Relationship of biotin to reproductive performance of Leghorn-type hens. Five floor pens with 14 Leghorn-type breeder hens each, in their 4th month of production, and 2 males per pen were fed a practical-type breeder diet composed largely of soybean meal and milo supplemented with unidentified hatchability factor sources and adequate levels of vitamins and minerals. Five additional pens were fed an identical ration supplemented with biotin at a level of 550 mcg./kg. of diet. Treatment was for a period of 7 months. A 3% improvement in production was obtained by biotin (550 mcg./kg.) supplementation, which was found to be highly significant (P less than or equal to .005) by chi-square analysis. A slight improvement was noted for feed efficiency. Biotin supplementation had no effect on egg size or adult livability. Fertility and hatchability were both significantly improved by biotin supplementation. Fertility and hatchability differences were found to be highly significant by chi-square analyses. Increased hatchability was due to a decreased number of early dead, late dead, and pipped embryos that failed to hatch.


Haloperidol: retrospect and prospect.

Haloperidol: retrospect and prospect.


Haloperidol update: 1975.

Haloperidol update: 1975.


The rapid control of the acute patient by haloperidol.


Adequate individualized dosages (AID) in perspective.


Efficient management of the acute psychotic patient: stabilization and maintenance with haloperidol.


Individual variability in response to haloperidol.


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.


Effect of gemfibrozil on lipolysis in dogs in vivo.


Sterility and fertility.

Sterility and fertility.


The management of children with chronic disease.


Vitamin A inhibition of murine melanoma.


The medical care of children in developed countries.


Effect of gemfibrozil upon platelet function and blood coagulation. Preliminary report.


Gemfibrozil: a new lipid lowering agent. Open forum.


Preliminary observations on the effect of gemfibrozil on the excretion of faecal bile acids.


Microvascular surgery.

Microvascular surgery.


Structure/activity relationship of gemfibrozil (CI-719) and related compounds.


Binding to plasma lipoproteins of chlorophenoxyisobutyric, tibric and nicotinic acids and their esters.


Extrinsic factors affecting the response to gemfibrozil.


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.


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.


Hyperlipidaemia in Scotland and the role of drug treatment.


Summary of present data from a clinical trial of CI-719.


The effect of CI-719 on lipolysis in rat adipose tissue.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


Sterilization of barbiturates by gamma-irradiation.


Pharmacokinetics of sulfadiazine upon different routes of administration in the rabbit.


The effect of molecular weight on the properties of films prepared from hydroxypropyl methylcellulose.


The interaction of some N-phenylanthranilic acid derivatives with cyclodextrins in phosphate buffers.


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.


Colorimetric and volumetric determination of organic base reineckates using ammonium vanadate.


Rapid sensitive colorimetric assay for determination of chlordiazepoxide.


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.


Isolation of dihydroflavonol from Pulicaria undulata (L.) Kostel.


Investgation of the Volatile oil of Saudi Lavandula dentata.


Age dependent acute toxicity of ethylmorphine.


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.


Proton microbeam analysis in air.

Proton microbeam analysis in air.


A preliminary investigation of nuclear resonant scattering as a new technique for the in vivo measurement of hepatic copper.


Self-shielding factors for TLD-600 TLD-100 in an isotropic flux of thermal neutrons.


The effect of obliquity in clinical thermograms.


Neutron flux uniformity in in vivo neutron activation analysis.


Effects of tissue inhomogeneities on dose patterns in cylinders irradiated by negative-pion beams.


Electrical conductance characteristics of some human erythrocyte membranes.


Dose variation in X-ray epilation for tinea capitis.


Independence of photoproduct formation on DNA conformation.


Bilirubin-sensitized photoinactivation of enzymes in the isolated membrane of the human erythrocyte.


A photochemical mid-ultraviolet dosimeter for practical use as a sunburn dosimeter.


The effect of environmental light exposure on drug-induced porphyria in the rat.


Evaluating the stability and reactivity of a light-sensitive probe by enzyme analysis.


The sunburning ultraviolet meter: design and performance.


Indication of fast triplet formation in bimolecular quenching of excited singlet states studied by conventional flash photolysis.


