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Biomedical subjects

A C McFarlane

Publications and source records attributed to A C McFarlane.

At least 19 recordsLinked to original sources
PubMed1999

Effects of clozapine for non-treatment-resistant patients with schizophrenia.

Clozapine is generally used for patients meeting criteria for treatment resistance. In this study clozapine was given to 19 patients with schizophrenia who did not meet these criteria and whose symptoms were mild to moderate in severity. Clozapine was associated with significant improvement in positive and negative symptoms and quality of life. A more modest improvement on a range of tests of cognitive functioning was also noted. These results suggest that consideration should be given to broadening the usual criteria for patients' eligibility for clozapine treatment.

Adult↗
PubMed1999

Interactions between growth hormone, insulin-like growth factor I, and basic fibroblast growth factor in melanocyte growth.

Melanocytes, highly differentiated neural crest-derived cells, are located in the basal layer of the epidermis, where they play a role in protecting against UV damage in the skin. Previous studies suggest that both growth hormone (GH) and the insulin-like growth factor I (GH/IGF-I) system may be important for melanocyte growth and function. We have therefore characterized the role of the GH/IGF system in melanocyte growth in vitro and its interaction with the local growth factor basic fibroblast growth factor (bFGF). Analysis of the effects of GH, IGF-I, and bFGF and combinations of these growth factors on melanocyte growth in vitro revealed that 1) GH stimulates the growth of melanocytes when combined with IGF-I, des(1-3)IGF-I [an analog of IGF-I that has a reduced binding affinity for IGF-binding proteins (IGFBPs)], or bFGF, either separately or in combination; 2) in contrast to the lack of effect of GH or bFGF alone, both IGF-I and des(1-3)IGF-I enhance melanocyte growth in a dose-dependent manner; and 3) IGF-I is more efficacious in eliciting a growth response at low concentrations compared to des(1-3)IGF-I. Using Western ligand blotting, affinity cross-linking, immunoprecipitation, RIA, and Northern analysis, we show that cultured human melanocytes synthesize and secrete minimal amounts of IGFBP. IGFBP-4 is the major IGFBP produced by these cells when cultured in complete growth medium or in the presence of either IGF-I or des(1-3)IGF-I alone. In conclusion, these studies provide support for a role for both GH and IGF-I in the growth of human melanocytes in vitro, involving synergy with bFGF. Low levels of melanocyte-derived IGFBP-4 may play a role in enhancing the modulation of IGF action.

Blotting, Northern↗
PubMed1999

GH-receptor distribution in the ovine foetal adrenal gland: ontogenic and functional studies.

In order to examine the role of GH in the regulation of foetal adrenal development and function, we have localized GH-receptor mRNA and protein in adrenal glands of ovine foetuses at specific stages of gestation. Adrenals from 60-75 day (n=4), 100-110 day (n=4) and 140-145 day (n=3) foetal sheep (term is 145-150 days) and non-pregnant adult animals (n=3) were dissected and fixed. GH-receptor mRNA localization was studied by in situ hybridization using a (35)S-labelled antisense cRNA probe, and protein by immunohistochemistry using a specific monoclonal antibody to the GH-receptor. At all ages studied, GH-receptor mRNA and immunoreactivity could be detected throughout the adrenocortical region. In adult adrenals, GH-receptor mRNA and immunoreactivity were also evident throughout the adrenocortical zone, with the strongest expression confined to a defined region of cells at the interface between the zona glomerulosa and zona fasciculata. Northern blot analysis of 100 day and 140 day foetal adrenals confirmed the presence of a 4.4 kb GH-receptor mRNA transcript, while immunoblotting of foetal adrenals at approximately 110 days of gestation revealed a 55 kDa GH-receptor species. To study the effect of GH on the function and growth of the immature foetal adrenal gland in vivo, chronically catheterized ovine foetuses (n=4), between 100 and 110 days of gestation, were given a pulsatile infusion of recombinant bovine GH (125 microgram/15 min, 24 pulses/24 h) for 72 h. Plasma cortisol and aldosterone levels were compared with age-matched controls receiving saline infusion alone (n=4). It was found that there was no difference in the basal plasma level of cortisol or aldosterone, and that infusion of GH did not alter steroid levels or gross adrenal size and morphology. These studies demonstrate strong expression of the GH-receptor in the developing ovine foetal adrenal cortex. However, in the immature foetus GH infusion is without effect on plasma steroid levels, suggesting that the steroidogenic action of GH in the ovine foetus may be gestationally dependent.

