sequelae of heart disease and stroke, and persons awaiting admission to adequate facilities elsewhere. Eighty percent of the increases were seen in extended care and rehabilitation beds and 20% in acute care beds. Seventy-seven percent of the increased patient days were attributable to females and only 23% to males. Since the major sources of increase in patient days were not related to conditions for which new, effective hospital care modalities are available, they call into question the appropriateness of the system's response to the health care needs of the elderly population.

Aged↗

Assessing the clinical effectiveness of preventive maneuvers: analytic principles and systematic methods in reviewing evidence and developing clinical practice recommendations. A report by the Canadian Task Force on the Periodic Health Examination.

This paper examines a process for evaluating clinical effectiveness and developing recommendations in which systematic methods are used to review evidence from published clinical research and to reach sound conclusions about appropriate medical policy. The methodology addresses four important components of the analytic process: (1) the criteria that must be satisfied for a clinical practice to be considered effective; (2) proper methods for reviewing evidence from published clinical research to determine whether a clinical practice meets these criteria (including methods for performing comprehensive literature reviews, for judging the quality of individual studies, and for synthesizing or pooling the results of multiple studies); (3) theoretical and practical concerns in translating the results of the scientific review into sound clinical practice recommendations; and (4) the importance of documentation, guidelines, and other safeguards to minimize the effect the reviewers themselves have on the objectivity and consistency of the analytic methods.

Epidemiologic Methods↗

The hyperserotonemia of autism.

The planned and ongoing studies of platelet function and composition should allow us to better define the alteration which we presume to be present in platelets of autistic subjects. Although much of the research focuses on serotonergic aspects, the more general research should permit a better delineation of the extent of the alteration and will protect against a premature narrowing of the inquiry. The methodological development which has been a necessary aspect of the work should contribute to an improved understanding of platelet function and composition, as well as result in improved clinical tools for the assessment of platelet functioning in neuropsychiatric disorders and hematology. As an example, improvements in short-term in vitro storage conditions to stabilize aggregation and shape change responses over time were found to be necessary, and are probably critical to an optimal comparison of these phenomena across groups. The identification of the platelet alteration which is responsible for the hyperserotonemia of autism should prove useful in several ways. It would be expected that assessment of the altered function would provide a marker with less overlap with the normal population than the multidetermined measure of blood 5-HT. Determination of the specific protein(s) involved in the altered platelet should lead directly to gene probes and chromosomal location. These, in turn, should prove useful for neonatal screening, subtyping, and more powerful genetic and family studies. Work of this sort might also allow early intervention and improved treatment. Finally, characterization of the physiological alteration would provide a basis for focusing studies of brain neurochemistry and should, as well, suggest modes of neuropharmacological intervention. The confidence that one can have in the basic finding of hyperserotonemia in autism and the potential benefits to be derived from its explication make further research in this area of great interest.

Adolescent↗

Acute care hospital utilization under Canadian national health insurance: the British Columbia experience from 1969 to 1988.

This paper uses hospital separation abstracts to assess trends in acute care hospital utilization in British Columbia over the first 18 years of publicly funded health insurance in the province. Between 1969 and fiscal year 1987-88, the overall separation rate decreased by 16%, accompanied by a 23% decrease in average length of stay. For the elderly, the separation rate increased by 14% and three quarter of this increase was for surgical procedures, mostly new high-technology procedures. For the nonelderly, separation rates decreased by 25%. Lengths of stay decreased in both age groups. Over the last two decades overall separation rates in British Columbia were higher than or equal to separation rates in the United States, and lengths of stay were consistently higher in British Columbia. Since access to hospitals by the elderly is similar in the two countries, lower hospital costs in Canada result from factors other than lower overall hospital utilization or decreased access for the elderly.

Acute Disease↗

Cesarean section in Ontario: practice patterns and responses to hypothetical cases.

A 40% random sample of Ontario's obstetricians were asked to respond to hypothetical scenarios for previous cesarean section, breech presentation and dystocia, and to describe their practice patterns. Their responses confirmed findings from other studies, which reported differences between physicians' responses to hypothetical cases and their actual practice. In this study, 18% chose a cesarean section for the hypothetical case of a patient who had previously undergone cesarean section and 2% chose a cesarean section for the hypothetical case of breech presentation. However, in practice, the obstetricians reported that they do cesarean section on 71% of their previous section patients and on 57% of their breech patients. Physicians in teaching hospitals were less likely than those in community hospitals to choose cesarean section for a woman who had previously undergone cesarean section both hypothetically and in practice. For breech presentation, no difference was found. The discrepancy between responses to the hypothetical cases and practice patterns could not be attributed to the absence of anesthesia services or to restrictive hospital policies.

Anesthesia Department, Hospital↗

Hospital care for elderly patients with diseases of the circulatory system. A comparison of hospital use in the United States and Canada.

