Central and regional hemodynamic effects of flosequinan for congestive heart failure.

The central and regional hemodynamic effects of flosequinan, a new orally administered vasodilator, were examined in 10 patients with moderate to severe congestive heart failure. A single-blind design was used to compare a standard dose of flosequinan (100 mg) with placebo. Flosequinan produced a statistically significant increase in cardiac output, primarily through its augmentation of stroke volume. This response was accompanied by significant reductions in systemic vascular resistances and right and left ventricular filling pressures. A reduction in pulmonary artery pressure and total pulmonary vascular resistance also was observed. The vasodilatory actions of flosequinan improved overall left ventricular performance; the inotropic indexes measured were not altered. There were no significant changes in upper limb, renal or hepatic-splanchnic blood flow or in the vascular resistances of these regions after flosequinan administration. The upper limb venous capacitance increased significantly. First-dose flosequinan evokes favorable central hemodynamic changes and improves overall left ventricular performance in patients with congestive heart failure. The acute augmentation in cardiac output, however, is not accompanied by a preferential alteration of flow to any of the major vascular regions studied.

Risk of noncardiac operation in patients with defined coronary disease: The Coronary Artery Surgery Study (CASS) registry experience.

It has been suggested that coronary artery bypass grafting (CABG) is efficacious in patients with severe coronary artery disease before they undergo a major noncardiac operation. The Coronary Artery Surgery Study (CASS) registry population was reviewed to identify variables affecting operative mortality and cardiovascular morbidity for noncardiac procedures, and to assess the influence of prior CABG on these surgical risks. Major noncardiac operations were performed on 1,600 registry patients between June 30, 1978, and June 30, 1981. Operative mortality for individuals without significant coronary artery disease (Group 1) was 0.5% (2/399) and for patients with such disease having CABG prior to a noncardiac procedure (Group 2), it was 0.9% (7/743) (Group 1 versus Group 2, p = 0.42). Patients with significant coronary artery disease undergoing noncardiac operation without prior CABG (Group 3) had an increased operative mortality, 2.4% (11/458) (p = 0.009). Group 2 patients had more severe angina symptoms (p less than 0.001) and more extensive coronary artery disease (p less than 0.001) on entering CASS than Group 3 patients. Postoperative chest pain occurred in 8.7% (40/458) of the Group 3 patients versus 4.5% (18/399) in Group 1 and 5.1% (38/743) in Group 2 (p = 0.004). No group differences were noted for the incidence of perioperative myocardial infarction or arrhythmias.(ABSTRACT TRUNCATED AT 250 WORDS)

Drug interactions: the effect of alcohol and meprobamate applied singly and jointly in human subjects. V. Summary and conclusions.

The design, analysis and conclusions of the series of experiments by Carpenter et al., Ashford and Cobby, and Cobby and Ashford [J. Stud. Alc., Suppl. No. 7, pp. 54-176, 1975] are reviewed. Mathematical models of the joint action of drugs were developed and data obtained to test the models by studying the action of alcohol and meprobamate singly and in combination in human subjects. The data proved to be too limited in the range of drug concentrations in the blood necessary to identify the single most appropriate model. Carpenter et al. analyzed the data by analysis of variance, which involves assumptions about the structure of the observation and the form of the distribution of the error terms. The analyses of Ashford and Cobby and Cobby and Ashford used the mathematical models, which represented pharmacological and physiological actions of the drugs. The majority of the results of the two analyses agreed; however in Experiment V Carpenter et al. combined drugs, doses and blood samples in one analysis anf found a significant influence of meprobamate dose on blood alcohol concentration (BAC) and homogeneous error terms. Cobby and Ashford analyzed absorption and elimination phases of each alcohol dose separately and found no influence of meprobamate on BAC and significant heterogeneity in the residual error terms. Both sets of analyses found a complex interaction between the pattern of abosorption and elimination of meprobamate and dose of alcohol. Carpenter et al. related the results of behavioral measures to drug doses, Ashford and Cobby to the concentrations of the drugs in the blood. Theoretically the models can analyze the pattern of behavioral results at each combination of doses but the data available were insufficient for the purpose. The modifications in experimental design and analytical techniques necessary to continue research in developing mathematical models are discussed.

Drug interactions: the effects of alcohol and meprobamate applied singly and jointly in human subjects. I. Theoretical considerations and literature review.