Target organ for a systemic effect of ultraviolet radiation.


Effects of pigment heterogeneity on fluorescence in photosynthetic units.


The non-chemiluminescent reaction of luminol with singlet oxygen.


Measuring subnanosecond fluorescent lifetimes using photon counting.


Emission spectrum differences in fluorescent blacklight lamps.


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.


Urinary chelates in penicillamine-induced cupuresis. Negative evidence for the involvement of a red-violet complex of copper and penicillamine in rabbits.


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.


Sleep-assisted instruction.

Sleep-assisted instruction.


Spontaneous remission in adult neurotic disorders: a revision and summary.


Initial drug abuse: a review of predisposing social psychological factors.


Tactile-kinesthetic space estimation: the influence of gravity.


Monaural and binaural temporal integration of noise bursts.


Spatial and fixation conditions affecting the temporal course of changes in perceived relative distance.


The world situation.

The world situation.


The promotion of health.

The promotion of health.


Asbetos--health hazards in perspective. Constructional uses.


Current information on the health risk of asbestos.


Safety measures when handling asbestos.

Safety measures when handling asbestos.


The menace of pollution--fact or fiction? Pollution: myth or menace?--measure it!


Planning for the control of pollution.

Planning for the control of pollution.


The assessment of health effects of pollution.


Chromosomal radiosensitization by bismuth in Vicia faba.


Rate of lens lesion development and of the age of mice at time of irradiation.


Labelling of glutamine acid with 113mIn for scintigraphic examinations of liver and spleen.


The influence of ionizing radiation on intestinal absorption of amino acids and their incorporation into proteins of the mucous membrane of the small intestine.


Comparative studies in the glomerular filtration, the effective renal plasma-flow and ING by some chronic renal diseases.


Nucleotide sequence analysis of coding and noncoding regions of human beta-globin mRNA.


Mutation rates in globin genes: the genetic load and Haldane's dilemma.


Structural studies on intact and deadenylylated rabbit globin mRNA.


The relationship between hnRNA and mRNA.


A comparison of nuclear and cytoplasmic viral RNAs synthesized early in productive infection with adenovirus 2.


Biogenesis of silk fibroin mRNA: an example of very rapid processing?


Visualization of the silk fibroin transcription unit and nascent silk fibroin molecules on polyribosomes of Bombyx mori.


Distribution of hnRNA and mRNA sequences in nuclear ribonucleoprotein complexes.


The structure of specific genes in chromatin.


The structure of DNA in native chromatin as determined by ethidium bromide binding.


Cellular skeletons and RNA messages.

Cellular skeletons and RNA messages.


Nonhistone chromosomal proteins and histone gene transcription.


Selective transcription of DNA mediated by nonhistone proteins.


Structure and function of the RNAs of brome mosaic virus.


Effect of 5'-terminal structures on the binding of ribopolymers to eukaryotic ribosomes.


Protein and RNA synthesis in cultured muscle cells.


mRNA structure and function.

mRNA structure and function.


Transcribed oligonucleotide sequences in Hela cell hnRNA and mRNA.


Ca++ controlled contraction-relaxation cycle in glycerinated amoeboid cells.


The relationship of the dispersion phase of chromocentric nuclei in the mitotic cycle to DNA synthesis.


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.


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.


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.


The comparative susceptibility of male and female and of mature and immature cats to infection with sub-periodic Brugia malayi.


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.


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.


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.


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.


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.


Organisation of the auditory receptor.

Organisation of the auditory receptor.


Problems of cochlear microphonic recording in man.


Electrophysiological study of the normal and pathological human cochlea. I. Presynaptic potentials.


Electrophysiological study of the normal and pathological human cochlea. II. Neural responses.


Trans-tympanic electrocochleography in the investigation of retro-cochlear disorders.


Principles in modeling biological systems.


Modeling action potentials.

Modeling action potentials.


Clinical use of auditory evoked potentials.


Properties of auditory brainstem evoked responses.


Contingent negative variations and differential hearing thresholds.


Electrophysiological measures of auditory perception.


Electrophysiological data and psychophysical measurement.


Some aspects of the rarely encountered aseptic meningitis in the epidermoid cysts evolution.


