Effects of diazepam on sleep, temperature, 5-hydroxyindoleacetic and homovanillic acids in cisternal cerebrospinal fluid of cats. The effects of diazepam (DZ) (0.3--1.5 mg/kg, i.p.) on sleep, cisternal cerebrospinal fluid (CSF) concentrations of 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA), and rectal temperature of cats were examined. The results showed that administration of DZ produced a significant increase (p = 0.02) in slow-wave sleep (SWS) with a peak occurring at a dose of 0.9 mg/kg. Further increase in doses of DZ decreased SWS. DZ administration produced no change in paradoxical sleep, rectal temperature, 5-HIAA or HVA CSF levels. Lack of correlation between various doses of DZ, and 5-HIAA or HVA concentrations in the presence of an increased percentage of SWS suggests a possible mode of DZ action mediated through a mechanism independent of monoamines. Usually monoamines are associated with normal sleep.


Effect of chronic treatment with desoxycorticosterone on the dipsogenic response of rats to isoproterenol and angiotensin. Administration of desoxycorticosterone (DOC) at a dose of 0.5 mg/kg/day to male rats for 6 weeks attenuated significantly the drinking response to acute subcutaneous administration of 5, 10 and 20 microgram isoproterenol/kg body weight. Chronic administration of DOC did not prevent the drinking response to acute intraperitoneal administration of angiotensin II (200 microgram/kg body weight). In contrast, the drinking response was enhanced compared with that of control rats given angiotensin II acutely. While attenuation of the drinking response to isoproterenol in DOC-treated rats may be attributed to depletion of renin from their kidneys, the mechanisms responsible for the enhanced drinking response to angiotensin II are not clearly understood.


Effects of dl-tranylcypromine on LD50 of pentobarbital in the rat. The LD50 of pentobarbital has been determined in rats with or without pretreatment with dl-, d- or l-tranylcypromine (5 mg/kg, i.p.). The LD50 of pentobarbital was reduced to almost one half by d- or dl-tranylcypromine as compared with the l-isomer. It is concluded that dl-tranylcypromine enhances pentobarbital toxicity by inhibition of its metabolism.


Effects of chloramphenicol reduction products on hemopoietic precursor cells in vitro. This study demonstrates that the nitroso, hydroxamic acid, and acetoxyhydroxamate nitrogenous reduction metabolites of chloramphenicol are not directly toxic to myelopoietic and immunopoietic bone marrow precursor cells as assessed by the in vitro colony-forming cell and precursor plaque-forming cells assays, respectively.


Estrogen-dependent differences in the acetylation of sulfadimidine in the rat. The influence of sex hormones on the acetylation of sulfadimidine was investigated in male and female rats, both intact and castrated. Sulfadimidine was administered intravenously in the dose of 40 mg/kg body weight, and unchanged and acetylated sulfadimidine (Ac-S) were then determined in urine and blood. It was found that the percentage of Ac-S was significantly higher in the urine of females than males. The concentration of sulfadimidine in blood was also higher in females than in males. While estrogenization raised the percentage of Ac-S in the urine of males and the concentration of unchanged sulfadimidine in blood, treatment with an androgen had no significant effect in females. The long-lasting stimulatory influence of estrogen in males and a normal percentage of Ac-S in gonadectomized females suggest an indirect action of estrogen. Possible mechanisms are discussed.


Assay of 3-carboxy-antipyrine in urine by capillary gas chromatography with nitrogen selective detection. Some preliminary results in man. An assay procedure is described for 3-carboxy-antipyrine in urine using gas chromatography with a support coated open tubular capillary column (Carbowax 20M), a solid injection system and nitrogen selective detection. 3-Carboxy-antipyrine was analyzed after derivatization with diazomethane and using 4-bromo-antipyrine as internal standard. Following extraction of the urine samples with a mixture of organic solvents linear calibration curves were obtained in the concentration range of 1--50 microgram/ml. The precision was established as +/- 5.0% (n = 5), and the lowest measurable concentration was 1 microgram/ml at a signal-to-noise ratio of 10:1. Preliminary results in 5 human volunteers showed that after orl administration of 500 mg antipyrine, 3.3 +/- 0.8% of the dose was excreted as 3-carboxy-antipyrine in 52 hours' urine. The compound was excreted completely in the unconjugated form.


An articulatory experiment on voice onset time in German stop consonants. The study investigates voice onset time (VOT) in German stop consonants and its relationship to place of articulation in a variety of phonetic environments. The outstanding findings are the consistently lowest values for the alveolars and the particular susceptibility of the VOT of bilabials to environmental variables like position in the utterance and stress. Highest values for velar stops are only achieved in initial position and medially before stress. Airflow measurements suggest a direct relationship between VOT and rate of articulation and airflow.


Identification of novel phonetic segments by children, adolescents and adults. The ability of children, adolescents and adults to employ completely novel phonetic information was examined. Three groups of subjects were tested for their ability to identify minimal pairs contrasting voiced and implosive stops in syllable-initial position. Children's performance on this task was significantly superior to both adolescent and adult performance.


Sentence intonation in Swedish.

Sentence intonation in Swedish. In 'A Prosodic Typology for Swedish Dialects' (Nordic Prosody 1978), BRUCE and GARDING proposed a schema for generating fundamental frequency patterns of statements in four Swedish dialects. Dialectal variation was obtained by timing word accents and sentence accent differently in a common frame expressing statement intonation. In addition to presenting the method, this paper also shows how it can be applied to two different interrogative frames, one for yes/no questions with non-inverted word order and one for inverted order.


[Speech sounds and speech signals--the perspective of a new phonometry (author's transl)]. Descriptive phonetics and instrumental phonetics have two entirely different empirical domains as their subject matters. On this basis, ZWIRNER's central problem of the theoretical relationship between sound category and sound realisation is re-formulated and discussed. It is shown how the traditional descriptive procedures of segmentation and decomposition can be connected with the segments of digital speech signals and the features analysed from them.


Mandible height and syllable-final tenseness. Mandible movements in the vowel-to-consonant transition manifest consistent differences between /t/ and /d/ in syllable final position. Both mandible position at its peak value near the articulatory release of the stop and velocity of its ascending movement in the transition are found to be apparently relevant to the tense/lax distinction, even though the reliability of these criteria for categorizing t/d data somewhat varies depending on the speaker. Some related characteristics of lingual movements and similar mandible characteristics for the k/g distinction are mentioned. The data were obtained by the computer-controlled X-ray microbeam system in cooperation with the University of Tokyo group.


Articulatory measurement and synthesis. Methods and preliminary results. The relations between area functions of the vocal tract and the acoustic result are of phonetic interest only if they can be interpreted in articulatory terms. We show which problems may arise if two-dimensional configurations of the vocal tract are to be transformed into area functions, and which relations exist between articulatory variables, area functions, and formant frequencies in an articulatory model.


Acoustic measurements of articulator motions. Methods for estimating articulatory data from acoustic measurements are reviewed. First, relations between the vocal-tract area function and formant or impedance data are pointed out. Then the possibility of determining a (discretized) area function from the speech signal itself is considered. Finally, we look at the estimation of certain articulatory parameters rather than the area function. By using a regression method, such parameters can even be estimated independently of any vocal-tract model. Results for real-speech data are given.


Dimensions in the perception of fortis and lenis plosives. The analysis of the production of fortis and lenis plosives in German has shown the importance of the duration ratio vowel/(vowel + closure) for the distinction. To complement these results a perception test was carried out in which 29 native speakers identified a randomised sequence of 220 stimuli from tape as one of the phrases 'Diese Gruppe kann ich nicht leid(e)n (leit(e)n)'. The stimuli were obtained from the two naturally produced originals by changing the ratios and the length of voicing in the plosive through computer processing. The test results indicate very conclusively that judgment can be reversed simply by changing the ratio to the appropriate ones found in production. There is a hierarchy of perceptual dimensions: duration ratio greater than formant transition greater than voicing.


Relationship of some open-field behaviors to amygdaloid kindled convulsions in Wistar rats. Repeated low-intensity electrical stimulation (kindling) of the amygdala eventually produces convulsive behavior in animals. The present study examined the relationship between behaviors displayed in a novel open-field situation with behavioral characteristics of the kindled clonic convulsion (CC). Wistar rats were given two open-field tests and were subsequently kindled to clonic convulsions. A multiple regression analysis indicated that rats which urinated more often in the open-field tests tended to show longer latencies to CC onset. Thus, open-field urination was a significant predictor of latency to CC onset. It is suggested that an emotionality construct may be related to rate of kindling.


Weight loss following LH lesions independent of changes in motor activity or metabolic rate. Lesions in the lateral hypothalamus (LH) which resulted in aphagia and a significant loss in body weight, did not reduce either the running wheel activity or the stabilimeter activity of the animals. Following recovery, the animals failed to regain the lost weight. They had normal food and water intakes under ad lib conditions, and ate food when water deprived. They did not drink when deprived of food. Both control and LH animals also had higher than normal oxygen consumption rates. However, the LH group was not higher than the controls postoperatively. These data argue against their being a unitary LH lesion syndrome and suggest that the chronic weight loss seen in animals with LH lesions is not a secondary consequence either of having disrupted the pituitary-thyroid axis, or of having changed the animals' spontaneous activity levels.


Piracetam impairs the overshadowing of background stimuli by an informative CS. The effects of Piracetam (100 mg/kg) on passive avoidance learning was investigated in a situation in which rats received multiple conditioning trials. The test was based on the untrained preference of rats for a dark, rather than a brightly lit compartment. After the initial black-white preference was tested, rats were restricted to the black compartment for conditioning. Different groups received different percentages of tone-shock pairings. After the conditioning trials the black-white preference was again tested. The saline-injected rats showed overshadowing of the background stimulus by the tone, in the group that had received 100% tone-shock pairings; and an acquired aversion to the background stimuli in the group that had received 0% tone-shock pairings. In the rats injected with 100 mg/kg Piracetam associative strength was partitioned indiscriminately between the tone and the background stimuli, regardless of the tone-shock pairings that had been received during conditioning.


