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PubMed1995

Posttreatment with EPC-K1, an inhibitor of lipid peroxidation and of phospholipase A2 activity, reduces functional deficits after global ischemia in rats.

In this study the effect of an inhibitor of lipid peroxidation and of phospholipase A2 activity, EPC-K1, on spatial learning deficit and neuronal damage following transient cerebral ischemia was evaluated. Global ischemia was induced by four-vessel occlusion (4VO) for 20 min in rats. EPC-K1 (10 mg/kg IP) was administered either a) 15 min before induction of ischemia, b) immediately after, or c) 30 min after onset of reperfusion. One week after surgery spatial learning was tested in the Morris water maze. EPC-K1 reduced the deficit in spatial learning when given immediately or 30 min after the onset of reperfusion but not when applied 15 min before ischemia. Neuronal damage in the CA1 sector of the hippocampus produced by 4VO was slightly, but not significantly attenuated by posttreatment. The present data demonstrate that posttreatment with EPC-K1 exerts a protective effect on deficits in spatial learning induced by 4VO. These results support the hypothesis that lipid peroxidation and activation of phospholipase A2 contribute to functional alterations of the brain during reperfusion following forebrain ischemia.

Animals↗
PubMed1999

Evoked potentials investigation of visual dysfunction after methanol poisoning.

OBJECTIVE: To present results of electrophysiologic investigations of the visual toxicity observed during the early stage of methanol poisoning. DESIGN: Retrospective, clinical study. SETTING: A 7-bed intensive care unit in a university hospital. PATIENTS: Nineteen patients admitted with a diagnosis of acute methanol poisoning. INTERVENTIONS: Visual evoked potentials were obtained within the first 48 hrs after admission; a clinical follow-up examination was performed in 11 patients, and 12 patients were followed up by visual evoked potentials beyond the same delay. Correlations between the occurrence of an optic neuropathy and clinical, biological, and electrophysiological data were studied. MEASUREMENTS AND MAIN RESULTS: A significant correlation was found between arterial pH and blood formate concentration (r2 = 0.58, p = .003), between blood formate and bicarbonate concentrations (r2 = 0.36, p = .02), and between delay from ingestion and blood formate concentration (r2 = 0.44, p = .017). Clinical outcome was correlated not only with the bicarbonate (p = .007), formate (p = .018), and methanol (p = .03) concentrations and arterial pH (p = .004) but also with a well-defined electrophysiologic pattern during the acute stage. An index of global cortical functioning > or =3 was associated with death, whereas a global cortical functioning index < or =2 was associated with survival (p = .0058). Moreover, a statistically significant difference in long-term visual impairment was found between the subgroup with abnormal wave III morphology or a global cortical functioning index of 1-2 and the subgroup with normal wave III morphology and a global cortical functioning index <1 (p = .015). Results of the electrophysiologic studies were expressed as retinal dysfunction and optic nerve injury. Five patients had normal findings on electrophysiologic examination. Ten patients had early signs of retinal dysfunction that were fully reversed in the eight patients who were followed. Ten patients had persistent electrophysiologic signs of optic neuropathy. CONCLUSIONS: Although reversible retinal dysfunction is evident in the early stage of human methanol poisoning, its absence does not preclude development of optic neuropathy. The occurrence of optic neuropathy and early electrophysiologic data are correlated.

Acute Disease↗
PubMed2001

Coadministration of melatonin and fluoxetine does not improve the 3-month outcome following ECT.

