Effects of norepinephrine applied to the lateral hypothalamus on schedule induced polydipsia. Intrahypothalamic injections of 3 doses of norepinephrine were administered to rats under conditions of 80 percent body weight reduction (prepolydipsia), 80 percent body weight reduction (schedule induced polydipsia), and normal body weight (postpolydipsia). The only significant reduction in water intake occurred with the highest dose of norepinephrine, under the prepolydipsic condition. The fact that norepinephrine failed to block schedule induced polydipsia indicates that this behavior is regulated by a different biochemical system than that of deprivation induced drinking.


Functional relationship of lateral hypothalamus and amygdala in control of eating. Cannulas were stereotactically implanted in the lateral hypothalamus and the ipsilateral amygdaloid cortical nucleus of 7 male albino rats, Wistar strain. After functional checking of the accuracy of implants by adrenergic elicitation of increased food intake, the animals were injected with combinations of noradrenaline, phenoxybenzamine or tolazoline, or placebo under 6 treatment conditions, while food-and water satiated. The elicitation of increased food intake in the satiated rat by adrenergic stimulation of the lateral hypothalamus was confirmed, and it was further found that simultaneous adrenergic stimulation of the amygdaloid cortical nucleus augmented this increase. However, simultaneous anti-adrenergic blockade in the amygdaloid cortical nucleus reduced eating to control level. The lack of response of the amygdaloid cortical nucleus to adrenergic stimulation in the satiated rat, under simultaneous stimulation of the lateral hypothalamus with either placebo or an adrenergic blocker, was also demonstrated. It was concluded that the amygdaloid cortical nucleus has a modulatory influence on eating behavior, which is dependent on the level of activity in the lateral hypothalamus, and further that this modulatory influence is necessary to the behavioral output of the hypothalamic system. This is the same relationship between the hypothalamus and amygdala previously demonstrated in regard to drinking behavior and these results are seen as supporting the behavioral generality of the functional relationships reported.


Differential effects of intraventricular administration of 6-hydroxydopamine on behavior of rats in approach and avoidance procedures: Reversal of avoidance decrements by diazepam. The administration of 6-hydroxdopamine (6-HD) and pargyline to rats produced similar selective decreases in responding during the conditioned stimulus (CS) on a discriminated avoidance test where the unconditioned stimulus (US) was shock and on an analogous conditioned approach test where the US was water. Approach behavior during the CS generally recovered, however, while avoidance decrements in the same rats remained for the duration of testing. This suggested that 6-HD-induced avoidance decrement was a result of two independent but interacting processes: (1) a decrease in conditioned behavior as reflected by the similar decrease in responding on both tests; and (2) a hyper-reaction to aversive stimuli that resulted in a tendency to selectively suppress avoidance behavior after the animal received shock. In support of this hypothesis, it was found that 6-HD-induced avoidance decrements could be reversed (1) by treatment with diazpam, a drug that releases suppressed responses; or (2) by delaying avoidance testing until conditioned responding had recovered, thus minimizing the interaction of the two processes.


Feeding following intraventricular injection of CA++, MG++ or pentobarbital in pigs. The effects on food intake, of injections into the lateral ventricle of Ca++, Mg++ or equimolar mixtures of the 2 ions have been studied in pigs. The chloride salts were made up in normal saline which together with 1.35 percent NaC1 was used as a control injection. Dosages of 12.5 mumoles, 25 mumoles, or 50 mumoles either Ca++ or Mg++ elicited increased food intake in the 30 min following the injection and there was a predominantly linear feeding response to increasing concentration of the two ions. Ca++ was more effective in eliciting increased food intake than Mg++. Equimolar mixtures of Ca++ and Mg++ of 6.5 + 6.5 mumoles, 12.5 + 12.5 mumoles or 25 + 25 mumoles also increased food intake linearly and the mixture of ions was more effective than equivalent concentrations of Ca++ or Mg++ alone. No antagonism between Ca++ and Mg++ was seen with respect to food intake. Intraventricular injections of 16 mumoles of sodium pentobarbital also elicited increased food intake in the 30 min following injection. It is suggested that the ions and the barbiturate probably act by deression of periventricular neurons, particularly in the medial hypothalamus which is adjacent to the third ventricle.


Apparatus for quantitative evaluation of visually guided pecking in the pigeon. An apparatus using a phase-locked loop is described which allows automated, differential counts of correct and incorrectly oriented pecks, elicited by apomorphine in the pigeon. This apparatus provides a unique and precise means for the study of this characteristic, visually guided behavior.


Effects of high-dose cyanate upon cerebral energy metabolism of the rat. The effect of sodium cyanate (25, 50, 75, and 100 mg/kg body weight i.p. daily for 10 days) upon cerebral metabolism and the EEG of Wistar rats was studied. This treatment resulted in a dose-related carbamylation of hemoglobin and left shift in the oxygen dissociation curve. Animals receiving the highest dose of cyanate developed a significant systemic metabolic acidosis. In brain there was dose-dependent decrease in phosphocreatine, TCO2 and cytoplasmic NADH/NAD+ ratio, reflecting the calculated drop in intracellular pH. Glucose levels were elevated despite a normal calculated energy charge, which suggests a balanced slowing of the energy-producing and energy-utilizing systems. The higher doses of cyanate produced spontaneous seizure activity on the EEG.


Relationship of brain levels of norepinephrine and dopamine to avoidance behavior in rats after intraventricular administration of 6-hydoxydopamine. Rats trained on a discriminated avoidance procedure showed long-term decrements in performance after intraventricular administration of 6-hydroxydopamine. Biochemical assay showed that DA levels were correlated with avoidance performance no matter when behavior was measured, but NE levels were most highly correlated with avoidance behavior at those times when suppression of responding appeared to be the major influence on responding. The data are discussed in terms of possible separate roles for NE and DA in avoidance behavior.


Effect of gastric emptying rate on the intestinal absorption of chloroquine in rats. After oral administration, chloroquine caused a dose-related delay in gastric emptying and in its own absorption from the small intestine in rats. Acetyl-beta-methylcholine (0.75 mg/kg i.p.) did not influence the intraperitoneal LD50 value of chloroquine (102 mg/kg) significantly, but reduced oral LD50 from 1,080 to 280 mg/kg. Acetyl-beta-methylcholine increased both the gastric emptying rate and the propulsion motility of the small intestine. As a consequence, the intestinal mucosal surface that had come into contact with the drug was increased in size, resulting in more rapid absorption of chloroquine. Infusion of chloroquine at a rate of 1 mg/min/kg into a mesenteric vein was tolerated by anaesthetized rats for hours. Increasing the dose, however, led to shorter survival times and eventually to death. It is concluded that gastric emptying may play an important role in the rate of intestinal absorption and in the oral toxicity of drugs.


Lack of protection by pyridoxine or hydrazine pretreatment against monosodium L-glutamate-induced seizures. Pretreatment of rats with hydrazine (100 mg/kg), a compound which raises brain gamma-aminobutyric acid (GAGA) 175 percent in 12 hr was not able to prevent the occurrence of seizures induced by monosodium L-glutamate (MSG). Pyridoxine (50 mg/kg) the cofactor essential in the conversion of glutamate to GABA, also failed to prevent convulsions induced by parenteral MSG administration. It is concluded that the mechanism of action of MSG-induced seizures is neither by decreasing brain GABA levels or interfering with the pyridoxine cofactor.


Modification of avoidance behavior in 6-hydroxydopamine-treated rats by stimulation of central noradrenergic and dopaminergic receptors. Rats showing reliable decrements in conditioned avoidance behavior after the intraventricular administration of 6-hydroxdopamine (6-HD) with pargyline pretreatment were given various dopaminergic and noradrenergic agonists. Intraventricular injections of DA or L-NE or intraperitoneal injections of apomorphine or L-DOPA reversed the avoidance decrements, often restoring performance to pre-6-HD-treatment levels. Furthermore, these agonists all produced behavior characteristic of activity in dopaminergic neurons. Clonidine, a noradrenergic agonist, also reversed avoidance decrements, but did not produce behavior characteristic of stimulation of dopaminergic neurons in the brain. Pretreatment with spiroperidol, a dopaminergic receptor blocker, prevented the recovery induced by all agonists, although clonidine-induced recovery was affected least. The results are discussed in terms of possible separate roles for dopaminergic and noradrenergic neurons in the brain in avoidance behavior.


Pharmacological effects of urotensins. I. Regional vascular effects of urotensins I and II in the rat. The effects of urotensins I and II were studied on blood space and inulin space (with 51Cr-labelled erythrocytes and 14C inulin) in organs obtained from rats anaesthetized with pentobarbital. The findings were matched with the effects of urotensins on blood pressure and on perfusion pressure in the isolated perfused rat hind limb (skeletal muscle), intestine, kidney, and lung. Blood space was greatly increased by urotensin I (50 mU/100 g body wt iv) in skeletal muscle, intestine (ileum), ear, renal cortex, medulla and papilla and in adrenal gland, but was decreased in liver and spleen. Blood space changes in these organs run in parallel with the blood-pressure-lowering effect of I. After urotensin II, no significant changes were observed in the above organs, with the exception of the renal cortex where an increase in blood space occurred. Urotensin I caused an increase in inulin space in skeletal muscle, intestine, diaphragm and adrenal, but mobilized extracellular fluid from liver, lung, spleen and ear. In the kidney, urotensin I increased the tissue/plasma inulin ratio in renal cortex, medulla and papilla, indicating water reabsorption. It is concluded that the blood-pressure-lowering effect of urotensin I in the rat is due to a potent vasodilatatory action, mainly exerted in skeletal muscle, mesenteric region, skin and kidney.


Learned taste aversions induced by high doses of monosodium L-glutamate. Learned taste aversions, as measured by increased time to complete 100 licks of a sweetened condensed milk solution, were demonstrated by laboratory rats 4 days after consumption of the milk solution paired with high oral doses of monosodium 1-glutamate (MSG). The hesitancy of the rats to consume milk on the test session cannot be simply attributed to direct action of the drug on motivation (e.g., hunger) or to drug debilitation. MSG has been reported to occasionally cause aversive effects in humans (Chinese restaurant syndrome), and the present experiments demonstrate that the effects of MSG are aversive to laboratory rats as well.


