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N Simpson

Publications and source records attributed to N Simpson.

At least 37 records · Page 2Linked to original sources
PubMed2000

Comparison of 26-item and 20-item versions of the Toronto Alexithymia Scale for psychiatric outpatients.

This study compared the 20-item revised Toronto Alexithymia Scale with the 26-item version for 257 psychiatric outpatients. Scores on the 20-item version significantly correlated with those on the 26-item inventory even when controlled for depressed mood. Furthermore, the 20-item scale showed greater internal consistency. Factor analysis for both versions indicated three subfactors but the factors in the TAS-20 accounted for greater common variance (92%) than for the factors in the TAS-26 (78%). The total variance accounted for by these factors on the TAS-20 (45%) was also greater than for the TAS-26 (38%).

Adult↗
PubMed2000

In vivo quantification of brain serotonin transporters in humans using [11C]McN 5652.

UNLABELLED: Abnormal brain regional densities of serotonin (5-hydroxytryptamine [5-HT]) transporters have been reported in postmortem studies in several neuropsychiatric conditions, such as major depression and schizophrenia. trans-1,2,3,5,6,10-beta-Hexahydro-6-[4-(methylthio)phenyl]pyrrolo-[2,1-a]-isoquinoline ([11C]McN 5652) is the first PET radioligand successfully developed to label 5-HT transporters in the living human brain. The purpose of this study was to develop an imaging protocol and analytic method to measure regional 5-HT transporter binding potential (BP) with [11C]McN 5652 in humans. METHODS: The arterial input function and brain uptake of (+)-[11C]McN 5652 and (-)-[11C]McN 5652, the active and inactive enantiomers, respectively, were measured in 6 healthy volunteers. RESULTS: (+)-[11C]McN 5652 concentrated in brain regions rich in 5-HT transporters (midbrain, thalamus, basal ganglia, and medial temporal lobe structures), whereas the uptake of (-)-[11C]McN 5652 was more uniformly distributed. Total distribution volumes (V(T)) were derived using kinetic 2-compartment analysis and graphic analysis. V(T) derived by both methods were highly correlated. (+)-[11C]McN 5652 regional V(T) ranged from 18 +/- 2 mL/g in the cerebellum to 46 +/- 13 mL/g in the midbrain. (-)-[11C]McN 5652 regional VT ranged from 10 +/- 2 mL/g in the cerebellum to 14 +/- 3 mL/g in the thalamus. (+)-[11C]McN 5652 V(T) were higher than (-)-[11C]McN 5652 V(T) in all regions, including the cerebellum, a region devoid of 5-HT transporters. Blocking experiments were also performed in baboons with saturating doses of citalopram and in humans with nonsaturating doses of paroxetine. Cerebellar and neocortical (+)-[11C]McN 5652 V(T) were unaffected by pretreatment with 5-HT transporter blockers. In areas of high receptor concentration (midbrain, caudate, and thalamus) 5-HT transporter blockers decreased (+)-[11C]McN 5652 V(T) to the level of cerebellum (+)-[11C]McN 5652 V(T). CONCLUSION: These experiments indicate that the use of the difference between (+)- and (-)-[11C]McN 5652 V(T) to define specific binding to 5-HT transporters leads to an overestimation of specific binding. 5-HT transporter BP was derived as the difference between the regional and cerebellar (+)-[11C]McN 5652 V(T). BP values were in good agreement with the distribution of 5-HT transporters in the human brain, except for regions of relatively low 5-HT transporter concentration, such as the prefrontal cortex, where no specific binding was detected using (+)-[11C]McN 5652. (+)-[11C]McN 5652 is an appropriate radiotracer to quantify 5-HT transporters in regions with relatively high concentration of 5-HT transporters, such as the midbrain, thalamus, and basal ganglia, and should prove useful in elucidating abnormalities of 5-HT transmission in neuropsychiatric conditions.

Adult↗
PubMed1999

Nitric oxide modulates HIV-1 replication.

Although nitric oxide (NO) production is increased in HIV-1-infected patients, and NO is known to inhibit the replication of several viruses, very little is known about the effects of NO on HIV-1 replication. In the present studies, we find that S-nitrosothiols (RSNOs), a class of NO donor compounds present in the human circulatory system, inhibit HIV-1 replication in acutely infected human peripheral blood mononuclear cells (PBMCs) and have an additive inhibitory effect on HIV-1 replication in combination with 3'-azido-3'-deoxythymidylate (AZT). RSNOs inhibit HIV-1 replication in acutely infected PBMCs at a step in the viral replicative cycle after reverse transcription, but before or during viral protein expression through a cGMP-independent mechanism. In the latently infected U1 cell line, NO donor compounds and intracellular NO production stimulate HIV-1 reactivation. These studies suggest that NO both inhibits HIV-1 replication in acutely infected cells and stimulates HIV-1 reactivation in chronically infected cells. Thus, NO may have a physiologic role in HIV-1 replication, and NO donor compounds, which have been used for decades in the treatment of coronary artery disease with limited toxicity, might be useful in the treatment of HIV-1 disease by inhibiting acute infection, reactivating latent virus, or both.

