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Biomedical subjects

B Parsons

Publications and source records attributed to B Parsons.

At least 19 recordsLinked to original sources

Air quality effects of traffic in a canyon-like street (Falmouth, U.K.).

It has been suggested that in relation to air quality impacts, roads with low (<20000 vpd) traffic flow need not be considered as significant. This study examines this suggestion more closely by comparing real-time monitoring of traffic related pollutants (NO2, PM10 and PAH) at two sites (including a 'canyon-street') in Falmouth, Cornwall in relation to traffic flow. For comparison, real-time monitoring data for NO2 and PM10 is also taken from a well ventilated site in Camelford, Cornwall. The data obtained suggest that roads with traffic flow considerably lower than 20000 vpd can give rise to pollutant levels which have implications for human health. The application of simple linear regression techniques to the data suggests that under certain conditions simple estimates can be made in relation to likely traffic-related air quality effects in canyon-like streets.

Air Pollutants↗

A national census of Irish general practice training programme graduates 1990-1996.

We followed the career pathways of all graduates of Irish general practice training schemes between 1990 and 1996 inclusive, with specific reference to their current positions, ten year aspirations, perceived barriers to their ideal career and attitudes to out of hours work. A postal survey using a structured questionnaire was performed. Addresses were identified for 253 of the 266 graduates (95%). A total of two hundred and nine responses were received (84% of those with an identifiable address). 173 (83%) have remained in general practice; 90% in Ireland and 60% in the same health board of their training programme. The preferred career option for 79% was to be a general practice principal; this differed significantly between males (89%) and females (74%) (p=0.016). Being a single-handed general practitioner was the preferred option for 2%; 43% considered this unacceptable. A half would prefer to work in a country town; one third considered a rural location as unacceptable. 'Out of hours' commitment and availability of local posts were the most commonly perceived barriers to career progress (53% and 45% respectively). 26% were not prepared to do any out of hours work; this differed significantly between males (10%) and females (30%) (p<.001). 17% have permanently left a career in general practice. Female general practitioners were not significantly more likely than male general practitioners to have left (19% vs. 14%, p=0.3). The most common reason given for leaving general practice was other career interest (78%). The significant increase in female general practice graduates over the past twenty years is highlighted. The vast majority of these female graduates wished to be a principal in a group practice and were prepared to undertake out of hours work. There is also a mismatch between career aspirations and the present structure of general practice in Ireland. The urgent need for changes in health system organisation to ensure that these intentions can be fulfilled is emphasised.

Career Choice↗

Childhood poisoning: access and prevention.

OBJECTIVES: To investigate the circumstances and means of access to six poisoning agents by children under 5 years of age and to make recommendations for countermeasures and strategies for implementation. METHODOLOGY: A case series study of access to six poisoning agents was conducted. Cases were identified prospectively through a poisons information centre and hospital emergency departments. Interviews were conducted with 523 parents and caregivers using a structured questionnaire. RESULTS: The majority of children (94.1%) accessed the agent in their own home or another home and, in 38% of cases (excluding mistakes in administration), the parent or caregiver was present in the immediate area at the time of the incident. In cases in which the child was alone in the room, caregivers were frequently involved in household duties (51%), with only 10% undertaking leisure activities and 8% on the telephone. The span of unsupervised time reported was 5 min or less in 79.5% of these cases. The means of access was generally during periods of use of the agent (75.3%), including just purchased, rather than when agents were in their usual storage place. CONCLUSIONS: There is little scope for improved supervision as a major intervention. Design and regulatory changes such as local safe storage for bench tops and while travelling, improved labelling and packaging, improved child-resistant packaging and its more general application are required. These and agent-specific interventions, including child-resistant bait stations for rodenticides and well covers for vaporizers, are more likely to prevent poisoning. The recent identification of childhood poisoning prevention as a national priority may lead to coordinated action to implement these and other preventive measures.

Australia↗

Suicidal behavior in bipolar mood disorder: clinical characteristics of attempters and nonattempters.