At least 50% of patients with manic depressive disorder (MDD) treated successfully with electroconvulsive therapy (ECT) will experience a relapse within the first year of follow-up. Sleep disturbances are very common in MDD and may constitute forerunners of relapse. In this study we tested the hypothesis that melatonin, a sleep-promoting hormone, would decrease the 3-month relapse rate after successful ECT. We included in the study patients with MDD successfully treated with ECT (post-ECT Hamilton Rating Scale for Depression [HRSD] < or = 10). Patients were blindly randomized to two groups, one receiving fluoxetine + placebo and one receiving fluoxetine + melatonin. Assessments (HRSD, Brief Psychiatric Rating Scale, Global Assessment of Function Scale, Global Depression Scale, Pittsburgh Sleep Quality Index, Mini-Mental State Exam, and pill count) were performed for 12 weeks after ECT. Ten of the 35 patients (28.5%) relapsed during the follow-up period. Relapse rates were similar in both groups of patients. Sleep reports were not improved by melatonin. Patients who achieved a higher functional state post-ECT relapsed less often. We conclude that the addition of melatonin to on-going fluoxetine treatment did not have a beneficial effect either on the 3-month outcome post-ECT or on the sleep reports of these patients.

Aged↗
PubMed2005

Predictors of change after long-term analytic group psychotherapy.

In a study of long-term (mean=32.5 months) analytic group psychotherapy we explored the relationships among six predictors shown to influence outcome in short-term group studies and five outcome variables (Global Assessment of Functioning [GAF], Global Symptom Index [GSI], Inventory of Interpersonal Problems-Circumplex [IIP-C], Global Improvement, and Chief Complaints), assessed after termination of therapy. In this study, we wanted to test whether the same variables also predicted patients' status at follow-up, 1 year after termination. Bivariate correlations and multiple regression analyses were used. Initial status and treatment duration up to 2.5 years turned out to be strong positive predictors of status at both time points. Contrary to findings from many short-term studies, presence of personality disorder, high initial severity, chronicity, and less optimistic expectations had no predictive power at either time. Higher age predicted a less favourable status at follow-up in secondary exploratory analyses. The findings suggest that different patients may benefit from long-term versus short-term group psychotherapy. More studies should examine patient aptitude and the significance of the time factor (Aptitude-Treatment Interaction [ATI-effects]).

Adult↗
PubMed2005

Global left ventricular function in cardiac CT. Evaluation of an automated 3D region-growing segmentation algorithm.

The purpose was to evaluate a new semi-automated 3D region-growing segmentation algorithm for functional analysis of the left ventricle in multislice CT (MSCT) of the heart. Twenty patients underwent contrast-enhanced MSCT of the heart (collimation 16 x 0.75 mm; 120 kV; 550 mAseff). Multiphase image reconstructions with 1-mm axial slices and 8-mm short-axis slices were performed. Left ventricular volume measurements (end-diastolic volume, end-systolic volume, ejection fraction and stroke volume) from manually drawn endocardial contours in the short axis slices were compared to semi-automated region-growing segmentation of the left ventricle from the 1-mm axial slices. The post-processing-time for both methods was recorded. Applying the new region-growing algorithm in 13/20 patients (65%), proper segmentation of the left ventricle was feasible. In these patients, the signal-to-noise ratio was higher than in the remaining patients (3.2+/-1.0 vs. 2.6+/-0.6). Volume measurements of both segmentation algorithms showed an excellent correlation (all P<or=0.0001); the limits of agreement for the ejection fraction were 2.3+/-8.3 ml. In the patients with proper segmentation the mean post-processing time using the region-growing algorithm was diminished by 44.2%. On the basis of a good contrast-enhanced data set, a left ventricular volume analysis using the new semi-automated region-growing segmentation algorithm is technically feasible, accurate and more time-effective.

Aged↗
PubMed1981

Relationship between segmental abnormalities and global left ventricular function in coronary artery disease: validation of a theoretical model.