Adult↗
PubMed1999

PET studies of binding competition between endogenous dopamine and the D1 radiotracer [11C]NNC 756.

NNC 756 ((+)-8-chloro-5-(2,3-dihydrobenzofuran-7-yl)-7-hydroxy-3-methyl-2,3,4,5- tetrahydro-1H-3-benzazepine) is a new high affinity dopamine (DA) D1 receptor antagonist. Labeled with C-11, it has been used as a PET radiotracer to visualize D1 receptors both in striatal and extrastriatal areas, such as the prefrontal cortex. The goal of this study was to evaluate several methods for derivation of D1 receptor binding potential (BP) with [11C]NNC 756 in baboons, and to use these methods to assess the vulnerability of [11C]NNC 756 binding to competition by endogenous DA. A three-compartment model provided a good fit to PET data acquired following a single bolus injection. BP values obtained with this analysis were in good agreement with values derived from in vitro studies. BP values measured following injection of the potent DA releaser amphetamine (1 mg/kg, n=2) were similar to values measured under control conditions. Kinetic parameters derived from single bolus experiments were used to design a bolus plus continuous infusion administration protocol aimed at achieving a state of sustained binding equilibrium. Injection of amphetamine during sustained equilibrium did not affect [11C]NNC 756 binding. Similar results were observed with another D1 radiotracer, [11C]SCH 23390. Doses of amphetamine used in this study are known to reduce by 20-40% the binding potential of several D2 receptors radiotracers. Therefore, the absence of displacement of [11C]NNC 756 by an endogenous DA surge may indicate important differences between D1 and D2 receptors in vivo, such as differences in proportion of high affinity states not occupied by DA at baseline. These findings may also imply that a simple binding competition model is inadequate to account for the effects of manipulation of endogenous DA levels on the in vivo binding of radiolabeled antagonists.

Amphetamine↗
PubMed1999

Desensitization to co-trimoxazole (trimethoprim-sulphamethoxazole) in HIV-infected patients: is patch testing a useful predictor of reaction?

OBJECTIVE: To establish the safety and efficacy of desensitization to co-trimoxazole in hypersensitive HIV-infected subjects. To assess if delayed hypersensitivity (type IV) to co-trimoxazole predicts those unable to be desensitized. METHOD: desensitization to co-trimoxazole, comprising trimethoprim (T) 0.4 mg and sulphamethoxazole (S) 2 mg initially with doubling dose daily, full strength co-trimoxazole (T/S 160 mg/800 mg) at 10 days. Patch testing with 4.5% and 9% co-trimoxazole in yellow soft paraffin, CMI Multitest. RESULTS: nineteen patients, 18 male and one female, were recruited and completed the desensitization regime. Of these 80%(15) achieved successful desensitization. Three of those who reacted did so within 18 days. All patients were successfully managed in an outpatient setting. There were no major adverse reactions. Of those reacting none gave a positive patch test to co-trimoxazole and all showed absent delayed type hypersensitivity reactions to recall antigens. CONCLUSIONS: co-trimoxazole desensitization is a safe and efficacious procedure, with a success rate of 80% using the above regime. Patch testing with co-trimoxazole gives no useful information about those that reacted.

Adult↗
PubMed1999

Accuracy of strategies for monitoring fetal heart rate in labor.

We investigated whether the accuracy of auscultation could be improved with the use of a heart rate meter. Six fetal heart rate (FHR) traces were presented in a random sequence to 30 subjects using a customized computer program in each of three modalities: auscultation by counting alone, auscultation with the aid of an FHR meter, and visual assessment. The following characteristics were assessed: baseline rate, baseline variability, periodic change, and interpretation of the trace. For baseline rate, counting was associated with consistent underestimation of the FHR, which became more evident as the heart rate increased. The variation observed with each method was greatest with counting. For baseline variability, the proportion of correct responses using a meter was comparable to visual assessment, whereas counting was significantly less effective in 4 of 6 traces. For periodic change, the use of a meter was superior to counting in 4 of 6 traces, but both were inferior to visual assessment in 4 of 6 traces. In the interpretation of the trace, the use of a meter was again superior to counting, but both were inferior to visual assessment. Discrepancies were most marked in the least reassuring traces. Assessment of the FHR is significantly more accurate with the aid of a heart rate meter, and reduces interobserver variation.

