[Role of the pituitary gland in calcium and magnesium metabolism in dogs and rats]. Epiphysectomy in dogs and rats was accompanied by a reduction of urinary excretion of calcium and magnesium, by an increase in the magnesium concentration in the blood plasma of dogs. Administration of epiphysial extracts induced an increase of diuresis in dogs on account of a greater rate of glomerular filtration and a fall of the tubular water reabsorption. Calcium and magnesium urinary excretion increased in dogs and rats as well; this was due both to an increase of their ultrafiltration and a reduction of reabsorption in the renal tubules. Consequently, the epiphysis took part in the regulation of metabolism of bivalent cations.


[Certain characteristics of blood sugar in women aged 16-29 years according to glucose tolerance test]. Glucose tolerance test was conducted in 370 women aged from 16 to 29 years. Adiposity proved to be accompanied by a significant accretion of the glycemia level on fasting stomach, and 1 and 2 hours after glucose load, with the increase in the excess of weight not over the normal level. Glycemia level on fasting stomach failed to differ significantly in persons with an inadequate weight from such in persons with a normal weight. In the group with a decreased weight there was a significant blood glucose elevation 1 and 2 hours after the glucose load. Genesis of the glycemia increase differed in the groups with eleveated and reduced body weight. There was found no significant difference in the distribution of 16-29-year-old women by glucose tolerance depending on the excess of body weight.


[Process of bile formation and bile composition in albino rats in acute adrenal cortex insufficiency and adrenal gland autologous transplantation]. Experiments were conducted on 84 male albino rats. A study was made of the state of the bile forming process 7, 14 and 30 days after bilateral adrenalectomy and adrenal gland autotransplantation. Investigations carried out showed inhibition of the bile formation with the corresponding changes in the chemical composition of bile to occur both in adrenalectomized animals and the rats with adrenal autotransplantation; in the second case, however, these changes were less pronounced. A gradual suppression of the intensity of bile production, cholate formation, bilirubin- and cholesterol secretion occurred in the adrenalectomized rats, whereas in the animals a significant shift in the direction of restoration took place as soon as in 7 days after autotransplantation. The first to become restored is the cholesterin secretory function in the liver, then the intensity of the cholate formation, particularly the glycocholic and desoxycholic acids, and bilirubin secretion. The intensity of bile secretion, as well as the sum total content of cholates in the bile, chiefly on account of taurocholic acid, failed to reach the initial level even by the 30th day after the adrenal gland autotransplantation.


Effect of gemfibrozil in vitro on fat-mobilizing lipolysis in human adipose tissue. Fat-mobilizing lipolysis was studied in rat and human adipose tissue during incubation in vitro by following the release of glycerol into the incubation medium. Gemfibrozil as well as clofibrate consistently and readily inhibited basal as well as noradrenaline-stimulated fat-mobilizing lipolysis in rat fat. With human adipose tissue no effect was observed with gemfibrozil and clofibrate on basal lipolysis. This may be due to the comparatively low rate of the nonstimulated fat-mobilizing lipolysis in human tissue incubated in vitro. When lipolysis was stimulated with noradrenaline as well as isoprenaline, however, both gemfibrozil and clofibrate significantly reduced the fat-mobilizing lipolysis. This inhibition of lipolysis was however not observed in all studies. When lipolysis had been stimulated with theophylline, no inhibition of lipolysis was obtained with either compound. The possibility that reduced fat-mobilizing lipolysis in adipose tissue may cause a lowering of plasma triglycerides by reducing the flow of FFA to the liver is discussed in some detail. It is also suggested that inhibition of lipolysis may be accompanied by increased activity of lipoprotein lipase as well as an increase in the FIAT process. However, the pharmacological implication of the above-mentioned findings, particularly for gemfibrozil, must await further studies, as fairly large doses, around 1 mg/ml of incubation medium, were needed to obtain inhibition of fat-mobilizing lipolysis.


Gemfibrozil in a group of diabetics.

Gemfibrozil in a group of diabetics. A group of 14 diabetic patients was treated with gemfibrozil during a variable length of time ranging from nine to 23 weeks in order to establish if a lowering effect on the cholesterol and triglyceride levels could be achieved, as it had been in the case of another group of non-diabetic patients. The present results showed that: (1) The drug is remarkably well tolerated. (2) With doses ranging between 400 and 800 mg per day the magnitude of the effect of the drug was less than that observed in our previous trial with non-diabetic subjects. The effect upon triglycerides seemed to be reduced more than that upon cholesterol when compared with results in higher-dose studies. (3) In this group of diabetic patients (3 insulin dependent, 11 maturity-onset type) control of the diabetic condition was never impaired and appeared in some cases to be slightly improved by gemfibrozil. (4) There was no evidence of undesirable interaction with any of the anti-diabetic drugs used.


The evaluation of lipoprotein changes during gemfibrozil treatment. During treatment with gemfibrozil, 1200 mg daily, total serum triglyceride levels were reduced in 7 of the 11 patients, owing chiefly to a fall in VLDL triglyceride levels. Total serum cholesterol responded variably, falling in a majority of patients with hypercholesterolaemia. High density lipoprotein cholesterol rose during treatment in patients who had either hypertriglyceridaemia or hypercholesterolaemia.


The use of saralasin to evaluate the function of the brain renin-angiotensin system. The demonstration that the components required for the generation of angiotensin II are present in the brain has led to the proposal that there is a brain renin-angiotensin system. To test this hypothesis, experiments were performed to determine if biologically active amounts of angiotensin II are formed when renin is injected into the cerebral ventricles. The effects of central administration of agents known to block the peripheral renin-angiotensin system were also investigated. It was shown that intraventricular renin increased water intake, blood pressure and ADH secretion and that these effects were blocked by saralasin. These findings indicated an interaction between injected renin, brain angiotensinogen and converting enzyme, resulting in the formation of angiotensin II in physiologically active concentrations. However, these experiments did not demonstrate a role for endogenous brain renin activity. Central administration of saralasin in normal animals did not decrease water intake, blood pressure or ADH secretion. These studies thus failed to demonstrate a physiological role for the proposed brain renin-angiotensin system in controlling water balance and blood pressure.


Angiotensin II blockade in normal man and patients with essential hypertension. Blood pressure effects depending on renin and sodium balance. 1) Saralasin was administered to 9 normotensive volunteers and 13 patients with essential hypertension after sodium depletion and sodium repletion. 2) In standing normotensive volunteers, angiotensin II inhibition induced significant hypotension if previously a cumulative sodium loss of at least 160-200 mEq had been induced. 3) In patients with essential hypertension, saralasin infusion induced either blood pressure reduction, no change or even significant blood pressure increase, depending on the prevailing state of sodium balance. 4) Following vigorous and prolonged sodium depletion induced by low sodium diet, with chlorthalidone and spironolactone, blood pressure became renin-dependent even in those patients who initially had exhibited a hypertensive response to saralasin, suggesting that under appropriate conditions, renin can play an active pressure role in all patients with essential hypertension. 5) Saralasin administration to patients with essential hypertension may not only be useful for recognizing renin dependency but may also, via the slight intrinsic agonistic effect of the compound, permit identification of overactivity of the sodium factor.


The role of renin in the control of blood pressure in normotensive man. In order to study the  role of renin in regulating blood pressure in normotensive states, saralasin (P113) was infused into normal subjects and patients with cirrhosis of the liver and ascites. In normal subjects on a normal sodium intake, P113 infusion had no effect on blood pressure. Only after the combined stress of a low sodium diet and the upright position did P113 lower the blood pressure. In two of the six cirrhotic patients, P113 caused a significant decrease in BP in the supine position. There was no consistent effect of the P113 infusion on plasma aldosterone or plasma renin activity in the normal or cirrhotic subjects.


Changes of blood pressure, plasma renin activity and plasma aldosterone concentration following the infusion of Sar1-Ile8-angiotensin II in hypertensive, fluid and electrolyte disorders. 1-Sarcosine, 8-isoleucine angiotensin II (Sar1-Ile8-AII) was infused intravenously in 5 normal volunteers and 66 subjects with various hypertensive, fluid and electrolyte disorders. Changes of blood pressure (BP), plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were studied. In normal subjects, Sar1-Ile-AII showed pressor (agonistic) activity, which was related to both dosage and sodium intake. Hyporeninaemic hypertensive subjects (pirmary aldosteronism) showed pressor responses to a smaller dose of this compound than the dose employed in normal subjects. Hyporeninaemic hypertensive subjects and normal volunteers after 3 days of high sodium intake showed significant elevations of BP and PAC and reduction of PRA. Changes of BP, PAC and PRA in normoreninaemic subjects including those with Bartter's syndrome, renal tubular acidosis or liver cirrhosis with ascites showed reduction of BP and PAC and elevation of PRA. The results indicate that the compound has both agonistic and antagonistic activities for blood pressure; which of these is obtained apparently depends upon endogenous angiotensin II levels, as well as the dosage employed. The results in subjects with high and low PRA suggest that the compound has antagonist and agonist actions at 3 sites of angiotensin II action, i.e. peripheral vascular bed, renin release mechanism from juxta-glomerular apparatus and the zona glomerulosa of the adrenals.


Angiotensin II blockade in hypertensive dialysis patients. Five hypertensive haemodialysis patients have been infused with saralisin. The infusion appears to be a simple diagnostic test separating patients into two groups. First, there are those whose blood pressure does not fall with saralasin pre-dialysis, but does fall with weight removal during dialysis; the blood pressure in these patients can be controlled by a reduction in pre-dialysis weight. Second, there are those whose blood pressure does fall with saralasin either pre- or post-dialysis; their arterial pressure does not fall with weight removal, but can be controlled by anti-hypertensive drugs. In two of the patients who responded to saralasin, the mechanism of the high blood pressure appeared to change from volume dependency, partial or complete, with suppressed renin release, to angiotensin dependency, partial or complete, as weight was removed during dialysis. These patients illustrate the importance of the interaction between volume and the level of angiotensin II in the maintenance of hypertension.


