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Biomedical subjects

S Browne

Publications and source records attributed to S Browne.

At least 19 recordsLinked to original sources
PubMed2001

Physiological changes during carbon dioxide inhalation in patients with panic disorder, major depression, and premenstrual dysphoric disorder: evidence for a central fear mechanism.

BACKGROUND: Inhalation of carbon dioxide (CO(2)) has been shown to produce more anxiety in patients with panic disorder (PD) than in healthy comparison subjects or patients with most other psychiatric illnesses tested, although premenstrual dysphoric disorder (PMDD) may be an exception. Several reasons have been proposed to explain CO(2) breathing effects in PD. We examined differences in respiratory response to CO(2) breathing in 4 groups to address these issues. METHODS: Patients with PD (n = 52), healthy controls (n = 32), patients with PMDD (n = 10), and patients with major depression without panic (n = 21) were asked to breathe 5% and 7% CO(2). Continuous measures of respiratory physiological indices were made. RESULTS: Carbon dioxide breathing produced the expected increases in all 4 respiratory variables measured. More patients with PD and PMDD had panic attacks than did controls or patients with major depression. Subjects who experienced panic during 5% or 7% CO(2) inhalation had the most extreme increases regardless of diagnostic group. Among patients with PD, baseline end-tidal carbon dioxide levels were significantly lower in those who subsequently had a panic attack during 5% CO(2) breathing than those who did not. CONCLUSIONS: Although CO(2) breathing causes a higher rate of panic attacks in patients with PD than other groups (except PMDD), the physiological features of a panic attack appear similar across groups. Once a panic attack is triggered, minute ventilation and respiratory rate increase regardless of whether the subject carries a PD diagnosis. These findings are compatible with preclinical fear conditioning models of anxiogenesis.

Administration, Inhalation↗
PubMed2001

The influence of food on the bioavailability of a twice-daily controlled release carbamazepine formulation.

Carbatrol, a new dosage form of carbamazepine (CBZ), was developed consisting of three different types of pellets (immediate release, controlled release, and enteric release). The objective of this study was to explore the influence of food on absorption of CBZ. This was a randomized, open-label, single-dose crossover study conducted in 12 healthy volunteers. Treatments were 2 x 200 mg Carbatrol with a high-fat meal, fasted, or sprinkled over applesauce (but otherwise fasted). Each subject received one dose of each treatment separated by a washout period of at least 2 weeks. CBZ bioequivalence was established based on the equivalence of AUC (extent of absorption) in all three conditions. Carbatrol may be taken with or without food or the capsule opened and sprinkled on food.

Adolescent↗
PubMed2000

Determinants of neurological dysfunction in first episode schizophrenia.

BACKGROUND: Although it is well recognized that individuals with schizophrenia display evidence of subtle neurological impairment, its aetiopathological and clinical significance continues to be unclear. METHODS: Patients presenting with a first episode of schizophrenia or schizophreniform psychosis (DSM-IV criteria) were examined using two previously validated neurological examinations. The majority (N = 35) were examined prior to their 'first ever' dose of neuroleptic while the remaining patients (N = 21) had been medicated for less than one month. The manner in which neurological functioning is influenced by symptomatology and handedness was ascertained. RESULTS: The majority of patients who were examined neuroleptic-naive displayed evidence of neurodysfunction. A combination of relative hand preference and symptomatology explained a significant proportion of the variance in neurological functioning. Mixed handedness among adults at the time of first presentation with schizophrenia was associated with more severe neurological impairment and a history of poorer scholastic attainment and pre-morbid social adjustment. CONCLUSIONS: Neurological soft signs are an intrinsic part of schizophrenia rather than a direct consequence of treatment. Early developmental processes are associated with the level of subsequent neurological impairment in first episode schizophrenia. However, symptomatology appears to have an influence on the apparent severity of neurological impairment.

Acute Disease↗
PubMed2000

The prevalence of comorbid substance misuse and its influence on suicidal ideation among in-patients with schizophrenia.

