[Frequency and natural history of several types of transpositions of the great arteries (TGA) in children (author's transl)]. The frequency and clinical differences between several types of TGA have been estimated. In a group of 52 patients with TGA three anatomic types were distinguished on the basis of the classification of Nadas (Fig. 1). The correlation between TGA type and sex, weight at birth, predominating clinical symptoms, most frequent clinical complications and survival time in children with this congenital malformation were investigated (Fig. 1-6). Type I was found almost five times more frequently in boys who had a higher than average weight at birth (Fig. 1-3). The most frequent clinical symtpoms were: cyanosis, early congestive heart failure and paroxysmal anoxemia (Fig. 4). Infants with this TGA type died much earlier than infants with other TGA types (Fig. 6). The frequency of type IIA was the lowest, similar in both sexes (Fig. 1). Among clinical symptoms cyanosis, paroxysmal anoxemia and systolic murmurs prevailed. No congestive heart failure was observed in this type (Fig. 4). Type IIC was more frequent in boys, but simultaneously it was the most frequent TGA type noticed in female infants (Fig. 1). Almost in all children heart murmurs were found, but only one of the examined cases with this type was affected by congestive heart failure (Fig. 4). The above-mentioned differences between clinical symptoms of several types of transposition of great arteries can be helpful when the adequate treatment is chosen.


[A study of the mortality of children with transposition of the great arteries treated at the Institute of Pediatrics, Medical Academy of Cracov, in 1966-1973 (author's transl)]. The mortality of children with transposition of the great arteries treated at the Institute of Pediatrics in 1966-1973 was assessed. The number of deaths among 52 observed children, 5 days to 8 years old, was analysed according to the sex and age of the children treated during 8 subsequent years (Fig. 1). It was shown that this congenital heart malformation occurred three times more frequently among boys than among girls, but mortality was the same in both groups examined (Table I). The period of 8 years was divided into 2 four-year periods because the surgical treatment of that condition was introduced only after 1970. According to the authors' observations all children who were treated conservatively during the first period (1966-1970) have died. During the second period (1970-1973) this malformation of the heart was diagnosed twice as often, in 35 cases, and there were only 21 deaths among these children (Table II). During that period the diagnosis of this malformation greatly improved, because in half of the cases observed the proper diagnosis was made in the first two weeks of life. This is a positive fact, because the possibility of successful septostomy is greater if the surgery is performed on younger infants.


[Significance of growth hormone for the regulation of ribonuclease activity in rat plasma (author's transl)]. The administration of growth hormone to hypophysectomized rats caused an increase of ribonuclease activity in plasma within the limits of 70 to 200 per cent. An injection of actinomycin D, simultaneously with the growth hormone, inhibited this effect.


[ECG in complete transposition of the great arteries according to the TGA type (author's transl)]. The ECG pattern in 36 infants with complete TGA has been presented. An attempt was made at correlating ECG changes and the type of TGA.


[Chest X-ray films in particular types of transposition of the great arteries (author's transl)]. The article has been based on the study of 46 cases of transposition of the great arteries including children aged one day to one year. No symptoms of interventricular septal defect were discovered in X-ray films, nor was it possible to define the type of transposition. The author also discussed the narrowing of the base of the heart. The shape of the base may be due not only to the small thymus shadown, but also to the position of the aortal arch in the central plane of the body.


[Palliative procedures in children with transposition of great arteries (author's transl)]. The authors presented their own experience in the treatment of newborns and infants with transposition of great arteries. Three groups of patients with different types of malformation (according to Noonan, Nadas and coll.'s classification) were observed. The first group included newborns with type I and II which needed the Rashkind baloon septostomy in the first week of life. In the second group of infants the Blalock-Hanlon surgical creation of ASD was effected. The third group of patients with the II A type of TGA needed pulmonary-systemic anastomosis and Blalock-Taussig operations were performed.


[Transposition of great arteries (the authors' own experiences in diagnostic procedures and treatment) (author's transl)]. In 18 months since the opening of the Paediatric Institute in Poznań, 20 cases of simple complete transposition of the great arteries were admitted to this hospital. The clinical material consisted of 19 neonates, 3-7 days old, and one 3-month-old infant. All children were in a severe condition, with deep central cyanosis, congestive heart failure and severe metabolic acidosis. Six of them died during the standard diagnostic procedures. Fourteen have been submitted to cardiac catheterization and angiocardiography, and in 13 ballon septostomy was performed. In two children surgical creation of an atrial septal defect was undertaken, in one case--6 months after a successful ballon septostomy. Twelve of the 14 children, in whom an atrial septal defect has been created by means of various methods, are alive and well.


[Cardiac surgery at the pediatric surgery clinical department of the Pediatric Institute, Medical Academy, Poznań (author's transl)]. In the 18 months since the opening of a new Pediatric Surgery Clinical Department of the Pediatric Institute in Poznań, an artificial heart-lung apparatus for perfusions in children was developed in collaboration with the PONAR-WIEPOFAMA factory. During this time 40 cardiac operations were performed including 11 open heart procedures. Among 40 cases operated, 6 died; 3 after open heart operations: 1 tetralogy of Fallot, and 2 cases of VSD combined with PDA and pulmonic valve stenosis. 3 infants died after surgery undertaken in the presence of severe uncontrollable heart failure. The overall mortality was 15%.


[Monitoring of cardiac rhythm changes during surgical operations with total cardiopulmonary bypass with haemodilution and hypothermia in infants and small children (author's transl)]. Surgical corrections of some serious cardiovascular anomalies in infants and small children were attempted within the last 2 years; 12 severely ill infants and children below the age of 3 years were operated. All, but one, were below 10 kg of body weight, and in all of them there was a considerable weight deficit, more than 30%. The risk of operation was undertaken because of the ineffectiveness of medical treatment and very bad prognosis. The following cardiovascular lesions were operated: large aortopulmonary septal defects, localized just above the valvular rings in 2 patients with severe pulmonary hypertension, with very good effect in both; tetralogy of Fallot - in 2 babies, in one with good effect; congenital mitral obstruction with pulmonary hypertension in one case, with good effect; total anomalous pulmonary venous return of supracardiac type in one child, decreased 1 week following operation; type 1 complete transposition of great arteries in one baby, deceased one day following operation; large ventricular septal defects, with systemic or nearly systemic pulmonary hypertension in 5 children, in one with long-term good effect. A modification of the Barrat-Boyes, Neutze and Simpson method, based upon a combination of surface and core cooling was applied. Thoracotomy was performed after surface cooling to 34-32 centigrades, and then a single venous cannula was inserted into the right atrium and an arterial cannula -- into the aorta. Deep cooling was obtained during perfusion, using a heat exchanger. The duration of cooling perfusion was, on an average, 20 min., and the patients were cooled to a temperature of 23-21 centigrades. The corrections were performed on relaxed and bloodless heart, during the circulatory arrest lasting for 20-65 min. (40 min. on an average). Following repair the patients were rewarmed to temperatures of 36-37 centigrades by warming perfusion lasting on the average 40 min., including assisted circulation, until a haemodynamically sufficient cardiac output was present. Silicated ACD-blood, diluted to a hematocrit value of 28-30 Vol. % by a polyelectrolyte buffered solution was used for priming and perfusion. During all the procedures any pH and HCO3 deviations were balanced currently. At the time of cooling perfusion, when the patient's rectal temperature fell down to 30-25 centigrades, the heart started to fibrillate. At temperatures above 26 degrees C ventricular fibrillation was sometimes preceded by sinus bradycardia, or sinoatrial block/arrest, with an AV nodal rhythm and gradually increasing intraventricular conduction slowing. In some cases high degree AV block appeared. At temperatures of 25-23 centigrades - slow fibrillation appeared, followed usually by a complete cardiac arrest.


[Endocardial fibroelastosis in infants observed at the children's ward of the County Hospital in Włocławek (author's transl)]. The authors have observed eight children suffering from endocardial fibroelastosis at the Children's Ward of the Ziemia Kujawska county hospital in Włocławek. The diagnosis was confirmed by autopsy. In five cases it was isolated fibroelastosis in the remaining three cases fibroelastosis was complicated by other heart malformations. In most of the patients severe symptoms appeared within the first six months of life. All the observed children died in the first two years of life. Death occurred within one day to six months after the appearance of symptoms. The main symptoms were present in ECG, X-rays and laboratory tests.


[Clinical diagnosis of supravalvular aortic stenosis in children (Wiliams's syndrome) (author's transl)]. Six cases of Wiliams syndrome have been observed. In 3 children the supravalvular aortic stenosis was diagnosed in infancy. The diagnosis was based upon the triad of symptoms: 1) supravalvular aortic stenosis, 2) typical appearance of the patient, 3) considerable mental disability.


[Difficulties in diagnosis in primary cardiomyopathies in infants (author's transl)]. Four children were observed in 1970-1973 in whom cardiomyopathy was diagnosed in early infancy. The symptoms were severe congestive cardiorespiratory failures accompanied by pulmonary infections. Considerable cardiomegaly, particularly the left ventricular and atrial hypertrophy, abnormal E.C.G. and mechanocardiographic records, rhythm and conduction disturbances were found in all cases.


[Content of phenobarbital in some tissues of the fetus and mother (author's transl)]. There were performed estimations of the phenobarbital content in the placenta and in the liver and kidney of the mother and fetus after prolonged administration of this drug to pregnant females. Phenobarbital was injected in two various doses: 1/10 LD50 and 1/20 LD50. The mean results of the determinations were in all examined tissues higher in the group receiving 1/20 LD50. These results were, however, statistically significant only in the placenta. No significant differences were found in the kidney of the fetus as far as the variability of results is concerned, but liver and placenta showed a highly significant variability in the group receiving 1/20 LD50. A positive correlation was found between the content of phenobarbital in placenta and liver, and the content in placenta and kidney in the 1/20 LD50 group. The ability of phenobarbital to pass through the placenta as well as the fairly high content of this drug found in the fetus tissues points out its possibility to damage the organs of the developing fetus, and by the same--the necessity to be careful during prolonged administration of this drug in pregnancy.


