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The goals of the orthopedic surgeon in the preoperative, operative, and postoperative phases of surgical reconstruction of the hip are presented. The surgeon works closely with other professionals in the care of the patient and depends especially on the physical therapist in the postoperative phase.

Physical therapy management of patients who undergo total prosthetic replacement of the hip at St. Margaret Memorial Hospital is an integral aspect of a multidiscipline process of rehabilitation. Patients requiring total hip replacement have a variety of medical problems and, subsequently, have postoperative conditions which influence the physical therapy plan of care. The scope and pace of our physical therapy program are governed by criteria which emphasize the medical status, individual capability, and motivation of each patient. Arbitrary postoperative time intervals are not considered in the design of our physical therapy program. In addition, physical therapists have responsibility beyond the delivery of quality service which includes collaboration with other members of the rehabilitation team in the development and evaluation of the total surgical program.

Sensory-specific and modality nonspecific average evoked potentials (AEPs) were recorded from the cortical areas and subcortical structures in two groups of cats: (1) normal cats which after conditioning were subjected to brainstem lesions and reconditioning; (2) cats with brainstem lesions and subsequent conditioning. A new waveshape of the visually evoked potenials developed in the visual cortex in the course of conditioning to light flashes (LF) in both groups of cats. In normal cats, a new component, with a peak latency from 80-100 msec and with reversed polarity, was observed in place of the late, longlasting, component of the preconditioning AEP. The latency of the new component is longer in cats with brainstem lesions. The first signs of waveform modification occurred relatively early in the process of learning, well before the animal learned to react consistently to the conditioned stimulus. Also, there seemed to be no clear relationship between the modified waveshapes of the AEPs and performance level during a particular session of conditioning. The modifications did not depend on habituation to the long-lasting exposure to light flashes presented alone. The new waveshape was preserved to a variable degree after brainstem lesions, that is, reconditioning never started with a potential characteristic for a naive animal. AEPs to licks in the auditory cortex, also changed during conditioning, although this modification was not so evident as in visual responses. In contrast to evident modifications of evoked responses in sensory specific structures during the process of conditiong, there were very small if any, changes in modality nonspecific structures, including brainstem reticular formation. Modality nonspecific responses were obtained from the brainstem reticular formation and motor cortex to light flashes and clicks, from the visual cortex to auditory stimuli and from the auditory cortex to light flashes. Only poorly developed evoked responses could be detected in the motor-sensory cortex during conditioning to light flashes although rhythmic EEG activity related to presentation of the conditioned stimulus (CS) was observed from this arena - thus indicating that they were not the same phenomena.

Rats were tested in a darkened chamber containing two levers, one of which turned on a dim light when depressed. Rats receiving non-contingent electrical stimulation of the lateral hypothalamus made many more lever presses than did unstimulated controls and made more presses on the light producing lever than on the inactive one. Pretests had shown that the electrical stimulation elicited consummatory behavior in the presence of appropriate goal objects. Dynamic hyperphagic rats maintained on a restricted diet made more total responses early in testing than did their controls which also received the same restricted diet. They also preferred the light producing lever, but not reliably more than did their controls. Static hyperphagic rats made fewer total responses than did their controls, both groups receiving food ad lib. Neither group showed any preference between the two levers.

Schedule-induced polydipsia was studied in rats on a variable second-order schedule in Experiments 1 and 2. Drinking occurred only following presentations of the pellet reinforcer and was not induced by a stimulus that was associated with pellet delivery. Moreover, it was shown that lever pressing for food was not competing with the opportunity to drink following the stimulus during non-reinforced intervals. In Experiment 3 a fixed second-order schedule was used, and only one animal drank following the presentation of the stimulus. A positive contrast effect was obtained with schedule-induced drinking in Experiments 1 and 2, and it was suggested that schedule-induced polydipsia shows behavioral interactions similar to those seen with food reinforced operants.

Male rats were selected for showing or not showing lordosis in response to manual stimulation. They were subsequently tested for mounting behavior with receptive females and for lordosis behavior in response to manual stimulation and to male mounting. Males showing lordosis as intacts displayed this behavior more readily following castration or castration and treatment with estradiol benzoate or testosterone propionate than males which did not show lordosis before castration. No group differences in mounting behavior could be detected under any of the endocrine conditions studied. It is suggested that the neural mechanisms mediated mounting and lordosis are dissociated and that individual differences in the occurrence of lordosis in male rats are due to differences in neural sensitivity to estrogen.

Inhibition of brain protein synthesis by anisomycin and acetoxycycloheximide was studied in mice for its biochemical and behavioral effects. By employing both drugs in low doses in a series of injections, we were able to maintain inhibition of protein synthesis of 80% or greater for up to 14 hr without causing detectable permanent physiological impairment. The drugs were employed as amnestic agents in mice trained to avoid footshock in a T-maze. As the duration of inhibition increased, the percentage of mice classed as amnesic increased. This amnesia could be reduced by increasing (a) the rate of acquisition, or (b) the number of training trials. Anisomycin was shown to cause a significant degree of amnesia for the escape component as well as the avoidance component of the learning. A single injection of anisomycin given 15 min prior to training did not cause significant changes in the acquisition or retention of avoidance conditioning, when comparison was made with saline-injected controls. Only additional injections given after training to prolong inhibition caused amnesia. Thus, those injections critical in obtaining amnesia were given at a time at which interference with acquisition could not have occurred, so the results bear clearly on memory processes.

Prey attack behavior was studied in two species of garter snakes (Thamnophis sirtalis and T. radix). Newborn, ingestively naive, and experienced snakes had their tongues severed surgically, while control groups retained their tongues. Attack latency, tongue flick frequency and an orientation-interest measure were recorded for each subject on responses to extracts prepared from species-characteristic prey. Feeding, as well as responses to prey extracts, were found to be suppressed almost totally in the tongueless naive snakes. A detongued adult, however, readily ate although its behavior was abnormal. Temporary blind and anosmic conditions did not have a significant effect on response rates of the tongueless or control groups. While importance of the tongue-Jacobson's organ system is demonstrated, the length of tongue removed and presurgery experience are important factors.

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.

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.

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.

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.

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 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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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 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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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, 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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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 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 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.

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 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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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 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.

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.

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.

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.

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.

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.

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.

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.

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.

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 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.

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.

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.

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.

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.