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PubMed1998

Amplitudes, durations, and timings of apically directed left ventricular myocardial velocities: I. Their normal pattern and coupling to ventricular filling and ejection.

BACKGROUND: The left ventricular (LV) major axis shortening is an important determinant of its global function. But unlike the LV minor axis dynamics, the long-axis dynamics have not been well characterized. We investigated the amplitudes, durations, and timings of LV long-axis myocardial velocities and related them to LV filling and ejection in normal healthy volunteers. METHODS AND RESULTS: Myocardial velocities from the basal, mid, and distal portions of the four LV walls were recorded from the apical window with spectral Doppler tissue imaging in 20 normal individuals. The timings, amplitudes, and durations were measured and compared both longitudinally and circumferentially. These were also related to mitral inflow and LV ejection. Analysis of the recordings indicated that there were three principal myocardial velocities: apically directed systolic velocity and atrially directed early and late diastolic velocities. The LV posterior wall had the highest shortening velocity and the amount of shortening. The lateral wall had the greatest amplitude of early diastolic lengthening velocity, amount of lengthening, and early to late lengthening velocity and integral ratios, probably indicating most favorable early diastolic properties. There was a striking synchrony in the myocardial velocities circumferentially. The myocardial velocities dropped progressively as the sampling site was moved distally and the LV apex was practically stationary. Although the onsets of the velocity profiles were simultaneous in the meridional orientation, their durations were shorter distally. All myocardial velocities preceded the corresponding blood flow velocities. They also ended before the corresponding blood flow velocities, this being more pronounced in the distal myocardial segments, indicating the presence of inertial factors responsible for the terminal portions of mitral and aortic flows. CONCLUSIONS: Recording of apically directed myocardial velocities gives valuable insights into the regional myocardial function. These velocities show significant regional variations in healthy normal individuals. It is speculated that analysis of regional myocardial velocities may have a role in the diagnosis of early myocardial disease.

Adult↗

PubMed2003

The impact of the duration of untreated psychosis prior to first psychiatric admission on the 15-year outcome in schizophrenia.

OBJECTIVE: There is a large amount of evidence to support the hypothesis that the duration of untreated psychosis (DUP) prior to first psychiatric admission adversely affects acute treatment response and short-term outcome in schizophrenia. However, only few prospective studies have attempted to address a possible association between DUP and long-term outcome. METHOD: Fifty-eight DSM-III-R schizophrenic patients were assessed at their first psychiatric admission and after a 15-year course of the illness. The 15-year outcome in different domains was compared between patients with different DUPs prior to the first psychiatric admission. RESULTS: A longer DUP was associated with more pronounced negative, positive and general psychopathological symptoms as well as a lower global functioning 15 years after the first psychiatric admission, even after effects of other factors, possibly related to the long-term outcome, were controlled for. CONCLUSIONS: The DUP prior to first psychiatric admission adversely affects the long-term outcome in schizophrenia. The findings underline the importance of establishing health service programs for early detection and treatment of schizophrenic patients with the aim to shorten the DUP and to consequently improve the course and outcome of schizophrenic patients.

Acute Disease↗

PubMed1998

Neurological abnormalities in schizophrenia: clinical, etiological and demographic correlates.

An increased rate of neurological abnormality (NA) is typically observed in samples of schizophrenic patients, but the origin and relevance of the NA remain unclear. To investigate this further, relationships were studied between the patient's degree of NA and a range of clinical, putative etiological and demographic characteristics among 60 patients with schizophrenia who had previously been shown to have an elevated rate of NA. No significant relationships were found between NA and demographic, etiological or most clinical history characteristics, including past and current neuroleptic exposure. However, an increased rate of NA was significantly related to current poor global functioning. In total, the findings suggest that NA may represent one manifestation of an early and rather stable disease process, with an additional fluctuating clinically related component.

Adult↗

PubMed1998

Training schizophrenic patients to manage their symptoms: predictors of treatment response to the German version of the Symptom Management Module.

This study examined whether patient demographic and clinical characteristics were predictors of differential treatment response in a sample of 57 schizophrenic patients who received the German version of the Symptom Management Module. Psychopathology, global functioning and knowledge about schizophrenia were assessed as dependent variables. Overall, patients improved over the treatment period on most dimensions of psychopathology as well as knowledge about psychosis. There was little evidence of differential treatment response as a function of either sociodemographic or clinical variables. However, gender was related to changes in psychopathology from pre- to posttreatment, with females improving less than males. Possible implications of these findings were discussed.