[Investigation on protein and protein fractions concentration in the serum of healthy children over one year old (author's transl)]. Protein concentration and the relative percentage of protein fractions in serum have been studied in 2 to 15 years old 226 healthy children. The mean values and standard deviation were calculated for every year of child life. The correlation analysis of all parameters investigated with the age of the children was also presented, as well as the relationships between the various parameters.


[Glycemia and the levels of free fatty acids in small-for-date born infants after monosaccharide load. Communication I (author's transl)]. In order to evaluate some aspects of carbohydrate metabolism in small-for-date born infants the authors have performed in them the glucose tolerance test. The glycemic reflex was estimated in relation to the free fatty acids level (FFA). This was done twice a year in the first half year of life and in the second one. We compared the results with data obtained form full-size born infants tested in the same of time. The group of small-for-date born (SRDB) infants included 23 infants in the first half year and 12 in the second one. The SFDB infants were loaded with glucose and galactose given to them in a dosis of 1 g of each sugar in a 15% solution. The following micromethods were applied: Hyvarinen and Nikkila for glucose, and Dole and Meinertz in Novak's modification for FFA. The level of glucose and FFA were estimated at fasting and after loading at 20, 40, 90, 120 and 180 minutes. In order to be able to evaluate the results, the authors performed the variance analysis. On the basis a significantly higher variability of FFA levels was found in comparison with glucose levels as well as a variability of the two parameters significantly higher in small-for-date born infants than in full-size born infants. In spite of that in standarized mean values a relationship between glucose and FFA levels was found in small-for-date born infants opposite to that in full-size born infants. In the former the glucose levels and free fatty acids were higher then in the latter. This phenomenon disappeared in the second half-year of life. The disappearance rate (as measured by coefficient K) was slightly higher than in the second half year. In the second half year this difference was not noted between the observed parameters in two groups of infants. If it may be concluded on the basis of the authors' observations, the higher levels of glucose in small-for-date born infants in their first half year of life could indicate some disturbance in glucose utilization and the higher level of FFA then usually found in fullsize born infants during the oral glucose tolerance test might be an additional proof for the above.


[Influence of reserpine on the libration of catecholamines in the brain and heart of rats in ontogenetic development (author's transl)]. The influence of reserpine on the level of noradrenaline and dopamine in the brain, and that of noradrenaline in the heart of rats in various age groups were investigated. It was found that the level of catecholamines in the brain and heart of young rats decreases much more rapidly and to a greater extent than in adult rats.


[Neurological-and-psychological analysis of children over six years old with hemiparesis (author's transl)]. The authors have carried out neurological-and-psychological analysis of children with congenital or acquired hemipareses. The psychological analysis was carried out according to Wechsler's scale for children and, if needed, by means of some other psychological tests. In a comparatively high number of children a lowering of the level of intellectual development was found, as expressed in terms of a low I.Q. This involved mainly children with congenital hemipareses. Moreover, a number of partial C.N.S. dysfunctions was found in these children, in particular a lowering of the visual-motor coordination function, the perception of spatial relations and graphic functions. Dysfunctions of speech of C.N.S. origin were found in five children, and they were more frequent (being as many as four cases) in children suffering from right-sided hemiparesis. In the conclusion of their paper the authors carried out an attempt at interpreting the results obtained and postulated the need of further investigations on these subjects.


[Somatic characteristics of Warsaw children, 3 1/2 to 7 years old (authors's transl)]. Anthropometric measurements of 1031 children, 3 1/2 to 7 years old, were carried out in Warsaw in 1970. The data collected characterize the present state of the physical development of Warsaw children in the aforesaid age interval. Arithmetic means and standard deviations were calculated for 13 somatic traits (body height) and weight, length of lower and upper extremities; length of the trunk; shoulder and hip width; chest circumference, width and depth, head circumference; width of distal femoral epiphysis, and subscapular skinfold) (Tables I to V). They have become the basis for drawing diagrams for the graphic method of assessing the level of development of these traits. Besides, the differences between the somatic traits found by examining Warsaw children in 1959, and the traits obtained in 1970 were analysed (Fig. 1 and 2). It results from this analysis that the children examined in 1970 were taller and heavier, and that there were also differences between the other parameters. This justifies the need to bring data of this kind up-to-date. A comparison of the body height and weight of children of Warsaw, and those of two other Polish cities (Lublin and Szczecin) and of rural children (Fig. 11 and 12) show a considerable predominance of Warsaw children; this confirms the necessity to work out regional standards of somatic development.


Effects of scopolamine and D-amphetamine on one-way, shuttle and inhibitory avoidance: a diallel analysis in mice. The effects of scopolamine (2.0 mg/kg) and d-amphetamine (3.0 mg/kg) on one-way, shuttle and inhibitory avoidance performance were evaluated in 3 strains of mice (A/J, DBA/2J and C57BL/6J) and their 6 reciprocal F1 hybrids. In the saline condition, intermediate inheritance was observed in the inhibitory task, complete dominance for superior avoidance in the one-way task, and hybrid superiority in the shuttle situation. Administration of d-amphetamine disrupted inhibitory performance in all strains. In the shuttle task no amphetamine effect was observed in C57BL/6J mice, while improvement was seen in A/J and DBA/2J mice, as well as in all the hybrid corsses. No drug effect was seen in the one-way task. As with d-amphetamine, scopolamine disrupged performance in the inhibitory task among the inbreds, but had negligible effects in the hybrids. In the shuttle task, only the A/J mice exhibited improved performance, while a small decline in response rate was seen in one-way avoidance. Results were interpreted in terms of tha role of scopolamine and d-amphetamine in modifying non-associative factors involved in avoidance, and the interaction between associative and non-associative factors in modulating avoidance response rate.


Effect of aluminum upon conditioned avoidance response acquisition in the absence of neurofibrillary degeneration. Aluminum induces neurofibrillary degeneration in cats but not rats. Cats develop a progressive encephalopathy in which an early manifestation is impaired learning-memory performance. At brain aluminum concentrations of 5 to 6 times that found in cat, rats demonstrate an initial transient weight loss and acquisition deficit immediately following intracranial injection. However, rats do not develop a progressive encephalopathy or a chronic learning deficit.


Behavioral thermoregulation in the study of drugs affecting body temperature. A method of measuring thermoregulatory behavior in the rat has been developed, which allows analysis of the mechanism of action of drugs which modify body temperature. The test measures the amount of time a rat will remain exposed to an infrared heat source before making an escape and this evidence has been used to divide drugs into those which act on the central thermostats and those which act on effector systems. A peripherally acting hypothermic drug (N-methyldiphenhydramine) increased the time of exposure to the heat lamp. Tri-iodothyronine increased body temperature and decreased exposure to the heat lamp. Intraventricular oxotremorine caused hypothermia but a decreased exposure to heat suggesting it acts to lower the set-point of the central thermostats. Both effects were blocked by atropine. The possibility that central cholinergic mechanisms in the hypothalamus have a function in determining the setting of the central thermostats is discussed.


Influence of central cholinergic pathways on performance on free-operant avoidance and DRL schedules. Lesions in the medial septum, as well as systemic injections of the muscarinic cholinergic blocker, scopolamine, increased responding maintained by free-operant avoidance or DRL contingencies. Systemic injections of the anticholinesterase, eserine, suppressed responding in both paradigms. The medial septal lesions eliminated the effects of these cholinergic drugs in the DRL paradigm byt did not reduce the effects of these drugs on free-operant avoidance. These results indicate that cholinergic drugs may affect behavior in the DRL paradigm primarily by acting on muscarinic cholinergic neurons that pass through the septum but affect free-operant avoidance mainly by acting on different cholinergic pathways that do not pass through the medial septum.


Effect of amitriptyline on avoidance learning in rats following olfactory bulb ablation. It has been established that following bilateral olfactory bulb ablation there occurs a performance deficit in rats exposed to aversive learning procedures. Associated with the behavioral deficit, there occurs a reduction in total cortical norepinephrine (NE). If the behavioural deficit observed is a sequitur or correlate of the NE reduction, then drug therapy aimed at increasing NE availability in the cortex should overcome the reduction in performance. Amitriptyline increases NE availability by inhibiting uptake mechanisms and increases the rate of synthesis of NE. Rats, previously bulb ablated, were treated with amitriptyline over a 10 to 14 day period and tested in aversive situations. It was demonstrated that the drug treated rats showed improved performance early in acquisition, and that the performance improvement was maintained when the treatment period was extended to 14 days. These results indicate that amitriptyline was inducing a true pharmacological effect, and that the improved performance could be correlated with increased NE availability in the cerebral cortex.


Relative potency of tetrahydrocannabinol derivatives on tonic immobility in chickens. Chickens were given varying dosages of delta 3-, delta 8-, and delta 9-THC and tested for duration of tonic immobility (TI). Although all derivatives had a profound facilitation effect, delta 9-THC was the most potent. These results are unusual in that TI is a well documented fear-potentiated reaction and THC generally has tranquilization-like effects.


Neurochemical correlates of alcohol preference in inbred strains of mice. C57B1/6J, a specific inbred strain of mice with high alcohol preference and DBA/2J, a specific inbred strain with poor preference for alcohol were studied. Brain content of acetylcholine, uptake of 14C-Choline by whole brain homogenate were significantly higher in the C57B1/6J mice whereas brain acetylcholinesterase was higher in the DBA/2J mice. No significant difference was found for the level of brain serotonin, uptake of 3H-norepinephrine or 3H-dopamine. Treatment with a specific inhibitor of choline transferase, 4-(1-napthylvinyl) pyridine salt (10 mg/kg, twice daily) shifted the selection of alcohol to water in the C57B1/6J mice. These findings suggest a direct involvement of central cholinergic mechanism in alcohol preference.


Role of dopamine in d-amphetamine-induced discriminative responding. In two-lever operant chambers, rats were trained in a food-reinforced discrimination task. Reward was contingent upon correct lever choices to the induced differential cue conditions of d-amphetamine (0.8 mg/kg) or saline throughout training on a differential reinforcement of low response rate (DRL-15 sec) schedule. Upon acquisition of discriminative response control the animals were pretreated with various neurochemical agents. Pretreatment with atropine, phentolamine, propranolol, methysergide or cinanserin did not block production of d-amphetamine lever responding. Nicotine and oxotremorine did not produce the amphetamine-like cueing effect. However, pimozide blocked the ability of animals to discriminate d-amphetamine and L-DOPA, in combination with Ro 4-4602 with or without amantadine, generated amphetamine-like responses. These results indicate a role of dopamine in the production of the amphetamine state and from the failure of apomorphine to exhibit the stimulus property of d-amphetamine and the antagonism by alpha-methyltyrosine of the d-amphetamine responding it is further suggested that this amphetamine state is produced via the releasing of newly synthesized dopamine.