Pharmacological effects of urotensins. II. Renal effects of urotensin I in the rat. Urotensin I decreased urine flow, glomerular filtration rate and renal plasma flow in intact and hypophysectomized rats. The antidiuretic effect of urotensin I differed from the that caused by AVT in that (a) the urine conductivity was not usually increased by the former, and (b) the rates of excretion of Na and K were different. The use of hypophysectomized rats and of Na-thioglycollate-treated urotensin I preparations indicated that the antidiuretic effect of urotensin I was not due to the release of endogenous ADH, nor was it caused by presence of AVT in the urotensin I samples.


Pharmacological effects of urotensins. III. Fate or Urotensin I in different vascular beds and in blood of the rat. The rates of disappearance of urotensin I, a peptide with a prolonged vasodepressor action, was studied in perfused isolated organs of the rat and in rat blood in vitro. The rates ranged from 29.9+/-3.2% in the perfused hind limb to 55.1 +/- 7.2% in the lungs. Urotensin I activity disappeared slowly during incubation with rat blood, the "half-life" being about 4 min. The fast removal or urotensin I by the organs contrasts with its long duration of action.


Increased disrupting effects of haloperidol on a conditioned avoidance response after 6-hydroxydopamine treatment. The influence of prior catecholamine depletion was studied on the behavioral depressant effects of haloperidol using a conditioned avoidance response. The butyrophenone disrupting effects on the avoidance behavior were significantly increased by 6-hydroxydopamine pretreatment.


Effects of prior drug experience on the establishment of taste aversions in rats. Groups of food and water deprived rats were injected with either 2 mg/kg d-amphetamine, 9mg/kg dl-fenfluramine or isotonic saline immediately after the first presentation of a 25 percent solution of condensed milk for a 30 min period. When animals were tested for aversion to condensed milk 8 days later both drugs were found to cause a highly significant decrease in total amounts drunk; in contrast saline injected animals showed significant increases in the amount drunk. However, it was found that the development of a conditioned taste aversion could be markedly attenuated or abolished altogether by providing groups of animals with experience of both drugs prior to aversion establishment, and that the degree of attenuation of aversion was proportional to the amount of prior experience. Novelty of drug administered would seem to be a critical variable in the establishment of taste aversions. The results are discussed with reference to some of the paradoxical aspects of drug induced taste aversions.


Comparison of the discriminative stimulus properties of delta9-THC and psilocybin in rats. Male albino rats were trained to respond differentially on the left or right lever in a 2-lever chamber on the basis of which drug had been given intra-peritoneally (IP) 30 min before experimentation. In 1 group 1.9 mg/kg of delta9-THC and control injections (vehicle) served as the discriminative stimuli associated with each lever and in another group the drug stimuli were 1.0 mg/kg of delta9-THC and 1.0 mg/kg of psilocybin. The results confirmed those of other experiments using different procedures; that delta9-THC can acquire discriminative control over responding. The fact that delta9-THC and psilocybin were also found to differentially control lever choice demonstrates that these 2 drugs probably produce discriminably different states in rats.


Pharmacological effects of urotensins. IV. Blood pressure-lowering effects of urotensin I in spontaneously hypertensive rats. The blood pressure lowering effect of urotensin I, a vasodilatory peptide obtained from urophyses of a bony fish species (Catostomus commersoni) was studied by tail plethysmography in conscious normotensive and in spontaneously hypertensive rats. Urotensin I (10 mU/100 g body weight i.v.) lowered the blood pressure, depending on the preinjection level. The lowering of pressure amounted to 12.4 +/- 1.28% of the preinjection level in normotensive rats, 17.9 +/- 1.46% in hypertensive females and to 28.9 +/- 1.06% in hypertensive males. The differences between the normotensive and each group of hypertensive animals were statistically significant (p less than 0.05 to p less 0.001). The blood pressure-lowering effect of urotensin I was less pronounced in female hypertensive rats than in hypertensive males of the same age. No significant difference was found in the preinjection blood pressure level between the group of younger (169-176 days) and older (247-249 days) male hypertensive rats. However, the blood pressure in the younger rats was significantly more affected by urotensin I than that in the older rats (p less than 0.05).


Electrical and mechanical activity of the isolated canine stomach perfused with homologous, in vitro, oxygenated blood. Electrical and mechanical activity was recorded from six totally isolated canine stomachs perfused with homologous blood oxygenated in vitro. Reactions to electrical vagal stimulation to cholinergic drugs and to pentagastrin were recorded. Electrical control activity, electrical response activity and mechanical response of isolated stomachs, observed in this in vitro system, were identical to those found in canine-isolated stomachs perfused with cross-circulated blood of living animals. It appears that when a living animal is included in the perfusion system of the isolated stomach, drugs used for gastric stimulation are rapidly metabolized and, due to this physiological clearance, repeated injections of stimulants can be given for several hours. Using the in vitro perfusion system, as in this experiment, injected drugs accumulate in the perfusion blood, as no clearance mechanism is available. Partial or total exchange of perfusion blood is therefore recommended. With these reservations, the in vitro system appears to be an easy method for the study of nonstimulated and stimulated electrical and mechanical activity of the totally isolated canine stomach.


Clofibrate pharmacokinetics: effect of elevation of plasma-free fatty acids. The pharmacokinetics of rho-chlorophenoxyisobutyrate (CPIB), the active metabolite of clofibrate were determined following intravenous administration in the rat. Serum CPIB concentrations were measured using an new TLC-GLC method. The results agree favourably with pharmacokinetics in human subjects after oral administration of clofibrate. Both clofibrate and free fatty acids (FFA) are extensively bound to circulating plasma proteins. When plasma FFA were elevated to about 2,000 muEq/1, the CPIB elimination half-life decreased form 19.3 h in controls to 7.3 h. Thus, elevation of FFA appears to significantly alter the pharmacokinetics of a highly bound drug.


Acceleration and pacing of copulatory performance of male rats by repeated aversive brain stimulation. Repetitive electric shocks applied to the dorsal midbrain (DM) paced the copulatory behavior of sexually experienced male rats. DM stimulation also accelerated the rate of copulation, the achievement of ejaculation and the resumption of copulation after ejaculation and increased the number of ejaculations in an hour test.


Influence of neonatal androgen on the display of territorial marking behavior in the gerbil. The effect of the presence or absence of androgen during the neonatal period on territorial marking behavior in the Mongolian gerbil was studied. Scent marking frequency was 20-40 fold greater in males than in females. Gonadectomy depressed marking in males but not in females. Testosterone propionate (TP) therapy completely restored marking in male but increased marking in intact and ovariectomized females to only one fourth that in males. Genetic males castrated within 2 days postpartum did not mark more frequently than TP-treated females after TP treatment in adulthood. Genetic females given a single TP injection within 6 days postpartum marked at male levels after TP treatment in adulthood. Males castrated after Day 2 and females given TP after Day 6 displayed marking frequencies intermediate between normal male and female levels after TP treatment in adulthood. This study suggests that sexual dimorphism in territorial marking behavior is due to a sex difference in the competency to respond to androgen, and it appears that development of this competency occurs during the neonatal period and is regulated, at least in part, by androgen. The onset of this differentiation process occurs earlier in the male than in the female.


Extralimbic mediation of emotionality and social cohesiveness effects. Long-Evans hooded rats were tested for emotionality and observed by pairs in an open field for 6 consecutive days. Postoperative observations indicated that both emotionality and social cohesiveness were dramatically altered by ventromedial and anterolateral hypothalamic lesions. Tegmental, interpeduncular and habenular lesions were shown to have no effect on these behaviors. Alterations in behavior observed following hypothalamic ablations were related to septal and amygdaloid effects, and the possibility of separate projection systems for emotionality and social cohesiveness was discussed.


Learning deficits produced by chronic and reversible lesions of the corpus striatum in rats. In a first experiment it was found that the reversible disruption of the normal activity of the corpus striatum (CN) of rats by microinjections of potassium chloride produced a marked impairment on the acquisition of a one-trial passive avoidance task. Two additional experiments showed the same performance deficits on the acquisition as well as on the retention of the task when the CN was electrolytically lesioned. Since two different methods of disrupting the functional integrity of the striatum were used, it can be concluded that the results are not due to the pecularities of a single method. These results further support the hypothesis of critical involvement of the CN in the integration and storing of learned information.


Long-term deficits after somatosensory cortical lesions in rats. Rats having either sham operations or one-stage bilateral lesions of the two somatosensory areas of the cortex were tested for acquisition of five tactile discriminations after postoperative recovery intervals of 14, 35, 180, 365 or 730 days. The group with lesions performed worse than its time-matched control group in every instance, and there was no evidence for recovery of function with the longer postoperative recovery periods. These results suggest that time per se is not a significant determinant of restitution after somatosensory cortical ablations.


Entrainment of the rat's activity rhythm by cyclic light following lateral geniculate nucleus lesions. The rhythmic running-wheel activity of rats is entrained by sensory input via the visual system. The retinal projection transmitting visual information essential for entrainment of the activity rhythm is unknown. Lesions of the lateral geniculate nucleus (LGN) disrupt two projections, the primary optic tract (POT) and the superior accessory optic tract (AOT-SF). It was found that activity remained entrained to a light cycle following LGN lesions. This indicates that the POT and the AOT-SF are not necessary for entrainment. The two remaining projections, the retinohypothalamic pathway and the inferior accessory optic tract (AOT-IF), are sufficient to maintain entrainment. In light of other investigations, it is suggested that the retinohypothalamic pathway is the key projection for synchrony of the activity rhythm with environmental illumination. It was also found that LGN lesions severely impaired the subjects' ability to learn a brightness discrimination.


Sensitivity of the rat gustatory system to the rate of stimulus onset. Responses of the rat chorda tympani nerve were obtained to stimulation of the tongue with both linearly rising anodal current of varying intensity and rate of rise and NaCl presented at different concentrations and rates of flow. The amplitude of the transient portion of the integrated chorda tympani response was a power function of the rate of current rise. The duration of the transient response paralleled the rising phase of the current and the neural response fell to a tonic level proportional to current intensity when the rising current reached its plateau. Anodal currents of different final intensities but presented at the same rate of rise produced transient responses of the same amplitude. Responses of single chorda tympani fibers exhibited the same phasic and tonic components that were characteristic of the whole nerve. When NaCl was presented to the tongue at different rates of flow, the chorda tympani response reflected a sensitivity to stimulus onset rate paralleling that shown to linearly rising current.