The use of saralasin in the recognition of angiotensinogenic hypertension. Specific antagonists of angiotensin II (AII) such as saralasin might theoretically be of great value in the recognition of angiotensinogenic hypertension. Evidence is presented to show the importance of overcoming any existing sodium overload and of administering saralasin first in small and then in larger amounts by infusion (or injection). When this was done in 600 hypertensive patients, 62 showed a fall in blood pressure of more than 10/8 mm Hg. Further tests in 50 of these subjects indicated that the fall in blood pressure was associated with high peripheral levels of plasma renin activity (PRA) and/or abnormal renal vein PRA ratios in 94%. The procedure rarely failed to detect even mild forms of angiotensinogenic hypertension. In 62 patients found to have angiotensinogenic hypertension, the responsible lesions included unilateral renal arterial stenosis with good contralateral renal function (29%), bilateral renal disease (21%), Cushing's syndrome (6%), small vessel disease or specific excess of renin production - without other detectable renal disease - (31%) and incompletely evaluated disorders (13%). Saralasin has been of great value in simply and reliably demonstrating the presence or absence of an angiotensinogenic component in a large group of hypertensive patients.


The effects of the angiotensin II antagonist saralasin on blood pressure and plasma aldosterone in man in relation to the prevailing plasma angiotensin II concentration. The effect of saralasin in lowering blood pressure and plasma aldosterone concentration in normal subjects, both sodium-replete and sodium-deplete, and in patients with various forms of hypertension, is closely related to the basal plasma angiotensin II concentration. These findings confirm and extend earlier studies of angiotensin II/arterial pressure and angiotensin II/aldosterone dose-response curves. They also emphasize the importance of the renin-angiotensin system in the control of aldosterone in sodium depletion and in renal hypertension.


Haemodynamic effects of Sar1-Ala8-angiotensin II in patients with renovascular hypertension. Sar1-Ala8-angiotensin II was infused intravenously (10 mug/kg/min) in 14 patients with renovascular hypertension, including 11 with renal artery stenosis. Brachial artery pressure and heart rate remained unchanged in six patients who were on a daily sodium intake of 130 mEq. In 12 tests performed after sodium depletion, the decrease in mean arterial pressure ranged from 13 to 76 mm Hg and showed a significant correlation with the plasma renin concentration prevailing immediately before the infusion of the drug (r = 0.81; p less than 0.001). The hypotensive response was due to a drop in total peripheral resistance. Heart rate and cardiac output showed slight increases 10 min after the start of saralasin infusion.


Comparative studies of the humoral and arterial pressure responses to Sar1-Ala8-, Sar1-Ile8 and Sar1-Thr8-angiotensin II in the trained unanaesthetized dog. The humoral and arterial blood pressure responses to Sar1-Ala8-, Sar1-Ile8- and Sar1-Thr8-angiotensin II were studied in sodium-depleted, trained, unanaesthetized dogs. Of the three angiotensin antagonists, Sar1-Thr8-angiotensin II appeared to be the best suited for clinical use. In the smallest amount that was found to be effective in reducing arterial pressure, it was devoid of agonist activity. Also, in marked contrast to Sar1-Ala8- and Sar1-Ile8-angiotensin II, Sar1-Thr8-angiotensin II was not shown to stimulate either catecholamine or aldosterone secretion.


Stimulating effects of angiotensin I, angiotensin II and des-Asp1-angiotensin II on steroid production in vitro and its inhibition by Sar1-Ala8-angiotensin II. Two of the agents known to block the renin-angiotensin-aldosterone system, namely Sar1-Ala8-angiotensin II and the nonapeptide SQ 20881, have been used to clarify the role of angiotensin II (AII) and its cogeners upon the steroidogenesis in isolated fasciculata cells from bovine adrenal tissue. It could be concluded that: (1) des-Asp1-angiotensin II is as active as AII on steroidogenesis from bovine fasciculata cells; (2) angiotensin I, although less potent, stimulates steroid production without being converted to AII or des-Asp1-AII, and (3) Sar1-Ala8-AII inhibits all three peptides in a competitive manner. The presence of a common receptor for all these three peptides is suggested.


Effect of adrenal arterial infusion of saralasin (P113) on aldosterone secretion. To test the role of the renin/angiotensin system in aldosterone regulation, Sar1-Ala8-angiotensin II (P113) was infused into the arterial blood supply of transplanted adrenal glands in conscious sheep. Effects on the aldosterone response to infused angiotensin II and III in sodium replete sheep were compared with effects in sodium deficiency. Adrenal arterial infusion of P113 up to 1,000 mug/h for 1-2h did not consistently alter the high aldosterone secretion rates of sodium-deficient sheep. However, infusion of P113 at 10 mug/h or more abolished aldosterone responses to angiotensin II infusion that caused high physiological blood levels of angiotensin II. These results are against the proposal of a primary proportional causal relationship between blood angiotensin II concentration and aldosterone secretion rate in sodium deficiency. They are also against the possibility that such a primary role is played by blood-borne angiotensin III.


Effects of saralasin on renal function of the rat. In the isolated perfused rat kidney, saralasin inhibits the vasoconstrictor effect of angiotensin II in a dose-dependent manner. At high infusion rates saralasin, by itself, increases renal vascular resistance and supresses renin release. Such an agonistic effect is not observed in the presence of high concentrations of angiotensin II. In acute renal failure induced by glycerol, saralasin has a beneficial effect on urine volume, solute excretion and plasma urea concentration only when it is administered together with an adequate volume of rat serum.


Effects of angiotensin antagonists in various forms of experimental arterial hypertension. The dependence of renal hypertension on increased levels of angiotensin II was investigated in conscious dogs at various stages of hypertension of four different types. Two of the most potent angiotensin inhibitors, Sar1-Ile8- and Sar1-Thr8-angiotensin II, were infused separately in various doses and at different times throughout the evolution of renal hypertension. The results of these experiments are consistent with the view that the renin-angiotensin system may participate in the acute and malignant phases of renal hypertension; they do not provide evidence for its participation when hypertension enters the chronic phase.


Effects of d- and l-amphetamine on dorsal and ventral hypothalamic self-stimulation in three inbred strains of mice. The effects of intraperitoneal injections of increasing doses of d- and l-amphetamine on self-stimulation behaviour in dorsal and ventral hypothalamic areas, were studied in BALB/c Orl., DBA/2 Orl, and C57BL/6 Orl inbred mice. Both isomers improved and disrupted self-stimulation as a function of the doses injected. However, the improvements obtained with d-amphetamine were higher than those obtained with 1-amphetamine. In contrast the 1 isomer generally provoked the highest disruptions. In addition, the three strains presented various sensitivities to d-amphetamine, which improved self-stimulation first in BALB/c (0.25 and 0.50 mg/kg), then in DBA/2 (0.50 and 1.0 mg/kg) and finally in C57BL/6 (2.0, 4.0 and 8.0 mg/kg). The dorsal hypothalamic self-stimulation system presented a greater sensitivity to d-amphetamine than the ventral system; while the two reward systems reacted identically to 1-amphetamine.  The differential effects observed are set into relationship with neurochemical data concerning the central catecholaminergic mechanisms.


Effects of selective forebrain depletions of norepinephrine and serotonin on the activity and food intake effects of amphetamine and fenfluramine. Selective forebrain depletions of either norepinephrine or serotonin were produced in separate groups of rats by placement of lesions in the brainstem noradrenergic area and in the dorsal and median raphé nuclei respectively. Rats with norepinephrine depleting lesions exhibited an attenuation relative to intact animals of both the anorexic and locomotor stimulatory effects of amphetamine. In contrast, depletion of serotonin by the raphé lesion enhanced the locomotor stimulation induced by amphetamine but did not affect the anorexic efficacy of amphetamine. Neither brain lesion, however, reliably altered the animals' response to either the anorexic or activity effects of fenfluramine.


Effect of magnesium deficiency on nonspecific excitability level (NEL) and audiogenic seizure susceptibility. Magnesium deficiency in weanling rats caused an increase in NEL and in audiogenic seizure susceptibility. These behavioral effects were apparent after eight days of magnesium restriction and could be reversed by dietary rehabilitation. Serum magnesium declined rapidly from 1.87 +/- 0.10 mEq/L to 0.91 +/- 0.24 mEq/L in two days. Cerebrospinal fluid (CSF) magnesium decreased gradually from 1.86 mEq/L, becoming significantly lower (1.44 +/- 0.23 mEq/L) after eight days. When deficient rats were injected IP with MgCl2, raising the serum magnesium concentration to 6.6 mEq/L, NEL decreased to normal while audiogenic seizure susceptibility remained. Both NEL and audiogenic seizure susceptibility in rats reflect central nervous system magnesium concentration, except when serum magnesium concentration is very high. Very high serum  magnesium concentration lowers NEL but does not reduce audiogenic seizure susceptibility if CSF magnesium is low.


Effects of pentobarbital on punished behavior at different shock intensities. Key-pecking by two pigeons was maintained initially under a schedule where the first response after five minutes had elapsed produced food. When every 50th response produced shock, responding was suppressed (punishment). Although rates and patterns of punished responding remained comparable when the shock intensity was reduced by half, pentobarbital produced much greater increases in both overall and local rates of responding at the lower shock intensity. Pentobarbital also produced larger increases in the low rates of responding immedicately following shock when the lower intensity shock was in effect.


Effects of lithium chloride on sleep patterns in the rat. Continuous EEG recordings were performed in rats both  after saline injections (control days) and after LiCl treatments. LiCl administration was always followed by an initial period of general distress and sleep inhibition during 2 to 3 hr after low toxic doses (1.5 mEq/kg) and a much more longer period (10 hr) after high toxic doses (3 mEq/kg). Once this state was overcome, the pharmacological effect of lithimia seems to potentiate sleep and particularly paradoxical sleep (PS). It appears that this potentiation of PS occurs once lithimia reaches levels used in human therapeutics.


Effects of monosodium glutamate on somatic development, obesity and activity in the mouse. Neonatal mice 1 and 5 days of age and older mice 25 days of age were injected with an increasing dose of monosodium glutamate (MSG) for a ten-day period and observed for at least 150 days. Both male and female animals in the 1- and 5-day age group treated with MSG showed large increases in weight over controls along with a shortened body length. The MSG group also showed decreases in locomotor and explatory behavior. The 25-day animals took much longer to show effects or failed to show any effects, indicating that the MSG-induced changes studied are age dependent. Possible methodological considerations accounting for conflicting reports in the MSG literature are discussed in light of the present findings.


