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Biomedical subjects

G M Anderson

Publications and source records attributed to G M Anderson.

At least 109 records · Page 6Linked to original sources
PubMed1993

Use of coronary artery bypass surgery in the United States and Canada. Influence of age and income.

OBJECTIVE: To compare overall rates of coronary artery bypass surgery (CABS) in several Canadian and US jurisdictions and to compare use by age and income groups in the two countries. DESIGN: Survey, using computerized hospital discharge abstracts. SETTING: All nonfederal hospitals in New York, California, Ontario, Manitoba, and British Columbia between 1983 and 1989. PATIENTS: All adult residents of the five jurisdictions who underwent CABS in a hospital in their jurisdiction. RESULTS: Between 1983 and 1989, the CABS rates were consistently highest in California and lowest in the Canadian jurisdictions. In 1989, the age-adjusted rate of CABS in California (112.5/100,000 adults) was 27% higher than in New York (88.4/100,000) and 80% higher than in the three Canadian provinces combined (62.4/100,000). The CABS rates increased for those aged 65 years and older and decreased for those aged 20 to 54 years in all five jurisdictions. In 1989, CABS rates were three times higher in California than in Canada for those aged 75 years and older, and the higher rates for those aged 65 years and older accounted for 75% of the overall difference in rates between California and Canada. In Canada, CABS rates for the nonelderly varied little by income of area of residence, but in New York and California, rates increased steadily with the income of area of residence. CONCLUSION: Control over the supply of resources in Canada is associated with markedly lower CABS rates for the elderly than found in the United States. While overall rates are lower in Canada, the Canadian universal health insurance system reduces the influence of income on access to CABS found in the United States. However, even without universal health insurance, CABS rates for the nonelderly living in the poorest areas in California are similar to the rates for those living in the poorest parts of Canada.

Adult↗
PubMed1993

The human platelet dense granule: serotonin uptake, tetrabenazine binding, phospholipid and ganglioside profiles.

The functioning and composition of human platelet dense granules were studied using granules purified by Percoll fractionation. Reserpine-blockable serotonin (5-HT) uptake by the dense granule fraction was characterized and also demonstrated in the crude membrane fraction. Tetrabenazine (TBZ)-displaceable [3H]ketanserin binding was used to label the granular 5-HT transporter. Scatchard analyses, Hill plots, displacement curves, and binding kinetics indicated that TBZ-displaceable [3H]ketanserin binding labeled a site similar to that previously reported for chromaffin granules and synaptic vesicles. Analysis of phospholipid profiles in platelet fractions revealed that most platelet lysolecithin was associated with the dense granule fraction. Ganglioside analysis indicated that the predominant platelet ganglioside, GM3, was highly enriched in the dense granule fraction. The data lend further support to the idea that the 5-HT transporter complex is similar in platelet dense granules, chromaffin granules, and synaptic vesicles. However, the ganglioside and phospholipid findings clearly distinguish the types of storage sites and raise questions concerning the functional roles of dense granule GM3 and lysolecithin.

Animals↗
PubMed1993

Platelet serotonin studies in hyperserotonemic relatives of children with autistic disorder.

Platelet serotonin (5-HT) studies were conducted with 12 hyperserotonemic and 12 normoserotonemic age-, sex-, and relationship-matched relatives of autistic probands. Each group consisted of 7 mothers, 4 fathers, and 1 sister of autistic children and adolescents. The density (Bmax) of platelet 5-HT2 receptor binding sites, labelled with [3H]-lysergic acid diethylamide (LSD), was significantly lower in 11 hyperserotonemic subjects compared to 12 normoserotonemic subjects (40.9 +/- 13.5 fmol/mg protein, 59.6 +/- 13.2; p < 0.004). The affinity (Kd) for [3H]-LSD binding did not differ. Although the density (Bmax) of [3H]-paroxetine binding did not differ between groups, there was a small difference in the affinity (Kd) for [3H]-paroxetine binding (hyperserotonemic 47.6 +/- 9.0 pM, normoserotonemic 54.8 +/- 12.1; p < 0.05). There were no significant differences in platelet 5-HT uptake, or in thrombin-stimulated 5-HT release. Basal, 5-HT-stimulated, and arginine-vasopressin (AVP)-stimulated inositol phosphate production, as well as basal, prostaglandin E1 (PGE1)-, and forskolin-stimulated cAMP production did not differ. There were significant correlations between whole blood 5-HT levels and LSD Bmax (rs = -0.63, N = 23, p < 0.002) and whole blood 5-HT levels and 5-HT uptake Vmax (rs = 0.56, N = 18, p < 0.02). However, [3H]-LSD labelled 5-HT2 binding and 5-HT uptake were not correlated with each other. Hyperserotonemia of autism may be heterogeneous with one subgroup of subjects with increased 5-HT uptake and another subgroup with decreased 5-HT2 binding.

