Effects of different aspirin formulations on platelet aggregation times and on plasma salicylate concentrations.

BACKGROUND: Early aspirin treatment is widely used to inhibit platelet activity and to reduce morbidity and mortality in patients presenting with an acute myocardial infarction or a stroke. A number of different aspirin formulations have been used for this purpose; however, a comparison of their effectiveness in inhibiting early platelet aggregation has not been determined. METHODS: In this study, we determined plasma salicylate concentrations and platelet inhibitory activities at various times after ingestion of three commonly used aspirin formulations: soluble aspirin (Alka-Seltzer), 325 mg, chewed baby aspirin, 324 mg, and whole compressed non-enteric coated aspirin, 324 mg. Twenty-four healthy volunteers, 18-39 years of age, participated in the prospective single-blinded triple-crossover study. Plasma salicylate concentrations and inhibition of arachidonic acid-induced platelet aggregation were determined on post-dose blood samples collected at 2.5, 5.0, 7.5, 10, 15, 20, 25, 30, and 40 min. All subjects crossed over to the other two formulations with at least 2 weeks between ingestions. RESULTS: The median platelet inhibition times for the chewed, soluble, and whole aspirin formulations were 7.5, 7.5, and 10.0 min, respectively. Soluble and chewed aspirin were found to inhibit platelet aggregation faster than whole aspirin (p<0.001); however, there were no significant differences in platelet aggregation times between the soluble and chewed formulations (p<0.163). Inhibition of platelet aggregation was found to occur at an average plasma salicylate concentration of 2.46 microg/mL, regardless of method of ingestion. CONCLUSION: The results indicate that soluble and chewed aspirin inhibit platelet aggregation in a shorter period of time than does whole aspirin. The results suggest that chewing baby aspirin or taking soluble buffered aspirin may be the preferred route of administration for early platelet inhibition.

The association between physical activity, physical fitness, and type 2 diabetes mellitus.

Recent studies have shown that cardiorespiratory fitness--an objective measurement of physical activity--is a strong predictor of type 2 diabetes. Self-reported physical activity is also associated with decreased risk of developing diabetes.

Comparison of various lipid, lipoprotein, and bilirubin combinations as risk factors for predicting coronary artery disease.

Studies were performed to determine if serum bilirubin, when combined with various lipid and lipoprotein risk factors, enhances our ability to predict coronary artery disease (CAD). This hypothesis was tested in a retrospective study of 644 middle-aged males who had undergone coronary angiography. The traditional risk factors of cholesterol, high density lipoprotein cholesterol (HDL-C), cholesterol/HDL-C ratios, triglycerides, age, cigarette smoking, and systolic blood pressure were tested by discriminant analysis, as were various cholesterol/bilirubin, cholesterol/(HDL-C+bilirubin), and low-density lipoprotein cholesterol (LDL-C)/(HDL-C+bilirubin) ratios. Each of these bilirubin-containing ratios was found to be an independent risk predictor when tested with the traditional risk factors. When the LDL-C/(HDL-C+bilirubin) ratio was included with the traditional risk predictors, it improved the prediction of severe CAD from 28.4 to 35.3% and the overall correct classification of CAD from 68.3 to 71.1%. When the 75th percentile was used as a cut-point, the diagnostic sensitivities obtained with cholesterol/(HDL-C+bilirubin) ratios (52.1%) and LDL-C/(HDL-C+bilirubin) ratios (51.7%) were better than those obtained with cholesterol/HDL-C ratios (40.4%) (P=0.033 and 0.048, respectively). LDL-C/(HDL-C+bilirubin) ratios also improved the prediction of severe CAD over those obtained with LDL-C/HDL-C ratios (43.4%); however, the changes were not statistically significant (P=0.096). If confirmed in other populations, serum bilirubin may be combined with LDL-C/HDL-C ratios, cholesterol/HDL-C ratios, cholesterol, or with various apolipoproteins to improve the prediction of CAD.

Association of smoking and low serum bilirubin antioxidant concentrations.