Role of cortex in Pavlovian discrimination learning. Two totally neodecorticate rabbits and two groups of normal rabbits were trained on a light-tone differentiation using a Pavlovian nictitating membrane response. The significance of the two stimuli involved in the differentiation was then reversed. Excellent initial differentiations were produced by both decorticates and normals, although there was some evidence of a small retardation of conditional response acquisition in the decorticates in this first stage of the experiment. Under reversal conditions the decorticates extinguished responding to the formerly positive conditional stimulus in fewer trials and produced more complete differentiation performances than normal animals. The decorticates, unlike the normal animals, failed to show a reduction in conditional response onset latencies during either differentiation or reversal training.


Effects of lateral hypothalamic lesions on consummatory behavior in developing rats. Bilateral lesions aimed at the lateral hypothalami of preweanling rats result in decreased weight gain and eventual death within 5 days after the operation. Ten-day-old rats with unilateral damage to the lateral hypothalamus show retarded growth, food and water intake regulatory deficits, and altered sensitivity to quinine adulteration of the water for up to 60 days of age. These results suggest that at least one neural mechanism that regulates food and water intake matures early in the postnatal life of the rat.


Analysis of feeding patterns in normal and vagotomized rabbits. Spontaneous meal sizes, intermeal intervals, and 24 hr feeding rhythms were monitored in normal and 60 day recovered vagotomized rabbits fed solid laboratory chow. Mean sizes of meals and intermeal intervals, and the circadian distribution of food intake did not differ between the two groups, but vagotomy was associated with increased frequencies of both smaller and larger than average meals. Positive meal to postmeal interval correlations were evident in intact but not vagotomized animals, whereas vagotomized animals displayed a meal to premeal interval correlation in the light phase that was not present in normal rabbits.


Development of olfactory-guided behavior in the golden hamster. Hamster pups were tested for an odor preference every day from 1-16 days of age with shavings from their home cage and with clean wood shavings. The hamster pups showed a clear preference for their home cage shavings by 8 days of age. They were then tested for preferences with other odor combinations. Tests for preference with other odor pairs indicate that this preference is due to a change in the hamsters rather than a change in the stimulus. In these tests the hamster pups did not demonstrate a preference for their home shavings over shavings in which a nonlactating female had lived. Further tests will have to be done to determine how specific the hamster pup's olfactory preferences are.


Water intoxication death following hypothalamic lesions in the rat. Rats received large, bilateral lesions of the ventromedial hypothalamus. Water or saline intakes, urine outputs and body temperatures were observed for up to 24 hr after surgery. Fifty percent of the operated animals drank excessively and died within 4-6 hr when permitted access to water. Urine outputs were low and symptoms of water intoxication were evident. When allowed access to saline, outputs rose and the number of animals which survived increased as the saline concentration increased. Body temperatures approached 40 degrees C during drinking, but did not differ from operated animals which refused to drink. It was concluded that the deposition of metallic ions strongly stimulates a hypothalamic drinking system which results in overhydration and water intoxication death.


Hippocampal conditioned responses in the absence of entorhinal input. Hippocampal unit responses to conditioned stimuli were analyzed in intact rats and in rats deprived of the input from the entorhinal cortex to the hippocampus. Cells in normal rats responded more intensely to a conditioned stimulus when it was applied within 1 min from a previous one. The rats with lesions had smaller conditioned hippocampal responses and, in addition, there were no differences between responses to stimuli applied after short or long intertrial intervals. No effects on gross conditioned behavior were noticed.


[Changes of visual fields in intracranial tumors outside the cerebral hemispheres]. Based on neurosurgical material of 1,746 brain tumours, the changes of the visual field determined by isopteric perimetry are discussed with their significe with regard to tumours of corpus callosum, lateral ventricles, brain stem ganglia, IIIrd ventricle, region of the sella and adjacent areas as well as posterior fossa. The proportion of unilateral blindness with primary opticus atrophy and of skotomas is strinkingly high, so that in cases of loss of vision, not readily explicable by ophthalmology, as well as in unilateral defects of the visual field, intracranial processes must be thought of.


[Aphasia syndromes in brain tumors. Clinico-pathological correlations]. A clinica-psychological and pathoanatomical analysis of 40 observations with neoplasms of the brain in the left dominant hemisphere and 4 observations with neoplasms in the right subdominant hemisphere, has been carried out. In 36 cases, a desintegration in the language in a form of aphasia, has been established, while in 4 cases this was not present. In 22 observations the established neuro-psychological syndrome completely indicated and coincided with the localization of the neoplasm in the corresponding part or parts of the brain, in 10 it only partialy coincided, while in 4 cases it did not coincide with the localization of the neoplasm in the brain. The established neuro-psychological syndrome in observations with neoplasms in the right subdominant hemisphere possesses only a tentative topico-diagnostical significance. In conclusion the authors consider that the established syndromes of aphasia in patients with neoplasms of the brain may be of a considerable significance and help in substantiating a precise topical diagnosis.


[Frequency pattern of alpha waves in the early stages of cerebrovascular circulation disorders]. In this study 201 EEG curves are interpreted belonging to patients suffering from incipient disturbances of the cerebral circulation. The patients were divided into 3 groups according to age (group I, 30-40 years; group II, 40-50 years; group III, 50 years and over). In group I there prevailed a rate of 11-12 alpha waves per sec., and a slower rate was hardly ever found; in group III the frequency pattern was quite different. This decreased frequency of the waves could be confirmed by statistics. We believe a direct link can be assumed to exist between a decrease in frequency and the beginning of disturbed cerebral circulation.


[Sjögren-Larsson syndrome].

[Sjögren-Larsson syndrome]. The observations made on a 27-year-old patient with ichthyosis, debility, psychoinfantilism, and Little's syndrome are reported. Clinically, the condition of the skin is similar to that associated with ichthyosis vulgaris. Histologically, however, the picture is largely that of ichthyosis congenita, the condition being even more pronounced than that of ichthyosis congenita mitis. This particular case may be placed within the class of transitional forms of hereditary ichthyoses, and it may thus be proved that the Sjögren-Larsson syndrome also has its 'formes de passage'. In the etiological determination of oligophrenias and infantile cerebral motor disorders it is always necessary to give attention to the probable presence of ichthyosiform conditions of the skin.


[Clinical experience with Leponex].

[Clinical experience with Leponex]. Until now the "neuroleptic threshold" (Haase) was considered to be the efficiency criterion of the antipsychotic effect of a neuroleptic substance and it was thought therefore that the extrapyramidal symptoms were a necessary although undesired side effect. The benodiazepine derivative Leponex developed by Sandox - Basel upsets this view because it has an excellent antipsychotic effect without creating definite extrapyramidal symptoms. It is noted for its quick soporfic effect after only a few minutes, for subdueing psychopathological productivity in a very impressive way, for acting rapidly on the "plus"-symptomatology typical of psychosis, as early as in the first days of treatment, and for its equally visible effect on the "minus"-symptoms, typical of psychosis, in the last third of an average period of treatment lasting 40 days. The clinic using Leponex (Dresden, Halle, Brandenburg-Görden) belonged to the clinical application programme of the Sandox - Basel firm. The article gives a summary of essential results and particulars about the treatment. A detailed evaluation of the case sheets which are at present being statistically reviewed will be given in the next paper.


The stimulus properties of morphine and ethanol. The present investigation sought (a) to establish the efficacy of morphine and ethanol as discriminative stimuli when each is paired with the administration of saline and (b) to compare, in a qualitative sense, the stimulus properties of the two drugs. Additional experiments examined the effects of treatment with naloxone or l-propranolol upon morphine and ethanol-mediated discriminated responding. Finally, the stereospecificity of the stimuli produced by morphine was determined by a comparison, in morphine-trained rats, of levorphanol and dextrorphan. Discriminated responding developed rapidly in both the morphine and ethanol groups. In tests in which ethanol was administered to morphine-trained animals and vice versa, no similarity to stimulus properties was apparent. Antagonism of discriminated responding induced by morphine and ethanol was attempted using naloxone and l-propranolol. Naloxone blocked the actions of morphine but was without effect upon ethanol. No evidence of antagonism of either drug by propranolol was found. When a range of doses of levorphanol (0.1-3 mg/kg) and dextrorphan (3-100 mg/kg) was tested in morphine trained animals, only levorphanol was able to substitute for morphine. The present results suggest that the stimulus properties of morphine represent typical opiate effects.


A comparison of the discriminative stimulus properties of R-2,5-dimethoxy-4-methylamphetamine (R-DOM) and S-amphetamine in the rat. The effects of 0.75 mg/kg of R-DOM and 1.0 mg/kg of S-amphetamine served as discriminative stimuli in the control of a two-lever discrimination response. Dose-response evaluation of the two agents indicated that in S-amphetamine-trained animals the drug effects produced by test doses of 0.5 to 2.2 mg/kg of S-amphetamine could be considered as a dose-dependent continuum of low to high stimulus intensity. In R-DOM trained subjects, low to moderate doses of R-DOM (0.5-1.5 mg/kg) produced dose-related discriminative responding, but the high dose of R-DOM (2.2 mg/kg) resulted in random responding. When animals trained to discriminate 1.0 mg/kg of S-amphetamine from saline were given 0.5 or 0.75 mg/kg of R-DOM, they tended to respond on the drug correct lever. However, higher doses of R-DOM (1.5 and 2.2 mg/kg) produced random responding. Similarly, animals trained to discriminate 0.75 mg/kg of R-DOM from saline exhibited correct responses following 0.5 and 0.75 mg/kg of S-amphetamine, but not after 1.5 and 2.2 mg/kg. These data suggest that low doses of R-DOM produce discriminative stimuli that are qualitatively different from those of higher doses. Stimuli following low doses of R-DOM also appear similar in some respects to those following low doses of S-amphetamine.


