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Biomedical subjects

R McClelland

Publications and source records attributed to R McClelland.

At least 19 recordsLinked to original sources
PubMed2003

Evidence of cardiac ischemia during seizures in drug refractory epilepsy patients.

The authors investigated whether patients with drug refractory epilepsy have cardiovascular abnormalities that might be related to a high frequency of sudden death. Twenty-three subjects underwent comprehensive cardiovascular evaluations before and during video-EEG monitoring. ST-segment depression occurred in 40% and was associated with a higher maximum heart rate during seizures. These data suggest that cardiac ischemia may occur in these patients.

Adult↗
PubMed2001

M-mode echocardiographic predictors of six- to seven-year incidence of coronary heart disease, stroke, congestive heart failure, and mortality in an elderly cohort (the Cardiovascular Health Study).

Previous studies have identified a number of echocardiographic variables that predict cardiovascular disease (CVD) events and mortality, but have not focused on a large elderly cohort. The purpose of this study was to determine whether M-mode echocardiographic variables predicted all-cause mortality, incident coronary heart disease (CHD), congestive heart failure (CHF), and stroke in a large prospective, multicenter, population-based study. In the Cardiovascular Health Study, a biracial cohort of 5,888 men and women (mean age 73 years) underwent 2-dimensional M-mode echocardiographic measurements of left ventricular (LV) internal dimensions, wall thickness, mass and geometry, as well as measurement of left atrial dimension and assessment for mitral annular calcium. Participants were followed for 6 to 7 years for incident events; analyses excluded subjects with prevalent disease. One or more echocardiographic measurements were independent predictors of all-cause mortality and incident CHD, CHF, and stroke. After adjustment for anthropometric and traditional CVD risk factors, LV mass was significantly related to incident CHD, CHF, and stroke. The highest quartile of LV mass conferred a hazards ratio of 3.36, compared with the lowest quartile, for incident CHF. Furthermore, incident CHF-free survival was significantly lower for participants with LV mass in the highest versus the 2 lowest quartiles (86% vs 97%, respectively, at 2,500 days). Eccentric and concentric LV hypertrophy, respectively, conferred adjusted hazards ratios, compared with normal LV geometry, of 2.05 and 1.61 for incident CHD, and 2.95 and 3.32 for incident CHF. Thus, in an elderly biracial population, selected 2-dimensional M-mode echocardiographic measurements were important markers of subclinical disease and conferred independent prognostic information for incident CVD events, especially CHF and CHD.

Aged↗
PubMed2001

Relation of hemodynamics and risk factors to ventricular-vascular interactions in the elderly: the Cardiovascular Health Study.

OBJECTIVE: To investigate the interaction between left ventricular (LV) geometry, carotid structure and arterial compliance in relation to hemodynamic stimuli and risk factors (plasma cholesterol, body mass index, insulin resistance, smoking habit, age, sex and race). DESIGN: Cross-sectional. METHODS: Echocardiography and carotid ultrasound were performed in 2375 elderly subjects without signs or history of prevalent cardiovascular disease, diabetes or renal disease (795 men; 298 non-whites; 1215 hypertensive), from the cohort of the Cardiovascular Health Study. Arterial compliance was estimated by the prognostically validated ratio of stroke volume to pulse pressure (SV/PP) as the percent deviation (Delta%) from the value predicted by individual age, heart rate and body weight. RESULTS: Intima-medial thickness (IMT) was higher in the presence of LV hypertrophy (LVH) in normotensive and hypertensive subjects and was greatest in the presence of concentric LVH. Maximum carotid lumen diameter (CLD) was also higher in the presence of LVH (and was greatest with eccentric LVH, in association with relatively high values for stroke volume). After adjusting for blood pressure, maximum carotid lumen diameter was directly correlated with stroke volume, and IMT to LV mass (all P < 0.001). Similarly, IMT was also related to maximum carotid lumen diameter, independently of prevalent risk factors (P < 0.001). SV/PP-Delta% was reduced in both groups with concentric LV remodeling (both P < 0.0001) or concentric LVH (both P < 0.05). Adjusting for risk factors did not affect these associations in normotensives, but made them insignificant in hypertensives. In normotensives, IMT was inversely related to SV/PP-Delta% (P < 0.001), independently of risk factors, whereas no significant relation was found in hypertensives. CONCLUSIONS: The magnitudes of carotid intima-medial thickness and lumen diameter parallel levels of LV mass and geometry, and are directly related to stroke volume and arterial stiffness; this interaction is most evident in the presence of normal blood pressure, whereas it is affected by other cardiovascular risk factors when arterial hypertension is present.