This study sought to examine the association between cigarette smoking and serum bilirubin antioxidant concentrations in 715 middle-aged men undergoing coronary angiography. The study involved 153 current smokers, 251 who quit smoking and 311 who never smoked. Serum bilirubin concentrations were divided into the following quartiles; 0.20-0.57, 0.58-0.73, 0.74-0.95 and 0.96-3.26 mg/dl. The percentage of individuals within each quartile were as follows; current smokers (42, 22, 24, 12), former smokers (22, 27, 23, 28), nonsmokers (16, 28, 27, 29). A total of 42% of the current smokers had bilirubin concentrations in the lowest quartile compared to 16% of the nonsmokers. Also, 12% of the current smokers had bilirubin concentrations in the highest quartile compared to 29% in the nonsmoking group. The Mantel-Haenszel chi-square test for association between ordered categorical variables was 30.6 (P < 0.0001). Subdividing the subjects according to maximum percent stenosis on angiography (< 10, 10-49, 50-100%) revealed a significant inverse association between smoking and bilirubin (< 0.01) within each subset. The data shows that smoking is associated with decreased serum bilirubin concentrations. In addition, it supports the hypothesis that cigarette smoking may increase the risk of coronary artery disease by lowering antioxidant concentrations and raising oxidized lipid and lipoprotein concentrations.

Patenting medical inventions.

Medical, dental, nursing, and biomedical personnel often perform critical research that can lead to patents. Similarly, patentable discoveries can be made during the normal course of medical practice, e.g., the development of new biocompatible polymers, improved dental materials, new or modified catheters, new laboratory diagnostic tests, and improved medical devices. Many inventions may not be patented in federal organizations due to the lack of information available on the patenting process. In this article, the financial benefits that can be derived from patenting inventions are discussed, as well as the different types of patents that can be obtained, the conditions for patentability, bars or restrictions to obtaining a patent, the importance of proper record keeping, and the steps to take toward getting an invention patented.

Association of low serum concentration of bilirubin with increased risk of coronary artery disease.

We examined serum bilirubin and various liver-function enzymes as possible risk factors for angiographically documented coronary artery disease (CAD). The studies involved a "training" set of 619 men for whom complete data on all risk factors considered were available, and a "test" set of 258 men for whom some risk factor data were not available. In both study groups, the liver enzymes were not related to CAD; however, In[total bilirubin] was inversely and statistically significantly related to the presence of CAD, both univariately and multivariately after adjustment for the established risk factors of age, total cholesterol, high-density lipoprotein cholesterol, smoking history, and systolic blood pressure. A 50% decrease in total bilirubin was associated with a 47% increase in the odds of being in a more severe CAD category. Our data suggest that serum bilirubin is an inverse and independent risk factor for CAD, with an association equivalent in degree to that of systolic blood pressure.

Comparison of lipid fatty acids on a concentration basis vs weight percentage basis in patients with and without coronary artery disease or diabetes.

Lipid fatty acid compositions are almost always expressed on a weight percentage basis rather than as weight or molar concentrations. With the former method of calculation, each fatty acid has an effect on the composition of the other fatty acids, an interdependence that can potentially lead to inaccurate and misleading results. Here we compare the concentrations per liter and the weight percentage compositions of cholesteryl ester and phospholipid fatty acids in individuals with and without coronary artery disease as well as free fatty acid compositions in individuals with and without diabetes. A new method for quantifying lipid fatty acids is also presented. Fatty acid results expressed as concentrations and those calculated on a weight percentage basis may lead to different conclusions, because significant differences between patient groups can be lost with the latter approach. We conclude that serum concentrations of lipid fatty acids are more accurate reflections of changes in lipid fatty acids than are weight percentage calculations, and are more easily interpreted in metabolic and therapeutic terms.

New extraction procedure and high-performance liquid chromatographic method for analyzing polyethylene glycol-400 in urine.

We describe a new, highly efficient method for extracting polyethylene glycol-400 from urine and for its analysis by isocratic reversed-phase high-performance liquid chromatography. This method is an improvement over previously published methods in that it does not require the use of ion-exchange resins and lyophilization prior to extraction, nor does it require the separation and analysis of the individual polymers of polyethylene glycol. The procedure described in this report entails extraction with a salt-solvent combination of ammonium sulfate and dichloromethane and analysis by reversed-phase high-performance liquid chromatography. The lower limit of detection was approximately 0.25 g/l with a 2-ml urine sample. Analytical recoveries of polyethylene glycol-400 added to urine at 2.5 and 5.0 g/l averaged 97 and 96%, respectively (n = 10). Within- and between-day coefficients of variation were less than 5% at 2.5 and 5.0 g/l. Studies of various urine samples from patients receiving polyethylene glycol-400 revealed no interferences from other urine substances.

