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Unlike asthmatics, healthy persons are relatively unresponsive to airway constrictors. By using partial expiratory flow-volume (PEFV) curves the authors have demontrated, in healthy subjects, dose-related decreases in flow rates following challenge with histamine and methacholine aerosols. With the use of semilogarithmic dose-response curves they have shown that 80 mg oral propranolol augmented, whereas oral pretreatment with 400 mg W10294A (an experimental bronchodilator) decreased, histamine and methacholine-induced airway constriction. However, 300 mg of orally administered aminophylline failed to modify the airway constrictor effects of histamine and methacholine. Moreover, variation was noted in induced airway constriction in healthy subjects with decreases in flow rates being greater in the morning than in the afternoon. The authors conclude that (1) propranolol augments whereas theophylline fails to prevent nonspecific induced airway constriction in healthy subjects. This suggests that the bronchodilator action of theophylline may be unrelated to its phosphodiesterase inhibitory activity, (2) control of volume history, by use of partial expiratory flow-volume curves, is useful in quantifying pharmacologic protection and augmentation of nonspecific induced airway constriction in healthy subjects and (3) conclusions resulting from observations of induced airway constriction in healthy subjects may be dependent upon the effects of diurnal variation.
Twenty healthy subjects eating normal diets made repeated five-day stool collections, the 10 females making their collections in four to six successive weeks. In most subjects there were striking variations in transit time, measured by Hinton's method. The variability of average faecal wet and dry weight, faecal volume, and the frequency of defaecation was equally great, suggesting that the transit time variations were genuine. The size of individual stools varied even more, often tenfold or more. Faecal water content was relatively constant. There were no significant differences between males and females, and in the females there were no obvious changes related to the phases of the menstrual cycle. The normal variability of colonic function should be taken into account in planning experiments and in interpreting existing data.
Ten healthy subjects have been given before and after treatment with phenobarbital the following intravenous charges: a) nicotinic acid; b) rifamicyn-SV; c) simultaneous administration of the two drugs. Along with confirmatory evidence of the wellknown increase in bilirubinaemia (prevalently unconjugated), we have observed phenobarbital to attempts partially yet significantly that effect. On the base of direct experience on rat liver, we hypothise phenobarbital to increase the pool of the Y protein carrying cholephilic organic anions into the hepatocytes.
The influence of Neoston--a relatively new analgesic, antipyretic, and anti-inflammatory agent--on performance in different tracking tests, on heart rate, on sinus arrhythmia and on subjective rating was objectivated. 15 healthy male and female subjects, aged from 19 to 27 years, took part in the sessions lasting about 2 1/2 hrs each. Two times two pills Neoston or a placebo were taken orally 2 and 5 hrs before the tests, making a total of 2 g. Performance in tracking was poorer on the whole with Neoston than with placebo, but only up to a maximum of 5%. Except one measurement point out of 10 all differences between the tests with the active drug and placebo were not statistically significant at the level of 5%. Yet a relatively uniform trend suggests a certain but only a small damping effect of Neoston. When relating the data of the second and third session on the data of the first session of each day, damping effects could be made more obvious. Hereby the influence of Neoston on tracking performance could be demonstrated to exist also statistically significant but to be practically almost irrelevant. In physiological variables as well as in subjective rating only small differences between the drug and placebo condition were measured. When relating the results to comparable research on the effects of alcohol, tranquilizers and stimulants, it is concluded that with Neoston in the relatively high dosage as used here, no real detrimental effects on traffic safety are to be expected.
In healthy volunteers, 500 ml of a 6% low molecular weight hydroxyethyl starch solution (Expafusin) was infused intravenously within 30 minutes. Blood samples for the measurement of rheological parameters were obtained before and after the infusion. Blood and plasma viscosity were significantly decreased after the infusion of HES. Red cell deformability as measured by a filtration technique was slightly improved. Red cell aggregation as measured by a light transmission method was markedly reduced. Repeated infusion of 500 ml Expafusin indicates that the improvement of the flow properties of blood can be maintained for more than 3 hours.
In 10 healthy subjects and 25 duodenal ulcer patients, gastric acid and pepsin and serum gastrin responses to cephalic-vagal stimulation induced by modified sham-feeding (MSF) were studied before and after vagotomy and atropinisation and compared with those to maximal stimulation with pentagastrin. When the MSF-induced peak acid output was normalised as a percentage of peak response to pentagastrin it was about 62% in healthy subjects and 66% in duodenal ulcer patients. Serum gastrin concentration was not changed significantly by modified sham-feeding either in normal subjects or in duodenal ulcer patients. Truncal vagotomy completely abolished gastric acid and pepsin responses to MSF in duodenal ulcer patients. Atropine almost completely suppressed gastric acid and pepsin responses to MSF in healthy subjects and reduced those in duodenal ulcer patients by about 62%. The combination of the modified sham-feeding and pentagastrin infusion resulted in augmentation of the acid output in duodenal ulcer patients but not in healthy subjects. This study shows that the cephalic phase results in a potent gastric acid and pepsin stimulation which is not accompanied by any change in serum gastrin concentration either in healthy subjects or duodenal ulcer patients and which is abolished by vagotomy and suppressed by atropine.
