Modeling flame extinction and reignition in large eddy simulations with fast chemistry.

This work seeks to support the validation of large eddy simulation models used to simulate fire suppression. The emphasis in the present study is on the prediction of flame extinction and the prevention of spurious reignition using a fast chemistry, mixing-controlled combustion model applicable to realistic fire scenarios of engineering interest. The configuration provides a buoyant, turbulent methane diffusion flame within a controlled co-flowing oxidizer. The oxidizer allows for the supply of a mixture of air and nitrogen, including conditions for which oxygen-dilution in the oxidizer leads to flame extinction. Measurements to support model validation include local profiles of thermocouple temperature and oxygen mole fraction, global combustion efficiency, and the limiting oxygen index. The present study evaluates the performance of critical-flame-temperature-based extinction and reignition models using the Fire Dynamics Simulator, an open-source fire dynamics solver. Alternate model cases are explored, each offering a unique treatment of extinction and reignition. Comparisons between simulated results and experimental measurements are used to evaluate the capability of these models to accurately describe flame extinction. Of the considered cases, those that include provisions to prevent spurious reignition show excellent agreement with measured data, whereas a baseline case lacking explicit reignition treatment fails to predict extinction.

Plasma 3-methylbutanal in man and its relationship to hepatic encephalopathy.

3-Methylbutanal is a volatile aldehyde which in the rat is derived, at least in part, from colonic bacterial breakdown of leucine. It has been proposed as a toxin of importance in the pathogenesis of hepatic encephalopathy in man. A rapid, reliable and highly reproducible method for estimating 3-methylbutanal in plasma is described using a gas-chromatograph with a head space-sampler. The mean plasma 3-methylbutanal concentration in non-fasting patients with hepatic encephalopathy, 0.244 mumol/litre (range 0-1.30) was not significantly different from the mean value in controls, 0.116 mumol/litre (0-0.349). Oral leucine feeding resulted in significant increases in plasma 3-methylbutanal concentrations in both control subjects and patients with cirrhosis. Peak leucine and 3-methylbutanal values occurred at approximately the same time and usually within 120 min of leucine ingestion. Pre-treatment with neomycin had no effect on the results of leucine feeding. No changes occurred in the clinical condition or psychometric performance of patients with cirrhosis fed leucine despite increases in plasma 3-methylbutanal of up to 700% over basal values. In man plasma 3-methylbutanal, at least in part, derives from ingested leucine independently of the action of colonic bacteria. The role of this compound in the pathogenesis of hepatic encephalopathy in man needs further exploration.

Effect of increased bile flow and bile acid secretion on the hepatic elimination of sodium valproate in the cat.

The effect of increased bile flow and hepatic bile acid flux on the systemic clearance and hepatic elimination of intravenously administered sodium valproate was studied in the bile fistula cat. Taurochenodeoxycholic acid (TCDC), tauro-3 alpha, 7 beta-dihydroxy-12-keto-5 beta-cholanoic acid (T12K), SC-2644, and secretin were infused intravenously to vary bile flow and biliary bile acid secretion. Control animals were infused with 0.15 mol/l NaCl. Less than 1% of the drug administered to controls appeared as unchanged valproate in the bile over 6 h. Although SC-2644, T12K, and secretin significantly increased biliary excretion of valproate, it did not exceed 2% of the intravenous dose. Biliary clearance was directly related to the rate of bile flow, but not to the bile acid flux. By contrast, 18-19% of the dose appeared in bile as metabolite in controls, and none of the choleretic agents significantly increased this percentage. As a result, systemic clearance of valproate was unaltered. We conclude that the movement of unchanged valproate into bile is consistent with a process of simple diffusion. The fact that choleretic agents do not increase metabolite excretion into bile suggests that metabolite formation may be the rate-limiting step in the hepatic elimination of valproate, rather than transport and excretion of metabolites into bile.

Ethanol elimination in males and females: relationship to menstrual cycle and body composition.