Electron-capture gas chromatography as a sensitive method for measuring subnanogram amounts of cholesterol in saliva and urine.

This is a sensitive method, suitable for measuring subanogram amounts of cholesterol. Cholesterol and the internal standard, epicoprostanol (5-beta-cholestan-3-alpha-ol), are derivatized with pentafluorobenzoyl chloride and detected by electron-capture gas chromatography. The pentafluorobenzoyl esters of cholesterol and the internal standard are easily formed and possess excellent chromatographic and electron-capturing properties. The lower limit of detection of the method, approximately 100 pg injected, is about 500-fold as sensitive as chromatographic methods involving flame-ionization detection. Within-day and between-day coefficients of variation were 4.2% and 8.2%, respectively, for determinations of a urinary cholesterol concentration of 570 micrograms/L (1.47 mumol/L). Such sensitivity permits analysis for cholesterol in (e.g.) physiological fluids, tissue samples, and cell cultures that contain very low concentrations of cholesterol.

Cortisol and the hypercholesterolemia of pregnancy and labor.

Lipids and lipoproteins are known to increase substantially during pregnancy and to decrease rapidly after delivery. The factors responsible for the changes have not been identified, however, they could be related to changes in one or more of the endocrine hormones. Since studies relating lipid and lipoprotein changes to cortisol or estradiol concentrations have not been made, we sought to perform such a study. For this study, we measured cholesterol, HDL-C, VLDL/LDL-C, cortisol, and estradiol concentrations from early gestation through delivery in 32 normal pregnant women. During the course of pregnancy, cholesterol increased from 145 to 211 mg/dl (45%); plasma cortisol increased from 8.6 to 17.8 micrograms/dl (107%); and urinary cortisol increased from 0.10 to 0.177 microgram/mg of creatinine (72%). Further significant increases in cholesterol (256 mg/dl, P less than 0.005) and cortisol (77.6 micrograms/dl, P less than 0.001) occurred during labor, and both decreased after delivery. Pooled correlations were calculated and both cholesterol and VLDL/LDL-cholesterol concentrations were found to be related to plasma cortisol as well as to urinary cortisol (P less than 0.001). Plasma estradiol concentrations increased during pregnancy, but not during labor. The results suggest that the increases in cholesterol during pregnancy and labor could be due, in part, to the metabolic and stress-related increases in cortisol. The studies also suggest that both pregnancy and labor and delivery might be useful "natural" models for studying hormonal mechanisms involved in lipid and lipoprotein metabolism.

A new protective factor in coronary artery disease. Very low density lipoprotein toxicity-preventing activity.

A newly discovered activity in human serum protects porcine aortic endothelial cells in culture from injury by very low density lipoproteins (VLDL). This factor, toxicity-preventing activity (TxPA), was measured in 29 relatively young men (43 +/- 8 years) who had undergone coronary angiography. The level of TxPA was found to be significantly reduced (P less than 0.001) in men who demonstrated more than 15% narrowing of their coronary arteries. Men (n = 18) who had 15% or less narrowing were found to have 104 +/- 48 units of TxPA while men (n = 11) with coronary artery disease had 48 +/- 24 units of TxPA. A value derived from the product of TxPA and the high density lipoprotein cholesterol (HDL-C) level divided by the non-HDL-C (total cholesterol-HDL-C) accurately separated 97% of the men into 2 groups. TxPA thus appears to be a new protective factor in coronary artery disease, which, when combined with total cholesterol and high density lipoprotein cholesterol values, provides an accurate classification of established coronary artery disease in these subjects.

Cholesterol, stress, lifestyle, and coronary heart disease.

Because of the recent report by the Lipid Research Group showing that a lowering of total cholesterol and LDL cholesterol lowered mortality due to coronary heart disease (CHD) and other similar studies, there can no longer be any doubt that cholesterol is a causal factor in the development of CHD. Since total serum cholesterol and LDL cholesterol are produced by the body, those interested in the prevention of CHD must give greater attention to factors which are associated with raised endogenous cholesterol. The major factors are increased dietary and body fat, emotional arousal, and the inability of the liver to clear the serum of low density lipoprotein. The beneficial effect of exercise on lowering one's risk of CHD reported in the literature may be mediated by a rise in HDL cholesterol and/or weight loss. All patients should have their total cholesterol/HDL measured. Those with elevated serum cholesterols should be encouraged to eat a low saturated low fat diet, exercise, maintain proper weight and avoid undue distress. Cigarette smoking should be discouraged. Blood pressure elevations not responsive to diet and exercise should be treated with medication. Cholesterol elevations not responsive to life style change, should be treated with Cholestyramine.

