In vivo intestinal calcium transport in infant rats: normal and growth retarded.

We compared the in vivo transport of calcium (Ca) in the jejunum + ileum of 1-, 2-, 3-, 4-, and 6-week old rats. In normal rats, net absorption and the estimated bidirectional fluxes of Ca (lumen-to mucosa and mucosa-to-lumen) normalized for differences in size of the intestine (mumoles/hour per g weight) were similar in the 1-, 2-, and 3-week old rats and significantly lower in the 6-week old than in the younger rats. Growth retardation (pups raised with mothers fed a diet deficient in protein) appeared to have suppressed net absorption and the bidirectional fluxes of calcium in the 4- and 6-week old rats, but to have slightly enhanced net absorption and the bidirectional fluxes in the 1-, 2-, and 3-week old rats. These findings suggested a change in the mechanism(s) for intestinal transport of Ca during maturation. Rate of gain in body weight expressed as g/day increased with age from 1.4 g/day between 1 and 2 weeks, to 6.1 g/day between 4 and 6 weeks of age. There was no correlation between rate of net Ca absorption from the jejunum + ileum and gain in body weight expressed as g/day or as percent per day.


Effect of retinoic acid and retinyl acetate feeding upon lipid metabolism in adrenalectomized rats.

Many reports have appeared in the literature suggesting that vitamin A may exert some of its effects via changes in adrenocortical activity. A series of experiments were performed in order to assess the possible role of the adrenal gland in vitamin A-induced lipid alterations in rats. Adrenalectomized, sham-operated, and intact rats were fed retinoic acid or retinyl acetate at several levels. Either 25 or 100 retinol equivalents (RE)/g dry diet were fed to male Sprague-Dawley rats for periods of 7 or 28 days. Neither compound had an effect on the concentration of liver glycerides, phospholipids, cholesterol, or total lipids. Vitamin A, especially in the form of retinoic acid, was found to induce an elevation of plasma triglycerides. The presence of the adrenal gland was not necessary for the induction of hypertriglyceridemia nor was there any indication of increased adrenocortical output (as measured by plasma corticosterone level) as a result of vitamin A feeding. There was a reduction in circulating retinol as a result of retinoic acid feeding at either 25 or 100 RE in sham-operated and adrenalectomized rats but not in unoperated rats. These experiments demonstrate that vitamin A, especially in the form of retinoic acid, fed at as low as 25 RE/g diet to the rat can induce hypertriglyceridemia, and that the adrenal gland does not mediate this effect.


Effect of intermittent feeding on glucose-insulin relationship in the chicken.

The effects of training to various rhythms of intermittent total starvation (ITS) or intermittent protein starvation (IPS) on the plasma glucose and the plasma insulin levels were studied in the growing chicken. Both types of feeding improved the glucose tolerance in spite of a decrease in the insulin response. After an oral glucose load, plasma free fatty acids showed opposite variations to plasma insulin and plasma glucose. The insulin released in response to a test meal was unchanged. In the ITS 1-1 group (1 day fasting-1 day feeding cycles), low glycemia-low insulinemia were observed during the fasting period of the cycle and high glycemia-hyperinsulinemia during the repletion period in response to the "adaptive hyperphagia." In the IPS 1-1 group (1 day feeding with the protein free diet-1 day feeding with the balanced diet cycles), glycemia was sustained at a high level during both periods of the cycle and insulinemia was depressed by feeding with the protein-free diet and highly stimulated by refeeding with the balanced diet. Therefore, in the chicken, intermittent feeding increases the insulin sensitivity of target tissues and modifies the B-cell sensitivity to glucose. The highest decrease in B-cell sensitivity to glucose was obtained with the protein free diet which further emphasizes the glucose-amino acid synergism previously observed for insulin release.


Outcome of early experience studies as affected by between-litter variance.

Studies of early experiences in animals in which the mother or the entire litter is manipulated often involve significant levels of between-litter variance. Such variance, if not accounted for either by analysis which considers litter as an independent source of variance, or by use of mean litter scores, may contribute to misleading treatment effects. This phenomenon is demonstrated for experiments utilizing analysis of variance procedures for data analysis.


Mechanism for fatty liver induction in rats fed arginine deficient diets.

