Sexual impairment of inexperienced male rats following pre- and postpuberal olfactory bulbectomy.

Olfactory bulbectomy of sexually inexperienced male rats prevented the occurrence of sexual behavior in most of the operated animals. This effect was observed in rats bulbectomized before puberty as well as after puberty. Bulbectomized rats which had heterosexual experience prior to the operation did not deviate from intact rats. Males living in cohabition with intact males prior to the operation showed only minor deficits in their mating performances. It was concluded that the olfactory lobe while of only minor importance for maintenance of mating once sexual behavior has been initiated, plays an important role in initiation of sexual behavior of the male rat. Furthermore, since treatment with testosterone of prepuberally bulbectomized rats did not stimulate the animals to sexual activity it was concluded that the sexual impairment following bulbectomy of isolated males presumably is not due to an impaired production of gonadal secretions.


Effects of enucleation in retinal degenerate mice.

Two experiments are reported which examine the effects of optic enucleation upon behavior of retinal degenerate C3H/HeJ mice. Enucleation did not affect acquisition of a two-way avoidance task. However, enucleated mice were more active than unoperated controls. The increased activity was not specific to the avoidance task since it also occurred in the closed field. The enucleation-induced increase in closed field activity did not depend upon age at time of testing or postsurgical recovery time. Several alternative explanations are considered, including the possibility that some information may be processed by the eye in the absence of traditionally conceived photoreceptors.


Influence of enucleation upon two-way avoidance behavior of rats, hamsters, chinchillas and BALB/cJ mice.

Several rodent species were blinded and their two-way avoidance behavior was compared to unoperated controls. Blindness facilitated avoidance learning in BALB/cJ mice, impaired learning in hamsters and had no significant effect on albino rats, hooded rats and chinchillas. Effects of blindness upon intertrial locomotor activity correlated well with effects of blindness upon avoidance learning. Preventing intertrial activity abolished the effect of blindness in mice, and did not change performance of blind albino rats.


Head mount for the control of infusion in freely moving animals.

The construction of a light weight head mount for the control of infusion in small laboratory animals is described. The head mount reduces restraint of the animal and includes a valve to seal the cannula so that the animal may be disconnected from the infusion system.


On hearing and inspiration in the composition of music.

The observation that composers experience inspiration as a source external to the self is considered, using reports of early and modern composers. This is related both to earlier psychoanalytic work on creative inspiration and to modern ego psychology. The postulation that an auditory sensory style in composers has early developmental roots and becomes their primary sensory mode is considered together with some possible determinants in its development.


The concept of akinesia.

The concept of akinesia deserves to be looked at again in the light of recent work on Parkinsonism, particularly those findings which have resulted from the use of L-dopa in Parkinsonian syndromes.  Akinesia and bradykinesia are integral parts of such syndromes, at times even constituting their essential element.  Akinesia belongs to a group of psychomotor syndromes, the semiology and pathogenesis of which were the subject of numerous discussions at the beginning of this century.  As we have pointed out elsewhere, akinesia cannot be defined solely in terms of its own characteristics: it must be understood equally in its paradoxical aspects--"paradoxical kinesia" in post-encephalitic Parkinsonism in particular, and "paradoxical akinesia" in Parkinsonian patients treated with L-dopa.


Dopamine metabolism in depressions, psychoses, and Parkinson's disease: the problem of the specificity of biological variables in behaviour disorders.

The probenecid technique was used in study of the central dopamine DA metabolism in patients with depressions, psychotic disorders, and Parkinson's disease.  The disturbances found were neither nosologically nor syndromally specific, but appeared to be symptom-specific.  Decreased DA turnover was associated with hypomotility, and increased DA turnover with hypermotility.  Decreased DA turnover was probably related aetiologically to the hypomotility: the symptoms subsided after replenishment of the DA deficiency.  The relation between increased DA turnover and hypermotility is still under investigation.  In view of the findings obtained, a plea is made for the development of a functional psychopathology, in which psychiatric syndromes are "dissected" into their constituent psychological dysfunctions.  This development is expected to stimulate human brain and behaviour research.  It can be achieved only by intensive collaboration between psychiatrists and experimental psychologists.


Psychiatric symptom profiles of patients with epilepsy: a controlled investigation.

A comparison was made of the mental state of patients with chronic epilepsy and matched controls with locomotor disorders, using a reliable psychiatric interview technique.  The symptom profiles of the two groups were similar.  The profiles of temporal lobe and other epileptics were also similar.  Epileptic patients with a high current psychiatric morbidity were characterized by a raised incidence of previous neurotic illness and raised neuroticism scores on the Eysenck Personality Inventory.


Schizophrenia and Cushing's syndrome cured by adrenalectomy.

A case of Cushing's syndrome in a woman aged 50 years is described, with psychosis of schizophrenic type.  The psychosis and endocrine disorder were subsequently cured by adrenalectomy.  Twenty-five years previously the patient had a typical schizophrenic psychosis treated in mental hospital with a deep insulin therapy and ECT.  The possibility is raised that deep insulin therapy could have induced the Cushing's syndrome through its non-specific stressor effect on the pituitary-adrenal axis.


Effect of depression on the speed of recall of pleasant and unpleasant experiences.

An experiment is described in which depressed patients were asked to recall pleasant or unpleasant experiences from their past life in response to a standard series of stimulus words.  The ratio between the time for recall of pleasant and unpleasant experiences was found to fall progressively with increasing severity of depression or of "neuroticism" and to be significantly related to each.  Among patients who scored relatively low on depression or neuroticism pleasant memories were recalled more speedily than unpleasant; among those who scored high this relationship was reversed.  Possible mechanisms to account for these findings are discussed.


Hierarchy of classes of personal illness.

A hierarchy of classes of personal illness model is proposed and was assessed using a new self-report measure, the Delusions-Symptoms-States Inventory (DSSI).  Of 480 psychiatric patients 93.3% had a symptom patterns conforming to the model.  It was additionally found that single syndrome patterns, within a particular class, occurred significantly more often than those not classifiable in any higher class.  Finally, the relationship between each possible pair of the 12 syndromes was examined.  Some of the implications of the model and the data are discussed in terms of the development, remission, assessment, and treatment of personal illness.


Survey of alcoholism and excessive drinking in a suburb of Buenos Aires.

A cross-sectional household survey of drinking patterns, categorized as alcoholism, excessive drinking, moderate drinking, and abstinence, was conducted in a middle and lower-class section of Greater Buenos Aires.  Alcoholism and excessive drinking were present almost exclusively among males, and were more prevalent among the lower levels of education, occupation, or residential area, and also among migrants.  Prevalence rates for males, aged 15 +, were: alcoholics 4.4% +/- 2.1 and excessive drinkers 12.2+/- 3.4.  Details of the methods, the implication of the findings, and comparisons with other surveys are reported and discussed.


Multicompartmental analysis of amino acid.  1. Preliminary data on concentrations, fluxes, and flow constants of tryptophan in affective illness.

The study of tryptophan metabolism using compartmental analysis suggested differences between males and females, and between control subjects and patients with affective illness, patients treated with tricyclic drugs, and those established on lithium therapy.  The total mass of tryptophan in the body may be reduced in people prone to affective disorder, and in depressed patients(ill and well)turnover of tryptophan seemed to be reduced.  The reduction of concentration of tryptophan in compartment S2 in affective illness could affect protein synthesis.


Sociology and the theory of responsibility: 'social background' as an excuse for crime.

The concept of social abnormality can be given a fairly precise meaning and is relevant to the theory of legal responsibility. Much work, however, would need to be done before it could take its place alongside mental abnormality as an excusing condition in the courts. The implications of such a plea would, moreover, be far reaching, two of the more obvious being the individualization of excuses and the relinquishing of the general preventive possibilities of punishment.


Late recovery from head injury: case report and review.

Some problems of prognosis in patients with head injury are reviewed, and a case of late and unexpected recovery from post-traumatic dementia presented. The possible mechanism of recovery is discussed with particular reference to normal pressure hydrocephalus.


Factors influencing the occurrence of schizophrenia-like psychosis in patients with temporal lobe epilepsy.

From a series of 255 patients who had undergone temporal lobectomy for the relief of intractable psychomotor epilepsy, all 47 patients with 'alien tissue' (small tumours, hamartomas, focal dysplasia) in the resected temporal lobe were contrasted with a group of 41 patients who showed mesial temporal sclerosis in their resected lobe. Five per cent of the mesial temporal sclerosis group and 23% of the alien tissue group were psychotic. A marked interaction occurred between psychosis and 'left handedness'. In the alien tissue group, females, especially left-handed females, were the most likely to have developed a schizophrenia-like psychosis.


Cortisol binding in plasma of men with unipolar and bipolar affective disorders.

Following an earlier report, plasma cortisol-binding capacity (CBC) was estimated in a new series of 11 men with unipolar depression and 11 men with bipolar illness admitted to hospital. The two groups were comparable except that the bipolar group tended to have more frequent episodes of illness and to have more family histories of affective disorder. There was no significant difference between the CBC values in each group.


Tricyclic antidepressants and tryptophan in unipolar depression.

Depressed patients (unipolar) were given one of the following combinations in an attempt to test aspects of the 'amine hypothesis' and to find a preferential therapy: (1) clomipramine; (2) clomipramine and tryptophan; (3) desipramine and clomipramine, and (4) desipramine and tryptophan. Treatment (2) should have given optimal potentiation of 5-HT neurones and (3) and (4) should have acted similarly on both serotoninergic and adrenergic pathways. In no group was there any evidence of accelerated recovery, indicating that the process of conversion to normal mood may be more complex than suggested by most versions of the amine hypothesis.


Urinary excretion of the sulphate and glucuronide of 3-methoxy-4-hydroxyphenylethyleneglycol in a manic-depressive patient.

The sulphate and glucuronide conjugates of 4-OH-3-methoxyphenylethyleneglycol (MOPEG) and 4-OH-3-methoxymandelic acid (VMA) have been serially studied in the urine of a manic-depressive patient before and after a therapeutic response to lithium carbonate. Excretion of both conjugates correlates with changes in mood. Some reasons to suggest that the sulphate might be a more useful measure of brain activity are stated.


Observations on the epidemiology of post partum mental illness.