Behavioral and neuropharmacological analysis of amphetamine and 2,5-dimethoxy-4-methylamphetamine in rats. A comparison of the behavioral pharmacology of DOM and amphetamine in rats indicated that lower doses (0.10-1.0 mg/kg) of the two agents had similar effects on schedule-controlled food-reinforced and shock-avoidance behavior. Similarities were also noted in their effects on horizontally directed motor activity when testing was preceeded by a period of acclimation. However, most doses of DOM tended to decrease unacclimated motor activity, while amphetamine increased this behavior. Neuropharmacological antagonism studies indicated that brain catecholamines (CA) and serotonin (5-HT) are involved in the behavioral effects of both DOM and amphetamine. Cinanserin, a 5-HT receptor blocker, attenuated the behavioral disruptive effects of both agents on food-reinforced responding. Cinanserin attenuated the effects of all doses of DOM and those of higher doses of amphetamine on shock avoidance. When given prior to lower doses of amphetamine, there was a greater behavioral stimulation than when amphetamine was given alone. Prior depletion of brain CA with alpha-methyltyrosine (alpha-MT) did not affect DOM induced disruption of food-reinforced responding, while alpha-MT attenuated the behavioral effects of all doses of DOM and amphetamine on shock avoidance. These data suggest that DOM and amphetamine share a similar component in their mechanism of action which depends on the availability of a releasable pool of brain CA.


Effects of diazepam and scopolamine on storage, retrieval and organizational processes in memory. The effects of intramuscular injections of diazepam (0.3 mg/kg) and scopolamine (8 mug/kg) on memory processes and subjective moods were studied in 36 volunteers. Subjects (Ss) were tested in groups of four in a double blind procedure with treatments distributed according to a Latin square design. Lists of words were presented to Ss who were then tested with an immediate free recall test prior to drug administration. Following injection delayed free recall and recognition tests were given. Subsequently two sets of lists were presented separately and tested in the same fashion. Two of the lists in the last set were composed of words falling into distinct categories. Memory was additionally analyzed by testing immediate recall of digit sequences and employing a visual recognition test. Subjective moods were evaluated with a rating questionnaire. Both diazepam and scopolamine impaired memory functions although the action of the latter drug was more pronounced and prolonged. The deficit appeared to be in the storage process leaving retrieval processes unaffected. Scopolamine in addition interfered with organizational processes. Subjectively, scopolamine also produced a larger sedative effect than diazepam.


The role of orosensory stimuli from ethanol and blood-alcohol levels in producing conditioned taste aversion in the rat. A taste-aversion paradigm was used to demonstrate that aversive consequences accompany the rapid oral ingestion of 5% (v/v) ethanol solutions. The learned taste aversion resulted from five 10-min self-administrations of alcohol mixed with an originally preferred flavor at a dosage of 1.69 g alcohol/kg body weight/day. In contrast, when the consumption of the alcohol solution was distributed throughout the day, a conditioned aversion was not obtained. This outcome was observed even though the distributed drinking animals were exposed to more orosensory stimuli and ingested more g/kg than the 10-min animals. The observation that those animals that drank their daily fluid in 10 min demonstrated higher peak blood-alcohol levels than the distributed animals supports the conclusion that a centrally mediated aversive state of inebriation must be present to produce a conditioned aversion.


Clinical studies with dopamine-receptor stimulants. Oral administration of ET-495 was found to cause worsening of psychiatric status in 4 out of 7 schizophrenic patients, and to induce a paranoid state and a syndrome of auditory hallucinosis in 2 non-schizophrenics. These observations were compatible with the hypothesized role of dopamine in schizophrenia. However, these psychotogenic effects were far less dramatic than those noted in other studies with amphetamine, methylphenidate or L-Dopa. Possible explanations for this differing psychotogenic potency of receptor stimulators versus presynaptic agonists are presented. Intravenous ET-495 and apomorphine did not show psychotogenic effects.


Dose-response effects of scopolamine on activity in an open field. The frequency of the responses, i.e., squares entered (ambulation), rearing and grooming, were recorded over 30 min for saline, and 0.25, 1.0, 2.0 and 4.0 mg/kg scopolamine treated groups. Scopolamine produced an inverted U dose-response curve for ambulation, an increase in rearing but no effect on grooming. All three responses decreased over time; scopolamine did not attenuate this rate of habituation. There did appear a dose-related time effect. It was concluded that scopolamine may have different effects on various responses recorded simultaneously over a range of doses. The results when compared to other experiments emphasized the importance of environmental factors in determining drug effects on behaviour.


Clinical laboratory test standards for a sample of schizophrenics. The normal ranges for 15 clinical laboratory tests for a pooled sample of 325 schizophrenics, largely chronic and hospitalized, are presented. Laboratory data came from pretreatment blood samples of subjects who were all participants in clinical psychotropic drug trials conducted through the Early Clinical Drug Evaluation Unit (ECDEU) Program of the National Institute of Mental Health. Both parametric means and ranges (mean +/- 2 standard deviations) and non-parametric medians and percentile ranges (2.5 and 97.5 percentiles) are reported. The results generally confirm the finding of increased variability in schizophrenic laboratory test data noted in the past. This, and implications of the method are discussed.


Treatment of Sydenham's chorea with a combination of L-dopa and a peripheral dopa decarboxylase inhibitor. Two male patients suffering from Sydenham's chorea were treated with a combination of L-Dopa and a peripheral decarboxylase inhibitor. This treatment markedly reduced in one patient and totally suppressed in the other the abnormal involuntary movements present in this disease.


[Accessory hepatic arteries and their nomenclatoric problems in radiology (author's transl)]. The numerous anatomical and radiological nomenclatures of hepatic arteries are compared and discussed. Our own material for the assessment of accessory hepatic arteries consisted of 220 anatomically prepared individuals and 74 angiograms. The individual branches in the normal case as well as all variations and their frequency are discussed. The present, often confusing nomenclature is critically reviewed and an attempt is made to establish a simple and clinically acceptable nomenclature. We propose to name the additional branches supplying the liver as 'arteria hepatica accessoria' with reference to the vessel from which they originate. Additional branches in the terminal branching (ramus accessorius) and vessels of the liver capsula should not be referred to as accessory hepatic arteries.


[Bone szintigram of osteopoikilosis familiaris (author's transl)]. Szintigraphic examination of two members of an Osteopoikilosis familiaris family demonstrates that the focus of the disease does not display any significant differences in metabolic behavior from that of other bone segments.


[Renal cancer today - suspicion, diagnosis or therapy? (author's transl)]. The present-day situation of recording and diagnosis of malignant renal tumours was investigated on 50 patients recently seen by us. It was found that the complex radiological diagnosis (composed of excretion urography, isotope nephrography, renoscintigraphy, renovasography and additional investigations) is very well suited to show renal cancer in all stages taking into consideration localisation, extent and relations to surrounding tissue. As ever, the difficulty for a clarifying diagnosis still lies in seeing the patient as early as possible. This is due to the almost exclusively uncharacteristic symptoms which, additionally, very frequently coincide with symptoms of other diseases. The only chief symptom is clearly 'painless haematuria'. Relatively large renal tumours also escape palpation. The possibility of tracing haematurias during screening tests with 'Reagnost haemoglobin' tablets is discussed.


Lesions of the trochlea tali. Osteochondral fractures and osteochondritis dissecans of the trochlea tali. Osteochondral fracture of the trochlea tali, which can result in osteochondritis dissecans of this trochlea, is often not recognized as such and therefore not adequately treated. The nonrecognition is mainly due to the fact that the fracture can either remain asymptomatic or produce symptoms of inversion-distortion; to a lesser degree it is also due to the fact that the lesion is not identified in the radiograph. In view of these facts it would seem necessary in all cases of distorsion to make an X-ray examination of the ankle, ascertaining that the trochlea tali is adequately visualized. Unless the symptoms abate within a week, radiological examination should be repeated. The same applies to patients whose initial recovery is followed by a relapse of symptoms. Surgical treatment of choice for osteochondral fractures. The symptomatology and therapeutic results in 46 osteochondral fractures studied were in agreement with data from the literature. Therapeutic results can be improved by earlier diagnosis and more adequate treatment of the condition.


Selective renal venography in the evaluation of a non-functioning hydronephrotic kidney. A case is presented in which extreme hydronephrosis simulated absence of the right kidney. The hydronephrosis occurred as a result of surgical ligation of the right ureter 10 years previously. There was no visualization of the excretory system by intravenous urography or retrograde pyelography. Abdominal aortography did not show the renal artery. Selective renal venography revealed a patent venous bed with splaying and thinning of the intrarenal veins. The contribution of renal venography is discussed in clarifying cases in which the kidney and the renal artery were not visualized.


Radiological features of pulmonary venous hypertension in pulmonary emphysema. In pulmonary emphysema, the normal features of pulmonary venous hypertension are often disturbed due to destruction of pulmonary tissue. The abnormal features are described.


Thermography in diagnosing deep venous thrombosis of the lower limb. Phlebography and thermography of the lower limbs were performed on 58 patients suspected on the basis of clinical examination to have deep venous thrombosis of the lower limb. Both thermography and phlebography were consistently positive in 34 and negative in 17 cases. The skin temperature was lowered in four cases evidently because of an arterial spasm caused by deep venous thrombosis. No significant temperature elevation was established in three anamnestically and phlebographically older cases.


Appendiceal abscess. A challenge in abdominal masses in children. In children, more frequently than in adults, appendicitis is complicated by abscess formation. Facing an abdominal mass, especially if it is in the lower abdomen, the radiologist should consider tumor formation, teratoma, malformation or abscess. If there is air within the mass, the diagnosis of abscess is likely; if there is a stercolith, the diagnosis of perforated appendicitis has to be made.


Clear-cell carcinoma of the kidney. Treatment with a precise technique using cobalt-60. The treatment of the postoperative tumor bed after removal of clear-cell carcinoma (hypernephroma) constitutes a challenge to radiation therapy. Precise planning will deliver adequate dosage to the kidney bed and para-aortic lymph nodes while avoiding excessive dosage to the spinal cord and contralateral kidney.


Carcinoma of the vulva.

Carcinoma of the vulva. The results of treatment of carcinoma of the vulva in patients referred to the Rotterdamsch Radio-Therapeutisch Instituut in the years 1965-1969 are reported. Electron beam therapy seems not to be the method of choice; surgery is to be preferred. Radiation therapy requires high doses (greater than or equal to 6 krad) and is frequently followed by severe induration with recurrent ulcerations.


Results of radioiodine (131/125I) therapy of hyperthyroidism. One individually calculated dose of 131I was sufficient to control the hyperfunction in 75% of the patients with Graves' disease and 85% of the patients with autonomous adenoma. The cumulative myxedema risk 10 years after therapy was: 15% in the patients with Graves' disease and nearly zero in patients with autonomous adenoma. Early results of 125I therapy of Graves' disease are presented. Peculiar aspects of thyroid function after destructive therapy of Graves' disease are discussed.