Adaptation, Psychological↗

PubMed1998

Slower and more variable reaction times in schizophrenia: what do they signify?

Extensive research has demonstrated that schizophrenic subjects are slower than normal comparison subjects on a range of reaction-time tasks. Some investigators have also observed that schizophrenic patients exhibit larger intraindividual variability in reaction times when performing these tasks than do normal comparison subjects. This study, using a lexical decision choice reaction time (CRT) task, explored the relation of mean CRT and it intra-individual variability (CRT-SD) to psychiatric symptoms and to performance on executive-motor tasks in 26 medication-free schizophrenic out-patients and 17 normal comparison subjects. Schizophrenic subjects had both significantly slower and more variable CRTs which were unrelated to general intellectual abilities (IQ). Among schizophrenic subjects, both CRT and CRT-SD were significantly related to severity of psychotic symptoms, failure to maintain cognitive set, and poorer motor coordination and global functioning. After controlling for mean CRT, CRT-SD showed unique covariation with clinical symptoms (positive, disorganized and tension/hostility). Conversely, mean CRT showed unique covariation with the failure to maintain cognitive set and with stereotypic mannerisms, independent of CRT-SD. These results suggest that slower CRT and increased intra-individual variability in CRT, while not fully independent of one another, may reflect separate aspects of symptomatic and cognitive dysfunction in schizophrenia.

Adult↗

PubMed1999

The construct validity of empowerment among consumers of mental health services.

Subscales of the Empowerment Scale (Rogers, E. S., Chamberlin, J., Ellison, M. L., Crean, T., 1997. A consumer-constructed scale to measure empowerment among users of mental health services. Psychiatr. Serv. 48, 1042-1047) were examined to see whether they fit a model of consumer empowerment that distinguishes self- and community orientations. In addition, the relationship of these two superordinate factors to several psychosocial factors was examined. Thirty-five participants in a partial hospitalization program were administered the Empowerment Scale and measures of quality of life, social support, self-esteem, psychiatric symptoms, needs and resources, global functioning, and verbal intelligence. Analysis of the subscales of the Empowerment Scale yielded two factors consistent with self- and community orientations to empowerment. Correlational analyses revealed that the two superordinate factors were associated with different sets of psychosocial variables. A self-orientation to empowerment was significantly associated with quality of life, social support, self-esteem, and psychiatric symptoms. Community orientation was correlated with self-esteem, resources, verbal intelligence, and ethnicity. The implications of these findings for a model of consumer empowerment are discussed.

Adult↗

PubMed1999

Rehabilitation of schizophrenic and other long-term mentally ill patients. Results from a prospective study of a comprehensive inpatient treatment program based on cognitive therapy.

A total of 28 long-term mentally ill patients, the majority schizophrenic, treated with cognitive therapy in the context of milieu-therapy and group therapy, were investigated at admission and discharge with regard to changes in symptomatology, quality of life, global functioning, need for medication, and perceived target complaints. The results showed a significant relief in perceived burden of illness and an improvement in quality of life. A better pre-admission functioning with regard to social functioning, occupational function, and symptoms predicted a more favourable outcome.

Adult↗

PubMed1999

Clinical benefits of a new piperidine-class AChE inhibitor.

Alzheimer's disease (AD) is associated with a deficiency of acetylcholine (ACh) in the forebrain that correlates with brain pathology and cognitive dysfunction. The most promising approach to enhancing central ACh neurotransmission has been the utilization of agents that inhibit cholinesterases which block its catabolism. Initially, the success of this strategy was limited by subtherapeutic levels of acetylcholinesterase (AChE) inhibition, tolerability problems and toxicity of the first agents. Donepezil HCI represents a new chemical class of AChE inhibitors, the piperidines. In clinical trials, donepezil has been shown to improve significantly cognition and global function in patients with mild to moderately severe AD, and has demonstrated an excellent tolerability and safety profile. These benefits, as well as a simple, once-daily dosing regimen, make donepezil a viable therapeutic option for AD patients.

Aged↗

PubMedDate not supplied

Fuzzy methods in tremor assessment, prediction, and rehabilitation.

