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Echocardiographic evaluation of global left ventricular function during high thoracic epidural anesthesia.

OBJECTIVES: To assess the effects of high thoracic epidural anesthesia on left ventricular (LV) diastolic filling and systolic function in patients without heart disease. DESIGN: Prospective study. SETTING: University hospital. PARTICIPANTS: 24 ASA physical status I and II patients scheduled for elective noncardiac surgery. INTERVENTIONS: Patients received high thoracic (HTE; n = 12) or low thoracic (LTE; n = 12) epidural anesthesia. MEASUREMENT AND MAIN RESULTS: Left ventricular diastolic filling was noninvasively determined by precordial echocardiography using a pulsed Doppler technique and with a newly developed acoustic quantification (AQ) method that automatically detects endocardial borders and measures cavity area. All measurements were performed in awake premedicated patients. In the HTE group, the extent of sensory blockade of T1-T5, at the least, was induced with 2% lidocaine 5 ml. During HTE, systolic blood pressure (119 +/- 16 vs. 108 +/- 14 mmHg, p < 0.01), heart rate (73 +/- 9.8 vs. 63 +/- 6.8 beats/min, p < 0.01), cardiac output (CO; 4.5 +/- 1.1 vs. 3.8 +/- 1.2 L/min, p < 0.05), and fractional area change (50 +/- 11 vs. 37 +/- 11%, p < 0.01) decreased significantly, whereas end diastolic area (9.4 +/- 1.4 vs. 10.3 +/- 1.1 cm2, p < 0.01) and end systolic area (4.8 +/- 1.3 vs. 6.0 +/- 1.1 cm2, p < 0.05) showed a significant increase. As a result, stroke volume was kept constant (63 +/- 14 vs. 60 +/- 19 ml). Pulsed Doppler derived indices such as peak velocity during the early filling (E) and the atrial contraction (A) phases, peak early to atrial velocity ratio (E/A), and acceleration time remained unchanged. AQ derived peak dA/dt during the early diastolic (D1) and the atrial contraction phases (D2) and D1/D2 also remained unchanged. In contrast, in the LTE group, no significant differences were noted in all systolic and diastolic indices obtained by pulsed Doppler and AQ method. CONCLUSIONS: High thoracic epidural anesthesia causes a decrease in CO without changing LV ejection and diastolic filling performance in healthy subjects.

Adult↗

Effect of electroconvulsive therapy in repetitive transcranial magnetic stimulation non-responder MDD patients: a preliminary study.

The aim of this study was to measure the effectiveness of ECT in-patients who had failed to respond to a course of repetitive transcranial magnetic stimulation (rTMS) treatment. Seventeen patients with severe MDD who had not responded to a course of rTMS were switched to receive ECT treatments. All the patients were assessed with the Hamilton Rating Scale for Depression, the Global Assessment Functioning Scale, the Global Depression Scale, and the Pittsburgh Sleep Quality Index. Response to the treatment was defined as a 50% decrease in HDRS final score and a final GAS higher than 60. Seven out of 17 patients responded to ECT. Three out of 5 non-psychotics and 4 out of 12 psychotic patients responded. ECT seems to be an effective treatment for 40% of patients who failed to respond to rTMS treatment. Whether this is a result of reduced responsiveness to ECT in rTMS-resistant patients or a consequence of small sample size requires further study.

Adult↗

Gradual development of protein-like global structures through functional selection.

This work focuses on streamlining the exploration of all possible sequences in an attempt to find polypeptides capable of folding into unique structures. Using a computer simulation, we have demonstrated the efficacy of constraining an 'active site' toward the correct configuration, in this case a particular conformation of a four-residue sequence, to bring about protein-like structure from a significant fraction of random sequences. The successive selections for a correct local configuration lead also to the gradual development of overall folding ability, helicity and compactness within 200 generations. The selection thus imposed alleviates an exhaustive search in sequence space.

Computer Simulation↗

Hypervolaemia improves global and local function and efficiency in postischaemic myocardium.