Simultaneous estimation of tubular and glomerular renal clearance with separate estimation of each side using a self-constructed whole-body measuring set. A measuring device for simultaneous determination of glomerular and tubular clearance with separation of both sides is described. The patient lies on a table. Two detectors mounted on the ceiling count the residual radioactivity in the body except in the kidneys which are shielded by a lead block. Two other detectors count the renal radioactivity. The total renal clearance is calculated by the whole-body clearance curve and plasma activity. The fraction cleared by each side is calculated by the renal activity time curve. Radiopharmaceuticals were: 99Tcm-EDTA and 131I-hippuran. Values for normal patients are given.


[Value of temperature profiles of injured legs (author's transl)]. In thermographic control studies of temperature profiles legs of 93 patients with a sprained ankle temperature phenomenon was observed, which super-imposes the hyperthermia due to inactivity. This complicates correct interpretation.


[Possibilities to evaluate hematogenous osteomyelitis of the extremities by thermography (author's transl)]. Single thermographic measurements and follow up studies in hematogenous osteomyelitis demonstrate that thermography can be used--under certain restrictions--as a supplementary diagnostic procedure to evaluate the activity of inflammatory bone disease.


[Angiographic differential diagnosis of hydronephrosis (author's transl)]. The diagnosis of hydronephrosis is made by excretory urography with late films and retrograde pyelography. Renal arteriography in hydronephrosis permits exact evaluation of vascular supply and parenchymal thickness. In three cases selective arteriography was performed because of a non-functioning kidney or suspected space-occupying lesion. The combination of arteriogram and urogram--if necessary together with percutaneous puncture--allows to differentiate between hydronephrosis, avascular tumors, renal cysts, polycystic renal disease, renal abscess, subcapsular renal hematoma, fibrolipomatosis, xanthogranulomatous pyelonephritis, and tuberculosis.


Dynamic aspects of colonic Crohn's disease. Changing patterns of the lesions in colonic Crohn's disease were studied in 86 patients who underwent multiple consequetive roentgen examinations. Local progression of lesions was seen in 56 out of 86 patients; rapid local advancement from mild to severe lesions was not uncommon. Temporary regression of lesions was only seen in 7%; definitive permanent healing on conservative treatment was not observed. Preoperative extension of lesions was seen in 29%, with ultimate involvement of the rectum in 7% and development of anal fistulae in 17%. Clinical implications of the findings are briefly discussed.


The use of the 99mTc-pertechnetate neck/thigh ratio as a test of thyroid function. A total of 100 patients were studied by standard thyroid function tests and the 99mTc-pertechnetate neck/thigh ratio was determined. This ratio or "trapping index" correlated closely with 131I uptake. The 99mTc test should be followed by scanning at 20 minutes to distinguish diffuse from localized thyroid disease. TSH stimulation and suppression studies can be done. It is recommended that this ratio be used in place of the standard 24-hour RAIU study, as it gives the same information at a saving in time, money, and radiation exposure.


Impaired ventilation in a patient with angiographically demonstrated pulmonary emboli. Matched regional ventilation/perfusion studies (V/Q) have traditionally been associated with ventilatory diseases, while mismatched V/Q studies have been associated more often with vascular abnormalities. The authors describe a patient with multiple pulmonary emboli who demonstrated matched ventilation and perfusion studies five hours after the onset of symptoms.


Choledochal cysts: roentgenographic techniques. Twenty-four cases of choledochal cysts were reviewed. Only 7 cases were definitely diagnosed preoperatively: 3 by 131I rose bengal scanning, 2 by intravenous cholangiography, 1 by oral cholecystography, and 1 by 99mTc sulfur colloid scanning followed by angiography. The highest percentage of definitive positive examinations was found in the 131I rose bengal scan (3 of 4), but the study most helpful in suggesting the diagnosis in a general way was the upper gastrointestinal series. The more frequent use of 131I rose bengal scanning and ultrasound should increase diagnostic accuracy.


Early neonatal pneumoperitoneum from progressive massive tension pneumomediastinum. Three cases of early neonatal pneumoperitoneum as a result of progressive massive tension pneumomediastinum are described. The important roentgenographic features include massive pneumomediastinum located both above and behind the heart, absence of free peritoneal fluid, pneumothorax, and air in the stomach. Laparotomy should be avoided in this condition.


B-scan ultrasound evaluation of the pancreas. Advantages and accuracy compared to other diagnostic techniques. Over 200 patients were examined by B-scan ultrasound for suspected pancreatic disease; in 94 cases a final diagnosis was proved. The diagnostic accuracy of ultrasound, upper gastrointestinal examination, isotope pancreatography, and arteriography is compared. The diagnostic ultrasound features of the various pancreatic disease processes are described. Pancreatic sonography provides the most accurate and least expensive method for evaluating the pancreas with no known patient morbidity. The upper gastrointestinal series and radionuclide study are complementary to sonography. Ultrasound should be the initial examination for the evaluation of patients with suspected pancreatic disease or epigastric mass.


Ultrasonic evaluation of pleural opacities. Forty-one patients with substantial pleural opacities on chest films were examined by A-mode and B-mode ultrasound. Ultrasonic examination provides an accurate means of differentiating pleural fluid from other conditions which produce such opacities and is superior to the chest films as a means of localizing fluid. With the gain setting used in this series, fluid collections less than 1 cm thick were missed and were probably obscured by reverberation from the ribs. M-mode scanning provides a simple and accurate means of localizing the diaphragm in nearly all patients, almost completely eliminating difficulties caused by subdiaphragmatic placement of the thoracocentesis needle.


Echographic evaluation of diaphragmatic motion in intra-abdominal diseases. Movement of the diaphragm can be evaluated with diagnostic ultrasound using B- and M-mode techniques. Ultrasonic scanning is a highly sensitive method of demonstrating generalized or localized abnormalities of diaphragmatic motion and is superior to fluoroscopy in several respects. There is no exposure to ionizing radiations, and a permanent record of the excursion of the diaphragmatic surface is obtained. This method has the additional advantage of providing a two-dimensional display of the upper abdominal quadrant, which may reveal the nature of the underlying disease process.


The late consequences of successful cancer treatment given children and adolescents. In managing malignant disease in children, one must keep in mind the unfavorable consequences that may be produced by chemotherapy and radiation therapy and which may require months or years to become manifest.


Possible genetic consequences of irradiation of tumors in childhood. Dysgenic and radiation-induced types of genetic risks are evaluated for the progeny of persons who received childhood tumor therapy. The dysgenic risks may be quite high for certain types of tumors. The genetic defects of greatest concern following paternal irradiation are likely to be those caused by dominant mutations and unbalanced translocations, whereas chromosomal trisomies may be most important following maternal irradiation. Ways of alleviating these risks are discussed.


Non-oncogenic sequelae of cancer chemotherapy. The delayed effects of anticancer drugs and late complications in 334 long-term survivors of childhood cancer were reviewed. Sequelae associated with chemotherapy were uncommon. Two men in the series exhibited disorders in reproductive function, possibly due to chlorambucil. A third male patient had cyclophosphamide-induced hematuria which persisted for two years after cessation of therapy. Other abnormalities were renal, hepatic, skeletal and cardiopulmonary, ascribed chiefly to radiotherapy, although the deleterious effect of drugs on irradiated organs cannot be excluded. The data indicate that the skillful and judicious application of chemotherapeutic agents produces a minimum of delayed consequences.


Uterine sarcoma.

Uterine sarcoma. Thirty-four cases of uterine sarcoma were studied with regard to their pathologic characteristics and response to treatment. Pathologic features did not always correlate with subsequent course. Combined therapy seems to enhance two-year survival in endometrial stromal sarcoma (ESS), although some patients may have low-grade tumors and hence represent a more favorable group. Adjuvant irradiation may improve local control rates in some mixed mesodermal sarcomas (MMS), but does not add appreciably to survival. It is of doubtful benefit in the leiomyosarcoma (LMS) group. When irradiation is employed, preoperative therapy is preferred except in the highly malignant mixed mesodermal sarcomas where prompt surgery seems indicated first. Supplemental brachytherapy may also be employed.


Exploitation of kinetic differences between normal and malignant cells. Some of the differences in the proliferative kinetics of normal and malignant tissues may be used to increase radiation damage to tumor cells. Of these various possibilities, some are still at a theoretical stage (mainly because there are no means of obtaining the needed data) but others, notably those involving a combination of cycle-linked chemotherapeutic and/or radiosensitizing drugs with radiation, may be exploitable now with the expectation of clinical benefit.


Cell cycle redistribution as a factor in multifraction irradiation. In the redistribution of cells through the division cycle between dose fractions, the sensitizing effect is greatest when small doses per fraction are used. Since nonproliferating tissues limit the dose in radiotherapy and will not be sensitized by redistribution, the more the dose is fractionated and the lower the dose per fraction, the better. However, regenerative response in the tumor could limit its radiocurability if overall treatment time were protracted. This could be circumvented if two or more fractions were given daily, allowing time for redistribution; the probability of irradiating cycling cells in sensitive phases would then be increased.


Radiotherapy and chemotherapy: some parallels and differences. The effects of exposure to ionizing radiations and to various chemotherapeutic agents on the survival of mammalian cells are compared. The relative importance of the cells' sensitivity, age response, proliferative state, and degree of oxygenation and the contributions of kinetic and repair phenomena are examined. Cell killing by high-LET radiations is influenced least by cellular or kinetic factors; thus tumors should show a relatively homogeneous response to this modality, while time-dose relationships should be of least importance. The effectiveness of antimetabolite therapy depends critically on the choice of the correct agents and on tailoring drug administration to the kinetics of both normal and malignant tissue.


Cell population kinetics in radiation therapy: relationship of cellular surviving fraction to RBE and OER. A two-component multitarget model of cellular radiation lethality was used to predict the effects of changing LET and oxygenation. It was assumed that with high-LET radiations there is a greater probability of direct and irreparable events and that hypoxia reduces the number of chemically-mediated indirect and reversible events. Cellular surviving fractions, relative biological effectiveness, and oxygen enhancement ratios were computed on this basis and compared with published experimental data. The model and program were then used to generate isoeffect curves for photons and neutrons, oxygenated and anoxic states, and various specific tissues and tumors.