Influence of lithium carbonate on the nucleic acid concentrations in the guinea-pig brain and liver.


Infectivity for mice of cercariae, schistosomules and intermediate forms of Schistosoma mansoni, obtained in vitro.


Experimental chemotherapy of schistosomiasis mansoni. XIV. Active derivatives of aminoethanephosphorothioate, disulfide, and isothiourea.


Evaluation of Borda & Pellegrino's technique in the quantitative diagnosis of hookworm infections.


Human rabies. II. Serological studies and intra-vitam virus isolation.


The crowding effect in Schistosoma mansoni infection of hamsters: influence on worm size.


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.


Autofluorescent hepatic particles in HB ag sero-positive patients (preliminary report).


Preliminary studies on the antischistosomal activity of topically applied oxamniquine.


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 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.


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.


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.


Alectopsylla unisetosa nov. gen., nov. spec. (Siphonaptera, Ischnopsyllidae) from Argentina.


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.


Mechanism of isotonic fluid transport in the intestinal tract and kidney tubules.


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.


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.


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.


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.


The effect of lysolecithin on the release of oleate from triolein by human post-heparin lipase.


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.


Assay of pyroglutamate hydrolase (5-oxoprolinase) in tissue homogenates.


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.


Tracheal reconstruction with perichondrial grafts. Since 1972 a series of experiments (Skoog, Ohlsén & Sohn, 1972; 1975; Ohlsén, 1976) has been performed to elucidate the potential of perichondrial grafts to generate cartilage. In 1974 Sohn & Ohlsén demonstrated in rabbits that tracheal cartilage could be reconstructed from free perichondrial grafts.  As these studies were carried out with an intact tracheal mucosa a series of experiments was conducted in rabbits, and reported in this paper, in which a tracheal section containing two cartiliages and the covering mucous membrane was removed and replaced with a free perichondrial graft taken from the ear. New cartilege formed in all animals.  The reconstructed portion of trachea was partly covered by ciliated cells of normal appearance, partly by low epithelium with microvilli.  These latter areas were mainly within the central parts of the regenerated mucosa. The use of perichondrial grafts for tracheal reconstruction was also studied in two series of dogs. In four dogs a tracheal section, consisting of two comlete cartilages with the covering mucosa, was completely removed.  The circumferential defect was reconstructed by free perichondrial grafats from rib cartilage.  They were placed on two fascial flaps which had been raised from the adjacent muscles, rotated into the defect and sutured for complete coverage. Regeneration of cartilage occurred in all dogs, producing a biologic framework.  The lining of the reconstructed tracheal section was completely restored by epithelialization from the surrounding mucosa.  Low epithelial cells were successively replaced by columnar ciliated cells typical of the respiratory tract. The morphological development of the regenerated epithelium was demonstrated by electron microscopy. The regenerated mucosa exhibited normal function by passing mucus across the reconstructed area. This was recorded by filming at low speed using Cardio-green as indicator. All the animals of this series developed tracheal stenosis within the reconstructed portion. Another experiment was therefore carried out in which four dogs were subjected to the same operative procedure. Postoperatively, however, during the phase of healing, a silicon tube was inserted and left in situ to maintain expansion of the reconstructed portion. By this means stenosis could be prevented with good regeneration of the mucosal lining.


Carcinoma of the external ear.

Carcinoma of the external ear. An analysis of 246 operated patients with 260 carcinomas of the external ears from the periods 1949-57 and 1962-67 is presented. Carcinoma of the external ear occurs in Denmark with a frequency of 1.2 cases per 100 000 inhabitants and constitutes approximately 6% of all skin cancers. In the present material 67% of the tumours were squamous-cell carcinomas and 30% were basal-cell carcinomas. These forms of tumours were most frequent in elderly men who have had outdoor employment. Half of these tumours were sited on the helix and lobe, while one quarter, respectively, were sited medially and laterally. 15% of the squamous-cell carcinomas recurred, 3% of the these with metastases of the regional lymph nodes. Of the basal-cell carcinomas 18% recurred but with no metastases of the regional lymph nodes. The frequency of recurrence did not depend on the site of the tumour on the ear, but it did increase with increasing tumour size. The 5-year survival rate without recurrence was 56% +/- 4% for the squamous-cell carcinomas, and for the basal-cell carcinomas 59% +/- 6.5%. It is concluded that surgical treatment is best suited for these tumours, and the minimum excision distance for basal-cell carcinomas of less than 3 cm in size should be 8 mm, while for squamous-cell carcinomas of the same size the distance should be 10 mm. For both forms of tumour where the greatest extent is more than 3 cm the excision distance should be at least 15 mm.