1. In the present study, we investigated the effects of blood volume on postischaemic function and efficiency. In 14 anaesthetized dogs, following recovery from a period of 15 min occlusion of the left anterior descending coronary artery, the effects of hypervolaemia (HYPER; 15% increased volume produced by fast infusion of Hespan; B Braun Medical, Irvine, CA, USA), normovolaemia (NORMO) and hypovolaemia (HYPO) were studied. 2. Although myocardial O2 consumption was not significantly increased by volume (6.37+/-0.94 vs 6.89+/-1.1 mL/min per 100 g for HYPO and HYPER, respectively), local work of the stunned myocardium was markedly elevated (8.8+/-1.7 vs 22.5+/-3.5 g.mm/ beat, for HYPO and HYPER, respectively; P < 0.05). External work of the heart was also significantly improved (71.8+/-12.7 vs 139.5+/-16.2 mmHg.L/min for HYPO and HYPER, respectively). These data indicate markedly improved efficiency produced by volume, because work was increased with no change in myocardial O2 consumption. 3. Local dysfunction was characterized by several parameters, including systolic bulge, end-diastolic length, delay to onset of shortening, end shortening time delay (EST) and tail work ratio. Hypervolaemia reduced EST compared with hypovolaemia (98.6+/-18.3 vs 110.7+/-14.9 msec, respectively; P < 0.05) and improved tail work ratio (28.0+/-7.0 vs 36.0+/-7.0%, respectively; P < 0.05), with no effects on systolic bulge, end-diastolic length and delay to onset of shortening. 4. Thus, even in the postischaemic myocardium, increasing work by volume is energetically efficient and is accompanied by partial improvement of local dysfunction.

Animals↗

Determining vulnerability to schizophrenia in methamphetamine psychosis using exploratory eye movements.

Patients with methamphetamine (MAP) psychosis whose psychotic symptoms continued after MAP withdrawal were observed at Saitama Prefecture Government Psychiatric Hospital. The purpose of the present study was to ascertain whether some of these MAP psychosis subjects have a vulnerability to schizophrenia. Forty-eight patients with MAP psychosis were divided into three groups based on clinical course: transient type, prolonged type and persistent type. Furthermore, the patients with the persistent type were divided into two groups: one group were moderately disturbed in social adaptive functioning and had Global Assessment Functioning scale (GAF) points >50, and the other group consisted of those who were severely disturbed in social adaptive functioning and who had GAF points of < or =50. These MAP patients were tested for exploratory eye movements, which are the vulnerability marker of schizophrenia, and were compared with 30 patients with schizophrenia and 30 healthy control subjects. The responsive search score of the severely disturbed group of patients of the persistent type was lowest, significantly lower than those of the transient type and the healthy controls. It did not differ from that of the schizophrenic subjects. These results suggest that the severely disturbed group of patients with the persistent type of MAP psychosis have a vulnerability to schizophrenia.

Adult↗

Hypothesis: the rate and scale of dispersal of freshwater diatom species is a function of their global abundance.

We have analysed the geographical records of a representative selection of extant diatom species from a freshwater pond. The more often a species is recorded in the ecological literature, the greater is its apparent global distribution. One explanation is that the frequently recorded species are globally abundant, whereas species that are infrequently recorded are globally rare. We suggest a model in which random dispersal is the dominant force driving large-scale distribution of species, with the rate and scale of dispersal largely determined by global population size. Thus species that are locally rare or abundant are likewise rare or abundant worldwide. It is predicted that many of the rarer diatom species will, with additional sampling effort, be shown to have wide geographical distribution, but this requires intensive studies focused on revealing species that are normally cryptic. The argument in favour of endemic diatom species is untenable, because it is not possible to disprove their existence elsewhere in the biosphere.

Diatoms↗

Global view on functional foods: European perspectives.

In the context of this presentation, European means the European scientific community, which, over the last decade, has been working on the concepts for functional foods, producing a number of documents including a consensus paper, guidelines and scientific publications. The Functional Food Science in Europe (FUFOSE) project has been quite a unique attempt to establish a strong scientific framework to justify the functional food concept, to discover and develop new functional foods that are primarily function-driven, and to substantiate claims scientifically. Being clearly positioned as part of nutrition, the functional food concept is, however, quite distinct from other approaches like food supplementation or food fortification, and functional foods are different from nutraceuticals, pharmafoods, vitafoods and 'alicaments', all terms that are not defined conceptually. Functional foods are food products to be taken as part of the usual diet in order to have beneficial effects that go beyond what are known as traditional nutritional effects. Moreover, these beneficial effects have to be demonstrated scientifically to justify two specific types of claim: the enhanced function claim or the reduction of disease risk claim. Functional food is a key concept for the future of nutrition as a science because it results from the implementation in nutrition of all the basic scientific knowledge that has accumulated over the past two or three decades. To the benefit of public health this progress cannot be ignored, it needs to be recognized fully and used. But, today, functional food is still mainly a scientific concept that serves to stimulate research and the development of new products.

Biotechnology↗

Global view on functional foods: Asian perspectives.

There is an old Chinese thought meaning that medicine and food are isogenic. In Japan, a national research project started to endorse the thought scientifically, with the birth of functional foods that are now known to function to reduce the risk of life-style related diseases. The science gave rise to a national policy in which some functional foods were legally approved in terms of Foods for Specified Health Use. China has also constructed a unique system for approving some functional foods. This paper pinpoints a recent trend of functional foods characteristic to Asia, with special reference to relevant topics in Japan.

Aging↗

Rox3 and Rts1 function in the global stress response pathway in baker's yeast.

