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PubMed1981

Advanced technologies of cardiovascular nuclear medicine and their evaluation in clinical practice.

Currently available advanced methods of cardiovascular nuclear medicine for the diagnosis of ischemic heart disease were studied. The methods included the multigate method by a large capacity gamma camera-computer (128 KW memory with multilayer disc) system which made it possible to acquire the data of either the first pass study or the equilibrium study in "imaging mode". Analyzed data were displayed on a color CRT using our moving image system (MIS) and dynamic image thus obtained serve to help for the high sensitive observation of the regional wall motion as well as the global function of the ventricles. Myocardial tomography by a 7 pinhole collimator designed by us was also reported. The myocardial tomogram obtained was proved to show more sensitivity than two dimensional myocardial scan by the conventional collimator to detect smaller lesion and the lesions at the inferior or posterior wall of the left ventricle. The cardiovascular nuclear medicine with recent advanced technologies was thought to be sensitive and useful method for the diagnosis of the ventricular performance and the myocardial ischemia.

Aged↗

PubMed2000

Hospital adjustment in personality disorder patients admitted to a therapeutic community milieu.

This study investigated aspects of adjustment to the therapeutic community milieu in a group of personality disorder patients. Eighty-one patients consecutively admitted to the Cassel Hospital for medium/long-term residential treatment between April 1994 and October 1997 comprised the sample. The adjustment to the milieu was rated on the Hospital Adjustment Scale, while outcome was evaluated at 6-monthly intervals using a battery of self-rated and rater-based instruments. The aims of the study were: (a) to identify demographic and pre-admission clinical variables that would predict adjustment to the therapeutic regime; (b) to study the relationship between hospital adjustment and external social adjustment; and (c) to investigate the hypothesis that hospital adjustment and internally and externally directed aggression do not predict clinical outcome. The results showed that pre-admission level of global functioning and a previous history of substance misuse are the most significant predictors of hospital adjustment. No significant association between hospital adjustment and external social adjustment was found. Neither hospital adjustment not level of aggressiveness predicted outcome at 12 months. The implications of these results for therapeutic community treatment of personality disorder are discussed.

Adaptation, Psychological↗

PubMed2005

[Heterogeneity of cognitive deficits in Alzheimer's and cognition therapy: research design ].

Numerous studies suggest that the clinical presentation of Alzheimer's disease (AD) is varied and that AD is thus a heterogeneous disorder. Evidence of this inter-individual variability has had an important impact on the approaches to the cognitive rehabilitation of AD, particularly in the early stages of the disease. Research has shown that, despite variable cognitive profiles, many preserved capabilities are observed in the first stages of AD and that the disease does not affect all cognitive functions globally. These preserved capabilities make it possible to apply cognitive interventions. However, numerous methodological difficulties are encountered in evaluating the effectiveness of these interventions, many of which are related to the heterogeneity of the deficits. The purpose of this article is to discuss this heterogeneity and its impact on methodological characteristics, especially participant selection and research design.

Alzheimer Disease↗

PubMed2006

Novel cholinesterase inhibitors as future effective drugs for the treatment of Alzheimer's disease.

Current pharmacotherapy for Alzheimer's disease involves compounds that are aimed at increasing the levels of acetylcholine in the brain by facilitating cholinergic neurotransmission through inhibition of cholinesterase. These drugs, known as acetylcholinesterase inhibitors, have been shown to improve cognition and global functions but have little impact on improving the eventual progression of the disease; however, there is evidence that other cholinesterases such as butyrylcholinesterase can play an important role in cholinergic function in the brain, and the long-suspected non-cholinergic actions of acetylcholinesterase, mainly the interference with the beta-amyloid protein cascade, have recently driven a profound revolution in cholinesterase drug research. Several disease-modifying agents are under development that target these enzymes and have hope of becoming the next generation of effective drugs in the treatment of Alzheimer's disease.

Acetylcholinesterase↗

PubMed2001

Current status and new developments with galantamine in the treatment of Alzheimer's disease.