Ethanol pharmacokinetics were determined following oral ethanol, 0.5 gm per kg, in nine normal women and 10 normal men, and related to total body water measured by 3H-water dilution and body fat determined anthropometrically. Ethanol pharmacokinetics were similar in the females throughout the menstrual cycle. No variation was seen in mean peak blood ethanol concentration or elimination rate in the midfollicular (Days 8 to 10) and midluteal (Days 22 to 24) phases. Mean peak blood ethanol values were significantly higher in females (88 +/- 3 mg per 100 ml) than in males (75 +/- 4 mg per 100 ml) (p less than 0.05), and the mean area under the ethanol concentration-time curve was significantly greater in females (241 +/- 12 mg X hr per 100 ml) than in males (177 +/- 11 mg X hr per 100 ml) (p less than 0.001). There was no significant sex difference in mean ethanol elimination rates. The mean apparent volume of distribution of ethanol in female (0.59 +/- 0.02 liter per kg) was less than in males (0.73 +/- 0.02 liter per kg) (p less than 0.001). Both apparent volume of distribution of ethanol and area under curve were significantly correlated with total body water suggesting that the sex differences in ethanol pharmacokinetics were due to sex differences in body water content. The sex differences in ethanol pharmacokinetics may partly explain reports of male-female differences in the natural history of certain ethanol-related disorders.

Treatment of alcohol-related liver disease with thioctic acid: a six month randomised double-blind trial.

A randomised double-blind trial of thioctic acid (alpha-lipoic acid), 300 mg/day versus placebo was carried out in 40 patients with pre-cirrhotic alcohol-related liver disease over a six month period. Twenty patients received the active drug and 20 placebo. Twenty-two of the 40 patients (55%) abstained from alcohol and showed significant improvements (p less than 0.01) in mean values for serum aspartate transaminase, serum glutamyl transpeptidase, and mean corpuscular volume. Seventeen of the 22 (77%) showed overall histological improvement on liver biopsy. The remaining 18 patients (45%) continued to drink but significantly reduced their mean daily alcohol intake (p less than 0.001). No significant changes occurred in their laboratory indices, but five of the 18 (28%) showed overall histological improvement. Changes occurred irrespective of treatment with thioctic acid, which suggested that, over six months, this drug did not influence the course of alcohol-related liver disease.

Placental transfer of ranitidine during steady-state infusions of maternal and fetal sheep.

The placental transfer of ranitidine was studied at pharmacokinetic steady state in anesthetized, full-term, pregnant sheep. Ranitidine was administered to the ewe in three preparations and to the fetus in three other sheep. In all experiments, dose size was based on the combined maternal-fetal weight. Steady-state plasma levels were reached within 4 hr by using an initial intravenous bolus dose followed by continuous infusion. Following maternal dosage, the mean maternal (jugular vein) steady-state concentration (CMss) at 4 hr was 842 +/- 66 ng/ml (SEM), the mean fetal (carotid artery) steady-state concentration (CFss) was 26.5 +/- 4.2 ng/ml, and the mean fetal umbilical venous steady-state concentration was 28.9 +/- 3.5 ng/ml. Both the fetal and umbilical plasma concentrations were significantly less than the maternal plasma concentrations (p less than 0.01). With fetal dosage, mean CMss was 414 +/- 42 ng/ml at 4 hr and was significantly less than the mean CFss value at the same time, which was 6890 +/- 360 ng/ml (p less than 0.005). Ranitidine was not bound extensively to plasma proteins in the ewe or the fetus (range 12-55% bound). The reversal of the CMss/CFss gradient with the change from maternal to fetal administration and the low binding of the drug shows that the gradient following maternal dosage cannot be explained by ion-trapping or differential plasma protein binding. As active placental transport is considered unlikely, the low fetal plasma concentrations are probably due to the presence of significant fetal elimination of ranitidine. Furthermore, the substantial gradient between maternal and umbilical venous plasma concentrations suggests that placental elimination of ranitidine should also be considered.