OBJECTIVE: Bipolar Disorder is associated with a higher frequency of attempted suicide than most other psychiatric disorders. The reasons are unknown. This study compared bipolar subjects with a history of a suicide attempt to those without such a history, assessing suicidal behavior qualitatively and quantitatively, and examining possible demographic, psychopathologic and familial risk factors. METHODS: Patients (ages 18 to 75) with a DSM III-R Bipolar Disorder (n = 44) diagnosis determined by a structured interview for Axis I disorders were enrolled. Acute psychopathology, hopelessness, protective factors, and traits of aggression and impulsivity were measured. The number, method and degree of medical damage was assessed for suicide attempts, life-time. RESULTS: Bipolar suicide attempters had more life-time episodes of major depression, and twice as many were in a current depressive or mixed episode, compared to bipolar nonattempters. Attempters reported more suicidal ideation immediately prior to admission, and fewer reasons for living even when the most recent suicide attempt preceded the index hospitalization by more than six months. Attempters had more lifetime aggression and were more likely to be male. However, attempters did not differ from nonattempters on lifetime impulsivity. LIMITATIONS: The generalizability of the results is limited because this is a study of inpatients with a history of suicide attempts. Patients with Bipolar I and NOS Disorders were pooled and a larger sample is needed to look at differences. We could not assess psychopathology immediately prior to the suicide attempt because, only half of the suicide attempters had made attempts in the six months prior to admission. Patients with current comorbid substance abuse were excluded. No suicide completers were studied. CONCLUSIONS: Bipolar subjects with a history of suicide attempt experience more episodes of depression, and react to them by having severe suicidal ideation. Their diathesis for acting on feelings of anger or suicidal ideation is suggested by a higher level of lifetime aggression and a pattern of repeated suicide attempts.

Adult↗

Association of aggressive behavior with altered serotonergic function in patients who are not suicidal.

OBJECTIVE: The purpose of this study was to determine whether aggression and serotonergic dysfunction are related in the absence of a history of suicidal behavior. Although serotonergic dysfunction has been implicated in aggressive and impulsive behavior, most studies of such behavior have included individuals with a history of suicide attempts. Low concentrations of CSF 5-hydroxyindoleacetic acid (5-HIAA) have been consistently associated with suicidal behavior, presenting a potential confound in the link between aggression and serotonergic dysfunction. METHOD: The authors examined the association between aggression and CSF 5-HIAA concentrations in a group of 64 patients who had different DSM-III-R axis I diagnoses and no past suicidal behavior. Aggressive (N=35) and nonaggressive (N=29) groups were defined by a median split on a six-item history of adulthood aggressive behavior. RESULTS: The aggressive group had significantly lower CSF 5-HIAA concentrations than the nonaggressive group. Aggressive individuals also scored significantly higher on self-report measures of hostility, impulsiveness, and sensation seeking. CSF 5-HIAA concentrations, however, did not correlate with self-reported hostility and impulsivity. CONCLUSIONS: There is an association between aggressive behavior and serotonergic dysfunction independent of suicidal behavior in patients with axis I disorders who exhibit relatively milder forms of aggressive behavior. Analogous to findings with suicidal behavior, a low concentration of CSF 5-HIAA is related to aggressive behavior but does not show the same relationship to the continuum of aggressive feelings and thoughts.

Adult↗

Neuroendocrine response to fenfluramine challenge in boys. Associations with aggressive behavior and adverse rearing.

BACKGROUND: There is evidence of relationships among serotonin, aggressive behavior, and a childhood history of socially adverse-rearing conditions. This study examines the prolactin response to fenfluramine hydrochloride challenge in young boys who show clinically significant aggressive behavior or who are raised in a social environment that is conducive to the development of chronic aggression. METHODS: A series of 34 younger brothers of convicted delinquents underwent standardized psychiatric and observation-based assessments of their social-rearing environments that were conducted during home visits. Approximately 2 years later, these boys underwent a reassessment of psychiatric status and an assessment of central serotonergic activity using the fenfluramine challenge procedure. RESULTS: Increasing degrees of aggressive behavior at either assessment were positively correlated with the prolactin response to fenfluramine challenge. Furthermore, adverse-rearing circumstances that were conducive to the development of aggressive behavior also exhibited positive correlations with the prolactin response. This association between adverse rearing and the prolactin response was statistically independent of that between aggression and the prolactin response. CONCLUSION: In young boys, aggressive behavior and social circumstances that are conducive to the development of aggressive behavior are positively correlated with a marker of central serotonergic activity.