Aged↗
PubMed2001

Gram's stain: the key to microbiology.

Gram's stain remains one of the most valuable methods we have for identifying isolates accurately and rapidly. Despite our long-standing familiarity with this method, it still warrants careful attention every step of the way--from preparation and QC of reagents to staining and interpretation.

Education, Continuing↗
PubMed2000

Validation of an outcome scale for use in adult psychiatric practice.

OBJECTIVE: To clarify the usefulness, acceptability, sensitivity, and validity of version 4 of the Health of the Nation Outcome Scale (HoNOS), a scale developed to meet the requirement for a clinically acceptable outcome scale for routine use in mental illness services. DESIGN: Patients with a range of mental illnesses were rated on the HoNOS at the beginning and end of an episode by interviews with mental health professionals. SUBJECTS: 934 patients from eight diagnostic categories were rated by 129 mental health professionals at 17 sites; 250 were also rated on a range of comparison scales. OUTCOME MEASURES: Comparison of patients' scores at the beginning and end of an episode using individual item scores, dimensional subscores, and the total score. RESULTS: HoNOS scores decreased by almost 50% between the beginning and end of episodes. They varied with the severity of the setting and discriminant analysis showed that the HoNOS had a moderate level of discriminatory power. Correlation analysis showed acceptable levels of agreement with independent scales, although the accuracy of ratings of some items at the beginning of an episode was affected by information deficits. CONCLUSION: The findings indicate that HoNOS is sensitive to change across time and to differences in illness type and severity, and has a sufficient degree of both construct and criterion related validity to fulfil the requirements of a mental health outcome scale for routine use in clinical settings.

Adult↗
PubMed1999

Risk factors for suicide independent of DSM-III-R Axis I disorder. Case-control psychological autopsy study in Northern Ireland.

BACKGROUND: The vast majority of suicides suffer from at least one mental disorder at the time of death. AIMS: To identify risk factors for suicide, particularly those independent of current DSM-III-R Axis I disorder(s). METHOD: A case-control psychological autopsy study comparing suicides with matched community controls. RESULTS: Independent risk factors for suicide included: Axis II (personality) disorder (particularly antisocial, avoidant and dependent); at least one of 12 life events (from the List of Threatening Experiences) during the previous 52 or 4 weeks (in particular, a 'serious problem with close friend, neighbour or relative'); current unemployment; previous history of deliberate self-harm; and contact with a GP within 26 weeks. Relative to individuals with no current mental disorder, the estimated risk of suicide in those with Axis I-Axis II comorbidity (OR 346.0) was significantly greater than that in those with Axis I disorder(s) only (OR 52.4). CONCLUSIONS: Suicide risk assessment may be enhanced by enquiry about the aforementioned independent risk factors, and attention to Axis I-Axis II comorbidity.

Case-Control Studies↗
PubMed1998

Differences in prevalence of and risk factors for subclinical vascular disease among black and white participants in the Cardiovascular Health Study.