A theoretical model of the heart, which suggests a direct relationship between segmental abnormalities of left ventricular (LV) wall motion (WM) and LV ejection fraction (EF), was tested using two-dimensional echocardiography (2DE) and multiple-gated equilibrium blood pool scintigraphy (MGES) in a population of 25 coronary artery disease patients. MGES was used to determine EF, and 2DE was used to develop a method of analysis of LV segmental WM abnormalities. Two orthogonal apical 2DE views were analyzed. The length of the end-diastolic segments in which normal contraction occurred during systole were measured in each view, summed and divided by the sum of the end-diastolic silhouette lengths. The fraction thus created was multiplied by 100 and defined as the percentage of normally contracting myocardium (%NCM). %NCM correlated well with EF determined by MGES (r = 0.94). Determination of %NCM was highly reproducible for the same observer (r = 0.98), as well as for two observers (r = 0.98), and the standard error of estimate was low in both cases (4%). These findings, in addition to confirming the theoretical model, provide a new technique to assess LV segmental WM abnormalities by 2DE.

Aged↗
PubMed1982

Evaluation of postresuscitation left ventricular global and segmental function by radionuclide ventriculography in sudden coronary death survivors of prehospital cardiac arrest: Correlation to subsequent short-term prognosis.

Previous data have shown that patients with significant left ventricular (LV) dysfunction, marked abnormalities in resting hemodynamics, and multiple vessel coronary artery disease (CAD) are at increased risk for sudden cardiac death. However, in-hospital assessment of ventricular function in the early postresuscitation period of out-of-hospital cardiac arrest has not been evaluated and related to short-term outcome. By using bedside radionuclide ventriculography (RNV) we evaluated LV ejection fraction (LVEF) and wall motion in 36 nonconsecutive patients within 24 hours of their episode of out-of-hospital cardiac arrest. There were 24 men and 12 women with mean age of 62.3 years (range 21 to 85 years). Total mortality of the entire group was 38.8% at 4 weeks. Eighteen patients had LVEF less than 0.30 and 18 had LVEF greater than 0.30. Mortality in the low LVEF group was 55.5% at 4 weeks versus 22.2% in patients with LVEF greater than 0.30 (p less than 0.05). Patients with normal LV wall motion had no short-term mortality (none of seven), while patients having abnormal LV wall motion had a significantly higher short-term mortality (14 of 29) (p less than 0.05). We conclude that out-of-hospital cardiac arrest survivors have a high incidence of severe LV dysfunction in the early postresuscitation period and that a significantly higher early mortality is seen in the group with LVEF less than 0.30. In addition, abnormalities of LV wall motion by RNV examination demonstrated poorer prognosis in the first 4 weeks than patients with normal LV wall motion.

Adult↗
PubMed1989

Noninvasive evaluation of global left ventricular function with use of cine nuclear magnetic resonance.

Previous reports have validated the accuracy of nuclear magnetic resonance (NMR) imaging for quantitating ventricular volumes and myocardial mass. In this study, a new rapid NMR imaging method, cine NMR imaging, was used to compare left ventricular volumes determined from the transverse plane and short-axis plane in healthy volunteers and patients with dilated cardiomyopathy. With use of the short-axis plane, left ventricular mass at end-systole and end-diastole were determined and left ventricular systolic wall thickening at three different levels was assessed. For validation in the current study, cine NMR imaging and two-dimensional echocardiographic measurements of left ventricular volumes were correlated. Left ventricular volumes of the normal volunteers (end-systolic volume = 34 +/- 3.8 ml, end-diastolic volume = 90.4 +/- 7.2 ml) and patients with cardiomyopathy (end-systolic volume = 173 +/- 28.3 ml, end-diastolic volume = 219.5 +/- 29.6 ml) obtained in the transverse plane were nearly identical to those obtained in the short-axis plane (normal volunteers, end-systolic volume = 30.3 +/- 3.5 ml, end-diastolic volume = 84.7 +/- 7.0 ml and patients with cardiomyopathy, end-systolic volume = 179.1 +/- 27.8 ml, end-diastolic volume = 227 +/- 30.9 ml) and correlated highly (r = 0.91) with volumes obtained by two-dimensional echocardiography. Assessment of left ventricular mass over a broad range using cine NMR imaging in a short-axis plane was identical at end-systole (normal volunteers, 117 +/- 10 g; patients with cardiomyopathy, 202 +/- 20 g) and end-diastole (normal volunteers, 115 +/- 10 g; patients with cardiomyopathy, 194 +/- 21 g).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2006

Age-related differences in cognitive function using a global local hierarchical paradigm.

