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Biomedical subjects

P M Ellis

Publications and source records attributed to P M Ellis.

At least 19 recordsLinked to original sources

Selective 5-HT1A and 5-HT2 receptor-mediated adrenocorticotropin release in the rat: effect of repeated antidepressant treatments.

The 5-HT receptor agonists, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) produced dose-dependent increases in plasma adrenocorticotropin (ACTH) in the male rat by activation of 5-HT1A and 5-HT2 receptors respectively. The ACTH response to DOI was enhanced by repeated administration of electroconvulsive shock (five over 10 days) but abolished by the tricyclic antidepressant, amitriptyline (20 mg/kg for 14 days). In contrast 21 days lithium treatment failed to alter DOI-induced ACTH release. Neither repeated electroconvulsive shock, nor amitriptyline, nor lithium altered the ACTH response to 8-OH-DPAT. These data are consistent with results from ligand binding and behavioural studies which suggest that the sensitivity of brain 5-HT2 receptors is increased by repeated electroconvulsive shock but attenuated by tricyclic antidepressant treatment. In contrast, our data suggest that the antidepressant treatments studied do not alter the sensitivity of the 5-HT1A receptors involved in ACTH release.

8-Hydroxy-2-(di-n-propylamino)tetralin

Platelet imipramine binding is increased in essential thrombocythaemia.

A decrease in platelet serotonin content is well recognized in myeloproliferative disorders, although the basis for this is unclear. The relationship between decreased platelet serotonin and the number of serotonin transport channels in the platelet membrane was explored indirectly by measuring the number of the closely associated imipramine binding sites. Imipramine binding parameters were determined in 12 patients suffering from either essential thrombocythaemia or polycythaemia rubra vera and in 10 healthy controls. The maximal number of imipramine binding sites (Bmax) was increased in both patient groups, significantly so in those suffering from essential thrombocythaemia. This increase contrasts with a decrease in binding in other conditions known to be associated with decreased platelet serotonin. This study thus demonstrates a discrepancy in terms of reduced platelet serotonin content and increased imipramine binding on platelets from patients suffering from essential thrombocythaemia. It is suggested that further investigation of the imipramine binding site in these disorders, in parallel with measures of platelet serotonin content and uptake, is warranted.

Adult

Platelet 3H-imipramine binding during recovery from depression.

Decreased binding of tritiated imipramine to platelets has been considered to be a potential biological marker of depression. However, it has been unclear how binding values alter during treatment and recovery. This study investigated imipramine binding parameters and depressive symptoms in 25 patients suffering from major depression at entry to the study and 1, 3 and 6 months later. Although the initial Bmax values were significantly lower in the depressed patients than in healthy subjects, it was not possible to establish a clear relationship between recovery from depression and Bmax. The power of this study to detect an effect of at least 10% of the variance in Bmax due to factors related to recovery from depression was 0.78.

Adult

Does metergoline selectively attenuate 5-HT mediated prolactin release?

Administration of the non-selective 5-HT receptor antagonist metergoline (0.5 mg/kg) to male rats attenuated the prolactin response to the 5-HT releasing agent d-fenfluramine (7.5 mg/kg) but not to the dopamine receptor antagonist haloperidol (1.5 mg/kg). In contrast, in healthy male volunteers, pretreatment with metergoline (4 mg orally) abolished the prolactin response to intravenous haloperidol (5 micrograms/kg). The findings suggest that in humans blockade of a prolactin response by a conventional oral dose of metergoline cannot be taken as evidence of involvement of 5-HT-mediated mechanisms.

Adolescent

Platelet tritiated imipramine binding in patients suffering from mania.

Platelet imipramine binding was measured in 16 patients suffering from DSM-IIIR mania and compared with binding values reported in depressed and healthy control subjects recruited in a parallel study (Ellis et al., 1990). Binding levels in the manic group did not differ from control values, but were higher than in the depressed group. Within the manic group, binding did not differ with severity of illness or the presence of depressive symptoms but there was a trend to lower values (comparable to those in the depressed group) with increasing duration of illness. This raises the possibility that changes in imipramine binding in depression and mania may be similar, consistent with the permissive hypothesis of serotonin function.

Bipolar Disorder

FACTOREP: a new tool to explore the dimensions of depression.

One promising research approach in the search for clinically meaningful diagnostic categories of depression has been the application of multivariate statistical techniques such as factor analysis to the evaluation of self-report and observer rating data. The contribution of factor analysis has been limited, however, by the application of traditional mathematical criteria in the analyses which typically produce too many factors. In this study, a criterion of replicability was applied with the aid of a factor matching procedure (FACTOREP). The Beck Depression Inventory (BDI) was examined using FACTOREP and two large samples of depressed patients. The results showed that only a large general factor was present. Beyond the BDI studies, there has been debate on the validity of the endogenous versus reactive depression conceptualization. Despite the limited number of endogenous items in the BDI, the results here did not confirm the presence of two clear factors that represented endogenous and reactive groups of items.

Affective Disorders, Psychotic

Down's syndrome in the Lothian region of Scotland--1978 to 1989.

