COMPUTER SIMULATION OF RESPIRATORY IMPEDANCE AND FLOW TRANSFER FUNCTIONS DURING HIGH FREQUENCY OSCILLATIONS

The usefulness of measuring respiratory flow in the airway andat the chest wall and of measuring respiratory input impedance(Z) to monitor high frequency ventilation was investigated bycomputer simulation using a monoalveolar 10–co-efficientmodel. The latter included a central airway with its resistance(Rw) and inertance (Iw), a resistive peripheral airway (Rp),a lumped bronchial compliance (Cb), alveolar gas compliance(Cgas), lung tissue with its resistance (Rl) and compliance(Cl), and chest wall resistance (Rw), inertance (Iw) and com-pliance(Cw).Gas flow in the peripheral airway (Vp), shunt flow through Cb(Vb), gas compression flow (lgas) and rate of volume changeof the lung (Vl) and of the chest (Vw) were computed and expressedas a function of gas flow in the central airway (Vc). For normalvalues of the coefficients. Vp/Vc was found to decrease moderatelywith increasing frequency and was still 0.75 at 20Hz. Peripheralairway obstruction (Rp x 5) considerably decreased Vp/Vc particularlyat high frequency. It did not change the relationship betweenthe two measurable flows. Vc and Vw, but increased the effectiveresistance at low frequency and shifted the reactance curveto the right. A reduced lung or chest wall compliance producedlittle change in Vp/Vc and Z except at very low frequencies;however, it decreased the phase lag between Viv and Vc. Finally,an increased airway wall compliance decreased Vp/Vc, but hadlittle effect on Z and Vw/Vc. It is concluded that measuringrespiratory impedance may help in detecting some, but not allof the conditions in which peripheral flow convection is decreasedduring high frequency oscillations.     

Trends in risk factors for vascular disease in Australia

Data from the National Heart Foundation Risk Factor Prevalence Surveys of 1980 and 1983 were analysed to detect national trends in risk factors for vascular disease in Australia. After statistical adjustment for differences in the demographic characteristics of the two populations of survey participants, our results show trends in smoking and blood pressure that are likely to result in a continuing fall in the incidence of vascular disease. There was a fall in the prevalence of current smoking from 32% to 29% but little change in the average daily consumption of cigarettes by current smokers. The prevalence of previously-undetected hypertension fell significantly from 10% to 7%. A small increase occurred in the proportion of all hypertensive patients who were treated and whose blood pressure was controlled, and a decline of 2.0 mmHg (P less than 0.0001) in mean diastolic blood pressures, but no significant change in mean systolic pressures. Mean total plasma cholesterol levels did not change; average levels of plasma triglycerides fell by 0.11 mmol/L (P less than 0.0001); and mean high-density lipoprotein cholesterol levels increased by 0.03 mol/L (P less than 0.0001). All indices of relative body weight increased between 1980 and 1983; mean body mass index rose by 0.23 with associated rises in the prevalence of obesity and of overweight status. The changes in other factors such as use of added salt, the consumption of alcohol, the level of physical activity and adherence to a special diet, all were in the desirable direction, although minor changes in the survey questionnaire might have served to exaggerate the apparent trends.     

Viral hepatitis in the US Navy, 1975-1984

The epidemiology of viral hepatitis in US Navy enlisted personnel was reviewed for the years 1975-1984. Hospital discharge summaries of all active duty enlisted personnel admitted to a US Navy treatment facility were used for the study. From 1975 to 1984, total first hospitalizations for viral hepatitis declined from 128 per 100,000 personnel (95% confidence interval (Cl) 118-139) to 56 per 100,000 personnel (95% Cl 50-63). The highest incidence of acute viral hepatitis (115 per 100,000 personnel) was found in the youngest age groups aged 24 years and less. Risk factors for acute hepatitis included a previous hospitalization with either drug abuse (relative risk = 363) or a sexually transmitted disease (relative risk = 25) listed among the discharge diagnoses. Having a medical job classification was also associated with an increased risk of acute hepatitis. The steep decline in the incidence of viral hepatitis during this 10-year period may have been due to decreasing drug abuse in the US Navy. Immunization of high-risk groups in the US Navy with hepatitis B vaccine could be an effective policy for the prevention of acute viral hepatitis.     

Effect of diltiazem on coronary blood flow distribution in dog heart under ischemia

Effect of intracoronary infusion of diltiazem (1 microgram/min) on regional myocardial blood flow (RMBF) was studied using 15-microns radioactive microspheres in 11 excised cross-circulated canine left ventricles. With total coronary blood flow (CBF) and heart rate (HR) held constant, regional ischemia was induced by ligating the left anterior descending coronary artery (LAD). Diltiazem at the dose used had no effects on ventricular Emax before and after LAD ligation. RMBF expressed by the counts divided by the counts averaged in all segments in each layer significantly (p less than 0.05) increased under diltiazem only in the low-flow region that had less than 50% RMBF before diltiazem; from 21% (+/- 12%) to 35% (+/- 18%) in the epicardial, from 22% (+/- 12%) to 32% (+/- 18%) in the midwall, and from 24% (+/- 10%) to 31% (+/- 12%) in the endocardial layers. We conclude that the beneficial effect of diltiazem on the ischemic heart involves a direct action on the coronary vascular system and does not necessarily depend on the concomitant changes in hemodynamics.     

Conformationally restricted analogues of the muscarinic agent N-methyl-N-(1-methyl-4-pyrrolidino-2-butynyl)acetamide

Conformationally restricted analogues of the selective partial muscarinic agonist N-methyl-N-(1-methyl-4-pyrrolidino-2-butynyl)acetamide (BM 5; 2) were synthesized. The compounds were tested for muscarinic and antimuscarinic activity in the isolated guinea pig ileum and in intact mice. They were found to be moderately potent muscarinic antagonists or weak partial agonists. The new compounds were less potent than 2 in inhibiting (-)-[3H]-N-methylscopolamine binding in the rate cerebral cortex. Thus, structural modifications of 2 in which part of the amide moiety has been connected with the methyl group in the butynyl chain to form a five-membered ring decrease affinity and in most cases abolish efficacy.     

Nuclease hypersensitivity of the rat cytochrome P450IA1 gene

The bovine pancreatic deoxyribonuclease I (DNAase I) hypersensitivity of the rat cytochrome P450IA1 gene was investigated. A nuclease-hypersensitive region was observed at approximately 3.2 to 5.1 kilobase pairs upstream of exon 1 in adult and fetal rat liver. This region did not necessarily correlate with gene expression following 3-methylcholanthrene induction, although it may determine the potential for inducibility of this gene.     

Pharmacological properties of fluphenazine-mustard, an irreversible calmodulin antagonist

We describe an improved synthesis and properties of fluphenazine-mustard, a potent phenothiazine having an alkylating chlorethylamine chain in its structure. The drug possesses anticalmodulin activity equivalent to the parent compound, but unlike fluphenazine dihydrochloride, the mustard derivative irreversibly antagonizes the ability of calmodulin to activate cyclic nucleotide phosphodiesterase. This property is partially calcium-dependent and can be overcome by coincubation with excess fluphenazine dihydrochloride. The compound irreversibly inactivated calmodulin when incubated with intact cells and caused single-stranded breakage of DNA. Fluphenazine-mustard possesses potent antiproliferative and cytotoxic properties against malignant cell lines that are likely to be mediated through both of these actions.