Influence of some biologically meaningful odorants on the vigilance states of the rat. In freely moving rats, mitral cells multiunit activity and vigilance states (EEG and neck muscles EMG) were recorded during stimulations by some odorous stimuli known from previous experiments to elicit distinct emotional behaviors. An awaking influence may be pointed out; the greatest awaking influence is noted for the opposite most biologically meaningful stimuli: odor of fox (predator of the rat) and odor of grouped rats. Mitral cells responsiveness is not only modulated by the biological meaning of the olfactory stimulus but is also under the control of the arousal level of the animal; it decreases from wakefulness (W) to slow wave sleep (SWS).


Conditioned suppression, heart rate and pulse volume: effects of instructions on extinction. Two experimental groups of undergraduate volunteers received five classical aversive conditioning trials with a tone conditioned stimulus (CS) and shock unconditioned stimulus (UCS). Control groups received either the CS alone or UCS alone. Subjects from one experimental group were subsequently instructed that they would not receive further shocks, while the other experimental group received no such instructions. The CS alone was then presented once to all four groups while subjects were engaged in a button-pressing task maintained by slide reinforcement. During this latter phase rate of button pressing was measured as well as heart rate and pulse volume. The last two measures being employed as indices of autonomic arousal. The results indicated that while instructions as to the absence of the UCS completely abolished the conditioned suppression of button-pressing, they had no effect upon the pulse volume CR. A heart rate CR was not obtained. These results reflect unfavourably upon theoretical formulations of conditioned suppression that emphasize the causal interdependence of motor and autonomic events or the primacy of either one.


Effects of sustained-release testosterone on marking behavior in the Mongolian gerbil. Utilizing subcutaneous silastic implants containing testosterone the effect of sustained low-level release of testosterone on marking behavior in castrated Mongolian gerbils was determined. Castration resulted in a decrease in marking frequency from 38 +/- 4 to 4 +/- 1. Sustained release of 6 micrograms testosterone per day from implants did not stimulate marking behavior. Daily release of 11 micrograms increased marking 550% after one week. Release of 17 micrograms per day was required to restore marking to intact levels. Similar release rates of cholesterol did not increase marking. Release rates which increased marking in males did not increase marking in females. The minimum effective sustained-release dose of testosterone necessary to stimulate marking in females was five times greater than that in males. This difference is not due to a sex difference in plasma testosterone removal rates, since the circulating half-life of 3H-testosterone measured by testosterone-specific radioassay was not different in castrated males (72 +/- 5 min) and females (66 +/- 4 min). The present data are consistent with the hypothesis that there is a sexual dimorphism in the testosterone responsiveness of the neural substrate regulating territorial marking behavior.


The effect of hysterectomy on hormone-induced lordosis behavior in hamsters. Ovariectomized-hysterectomized (OH) and ovariectomized-sham hysterectomized (OSH) hamsters were tested for lordosis behavior following treatments including either 1, 5, or 10 micrograms estradiol benzoate (EB) in combination with 0.1, 0.25, and 0.5 mg progesterone. Few animals responded at the 1 microgram dose of EB and there were no differences in latency to the first display of lordosis or in the total lordosis duration among responding animals in the 5 and 10 micrograms EB groups. However, there was significantly more positive tests in the OSH group injected with 5 micrograms EB than in the OH group and this difference approached statistical significance in the 10 micrograms EB groups. The results are compared to similar studies in rats and possible mechanisms for the effects of hysterectomy are discussed.


Effects of focal vs generalized kindled convulsions from anterior neocortex or amygdala on CER acquisition in rats. Kindling of the anterior neocortex (AC) was shown to produce a brief focal motor seizure, characterized by a clonic-tonic-clonic response of the forelimbs with the animal in a prone posture. These same brief seizures, as previously reported, did not produce retrograde amnesia in a CER paradigm. With repeated evocations, over several days, the AC convulsions exhibited a dramatic increase of the second clonic phase (generalized) and came to appear similar to amygdala kindled convulsions. These generalized AC convulsions, like briefly kindled amygdala convulsions, produced good retrograde amnesia for a CER. With extensive amygdala kindling prior to CER training, a severe CER acquisition deficit was observed. These latter as well as other data suggest that protracted amygdala kindling produces a subsequent reduced ability to acquire fear motivated responses.


The effects of lithium upon drinking in the pigeon and rat. Single administrations of LiCl in fluid deprived pigeons produced immediate and sustained drinking which was (a) significantly greater than in NaCl-injected birds, (b) a function of the dosage of lithium, and (c) persistent for several days following the highest dosage used. Experiment 2 employed the same procedures to examine the effects of lithium upon fluid consumption in the rat. Results indicated that single administrations of lithium had little effect on water consumption.


Dual effects of 2-deoxy-D-glucose on food intake in the rat: inhibition at night and stimulation in the day-time. The effect of 2-deoxy-D-glucose on food intake in rats has been reexamined. The effects were compared following administration of 2-DG IP (250, 500, 750 mg/kg and saline) either at the beginning of a 12-hr dark or 12-hr light period. Ad lib food intake was recorded during the subsequent 24 hours. In the day-time 2-DG enhanced food intake. The increase was not dose-dependent. It was apparent only during the first four hours and was compensated during the following eight hours. At night, an inhibition in food intake was observed. This inhibition was mainly manifested during the first four hours and was not dose-dependent. However, a dose related compensation during the subsequent hours resulted in a dose-dependent inhibition of the nocturnal intake. A second expermient indicated that after an overnight fast 2-DG also inhibited the high food intake induced in the day-time. In a third experiment, insulin 10 IV SC combined to 2-DG was shown to further increase food intake in the day-time. At night the combined administration of insulin and 2-DG cancelled their respective opposite effects and no change of food consumption was observed. The results are interpreted in terms of the contrasted neuroendocrine and metabolic patterns prevailing in the two parts of the diurnal cycle.


Thermotaxis in neonatal rat pups.

Thermotaxis in neonatal rat pups. Deprived and nondeprived 3- and 6-day-old rat pups were tested on a thermal gradient for thermotaxis. Deprived 3-day olds demonstrated a marked thermotaxic responsiveness that was not observed in nondeprived 3-day olds or in deprived and nondeprived 6-day olds. Deprived 3-day olds did not show a strong thermal orientation immediately, but the distance moved by pups increased with repeated trials on the gradient. These findings demonstrate that neonatal rats are capable of thermotaxis, but that factors of age, deprivation and repeated handling determine pups' responsiveness to thermal gradients.


Conditioned diastolic blood pressure.

Conditioned diastolic blood pressure. Four groups of normotensive subjects were used in an experiment designed to: (a) replicate earlier data, (b) determine whether heart rate and respiration rate changes accompanied the development of acquired bi-directional diastolic blood pressure responses, and (c) investigate whether males and females acquired diastolic blood pressure responses at differential rates. Observations were carried out over one baseline and eight consecutive one-hour training sessions. Analyses of the blood pressure scores revealed subjects were able to acquire a bi-directional response, thereby confirming earlier reports. From subsequent analysis of the heart rate and respiration rate scores and from intercorrelations between diastolic blood pressure, heart rate, and respiration rate, no consistent relationships or patterns emerged. Comparisons of male and female blood pressure performance failed to yield evidence of reliable sex differences.


Developmental aspects of sucrose-induced obesity in rats. Daily caloric intakes and body weights were measured from weaning to 70 days of age in male Sprague-Dawley rats given access to either a standard laboratory diet and water, or the standard diet, a 32% sucrose solution and water. Lee index of obesity (3 square root body weight/naso-anal length) and fasting blood glucose levels were determined at 46, 57, and 70 days of age. Animals were sacrificed at 70 days, and body composition analyses were performed. Aniamls given access to the sucrose solution consumed significantly more calories per day than animals given only the standard diet. Sucrose animals took approximately 50 to 60% of their daily caloric intake from the sugar solution. Despite the greater caloric intakes of the sucrose animals, sucrose and control animals did not differ in body weight. While there were no differences in body weights between the two groups, the Lee Index of obesity was significantly greater in the sucrose animals than in controls as early as 46 days of age. Fasting blood glucose levels were significantly lower in sucrose animals than in controls at both 46 and 57 days of age. Direct determinations of body compositions when animals were 70 days of age revealed that animals with access to sucrose had significantly greater percentages of body fat and lower percentages of body protein than controls.


Similarities in the regulatory patterns of pregnant and cycling rats. The patterns of food intake, water intake and body weight of the female rat during the estrous cycle and pregnancy were determined. During the 4-day estrous cycle, intake and body weight were reduced on the day of ovulation. In contrast, animals with 5-day estrous cycles reduced intake and body weight for 2 days, the day prior to ovulation as well as on the day of ovulation. Intake of pregnant rats around the time of birth was compared to that of cycling females and similarities were observed. The peripartum pattern of food intake was systematically related to the length of the gestation period. Rats that littered 22 days after mating showed depressed food intake only on the day of birth. Those with 23-day gestation periods decreased food intake both on the day of birth and on the following day. The similarities in the intake patterns during 4- and 5-day estrous cycle to that of the peripartum segment of 22- and 23-day pregnancies suggest that there may be common neuroendocrine factors controlling these behaviors during the two reproductive periods.


Sex, age and shock-intensity as factors in passive avoidance. Sex, age and shock-intensity were studied in a step-through passive avoidance test. In adult rats (140 days) males showed more inhibition of a previously punished approach response. No sex differences were observed in young adult animals (60 days). In prepuberal animals (30 days), on the other hand, it was the females which showed more response inhibition. In prebuberty females showed far more response inhibition than in adulthood. Even when using 1.6 mA as a reinforcer, only 17% of the adult females showed inhibition after punishment of the entering response.