Arginine deficiency is known to lead to marked alterations in pyrimidine biosynthesis and the excessive loss of urinary orotic acid. Orotic acid feeding is known to lead to hepatic steatosis. These studies show that arginine deficiency also results in a marked increase in liver lipids in the rat. The majority of the increased liver lipid can be accounted for by triglyceride accumulation. Increased liver lipid infiltration was found to be independent of the sex of the rat. Accompanying this increase was a decrease in serum triglycerides and cholesterol concentrations. Fatty infiltrations induced by arginine deficiency could be reversed by refeeding an arginine enriched diet. Adenine supplementation (0.30%) to the arginine deficient diet also completely prevented the induction of fatty livers. Adenine supplementation resulted in a dramatic increase in urinary orotic acid excretion in the arginine deficient rat. Guanine supplementation (0.5%) to an arginine deficient diet reduced but did not prevent the induction of fatty livers. The similarities of fatty livers induced by arginine deficiency and orotic acid feeding are discussed.


Lanthanide markers in a single sample for nutrient studies in humans.

Multiple Lanthanide markers were used to develop procedures for determinations of intake and apparent utilization of four nutrients using data from fecal analysis and known concentrations of markers in nutrients. Terbium oxide was given as the intake marker. All foods contained the other non-absorbed markers, each marker in direct proportion to the amount of a specific nutrient in each food. Nutrient markers were oxides of samarium, scandium, ytterbium, and europium. Fecal collection and subsequent analysis of nutrients and markers were completed. Fecal marker concentration stabilized 2 days following initiation of the marker regime. Thus, after 3 days, a single grab sample could be utilized to analyze for nutrient utilization. The ratio of nutrient marker proportional to nutrient and intake to nutrient excretion provides the data for the calculation of apparent utilization for as many nutrients as nutrient markers incorporated into the food. When direct and marker methods of determining nutrient intake and apparent utilization were compared, no significant differences were found for gross energy, fat, protein, and calcium.


Essentiality of amino acids for the growing kitten.

The effect of deleting each of the amino acids known to be essential for the young rat was determined in post weanling kittens fed a purified diet containing only L-amino acids as the source of dietary nitrogen. When any one of the 10 amino acids (arginine, lysine, histidine, isoleucine, leucine, methionine, phenylalanine, threonine, tryptophan, valine) were deleted from the diet food intake decreased, the kittens lost weight, and there was a dramatic drop in each corresponding amino acid in the blood plasma; indicating that each of the above amino acids is essential for the kitten. Deletion of all the amino acids except the 10 essential amino acids plus alanine resulted in a decreased weight gain to about 1/3 normal; indicating that although all the other amino acids could be synthesized, one or more of the dispensable amino acids may be required for maximal growth. When any one of the essential amino acids was decreased to one-half that present in the basal diet, there was no decrease in weight gain, indicating that the high protein requirement of the kitten is not the result of an unusually high requirement for the essential amino acids.


Statistical analysis of epidemiological data from a chromium chemical manufacturing plant.

A statistical analysis was performed on reported bronchogenic carcinoma incidence in a group of chromium chemical manufacturing workers over the period 1929 to 1977. The purpose was to determine if post-1950 process improvements corresponded to favorable trends in morbidity. Because the paucity of data on the population at risk prevented meaningful calculations of SMR's, a recently developed method called "probability window analysis" was used to evaluate for statistically valid changes in the "numerators" or number of reported cases. A significant downward trend in reported bronchogenic carcinoma was found which coincided with major process improvements made in 1951 and 1961. Although adjustment for all competing risk factors was not possible because of insufficient data on the population at risk, the improved working environment has to be considered a major contributing factor to the favorable trend.


Campylobacter enteritis in children.

In 37 children with Campylobacter enteritis seen over a 6-month period, ages ranged from 2 weeks to 15 years. The sex ratio (male:female) was three:two. Fever, diarrhea, and bloody stools occurred in about 90% of patients. Blood appeared in the stools characteristically 2 to 4 days after onset of symptoms. Over 90% of older children developed abdominal pain. Vomiting was mild and occurred in 30% of patients. Dehydration was not a feature. Infection occurred in all social classes and was not associated with parental occupation, travel, or animal contact. The illness often presented characteristically and a rapid laboratory diagnosis could be made in patients presenting acutely by direct phase-contrast microscopy of stools. The organism persisted in the stools for up to seven weeks in untreated patients, but could no longer be cultured after 48 hours of therapy with erythromycin, to which all strains were highly sensitive. Significant serologic responses were elicited using a serum bactericidal assay. The Skirrow-type selective medium used by us could be improved by increasing the concentration of polymyxin B sulfate to 5 microgram/ml.