1-Methyl-3-isobutylxanthine↗
PubMed1993

Ischaemic and hypoxic preconditioning enhance postischaemic recovery of function in the rat heart.

OBJECTIVE: The aims were (1) to determine whether ischaemic and hypoxic preconditioning enhance recovery of left ventricular function after global ischaemia in the rat, and (2) to evaluate the effects of selective adenosine A1 receptor antagonists on ischaemic and hypoxic preconditioning. METHODS: Isolated rat hearts, perfused at constant pressure, were subjected to 30 min ischaemia and 30 min reperfusion. Control hearts were compared to hearts preconditioned with 5 min ischaemia in the presence or absence of the adenosine A1 antagonist A1433U (10 microM), and hearts preconditioned with 5 min hypoxia in the presence or absence of the adenosine A1 antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 5 microM). Recovery of left ventricular function was assessed by percent recovery of preischaemic rate-pressure product. RESULTS: Control hearts recovered 64(SEM 4)% of preischaemic rate-pressure product after 30 min reperfusion, whereas ischaemic and hypoxic preconditioned hearts recovered 86(3)% and 94(5)%, respectively (p < 0.05 v control). Despite enhanced recovery of postischaemic ventricular function, ischaemic and hypoxic preconditioning reduced the time to onset of ischaemic contracture from a control value of 12.6(0.6) min to 9.3(0.7) and 9.0(0.6) min, respectively (p < 0.05). Neither adenosine receptor antagonist blocked preconditioning. Ischaemic preconditioned hearts recovered 80(5)% of preischaemic function in the presence of A1433U, and hypoxic preconditioned hearts in the presence of DPCPX recovered 85(4)%. CONCLUSIONS: Ischaemic and hypoxic preconditioning enhance recovery of function following global ischaemia in the rat. The observations that adenosine receptor antagonists do not block the salutary effects of ischaemic or hypoxic preconditioning suggest that adenosine is not the sole mediator of preconditioning.

Animals↗
PubMed1993

Potentiation of the vasospastic response to angioplasty by pretreatment with fluoxetine. A study in the atherosclerotic rabbit.

There is evidence that angioplasty-induced vasospasm is mediated by serotonin (5-hydroxytryptamine [5-HT]) release from platelets. We tested the hypothesis that pretreatment of the atherosclerotic rabbit with fluoxetine, a platelet-uptake inhibitor of 5-HT, would reduce vasospasm after balloon angioplasty. Short-term administration of fluoxetine reduced platelet 5-HT uptake to 4% of baseline. Daily administration of fluoxetine for 7 days reduced whole-blood 5-HT levels to 28% of baseline. Thus, fluoxetine inhibited platelet 5-HT uptake in this model as predicted. Contrary to our expectations and despite the substantial reduction in whole-blood 5-HT levels, pretreatment with fluoxetine for 1 week resulted in augmentation of angioplasty-induced vasospasm in atherosclerotic rabbits. Intraperitoneal administration of fluoxetine produced vasoconstriction in normal rabbits that was augmented by 5-HT and not reversed with LY53857, a specific serotonin receptor antagonist. We postulate that this new observation is probably a result of the inhibition of the clearance mechanism for serotonin, with resultant enhancement of the effect of serotonin released by the activated platelets that are deposited on the vessel wall surface at the time of angioplasty. A direct effect of fluoxetine on serotonergic receptors is a second possible mechanism for the observed effect.

Angioplasty↗
PubMed1993

Comparison of hospital costs in California, New York, and Canada.