Gastric emptying and cholecystokinin in the control of food intake in suckling rats. The rate of gastric emptying was determined in three-day old suckling rats. The gastric loads were given by gavage, and, after from 5 to 100 min, emptying was determined by removing the stomach and weighing the contents. Results were expressed as percentage of load still remaining in the stomach at one hour. The gastric loads in increasing order of speed of emptying were 1.0 M Na acetate, heavy cream, 0.5 M NaCl, milk, corn oil, 0.15 M lactose, 0.3 M glucose, 0.15 M NaCl, acidic water, and water. The rate of emptying was compared to the effectiveness in previous experiments of the same gastric loads in depressing intake. There was no significant correlation between rate of gastric emptying of the loads and their effectiveness in producing satiety. The octapeptide of cholecystokinin (80 Ivy dog units or 2.7 micrograms/kg i.p.) significantly depressed intake (measured as weight gain) of suckling rats of 1 1/2 hours, but the same dose did not slow gastric emptying. These findings indicate that rate of gastric emptying does not determine satiety in the suckling rat.


A study of olfaction and gustatory senses in sheep after olfactory bulbectomy. The importance of taste and smell in discrimination of sodium salts was examined in normal and anosmic sheep. To test for anosmia, faeces of pig, calf and sheep were used as noxious odours. Intact sheep, and sheep with one olfactory bulb removed avoided the aversive stimulus whereas following total bulbectomy, the faecal odour was no longer a deterrent. Olfactory bulbectomy did not affect food intake but changes in fluid intake, urinary loss and electrolyte excretion were apparent. In two-choice preference tests, normal sheep showed a marked aversion for 0.48 M NaHCO3 and 0.51 M NaCl when compared to water. Following either unilateral or bilateral olfactory bulbectomy the aversion for sodium salts persisted but was less extreme. This suggests that in the final discrimination of sodium salts the sense of taste is dominant but olfaction or the olfactory bulb may have a minor role.


Effects of distribution of the drug unconditioned stimulus on taste-aversion learning. Rats injected with lithium chloride after exposure to a taste or olfactory stimulus learn stronger aversions to these cues if the drug is administered in two small injections 35 min apart than if all of the drug is given in a single injection. This facilitation of conditioning produced by distribution of the drug unconditioned stimulus occurs with both low and high lithium doses (Experiments 1 and 2), is more evident in male than in female rats (Experiment 1), and is directly related to the amount of the flavored solution consumed prior to drug treatment (Experiment 4). Increasing the interval between two small drug injections beyond an optimal value results in a progressive loss of the facilitation of conditioning (Experiments 2 and 3), and the optimal drug distribution interval may be shorter for olfactory cues (Experiment 3) than for taste stimuli (Experiments 1 and 2). Control observations (Experiments 5A and 5B) showed that the drug distribution effect is not due to handling or other non-drug factors involved in giving two rather than only one injection. The phenomenon is consistent with recently-proposed models of conditioning and suggests that the differential effectiveness of various drugs in taste aversion conditioning may be related to differences in the time course of the unconditioned drug effects.


A polygraphic analysis of mounting and ejaculation in the New Zealand white rabbit. The duration and intensity of some components of the male copulatory pattern was studied in ten male (seven experienced, three inexperienced) and two female New Zealand white rabbits by using high speed cinematography, accelerometry and by recording the pressure of the seminal vesicles. Duration of mounts varied greatly within and among subjects. Effective mounts, i.e., those terminating in ejaculation, lasted less (2.61 +/- 1.50 sec, mean +/- SD; n, 59) than ineffective mounts (3.08 +/- 2.16 sec, mean +/- SD; n, 199). Frequency of pelvic thrusting was significantly higher in effective (13.54 +/- 1.11 sec, mean +/- SD; n, 59) than in ineffective mounts (12.08 +/- 0.98 sec, mean +/- SD; n, 176). No pelvic thrusting occurred during intromission which usually lasted less than one second (722 +/- 266 msec SD; n, 43). Shortly after intromission (230 +/- 107 msec, mean +/- SD; n, 32) the pressure of the seminal vesicles raised. This rise in pressure outlasted copulation (1040 +/- 369 msec, mean +/- SD; n, 32). The mounting pattern of inexperienced rabbits was similar to that of experienced rabbits. The mounting pattern of females differed from that of males both in rate of pelvic thrusting and duration of pelvic thrusts.


VMH obesity reduced but not reversed by scopolamine methyl nitrate. Chronic administration of scopolamine methyl nitrate, at doses much greater than required to block vagally mediated insulin secretion, reduced static phase VMH obesity by only 31%. At least 59% of the obesity persisted even when the initially effective dose (0.15 mg/Kg, 4 times/day) was increased eight-fold. The larger dose also did not prevent VMH hyperphagia and weight gain when scopolamine treatment was begun before the lesion. By ten days after the lesion, reduced gastrointestinal motility apparently prevented further weight gain. These results suggest that much of the obesity caused by VMH lesions is independent of vagally mediated insulin secretion or other excess vagal efferent activity. The doses used in this experiment were large in order to provide strong evidence for this conclusion.


A simple and versatile avoidance chamber for mice requiring no shock scrambler. We present a simple two-chamber apparatus for avoidance training of mice which does not require a shock scrambler. This apparatus can be used for active, passive and discriminated (Go-No-GO) avoidance tasks.


Duodenal pathology in rats following cold-restraint stress. Rats were found to develop duodenal abnormalities as a monotonic function of stress: following a 41-hr fast, 17% had lesions; when cold stress was superimposed during the last 14 hr of the fast, 38% had lesions; when restraint was superimposed upon the last 17 hr of the fast and accompanied exposure to cold, 83% had lesions. Amount of duodenal pathology correlated across experimental groups with amount of gastric pathology seen, but for individual animals, presence of gastric and duodenal pathology did not necessarily co-vary. The existence of gastric and duodenal pathology in stressed rats mirrors that found in stressed humans and thus gives credence to the notion that the rat is a useful animal for study of acute, stress-induced gastro-duodenal disease.


A role of female preputial glands in social behavior of mice. Female mice reared by mothers with preputial glands preferred females with preputial glands over females deprived of preputial glands (p less than 0.02). Furthermore, such females preferred odors from males with preputial glands to odors from males without such glands (p less than 0.01). Females reared by mothers without preputial glands showed greater preferences for the odor of preputialectomized males (p less than 0.02) and females (p less than 0.01) than nonpreputialectomized animals. Odors common to males and females, emanating from preputial glands of the mother apparently influence early postnatal mice and determine their preferences in later life.


Concurrent drinking by pigeons on fixed-interval reinforcement schedules. Three experienced pigeons were exposed to at least ten consecutive 100-min sessions on each of three food-reinforced fixed-interval (FI) schedules: FI 50-sec, FI 100-sec and FI 200-sec. Water was freely available. Drinking was largely confined to the first third of each fixed interval, and the mean sessional water intake was directly related to the food-reinforcement rate for each animal. The animals drank very quickly, i.e., 3--4 ml/sec, but the drinking bouts were brief, i.e., 0.8--1.4 sec, and infrequent, i.e., 2--5/hr. The parameters describing concurrent drinking in the pigeon are strikingly different from those describing rats' drinking under similar reinforcement schedules, which may contribute to the difficulty in demonstrating schedule-induced polydipsia in the pigeon.


Forebrain lesions and food intake in pigeons. Thirty pigeons were randomly assigned to one of four groups: those receiving bilateral ablation of the archistriatum, the neostriatum, the nucleus stria terminalis, or those receiving a sham operation. All groups showed a non-significant temporary postoperative decrease in food intake, a non-specific effect attributed to the surgery. However, the duration of the hypophagia in the archistriatum- and nucleus stria terminalis-ablated groups was slightly longer (four weeks instead of three). A slight increase in body weight occurred in the nucleus stria terminalis-lesioned group, in spite of decreased food intake. These results, especially that there is no persistent hypophagia following archistriatum and nucleus stria terminalis lesions, are discussed in relation to the suspected role of several forebrain structures in feeding behavior.


Legal defense as ego defense: a special form of resistance to the therapeutic process. Forensic psychiatric concerns may be invoked defensively by the trainee as a resistance to the therapeutic process. The author briefly reviews this issue and its clinical manifestations, recognition, and supervisory management.


Treatment of narcissistic problems in time-limited psychotherapy. Time-limited psychotherapy is being used with an expanding variety of emotional disorders, often as the treatment of choice. Clinical experience indicates that this form of treatment can produce major and enduring improvements. Persons suffering from major narcissistic problems generally are assumed to be impervious to time-limited treatments. However, long-term treatment is becoming less feasible because of financial considerations. Time-limited psychotherapy can provide circumscribed symptomatic relief by fostering increased use of defensive intellectualization and related ego-coping skills. Transference interpretations directed toward connecting maladaptive behavior patterns outside of therapy to past childhood relationship patterns proved most effective.


Dropouts and terminators from a community mental health center: their use of other psyciatric services. Differences in patterns of utilization of psychiatric services were studied in 178 adult outpatients who either had dropped out of, or had terminated from treatment with the consent of their therapists. The Monroe County Psychiatric Case Register was employed to determine the use of psychiatric services by these patients within a period of two years before and two years after their admission to a community mental health center (CMHC). Dropping out of treatment was associated with a pattern of utilization of multiple psychiatric facilities. Of those individuals who made contact with a psychiatric facility both prior to and subsequent to their admission to the CMHC, the dropout group made, on the average, approximately twice as many contacts per person as the terminator group.


The role of the clergy in community mental health service: a critical assessment. Efforts to expand mental health manpower have taken three major directions: (1) increased use of consultation, (2) creating entirely new roles, and (3) offering training to persons engaged in roles or occupations presumably at strategic points of contact between the public and the mental health system (clergy, police, hairdressers, and bartenders). In this paper the role of modern clergy is examined along several dimensions in order to provide a more rational basis for determining their true potential as mental health service extenders or gatekeepers. Role aspects examined are: public acceptance, approachability, community stature, role separation, and professional identity. Clergy  seem to be both appropriate and available as mental health resources.


Problems of foreign born psychiatrists.

Problems of foreign born psychiatrists. This paper describes problems incurred by those psychiatrists practicing in the United States who were born outside of the United States of America. It describes issues related to practice, politics, and understanding of a culture alien to them. It also focuses on some of the advantages of being a foreigner in the field. In conclusion, the paper recommends specific training to be incorporated in residency programs to address issues identified by the author.


