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At least 775 records · Page 43Linked to original sources

PubMed1997

Cellular mechanisms for developmental toxicity of chlorpyrifos: targeting the adenylyl cyclase signaling cascade.

Developmental neurotoxicity caused by chlorpyrifos exposure is generally thought to target cholinesterase but chlorpyrifos may also act on cellular intermediates, such as adenylyl cyclase, that serve global functions in the coordination of cell development. In the current study, neonatal rats were exposed to apparently subtoxic doses of chlorpyrifos (no weight loss, no mortality) either on Postnatal Days 1-4 or on Postnatal Days 11-14, and the effects on components of the adenylyl cyclase cascade were evaluated in brain regions that are enriched (forebrain) or sparse (cerebellum) in cholinergic innervation, as well as in a nonneural tissue (heart). In all three, chlorpyrifos evoked deficits in multiple components of the adenylyl cyclase cascade: expression and activity of adenylyl cyclase itself, functioning of G-proteins that link neurotransmitter and hormone receptors to cyclase activity, and expression of neurotransmitter receptors that act through this cascade. Disruption of signaling function was not restricted to transduction of cholinergic signals but rather extended to adrenergic signals as well. In most cases, the adverse effects were not evident during the immediate period of chlorpyrifos administration, but appeared after a delay of several days. These results suggest that chlorpyrifos can affect cell development by altering the activity and reactivity of the adenylyl cyclase signaling cascade, a major control point for trophic regulation of cell differentiation. The effects are not restricted to cholinergic targets, nor even to the central nervous system. Hence, disruption of cell development by chlorpyrifos is likely to be more widespread than previously thought.

Adenylyl Cyclases↗

PubMed1997

Integrative and interactive studies of the cardiac system: deciphering the cardionome.

The cardiac system, denoted as the Cardionome, represents one of the most exciting challenges to human ingenuity. Critical to our survival, it consists of a tantalizing array of interacting phenomena, from ionic transport, membrane channels and receptors through cellular metabolism, energy production, fiber mechanics, microcirculation, and electrical activation to the clinically observed global functions. These are measured by pressure, volume, shape, coronary flow, heart rate, and other changes. It is a complex interactive system requiring the intense efforts of capable scientists in the life sciences, including medicine, exact sciences, engineering and biomedical technology devoted to address these multivariable, multidisciplinary challenges, so as understand and control the pathologies involved. Here we present some of our past interactive studies and highlight two new models, one demonstrating micro to macro integration, and one involving tissue-organ interaction of various parameters. These models yield new insights into cardiac performance.

Animals↗

PubMed1984

Clinical value of phase and amplitude images and left ventricle time-activity curves in assessing patients with acute myocardial infarction.

The purpose of this study was to assess the clinical usefulness of phase and amplitude images and of the left ventricle time-activity curve (LVTAC) obtained by equilibrium gated radionuclide ventriculography (EGRV) in patients with acute myocardial infarction (AMI). Fifty-six patients were studied within 4 days of the onset of AMI by EGRV; of these 49 also underwent first-pass (FP) angiocardiography, for comparison with EGRV, and 21 underwent repeated EGRV 3 months after AMI. Phase and amplitude images were obtained by Fourier analysis. LVTAC analysis was performed by a third degree polynomial fitting to determine peak ejection rate (PER) and peak filling rate (PFR). A substantial equivalence of EGRV and FP methods was demonstrated, as regards left ventricle ejection fraction (LVEF), while a sharp superiority of EGRV with Fourier analysis was shown with regard to the sensitivity of RWM abnormality detection. With only one exception all the cases showed RWM abnormalities, while LVEF was normal in 21 of 27 patients with less than three affected segments. The most sensitive global function index was the LVPFR. In the acute phase regional dyskinesis was observed in 14 of 56 patients. About 40% of our cases showed an improvement of the kinetic abnormalities 3 months after AMI. The highest rate of improvement was observed in the group with ECG patterns of limited infarction and with normal LVEF.

Adult↗

PubMed1990

Role of single photon wall motion and perfusion studies in the evaluation of patients with suspected coronary artery disease.