Brain 5-hydroxytryptamine correlates of behavior: studies involving spontaneously hypertensive (SHR) and normotensive Wistar rats. Brain area 5-hydroxytrhptamine (5-HT) turnover and behavioral correlates were compared in spontaneously hypertensive rats (SHR) and normotensive Wistar rats. SHR appeared to have hyperfunctional 5-HT systems as evidenced by the finding that brain area 5-HT turnover times were 53% lower in SHR, with significant changes seen in the limbic forebrain. SHR, while less active upon initial testing of spontaneous motor activity than Wistar rats, did not habituate as readily to the testing procedures as evidenced by higher activity than Wistar rats in repeated testing stiuations. In the light of other data indicating that 5-ht systems are predominantly inhibitory to ongoing behavior, these data suggest that habituation, as determined in this study, is an active process that is retarded in the SHR because of hyperfunctional 5-HT systems. Spontaneous activity of SHR was inhibited less than that of Wistar rats by a conditioned stimulus which is consistent with the observations of others that 5-HT systems tend to suppress responsiveness to external stimuli. While spontaneous activity data suggested that SHR were more emothinal than Wistar rats, the SHR also exhibited a higher avoidance rate in an unsignaled shuttle avoidance procedure which is usually indicative of a lower emotional state.


Abnormal open field behavior after anterolateral hypothalamic injection of 6-hydroxydopamine. To investigate the importance of forebrain catecholamine terminals in open field behavior, rats were microinjected bilaterally in the medial forebrain bundle at the level of the anteralteral hypothalamus with 6-hydroxydopamine (6-OHDA), a specific catecholaminergic neurotoxin. These 6-OHDA microinjections produced extensive loss of forebrain catecholamine terminals; identical vehicle microinjections did not. When 6-OHDA rats were given 8 open field (OF) tests in the first or the fifth postinjection week, they had a longer latency to enter the OF, crossed fewer squares and reared less than normal rats or rats microinjected with vehicle. The abnormal OF behavior of 6-OHDA rats was not a generalized loss of locomotor activity because 6-OHDA rats were normally active in the home cage. The abnormal OF behavior of 6-OHDA rats was also not a result of a generalized lack of reactivity because the OF test elicited an increase of plasma corticosterone in 6-OHDA rats. The possibility that 6-OHDA rats were abnormal in the OF because they were hyperractive to it was not consistent with the observations that the OF activity of 6-OHDA rats did not change with repetitive testing, 6-OHDA rats did not defecate more than vehicle rats, and 6-OHDA rats did not display freezing behavior. These results suggest, but do not prove, that the abnormal OF behavior of 6-OHDA rats reflects a deficit of exploratory behavior that is correlated with extensive loss of forebrain catecholamine terminals.


The discriminability of apsirin in arthritic and nonarthritic rats. Aspirin, 56 mg/kg IP, was shown to be mildly, but significantly discriminable from saline in a group of 12 nonarthritic rats exposed to a 2-lever fixed ratio 10 drug discrimination protocol for 56 trials. In a concurrently-tested group of 12 rats made arthritic by injection of Mycobacterium butyricum into a hind paw, the discrimination of aspirin from saline was enhanced. The results exemplify how drug discriminability may vary depending on the pathological state of the subjects exposed to drug-discrimination training.


Behavioral, biochemical and histological effects of prenatal administration of progesterone in the rat. Pregnant Wistar rats were injected with progesterone (1.5 mg/kg) between Days 8 and 21 of gestation and the behavioral, biochemical and histological effects of this treatment were observed in the offspring. The progesterone offspring weighed less than the control animals during this weaning and were retarded on one measure of exploratory activity in the open field. None of the other 29 tests used showed any significant difference apart from a 9% increase in the amount of brain DNA in the progesterone animals. It was concluded that these differences were fortuitous and that progesterone has no consistent or significant effects on brain development in rodents following prenatal administration.


Carbachol, angiotensin-II, ventircular spread and water balance in rats. Injections into the preoptic areas and anterior hypothalamus of a little as 1.0 ng/mu1 carbachol (5.5 X 10(-6) M, 11 pmols total dose) and 0.1 ng/mul angiotensin-II (10(-7) M, 0.2-0.4 pmols) were dipsogenic or antidiuretic-natriuretic. Lateral ventricular (VL) thresholds for drinking also were 11 pmols for carbachol and 0.2 pmols for angiotensin. The low VL threshold for carbachol supports, without proving, arguments that a limbic cholinergically-coded thirst circuit could reflect leakage form placements near VL to the third ventricle. In contrast, VL thresholds for antidiuresis-natriuresis were 110 pmols for carbachol and 2 pmols for angiotensin. Carbachol was more effective rostral to the paraventricular nucleus and angiotensin dorsal to the supraoptic nucleus. However, lower thresholds in these areas were insufficient to localize receptors, since all cannulas positive for antidiuresis-natriuresis traversed ventricles, and cannulas not traversing ventricles were negative.


Quantitative determination and identification of pharmaceuticals by means of Gran's potentiomentric method. A method is proposed both for the quantitative determination and identification of pharmaceuticals, based on the data of a single pH-metric titration. As a new identification criterion the pK-value of the pharmaceutical is proposed. The latter is conveniently determined using the Gran's graphical method. A new equation is derived for the data treatment of very weak bases, where the Gran's original method can not be applied directly. The proposed method is applied with determination and the identification of many pharmaceuticals weak and very weak acids and bases.


Application of some polymers in the physiocochemical design of tablet formulation. Polyethylene glycol 4000 did not apprecialbly affect the rate of drug release from tablets. The use of sodium alginate the a tablet binder showed variable effects on the rate of drug release from the tablet i.e. The incorporation of only 2.5% of sodium alginate caused enhancement in the release rate of the drug based on its action as disintegration inducer. On the other hand, the incorporation of 20, 35 and 50% of sodium alginate showed a pronounced retardation in the rate of drug release from the tablets. This retardation was more pronounced in acid than in alkaline media. Accordingly, sodium alginate could be favourably suggested as tablet binder when retarded gastric absorption is the therapeutic aim required. Carbopol 940 when used as a tablet binder in a concentration of 2.5%, showed a marked enhancement of the release rate of the drug. On the contrary, it exerted a remarkable retardation in the rate of drug release from the tablets when incorporated in the relatively large proportions of 20, 35 and 50%. This retardation was more pronounced in alkaline than in acid media. Accordingly, Carbopol 940 would be favourably suggested in the physiocohemical design of prolonged-release tablet formulations.


Ethyl cellulose as a potential sustained release coating for oral pharmaceuticals. This current study was motivated, and designed in an attempt to determine the possible application of the inert, pH-insensitive, ethyl cellulose polymer as a potential sustained-release coating for oral pharmaceuticals. Coating was effected using two relatively recent techniques, namely microencapsulation by phase separation coacervation, induced by temperature change, and drug entrapment by flocculation, induced by nonsolbent addition. Chloramphenicol was used as a model drug. Results of this study revealed the fact that ethyl cellulose proved to be a potential sustained-release coating for oral dosage forms. Moreover, the effect of the coating/core ratio was exhibited both qualitatively and quantitatively. This finding could help in the design of programmed or timed-release drugs. Accordingly, this study could be considered a successful attempt towards the utlization of ethyl cellulose in of the design of sustained-release oral pharmaceuticals.


New generalized equations for multiple dose kinetics by i.v. injection. New generalized equations for one compartment open model system with rapid i.v. injections for multiple dose kinetics are developed. The model assumers the first order elimination. Equations are developed for the maximum and minimum amounts of drug in body after n and infinity number of doses. The methods for calculating rate of accumulation is presented and the relationship bewteen, f (fraction of drug present in the compartment at the time of repeated dosing), t1/2 and the dosing interval, tau.


Synthesis of 1.2.3.4-tetrahydro-2.4-dioxoquinazoline derivatives for pharmacological study. The condensation of 4-chloroanthranilic acid with several substituted monophenylureas is described. Reacting equimolecular amounts of the haloanthranilic acid with monophenylurea, p-tolylurea, p-methoxyphenylurea, p-ethoxyphenylurea, p-bromophenylurea, p-chlorophenylurea and m-chlorophenylurea--by fusion in a pressure bottle--yielded the corresponding 7-chloro-3-aryl-.2.3.4-tetrahydro-2.4-dioxoquinazoline (1a--g). On the other hand, o-substitute phenylureas, instead of affording the expected condensation products, yielded a compound which was shown to be 7-chlorobenzoyleneurea (2), the formation of which is accounted for.


Quantitative determination of ruscogenin in Ruscus species by densitometric thin-layer chromatography. A densitometric t.l.c. method of quantitative determination of ruscogenin was elaborated. After separation with the aid of t.l.c., the colourless ruscogenin spots were located with the aid of a p-dimethyl-aminobenzaldehyde solution and were submitted to densitometry. It was found that under the selected conditions a linear dependence exists between the betaI% value and lgC within the range of 0.5--10 mug ruscogenin. The determination of ruscogenin is done in the presence of the remaining components of the sample. The method is free of any systematic error. The method was applied in the determination of the ruscogenin content of the above-ground and underground part of Ruscus aculeatus and R. hypoglossum, extracts of the same plants, and capsules with further to the R. aculeatus extract also contained bioflavonoids. It was found that the content of ruscogenin in the underground and the above-ground parts of R. hypoglossum is 0.14 and 0.10%, respectively, while for R. aculeatus the respective values are 0.12 and 0.08%. The extract contains 1.6% ruscogenin, and the capsules 0.09 mg each.


Investigations of nicandrenone--a withanolide-like aromatic plant steroid from Nicandra physaloides. On the basis of IR, UV, ORD, NMR and high resoluted mass spectral data as well as chemical transformations, evidence for structure 1 of the D-homo-aromatic plant steroid nicandrenone from Nicandra physaloides (Solanaceae) was given. The sterochemistry of both epoxy lactol functions in this compound was established using intramolecular hydrogen bonding investigations. Biogenetical aspects are discussed.


Cardiovascular activity of 9-hydroxy-ellipticine. The cardiovascular activity of 9-hydroxy-ellipticine (9-OH-E) has been studied on anaesthetized dogs. The drug has been administered intravenously in one dose ranging from 1 to 10 mg/kg. The variations in the myocardial contractility, the systemic haemodynamics, the respiration and the general metabolism of the anaesthetized dogs were studied to make evident the mechanism of 9-OH-E cardiostimulating action. 9-OH-E from 5 mg/kg i.v. stimulates the contractility of myocardium and improves the cardiac performances of the anaesthetized dogs. This heart-stimulating action is long-lasting and is not accompanied by any modification in the arterial blood pressure. It is inhibited or at least strongly attenuated by beta-adrenergic blocking agents and by the depletion of catecholamines.