Cannula for intracerebral administration of experimental substances. Two reliable intracerebral cannulas, with a protective cap and a locking arrangement of the extension tube can be made from inexpensive regular and dental disposable needles and syringes. The preparation and use of these alternative cannula systems which enable the prolonged intracerebral infusion of experimental substances in unrestrained, freely moving animals is described.


Amplitude modulator-demodulator system for recording electroencephalographic signals with a standard 1/4 inch magnetic tape deck. Circuit diagrams and a sample oscilloscopic tracings are provided for a simple modulator-demodulator system which permits the recording of low frequency bioelectric phenomena with an entertainment type tape recorder. The system is economical and easy to use. Several of the systems have been used successfully in routine laboratory applications for more than a year.


Effects of growth hormone on brain biogenic amine levels. The effects of IP administered bovine growth hormone (GH) on regional brain serotonin, 5-hydroxyindoleacetic acid (5-HIAA) and norepinephrine levels in rats were examined. GH decreased the levels of both monoamines and 5-HIAA in the diencephalon and brainstem while not affecting telencephalic concentrations. In hypophysectomized rats, however GH produced significant elevations of monoamine and 5-HIAA levels in all brain regions. In normal rats the decreases in norepinephrine content produced by GH were correlated with a reduction in the stimulatory action of d-amphetamine on general activity levels. These results demonstrate that GH can affect brain biogenic amines and that these effects have behavioral consequences.


Phenobarbital during pregnancy alters operant behavior of offspring in C57BL/6J mice. Offspring of C57BL/6J injected daily with phenobarbital for the last third of pregnancy responded less than control animals when maintained on various fixed ratio schedules of reinforcement. The response decrement became more pronounced as the schedule demands were increased and was noted in offspring of both sexes. The higest dose (80 mg/kg) was less effective than the 2 lower doses (20 mg and 40 mg/kg) in producing the decrement which may reflect a selection factor due to high neonatal mortality previously reported at this dose. The study provides no evidence of the mechanism mediating the long term behavioral abnormality but does  clearly extend the finding of such changes to doses which do not produce increased neonatal mortality or noticeable morphological changes.


Effect of cobra neurotoxin on retention of a brightness discrimination in rats. In view of some recent evidence that blockade of nicotinic acetylcholine receptors might interfere with memory recall, the possibility that intracranial injections of purified corbra neurotoxin, an irreversible nicotinic receptor blocker, would produce long-lasting amnesia was explored with a brightness discrimination habit in rats. The results indicate that even the highest tolerable dose of neurotoxin had no detectable effect on memory recall.


Chlordiazepoxide and preference for free food in rats. Rats continued to lever press for food when a bowl of free food was placed in the experimental chamber. Chlordiazepoxide increased the amount of free food consumed, and tended to reduce the amount of lever pressing. It is argued that the drug decreased container neophobia in the animals, rather than acting like an increase in food deprivation.


Crossover effects in experimental investigations with human subjects. Simple crossover studies with drugs may introduce artifactual results. Volunteers are frequently less apprehensive when tested on the second occasion and experimental medication may result in different performance measures. Empirical evidence is given to demonstrate this point and a suggestion is made as to how it can be overcome.


Natriuresis, kaliuresis and diuresis in the rat following microinjections of carbachol into the septal area. The effects of intraseptal injection of carbachol on natriuresis, kaliuresis and diuresis has been studied in conscious, unrestrained water-loaded male rats. Urinary sodium and potassium excretion increased following injections into the septal area. The intensity of the natriuresis and kaliuresis was dose-related. An antidiuretic effect was also observed. The Na+/K/ ratio increased with increasing doses of carbachol, indicating that the rise in urinary sodium exceeded that of potassium. Systematic mapping of the septal area yielded about the same results for all sites, excepting a zone located in the anterior-dorsal part of the medial nucleus which appeared more sensitive. The natriuretic effect of intraseptal carbachol in adrenalectomized rats demonstrated the secondary role played by the adrenals. Contrariwise the decrease of the natriuretic effect observed either in hypophysectomized rats or in rats bearing a median eminence lesion receiving intraseptal carbachol showed the important participation of these structures in urinary Na+ excretion. Adrenalectomy or median eminence lesions did not modify the kaliuretic response while hypophysectomy produced a transitory diminution. This fact favours the hypothesis of different mechanisms involved in Na+ and K+ excretion following intraseptal carbachol. These results leave open the question as to mechanism of action but suggest a possible role of the pituitary in mediating the responses. Also, the possibility of a role played by hemodynamic shifts is suggested.


Variations in alcohol metabolism: influence of sex and age. Alcohol-induced sleep time was measured subsequent to the intraperitoneal injection of a 3.5 g x kg-1 dose. The old male group had a sleep time approximately 4 times that of the young male group and approximately twice that of the old female group. Blood alcohol concentrations at time of awakening were nearly identical in all groups, indicating the difference in sleep time is not due to an altered CNS sensitivity. Measurement of in vivo alcohol disappearance rate indicates the old male group is different from the other groups because of a slower rate of alcohol metabolism. Although changes in hepatic alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activities were seen, the changes do not explain the observed decrease in alcohol metabolism observed in the old male group. These data provide further evidence that hepatic ADH and ALDH activities are not rate limiting in alcohol metabolism.


Facilitation of the long term memory store with strychnine: a reexamination. Contrary to previous findings, some recent studies have reported that several daily injections of strychnine, beginning 24 hr after learning, facilitates subsequent retention. The present paper reports 3 studies using mice which suggest that strychnine has no effect on retention when the learning-injection interval is 24 hr. This absence of an effect was found using a range of strychnine doses. Furthermore, the absence of the facilitation effect was found not to be due to any failure of animals to learn prior to injection or to the fact that all animals performed asymptotically on the retention test.


Scopolamine effects on delayed spatial alternation in the rat. Rats were trained to press two levers in alternation on discrete trials spaced 10 sec apart. During the final sessions of alternation training, error responses per opportunity on the trials that followed reinforced trials (initial trials) did not differ from error responses per opportunity on repetitive (correction) trials (Experiment 1). Scopolamine did not increase the rats' tendency to perseverate: drug treatment did not cause the error responses per opportunity to increase over runs of consecutive error responses (Experiment 2). Scopolamine did not impair performance when alternation was controlled by visual stimuli present in the external environment at the time of the response (Experiment 3). The disruption in delayed alternation performance produced by scopolamine was attributed to effects on stimulus discrimination, resulting in impairment of control of responding by stimuli not present in the environment at the time of the response.


Release and binding of protein and enzymes from and to water-shocked vesicles obtained from rat liver mitochondria. Release and binding of aspartate aminotransferase, malate dehydrogenase and protein from and to water-shocked vesicles obtained from rat liver mitochondria was shown to occur. The characteristics of this phenomenon were shown to depend on the effectors used. They were in some way different from those observed with whole mitochondria under similar conditions.


Effect of prostaglandins in vivo on enzymes involved in thyroid carbohydrate metabolism. Treatment of adult guinea pigs with prostaglandins produces changes in the levels of enzymes involved in carbohydrate metabolism of the thyroid gland. A decrease in glucose-6-phosphate dehydrogenase activity is observed with a concomitant increase in 6-phosphogluconic dehydrogenase; the glycolytic enzymes appear unaffected by the same treatment. The results indicate that prostaglandins do not have the biochemical effects obtained with thyrotropin and cAMP administration, showing that these compounds play an antagonistic role in comparison with the above mentioned stimulating agents.


Change in electrophoretic mobility of human erythrocyte as the result of membrane shape change in vitro. Shape change of human erythrocyte due to the membrane externalization induced by incorporation of excess lysolecithin or by hypertonic treatment in vitro, was accompanied by a decrease in the electrophoretic mobility of the cell. No change in sialic acid content of the membrane, mostly responsible for the cell surface charge, was observed in any of these treatments. Therefore, the membrane externalization seems to cause a redistribution of the surface charge and the resulting alteration of the electrophoretic mobility of the cell. Heating at 48 degrees C for 1 hour induced both the shape change and change in the mobility, but at the same time it reduced the membrane sialic acid content.


Red blood cell ghosts: hollow membranes or solid bodies? Human red blood cell ghosts prepared by a widely used hypotonic lysis method are shown to be not hollow membranes but are solid bodies of distorted shapes.


The effects of cholera enterotoxin on intestinal tissue water as measured by nuclear magnetic resonance (NMR) spectroscopy. Cholera enterotoxin has been postulated to change the configuration of the intracellular protein-water system, altering the permeability of the cell to water. Using nuclear magnetic resonance (NMR) spectroscopy, this protein-water relationship can be examined. Small intestinal loops in the rat were injected with 0.5 ml of either Schwarz/Mann cholera enterotoxin (40 mug/cc saline solution) or normal saline. Full thickness segments of intestine from each loop were taken and percentage water (using a gravimetric procedure which includes a correction for fat) and NMR relaxation times were determined. The mean value +/- S.D. for tissue water was 79.49 +/- 2.65% in the controls and 84.52 +/- 2.01% in the cholera specimens (p less than .001). T1 (spin-lattice) relaxation times were 521.22 +/- 69.5 msec in the controls and 667.96 +/- 119.25 msec in cholera tissue (p less than .001). T2 (spin-spin) relaxation times were 62.34 +/- 9.59 msec in controls and 80.35 +/- 21.46 msec in cholera tissue (p less than .02). These findings are consistent with the theory that cholera enterotoxin acts to alter intracellular protein-water relationship.