This study is based on a sample of 35,486 consecutive confinements in Cardiff (1965-72) which gave rise to 67 cases of post partum mental illness. No difference was found between these cases and all resident Cardiff maternities for the same period in respect of social class, maternal parity, weight gain in pregnancy, length of gestation, birth weight, and sex of infant. A statistically significant cyclic variation in month of conception and date of birth was found with a peak frequency among conceptions in the first quarter of the year. The bearing this finding may have on the prevention of post partum mental illness and the implications of the observation that post partum mental illness and the functional psychoses have a remarkably similar temporal behaviour are discussed.


Survey of incapacity associated with mental handicap at Rampton and Moss Side Special Hospitals: a comparison with the 1970 National Survey.

The results of a survey carried out at Rampton and Moss Side Special Hospitals into physical and behavioural incapacity associated with mental handicap are described and compared with the findings of the 1970 National Survey. The Special Hospital patients were found to be less mentally handicapped than similar patients in subnormality hospitals in the National Health Service. The prevalence of physical incapacity associated with mental handicap was also lower in the Special Hospitals but the Special Hospital patients were assessed as more behaviourally disordered. In both surveys the incapacities present were concentrated in the severely mentally handicapped patients. In the Special Hospitals survey the women, when compared with the men, were found to be more behaviourally disordered and to suffer from a greater degree of multiple severe incapacity. All the differences found between the two surveys are consistent with the statutory criteria for admission to a Special Hospital.


Reliability of prisoners' attitudes to their drinking behaviour.

A sample of male prisoners was examined by means of a questionnaire and subsequently by a structured interview. Control subjects who denied heavy drinking were used to study test-retest reliability of a group who admitted that drinking was a problem and a third group who admitted heavy drinking but denied problem drinking. Non-heavy drinkers and the heaviest drinkers are shown to be the most reliable and the intermediate group least reliable.


Platelet monoamine oxidase activity during the course of a schizophreniform psychosis.

A case is reported in which platelet monoamine oxidase (MAO) activity fluctuated in the course of a schizophreniform psychosis in a way which suggests a direct relationship between low levels of MAO activity and the psychosis.


Behavioral and electrophysiological effects of phenylethanolamine and 2-phenylethylamine.

The electrophysiological and behavioral effects of phenylethanolamine (OHPEA) and of its precursor 2-phenylethylamine (PEA) were studied in mice and rabbits. In animals pretreated with MAOI, PEA was found to exert strong amphetamine-like effects, EEG alerting, reduction of visual evoked responses, increased locomotor activity, and blockade of tonic seizures induced by electroshock. OHPEA exerted weaker amphetamine-like effects. Inhibition of dopamine-beta-hydroxylase increased most of the effects of PEA. In non-pretreated animals, OHPEA was found to shorten electroshock latency and to prolong the duration of visual evoked responses. PEA (but not OHPEA) potentiated the excitement induced by delta9-tetrahydrocannabinol in MAOI-pretreated mice. Reserpine pretreatment reduced but did not abolish the CNS effects of OHPEA and PEA. One may speculate that endogenous PEA is more likely to serve as a modulator for ergotropic functions than is endogenous OHPEA.


Norepinephrine and serotonin: specificity of release with rewarding electrical stimulation of the brain.

Using a push-pull cannula method the amygdala of rats was perfused to examine the release of labeled norepinephrine (NE) and labeled serotonin (5-HT) during electrical stimulation of the brain (ESB) determined by prior behavioral testing to be rewarding or non-rewarding. Simple sensory stimulation was used during perfusion to examine further the degree of specificity of release of these amines. Highly rewarding ESB, but not the sensory stimulation, was accompanied by release of both NE and 5-HT. Varying current intensity had significant effects on the amount of these amines released. Furthermore, non-rewarding ESB was accompanied by inhibition of release of NE and 5-HT and a control substance, urea, was not significantly released during rewarding ESB. The results were discussed as implicating both noradrenergic and serotonergic mechanisms in the mediation of reinforcement.


The effects of nicotine on two-way avoidance conditioning in bi-directionally selected strains of rats.

Rats of both sexes from the genetically selected Roman High Avoidance (RHA), the Roman Low Avoidance (RLA) and the Roman Control (RCA) strains were given one 30-min session of two-way escape-avoidance conditioning (30 trials) in a shuttle box with a buzzer as the conditioned stimulus and shock as the unconditioned stimulus in a factorial design involving three time intervals (0, 15 and 30 min) following one subcutaneous injection of saline or of nicotine in five doses (0.05, 0.1, 0.2, 0.4, or 0.8 mg/kg of body weight). Six measures relating to performance were analysed in whole or part. While the number of avoidance responses showed the expected strain differences, no effect of dose or delay interval could be detected. Avoidance and escape latencies and intertrial activity showed some effects of these variables, especially in interaction with sex and strain. Dose determined pre-sessional activity, but its effect was strain dependent. The failure to confirm previous findings is discussed in the context of other instances in the literature, and the results of an operant experiment confirming the continuing sensitivity of the Roman strains to the effects of nicotine are reported.


Human auditory evoked responses during hangover.

Auditory evoked responses (AER) to trains of 6 click stimuli (1 click/sec) were studied in 9 subjects under hangover, tired control, and normal control conditions in order to find out whether the symptoms of hyperexcitability during hangover have a correlate in the characteristics of the AER. In addition, the audiograms were measured. AERs to the first click in a stimulus train were markedly smaller during hangover than in the other 2 states. The amplitude levels of the AERs during the repetition of the click stimulus were, however, similar under all three conditions. The audiograms obtained in the three states were similar except for a very slight decrease of auditory threshold sensitivity during hangover as compared with the tired control condition. The results show that the effects of hangover on AERs resemble those of alcohol intoxication. The symptoms of hyperexcitability during hangover cannot be explained in terms of increased peripheral sensitivity.


The effect of microinjections of amphetamine into the neostriatum and the nucleus accumbens on self-stimulation behaviour.

The effect of micro-injections of dexamphetamine chloride into the neostriatum, the nucleus accumbens, the anterior hypothalamus, and the ventricular system on self-stimulation with electrodes in the ventral tegmentum was studied. Unilateral injections of 10 mug into the anterior hypothalamus produced no effect. Injections into the neostriatum tended to depress the self-stimulation rate, whereas injections into the nucleus accumbens increased the rate markedly. Bilateral injections (2 times 2.5 mug and 2 times 5 mug amph.) into the nucleus accumbens were more effective than unilateral injections and were as effective as systemic injections of 1 mg/kg amphetamine (i.p.). Bilateral injections into the neostriatum also increased the self-stimulation rate. Injections of 10 mug into the ventricular system resulted in a smaller increase which was not statistically significant. These results are discussed in relation to the involvement of the dopaminergic system in the maintenance of self-stimulation behaviour.


Dose effects of smoked marihuana on human cognitive and motor functions.

Graded doses of marihuana were administered to five adults in a longitudinal repeated-measurements design. Speed of response was the basic parameter measured accross tests of increasing cognitive involvement. Marihuana produced significant dose-response effects of impaired performance in all test scores. However, single automatic motor abilities demonstrated greater sensitivity than tests of greater complexity. Evidence is presented for tolerance development.


Morphine sensitivity and tolerance: a genetic investigation in the mouse.

Sensitivity and tolerance to morphine were determined in 2 strains of mice, BALB/cBy and C57BL/6By, their reciprocal F1 hybrids and seven of their recombinant inbred strains. Sensitivity was established based on locomotor activity following the administration of saline, 10 or 20 mg/kg of morphine hydrochloride while tolerance was established according to the "hot plate" method following the single or repeated administration of saline, 5, 10, or 20 mg/kg of morphine hydrochloride. Results indicate that both sensitivity and tolerance to morphine are genotype-dependent and their inheritance is characterized by dominance or partical dominance. Further clarification of the genetic relationship of sensitivity, tolerance and analgesia to morphine must await analysis of the brain morphine-binding protein currently being conducted.


Effects of heroin on lever pressing for intracranial self-stimulation, food and water in the rat.

Male rats maintained with continuous access to levers for intracranial self-stimulation (ICSS), water, and food were subjected to five consecutive daily injections of heroin (5 mg/kg). Rates of lever pressing for ICSS were increased in 8 rats, 2--6 hrs after administration of heroin. Rates of lever pressing for water and food were not significantly changes during this period. Naloxone (5 mg/kg) pretreatment attenuated by 82% the facilitative effect of heroin on ICSS. A second group of 8 rats maintained at reduced ICSS rates failed to show an increase in lever pressing for ICSS with heroin. The facilitative effect of heroin described in this study is consistent with previously reported studies describing the effects of morphine on ICSS.


Effects of morphine and heroin on discrimination learning and consolidation in mice.

Morphine and heroin were administered to mice learning to swim toward a light source (L procedure) or toward the dark (D procedure), in a Y water maze, under pre and post-trial drug treatment conditions. In the pre-trial experiments a clear disrupting effect on performance with the two procedures followed administration of both drugs, but for the L performance never fell below the 50% level of correct choices. Analysis of the performance within each session demonstrated a disruption in the long term memory consolidation mechanism. The administration of naloxone, or alternatively, discontinuation of the treatment, was followed by a gradual improvement, in performance by the treated animals. In both procedures, a performance disruption also followed the administration of the drugs immediately after each experimental session.


Modifications by lithium of behavioral responses to methamphetamine and tetrabenazine.

Different groups of mice were injected s.c. daily with lithium chloride in three doses(0.52, 1.58 and 4.72meg/kg) or with saline for a period of 3 weeks. Lithium administered acutely or chronically did not affect spontaneous locomotor activities. However, methamphetamine-induced hyper-locomotor activities were inhibited in the lithium groups as compared with those in the saline group, while the hyper-locomotor activities induced by tetrabenazine in the nialamide-pretreated animals were reduced to some extent but not significantly by lithium. Tetrabenazine brought about an initial transient increase followed by a decrease of spontaneous locomotor activities in the lithium groups, whereas it induced only a decrease of the activities in the saline group. In addition, jumping and vertical jumping behaviors, which were not observed in the saline group, occurred 30-60 min after tetrabenazine in the lithium groups. These effects of lithium tended to increase with an increase of the doses administered and with a prolongation of its daily administration. The results demonstrate that lithium modifies behavioral responses to methamphetamine and tetrabenazine.


A genetic analysis of the response to morphine in mice: analgesia and running.

