Sexual activity and erectile dysfunction in elderly men with angiographically documented coronary artery disease.

We studied the prevalence of erectile dysfunction (ED) in elderly men, aged 65 years or above, with coronary artery disease (CAD) documented by coronary angiography. A total of 123 men (112 men with CAD and 11 men without CAD), mean age 74.6+/-5.9 years, was included. To detect ED and assess its severity, all participants were asked to complete the Sexual Health Inventory for Males (SHIM) questionnaire. Lack of sexual activity was more prevalent among men with CAD relative to men without CAD (31.3 vs 0.0%). Among the sexually active men, ED was more prevalent among men with CAD relative to men without CAD (85.7 vs 72.7%). A general linear model showed that age was the only factor associated with SHIM scores among the sexually active men with CAD (P=0.001). Other factors, such as the number of occluded coronary arteries, diabetes mellitus, hypertension, smoking, various medications and marital status, were not associated with SHIM scores in elderly men with CAD. We conclude that lack of sexual activity and ED are very common in elderly men with CAD. Among the sexually active men with CAD, ED severity is associated only with age.

The detection of IgG anti-hepatocyte antibodies by ELISA in sera of patients with chronic active hepatitis: correlation with disease activity.

Anti-hepatocyte membrane IgG antibodies were detected in serial dilutions of sera from patients with chronic active hepatitis using an enzyme linked immunosorbent assay with isolated rat hepatocytes as the antigenic substrate. The assay is rapid, reliable and reproducible. Antibodies to hepatocyte membrane antigens were detected in 24 out of 31 (77%) patients with autoimmune chronic active hepatitis. Four of these patients were negative in a 1/10 dilution but became positive on progressive dilution. In 12 patients, liver biopsy was performed at the same time as serum was obtained. In these patients, the titre of antibodies to hepatocyte membrane antigen correlated significantly with the overall biopsy score of disease activity and particularly with the degree of portal tract infiltration. In 2 patients followed serially, titres of anti-hepatocyte membrane antibodies fell progressively in parallel with clinical, biochemical and histological evidence of improvement in the liver disease. The estimation of titres of antibodies to hepatocyte membrane antigens using isolated rat hepatocytes as the antigenic substrate may assist in the diagnosis, assessment of disease activity and follow-up of individual patients with chronic active hepatitis.

A comparison of cardiovascular and catecholamine responses to three stimuli in mild hypertension.

In five males with mild essential hypertension, simultaneous hemodynamic and arterial and venous plasma catecholamine responses to three stimulation tests (mental arithmetic, isometric handgrip exercise, and cold) were studied. Plasma norepinephrine (NE), epinephrine (EPI), and dopamine (DA) were measured radioenzymatically. Isometric exercise was the best stimulus for systolic and diastolic blood pressure and NE. Mental arithmetic produced the highest levels of plasma EPI, but there was great intersubject variability. Dopamine levels did not increase with any of these stimuli. Consistent arterio-venous differences across the forearm were seen for EPI but not NE, consistent with local production of NE. Isometric exercise produced the closest correlations between peripheral plasma catecholamine levels, blood pressure, and heart rate. Good correlations were seen with mental arithmetic, but with the stimulus of cold correlation was poor.

Different norepinephrine disappearance rate in venous and arterial plasma in man.

The disappearance of norepinephrine in both arterial (radial) and venous (antecubital) plasma was studied in five patients with mild essential hypertension following isometric exercise and norepinephrine infusion. Arterial levels of epinephrine throughout the study and of norepinephrine during norepinephrine infusion were consistently higher than venous levels, indicating that both amines are removed by passage through the forearm. Following infusion the disappearance rate of norepinephrine from arterial plasma was faster than from venous plasma. After isometric exercise there was a delay in fall of venous levels, consistent with a delayed efflux of norepinephrine from local tissues. Arterial plasma levels probably reflect total body contribution whereas venous plasma levels presumably reflect additional local removal and/or release from the forearm.

Increased sympathetic activity in renovascular hypertension in man.

1. Concentrations in venous plasma of adrenaline, noradrenaline and dopamine were measured in samples collected simultaneously from three different sites in three varieties of hypertension. 2. In adrenal venous plasma, levels of catecholamines were increased in renovascular hypertension (n = 8) and decreased in primary aldosteronism (n = 8) when compared with essential hypertension (n = 9). 3. Concentrations were similar in antecubital and low inferior vena caval plasma, where noradrenaline was higher in renovascular hypertension. 4. Altered adrenal venous in renovascular hypertension and in primary aldosteronism. 5. Adrenal venous catecholamines deserve further study as an index of sympathetic activity.