Adrenal Glands↗
PubMed1998

Predicting the development of posttraumatic stress disorder from the acute response to a traumatic event.

Posttraumatic stress disorder (PTSD) is a psychiatric condition that is directly precipitated by an event that threatens a person's life or physical integrity and that invokes a response of fear, helplessness, or horror. In recent years it has become clear that only a proportion of those exposed to fear-producing events develop or sustain PTSD. Thus, it seems that an important challenge is to elucidate aberrations in the normal fear response that might precipitate trauma-related psychiatric disorder. This paper summarizes the findings from recent studies that examined the acute and longer term biological response to traumatic stress in people appearing to the emergency room immediately following trauma exposure. In the aggregate, these studies have demonstrated increased heart rate and lower cortisol levels at the time of the traumatic event in those who have PTSD at a follow-up time compared to those who do not. In contrast, certain features associated with PTSD, such as intrusive symptoms and exaggerated startle responses, are only manifest weeks after the trauma. The findings suggest that the development of PTSD may be facilitated by an atypical biological response in the immediate aftermath of a traumatic event, which in turn leads to a maladaptive psychological state.

Animals↗
PubMed1997

Relationships between changes in symptom ratings, neurophysiological test performance and quality of life in schizophrenic patients treated with clozapine.

This study examined the correlations between reduction in symptoms, changes in neuropsychological test performance and improved quality of life in 19 schizophrenic outpatients treated with clozapine. Reduction in both negative symptoms and general psychopathology was associated with a better quality of life. Some improvement in neuropsychological test performance was found, with a variable pattern of association with change in psychopathology. Improved verbal fluency was associated with reduction in negative symptoms, while improved verbal concept formation was associated with reduction in positive symptoms.

Adult↗
PubMed1997

Psychiatric morbidity following a natural disaster: an Australian bushfire.

This study investigated the prevalence of mental health problems after a major bushfire in Australia and examined the validity of the General Health Questionnaire (GHQ) (Goldberg 1978) against the Anxiety, Affective and Post-Traumatic Stress Disorder modules of the Diagnostic Interview Schedule (DIS; Robins et al. 1981). Study 1 was carried out 12 months after the Ash Wednesday bushfires and sought to include all the victims of the fires. Study 2 was conducted 20 months after the fires and included a sample of victims who had experienced major losses in the fires. Twelve months after the fires, 42% (n = 1,526) of the victims were defined as a potential psychiatric case using the GHQ. This rate indicated a significantly greater level of morbidity than found in communities that have not experienced a natural disaster. Twenty months after the fires, 23% (n = 43) were defined as "cases". The 28-item GHQ was found to be a valid instrument for defining the presence of psychiatric disorder in a disaster-effected community. The findings demonstrated that lasting psychiatric morbidity is associated with natural disasters.

Australia↗
PubMed1997

The assessment of disability and handicap in musculoskeletal disease.

The method for assessment of disability and handicap is particularly important in chronic musculoskeletal diseases. Outcome measures should be valid and show a responsiveness to change such that longitudinal studies of the diseases and their interventions can be carried out effectively. Psychosocial aspects may significantly influence these diseases and the instruments themselves. Researchers need to take these issues into account.

Clinical Trials as Topic↗
PubMed1997

The association between external weather conditions and pain and stiffness in women with rheumatoid arthritis.