A composite measure of subclinical vascular disease has been developed in the Cardiovascular Health Study (CHS). In previous reports, we measured the prevalence of subclinical disease among the original 5201 participants in the CHS, the relationship of risk factors to subclinical disease, and the association of subclinical disease to clinical coronary heart disease. In 1992 to 1993 (year 4 of the study), a larger cohort of 424 black women and 248 black men was added to the study. In this study, we have compared the prevalence of subclinical disease among blacks and whites in the CHS and the association with cardiovascular risk factors. The prevalence of subclinical disease for all participants (aged > or =65 years) was 41.3% for white women, 39.7% for black women, 41.9% for white men, and 43.7% for black men. The prevalence increased with age. The risk factor associations for subclinical disease were similar among blacks and whites. In multivariate analysis, age, systolic blood pressure, LDL cholesterol, smoking, and family history of myocardial infarction were independently associated with subclinical disease among both black and white women, while for white men, systolic blood pressure, use of antihypertensive medication, smoking, body mass index, and diastolic blood pressure (inverse) were related to subclinical disease. In black men, blood triglyceride level, use of antihypertensive medications, and family history of myocardial infarction (inverse) were associated with subclinical disease.

Black or African American↗
PubMed1997

Mental disorders and suicide in Northern Ireland.

BACKGROUND: The aim of this part of the Northern Ireland Suicide Study was to investigate the prevalence of DSM-III-R axis I (clinical syndrome) and axis II (personality) disorders among suicides (14 years and older) in Northern Ireland during a one-year period. METHOD: A psychological autopsy study based on a variety of documentary sources and interviews with bereaved informants and health care professionals. RESULTS: Ninety per cent of suicides (106/118) had a current axis I and/or an axis II mental disorder. At least one current axis I disorder was diagnosed in 86% of suicides (102/118), and at least one axis II disorder was diagnosed in 44% (52/118). Suicides under 30 years (92% male) were less likely to have a current axis I disorder (68%; 26/38) than those 30 years and older (95%; 76/80). Psychiatric comorbidity was present in 55% of suicides (65/118). The time between the last contact with a health care professional and death was greater among suicides under 30 years and male suicides. CONCLUSIONS: Notwithstanding the aetiological complexity of suicide, the prevention, recognition and treatment of mental disorder will continue to play key roles in suicide prevention.

Adolescent↗
PubMed1997

Diagnosis of schizophrenia: future ethics.

The healthcare burden, to the affected individual, their family and to society, caused by the schizophrenias provides a strong moral appeal for non-discriminatory allocation of resources for both research and service provision. Nevertheless, the anticipated advances in clinical research findings are likely to lead to a new healthcare situation where a number of values and moral appeals are likely to be in conflict. The sources of these conflicts are explored with respect to the nature and origin of the schizophrenias, the challenges of pre-clinical and possible prenatal diagnosis. It is argued that the ethical problems associated with discovery of early markers for the development of schizophrenia should be anticipated and appropriate guidelines developed in advance of their realisation. Experience of other screening programmes strongly cautions against the introduction of such markers before the benefits and safety aspects have been clearly defined.

Abortion, Induced↗
PubMed1995

Oxidation of aminopyrine by hypochlorite to a reactive dication: possible implications for aminopyrine-induced agranulocytosis.

Aminopyrine is associated with a high incidence of agranulocytosis. It is known to be oxidized by peroxidases and hypochlorous acid to a blue cation radical. It has been proposed that the mechanism by which hypochlorous acid oxidizes aminopyrine to a cation radical involves N-chlorination followed by loss of a chlorine radical. Another possible mechanism is loss of HCl to form an iminium ion and subsequent reaction with another molecule of aminopyrine and a hydrogen ion to form two radical cations. This mechanism would lead to incorporation of a hydrogen from water; however, using a deuterated analog, we found no hydrogen incorporation, thus providing strong evidence against this mechanism. Using a stopped-flow diode array spectrophotometer to study the reaction between aminopyrine and hypochlorous acid, an intermediate with a lambda max at approximately 420 nm was observed in the formation of the cation radical. We propose that this represents a dication formed by the loss of chloride ion from N-chloroaminopyrine. This intermediate is very reactive, with a half-life of approximately 15 ms, and in addition to being the precursor of the cation radical, it also appears to react with two molecules of water to form several other products that were observed and are consistent with the proposed dication intermediate. Similar stable products were formed when amino-pyrine was oxidized by the combination of myeloperoxidase, hydrogen peroxide, and chloride or activated neutrophils. The reactive dication formed by neutrophil-derived hypochlorous acid could be responsible for aminopyrine-induced agranulocytosis.