Antithrombotic effects of sulfinpyrazone in animals: influence on fibrinolysis and sodium arachidonate-induced pulmonary embolism. It has been shown that sulfinpyrazone stimulates fibrinolytic activity in various in vitro and in vivo test systems. In rats with kaolin-induced paw oedema this compound is able to restore the markedly prolonged euglobulin clot lysis time in an oral dose of 30 mg/kg, whereas salicylate and dipyridamole are somewhat less active in this respect. Beside these effects, sulfinpyrazone protects rabbits from arachidonate-induced sudden death after a single oral dose of 10-30 mg/kg.


Effects of calcium infusion on secretion and motor activity of totally isolated canine stomach perfused with homologous blood. Isolated, ex vivo perfused, canine stomachs were used for this study. Gastric secretion, myoelectrical activity and mechanical activity were recorded during stimulation of gastric function with pentagastrin or histamine alone or combined with calcium gluconate. Secretagogues and calcium were infused into the gastric arterial circulation. Hypercalcemia induced significant inhibition of pentagastrin, stimulated gastric secretion, but did not affect the secretion stimulated by histamine. Hypercalcemia also induced an increase of frequency of cycles of electrical control activity and a decrease of mechanical activity of the gastric antrum. The effect of hypercalcemia on gastric motor function was similar in the nonstimulated stomach and during the infusion of secretagogues used in this experiment.


Influence of surgical manipulations on hexobarbital effects in rats. In rats the hexobarbital metabolism is impaired after different surgical procedures leading to muscle damage. This leads to a prolongation of the hexobarbital action. The prolonged effect of hexobarbital in rats with lymphostatic encephalopathy is considered an unspecific consequence of the tissue damage during lymphectomy.


Sex and genetic differences in the elimination of sulphadimidine in rats. Rats of five inbred strains and two random-bred stocks were intravenously given sulphadimidine (40 mg/kg body weight). A relatively low percentage of acetylsulphadimidine (Ac-S) in urine and absence of strain differences were found in males, whereas two phenotypes can be distinguished in females: (1) high percentage of Ac-S in urine, and (2) low percentage of Ac-S in uirne. An autosomal control of these differences is suggested. A dominant allele which determines the high percentage of excreted Ac-S manifests itself only in female endo-environment.


The observation and analysis of cancer deaths among classified radiation workers. The extent to which occupational radiation exposure contributes to cancer mortality is an influence on future world energy policy. It is also a factor in deciding the level  of expenditure to reduce radiation levels experienced by workers. Here we discuss some of the difficulties in analysing the situation  and present the results of some calculations which estimate the expected age-specific radiation mortalities from all inducible cancers and also from leukaemia separately. Using a high value for the average occupational exposure and a conservative estimate of the associated risk, we find that a survey of mortality among radiation workers must run over many years before sufficient data would be accumulated to resolve the effects of radiation-induced neoplasms from those arising from other causes. We show the advisability of determining the cause of death both of persons who remain employed in the industry and all for only a short time. Our estimates are based on maintenance of an occupationally exposed dose of one rad per person per year during the period of the survey which may extend over several decades. However, scaling of the estimates to any other exposure rates is easily performed. We also give estimates of the lowest risk coefficients detectable in a given observation time. Since for a work force of 3000 these lowest detectable values are an order of magnitude larger than those expected, it is clear that only a national or international survey can produce data adequate for even modest objectives.


The influence of cosmetics and ointments on the spectral emissivity of skin. Measurements of the spectral emmissivity, epsilon (lambda), of human skin described in a previous paper were performed with a modified monochromator by comparing the radiation from the skin with blackbody radiation in the wavelength range between 2 and 14 mum. Using the same equipment the spectral emissivity has been measured of skin which had been covered with different cosmetics and ointments. From these data it is possible to predict theoretically the apparent temperature difference as seen by an infrared scanner or radiometer with a detector of which the spectral detectivity, D (lambda), is known. These values are compared with the readings of a Bofors Thermograph with an InSb detector. When talcum venetum has been applied to the skin, a greater apparent temperature diffenence must be expected for thermographic cameras equipped with a HgCdTe detector than for cameras with InSb detectors.


Stripping-theory analysis of thick-target neutron production for D + Be. The Serber theory for deuteron stripping is employed to predict the shape of the neutron energy spectrum produced by 35 MeV deuterons (D+) on a thick beryllium target. In particular, the observation that the maximum of the neutron energy spectrum (at 0degrees relative to the deuteron beam direction) occurs at approximately 0-4Ed, where Ed is the incident deuteron energy, is explained reasonably well by the calculations. The explanation stems mainly from the fact that the stripping theory for thin targets predicts a narrow maximum at 0-5Ed, and thick target effects shift the maximum downward in energy to approximately 0-4Ed. A number of recent spectral measurements are in agreement with these predictions for a wide range of target materials and incident deuteron energies. The application of this theory also accounts for the previously observed Dd2-99 dependence of the absorbed dose in tissue,per unit charge of D+ ions on target, in the direction of the incident beam. This approximate Ed3 dependence is shown to be a characteristic property of deuteron stripping in a thick target and follows directly from the calculations that predict the neutron energy spectrum.


Further results in nuclear scattering radiography. A further investigation of the nuclear scattering of 500-1000 MeV protons is described. Three-demensional information on the desity distribution within carbon, CH and H2O phantoms is obtained with a volume resolution of 2 mm3. The separation of scattering on hydrogen from that on heavier nuclei, such as carbon and oxygen, is demonstrated, providing the statistics are sufficient. Some preliminary measurements on animals are reported, but with a volume resolution limited by statistics to 43 mm3.


Gamma dosimetry with Al2O3 thermoluminescent phosphor. Preparation of thermoluminscence (TL) dosimetric grade A12O3 powder and pellets five times more sensitive than TLD-100 is described. Glow peaks at 50, 125, 250, 325, 475 and 625 degrees C with emission in the blue region have been observed; Si and Ti have been identified as the impurities responsible for TL in  this phosphor. Studies of the TL growth rate with exposure showed that the 250 degrees c peak grew linearly up to 400 R and then at a supralinear rate of (exposure). The growth of the 475 degrees c peak was almost linear at a rate of (exposure) 1-05, while that for the 625 degrees C peak was sublinear at (exposure) 0-85. The 250 and 475 degrees peaks together show a linear response up to 40 000 R. The phosphor had no light sensitivity and is very well suited for gamma dosimetry as pellets or powder. Studies of sensitization and supralinearity, with sensitizing exposure, sensitizing anneal temperature and test gamma and alpha exposures are reported. Initially filled 625 degrees C TL related traps were found to be essential for sensitizaiton. Supralinearity and sensitization in Al2O3 phosphor could be consistently explained by the deep trap model.


The interaction of salts, amides, and water. Infrared and Raman spectra are presented for salt solutions in N-methyl formamide and N,N'-dimethylformamide. Viscosities are reported for many of these solutions. Spectroscopic and viscosity data are also given for amide-salt solutions containing water. The three-component systems exhibit a hydrogen-bonding strength of water proton greater than amide proton, and an acceptor strength of Cl- greater than amide carbonyl oxygen greater than water oxygen. The salt cation is deduced by means of viscosity measurements to interact strongly with the amide carbonyl oxygen, even in the presence of appreciable quantities of water. Association of amides by hydrogen bonding through halide ions is also indicated.


Effect of the hepatocarcinogen ethionine on hepatic messenger RNA synthesis. An experiment was conducted to determine if any changes resulted in the proportion of hepatic messenger RNA following treatment with ethionine, a hepatocarcinogen. The relative specific activity of the total RNA isolated from nontumor-like tissues was increased in Sprague-Dawley rats fed ethionine. However, the percentage of total RNA that was message was found to be decreased in the ethionine-treated rats.


Hyperosmotic oxidation of glucose and decarboxylation of histidine in the gastric mucosa. Paired slices of rat gastric mucosa were incubated with labeled glucose or histidine in isosomotic solution of 3-fold hyperosmotic solutions concentrated in NaCl, KCl, or ethanol. The rate of (1-14C)glucose oxidation to 14CO2 in isosmotic solution was reduced by 74% in hyperosmotic NaCl and by 28% in hyperosmotic KCl. The rate of (6-14C)glucose oxidation to 14CO2 in isosmotic solution was reduced by 64% in hyperosmotic NaCl and by 53% in hyperosmotic KCl. Reductions of glucose oxidation in hyperosmotic ethanol were not significant. The ratio of 14CO2 formed from (1-14C)glucose to that formed from (6-14C)glucose was not significantly changes by hyperosmotic NaCl or ethanol, but was significantly raised by hyperosmotic KCl. The rate of (carboxyl-14C)histidine decarboxylation in isosomotic solution was reduced significantly by 48% in hyperosmotic NaCl, by 30% in hyperosmotic KCl, and by 27% in hyperosmotic ethanol. We conclude that hyperosmotic solutions reduce glucose oxidation and histidine decarboxylation by rat gastric mucosa in the order of potency: NaCl greater than Kcl greater than or equal to ethanol. Thus hyperosmotic solutions inhibit the source of metabolic energy for stimulated acid secretion, the citric acid cycle, and the formation of the secretagogue histamine.


Subcellular distribution and electrophoretic behavior of aminopeptidase in human placenta. The activity of aminopeptidase was found by differential centrifugation to be distributed in the three main subcellular sites of human placenta: the lysosomal-mitochondrial, microsomal, and supernatant fractions. Placental lysosomes were isolated from the lysosomal-mitochondrial fraction and identified by electron microscopy. The lysosomal and microsomal aminopeptidases presented different electrophoretic patterns, suggested the existence of multiple molecular forms of aminopeptidase within the human placenta. Serum aminopeptidase appearing during pregnancy showed the same bands as those of the lysosomal enzyme. This finding suggests that the increased aminopeptidase in pregnancy serum may originate from the lysosomes of the placenta. Placental aminopeptidase bands were absent in fetal serum. The supernatant contained most of the total activity, which turned out to be due to contamination of this fraction by retroplacental blood.