The considerations necessary to describe the effects of combinations of drugs in a biological system are reviewed. The terms which express these effects-additive, potentiative, antagonistic, synergistic-have not had specific operations applied to them and mathematical models have been sought to define these operations. The models should (1) describe the nature of the action of single drugs, (2) classify the results of drug combinations, (3) provide a set of operations for deciding the outcome of combinations, and (4) predict all possible results of a combination from a knowledge of each drug acting alone. Research on the effects of alcohol and meprobamate and their interactions is reviewed, including behavioral and pharmacological studies and also some studies of the interaction of alcohol with other drugs. The task of characterizing the relation between the drug and response is formidable because complex physiological and biochemical processes determine the relationship between administered and effective dose and are further complicated by route of drug administration and various time relations. The descriptions of biochemical and physiological events seem well advanced; those of behavior are not. Much of the behavioral research assumes that a single dose is representative of all doses of the drug, and that combinations of the drugs and additivity of effects can be determined without a rigorous definition or means of application. [Bibliography of 249 items.]

Drug interactions: the effects of alcohol and meprobamate applied singly and jointly in human subjects. II. Five experiments.

Five experiments were conducted to study the effects of alcohol and meprobamate, administered singly and in combination, at doses up to 1.20 g of alcohol per kg of body weight and up to 30 mg of meprobamate per kg. Most of the 158 men were of college age (range, 21-49). In all experiments it appeared to the subjects that both drugs were administered, alcohol as a 25% solution in orange juice and meprobamate as 10 tablets. One hour after the men took the meprobamate they had 1 hr to drink the beverage. Before and at 1/2 hr intervals after administration of the drugs blood samples were taken and behavioral response measured by means of a visual-motor coordination tracking task (Stressalyzer). An experimental session lasted 6 hr. In Experiment I (E-I) each of 12 men was tested on 2 days, after 0, 1.00 or 1.20 g of alcohol per kg and 0 or 25 mg of meprobamate per kg. In Experiment II (E-II) 56 men were tested (8 per group) after 0, 5, 10, 15, 20, 25 or 30 mg of meprobamate per kg and alcohol placebo. In Experiment III (E-III) 40 men were tested (8 per group) after 0, 0.25, 0.50, 0.75, or 1.00 g of alcohol per kg and meprobamate placebo. In Experiment IV (E-IV) 25 men (5 per group) received meprobamate 3 times a day (total daily dosage, 0, 7, 14, 21 or 28 mg per kg) for 12 days. On days 8 to 12 all subjects drank alcohol, as in E-III. In Experiment V (E-V) 25 subjects (5 per group) were tested on 5 days, drinking each day the same doses of alcohol as in E-III and all received the same doses of meprobamate as in E-IV.

Ethanol-induced mouse strain differences in locomotor activity.

C57BL/6J mice showed dose dependent devreases in locomotor activity with increasing IP doses of ethanol (0.0, 0.75, 1.50 and 2.25 g/kg), while BALB/cJ mice showed dose dependent increases in activity; both strains were equally active with saline. Whether this finding represents decreased CNS responsivity in C57BL mice to ethanol's excitatory effect or increased response to its depressant action at sub-hypnotic doses is unclear, since anesthetic doses produce anesthesia of far shorter duration in the C57BL strain than in the BALB strain. It is possible that the biphasic action of alcohol is under the control of separate and distinct mechanisms, rather than a common one, and that these two mechanisms are differentially affected by alcohol. Endogenous as well as ethanol-induced neurochemical differences in biogenic amines may also be correlated with the gentic variation in CNS responsivity towards alcohol.

Cognitive moderators of alcohol's effects on anxiety.

The present study was designed to test the prediction from the attention-allocation model that intoxication in the absence of a pleasant distractor will fail to produce anxiolytic effects. A second prediction, that the sequence of intoxication and exposure to the anxiety-producing situation would influence alcohol's effects, was also tested. Subjects were male social drinkers who received an 0.85 g/kg dose of alcohol or a placebo. Conventional statistical analysis of the results indicated an anxiolytic effect of alcohol on heart rate but a problem with this analysis is identified. An alternative interpretation provides no support for an anxiolytic effect. Exposure to the anxiety-producing stimulus prior to intoxication led to greater heart rate reactivity than if it followed intoxication.

Effect of alpha-methyl-p-tyrosine on dose-dependent mouse strain differences in locomotor activity after ethanol.

Ethanol had biphasic effects on locomotor activity in C57Bl and BALB mice, but at different doses in the two strains. Catecholamine depletion attenuated activity increases in both strains but did not affect decreases.