OBJECTIVE: To estimate the prevalence, and identify the clinical correlates of comorbid substance misuse (abuse or dependence) among readmissions with schizophrenia, particularly to establish whether comorbid substance misuse is associated with higher rates of depressive symptoms and suicidal ideation. METHOD: Over 12 months, consecutive readmissions from a catchment area psychiatric service with DSM-IV schizophrenia/schizoaffective disorder were assessed using clinical assessments of symptomatology including depression, insight and compliance. Comorbid substance misuse was diagnosed using DSM-IV criteria. RESULTS: Of 102 readmissions 40% had lifetime, while 20% had current comorbid substance misuse and were predominately young males. Comorbid substance misuse had no statistically significant impact on positive, negative or depressive symptomatology. However, those currently misusing substances reported more suicidal ideation compared with past or non-substance misusers. CONCLUSION: Readmissions with comorbid substance misuse were more likely to report suicidal ideation, and may represent a group of individuals who are at higher risk of suicide.

Adult↗
PubMed2000

Determinants of quality of life at first presentation with schizophrenia.

BACKGROUND: Quality of life (QOL) has gained importance as a global measure of social and clinical outcome in schizophrenia. AIMS: To identify the clinical correlates of QOL at the time of first presentation with schizophrenia. METHOD: Over two years, consecutive first-episode psychosis patients presenting to a catchment area psychiatric service underwent validated clinical assessments of premorbid adjustment, illness duration, symptoms and QOL. RESULTS: At presentation, subjects already had a diminished QOL. Although independent of gender and age at onset of psychosis, QOL was influenced by premorbid adjustment, duration of untreated psychosis and symptoms. CONCLUSIONS: Reducing the duration of untreated psychosis may have a beneficial effect on the subsequent QOL of patients presenting with schizophrenia. First-episode patients with a protracted duration of untreated psychosis or impaired premorbid adjustment may warrant specific treatment interventions to prevent the development of secondary handicaps.

Adult↗
PubMed1999

Dysphoric subjective response to neuroleptics in schizophrenia: relationship to extrapyramidal side effects and symptomatology.

OBJECTIVE: Subjective reports of dysphoric responses to neuroleptic medication are common in clinical practice. However, cognitive and affective side effects of neuroleptic medications are difficult to differentiate from the symptoms of schizophrenia. We sought to elucidate the relative contribution of extrapyramidal side effects and symptomatology to dysphoric response. METHOD: Fifty clinically stable outpatients with schizophrenia attending a rehabilitation centre were assessed for extrapyramidal side effects and symptomatology before completing the drug attitude inventory (DAI). RESULTS: Presence of extrapyramidal side effects, found in 28 patients (Z = -1.99, p = 0.05), and severity of negative symptoms (r = -0.47, p = 0.001) were independently associated with dysphoric response, explaining a significant proportion of the variance (R = 0. 53, R(2) = 25.2%, F = 9.27, df = 2, p = 0.0004). CONCLUSIONS: Patients who report a dysphoric response which they associate with neuroleptic medications have more extrapyramidal side effects and more severe negative symptoms. While these responses may be part of the negative symptoms of the illness or due to other factors such as depression, we raise the possibility that they may be clinically indistinguishable from, and be a subjective measure of, the so-called 'neuroleptic-induced deficit syndrome'.

Adult↗
PubMed1999

Investigation of female survival benefit in metastatic melanoma.