Studies on 5-hydroxyuridine (isobarbituridine): X. Isolation and tentative identification of 5-hydroxymethyluridine from ribosomal RNA. Yeast ribosomal RNA was hydrolyzed to its constituent nucleosides with the aid of snake venom and bacterial alkaline phosphatase. Lyophilized hydrolysate was labeled with radioactive 5-hydroxyuridine and applied to partition chromatography. It was found that some components of rRNA are held on the column and can be eluted with water. Eighty-nine percent of the label, a large portion of cytidine, and several unidentified compounds were found in the water wash. The direct application of the wash concentrate to ascending paper chromatography in saturated butanol-H2O resulted in the separation of three distinct UV-absorbing bands. Further resolution and characterization of one band of unidentified material revealed the presence of an additional nucleoside. On the basis of chromatographic and electrophoretic behavior and UV-absorption spectra, it was tentatively identified as 5-hydroxymethyluridine.


[Acute homonymous henianopsias. The syndrome of perfusion disorders in the flow area of the anterior chorioideal artery]. The author, after giving an outline of the anatomical conditions, describes the clinical picture of disorders of blood supply to the anterior choroid artery. By references to two typical cases it is shown that loss of sight in the same vertical half of the visual field for each eye is the leading symptom, a more exact analysis of visual field effects allowing further topical conclusions to be drawn.


[Changes in cerebral metabolism during experimental anuria]. After experimental ureterotomy in mice, the changes which occurred in cerebral metabolism were studied. A significant increase in the cerebral glucose and glycogen level as well as of degradation power was noticed 25 hours after the operation. The level of lactic acid production in the same period of renal insufficience indicated a gradual decreasing tendency. These results as well as further details are discussed with regard to the underlying disturbances.


[Information-theoretical error analysis of a form-comparison test]. An attempt has been made to make an error analysis, by both the conventional and information theoretical mode of evaluation, of the results of a forms comparison test used for diagnosing the sensory and optical capacity of differentiating. A total of 423 test subjects were available for this program. Data for the standardization of this test and for the evaluation of test results was derived from the results of this investigation.


[Taking offense and illness - the pathology of interaction as seen by a psychiatrist (author's transl)]. Theories of interaction matter not only for psychoreactive disturbances, pathologic forms and sequelae of interaction may influence or even determine origin and course of psychoses. Present treatment or schizophrenic problems contains the danger that psychogenetic theories are sharply confronted with biologic concepts. As fas as we know today both are equally ligitimate. Purely psychogenetic theories like that of Bateson do not always avoid the temptation to ask and answer questions of guilt. This is therapeutically nearly always useless and may lead to arrogance. Psychotherapy of endogenous psychoses - up to now mostly only a demand - cannot be realized by adopting a model theory. It is more a question of the attitude of the physician.


[Aspects of psychoanalytic and behavioral procedures in chronic schizophrenics as illustrated by a case presentation (author's transl)]. Psychoanalytic and behavioral aspects were discussed in the presentation of a hebephrenic's nine year treatment. The psychoanalytic approach to chronic schizophrenia can provide precious information for behavioral analysis. Achieving the therapeutic goal of social and professional rehabilitation may be facilitated by behavioral group psychotherapy which emphasizes self control techniques as well as contingent reinforcement and behavioral rehearsal.


[Anthropologic foundation and psychologic consequences of political orientation toward right or left. An existential-psychoanalytic study on the phenomenology of political radicalism]. The author searches for an explanation for the fact that an originally only spatial and not "loaded" pair of concepts like "right and left" could gain in our time such high-tension content in political terms. He suspected underlying anthropologic connections and tried to elucidate them with existential analysis. He found that the basis can be seen in the physical constitution of man. Physical experience first transmits the concepts of right and left. The "asymmetric" symmetry of our bilateral physical organisation makes experiencing right and left possible. On this basis the mental concepts of our existence would be imposed in noethic-ethic categories. And these would become active in our political world. This is demonstrated on a case of H.E. Richter. Following Richter'd ideas the psychodynamic rules of political-structural disparities could be shown. The "rights" as repressors dominate the "lefts" as the depressed which now protest in their dispair. As extreme forms the two polarized radicals who now fanatically stylize the other as the enemy, will fight to the death their own denied opposite side psychodynamically. Bizarre ideal visions lead to legalization of terror and brutality. As missing how they are linked in psychiatric terminology paranoid types result extending to the formation of genuine (political) obsessions. For both catathymia of outlook and language are characteristic which show eminent loss of a picture of the world.


[Parental child-rearing styles, neuroticism and hostility of juvenile criminals (author's transl)]. It was the purpose of this study to examine the relation of parental child-rearing styles, as reported (inventory) by juvenile criminals, and the neuroticism and hostility of juvenile criminals (sample of 171 subjects). Factor analysis of inventory data resulted in the isolation of three parental child-rearing styles, labeled affection-support, rejection-hostility and control-strictness. The child-rearing styles of rejection-hostility and control-strictness were found to be significantly correlated with four factors of hostility (set of inventory scales), aggressive tension (anger, rage), reactive hostility, guilt proneness, suppression of hostility, and with two questionnaire measures of neuroticism.


[Comparison of chemical and radiochemical methods in determination of steroid hormones]. While in some cases steroids can be measured directly in serum or plasma by radioimmunoassay (RIA), in other cases, especially when analyses are carried out in urine, the samples must be processed before RIA can be performed. The operations involved in the preparation of urinary or blood extracts suitable for the RIA of steroid hormones are examined and compared in terms of practicability with the analytical procedures currently used for the chemical determination of the same steroids or their metabolites.


[Problems with standardization of the radioimmunologic determination]. Radioimmunoassay is an analytical procedure in which a radioactive tracer acts as an indicator and a specific antibody acts as a reagent. The requirements which have to be met to guarantee the validity of the assay are the essential characteristics of each microanalytical procedure, namely the sensitivity, specificity, precision and accuracy. The optimization of the assay demands than a careful examination of these factors, which first depend on the properties of the reagents. The consistency of the results is based on the identity, as far as the immunoreactivity is concerned, between the substance to be assayed in the biological sample and the substance used as a standard to build up the calibration curve. The immunoreactivity of the tracer can instead be lower than that shown by the standard, although it must not be too different. The features of all the reagents are reviewed and discussed, mainly those of the antiserum which affect the specificity of the assay. The most diffuse RIA techniques are reviewed and divided in gross categories, according to the methods used for the separation of the free and antibody-bound hormone. The different steps of the analytical procedure are investigated, taking into consideration the most important parameters which affect the assay, mainly the time and temperature of the incubation step. The practical ease of the analysis is definitely an essential factor of choice, provided that it could be associated to reproducible and accurate results. A severe quality control of each reagent and of the assembled set must be carried out to assure the consistency of the analytical data. In the particular case of radioimmunoassay the quality control must be extended to all the steps of the assay both before and after the analytical procedure itself, in order to assure the maximal clinical validity of the diagnostic determination.


[Socio-cultural alientation and heroin addiction]. Heroin addiction is approached in this paper as a sociological process which takes place as a refusal of, or alienation from, the conventional social system, with, at the same time, attraction towards an alienated world, which gives recognition and identity to the subject. Three phases are identifiable in such process: 1) The subject is unable to copy or identify with an adult sexual model (normally, the parent of the same sex). This may reach the level of rejectal of the model. 2) The subject does not succeed in obtaining legitimate goals and benefits. This failure may only be imaginary, but involves a condition of subjective suffering. 3) The subject cannot establish good and significant relationships with nonaddicted peers, and consquently lives in isolation. The three phases are evident in a study carried out by the Author on 750 eddicts from New York and Puerto Rico. The integration into the deviant addict culture, which follows the triple failure outlined above, must be treated with training and resocialization techniques.


[Prospects for the use of in vitro radioimmunological technics in pediatrics]. The Author first of all outlines the advantages which in vitro radioimmunological techniques offer at the pediatric age level and particularly for newborn babies, in relation to the minimal amount of blood necessary for this type of examination and the fact that exposure of babies to ionizing radiation is avoided. He subsequently reports on what can already be achieved using these methods in the field of functional diagnostics at the pediatric age level, especially in the field of endocrinology. Then he indicates the areas which appear to be most promising for exploration, among them the use of in vitro radioimmunological techniques on the blood of the umbilical cord, on the amniotic fluid, and lastly in monitoring the plasmatic kinetics of drugs especially at the pediatric age level.


[Evaluation of the penal treatment].

[Evaluation of the penal treatment]. Evaluative research in the penal field has had two main characteristics: first, there has been a pre-occupation with the objective of treatment to the almost complete exclusion of any other, and second, there has been a concern with the demonstration of effects without a corresponding attempt to understand the nature of the treatment process. This has been because the research has proceeded on an inappropriate "medical" view of penal treatment on which it is assumed that the "cure" of the offender is the major task and that the nature of treatment is relatively easy to understand. The main achievement of this research has been to show that, by and large, penal treatments differ very little in their capacity to reform. The importance of this result should not be underestimated. It has helped to bring about a changed view of delinquency and its treatment which in the long term will have far reaching effects on penal practice. In the shorter term the effects on evaluative research are likely to be two-fold. First it opens the way for evaluation to proceed on a wider front. Instead of needing to pay so much attention to reformative aspects, the researcher will be more free to compare penal measures with respect to such things as their economic and social costs, their cpacity for general deterrence, the protection afforded to the public from the activities of known criminals, and the extent to which they satisfy requirements of justice and humanity.


[Diagnostic and prognostic value of the separated renin in hypertension due to monolateral nephropathy]. Renin activity in renal vein plasma and in peripheral plasma was measured in twentytwo hypertensive patients presenting unilateral renal artery stenosis or other unilateral renal abnormalities. A discrepancy between peripheral and renal vein renin levels was noted only in one case. In seven patients the difference between the renal vein renin of the diseased kidney and that of its contralateral mate was very significant. They responded successfully to surgery for hypertension, confirming the predictive value of a renal vein renin ratio greater than 1.5. In all the other patients with less significant differences between the renin levels of the two kidneys surgery was not performed because they benefited from the hypotensive therapy.


[Importance of digitalemia for a correct therapeutic attitude using cardioactive glycosides]. Recent advances in the quantitation of plasma or serum levels of cardiac glycosides promise to add a new dimension to pharmacologic studies and to the evaluation of clinical problems involving these drugs. A rapid radioimmunoassay technique has been described for the determination of serum digoxin and beta-metyldigoxin concentration in the range encountered clinically. Patients judged clinically to show digitals toxicity in general had higher levels. A relable estimate of serum digoxin and beta-metyldigoxin concentration, considered in the clinical context, has been found to be useful in arriving at acute management decisions.