Tremor is a disabling condition for a large segment of population, mainly elderly. To the present date, there are no adequate tools to diagnose and help rehabilitation of subjects with tremor, but recently there is a tremendous surge of interest in the research in the field. We report on the use of fuzzy methods in applications for rehabilitation, namely in tremor diagnosing and control. We synthesize our results regarding the characterization of the tremor by means of nonlinear dynamics techniques and fuzzy logic, and the prediction of tremor movements in view of rehabilitation purposes. Based on linear and nonlinear analysis of tremor, and using fuzzy aggregation, the fusing of tremor parameters in global functional disabling factors is proposed. Nonlinear dynamic parameters, namely correlation dimension and Lyapunov exponent is used in order to improve the assessment of tremor. The benefits of the fuzzy fused tremor parameters rely on more complete and accurate assessment of the functional impairment and on improved feedback for rehabilitation, based on the fused parameters of the tremor. Further steps in rehabilitation may require external muscular control. In turn, the control of tremor by electrical stimulation requires movement prediction. Several neural and neuro-fuzzy predictors are compared and a neuro-fuzzy predictor is presented, allowing us five-step ahead prediction, with an RMS error of the order of 10%. The benefits of the neuro-fuzzy predictor are good prediction capability, versatility, and apparently a high robustness to individual variations of the tremor. The reported research, which extended over several years and included development of sensors, equipment, and software, has been aimed to development of products. The results may also open new ways in tremor rehabilitation.

Aged↗

PubMed2000

Health-related quality of life in patients with anaplastic astrocytoma during treatment with temozolomide.

One of the objectives of this phase II study was to determine whether temozolomide (TMZ) improved the health-related quality of life (HRQL) of patients with recurrent anaplastic astrocytoma (AA). HRQL was assessed at baseline (pretreatment) and every 4 weeks at each treatment cycle using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) (version 2.0) and the Brain Cancer Module (BCM20). Changes from baseline in the scores of seven preselected HRQL domains (role and social functioning, global QL, visual disorder, motor dysfunction, communication deficit and drowsiness) were determined at 6 months as well as prior to, and at the time of, disease progression. The significance of the changes was assessed by calculating statistical significance, effect sizes and the proportions of patients with improvement in their HRQL scores (changes of >/=10 points). After 6 months of treatment, patients who were free of progression of disease reported either an improvement or maintenance of all the preselected HRQL domains scores. Patients with disease progression by 6 months usually experienced improvement in HRQL before progression, but there was a sharp decline in most of the preselected domains at progression. We conclude that treatment of recurrent AA with temozolomide is associated with significant HRQL benefits.

Adult↗

PubMedDate not supplied

Tachycardia-induced primate model of heart failure in cardiovascular drug discovery.

Congestive heart failure (CHF) is a complex, multifactoral disease involving genetic and environmental factors that represents a large unmet medical need. There are currently many animal models of CHF that have provided some insight into the etiology of this disease. However, due to the complex interactions of environmental and genetic components of this disease most animal models are somewhat limited. Nonhuman primates offer a unique opportunity to investigate the genetic aspects of this complex disease due to their close genetic and phenotypic similarity to humans. Here we describe a novel tachycardia-induced primate model of CHF characterized by depressed global function that progresses to a symptomatic stage consistent with clinical data. No animal model, including this one, can exactly mimic the clinical pathophysiology of CHF. However, this tachycardia-induced primate model of CHF has similarities to the dynamic state of CHF in humans and affords the opportunity to evaluate changes in gene expression using genomic and proteomic technologies throughout the progression of the disease.

Animals↗

PubMedDate not supplied

Quantitative analysis of technetium 99m 2-methoxyisobutyl isonitrile single-photon emission computed tomography and isosorbide dinitrate infusion in assessment of myocardial viability before and after revascularization.