Epidemiological studies show female survival benefit in advanced metastatic melanoma. In investigating a possible mechanism for this female survival benefit, we have previously reported that the female steroid 17beta-oestradiol significantly reduces invasion of a human melanoma cell line (A375-SM cells) and ocular melanoma cells through fibronectin. Neither cell type was found to possess oestrogen receptor-alpha. The aim of the current study was to obtain further information on the extent to which progression of cutaneous melanoma might be sex steroid sensitive by (a) examining the relationship between circulating sex steroids, sex hormone binding globulin and disease progression; (b) examining the relationship between sex steroid structure and the ability of steroids to reduce invasion of a melanoma cell line in vitro; and (c) examining the effects of sex steroids on proliferation of these cells in vitro. We report a significant reduction in circulating oestrone with disease progression in male but not female patients. Examining steroids for their ability to inhibit invasion of A375-SM cells through fibronectin in vitro, oestrogenic compounds (17beta-oestradiol and oestrone) were found to inhibit invasion; in this respect, oestrone was approximately 50 times more potent than 17beta-oestradiol; steroids lacking the benzene ring structure did not inhibit invasion, indeed dehydroepiandrosterone (DHEA) which acts as a precursor to androgenic steroids significantly enhanced invasion. Proliferation of A375-SM cells was unaffected by 17beta-oestradiol, oestrone or dihydrotestosterone when cells were cultured on plastic; in contrast, all three steroids induced modest proliferation of cells when grown on fibronectin with dihydrotestosterone the most mitogenic of the three steroids. These data are consistent with sex steroids playing a role in melanoma progression.

Adolescent↗
PubMed1999

Subjective and external assessments of quality of life in schizophrenia: relationship to insight.

OBJECTIVE: This study assessed the manner in which insight influenced schizophrenic patients' evaluation of their objective life conditions and the concurrent validity between patients' and clinicians' assessments of patients' global quality of life. METHOD: Forty out-patients who fulfilled DSM-III-R criteria for schizophrenia were independently interviewed using the Lancashire Quality of Life Profile and the Standard of Living Interview. Insight was assessed using a self-report questionnaire, the Insight Scale. RESULTS: For insightful patients there was a significant but modest correlation between objective and subjective indicators of quality of life. Likewise, a significant correlation between subjective and external evaluations of global quality of life was limited to those individuals who had good insight. CONCLUSION: Diminished insight may limit the usefulness of the self-report methodology for assessing quality of life for some individuals with schizophrenia.

Adolescent↗
PubMed1999

Instructional set and physiological response to CO2 inhalation.

OBJECTIVE: Previous studies have suggested that manipulations in patient instructions before inhalation of carbon dioxide (CO2) may blunt its anxiogenic effects. The authors examined the effects of a range of instructional types on panic rates and physiological responses to CO2 inhalation. METHOD: Thirty-seven patients with panic disorder and 16 normal subjects were exposed to CO2 inhalation under one of three instructional conditions: 1) reassurance (reiterated safety assurances), 2) control dial (patients were instructed on using an operative dial to reduce the concentration of CO2 in the breathing canopy), and 3) basic instructions (standard information). Perceived breathlessness was measured with the Borg Scale of Respiratory Exertion. RESULTS: Manipulation of instructional sets did not affect panic rates among patients. The reassurance condition, however, produced a significant reduction in perceived breathlessness. CONCLUSIONS: CO2-induced panic is a robust biological effect that occurs independent of cognitive set changes, such as illusion of control or reassurance of safety. Conclusions drawn from this study are bolstered by the fact that it is methodologically rigorous: it had a large number of subjects, used random assignment to one of three instructions, included a full array of both subjective and biological measures, and included independent ratings.

Administration, Inhalation↗
PubMed1999

Rehabilitation programmes and quality of life in severe mental illness.

Quality of life is increasingly identified as a key outcome measure for evaluating the efficacy of community mental health services and novel antipsychotics. However, there is a relative paucity of research on the impact of rehabilitation programmes on quality of life. This report outlines the results of two 'naturalistic' studies carried out in a catchment area psychiatric service to evaluate the benefits associated with a supported employment programme and a psychosocial/educational intervention. The findings suggest that outpatient based programmes which provide opportunities for vocational or prevocational rehabilitation may have significant quality of life benefits for individuals with severe mental illness.

Adult↗
PubMed1998

Coenzyme Q10 administration increases brain mitochondrial concentrations and exerts neuroprotective effects.