Case conference from Cornell. Case 6: depression and hypochondriasis in a patient with peptic ulcer disease. We are going to present a patient who was admitted to the hospital with a major depressive disorder. Somatic complaints and hypochondriasis were prominent in her symptomatology and occurred in a setting of known ulcer disease. Dr. Richard Breslow will present the case and a discussion of psychological aspects of ulcer disease. I will discuss the treatment of patients with hypochondriacal depressions.


[Some considerations on psychotherapy training for physicians in the psychiatric clinic--demonstrated by the example of the Medical School Hannover (author's transl)]. The essay outlines the strained situation in which psychotherapeutic training in the Psychiatric Clinic nowadys takes place. First, the official training rules for the intending psychotherapist in the Psychiatric Clinic of the Medical School, Hannover, are described. By that, a series of general structural problems is delineated, which influence the organization of the training in psychotherapy within the broader frame of psychiatry and its different institutions, especially its integration into a hospital with a predominantly social-Psychiatric orientation: Admission of candidates according to the criterion of clinic membership (instead of personal qualification); limitation of the instruction period according to the time of clinic membership (at most three or four years); therefore early start of psychotherapeutic treatment with generally rather difficult, severely disturbed patients; treatment with modified psychoanalytic procedures, which in general presuppose an experience in psychoanalytic treatment of many years; self-experience usually in a psychoanalytic group, without own experience with a therapeutic face-to-face-relation and the therapeutic regression possible in this dyade; finally the strain--felt as a conflict by many candidates--between the pressure for action in the daily practice of social psychiatry, and the rather temporizing and permissive attitude of the psychotherapist, where the reflection of action is most important. The theoretical teaching of psychotherapy as well as supervision have to respond to these structurally defined conditions. The essay describes the hitherto existing experiences in the Psychiatric Clinic of the Medical School, Hannover, in Regard of the difficulties, but also the changes of the transfer of psychotherapeutic theories and methods to psychiatrists and--perhaps--physicians in general. It demonstrates, too, some possible attempts for practicably solving the specific problems of a psychotherapeutic traning which is not oriented toward maximum requirements, but toward realizibility withan an given social frame for the sake of patients who probably would not find treatment elsewhere.


[Experiences, ideas, confusions with education for social und milieu therapy in a school and advanced training of therapeutic personel in Bethel (author's transl)]. The author, agent of advanced training, reports--on the background of ten years organisationel development in a large psychiatric institution (Bethel)--his experiences under the special view of training therapists of all kind, mainly nonacademic personel. This all is done in many different and interdependent courses, a small department of a school within. The problems, in his view, are that education for all professions in Germany don't prepare really--in the sense of giving personal and pragmatic competence--for psychiatric work with the sick or handicapped and other professionels. So advanced training courses must help during people work in the institution. The author is confused but sure, that the best training evidently can't enable people in the central point--beeing encouraged to stay beside and with the sick people, if there is not growing a community of helpers together and with the patients. So education, studies and training are very important. But it seems that it doesn't work without sharing personal existance together, personel and sick.


[Sociopsychiatric additional training at the Medizinische Hochschule Hannover (author's transl)]. The development of sociopsychiatric additional training (abbreviated SPZA in the German text) is closely connected with the development of the psychiatric hospital of the Medizinische Hochschule Hannover (MHH) from a level of psychiatric keeping aloof from everyday problems arising in a community, towards a type of medical care which remains close to community problems by paying attention to all the sectors that go into creating abnormal patterns in a community. The most important and still unsolved problems of the future are represented by the alternative of a jobspecific or comprehensive continuing education across the boundaries set by individual groups of professions (at present, SPZA is intended to look after several non-academic groups of professions) and  are also represented by the alternative of continuing education bound to one institution or on a regional basis comprising several institutions. It is the aim of  SPZA to create a therapeutically favourable environment and to establish therapeutic relationships in psychiatry, i.e. to reflect upon and to change the patterns of psychiatry, its attitude, and its institutions. The teaching aims are: Shaping of psychiatric institutions according to basic human requirements, in line with the continuing education concepts of the DGSP; furthermore, realization of the therapist's own share and the share of external sources in the therapeutic communicative process incorporating reflection of the pwn and externally conditioned socialisation; also, the acquisition of the technique of favourable communication, achieved by self-observation and reflection of the therapist's own patterns of behaviour in his capacity as a person dedicated to helping the patient. Another teaching aim is to head and guid therapeutic groups in accordance with the innate propensities and tendencies of the participants and the practical requirements of the institutions concerned. From the didactic point of view, self-experience, communication of theories, and the practising of the new patterns of behaviour desired by the participants themselves, are combined.


[Concepts on the supraregional sociopsychiatric continuing education of female and male nurses within the competence of the "Landschaftsverband Westfalen-Lippe" (author's transl)]. The new activities of nurses working in the field of psychiatry, resulting from the realisation of sociopsychiatric and sociotherapeutic concepts, have led to an expansion of the "job description" of the nursing personnel. Intensive measures for additinal training and continuing education will have to be taken to acquaint this personnel with these new tasks. Such measures have already been initiated from 1969 onwards in various places within the Federal Republic of Germany. For the psychiatric hospitals looked after by the Landschaftsverband Westfalen-Lippe, a continuing education commission which comprises co-workers of various job categories and institutions, developed a continuing education concept about which this article reports in detail with regard to target aims and tasks to be tackled.


[Central continuing education measures for female and male nurses of the Westphalian Provincial (Psychiatric) Hospitals and Clinics (Westf. Landeskrankenhüser und Landeskliniken) (author's transl)]. The article reports on planning, organisation and realisation of measures for the continuing education of female and male nurses of the Westphalian Provincial (Psychiatric) Hospitals as laid down by the Continuing Education Commission of the Landschaftsverband Westfalen-LIppe (a semi-governmental organisation embracing many activities, including the care of psychiatric patients.) The article discusses in detail the teaching aim and the contents of the continuing education programme, the composition of the group of participants, and the mode of working practised in the training course which must be most closely related to actual practice.


[Psychosocial care structures in urband and rural districts (author's transl)]. The present study is based on a complete institutional and personal coverage of psychosocial care institutions in nine local regions within the Federal Republic of Germany. The study was carried out by means of a short structured questionnaire and was supported by local psychosocial working groups. The following questions were considered on the basis of a sociodemographic differentiation, in urband and rural districts: 1. To what extent do differences appear between urban and rural districts with regard to outpatient-, inpatient- and complementary treatment facilities? 2. To what extent do differences appear in regard to the quantity and quality of specialized professional personel operating there? 3. In what way, and to what extent, compensatory care mechanism do exist? The results show important and systematic differences with regard to the outpatient, inpatient and complementary treatment facilities. Rural districts are characterised by an emphasis on inpatient facilities, including homes, as well as by a marked lack of outpatient facilties, especially of a psychotherapeutic nature. Psychosocial professions with high qualifications, especially in psychotherapeutic respect, are mainly found in regions characterised as urban, while they are nearly completely absent in rural districts. In addition the results point at a underprivileged treatment structure of rural district. However there are indications of compensatory care mechanisms. This means that persons without any specialized training are often engaged in treatment jobs requiring specialisation. This applies in particular to the complementary field of patient care. The article discusses overlapping problems of proper geographic distribution of psychosocial treatment facilities in accordance with actual requirements. Furthermore political conclusions resulting from this aiming at improvementsof the care structure for mentally ill persons are discussed.


Technologist performance in fluoroscopic gastrointestinal examinations: an alternative for a small department. In this small rural community hospital, the performance of gastrointestinal examinations by a radiologic technologist has proven to be highly successful. This success has been demonstrated both in terms of increased cost-effectiveness and diagnostic quality.


Adaptation of the technique for radiography of the glenohumeral joint in the lateral position. This article emphasizes the importance of obtaining opposing right angle views of the shoulder as a routine part of the examination. It analyses standard projection techniques and presents an adaptation of the transaxillary axial projection that is invaluable to the radiologist in diagnosing that eight per cent of lesions that can be missed by not using this projection.


One more look at the mandibular condyle. A great deal of attention has been given over the years to the development of highly specialized x-ray equipment that, in many instances, has reduced the complex nature of the radiographic procedure. However, it is impossible, and probably always will be, to design equipment that will automatically produce the proper radiographic position. This will remain a distinct function of the technologist, and the individual's skill will have great bearing on the quality of the radiograph. One need only review the literature to realize how innovative our profession has been in developing countless numbers of radiographic positions for demonstrating specific anatomical regions. Moreover, many useful radiographic positions can be found that, for various reasons, never gained the level of acceptance perhaps anticipated by their originators. Consequently, the practical value of these positions often escapes our attention. To illustrate this point, I have selected a radiographic position described some thiry years ago for visualization of the mandibular condyle. It is my intent to demonstrate the practical value of this projection, as well as that of some others not usually thought of, for radiography of the mandibular condyle.


Technical writing in the radiologic technology curriculum. Although courses in technical writing are no longer suggested in the Curriculum Guide for Programs in Radiologic Technology, the writer believes that writing is essential to the growth of the profession and development of the professional. Emphasis is placed on some of the benefits that accrue to students who are exposed to technical writing as part of their technology curriculum.


Log10 technique charts.

Log10 technique charts. The purpose of this article is to offer a reliable and easily formulated alternative to random technique selection or control panel roulette when producing diagnostic radiographs. This system requires only minutes to complete and will reduce the radiation dose to patients, the radiographic film wasted, and the time lost repeating examinations.


Causes of late death due to hydrocephalus and myelomeningocele. Analysing 149 late deaths occurring between the years 1958 and 1977, the postoperative survival rate independent of age was in 33% less than three months and another 33% less than one year. The causes of death in the different age groups have been analysed following the scheme proposed by Petren: The most common cause of death was infection (65%), 20% of the children died with an indefinite final diagnosis, but this percentage has decreased since the introduction of computer tomography. Since 1968 the number of late deaths has been reduced mainly because of a decrease of local infections, better follow-up of the children and last but by no means least a better cooperation with the parents.