In an effort to determine how lower health care expenditures in Canada as compared with the United States translate into actual hospital services received, we examined discharge rates, lengths of stay, and the case-mix index (calculated from diagnosis-related group weights) for those 65 years of age and older hospitalized with cardiovascular disease in the United States and two Canadian provinces, Manitoba and Ontario, in 1981 and 1985. We expected that the effect of the prospective payment system might be reflected in changes between 1981 and 1985. Discharge rates for medical treatment of cardiovascular diseases were 2.9 percent higher in the United States than in Canada in 1981, but 1.8 percent lower in 1985; however, the case-mix index was 3.0 percent lower in 1981 and 4.8 percent higher in 1985. The case-mix index for combined medical and surgical discharges was 5.0 percent lower in the United States in 1981, but 10.7 percent higher in 1985. U.S. surgical discharge rates were 20 percent lower in 1981, but 20 percent higher in 1985. Rates of coronary bypass surgery were much higher in the United States in both years, but increased rapidly in both countries, particularly among those 75 and older. Elderly Canadians appeared to have access to cardiovascular surgery, with the exception of coronary bypass surgery, and to other hospital care for cardiovascular disease similar to that of elderly people in the United States.

Aged↗

Recent trends in cesarean section rates in Ontario.

After increasing steadily for 15 years the cesarean section rate in Ontario stabilized at 20.2 per 100 deliveries in the fiscal years 1986-87 and 1987-88. An important factor in the stabilization was a decrease in the rate of repeat section. The diagnosis and management of dystocia and fetal distress continue to put upward pressure on the cesarean section rate, which is higher than would be expected if recent practice guidelines had been fully implemented. There is a need for further research into the appropriate management of labour and delivery and into more targeted techniques for bringing practice into line with appropriate standards of care.

Breech Presentation↗

Do practice guidelines guide practice? The effect of a consensus statement on the practice of physicians.

Guidelines for medical practice can contribute to improved care only if they succeed in moving actual practice closer to the behaviors the guidelines recommend. To assess the effect of such guidelines, we surveyed hospitals and obstetricians in Ontario before and after the release of a widely distributed and nationally endorsed consensus statement recommending decreases in the use of cesarean sections. These surveys, along with discharge data from hospitals reflecting actual practice, revealed that most obstetricians (87 to 94 percent) were aware of the guidelines and that most (82.5 to 85 percent) agreed with them. Attitudes toward the use of cesarean section were congruent with the recommendations even before their release. One third of the hospitals and obstetricians reported changing their practice as a consequence of the guidelines, and obstetricians reported rates of cesarean section in women with a previous cesarean section that were significantly reduced, in keeping with the recommendations (from 72.2 percent to 61.1 percent; P less than 0.01). The surveys also showed, however, that knowledge of the content of the recommendations was poor (67 percent correct responses). Furthermore, data on actual practice after the publication of the guidelines showed that the rates of cesarean section were 15 to 49 percent higher than the rates reported by obstetricians, and they showed only a slight change from the previous upward trend. We conclude that guidelines for practice may predispose physicians to consider changing their behavior, but that unless there are other incentives or the removal of disincentives, guidelines may be unlikely to effect rapid change in actual practice. We believe that incentives should operate at the local level, although they may include system-wide economic changes.

Cesarean Section↗

Trends in use of medical services by the elderly in British Columbia.

We analysed physician fee-for-service use in British Columbia from 1974-75 to 1985-86. Over the study period use increased by 5.3% per year. This can be factored into increases attributable to changes in the age structure of the population (0.4% per year), general population growth (1.8%, for a combined annual "population effect" of 2.2%) and age-specific increases in per-capita use (3% per year). The average annual increase for people aged 75 years or more was 5.5% per capita. The area with the fastest growth in use by the elderly was specialist care, particularly diagnostic services. The average number of specialists seen by people aged 75 years or more doubled over the study period. Our results suggest that increased per-capita use among the elderly that is unrelated to aging of the population should be the main focus of future policy attention. Additional analyses are needed to determine the underlying dynamics of this dramatic increase in rates of use among the elderly.

Adolescent↗

Controlling health expenditures--the Canadian reality.

Canada and the United States have conducted a large-scale social experiment on the effects of alternative ways of funding expenditures for health care. Two very similar societies, with (until recently) very similar systems of providing health care, have adopted radically different systems of reimbursement. The results of this experiment are of increasing interest to Americans, because the Canadian approach has avoided or solved several of the more intractable problems facing the United States. In particular, overall health expenditures have been constrained to a stable share of national income, and universality of coverage (without user charges) eliminates the problems of uncompensated care, individual burdens of catastrophic illness, and uninsured populations. The combination of cost control with universal, comprehensive coverage has surprised some American observers, who have questioned its reality, its sustainability, or both. We present a comparison of the Canadian and American data on expenditures, identifying the sectors in which the experience of the two nations diverges most, and describing the processes of control. In any system, cost control involves conflict between providers and payers. Political processes focus this conflict, whereas market processes diffuse it. But the stylized political combat in Canada may result in less intrusion on the professional autonomy of the individual physician than is occurring in the United States.