Cardiovascular nuclear medicine procedures are useful to characterize coronary artery disease by measuring changes in perfusion, myocardial metabolism, cellular integrity, and regional or global function. Coronary angiography, while an excellent indicator of anatomic changes in arterial lumenal diameter, is a poor predictor of downstream perfusion, since neither the length of the stenosis nor absolute lumenal diameter is considered. Even if the anatomy is known, perfusion measurements provide information about ischaemia and ventricular dysfunction that is helpful for planning therapy. New technetium 99m-labelled perfusion agents are likely to improve the certainty of diagnosis due to their higher photon flux. The development of techniques for continuous ventricular function monitoring during daily activities provides an opportunity for detecting the impact of silent ischaemia on cardiac function. The role of the radionuclide imaging procedures in classifying patients with coronary disease is discussed in light of the pathophysiology of ischaemia and necrosis.

Coronary Disease↗

PubMed1995

Speech and language disorders in patients with high grade glioma and its influence on prognosis.

One hundred and sixteen patients with high grade glioma were entered into a prospective phase two study and treated with accelerated radiotherapy from 1988 to 1993. In this cohort of patients we analysed speech deficit as a subdivision of global functional status in terms of incidence, category and prognosis for survival. Forty three patients (37%) had a speech deficit at presentation. Eighty percent of these had a component of expressive dysphasia, associated with considerable degree of awareness and distress. The overall median survival was 9.5 months. On univariate analysis, median survival in patients with speech difficulties (6 months) was worse than patients with normal speech (10.5 months) (log rang p = 0.005). Multivariate analysis established independent significance from age, Karnofsky Performance Status (KPS), gender, histological grade, extent of surgery and seizures. This paper highlights the importance of assessing individual categories of functional disability which in patients with high grade glioma include mobility, cognitive function and communication. Each of these factors may seriously affect an individual's activities of daily living, hence quality of life and separate analysis has a number of clinical implications. Firstly, with over a third of patients suffering speech difficulties, adequate speech therapy facilities should be freely available to score the degree of deficit, devise coping strategies and institute communication therapy. Secondly, an understanding of prognostic factors aids the critical analysis of phase two studies and the design and stratification of future prospective trials which should include an analysis of speech deficit. Thirdly, separating individual patients into good and bad prognostic groups can assist strategic management decisions.

Adult↗

PubMed1990

A controlled evaluation of inpatient crisis treatment for acute schizophrenic episodes.

Acutely ill chronic schizophrenic patients requiring hospitalization were assigned to either an intensive crisis oriented (five day) or a short term (twenty-one day) inpatient unit. Despite intensive psychosocial treatment and initial rapid symptom reduction, the crisis patients could not be successfully discharged earlier than the short term patients. The crisis patients more frequently utilized day hospital aftercare and did not differ from the short term patients in symptom level or global functioning at three month follow-up. Limitations of very brief crisis oriented inpatient care for acutely ill schizophrenia patients are discussed.

Acute Disease↗

PubMed1984

[Digital subtraction angiocardiography--an alternative to traditional angiocardiography?].

Intravenous (i.v.) digital angiography has been extensively and successfully used for studying peripheral arterial vessels. Its application in the heart now results in high resolution images of the cardiac chambers. Accuracy and reproducibility of left ventricular volume determination equal that of conventional cineangiocardiography. Thus, left ventricular regional and global function can be analyzed quantitatively at rest and during exercise with higher simplicity and lower risk even on an outpatient basis by i.v. digital subtraction angiocardiography. To date, however, the coronary artery system cannot be visualized by digital image processing using i.v. injection of contrast medium, i.e., in patients win whom the coronary arteries have to be examined, selective arteriography for the future, too, will be combined with direct left ventricular angiocardiography. Regarding clinical experience till now, digital subtraction angiocardiography must be characterized as a complementary rater than an alternative method to conventional cineangiocardiography.

Angiocardiography↗

PubMed1989

Unipolar and bipolar schizoaffective disorders: a comparative study. I. Premorbid and sociodemographic features.