[Direct radioimmunologic determination of T 3 in the serum]. A convenient, precise and repeatable radioimmunological method has been developed for measuring triodotironine (T3) in the serum. The dosage is made in the presence of 600 mug (micrograms) of Merthiolate in all tubes, in order to inhibit a link between the T3 and the vector proteins, and of HSA in the standards to keep them in the same condition as the samples. The method normally distinguishes 10 pg of T3 which correspond to a concentration of 0.4 ng/ml, from the point in which 25 mul of the serum are utilized. The following results have been obtained by this method: hypothyroids (14): 0.37 +/- 0.31 ng/ml; normal thyroids (51): 1.44 +/- 0.52 ng/ml; hyperthyroids (22); 4.62 +/- 1.21 ng/ml.


[Radioimmunologic determination of plasmatic triiodothyronine. Verification of operative parameters; 1st clinical results]. The experimental determination of the operative parameters of two radioimmunoassay (RIA) systems for the determination of triiodothyronine (T3) level directly in serum is described. The two systems differ both for the agents blocking the aspecific T3-serum protein bindings (sulphonic acid, 8-aniline, 1-Naphtalene in borate buffer: bor-ANS-RIA and Merthiolate in phosphate buffer: PO4-Merth-RIA) and for the methods adopted for compensating the aspecific serum interferences (T3,4 free serum for bor-ANS-RIA and Human Serum Albumine HSA 8% for PO4-Merth-RIA. The tracers are T3-I125 (spec. act. 500 Ci/g for bor-ANS-RIA and 1000 Ci/g for PO4-Merth-RIA). The antisera have been raised in rabbit (T3-bovine SA conjugate for bor-ANS-RIA and T3-HSA conjugate for PO4-Merth-RIA). The incubation conditions are 2degreesC X 24 h for bor-ANS-RIA and room temp. X 2 h for PO4-Merth-RIA. For both systems, the Bound-Free (B-F) separations are carried out by charcoal-dextrane adsorption, 4 mg/tube, 10 min contact. Indicatively, the lowest detection limits of the two systems are about 8 pg T3 for ANS and about 6 pg T3 for Merth. Evidence of parallelism and even superimposition is provided for both assays between the dose-response curve and the serum dilution curve. The calibration curves of the employed antisera are reported (final titres: 1/1000 for ANS and 1/2500 for Merth). 4 different incubation conditions for ANS and 2 for Merth are described and the reasons of choice of the mentioned conditions statistically elucidated. Acceptable statistical comparison between "sample-blank" and the "blank" of the diluents of the employed standard preparations are presented and discussed. F-countings vs. B-countings functions are reported (regression line -- equations: F = 0.93 B + 0.07, n = 15, r = 0.993 for ANS and F = 0.95 B -- 0.02, n = 14, r = 0.992 for Merth) demonstrating the possibility of alternative countings. The recovery regression lines (found f vs. expected e) have equations: f = 1.01 e + 0.08, n = 10, r = 0.999 for ANS and f = 1.08 e -- 1.64, n = 9, r = 0.995 for Merth, implying a practically quantitative recovery in both cases. Thyroxine (T4) cross reaction study has been undertaken under a quite new optics re-calculating the regression lines -- equations of the T3 recovery in the presence of added T4; in that case, the following equations are valid: f = 1.05 e + 0,13, n = 10, r = 0.992 for ANS and f = 1.07 e + 2.26, n = 18, r = 0,985 for Merth. Reducing the maximum added T4 to 1 ng/tube, the cross reaction can be considered as negligible. T3 levels for normal subjects are finally reported: 1.50 +/- 0.80, n= 37 for ANS and 1.40 +/- 0.68, n = 40 for Merth (ng T3/ml, means +/- 2SD).


[Radioimmunologic determination and analysis for saturation of the thyroid hormones: comparison and use in the practical clinic]. Reliability of a recent method of assay by saturation analysis for assessment of thyroid status, which is to be recommended for its practicability and technical improvement, has been verified. Its diagnostic efficiency in more than 3,000 assays has been evaluated. On the whole T3 Uptake (T3U) and serum Thyroxine (T4D) determination showed a quite good accuracy, that decidely improved when both the tests were carried out and the Free Thyroxine Index (Free Thyopac Index) was drown. Moreover the present availability of the radioimmunological determinations of triiodothyronine allowed to assay simultaneously both thyroid hormones in normal euthyroid subjects, in pregnancy, in hyperthyroid, hypothyroid and goitrous patients. Results obtained have been analysed and discussed and clinical conditions pointend out where determination of both hormones may be useful.


[Clinical use in the radioimmunologic determination of plasmatic TSH]. Clinical value of plasma TSH radioimmunoassay in various thyroid diseases (primary hypothyroidism, hyperthyroidism and simple goiter) is discussed. In particular, the results obtained of plasma TSH after TRH administration either in thyroid disease either in various disorders of endocrinologic interest (massive obesity, Laurence-Moon Biedl's syndrome, true precocious puberty, congenital adrenal hyperplasia, Klinfelter's and Turner's syndromes) are discussed.


[Changes in the secretion of somatotropin and insulin in hyperthyroidism]. Twenty hyperthyroid patients were investigated for growth hormone (GH) and immunoreactive insulin (IRI) secretion in response to insulin hypoglycaemia, arginine infusion and glucose-induced hyperglycaemia. GH response to either insulin hypoglycaemia or arginine infusion was significantly reduced in these patients compared with 20 normal subjects. Thyrotoxic patients also displayed an abnormal GH pattern after a 100 g oral glucose load: in fact, serum GH underwent a paradoxical increase in spite of abnormally high levels attained by blood glucose. IRI secretion was also clearly reduced in response to arginine infusion and moderately blunted after oral glucose. In a group of patients re-evaluated under euthyroid conditions, a fair increase of GH response to the provocative stimuli jointly with the restoration of a normal suppressibility of serum GH by glucose were noted; by contrast, no significant change of IRI response to arginine or glucose took place. Likewise, the impairment of glucose tolerance was not improved. These findings indicate that an impairment of GH and IRI secretion is present in hyperthyroidism. The possibility that a potentiation of the catecholamine effects caused by the thyroid hormones is involved in this alteration deserves consideration.


[Human chorionic somatommamotropins (HCS or HPL) : radioimmunologic determination and clinical significance]. The AA. have studied a new standardized radioimmunologic method for the routine determination of HCS. All the steps of the analysis have been studied, in particular those concerning the reability test and the precipitation of the complex with PEG. The best conditions were found when PEG 6000 is used at a concentration between 14-16 g in 100 ml (v/w), dissolved in veronal buffer, pH 7.4--9.4, with a dilution of protein (bovine serum) 1:4 in the incubation mixture. The reability test have given very good results. The c.p.m. of the analysis are plotted with a logit plot by computer which directly gives the values in ng/ml of the hormone in the plasma sample. The results obtained with this method are compared with those of the literature; the most striking difference in the present method appears in the last trimester of pregnancy in which the result have a low S.D. and can give a good help in clinical management of pregnant patients.


[Diazoxide test in the diagnosis of arterial hypertension: modifications in the levels of renin and aldosterone in blood of patients with various restrains of the renal function]. The AA. have applied the diazoxide test for the screening of primary hiperaldosteronism to 22 nephropatic patients suffering from hypertension and with different degrees of renal function. In 22 patients an increase in PRA and aldosterone values always followed the diazoxide infusion. Only one patient, likely suffering from primary aldosteronism, showed no increase in PRA and aldosterone values. The diazoxide infusion had no influence on renal, pancreatic and cardiovascular function. Therefore, this can be considered as a valid test easy to be performed in a short time, also in nephropatic patients who are very sensitive to pharmacological noxae.


[Frequency of antigen associated to hepatitis due to virus B (HBAg) and of antibody (HBAc) in healthy subjects and during of course of acute and chronic hepatitis. Radioimmunologic study]. Among the several methods employed for the detection of hepatitis B antigen (HBAg) and hepatitis B antibody (HBAb), radioimmunoassay is considered to be the most sensitive and specific. This paper describes a radioimmunoprecipitation test (RIP) for HBAg and HBAb standardized in our laboratory; it consists of a double-antibody precipitation test in a micro-titer system employing 125I-labeled HBAg. The test is compared with double immunodiffusion (ID) and with counterimmunoelectrophoresis (CEP) in the detection of HBAg and HBAb in healthy persons and in patients with acute and chronic liver disease. RIP is 20,000 times more sensitive than ID and 2,500 times than CEP when HBAg is tested, and 40,000 times more sensitive than ID and 10,000 times than CEP for the antibody detection. Moreover the method is reproducible and specific for HBAg and HBAb. With this test the frequency of HBAg in healthy persons was 0% in subjects without any known contact with antigenic material, 0.80% in hospital personnel and 1.17% in high risk personnel (laboratory technicians, blood products workers, ecc.). In acute viral hepatitis the frequency of HBAg was 90% at the admittance to the hospital and 70% at the dimission, while CEP detected a frequency of 85% and 20% respectively. In chronic liver disease the frequency of HBAg with the RIP method was 83.3% in chronic persistent hepatitis, 42.8% in chronic aggressive hepatitis, 23% in cryptogenic cirrhosis and 16.6% in alcoholic cirrhosis. The frequency of HBAb detected with RIP was 4.50% in subjects without any known contact with antigenic material, 6.45% in hospital personnel, 0.41% in high risk personnel, 20% in acute viral hepatitis at the admittance to the hospital and 50% at the discharge, 25% in chronic persistent hepatitis, 14.2% in chronic aggressive hepatitis, 15.3% in cryptogenic cirrhosis and 50% in alcoholic cirrhosis. The high frequency of antibody in healthy persons with no history of hepatitis or parenteral exposure to blood transfusion suggests a widespread diffusion of hepatitis B infection and the possibility of a nonparenteral route transmission. The frequency of HBAg and HBAb in chronic liver disease as detected by a very sensitive method rises the question of a possible role of hepatitis B virus in the pathogenesis of the disease.