BACKGROUND: Assessment of viable myocardium in territories of hypoperfused myocardium is important for predicting functional recovery after revascularization. This study was designed to evaluate quantitative analysis of 99mTc-labeled 2-methoxyisobutyl isonitrile (MIBI) myocardial perfusion imaging combined with isosorbide dinitrate (ISDN) infusion to detect myocardial viability in patients with chronic coronary artery disease before and after revascularization. METHODS AND RESULTS: Twenty-seven consecutive patients with previous myocardial infarction and left ventricular dysfunction (left ventricular ejection fraction 35.2% +/- 13.5%) referred for coronary artery bypass (CABG) were studied with 99mTc-labeled MIBI single-photon emission computed tomography at rest and during ISDN infusion before CABG followed by resting imaging after CABG. Quantitative analysis was performed with circumferential profiles. Left ventricular function (global and regional) was assessed by radionuclide ventriculography before and after CABG. Out of 212 abnormal perfusion segments with resting 99mTc-labeled MIBI SPECT, 99 segments (47%) showed improved uptake of 99mTc-labeled MIBI during ISDN infusion. The mean ratio of myocardial uptake was 0.58 +/- 0.25 (resting 0.53 +/- 0.23; p < 0.05). After CABG, of 212 segments with hypoperfusion, 108 segments (51%; p > 0.05 vs ISDN) showed improved uptake of 99mTc-labeled MIBI. The mean ratio of myocardial uptake was 0.60 +/- 0.26 (resting 0.53 +/- 0.23; p < 0.05). The concordance between the improvement of post-CABG wall motion and that of pre-CABG ISDN perfusion imaging was 83%, between the improvement of wall motion and perfusion imaging after CABG 94%, and between the improvement of pre-CABG ISDN and post-CABG perfusion imaging 83%, respectively. CONCLUSION: ISDN infusion can improve the uptake of 99mTc-labeled MIBI in hypoperfused myocardium and increase the efficiency of 99mTc-labeled MIBI in the detection of viable myocardium in patients with previous myocardial infarction and left ventricular dysfunction.

Coronary Artery Bypass↗

PubMedDate not supplied

Enhanced detection of reversible myocardial hypoperfusion by technetium 99m-tetrofosmin imaging and first-pass radionuclide angiography after nitroglycerin administration.

BACKGROUND: Reversal of ischemia after myocardial infarction by revascularization is worthwhile only if viability exists in a sufficiently large portion of the left ventricle. METHODS AND RESULTS: To determine myocardial hypoperfusion reversibility and its influence on segmental and global function, we studied 50 patients after myocardial infarction. Three technetium 99m-tetrofosmin scintigraphies were performed: 1 at rest, 1 after 0.6 mg sublingual nitroglycerin (NTG), and 1 after injection at peak stress. First-pass multigated radionuclide angiography was obtained at rest and after NTG. Each patient also underwent a stress redistribution-reinjection thallium-201 scintigraphy. During stress 99mTc-tetrofosmin, 104 segments had normal uptake, 51 showed moderately reduced uptake, and 186 had severely reduced uptake. Of these 186 segments, 33 (18%) improved at rest, and 41 (22%) improved only after NTG. Fifty-nine (79%) of these segments with improved uptake were also found to have reversible defects on 201TI imaging. In the 26 patients with ventricular dysfunction, a 73% agreement was found between the functional and 99mTc-tetrofosmin uptake post-NTG improvement, whereas a 69% agreement was found with thallium reinjection. No significant differences were seen between 99mTc-tetrofosmin and 201T1 imaging. CONCLUSION: Nitroglycerin administration during 99mTc-tetrofosmin scintigraphy improves the detection of myocardium with reversible hypoperfusion in patients with a previous myocardial infarction.

Adult↗

PubMed2004

Selective recognition of distinct classes of coactivators by a ligand-inducible activation domain.

How nuclear receptors (NRs) coordinate the sequential, ligand-dependent recruitment of multiple coactivator complexes (e.g., SRC complexes and Mediator) that share similar receptor binding determinants is unclear. We show that although the receptor binding subunits of these complexes (i.e., SRCs and Med220, respectively) share overlapping binding sites on estrogen receptor alpha (ERalpha), information contained in the receptor-coactivator interface allows the receptor to distinguish between them. In support of this conclusion, we have identified an ERalpha AF-2 point mutant (L540Q) that selectively binds and recruits Med220, but not SRCs, both in vitro and in vivo. In cells expressing this mutant, the recruitment of Med220 to the pS2 promoter is delayed, and the expression of the vast majority of estrogen target genes is impaired, suggesting a nearly global functional interdependence of these coactivators. Collectively, our results suggest that "facilitated recruitment," rather than competition, drives the sequential recruitment of SRC complexes and Mediator by NRs.

Binding Sites↗

PubMed2003

Molecular genetics of leaf senescence in Arabidopsis.

Leaf senescence is a developmentally programmed degeneration process that constitutes the final step of leaf development and is controlled by multiple developmental and environmental signals. In addition to the information obtained from other plants, Arabidopsis has, as a model system, contributed to our understanding of this complex phenomenon in molecular genetic terms. Recent discoveries have identified several genetic mutants and potential regulatory components in Arabidopsis. Identifying further mutants that exploit novel biological resources, screening Scheme and a global functional analysis of senescence-associated genes in Arabidopsis should increase our understanding of the complex regulatory networks.