Two progenitor strains, BALB/cBy and C57BL/6By, their reciprocal F1 hybrids, and seven of their recombinant-inbred derived lines were used to examine the genetic basis of the response to thermal pain, and morphine analgesia at doses of 2.5, 5.0 and 10.0mg/kg. Both the latency of response to thermal pain and the analgesic response differed significantly among the various strains tested. Strong genetic determinants appear to control their responses. Analyses of the data did not permit clarification regarding the linkage of these determinants. Photoelectric activity cages were used to test the running response of the same strains to 12.5, 25 and 40 mg/kg morphine sulfate. The genetic determinants for running activity were different from those for analgesia. There is clear evidence for two or more loci controlling the behavior at 60 and 75 min after injection, but not enough information to define the loci involved.


Effects of scopolamine, physostigmine and chlordiazepoxide on punished and extinguished water consumption in rats.

It has been postulated that behavioral inhibition due to punishment or extinction may be mediated by brain acetylcholine, and drugs which have disinhibitory action are thought to interact with this system. This notion was tested by comparing the effects of scopolamine, physostigmine and chlordiazepoxide on punished and extinguished water consumption. Scopolamine hydrobromide (0.3, 0.5 mg/kg, i.p.), a centrally and peripherally acting antimuscarinic agent and physostigmine sulfate, (0.3 mg/kg, i.p.), a centrally and peripherally acting acetylcholinesterase inhibitor, lowered both non-punished and punishment suppressed water intake and lick rate, whereas their quaternary analogs which primarily act in the periphery, had no significant effect at comparable dose levels. Scopolamine and physostigmine suppressed punished water consumption at lower dose levels than nonpunished intake. In contrast, chlordiazepoxide (5.0, 10.0, 20.0 mg/kg, i.p.) enhanced punished as well as non-punished water intake. In a further experiment comparing punishment and extinction suppression, scopolamine and physostigmine did not affect punished or extinguished water intake; chlordiazepoxide (5.0, 10.0, 20.0 mg/kg) reliably increased punished, but not extinguished licking on the water nozzle. These results suggest (1) that scopolamine and chlordiazepoxide do not act via a common mechanism, and (2) that punishment and extinction suppression are not a pharmacological entity.


Effects of single and multiple dose LSD on endogenous levels of brain tyrosine and catecholamines.

The effects on brain catecholamines of seven daily doses of d-LSD 520 mug/kg injected i.p. to Sprague-Dawley rats on a tolerance dosage schedule (L X 7) were compared with the effects of a single dose of LSD (L X 1) 520 mug/kg or 1040 mug/kg, over a 90 min time course. Compared to saline controls, after a single dose of 520 mug/kg LSD, there was a significant decrease in brain norepinephrine at 30 to 60 min, a rise in dopamine at 60 min, and a small rise in brain tyrosine at early time points followed by significant decline from control levels after 60 min. The effects of a single dose of 1040 mug/kg LSD were similar to the 520 mug/kg dose but were greater in both magnitude and duration of the brain catecholamine changes. After a tolerance dosage schedule there were significant changes in the response of brain catecholamines to 520 mug/kg LSD. The rise in brain dopamine at 60 min was abolished, brain tyrosine was uniformly below both saline and L times 1 animals, and brain norepinephrine returned to control levels slightly faster.


The effect of lithium on urinary MHPG in unipolar and bipolar depressed patients.

Twenty-four hour urinary excretion of 3-methoxy-4-hydroxphaeylglycol (MHPG), the metabolite thought best to reflect brain norepinephrine metabolism, was studied longitudinally in ten depressed patients before and during the acute and chronic phases of lithium treatment. Five of the patients were identified as bipolar I (prior history of mania), 3 as bipolar II (history of hypomania) and 2 as unipolar (history of depression). During acute lithium administration (first week) there was no consistent pattern of change in MHPG. Comparing the predrug period with the third and fourth week of treatment, all of the responders showed an increase in MHPG, while the non-responders showed no change or a decrease. It is concluded that the change in clinical state is the most important variable contributing to MHPG changes in these patients. There was a tendency for the pretreatment MHPG excretion to be low in the patients who went on to show a clear-cut antidepressant response to lithium compared to those who were unequivocal non-responders. The predrug MHPG for the bipolar patients (prior history of mania) was significantly lower than the unipolar patients, a difference which apparently contributes to the lower MHPG in the lithium responders, all of whom were in the bipolar group.


Assessment of tolerance to barbital by means of drug discrimination procedures.

This study was designed to determine the relative development of tolerance to the discriminative-stimulus and hypnotic properties of barbital. By selectively reinforcing lever presses only in the presence of one of the drug stated, rats were trained in a Skinner Box to discriminate the effect of sodium barbital (80 mg/kg) injection from that of saline injection. After the rats were well trained, the administration of daily hypnotic doses of barbital (240 mg/kg) for 8 days produced marked tolerance to the hypnotic effect of the barviturate in all animals. The ability of the 80 mg/kg dose to serve as a discriminative stimulus was not impaired in animals which had been trained with the drug as the condition during which bar presses had been reinforced (SD condition). Animals for which bar presses had gone unrewarded under barbital (Sdelta condition) displayed a tendency to develop tolerance to the stimulus properties of barbital. These findings are interpreted in the light of dose-effect studies, and it is suggested that the acquired polarity of the drug condition determined by its assignment as Sd or Sdelta may influence the discriminability of the drug in future exposures.


Chlordiazepoxide effects on reactions to novelty and activity with and without prior drug experience.

Reactions to novelty, rearing and ambulation were observed in rats following saline or chlordiazepoxide injections either with or without prior drug experience. Drug suppression of the former two response was evident but there was no indication of prior drug experience being effective. However, experience appeared to negate the compound's depressant effect on ambulation shown by inexperienced subjects. It was concluded that inhibitory influences of chlordiazepoxide on reactions to novelty and rearing can not be ascribed to the aversive effects of a novel drug state.


Food- and drug-reinforced responding: effects of DITA and d-amphetamine.

Intravenous pretreatment with DITA (0.1 - 1.0 mg/kg) decreased the rate of food-reinforcement lever pressing in rhesus monkeys. Response rate decreases were dose-dependent but showed the development of tolerance. Self-administration of DITA was initiated and maintained in each of three monkeys when 30 lever presses were required to produce each injection. Maximal response rate during periods of drug availability was maintained by 0.03 mg/kh/injection while higher and lower doses (0.01 and 0.10 mg/kg/injection) maintained lower response rates. Response rate in periods of food availability immediately preceding drug periods was relatively constant across session; response rate in periods of food availability immediately following drug periods, however, decreased with increasing amounts of drug self-administered. Replication of initial self-administration doses produced results comparable to original determinations in contrast to the tolerance observed with DITA effects upon food-reinforced responding. DITA was about 3 times less potent than d-amphetamine in maintaining response rates in drug periods and in decreasing the rate of subsequent food-reinforced responding.


Ethanol as a reinforcer for rats: effects of concurrent access to water and alternate positions of water and ethanol.

Water and ethanol solutions were concurrently made available on a continuous reinforcement schedule to 4 food-deprived male albino rats during daily 1-hr sessions in an operant conditioning chamber equipped with 2 levers and 2 liquid dippers. The number of ethanol reinforcements substantially exceeded the number of water reinforcements for each rat at each concentration studied (8, 16, and 32% w/v). Water reinforcements were low in number and did not vary with ethanol concentration. As the ethanol concentration was increased, the number of ethanol reinforcements obtained decreased, while the quantity consumed (mg/100 g of body weight/hr) increased. The highest rate of responding occurred at the beginning of the session.


Scopolamine and amphetamine effects on discrimination: interaction with stimulus control.

A parametric examination of the interaction between drug-induced behavioral changes and the degree of predrug stimulus control was conducted with rats. A discretetrial simultaneous discrimination was used, with the controlling stimuli varied over 6 values of distinctiveness. The effects of graded doses of scopolamine, d-amphetamine, and methylscopolamine on these performances were studied, with both scopolamine and d-amphetamine showing no increase in error rate under strong stimulus control, and dose-related increases in error rate under weak stimulus control. The similar interaction between drug effect and stimulus control for scopolamine and d-amphetamine indicates that the interaction reflects the degree of susceptibility of the behaviors to drug action, rather than two specific drug-behavior interactions. Methylscopolamine produced a slight effect on error rate and no significant interaction with stimulus control. A decrease in the number of trials responded to was found with both scopolamine and methylscopolamine, but not with d-amphetamine.


Tolerance to the effect of delta9-tetrahydrocannabinol in mice on intestinal motility, temperature and locomotor activity.

The onset and duration of tolerance to three effects of delta9-tetrahydrocannabinol (delta9-THC) given orally to mice were compared. The effects of delta9-THC studied were: hypothermia, the depression of intestinal motility and the effect on spontaneous locomotor activity. When mice were dosed and tested at 24 hrs intervals it was apparent that tolerance was complete to its hypothermic and locomotor depressant effects after the first doses and to depression of intestinal motility after the fourth dose. Duration of tolerance also differed so that the normal hypothermic response had returned after 12 dose-free days, but not after 5 drug-free days; the effect on locomotor activity had returned within 4 days; and apparent partial tolerance to the depressant effect of an acute challenging dose of delta9-THC on intestinal motility still existed after 19 dose-free days. It is apparent that the time of onset and the duration of tolerance to delta9-THC in mice showed a different pattern in the three parameters studied. It seems unlikely therefore that any one mechanism, such as metabolic tolerance, explains all the results observed and that several mechanisms should be explored to explain the phenomenon of tolerance to delta9-THC.


Neuroleptic-induced deficits in food and water regulation: similarities to the lateral hypothalamic syndrome.

The role of central dopaminergic mechanisms in the regulation of food and water intake was assessed by examining the effects of haloperidol and pimozide on various measures of feeding and drinking in rats. Haloperidol (0.20 mg/kg) or pimozide (0.45 mg/kg) did not significantly affect 1-hr water intake in response to 24 hrs of water deprivation, nor did they influence 2-hr food intake after 24 hrs food deprivation. However both pimozide and haloperidol significantly reduced drinking in response to injections of hypertonic saline. In addition, animals pretreated with these drugs drank less than controls in the absence of food (a measure of "non-prandial" drinking), and drank less than controls when the water was adulterated with quinine (a measure of "finickiness"). These drugs also significantly reduced food intake in response to injections of insulin and attenuated amphetamine anorexia. These deficits are similar to those observed after electrolytic lesions of the lateral hypothalamus or after 6-hydroxydopamine lesions of the substantia nigra. Because haloperidol and pimozide block central dopaminergic receptor sites, the present findings are consistent with the hypothesis that part of the lateral hypothalamic syndrome is the result of damage to the dopaminergic nigro-neostriatal projection. Finally, the data suggest that the changes in feeding and drinking induced by haloperidol and pimozide reflect genuine homeostatic deficits rather than being due to a neuroleptic-induced motor dysfunction.