[Radioimmunoquantization of the HBAg in clinical liver diseases]. The two-step direct radioimmune test RIA used to detect hepatitis B virus associated antigen (HBsAg) appeared to be more sensitive than other immunologic assays. RIA demonstrated as HBsAg positive 90% of 20 patients with posttransfusion hepatitis; 88% of 50 patients with acute viral hepatitis; 100% of 13 patients with chronic active hepatitis and 35% of 20 patients with cirrhosis; on the other hand with positivity for HBsAg in the same patients appeared to be lower by AGD, CIEP and CF. The quantitation of HBsAg by RIA has been performed with a dose response curve obtained by use of HBsAg (ad) standard. The quantitative HBsAg data of an eight week follow-up of fully recovered 15 patients with acute B-hepatitis are reported. In the first week it appeared a distribution of the HBsAg levels into three classes of values. The concentration of HBsAg in the serum became lower week by week and in the 8th week the HBsAg was no longer detectable. The radioimmunoquantitation of HBsAg in the serum of patients suffering from chronic active hepatitis and cirrhosis showed levels of antigenaemia ranging between 17 and 5100 ng ad equivalent/ml. The use of a dose response standard curve in order to quantify HBsAg in the serum represents a further increased sensitivity of RIA.


[Incidence of HBsAg in persons living with HBsAg carriers]. The prevalence of HBsAg was studied, by Counterelectrophoresis and Radioimmunoassay, in 232 household contacts of 65 HBsAg carriers. The overall incidence of HBsAg in household contacts was 14,65%, as compared with the generally accepted figure of about 1% in the general population in Italy. As far as the prevalence of HBsAg and abnormal liver function tests is concerned, no differences were found between contacts of carriers with Chronic Active Liver Disease and contacts of asymptomatic carriers. The prevalence of HBsAg was similar in spouses (13,5%) and in blood relatives (15,3%) of carriers. It is concluded that: 1) Household contacts of HBsAg carriers are at higher risk of acquiring HBsAg infection than the general population. 2) Such risk is not increased by the presence of Chronic Active Liver Disease in the index cases. 3) Further studies are required in order to clarify the relative roles of environmental and genetic factors as determinants of HBsAg transmission.


[New pathogenetic aspects of hepatitis B in relation to finding HBAg inhibitor in the intestinal mucosa and human feces]. Hepatitis B antigen (HBAg) positive sera became negative after in vitro incubation with homogenates of human faeces or intestinal mucosa. This was found to occur in all sera tested by various methods. These findings suggest the existence in the human intestine of a substance able to inactivate the HBAg and that it is not an antibody or of the nature of interferon. The presence of an inhibitor could explain why B-type hepatitis is seldom if ever faecally transmitted and also the low oral infectiousness of the B virus.


[Sensitivity and various radioimmunologic procedures for the research and typization of the antigen and antibody of hepatitis B]. The kinetics of solid-phase radioimmunoassay (SPRIA) procedures for HBsAg detection were explored. Most HBsAg-positive sera showed an evident prozone phenomenon and the optimal reaction zone occurred at considerable dilution rates. Subsequent dilutions (in negative serum) resulted in a linear decrease of counts, plotted on log-logit graphs, to the lowest level of positivity (cpm positive serum/cpm negative sera=2.1/1). As compared with commercial solid-phase substrates, the sensitivity of HBsAg detection was enhanced when the SPRIA procedure was carried out in small polystyrene tubes, previously coated with purified antibody by simple contact. Various SPRIA procedures were described for HBsAg typing and suggested also as confirmatory tests for suspect positive sera. The sensitivity and the kinetics of three methods for the detection of anti-HBsAg antibody (anti-HBs) were investigated. These methods are based upon the neutralization of a standard dose of HBsAg (methods A and B) or upon the competitive inhibition of labeled antibody (method C). One of these methods fits the combined detection of HBsAg and anti-HBs. Finally, some SPRIA procedures were suggested for anti-HBs typing and some applications were shown.


[Geographical differences in the incidence of Australia antigen in chronic liver diseases]. In order to evaluate the role of the Australia Antigen and of the many other factors commonly invoked in the etiology of chronic liver diseases a series of study have been performed by radioimmunoassay on: a group of blood donors who showed persistent antigenemia and two groups of patients with chronic hepatitis who were studied respectively at Brescia General Hospital and at the Departement of Internal Medicine of the University of Naples. The results were as it follows: 1) Liver damage, from mild to severe (from transient increase of GOT and GPT levels to cirrhosis) was present in 69 out of 145 blood donors with persistent antigenemia. 2) Antigenemia was more frequent in the neapolitan group of patients not only when considering the entire study population (39%) but also when the cirrhotic group was considered (40.7%). In the Brescia study group the figures were 11.7% and 8.6% respectively. 3) Comparable high incidence of antigenemia was present in both groups when only patients with chronic aggressive hepatitis and liver carcinoma were considered. 4) When only patients with chronic persistent hepatitis and chronic aggressive hepatitis were considered the incidence of antigenemia was remarkably different.


[HBAg-RIA as a parameter of functional evaluation of viral hepatitis]. The investigation of HBAg by RIA appears to be very helpful in the diagnosis and follow-up of viral hepatitis. In most cases, a prolonged antigenemia is more strongly indicative of chronic evolution of the illness than other parameters. The persistence of HBAg, therefore, is significant for the persistence of viral infection.


[Detection of anti-HBAg by solid phase radioimmunoassay using labeled human antibody]. A new solid-phase radioimmunoassay technique for the detection of anti-HBAg is described. The test is characterized by a neutralization step of guinea-pig anti-HBAg by means of HBAg-RIA positive pooled sera. The first results obtained using this technique gave 21 anti-HBAg positive sera (26.9%) among 78 institutionalized subjects. One of these sera was HBAg positive at the same time.


[Radioimmunologic determination of hepatitis antigen and its clinical implications]. The AA. carrie out an analysis of the results obtained by means of the radioimmunologic method and concludes as follows: 1) Au-positive acute hepatitis represent the more largely diffused form among adult people; 2) from a clinical point of view, it seems appropriate to modify definitions of A and B hepatitis, of infectious hepatitis or serum hepatitis, classifying this disease as follows: a) hepatitis with positive antigenemy; b) hepatitis with negative antigenemy; and this independently from the anamnestic and epidemiologic elements. In the second part of this report, the AA., after introducing some considerations on the effects of the therapy by means of steroids, illustrate the data concerning a study carried out on a group of Au-positive and Au-negative subjects, subdivided into treated and non treated patients. From these analysis, even if a statistical survey has not been made, no elements are noticed, able to differentiate the behaviour of the two groups of hepatitis studied, in comparison with the therapy by means of steroids. One single Au-negative case, within a certain period of time, after the therapy with steroids, showed the presence of a positivity of immunologic phenomena only by the radioimmunoassay.


[Research on Au antigen by radioimmunologic method: retrospective study on 2491 transfusions]. The AA. have researched Au antigen by solid phase radioimmunoassay technique (RIA) in 2491 sera kept in freezer and relative to as many transfusions made in the 7 previous months and already selected for Au antigen by electrosyneresis. In base of the retrospective analysis, the AA. noticed that 82 patients had received 91 RIA positive transfusions. Precise clinical news could be collected on 50 patients, while laboratory tests relative to Au antigen and transaminase were carried out on 42 patients. In this group there were 4 Au positive ictero-hepatitises and 4 probable hepatitises with only change of transaminase without Au antigen. Two patients showed the presence of Au antigen only. In the control sample of 50 patients who have received the same number of RIA negative transfusions, the AA. found a moderate alteration of transaminase in 2 patients. Three patients showed the presence of Au antigen without any alteration. The Authors have also determined both the relationship between Au positive transfusions and the hepatitises which were observed afterwards, and the possible reasons for the low incidence of hepatitises related to the number of Au positive transfusions.


[Detection of Australia antigen by radioimmunoassay during a course of viral hepatitis]. The AA. carried out the research of Australia Antigen by radioimmunoassay (RIA) as well as with counter-electrophoresis technique (CE) on 142 patients with acute viral hepatitis. For comparison the RIA determination of the Australia Antigen was also performed on 26 blood donors, already established Au positive by a preliminary screening with CE method. On the 142 patients examined, the RIA permitted the detection of 19 as Au positive above the number evidenced by the less-sensitive CE technique. The Au antigen levels, determined quantitatively in conventional units (c.u./0,1 ml of serum), continually decreased with the progress of the disease toward recovery. Yet, in 23 cases (44,3%), the antigen was still present in the serum after normalization of transaminases. The AA. call attention to the importance the Au positive hepatitis convalescents and Au positive blood donors could have in the transmission of the disease. The antigen levels of blood donors, when determined with RIA, were found comparable to those observed in the acute phase of viral hepatitis.


[Incidence of HBAg in various liver diseases (comparison between radioimmunologic methods and methods of passive hemagglutination)]. In order to determine the frequency of HBAg in Campania, the AA. have examined a large number of liver patients accurately selected and subdivided in five classes: acute hepatitis, chronic hepatitis, cirrhosis, hepatocarcinoma, and various liver diseases. They have employed radioimmuno assays (RIA) with human and guinea pig antibodies and techniques of passive haemoagglutination. The percentage of HBAg positive subjects among the various classes of liver diseases determined with these techniques is significantly higher than the one remarked by the AA. in 1972 by electrosineresis on the same population. Both RIA and haemoagglutination supply satisfactory results, although for haemoagglutination one must remember the subjectiveness of the reading.


[Variations of functional parameters in chronic aggressive HBAg positive and negative hepatitis by means of radioimmunologic method (preliminary note)]. 43 subjects, affected by chronic aggressive hepatitis (CAH) have been divided into two groups according to the presence of HBAg. No statistically significant differences between the two groups have been provided. The two classes of subjects (HBAg + and -) were also divided into the already treated (with immunosuppressive drugs) and untreated to investigate the eventual differences existing between the two classes. The results of this division was that previously treated subjects present a lower total bilirubin (P less than 0.05) in respect to those that were not treated previously. The results of all the other comparisons carried out and the tested correlations were negligible. In conclusion, bearing in mind the inadequate methods used up to now to research the HBAg, the transversal studies show that CAH patients are both affected by the same syndrome, whether the HBAg is positive or negative. However, it is probable that it is not the carrier state of HBAg which enables the liver disease evolution but the liver disease itself enables the cellular immunity disorders that often appear in the course of CAH.