Cell kinetics, models, and cancer treatment--some principles for the radiation oncologist. The radiation oncologist must attempt to apply the developments in the laboratory to the clinical situation in a manner that will result in a therapeutic gain. The possible influences of radiation fractionation and protraction, cell renewal and recruitment of normal or tumor tissues, differences in acute and late radiation effects and possible chemotherapy-radiation interactions are all factors that can affect the ultimate result. In order to develop a therapeutic gain, the effect on the tumor must be greater than on the normal tissues.


The prevention of Ehrlich ascites tumor using intraperitoneal colloidal 198Au. Dose vs. size of inoculum. Previous work has shown that radioactive colloids can cure Ehrlich ascites tumor. In this experiment, the dose of colloidal 198Au needed has been correlated with the number of tumor cells inoculated. On Day 1, varying numbers of Ehrlich cells (10(2), 10(3), 10(4), 10(5), 10(6)) were injected intraperitoneally into 310 BALB/c male mice. Two hours later, varying doses (10, 20, 40, 80, and 160 muCi) of 198Au were injected intraperitoneally. Controls were injected with normal saline. Generally, the lower cell inoculums and higher doses of 198Au yielded better survival rates.


Instant selective arterial occlusion with isobutyl 2-cyanoacrylate. Isobutyl 2-cyanoacrylate (IBC) delivered selectively in small doses produced immediate occlusion of the injected arteries in dogs without significant undesired sequelae. In one patient, pelvic hemorrhage was promptly stopped by a similar technique. In another patient, who was on chronic renal dialysis and judged too ill for nephrectomy, IBC occluded both renal arteries and terminated a life-threatening renal protein loss.


Multiple gastric ulcers: a radiographic sign of benignity? Twenty-nine cases of multiple synchronous gastric ulcers are reviewed. Twenty-three were benign and 6 were malignant. Seven illustrative cases are presented. Multiplicity of gastric ulcers is not a reliable sign of benignity and may complicate rather than clarify diagnostic evaluation.


Controversy, alternatives, and decisions in complying with the legal doctrine of informed consent. The complexities involved in conforming with the legal doctrine of informed consent at present are seemingly limitless. This communication is designed to acquaint the physician attempting to comply with this legal doctrine with an experience gained during the last four years. The major points are aimed at the most frequently asked questions and decisions involved in its implementation. An alternative approach to the question of how and whom to inform is provided, which may make the task easier for those seeking to inform their patients.


Peliosis hepatitis.

Peliosis hepatitis. The angiographic findings in a patient with peliosis hepatitis are described. Histologically, multiple blood-filled cystic spaces are seen, often communicating with the hepatic sinusoids. There is evidence that steroid therapy may be a causative factor. The differential diagnosis is discussed.


Radiographic evaluation of patients with schistosomiasis. Plain films of the abdomen in advanced states of schistosomiasis reveal massive splenomegaly without evidence of splenic calcification. The liver may be enlarged in the early stages but ultimately decreases and becomes small. Ascites is evident in far advanced disease. Chest films are negative in the early stages, but in advanced disease, dilated pulmonary arteries, right ventricular enlargement, and dilatation of the azygous vein may be recognized. Granulomata are seen as multiple small rounded densities scattered throughout both lung fields. The routine barium swallow will reveal unsuspected esophageal varices. Nine patients were studied preoperatively by panhepatic angiography and 14 post-operatively following splenorenal shunt. Thrombosis of the shunt and hepatic encephalopathy were common postoperative complications.


Roentgenographic manifestations of methadone-induced pulmonary edema. Twenty cases of methadone-induced pulmonary edema confirmed by clinical, laboratory and roentgenographic findings were extensively reviewed and the roentgenographic manifestations defined in terms of patterns, distribution, and duration of the process. Drug tolerance is a major factor in determining the severity of toxicity. Roentgenographic clearing in 48 hours or less, clinical improvement and pathogen-free sputum aspirates serve to differentiate edema from pneumonia.


Coronary vascular patterns during occlusion arteriography. The arteriograms from 18 studies in which the catheter accidentally occluded the right coronary artery were analyzed and compared with successful studies in 25 patients with normal coronary arteries and 20 patients with coronary artery stenosis. The occlusion arteriograms showed distinct early filling of the anterior cardiac veins and occasionally retrograde filling of the left circumflex artery. Although there were no serious complications due to occlusion arteriography in our patients, the potential for producing ventricular tachycardia, ventricular fibrillation or cardiac arrest must be borne in mind. Angiographers should be aware of these filling patterns in order to recognize them as artifacts of the technique and not as manifestations of disease.


Lymphangiographic findings in histoplasmosis. The lymphangiographic findings of histoplasmosis in an 11-year-old girl are presented and correlated with the histopathology of a mediastinal lymph node. Nonconfluent lymphadenographic defects with discrete margins measuring 2-4 mm in diameter were seen, corresponding to the microscopic demonstration of nodal granulomas of the same size. This is quite different from the lymphadenographic pattern usually present in lymphoma but might be seen in certain stages of other granulomatosis diseases.


Early-onset gouty arthritis.

Early-onset gouty arthritis. Five cases of early-onset gouty arthritis are presented, with roentgenographic abnormalities evident in the first two decades of life. Three patients suffered from "primary" gout; classification of the other two patients was difficlut because of associated mental retardation, hypothyroidism and psoriasis. Radiographic alterations included soft-tissue masses and calcification, with typical erosive abnormalities and predilection for the hands and feet. The sacroiliac joints were abnormal in two patients.


A positron-emission transaxial tomograph for nuclear imaging (PETT). An apparatus was developed for obtaining emission transaxial images of sections of organs containing positron-emitting radiopharmaceuticals. The detection system is a hexagonal array of 24 NaI(T1) detectors connected to coincidence circuits to achieve the "electronic" collimation of annihilation photons. The image is formed by a computer-applied algorithm which provides quantitative reconstruction of the distribution of activity. Computer simulations, phantom and animal studies show that this approach is capable of providing images of better contrast and resolution than are obtained with scintillation cameras. Advantages of positron vs. single photon reconstruction tomography are discussed.


Effects of indomethacin and prostaglandin F2alpha on parturition in the hamster. In the hamster administration of indomethacin twice a day on days 14 to 16 of pregnancy delayed the onset of parturition; a delay of 5 and 8 hours was observed following treatments of 300 or 600 mug/injection of indomethacin, respectively. Injection of PGF2alpha to the indomethacin treated hamsters on day 15 of pregnancy, on the other hand, advanced the onset of parturition. Treatments of indomethacin and/or PGF2alpha did not affect the duration of parturition.


Induction of term labor with intravenous prostaglandin F2alpha (a comparison of two dosage schedules). The efficacy of intravenous Prostaglandin F2alpha (PGF2alpha) infusion for induction of labor in two different dosage schedules was studied in 90 women between 36 and 43 weeks of gestation. The rate of PGF2alpha infusion was increased at four-hour intervals in 36 women in the low dosage group and every hour in 54 women in the high dosage group, never exceeding an infusion rate of 20 mug/min. in either group. Labor was successfully induced in approximately 90% of the patients in each group. There was no statistically significant difference in the mean induction-delivery interval between the two groups at the 5 percent level. Intravenous PGF2alpha was found to be effective and safe for both mother and infant in the dosage schedules used in this study for induction of labor.


Serial intramuscular injections of 15(S)-15-methyl-prostaglandin F2alpha in the induction of abortion. Abortion was successfully induced in 62 of 68 patients in the 9th to the 26th week of pregnancy be serial intramuscular administration of 15(S)-15-methyl-prostaglandin F2alpha (15-ME-PGF2alpha). In 6 patients who failed to abort after 24 hours of prostaglandin administration, a concomitant infusion of oxytocin was initiated; 5 of these patients aborted within 12 hours of the combined therapy. A single patient failed to abort, even with the combined therapy, and underwent surgical evacuation. The mean abortion time in the 67 successful inductions was 14.56 hours. Parous patients aborted somewhat fasteter, mean 13.98 hours, as compared to nulliparous patients, mean 15.02 hours, but this difference was not statistically significant. In this study initial intramuscular injection of 100 mug 15-ME-PGF2alpha was followed in 1 hour by 250 mug and then 250 mug every 2 hours with concomitant oxytocin therapy initiated after 24 hours. The results with this dose schedule were compared to the results obtained in a previous study with a higher dose schedule, an initial dose of 100 mug 15-ME-PGF2alpha, followed in 1 hour by 250 mug then 500 mug every 2 hours. There was significant difference in the mean abortion time and the incidence of side effects between the 2 dose schedules. The mean abortion time for patients with gestational ages 16 weeks and less was the same with both dose schedules, however patients with gestational ages of 17 weeks and higher aborted somewhat faster with the higher dose schedule. It might therefore be advisable for patients with gestations of 17 weeks and higher to be treated with the higher dose schedule. In earlier gestations patients could be started on the  lower schedule, and if abortion had not occurred within 15 hours the dose of 15-ME-PGF2alpha could then be increased to 500 mug every 2 hours.


Induction of midtrimester abortion by serial intravaginal administration of 15(S)-15-methyl-prostaglandin F2alpha (THAM) suppositories. Midtrimester abortion was successfully induced in 13 of 22 patients by serial intravaginal administration of 15(S)-15-methyl-prostaglandin F2alpha (THAM) suppositories. Nine patients, 4 nulliparas and 5 multiparas, failed to abort after 24 hours of prostaglandin administration and a concomitant infusion of oxytocin was initiated. Seven of the nine patients aborted within 7 hours of the combined therapy and one patient on methadone maintainence aborted after 17.5 hours of combined therapy, 41.5 hours after the first dose of prostaglandin. A single patient failed to abort, despite the concomitant prostaglandin-oxytocin administration and underwent surgical evacuation. The mean abortion time for the 21 successful abortions was 22.56 hours. Nulliparous patients aborted somewhat faster, mean 21.79 hours, than multiparous patients, mean 23.80 hours, but this difference was not statistically significant. In this study, one patient aborted in less than 12 hours, and 62% of the successful cases aborted within 24 hours. The plasma levels of 15-ME-PGF2alpha were analyzed by radioimmunoassay in 10 patients. Plasma prostaglandin levels rose significantly 30 minutes after the insertion of the first suppository, but there was a wide variation in levels from patient to patient. It was observed that the 2 patients with the highest levels had the fastest abortion times and episodes of gastro-intestinal side effects appeared related to a rise in prostaglandin levels. Sixty-four percent of the patients in this study had no gastro-intestinal side effect related to prostaglandin administration.