Coenzyme Q10 is an essential cofactor of the electron transport chain as well as a potent free radical scavenger in lipid and mitochondrial membranes. Feeding with coenzyme Q10 increased cerebral cortex concentrations in 12- and 24-month-old rats. In 12-month-old rats administration of coenzyme Q10 resulted in significant increases in cerebral cortex mitochondrial concentrations of coenzyme Q10. Oral administration of coenzyme Q10 markedly attenuated striatal lesions produced by systemic administration of 3-nitropropionic acid and significantly increased life span in a transgenic mouse model of familial amyotrophic lateral sclerosis. These results show that oral administration of coenzyme Q10 increases both brain and brain mitochondrial concentrations. They provide further evidence that coenzyme Q10 can exert neuroprotective effects that might be useful in the treatment of neurodegenerative diseases.

Administration, Oral↗
PubMed1998

Quality of life in schizophrenia: insight and subjective response to neuroleptics.

The relationship between quality of life, insight, and subjective response to neuroleptics was assessed in a selected group of clinically stable outpatients with schizophrenia. A significant portion of the variance in these individuals' quality of life was explained by a combination of protracted illness duration and the presence of a dysphoric response to neuroleptics. However, there was no significant relationship between quality of life and the level of insight these individuals had into the nature of their illness. The development of treatment strategies to alleviate neuroleptic-induced dysphoria may enable outpatients with schizophrenia to benefit from rehabilitation programs devised to improve quality of life.

Adult↗
PubMed1998

Spontaneous abnormal involuntary movements in first-episode schizophrenia and schizophreniform disorder: baseline rate in a group of patients from an Irish catchment area.

OBJECTIVE: This study investigated the rate of spontaneous abnormal involuntary movements in a group of patients presenting with a first episode of schizophrenia or schizophreniform psychosis. METHOD: Seventy-nine patients with a first episode of schizophrenia or schizophreniform psychosis who presented to a catchment area psychiatric service over a 3-year period, and who were neuroleptic-naive or had been medicated for less than 1 month, were examined for the presence of involuntary movements with use of the Abnormal Involuntary Movement Scale. RESULTS: Six patients (7.6%) had spontaneous dyskinesia as defined by the criteria of Schooler and Kane, and nine other patients had mild orofacial involuntary movements. The patients with spontaneous dyskinesia had completed significantly fewer years of education than the patients without dyskinesia. Spontaneous involuntary movements were unrelated to age at presentation for treatment. CONCLUSIONS: Spontaneous abnormal involuntary movements were evident among a proportion of patients with first-episode schizophrenia or schizophreniform psychosis at baseline presentation and were associated with reduced educational attainment. This finding supports previous suggestions that abnormal involuntary movements in schizophrenia may be related to the pathophysiology of the illness and therefore cannot be attributed entirely to the adverse effects of neuroleptic medication.

Adult↗
PubMed1996

Cocaine and butyrylcholinesterase (BChE): determination of enzymatic parameters.

In humans, the plasma enzyme, butyrylcholinesterase (E.C. 3.1.1.8), metabolizes cocaine to the water-soluble, pharmacologically inactive compounds, ecgonine methylester and benzoic acid. Homogeneous enzyme was purified from human plasma and used to determine the enzyme kinetic parameters of Km and Vmax with cocaine as the substrate. The KM (11.9 microM) indicates that cocaine is tightly bound to the four active sites of the native tetramer. The Vmax (1.17 microM/min) is 50-fold greater than cocaine catalytic antibodies. Administration of purified human butyrylcholinesterase to a cocaine-intoxicated patient would be expected to shift the metabolism to the inactive metabolites and reduce the toxicity.

Benzoates↗
PubMed1996

Quality of life in schizophrenia: relationship to sociodemographic factors, symptomatology and tardive dyskinesia.

The influence of sociodemographic, clinical and treatment factors on the quality of life of patients with schizophrenia has yet to be fully defined. We evaluated the quality of life of patients with schizophrenia who were attending a catchment area rehabilitation centre, in order to establish its clinical correlates. These patients had a poor to moderate quality of life which was inversely related to negative symptom severity, illness duration, the cumulative length of previous hospitalization and patient age. Patients residing in hostels or group homes had a poorer quality of life than those living independently or with their family. The presence of tardive dyskinesia was associated with a poorer quality of life. This association merits further investigation.

Adolescent↗