Surgical treatment of the rheumatoid thumb. Special reference to the metacarpophalangeal joint.


Cellular patterns in the early phase of healing wounds in children. Cellular patterns of the healing incisional wound were studied in 55 pediatric surgical patients by the CELLSTIC method. This wound drain, specially developed for this purpose, consists af a standard-sized, viscose cellulose sponge, inside a thin silicone rubber tube. When left between the wound edges, wound exudate flows outwards through the drain, allowing its cells to attach to the sponge surface. The sponge serves as a framework where the cells may migrate, divide and transform. During the first 12 hours the cellular pattern in the sponge resembles that of peripheral blood, whereafter the number of polymorphonuclear leukocytes, almost exclusively neutrophils, gradually increases. Later on lymphocytes and monocytes invade. The first fibroblasts were seen at the end of the third postoperative day.


Studies on healing of Debrisan-treated wounds. Debrisan (Pharmacia AB, Sweden) is a highly hydrophilic dextran polymer in the form of dry, spheric beads. When dry Debrisan beads are placed on a wound, the wound secretions are sucked up into and between the beads. No crust is formed on the wound. Bacteria granular substances are removed with the secretions. Treatment with Debrisan was found to be very effective in cleansing discharging wounds. Since Debrisan treatment removes substances from the wound area, e.g. prostaglandins, this might affect the process of repair. The morphology of wounds was studied with the aid of histological and histochemical methods. In 15 patients, donor sites on one thigh, treated with Debrisan, were compared with donor sites on the contralateral thigh, subjected to open treatment. In pigs, comparison was made between Debrisan-treated with Vaseline-gauze-covered dermal burns. In man, the inflammatory reaction was less pronounced in the Debrisan-treated wound and located more superficially then in the wound left open, where perivascular inflammatory cell infiltrates were found even deep in the dermis. In pigs the burns exhibited similar differences. Thus the inflammatory reaction in the Debrisan-treated wounds was less pronounced than in the control wounds. Debrisan beads were never seen below the wound surface. No unfavourable influence of Debrisan treatment was observed on the process of repair.


Linguistic relativity and the diagnosis of schizophrenia.


Psychophamacological treatment.

Psychophamacological treatment.


Schizophrenia and sensitivity to the family environment.


Exposure to trichloroethylene I. Uptake and distribution in man. Fifteen healthy male subjects were exposed to about 540 and 1,080 mg/m3 of trichloroethylene (TRI) in the air during rest and exercise on a bicycle ergometer. Each subject was exposed during four 30-min periods. The arterial blood concentration increased linearly with the concentration in the alveolar air. The uptake of TRI was about 55% of the supplied amount at rest. At a work load of 150 W during the fourth period the percentage uptake decreased to about 25%. For one fairly thin subject the uptake was near zero at the end of exposure. This development was probably due to the relatively low solubility of TRI in blood and tissues. The uptake of TRI may be estimated from pulmonary ventilation and the concentration in alveolar and inspiratory air.


Exposure to trichloroethylene II. Metabolites in blood and urine. Fifteen men were exposed to trichloroethylene (TRI) in three different ways with regard to the concentration of TRI in the air as well as exercise on a bicycle ergometer. The total amount of TRI supplied and taken up by each person was measured. The concentrations of trichloroethanol (TCE) and trichloroacetic acid (TCA) were determined in blood and urine. In spite of large differences in uptake, there were only small differences in the concentration of TCA in blood during the day of exposure. There was a large scatter for the values of TCA in urine within each group. The concentration of TCE in arterial blood increased during exposure. Thereafter the concentrations were almost constant for 2 h and differed among the groups. These results can be interpreted as being due to balanced rates of the formation and elimination of TCE. The levels mentioned were related to the uptake of TRI. The same was found for the rate of excretion of TCE in urine when calculations were made from the morning sample obtained the day after exposure.