Aggression↗

The effect of pH on the Ca2+ affinity of the Ca2+ regulatory sites of skeletal and cardiac troponin C in skinned muscle fibres.

It is known that intracellular pH drops rapidly after the onset of ischemia in cardiac muscle and may play some role in the rapid drop in force that ensues. It is also known that alpha 1-adrenoceptor agonists alkalinize intracellular pH by stimulating Na+/H+ exchange and may represent a mechanism which facilitates recovery of intracellular pH from acidosis. Lowering or raising pH shifts the Ca2+ dependence of force development in muscle fibres to higher or lower free Ca2+ concentrations, respectively, yet the precise mechanism is unknown. To investigate this phenomenon we have used skinned skeletal or cardiac muscle fibres whose endogenous troponin C (TnC) has been replaced with chicken skeletal TnC labelled with DANZ (STnCDANZ) or recombinant cardiac TnC labelled with IAANS (CTnC3(C84)[AANS), respectively. The fluorescence of the STnCDANZ or CTnC3(C84)IAANS was enhanced by Ca2+ binding to the Ca(2+)-specific (regulatory) site(s) of STnC or CTnC when incorporated into skinned fibres, and was measured simultaneously with force. When the pH was changed from 7.0 to 6.5 or 7.5 the shift in the Ca2+ dependence of force paralleled the shift in fluorescence. Since the force and fluorescence shift in parallel as the pH is lowered or raised, it can be concluded that these changes in Ca2+ sensitivity are caused by a decrease or increase, respectively, in the Ca2+ affinity of the Ca(2+)-specific site(s) of TnC. Since lowering or raising the pH also resulted in lower or higher, respectively, maximal Ca2+ activated force while maximal fluorescence remained unchanged, it is possible that H+ may act indirectly, as well, by reducing or increasing, respectively, the number or type of crossbridges attached to actin and thereby alter the crossbridge induced depression or elevation, respectively of the observed TnC Ca2+ affinity. Experiments with 2,3-butanedione monoxime, however, where force-generating crossbridges were greatly reduced, indicated that the pH effect may be primarily related to a direct change in the Ca2+ affinity to the regulatory sites of TnC.

Amino Acid Substitution↗

Platelet serotonin 2A (5-HT2A) receptor characteristics and parenting factors for boys at risk for delinquency: a preliminary report.

OBJECTIVE: This study examined the cross-sectional association between platelet membrane serotonin 2A (5-HT2A) receptor variables in children and characteristics of their parents that place these children at risk for antisocial behavior. METHOD: As part of a larger prospective study investigating predictors of antisocial behavior, 38 younger brothers of convicted delinquents provided platelet samples; samples from 34 boys (mean age=8.3 years) were usable. The authors determined the density (Bmax) and affinity (Kd) of platelet membrane 5-HT2A receptors by using [3H]lysergic acid diethylamide. They also measured parental characteristics related to serotonergic dysfunction in prior studies, the quality of parent-child interactions, and psychiatric profiles of the boys who provided platelets. RESULTS: Bmax was significantly lower in boys whose parents had histories of substance abuse or incarceration. Bmax was also inversely related to harsh parenting; boys raised in environments characterized by frequent parental physical punishment and anger had a significantly lower Bmax. Bmax was not related to boys' disruptive behavior. CONCLUSIONS: In boys at risk for antisocial behavior, the density of 5-HT2A receptors on platelets is inversely related to parental factors known to place youth at risk for antisocial behavior.

Antisocial Personality Disorder↗

Neuroleptics up-regulate adenosine A2a receptors in rat striatum: implications for the mechanism and the treatment of tardive dyskinesia.

