Haemodynamic effects of DPI 201-106, following single intravenous dose administration to patients with moderate cardiac failure

DPI 201–106 is a novel compound unrelated to other cardioactiveagents and has been shown to have an inotropic effect in animalpreparations. The drug was given by intravenous infusion (20mg over 10 min) to 10 patients with moderate cardiac failureand the haemodynamic effects measured at intervals up to 1 hfollowing infusion. Maximal effects were seen immediately followingthe infusion of DPI 201–106. Cardiac index showed an increasefrom baseline 2·72 (0·16) 1 min^-1 m^-2 to 3·18(0.21) 1 min^-1 m^-2 at the end of infusion (P<0·001).Subsequent values were not significantly raised. Pulmonary capillarywedge pressure and pulmonary artery pressure fell from 27·6(3·2) and 36·9 (4·4) to 15·3 (3·6)and 24·2 (4·9) mmHg, respectively (P<0·001in both cases). A statistically significant effect on cardiacindex was not seen at 1 h. However, pulmonary pressures remainedreduced at this point. Radionuclide ejection fraction showeda significant increase from 15·4 (1·5) to 21·9(2·2)% (P<0·005) at the end of infusion, andmaintained a significant increase at 1 h. Having demonstratedbeneficial, acute haemodynamic effects in this study, furtherwork should be undertaken with DPI 201–106 to investigatethe effect of chronic treatment in patients with cardiac failure.     

创伤病人的手术与焦虑状态调查

采用状态——特质焦虑问卷及１０项躯体性焦虑测试题，对４０例外科创伤病人手术前后的焦虑状态调查显示：术前状态焦虑量表评分显著高于术后；术前躯体性焦虑评分显著高于术后；高特质焦虑评分亚组与低特质焦虑评分亚组术前状态焦虑评分无显著差异，但术后则前者显著高于后者；急诊手术者手术前后状态焦虑评分显著高于择期手术者。     

Synergy between the genes for butyrylcholinesterase K variant and apolipoprotein E4 in late-onset confirmed Alzheimer's disease

The allelic frequency of the gene for the K variant of butyrylcholinesterase (BCHE-K) was 0.17 in 74 subjects with late-onset (age > 65 years) histopathologically diagnosed Alzheimer's disease (AD), which was higher than the frequencies in 104 elderly control subjects (0.09), in 14 early-onset cases of confirmed AD (0.07) and in 29 confirmed cases of other dementia (0.10). The association of BCHE-K with late-onset AD was limited to carriers of the epsilon 4 allele of the apolipoprotein E gene (APOE), among whom the presence of BCHE-K gave an odds ratio of confirmed late-onset AD of 6.9 (95% C.I. 1.65-29) in subjects > 65 years and of 12.8 (1.9-86) in subjects > 75 years. In APOE epsilon 4 carriers over 75 years, only 1/22 controls, compared with 10/24 confirmed late-onset AD cases, had BCHE-K. We suggest that BCHE-K, or a nearby gene on chromosome 3, acts in synergy with APOE epsilon 4 as a susceptibility gene for late-onset AD.      

The salivary microbiota as a diagnostic indicator of oral cancer: A descriptive,non-randomized study of cancer-free and oral squamous cell carcinoma subjects

Background  

The purpose of the present investigation was to determine if the salivary counts of 40 common oral bacteria in subjects with an oral squamous cell carcinoma (OSCC) lesion would differ from those found in cancer-free (OSCC-free) controls.     

Effects of Toluene Inhalation on Carbon Dioxide Production and Locomotor Activity in Mice

Effects of Toluene Inhalation on Carbon Dioxide Production andLocoraotor Activity in Mice. BUSHNELL, P. J., EVANS, H. L.,AND PALMES, E. D. (1985). Fundam. Appl. Toxicol.. 5,971-977.Rapid and noninvasive tests of locomotor activity (LA) and carbondioxide production (minute volume expired CO₂, or _ECO₂)in mice were sensitive to the effects of inhaled toluene. Comparedto sham exposures, toluene at 100 ppm had no effect on LA or_ECO₂; at 1000 and 3000 ppm, LA increasedduring exposure, while _ECO₂ was suppressedfor 6 to 24 min at the beginning of exposure. In a nominal 10,000-ppmexposure, toluene levels were increased from 1000 to 10,500ppm in 60 min. At these levels, toluene abolished LA at concentrationsabove 8000 ppm, and suppressed _ECO₂ throughoutexposure. During recovery from toluene-induced narcosis, bothLA and _ECO₂ were elevated above control.In other studies, groups of mice inhaled toluene daily at 0,100, 1000, or 3000 ppm, 5 hr/day for 8 or 90 days, and weretested individually 30 to 90 min after termination of exposure.Under these conditions, toluene decreased postexposure _ECO₂ for 1–2 weeks, altered the weekly patternof change in _ECO₂, and did not affect LA.No effects of repeated, daily exposure to toluene were observedon body weight. These results demonstrate the utility of thepresent method to detect changes in LA and metabolic rate resultingfrom toluene inhalation, and suggest that different mechanismsare involved in the behavioral and metabolic responses to tolueneinhalation.     

Carbon Dioxide Production by Individual Mice as an Index of Behavioral and Metabolic Activity

Carbon Dioxide Production in Individual Mice as an Index ofBehavioral and Metabolic Activity. BUSHNELL, P. J., EVANS, H.L., AND PALMES, E. D. (1985). Fundam. Appl. Toxicol.. 5,962-970.A noninvasive method for simultaneous real-time determinationof spontaneous locomotor activity (LA) and CO₂ production (asminute volume expired CO₂, or _ECO₂) in miceis described. As an apical measure of overall metabolic activity,_ECO₂ proved sensitive to changes in manyphysiological processes, including behavioral activity. In normalmice, LA (as photobeam breaks) and _ECO₂ werepositively correlated (r = 0.73), and stable over repeated dailytests. Food deprivation for 18 hr overnight increased LA whiledecreasing _ECO₂. Stimulation of peripheralsympathetic activity, either by exposure to cold air or by injectionof epinephrine, increased _ECO₂ without affectingLA. Intoxication with pentobarbital produced a biphasic changein both measures: anesthetic doses increased LA and _ECO₂ during induction and recovery, and reduced themduring the period of anesthesia itself. These results characterize_ECO₂ as an easily quantifiable, compositeindex of behavioral and metabolic activity in mice. This measure,along with its covariation with LA, may provide better informationabout toxic effects than any single screening test.     

X-radiation induces 8-hydroxy-2'-deoxyguanosine formation in vivo in rat mammary gland DNA

Ionizing radiation is a carcinogen that induces oxidative DNA damage. 8- Hydroxy-2'-deoxyguanosine (8-OHdG) is a relatively abundant, mutagenic lesion that is widely regarded as a reliable index of oxidative DNA damage. The purpose of this study was to examine the effects of X- radiation on levels of 8-OHdG in the context of an experimental model for breast cancer in which chronic radiation exposure has been shown to be carcinogenic in Sprague-Dawley rats. A secondary objective of this study was to determine if the use of phenol during DNA isolation affected the concentration of 8-OHdG subsequently measured. Our results indicate that a profoundly carcinogenic dose of radiation induced a small but significant increase in 8-OHdG concentration in mammary gland DNA, and that the use of a phenol-based versus a salt-based method of DNA isolation had no significant impact on the levels of 8-OHdG detected in either control or irradiated tissue.