Seventy-two schizoaffective patients were investigated longitudinally (mean follow-up period 25.6 years). Unipolar (n = 37) and bipolar (n = 35) schizoaffectives were compared. Relevant differences in sociodemographic variables were found between the two groups, especially in: (a) sex distribution (more females among unipolar schizoaffectives), (b) social class, (c) occupational and educational level (higher in bipolars), and (d) premorbid personality (obsessoid and low-self-confidence personality types were more frequent in unipolars). Surprisingly there was no difference in age of onset, but some factors were identified that elevated the age of onset in bipolar and reduced it in unipolar schizoaffectives, which may explain this finding. Among bipolars there were more frequent relapses, but there was more suicidal symptomatology in unipolars. No differences were found with regard to long-term outcome, i.e. disability (Disability Assessment Schedule), level of functioning (Global Assessment Scale) or psychopathology at follow up.

Adult↗

PubMed1989

Unipolar and bipolar schizoaffective disorders: a comparative study. III. Long-term outcome.

Seventy-two schizoaffective patients were investigated longitudinally (mean follow-up period 25.6 years). Long-term outcome of unipolar (N = 37) and bipolar (N = 35) schizoaffectives was compared. Different aspects of outcome were investigated separately using standardized instruments of evaluation. No differences were found between unipolar and bipolar schizoaffective patients with regard to global functioning (GAS), disability (WHO/DAS) or psychopathological symptomatology at follow-up. There were also no differences in social consequences of the illness, i.e. downward occupational and downward social drift, premature retirement and achievement of the expected social development.

Adult↗

PubMed1995

An epidemiological and clinical approach to adolescent suicide. A comparison between suicidal and non-suicidal clinical groups in a health foundation center for French students.

Suicidal behaviour among young people represents a major public health problem. This study seeks to compare the major sociological, clinical, schooling and family features of suicidal and non-suicidal subgroups of adolescents hospitalised in the Health Foundation Center for French Students of neufmoutiers en Brie (France). All these adolescents suffered from the severe mental disorders. The adolescents from the suicidal subgroup presented significantly fewer psychoses and more mood disorders than those of the non-suicidal subgroup. Half of the patients from the suicidal subgroup presented some features of personality disorders, mostly borderline personality disorders. Nevertheless, their global functioning was more frequently improved between admission and discharge than was the case for the non-suicidal group.

Adolescent↗

PubMed1992

Schizoaffective disorders with and without onset in the puerperium.

The premorbid and sociodemographic features, long-term course and long-term outcome (on average 23.8 resp. 26.8 years after onset of illness) were compared in 30 female schizoaffective patients with onset of their illness during the puerperium and 60 female schizoaffective patients with onset at other times. The majority of premorbid and sociodemographic variables as well as course parameters were similar in the two groups. Most of the few differences (in age at first manifestation, marital state at onset, presence of stable heterosexual relationship before onset, acuteness of onset, presence of life events) are closely connected with the inclusion and exclusion criteria applied for the puerperal disorders (exclusion of patients with preexisting illness or psychiatric symptoms during pregnancy, inclusion only if onset was within 6 weeks of parturition). The puerperal schizoaffective disorders began more frequently with a schizomanic episode and less frequently with a schizodepressive episode than did the non-puerperal schizoaffective disorders, a finding which perhaps reflected the "pathoplastic" role of the puerperium on psychotic disorders. Several significant differences were found regarding the long-term outcome (frequency of persistent alterations, level of global functioning and disability, non-achievement of the expected social development, loss of autarky), confirming earlier findings that puerperal disorders generally have a better outcome than other psychotic disorders.

Adolescent↗

PubMed1995

A placebo-controlled trial of fluoxetine added to neuroleptic in patients with schizophrenia.