[Identification of antigen of hepatitis MS2 in the menstrual blood]. 35 samples of menstrual blood were examined and HBAg has been found (with the RIA method) always and only at the same time with venous antigenemia. HBAg has been also found in one only among four samples of cervicouterine secretions taken during antigenemia and far from the menstrual period.


Noncalcified pleural plaque presenting as extrapleural mass. Noncalcified pleural plaques may present as extrapleural masses. This benign entity must be considered in a differential diagnosis of pleural lesions. A case report is presented and the literature is reviewed.


Diagnosis and treatment of cysts of the breast. The diagnosis and treatment of cysts of the breast are described. Surgical intervention in the vast majority of affected patients may be avoided by pneumocystography, a procedure involving puncture of the cyst, aspiration of its contents, air insufflation and interpretation of radiographs obtained in at least two planes. A smooth inner wall of the cyst indicates the common benign lesion. Irregularity of the inner wall is an absolute indication for surgical excision of the lesion.


Cisternography of the chiasmatic and interpeduncular cisterns in mediotemporal expanding lesions. A combined angiographic-cisternographic approach is described by which small tumours originating from the medial wall of the temporal lobe can be detected, even when conventional neuroradiological techniques failed to do so. The cisternographic technique used in these cases is described in detail and other applications of this procedure are demonstrated.


[Rare case of an adult teratoma of the stomach (author's transl)]. The teratoma is a dysgenetic tumor consisting of tridermal differentiation products. The most common classification is made according to maturity - benign adult teratoma and malign nonmature embryonal teratoma. In the case demonstrated, a 15-year-old male suffers from tiredness, paleness and pains in the epigastrium. The radiological examination showed a tumor in the size of a fist with a number of teeth located partly within the stomach. The histological findings after operation confirmed the diagnosis of a coetaneous (= adult) gastric teratoma. The discussion shows that all cases of gastric teratoma published until 1972 are male, in 77% under the age of 1 year, in 13% under the age of 10, and only in 10% over the age of 10 years.


Radiological topography and classification of angioma-like arterial networks in cerebro-vascular collateral circulation. The radiological appearance and localization of collateral cerebrovascular networks are described. The development and distribution of these arterial networks is due to the site of internal carotid artery stenoses. Including interposed arterial nets, the following types are classified: (1) basal arterial networks near the carotid siphon; (2) arterial networks in the region of the basal ganglia (Moyamoya syndrome); (3) ethmoid arterial networks; (4) arterial networks on the cerebral convexity representing transdural external-internal carotid anastomoses, and (5) circumscribed arterial networks interposed in the course of a major cerebral vessel. The differential diagnostic criteria and aetiological factors of these anastomotic intracranial networks are discussed.


Selective bronchial arteriography in children. Twenty nine selective bronchial arteriographies were carried out in 25 children. In 5 cases the findings were normal. In 1 case an aneurysm of the bronchial artery was demonstrated as the source of the bleeding into the bronchus in a case of Rendu-Weber-Osler syndrome. In 1 case a plasmocytoma and in another one a congenital haemangiomatous network with many anastomoses to the pulmonary circulation was demonstrated. In most cases of chronic inflammatory pulmonary disease, the bronchial arteries were dilated and bronchopulmonary anastomoses were visualized. These changes seemed to be a measure of the extent of the disease and of the severity of the functional disturbance in pulmonary tissue, even when only regional. Selective bronchial arteriography is recommended in all cases of haemoptysis, in chronic pulmonary collapse and in chronic inflammatory lung disease in order to determine the source of the bleeding and the extent of involvement of the pulmonary interstitium.


Extramedullary hematopoiesis in the posterior mediastinum. Intrathoracic extramedullary hematopoiesis is a rare finding seen in some cases of chronic hemolytic anemia. A case of a 56-year-old man with congenital spherocytosis and characteristic lobulated masses in the posterior mediastinum, considered to be ectopic hematopoietic tissue, is reported. Biopsy in such cases is not necessary and may be dangerous.


The differential diagnosis of Crohn's disease by conventional radiological examination. The difficulties in the differential diagnosis of Crohn's disease are discussed on the basis of 35 patients observed at the Kantonsspital of Lucerne. The value of various radiographic signs as indicators of the stage and duration and the activity of the disease is critically analysed. Functional radiological signs, such as spasm, hypertonia and edema of the intestinal folds cannot be interpreted as early signs of Crohn's disease. On the other hand, advanced radiological lesions may be found although the disease is clinically acute and of recent onset. Sometimes, the radiological differential diagnosis against advanced ulcerative colitis or acute ileitis is made only on the basis of follow-up studies and the evolution of the lesions.


[Plain film diagnosis in coarctation of the aorta]. The authors emphasize the importance of plain films in showing abnormalities of the aortic arch, which should permit the early radiographic diagnosis of coarctation of the aorta, before the late appearance of rib notching and cardiac enlargement. These anomalies include the elongated aortic arch, the 'figure-3' sign, the 'double indentation' sign, and the dilatation of the ascending aorta. The plain film diagnosis in newborns and infants is difficult, because of subtle or absent change of the aortic arch. Cardiomegaly with left ventricular hypertrophy may give the diagnostic clue.


Radiobiology and the role of the radiobiologist in the context of a teaching-oriented radiation oncology department. This discussion concerns the function of a radiobiologist in the radiation oncology department of a hospital which maintains a radiation oncology training program. This involves teaching and research, both of which contribute to the oncology residents' total learning experience. The teaching commitment emphasizes the radiobiological basis of clinical problems, and makes use of both lectures and clinical experience to generate the teaching situations. As a part of the research commitment, the radiobiologist acts as an interface between clinical experience and research. He accomplishes this by maintaining a research program oriented toward clinical problems and organizing a research rotation during which the oncology trainees are able to participate in a specific research project. Radiobiology teaching and research must be relevant to the clinical experience of the oncologist.


Experimental investigation of source-block distance to source-surface distance ratios for cuboid and beam-divergence-shaped shadow blocks for cobalt-60 teletherapy. The partial transmission zone (PTZ) measured in air and its radiation shadow components are identified quantitatively and qualitatively for both cuboid and beam-divergence-shaped blocks. Source-block distance (SBD) and source-surface distance (SSD) are varied to produce SBD/SSD ratios from 0.71 to 0.86. The variation of the magnitude of the radiation shadow components as a function of SBD/SSD is explained in terms of a radiation shadow model. The clinical significance of PTZ minimization and a comparison between PTZs of 'shaped' and 'nonshaped' blocks is discussed. For small ratios of SBD/SSD the beam-divergence-shaped blocks produce smaller medial and lateral PTZs, whereas for larger ratios in the order of 0.9 the medial PTZ is also small for the cuboid blocks. Both PTZs, in general, decrease with increasing SBD/SSD ratios and for both cuboid and beam-divergence-shaped blocks.


Autologous blood clot embolization into a bleeding renal artery pseudoaneurysm. A young girl suffering from anuria due to periarteritis nodosa developed severe bleeding after left kidney needle biopsy. Angiography revealed, in addition to changes in the renal vascular tree, two saccular pseudoaneurysms in the course of a lobar artery in the left kidney. These caused life-threatening bleeding from the urinary tract. An autologous blood clot was injected into the bleeding artery by selective catherization, which resulted in cessation of bleeding for a period of 15 h, and thus permitted the performance of surgical intervention - nephrectomy - under more suitable conditions.


A rapid, simple and more sensitive method for the demonstration of central catecholamine-containing neurons and axons by glyoxylic acid induced fluorescence: I. Specificity. Perfusion fixation with a mixture of paraformaldehyde and glyoxylic acid facilitates the histochemical demonstration of catecholamine-containing brain neurons. With this fixation, sections can be cut reproducibly with a cryostat and the fluorophore developed by immersion in glyoxylic acid without freeze-drying. Large sections of brain can be examined by fluorescence microscopy within 1 hour of fixation or stored for later examination. The properties of the fluorophore and the location of the fluorescent elements is identical with the neurons and terminal arborizations demonstrated by previous glyoxylic acid methods. Monoamine oxidase inhibition before fixation results in moderately increased fluorescence of terminals and perikarya, while all glyoxylic acid induced fluorescence is abolished by pre-treatment with reserpine. The rapidity and simplicity of this technique may make fluorescence histochemistry of central catecholamine pathways more accessible to psychopharmacologists.


Chlorpromazine induced hyperphagia in the rat. During a four month period, 20 rats treated with subcutaneous injections of chlorpromazine (CPZ), at any dose tested, gained less weight than saline treated controls. However, increased feeding did occur on the first day of CPZ treatment if the animal was drug free for at least two days prior to treatment. The "first day" hyperphagia was a time limited response that did not occur until 8 hours after CPZ injection and lasted only one day. During the period of hyperphagia, treated animals showed increased motivation to obtain food. Although sedation is a marked effect of CPZ and may be the reason for the delayed onset of hyperphagia, sedation with a different drug does not cause hyperphagia. It is suggested that accumulation of a metabolite of CPZ may interfere with the feeding response and cause the hyperphagia to disappear after the first day of treatment.


A developmental study of the effects of 5,7-dihydroxytryptamine on regional tryptophan hydroxylase in rat brain. Tryptophan hydroxylase activity rises rapidly after birth in 5 distinct regions of the rat CNS. Near-adult levels of activity are recorded by 22 days of age in the cell-body rich regions of the brainstem and by 42 days in the terminal-rich areas, hypothalamus and remaining forebrain. The intracisternal injection of 40 mug 5,7-dihydroxytryptamine on day 2 after birth results in a near-total depletion of tryptophan hydroxylase in all CNS regions analyzed 6 or 12 days after drug administration. Enzyme activity recovers (to 11-24% of age matched controls) between day 12 and 20 after 5,7-dihydroxytryptamine in hypothalamus, midbrain and pons medulla oblongata. The growth of 5,7-DHT-treated animals is retarded between 3 and 40 days after drug administration.


Dose-ranging studies of clonazepam in man. A potent benzodiazepin derivative, clonazepam, was studied over a range of single doses to determine tolerance for the drug. The best tolerated doses were 0.5 and 1 mg. Higher doses were associated with considerable evidence of sedation, more easily detected by clinical questioning and observation than by commonly used self-reporting scales or motor tests.