When the components of health care spending are broken down, hospital spending accounts for the largest portion of the total. This DataWatch compares hospital spending in two U.S. states with spending in two Canadian provinces, to gain better understanding of the recurring differences in hospital spending reported by the two countries. To make the data comparable, the study combines different hospital output measures into a composite measure that is converted into U.S. dollars and applied to data from both countries. In 1987 hospital costs per person were about one-third higher in the United States than in Canada. Results suggest that the higher U.S. costs are due primarily to higher unit costs rather than to differences in output.

California↗
PubMed1993

Trends and determinants of prescription drug expenditures in the elderly: data from the British Columbia Pharmacare Program.

This paper uses claims data from the prescription drug program for the elderly in British Columbia to describe temporal trends in prescription drug use and the determinants of those trends. Drug expenditures under the program increased by 317% from $21.6 million in 1981-82 to $90 million in 1988-89. Of the $68.4 million-dollar increase in overall expenditures, 34% was due to new drugs, 24% to increased age-specific utilization rates of old drugs, 21% to increased prices of old drugs, and 14% to the increased size of the elderly population. The analysis indicates that 61.5% of new drug expenditures can be attributed to four specific drugs and that the relative importance of price and utilization rates in determining changes in expenditures on old drugs varies by drug category. The paper provides a framework for understanding and predicting expenditures for drug benefit plans.

Age Factors↗
PubMed1993

Cerebrospinal fluid monoamine precursors and metabolites in human neonates following in utero cocaine exposure: a preliminary study.

BACKGROUND: Cocaine acts in the central nervous system by increasing dopamine release and inhibiting the reuptake of dopamine and other monoaminergic neurotransmitters. Prenatal cocaine exposure may cause neurochemical changes in developing monoaminergic neurons and might alter brain structure and function. No data have been published on central nervous system monoamine precursors and metabolites in human neonates exposed prenatally to cocaine. METHODS: Cerebrospinal fluid (CSF) was obtained from neonates undergoing lumbar puncture to rule out infection. The CSF was analyzed for the neurotransmitter precursors and metabolites tryptophan, tyrosine, 3-methoxy-4-hydroxyphenylglycol, homovanillic acid, and 5-hydroxyindoleacetic acid. Drug exposure was ascertained by medical record review and urine and meconium assays. RESULTS: Eleven neonates were cocaine-exposed, based on positive meconium or urine assays for benzoylecgonine; 20 were unexposed, based on both negative history and assay. The exposed and unexposed groups did not differ significantly in gender, perinatal stress, clinical illness, or exposure to other illicit drugs, but did differ in mean gestational age, growth parameters, and exposure to cigarettes. Cocaine-exposed neonates had significantly lower levels of CSF homovanillic acid (mean 148.1 vs 218.5 ng/mL, P = .01). The magnitude of this difference was similar after correcting for each of four potential confounding factors, although no longer statistically significant in all cases (P values ranged from .044 to .17). No significant differences were observed for tyrosine, tryptophan, 5-hydroxyindoleacetic acid, or 3-methoxy-4-hydroxyphenylglycol. CONCLUSIONS: These preliminary results suggest an association between prenatal cocaine exposure and decreased CSF homovanillic acid, the principal metabolite of dopamine. Prenatal cocaine exposure may result in changes in central dopaminergic systems in the human neonate.

Biogenic Monoamines↗
PubMed1992

Activators of protein kinase C decrease serotonin transport in human platelets.

Treatment of human platelets with activators of protein kinase C (PKC) for 5-20 min resulted in substantial reductions in the rate of platelet serotonin (5-HT) transport. The mean Vmax observed after 5 min treatment with 1 microM 4-beta-12-tetradecanoylphorbol 13-acetate (beta-TPA) was 66% (n = 16, P = 0.0001) of the control value. 5 min of treatment with 1 microM mezerein reduced uptake to 78% (n = 3, P = 0.01) of control. Both beta-TPA and mezerein had little effect on the Km of transport and had EC50 values of approx. 100 mM when a 20-min treatment period was used. The maximum effects of both were reached at approx. 20 min and could be blocked with staurospine. The beta-TPA effect was stereospecific, as alpha-TPA did not alter platelet 5-HT uptake. Although the PKC activators may have altered transmembrane ion-gradients for Na+ and Cl-, which are co-transported with 5-HT, minimizing ion-gradient changes had little effect on the observed reductions in transport. The PKC activators also had little or no effect on platelet 5-HT release or on the number (Bmax) of 5-HT transporters expressed at the platelet surface. The data indicate that PKC activation may down-regulate the activity of the 5-HT transporter in platelets. Apparently, most of this effect is mediated through mechanisms other than changes in ion-gradients, reductions in the number of available transporters, or increased 5-HT release. The apparent regulation of 5-HT transport by PKC may have important implications in platelet and neuronal functioning.