A study of Down's syndrome in Lothian for the years 1978-1989 revealed a significantly higher than expected incidence of cases in 1987. The increased incidence was particularly significant among women aged 35 years or more. The increase could not be attributed to demographic changes on birth rates or to the age distribution of the women concerned. A temporal association between the cluster of cases and the events at Chernobyl in April 1986 was demonstrated. However, according to current understanding, there is no biologically plausible explanation to link the 2 events, given the reported levels of radioactive fallout in the Lothian region, resulting from the Chernobyl disaster. An explanation for the increased incidence of Down's syndrome in 1987 remains outstanding.

Abnormalities, Radiation-Induced

Circadian variation in platelet imipramine binding during the day in healthy subjects.

Platelet tritiated imipramine binding values in healthy controls vary considerably from study to study. A possible contributor to such variation might be a circadian rhythm affecting binding, although previous studies of this have been contradictory. Platelet imipramine binding was examined in 12 healthy, medication-free subjects studied at 8 a. m., 11 a. m., 4 p. m., and 10 p. m. during one day. Imipramine binding was determined on platelet membranes, using 0.8-8 nM 3H-imipramine, and nonspecific binding was defined by 50 microM desipramine. All samples from a given individual were assayed simultaneously. The intra-assay coefficient of variation was 6.3 percent. There was no evidence of significant differences in binding capacity or affinity (Bmax or Kd) at different times of day. Circadian variation was explored using COSINOR analysis (DeMet et al., 1989). There was no evidence of circadian variation in binding using this model, even when only the variable portion of binding was considered for each individual. Intraindividual variation in binding was substantial, with a mean coefficient of variation of 29 percent for Bmax and 38 percent for Kd. The possible basis of this variation is unclear, but may reflect the presence of "occult" binding sites in the membrane, or the effect of endogenous modulators of binding. The interrelationship of Bmax and Kd may also be a factor. It was considered that low-affinity binding did not account for a significant part of the variation in Kd in this assay. The utility of imipramine binding as a biological marker of depression may be limited by such levels of intraindividual variation in binding parameters.

Adult

Clinical information in psychiatric practice: what do doctors know, what do they think is known and what do they record?

Deficiencies in recording clinical information are a widespread problem in both psychiatry and medicine. Previous studies have not established whether information not recorded in the notes is nonetheless known to clinicians. This study compared both the information known to individual clinicians and that recorded in the notes with previously established criteria. Overall, individual clinicians recalled more information than was recorded in the notes (median values: clinicians 47-63% of criteria; notes 42%) and when all this individual knowledge was pooled, 88% of the preset criteria were satisfied. Consultants, but not more junior staff, recalled significantly more about subsections of the history which they considered to be especially relevant to the management plan for a given patient. Only a third of data not known to clinicians, but thought by them to be recorded in the notes, was actually present. The implications of these findings for clinical audit and medical education are discussed.

Clinical Competence

Relevance to prenatal diagnosis of the identification of a human Y/autosome translocation by Y-chromosome-specific in situ hybridisation.

Routine cytogenetic analysis of an amniotic fluid sample revealed a large brightly fluorescent region in the short arm of chromosome 14 in an otherwise normal male karyotype (46,XY,14p+ + +). This site was also present in the paternal karyotype. In situ hybridisation to a Y-chromosome-specific DNA probe confirmed that the father had a Y/14 translocation. The incidence of two hybridisation bodies (large hybridisation sites), detecting both the translocated Y chromatin and the normal Y chromosome, was lower in interphase nuclei (44.3%) than in metaphase spreads (95.2%). The relevance of these observations to the potential use of in situ hybridisation to interphase nuclei for prenatal diagnosis is discussed.

Adult

Platelet tritiated imipramine binding in psychiatric patients: relationship to symptoms and severity of depression.

The clinical and research significance of reduced imipramine binding has remained unclear despite considerable investigation. This study used an assay of demonstrated reliability to investigate the clinical correlates of imipramine binding to platelets in 63 depressed and 33 nondepressed psychiatric patients and 40 healthy control subjects. Both patient groups had Bmax values significantly lower than those of the healthy controls. Unequivocal associations between binding parameters and individual symptoms or groups of symptoms were not established, but a negative correlation between Kd and the number of adverse life events experienced in the preceding 6 months was apparent. These findings provide no support for the view that reduced binding is a trait marker for susceptibility to depression and cast doubt on its specificity as a state marker for the syndrome of depression.

Adult

The occurrence of equine arteritis virus in Australia.

This paper reports the first isolation of equine arteritis virus (EAV) in Australia and serological evidence of exposure to EAV in Australian horses. Twelve Standardbred stallions imported from North America were found to shed EAV in semen. One hundred and seven stallions were tested for serum antibodies to EAV and 73% of Standardbred stallions tested were seropositive as compared to 8% of Thoroughbred stallions. Serum antibody was detected in 71% of Standardbred mares, 6% of Standardbred racehorses and 1% of Thoroughbred mares and racehorses. Examination of stored serums demonstrated that EAV had been present in Australia since at least 1975.

Animals

Australasian field trials of the Mental and Behavioural Disorders section of the draft ICD-10.

Field trials of the "Mental and Behavioural Disorders" section of the 1987 draft of the ICD-10 have been co-ordinated for the World Health Organisation by a number of regional centres. The design of the field trials and the major features of ICD-10 are briefly discussed. The results of the field trial in the Western Pacific region are described, and compared with the results of the original DSM-III field trials. ICD-10 appears to be an acceptably reliable diagnostic system, and the ratings of its feasibility and utility by participating clinicians suggest that it will be seen as a distinct advance over ICD-9.

Australia