Alcohol abuse has a potential association with unfavourable clinical course and brain atrophy in patients with status epilepticus.

AIM: To evaluate chronological changes on serial magnetic resonance imaging (MRI) examinations and clinical prognosis in patients with status epilepticus (SE), as well as the effect of alcohol abuse and heavy alcohol use on clinicoradiological findings. MATERIALS AND METHODS: This retrospective, single-centre study was approved by the institutional review board. Among 345 patients with seizures between January 2010 and October 2021, 27 patients with SE who had undergone both initial MRI (within a week after onset) and follow-up MRI (within 1 month after the initial MRI) were included. Five and three patients with concurrent or previous alcohol abuse and heavy alcohol-use history were included, respectively, and they were classified into the AL (Alcohol use) group. The remaining 19 patients were classified into the non-AL group. Two neuroradiologists independently evaluated both initial and follow-up MRI examinations of each patient; MRI findings were compared between the AL and non-AL groups using Fisher's exact test. In 15 patients, including four patients from the AL group, clinical information 6 months after the onset of SE was available; this information was compared between the two groups. RESULTS: Brain atrophy (5/8 versus 2/19, p=0.011; odds ratio, 12.29 [95% confidence interval, 1.32-189.2]) and unfavourable clinical course with uncontrollable seizures (3/4 versus 1/11, p=0.033; odds ratio, 30[1.43-638.19]) were significantly more frequent in the AL group than in the non-AL group. CONCLUSION: Among patients with SE, alcohol abuse and heavy alcohol-use history were associated with unfavourable seizure control and brain atrophy.

Two-step relaxation mode analysis with multiple evolution times applied to all-atom molecular dynamics protein simulation.

Proteins implement their functionalities when folded into specific three-dimensional structures, and their functions are related to the protein structures and dynamics. Previously, we applied a relaxation mode analysis (RMA) method to protein systems; this method approximately estimates the slow relaxation modes and times via simulation and enables investigation of the dynamic properties underlying the protein structural fluctuations. Recently, two-step RMA with multiple evolution times has been proposed and applied to a slightly complex homopolymer system, i.e., a single [n]polycatenane. This method can be applied to more complex heteropolymer systems, i.e., protein systems, to estimate the relaxation modes and times more accurately. In two-step RMA, we first perform RMA and obtain rough estimates of the relaxation modes and times. Then, we apply RMA with multiple evolution times to a small number of the slowest relaxation modes obtained in the previous calculation. Herein, we apply this method to the results of principal component analysis (PCA). First, PCA is applied to a 2-µs molecular dynamics simulation of hen egg-white lysozyme in aqueous solution. Then, the two-step RMA method with multiple evolution times is applied to the obtained principal components. The slow relaxation modes and corresponding relaxation times for the principal components are much improved by the second RMA.

Human T lymphotropic virus type 1 infection influences hepatitis C virus clearance.

To explore the effect of human T lymphotropic virus type 1 (HTLV-1) infection on hepatitis C virus (HCV) infection, a survey for these viral infections was conducted that involved 2280 residents in an area in which HTLV-1 and HCV are endemic. The response of patients with HCV and HTLV-1 to interferon (IFN)-alpha treatment was also assessed. Antibody to HCV was detected in 13.8% of the residents tested, and antibody to HTLV-1 was detected in 15.4%. The prevalence of HCV RNA was significantly higher among residents who had antibodies to both HCV and HTLV-1 than in those who had antibodies to HCV only (P<.05). Sustained elimination of HCV RNA by IFN was significantly more frequent among patients with HCV alone than among those with HCV and HTLV-1. By logistic regression analysis, HTLV-1 infection was associated with nonresponse to IFN treatment. Thus, HTLV-1 infection affects the clearance, both natural and in association with IFN treatment, of HCV.

Generalized-ensemble algorithms for molecular simulations of biopolymers.