Preoperative condition of neonates who have ultimately died. In a retrospective study the case sheets of 42 neonates are examined. They were infants with oesophageal atresias, small and large intestinal atresias, exomphalos and gastroschisis, diaphragmatic hernia, intestinal obstruction as well as two children with a ruptured spleen secondary to birth trauma. Various laboratory investigations such as the pH, pCO2, standard bicarbonate and serum electrolytes as well as the child's weight on admission and, if possible, the birth weight were evaluated. There was no definite relationship between the preoperative laboratory values and the chances of survival of surgical neonates except if the values were extreme. Infections and septicaemia were the most important causes of postoperative complications.


Factors contributing to the mortality associated with open-heart surgery in infants. About 40% of children born with congenital heart disease die within the first year of life unless treated surgically. The results of surgery have improved with increasing experience. Currently, the mortality rate of open-heart procedures performed during the first year of life have decreased to about 25%. The present study analyses the causes of death in 53 infants who underwent open heart surgery at the Hospital for Sick Children, Great Ormond Street, London between 1973--1977. Fifty-three deaths represented 25% of the total 212 operated infants. Causes of death and possible contributing factors are discussed under the following headings: Inoperable lesions (18), poor preoperative condition (8), mistake in pre-, intra- and postoperative management (15), infection (2) and unclear (10). It is suggested that earlier diagnosis and operation may improve the results. The purpose of this study was to identify problems in the management of critically ill infants with congenital heart disease and thus improve their prognosis in future.


Congenital cardiac malformation in infants and children. There were 51 deaths following cardiac operation in children under one year of age. Nearly all these children were operated upon without using a cardiopulmonary bypass. The commonest cause of death was intra- or postoperative cardiac arrest usually occurring in patients with complex cardiac anomalies. The second most commonest cause was repiratory deficiency. In children between the ages of 2 and 14 years (91 deaths in 1859 patients, i.e. a mortality of 4.64%), the commonest cause of death was cardio-vascular insufficiency usually caused by the operation. In patients with tetralogy of Fallot (147 deaths amongst 709 patients) one must distinguish between right sided and left sided cardiac insufficiency. Here the next commonest cause of death was bronchopneumonia with septicaemia usually as a result of long term artificial respiration. Other causes of death such as haemorrhages and embolic phenomena are much less important. In order to lower the mortality, better postoperative treatment in an intensive therapy unit especially for children undergoing cardiac operations is suggested.


Fatal complications after pacemaker implantation in a baby. In a three day-old infant with congenital heart block a pacemaker had to be inserted. Prolonged intravenous pacing led to septicaemia with fatal thrombotic complications. The potential spread of infection along the electrodes, and the danger of the presence of an intracardiac foreign body, suggest that myocardial electrodes may be superior in small infants.


Oesophageal atresia and/or tracheo-oesophageal fistula ... a study of mortality. Four hundred and fifteen babies with oesophageal atresia and/or tracheo-oesophageal fistula were admitted to the Royal Children's Hospital, Melbourne during the thirty year period, 1948--1977. Three hundred and fifty-six had proximal oesophageal atresia with a distal tracheo-oesophageal fistula; one of this group also had a proximal fistula. Three hundred twenty-eight were managed surgically with two hundred forty survivals. Factors affecting mortality in this group have been analysed and their therapeutic implications considered. There was a 50% mortality in the babies, numbering six in all, with proximal oesophageal atresia with a proximal tracheo-oesophageal fistula, but only one of the deaths in this group was regarded as being avoidable. Thirty-two babies had oesophageal atresia without an accompanying fistula, and in this group there was a relatively high mortality which was multi-factorial. In particular, factors included the association of this type of atresia with other anomalies incompatible with life, prematurity and technical problems. Twenty-one babies had an isolated "H" tracheo-oesophageal fistula with two deaths; one was a very early death reflecting the problems of neonatology a quarter of a century ago. The other died of a recurrent tracheo-oesophageal fistula and subsequent complications, and it is believed that this death would have been avoided by the present day approach.


General survey of the causes of death in patients who died postoperatively in pediatric surgery. The study is based on 427 patients who died between 1949 and 1976 and who were subjected to a post mortem examination. The years 1949 to 1969 (Group A) and the years 1970 to 1976 (Group B) were compared. Following important results were discovered: The underlying disease as a cause of postoperative death was reduced from 18.5% in Group A to 13.3% in Group B. Postoperative deaths secondary to associated malformations increased from 2.5% to 6.1%. Postoperative deaths due to a wrong diagnosis remained constant at 3%. Deaths due to wrong medical treatment decreased from 18% to 5.1%. Deaths due to postoperative infection increased from 17% to 46.2%. The explanation for this change is that modern intensive care keeps many patients alive who formerly died before the onset of infection. Deaths secondary to postoperative shock remained practically constant at 3% and 4% respectively. Deaths due to postoperative pneumonia decreased from 31% in Group A to 13.3% in Group B. The therapy for pneumonia has therefore markedly improved. The largest number of postoperative deaths was found in newborn infants. However, their part in the total numbers of postoperative deaths is definitely becoming smaller. Amongst the newborn infants there was the highest number of postoperative deaths caused by infections.


Discussion on atresia of oesophagus.

Discussion on atresia of oesophagus. Combined malformations and dysmaturity are still the most important causes of postoperative complications and deaths in the treatment of congenital oesophageal atresia. Better results can only be expected if methods of therapy of these associated conditions can be improved.


Intestinal obstruction in neonates: causes of death. Infectious complications such a peritonitis, septicaemia and pneumonia are the most important factors causing postoperative death in surgery of intestinal obstruction in children. In a series of 237 patients with intestinal obstruction with 21 fatalities, the percentage of deaths due to infection was 85.7%. In 1967 to 1976, 259.301 children died in Germany, among them 1541 suffering from intestinal obstruction (0.6%); that means 3.1% of the 49.540 patients who died of intestinal obstruction were children. The mortality of intestinal obstruction in infancy and childhood had fallen to one third of the original during this period, but the mortality in newborn infants fell only by 50%. This correlates with the decreasing birth rate, so that the lower death rate due to intestinal obstruction seems to be explained by a lower number of neonates. The literature shows that relative mortality (20%) from intestinal obstruction in the newborn has, however, remained constant during the last 20 years.


Causes of death in Hirschsprung's disease: analysis and conclusions for therapy. The mortality occurring in a series of 310 patients with Hirschsprung's disease is analysed. Forty-one (13%) died, 13 (4.5%) soon after a pullthrough operation. Anastomotic leaks were the largest cause of death in this latter group, but enterocolitis remains the most important cause of overall mortality.


Postoperative mortality in Hirschsprung's disease. The main factor causing a fatal outcome as well as the serious life threatening complications is anastomotic dehiscence. On the basis of our retrospective study we will sum up the following possible factors (not in order of importance): 1. Faulty suture techniques. 2. Pelvic seroma, haematoma or abscess with breakthrough into the lumen. 3. Tension on the suture line. 4. Deficient blood supply of either the distal colon, stump or the remaining rectum. Finally we would, on the basis of our study, like to make a plea for more and better colostomies or ileostomies; preoperatively as therapy in the sick child whose condition does not improve promptly with a rectal tube and, lastly, as postoperative cover to protect whatever anastomosis has been performed.


Imperforate anus: an analysis of mortalities during a 25-year period. A careful analysis of 53 deaths in a series of 284 patients suggests the following points are important in reducing risk: 1. Imperforate anus is a complicated lesion which should only be done by experienced surgeons in a large-volume pediatric surgical center in order to avoid the wrong choice of procedure. 2. A careful colostomy technique is essential to avoid herniation, prolapse, evisceration or obstruction. 3. Hyperchloremic acidosis from a large rectourinary fistula into the distal blind pouch of a colostomized high type lesion must be watched for. 4. The mucocutaneous junction (natural or surgical) must be kept free from stenosis to avoid fecalomas or enterocolitis-sepsis sequelae. 5. Neonatal pullthrough should be avoided as they carry an increased risk, make handling of fistulas difficult, and may lead to the placement of the bowel outside of the continence muscles.


Causes of postoperative mortality in anorectal malformations: analysis and conclusions regarding therapy. We studied 279 cases of rectal malformation in the hospitals of Munich, Berne and Lucerne in order to evaluate the mortality in this condition. 51 children died, an overall mortality of 18.2%. Three fourths of these fatalities were due to associated severe malformations, prematurity or brain damage respectively. Eleven children died because of postoperative infections. In the future the use of appropriate measures to avoid these complications should be attempted.


Postoperative causes of death in pediatric surgery: analysis and conclusions for the therapy. The mortality of children with posterolateral diaphragmatic hernia (PDH) is mainly dependent upon the degree of lung hypoplasia. Other less significant factors are dysmaturity, associated anomalies, infection and haemorrhages. Children with grave cyanosis from PDH immediately after birth have a poor prognosis due to persistent foetal circulation with pulmonary vascular hypertension and right-left shunting. A better understanding and treatment of this persistent foetal circulation may considerably improve the surgical mortality, though in some cases the lung hypoplasia may be too far advanced.


Causes of death in operated neonates with diaphragmatic defects. The causes for the high mortality in neonates with diaphragmatic hernia are manifold. These cases have to be classified as being in the "fatal zone" of Boix-Ochoa. Analysis of our patients showed that 27 patients belonged to this group, 15 of whom died. The causes of death were hypoplasia of both lungs in 1 case and intracranial haemorrhage in 1. In 6 neonates there were additional complex cardiac malformations and in 1 other severe malformations. The foetal circulation persisted in 3 infants and a tension pneumothorax was the cause in 2, an intestinal obstruction the cause of death in 1 infant. In these 5 last-mentioned children, improvements in treatment might have possibly prevented death.


Mortality after operation for hiatus hernia. When we started this investigation we were convinced that we would not be able to collect enough fatal cases to enable us to analyse the various causes of death following operation for hiatus hernia. To our surprise, inquiries made at 53 paediatric surgical centres produced a total of 67 fatalities. Most of these deaths could have been prevented if the following rules would have been followed: 1. The diagnosis must be made early and therapy must be commenced as soon as possible before there is a deterioration of the patient's general state of health increasing the risk of operation. 2. It is important to be familiar with the various operative techniques and the possible complications which they can produce. 3. Follow-up examinations are essential as certain complications will be detected by the patient himself only too late! Mortality and morbidity of hiatus hernia should be very small if the correct treatment has been carried out. Nissen's fundoplication, Rehbein's hiatal plasty and gastropexy, Lortat-Jacob/Grob's oesophagogastropexy and their modifications, all carry a low mortality and are followed by good results stopping the gastro-oesophageal reflux.