Exposure to trichloroethylene III. Psychological functions. The effect of exposure to the solvent trichloroethylene (TRI) on the performance of tests of numerical ability, reaction time (simple and choice), and short-term memory was studied in 15 healthy male subjects. The subjects were tested individually on three different occasions during exposure to 540 and 1,080 mg/m3 of TRI in inspiratory air and under control conditions, respectively. At predetermined times during the three 70-min exposure periods, samples were taken of the subjects' alveolar air. Neither the reaction time tests nor the short-term memory test showed any signs of performance decrement during exposure to TRI as compared to those administered under control conditions. However, a statistically significant decrement in performance was obtained on the test of numerical ability during exposure to TRI. The results as a whole indicate that there should not be any risk of an acute effect on central nervous functions at concentrations which do not considerably exceed the Swedish threshold limit value for the solvent (160 mg/m3).


Relationships between lead absorption and peripheral nerve conduction velocities in lead workers. The motor sensory, and mixed nerve conduction velocities of median and posterior tibial nerves were measured in 39 lead workers whose blood lead (PbB) concentrations ranged from 2 to 73  mug/100 g with anaverage of 29 mug/100 g. The PbB concentrations significantly correlated with the maximal motor nerve conduction velocities (MCV) and mixed nerve conduction velocities (MNCV) of the median nerve in the forearm and with the MCV of the posterior tibial nerve. Erythrocyte delta-aminolevulinic acid dehydratase (ALAD) activity correlated similarly with the MCV and MNCV of the median nerve in the forearm, and the 24-hour urinary lead excretion following the intravenous administration of CaEDTA (20 mg/kg) (lead mobilization test) correlated with the MNCV. But no parameter correlated with the sensory nerve conduction velocities. By multiple regression analysis, a combination of the three parameters of lead absorption was found to correlate significantly with the MCV and MNCV of the median nerve in the forearm. The MCVs of the median and posterior tibial nerves in lead workers were significantly delayed in the PbB range of 29-73 mug/100 g (mean 45), in the lead mobilization test range from 173 to 3,540 mug/day (mean 973), and the ALAD activity range from 4.4 to 19.4 u. (mean 14.0), respectively.


Magnetic measurements of pulmonary contamination. The magnitic determination of pulmonary contamination is based on the remanent magnetization of ferromagnetic contaminating particles. The remanent field of the externally magnetized particles is proportional to their amount and shows their distribution. Although only magnetizable particles are detected with this method, the amount of the inhaled ferromagnetic substance can be used when the total dust exposure of the worker is estimated. In this work five shipyard welders were studied. First the particles disposed to the lungs were externally magnetized and then their distribution was mapped with a sensitive magnetometer. The magnitudes of the remanent fields measured from the welders differed from the fields measured from controls by several orders of magnitude. The radiographic findings showed a good correlation with the magnetic measurements, and further experiments will prove whether this method can partly replace presently used radiological investigations.


Cardiopulmoanry bypass hemorrhage: a surgeon's point of view.


Of death and euthanasia.

Of death and euthanasia.


The Whampoa-Kallang malaria outbreak, 1974-5.


Malignant melanomas of the upper respiratory tract.


Photo coagulation in the management of retinal disorders--a preliminary report.


Quality of life and the right to live.

Quality of life and the right to live.