Galantamine is a newly available cholinergic drug that offsets reductions in central cholinergic neurotransmission in Alzheimer's disease (AD) by specifically and reversibly inhibiting acetylcholinesterase (AChE) and by allosterically modulating nicotinic cholinergic receptors. The clinical impact of this latter mechanism of action has not been fully elucidated. Galantamine has favourable pharmacokinetic features including linear elimination kinetics, a relatively short half-life and high oral bioavailability. The efficacy of galantamine has been studied in an extensive clinical development program. During randomised, double-blind, placebo-controlled trials of up to 6 months' duration, galantamine 16 and 24 mg/day consistently produced a broad spectrum of beneficial effects on cognitive and non-cognitive AD symptoms. Patients' cognition, global function and abilities to perform both instrumental and basic activities of daily living were maintained, the emergence of behavioural symptoms was postponed and apparent reductions in caregiver burden were seen. In long-term studies (> or = 12 months), galantamine maintained cognitive and functional abilities at or near baseline levels for at least 12 months. Again, these benefits were associated with decreases in caregiver burden. The incidence of adverse events, which are typically mild or moderate in severity, is generally low with galantamine. Cholinergically mediated adverse events affecting mainly the gastrointestinal system can be minimised using the recommended slow dose-escalation regimen. Galantamine may therefore help reduce the overall burden and cost involved in caring for AD patients. Being approved for the treatment of mild-to-moderately severe AD in both the US and in Europe, with trials of its efficacy in other dementia types already yielding positive results, galantamine ranks as a first-line therapy for dementia.

Aged↗

PubMed2004

The benefits and risks associated with cholinesterase inhibitor therapy in Alzheimer's disease.

The 'second-generation' cholinesterase inhibitors (ChEIs), donepezil, galantamine and rivastigmine, are a class of medications that are currently approved for the treatment of mild-to-moderate Alzheimer's disease (AD). These medications have proven efficacy in improving cognition, behaviour, activities of daily living, and global functioning in mild-to-moderate AD. They have also been shown to reduce caregiver stress and to delay time to nursing home placement. Two separate meta-analyses have indicated that ChEIs confer a modest but significant therapeutic benefit in the treatment of AD, despite higher rates of treatment discontinuation and side effects than placebo. There is growing evidence to support their efficacy in treating moderate-to-severe AD. ChEIs are generally well-tolerated, with side effects that tend to be dose-related and are most problematic during dose titration. The most common adverse effects, related to cholinergic stimulation in the brain and peripheral tissues, include gastrointestinal, cardiorespiratory, extrapyramidal, genitourinary, and musculoskeletal symptoms, as well as sleep disturbances. Few clinically significant drug-drug interactions with ChEIs have been identified. Three head-to-head trials of ChEIs in the treatment of AD have been published to date, but are limited due to their open-label design, rates of titration, and the drug dosage levels utilised. Further study is needed to examine other indications for ChEIs, as well as their combination with newer treatments, such as memantine.

Aged↗

PubMed2001

Attachment styles and personality disorders as predictors of symptom course.

Adult attachment styles and personality disorders (PDs) show some conceptual and empirical overlap and both may complicate the course of symptoms among psychiatric patients. In this naturalistic prospective study, 149 patients with affective, anxiety, substance use, and other disorders were interviewed shortly after entering treatment, which included psychotherapy, pharmacotherapy, or both. Follow-up interviews were conducted 6 and 12 months later. Attachment styles, DSM-III-R PDs, and symptoms were assessed using structured interviews and consensus ratings. At intake, borderline, avoidant, and dependent PD features correlated consistently with symptom severity and secure attachment correlated inversely with two of four symptom scales. Secure attachment was linked with greater relative improvement in global functioning and a more benign course of anxiety symptoms over 6 months. Borderline PD features predicted less relative improvement of depressive symptoms over 6 months. These findings clarify the relations between attachment styles and PD features and they point to potential mediators of treatment response.