Aging↗

PubMed2002

Automatic recognition of cortical sulci of the human brain using a congregation of neural networks.

This paper describes a complete system allowing automatic recognition of the main sulci of the human cortex. This system relies on a preprocessing of magnetic resonance images leading to abstract structural representations of the cortical folding patterns. The representation nodes are cortical folds, which are given a sulcus name by a contextual pattern recognition method. This method can be interpreted as a graph matching approach, which is driven by the minimization of a global function made up of local potentials. Each potential is a measure of the likelihood of the labelling of a restricted area. This potential is given by a multi-layer perceptron trained on a learning database. A base of 26 brains manually labelled by a neuroanatomist is used to validate our approach. The whole system developed for the right hemisphere is made up of 265 neural networks. The mean recognition rate is 86% for the learning base and 76% for a generalization base, which is very satisfying considering the current weak understanding of the variability of the cortical folding patterns.

Artificial Intelligence↗

PubMed2000

Genomic approaches to plant disease resistance.

Genomic approaches are beginning to revolutionize our understanding of plant disease resistance. Large-scale sequencing will reveal the detailed organization of resistance-gene clusters and the genetic mechanisms involved in generating new resistance specificities. Global functional analyses will elucidate the complex regulatory networks and the diversity of proteins involved in resistance and susceptibility.

Genes, Plant↗

PubMed2005

Effects of rivastigmine treatment on the neuropsychiatric and behavioral disturbances of nursing home residents with moderate to severe probable Alzheimer's disease: a 26-week, multicenter, open-label study.

BACKGROUND: Alzheimer's disease (AD) is the most common form of dementia and is characterized clinically by a gradual decline in cognitive performance, an increasingly impaired ability to perform activities of daily living, and neuropsychiatric and behavioral disturbances. OBJECTIVE: The goal of this study was to assess the effect of rivastigmine on the neuropsychiatric and behavioral disturbances of nursing home residents with moderate to severe probable AD and to evaluate the safety and tolerability of rivastigmine in this population. METHODS: This prospective, 26-week, open-label study was conducted in 13 centers in the United States and involved a total of 29 nursing homes. The effects of rivastigmine 3 to 12 mg/d for 26 weeks were assessed in nursing home residents with moderate to severe probable AD. Efficacy was evaluated using the Neuropsychiatric Inventory-Nursing Home (NPI-NH) scale for neuropsychiatric and behavioral disturbances; the Mini-Mental State Examination and the naming subset of the Alzheimer's Disease Assessment Scale-Cognitive subscale for cognitive performance; and the simplified Clinician's Interview-Based Impression of Change Plus Caregiver Input for global functioning. RESULTS: A total of 173 patients (141 women, 32 men; mean [SD]age, 82.6 [5.9] years) were enrolled. After 26 weeks of rivastigmine treatment, the mean (SD) change from baseline for all treated patients in the observed cases population was -2.5 (16.4) (n = 100; P = 0.138); it was -0.8 (16.5) (n = 149; P = 0.576) for the last-observation-carried-forward population. Patients with at least 1 neuropsychiatric symptom present at baseline showed a 3.2-point mean improvement in NPI-NH total score (n = 92; P = 0.062), with 49% of these patients demonstrating a clinically meaningful (ie, > or = 30%) reduction from baseline. At 26 weeks, scores for 8 of the 12 neuropsychiatric and behavioral disturbances in patients with the specific symptom present at baseline showed statistically significant improvements from baseline (delusions [n = 32; P = 0.007], hallucinations [n = 15; P < 0.001], agitation [n = 58; P = 0.044], apathy/indifference [n = 37; P < 0.001], irritability/lability [n = 50; P < 0.001], aberrant motor behavior [n = 32; P < 0.001], nighttime disturbances [n = 22; P < 0.001], and appetite/eating changes [n = 28; P = 0.002]) in the observed cases population. Limitations of this study include that it was open label and not restricted to patients with behavioral disturbances at baseline. CONCLUSION: In the current study, rivastigmine treatment for 26 weeks in nursing home residents with moderate to severe probable AD was associated with decreased NPI-NH item scores for a wide range of behavioral disturbances in the subgroup of patients with behavioral symptoms at baseline.

Aged↗