Experience of a comprehensive infertility clinic in the Department of Obstetrics and Gynaecology, University of Singapore. The diagnosis, treatment, and pregnancy outcome for 709 infertile couples who attended the comprehensive infertility clinic of the University of Singapore's Department of Obstetrics and Gynecology from 1970-1974 are presented.  Investigations for most of the couples were completed within 3 months.  This short investigative period was attributable primarly to the use of laparoscopy to diagnose female infertility.  In 22.5% of the 709 cases infertility was due to ovulation problems.  After treatment eith either clomiphene, human pituitory gonadotrophin, or a combination of clomiphene and human chorinic gonadotrophin, pregnancy was achieved in 30.6% of the cases.  11.7% or 83 of the 709 infertility cases were attributed to blocked tubes.  28 of these patients received tubal surgery, but only 14.3% or 4 of these cases resulted in pregnancy.  In 14.7% of the 709 cases, infertility was attributed to endometriosis.  90% of the patients with endometriosis were asymptomatic, and the liesons discovered by laparoscopy, were very small.  Pregnancy eventually occurred in 27.6% of the cases treated for endometriosis.  In 5.8% of the 709 cases infertility was due to mixed gynecological problems, and after treatment, conception occurred among 31.7% of the cases.  For 23.1%, or 147 of the 709 couples, infertility was attributed to either oligospermia or azoospermia.  85 of the 147 patients were given hormone therapy and in 12.9% of these cases pregnancy was achieved.  14 of the 147 patients were treated with antibotics for 3-6 months and in 14.3% of these cases pregnancy was achieved.  9 of the 147 patients were surgically treated and in 4 of these cases pregnancy later occurred.  20 of the 147 couples were treated with artifical insemination of donor semen and in 25.0% of these cases pregnancy occurred.  Another 19 of the 147 cases were treated with artificial insemination with the husband's semen and conception occurred in 26.8% of these cases.  The remaining 22.1% of the 709 couples were apparently normal and 47.8% of these untreated couples later achieved pregnancy.


Rheumatoid arthritis in Singapore, a clinical study.


The pattern of traumatic spinal cord lesions in Singapore--an analysis of 70 patients admitted to the spinal unit, Department of Rehabilitation Medicine, Tan Tock Seng hospital.


Pyloric stenosis in the ethnic groups of Singapore.


Cardiac beri-beri presenting with shock.


Dermal icteric zones and serum bilirubin levels in neonatal jaundice.


Pulmonary sarcoidosis in a Chinese woman.


Clinical laboratories: influence of increased productivity and new laboratory instruments on health care.


Fluid resuscitation of burn patients: does clinical "success" necessitate "excess".


Schizophrenia: a bag of dilemmas.

Schizophrenia: a bag of dilemmas.


Cryotherapy.

Cryotherapy.


Cryosurgery for benign and malignant skin lesions: treatment with a new instrument. The Foster "Froster" unit is a new and simplified liquid nitrogen system for use in dermatologic cryosurgery. The details of its operation are described and its use in various benign, premalignant, and malignant lesions is discussed. In malignant lesions, not only type, but frequently location, is important when deciding whether to use cryosurgery as the first, alternate, or adjunctive choice of therapy. Benign and premalignant lesions which respond best are sebaceous hyperplasia, dermatofibromas, actinic keratoses, leukoplakias, lentigines, and certain seborrheic keratoses and verrucae. Initial promising results have been reported in cases of swimming pool granuloma and chromoblastomycosis. Application of the described technics in one's clinical practice must depend primarily on the level of knowledge of skin lesions and on the degree of skill attained in cryosurgical methods.


Inbreeding as measured by isonymy and by pedigrees in Kippel, Switzerland.


The genetics of affective disorder and genetic counseling.


Variables in the outcome of genetic counseling.


Changes in the clinical picture of schizophrenia. Records of all patients admitted to inpatient facilities of a state department of mental health from 1948 to 1952 and from 1965 to 1969 and diagnosed schizophrenic were reviewed to determine diagnostic trends, if any. The percentage of diagnoses of the catatonic subtype showed a general decline, the hebephrenic subtype showed a marked decline, the paranoid subtype a general increase, and the nonclassical subtypes a marked increase. Analysis of the symptoms for the subtypes and comparison between subtypes did not reveal any particular symptoms to be totally characteristic of a specific subtype. Many symptoms occurred with approximately equal frequency in all subtypes. Comparison of patients' symptoms for the two periods did not reveal wide qualitative variation between periods. However, there were large quantitative variations. We conclude that the apparent change in schizophrenia is but a moderation of primary symptoms.


Delinquency, sex and family variables.

Delinquency, sex and family variables.


Septicemia, gastroenteritis, cholecystitis due to Arizona sp.


Demographic studies in a Brazilian  population of Arabian origin.


Negative blood cultures in infective endocarditis: a review.