While research suggests that normal ageing is associated with compromised divided attentional processing abilities, such studies are comparatively few in comparison to other areas of attention (e.g. selective attention). The current study sought to examine age-related effects in divided attention using a global/local paradigm in three normal healthy age groups: younger adults (20-40 years), middle-aged (40-60 years), and older adults (61-80 years). In three experiments we sought to examine the ability to process local/global stimuli, ability to divide and switch attention, as well as the influence of a cue on target performance. Experiment 1 revealed global precedence and interference for all age groups; older adults were overall significantly slower in their response times. Experiments 2 and 3 suggest an age-related impairment in dividing and switching attention, which may begin as early as middle age. The findings are considered to reflect reduced inhibitory mechanisms, as well as possible neurobiological changes in the normal ageing process.

Adult↗
PubMed2004

Myocardial performance index, a Doppler-derived index of global left ventricular function, predicts congestive heart failure in elderly men.

AIMS: There is limited data on echocardiographic and Doppler indices of cardiac function as predictors for congestive heart failure (CHF) in the general population. Myocardial performance index (MPI, also denoted TEI-Doppler index) reflects both left ventricular (LV) systolic and diastolic function. METHODS AND RESULTS: We compared eight different echocardiographic and Doppler indices of cardiac function as predictors of CHF using a population-based cohort of 552 seventy-year-old men without CHF and significant valve disease at baseline (median follow-up time 8.2 years). In a stepwise multivariable Cox proportional-hazard analysis including the different indices of cardiac function, high MPI (above the 90th percentile of MPI [> or =0.91]), abnormal LV wall motion score index and a pseudo-normalized/restrictive E/A-ratio pattern independently predicted future CHF morbidity. After adding traditional CHF risk factors (age, previous myocardial infarction, hypertension, diabetes mellitus, hyperlipidaemia, smoking, LV hypertrophy and body mass index) to the above model, only a high MPI remained a significant predictor (hazard ratio 4.72, 95% CI 1.75-12.76, p=0.002). CONCLUSION: MPI provides important prognostic information for the risk of future CHF, beyond other measurements of cardiac function and traditional heart failure risk factors in elderly men. MPI seems to be a clinically relevant indicator of cardiac function and may prove to be a valuable tool in assessing the risk of future CHF.

Aged↗
PubMed2004

An echocardiogram-based 16-segment model for predicting left ventricular ejection fraction improvement.

An important goal of cardiac revascularization is to improve the left ventricular ejection fraction, which is an important clinical determinant of the long-term outcome for patients with coronary artery disease. Regional myocardium function improvement may be expected from revascularization when viable myocardium is detected using non-invasive cardiac imaging. However, the quantitative relation between regional myocardial function recovery and global heart function improvement has not been determined and there is no tool to predict the amount of ejection fraction improvement prior to revascularization. A 16 segment biomechanical model of the left ventricle is proposed to establish the relationship between the ejection fraction improvement and the viable segments detected by echocardiography. With the assumption that the viable segments would potentially improve contractility after revascularization, the ejection fraction improvement is estimated for all possible wall motion score improvement in viable segments. The model shows that the ejection fraction improvement is linearly related to the contractility in the normal segments and a weighted sum of the numbers of viable segments that recover to normal or hypokinetic contractility. The predictive value of the model is illustrated for a group of patients reported in the literature. The model predictions of the post-revascularization ejection fraction are very close to the follow-up data with a very strong correlation (R2 = 0.92). By predicting the ejection fraction improvement, the model may provide a tool for evaluating the efficacy of revascularization and for selecting patients who would benefit from revascularization.

Coronary Disease↗
PubMed2003

Functional characterization of global genomic DNA repair and its implications for cancer.