Postoperative deaths in children with portal hypertension. 69 children suffering from portal hypertension have been analysed. 5 of these patients died following shunt surgery, 2 after palliative surgery and 2 died in a state of haemorrhagic shock before any treatment could be commenced. In all those patients who died following shunt surgery, thrombosis in some part of the portal vein was found at post mortem. This led to partial liver necrosis.


Fatal peritonitis.

Fatal peritonitis. We analysed 117 cases of peritonitis in children. They were divided into two groups: -- Newborn and very young infants with peritonitis. -- Older children with peritonitis. The different causes in every group were studied, and it was attempted to find the particular criteria for each cause. The mortality in newborn and young infants is high, but resuscitation methods and appropriate surgical therapy are giving encouraging results. In older children the mortality from peritonitis is low and more or less resembles that in adults.


Mortality of preoperative peritonitis in newborn infants without intestinal obstruction. Within a period of 15 years 649 neonates were subjected to laparotomy; 60 (9%) of these patients died. Eighty-seven of the patients had a peritonitis already preoperatively without intestinal obstruction. Many of these were cases of ruptured omphaloceles or gastroschisis. In 17 infants a spontaneous intestinal perforation was the cause of the peritonitis. In 13 there was a preexisting meconium peritonitis. Seven children suffered from gangrenous intestine. Further causes for preoperative peritonitis were a complicated enteritis in 7 and a perforated appendix in 2 cases. Twenty-five or 29% of the children died. The highest mortality was found in children with ruptured omphalocele. It was 50% followed by gastroschisis with 36%. The mortality in patients with spontaneous intestinal perforation was rather similar, and the same high fatality rate was observed in infants with gangrenous intestine. In 28% of the children no cause for the peritonitis could be discovered. The high mortality rate is primarily due to the infants' bad general condition, i.e., low birth weight, prematurity and additional severe malformations.


Postoperative death in paediatric urology. In the combined experience of two paediatric urologists over a 25 year period only 4 fatalities relating directly to the surgical procedure could be identified. Two other deaths are presented and retrospectively most of the fatalities could have been avoided by present day management but not at the time they occured. Operative mortality in relation to paediatric urology is discussed fully and it is suggested that death related to the immediate surgery should be fully avoidable in relation to paediatric urology. Death from renal failure is a different problem and is unrelated to this paper.


Malformations of the urinary tract.

Malformations of the urinary tract. Between 1967 and 1977, 1500 children with malformations of the urinary tract were operated upon at the paediatric surgical department of the University of Tubingen. Ten children died in the early postoperative period or later on: Two patients died after operative correction of bladder extrophy following pneumonia and pyelonephritis and uraemia and urinary infection respectively. One child with a myelomeningocele had an ileal conduit performed and died two days after operation of peritonitis and urinary ascites. Two older children with reflux died in spite of successful ureteroneocystostomy, one following a cerebral haemorrhage and the other because of hypertension and uraemia. Five children with mechanical urinary obstruction died after discharge of uraemia and urinary infection. The following reasons for the deaths could be found: -- In two cases wrong indication for operation. -- In one case a technical fault at operation. -- In two cases the diagnosis was made too late. -- In five cases the wrong type of operation was used.


Malformations of the lungs.

Malformations of the lungs. The postoperative fatal cases following lung resections and those following drainage of pleuropulmonary suppuration have been evaluated. It has been shown that prognosis is significantly better when resections of the lung are carried out than when septic processes in the pleural cavity occur, although the operative interferences in cases of resection are much more extensive than the insertion of a suction catheter for empyema. It was found that with today's methods of anaesthesia and resuscitation even extensive operations on the lung are less risky than bacterial infections.


Malformations of the lungs: analysis of the postoperative deaths and conclusions for improvement in therapy. Complications of pulmonary surgery in childhood which should be prevented are: 1. Wrong indication for thoracotomy. An exact preoperative diagnosis including angiography is necessary to diagnose exactly the morphological abnormalities (i.e. arteriovenous fistulae). 2. Technical mistakes: Identifying vascular connections in cases of sequestrations of the lung which may transverse the diaphragm; priority of ligation of the vessels in pulmonary resections carried out for arterio-venous fistulae, i.e. the artery must be ligated first then the vein. If haemorrhage will occur from the vena cava, longitudinal clamps must be applied. Blindly carried out punctures of the lung are contraindicated. Pleural drainage catheters should be placed one intercostal space higher than the hole where they pass through the skin. In cases with cysts of the lung (i.e. echinococcus) where there is a danger of a rupture of the cyst into a bronchus, unilateral intubation is indicated.


The immunological state of the neonate following surgery--consequences for immunotherapy of neonatal septicaemia. In addition to an innate functional dysmaturity of the neonate's immune system, operation, anaesthesia, and intensive care measures can significantly worsen this physiological immune deficiency. Given the fact that antimicrobial therapy as well as progress in intensive care of infected operated neonates and prematures did not significantly decrease the high mortality rate in this patient age group we began performing fresh-blood exchange transfusions as supportive immunotherapy in the treatment of neonatal septicaemia. Since indication for exchange transfusion has been adopted as early as septicaemia was suspected only 46% of the operated neonates (13 out of 28) died of their infection, compared to 82% of the patients (23 out of 28) who did not undergo exchange transfusion.


Myelomeningocele; an analysis of deaths following early closure of the back lesion. In three separate series of patients with open myelomeningocele treated in the neonatal period, meningoventriculitits was found to be the commonest cause of post-operative death. Improved neonatal surgical centres and less pressure on the nursing staff have reduced the incidence of this complication.


Causes of death in 31 newborn infants with myelomeningoceles. Eight of the ten premature infants died during the first ten days. Six of these were in poor general condition with cyanosis, respiratory distress or aspiration of amniotic fluid. One child died after a fit before he was operated upon for his myelomeningocele. Ventricular haemorrhages were found in two premature infants. Seven of the premature infants died of an infection. In 23 infants the myelomeningocele was not covered by a membrane. Approximately 75% of the infants, i.e. 15, died during the first week of life. A meningitis was found in five infants; in four cases it was due to E. coliand in one, due to klebsiella. It, therefore, appears from studying our case material that deaths in newborn infants with myelomeningocele depends on the following facts: 1) maturity, 2) associated malformations, 3) whether the myelomeningocele is covered by a membrane or not.


Causes of late death due to hydrocephalus and meningomyeloceles. In conclusion, it can be said that operative treatment of hydrocephalus was carried out almost exclusively using the Holter valve and the Rickham reservoir. There was a lack of experience with other drainage systems. Of the 291 children operated in this clinic, 274 were evaluated. The fate of the other 17, all of whom were foreigners who returned to their countries, is unknown. A considerable number of children in the late death group did not come regularly to the postoperative care unit or came too late for control investigations, or died at home or in paediatric departments far away from this centre.


The use of high pressure liquid chromatography (HPLC) for the separation of radiolabeled arachidonic acid and its metabolities produced by thrombin-treated human platelets. I. The validation of the technique. We have developed a technique for the rapid separation and quantitative collection of thromboxane B2 (TXB2), PGE2, PGD2, PGF2 alpha, 12-hydroxy-5,8,10 heptadecatrienoic acid (HHT), 12-L-hydroxy-5,8,10,14 eicosatetraenoic acid (HETE), and arachidonic acid released from thrombin treated human platelets. Platelets were pre-labeled with 3H-arachidonic acid and then isolated by gel filtration. They were then exposed to thrombin for various intervals and separated by centrifugation. Aliquots of the cell-free medium were applied directly to a high pressure liquid chromatograph containing a fatty acid column as the stationary phase. A quarternary solvent system containing tetrahydrofuran (THF), acetonitrile (CH3CN), water and acetic acid (HOAC) resolved and eluted the arachidonic acid metabolites within 30 minutes. Since no sample preparation is required and since the solvent system does not quench the counting efficiency of a standard liquid scintillation fluor the technique permits rapid separation and quantitation of radiolabeled arachidonic acid and its metabolites.


Facilitation of suction termination using extra-amniotic prostaglandins in gel. Extra-amniotic prostaglandin E2 (PGE2) suspended in a slow release gel (Tylose) was instilled in 35 patients prior to a planned surgical termination in an attempt to dilate the cervix, minimize cervical trauma, and reduce the possible risk of cervical trauma, and reduce the possible risk of cervical incompetence and its sequelae. Dilatation occurred in all patients to a minimum of 8 mm and 74% aborted before surgical evacuation performed 6 to 24 hours after injection. No serious side effects occurred. Extra-amniotic PGE2 in gel should be considered as a primary procedure when the cervix is obviously immature on examination. If the cervix is found to be tight and unyielding at surgical dilatation, the latter procedure should be dicontinued and PGE2 in gel injected.


The systemic absorption from the vagina of prostaglandin E2 administered for the induction of labour. The absorption rates of PGE2 released from tablets, gel and pessary bases inserted into the vagina for the induction of labour in a total of 27 patients have been measured by means of serial plasma 15-keto-PGE2 levels. The results are discussed with a view to obtaining both the optimum dose of PGE2 and vehicle of release.


Modulation of the adherence of human lymphocytes to measles-infected cells by prostaglandin E1: a differential effect on lymphocyte subpopulations. Prostaglandins of the E series (PGE) may serve as important regulators of human immune responsiveness. The present study was designed to examine the possibility that PGE may effect human lymphocyte function by the modulation of surface receptors. The presence of surface binding sites on human lymphocytes for measles virus antigens was studied using a rosette adherence assay. We observed that the addition of PGE1 increased the proportion of measles-infected cells (Hela-Kll) with adherent lymphocytes (75% increase at 3 x 10(-6) M PGE1). PGE was observed to enhance the adherence of purified normal peripheral T cells (87%) and T lymphoid cells (Molt 3) (27%). In contrast, no significant change in normal peripheral B cell or B lymphoid cell (Raji) adherence was observed with the addition of PGE. These results are consistent with a selective modulation of surface measles virus binding sites by PGE1 on T and not B lymphoid cells.