Kinetics of the light flash of the living firefly: a supramolecular process. The light intensity vs. time curve of the light flash of the living firefly has been measured. Unlike the purified firefly enzyme system in aqueous solution, the living system does not show light decay conforming to a double exponential time curve, to simple first or second order decay, or to solid-state Elovich kinetics. Light decay of the living flash does show linearity in a probit vs. square root of time plot, which may indicate a reaction rate-limited by cooperative interactions of a biological phase transition. The observation that the kinetics of the firefly light system differ in the living cell from those in the purified system suggests that in the living system supramolecular factors control the rate of the reaction.


[Mutism as permanent catatonic condition]. The history of a case of mutism, where the patient had been silent for more than twenty-five years, caused by the author to study and discuss this relatively infrequent catatonic symptom which is a type of schizophrenia, with frequent references being made to the results of psychiatric studies made by authors ranging from Kahlbaum to Leonhard. Permanent mutism as a possible phenomenal form was logically classified, by Leonhard, as a type of mannered catatonia.


[Attitude changes in alcoholics - demonstrated in phasic course of treatment]. The constant change in attitude to personal "alcohol problems" of patients treated on an inpatient or out patient basis is described with reference to the phasic course of treatment and the deviations therefrom. It is essential that this be taken into account in both group and individual therapy, more especially as this will lead to favorable psychagogic and psychotherapeutic approaches.


[Some psychodiagnostic relevant personality variables of mothers of psychosocially abnormal children and adolescents]. One hundred mothers of psychosocially abnormal children and juveniles were subjected to a clinical and psychological examination by means of the INR questionnaire containing 70 questions to be answered. Neurotic and near-neurotic personalities and behavior patterns could be objectified in 71 percent of the subjects. Only 29 percent of the mothers tested gave normal psychological test results. The two groups of subjects were different in regard of both the intactness of marital relations and the ideational images of, and reasons given by, their children. The relatively large number of mothers showing negative psychological test results again underscores the need for intensive medical and psychological care of such persons and parents, respectively, in order to be able to make subsequent and effective corrections of psychic maldevelopments in adolescents.


[Psychotropic drugs for behavior disorder treatment in oligophrenic epileptics]. Forty-one patients were treated with promazine, a phenothiazine derivative, for an average of 266 days. The average daily dose was 200 mg. Thirty patients were treated with levomepromazine for an average of 115 days, the daily dose being about 130 mg. The two groups of patients were examined for their contactual, impulsive, and affective behavior before, during, and after treatment. The positive results obtained justify the use of the above-mentioned psychopharmaceuticals for the therapy of abnormal behavior of oligophrenic epileptics.


[Future of neuropsychology].

[Future of neuropsychology]. The future development of neuropsychology as an independent discipline, which has as its principal subject the relationships between the brain as a material substrate and the psychic behavior shown by human beings as well as animals, is discussed on the basis of a schematic presentation of the possible structure of this discipline (general, genetic, clinical and pathological, and applied neuropsychology.


[Role of countertransference in complex psychotherapy]. The psychotherapist has a key position in any psychotherapeutic situation, participating in the psychotherapeutic process with all his personality and responding both consciously and unconsciously to the patient and the entire psychotherapeutic system. Countertransference consists of those actions and emotional manifestations on the part of the psychotherapist, which originate from his unconscious strata as a reaction to the overall situation. The existence of countertransference and its possible interference with, and perhaps adverse effect on, the psychotherapeutic process require close scientific and social controls. Also, it will be necessary to make "self-experience" psychotherapy (educational analysis) a required subject. Countertransference also has important perception- and empathy-promoting functions.


[Problems and aspects of cooperation between pedagogs, youth health professionals and pediatric neuropsychiatrists in rehabilitation of behavior and achievement disorders in children with normal intelligence]. In those cases where the subjects involved tend to show pathological psychophysical reactions, it is necessary for a cooperative effort to be made by pedagogs, psychologists, and medical experts (pediatricians and pedoneuropsychiatrists). This may be realized by patient-related corrdinative consultations or psychotherapeutic treatment and subsequent individual pedagogic promotion and encouragement depending upon the degree of manifestation and generalization of the disorders. The use of various methods (modified but predominantly pedagogic and directive approaches and chiefly psychological and nondirective methods of treatment, respectively) involve different responsibilities of experts for the process of rehabilitation (in regard to both time and content). Also, the authors show that this is not in contradiction to general objectives of education and training and that every effort is made to reconcile medical and psychological objects with pedagogic requirements.


[Lymphocyte sensitivity to brain specific glycoprotein in multiple sclerosis]. The lymphocytes of seven out of eight multiple sclerosis patients were sensitized to brain-specific glycoproteins that had been isolated from extracts of human white matter and purified by means of affinity chromatography utilizing specific antibodies as immunoadsorbents. The diagnosis of multiple sclerosis for the eighth patient, whose lymphocytes were not sensitized, was doubtful. A significant correlation between the severity of the disease and degree of lymphocyte sensitization was not obtained, although the most disabled patient showed the greatest sensitization.


[Sex distribution of EEG phenomena with particular reference to subcortical dysfunctions]. The most constant or continually recurring sexual difference observed from childhood through to old age and determined from the results of a total of 1500 electroencephalograms was a considerable increase in beta activity occurring in female individuals at an earlier time and at a higher rate. The more frequent observation in male individuals of a "pure" alpha electroencephalogram may be interpreted as suggesting a slight decrease of vigilance in them. The percentage of abnormal electroencephalographic results was highest in females, the proportion being 62.5%:51.5% and the functional disorders occurring chiefly in the form of subcortical dysfunctions (30%:20%). Low voltage was found to be predominant in males. More frequent occurrence in the female sex of weakness of the brainstem and a more sensitively reacting formatio reticularis may be considered a possible explanation; also, attempts are made to bring the results obtained into causal or reciprocal relation to psychic conditions. Beta activity is perhaps a parameter of emotionality.


[O2 multistep method as a supplement to therapy of standard brain energy balance disorders]. The possibility of improving the brain's energy state by the O2 multistep method is discussed. An outline is given of several variations of the O2 multistep method, and this is followed by a discussion of the results of studies of the increase and decrease in concentration of high-energy phosphates in the brains of rats during and after the O2 multistep process. In conclusion, the author reports a twin series of tests where psychic irritations lasting for a short time only were triggered and in which such irritations were suppressed through using the O2 multistep procedure.


[The EEG in subacute sclerosing panencephalitis (SSPE)]. This article gives an overview of electroencephalographic results obtained in the case of subacute sclerosing panencephalitis. Severe disturbances of background activity have been observed in all patients. Repetitive complexes usually occur transitorily, so that they cannot always be detected in individual cases. Repetitive complexes must be regarded as being typical of the disease, and consideration must be given in this connection to their particular characteristics (repetition frequency, constancy of form, relations to disorders characterized by myoclonus) and the clinical picture.


[Extrapyramidal syndromes as side-effects of metoclopramide (Cerucal) medication]. The authors, by describing their own observations made on eight patients showing extrapyramidal syndromes as side effects of metoclopramide (Cerucal) medication, report the various kinds of possible side effects, discussing their conformity with side effects produced by conventional neuroleptics and showing methods of treatment. Metoclopramide is known to produce three froms of extrapyramidal and motor side effects, namely: 1. Dyskinetic syndrome; 2. acathisia; and 3. Parkinson's syndrome. Therapy is in the following form regardless of the particular side effect produced by the said drug: 1. Administration of antiparkinsonian remedies; 2. administration of coffein; and 3. discontinuation or drastic reduction, respectively, of the daily dose of Cerucal.


[Delimitation and cooperation between pediatric neuropsychiatry, child health protection, psychology and pedagogy in the diagnosis, treatment, and rehabilitation of behaviorally disturbed children with normal intelligence]. This article describes the complexity and dynamics of the disease with reference to the diagnosis of "behavioral disorder in the case of normal intelligence". In addition, the authors discuss differences in manifestation and the need for cooperation between experts in pedoneuropsychiatry and clinical psychology, on the one hand, and pedagogics and special education, on the other.


[Adrenoleukodystrophy. Clinical-pathologic case history and literature review]. This article presents the clinical and pathological history of a 10-year-old boy with adrenoleukodystrophy as well as a tabular survey of 17 additional cases of which the necropsy records were published in the literature. So far as the case of adrenoleukodystrophy directly observed by the authors themselves is concerned, commencement of the disease was in the seventh year of life, with symptoms of Addison's disease and diffuse inflammatory cerebral sclerosis being observed at about the same time. The cerebral disease manifested itself as a progressive pseudobulbar and pyramidal tract symptomatology and as a progressive cerebral psychosyndrome reminiscent of an endocrinal psychosyndrome. Morphologically, the adrenoleukodystrophy was characterized by severe dystrophy of the cortex of the suprarenal gland and the brain are considered the points of action of a still unknown noxa.e suprarenal gland as well as by extensive sudanophilic processes of decomposition in the cerebromedullary substance, putamen, pallidum, and thalamus. Striated cells and cytoplasmic filamentous inclusions observed in the brain and suprarenal glands in a number of cases reported in the literature were not found by the present authors. The cortex of th


[The nosotropic effects of psychopharmaceuticals]. The spectrum of pharmacogenic pathomorphosis has been found to be also dependent upon the forms of disease, i.e., the special morbogenic factors. Two opposed types of nosotropy of psychopharmaceuticals, namely, protective and nosogenic nosotropy, are considered in dependence on the pharmacotherapeutic effect produced and the mode of clinical action. Protective and nosogenic nosotropy may be observed to be active simultaneously and result in characteristic paradoxes of the psychopharmacotherapy of endogenous psychoses.


[Rheoencephalographic examinations of a patient with "coughing syncopes"--a contribution to etiology]. This is a report of a patient showing the clinical picture of syncopes due to coughing, who has been examined by rheoencephalography. Three different varitions of syncopes due to coughing are discussed with particular reference to the factors involved.


[Preliminary results of imurek treatment of multiple sclerosis]. The authors, after presenting a survey of the literature on the treatment of multiple sclerosis with immunosuppressants, report their experience with Imurek. Of 53 patients with a chronic and progressive course of the disease, objective improvement could be observed in 17. In 20 patients the symptomatology remained unchanged, although 4 of them reported subjective improvement. In 16 patients, progression of the disease could not be stopped. Better results of treatment could be obtained for those forms of the disease where the course was, first, in the form of what may be referred to as outbursts and, later, in a chronic and progressive form. -Possible side effects are pointed out.


