Validation of a turbulent Kelvin-Helmholtz shear layer model using a high-energy-density OMEGA laser experiment.

Following the successful demonstration of an OMEGA laser-driven platform for generating and studying nearly two-dimensional unstable plasma shear layers [Hurricane et al., Phys. Plasmas 16, 056305 (2009); Harding et al., Phys. Rev. Lett. 103, 045005 (2009)], this Letter reports on the first quantitative measurement of turbulent mixing in a high-energy-density plasma. As a blast wave moves parallel to an unperturbed interface between a low-density foam and a high-density plastic, baroclinic vorticity is deposited at the interface and a Kelvin-Helmholtz instability-driven turbulent mixing layer is created in the postshock flow due to surface roughness. The spatial scale and density profile of the turbulent layer are diagnosed using x-ray radiography with sufficiently small uncertainty so that the data can be used to ~0.17 µm) in the postshock plasma flow are consistent with an "inertial subrange," within which a Kolmogorov turbulent energy cascade can be active. An illustration of comparing the data set with the predictions of a two-equation turbulence model in the ares radiation hydrodynamics code is also presented.

Dynamic Hohlraums as x-ray sources in high-energy density science.

The first demonstration of laser driven dynamic Hohlraums (LDDH) as a spectrally smooth backlighter source for opacity and temperature measurements through absorption spectrometry of materials in local thermodynamic equilibrium at temperatures >150 eV has been made. This is a crucial temperature regime for future astrophysics and ignition fusion experiments at the nearly completed National Ignition Facility (NIF) [E. I. Moses and C. R. Wuest, Fusion Sci. Technol. 47, 314 (2005)] at the Lawrence Livermore National Laboratory. The new backlighter consists of a LDDH filled with either krypton or argon that implodes to create an x-ray flash. The properties of this x-ray flash have been measured in experiments at the Omega laser [T. R. Boehly et al., Opt. Commun. 133, 495 (1997)] at the Laboratory for Laser Energetics in Rochester, New York, satisfying all requirements imposed by future experiments: (1) the emission spectrum extends to at least 5.5 keV, well above the maximum x-ray energy ( approximately 3.5 keV) obtained from the previously "best" opacity backlighters (uranium M-shell emission backlighters); (2) the spectrum is smooth and featureless (intensity variation <6% rms), allowing absorption spectrometry through experimental samples; (3) the emission source size is sufficiently small (<50 microm) for projection backlighting through future samples; (4) the emission is bright enough (and twice as bright as imploding hydrogen-filled capsules) for gated spectrometer measurements; (5) the emission duration is optimized ( approximately 100 ps) for the current and future generations of spectrometers; and (6) by using only a small number of beams with limited energy and symmetry for the backlighter (10 out of 60 beams in the Omega experiments), the majority of laser beams are left available for heating sample materials to >150 eV.

Determinants of coronary sinus noradrenaline in patients with ischaemic heart disease: coronary sinus catecholamine concentration in relation to arterial catecholamine concentration, pulmonary artery oxygen saturation and left ventricular end-diastolic pressure.

Arterial and coronary sinus noradrenaline (NA) and adrenaline (A) concentrations, cardiac output, pulmonary artery oxygen saturation (PAO2), coronary sinus oxygen saturation, left ventricular end-diastolic pressure (LVEDP), and arterial pressure were examined in 21 patients with ischaemic heart disease at rest and during exercise before and after intravenous propranolol. The heart had a net uptake of A and a net release of NA. It can be estimated that at least 50% of NA in the coronary sinus derived from the heart. NA in the coronary sinus and in the arterial blood originated therefore, at least partially, in different tissues. The NA concentration showed close correlation with PAO2, but not with cardiac index or arterial blood pressure. Multiple regression analysis also revealed a relationship between LVEDP and arterial and coronary sinus NA independent of PAO2. A very close correlation between arterial and coronary sinus NA (r = 0.93, P less than 0.001) indicates that they are largely controlled by the same factors.

Heart rate-lowering calcium antagonists in hypertensive post-myocardial infarction patients.