Yeast respond to a variety of stresses through a global stress response that is mediated by a number of signal transduction pathways and the cis-acting STRE DNA sequence. The CYC7 gene, encoding iso-2-cytochrome c, has been demonstrated to respond to heat shock, glucose starvation, approach-to-stationary phase, and, as we demonstrate here, to osmotic stress. This response was delayed in a the hog1-delta 1 strain implicating the Hog1 mitogen-activated protein kinase cascade, a known component of the global stress response. Deletion analysis of the CYC7 regulatory region suggested that three STRE elements were each capable of inducing the stress response. Mutations in the ROX3 gene prevented CYC7 RNA accumulation during heat shock and osmotic stress. ROX3 RNA levels were shown to be induced by stress through a novel regulatory element. A selection for high-copy suppressors of a ROX3 temperature-sensitive allele resulted in the isolation of RTS1, encoding a protein with homology to the B' regulatory subunit of protein phosphatase 2A0. Deletion of RTS1 caused temperature and osmotic sensitivity and increased accumulation of CYC7 RNA under all conditions. Over-expression of this gene caused increased CYC7 RNA accumulation in rox3 mutants but not in wild-type cells.

Alleles↗

Tissue Doppler imaging for the evaluation of patients with hypertrophic cardiomyopathy.

PURPOSE OF REVIEW: To discuss the role of tissue Doppler imaging for assessing regional myocardial function in patients with proven or suspected hypertrophic cardiomyopathy and review its application in clinical practice for diagnosis, estimation of filling pressures, and monitoring of treatment. RECENT FINDINGS: Patients with hypertrophic cardiomyopathy have very abnormal systolic and diastolic myocardial function, even if global systolic function of the left ventricle appears normal. Regional function is most abnormal in walls that are markedly hypertrophied, but it is also abnormal in segments that are not affected by hypertrophy, and it is depressed in patients who have a mutation for hypertrophic cardiomyopathy but have not yet developed clear phenotypic changes. Genetic diagnosis remains difficult especially in sporadic cases, due to the very large number of mutations that have been identified; the hypertrophy may represent a nonspecific compensatory response to any mutation that impairs myofibrillar function. Subclinical changes especially affect long-axis ventricular function, and tissue Doppler imaging is the most sensitive test to identify reduced velocities of long-axis shortening and early diastolic lengthening of the left ventricle, prolonged contraction and relaxation times, and reduced strain in affected segments, both in patients with hypertrophy and in asymptomatic subjects with mutations. It can also discriminate well between hypertrophic cardiomyopathy and athlete's heart, and can be used with standard echocardiographic measurements to estimate left ventricular filling pressure or to monitor treatment. SUMMARY: Tissue Doppler imaging can now be usefully incorporated into the routine echocardiographic study of patients with proven or suspected hypertrophic cardiomyopathy.

Blood Flow Velocity↗

Randomized, double-blind 6-month comparison of olanzapine and quetiapine in patients with schizophrenia or schizoaffective disorder with prominent negative symptoms and poor functioning.

This study compared the effects of olanzapine (OLZ) with those of quetiapine (QUE) for improving negative symptoms in patients diagnosed with schizophrenia or schizoaffective disorder who had prominent negative symptoms and marked deficits in social or occupational functioning. In this 6-month, multicenter, double-blind clinical trial, patients were randomized to treatment with OLZ (n = 171, 10-20 mg/d) or QUE (n = 175, 300-700 mg/d). Patients were treated at community mental health centers and assigned case managers who developed individualized psychosocial treatment plans. The primary efficacy measure was the reduction in negative symptoms using the Scale for the Assessment of Negative Symptoms. Secondary measures assessed changes in functioning, psychopathology, and treatment tolerability. Treatment with OLZ or QUE led to a significant reduction in negative symptoms, with no between-group difference (P = 0.09). Both treatment groups also showed significant improvement on most efficacy measures. Olanzapine-treated patients showed significantly greater improvement on positive symptoms and on several measures of functioning including Global Assessment of Functioning Scale, Quality of Life Instrumental Role domain, and level of effort in psychosocial or occupational rehabilitation programs. Significantly more OLZ-treated patients completed the study (52.6% OLZ, 37.7% QUE, P = 0.007). Treatment differences in safety were relatively small and not thought to be clinically relevant. Patients with schizophrenia who manifest prominent negative symptoms and marked functional deficits demonstrated significant improvement in negative symptoms after treatment with OLZ or QUE. Greater improvement in positive symptoms and a greater study completion rate may hold relevance to enhanced functional outcomes observed after OLZ therapy.

Adult↗

Assessment of global left ventricular function: comparison of cardiac multidetector-row computed tomography with angiocardiography.