[Indications for study of adrenal function by measurement of the cortisol secretion rate]. Results of routine methods for measurements of plasma cortisol and his urinary metabolites have been comparated with those of cortisol secretion rate (CSR) measured by simple isotopic dilution; the latter appears for his specify and precision, to be the most suitable for an exact evaluation of cortisol production by the adrenals. In normal subjects CSR resulted slightly lower than those reported in the literature; in obese subjects CSR was slightly higher than in normals, also when it was related to the urinary creatinine. In the patients with Cushing's syndrome, CSR was considerably higher, with no overlap with the obese subjects. The CSR was also useful in showing values lower than normal, in hypopituitarism, and in confirming hormone abnormal findings in thyroid diseases.


[Hepato-Quick: a new diagnostic test for liver diseases (author's transl)]. The AA. have adopted usual biohumoral examinations and the Hepato-Quick test for a group of patients affected by various liver diseases. Hepato-Quick contains thromboplastine from monkey brain and plasma absorbed on barium sulphate. It is particularly sensitive for II, VII and X factor and it does not react on deficit of V factor and fibrinogen both already present with optimal concentration in the Hepato-Quick test. II, VII and X factor are synthetized by the liver and reveal in an outstanding way every hepatocytic lesion: therefore is the Hepato-Quick test a fine and responsive test for the liver function and in order to control the liver diseases, especially if chronic. We have seen the new test is strong altered by hepatic cirrhosis, but there are no significant alterations in different liver diseases.


[Comparative aspects of penal sanctions]. A conference on comparative aspects of criminal sanctions has been held at the Aspen Institute, Berlin, on February 2 to 6, 1976, assembling experts from Europe and from the United States, The focus has been on guidelines for prevention of crime and treatment of offenders, with a view to examine differences and convergences among various national criminal justice systems. Specific tropics under discussion have been: the goals of dention, alternatives to detention, sentencing and releasethe conditions of detention, the future of research in the field. Priority areas for further study were considered to be: prevention of crime, arrest and sentencing procedures, grievances procedures, the dangerous offender, protection of victims, of jurors and of witnesses, treatment of juveniles, information of the public.


[A new standardized method for determination of the bleeding time]. The standardized bleeding time is considered a valuable measure of the platelet role in haemostasis. It is particularly useful for the evaluation of drugs that affect platelet functions. Measurements of the bleeding time were performed using a new system which was designed following the instructions of Mielke and co-workers with some variations of the described method. The standardized bleeding time proved to be a high reproducible and sensitive technique.


[Methods of evaluation of problems related to drug abuse]. The enactment of a new drug law in Italy, brinaing with it special requirements for reporting on distribution of many controlled substances, provides an opportunity for the construction of an information system that can greatly assist in planning drug-related programmes. The Author summarizes the various types of drug information that can be collected from various points in the reporting network and suggests this system could be operated at relatively low cost of it were implemented in Italy in the very near future.


[Micro-method for determining serum bilirubin (author's transl)]. A single, rapid, precise and automatizzable micro-method for determining serum bilirubin has been described. The method requires a little while of serum. It is possible reader the bilirubin concentration at last of 30 mg/100 ml without of serum dilution. The determination of "direct bilirubin" has been examined in connection with the reaction time. The reliability of the our diazo-method has been established by comparison with well-known diazo-methods and by demonstrating the effect of hemolysis.


[Territorial experiment: inter-relational evolution of a group of inmates in the course of an extra-institutional working experiment]. The Authors analize the interrelational evolution of a group of inmates during an outside working activity, with relation to the resocializing experiences which consider the insertion in the area of individuals subjected to detentive security measures. Such evolution, in relation with the influences of the social enviornment one was associated with, was associated with, was marked by an initial cohesion stage between members (of defensive significance), followed by a gradual research of a personal autonomy, in parallel with the acquisition of a reassuring and stabilized role. The utilization of a social space according to the conventional parameters used in the area (with particular concern towards syndical dynamics and rules), reached at the cost of self-exposure, has confirmed the reached maturity and the self balance in proposing themselves to the others as subjects active in their own resocialization, sharing the acquired social rights. Beside the situation concerning the side of the group in its insertion progress, the Authors take into examination the side of the free community in tis receptivity and availability towards the group members, analizing the interactions with the environment as therapeutical moment.


Transsexualism and social attitudes. A case report. After a brief review of the literature, a case of a male-to-female transsexual, with a 4-year follow-up, is presented. The etiological factors and some social responses to this pathology are discussed.


[Genetics of psychoses under a new aspect]. To analyze the biological pathways of the genetical activity in psychoses is growing more and more to an important goal. The research in this field should be started on the assumption of a multifactorial hereditary system controlling the somatic base of mental illness in a specific way as can be argued from twin and family studies. Screening the present data, there is strong evidence that the metabolism of affective psychoses is characterized by quantitative deviations only concerning the 5-hydroxytryptamine and norepinephrine turnover particularly. The biochemical findings in schizophrenic psychoses are suspicious for qualitative abnormities too. There are some indications of toxic products in the catecholamine metabolism and of antibodies against brain substances. All these disturbances could be caused by structural gene mutants or by mutations of the genetical regulatory system changing the sensitivity for the environmental stimulus. The simultaneous investigation of simple inherited serum groups is described as a useful tool for biological marking of the responsible genotypes.


EEG examination during delirium tremens. In 30 male patients several EEG examinations could be carried out during delirium tremens (d.t.) or shortly thereafter. Most of the patients showed a normal EEG or changes which can be explained with regard to sedation through medication. 1 patient showed generalized paroxysmal spike wave bursts. On account of experimental results, we may assume that a transitory cerebral excitibality change occures in d.t. This pathophysiological basis explains the normal EEGs and paroxysmal bursts during d.t. 4 cases showed passages of pronounced diffuse slow activity during d.t. partly accompanied by thythmic bilateral slow waves. These changes point to a complication of d.t. that occurs because of another disease which results in cerebral functional disturbances as in other organic psychoses.


Delusional perception and delusional notion linked to a perception. It is a neglected psychopathological fact that Schneider clearly differentiated the delusional notion linked to a perception ("wahrnehmungsgebundener Wahneinfall") from the delusional perception ("Wahnwahrnehmung"). When this distinction is not taken into account, it is very likely that the probability of a false positive rating for the delusional perception is increased. A possible practical aid to help operationalize the differential "diagnosis" between these two symptoms is offered. The section on "delusional" phenomena in Wing's present-state examination is then discussed in the light of these distinctions.


Late suicide in former mental patients.

Late suicide in former mental patients. Results from the long-term follow-up studies "The Enquĕte of Lausanne" are presented, concerning the incidence of suicide in old age of former mental patients. Among 1,891 studied deaths, 107 (5.6%) known suicides occurred; the suicide rate for all diagnostic groups, except mental retardation (only females), being considerably higher than in the general Swiss population of the same age, especially for depressions, alcoholism, neurotic and psychopathic personality disorders.


[Individual conditions of pharmacogenic confusion conditions. Comparison of amitriptyline and clozapine]. The literature was surveyed concerning the frequency and conditions for confusional states and deliria following Amitriptyline and Clozapine treatment, and certain discrepancies were noted. As a result a retrospective comparative investigation was carried out as to the frequency and the conditions for such events in a group of patients treated along the same lines. While our experience with Amitriptyline is not different from that reported by others, this does not seem to be the case with Clozapine. Confusional states and deliria are four times as frequent as the average reported in the literature; it is clear that they depend on conditions different from those of confusional states and deliria due to Amitriptyline; there is a slightly significant (p less than 0.05) correlation between the appearance of confusion and a temperature of over 37.5 degrees C. The anticholinergic properties of Amitriptyline and of Clozapine cannot explain the difference in frequency, nor the differing conditions for the appearance, of pharmacogenic confusional states and deliria with those two substances.


[Crohn's disease of the colon: anatomo-radiological correlations (author's transl)]. The epicritic revision of 74 histologically proved cases permits the authors to dwell on the radiological features of the diseased colon; their correlations with pathological findings and their differential diagnosis are discussed. A number of radiographs are presented as examples.


[The clinical and radiological pictures of ulcerative colitis and Crohn's disease (author's transl)]. The differential diagnosis of ulcerative colitis and Crohn's disease is discussed in the light of the clinical and radiological pictures noted in 16 cases. A number of radiographs are presented.


[The radiological picture of parietal modifications in the large intestine due to extrinsic masses (author's transl)]. About 600 cases of extrinsic masses in the large intestine have been examined by double contrast clysma; radiological signs of modifications in the intestinal walls are discussed with special reference to the distinction between compression, adherence, infiltration, etc. Some cases are reported.


[Radiotherapy of giant-cell tumour of the vertebral column (author's transl)]. Five cases of successfully irradiated giant-cell tumours of the backbone, are reported; the problems of the radiotherapy of such tumours are discussed.


[Complications observed in the radiosurgical management of cervical cancer (author's transl)]. Radiosurgical management, using 192Ir instead of radium, was carried out in 58 cases of cervical cancer. The complications are described and discussed on relation to the dose employed.


Changes in the bacterial cecal flora of mice infected with Trichuris muris (Schrank, 1788). Cecal microorganisms of mice were categorized and enumerated weekly during the developmental cycle of infection with the whipworm, Trichuris muris. The cecal bacterial population consisted of Escherichia coli, Proteus spp, Acinetobacter lwoffi (Mima polymorpha), aerobic lactobacilli, staphylococci, enterococci, and anaerobes (bacteroides, streptococci, and lactobacilli) in control and T. muris-infected mice. The aerobic lactobacilli and the anaerobes constituted the greatest number of organisms in both groups. In week three there was a decrease in the number of these organisms, and in week four fewer of these and of all other organisms in the worm-infected mice when compared to controls. The most significantly reduced bacterial counts were observed during the period of T. muris self-cure.