In complex systems with many degrees of freedom such as peptides and proteins, there exists a huge number of local-minimum-energy states. Conventional simulations in the canonical ensemble are of little use, because they tend to get trapped in states of these energy local minima. A simulation in generalized ensemble performs a random walk in potential energy space and can overcome this difficulty. From only one simulation run, one can obtain canonical-ensemble averages of physical quantities as functions of temperature by the single-histogram and/or multiple-histogram reweighting techniques. In this article we review uses of the generalized-ensemble algorithms in biomolecular systems. Three well-known methods, namely, multicanonical algorithm, simulated tempering, and replica-exchange method, are described first. Both Monte Carlo and molecular dynamics versions of the algorithms are given. We then present three new generalized-ensemble algorithms that combine the merits of the above methods. The effectiveness of the methods for molecular simulations in the protein folding problem is tested with short peptide systems.

Temperature dependence of distributions of conformations of a small peptide.

Multicanonical Monte Carlo simulations of the pentapeptide Met-enkephalin were used to study its low-energy conformations in detail. The resulting conformations are classified into six categories of similar structures based on the pattern of intrachain hydrogen bonds. Several thermodynamic quantities such as the distributions of hydrogen bonds and those of backbone dihedral angles were obtained as a function of temperature. From these results, it was concluded that at least four of the six categories are well-defined local minimum energy states. These four categories are in agreement with our prior results based on root-mean-square interatomic distances.

Multiple atherosclerotic coronary aneurysms in association with acute myocardial infarction.

A 60-year-old woman with multiple coronary aneurysms, complicated with acute infero-posterior myocardial infarction is presented. The cine-coronary arteriogram disclosed a diffuse dilatation of epicardial coronary arteries associated with multiple aneurysms, fusiform ones in the right coronary and the left circumflex coronary arteries and saccular ones in the left anterior descending coronary artery. Distal run-off was poor. Ventriculography revealed a decrease in the ejection fraction (36%) and segmental abnormal wall motion at the apical and infero-posterior regions. The cause of the aneurysms appeared to be atherosclerotic. We suggested that coronary embolization was the cause of acute myocardial infarction in this case.

Coronary arterial spasm in single coronary artery.

A 48-year-old man developed severe chest pain and became unconscious. Coronary cineangiography revealed single coronary artery of the type L2b by Sharbaugh and White. Ergonovine, 0.2 mg i.v., produced coronary arterial spasm in the right coronary artery. This case suggests that coronary arterial spasm might be a cause of sudden death in patients with single coronary artery. However, an association of single coronary artery and coronary arterial spasm might be coincidental.

Usefulness of the Valsalva maneuver in management of the long QT syndrome.

Exercise or isoproterenol infusion may evoke ventricular arrhythmias in patients with the long QT syndrome. We examined the electrocardiographic effects of the Valsalva maneuver in eight patients with the long QT syndrome and nine healthy subjects. The Valsalva maneuver lengthened the QTc interval in both groups, but the lengthening was greater in the patients. In the patients who were having frequent attacks of ventricular tachycardia, the Valsalva-induced prolongation of the QTc interval was particularly remarkable and was associated with the development of T-wave alternans and short runs of ventricular tachycardia. Propranolol effectively suppressed the lengthening of the QTc interval during Valsalva strain and prevented Valsalva-induced ventricular arrhythmia. These results suggest that the Valsalva maneuver may be useful in evaluating the risk of ventricular tachyarrhythmias and the efficacy of drug treatment in patients with the long QT syndrome.

Reelevation of ST segment on precordial mapping in natural time course following acute anterior myocardial infarction.

Serial recordings of ST segment mapping were performed in 15 patients with acute anterior myocardial infarction. Reelevation of ST segment was observed in all cases between 12 hours and one week after infarction without clinical evidence of reinfarction. There was significant correlation between the magnitude of the sum of ST reelevation (sigma ST) and time to the peak of ST reelevation. The higher was sigma ST at the peak, the later was the appearance of the peak of ST reelevation. sigma ST recorded between 24 and 72 hours after infarction correlated with the extent of abnormal Q (NQ) in the precordial mapping as well as the percent of abnormally contracting segment (%ACS) on left ventricular angiography examined after 4 weeks following infarction. However, there was no correlation between sigma ST recorded at 12 hours after infarction and NQ studied at 4 weeks after infarction. The results indicate that the magnitude of sigma ST changes in time during the course after infarction and that the time of recording is important when sigma ST is used for the estimation of infant size. Reelevation of ST segment should be considered in the study of therapeutic intervention in acute myocardial infarction.