OBJECTIVES: To analyse effects of a heart rate-lowering calcium antagonist in hypertensive post-myocardial infarction patients. DESIGN AND METHODS: From three large, randomized, placebo-controlled, secondary prevention trials investigating verapamil or diltiazem (the first and second Danish Verapamil Infarction Trials and the Multicentre Diltiazem Post-Infarction Trial) data from a total of 1,325 hypertensive post-myocardial infarction patients (drugs = 667, placebo = 658) were pooled to assess effect of blinded therapy on mortality and event rates. RESULTS: Treatment with heart rate-lowering calcium antagonists was associated with significant reduction in event rates [21.4 versus 27.4%; risk ratio (RR) = 0.76, confidence interval (CI) = 0.61 -0.95, P= 0.013]. Mortality rates in the treatment group were 15.1 versus 17.5% in the control group (RR = 0.87, CI = 0.66-1.13, P= 0.296). Among the subset of 964 hypertensive patients without pulmonary congestion, there was some reduction in mortality rate (11.3 versus 15.3% in the control group; RR = 0.72, P= 0.066) and significant reduction in event rates (18 versus 24.4% for control group; RR = 0.70, P= 0.011). In patients with pulmonary congestion and hypertension, however, calcium antagonists were associated with a 25% increase in mortality (RR = 1.25, P= 0.339), while event rate RR was 1.00. After an adjustment for significant covariates, RR for mortality in treatment versus control groups was 0.76 (P= 0.159). For event rates, RR was 0.74 (P= 0.057). CONCLUSIONS: Heart rate-lowering calcium antagonists decrease event rates in hypertensive post-myocardial infarction patients, but only in those without pulmonary congestion.

Verapamil and risk of cancer in patients with coronary artery disease. DAVIT Study Group. Danish Verapamil Infarction Trial.

The risk of cancer in users of verapamil was assessed in a long-term follow-up of 1,775 patients who were randomized to verapamil or matching placebo in the Danish Verapamil Infarction Trial-II in the years 1985 to 1987. During 10,474 patient-years, no increased risk of cancer was observed for the verapamil-treated men or women compared with the age- and sex-matched background population.

Nonsteroidal anti-inflammatory drugs after acute myocardial infarction. DAVIT Study Group. Danish Verapamil Infarction Trial.

The effect of nonsteroid anti-inflammatory drugs (NSAIDs) after acute myocardial infarction was studied in a retrospective study of 88 patients who were receiving regular NSAID treatment at randomization in the Danish Verapamil Infarction Trial II. There were no significant differences in mortality or major events between NSAID-treated patients versus controls (1,687); however, in a multivariate analysis a nonsignificant beneficial trend in favor of NSAIDs was observed.

Verapamil and angiotensin-converting enzyme inhibitors in patients with coronary artery disease and reduced left ventricular ejection fraction.

Verapamil is effective as antianginal medication but contraindicated in patients with congestive heart failure. Angiotensin-converting enzyme (ACE) inhibitors improve survival in patients with congestive heart failure but have limited effect on patients with angina pectoris. No studies have been published on the combined treatment with verapamil and ACE inhibitors in patients with stable angina pectoris and left ventricular dysfunction. We performed an open study in 14 patients with angina pectoris and ejection fraction < 40%. The patients received verapamil 180 mg and trandolapril 2 mg twice daily for 3 months. We found a significant increase in ejection fraction from 28 +/- 6 to 35 +/- 11 (p < 0.03), wall motion index from 1.0 +/- 0.3 to 1.2 +/- 0.3 (p < 0.03), exercise duration from 6.9 +/- 2.5 to 7.7 +/- 2.9 minutes (p < 0.01), and ratio of exercise to rest rate-pressure product from 2.2 +/- 0.4 to 2.5 +/- 0.6 (p < 0.02). Use of nitroglycerin and number of angina pectoris attacks were both significantly reduced after 3 months of treatment. These findings support the hypothesis that the combination of verapamil and trandolapril is useful in patients with attenuated left ventricular function and angina pectoris.

