Postmortem analysis of subcortical monoamines and amino acids in Tourette syndrome.
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Adult↗
Biomedical subjects
G M Anderson
Publications and source records attributed to G M Anderson.
Pathogenesis of Tourette syndrome. Clues from the clinical phenotype and natural history.
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Humans↗
Neuroendocrine and behavioral effects of naloxone in Tourette syndrome.
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Behavior↗
Use of high-performance liquid chromatography for assay of glutamic acid decarboxylase. Its limitation in use for post-mortem brain.
Rat brain, obtained 10 min after death, contained high levels of endogenous gamma-aminobutyric acid (GABA) and glutamic acid. Incubation of this brain homogenate at 37 degrees C indicated decrease of GABA with time due to degradation by GABA-transaminase. Reported high-performance liquid chromatographic (HPLC) methods for glutamic acid decarboxylase (GAD) assay depend on the difference between the GABA content of the reaction mixture after and before the incubation period. None of the methods considered the degradation of GABA during incubation. Furthermore, during determination of the Michaelis constant (KM) for the reaction none of them considered the endogenous substrate. Here we have focused on these factors which seriously affect the maximum velocity (Vmax) and KM values during GAD assay by the HPLC technique. By a simple and rapid HPLC technique we have measured GAD activity in post-mortem rat brain after removing endogenous glutamic acid by charcoal treatment and using gabaquline to prevent GABA degradation during incubation period. By this method a Vmax value of 46 +/- 4 nmol/h/mg protein and a KM value of 7.5 +/- 0.6 mM were observed for GAD activity of crude brain homogenate. For a comparative study, we have carried out radiometric assay of GAD activity from the same sample and observed a Vmax of 48 +/- 6 nmol/h/mg protein and KM of 6.9 +/- 0.4 mM.
Animals↗
Recent trends in acute care hospital utilization in Ontario for diseases of the circulatory system.
OBJECTIVE: To describe trends in the use of acute care hospital services for diseases of the circulatory system in Ontario. DESIGN: Observational study. DATA EXTRACTION: Information on diagnoses, procedures and demographic characteristics was obtained from routinely collected computerized abstracts of separations from all acute care hospitals in Ontario during 1979-80, 1983-84 and 1988-89. The data were combined with population estimates to calculate overall separation rates and rates specific for age, diagnosis and procedure. Resource intensity weights were used to estimate changes in resource use. MAIN RESULTS: The overall separation rate increased by 3% and the resource-intensity-weighted separation rate by 12% from 1979-80 to 1988-89. The overall medical separation rate increased by 2%, whereas the surgical rate increased by 12%. The surgical separation rate increased among patients 55 to 79 years of age but decreased in all the other adult age groups. The separation rates for coronary artery bypass surgery and cardiac valve surgery increased rapidly among patients 65 years of age or older. The medical separation rate decreased for patients of all ages except those less than 5 years and those 80 years or more. The medical separation rates decreased by less than 1% for diagnoses related to ischemic heart disease (IHD) and increased dramatically for coronary artery revascularization. CONCLUSIONS: The increasing elderly population has not resulted in large increases in acute care hospital utilization for diseases of the circulatory system. The impact of an aging population has been balanced by decreased utilization rates in the younger groups. The intensity of hospital care has risen primarily because of increases in surgical rates, especially in the elderly population. The large decrease in the rate of death from IHD over the past two decades has not been associated with similar decreases in acute care hospital utilization for this disorder.
Acute Disease↗
Opinion leaders vs audit and feedback to implement practice guidelines. Delivery after previous cesarean section.
A randomized controlled trial with 76 physicians in 16 community hospitals evaluated audit and feedback and local opinion leader education as methods of encouraging compliance with a guideline for the management of women with a previous cesarean section. The guideline recommended clinical actions to increase trial of labor and vaginal birth rates. Charts for all 3552 cases in the study groups were audited. After 24 months the trial of labor and vaginal birth rates in the audit and feedback group were no different from those in the control group, but rates were 46% and 85% higher, respectively, among physicians educated by an opinion leader. Duration of hospital stay was lower in the opinion leader education group than in the other two groups. The overall cesarean section rate was reduced only in the opinion leader education group. There were no adverse clinical outcomes attributable to the interventions. The use of opinion leaders improved the quality of care.