Comparison of progressive-ratio performance maintained by cocaine, methylphenidate and secobarbital.

Cocaine, methylphenidate and secobarbital were compared on a drug maintained progressive-ratio procedure in baboon subjects. Trials, scheduled throughout the day, occurred at a minimum interval of 3 hrs after completion of the preceding trial. A ratio response requirement on the "initiate" lever was required during each trial which terminated in a single intravenous infusion of drug. A drug was introduced on the progressive-ratio procedure with a low ratio requirement in order to obtain a baseline performance of a high stable frequency of trial completion. The ratio requirement was systematically increased every 7 days until the "breaking point" when the rate of completing trials fell below a criterion level. Within-subject comparison revealed that cocaine produced higher breaking points than methylphenidate at the same absolute dose, 0.4 mg/kg. At the range of doses studied, manipulation of doses of methylphenidate (0.1-0.8 mg/kg) and cocaine (0.4-1.6 mg/kg) had little effect on breaking point. In contrast, increasing doses of secobarbital (6.0 and 12.0 mg/kg) produce higher breaking points within the same subjects.


The effect of adrenaline, tyramine and guanethidine on two-way avoidance conditioning and on pseudoconditioning.

Adrenaline (0.5 mg/kg) or guanethidine (10 mg/kg) given i.p. depressed performance of pseudoconditioned shuttle responses by rats. In a previous paper it had been shown that tyramine (5 mg/kg) had an opposite effect (Izquierdo, 1974a). Pre-trial administration of any of the three drugs also depressed two-way avoidance conditioning. Following posttrial administration, only guanethidine had a deleterious effect on retention. Since none of these drugs is believed to reach the brain in significant amounts following systemic injection, the present results suggest that peripheral factors may influence both conditioned and pseudoconditioned shuttle behavior.


The effects of protriptyline and clomipramine in vitro on the uptake of 5-hydroxytryptamine and dopamine in human platelet-rich plasma.

The effects of protriptyline and clomipramine, at concentrations of 10(-7)M to 10(-4)M, were studied in vitro on the uptake of 5-hydroxytryptamine and dopamine uptake in human platelet-rich plasma. It was found that the tertiary amine, clomipramine, was a more potent inhibitor of 5-hydroxytryptamine uptake than the secondary amine, protriptyline. The activity of both compounds was competitive but it was thought unlikely that they acted through tryptamine receptor sites as methysergide 2.5 X 10(-8)M had very little effect on 5-hydroxytryptamine uptake. Neither tricyclic antidepressant had any marked effect on dopamine uptake.


Personality characteristics, body image and social attitudes of organ transplant donors versus nondonors.

Thirty adults willing their body at death to medical science were compared on a number of personality variables with 30 nondonors, both groups equated for age, education, and socioeconomic status.  Donors are internally directed, masters of their fate; nondonors rely on chance or luck to explain outcome.  A more definite body image characterizes donors while nondonors are more concerned about body integrity.  Donors accept their mortality while nondonors worry more about death.  At the fantasy level donors display more hostility, depression, and guilt, and the prospective act of donation may represent an attempt at atonement.  Donation represents a convenient and socially acceptable outlet for expression of humanitarian needs by donors.


Ultradian rhythms in walking gastric activity.

Ninety to 120 min ultradian rhythms have been described in physiologic and behavioral functions relating to biologic drives.  Gastric contractility rhythms were examined in isolated fasting volunteers to supplement behavioral observations of "oral" drives.  A clear ultradian rhythms was observed, indicating inherent physiologic oscillation in stomach contractions.


Phasic heart rate responses: different patterns in black and in white newborns.

Click stimuli were presented during sleep to newborns from a low socioeconomic class urban population in Northeastern United States.  Eighty-three black newborns showed less immediate poststimulus deceleration than did 67 white newborns.  This difference was independent of heart rate level, and could not be accounted for by any of the perinatal variables studied, including birthweight and gestational age.  These results suggest that in this population, black newborns differ from white newborns in the pattern of phasic heart rate responses to stimuli.  This constitutes evidence for an additional difference in heart rate regulation in black as compared to white newborns from this population, since prior work reported differences in tonic heart rate level during sleep between black and white newborns.


Behaviorally conditioned immunosuppression.

An illness-induced taste aversion was conditioned in rats by pairing saccharin with cyclophosphamide, an immunosuppressive agent.  Three days after conditioning, all animals were injected with sheep erythrocytes.  Hemagglutinating antibody titers measured 6 days after antigen administration were high in placebo-treated rats.  High titers were also observed in nonconditioned animals and in conditioned animals that were nor subsequently exposed to saccharin.  No agglutinating antibody was detected in conditioned animals treated with cyclophosphamide at the time of antigen administration.  Conditioned animals exposed to saccharin at the time of or following the injection of antigen were significantly immunosuppressed.  An illness-induced taste aversion was also conditioned using LiCl, a nonimmunosuppressive agent.  In this instance, however, there was no attenuation of hemagglutinating antibody titers in response to injection with antigen.


Changes in serum dopamine-beta-hydroxylase activity during group psychotherapy.

This psychobiological study investigates married-coupled group psychotherapy from pre- and postsession serum dopamine dopamine-beta-hydroxylase (DBH) determinations, the Free Association Test (FAT), and a Postsession Questionnaire (PSQ).  Experimental manipulations permit controls for the assessment of DBH variations.  Group, gender, and individual linear regression analyses are interpreted by a stressor-destrssor typology.  DBH levels significantly increase during psychotherapy.  Increments are comparable with those from physical work.  Most variability in DBH is predicted from a small set of psychological variables.  Psychological stressors and destressors show psychobiochemical individuality.  Implications of psychological stressors for psychosomatic vulnerability are discussed.


Eating responses of obese and nonobese humans during dinner meals.

Observations of eating responses of obese and nonobese subjects were made in meal settings. Seven obese and seven nonobese male undergraduates were videotaped as they ate four dinner meals, two low and two high in preference, under low and high hunger conditions. As hunger and preferences increased, the amount of food eaten, the meal length, and the number of bites significantly increased. Time per bite decreased as hunger and preference increased. Obese subjects ate more grams per second than the nonobese subjects. Obese subjects also ate more high preference food and less low preference food than nonobese subjects. These findings are discussed in terms of Schachter's theory of differential stimulus orientation of obese and nonobese people and in terms of the set-point theories of Nisbett and Sclafani and Kluge.


Clinical evaluation of the 350-kV chest radiography system.

A chest radiography unit employing 350 kV was evaluated and found to be superior to conventional low-kV systems. Visualization of air/soft-tissue boundaries, mediastinal structures, the retrocardiac area, and lung apices was improved. Other benefits of the high-kV system include reproducibility, reliability, rapid installation, and economy of operation.


Efficacy of combined liver-lung scintillation imaging.

Of 116 patients who had undergone combined liver-lung scintillation imaging, 23 with negative studies had abnormal subphrenic spaces at operation, and 5 with positive studies had abnormal subphrenic spaces at laparotomy (hematomas, bile spillage, serous fluid or abscess); 4 of 6 nonexplored positive studdies showed resolution of defects on serial imaging. Other information obtained included abnormalities intrinsic to liver, lungs or spleen; evidence suggestive of left subphrenic pathology; and reliable information about the right subphrenic space even in the presence of intrathoracic pathology, including effusions.


Aneurysms of the coronary arteries in the adult. Clincial and angiographic features.

One thousand coronary arteriograms were reviewed to determine the incidence, clinical presentation and angiographic features of aneurysms of the coronary artery (ACA) in adults with angina. Criteria for the angiographic diagnosis are described and the angiographic aspects are emphasized. The incidence of ACA was 1.1%. Saccular and fusiform aneurysms were seen. Single aneurysms were present in 7 patients. One patient had an abdominal aneurysm. Five patients underwent surgery; two had postoperative selective coronary angiography one year later and all five underwent follow-up left ventricular angiography. The most likely etiology of the aneurysms in this series is atherosclerosis.


A spectrum of renal tubular ectasia and hepatic fibrosis.

Renal tubular cystic disease and hepatic fibrosis exhibit a specific genetic pattern and pathological findings. The renal collecting tubules are dilated and the liver shows fibrosis with proliferation and dilatation of the bile ducts. The findings fall into a spectrum with marked renal disease and mild liver involvement at one end and mild renal involvement with severe liver disease at the other. Between these extremes lies an intermediate form which is genetically and pathologically similar, but exhibits a wide range of clinical and radiological findings due to the variability of renal and liver involvement.


Continuous ultrasound B-scanning of palpable breast masses.

Of 210 pathologically confirmed palpable breast masses examined by continuous ultrasound B-scanning using a 2.5- or 7-MHz transducer and mammography, fluid filled cysts more than 1 cm in diameter were diagnosed accurately in 75 cases. Of the 103 solid masses studied by echography, 31 were circumscribed (29 benign fibroadenomas and 2 circumscribed medullary carcinomas) and 72 were not. Infiltrating carcinoma represented the majority of the latter type, although 2 cases of chronic inflammation had the same echographic appearance. Thirty palpable breast masses less than 2 cm in diameter were not delineated with the 2.5-MHz transducer, and biopsy showed benign disease. The combiantion of mammography and continuous ultrasound B-scanning of palpable breast masses improved the diagnostic accuracy obtained with mammography alone and aided in the differentiation of nondiagnostic mammograms.


Phase 1 study of high-dose metronidazole: a specific in vivo and in vitro radiosensitizer of hypoxic cells.

Metronidazole was administered orally to 25 patients and its maximum concentration in blood and tumor tissues, its ability to cross the blood/brain barrier and concentrate in the cerebrospinal fluid and brain tumor tissue, its immediate and long-term toxicity, and its enhancement of irradiation in normal tissue were studied. Maximum blood concentrations of 700-1,200 muM (120-220 mug/ml) were obtained at four hours with doses of 6 g/m2. Moderate and transient nausea and vomiting were the only immediate signs of toxicity. No long-term toxicity was found up to 18 months after administration of the drug. These data indicate that metronidazole can feasibly be adminstered in clinical trials of fractionated radiotherapy using dosages ranging from 9.5 to 11 g three times a week for three to four weeks.