Long-term effects of diltiazem and verapamil on mortality and cardiac events in non-Q-wave acute myocardial infarction without pulmonary congestion: post hoc subset analysis of the multicenter diltiazem postinfarction trial and the second danish verapamil infarction trial studies.

The main objective of this retrospective analysis was to evaluate the long-term effect of the heart rate-lowering calcium antagonists verapamil and diltiazem on the incidence of combined cardiac events and all-cause mortality in patients who had experienced a non-Q-wave acute myocardial infarction (AMI), but who did not also have pulmonary congestion. In addition, factors having an independent association with these 2 outcomes were identified. Of 817 non-Q-wave patients, 81 (9.9%) died during 12 to 52 months of follow-up. The unadjusted mortality rate was 42% lower in patients randomized to calcium antagonist therapy than placebo (7.2% vs 12.4%, p = 0.010). Non-Q-wave patients who died during follow-up were older than patients who survived (62 vs 58 years, p = 0.001). Other factors found to have an independent association with all-cause mortality included diuretic use (RR 2.79), diabetes mellitus (RR 2.86), and New York Heart Association class >I (RR 1.73). The covariate adjusted all-cause mortality risk ratio associated with randomization to calcium antagonist therapy was 0.65 (95% confidence interval [0.40 to 1.05, p = 0.079]). Overall, 153 patients (18.7%) died or had nonfatal reinfarction. The unadjusted combined event rate was 31% lower in patients randomized to calcium antagonist therapy than to placebo (15.2% vs 21.9%, p <0.006). Factors found to have an independent association with cardiac events included age, diabetes (RR 2.82), diuretic use (RR 2.04), and previous AMI (RR 1. 71). In addition, randomization to the calcium antagonist group had a significant independent association with reduced cardiac events (p = 0.031). The covariate adjusted event rate RR associated with randomization to the calcium antagonist group was 0.69 (95% confidence interval [0.49 to 0.97]). In conclusion, the heart rate-lowering calcium antagonists diltiazem and verapamil may play an important role in reducing long-term mortality and reinfarction in non-Q-wave AMI without pulmonary congestion.

Cardiac event rates after acute myocardial infarction in patients treated with verapamil and trandolapril versus trandolapril alone. Danish Verapamil Infarction Trial (DAVIT) Study Group.

Angiotensin-converting enzyme (ACE) inhibitors improve survival in patients with congestive heart failure (CHF) after an acute myocardial infarction (AMI), but mortality may be as high as 10% to 15% after 1 year. Verapamil prevents cardiac events after an AMI in patients without CHF. We hypothesized that in postinfarct patients with CHF already prescribed diuretics and an ACE inhibitor, additional treatment with verapamil may reduce cardiac event rate. In this multicenter, double-blind study, patients with CHF receiving diuretic treatment were consecutively randomized to treatment with trandolapril 1 mg/day for 1 month and 2 mg/day the following 2 months (n = 49), or to trandolapril as mentioned plus verapamil 240 mg/day for 1 month and 360 mg/day for 2 months (n = 51). Trial medication started 3 to 10 days after AMI. All patients were followed for 3 months. End points in the trandolapril/trandolapril-verapamil groups were death 1/1, reinfarction 7/1, unstable angina 9/3, and readmission for CHF 6/2. The 3-month first cardiac event rate was 35% in trandolapril-treated patients and 14% in trandolapril-verapamil-treated patients (hazard ratio 0.35, 95% confidence interval 0.15 to 0.85, p = 0.015). These data suggest that verapamil reduces cardiac event rates in post-AMI patients with CHF when added to an ACE inhibitor and a diuretic.

Treatment with verapamil after an acute myocardial infarction. Review of the Danish studies on verapamil in myocardial infarction (DAVIT I and II).