1. The influence of mental stress, 30 min Kraepelin's arithmetic test under noise on the plasma concentration and urinary excretion of prostaglandin (PG) F2 alpha was studied in patients with essential hypertension and in healthy subjects. 2. Before the arithmetic test the plasma PGF2 alpha in hypertensive patients was significantly higher than in healthy subjects. The mental stress produced a significant increased in plasm PGF2 alpha in healthy subjects but not in patients with essential hypertension. 3. Three hour urine excretion of PGF2 alpha before stress was about two times lower in hypertensive patients than in healthy subjects. After exposure to stress a significant decrease in urinary excretion of PGF2 alpha was found in healthy subjects, but not in hypertensive patients. 4. The stress-induced increase in plasma PGF2 alpha of healthy subjects may reflect elevated brain PGF2 alpha synthesis. The individual differences in response to stress in hypertensive patients may result from specific impairments in synthesis and/or prostaglandin turnover.
The ability of an amino acid mixture given intraduodenally or intravenously to stimulate gastric secretion is compared in healthy subjects and in duodenal ulcer patients. Graded amounts of amino acids by both routes produced a similar increase in acid output in healthy subjects, reaching about 30% of the maximal response to pentagastrin. Serum gastrin concentrations remained virtually unchanged but serum alpha amino acid nitrogen levels were about twice as high with intravenous as with intraduodenal administration. Intravenously administered amino acids produced a significantly higher acid output in patients with duodenal ulcer than in healthy subjects, but did not produce a significant increase in gastric acid or pepsin secretion when combined with a pentagastrin infusion as compared with pentagastrin alone. Cimetidine (2 mg/kg/h) added to intravenous amino acid infusions caused almost complete suppression of acid secretion. This study indicates that amino acids are capable of stimulating gastric secretion after intraduodenal and after intravenous administration. The response to the latter is significantly higher in patients with duodenal ulcer than in healthy subjects, does not appear to involve gastrin release, is not affected by pentagastrin, and is strongly suppressed by histamine H2-blocker.
1. Ten patients with essential hypertension and ten healthy men were submitted to mental stress consisting of Kraepelin's arithmetic test combined with noise. Concentrations of plasma and urine catecholamines and of their metabolites as well as plasma renin activity before and after the test were studied. 2. In both groups a significant increase of noradrenaline and adrenaline in blood and noradrenaline in urine was observed. The urinary excretion of dopamine fell significantly in both groups after stress. 3. After mental stress a significant increase in urinary excretion of 3-methoxy-4-hydroxyphenylglycol was observed in both groups. The excretion of vanillylmandelic acid decreased significantly only in healthy subjects. 4. The plasma renin activity rose significantly in both groups but the increase was more pronounced in healthy subjects.
The concentration of thiocyanate in the serum of eight test subjects with renal failure and seven healthy control subjects was measured, as it declined with time, after oral doses of thiocyanate or i.v. injections of nitroprusside had been administered. Additional measurements were taken, on the healthy subjects only, of the concentrations of thiocyanate in the urine, and also of the influence of an increased chloride intake on the rate of elimination of thiocyanate. For the healthy subjects an elimination half-life of between one and five days (mean c. 3 days) was found. Increasing the chloride elimination rate to approximately twice normal did not significantly speed up the rate of thiocyanate elimination. The amounts of thiocyanate which had been administered as doses reappeared almost exclusively in the urine. For the subjects with renal failure, the elimination half-life had a mean value of approximately nine days. The elimination constants were found to be proportional to the creatinine-clearance rates. The ke value at a creatinine-clearance of zero ml/min was approximately 15% of the ke value at a creatinine-clearance rate of 120 ml/min. The distribution volumes for thiocyanate were greater for the patients with renal failure than for the healthy subjects. The conclusions for therapies using nitroprusside are discussed.
Levels of immunoglobulins in serum were determined in 41 healthy subjects and 128 professional blood donors. In healthy subjects mean levels +/- S.D. were: IgG 1260 +/- 492.9 mg/dl, IgM 62.4 +/- 18.2 mg/dl, and IgA 183.4 +/- 70.1 mg/dl. Of 128 blood donors 112 were hepatitis Bs antigen (HBsAg) negative and 16 were positive. A significant (P is less than 0.001) elevation of all three immunoglobulins was observed in HBsAg positive group suggesting increased antibody formation due to persistance of antigen.