[Estimation of the frequency of reno-vascular hypertension among unselected hypertensives (author's transl)]. In practical terms the frequency of renovascular hypertension can only be measured from groups of hospitalized hypertensives, in which severe forms and young subjects are over-represented, thus leading probably to an overestimate. Using a group of 1 009 consecutively hospitalized hypertensives, the frequency of renovascular hypertension was measured in 18 subgroups defined by sex, age (three classes) and blood pressure (three classes). For each subgroup the specific rate was then multiplied by the prevalence of the corresponding category in the population of unselected 20-64 years old hypertensives. This method led to the following conclusions: about 2% of the unselected hypertensives would be candidates for surgical correction of renovascular hypertension and 0.5% would be cured.


Concordance of blood pressure in spouses. It has been known for some years that familial aggregation of blood pressure levels occurs in adults. The question of how much of this aggregation can be attributed to genetical inheritance, and how much to a shared environment, is not yet resolved. Evidence of the influence of a common environment on blood pressure levels can be gained from examining spouses who are not genetically related. In a family study of blood pressure levels in children, 452 of the parents had had a single continuous marriage. These spouses had a small but significant association with respect to blood pressure, and this association varied with length of marriage. Different interpretations of this result are discussed in relation to those from longitudinal studies.


[A method for studying social security records in epidemiology. Use in a study on the prognosis of chronic bronchitis (author's transl)]. A method is presented to study, in an epidemiological research, the social security records. This study is based upon records of workers affiliated to the french social security general system. To obtain data which may be compared, it was necessary to take the legislation as a basis; this legislation gives the data which must be in the records. A study of laws and rules has been done to find out these data in the medical record and in the administrative one. A questionnaire is presented. This basic questionnaire should be modified according to the precise objectives of each study and to the characteristics of the population sample. To illustrate this method, some results of a study of chronic bronchitis risk factors are presented in the second part. These results concern 950 men, born in France, aged 30 to 59 in 1960 an still alive in 1972. The study of the long reductions of the ability to work, happened from 1960 to 1971, confirm the disabling character of the group "chronic bronchitis, asthma, emphysema, respiratory insufficiency" which follows immediately cardiovascular and rheumatic diseases. The total number of beneficiaries of the social security is already very important and the whole population will be soon concerned. The use of the social security records as data source could give very interesting informations about morbidity. So, it is possible to study representative samples of the general population or of some particular groups, which has up to now, been done only in a slight extent.


Errors in the measurement of total respiratory resistance and reactance by forced oscillations. The total respiratory resistance determined by means of the forced oscillation technique during spontaneous breathing demonstrates a variability which may be due (1) to variations of the resistance itself, (2) to the superposition of rapid oscillatory and slow respiratory signals, (3) to the presence in the breathing signals of harmonics the frequency of which is the same as that of the oscillations. In the present study we investigate the importance of the third cause of variability, in a mechanical system in which causes 1 and 2 have been excluded. It is shown that the presence of high frequency components in breathing is an important source of error in the measurement of instantaneous resistance and reactance. The error is larger at higher frequency and amplitude of breathing, lower frequency and amplitude of forced oscillations, and in the presence of a high respiratory impedance. The error is likely to be negligible when the frequency of the forced oscillation is high (e.g. 30 Hz). At lower frequencies, theinfluence of harmonies in breathing can be corrected by calculating average resistance or reactance values over one or more respiratory cycles.


Response to CO2 of intrapulmonary chemoreceptors in the emu. We studied discharge frequencies of 12 intrapulmonary chemoreceptors in the paleopulmonic lung of an emu (Dromiceius novaechollandiae) during unidirectional, artificial ventilation when step changes and static CO2 concentrations were given. Discharge frequency in afferent neurons from the receptors increased as intrapulmonary CO2 decreased. The response of the receptors to various static intrapulmonary CO2 concentrations was similar to that previously demonstrated for the duck and chicken. The median sensitivity of the emu receptors at one-half maximal discharge was 4.6 imp-(sec-0.01 F1CO2)-1. Discharge frequencies altered phasically in nine of 12 receptors when step changes in CO2 of 3.3% at 1.6 Hz were given in the unidirectional gas stream while four of 12 modulated their discharge when the CO2 changes were as rapid as 3.2 Hz. Hence, some receptors can respond to rapid fluctuations in CO2 in their microencironment. We conclude that intrapulmonary chemoreceptors in the paleopulmonic lung of the emu exhibit similar characteristics to those in birds that possess varying amounts of neopulmonic parabronchi, such as the duck and chicken.


Measurement of 'closing volume' initiated from functional residual capacity. Comparison of the nitrogen method closing volume (CV) test, with oxygen inspiration initiated at residual volume (RV method) and functional residual capacity (FRC method), was made in 91 seated normal subjects. For RV and FRC methods, respectively CV%VC (mean+/-SD) was 14.4% (+/-6.2) and 17.5%(+/-7.5) (P=0.005); slope of Phase III of CV trace was 0.99% N2/1 (+/-0.76) and 1.66% N2/1(+/-1.07) (P=0.005); size of cardiogenic oscillations was 1.05% N2(+/-0.42) and 1.21% N2(+/-0.40) (P=0.001). These data confirm earlier predictions, based on a calculated increased lung top to bottom N2 gradient in the FRC method. Support for this mechanism was obtained in 5 additional normal subjects in whom the increased CV%VC, slope of Phase III and size of cardiogenic oscillations with the FRC method were eliminated when the top-to-bottom N2 gradient was reduced by breathing a reduced FIN2. Measurements made using the classical RV method cannot be directly compared to those using the FRC method.


Hypoxia and carbon dioxide as separate and interactive depressants of ventilation. The respiratory frequency, tidal volume and ventilization responses of 20 conscious cats to hypoxia, at controlled levels of alveolar CO2, revealed a characteristic steady state response in the majority of animals which indicated a negative interaction of stimuli on tidal volume and minute volume of ventilation, but a positive interaction on frequency. Another series of studies, conducted on seven conscious cats, sought to identify hypoxic response thresholds and depression thresholds, by determining responses over a wide range of hypoxic stimulus intensities, and at different controlled alveolar PCO2. Response threshold was at about 65 torr PAO2. Under eucapnic conditions, ventilation began to fail at PAO2 about 30 torr due to failure of tidal volume. The frequency continued to increase even in the lowest range of PAO2. With hypocapnia no failure of ventilation, frequency, or tidal volume was seen even at the lowest PAO2, but with hypercapnia, the tidal volume began to fail at PAO2 about 50 torr. The minute volume however, continued to increase into the lowest range of PAO2, because the frequency continued to respond at a rate greater than the tidal volume was failing. The results are discussed in terms of interactive depression manifest through the coupled responses of peripheral and central mechanisms.


Amount and rates of CO2 storage in lung tissue. The slope of the lung tissue CO2 dissociation curve and the rate of storage of CO2 in the lung tissue were studied at 22 degrees C and at 37 degrees C in 21 isolated, bloodless dog lungs with a total of 465 separate observations. Results at the two temperatures were similar. The slope of the tissue dissociation curve of lung tissue at a PCO2 of 40 torr was approximately 0.3 ml CO2 X 100 g wet tissue-1 X torr-1. Normally, this storage was 90% complete in about 5 seconds. After carbonic anhydrase inhibition by acetazolamide, the total storage capacity was unchanged, but the rate at which storage occurred decreased significantly, so that it took about 25 seconds for 90% of the storage to be completed.


A turbidimetric assay method for studying antibody-induced lysis of hapten-coated erythrocytes. A method is described, based on the application of trubidimetry for study of antibody-mediated complement-dependent lysis of hapten-coated erythrocytes. The procedure is simple, reliable and sensitive. Time-rate studies over the entire range of interaction between the reactants are possible, with a minimal consumption of materials and time. The method also gives the possibility of adding substances to the reaction mixture, even at high concentrations, without introducing errors by multiple handling and washing.


Ultrastructural changes in HEp-2 cells treated with staphylococcal alpha-toxin. The effect of highly purified staphylococcal alpha-toxin on HEp-2 neoplastic cells growing in culture was studied by electron microscopy. In addition to some nuclear modifications, the most significant morphological changes were in mitochondrial structure, alpha-toxin seems to induce a defined sequence of changes in mitochondrial configuration which can be summarized as an earlier phase of 'condensation' of mitochondrial structure and a later phase of mitochondrial swelling with an intermediate 'transitional' configuration. The significance of these findings is discussed in the light of the present state of knowledge of the biological characteristics of staphylococcal alpha-toxin.


The role of nuclear medicine procedures in clinical nephrology: current clinical status and future directions. This review discusses the use of radionuclides in nephrology. Radioactive materials may be used for measurements of renal function (glomerular filtration rate, renal plasma flow) and for renal imaging. The compounds of choice for GFR and RPF measurements are 125I iothalamate and 125I orthoiodohippurate, respectively. Neither is the ideal agent since the radiolabeled yields a high radiation dose. No single agent has emerged as the best for renal imaging, however, a great many have been introduced in the last few years and their relative merits are reviewed here. The rationale for use of radionuclides in nephrology is based on an awareness of the pathophysiology of the disease process and of the physiologic handling of the radiopharmaceutical used in the diagnostic study.


The capnogram in the study of chronic obstructive lung disease. The purpose of this study is: 1) to emphasize the importance of the capnogram in the investigation of ventilatory disorders of the obstructive type; 2) to propose a numerical parameter representative of the capnogram; 3) to ascertain, by means of this parameter, possible correlations between capnogram changes and other tests of lung function. This parameter enables a quantitative criterion to be substituted for a descriptive one in assessment of the capnogram; The study covered 245 patients with chronic obstructive lung disease; We observed that as the capnographic tracing becomes more and more pathological, the lung function tests show progressive deterioration.


Trace elements in biological systems: nuclear techniques app. Nuclear techniques are very useful in the simultaneous determination of many trace elements in biological samples; the sensitivity depends on the method and on the elements in study and in many cases is better than 0;1 ppm. Proton-induced X-ray fluorescence and alpha-particle elastic diffusion techniques are described; the methods of sample preparation, the sensitivity obtained and some experimental results are included.


Deadtime correcton in high count rate quantitative dynamic studies with computer-assisted Anger-cameras. The use of tracers with high radioactivity in rapid dynamic quantitative studies (such as radioisotope angiocardiography), performed by the Anger-camera and data-processor, makes it possible to obtain a high counting ratemfor correct interpretation of the results of the analysis of activity/time curves in regions of interest, the authors determined, under different working conditions, the deadtimes of two Anger-cameras (Pho-gamma HP and Radicamera II), both connected to a data-processing system (Med-II). The problems inherent in this determination are analyzed and discussed. A computer program for curve correction was written and some examples of applications of it are presented, including an experiment to test the accuracy of the correction.