Relationship between cortisol and cholesterol in men with coronary artery disease and type A behavior.

To further understand the hormonal mechanisms linking behavior pattern and coronary artery disease (CAD), we investigated the relationship between 0930-hour plasma cortisol and cholesterol in relatively young males who had undergone coronary angiography and in a subgroup of individuals who had undergone the structured interview for classification of behavior pattern. A statistically significant association (p less than 0.05) was found between cortisol and cholesterol for individuals who had either minimal CAD (20% to 49% narrowing) or significant CAD (greater than or equal to 50% narrowing), but not for subjects without CAD. An association between cortisol and cholesterol was also found to be significant for the subgroup of individuals with Type A-1 behavior pattern, but not for those with Type A-2, X, or B behavior patterns. The findings suggest that hormonal mechanisms involving cortisol and cholesterol metabolism may be operative in individuals with CAD as well as in individuals with Type A-1 behavior.

Isolation and chromatographic analysis of unidentified fluorescence in biological fluids of patients with chronic renal disease.

An unidentified fluorescent substance has recently been shown to increase in serum of patients with chronic renal failure. Further studies were made to gain more information as to its identity and to determine if it is present in other biological fluids. Molecular-exclusion chromatography and thin-layer chromatography provide evidence that the substance is present in dialysis fluids and ultrafiltrates of patients with chronic renal disease as well as in urine of normal individuals. Normal urine levels were 10-fold higher than the levels in serum of patients with chronic renal disease, and these serum levels were 50- to 110-fold higher than the levels in normal serum. The unknown substance is highly water soluble and has an emission maximum of 415 +/- 5 mm and a relative molecular mass of less than 1,000. The described combination of gel chromatography and thin-layer chromatography is suggested as a useful approach for its isolation and subsequent identification.

A rapid method of evaluate acute ethanol intoxication in mice.

A simple technique for the evaluation of ethanol intoxication based on the ability of mice to remain on a bar suspended above an electrified grid is reported. The characteristics that make this model useful to measure ethanol induced intoxication include: (a) low variability; (b) high sensitivity; (c) rapidity; (d) requires no previous training of animals to be tested; (e) objective scoring which can be quantified; and (f) dose-dependent correlation between brain and blood ethanol levels and bar holding response.

Albumin-bound fluorescence in serum of patients with chronic renal failure.

A band that is strongly fluorescent and migrates electrophoretically with serum albumin is commonly found in electrophoretograms of sera from patients with chronic renal failure. We sought to determine whether the fluorescence originates from binding of certain still-unidentified metabolites or drugs, from an abnormal albumin species, or from some other protein entity. Molecular-exclusion column chromatography, polyacrylamide gel isoelectric focusing, and cellulose acetate electrophoresis, along with results of charcoal treatment and alcohol extraction, provided evidence that the fluorescence comes from fluorescent ligands tightly bound to albumin. The fluorescent intensity of the albumin fraction, isolated by molecular-exclusion chromatography, coincides with the albumin-associated fluorescence determined electrophoretically and with the intensities of the fluorescence emission spectrum for serum. A fluorescent species with an emission maximum of 415 +/- 5 nm, separated by thin-layer chromatography, appears to account for the increased serum fluorescence.

Analysis for diazepam and nordiazepam by electron-capture gas chromatography and by liquid chromatography.

We describe the use of electron-capture gas chromatography or reversed-phase "high-performance" liquid chromatography for concurrent analysis for diazepam and nordiazepam in serum. In the gas-chromatographic analysis our use of a new chemically deactivated stationary liquid phase, SP 2250-DB (Supelco, Inc.), resulted in improved chromatographic sensitivity and peak symmetry for the two benzodiazepines as compared to that obtained with either OV-17or OV-1 phases. Steady-state concentrations of diazepam and nordiazepam in serum as determined by gas-liquid chromatography correlated closely with those found by liquid-liquid chromatography.