Radiological manifestations of radiation-induced injury to the normal upper gastrointestinal tract.

Radiation-induced injury to the normal esophagus, stomach, and duodenum in patients with advanced cervical carcinoma who received high para-aortic lymph-node irradiation to an average tumor dose of 5,000 rads is discussed. Radiation esophagitis is usually the result of mediastinal irradiation for bronchogenic carcinoma. The most consistent radiological finding is abnormal motility, with esophageal stricture and/or ulceration occurrring less frequently. Radiation gastritis usually presents as pyloric ulceration or irregular contractions of the antrum, simulating gastric carcinoma. Postbulbar duodenal mucosal thickening, ulceration, and strictures may occur. Pertinent clinical features, pathogenesis, and pathological correlations are discussed.


Evaluation of B-mode ultrasound as a means of improving radium dosimetry in the treatment of gynecologic cancer.

The radiation dose to the base of the bladder and anterior rectal wall during radium applications for gynecologic cancer is a function of the distances between the source and the bladder and rectum. Precise measurement of these distances depends on a number of factors and cannot be obtained with current radiographic localization techniques. B-mode ultrasound is useful as a means of supplementing available information. While it is not necessarily more accurate than standard radiographs, it offers a three-dimensional appreciation of pelvic anatomy and does appear to be more accurate than transverse axial tomography.


The response of a human malignant melanoma cell line to high LET radiation.

The response of a human malignant melanoma cell line in vitro to high linear energy transfer radiation was studied utilizing the neutrons produced by the reaction of 16 and 50 MeV deuterons on beryllium. The relative biological effectiveness (RBE) relative to cobalt-60 gamma radiation was determined under conditions of complete oxygenation. The data indicate that the radioresistance ascribed to malignant melanoma in vivo is not an intrinsic quality of the cell but rather may be mediated by the in vivo environment.


Depth resolution: a mechanism by which high kilovoltage improves visibility in chest films.

Depth resolution, a measure of the thinnest layer of tissue which will cast a detectable radiographic shadow, significantly limits visibility in conventional chest technique. Depth resolution, averaged over the chest area, improves with increasing kilovoltage, and thin, soft tissues can be seen more readily. The visibility of calcifications increases with kilovoltage in some areas of the chest and decreases in others, which is again explained by depth resolution. Densitometric data verify the mechanism involved: the latitude of the radiographic image matches that of the conventional film at high kilovoltages, so that more chest images are recorded at high contrast where visibility is best.


Resolution of field-emission x-ray sources.

The physical designs of field-emission and conventional x-ray tubes are compared, and the physical and geometric source properties are translated into optical and resolution characteristics using modulation transfer functions calculated for idealized and practical sources and verified by star test pattern measurements. The field-emission design has several advantages: axial symmetry, circular shape, and a relatively favorable intensity distribution of the focal spot; in addition, the focal spot size is independent of the tube current. These advantages greatly enhance uniformity over the field of view and may increase resolution by a factor of 2 for a given nominal source size, thus largely ofsetting the greater physical size of present field-emission sources.


The steepness of the dose-response curve in radiation therapy. Theoretical considerations and experimental results.

The random nature of cell killing by ionizing radiations sets an upper limit on the steepness of the dose-response (D-R) curve for tumor cure. This theoretical limit was approached but not reached in a carefully controlled experimental system. It would seem unlikely that this result could be achieved in clinical practice because of the potential importance of tumor heterogeneity and treatment error in decreasing the slope of the D-R curve. In attempting to achieve a high degree of precision in treatment administration, the therapist, particularly in a multitreatment course, is aided by certain statistical rules which are applicable to random errors.


Time/dose relationships in experimental radiation cataractogenesis.

The response of the mammalian lens to fractionated radiation exposures was evaluated as a model system for predicting delayed radiation effects on normal tissue. Only the heads of male Ha/ICR mice were irradiated with 14 different time-dose schedules and followed for cataractous changes. A log-log plot of dose vs time yielded a line with a slope of 0.303 and ordinate intercept of 1050 R; a similar plot for dose vs fraction number yielded a slope of 0.382 and ordinate intercept of 835 R. Results suggest that the lenticular response to radiation may be a useful model for studying late effects.


The radioprotective effects of vasopressin on the gastrointestinal tract of mice.

Three-hundred Balb/C mice were used to assess the effect of vasopressin on the response of the gastrointestinal tract to irradiation. Median lethal doses were determined for control and vasopressin treated animals in which the whole abdomen was irradiated. There was a significant difference in LD50/6 (882 +/- 27 for controls vs. 1051 +/- 23 for vasopressin-treated animals). In addition studies demonstrated a significant difference in the survival rate of jejunal crypts at 800 and 1,000 rads.


An assessment of RBE of Californium-252 for C57-Black/6 mouse fibrosarcoma by a precise afterloading technique.

Afterloading techniques were developed for the in vivo assessment of the RBE of californium-252 with respect of radium-226 using a fibrosarcoma in mice. The afterloading holder positions sources so that the tumor is uniformly irradiated. Using the end points of tumor volumetric studies up to 150 days after irradiation, it was found that the RBE ranged from 5-8 at clinically relevant dose rates and total doses.


Cell cycle progression of murine sarcoma cells after x irradiation or heat shock.

DNA histograms of exponentially growing EMT-6 cells in vitro were obtained at regular time intervals after exposure at 300 rads of x rays or one hour of heat shock at 43 degrees C. After either treatment, about 70% of the cells retained clonogenicity. Irradiation induced the expected block in the G2 + M phase, resulting in an increase of cells in that phase during the first 5 hours after exposure. Heat shock caused a block in both the S and G2 +M phases.


Sialography: a simplified technique.

A simplified method of sialography is described. A wedged catheter tip positioned in the duct prevents backward leakage of contrast material into the oral cavity.


Use of a double screen-film combination in bedside chest roentgenography.

A double-screen/double-film combination in a single cassette overcomes technical difficulties encountered in bedside radiography with mobile equipment.


Prevention of leakage of low-melting-point metals from styrofoam molds.

Leakage of low-melting-point metals from the underside of polystyrene molds can be prevented by applying a silicone caulking material to the bottom of the mold and pressing the mold on a metal plate before pouring.


Problems of posterior fields.

Problems arising with the use of posterior fields can be solved by the undercouch technique. Treatment couches with a large window covered with transparent Mylar polyester (D) film can support the patient and do not interfere with the supervoltage beam.


Incompatibility of diphenhydramine hydrochloride (Benadryl) with meglumine iodipamide (Cholografin).

Diphenhydramine hydrochloride (Benadryl) and meglumine iodipamide (Cholografin) were mixed in varying proportions and found to consistently form a dense amorphous precipitate. This is not mentioned in the package insert of either agent. All physicians who administer these compounds should be aware of this phenomenon.


An afterloading applicator for intracavitary vaginal irradiation.

An afterloading apllicator for intracavitary vaginal irradiation that employs 137Cs sources in a T-shaped irradiator is described.


Gonadal shield.

A secondary gonadal shield for use in the pelvic irradiation of males was designed and built using material and apparatus available with the Cerrobend blocking system. The gonadal dose was reduced to approximately 1.5 to 2.5% of the given dose.


On the importance of teaching undergraduate radiology.

Radiology is a teaching tool that should be utilized throughout the four years of training of medical students. There are, however, not enough radiologists in academic life to teach radiology and recruit students to the specialty.


Radiology of athletic injuries: football.

During a 17-year period, 33 injuries produced radiographic abnormalities in 26 members of a professional football team. Sites of injury were correlated with playing position and protective equipment worn at the time of injury. Fractures of multiple transverse processes of the lumbar spine are reported in offensive halfbacks and offensive ends. Two linebackers and one center sustained fractures of the mid-forearm. Several related reports of the morbidity and mortality of football injuries are also discussed.


The clinical significance of cervical esophageal and hypopharyngeal webs.

One thousand consecutive cinefluorographic examinations of the hypopharynx and cervical esophagus were reviewed to determine the incidence of webs in a population routinely referred for upper gastrointestinal examination. The age, sex, and incidence of iron deficiency anemia in patients with webs were compared with those of the controls, and dysphagia and associated diseases were noted. 5.5% of the patients had one or more webs; these patients had a similar sex distribution to the control group but were generally older. Both groups had the same incidence of iron deficiency anemia. None of the patients with webs met the criteria for Plummer-Vinson syndrome. The authors believe that most cervical esophageal and hypopharyngeal webs are of no clinical significance.


Arteriographic demonstration of collateral arterial supply to the liver after hepatic artery ligation.

Eight patients were studied arteriographically after hepatic artery ligation (done to control bleeding in 6). Sources of arterial flow to the liver after ligation were (a) replaced or accessory hepatic artery; (b) interlobar collaterals in the liver; (c) right inferior phrenic artery; (d) through the gastroduodenal artery from arterial branches in the pancreas, duodenum, and omentum; (e) fine collateral branches of the gastroduodenal artery as they pass into the porta hepatis; and (f) recanalization of the ligated hepatic artery. Collateral vessels, seen as early as four hours after ligation, increase in size and number during the following six months.


Pharmacoangiographic evaluation of the hemodynamic significance of coronary artery stenoses.

Acute stenoses of varying degree were produced in the circumflex arteries of 5 calves, and chronic stenoses which reduced blood flow by about 50% were effected in the left anterior descending coronary arteries of 14 dogs. Selective vasodilators or amyl nitrite increased blood flow more than 100% in nonstenotic arteries, but less in stenotic ones. Increased transstenotic blood flow was associated with an increased pressure gradient and increased frequency of collateral circulation. Collateral circulation was sometimes recognizable when the pre- and postvasodilatory angiograms were compared but not when the angiograms were examined individually. The altered flow patterns demonstrated by comparative studies may be a very sensitive index of collateral circulation.


Control of experimental traumatic renal hemorrhage by embolization with autogenous blood clot.

Hemorrhage from artificially produced renal lacerations was controlled by selective arterial embolization with either plain or Amicar-mixed autogenous blood clot in ten dogs. The laceration sites healed as renal scars. Despite the presence of scattered, small renal infarcts caused by the embolization, hypertension did not develop in any dog during the two-month follow-up. No long-term differences could be detected between kidneys embolized with plain or modified clot. Although it is recognized that dogs have a more active fibrinolytic system than humans, the results of this study suggest that selective arterial embolization is a feasible method for controlling renal hemorrhage.