OBJECTIVE: Evaluation of left ventricular function using electrocardiogram (ECG)-gated multidetector row CT (MDCT) by using 3 different volumetric assessment methods in comparison to assessment of the left ventricular function by invasive ventriculography. METHODS: Thirty patients with suspected or known coronary artery disease underwent MDCT coronary angiography with retrospective ECG cardiac gating. Raw data were reconstructed at the end-diastolic and end-systolic periods of the heart cycle. To calculate the volumes of the left ventricle, 3 methods were applied: The 3-dimensional data set (3D), the geometric hemisphere cylinder (HC), and the geometric biplane ellipsoid (BE) methods. End-diastolic volumes (EDV), end-systolic volumes (ESV), the stroke volumes (SV), and ejection fractions (EF) were calculated. The left ventricular volumetric data from the 3 methods were compared with measurements from left ventriculography (LVG). RESULTS: The best results were obtained using the 3D method; EDV (r = 0.73), ESV (r = 0.88), and EF (r = 0.76) correlated well with the LVG data. The EDV volumes did not differ significantly between LVG and the 3D method (P = 0.24); however, ESV, SV, and EF differed significantly. The ESV were significantly overestimated (P < 0.01), leading to an underestimation of the SV (P < 0.01) and the EF (P < 0.01). The HC method resulted in the greatest overestimation of the volumes. The EDV and the ESV were 31.8 +/- 37.6% and 136.4 +/- 92.9% higher than the EDV and ESV volumes obtained by LVG. Bland-Altman analysis showed systematic overestimation of the ESV using the HC method. CONCLUSION: MDCT with retrospective cardiac ECG gating allows the calculation of left ventricular volumes to estimate systolic function. The 3D method had the highest correlation with LVG. However, the overestimation of the ESV is significant, which led to an underestimation of the SV and the EF.

Adult↗

Inter-rater reliability of global assessment of functioning in a clinical setting.

Four studies on the inter-rater reliability of a proposed Axis V version for DSM-IV and of the CGAS involving 162 child and adolescent patients and 20 clinicians showed moderate agreement (intraclass correlation: 0.53-0.66). This was comparable to previous versions of Axis V, but lower than that reported for the CGAS. More detailed description of anchor points did not increase reliability nor there were differences in agreement when rating current or previous functioning.

Achievement↗

Deletion of the alternative sigma factor sigmaB in Staphylococcus aureus reveals its function as a global regulator of virulence genes.

A deletion of the sigB operon was constructed in three genetically distinct Staphylococcus aureus strains, and the phenotypes of the resulting mutants were analyzed. Compared to the corresponding wild-type strains, the DeltasigB mutants showed reduced pigmentation, accelerated sedimentation, and increased sensitivity to hydrogen peroxide during the stationary growth phase. A cytoplasmic protein missing in the DeltasigB mutants was identified as alkaline shock protein 23, and an extracellular protein excreted at higher levels in one of the DeltasigB mutants was identified as staphylococcal thermonuclease. Interestingly, most sigB deletion phenotypes were only seen in S. aureus COL and Newman and not in 8325, which was found to contain an 11-bp deletion in the regulator gene rsbU. Taken together, our results show that sigmaB is a global regulator which modulates the expression of several virulence factors in S. aureus and that laboratory strain 8325 is a sigmaB-defective mutant.

Bacterial Proteins↗

Conditional knockout mice reveal distinct functions for the global transcriptional coactivators CBP and p300 in T-cell development.

The global transcriptional coactivators CREB-binding protein (CBP) and the closely related p300 interact with over 312 proteins, making them among the most heavily connected hubs in the known mammalian protein-protein interactome. It is largely uncertain, however, if these interactions are important in specific cell lineages of adult animals, as homozygous null mutations in either CBP or p300 result in early embryonic lethality in mice. Here we describe a Cre/LoxP conditional p300 null allele (p300flox) that allows for the temporal and tissue-specific inactivation of p300. We used mice carrying p300flox and a CBP conditional knockout allele (CBPflox) in conjunction with an Lck-Cre transgene to delete CBP and p300 starting at the CD4- CD8- double-negative thymocyte stage of T-cell development. Loss of either p300 or CBP led to a decrease in CD4+ CD8+ double-positive thymocytes, but an increase in the percentage of CD8+ single-positive thymocytes seen in CBP mutant mice was not observed in p300 mutants. T cells completely lacking both CBP and p300 did not develop normally and were nonexistent or very rare in the periphery, however. T cells lacking CBP or p300 had reduced tumor necrosis factor alpha gene expression in response to phorbol ester and ionophore, while signal-responsive gene expression in CBP- or p300-deficient macrophages was largely intact. Thus, CBP and p300 each supply a surprising degree of redundant coactivation capacity in T cells and macrophages, although each gene has also unique properties in thymocyte development.

Alleles↗