Cesarean Section↗
Reproducibility and temporal stability of ADP-induced platelet aggregation: comparison of the anticoagulants sodium citrate and D-phenylalanyl-L-prolyl-L-arginyl-chloromethyl ketone.
We compared the reproducibility and temporal stability of ADP-induced aggregation of platelet-rich plasma anticoagulated with citrate or with D-phenylalanyl-L-prolyl-L-arginyl-chloromethyl ketone (PPACK), a thrombin inhibitor. Citrate- or PPACK-platelet-rich plasma (PRP) was stored at room temperature in capped plastic tubes or in plastic syringes from which all air was expelled. At intervals over 1-5 hr after venipuncture, platelet aggregation was induced by 1-1.5 microM ADP. Initially, the aggregation of PPACK-PRP was nearly twice that of citrate-PRP. The response of PPACK-PRP stored in the syringe remained essentially constant over the interval of study, in contrast to the responses of the other samples which declined with time. The improved stability of the response obtained from samples anticoagulated with PPACK was due to the absence of citrate, since PRP containing both citrate and PPACK became less responsive over time in a manner similar to PRP which contained only citrate. Anticoagulation with PPACK rather than citrate results in a more reproducible and stable aggregation response and more closely reproduces the in vivo environment of the platelet.
Adenosine Diphosphate↗
Signal-to-noise optimization of HPLC-fluorometric systems and their application to the analysis of indoles.
The signal-to-noise optimization of high performance liquid chromatographic (HPLC) flow-cell fluorometric systems is described and the possibilities for further improving limits of detection for indoles is discussed. Application of HPLC-fluorometry to analyses in rat cerebrospinal fluid (CSF), human lumbar CSF, and human blood is presented. Finally, the intriguing clinical finding of hyperserotonemia in autism is discussed.
Animals↗
Obstetrical attitudes and practices before and after the Canadian Consensus Conference Statement on Cesarean Birth.
This paper describes one aspect of a research program aimed at reducing the incidence of cesarean section in Ontario for women with a previous cesarean section or a breech presentation. Using data from multiple sources--surveys of obstetricians, and hospital administrators, and hospital record statistics, the authors attempt to assess the response of obstetricians to pressure to change their practice. This pressure comes principally from the Canadian Consensus Conference Statement on Cesarean Birth, released in June 1986 and subsequently endorsed by a number of professional organizations. The Statement provides clear guidelines for the management of labour in women with previous cesarean section or a breech presentation. The findings present a number of interpretive challenges. Based on their response to hypothetical cases obstetricians are favourably disposed to considering a trial of labour for women with previous cesarean section and breech presentation. However, both their reported practices, as well as hospital statistics indicate the continued high prevalence of cesarean section, though there is a small decline in cesareans for previous cesarean section. There was no evidence that hospitals lacked appropriate facilities for a trial of labour or had unduly restricted formal policies. Furthermore, although awareness of and agreement with the Consensus Statement recommendations was high, when questioned on the actual details of the recommendations, obstetrician's recall was surprisingly low. Respondents tended to err in the direction of choosing more conservative measures than those recommended by the Statement.(ABSTRACT TRUNCATED AT 250 WORDS)
Attitude of Health Personnel↗
Emergence of self-destructive phenomena in children and adolescents during fluoxetine treatment.
Self-injurious ideation or behavior appeared de novo or intensified during fluoxetine treatment of obsessive-compulsive disorder in six patients, age 10 to 17 years old, who were among 42 young patients receiving fluoxetine for obsessive-compulsive disorder at a university clinical research center. These symptoms required the hospitalization of four patients. Before receiving fluoxetine, four patients had major risk factors for self-destructive behavior including depression or prior suicidal ideation or self-injury. Three hypotheses concerning the apparent association between fluoxetine and these self-injurious phenomena are discussed: (1) coincidence; (2) disorganization of vulnerable individuals secondary to drug-induced activation; and (3) a specific serotonergic-mediated effect on the regulation of aggression.
Adolescent↗
A comparison of cost-sharing versus free care in children: effects on the demand for office-based medical care.