On the evaluation of medical students in radiology.

What a medical student has learned in radiology needs to be evaluated, not only to appraise the student's mastery of the subject but to determine the efficiency of teaching methods. A two-phase written/oral test for all students completing the fourth-year elective is described.


The peripheral zone of increase density in cranial computed tomography.

The band of increased attenuation seen on in vivo CCT images of adults, frequently designated as the cerebral cortex, has been proved clinically and experimentally to be an artifact in the reconstructed image. Recognition of this artifact may be of help in identifying intracranial lesions, such as shallow subdural hematomas. Attenuation values of isolated cortex and white matter were also studied and do not account for the band of high attenuation.


Cerebral hypervascularity and early venous opacification in status epilepticus. A case report.

Cerebral hyperperfusion and early draining veins directly resulting from status epilepticus can be demonstrated angiographically. Postmortem examination of the brain excluded other possible causes of hyperemia and early venous drainage.


Metastases to the medulla of the spinal cord: myelographic features.

Intramedullary metastases to the spinal cord of non-neurogenic origin are exceedingly rare, comprising fewer than 1.6% of all metastases affecting the spinal canal and its contents. Plain films are normal. Irregular fusiform widening of the spinal cord is the most common myelographic feature, although nodularity is also present. Complete blockage is very rare. The authors describe the radiological features in 4 cases of intramedullary metastases of non-neurogenic origin. The differential diagnosis is discussed, and some pathogenetic mechanisms are postulated. It is important to recognize intramedullary metastases in order to plan the proper management.


Regional pulmonary function in supine patients with mitral valve disease.

Supine tidal volume regional ventilation and perfusion images obtained in the posterior and lateral projections demonstrated several alterations in patients with mitral valve disease. Reversal of the gravitational perfusion gradient correlated with pulmonary venous and arterial hypertension; the supine studies reliably distinguished normal subjects from mitral patients. The reversed gradient was from posterior-base to anterior-apex. Focal defects were common and contributed to the reversed gradient in 50% of patients. Perfusion defects larger than those of ventilation, simulating emboli, occurred in 32%, particularly in the middle lobe and superior segment areas. Relative hypoventilation of the left lung was seen in 44% of these patients.


Molecular conformation prostaglandin A1 monoclinic crystalline polymorph.

The molecular conformation of the monoclinic crystalline polymorph of prostaglandin A1 has been determined by X-ray diffraction techniques. The space group is P21 with a = 13.637(2), b = 7.567(1), c = 10.576(2) A, beta = 107.37(3) degrees; Dc = 1.073 g.cm-3 for Z = 2. The molecular conformation is characterized by the nearly parallel arrangement of the C1-C7 and C13-C20 side chains, with a general flattening of the overall structure when compared with the orthorhombic polymorph. The cyclopentenone moiety assumes a C8 envelope conformation with C8 and O9 displaced +0.29 A and -0.18 A from the C9-C10=C11-C12 plane respectively. Concerted, small varations of the torsion angles, primarily about the C8-C12, C14-C15 and C16-C17 bonds, bring the monoclinic and orthorhombic conformations into coincidence.


Effect of prostaglandin E2 on the pressor response to periarterial stimulation and norepinephrine of the isolated perfused rabbit kidney.

The interaction of prostaglandin E2 (PGE2) and aspirin with the responses to peri-arterial stimulation (PS) and norepinephrine (NE) was studied in the isolated kidney of rabbit perfused through the renal artery at constant flow with Krebs' solution. NE and PS increased vascular perfusion pressure of kidney and caused a contraction on the isolated rabbit aortic strip superfused with the effluent from kidney. Addition of PGE2 to the perfusion medium decreased the PS-induced rise in perfusion pressure without changing the effect of exogenous NE. In contrast, addition of aspirin to the perfusion medium induced a potentiation of the response to PS but not to NE. These results suggest that PGE2 modulates the effect of PS probably by inhibiting the releases of NE from sympathetic nerve endings.


Partition of PGE between renal venous plasma and urine during renal ischemia.

Radioimmunoassay was used to study the effects of renal ischemia on the distribution of PGE-like material between renal venous plasma and urine in anesthetized dogs. Renal venous and urinary concentrations of these substances were equal during control, ischemia and recovery periods. This relationship obtained despite significant increases in the concentration of PGE of both compartments during the ischemic insult. The renal secretion rates of PGE, calculated as the product of renal plasma flow and renal venous concentrations, was reduced during ischemia while urinary excretion, was unchanged. The evidence suggests that the increased PGE concentrations observed in both compartments during renal ischemia are primarily due to a dilutional factor rather than an increased synthesis. Furthermore, the data suggest that the net secretion of renal PG's per unit time may, in fact, be reduced during renal ischemia.


In vitro ovulation of trout oocytes: effect of prostaglandins on smooth muscle-like cells of the theca.

Ovulation (active expulsion of oocyte from the mature follicle) of trout follicles matured in vivo can be induced in vitro by adding PGF2alpha at doses of 1 and 5 mug/ml. PGE2 is ineffective. The in vitro induction of ovulation by PGF2alpha is inhibited in a calcium free medium or by inhibitors of calcium influx, particularly by Mn++ and La+++, suggesting the ovulation process implies active contraction of the smooth muscle cells of the theca. A significant but partial inhibition is also observed with cytochalasin B (1 and 5 mug/ml) demonstrating that contraction of other cell types than muscle, containing actin-like filaments, may also participate in the process.


The effects of prostaglandins PGE1, PGE2, PGF1a, and PGF2alpha on canine synovial perfusion.

In these experiments we have examined the effects of PGE1, PGE2, PGF1alpha and PGF2alpha on synovial perfusion in the normal canine synovial microcirculation. The effects of the drugs on synovial perfusion were determined indirectly from the changes produced in the rate of clearance of 133Xenon from the joint by their intra-articular injection. Prostaglandins PGE1 and PGE2 were found to be strongly vasodilator with PGE1 being the more active. PGF1alpha appeared to have little or no vasoactive properties in doses up to 1 ugm. (2.8 times 10(-5M)) in our preparation while PGF2alpha was vasodilator at this high dosage only. Neither SC19920 nor diphloretin phosphate antagonished the effects of PGE1 in these experiments.


Prostaglandins and renal function. II. The effect of prostaglandin inhibition on autoregulation of blood flow in the intact kidney of the dog.

In order to evaluate the effect of prostaglandin release on renal autoregulation in the intact kidney of the dog, pressure-flow curves were obtained before and after the administration of either indomethacin or meclofenamate, two potent prostaglandin synthetase inhibitors. After drug administration renal venous prostaglandin E decreased in each of eight studies with a mean change from 286 to 141 pg/ml (p less than .001). In addition, prostaglandin inhibition was associated with a 31 percent decrease in renal blood flow and 58 percent increase in renal resistance. Yet, as renal perfusion pressure was decreased by aortic constriction, the change in flow per pressure reduction and the percent change in renal resistance were not significantly different after prostaglandin inhibition when compared to control values in the same animals. The magnitude of the pressure range over which autoregulation was maintained was also similar in the two groups although both the initial and lowest level of autoregulation were slightly higher after prostaglandin inhibition. It is concluded that the administration of these prostaglandin synthetase inhibitors does not significantly impair renal autoregulation in the intact dog kidney.


Action of prostaglandin F2alpha on pregnancy in hamsters: luteolytic and extra-ovarian effects.

Pregnancies in hamsters may be terminated by 10 mug PGF2alpha administered b.i.d. on days 4, k and 6 of gestation. Small (250 mug and above) daily injections of progesterone on the same days will reverse this PG effect; in contradistinction, 10 mg of progesterone per day failed to maintain normal pregnancies in hamsters spayed on day 5. Daily administration of 3 mg of progesterone and 1 mug of estrone essentially normalized the gestation; administration of PGF2alpha at 10 mg on days 5, 6 and 7 of pregnancy in steroid-maintained rats, resulted in pregnancy termination in all animals, while 1 mg was partly effective. These data demonstrate an extra-ovarian site of action of prostaglandin F2alpha on pregnancy in hamsters.


Intrauterine instillation of prostaglandin F2ALPHA IN EARLY PREGNANCY.

Intrauterine PGF2alpha (5mg) was administered for termination of early pregnancy in 14 healthy volunteers. With 11 complete abortions, the efficiency rate of this technique is below conventional methods. In addition, the incidience of infection was high occuring in 12 out of 14 subjects. Because of persistent bleeding, six patients underwent a dilatation and curettage. Other significant side effects included transient hypertension, pain, nausea and restlessness. In the patients with a complete abortion, the mean plasma progesterone concentration fell 37% after 8 hours post PGF2alpha instillation and 90iod and 75% over the next 14 days.


Induction of temporary sterility in female hamsters by an intraperitoneal silastic-PVP-PGF2alpha tube.

In the female hamster, temporary sterility for a period of 10 or 15 days was induced by an intraperitoneal Silastic-PVP-tube containing 3.5 or 1.0 mg of PGF2alpha, respectively. All Silastic-PVP-PGF2alpha tube hearing animals regained fertility and delivered normal litters at various times after the placement of the tube. The release rate of 3-H-PGF2alpha from the Silastic-PVP tube was described and their potential use as a drug delivery system discussed.


Peripheral plasma progesterone and utero-ovarian prostaglandin F concentrations in the cow around parturition.

The concentration of prostaglandin F in utero-ovarian venous plasma and proseterone in jugular venous plasma were determined by radioimmunoassay in 3 cows over the last 2-3 weeks of gestation. Utero-ovarian prostaglandin F concentrations did not show and consistent pattern in two hours of three cows until 48-72 h before term when the levels rose sharply from 1 ng/ml to maximum 4-9 ng/ml during labour. The concentration of prosterone in jugular venous plasma tended to fall gradually over the last 20 days of gestation with a further fall occurring 48-36 h before delivery.


Pre-ovulatory changes in follicular fluid prostaglandin F levels in swine.