Adult↗

PubMed2006

Six-year follow-up of three treatment programs to personality disorder.

Previous studies of long-term outcome for personality disorder (PD) were either retrospective in design or did not include a control condition. In this paper we report results for three PD cohorts (N = 111) treated in two different specialist psychosocial programs (step-down and long-term inpatient) and in general psychiatric treatment as usual (TAU), which were prospectively followed up for 72-months after intake. The three PD samples were compared on symptom severity, social adjustment, global functioning and other clinical indicators (self-mutilation, parasuicide and readmission rates) at intake, 6, 12, 24, and 72 months. Results indicated that a specialist step-down model showed significantly greater change than a purely inpatient model and TAU in most key dimensions of functioning, a difference maintained at 72-months follow-up. Improvement in the samples was not associated with amount of intercurrent treatment received in the year prior to the follow-up assessment. This study confirms that a step-down program retains significant improvement associated with a specialist psychosocial approach for PD. However, this conclusion should be qualified by design limitations. The samples were not randomly allocated to the three conditions and the naturalistic geographical allocation used in the study created a potential for a number of confounds. Whilst we used extensive statistical controls, the possibility that the differences found between the groups may be due to population differences cannot be discounted.

Adult↗

PubMed2004

Impacts of motivation for change on the severity of alcohol use by patients with severe and persistent mental illness.

OBJECTIVE: This study examined the effect of motivation for change, measured by the Stages of Change Readiness and Treatment Eagerness Scale (SOCRATES), on alcohol use severity among alcoholic patients with severe and persistent mental illness. METHOD: At a Veterans Affairs hospital, 390 dually diagnosed patients were recruited and assessed for motivation for change, alcohol use severity, psychotic symptoms and global functioning at baseline and 9-month follow-up. RESULTS: Regression analyses showed that patients who were highly ambivalent about their alcohol use at baseline consumed significantly more alcohol 9 months later, on the basis of Addiction Severity Index ratings (p < or = .01), than patients who felt less ambivalent. CONCLUSIONS: The findings suggest that increased awareness of alcohol-related problems is essential to reducing alcohol use severity for alcoholic patients with severe and persistent mental illness. The implications and limitations of the findings are discussed.

Adult↗

PubMed2004

Suppression of histone H1 genes in Arabidopsis results in heritable developmental defects and stochastic changes in DNA methylation.

Histone H1 is an abundant component of eukaryotic chromatin that is thought to stabilize higher-order chromatin structures. However, the complete knock-out of H1 genes in several lower eukaryotes has no discernible effect on their appearance or viability. In higher eukaryotes, the presence of many mutually compensating isoforms of this protein has made assessment of the global function of H1 more difficult. We have used double-stranded RNA (dsRNA) silencing to suppress all the H1 genes of Arabidopsis thaliana. Plants with a >90% reduction in H1 expression exhibited a spectrum of aberrant developmental phenotypes, some of them resembling those observed in DNA hypomethylation mutants. In subsequent generations these defects segregated independently of the anti-H1 dsRNA construct. Downregulation of H1 genes did not cause substantial genome-wide DNA hypo- or hypermethylation. However, it was correlated with minor but statistically significant changes in the methylation patterns of repetitive and single-copy sequences, occurring in a stochastic manner. These findings reveal an important and previously unrecognized link between linker histones and specific patterns of DNA methylation.

Arabidopsis↗

PubMed2005

Rivastigmine for Alzheimer's disease.