Agranulocytosis↗
PubMed1994

Dual immunocytochemical analysis of oestrogen and epidermal growth factor receptors in human breast cancer.

Recent studies have demonstrated a consistent inverse relationship between oestrogen receptor (ER) and epidermal growth factor receptor (EGFR) levels in female human breast cancer. Serial cross-section studies have suggested that separate populations of ER+/EGFR- and ER-/EGFR+ cancer cells exist in tumours deemed by immunocytochemical assay (ICA) to be positive for both. We have developed a dual ICA that is able to stain for both ER and EGFR on a single 5 microns frozen section sample of breast tissue. Twenty-two samples of female human breast cancer tissue that exhibited positivity for ER and EGFR by ER-ICA using the H222 monoclonal antibody and EGFR-ICA using the EGFR1 monoclonal antibody underwent the dual ICA. There was a significant correlation in receptor positivity between the single and dual assays for both ER (rs = 0.801, P < 0.001) and EGFR (rs = 0.831, P < 0.001). Individual cancer cells exhibited one of three staining patterns: nuclear staining only (ER+/EGFR-), membrane-associated and cytoplasmic staining only (ER-/EGFR+) or no staining (ER-/EGFR-). No cancer cells exhibited both nuclear and membrane/cytoplasmic staining. This is the first description of a simultaneous dual immunocytochemical assay system for ER and EGFR in clinical breast cancer specimens. The results suggest that ER and EGFR expression are mutually exclusive within an individual breast cancer cell in vivo with separate populations of ER+/EGFR- cells, ER-/EGFR+ cells and ER-/EGFR- cells coexisting.

Adult↗
PubMed1993

The postconcussional syndrome: social antecedents and psychological sequelae.

The study consisted of a prospective investigation of 45 consecutively admitted patients who had sustained a mild head injury. In all cases the duration of post-traumatic amnesia was less than 24 hours. Head injury patients had an average of three adverse life events in the year preceding injury compared with 1.5 for controls. Using the PSE, 39% of the group were diagnosed psychiatric cases at six weeks after the injury. For cases the mean level of chronic social difficulties (3.3) was four times that for non-cases (0.8). Six months after injury, 28% of the head injury group had three or more symptoms. These chronic cases were on average ten years older than those whose symptoms had remitted. Chronic cases had, on average, three social difficulties, twice as many as found among those whose symptoms had remitted. The emergence and persistence of the postconcussional syndrome are associated with social adversity before the accident. While young men are most at risk of minor head injury, older women are most at risk of chronic sequelae.

Adolescent↗
PubMed1991

Hormone sensitivity in breast cancer: influence of heterogeneity of oestrogen receptor expression and cell proliferation.

The percentage of oestrogen receptor (ER) positive cells in a series of 118 breast cancers has been examined by immunohistochemistry in relation to patients' response to endocrine therapy. Positive and negative predictive values have been used to calculate appropriate cut-off points. The rate of response to treatment was significantly higher in women with receptor positive tumours, especially where the tumours contained more than 70% positive cells. Tumours that were apparently negative for ER expression rarely responded to endocrine therapy. The hormone sensitivity of ER positive breast cancer was also influenced by the rate of tumour cell proliferation, with tumours expressing high levels of Ki67 immunostaining rarely responding to therapy.

Antibodies, Monoclonal↗
PubMed1991

Relationship between the pharmacokinetics and iron excretion pharmacodynamics of the new oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one in patients with thalassemia.