Alkaloids↗
PubMed1992

Platelet and whole blood serotonin content in depressed inpatients: correlations with acute and life-time psychopathology.

Platelet or whole blood serotonin content did not differ significantly in patients with major depression compared to healthy controls, but within the patient group, platelet serotonin levels correlated negatively with severity of depression (r = -0.49, p = 0.007). Levels were 39% lower in patients who had made a suicide attempt compared to nonattempter patients (47.2 +/- 27.3 versus 77.6 +/- 41.7 ng/10(8) platelets, p = 0.04). Conversely, comorbid borderline personality disorder (85.3 +/- 41.5 ng/10(8) platelets) was associated with 31% greater platelet serotonin content than nonborderline patients (58.9 +/- 31.1 ng/10(8) platelets) and 27% greater than healthy controls (62.4 +/- 19.8 ng/10(8) platelets). A pronounced seasonal variation in whole blood and platelet serotonin content was found in both patients and controls, largely due to lower levels in summer. Excluding cases tested in the summer abolished the statistically significant differences in patients with and without comorbid borderline personality disorder (BPD). Nevertheless, BPD attempters had lower serotonin levels than BPD nonattempters but higher serotonin levels than non-BPD attempters. Current hostility and a life-time history of aggression were positively correlated with platelet serotonin content (r = 0.44, p = 0.04 and r = 0.41, p = 0.06). This study provides evidence for an association between lower platelet serotonin content and depression and suicidal behavior, and association of higher platelet serotonin content and comorbid borderline personality disorder and behavior traits such as aggressivity.

Adult↗
PubMed1992

Effect of amygdala kindling on the in vivo release of GABA and 5-HT in the dorsal raphe nucleus in freely moving rats.

Our laboratory has previously reported a significant subsensitivity to iontophoretically applied GABA (gamma-aminobutyric acid) in dorsal raphe neurons of amygdala-kindled rats. This subsensitivity was selective for GABA and persisted at least 3 months after the last kindled seizure. In the present series of experiments, we explored mechanisms by which kindling could result in persistent GABA sensitivity changes, using in vivo microdialysis to quantitate neurotransmitter [including GABA and 5-hydroxytryptamine (5-HT)] release in the dorsal raphe nucleus of awake, unrestrained amygdala-kindled rats. Depolarization-induced release of GABA is markedly increased in the dorsal raphe nucleus in amygdala-kindled animals. This change in depolarization-induced GABA release appeared to be graded, dependent upon the stage to which the animal is kindled. Thus GABA release is increased in animals kindled to Stage 2 and even greater in animals kindled to Stage 5 seizures. The change in GABA release is also selective, since no consistent change in the release of other putative amino acid neurotransmitters or 5-HT was observed in these same animals. We hypothesize that this increase in depolarization-induced release of GABA in the amygdala-kindled animal underlies the development of subsensitivity to GABA in dorsal raphe neurons.

Amino Acids↗
PubMed1992

Differentiation of Neuro-2a neuroblastoma cells by an antibody to GM3 ganglioside.