Prostaglandin levels in endometrial jet wash specimens in patients with dysmenorrhea before and after indomethacin therapy. A patient with functional primary dysmenorrhea of over two years duration was subjected to the endometrial jet wash technique during the period of active menstrual flow. Prostaglandin F analysis of the jet washings revealed significantly elevated levels during menstruation over normal control levels. Following indomethacin therapy, jet wash prostaglandin F levels were dramatically reduced and the patient became asymptomatic. A cause and effect relationsship between prostaglandin F and dysmenorrhea is suggested by these studied.


Prostaglandin F levels in endometrial jet wash specimens during the normal human menstrual cycle. The Gravlee endometrial jet wash technique has been used to collect uterine fluid in normal human volunteers for Prostaglandin F analysis throughout the human menstrual cycle. Uterine washings so obtained demonstrated a cyclicity in prostaglandin F content with low concentrations found during the proliferative phase and a 3-4 fold rise occurring during the secretory phase. Menstrual fluid prostaglandin F content collected with the jet wash technique gave the highest total concentrations.


Anti-implantation effect of prostaglandins in the rat. PGF2alpha and PGE2 have been instilled in small amounts (5mug) into the uterine horns of pregnant rats at different intervals following mating. Unilateral as well as bilateral injections have been used. Three parameters have been taken into consideration at laparotomy performed on the 13th day of pregnancy: a) the number of implantation sites; b) the number of viable fetuses; and c) the number of corpora lutea present on the ovarian surface. Both PGs proved able to inhibit implantation, to affect the development of embryos and to exert some luteolytic activity when given between D-1 and D-6 of pregnancy.


Stimulation and inhibition of biosynthesis of prostaglandins in human skin by some hydroxyethylated rutosides. The effect of some hydroxyethylated rutosides on the biosynthesis of prostaglandins was studied in the microsomal fraction of human skin homogenates. Microsomes were incubated with mono-0-hydroxyethyl-7-rutoside (mono-7-HR), di-0-hydroxyethyl-7',4-rutoside (di-HR), tri-0-hydroxyethyl-7,3',4'-rutoside (tri-7,3',4'-HR), tetra-0-hydroxyethyl-5,7,3',4'-rutoside (tetra-HR) and a mixture of hydroxyethylated compounds (HR). Prostaglandins were determined by bioassay after organic solvent extraction and silicic acid chromatography of the incubates. Mono-7-HR, di-HR and HR stimulated the biosynthesis. In contrast, tri-7,3',4'-HR and tetra-HR inhibited the formation of prostaglandins. Previously effects have been reported on inflammatory reactions and aggregation of thrombocytes by these compounds. Some of these effects may be explained by changes in the biosynthesis of prostaglandins.


Changes in prostaglandin concentration in blood subjected to repetitive freezing and thawing. Successive freezing and thawing of whole blood results in a consistently higher yield of various prostaglandin (PG) compounds. Evaluations were made with radioimmunological assay. The increase in PG concentrations seems to be more associated with cell fragmentation and not with the dissociation of albumin-PG complex. Our data suggest that there may be some dissociation of non-albumin-PG complexes. Artifactually high PG concentrations due to in vitro PG synthetase activity appears minimal at least with respect to indomethacin blocking of this enzyme. There are, in general, only slight differences in PG concentrations in samples with and without indomethacin.


Effects of prostaglandins of the E-series on pulmonary and systemic circulations of newborn goats during normoxia and hypoxia. Effects of exogenous prostaglandins of the E-series on pulmonary and systemic circulations of newborn goats were investigated during normoxia and hypoxia. Pulmonary arterial infusion of prostaglandins E1 and E2 decreased pulmonary vascular resistance 20% and 14%, respectively, without systemic effects. Prostaglandin E1 abolished the pulmonary pressor response to hypoxia. Prostaglandin E2 was less effective in counteracting this hypoxic response. The increased pulmonary vascular resistance and augmented response to hypoxia following indomethacin administration was reversed by prostaglandin E1. Infusion of prostaglandin E1 directly into the pulmonary circulation may be of benefit to the distressed newborn with elevated pulmonary vascular resistance.


[Concepts and advantages of short tests in psychopathology]. The term 'short test' (Kurztest) can signify a number of diverse concepts. An attempt was made to arrange these concepts systematically. This may have practical significance, as short tests in psychopathology assume growing importance and the terminology for purposes of communication will become more differentiated and precise. Short tests need not be of lower quality than normal procedures. On the contrary, particularly in the area of psychopathology, short tests can have a higher validity and reliability.


[Group experiment to investigate judgement-convergence and the assessment of reality in schizophrenics presented with visual stimuli]. Eight acute schizophrenics were examined individually and in groups as to their congruence of judgement and as to their accuracy in estimations in response to various visual stimuli; they were compared in these respects with neurotics. The analysis of variance of the power of judgement showed: (a) there was no difference in the two groups of patients beyond what could be expected by chance alone, and (b) the congruence of judgement was the same in both groups. The analysis of variance of the accuracy in estimations showed that with increasing numbers of stimuli in the visual field the schizophrenics became less and less precise in their estimates. It was demonstrated under what conditions social-psychological findings can be applied to schizophrenic psychoses.


[Delirium metabolicum and rigid involutional depression in older age]. A melancholic-schizophrenic mixed psychosis is described in a 64-year-old man. It was diagnosed as a 'rigid (or catatonic) involutional depression' (Medow, 1922), showing besides hypochondriacal, nihilistic and micromanic delusions, a transient delusional syndrome of 'Delirium metabolicum' (Mendel, 1902), with zo-anthropy. An attempt was made to avoid the differential diagnostic classification of that clinical picture into involutional melancholia (296.0) and paranoid psychosis of involutional age (197.1) which, as in so many psychoses of the older age groups, is quite inadequate. Thus the psychopathological phenomena of the psychosis, which after all are the only reliable data, were attributed on the one hand to the senile deterioration and slight but demonstrable arteriosclerosis of the brain, and on the other hand, to the conspicuous premorbid characteristics which correspond to an anankastic psychopathy with a depressive-inadequate basic mood. It was considered as likely that the Delirium metabolicum represented an exogenous (organic) psychotic syndrome, and that the precipitation of the psychosis as well as its development into an enfeebled endstate was due to an organic brain lesion, while the catatoniformpsychomotor phenomena and the melancholic stupor were crystalisations of traits in the premorbid personality.


[Aggresive acts of psychiatric inpatients as reported by nursing staff. A retrospective study]. Method. Questionnaire method with reconstruction of the serious incidents by interview and documents. Results. 253 members of staff remembered 626 aggressive acts which happened to them in the course of a year. Slight acts were caused more often by women than by men, and were directed more frequently against the junior than the senior staff - contrasting in both points with the serious acts. One in every four qualified nurses over the age of 50 shows today a verifiable physical defect resulting from an aggressive act by a patient at one time or another. The clinical-psychological and therapeutic background and consequences of aggressive incidences are briefly presented.


[Methylphenidate addiction--Reversal of effect on withdrawal]. A case history of a prolonged ritalin addiction (18 years) is given, describing the symptoms and the diagnostic categorisation. Because of the remarkable, somewhat atypical withdrawal symptoms, it is suggested to conceive these withdrawal symptoms as an expression of a 'reversal of effect on withdrawal' in the sense of a continuing, independent manifestation of counter regulatory, protective and specific mechanisms.


[Long-term EEG investigations at the withdrawal of young polytoxicomanic addicts]. Serial EEG examinations (an average of three recordings in 14 weeks) are reported from adolescent inpatients (19 in number) who had been weaned of multiple drug abuse of an average duration of 2 years. At first examination seven had a normal EEG, 11 had a moderately abnormal EEG, and one had a markedly abnormal one. At final examination 13 had a normal EEG, five had a moderately abnormal EEG and three had definitely abnormal EEG's. The majority of the patients showed a decrease (significant at the 5% level), others an increase in EEG abnormalities. The relationship between the EEG changes in the course of the series on the one hand and the previous drug abuses is discussed.


[Distribution of hepatitis B antigen in Cordoba, Argentina]. This article presents the results obtained in the search for the hepatitis B antigen by the counter-immunoelectrophoresis technique in sera of more than 50.000 persons from Córdoba, Argentina. Groups of voluntary blood donors, general population, 20 years old army recruits, patients, with acute hepatitis and patients admitted to a hospital due to other diseases were included in this study. In the apparenly healthy population the positivity of the test ranged between 0.33 to 0.53 percent; the highest rate was found among the recruits. In the group of patients with acute hepatitis, 38.53% of the sera were positive. No statistically significant differences were observed in the monthly distribution of the hepatitis B antigen during the period of study. These results are compared with those found by other workers in different countries. This study shows the importance of the early detection of the hepatitis B antigen in blood donors, to reduce the incidence of hepatitis transmitted by transfusions. The importance of establishing centers for the standardization and control of reagents, as well as for the training of laboratory personnel is emphasized.


[Nocardia isolated from the respiratory tract]. Twelve strains of Nocardia isolated from sputa, bronchial washings and pleural fluids, were studied. The classification was based on the following characteristics: a) acid-fastness; 2) ability to disolve crystals of tyrosine and xantine; 3) hydrolysis of casein; 4) growth in dilute gelatin medium (0.4%) and 5) galactose acidification. Direct cultivation of the clinical material in Czapek liquid culture medium without carbon source and containing a paraffin rod (pariffin-bait technic), as well as the routin T.B. sputum digestion and concentration with NaOH solution followed by its cultivation in Loewenstein's medium, were employed for the isolation of Nocardia. The sensitivity of the strains to tuberculostatic drugs was investigated using the Canetti's method, as was the ability to growth in Sabouraud and lactrimel culture media supplemented with 100 mug/ml of rifamycin. Finally the pathogenicity test was carried out by intraperitoneal and intramuscular inoculation in guinea-pigs. All the strains were classified as Nocardia asteroides. Seven starins were isolated from patiens with lung conditions of no nocardial etiology. The diagnosis of nocardiosis of the lung was demonstrated in the remaining five patiens by microscopical observation of Nocardia in clinical specimens, by the repeated cultures obtained from these materials and, finally, by the fact that an improvement of the clinical symptomatology was obtained by sulfa administration.