Using data from the community based RAND Health Insurance Experiment, the effect of cost-sharing versus free care on the use of office-based medical care in children was examined. Children from families on cost-sharing plans had a 22 percent lower probability (P less than 0.005) of having an episode of care during the study year. Both the number of episodes of care and total charges for outpatient professional services were 30 percent lower (P less than 0.005) with cost-sharing. cost-sharing reduced average charges for medical services by 30 percent (P less than 0.01) and pathology charges by 45 percent (P less than 0.005). cost-sharing reduced medical services received by 26 percent (P less than 0.05) and pathology services received by 43 percent (P less than 0.05) but did not have a significant effect on either the price for medical services or pathology services. It was concluded that there is a large difference between cost-sharing insurance plans and free care in the demand for office-based medical care in children. Cost-sharing results in children receiving fewer services, not lower priced services.
Child↗
Synergistic activation of a human promoter in vivo by transcription factor Sp1.
Many eucaryotic promoters contain multiple binding sites for sequence-specific DNA-binding proteins. In some cases, these proteins have been shown to interact synergistically to activate transcription. In this study, we address the possibility that the transcription factor Sp1 can synergistically activate a native human promoter in a cellular context that closely resembles that of a single-copy gene. Using DNase I footprinting with affinity-purified Sp1, we show that the human argininosuccinate synthetase (AS) promoter contains three sites that bind Sp1 with different affinities. These binding sites were mutated to abolish Sp1 binding, individually and in all possible combinations, to generate a series of AS promoter-chloramphenicol acetyltransferase (CAT) expression constructs. Mutations designed to increase Sp1 binding were also introduced at each site. The in vivo transcriptional activity of these mutant AS promoter-CAT constructs was then measured in stably transfected human RPMI 2650 cell lines. Our results show that each of the three Sp1-binding sites contributes to full activation of the human AS promoter and that the relative contribution of each site correlates well with its in vitro affinity for Sp1. More importantly, we find that the three Sp1-binding sites when present in the same promoter activate transcription to a level that is 8 times greater than would be expected given their individual activities in the absence of the other two sites. Thus, we provide direct evidence that Sp1-binding sites in their native context in a human promoter can interact synergistically in vivo to activate transcription. The ability to activate transcription synergistically may be the reason that many cellular promoters have multiple Sp1-binding sites arranged in tandem and in close proximity.
Argininosuccinate Synthase↗
Serotonergic responsivity in eating disorders.
Evidence suggests that serotonin may play a role in the pathogenesis of eating disorders. In this ongoing study, serotonin-mediated physiological responses and whole-blood serotonin content are measured in young women with an eating disorder during the active phase of the illness and at the conclusion of inpatient treatment. The responsivity of central nervous system (CNS) serotonergic pathways is assessed by neuroendocrine challenge with a 60-mg oral dose of dl-fenfluramine, an indirect serotonin agonist, whereas the responsivity of the platelet serotonin2 (5-HT2) receptor complex is evaluated by measurement of the magnitude of serotonin-amplified platelet aggregation. Compared with normal controls, eating-disorder patients have exhibited a trend toward reduced prolactin responses to fenfluramine challenge at both the initial and followup assessments. Patients also have exhibited a substantially wider range of serotonin-amplified platelet aggregation responses than have controls; normal-weight bulimic patients have had significantly greater responses than both anorexic restrictors and normal subjects. These preliminary results suggest potential alterations in serotonin-mediated responses in eating-disorder patients that may vary with the diagnostic subgroup.
Adolescent↗
Board certification and practice style: an analysis of office-based care.
BACKGROUND: The relationship between family practice certification and practice style has important health policy implications. We used data from the RAND Health Insurance Experiment to study the relationship between family practice certification and (1) patient characteristics including age and sex of patients, and (2) facets of practice style including probability of hospital admission, number of visits in an episode of care, number of physicians seen per episode, total charges per episode, charges per service category, and inputs per service category. METHODS: Data on health care service utilization by a sample of 5554 nonelderly individuals over a 1-year period were used to define episodes of care. Multivariate regression techniques were used to measure the association between family practice certification and patient characteristics and between family practice certification and practice style, controlling for the effects of patients characteristics. RESULTS: Patients of certified family physicians were an average of 3 years younger than patients of noncertified family physicians, but other demographic characteristics were similar. Certified family physicians had higher pathology services charges and inputs, but no statistically significant differences in other measures of charges and inputs. CONCLUSIONS: Certified and noncertified family physicians treat similar patients. Certification in family practice is not associated with major differences in total service charges, but is associated with differences in the use of laboratory diagnostic services.