The concentration of prostaglandin F (PGF) has been measured by radioimmunoassay in follicular fluid collected from follicles at various time intervals after treatment of prepuberal gilts with pregnant mare serum gonadotropin and human chorionic gonadotropin to induce ovulation. A high proportion of animals will ovulate 116 +/- 8 hr after treatment. Pre-ovulatory follicles can be identified on the basis of gross morphological apperance 10-12 hr before the predicted time of ovulation. The concentration of PGF in fluid from follicles judged not to be pre-ovulatory was relatively constant at about 0.45 ng per g and appeared to be independent of the time of sampling. An increase in the concentration of PGF was observed in fluid collected from follicles classified as destined to ovulate. This increase became more pronounced as the time of ovulation approached and reached a maximum at or about the time of follicle rupture. These data provide evidence in support of a role for prostaglandins in the ovulatory process in the pib.


Effect of PGE1 on gluconeogenesis and glycerol esterification in perfused liver of fasted rats.

Using perfused livers of rats fasted for 48 hours, glucose production and incoroporation of 2-14C pyruvate (trace dose) into perfusate glucose were studied. Both were found to be inhibited by PGE1 (infuced at a concentration of 0.5 mu/min) by about 60%. The incorporation of 1-14C glycerol into perfusate glucose and into glycerol-glyceride part of the liver glycerides were also studied, using the same test conditions. The former incorporation was significantly inhibited (56%) and the latter strongly stimulated (360 %) by PGE1. PGE1 had no effect on glucose production in a perfusate overloaded with sodium pyruvate, nor on pyruvate carboxylase and phospho-enolpyruvate carboxykinase activity. this was in contrast with the results obtained in perfusions with a trace dose of 2-14C pyruvate. The results showed that PGE1, at the physiological concentration used, stimulated the incorporation of 1-14C glycerol into glycerol-glyceride part of liver glycerides and, when there was no overload of pyruvate present in the perfusion medium, inhibited gluconeogensis at some point, possibly, but perhaps not exclusively, between the glycerol and glucose steps.


Bronchopulmonary effects of prostaglandin F2alpha and three of its metabolites in the dog.

The airway and lung dynamics of porstaglandin F2alpha (PGF2alpha) and three of its metabolites were examined in the spontaneously ventilated, pentobarital anesthetized dog. Changes in expirtaory flow rate, tidal volume, respiration rate, lung resistance and dynamic lung compliance were evaluated and compared quantitatively. In a dose range of 0.3-3.0 mu/kg i.v., PGF2alpha and its 13, 14-dihydrometabolite were found to be exceptionally potent agents. This metabolite was approximately twice as potent as PGF2alpha on most parameters studied. Two other metabolites, 15-keto-PGF2alpha and 15-keto-13, 14-dihydro-PGF2alpha, were only slightly effective, even in a dose range of 1.0-30.0 mu/kg i.v. These latter two metabolites produced dose-response curves with significantly shallower slopes than PGF2alpha and were shown to be at least thirty-five times less potent than the parent compound. Therefore, oxidation of PGF2alpha at the carbon-15 position by 15-hydroxy prostaglandin dehydrogenase appears to produce compounds with minimal in vivo bronchopulomary activity.


Hormone changes occurring during second trimester abortion induced with 15 (S)-15-methyl prostaglandin F2alpha.

Changes in progesterone, human placental lactogen (HPL), cortisol and estradiol-17B were measured during second trimester abortion induced by I.M. 15-methyl PGF2alpha. A rapid decline in progesterone and HPL was found, indicating perhaps an initial effect on the placenta. A rapid rise in cortisol was found, but it is not clear if this is due to stress or part of the termination mechanism. The changes of estradiol were not as distinct and may reflect opposite effects of the prostaglandin on the placenta and adrenals. Similar hormonal changes were observed regardless of the duration of gestation.


Acute renal insufficiency in the rabbit by glycerol.

The appearance of an acute renal insufficiency in the rabbit, after glycerol injection (10, 13 or 15 ml/kg of a 50% solution) is investigated. After a 24 hours of intoxication, especially in the ten following days, cylinders, erythrocytes and renal cells appear in the urine sediment. Proteinuria appears after 24 hours and practically disappears after 72 h. Glucosuria persists from 24 hours to 6 days. Haemoglobinuria is intense after 24 and 48 hours and persists slightly about 6 days. Na, K and Cl elimination in urine diminishes clearly in all animals. Plasma K increases in non-surviving animals and does not change in those surviving. Plasma Na does not change in the dying ones, and decreases in those surviving. In non-surviving animals, pH, pCO2 and CO3H minus decrease sharply. In the surviving ones pCO2 decreases clearly after 24 hours, increasing afterwards slowly to normal values. pH increases, slightly during the first 48 hours, and then neatly during approximately 6 days. Standard CO2H minus does not change during the first 48 hours, increasing afterwards during 6 to 7 days. Histologically, the chief lesion is a vacuolar degeneration of the proximal tubule. The possible mechanisms of such alterations are discussed.


Biochemical changes in Pinus pinea seeds. II. The stimulation is isocitrate lyase and malate dehydrogenase activities by exogenous growth substances.

Treatment of intact pine seeds with plant hormones and steroid substances for several days, after an initial 24 hour immersion in different hormone solutions, resulted in a substantial increase in the specific activity of isocitrate lyase and malate dehydrogenase than the observed in the corresponding control solutions. Fresh weights did not show any increase, because water uptake was reduced in presence of plant hormones (indolacetic acid, kinetine and giberellic acid). However, dry weights were consistently greater than those of the control solutions.


[Dehydrogenase denaturation by guanidine hydrochloride measured by fluorescence (author's transl)].

Denaturation and subsequent renaturation of the enzymes Lactate, Glucose-6-phosphate, Glutamate and Alcohol dehydrogenases, by means of fluorescence spectra and the variation of enzyme activity in each conformational state, have been studied. The denaturating agent has been Guanidine chloride in a range of concentration from 0.5 to 6 M. Special behaviour has been observed in each enzyme in the presence of the denaturating agent. The action of this agent is compared with that of urea. The renaturation percentages obtained are relatively low. Interaction between the denaturating agent and the aminoacids producing the fluorescence of the enzymes is observed.


Behaviour of lymphocytes from cancer patients and normal individuals cultured with phytohaemagglutinin.

Blood lymphocytes from cancer patients with solid tumours without any previous immunosuppressive treatment and from normal individuals, were cultured in vitro with a wide range of phytohaemagglutinin (PHA). Sixty two per cent of all the cancer patients studied show a minimal of no response to PHA in comparison with the normal population. The rest (38%), show a quantitative identical response than normals. However, the maximal response in these patients occur in the high PHA doses, while the normal individuals show their maximal activity with low PHA doses. The low or no PHA response showed by the 62% of patients, may indicate they have impaired cellular immunity. The high response showed by the other 38%, may indicate that the patients of this group have high cellular immunity capacity. This immunity, however, higher PHA doses are required to reach the maximal response compared with the seems to be different from that of normal individuals, since higher PHA doses are required in cancer patients to reach maximal response. These results also suggest that a large range of PHA doses may be important to detect the degree of cellular immunity in cancer patients compared with the normal population. One or two random PHA doses, may not show a distinction.


[Effect of amitriptyline and nortriptyline on the intracular pressure and aqueous humor dynamics in rabbits (author's transl)].

Both amitriptyline and nortriptyline applied conjunctivally produced pupil size enlargement, intraocular pressure decrease and a fall in aqueous humor formation. Phenoxybenzamine and superior cervical sympathetic ganglionectomy prevented the amitriptyline or nortriptyline inducing intraocular pressure changes. Either systemic administered or conjunctivally applied amitriptyline or nortriptyline, potentiated the effects on the pupil and intraocular pressure of exogenously norepinephrine.


[Effect of 6-hydroxydopamine intracerebrally injected on reproduction in rats (author's transl)].

The effect of 6-hydroxidopamine (6-OH-DA) --250 mug-- intracerebrally injected on rat ovulation has been studied. Administration of 6-OH-DA in the nucleus accumbens septi and its heigbhourhood, inhibited follicle rupture, causing ovarian cycles with leucocitary phases in nearly all cases. The ovaries present a deep lutteynitation. Administration of 6-OH-DA in the strio-hypothalamic tract gives rise to a estrogenic cycle and to a normal number of oocytes in the tubes. The study of the fibrillar degeneration leads us to assumption of a probable adrenergic connections of the nucleus accumbens septi with the lateral hypothalamic area, preoptic area and olfactory tubercule. The influence of the nucleus accumbens septi on the mechanisms of follicle rupture is stressed.


[Effect of various coumarins on the intestinal absorption of galactose in vivo (author's transl)].

The effect of various coumarins on the active transport of galactose by small intestine in chick and rat was studied, using the in vivo technique of sucessive absorptions. A 10(-4) M concentration of the different coumarins inhibits the absorption of galactose in the chick. This effect persists in successive absorptions without coumarin. In rat, inhibition of galactose active transport by coumarins was observed at 10(-3) M concentration.


Active transport of sugars by the intestine of snail (Cryptomphalus hortensis Müller).

Sugar transport by sacs of everted intestine of snail have been measured in vitro at 30 degrees C. D-galactose, D-glucose and 3-O-methylglucose were actively transported against a concentration gradient from the mucosal to the serosal compartment. The transport of these sugars was inhibited by 5 times 10(-8) to 10(-6) M phlorizin. L-arabinose was also accumulated in the serosal compartment against a concentration gradient; in this case, transport was not affected by phlorizin. The snail intestine did not show any ability for D-fructose active transport but there was a clear uptake of this sugar by the tissue. The O2 uptake of the snail intestine was not significantly affected by the presence of either sugars or phlorizin.


Effect of anaerobiosis, dinitrophenol and fluoride on the active intestinal transport of galactose in snail.

The active transport of galactose across the intestinal wall (everted sacs) of the snail Cryptomphalus hortensis Müller has been studied in vitro, under several metabolic conditions. Anaerobiosis does not change the serosal/mucosal galactose gradients which are developed in oxygen atmosphere. Dinitrophenol (10(-4) M) greatly increased the O2 uptake by the tissue and clearly inhibits the sugar transport. At 5 times 10(-4) M concentration, DNP totally prevents the uphill transport while the O2 uptake is normal. The inhibition produced by DNP does not increase by anaerobiosis. Fluoride inhibits the galactose transport and also the O2 uptake. It is deduced that in snail intestine the energy for the active transport of galactose can be supplied by aerobic as much as by anaerobic metabolism. The inhibition by dinitrophenol seems to be independent of its uncoupling action on the oxidative phosphorylation. The inhibitory effect of NaF may be due both to glycolisis inhibition and to alteration of the digestive epithelium.