Neuroleptics, which are potent dopamine receptor antagonists, are used to treat psychosis. In the striatum, dopamine subtype-2 (D2) receptors interact with high-affinity adenosine subtype-2 (A2a) receptors. To examine the effect of various neuroleptics on the major subtypes of striatal dopamine and adenosine receptors, rats received 28 daily intraperitoneal injections of these drugs. Haloperidol (1.5 mg/kg/day) increased the density of striatal D2 receptors by 24% without changing their affinity for [3H]sulpiride. Haloperidol increased the density of striatal A2a receptors by 33% (control, 522.4 +/- 20.7 fmol/mg of protein; haloperidol, 694.6 +/- 23.6 fmol/mg of protein; p < 0.001) without changing their affinity for [3H]CGS-21680 (control, 19.2 +/- 2.2 nM; haloperidol, 21.4 +/- 2.3 nM). In contrast, haloperidol had no such effect on striatal dopamine subtype-1 (D1) and adenosine subtype-1 (A1) receptors. Binding characteristics and the pharmacological displacement profile of the increased [3H]CGS-21680 binding sites confirmed them as A2a receptors. Comparing different classes of neuroleptics showed that the typical neuroleptics haloperidol and fluphenazine (1.5 mg/kg/day) increased D2 receptor densities, whereas the atypical neuroleptics sulpiride (100 mg/kg/day) and clozapine (20 mg/kg/day) did not (control, 290.3 +/- 8.7 fmol/mg of protein; haloperidol, 358.1 +/- 6.9 fmol/mg of protein; fluphenazine, 381.3 +/- 13.6 fmol/mg of protein; sulpiride, 319.8 +/- 18.9 fmol/mg of protein; clozapine, 309.2 +/- 13.7 fmol/mg of protein).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Seasonal rhythm of platelet [3H]imipramine binding in adolescents who attempted suicide.

OBJECTIVE: This study was designed to determine the seasonality of serotonin functions among adolescents who attempt suicide. METHOD: Platelet [3H]imipramine binding was assessed over a period of 18 months in 98 adolescents who attempted suicide and a comparison group of 23 never-suicidal youths with conduct disorder. RESULTS: [3H]Imipramine (Bmax) was uncorrelated with age, but showed considerable seasonal variability over time in those who had attempted suicide. CONCLUSIONS: [3H]Imipramine binding density in adolescents who attempted suicide exhibited significant seasonality, reaching a nadir in late winter/early spring.

Adolescent↗

Adenosine receptor antagonists potentiate dopamine receptor agonist-induced rotational behavior in 6-hydroxydopamine-lesioned rats.

Adenosine receptor antagonists, DMPX, PACPX and theophylline, produce contralateral rotations in unilateral 6-hydroxydopamine-lesioned rats. DMPX and theophylline markedly increase rotations produced by bromocriptine (a dopamine D2 receptor agonist) and/or SKF38393A (a dopamine D1 receptor agonist). All of these effects are inhibited by CGS21680C (an adenosine A2 receptor agonist). These findings suggest synergistic interactions among D1, D2 and A2 receptors that may be relevant to the treatment of Parkinson's disease.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Differential visualization of dopamine D2 and D3 receptors in rat brain.

The mRNA for the dopamine D3 receptor is confined to limbic regions and the D3 receptor may be a target for antipsychotic medications. We used quinpirole and domperidone to try to visualize D3 and dopamine D2 receptors selectively in rat brain, using in vitro autoradiography and digital subtraction. We used 125I-sulpiride, a ligand with high affinity for the D2 receptor in brain and for the D3 and D2 receptors in transfected cells. Our data indicate that the D2 receptor is present in much greater density than the D3 receptor in rat brain, even in limbic regions.

Animals↗

Human sexual orientation. The biologic theories reappraised.

Recent studies postulate biologic factors as the primary basis for sexual orientation. However, there is no evidence at present to substantiate a biologic theory, just as there is no compelling evidence to support any singular psychosocial explanation. While all behavior must have an ultimate biologic substrate, the appeal of current biologic explanations for sexual orientation may derive more from dissatisfaction with the present status of psychosocial explanations than from a substantiating body of experimental data. Critical review shows the evidence favoring a biologic theory to be lacking. In an alternative model, temperamental and personality traits interact with the familial and social milieu as the individual's sexuality emerges. Because such traits may be heritable or developmentally influenced by hormones, the model predicts an apparent nonzero heritability for homosexuality without requiring that either genes or hormones directly influence sexual orientation per se.

Animals↗

Psychiatric manifestations of Lyme borreliosis.