Radioenzymic measurement of norepinephrine, epinephrine, and dopamine: stability, enzymic activity, and sensitivity.

We investigated factors affecting sensitivity and reproducibility of radioenzymic (catechol-O-methyltransferase) measurement of plasma catecholamines. There was no apparent deterioration of catecholamine during storage at -20 degrees C for 240 days. Accuracy and sensitivity of the assay depended mostly on the method of transferase preparation; its preparation by adjusting the pH to 6.8 before fractionation with ammonium sulfate resulted in an unsuitable enzyme with a relatively high background-radioactivity count, particularly for neorepinephrine and dopamine.

Effect of sampling site and conditions on plasma levels of noradrenaline, adrenaline and dopamine.

Levels of noradrenaline, adrenaline and dopamine were measured simultaneously from different sites, during stimulation and during noradrenaline infusion. Levels of the three catecholamines were similar in low inferior vena cava and a forearm vein. The ratio between adrenal venous and peripheral levels averaged 49:1 for adrenaline but only 4:1 for noradrenaline, consistent with other significant sources for noradrenaline apart from the adrenal. Levels of dopamine were only slightly higher in adrenal venous blood, consistent with the adrenal being a minor source in these subjects. Forearm arteriovenous differences for adrenaline and noradrenaline demonstrated significant removal of these amines across this vascular bed. To monitor sympathetic responses, venous noradrenaline appears satisfactory, but venous adrenaline would miss responses detected by arterial levels. Sympathetic responses were not reflected by changes in either arterial or venous dopamine.

Variability of plasma catecholamine levels: age, duration of posture and time of day.

1. In order to define factors which influence plasma catecholamine levels, and which might be controlled in the interests of reproducability and comparability, plasma noradrenaline plus adrenaline (NA + A) was measured repeatedly in normal subjects by a double isotope technique. 2. Age and posture were important determinants for plasma NA + A levels, whereas time of day was less important. 3. Levels were higher in old men aged 70--92 years than in young men aged 19--28 years, measured after 30 min or 9 h (overnight) recumbency, or after 5 min standing. 4. Duration of recumbency and of upright posture were both important. Recumbent levels were lower after 9 h (overnight) than after 30 min (mid-morning). Upright posture caused an increase in levels within 2 min. Levels peaked between 5 and 20 min, were lower after 12 h than after 20 min, but upright levels were always higher than levels after 9 h recumbency. 5. During continuous recumbency, levels were lowest at 24.00 h, and increased thereafter. During a second hospitalisation, levels at 09.00 h were again higher than levels at 06.00 h after overnight recumbency. 6. Variability of levels obtained by repeated sampling was lower while sitting, during a normal upright day, than after 30 min recumbency. Upright legels may be a better index of cardiovascular sympathetic activity.

Tne density of adrenergic nerves at various levels in the guinea-pig lung.

1. Gunea-pig tracheal and lung segments were systematically examined for adrenergic nerves using the fluorescence histochemical technique. Fluorescence in nerves was enhanced with alpha-methylnoradrenaline or by pretreating animals with nialamide. 2. There was a progressive decrese in density of fluorescent fibres in airway smooth muscle from the laryngeal end of the trachea, which was densely innervated, to the bronchioles, which contained only occasional fibres. This was despite obvious fluorescence in blood vessels in the lung. 3. It is suggested that, if adrenergic nerves are involved in reflex bronchodilatation in this species, they directly control larger airways and other factors, e.g. non-adrenergic inhibitory nerves, may be important in the control of smaller airways.

The uptake kinetics and metabolism of extraneuronal noradrenaline in guinea-pig trachea as studied with quantitative fluorescence microphotometry.