Kidney kallikrein and phospholipase activities in Milan spontaneously hypertensive rats. Renal kallikrein and phospholipase activities were evaluated in a strain of spontaneously hypertensive rats developed by Dr. Bianchi in Milan (MHR). MHR showed lower than normal kallikrein and phospholipase activities before, at 3 weeks of age and following the development of hypertension. Kallikrein and phospholipase activities were directly correlated both in normotensive and spontenously hypertensive rats. The data suggest that MHR have a genetic defect in kallikrein and phospholipase activities, which may play a pathogenetic role in the development of high blood pressure.


Effect of prostaglandins on in vitro synthesis of progesterone and oestradiol-17 beta in placenta from early human pregnancy. In vitro synthesis of progesterone and estradiol-17 beta from endogenous precursors was studied in the placenta from women in early stage of gestation (less than 7 weeks). Radioimmunoassay techniques were used to measure progesterone and estradiol-17 beta. It was shown that placental tissue from as early as six weeks of gestation can synthesize both progesterone and estradiol-17 beta in vitro. Prostaglandins F2 alpha and E2 in concentration of 100 micrograms/ml of the incubation media did not have any significant effect on the in vitro synthesis of progesterone and estradiol-17 beta in the placental tissue. It seems unlikely that the abortifacient effect of natural prostaglandins PGE2 and PGF2 alpha is due to their direct action on the synthesis of progesterone and estradiol-17 beta in the placenta.


The identification of an epoxy-hydroxy acid as a product from the incubation of arachidonic acid with washed blood platelets. An epoxy-hydroxy compound, 10-hydroxy-11,12-epoxy-eicosa-5,8,14-trienoic acid, has been identified as a product on incubation of arachidonic acid with washed blood platelets from human, horse, cat, dog and rabbit. Gas chromatographic - mass spectrometric (GC-MS) evidence of structure is discussed.


III - Prostaglandin hyperalgesia: relevance of the peripheral effect for the analgesic action of opioid-antagonists. Morphine injected into the rat cerebral ventricles had a marked analgesic effect, while no effect was observed with pentazocine and naloxone or nalorphine caused a strong hyperalgesia. Administered systemically (IP) naloxone and nalorphine caused a transitory analgesia followed by a long lasting hyperalgesic effect; morphine and pentazocine showed only an analgesic effect. It was concluded that the site of analgesic action of opioid-antagonists is peripheral rather than central. The peptidase-resistant enkephalin-analog, BW 180c, which does not cross the blood brain barrier, caused a marked analgesia by IP administration to paws made hyperalgesic by PGE2 or carrageenin. It is suggested that agents derived from morphine, morphine-antagonists, enkephalins or cGMP devoid of central effect but having a strong peripheral effect may constitute a new class of safer analgesics.


A unique affinity and adaptation of renomedullary interstitial cells for hypertonic medium. Collagenase-dispersed cells of renal papillary tissue from adult mongrel dogs were directly inoculated in a modified M.E.M. (Eagle's) giving an osmolality of approximately 1,000 mOsm/L by addition of urea and sodium chloride, and were cultured in an atmosphere of 95% air-5%CO2 at 37 degrees C. Within twelve hours after inoculation, spindle-shaped cells attached firmly to the surface of culture dishes, while the other cellular components of the inner medulla remained floating in the medium. After several days in culture, the colonies grew to form a confluent cell layer, which was composed of almost homogenous cells giving spindle-shape. These cells kept on the major characteristics of renomedullary interstitial cell (RIC) in morphology as well as in function to produce prostaglandin E. These results appear to be principally attributable to the unique characteristics of RIC, one of which is affinity for high osmolality and the other is different behavior in attachment to the dish. As the procedure proposed here was relatively simple and did not require a long period up to the development of monolayer, it would provide a promising model "in vitro" to study the humoral regulation of prostaglandin production.


Effects of prostaglandin E2 and F2 alpha on the absorption and portal transport of sugar and on the local intestinal circulation. With the isolated jejunum loop technique investigations of prostaglandin E2 and F2 alpha were made on canine intestinal absorption and transport of glucose and on the circulation of the intestinal loop. These compounds decreased glucose absorption; intra-arterial prostaglandin administration decreased the portal transport of glucose, but intraluminal administration caused an increase. PGE2 enhanced the circulation of the intestinal loop; intra-arterial PGF2 alpha diminished this circulation, whereas on intraluminal PGF2 alpha had no significant effect.


The mouse anti-morphine constipation test--a simple laboratory test of the gastrointestinal side-effect potential of orally administered prostaglandin analogues. A test is described which is simple, reliable and highly sensitive to the diarrhoea-inducing properties of orally administered prostaglandin analogues in mice. Comparison with human data shows similar orders of relative potency.


Pulmonary and systemic vascular responses to 6-keto-PGE1 in the conscious lamb. 6-Keto-PGE1 is a potent direct dilator of the pulmonary and systemic circulations of the newborn lamb under both normoxic and hypoxic conditions. Its threshold dose is similar to that of PGI2 and PGE1. Under hypoxia, 6-keto-PGE1 appears equally effective on the pulmonary and systemic circulations, while under normoxia it predominantly affects the systemic circulation.


Differential effects of probenecid on the levels of endogenous PGF2 alpha and TXB2 in brain cortex. Probenecid in single or repeated doses does not modify levels of PGF2 alpha and TXB2 in rat brain cortex. After administration of subconvulsant dose of pentamethylene tetrazole (PMT) PGF2 alpha increases sharply and rapidly declines subsequently, whereas the elevation of TXB2 is smaller but of longer duration. After probenecid pretreatment PGF2 alpha levels do not decline up to 30 minutes after the initial peak and are still elevated after 60 minutes. Levels of TXB2 tend to be reduced after pretreatment. Differences in transport process or in biosynthetic compartments for these arachidonic acid (AA) metabolites may account for the observed data.


Some biological activities of a series of 9a-homo-9,11-epoxy prostanoic acid analogues. A number of stereochemical variants at C-8, C-12 and C-15 of 9a-homo-9,11-epoxy prostaglandins (PGs) have been examined for in vivo activity on blood pressure, bronchial resistance, tracheal segment pressure, heart rate and on intestinal and uterine contractility in artificially respired anaesthetised guinea-pigs; and on blood pressure and blood platelet aggregation in rats (using the extra-corporeal filter-aorta loop technique). In vitro tests for smooth muscle activity were carried out on the isolated rat fundus strip, the guinea-pig tracheal chain and the rat uterus. The following was found: 1. In the guinea-pig, in vivo, all the homo-epoxy PGs were vasopressor and bronchoconstrictor following bolus injections of 250 micrograms i.v. The effects on heart rate, and intestinal and uterine contractility were equivocal. The configurations at the chiral centres, C-8, C-12 and C-15 play an important role in determining potency. The 15-(S)-hydroxy derivatives were the most potent in stimulating vascular and respiratory muscle. The 8-iso configuration appeared to enhance potency amongst the 15-(S)-hydroxy compounds. The 15-(R)-hydroxy configuration markedly reduced constrictor potency. The same pattern of activity was seen on rat blood pressure, in vivo. The 15-(S)-hydroxy configuration combined with the 8-iso configuration had the most potent constrictor activity, while the 15-(R)-hydroxy group negated this and even led, in the case of the natural configuration at C-8 and C-12, to vasodepression. 2. In vitro, the activity on the rat fundus and guinea-pig tracheal chain followed the same pattern. The 15-(S)-hydroxy derivatives were very much more potent than the 15-(R)-hydroxy derivatives at contracting the smooth muscle preparations. Uterine muscle appeared to be relaxed by the PGs with the natural configuration at C-8 and C-12, with the 15-(R)-hydroxy compound exhibiting greater activity. 3. Inhibition of ADP-induced rat blood platelet aggregation after "intra-arterial" administration was shown only by the derivatives with a single change in the natural configuration either at C-8 or at C-15. Additional changes either resulted in inactivity or, in the case of the 8,12-di-iso-15-(S)-hydroxy compound, even reversed the effect to aggregation. The inhibition of aggregation was long lasting with both the 8-iso-15-(S)-hydroxy derivative and the 8,12-nat-15-(R)-hydroxy derivative. In the case of the latter compound, GBR-30731, activity increased during the 30 min after administration. GBR-30731 deserves further investigation as a platelet aggregation inhibitor because of its relatively low smooth muscle stimulant (sometimes even relaxant effects) and its long lasting platelet aggregation inhibiting activity.


[Value of visual evoked potentials in multiple sclerosis (MS). Comparative study of results obtained by light flash and checkerboard reversal stimulation]. Evoked visual potentials were studied in 12 subjects diagnosed or suspected of having MS. A comparison was made between these subjects and results obtained with single eye stimulation using a flash of light (101 subjects) or by using a reversible checker-board pattern (58 subjects). Reversible checker-board pattern simulation showed pathological unilateral or bilateral increase in the latency of the main positive spike in the response of 80% of the verified MS cases and 50% of the probable or possible MS cases. These percentages were 25% lower when flashes of light were used as stimulation. 58% of those patients who have never presented ophtalmological symptoms have abnormal latency in responses invoked by the reversible checker-board pattern, as opposed to 20% using flashes of light for stimulation. Study of E.V.P. in normal subjects indicates that the better results obtained with reversible checker-board stimulation can be attributed to greater reproductibility of the response. Analysis of the overall morphology of the responses significantly increases E.V.P. examination efficiency when using flashes of light as stimulation. However, in our series, it does not change the results obtained by only calculating the latency of response to reversal of a checker-board pattern.