Cardiotocography↗
PubMed1998

Test-retest variability of serotonin 5-HT2A receptor binding measured with positron emission tomography and [18F]altanserin in the human brain.

The role of serotonin in CNS function and in many neuropsychiatric diseases (e.g., schizophrenia, affective disorders, degenerative dementias) support the development of a reliable measure of serotonin receptor binding in vivo in human subjects. To this end, the regional distribution and intrasubject test-retest variability of the binding of [18F]altanserin were measured as important steps in the further development of [18F]altanserin as a radiotracer for positron emission tomography (PET) studies of the serotonin 5-HT2A receptor. Two high specific activity [18F]altanserin PET studies were performed in normal control subjects (n = 8) on two separate days (2-16 days apart). Regional specific binding was assessed by distribution volume (DV), estimates that were derived using a conventional four compartment (4C) model, and the Logan graphical analysis method. For both analysis methods, levels of [18F]altanserin binding were highest in cortical areas, lower in the striatum and thalamus, and lowest in the cerebellum. Similar average differences of 13% or less were observed for the 4C model DV determined in regions with high receptor concentrations with greater variability in regions with low concentrations (16-20%). For all regions, the absolute value of the test-retest differences in the Logan DV values averaged 12% or less. The test-retest differences in the DV ratios (regional DV values normalized to the cerebellar DV) determined by both data analysis methods averaged less than 10%. The regional [18F]altanserin DV values using both of these methods were significantly correlated with literature-based values of the regional concentrations of 5-HT2A receptors determined by postmortem autoradiographic studies (r2 = 0.95, P < 0.001 for the 4C model and r2 = 0.96, P < 0.001 for the Logan method). Brain uptake studies in rats demonstrated that two different radiolabeled metabolites of [18F]altanserin (present at levels of 3-25% of the total radioactivity in human plasma 10-120 min postinjection) were able to penetrate the blood-brain barrier. However, neither of these radiolabeled metabolites bound specifically to the 5-HT2A receptor and did not interfere with the interpretation of regional [18F]altanserin-specific binding parameters obtained using either a conventional 4C model or the Logan graphical analysis method. In summary, these results demonstrate that the test-retest variability of [18F]altanserin-specific binding is comparable to that of other PET radiotracers and that the regional specific binding of [18F]altanserin in human brain was correlated with the known regional distribution of 5-HT2A receptors. These findings support the usefulness of [18F]altanserin as a radioligand for PET studies of 5-HT2A receptors.

Adult↗
PubMed1998

Reliability and validity of the PAS-ADD Checklist for detecting psychiatric disorders in adults with intellectual disability.

The PAS-ADD Checklist is a screening instrument specifically designed to help staff recognize mental health problems in the people with intellectual disability for whom they care, and to make informed referral decisions. The instrument consists of a life-events checklist and 29 symptom items scored on a four-point scale. Scores are combined to provide three threshold scores. The crossing of any of these thresholds indicates the need for a fuller assessment. The items are worded in everyday language, making the Checklist suitable for use by individuals who do not have a background in psychopathology. The present paper presents the results of a number of studies evaluating the reliability and validity of the Checklist. Factor analysis of Checklists completed on a community sample of 201 individuals yielded eight factors, of which seven were readily interpretable in diagnostic terms. Internal consistency of the scales was generally acceptable. Inter-rater reliability in respect to individual items gave a fairly low average Kappa of 0.42. However, agreement on case identification, the main purpose of the Checklist, was quite good, with 83% of the decision being in agreement. Validity in relation to clinical opinion was also satisfactory, case detection rising appropriately with the clinically judged severity of disorder. The PAS-ADD Checklist is published and distributed by the Hester Adrian Research Centre, Manchester, England, from where further information and order forms are available on request.

Adolescent↗
PubMed1998

Reliability and validity of the Mini PAS-ADD for assessing psychiatric disorders in adults with intellectual disability.

The Mini PAS-ADD is an assessment schedule for psychiatric disorders in people with an intellectual disability. It is designed to provide a link between the mental health expertise of psychiatrists and psychologists, and the detailed knowledge of individual service users possessed by support staff. In broad terms, the aim of the Mini PAS-ADD is to enable non-psychiatrists accurately to recognize clinically significant psychiatric disorders in the people who they care for, so that they can make informed referral decisions. The instrument comprises 86 psychiatric symptoms and generates a series of subscores on: depression, anxiety and phobias, mania, obsessive-compulsive disorder, psychosis, unspecified disorder (including dementia), and pervasive developmental disorder (autism). The present paper reports the results of a study investigating internal consistency, inter-rater agreement and validity in relation to clinical opinion, using a sample of 68 people with intellectual disability who were in contact with psychiatric services. In terms of the instrument fulfilling its main intended function, i.e. accurate case recognition, the crucial question was whether the support workers, with their lesser knowledge of psychopathology, were also able to correctly identify cases identified by expert clinicians. The validity results in this respect (81% agreement on case recognition) were sufficiently good that it is to be anticipated that the Mini PAS-ADD should have a significant impact on the identification of psychiatric disorders in the community of people with intellectual disability.