Effect of acetazolamide on glomerular balance and renal metabolic rate. Glomerulotubular balance, defined as proportionality between filtered and reabsorbed sodium during inhibition of sodium reabsorption in the thick ascending limb of Henle's loop (diluting segment), was examined in anaesthetized dogs by gradual reduction of renal arterial pressure. In control experiments, glomerulotubular balance applied over the whole rante of glomerular filtration rate (GFR) examined but was absent after acetazolamide administration (30 mg/kg/body wt) at GFR above 50% of control. Hence, the inhibitory effect of acetazolamide varied with GFR. At control GFR, acetazolamide reduced tubular sodium reabsorption by 32 +/- 2% chloride reabsorption by 34 +/- 3%, and bicarbonate reabsorption by 52 +/- 2%; no significant effect was observed at GFR below 50% of control. For each bicarbonate ion, three sodium ions and two chloride ions were inhibited. Measurements of renal oxygen consumption and heat accumulation rates showed that acetazolamide did not reduce renal metabolic rate significantly. It is proposed that energy-requiring hydrogen ion secretion occurs at unchanges rate during variations in GFR but that back leakage of hydrogen ions varies with bicarbonate concentration in tubular fluid. Net secretion of hydrogen ions is associated with bicarbonate transport into the intercellular space and is linked with sodium reabsorption. The concentration difference of bicarbonate salts over the tight junction (zonula occludens), which is much less permeable to bicarbonate than to sodium chloride, provides the osmotic force for reabsorption of water and sodium chloride from the tubular lumen into the intercellular space. Glomerulotubular balance is mediated by variations in filtered amounts of bicarbonate.


Blood pressure measurement of all five fingers by strain gauge plethysmography. The aim of the present paper was to study the methodological problems involved in measuring systolic blood pressure in all five fingers by the strain gauge technique. In 24 normal subjects, blood pressure at the proximal phalanx of finger I and both at the proximal and the intermediate phalanx of the other fingers was measured using a 24-mm-wide cuff. Blood pressure at the proximal phalanx was higher than that at the intermediate phalanx in all fingers except finger V. The difference of blood pressure values corresponded well with circumference of the finger. In 15 normal subjects, blood pressure at the proximal phalanx was compared in fingers I, III, IV, and V, using 16, 20, 24 and 24 mm wide cuffs. Finger blood pressure was closest to arm systolic blood pressure when a 24-mm or 27-mm-wide cuff was used in fingers I, III, and IV, and with a 20-mm-wide cuff in finger V. As the standard deviation of the mean values was larter with the 27-mm-wide cuff than with the 24-mm-wide cuff, the 24-mm-wide cuff was considered to be most suitable for clinical use in fingers I, II, III, and IV. By using the 20-mm-wide cuff in finger V and the 24-mm-wide cuff in the other fingers, normal value of finger blood pressure was determined for both proximal and intermediate phalanxes.


Intra-arterial infusion of prostaglandin E1 in normal subjects and patients with peripheral arterial disease. Acute vasodilatation was produced by infusion of prostaglandin E1 (PGE1) in the femoral artery in 6 patients with occlusive arterial disease of the legs and in 3 normal subjects. The effect on blood flow and on blood pressure was measured at different segments of the leg with the strain gauge technique, isotope clearance technique, and photoelectric technique. Skin temperature was measured at different levels by using thermocouples. The blood pressure on the legs decreased at all segments during vasodilatation as well in patients as in controls. The blood flow increased in all segments in normal controls. In patients the blood flow increased proximally in the legs. Distally, however, no increase could be demonstrated. As a good effect of PGE1, on ischaemic rest pains has been reported, mechanisms other than vasodilatation should probably be considered.


Salicylate- and aspirin-induced uncoupling of oxidative phosphorylation in mitochondria isolated from the mucosal membrane of the stomach. The hypothesis that the damaging effect on the stomach mucosa of salicylic acid and its derivatives is ascribable to an uncoupling of oxidative phosphorylation has been investigated by testing of mitochondria isolated from the corpus gland area of mini-pig gastric mucosa. Mitochondria, influenced by salicylate or acetylsalicylate (0.7-5.6 mmol/l), demonstrated increased respiration rate, decreased respiratory control ratio, and decreased P/O ratio when tested in vitro. Uncoupling of oxidative phosphorylation occurred at a salicylate concentration between 3.5 and 5.6 mmol/l.


Influence of hypoxia and hyperoxia on subcutaneous adipose tissue blood flow in man. Subcutaneous adipose tissue blood flow (ATBF) was measured by the 133Xe washout method in normal men breathing oxygen at partial pressures from 0.1 to 2 atmospheres. Breathing oxygen at partial pressures of 0.1 and 1 atm. increased and reduced ATBF by 56% and 26%, respectively as compared to air breathing. These effects were highly significant. Breathing of oxygen at 2 atm. partial pressure had no consistent effect on ATBF, although considerable changes--positive or negative--could been seen in some experiments. Oxygen-breathing at 1 atm. partial pressure is associated with a slight hyperventilation and fall in PACO2. This was shown to be without importance for the effect of oxygen on adipose tissue blood flow.


The metabolism in man of intravenously injected iodine-labelled trascobalamin I not saturated with cobalamin. Transcobalamin I not saturated with cobalamin was purified. After iodine-labelling, a fraction of approximately 0.6 retained its cobalamin-binding capacity. Iodinated protein was used for turnover studies in three healthy subjects. The plasma curves obtained were identical to those of iodinated transcobalamin I saturated with cyanocobalamin. The cobalamin-binding capacity of the iodinated protein was determined on microcolumns containing insolubilized cobalamin. The binding capacity decreased rapidly, only 50% of the initial unsaturated cobalamin-binding capacity remaining after 0.2 to 0.3 days. It is concluded that the turnover of transcobalamin I not saturated with cobalamin does not differ from the turnover of transcobalamin I saturated with cyanocobalamin, and that transcobalamin I saturated with cobalamin in vivo is metabolized at the same rate as is transcobalamin I saturated with cyanocobalamin in vitro.


An automated micromethod for the determination of serum iron. A rapid, automated micromethod is reported for the determination of serum iron with the AutoAnalyzer I system. 95 mul of serum is required, and the analysis is run at a speed of 50 samples per hour. Copper does not interfere with the iron analysis. Total iron-binding capacity can be measured with this method. Reference values for the serum iron concentration in children 6 weeks to 6 years old are presented.


The estimated daily loss of trace elements from normal skin by desquamation. The content of 21 elements (As, Au, Br, Ca, Cd, Co, Cr, Cs, Cu, Fe, Hg, K, La, Mo, P, Rb, Sb, Sc, Se, W and Zn) in normal epidermis has been determined with the aid of neutron activation analysis. The dermal loss of these elements via desquamation has been calculated in view of its possible importance in balance studies. For the bulk elements Ca, K and P, the calculated daily loss is considered to be negligible. For some of the trace elements, however, the loss may be appreciable. The daily loss of Fe by desquamation may be as much as one fourth of the daily urinary iron excretion; the corresponding fraction for Co, Cu, and Zn is one tenth.


Positional fatty acid composition in total and acetone-precipitated amniotic fluid lecithin. The fatty acid composition of lecithin has been determined separately at the 1- and 2-position in 22 samples of amniotic fluid. Palmitic acid (16:0) was the main fatty acid present at both carbon atom positions throughout the last trimester. Myristic acid (14:0) was present in very small amounts only. There was no evidence of 1-palmitoyl/2-myristoyl lecithin being present in more than trace amounts before 35 weeks of gestation. The positional specificity of the methylation pathway is therefore doubtful. Acetone precipitation of lecithin did not alter the observed fatty acid composition at either position, indicating that this procedure precipitates the different lecithin subspecies in equal proportion, without any preference for disaturated species. This method therefore fails to isolate a lecithin fraction with a specific fatty acid composition.


Amniotic fluid palmitic acid concentrations and prediction of fetal lung maturity. A method for rapid determination of total esterified palmitic acid concentration (TEPAC) in amniotic fluid is described. The correlation coefficient between the TEPAC and the lecithin concentration was 0.93 in 123 samples of amniotic fluid obtained during the last trimester. The respiratory distress syndrome (RDS) occurred in 73% of the cases studied with TEPAC less than mmol/l in predelivery samples. The RDS was not observed with higher concentrations except in cases of maternal diabetes mellitus. The predictive value of total esterified fatty acid studies was confirmed to the concentration of palmitic acid recorded, and no specific fatty acid distributions or ratios were reliable in identifying RDS or estimating gestational age.


Fibrinolytic activity in wound secretions. Debrisan, a highly hydrophilic dextran polymer, was previously shown to be effective in cleaning infected wounds. The dry beads remove wound secretions from the wound surface under gel formation. The gel can then be analysed. A high fibrinolycic activity on fibrin plates and high levels of fibrin/fibrinogen degradation products were found in the secretions from 12 wounds. Low of plasminogen, antithrombin III and the absence of coagulable fribinogen also indicated a high fibrinolytic activity. A higher fibrinolytic activity on heated than on unheated fibrin plates, and the insignificant effect of local application of EACA suggest the presence of other proteolytic enzymes than plasmin.


Innervation of human axillary sweat glands. Histochemical and electron microscopic study of hyperhidrotic and normal subjects. Adrenergic nerves were demonstrated by formaldehyde-induced fluorescence and cholinergic nerves using thiocholine techniques to demonstrate acetylcholinesterase activities at the light and electron microscopic levels. The specimens were taken during surgery from the axillae of hyperhidrotic patients and normal voluntary controls. No fluorescent nerves were found around eccrine or apocrine sweat glands in hyperhidrotic or normally sweating axillae. Both eccrine and apocrine sweat glands exhibited a nerve network showing acetylcholinesterase activity. There was no marked difference in the innervation patterns or in the intensity of the acetylcholinesterase reaction of the nerves in the hyperhidrotic patients or normal subjects. Ultrastructurally the acetylcholinesterase-positive nerves were seen in the vicinity of both eccrine and apocrine glands, but these nerves were outside the basement membrane.