Adolescent↗
Mechanisms of ATP depletion in the cold-stored heart.
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Adenosine↗
Giant two-dimensional gel electrophoresis: methodological update and comparison with intermediate-format gel systems.
Two-dimensional (2-D) gel electrophoresis methods for separating complex mixtures of proteins have not changed fundamentally since their original description in the late 1970's. Nevertheless, 2-D gel resolution has improved substantially as a result of a series of incremental modifications. One of these was the development of the "giant-gel" format, using gels measuring at least 30 x 30 cm to provide the highest resolution 2-D gel system available. As originally described, this procedure has several important limitations: it requires custom-built equipment; it is expensive in terms of time, reagents, film and support matrices; and it generates gels which are difficult to manupulate, particularly for silver staining. This report describes modifications in the giant gel procedure to permit use of a commercially available gel apparatus and to obtain giant gels of improved mechanical strength suitable for silver staining. The resolution of giant gels is compared with that obtained using two systems currently being marketed for use by laboratories performing large numbers of 2-D gel analyses. The smaller format gels resolved fewer proteins, by 30-40%, compared with the giant gels. This difference in resolving power suggests that giant gels will continue to be useful in selected applications.
Autoradiography↗
Serotonin in human lumbar cerebrospinal fluid: a reassessment.
An inter-laboratory comparison study was carried out in order to ascertain mean levels of serotonin (5-HT) in human lumbar cerebrospinal fluid (CSF). Analyses were performed using high performance liquid chromatography (HPLC) coupled with either electrochemical (LC-EC) or fluorometric (LC-F) detection. With the detection limits obtained (7-8 pg/ml for LC-EC, 7-15 pg/ml for LC-F) 5-HT was not usually detected in human lumbar CSF. The findings indicate that the true mean concentration of CSF 5-HT is less than 10 pg/ml. This upper limit is substantially lower than all previous reports of 5-HT concentrations in normal human lumbar CSF. The extremely low concentrations of 5-HT present in CSF make it unlikely that CSF 5-HT will be of clinical utility in assessing central serotonergic function.
Chromatography, High Pressure Liquid↗
Growth hormone and prolactin response to methylphenidate in children with attention deficit disorder.
Utilizing a double-blind, drug-placebo design, we examined growth hormone (GH) and prolactin (Pro) response to oral administration of methylphenidate (MPH) in 14 boys (ages 7.0-12.4 years) with Attention Deficit Disorder (ADD). Four conditions representing three different MPH doses (0.3 mg/kg O.D., 0.3 mg/kg B.I.D., 0.6 mg/kg O.D.) and Placebo were compared in each subject, each condition lasting for a period of 3 weeks. GH and Pro response were measured both as maximum peak GH (DGH) or nadir of Pro (DPro) as well as area under the curve for the first four hours after MPH administration (AUCGH, AUCPro). Behavioral measures included parent ratings on the Yale Children's Inventory and teacher ratings on the Yale and Conners Behavior Rating Scales and Kagan's Matching Familiar Figures Test (MFFT). Prolactin response as measured by AUCPro was significantly increased after MPH compared to placebo (t = 2.04, p less than 0.05, placebo vs all doses MPH). This difference observed for AUCPro between placebo and MPH was evident as well when we considered the number of times AUCPro declined after MPH as compared to placebo (p = .018, Fisher's exact test). Within-subjects analysis of covariance demonstrated significant correlations between the improvement in reaction time on the MFFT and 1) GH response (AUCGH, r = .58, p less than .001) and 2) prolactin response (AUCPro, r = .40, p less than .05) and between improvement in attention as measured on the Yale BRS and GH response (AUCGH, r = .57, p less than .05). Our findings suggest that measures other than GH and prolactin may be more desirable measures of brain catecholaminergic functioning.
Attention Deficit Disorder with Hyperactivity↗