Alzheimer's disease is the most common form of neurodegenerative dementia and poses considerable health challenges to both patients and their families. Rivastigmine is a powerful slow-reversible, noncompetitive carbamate cholinesterase inhibitor that is approved for the treatment of mild-to-moderate Alzheimer's disease. Randomized, double-blind, placebo-controlled trials of up to 6 months duration have shown beneficial effects of rivastigmine compared with placebo in measures of cognition and global functioning. Less rigorous but growing data suggest that the beneficial effects may endure for up to 5 years, extend to more advanced stages of Alzheimer's disease and may occur in noncognitive domains, such as activities of daily living and the behavioral symptoms of Alzheimer's disease. Evidence from controlled studies also supports the use of rivastigmine for cognitive and behavioral symptoms in Alzheimer's disease associated with vascular risk factors, dementia with Lewy bodies and Parkinson's disease dementia. Early and continued treatment of Alzheimer's disease with rivastigmine maximizes the observed beneficial effects. The most prominent adverse effect of rivastigmine is centrally mediated cholinergic gastrointestinal events, which can be minimized by slower dose-escalation intervals and administration with a full meal. Therapeutic dosing is 6-12 mg/day given twice daily, with higher doses having the potential for greater benefits.

Alzheimer Disease↗

PubMed1997

Management of lipid disorders in the elderly.

Cardiovascular disease has been inseparable from aging in developed societies and, as a result, it is the commonest cause of mortality in elderly populations. Atherosclerosis is associated with the progressive vascular accumulation of cholesterol-laden lipoproteins, and is linearly associated with the plasma level of low density lipoprotein (LDL) cholesterol. Clinical trials in patients aged < 65 years have conclusively shown that treatment of hypercholesterolaemia decreases the incidence of cardiovascular events and total mortality. However, few conclusive data are available regarding the treatment of hypercholesterolaemia in elderly patients. Extrapolation from clinical trials suggests that lipid lowering treatment in well selected elderly patients is effective in preventing cardiovascular events and is an efficient use of healthcare resources. In addition to cholesterol, high triglyceride and low high-density lipoprotein levels appear to be significant predictors of coronary artery disease in elderly patients. We do not advocate the indiscriminate screening of healthy elderly patients who have no other cardiovascular risk factors, because the marginal overall benefits are probably small and the costs of widespread screening and treatment high. On the other hand, chronological age itself cannot be considered a barrier to the screening and treatment of patients who have a good quality of life but have other cardiovascular risk factors and/or definite cardiovascular disease. Subgroup analysis of major clinical trials suggests that the aims of treatment should be to lower the LDL cholesterol level to 3.2 mmol/L (125 mg/dl), or the total cholesterol level to 5.2 mmol/L (200 mg/dl). Occasionally, multiple drug therapy is required to achieve this target, but statins (HMG-CoA reductase inhibitors) are the most commonly used first-line agents. With aggressive lowering of plasma lipid levels in this way, a reduction in clinical events is paralleled by regression of atheroma detectable by angiography, and an improvement in endothelial function. Global reduction of risk factors in elderly patients should always be undertaken, including dietary therapy, weight reduction in viscerally obese patients, postmenopausal estrogen replacement, smoking cessation, treatment of hypertension and control of diabetes mellitus. A secondary cause of dyslipidaemia should also be sought. The role of antioxidants is still not clear, but they are probably of little benefit in elderly patients. With the widespread use of effective, well tolerated treatments for lipid disorders in younger patients, significant improvements have already been attained in the morbidity and mortality associated with coronary artery disease. Since the current life expectancy at age 65 years is nearly 20 years in most Western countries, secondary prevention may increase the quality of life and the independent lifespan, even if eventual mortality is not delayed.

Aged↗

PubMed2003

Donepezil: in vascular dementia.

Vascular dementia (VaD), caused by stroke or small vessel disease, is the second most common form of dementia after Alzheimer's disease (AD). Donepezil, an acetylcholinesterase inhibitor currently indicated for use in patients with mild to moderate AD, has recently been evaluated in VaD. Donepezil 5 or 10mg once daily provided significant improvements in cognition, as determined by the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), relative to placebo, after 24 weeks in patients with VaD. Pooled data from two, randomised, double-blind, phase III trials showed that the least-squares mean change from baseline score effect size for the ADAS-cog was -1.79 for donepezil 5mg once daily (p < 0.001) and -2.28 for donepezil 10mg once daily (p < 0.001) at 24 weeks (observed cases). Significant improvement in global functioning occurred with donepezil 5mg once daily compared with placebo (p = 0.003), but not with donepezil 10mg once daily, as measured by the Clinician's Interview-Based Impression of Change-plus version score (pooled data, observed cases). Donepezil was generally well tolerated in patients with VaD. Most adverse events were mild to moderate in nature, with diarrhoea and nausea being the most common.