Intelligence and phenylketonuria: effects of diet termination.

Trends in intellectual functioning before and after diet termination were examined in 30 children with PKU treated before 6 weeks of age and on a liberal diet for a mean of three years since the mean age of 59 months. Comparisons of trends in pre- and posttermination IQ scores with the linear spline technique revealed no significant differences. Comparisons of pretermination IQ scores with posttermination scores and scores from the most recent evaluation also yielded no significant differences. These data fail to support a relationship between termination of diet and impairment of intellectual functioning, at least during this period of observation.


Impaired growth in hyperkinetic children receiving pemoline.

Decreased longitudinal growth was observed in 24 hyperkinetic children receiving pemoline therapy. Mean height velocity was 3.67 +/- 0.25 cm/year during therapy but 5.35 +/- 0.42 cm/year after treatment had been discontinued (P less than 0.01). There appeared to be an inverse relationship between growth velocity and drug dosage. All patients receiving less than the median dose of 3.72 mg/kg grew 4 cm/year or more, while seven of 12 patients receiving more than this dose grew at a slower rate. Body weight, basal and stimulated growth hormone values, and plasma somatomedin concentrations were not significantly altered by pemoline treatment, suggesting that this drug may have a direct effect on cartilage metabolism.


Refractory infantile diarrhea due to primary bile acid malabsorption.

A boy is described who had severe, refractory diarrhea beginning soon after birth. Prolonged parenteral alimentation was required to support life. Investigations of bile acid metabolism showed impaired intestinal absorption of bile acids. Contracted bile acid pool sizes resulted, with low intraluminal bile acid concentrations and severe, malabsorption of water and fat. Bile acid malabsorption is a cause of refractory infantile diarrhea.


Laboratory measures of copper metabolism in the differentiation of chronic active hepatitis and Wilson disease in children.

The accuracy of the serum ceruloplasmin level in distinguishing chronic active hepatitis from Wilson disease was compared to the 24-hour urinary copper excretion and hepatic copper content in 20 untreated patients with chronic active hepatitis and 25 with Wilson disease. Serum ceruloplasmin levels were decreased in five patients (25%) with chronic active hepatitis and were normal in seven patients (28%) with Wilson disease at the time of diagnosis. The 24-hour urinary copper excretion failed to provide accurate discrimination between the two groups, being elevated in all patients with Wilson disease and in five of eight patients with chronic active hepatitis studied. All patients with Wilson disease had hepatic copper levels greater than 400 microgram/gm dry weight, whereas patients with chronic active hepatitis had levels less than 300 microgram/gm dry weight. The discriminatory value of hepatic copper concentration makes this the most reliable test for differentiating chronic active hepatitis and Wilson disease in children and adolescents. The serum ceruloplasmin level may not be significantly accurate for definitive diagnosis in this age group.


Reye syndrome in siblings.

Reye syndrome in siblings was seen in three of 85 families; the incidence of RS in these family groups appears to exceed that of the general population. The interval between development of RS in the first and second siblings was two to 11 days and related to the incubation period of the initial viral infection. In five of the children this infection was chickenpox and in two, an unspecified upper respiratory illness. To assess the role of genetic factors, HLA typing was performed on these siblings; a common genetic marker indicating susceptibility to RS was not identified. All families resided in rural and suburban areas; exposure to a common environmental toxin was not identified.


Urine culture in the evaluation of suspected neonatal sepsis.

Clinical records of patients in a neonatal intensive care unit were reviewed to determine the efficacy of obtaining a urine culture in the detection of neonatal sepsis. During a 12-month period, 188 sets of concomitant blood and urine cultures were obtained in infants less than 72 hours of age (early onset group) and 189 sets of cultures in infants over 72 hours of age (late onset group). Blood cultures were positive in nine instances in the early onset group and 11 instances in the late onset group. All but one blood culture in each group  was accompanied by a negative urine culture. Urine cultures alone were positive in two instances in the early onset group and 13 instances in the late onset group (P less than 0.05). Symptoms did not differentiate infants with bacteremia from infants with bacteruria. Culture of the urine was shown to be necessary for the detection of a significant number of late onset infections. Urine culture in the early onset age group had a significantly lower yield, and the risk of suprapubic bladder tap in this group may not be justified.