Update: prevalence of Salmonella in pork sausage.

One hundred seventy-five samples of fresh pork sausage representing thirty-five different commercial brands from six different retail stores were examined for the presence of salmonellae by standard enrichment, plating, biochemical and serological techniques. Contamination levels varied from 0 to 50% among stores and from 0 to 28% among brands. Prior research implied reduced prevalence of salmonellae in fresh pork sausage; however, these results indicate no variation in prevalence since 1969.

Use of chuck muscles and their acceptability in restructured beef/surimi steaks.

Ten major muscles along with any unidentifiable lean, were carefully excised from 16 Choice square-cut chucks Yield Grade 2, and placed according to previously determined tenderness rankings, into one of three muscle groups. Group 1 was composed of the most tender muscles, and contained the infraspinatus, longissimus, and triceps brachii. Group 2 contained intermediate tenderness muscles and was composed of the serratus ventralis, deep pectoral, and complexus. Group 3 contained the least tender muscles and was composed of the biceps brachii, supraspinatus, rhomboideus, trapezius, deltoids, and neck muscles. Each group was restructured into beef/surimi steaks and was evaluated. Total muscle yield before trimming accounted for 66.2% of the chuck. Careful fat trimming, desinewing, and internal seam cutting on individual muscles resulted in 34.7% lean available for the restructuring of steaks. The triceps brachii, longissimus, supraspinatus, and infraspinatus required the least trimming and were easiest to excise. These muscles made up 49% of the trimmed meat and 13.7% of the total chuck. Steaks were evaluated by a consumer sensory panel for tenderness, flavor, overall preference, and intent to purchase. There were no differences detected by consumers among the muscle groups for the sensory traits studied. Tenderness and flavor were rated equal to intact steaks for all muscle groups studied. The consumer sensory panel indicated that Groups 1 and 2 would be purchased twice a month and Group 3 once a month.

Effect of added water, sodium erythorbate and storage time on the functional properties of prerigor beef preblends in a model system.

Singular and combined effects of added water, sodium erythorbate and storage time on salt soluble protein extractability, bacteriological and chemical characteristics of preblended hot-boned beef were evaluated. Waterholding and gel forming capacities of preblended hot-boned beef containing either 0, 10 or 20% added water were determined. Significant interactions between added water level and storage time on microbial counts and between sodium erythorbate level and storage time on thiobarbituric acid values and residual nitrite levels were noted. The presence of sodium erythorbate resulted in a more (P < 0·05) rapid rate of nitrite disappearance, but it did not affect (P > 0·05) microbial counts. Salt-soluble protein extractability was not affected (P > 0·05) by added water, but more protein could be extracted with increasing storage time. A trend existed to suggest that the presence of added water in the meat preblends slightly improved the gel formation and waterholding capacities.

Physical and sensory attributes of hot-processed and conventionally chilled hams and bellies from electrically stimulated and non-stimulated pork carcasses.

Forty-eight fresh hams and bellies were obtained from 24 market weight hogs (x = 94·5 kg) of which twelve were electrically stimulated (ES) by pulsing current immediately after exsanguination. The left side of each non-stimulated (NS) carcas was fabricated after conditioning for 3h post mortem at 17°C (NS hot-processed). The left sides of ES carcasses were fabricated 1 h pm. The right sides were fabricated following a 24 h cooler chill at 2°C (conventionally chilled: CP). Hams from ESCP carcasses had higher (P < 0·05) smokehouse yields than hams from NS carcasses. Hams that were hot-processed had higher smokehouse yields than the NSCP hams. Time of fabrication (1, 3 or 24h post mortem) did not affect smokehouse yields. Conventionally chilled bellies obtained from ES carcasses showed higher (P < 0·05) residual nitrite levels than those front electrically stimulated hot-processed (ESHP) carcasses. No differences were found for residual nitrite levels in the non-electrically stimulated sides. Panelists were unable to detect any sensory differences from the bacon strips. Sensory scores of ham slices were more juicy for non-stimulated hot-processed carcasses (NSHP) than those from ESHP carcasses. Panelists found the ham slices from NSCP carcasses to be more tender (P < 0·05) than those from electrically stimulated cold-processed (ESCP) carcasses. Results from this study clearly indicated that hot-processing of pork can provide hams and bellies that are acceptable for the production of cured hams and bacon of comparable quality and yield to those currently being produced under conventional processing methods.