OBJECTIVE: To determine the self-reported prevalence of weather sensitivity in a sample of female patients with rheumatoid arthritis (RA), and to determine if there is objective evidence of associations between weather and pain and stiffness in female patients with RA. METHODS: Fifty-three female patients residing in the Sydney metropolitan area participated in a study on the psychological determinants of disability from 1985 to 1987. During the study, subjects recorded pain on a visual analog scale and duration of morning stiffness for 14 day periods at 3-4 monthly intervals over 1-3 years (X = 15.7 months). After completion of the study, data on weather conditions were collected from the Bureau of Meteorology for the days that pain and stiffness records were made. Descriptive statistics and autoregression were used to analyze the data. RESULTS: Sixty percent of subjects reported that they were sensitive to weather. Six weather variables made a statistically significant contribution to daily pain score (p < 0.0001). However, they accounted for only 2.5% of the variance. Two weather variables contributed to duration of morning stiffness (p < 0.0001), but again these variables accounted for only a small portion of the variance (1.1%). A separate analysis for pain was carried out on the data from subjects who reported being weather sensitive. The results were consistent with those of the other analyses, with 2 variables accounting for only 1.7% of the variance (p < 0.0001). CONCLUSION: On the basis of these results it appears that weather makes only a minimal contribution to pain and stiffness in women with RA. The study may have been limited by its use of static measures of weather variables and pain. Further research using dynamic measures of pain and weather and a more extensive range of weather variables is needed.

Arthritis, Rheumatoid↗
PubMed1996

Enlarged frontal P300 to stimulus change in panic disorder.

This study investigated event-related potential (ERP) indices of information processing in sufferers of panic disorder (PD). ERPs were recorded from 14 PD patients and 15 controls during an auditory target detection task. The task required subjects to discriminate infrequent target tones (p = .14; 2000 Hz) from frequent (p = .72; 1000 Hz) and infrequent (p = .14; 500 Hz) distractor tones. A frontal P300 (P3a) identified in the PD group was characteristic of activity that would be expected to novel, task-irrelevant stimuli and is consistent with junctional pathology involving the prefrontal-limbic pathways. This study provides psychophysiological evidence of an abnormality in PD of the brain's processing of physical changes in the stimulus field that occurs even under conditions of low stimulus load. It may assist in helping to understand the breakdown in information processing that occurs in PD under high load conditions such as crowds and supermarkets.

Adult↗
PubMed1996

Effect of atrial natriuretic factor on corticotrophin-releasing hormone-induced adrenocorticotrophin release in the mature ovine foetus.

1. Atrial natriuretic factor (ANF) and its analogues have been shown previously to inhibit corticotrophin-releasing hormone (CRH)-induced adrenocorticotrophin (ACTH) release, both in vivo and in vitro, and it has been suggested that ANF may be a, or the, physiological ACTH-inhibitory factor. To determine whether ANF is relevant in the regulation of ACTH secretion in the ovine foetus, the present study examines the effect of ANF on CRH-stimulated ACTH release in the mature ovine foetus. 2. Five chronically cannulated foetuses, studied between 129 and 140 days of gestation (term 145-150 days), received intraarterial infusions of ovine CRH (4 micrograms/h) 120 min after the start of a sustained infusion of human ANF5-28 (10 micrograms/h) or saline (1.2 mL/h). Appropriate control experiments were performed, with foetuses receiving ANF or saline infusion only. CRH, ACTH, ANF and cortisol levels were measured by sensitive and specific radioimmunoassays. Each animal received all four treatments, with the order being randomized and 2-3 days being allowed between experiments. 3. It was found that pretreatment (120 min) with ANF5-28 (at levels devoid of significant cardiovascular actions) had no effect on mean basal or peak ACTH and cortisol levels during CRH infusion. Given the current experimental parameters, these results suggest that ANF does not acutely modulate basal or CRH-stimulated ACTH and cortisol release in the mature ovine foetus.

Adrenocorticotropic Hormone↗
PubMed1996

Artificial neural networks: a prospective tool for the analysis of psychiatric disorders.

Artificial neural networks are computer simulations of biological parallel distributed processing systems. They are able to undertake complex pattern recognition tasks, including diagnostic classification, prediction of disease onset and prognosis, and identification of determinants of clinical decisions. These capabilities have been utilized in general medicine, but as yet there has been little application of artificial neural networks in psychiatric research. Artificial neural networks can also be used to create models of brain function, providing a paradigm for cognition and the organization of neural systems that demonstrates how changes at the cellular level can affect information processing. These models are able to encompass both the biological and the behavioral dimensions of psychiatric disorders.

Humans↗