The most versatile cellular pathway for dealing with a large variety of structurally-unrelated DNA alterations is nucleotide excision repair (NER). Most genomic damage, if not repaired, may contribute to mutagenesis and carcinogenesis, as well as to cellular lethality. There are two subpathways of NER, termed global genomic repair (GGR) and transcription-coupled repair (TCR); While GGR deals with all repairable lesions throughout the genome, TCR is selective for the transcribed DNA strand in expressed genes. Proteins involved in the initial recognition of lesions for GGR as well as for TCR (i.e. RNA polymerase) may sometimes initiate gratuitous repair events in undamaged DNA. However, the damage recognition enzymes for GGR are normally maintained at very low levels unless the cells are genomically stressed. Following UV irradiation in human fibroblasts the efficiency of GGR is upregulated through activation of the p53 tumor suppressor gene. The transactivation role of p53 includes control of expression of the genes, XPC and XPE, which are implicated in GGR but not TCR. These inducible responses are essential for the efficient repair of the most prominent lesion produced by UV, the cyclobutane pyrimidine dimer (CPD). They are also clinically relevant, as we have shown them to operate upon chemical carcinogen DNA damage at levels to which humans are environmentally exposed (e.g. through smoking). Thus, for benzo(a)pyrene (at 10-50 adducts per 10(8) nucleotides) repair was essentially complete within 1 day in p53(+/+) human fibroblasts while no repair was detected within 3 days in p53(-/-) cells. The levels of all four DNA adducts formed by benzo(g)chrysene, also exhibited p53-dependent control in human fibroblasts. However, unlike humans most rodent tissues are deficient in the p53-dependent GGR pathway. Since rodents are used as surrogates for humans in environmental cancer risk assessment it is very important that we determine how they differ from humans with respect to DNA repair and oncogenic responses to environmental genotoxins.

DNA Repair↗
PubMed2003

Angiographic findings, time course of regional and global left ventricular function, and clinical outcome in diabetic patients with acute myocardial infarction treated with primary percutaneous transluminal coronary angioplasty.

There is scarce information available about the outcome of diabetic patients with acute myocardial infarction (AMI) treated with percutaneous transluminal coronary angioplasty (PTCA). We sought to compare left ventricular (LV) function, and angiographic and clinical outcomes in diabetics versus nondiabetics with AMI treated with primary PTCA. This study examined 720 consecutive patients with AMI treated with primary PTCA, 102 of whom had diabetes. Six-month follow-up coronary angiography was obtained in 560 patients (88% of eligible patients). In a subgroup of 284 patients, LV function was serially determined by 2-dimensional echocardiography. During 6-month follow-up no significant differences were observed between diabetics and nondiabetics with regard to restenosis rates (31.6% vs 28.2%, p = 0.6), recovery of LV function (6-month wall motion score index: 1.8 +/- 0.7 vs 1.8 +/- 0.7, p = 0.88; 6-month LV ejection fraction: 48.5 +/- 12% vs 51.2 +/- 13%, p = 0.173), nonfatal re-AMI rates (2.9% vs 1.3%, p = 0.2), and target vessel revascularization rates (21.6% vs 16.8%, p = 0.2). Early and late mortality were higher in diabetics than in nondiabetic patients (8.8% vs 4.2%, p = 0.045 and 11.7% vs 5.5%, p = 0.016, respectively). By Cox analysis, diabetes was an independent predictor of both early (odds ratio [OR] 2.4, 95% confidence interval [CI] 1.1 to 5.3, p = 0.03) and late mortality (OR 2.37, 95% CI 1.16 to 4.84, p = 0.017) as well as 6-month major adverse cardiac events (MACEs): death, re-AMI, target vessel revascularization (OR 1.51, 95% CI 1.04 to 2.18, p = 0.03). Thus, diabetes is an independent predictor of clinical outcome even if PTCA is used as the primary reperfusion strategy.

Adult↗