BACKGROUND: Lyme borreliosis (Lyme disease), a tick-borne spirochetal illness, has later manifestations that may include arthritic, neurologic, ophthalmologic, and cardiac symptoms. Recent reports suggest psychiatric symptoms may also be part of the clinical picture. METHOD: Using a structured interview (SCID), we interviewed three patients who had developed a psychiatric disorder for the first time after infection with Borrelia burgdorferi. RESULTS: During Lyme borreliosis, one patient had major depression and panic disorder, one patient had an organic mood syndrome with both depression and mania, and the third patient had panic disorder. These disorders remitted after adequate antibiotic treatment. CONCLUSION: While depression has been previously linked to neuroborreliosis, this is the first report to link panic disorder and mania with borrelial infection. Because of the rapid rise of Lyme borreliosis nationwide and the need for antibiotic treatment to prevent severe neurologic damage, mental health professionals need to be aware of its possible psychiatric presentations.

Adult↗

Regional studies of serotonin and dopamine metabolism and quantification of serotonin uptake sites in human cerebral cortex.

An increasing number of studies have indicated that neuronal metabolism of serotonin (5-HT) and other monoamines may be altered in patients with affective disorders and in completed suicides. However, studies have yielded discordant results. The purpose of this study was to determine the regional variation of 5-hydroxyindolacetic acid (5-HIAA), homovanillic acid (HVA), (5-HT) and 5-HT uptake sites within the human cerebral cortex. Our sample consisted of 19 patients who died suddenly and accidently. Cortical concentrations of 5-HIAA, HVA and 5-HT were measured in six regions using an HPLC. 5-HT uptake sites in cortex were examined using [3H]-Paroxetine. 5-HT values within each brain were fairly constant in cortical regions studied except for the posterior parietal areas. By contrast, 5-HIAA values showed a trend towards a rostro-caudal increase, with peak values seen at sections corresponding to the post-central gyrus and the occipital pole. Using the ratio of 5-HIAA/5-HT as a crude index of 5-HT turnover, there was a progressive rostro-caudal increase of values which achieved statistical significance: the posterior superior parietal area and the occipital pole displayed a greater ratio than the other four cortical regions. HVA values were highest in the pre-central region and decreased both rostrally and caudally. 5-HIAA and HVA values were correlated positively in 5 of 6 cortical areas, while 5-HIAA and 5-HT were correlated in areas 4 and 5. Results obtaining using [3H]-Paroxetine suggest that 5-HT uptake sites in the human cortex are distributed rather uniformally and are not correlated with 5-HT levels.

Adolescent↗

Adrenergic effects on the biology of the adult mammalian cardiocyte.

BACKGROUND: To delineate the mechanism(s) of catecholamine-mediated cardiac toxicity, we exposed cultures of adult cardiac muscle cells, or cardiocytes, to a broad range of norepinephrine concentrations. METHODS AND RESULTS: Norepinephrine stimulation resulted in a concentration-dependent decrease in cardiocyte viability, as demonstrated by a significant decrease in viable rod-shaped cells and a significant release of creatine kinase from cells in norepinephrine-treated cultures. Norepinephrine-mediated cell toxicity was attenuated significantly by beta-adrenoceptor blockade and mimicked by selective stimulation of the beta-adrenoceptor, whereas the effects mediated by the alpha-adrenoceptor were relatively less apparent. When norepinephrine stimulation was examined in terms of cardiocyte anabolic activity, there was a concentration-dependent decrease in the incorporation of [3H]phenylalanine and [3H]uridine into cytoplasmic protein and nuclear RNA, respectively. The decrease in cytoplasmic labeling was largely attenuated by beta-adrenoceptor blockade and mimicked by selective stimulation of the beta-adrenoceptor, but alpha-adrenoceptor stimulation resulted in relatively minor decreases in cytoplasmic labeling. The norepinephrine-induced toxic effect appeared to be the result of cyclic AMP-mediated calcium overload of the cell, as suggested by studies in which pharmacological strategies that increased intracellular cyclic AMP led to decreased cell viability, as well as studies that showed that influx of extracellular calcium through the verapamil-sensitive calcium channel was necessary for the induction of cell lethality. Additional time-course studies showed that norepinephrine caused a rapid, fourfold increase in intracellular cyclic AMP, followed by a 3.2-fold increase in intracellular calcium [( Ca2+]i). CONCLUSIONS: These results constitute the initial demonstration at the cellular level that adrenergic stimulation leads to cyclic AMP-mediated calcium overload of the cell, with a resultant decrease in synthetic activity and/or viability.

Animals↗