A monoclonal antibody against GM3 ganglioside (GM3Ab) was found to trigger differentiation of Neuro-2a cells in culture. The differentiation of Neuro-2a cells by GM3Ab was accompanied by increased levels of intracellular serotonin and amino acid neurotransmitters viz. aspartate, glutamate, glutamine, glycine and taurine. Further study indicated that the increase in the serotonin level was not due to a higher rate of serotonin synthesis but rather to a higher rate of active transport of serotonin from the medium. Studies on the cell surface gangliosides revealed that unlike the proliferating cells, the GM3Ab-mediated differentiated cells contained higher gangliosides in addition to GM3 and GM2 gangliosides. Analysis of total cellular proteins indicated the appearance of a 25 kDa protein, pI 5.4, in the GM3Ab-treated cells--a small amount of this protein was observed in dibutyryl cAMP (Bt2cAMP)-treated cells, however, the protein was totally absent in the 5-bromo-2'-deoxyuridine (BrdU)-treated cells. Investigation of the mode of action of GM3Ab indicated that the cellular differentiation was due to increased cAMP accumulation resulting from an increase in the adenylate cyclase activity. Further studies with different agents affecting protein kinase C (PKC) activity and direct assay of PKC ruled out the possibility that GM3Ab mediated its effect via PKC. This GM3Ab-induced differentiation could be inhibited by protein kinase A (PKA) inhibitor, H8, but could not be inhibited by sphingosine, an inhibitor of PKC. Pertussis toxin could mimic the effect of GM3Ab, suggesting that GM3Ab caused the elevation in the adenylate cyclase activity by reducing the Gi-protein inhibition of the adenylate cyclase. The data suggests that GM3Ab, after interaction with cell surface GM3, elevated intracellular cAMP level by withdrawing the inhibitory effect of some undefined factor(s) present in culture medium which normally keeps adenylate cyclase activity low through activation of Gi-protein.

Amino Acids↗
PubMed1992

Coronary artery bypass grafting in Canada: What is its rate of use? Which rate is right?

We reviewed recent reports from administrative databases and clinical registries addressing the utilization of coronary artery bypass grafting (CABG) in Canada. The Canadian CABG rate per 100,000 people increased from 31.1 to 43.2 between 1981-82 and 1986-87. Between 1981 and 1986 the rate in the United States increased from 69.9 to 95.3 per 100,000, consistently about two times the Canadian rate. Provincial data have shown particular growth in utilization among elderly people. However, in the United States the 1985 CABG rate was twice as high as the aggregated age-specific rates for Ontario and Manitoba among people 65 to 74 years of age and four times higher among those 75 years or more. Limited registry data suggest that the Canadian CABG case mix is similar to the case mix in major US centres and that, utilization growth notwithstanding, the procedure is largely applied to patients who should, in theory, benefit (i.e., those with severe angina, impaired left ventricular function and left main-stem or triple-vessel disease). However, chart audits and registry evaluations using explicit criteria are needed to compare the use of CABG in Canada and the United States. In addition, Canadian data show moderate regional and municipal variations, the 1986-87 rates per 100,000 population in major census metropolitan areas varying from 19.5 to 46.9. Areas with consistently low rates raise particular concerns about impaired access to CABG. Reasons for variations should therefore be a research priority.

Adult↗
PubMed1992

Platelet dense granule release reaction monitored by high-performance liquid chromatography-fluorometric determination of endogenous serotonin.

The platelet dense granule release reaction was monitored by measuring the serotonin content of platelets collected by filtration following release. Sensitive HPLC-fluorometric analysis permitted release to be assessed using small (25-50 microliters) volumes of plasma and whole blood. Release could be examined for periods as short as 1 s due to the rapid stoppage effected by filtration. The half-life of thrombin-stimulated (1 U/ml) release was 2-3 s, the EC50 values observed for thrombin-stimulated release over a 60-s release period were 0.01-0.03 U/ml for diluted whole blood and plasma samples.

Blood Platelets↗
PubMed1992

Double-blind, crossover trial of fluoxetine and placebo in children and adolescents with obsessive-compulsive disorder.

Rigorously designed clinical trials have demonstrated the efficacy and safety of fluoxetine in adults with major depressive disorder and obsessive-compulsive disorder (OCD) but not in patients below 18 years old. This report describes a randomized, double-blind, placebo-controlled, fixed-dose (20 mg qd) trial of fluoxetine in 14 children and adolescents with OCD, ages 8 to 15 years old; the study was 20 weeks long with crossover at 8 weeks. Obsessive-compulsive symptom severity was measured on the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) and the Clinician's Global Impression-Obsessive Compulsive Disorder scale (CGI-OCD). The CY-BOCS total score decreased 44% (N = 7, p = .003) after the initial 8 weeks of fluoxetine treatment, compared with a 27% decrease (N = 6, p = .13) after placebo. During the initial 8 weeks, the magnitude of improvement for the fluoxetine group significantly exceeded that for the placebo group as measured by the CGI-OCD (p = .01) but not by the CY-BOCS (p = .17). The most common drug side effects were generally well tolerated. The results suggest that fluoxetine is a generally safe and effective short-term treatment for children with OCD.

Adolescent↗