Administration, Oral↗

PubMed2004

Efficacy and safety of donepezil in patients with Alzheimer's disease: results of a global, multinational, clinical experience study.

BACKGROUND: Donepezil has consistently been shown to be effective and well tolerated in the symptomatic treatment of Alzheimer's disease in placebo-controlled clinical trials. It has been shown to provide significant benefits in cognition, global function and activities of daily living in patients with mild-to-moderate Alzheimer's disease. However, in order to control for confounding factors, some clinical trials of donepezil have excluded patients with comorbid illness and concomitant medication use. OBJECTIVE: The objective of this study was to evaluate the efficacy, tolerability and safety of donepezil in a wider and more diverse sample of patients and centres than previous trials, reflecting routine clinical practice. METHODS: In this 12-week, open-label, multicentre trial, patients with probable mild-to-moderate Alzheimer's disease received donepezil 5 mg/day for 28 days, after which the dosage was increased to 10 mg/day according to the investigating clinician's judgement. Patients were enrolled at 246 study centres in 18 countries worldwide. Cognition was assessed by a trained clinician using the Mini-Mental State Examination (MMSE) at baseline, week 4 and week 12 (or last visit). Changes in patient activity and social interaction were evaluated using a caregiver diary. Each week, caregivers recorded their impression of change compared with baseline on three aspects of patient behaviour using a 5-point scale. Efficacy analyses were performed on the intent-to-treat population. Significance was determined using the paired t-test (0.05 significance level). Tolerability and safety were assessed by monitoring adverse events, physical examinations, vital signs, clinical laboratory test abnormalities and ECG findings throughout the study. RESULTS: A total of 1113 patients received donepezil (mean baseline MMSE score [+/-SD] 18.74 +/- 5.21). 989 (88.9%) patients completed the study; 59 (5%) patients discontinued because of adverse events. Most patients were taking at least one concomitant medication (n = 802; 72%) and had at least one comorbid medical condition (n = 745; 67%) on study entry. Donepezil significantly improved cognition compared with baseline at weeks 4 and 12, and at week 12 using a last observation carried forward (LOCF) analysis (all p < 0.0001). Mean change from baseline MMSE score (+/-SE) at week 12-LOCF was +1.73 +/- 0.10. Donepezil was also associated with significant improvements in patient social interaction, engagement and interest, and initiation of pleasurable activities at all weekly assessments and week 12-LOCF (all p < 0.0001). Donepezil was generally well tolerated; adverse events were consistent with the known safety profile of donepezil. CONCLUSION: Donepezil treatment resulted in statistically significant improvements in cognition and patient activity and social behaviour, and was generally well tolerated despite high levels of comorbid illness and concomitant medication use. The results of this open-label study in a large patient population are consistent with those from controlled trials and support that donepezil is effective in the treatment of mild-to-moderate Alzheimer's disease in everyday practice.

Adult↗

PubMed2005

Risperidone: a review of its use in the treatment of bipolar mania.

Risperidone (Risperdal) is an atypical antipsychotic with high affinity for 5-hydroxytryptamine (5-HT)2A, dopamine D2 and alpha1- and alpha2-adrenergic receptors. Risperidone is now approved in the UK and the US for use in bipolar mania. Risperidone < or =6 mg/day, as monotherapy or adjunctive therapy with first-line mood stabilisers, significantly improves moderate and severe bipolar mania and improves global functioning over 3 weeks. Improvements in Young Mania Rating Scale (YMRS) scores in double-blind trials were greater with risperidone than with placebo over 3 weeks, and similar to those with haloperidol over 3 and 12 weeks. Risperidone was reasonably well tolerated. Limited data are available on the combination of risperidone and carbamazepine. Risperidone, as monotherapy or combined therapy with lithium or valproate semisodium, is an effective treatment option in bipolar mania.