1 Extraneuronal uptake of noradrenaline and alpha-methylnoradrenaline into single cells of guinea-pig tracheal smooth muscle have been studied by means of quantitative fluorescence microphotometry. 2 Fluorescence brightness due to accumulation of alpha-methylnoradrenaline was dose-dependent and was increased by the catechol-O-methyltransferase inhibitor drugs, tropolone or beta-thujaplicin (200 micrometer) but not by 3,4-dimethoxy-5-hydroxybenzoic acid (200 microgram). 3 Fluorescence brightness due to accumulation of noradrenaline was increased if animals were pretreated with the monoamine oxidase inhibitor drug, nialamide. 4 The study suggests that metabolism of amines by catechol-O-methyltransferase and monoamine oxidase can occur subsequent to extraneuronal uptake is guinea-pig tracheal smooth muscle. 5 The uptake of noradrenaline into tracheal smooth muscle was concentration-dependent, saturable, and had a Km of 156 micrometer.

Failure of methyclothiazide to lower home blood pressure level in "essential" hypertensive and normotensive young men, despite significant plasma volume contraction.

Home blood pressure measurements were used to assess the effect of methyclothiazide in young essential hypertensive and normotensive males. Although plasma volume was reduced by approximately 10 percent, blood pressure was not reduced in either group. The lack of effect on blood pressure was probably not attributable to dosage employed, as doubling the dose (5 to 10 mg) in the normal subjects (who were equilibrated on constant diet) did not significantly increase changes in plasma volume, plasma renin activity, aldosterone excretion, urine sodium or blood pressure. The higher dose did result in greater changes in plasma potassium and uric acid. Homeostatic mechanisms which limit the volume mediated and other antihypertensive effects of methyclothiazide apparently achieved complete compensation in these young males. This suggests that thiazide diuretics may not be the drug of first choice in the treatment of hypertension in young adults. Further studies with other diuretics are clearly necessary before the significance of these findings can be fully assessed.

Some evidence for the maturity of peripheral adrenergic nerves in new-born guinea-pigs.

The fluorescence histochemical technique of Falck and Hillarp revealed a similar distribution and density of peripheral adrenergic nerves in new-born and adult guinea-pigs. The accumulation of tritiated noradrenaline by tracheae from new-born guinea-pigs, assumed to be uptake into adrenergic nerves, was not less than the accumulation by tracheae from adult animals. There was equal potentiation by cocaine (1 x 10(-5)M) of responses to noradrenaline on tracheal chain preparations taken from new-born and adult guinea-pigs. The evidence supports the hypothesis that the guinea-pig has a functional, well differentiated peripheral adrenergic nervous system at birth. This would account for the apparent inability to produce a long-lasting sympathectomy by administration of 6-hydroxydopamine to new-born guinea-pigs.

A histochemical study of extraneuronal accumulation of noradrenaline in the guinea-pig trachea.

1. Accumulation of noradrenaline in extraneuronal tissue of the guinea-pig trachea has been studied by the use of the fluorescence histochemical technique of Falck and Hillarp.2. After incubation in solutions of noradrenaline, fluorescence developed in cellular structures (tracheal smooth muscle, vascular smooth muscle and endothelium, fibroblasts and chondroblasts), in the intercellular matrix of the cartilage and throughout the loose connective tissue of the adventitia and submucosa.3. The effect of various experimental procedures on the development of this fluorescence has been examined i.e. incubation with noradrenaline at reduced temperature (0 degrees C), removal of fluorescence by washing with Krebs solution at 37 degrees C or 0 degrees C, incubation with phenoxybenzamine (10(-4)M) or metanephrine (10(-4)M).4. From these observations it has been concluded that noradrenaline accumulates in the trachea:(a) in cellular structures where it is firmly bound, i.e. not easily removed by washing at 0 degrees C, and where the accumulation is prevented by phenoxybenzamine, metanephrine or cold.(b) in the intercellular matrix of the cartilage where it is also firmly bound, but where the accumulation is not prevented by phenoxybenzamine, metanephrine or cold. This probably represents binding to sulphated mucopolysaccharides.(c) in the adventitia and submucosa where it is loosely bound and easily removed by washing.5. Some implications of these findings in pharmacological experiments with guinea-pig trachea are discussed.

Histochemical localization of adrenergic nerves in the guinea-pig trachea.

1. Specific catecholamine fluorescence was demonstrated in guinea-pig trachea in fine, varicose, nerve fibres running parallel to the tracheal smooth muscle fibres.2. The density of nerves in tracheal smooth muscle was greater at the laryngeal end than at the bronchial end of the trachea.3. The findings confirm pharmacological evidence for an adrenergic innervation of the guinea-pig isolated tracheal chain preparation.