The effect of verapamil on death, reinfarctions, and major events, i.e. death or reinfarction after a myocardial infarction has been investigated in 2 Danish double-blind placebo-controlled verapamil infarction trials (DAVIT I and II). DAVIT I was an early intervention trial that demonstrated a statistically nonsignificant reduction in mortality and reinfarction after 6 months of treatment. DAVIT II was a later intervention trial that demonstrated a nonsignificant reduction in the 18-month mortality rate [p = 0.11, hazard ratio 0.80; 95% confidence limits (CL) 0.61 to 1.05], a significant reduction in the reinfarction rate (p = 0.04, hazard ratio 0.77; CL 0.58 to 1.03), and in the major event rate (p = 0.03, hazard ratio 0.80; CL 0.64 to 0.99) in the verapamil group compared with the placebo group. In patients without heart failure in the coronary care unit, a statistically significant reduction in the 18-month mortality rate (p = 0.02, hazard ratio 0.64; CL 0.44 to 0.94), the reinfarction rate (p = 0.02, hazard ratio 0.67; CL 0.46 to 0.97), and the major event rate (p = 0.01, hazard ratio 0.70; CL 0.52 to 0.93) was observed in the verapamil group compared with the placebo group. No significant differences were found in patients with heart failure. Meta-analyses of DAVIT I (for patients alive at day 8) and DAVIT II showed a statistically significant reduction in the odds ratio of mortality (22%), reinfarctions (27%), and the major event rate (21%) in verapamil-treated patients. It is concluded that long term treatment with verapamil after an acute myocardial infarction is associated with a significant reduction in overall mortality, major events, and reinfarctions, with the greatest effect in patients without heart failure.

Secondary prevention with calcium antagonists after acute myocardial infarction.

Experimental studies have demonstrated that the 3 calcium antagonists nifedipine, diltiazem, and verapamil have a comparable effect in the prevention of myocardial damage during ischaemia. Secondary prevention trials after acute myocardial infarction, which aimed at improving survival and preventing reinfarction, nevertheless demonstrated pronounced differences between the 3 drugs. Nifedipine had no effect on reinfarction or death. Diltiazem had no overall effect but prevented first reinfarction or cardiac death (cardiac events) in patients without heart failure, and increased cardiac events in patients with heart failure before randomisation. Verapamil prevented first reinfarction or death (major events); the most pronounced effect was found in patients without heart failure before randomisation. Verapamil did not have detrimental effects in patients treated for heart failure before randomisation. Differences between trials and between drugs explaining the different clinical findings are evaluated.

Postinfarct treatment with verapamil. Effect of verapamil in patients with hypertension.

In the Danish Verapamil Infarction Trial II (DAVIT II), treatment with verapamil 360 mg/day improved reinfarction-free survival compared with administration of placebo. Verapamil appears to effectively prevent reinfarction and sudden death, i.e. sudden events (hazard ratio 0.78 compared with placebo, 95% confidence limits 0.62 to 0.99). In a retrospective analysis of data from DAVIT II, verapamil treatment in patients with systemic hypertension prevented reinfarction significantly better than placebo (15 of 149 verapamil recipients compared with 27 of 152 placebo recipients reinfarcted, p = 0.04). Similarly, first cardiovascular events, i.e. first reinfarction, first stroke or death, were prevented more effectively by verapamil treatment than by administration of placebo (29 verapamil recipients vs 42 placebo recipients had first cardiovascular events, p = 0.07).

Atherosclerosis in Watanabe heritable hyperlipidaemic rabbits. Evaluation by macroscopic, microscopic and biochemical methods and comparison of atherosclerosis variables.

The spontaneous development of atherosclerotic disease in 38 homozygous and 34 heterozygous Watanabe heritable hyperlipidaemic rabbits was evaluated by qualitative and quantitative light microscopy in aorta, coronary, pulmonary and renal arteries, by naked eye and macroscopic morphometric estimation of aortic atherosclerosis extent and by biochemical analysis of aortic cholesterol content. No noteworthy atherosclerosis was demonstrated within 19 months in heterozygous rabbits. In homozygous rabbits, atherosclerotic lesions were seen from the age of 4 months and progressed with age. All 19-month-old rabbits had severe atherosclerotic disease. As much as 64% of the variation in atherosclerosis extent/severity could be explained by serum cholesterol and age. A highly significant correlation between the various methods for quantitation of atherosclerosis extent and/or severity was demonstrated, suggesting that quantitative microscopy, macroscopic morphometry and determination of aortic cholesterol content may be equally valid as a measure of atherosclerosis in WHHL rabbits and are therefore interchangeable.