Attitude of Health Personnel↗

Serotonergic responsivity in male young adults with autistic disorder. Results of a pilot study.

Altered serotonergic function has been postulated to exist in autistic disorder. Central serotonergic responsivity was assessed with a neuroendocrine challenge test in seven male young adults with autistic disorder and in seven age- and gender-matched healthy controls. Binding indexes and physiologic responsivity of the platelet serotonin-2 (5-HT2) receptor complex were also measured, as was whole-blood serotonin content. Compared with controls, autistic subjects had substantially blunted prolactin release in response to a 60-mg oral dose of fenfluramine hydrochloride, an indirect serotonin agonist [corrected]. Furthermore, the magnitude of serotonin-amplified platelet aggregation, mediated by the platelet 5-HT2 receptor complex, was reduced in the autistic group, as was the mean number of platelet 5-HT2 receptor sites. Among autistic subjects, fenfluramine-induced prolactin release correlated positively with the serotonin-amplified platelet aggregation response and negatively with whole-blood serotonin content. The results of the present study are compatible with the hypothesis that central serotonergic responsivity is decreased in male autistic young adults. Correlations between central and peripheral serotonergic measures in autistic subjects suggest that systemic alterations in serotonergic function may occur in autism.

Adult↗

Effects of desipramine and fluvoxamine treatment on the prolactin response to tryptophan. Serotonergic function and the mechanism of antidepressant action.

It has been hypothesized that enhancement of brain serotoninergic (5-HT) function is involved in the mechanism of action of some antidepressants. To test this, the prolactin response to intravenously administered tryptophan, a clinical measurement of 5-HT function, was assessed before and during antidepressant treatment. Depressed patients received the tricyclic desipramine hydrochloride (N = 24) or the 5-HT reuptake inhibitor fluvoxamine maleate (N = 30). The prolactin response was significantly enhanced after long-term treatment (4 weeks) but not as reliably increased after short-term (1-week) desipramine treatment. Fluvoxamine enhanced the prolactin response after both short- and long-term treatment. Enhancement of the prolactin response was not clearly correlated with clinical improvement. The results of this study are consistent with preclinical evidence of enhanced 5-HT function during treatment with these classes of antidepressants, but also indicate that enhanced 5-HT function is not a sufficient condition for antidepressant efficacy.

Antidepressive Agents↗

Whole blood serotonin and tryptophan in autism: temporal stability and the effects of medication.

Whole blood serotonin (5-HT) was significantly increased in a drug-free autistic group (n = 17) compared to age- and sex-matched normal control (n = 20). Blood tryptophan (TRP) values and platelet counts were similar in unmedicated autistics and normal subjects; but whole blood concentrations of TRP were significantly lower, and 5-HT values tended to be lower in the medicated group compared to unmedicated autistics. Highly significant intraclass correlation coefficients and low mean percentage differences were found for repeated measures over a year's period of whole blood 5-HT and the platelet count in the unmedicated but not in the medicated group. Blood TRP values were highly variable over time in both the medicated and drug-free autistic groups.

Adolescent↗

Plasma debrisoquin levels in the assessment of reduction of plasma homovanillic acid. The debrisoquin method.

Plasma concentrations of unconjugated homovanillic acid (pHVA) reflect both central nervous system (CNS) and peripheral dopamine metabolism. Debrisoquin sulfate (DBQ) blocks peripheral, but not CNS, production of HVA from dopamine. Administration of DBQ has been used to decrease the proportion of peripherally produced HVA in pHVA measurements, making such measurements more reflective of CNS turnover of dopamine. We studied the relationships between DBQ dose, plasma DBQ (pDBQ) levels, and changes in pHVA in a group of 21 subjects (9 normal controls and 12 with Tourette's syndrome). DBQ dose was moderately correlated with pDBQ levels (r = 0.63, p = 0.002). Subjects (n = 8) with mean pDBQ levels above 60 ng/ml had a 48% to 66% decrease in mean pHVA levels; this may reflect nearly complete inhibition of peripheral HVA production. Subjects (n = 13) with mean pDBQ levels below 55 ng/ml had decreases in pHVA levels from 10% to 58%. No debrisoquin was detected in cerebrospinal fluid samples. These data suggest that pDBQ levels above 60 ng/ml are sufficient to assure substantial inhibition of peripheral HVA production and that monitoring pDBQ levels may be useful when employing this method for studying CNS metabolism.

Adult↗