Adult↗
PubMed1997

Validity of the PAS-ADD for detecting psychiatric symptoms in adults with learning disability (mental retardation).

The Psychiatric Assessment Schedule for Adults with Developmental Disability (PAS-ADD) is a semi-structured interview for use with respondents who have learning disability and for key informants. This report investigates the ability of the instrument to detect symptoms that had been found to exist during routine clinical assessment of the patients. Field trials involved 95 referred patients with learning disability and a key informant for each sample member. Clinical opinions of the referring psychiatrists were sought using a symptom checklist. Referrer checklist symptoms and PAS-ADD data were both factor analysed. Validity testing involved (a) computation of correlations between PAS-ADD factors and checklist data and (b) comparison of PAS-ADD and referrers' diagnoses. Results indicated good validity for the PAS-ADD in relation to psychotic symptoms and depressive symptoms. Anxiety symptom identification was not well validated, probably due to small numbers. Expansive mood identified by the referrers was not detected by the PAS-ADD because there is currently no corresponding section in the interview. Where the PAS-ADD produced a diagnosis (in 58 members of the sample), 44 were in agreement with the referrer. Probability of diagnosis by PAS-ADD increased with the number of relevant active symptoms identified by the referrer. The PAS-ADD has been shown in a previous report to have the sensitivity to detect mental disorders not known to psychiatric services. For psychotic and depressive conditions, our results showed that symptom detection was in good agreement with the information provided by the referring psychiatrists on their patients. The PAS-ADD needs a section on hypomania and further investigation of its detection of anxiety disorders.

Adolescent↗
PubMed1997

Central nervous system relapse in acute promyelocytic leukaemia in patients treated with all-trans retinoic acid.

All-trans retinoic acid (ATRA) is currently recommended as standard treatment for acute promyelocytic leukaemia (APL). However, there has been increasing concern that ATRA is associated with unusual sites of relapse. We present three cases of APL previously treated with ATRA who ultimately relapsed within the central nervous system (CNS) and hypothesize that, by up-regulating intercellular adhesion molecules, ATRA may facilitate the passage of malignant promyelocytes across the blood-brain barrier.

Adult↗
PubMed1997

Audit of neonatal screening programme for phenylketonuria and congenital hypothyroidism.

The performance of the neonatal screening programme was audited against clinical standards in the Bath clinical area from 1 April 1994 to 31 March 1996. The standards and policy were agreed by local service provider representatives of the screening and were audited, using laboratory and child health computer systems and medical records. Two annual reports were produced with recommendations for improvement communicated to representatives of the service. Thus the first audit loop has been completed. The audit shows that the coverage of the service is excellent, with all eligible babies being offered screening; those with congenital hypothyroidism or phenylketonuria receive appropriate treatment by the 28 day standard. The process works extremely well, although areas for improvement have been identified, to increase the efficiency of the service. It is concluded that an effective and efficient audit cycle can be established, to monitor and improve the performance of the neonatal screening service.

Age Factors↗
PubMed1997

How can adolescents' health needs and concerns best be met?

BACKGROUND: A previous survey of letters to 'agony aunts' revealed that adolescents have many concerns about their health. AIM: To discover the views of adolescents on a range of issues including the venues where they would like to be seen, the doctors they would like to consult, and the subjects they would like to discuss. METHOD: A questionnaire was distributed to adolescents in a variety of school settings and distributed through a popular teenage magazine. RESULTS: A total of 525 replies were received. Most adolescents had visited their general practitioner (GP) in the previous year. Most would prefer to see a teenage health specialist at a venue other than their local surgery, and to have the option of a 'drop-in' service. Responders were worried about a wide range of health issues. They had strong opinions on the type of doctor they would like to consult and the style of surgery they would prefer. Concerns were expressed about confidentiality. CONCLUSION: In the short term, surgeries could be made more 'user-friendly' for adolescents. In the longer term, the authors propose liaison between GPs and paediatricians with a special interest in teenage health to provide a confidential, combined youth service, with ideas on service development based on the expressed wishes of the adolescent population.

Adolescent↗