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Biomedical subjects

P B Mitchell

Publications and source records attributed to P B Mitchell.

At least 55 records · Page 3Linked to original sources
PubMed1997

Exclusion of linkage between bipolar affective disorder and chromosome 16 in 12 Australian pedigrees.

Several recent reports of possible susceptibility loci for bipolar affective disorder (BAD) have identified sites on a number of chromosomes. Specifically, two Danish studies have suggested the presence of a susceptibility locus for BAD on chromosome 16p13. As the first step of a whole genome scan, we screened 12 Australian families with markers at 16p13 and also a number of markers spanning the entirety of chromosome 16. Linkage analysis was undertaken using both the parametric lod score method (two- and multipoint) with different models and diagnostic thresholds, and the nonparametric affected pedigree member (APM) method. Results of lod score analysis convincingly excluded the 16p13 region from linkage to BAD in these families, while APM provided no support for linkage. Furthermore, using the broad definition of BAD, with individuals affected by bipolar I and II and recurrent unipolar disorders included, the entire chromosome was excluded from linkage to BAD with autosomal-dominant transmission at a maximum age-specific penetrance of 60%, and with autosomal-dominant and recessive modes of transmission at a maximum age-specific penetrance level of 90%. Diagnostic thresholds which did not include unipolar affected individuals were somewhat less informative. However, a majority (between 63-96%, depending upon the model) of the chromosome was clearly excluded using narrow diagnostic thresholds. Moreover, no positive lod scores were obtained at theta = 0.00 for any tested model or diagnostic threshold. Our results indicate that no linkage exists between BAD and chromosome 16 markers in this group of Australian families.

Australia↗
PubMed1997

Parental sex effects in bipolar affective disorder pedigrees.

A combined linkage analysis was performed on chromosome 18 data and produced modest evidence in three of four data sets for linkage of a susceptibility locus for bipolar disorder to markers on chromosome 18p. All data sets showed a preponderance of females among affected individuals. When this was taken into account, no convincing evidence was obtained for excess transmission from mothers compared to fathers. In addition, there was no evidence for differences in the proportions of affected offspring from affected fathers and mothers. We conclude that these combined data do not support previous suggestions of a maternal effect on transmission of bipolar affective disorder.

Adolescent↗
PubMed1997

High levels of Gs alpha in platelets of euthymic patients with bipolar affective disorder.

OBJECTIVE: Previous investigations have suggested the involvement of signal-transducing guanine-nucleotide-binding proteins (G proteins) both in the mechanism of action of lithium and in the pathophysiology of bipolar affective disorder. To determine whether such G protein abnormalities are a trait phenomenon, the authors investigated the levels of G protein alpha subunits in platelets and lymphocytes of euthymic patients with bipolar affective disorder. METHOD: Selective antibodies were used to quantitate levels of G protein alpha subunits regulating adenylylcyclase activity (Gs alpha-both 45- and 52-kDa forms- and Gil-2 alpha) and those regulating phosphoinositide turnover (Gq/11 alpha) in both platelets and lymphocytes of 44 euthymic patients with bipolar affective disorder and 27 matched comparison subjects. RESULTS: Levels of both Gs alpha 45 and Gs alpha 52 were higher in the platelets of the euthymic bipolar patients (both bipolar I and bipolar II) than in those of the comparison subjects. CONCLUSIONS: These findings are consistent with previous reports of high Gs alpha levels in bipolar affective disorder and, furthermore, suggest that such levels may be a trait abnormality for this condition.

Adult↗
PubMed1997

Drug interactions of clinical significance with selective serotonin reuptake inhibitors.

The selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs) have internationally become the accepted 'benchmark' class of antidepressants. It has become clear, however, that there are a number of clinically significant interactions between SSRIs and other medications. The most frequently described interactions are pharmacokinetic, which are far more prevalent than pharmacodynamic interactions. This article details those medications that may interact significantly with the SSRIs, and provides clinical guidelines for minimising the likelihood of such complications. The most common pharmacokinetic interactions are caused by an inhibitory effect of the SSRIs on the hepatic cytochrome P450 (CYP) metabolic system. The SSRIs differ in their potency in inhibiting a number of important CYP isoenzymes (CYP1A2, CYP2C9/10, CYP2C19, CYP2D6 and CYP3A3/4). The major outcome of concern in relation to pharmacodynamic interactions is the development of the 'serotonin syndrome'. While combination of the SSRIs with the irreversible monoamine oxidase inhibitors is the most recognised cause of this syndrome, concurrent administration with moclobemide, tryptophan or selegiline (deprenyl) may also lead to a similar outcome.

Antidepressive Agents, Tricyclic↗
PubMed1996

Nonlinkage of D6S260, a putative schizophrenia locus, to bipolar affective disorder.

To examine whether genes that predispose to schizophrenia also confer a predisposition to other psychiatric disorders such as bipolar affective disorder (BAD), we tested for linkage between the recently identified schizophrenia susceptibility locus D6S260 and the inheritance of BAD in 12 large Australian pedigrees. We found no evidence for linkage over a region of 12-27 cM from the D6S260 locus, depending on the model used. Our results therefore do not provide support for the continuum theory of psychosis.

Australia↗
PubMed1995

Novel French antidepressants not available in the United States.

There is little awareness in the United States and other English-speaking countries of a number of novel antidepressant drugs that have recently been developed and marketed in France. This review focuses on tianeptine, amineptine, minaprine, medifoxamine, and modafinil--examining both their pharmacological actions and their clinical efficacies. Their potential for further research or marketing in the United States is discussed.

Animals↗
PubMed1994

The management of depression. The place of the new antidepressants. Part 1. General overview.

The introduction of the selective serotonin reuptake inhibitors, moclobemide and mianserin has been a major advance in the treatment of depression, and is already leading to major shifts in the pattern of antidepressants prescribing. These antidepressants are safe, well tolerated and effective, and in conjunction with older agents such as the tricyclics, provide the clinician with a broad range of treatments for this common and disabling disorder. This two-part review will focus on the management of depression in general practice.

Algorithms↗
PubMed1994

The management of depression. Part 2. The place of the new antidepressants.

Four years since the introduction of fluoxetine into Australian clinical practice, and two years since the availability of moclobemide, it is now possible to comment with some degree of certainty about the place of the new antidepressants. There do not appear to be any major complications or adverse effects associated with the recently marked antidepressants. While these medications clearly share their own similar and specific side effects, these problems are less frequent and severe than those experienced with the TCAs. Additionally, it has become obvious that they have fewer cardiac effects and possess a lower toxicity on overdose than the older classes of antidepressants. The differences in adverse effects between the various SSRIs appear to be minimal. Does this mean that the SSRIs, moclobemide and mianserin should be the treatment of first choice for depression? On balance, the evidence presented in this article would suggest rather that the new agents and TCAs should all be considered first-line agents. While discontinuation rates due to adverse effects are clearly less frequent with the new antidepressants, the currently available data do not indicate any difference in drop-out rates when discontinuation due to lack of efficacy is also incorporated into the equation. Irrespective of cost issues, the possible greater effectiveness of the TCAs in melancholic depression must also be taken into account. In conclusion, the advent of the SSRIs, moclobemide and mianserin has clearly been a major advance in the treatment of depression, and is already leading to major shifts in the pattern of antidepressant prescribing.(ABSTRACT TRUNCATED AT 250 WORDS)

Antidepressive Agents↗
PubMed1992

Psychotropic medications.

A number of new psychotropic drugs are now available and new uses have been found for old ones. The author highlights these changes.

Humans↗
PubMed1991

Treatment of bipolar disorder.