Centrally active phenethylamines.

Centrally active phenethylamines. The two-carbon homologs of two potent psychotomimetic agents are described. Unlike the parent isopropylamine compounds (4-methyl-2,5-dimethoxyamphetamine, DOM, STP; and 4-bromo-2,5-dimethoxyamphetamine, PBR, 4-BR) these phenethylamines lead to an intoxication state which is, in normal subjects, of short duration and of greatly increased sensory enhancement, but which does not superimpose hallucinogenesis. These two phenethylamines, 4-methyl-2,5-dimethoxyphenethylamine (II) and 4-bromo-2,5-dimethoxyphenethylamine (III), are active in man at oral levels of 0.1 to 0.2 mg/Kg, approximately one tenth the potency of their three-carbon counterparts.


Dose-related effects of central noradrenaline stimulation on behavioural arousal in rats. The general activity of rats in an open field test situation was observed following the central administration of isotonic saline and 0.5 and 2.0 mug of noradrenaline into the locus coeruleus. A significant increase in activity was found following the 0.5 mug, but not the 2.0 mug dose. The results are consistent with other reports indicating that low doses of centrally administered noradrenaline produce behavioural arousal whereas higher doses may result in behavioural depression. In addition, these findings suggest that the noradrenergic neurons arising from the locus coeruleus may be important for the arousal status of rats.


Dipsogenic effects of intra and extracellular thirst stimuli before and after chronic DFP treatment. The water intake of rats was observed following subcutaneous administration of intra and extracellular thirst stimuli (hypertonic saline, polyethylene glycol, angiotensin, and isoproterenol) before and after chronic treatment with the anticholinesterase agent, diisopropyl fluorophosphate (DFP), and its arachis oil vehicle. Only hypertonic saline and isoproterenol reliably increased water intake in both groups prior to chronic treatment. After chronic treatment hypertonic saline produced the same degree of water intake in the DFP-treated and control animals, but isoproterenol appeared to produce a greater degree of water intake in the DFP-treated than in the control rats. These results suggest that there are no gross disturbances in the mechanisms underlying intra and extracellular thirst stimuli following the development of tolerance to DFP.


Effects of perphenazine on imipramine metabolism in man. In previous studies we have shown that perphenazine inhibits the metabolism of nortriptyline and imipramine. In this study the metabolism of 14C-imipramine and 14C-desipramine was studied before and during treatment with perphenazine. Studies on the imipramine and desipramine metabolites in urine showed that the major effect of perphenazine is an inhibition of the 2-hydroxylation of imipramine and desipramine. This causes a decreased formation and excretion of non-conjugated and glucuronide bound hydroxy metabolites and accumulation of imipramine and desipramine. There was some relationship between the dose of perphenazine and the decrease in total urinary excretion but the individual variations in response were pronounced (2-3-fold).


D & L amphetamine stereoisomers: comparative potencies in affecting the firing of central dopaminergic and noradrenergic neurons. The effect of the d- and l-isomers of amphetamine on the activity of dopaminergic neurons in the substantia nigra zona compacta and noradrenergic neurons in the locus coeruleus was studied in anesthetized and gallamine paralyzed rats using single unit recording techniques. d- and l-Amphetamine administered intravenously were equally effective in depressing the activity of locus coeruleus cells. However, although d-amphetamine was a potent inhibitor of substantia nigra dopamine containing cells, l-amphetamine was ineffective in causing more than a 45% inhibition of over half of the DA cells studied, even when given in nearly lethal doses. In the remaining dopamine neurons l-amphetamine was only 0.2 to 0.05 times as potent as d-amphetamine in producing both 50 and 100% inhibition of firing rate. These findings, when combined with recent biochemical studies by other authors, suggest that l-amphetamine, at low doses, has a preferential effect on noradrenergic as compared to dopaminergic neurons. The consequences of these findings for the interpretation of studies in which d- and l-amphetamine have been used as pharmacological tools to determine the catecholamine system responsible for a particular behavior in man and animals is discussed.


Fenfluramine: evidence for a neurotoxic action on midbrain and a long-term depletion of serotonin. A single injection of fenfluramine (100 mumol/kg) produced evidence of neurotoxicity in cresyl violet or silver stained sections of rat brain which was restricted to the serotonergic (B-9) cell group located in the ventromedial midbrain tegmentum. Reacting cells throughout this region exhibited an irregular shape and an intense staining of the cytoplasm, while in the caudal 1/4 of this region the reacting cells also exhibited a perineuronal space. These effects were greatly reduced in the rostral 3/4 of B-9 at 14 and 30 days after fenfluramine. In the caudal 1/4 of B-9 the neurotoxic actions remained prominent and included signs of cellular dissolution. These signs of an irreversible degenerative effect of fenfluramine on cells in the caudal 1/4 of the B-9 region were identical to those seen after p-CA, while the effects in the rostral 3/4 of B-9 were not as prominent. The differential neurotoxic effects of fenfluramine and p-CA on cells in the rostral 3/4 of B-9 were associated with a differential effect on serotonin content of hippocampus and amygdala.


Methylene reductase: responsible for the in vitro formation of formaldehyde from 5-methyltetrahydrofolic acid. Formaldehyde formation from 5-methyltetrahydrofolic acid, as well as its further reaction with beta -phenylthanolamine to form a tetrahidroisoquinoline derivative, is activated in rat crude tissue extracts by the addition of menadione to the incubation mixtures. FAD also stimulates the process in the presence of oxygen, but fails to do so in the absence of the latter compound. Together, FAD and menadione maximally stimulate the formation of formaldehyde, or of the amine derivative, under anaerobic conditions. These properties of the "formaldehyde-forming enzyme" correlate to those previously reported for methylene reductase and strongly suggest that both enzyme activities are identical.


H3-p-chloroamphetamine: cerebral levels and distribution. Whole-brain levels of radioactivity were assessed at 0,2,6,12, or 24 hours, 1 1/2,2,7,10, and 14 days after intraventricular injection of H3 -p-CA. Urinary excretion and peripheral distribution were also followed for one week. The rate of elimination of total radioactivity from brain is biphasic with a T 1/2 of 1.2 hours and 2.5 days after intraventricular and 4.2 hours and 1.9 days after intraperitoneal injection of p-CA. The distribution into cerebellum, neocortex, brainstem, and telencephalon was studied at 1 hour, 2,3,5, and 7 days after injection. At both three and seven days, the radioactivity is still present in all the areas of the brain. The contribution of H3-p-CA to total radioactivity in the toluene extractable fraction was measured. By twelve hours, four chromatographically distinct peaks of radioactivity can be isolated from the toluene extract. The radiolabel in the subcellular fractions was also determined. There is a significant shift of radiolabel from the supernatant to organelle-bound phases between three and seven days.


Regional distribution of norepinephrine and dopamine in brains of depressive suicides and alcoholic suicides. Norepinephrine (NE) and Dopamine (DA) were measured in 30 brain areas of depressive suicides and alcoholic suicides and in controls who had died of natural causes, in an effort to test directly the "catecholamine hypothesis" of depressive illness. Levels of NE were highest in the hypothalamus, tegmentum of pons, red nucleus and mesencephalic tegmentum; lowest in centrum semi-ovale, hippocampus and cingulate gyrus. Highest values for DA were found in the putamen, head of caudate, substantia nigra, globus pallidus, red nucleus and a few areas of the hypothalamus; lowest in cerebral cortex, ventral pons and thalamus. Our data showing a slight increase in NE levels in four areas of the suicide brains is probably of little clinical importance. In no case were the NE or DA levels in the suicide brains significantly less than in the controls. Alteration of monoamine metabolism as an etiologic factor in depressive illness remains a possibility if the mechanism involves blocking of the uptake of amines into neurons or changes in membrane permeability. It is unlikely that an alteration of amine metabolism per se is involved, since four selected metabolizing enzymes previously studied showed no difference in activity and the present study shows no depletion of amines.


The effects of dimethylaminoethanol (deanol) on cerebral cortical neurons. 2-Dimethylaminoethanol and acetylcholine were iontophoretically tested on deep, spontaneously firing, neurons of the rat cerebral cortex. All identified corticospinal cells and 71% of the unidentified ones were excited by Deanol. Eight percent of the latter group were inhibited. All but one neuron responded similarly to ACh and Deanol, when both substances were tested on the same neuron. Atropine reversibly blocked these responses. The implications of these observations are discussed with regard to cholinergic synapses in the brain and the rationalization of the therapeutic use of Deanol.


Effects of molindone on central dopaminergic neuronal activity and metabolism: similarity to other neuroleptics. The effect of molindone on the activity of dopaminergic (DA) neurons in the rat midbrain and on DA metabolism in the striatum and olfactory tubercles was studied using extracellular single unit recording and biochemical techniques respectively. Molindone in low intravenous doses (0.4-0.8 mg/kg) was found to reverse d-amphetamine and apomorphine induced depression of DA neurons and to block apomorphine induced depression of these cells. Molindone was also found to increase dopamine synthesis and dihydroxyphenylactic acid levels in the striatum and olfacotry tubercles. In all of these respects molindone behaves identically to most classical neuroleptics. However, unlike most antipsychotic drugs previously tested, molindone failed to increase the baseline firing rate of DA cells and blocked haloperidol induced increases in DA neuron activity. In this regard molindone most closely resembles thioridazine and clozapine. Possible mechanisms of action of molindone are discussed based on these findings.


Metabolic O-demethylation of the psychotomimetic amine 1-(2, 5-dimetroxy-4-methylphenyl)-2-aminopropane. In an effort to more fully characterize the metabolic fate of the psychotomimetic amine (1-(2, 5-dimethoxy-4-methylpheny.)-2-aminopropane (DOM, STP), the formation of the two possible monophenols and the p-hydroquinone metabolites of the parent drug by 10,000 X g supernatent fractions of rabbit liver homogenates has been investigated. All three metabolites have been fully characterized and quantitatively estimated by chemical ionization mass spectrometry with the aid of deuterium enriched compounds. The stereochemical course of the mono-O-demethylation reactions has been shown to proceed with enantiomeric enrichment of the S-aminophenols. The mechanistic implications concerning the mode of action of the parent drug and metabolic O-demethylation are discussed.