Plasma amino-acid patterns in liver disease.

Plasma amino-acid concentrations were measured in 167 patients with liver disease of varying aetiology and severity, all free of encephalopathy, and the results compared with those in 57 control subjects matched for age and sex. In the four groups of patients with chronic liver disease (26 patients with chronic active hepatitis, 23 with primary biliary cirrhosis, 11 with cryptogenic cirrhosis, and 48 with alcoholic hepatitis +/- cirrhosis) plasma concentrations of methionine were significantly increased, while concentrations of the three branched chain amino-acids were significantly reduced. In the first three groups of patients plasma concentrations of aspartate, serine, and one or both of the aromatic amino-acids tyrosine and phenylalanine were also significantly increased, while in the patients with alcoholic hepatitis +/- cirrhosis plasma concentrations of glycine, alanine, and phenylalanine were significantly reduced. In the three groups of patients with minimal, potentially reversible liver disease (31 patients with alcoholic fatty liver, 10 with viral hepatitis, and 18 with biliary disease) plasma concentrations of proline and the three branched chain amino-acids were significantly reduced. Patients with alcoholic fatty liver also showed significantly reduced plasma phenylalanine values. Most changes in plasma amino-acid concentrations in patients with chronic liver disease may be explained on the basis of impaired hepatic function, portal-systemic shunting of blood, and hyperinsulinaemia and hyperglucagonaemia. The changes in patients with minimal liver disease are less easily explained.

Pharmacokinetics of the H2- receptor antagonist ranitidine in man.

1 Ranitidine pharmacokinetics were studied in six healthy volunteers. Following an overnight fast, doses of 20 mg intravenously 20, 40 and 100 mg orally and 100 mg orally with a standard meal, were administered to each subject on separate occasions. 2 Following intravenous administration there was a bioexponential decline in plasma levels from 576 +/- 56 ng/ml at 4 min to 10 +/- 2 ng/ml at 8 h. The distribution half-life (T 1/2 alpha) was 6.1 +/- 0.9 min, elimination half-life (T 1/2 beta) was 1.9 +/- 0.1 h, the volume of distribution (Vd beta) was 115 +/- 7 l and systemic plasma clearance (Cltp) was 709 +/- 62 ml/min. 3 Following 20 mg oral doses, peak levels were reached at 1.6 +/- 0.2 h and the systemic availability was 88 +/- 10%. Elimination half-life (T 1/2 beta) was unaffected by dose and the area under the curve increased linearly with dose and was unaffected by food. 4 Renal excretion (24 h) of unmetabolized ranitidine accounted for 50-70% of the dose with a further 1-3% appearing as desmethyl ranitidine.

Fetal hepatic function: the disposition of propranolol in the pregnant sheep.

The placental transfer, and maternal and fetal disposition, of the beta-adrenoreceptor blocking drug propranolol were studied in the pregnant sheep near term. In separate studies, propranolol (1 mg/kg) was administered peripherally or into the portal vein as an i.v. bolus, to either mother or fetus. Both mother and fetus were provided with vascular and bile duct cannulae, enabling plasma concentrations and biliary excretion of the drug to be measured over 6 hours. Placental transfer of propranolol was rapid and bidirectional. Comparison of the systemic blood levels obtained after peripheral and portal dosage indicated that hepatic extraction was much more efficient in the adult. This was supported by an apparent/true biliary clearance ratio of approximately 20 in the adult, and only 2-3 in the fetus. These studies show that the fetus near term is exposed to propranolol administered to the mother at a time when its ability to clear the drug is not fully developed.

The association of chronic active hepatitis with pyoderma gangrenosum.

This report deals with a 25-year-old man with chronic active hepatitis and cirrhosis who developed the rare complication of pyoderma gangrenosum which improved rapidly following the commencement of prednisolone.