Time- and concentration-dependent increases in cell proliferation in rats and mice administered vinyl acetate in drinking water.

Chronic administration of vinyl acetate (VA) in drinking water to rats and mice has produced upper digestive tract neoplasms. These tumors were believed to arise from the intracellular metabolism of VA by carboxylesterases to cytotoxic and genotoxic compounds. We hypothesized that prolonged VA exposure at high concentrations would induce cytotoxicity and a restorative cell proliferation (CP). These endpoints were measured in F-344 rats and BDF1 mice administered drinking water containing 0, 1000, 5000, 10,000, or 24,000 ppm VA for 92 days. On test days, Days 1, 8, 29, and 92, upper digestive tract histopathology and oral cavity CP (pulsed 5-bromodeoxyuridine [BrdU] to measure S-phase DNA synthesis) were evaluated. Analysis of test solutions showed that VA spontaneously hydrolyzed, slowly releasing acetic acid and thereby lowering pH. Statistically significant, concentration-related increases in CP occurred in basal cells of the mandibular oral cavity mucosa of mice at 10,000 and 24,000 ppm but only after 92 days. CP increases were approximately 2.4- and 3.4-fold above controls and were considered to be toxicologically significant. Some statistically significant increases in CP were also measured in the oral cavity mucosa of rats; however, these changes were considered to be of equivocal biological relevance. No histopathological evidence of mucosal injury was seen in either species. The absence of cytotoxicity in the upper digestive tract mucosa suggests that the increased CP at high administered VA concentrations may be due to a mitogenic response, ostensibly from the loss of cell growth controls in oral cavity mucosa.

The self-association of zinc-free human insulin and insulin analogue B13-glutamine.

The self-association of Zn-free human insulin, Zn-free insulin analogue B13-glutamine, 2-Zn insulin and cobalt(III) human insulin in the millimolar concentration range has been investigated by measuring the osmotic pressure at pH 7.5 in 0.05 M NaCl, 25 degrees C. The pH dependence of association has been measured in the pH range 6.8-9. For all insulins, except Zn-free human insulin, the major association state has been found to be the hexamer. Maximal association of hexamer has been observed for Zn-free human insulin at high concentration (2-7 mM) and physiological pH. At concentrations less than 1 mM and pH greater than 7.0, dissociation to a lower state than the hexamer is found. The conclusion has been drawn that, in the absence of metal ions, human insulin and insulin analogue B13-glutamine associate to the hexamer in the physiological pH range at concentrations in the millimolar range.

Effect of verapamil on reinfarction and cardiovascular events in patients with arterial hypertension included in the Danish Verapamil Infarction Trial II. The Danish Study Group on Verapamil in Myocardial Infarction.

An increased incidence of reinfarction and cardiovascular events has been reported in patients with hypertension recovering from acute myocardial infarction. We studied the effect of intervention with verapamil on the development of myocardial infarction and cardiovascular events in 301 patients with hypertension enrolled in the Danish Verapamil Infarction Trial II. During the second week after the index infarct, patients were randomly assigned to treatment with verapamil 360 mg per day (n = 149) or placebo (n = 152) and followed-up to 18 months (mean 16 months). The 18 months first reinfarction rates were 12.5% in verapamil and 19.8% in placebo treated patients (hazard ratio 0.53, 95% confidence limits 0.28-1.00, P = 0.04). The first cardiovascular event rates were 21.8% in the verapamil and 29.3% in the placebo group (hazard ratio 0.66, 95% confidence limits 0.41-1.06, P = 0.07). In this retrospective analysis of patients with hypertension included in the Danish Verapamil Infarction Trial II, intervention with verapamil reduced cardiovascular events primarily due to a substantial reduction in reinfarctions.