The gastric acid response to i.v. injection of 0.15 U of soluble insulin/kg b.w. was determined in healthy subjects and duodenal ulcer patients during intragastric perfusion with water, 0.1 M HC1, and alkaline buffer (pH 8.3). Perfusion with hydrochloric acid significantly reduced the peak gastric acid output following insulin in 6 healthy subjects (reduction 45%, p less than 0.05) but had no significant effect on the peak gastric acid response to insulin in 7 DU patients (reduction 16%, p greater than 0.05). The 2.5-hour gastric acid response to insulin was, however, significantly reduced in both groups (56% and 35%, respectively) by exogenous acidification of the stomach. The gastric acid response to insulin hypoglycaemia in 3 DU patients was the same with intragastric water and alkaline buffer perfusion. The reduction of the gastric acid response to insulin hypoglycaemia by intragastric acidification corresponded to a reduced volume secretion and could not be ascribed to increased back diffusion of hydrogen ions or duodenal inhibition. These findings suggest that the gastric acid response to insulin hypoglycaemia is inhibited by a low intragastric pH in man, and that DU patients are less sensitive to the inhibitory mechanism than healthy subjects.
The level of cAMP was determined in isolated cells from bone marrow and peripheral blood of healthy subjects and patients with proliferative syndrome (acute and chronic myeloid leukaemia and chronic lymphatic leukaemia). In the investigations tritiated cAMP (3H-cAMP) was used and for binding of endogenous as well as exogenous cAMP protein isolated from bovine muscles was used. The mean cAMP level in peripheral blood granulocytes of healthy subjects was 27.90+/-3.82 pmol/10(7) cells and in normal lymphocytes it was from 11 to 18 pmol/10(7) cells. Much higher concentrations of cAMP: 56.4+/-16.25 and 52.7+/-11.02 pmol/10(7) cells were observed in myelocytes and metamyelocytes isolated from the bone marrow of healthy subjects. Lowering of cAMP concentration (below 4 pmol/10(7) cells) was observed in the lymphocytes of patients with chronic lymphatic leukaemia, while a higher cAMP concentration (above 90 pmol/10(7) cells) was found in the myeloblasts of patients with acute myeloid leukaemia.
In sleep studies of (a) patients with the "fibrositis syndrome" and (b) healthy subjects undergoing stage 4 sleep deprivation, we observed in both groups the anomalous presence of alpha-rhythms in the non-rapid-eye-movement (NREM) sleep EEG. This phenomenon has been termed alpha-delta sleep. In the healthy subjects stage 4 deprivation was accompanied by the temporary appearance of muscoloskeletal and mood symptoms comparable to the symptoms seen chronically in the patients. It is suggested that the external arousing stimulus, which induced alpha-delta sleep in the subjects, is paralleled in the patients by an internal arousing mechanism. Such a mechanism, acting in competition with the NREM sleep system, would impair the presumed restorative function of NREM sleep and lead to the development of symptoms. It is proposed that the "fibrositis" symptom complex be considered a "non-restorative sleep syndrome". Evidence froms presented in support of the hypothesis that a disorder of serotonin metabolism serves as a basis for both the EEG sleep disturbance and the symptoms.
Normal human plasma contains not only active renin but also an inactive form of renin which, after exposure to low pH, can generate angiotensin I from renin substrate. When healthy volunteers were given first a diet containing 400 mmol sodium and then a diet containing 10 mmol sodium for 4 days the changes in salt intake stimulated large changes in active plasma-renin and smaller changes in inactive renin. Inactive renin comprises a larger fraction of total renin in plasma of salt-loaded healthy subjects than salt depleted subjects. When plasma of healthy men on a high-salt diet was applied to a column of 'Sephadex G-100', renin eluted in two peaks, corresponding to big renin (60 000 daltons) and normal renin of lower molecular weight (40 000 daltons). Active and inactive forms of renin were present in both peaks. Plasma from salt depleted healthy subjects showed a large single peak of renin activity with a maximum at 40 000 daltons. These studies demonstrate that both big and small renin can exist as inactive or active enzyme. Big renin, previously found in certain diseases and in pregnancy, is also present in normal human plasma. These observations suggest a possible physiological role for big renin.
The frequency of Hepatitis Bs antigen and antibody was determined in healthy subjects and patients with acute and chronic liver disease. The frequency of HBs Ag in healthy subjects was 2.9% and HBs Ab 35%. The high prevalence of antibody in normal individuals suggests a constant non-parenteral sub-clinical exposure to hepatitis virus. Thirty-three per cent patients with acute viral hepatitis, 20% with cirrhosis and 10% with hepatocellular carcinoma were HBs Ag positive, while HBs Ab was detected in 22% cases of acute viral hepatitis and 37% with other liver disorders. This pattern of prevalence of HBs Ab suggests that hepatitis B virus may be an important etiological agent in acute and chronic liver disease in Pakistan.
An antiglobulin reagent containing anti-IgG, -C4c, -C4d, -C3c, and -C3d was used to test red blood cells from healthy subjects and from patients in hospital. In tests read macroscopically on opal tiles, no positive reactions were found in the healthy subjects. Positive reactions were, however, observed in 7% of the hospital patients. Further tests with monospecific reagents showed the positive reactions to be due to the presence of C4d and C3d on the red cells. All patients with positive antiglobulin reactions had serious disease, in most cases associated with abnormal antibody production or abnormal immunoglobulin levels.