Following a 2-week placebo lead-in, schizophrenic patients were randomly assigned to fluoxetine 20 mg/day or placebo added to depot neuroleptic for a 6-week, double blind trial. All patients had received a stable dose of depot neuroleptic for at least 6 months and did not meet criteria for depression. Serum samples were obtained at baseline and at weeks 4 and 6. Scores on the negative symptom subscale of the Brief Psychiatric Rating Scale (BPRS) were significantly lower at week 6, controlling for baseline scores, in patients receiving fluoxetine (n = 20) compared to patients receiving placebo (n = 21). Measures of psychosis, depression, global functioning and extrapyramidal symptoms (EPS) did not differ between groups at week 6. Fluoxetine administration was associated with a mean 65% increase in serum fluphenazine concentrations in 15 patients and a mean 20% increase in serum haloperidol concentrations in three patients. The change in negative symptoms at week 6 did not correlate with serum concentrations of fluoxetine or norfluoxetine, but did inversely correlate with S-norfluoxetine, an active stereoisomer of fluoxetine. For these chronically ill patients, fluoxetine significantly improved negative symptoms and did not worsen EPS, despite causing substantial elevation in serum concentrations of neuroleptics.

Double-Blind Method↗

PubMed2002

Impaired fibrinolytic capacity in rheumatic mitral stenosis with or without atrial fibrillation and nonrheumatic atrial fibrillation.

Chronic atrial fibrillation (AF) has often been associated with systemic embolization, and patients with mitral stenosis (MS) have the highest thromboembolic risk. Increased risk of thromboembolism could be in part due to impaired fibrinolytic function. Global fibrinolytic capacity (GFC) is an innovative technique for evaluating the entire fibrinolytic system. The aim of our study was to evaluate fibrinolytic activity in patients with rheumatic and nonrheumatic chronic AE To investigate fibrinolytic activity, we assessed GFC in peripheral blood samples of 32 patients with nonrheumatic AF (14 women; mean age, 56 +/- 1 years), 30 patients with rheumatic MS and AF (23 women; mean age, 35 +/- 9 years), and 32 patients with rheumatic MS and sinus rhythm (24 women; mean age, 36 +/- 8 years). The control group comprised 30 healthy adult subjects in normal sinus rhythm. Patients with chronic AF (rheumatic and nonrheumatic) had lower GFC than did the controls (P = .0001). The rheumatic AF group also showed decreased levels of GFC compared with the nonrheumatic AF group, with the rheumatic MS and sinus rhythm group, and with controls (P = .03, P = .02, P = .0001, respectively). GFC was lower in patients with rheumatic MS and sinus rhythm than in controls (P = .003). Although there were correlations between GFC and mitral valve area, transmitral mean gradient, left atrial diameter, and mitral calcification in patients with rheumatic MS, multivariate analysis showed only transmitral gradient as an independent factor affecting GFC. Patients with AF have decreased GFC, a finding that suggests the presence of a hypofibrinolytic state. Fibrinolytic dysfunction was more pronounced in rheumatic MS patients with AF than in those with nonrheumatic AF. Moreover, patients with rheumatic MS and sinus rhythm had decreased global fibrinolytic activity. Hypofibrinolysis documented by decreased GFC can be one of the important causes of increased risk of embolism in patients with AF and rheumatic MS.

Adult↗

PubMed1991

The effects of pretreatment with nitroglycerin on ischemic left ventricular dysfunction during coronary angioplasty.

To evaluate the degree to which nitroglycerin reduces myocardial ischemia and dysfunction induced by transient coronary occlusion, 19 patients were studied during coronary angioplasty of the left anterior descending coronary artery. After a control occlusion of 60 seconds, 0.2 mg nitroglycerin was administered intravenously and the occlusion was repeated for 60 seconds. Before and during the occlusion period, pulmonary capillary wedge pressure was measured, the intracoronary ECG was recorded, and ventricular volumes, ejection fraction, and regional systolic shortening were obtained by digital subtraction angiography. Nitroglycerin caused a significant fall in pulmonary capillary wedge pressure before (10 vs. 7 mmHg) and at 60 seconds occlusion (18 vs. 14 mmHg), but did not significantly delay the rise in wedge pressure (37 vs. 44 seconds). End-systolic left ventricular volume at 60 seconds of occlusion was reduced by nitroglycerin (77 vs. 68 ml), whereas regional shortening of the ischemic segments remained unchanged (22 vs. 23%). Nitroglycerin did not delay the onset of ischemic ST-segment elevation (14 vs. 14 seconds) and had no effect on the changes of ST elevation in the intracoronary ECG (1.9 vs. 1.9 mV). These findings suggest that intravenous nitroglycerin reduces filling pressure and slightly improves left ventricular global function during acute coronary occlusion. Nitroglycerin, however, has little effect on ischemia-induced regional dysfunction and on ST-segment elevation in the intracoronary ECG.