[Serologic survey on human leptospirosis in Argentina]. This paper presents the results obtained with the sera of persons having direct or indirect contact with ethiological agents of leptospirosis. Exposure could have ocurred during the performance of their duties, by contact with contaminated habitats and/or animals. One thousand thirty eight sera from persons living in different regions of Argentina were received at the laboratory and studied by the microscopic agglutination tecnique. Of these, 164 were positive (15.7%) to serveral serotypes. One hundred thirty eight sera of the 857 males studied (16.1%) were positive, and 16 out of 173 female sera (15%) were positive. Males between 31 and 40 years of age had the highest proportion of positives (21.7%); however, among females the group between 21 and 30 years of age had the highest rate (14.2%). Most of the sera reacted to L. brastislava (15%), followed by L. icterohaemorrhagiae (17.7%) and L. butembo (14%), with nine other serotypes at lower rates.


[Experimental Junin virus infection in the mouse: rototype of the disease]. As previously postulated, the pathological changes which develop in 1-4 day old mice after intracerebral inoculation of 1-1000 DL50 of Junín virus prototype strain (XJ), was designated as experimental hemorrhagic fever of the mouse EHFm. In this paper, virus distribution, hematological alterations, interferon and circulating antibody responses are described. A mortality of 93.45% occurred between 9 and 20 days post-infection (p.i.), with 81.6% of death occurring between 11 and 18 days p.i. This last period can be considered to be the critical period of the disease. The study of virus distribution shows that the brain, where the virus was inoculated, was the only place where virus could be detected 48 hs, p.i. Four days p.i., the titer in the brain increased remarkably and virus was detected in the blood. Virus, within the same values, could be isolated up to the 10th. day. Invasion of liver and spleen occurred on the 10th. and 15th. days p.i., respectively (Fig. 1). The onset of clinical symptoms coincided with widespread disemination of the virus. CF antibodies were found only 15 days p.i., with a titer of 1/64. Neutralizing antibodies remained below detection levels during the whole experiment (Fig. 1). Surviving mice (6.3%) had high circulating antibody titers 40 days p.i. This result would indicate that the morobidity of EHFm is aproximately 100% (Table 1). Poor interferon response was registered in all the organs examined, indicating a low intereron producing ability for Junin virus6. Total leukocytes and lymphocyte counts showed a slight tendecy to drop, although the values were within normal range during the first ten days (Table 2, Fig 1). On day 14 p.i., a statistically significant decrease (p less than 0.001) was found. This leuko-lymphopaenia continued until death of the animals. It is expected that the data presente here would contribute to a better understanding of the Junin virus infection in the newborn mouse, the experimental animal used.


[Action of thyroid hormones on the calorigenic effect of adrenaline]. The present investigation was undertaken in order to appraise the interaction between thyroxine and epinephrine in dogs exposed to acute cold. In normal, then successively thyroidectomized, adrenal demedullated and thyroxine restored dogs, epinephrine was infused in basal condition and during acute cold exposure. In thyroidectomized dogs epinephrine lost its calorigenic effects. So it did in thyroidectomized and adrenal demedullated dogs. Conversely, when dogs were restored in thyroxine, epinephrine recovered its calorigenic effect. Evidence for thyroxine-catecholamine interaction can be seen in basal condition as during acute cold. Nevertheless, this interaction is more obvious during shivering thermogenesis.


[Biochemical study of cultured hepatocytes obtained from normal adult rats]. A method has been developed for the preparation of hepatocytes that contained 98.6% of that cell type with a yield of 50%. No change was detected in the DNA content per nucleus but losses were noted in RNA and proteins in freshly isolated hepatocytes. The hepatocytes have been kept alive for long periods in suspension or static cultures without any mitoses being observed. However DNA content doubled over a period of two weeks. This level was maintained during the third week. Tritiated thymidine incorportation similarly increased for a period of two weeks and then remained constant. RNA content went down rapidly to one fourth of the original level and remained unchanged thereafter. The protein content did not vary significantly. Incorporation of labelled leucine into proteins has also been measured at various periods of time following isolation of the cells. Even after 62 days in suspension culture, the hepatocytes continued to incorporate leucine into proteins. The incorporation of leucine proceeded through the normal pathway since the presence of t-RNA-bond-leucine was observed. The results reported here suggest that the hepatocytes are arrested in the G2 phase of the cell cycle.


[Correlation between intradermal reaction and immunoelectrophoresis in human hydatidosis]. The results obtained by the immunoelectrophoresis (IEP) aand Casoni intradermal (IDR) tests in a group of 50 hydatidosis patients in which the presence of cysts was later confirmed at surgery, are analyzed. The sensitivity of the IEP test was 74%; the IDR test was positive in 54% of these patients and there was no correlation between the results of the two tests in 24% of the cases. The low sensitivity observed for the IDR test, its known nonspecificity and its poor correlation with IEP test results do not enable us to recommend its use for the diagnosis of hydatid disease or for the selection of cases in which an immunodiagnostic confirmation is feasible. This recommendation would be possible if appropriate antigens regarding specificity and reactivity were available, and could be employed with standardized methods to read and evaluate cutaneous reactivity.


[The effect of pretreatment with enzyme inducers on the acute toxicity of DDT (1, 1-bis-(p-chlorophenyl)-2,2,2-trichloroethane) in rats]. A study was undertaken to investigate the influence of various hepatic enzyme inducers on the acute toxicity of the organohalogenated insecticide DDT. Adult female rats were pretreated with sodium phenobarbital (50 mg/kg/day during 5 days), 3-methylocholanthrene (20 mg/kg/day during 3 days), and norethandrolone (20 mg/kg/day during 14 days), and were then given 150 mk/kg of DDT per os. Phenobarbital was shown to lower the toxicity of DDT, norethandrolone had the opposite effect, and 3-methylcholanthrene was without any significant effect. After a phenobarbital pretreatment, the cerebral concentration of DDT was lowered, possibly as a result of an increased biotransformation of DDT to DDD in the liver. On the other hand, norethandrolone did not appear to modify the hepatic conversion of DDT to DDD, nor the cerebral concentration of DDT. Further studies are needed to explain the potentiating effect of norethandrolone on the acute toxicity of DDT.


[Fishing seawater microbiology of the Mar de Plata]. This work deals with different groups of microorganisms in the polluted water of the fishery section of Mar del Plata harbour and in the way followed by the fisher's boats. Bacteriological determinations were: total count, MPN of coliforms, proteolitic and anaerobic bacteria. These groups were selected because of their activity in fish spoilage and/or infection. The microbial groups were studied as follows: direct plate count for total number, most probable number (MPN) for coliforms and fecal type strains according with Mc Crady tables; proteolitic and anaerobic bacteria were cualitatively tested, cuantitative determinations are given in two tables. Obtained results show a heavy water pollution that rapidly decreases towards the harbour entrance.


RNA profile of blood cells from LSD-affected persons. This work shows the existence of differences in RNA profiles as obtained from blood cells of two LSD-affected persons. These had received slightly different concentrations of LSD yet their RNA profiles between them, and those of control patients, are remarkably different, especially regarding the 4S peaks. Further work is now being done in our laboratory in order to understand the meaning of these important differences.


Fine structure of chick embryonic parathyroid glands cultured on media with different concentrations of calcium. An electron microscopical study of parathyroid glands from 13-day old chick embryos cultured for 2 days on media with different concentrations of calcium was conducted. The same as in non-cultured embryonic glands, the cells in all cultures contained a moderate amount of rough endoplasmic reticulum and a large Golgi complex with many cisternae, vacuoles, vesicles, coated vesicles and small prosecretory granules. In addition, large secretory granules, which are very rare in the non-cultured controls appeared frequently in the cultures and were especially numerous in the glands cultured on high-calcium medium. The fact that the amount of secretory granules varied according to the concentration of calcium in the medium is interpreted as indicating that the rate of parathyroid hormone secretion in the embryo is already responsive to variations in the concentration of calcium. To the extent that in vitro results may be accepted as representative of what happens in vivo these results support the idea that the embryonic gland may be controlled by variations in the calcemia as the adult gland does.


[Effect of rotting corn straw on the development of bacteria of the Azotobacter group]. The effects of the addition of ground maize straw, nitrogen compounds, ground lucern and water to soils incubated at 30 degrees C in Erlenmeyer flasks, on Azotobacter chroococcum growth have been studied. The results showed that the highest number of Azotobacter in soils treated with different percentage of ground maize straw without addition of nitrogen compounds and with water at 100% field capacity appeared as soon as the 5th day, reaching a maximun on the 20th day when the following numbers of bacteria were observed: control, 1,5 times 20(6); straw 1% 30 times 10(6),  2%, 33 times 10(6) and 4%, 77 times 10(6) per gram of air dried soil. This enables us to assume that the anaerobic decomposition of straw (cellulose and hemicellulose principally) in nature leads to the indirect utilization of its energy for a high asymbiotic microbiogical soil fixation of atmospheric nitrogen.


Cardiac metabolism and electromechanics of human heart. The effects of substrates on the metabolic inhibitor-induced changes in the action potential and contraction of papillary muscles obtained from patients undergoing corrective open-heart surgery were studied. Anoxia produced a marked shortening of the action potential duration and a decrease in the resting potential, rate of rise of action potential, effective refractory period, and contractility. In anoxic muscle, although glucose completely restored the action potential duration, effective refractory period, and resting potential to control levels, it was unable to completely restore the contractility to the control level. Substrate depletion and metabolic inhibitors (iodoacetate, dinitrophenol) produced effects similar to that of anoxia, but at a faster rate. Glucose restored the action potential and, to a lesser extent, contractility to the control level in dinitrophenol-treated muscle but was ineffective in so doing the iodoacetate-treated muscle. Pyruvate, however, was effective in restoring the action potential and contracility in iodoacetate-treated muscle. Pretreatment of the muscle with glucose and, particularly, with glucose plus insulin prevented the combined effects of anoxia and lack of glucose on the action potential and contractility for a prolonged period. These results suggest that intravenous infusion of glucose and insulin before and during surgery might prevent or reduced the effect of anoxia on the electrical and mechanical activity of the heart during open-heart surgery.