Single-dose and steady-state pharmacokinetics of the new oral iron chelator, 1,2-dimethyl-3-hydroxypyrid-4-one (L1) were studied in 14 patients with thalassemia and correlated with iron excretion. Food prolongs the rate of absorption of L1, but it does not affect significantly the extent of absorption measured by the area under the plasma concentration-time curve. Similarly, it does not affect the chelation potential of the drug. The mean elimination half-life of the drug is 3 hours, suggesting that a divided dose every 8 hours may assure better chelation. Our steady-state studies reveal that urinary iron excretion is independently influenced by body iron load (measured by ferritin levels) and by steady-state trough concentrations of the drug. While patients were receiving an unchanged regimen of 75 mg/kg/day, we have detected a gradual and significant decrease in trough concentrations in the presence of unchanged patients' compliance monitored by the Medication Event Monitoring System, diaries, and pill count. These findings suggest self-induction of L1 metabolism or decreased absorption during long-term therapy. Because of the concentration-dependent iron excretion, patients may need increasing doses to achieve negative iron balance.

Adolescent↗
PubMed1990

Intra-habenular injection of 6-hydroxydopamine produces impaired acquisition of DRL operant behavior.

The anatomical connections of the habenula complex indicate it provides a relay between limbic forebrain and midbrain. Somewhat paradoxically, consequences of nonspecific lesion of the habenula are ambiguous with little change in basic response evident within simple behavioral paradigms. However, the potential functional importance for this relay has more recently been indicated by the demonstration of deficits in the ability of lesioned animals to alter behavior appropriate to both internal and external stimuli in more demanding behavioral tasks. Doubts concerning the importance of the habenula remain because of the large number of descending fibers of passage through the habenula. To provide more substantive evidence, 6-hydroxydopamine was injected into the habenula of rats to provide more limited lesion of catecholaminergic terminals. Animals were subsequently trained on an operant DRL 20-s schedule for which deficits have been reported following nonspecific lesion of the habenula. Lesioned animals showed a tendency to overrespond and were significantly less efficient on the schedule with decreased number of reinforcements received relative to controls. While the neurotoxic lesion procedure used does not differentiate noradrenergic and dopaminergic damage, the importance of intact catecholaminergic systems within the habenula for effective DRL acquisition is consistent with the suggested importance of the habenula for feedback regulation of dopamine within the ventral tegmental area through ascending dopamine fibers to the habenula.

Animals↗
PubMed1989

Improving the validity of the GHO30 by rescoring for chronicity: a failure to replicate.

To replicate the finding by Goodchild and Duncan-Jones (1985), that rescoring the GHQ30 in order to take account of chronicity would improve its validity, a random sample of 244 people completed the GHQ. Of these 102 also took part in a second interview in which they were administered the PSE. There was no evidence that the new scoring scheme improved correlations between the GHQ and other measures of morbidity nor did this improve its sensitivity or specificity when validated agaist the PSE.

Adult↗
PubMed1989

Communication skills training for medical students: an integrated approach.

Skills of communication are not easily taught to medical students. Three main clinical departments (general practice, medicine and mental health) of the Medical Faculty of the Queen's University, Belfast, introduced an integrated course in January 1988 to teach the basic principles. The course is held at the beginning of clinical training and is an integral part of the introductory clinical course. It was introduced in response to the Report of a Working Party of the Education Committee of the General Medical Council (1987) which advocated the need for improved training in history-taking and communication. It is a 12-week course and every Monday and Friday afternoon from 1400 to 1700 hours 12 students are seconded from ward work, four to the Department of Medicine, four to the Department of General Practice and four to the Department of Mental Health. Hand-outs about information to be obtained and interview style are standardized and the principles to be followed are clearly defined in an aide-mémoire. Staff from the Departments of General Practice and Mental Health experienced in teaching communication by videotape feedback and analysis of consultations prepared 12 tutors for their role and responsibilities. Procedures to be followed were carefully explained to all students beforehand. General practice and psychiatry traditionally have established teaching programmes in communication but the inclusion of the Department of Medicine has made a significant impact. Students have come to realize that the taking of a good history demands as much skill as the physical examination of the patient and is an important aspect of any clinical assessment.

Communication↗