Animals↗

PubMed2005

A randomized, double-blind, placebo-controlled pilot trial of safety and tolerability of two doses of divalproex sodium in outpatients with probable Alzheimer's disease.

OBJECTIVE: The Alzheimer's Disease Cooperative Study (ADCS) is conducting a clinical trial to address whether chronic valproate treatment can delay emergence of behavioral symptoms in outpatients with AD. Since there were no data on the safety and tolerability of divalproex sodium in outpatients with dementia, we undertook a pilot study to inform the design of the ADCS study. METHODS: We recruited 20 outpatients with probable AD, MMSE 10-20, without history of agitation or psychosis. This was a 10-week randomized, double-blind, placebo-controlled study assessing the safety and tolerability of 1,000 mg/day and 1,500 mg/day of divalproex sodium delayed-release for 8 weeks followed by extended-release for 2 weeks. Other outcome measures addressed cognition, function, global status, side effects, and laboratory data. RESULTS: Participants assigned to active treatment ingested approximately 30% less of their prescribed study medication compared to those receiving placebo (p < .05 Wilcoxon Rank Sum test). The average tolerated dose for all participants at week 8 was 810 mg/day or 11.5 mg/kg/day, similar to the dose tolerated by nursing home patients. The most common side effects were sleepiness and tiredness, with worse cognitive performance in those assigned to 1500 mg/day. CONCLUSIONS: These results were used to design the multi-center ADCS trial. Doses of less than 1000 mg/day of divalproex sodium were the maximum tolerated by these outpatients with AD. A larger study of divalproex sodium dose tolerability is needed to define treatment in outpatients with Alzheimer's disease.

Aged↗

PubMed2004

Testing psychometric properties of the standard Chinese version of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire 30 (EORTC QLQ-C30).

BACKGROUND: Because cancer is now the first and second leading causes of death in both of urban and suburban area in China, there are increasing demands for measurement tools to assess quality of life in Chinese cancer patients. The objective of this study was to evaluate the psychometric properties of the standard Chinese version of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire 30 (EORTC QLQ-C30, version 3.0). METHODS: The questionnaire was administered before, during, and after treatment of 143 patients with breast, gynecological, or lung cancer in six hospitals in China. RESULTS: Cronbach's alpha coefficients for multi-item scales were greater than 0.70 before and during treatment, except for the cognitive functioning scale. Multitrait scaling analysis showed that most of the item-scale correlation coefficients met the standards of convergent and discriminant validity. All scales and items exhibited good reproducibility, criterion-related validity, and construct validity. Score changes over time were observed in the following scales: physical, role, and social functioning; global quality of life; fatigue; nausea/vomiting. Score changes were also observed in the appetite loss item. CONCLUSION: The standard Chinese version of the EORTC QLQ-C30 is overall a valid instrument to assess the quality of life of Chinese cancer patients.

Adult↗

PubMed2006

Comparison of psychosocial outcomes in head and neck cancer patients receiving a coping strategies intervention and control subjects receiving no intervention.

This feasibility study aimed at comparing psychosocial outcomes in head and neck cancer patients receiving the Nucare program with a group of control subjects receiving no intervention. A prospective, nonrandomized study design was used. The Nucare program, a short-term psychoeducational coping strategies intervention, was the test intervention. Control subjects were matched to intervention subjects by cancer stage and time since cancer diagnosis. Outcomes were quality of life and depressive symptoms evaluated at baseline and 3 to 4 months later. One hundred thirty-eight subjects were recruited, and outcome data were available on 101 subjects. At outcome evaluation, compared with their baseline scores, the intervention group had improved physical and social functioning, global quality of life, fatigue, sleep disturbance, and depressive symptoms; the control group showed no changes in quality of life or depressive symptoms. The results suggest that the Nucare program may improve quality of life and reduce depressive symptoms in head and neck cancer patients.

Adaptation, Psychological↗