Predictors of sudden death and death from pump failure in congestive heart failure are different. Analysis of 24 h Holter monitoring, clinical variables, blood chemistry, exercise test and radionuclide angiography.

One hundred and ninety consecutive patients discharged with congestive heart failure were examined with clinical evaluation, blood chemistry, 24 h Holter monitoring, exercise test and radionuclide angiography. Median left ventricular ejection fraction was 0.30, 46% were in New York Heart Association class II and 44% in III. Total mortality after 1 year was 21%, after 2 years 32%. Of 60 deaths, 33% were sudden and 49% due to pump failure. Multivariate analyses identified totally different risk factors for sudden death: ventricular tachycardia, s-sodium < or = 137 mmol/l, s-magnesium < or = 0.80 mmol/l, s-creatinine > 121 mumol/l, and maximal change in heart rate during exercise < or = 35 min-1, and for death from progressive pump failure: New York Heart Association class III + IV, delta heart rate over 24 h < or = 50 min-1, low ejection fraction, high resting p-noradrenaline, s-urea > 7.6 mmol/l, s-potassium < 3.5 mmol/l, and maximal exercise duration < or = 4 min. In conclusion, this study demonstrated different risk factors for sudden death and for death from progressive pump failure.

Effect of verapamil on the prognosis of patients with early postinfarction electrical or mechanical complications. The Danish Verapamil Infarction Trial II (DAVIT II).

The Danish Verapamil Infarction Trial II (DAVIT II) demonstrated from the second postinfarction week, that long term treatment with verapamil significantly improved reinfarction free survival after an acute myocardial infarction (AMI). The present post hoc analysis of DAVIT II was undertaken with the purpose of evaluating the effect of treatment with verapamil in patients with early electrical complications, i.e. ventricular or atrial fibrillation, ventricular tachycardia, or second or third degree atrioventricular block, with or without mechanical complication, i.e. heart failure, during the first post-AMI week. In the placebo group, the 18-month mortality rate was lowest (9.5%) in patients without electrical or mechanical complications, highest (24.6%) in patients with electrical events only, and in-between (17.5%) in patients with mechanical problems regardless of presence of electrical complications. Verapamil significantly reduced the 18-month mortality rate in patients with early electrical without mechanical complications (60% reduction, P = 0.02), and in patients without mechanical complications (35% reduction, P = 0.02). Verapamil did not change the mortality rate in patients with mechanical complications.

Evaluation of a method used to test for potential toxicity of carpet emissions.

After a private testing laboratory had reported mortality, neurotoxicity, and respiratory irritation in mice exposed to emissions from heated carpet in a modified application of the sensory irritation test (ASTM E981-84), the studies reported in this paper were conducted to evaluate the method used in testing for carpet toxicity and to see if the reported findings were reproducible. Mice were exposed head-only to offgasses generated by heating carpet (AT #3) to temperatures that ranged from 37 to 70 degrees C. Control mice were simultaneously exposed to heated air. The animals were evaluated for mortality, clinical signs and respiratory irritation. Neurotoxicity was evaluated using functional observational battery and motor activity monitoring. Pathological evaluations of organs and tissues, including the nervous system, were also conducted. The carpet samples heated to higher temperatures produced greater concentrations of total volatile organic compounds than those heated to 37 degrees C. Both carpet-exposed and control mice displayed some effects, such as body weight loss, mortality and pathological lesions, that were due to the exposure system. There was no mortality or neurotoxicity, nor were there clinical signs or pathological lesions as a result of carpet exposures. Mice exposed to carpet heated to 70 degrees C had slightly decreased respiratory rates and an increased incidence of breathing patterns indicative of sensory irritation. Therefore, none of the results reported by the private testing laboratory could be reproduced when this carpet was heated to temperatures below 70 degrees C, and slight sensory irritation was the only effect observed at the 70 degrees C test conditions. Effects from the exposure system itself made interpretation of results difficult, and concurrent controls were considered essential for interpretation of data.