OBJECTIVE: To review the current status of the management of bipolar disorder (manic-depressive illness). DATA SOURCES AND STUDY SELECTION: Controlled clinical trials as well as some recent important open studies are examined. DATA EXTRACTION AND SYNTHESIS: Lithium carbonate remains the mainstay of both the acute and prophylactic treatment of this condition. We highlight specific contentious issues in prophylactic management with lithium, that is, indications for initiating long-term treatment, preferred serum concentrations, timing of the dose, duration of treatment and frequency of laboratory monitoring. In recent years, several alternatives to lithium have been demonstrated as effective in both the acute and prophylactic treatment of patients either unable to tolerate or inadequately responsive to this agent. There is now considerable evidence that carbamazepine is of similar efficacy to lithium and more recent studies suggest that valproate may also be as therapeutic. We outline details of the clinical roles of each of these agents, with guidelines concerning monitoring and adverse effects.

Anticonvulsants↗
PubMed1991

Unilateral or bilateral electroconvulsive therapy for depression? A survey of practice and attitudes in Australia and New Zealand.

OBJECTIVE: We report the findings of the first survey of the practice of electroconvulsive therapy (ECT) for the treatment of depression in Australia and New Zealand. The major aim was to examine the frequency of use of unilateral and bilateral electrode placement, as bilateral ECT has been recently recommended as the treatment of choice by the Royal College of Psychiatrists (UK). DESIGN: A questionnaire about details of ECT given in the second half of 1989 was forwarded to the medical superintendents of 130 psychiatric hospitals and units in Australia and New Zealand. RESULTS: Reports were received from 96 psychiatric institutions representing a response rate of 74%. In these units, 915 patients were treated with ECT during the study period. In contrast to depressed patients in the United Kingdom or the United States, a majority of Australian and New Zealand patients given ECT were found to receive unilateral ECT (63%). There were marked regional differences in practice, with patients in New South Wales being more likely to receive unilateral ECT, and those in Queensland and New Zealand bilateral ECT. In the majority of units, bilateral ECT was not considered to be indicated in preference to unilateral ECT for either severe, suicidal or psychotic depression. CONCLUSION: The discrepancies between regional practices probably reflect the current uncertainty regarding the balance between the relative efficacy and morbidity of these two forms of treatment. Until these central issues of relative efficacy and morbidity are clarified, it would be inappropriate for local professional bodies to recommend a preferred mode of ECT administration.

Attitude of Health Personnel↗
PubMed1991

Endocrine and amine responses to D,L-fenfluramine in normal subjects.

To investigate indirectly the central neurotransmitter mechanisms of D,L-fenfluramine-induced hormone release, prolactin, adrenocorticotropic hormone, cortisol, growth hormone, 3-methoxy-4-hydroxyphenylglycol (MHPG), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5HIAA) responses to D,L-fenfluramine (60 mg, oral) were examined in a single-blind, placebo-controlled trial in 14 normal subjects. As compared with placebo, D,L-fenfluramine significantly increased both prolactin and cortisol. There was a significant correlation between the cortisol and prolactin responses. HVA levels were also significantly increased, but there were no changes in MHPG or 5HIAA. The elevation in HVA significantly correlated with increases in both prolactin and cortisol. These findings are consistent with recent animal studies suggesting that D,L-fenfluramine-induced prolactin and cortisol release may be mediated, at least in part, by catecholaminergic systems.

Adult↗
PubMed1991

Effort thrombosis: recognition and management while underway.

Effort thrombosis of the axillary and subclavian veins is an uncommon cause of upper extremity swelling. Prompt recognition and treatment of this disorder is important in order to minimize the complications of pulmonary embolism and postphlebitic syndrome that can occur with this condition. This can be very challenging while underway or in the field. A sailor who developed effort vein thrombosis while underway on board the aircraft carrier USS Abraham Lincoln is presented to review the presentation and management of this disorder, particularly as it applies to active duty military personnel.

Adult↗