Adult↗

PubMed2001

Clinical aspects of Alzheimer's disease.

Alzheimer's disease (AD) is the most common of the dementing disorders. AD begins insidiously and progresses gradually; it is characterized clinically not only by an impairment in cognition, but also by a decline in global function, a deterioration in the ability to perform activities of daily living, and the appearance of behavioral disturbances. No definitive tests for the diagnosis are available, and AD is a diagnosis of inclusion based on patient history, physical examination, neuropsychological testing, and laboratory studies. Disease progression is highly variable, and median survival after the onset of dementia ranges from 5 to 9.3 years. Early recognition of AD allows time to plan for the future, and to treat patients before marked deterioration occurs.

Aged↗

PubMed1999

Deficit syndromes in schizophrenic patients 15 years after their first hospitalisation: preliminary results of a follow-up study.

This study is a follow-up study on broadly defined schizophrenic disorders. Patients were assessed standardized at the time of their first hospitalization (admission and discharge) and reassessed in an standardized manner 15 years later. The aim of the analyses presented here was to evaluate the frequency of patients with markedly expressed negative symptoms in terms of deficit syndrome and to analyze which of the variables assessed at the time of first hospitalization were predictive concerning deficit syndromes at follow-up. Results indicate that nearly one third of patients have developed a deficit syndrome 15 years after their first hospitalization. These patients are characterized by severe impairments in important areas of life, such as partnership or employment. Furthermore, apart from more pronounced negative symptoms, these patients also have more paranoid-hallucinatory symptoms than schizophrenic patients without deficit syndromes. Predictive signs for non-development of a deficit syndrome 15 years later were good global functioning, female gender, pronounced depressive symptoms and good treatment response concerning negative and paranoid-hallucinatory symptoms at first hospitalization. A longer duration of symptoms prior to first hospitalization, lack of a partnership, pronounced negative symptoms at admission and at discharge were predictive of developing a deficit syndrome. Results are discussed with regard to the literature and to methodological limitations.

Adult↗

PubMed2006

The Nudix hydrolase superfamily.

Nudix hydrolases are found in all classes of organism and hydrolyse a wide range of organic pyrophosphates, including nucleoside di- and triphosphates, dinucleoside and diphosphoinositol polyphosphates, nucleotide sugars and RNA caps, with varying degrees of substrate specificity. Some superfamily members, such as Escherichia coli MicrotT, have the ability to degrade potentially mutagenic, oxidised nucleotides while others control the levels of metabolic intermediates and signalling compounds. In prokaryotes and simple eukaryo tes, the number of Nudix genes varies from 0 to over 30, reflecting the metabolic complexity and adaptability of the organism. Mammals have around 24 Nudix genes, several of which encode more than one variant. This review integrates the sizeable recent literature on these proteins with information from global functional genomic studies to provide some insights into the possible roles of different superfamily members in cellular metabolism and homeostasis and to stimulate discussion and further research into this ubiquitous protein family.

Animals↗

PubMed2007

Epigenetic control of nuclear architecture.

The cell nucleus is a highly structured compartment where nuclear components are thought to localize in non-random positions. Correct positioning of large chromatin domains may have a direct impact on the localization of other nuclear components, and can therefore influence the global functionality of the nuclear compartment. DNA methylation of cytosine residues in CpG dinucleotides is a prominent epigenetic modification of the chromatin fiber. DNA methylation, in conjunction with the biochemical modification pattern of histone tails, is known to lock chromatin in a close and transcriptionally inactive conformation. The relationship between DNA methylation and large-scale organization of nuclear architecture, however, is poorly understood. Here we briefly summarize present concepts of nuclear architecture and current data supporting a link between DNA methylation and the maintenance of large-scale nuclear organization.

Animals↗