[Role of the amygdala in the occurence of oro-alimentary signs of during epileptic seizures in man (author's transl)]. The authors study the role of amygdala dysfunction in cases of oro-alimentary signs occuring in seizures recorded during a series of stereo-electroencephalographic investigations (S.E.E.G.) carried out for neurosurgical purposes. The patients under study have an epilepsy that is resistant to drug therapy. This work concerns 89 seizures with "oro-alimentary motor activity" recorded in 59 patients with whom it was possible to establish sufficiently rigourous anatomical - electrical - clinical correlations. This study enabled us to show that : --a seizure characterized by "oro-alimentary motor" signs (with the exclusion of swallowing movements) is related to a discharge that directly involves the amygdala. --a critical discharge affecting the anterior temporal region is expressed as : oro-alimentary activity either accompanied or not by other signs (breaking contact is exceptional). --late "oro-alimentary motor activity" also indicates disorganization of the amygdala, but offers no conclusion on the origin of the discharge.


[Semiological comparison of spontaneous and bemegride-induced epileptic seizures (author's transl)]. The authors view an epileptic seizure as a series of symptoms which they can localize on the bases of data taken from stereoelectroencephalography literature. They reconstruct and compare the presumed organization (origin and propagation) of the discharge in 100 epileptic subjects. Both spontaneous and megimide-induced seizures are considered. The results involve 34 subjects with quite similar spontaneous and induced seizures. Comparison of the two critical modalities show that : 1) There is no variation in the chronological relationship of the symptoms. 3) There are differences in the symptomatology. These differences may be interpreted as non-uniform response of involved structures to the source of activation, or as involvement of new structures.


[Respiration and night sleep in children "at risk" for sudden and unexpected death (author's transl)]. Polygraphic recordings were used to study respiration and night sleep in 26 such children. These children, who were "at risk" for sudden and unexpected death, could be divided into two groups : near-miss (NM) (15 cases), and those who were brothers, sisters, or cousins of a child who had died suddenly and unexpectedly (8 cases), or had periodic respiration (RP) (3 cases). No significant differences were found between the groups in respiratory tests, except for a significantly lower RP rate in the NM group and an increase in number of isolated pauses. Sleep organization was similar in both groups, though there was a significantly higher rate of active sleep (SA) in the NM group more than 2 months old. The highest respiratory indices were noted in the extreme cases of a non-NM group (including 2 brothers of infants who had died unexpectedly). Treatment with Diphemanil methylsulfate (Prantal) reduced the number of SA and respiratory pauses of the NM infants less than 2 months old.


[Sleep apnea synrome : effects of chlorimipramine in subjects with stable body weight (author's transl)]. Beneficial effects have been attributed to Chlorimipramine in the treatment of sleep apnea syndrome (SAS). However, there were no quantitative evaluations of these effects. Polygraphic studies were made before and after chlorimipramine treatment (75 mg per day for 3 to 16 months). The 3 SAS subjects, whose weight remained stable throughout the course of treatment, showed no evidence of reduced hypopnea and apnea during sleep.


[Comments on sleep in Korsakoff's syndrome]. Twenty recordings of night sleep were made on ten patients with Korsakoff's syndrome. A large increase in time spent awake and in stage I sleep is reported as well as confused sleep cycles, increased ocular density in case of confabulation and dream accounts recalling mental activity from the previous day. Hippocampomamillary dysfunction appears to be responsible for disturbances in the cycles.


[Assisted ventilation of newborn infants during sleep. Study of factors modifying adaptation to ventilation]. During sleep, of ventilated newborns and young infants, spontaneous respiratory movements may occur, unrelated to the ventilation impulsions. The respiratory pattern is then classified as "active". On the contrary, the respiratory pattern is classified as "passive", when all respiratory movements are related to the ventilation insufflation. The factors which influence the dependence on the ventilator are studied in a group of 20 newborn and young infants. Prematurity, some biological data such as hyperoxia, hypocapnia, seem to favor this dependence. A rapid rate of ventilation (superior to 30/minute) is rarely related to an active respiration; a slow rate of ventilation seems favor this respiratory pattern. It is clear that adaptation to artificial ventilation is better during quiet sleep than during active sleep. Some physiopathological considerations are developed.


Electroencephalographic affects of an anti-inflammatory analgesic: mefenamic acid. A study of the electroencephalographic patterns observed following iv administration of increasing doses of mefenamic acid in acute experiments on curarized cats and rats and the possible modification of these effects by naloxone was carried out. Mefenamic acid produced in both species a progressive and dose-related increase of the voltage of the baseline patterns. With high doses, besides slow waves and fusiform complexes, an irritative activity with spikes and complexes of polyspikes was observed. The recovery of the basal activity was obtained within 15 min, except for the highest dose, under which the effect lasted 30 min after administration. Cats displayed a higher sensitivity than did rats. Naloxone did not modify the EEG effects of mefenamic acid, neigher in rats nor in rats. This fact suggests that the locus of action of these drugs is different. Mefenamic acid appears to act centrally with relatively short-lasting depressant effects at low doses and facilitating or stimulant effects at high doses.


Further characterization of the inhibition of aldehyde dehydrogenase activity by pargyline. The in vivo inhibition of low Km mitochondrial aldehyde dehydrogenase (AlDH) activity by pargyline was not maximal until more than 30 minutes after i.p. injection. Enzyme activity returned to control levels within 36 hours of drug injection but the return of activity was slowed by cycloheximide pretreatment. Female rats and higher basal total and low Km mitochondrial AlDH activities than did males. Injection of pargyline inhibited low Km mitochondrial AlDH activity more in males than in females. Incubation of rat liver microsomes with an NADPH-generating system and pargyline produced an in vitro inhibitor of low Km mitochondrial AlDH activity. Pretreatment of rats with phenobarbital increased the AlDH inhibitor produced by incubation of their microsomes with pargyline. Injection with benzylpropargylamine, N-demethylated pargyline, also preferentially inhibited the low Km form of mitochondrial AlDH activity. Neither pargyline nor benzylpropargylamine injections affected microsomal AlDH activity. Total AlDH activity, measured with 5mM propionaldehyde, in rat liver 100,000g supernatant was not changed by administration of either drug. Supernatant activity assayed with 50 microM propionaldehyde was inhibited by both pargyline and benzylpropargylamine treatment.


Interaction of mestranol with taurocholate uptake by isolated rat hepatocytes. Cellular uptake interactions between mestranol and taurocholate at concentrations between 50 and 1000 microM in the medium were studied in isolated hepatocytes. Rat liver cells exposed to medium containing mestranol and taurocholate attained up to twice as large a concentration of mestranol as those exposed to mestranol without the presence of the bile acid in medium. In contrast, taurocholate concentration in cells exposed simultaneously to taurocholate and mestranol was one fourth of the concentration in cells exposed to taurocholate alone.


Tissue binding of warfarin.

Tissue binding of warfarin. The binding of C-14 warfarin to liver, kidney, and skeletal muscle was evaluated among rats ranging in age from 29 to 832 days. Binding extensiveness was greatest for liver and least for skeletal muscle. The mean fraction bound remained relatively constant for each tissue among animals of all but the oldest age group. The oldest animals exhibited a lower fraction bound in each tissue. The influence of decreased tissue binding on its temporal profile in the blood is discussed.


Elimination of allopurinol by the perfused rat liver preparation. The elimination of allopurinol was studied in the perfused rat liver preparation. When tracer input [14C]-allopurinol concentrations (0.04 to 0.17 microgram/ml) were delivered under constant flow rate (10 ml/min/liver) only once through the rat liver, the steady-state hepatic extraction ratios were high (0.87 +/- 0.03). But at higher input allopurinol concentrations (3.3 to 17 micrograms/ml), concentration-dependent elimination of allopurinol was observed. The steady-state hepatic extraction ratio was drastically reduced with increases in input concentrations. At very high input concentrations of allopurinol (17 micrograms/ml) the hepatic extraction ratio was virtually zero. These findings inferred that the rat liver may play only a moderate role in the elimination of allopurinol in the intact animal.


The effects of allopurinol on skeletal muscle microcirculation in normal and dystrophic mice. Allopurinol lowers peripheral vascular resistance in dogs, and it has beneficial effects upon muscular dystrophy patients. Since it has been suggested that muscular dystrophy may result from muscle ischemia, we decided to investigate the effects of allopurinol on skeletal muscle blood flow in normal and dystrophic mice. Arterioloar red cell velocity and diameters were measured in the cremaster muscle and used to calculate blood flow. Allopurinol (5 mg/kg, i.p.) resulted in an 81% increase in arteriolar blood flow in normal mice and a 102% increase in dystrophic mice. Such an increase in microcirculatory perfusion could be a mechanism contributing to the clinical effects of allopurinol.


The effect of tumor localizing porphyrins on the conversion of fibrinogen to fibrin. The interaction of hematoporphyrin IX and two synthetic porphyrin tumor localizers, meso-tetra (4-carboxyphenyl) porphine (TCPP) and mesotetra (4-sulfonatophenyl) porphine (TPPS4) with fibrinogen was investigated in the presence and absence of light. Both TPPS4 and TCPP were found to bind to fibrinogen in greater than a 1/1 mole ratio in the absence of light. Chromatographic analysis indicated that during illumination TPP4 bound to fibrinogen to a greater extent that did either TCPP or hematoporphyrin. Both TCPP and TPPS4 were found to exhibit a greater inhibitory effect on clotting in the presence of light than did hematoporphyrin. In the absence of light and added Ca2+, both TCPP and TPPS4 were found to stimulate clotting at very specific porphyrin/fibrinogen concentration ratios, with TPPS4 being the more potent stimulator of the two. Hematoporphyrin exhibited little or no effect on clotting times. Fibrinogen, photoirradiated in the presence of the porphyrins was found to inhibit the clotting of unirradiated fibrinogen. A comparison of the stimulatory effects on clotting times by either calcium or TCPP and TPPS4 indicated that the porphyrins were capable of eliciting a greater stimulatory response than did calcium. The magnitude of the stimulatory response caused by the porphyrins alone was substantially reduced in the presence of calcium although the overall stimulatory response was increased but not additive. This suggests some interaction between either the calcium and porphyrin molecules or similarities in the respective stimulatory mechanism(s) involved. A possible correlation between these observations and the porphyrins ability to localize in tumors is also discussed.