[Posterior hypothalamus action on gastric secretion (author's transl)].

Three groups of cats with surgically created total gastric pouches were employed in this experiment. They were divided as follows: in one group the innervation of the pouch was left intact; in another group the symphathetic innervation of the pouch was removed; and in the third group the pouch was completely denervated. It was seen that an infusion of histamine induced gastric secretion in all three groups. And when the secretion became constant it proved to be less acidic and more abundant in the sympathectomized group and also in the group that had suffered complete denervation. It was observed now that stimulating the posterior hypothalamus of the innervated group produced, in all of the cats, a decrease in the amount of acid secreted per unit of time. Consequently, it was seen that a symphathectomy did not eliminate the gastric effects produced when the posterior hypothalamus was stimulated. Specifically, stimulation of the posterior hypothalamus produced an increase in the amount of secretion rather than a decrease. The increase produced in these animals can be shown not to be due to irradiation of the anterior hypothalamus as the same response is obtained when a symphathectomy is combined with a vagotomy. It is, therefore, believed that it may be concluded that the Posterior hypothalamus does not produce its effect exclusively through its nervous pathways. It is believed its effect may possibly be mediated by an unknown substance liberated upon stimulation which then reaches the stomach by way of its blood supply.


Isocitrate lyase activities in Pinus pinea seeds.

Some features of cytoplasmic and glyoxysomal isocitrate lyase obtained from stratified and germinated P. pinea seeds, respectively, are described. Both activities showed a different electrophoretic mobility on cellulose acetate and elution behaviour on Sephadex G-200. Cycloheximide inhibited the increase of both activities during the first days of germination. Chloramphenicol did not show the same effect.


[Radioimmunologic method for the measurement of plasmatic LH in humans (author's transl)].

A simple radioimmunologic method for the measurement of plasmatic LH concentration is described. This procedure utilizes a second antibody for the separation by precipitation of the bound from the free hormone. LH is labelled with 125I by means of a modified Greenwood and Hunter Chloramine T procedure. Three reference compounds, LER-907, MRC 68/40 and 2nd IRP-HMG, have been compared. The daily plasma concentrations of LH along the menstrual cycle in 12 young normal women and the changes induced by 100 mug LHRH were measured, validating the method used since it is capable of detecting the expected variations.


Marihuana metabolites in urine of man. V. Characterization and separation of polar metabolites of delta-9-tetrahydrocannabinol.

Extraction of human urine with ether at pH 12 and thin-layer chromatography using two solvent systems permitted separation of several polar metabolites of delta-9-tetrahydrocannabinol (THC), not previously isolated by these techniques. These metabolites appeared as conjugates and are probably dihydroxy alcohols.


Identification of a metabolite of thioridazine and mesoridazine from human plasma.

The major unknown component present in the plasma of all subjects given thioridazine (la) or mesoridazine (lb) has been identified by TLC, GC, and mass spectrometry as thioridazine side-chain sulfone (sulforidazine) (1c).


Pharmacological actions of some simple analogues of reserpine. I. Analgesic effects.

In view of the fact that reserpine treatment lowers pain threshold, structural analogues of reserpine molecule were tested against thermal and visceral pain. Some compounds belonging to piperidino- and morpholino derivatives of acetanilide showed promising analgesic activity. These compounds in earlier studies had shown tranquillizing effect. Combination studies with meperidene, phenylbutazone, phenazone and meprobamate did not significantly change the analgesic activity in thermal methods but the test-compounds were potentiated by phenylbutazone and phenazone in writhing test.


Pharmacological actions of some simple analogues of reserpine. II. Anticonvulsant effects.

Reserpine analogues obtained from strip-down parts of the parent molecule were studied for their effects on experimental convulsive seizures and amphetamine antagonism. The unsubstituted and M-methoxy substituted piperidino- and morpholino acetanilides derived from A, B and C rings or reserpine showed prominent anticonvulsant activity as against the known lowering of threshold activity by reserpine. Methoxy morpholino derivative showed prominent activity with least sedative effect. gamma-Piperidino acetanilide showed a dual effect such that at higher doses it itself produced clocin covulsions. The effects were non-specific since they unpreferentially antagonized the maximal electrochock, Metrazol and strychnine convulsions Compounds derived from C, D and E rings of reserpine did not significantly increase or decrease the seizure thresholds.


Characteristics of uptake of [3-H](plus or minus)-metaraminol by human fallopian tube.

The characteristics of accumulation of 5 X 10 minus8M [3-H] (plus or minus)-metaraminol were studied in isolated human fallopian tube. In both the ampulla and isthmus, the amine was concentrated against the concentration gradient; Accumulation  was inhibited by noradrenaline, cocaine, and ouabain but not by oxytetracycline or normetanephrine. It was concluded that [3-H] (plus or minus)-metaraminol was accumulated in the adrenergic nerves present in the human fallopian tube.


Dose dependent kinetics of carbamazepine in the monkey.

The blood concentration-time curve of carbamazepine in monkeys following intravenous infusion of the drug at two different levels was determined using a specific gas liquid chromatographic assaymconcentration values measured over a two and one-half decade concentration range during zero order infusion as well as the decay portion of the curve for both doses were computer fit using a nonlinear least-squares program and found to follow Michaelis-Menten kinetics. There was little change found in the volume of distribution for carbamazepine from monkey to monkey, however, marked differences were noted in the metabolic rate constants.


Comparison of 3,4-dimethoxyphenylethylamine treated plasma from chronic schizophrenics and controls.

Plasma samples were collected from chronic schizophrenic patients not on drug therapy and from non-psychotic hospital volunteet controls and incubated with 3,4-dimethoxywhenylethylamine (DMPEA) when injected into monoamine oxidase inhibitor (MAOI) pretreated mice who were then aggregated (groups of 5 ea.) for four hours, the two kinds of plasma produced results so similar that no differences between them could be observed. Doubling the amount of plasma and DMPEA likewise failed to differentiate plasma origin. In our hands no differentiation between plasma samples from control subjects and schizophrenic patients could be determined under the conditions employed.


Alcohol drinking in the rat after destruction of serotonergic and catecholaminergic neurons in the brain.

Rats were offered solutions of ethyl alcohol that were increased in strength from 3-30% concentration over a 12 day interval. Then, 50 mug 5,6-dihydroxytryptamine (5,6-DHT), 200 mug 6-hydroxydopamine (6-OHDA), or 100 mug 5, 7-dihydroxytryptamine (5,7-DHT) were injected acutely into the lateral cerebral ventricle in a 20 mul volume. The selection of ethyl alcohol was enhanced following the lesioning of serotonergic neurons by 5,6-DHT in terms of preference-aversion curves as well as the gm/kg intakes. Conversely, a similar destruction of dopamine and norepinephrine containing neurons by 6-OHDA marked suppressed alcohol preference and the overall intake of this fluid. 5,7-DHT had an intermediary effect of alcohol intake. These findings support the concept that the selection or rejection of alcohol may depend on an imbalance in the neuronal activity of either monoaminergic system in the brain of the rat.


Effects of methamphetamine on the isolated rat phrenic nerve-diaphragm preparation.

Low concentrations of methamphetamine facilitated twitch, while higher concentrations produced dose-dependent blockade of twitch indirectly elicited. Methamphetamine facilitated twitch elicited by direct stimulation; These findings suggest that methamphetamine-induced enhancement in physical endurance and performance in moderate doses, and muscle weakness at high doses, may be attributed to drug effects at a peripheral site of action.


Differences of reabsorption of unconjugated BSP and BSP-glutathione from the rat biliary tree after retrograde intrabiliary injection.

It has been shown that water and electrolytes are reabsorbed from the biliary tract of the rat. Furthermore there are some suggestions for the reabsorption of organic compounds during their passage down the biliary tract. Our results presented in this paper demonstrate a different mode of biliary excretion of unconjugated BSP [BSP-U] and BSP- glutathione [BSP-GSH] after retrograde intrabiliary injection, BSP-GSH is excreted to a much greater extent than BSP-U within the first 5 minutes after retrograde administration. In other terms BSP-GSH is reabsorbed to a lesser extent than BSP-U. Additionally the reabsorption of BSP-U and BSP-G after retrograde injection seems to be dependent on the concentration and the contact time in the biliary tree. It is suggested that the different biliary excretion of BSP-U and BSP-GSH after intravenous injection might be explained partly by a different reabsorption mode.


[Method for the isolation of human glomerular basement membrane (author's transl)].

In order to obtain pure glomerular basement membrane for chemical analysis, we could develop the following method. The isolated glomeruli are treated with a 0.08% polyoxyethylene-sorbitaine-monooleate for 3-5 minutes and they are homogenized in this detergent. The homogenate obtained is placed in a sucrose gradient with the specific density between 1021 to 1081. After standing for 30 minutes in a refrigator, the homogenate was separated into three layers. The uppermost layer contained fragmented cell debris, the second layer was consisted of the endothelial and epithelial cells. In the third layer, which was clearly separated from upper two layers by the translucent zone, the basement membrane were found. The position of the third layer is different in normal and pathological glomeruli, and the width of the layer is very narrow. According to this method only a very little contamination with other glomerular cell fraction is observed. The application of the 0.08% polyoxyethylene-sorbitane-monooleate did not induce any appreciable change in the structure of basement membrane, because carbohydrate composition and sialic acid content of this preparation were essentially identical with the data reported by several authors who prepared basement membrane by ultrasonic method. Electron microscope also revealed that the isolated glomerular basement membrane preserved lamina densa completely attached with partly stripped lamina rara interna and externa. Our method to break glomeruli is inexpensive and less time-consuming than the breakage with ultrasonic vibration. Isolation procudure with density gradient is obviously superior to the simple centrifugation or settling method adopted by others.


[Prophylaxis of acute gastric erosions with vitamin A in the rat (author's transl)].

The protective effect of Vitamin A against stress-induced ulcerations of the gastric mucosa was investigated by the hypoxic stress model of the rat. The incidence of acute mucosal erosions in the main stomach was significantly reduced by intramuscular application of 125 000 - 500 000 U Vitamin A/kg body weight prior to or immediately after the onset of stress. A dosage smaller than that or an application 2 hours after the onset of stress had no influence on the development of the acute mucosal erosions.