Increased exercise tolerance after oral diltiazem, a calcium antagonist, in angina pectoris.

Effects of diltiazem, a recently introduced calcium antagonist, on exercise performance were studied in nine coronary disease patients with effort angina. The duration of exercise before the onset of angina and the time to the onset of ischemic ST depression 2 hours after 90 mg of oral diltiazem were compared with those 2 hours after oral placebo and a few minutes after 0.3 mg of sublingual nitroglycerin. Diltiazem prolonged the duration of exercise in all nine patients (average 2.5 minutes, p less than 0.001) and delayed the onset of ischemic ST depression (average 2.4 minutes, p less than 0.001). The increment of the duration of exercise and the time to the onset of ischemic ST depression following 90 mg of oral diltiazem were almost equivalent to that following sublingual nitroglycerin. These results in fixed coronary atherosclerosis indicate the clinical antianginal efficacy of diltiazem which persists for at least 2 hours after oral administration.

The effect of graded coronary stenosis on myocardial blood flow and left ventricular wall motion.

The effect of graded coronary stenosis on resting regional myocardial flow and left ventricular (LV) wall motion was studied in 18 anesthetized dogs. The left circumflex coronaary artery (LC) was constricted. The degree of LC stenosis and the changes in LV wall motion were determined by cineangiography of the coronary artery and LV. Regional myocardial flow was determined by tracer microspheres (TM), labeled with two different isotopes, Sr85, Sc46 or Ce141. The first TM1 and the second TM2 were infused after LC stenosis, and during a temporary complete LC occlusion respectively. Resting flow in areas with 70% stenosis was reduced, with a greater reduction of subendocardium and posterior papillary muscle, but minimum impairment of LV wall motion. No ST elevation was found. Animals with 80--90% stenosis showed a marked reduction of flow and wall motion, a significant ST-elevation and a delayed antegrade run-off in coronary arteriography.

Effects of collateral circulation on regional myocardial blood flow and left ventricular wall motion (A preliminary note).

The effect of collateral circulation on regional myocardial flow and wall motion of left ventricle was studied on 5 anesthetized dogs with a surgically implanted constrictor on the left circumflex coronary artery (LC). The grade of LC stenosis and wall motion of left ventricle (LV) were determined by cineangiography of the coronary artery and LV at the period of acute and chronic occlusion. Regional myocardial flow was determined by tracer microspheres (TM), labeled with four different isotopes, Sr85, Cr51, Sc46, Ce141. The first TM1 was infused after LC stenosis, TM2 during a temporary complete LC occlusion at the period of acute occlusion; TM3 and TM4 in a similar way 3 to 4 weeks after the acute LC stenosis. Three to four weeks after LC stenosis, i.e. chronic period of occlusion, the degree of LC stenosis progressed from 70--80% to 100% occlusion, but collateral flow and collateral vessels to the ischemic LC area were increased together with an improvement of wall motion of the ischemic LC area. The results may support the idea that collaterals may be an effective compensatory mechanism for ischemia. In contrast to an increase of collateral flow to the ischemic LV free wall in all five dogs, an increase to the posterior papillary muscle was found only in two out of five dogs.

Effect of graded coronary stenosis on regional myocardial blood flow and left ventricular function.

Dogs with 70% stenosis of the left circumflex coronary artery showed a reduction of myocardial blood flow with a minimal impairment of left ventricular wall motion. Eighty to ninety percent stenosis produced a marked reduction of flow and wall motion, and ST elevation close to 100% occlusion, but delayed antegrade run-off was found. The effectiveness of collaterals to protect against left ventricular dysfunction was supported.