Dosage of digoxin in premature infants.

The pharmacokinetics and pharmacodynamics of digoxin in premature infants was studied. During maintenance therapy, after a total digitalizing dose of 30 microgram/kg, the measured digoxin level was related inversely to body weight at birth and to estimated gestational age. The serum digoxin levels found in the immature and smaller infants were two to three times the values usually reported to be toxic in older children. Based on these findings, a second group of premature infants was digitalized with 20 microgram/kg; in this group, the serum digoxin levels were below the toxic range, irrespective of gestational age or birth weight. The cardiac effects of digoxin, i.e., shortened left ventricular pre-ejection period and ejection time as determined by echocardiography, were similar in the two groups. For both groups, the half-life of digoxin in the serum was twice that reported for term infants and children. Since digitalis effect is obtained with lower dose and serum concentration, we recommend that this dose be used in premature infants.


Constriction of the fetal ductus arteriosus after administration of indomethacin to the pregnant ewe.

The prostaglandin synthetase inhibitor indomethacin was given orally or intravenously to pregnant ewes. This resulted in the fetal pulmonary to systemic arterial mean blood pressure difference across the ductus arteriosus rising significantly, presumably secondary to constriction of the ductus arteriosus. The pressure difference was due to pulmonary arterial hypertension, and not due to a fall in systemic arterial mean blood pressure. Fetal arterial blood gas tensions and pH values were normal throughout. In five experiments the pressure difference could be promptly but temporarily reversed by the administration of PGE1 into the fetal inferior vena cava. Indomethacin was present in fetal blood, and maternal plasma prostaglandin levels were suppressed. Indomethacin administration during pregnancy causes constriction of the fetal ductus arteriosus and fetal pulmonary arterial hypertension which, if severe, may cause rapid fetal death. It is possible that this mechanism may be one cause of persistent pulmonary hypertension or tricuspid insufficiency or both in the newborn infant.


Pharmacokinetic profile of caffeine in the premature newborn infant with apnea.

The pharmacokinetic profile of caffeine was studied in 32 premature newborn infants with apnea: 12 following a single intravenous dose; 3 after a single oral dose; 7 during treatment with an initial empirical (high) maintenance dose schedule; and 10 during treatment with a revised (lower) dose schedule. Mean (+/- SE) AV d, t 1/2, ke1, and clearance following a single intravenous dose were 0.916 +/- 0.070 1/kg, 102.9 +/- 17.9 hours, 0.009 +/- 0.001/hours and 8.9 +/- 1.5 ml/kg/hour, respectively. Rapid absorption was noted with plasma concentrations of 6 to 10 mg/l achieved within 30 minutes to two hours following an oral dose of 10 mg/kg. Cpss of caffeine in infants given a high empirical dose (11.2 +/- 1.5 mg/kg/day) ranged from 22.5 to 84.2 mg/l (mean  = 45.3) whereas a dose schedule based on kinetic data (2.5 mg/kg/day) yielded plasma concentrations ranging from 7.4 to 19.4 mg/l (mean = 13.7). We suggest a loading dose of 10 mg/kg intravenously or orally followed by a daily maintenance dose of 2.5 mg/kg/day administered as a single dose for the treatment and prevention of neonatal apnea.


Treatment of glutaryl-CoA dehydrogenase deficiency (glutaric aciduria). Experience with diet, riboflavin, and GABA analogue.

The autosomal recessive inherited disorder glutaryl-CoA dehydrogenase deficiency (glutaric aciduria) runs a progressive course with severe choreoathetosis and dystonia, eventually leading to total helplessness and early death. Theree patients were observed during therapeutic trials with a protein-low diet, riboflavin and GABA analogue. Diet and riboflavin had a slight-to-moderate effect on the clinical symptoms; the excretion of glutaric acid and 2-amino-adipic acid decreased considerably during treatment. Regression of neurologic symptoms was observed during treatment with GABA analogue. It is concluded that the patients should be treated as early as possible with protein-low diet, riboflavin, and GABA analogue.


Effects of a model on eating behavior: the induction of a restrained eating style.

An experiment was conducted to assess the effects of a same-sex model on females' eating behavior. The model ate either a large or small quantity along with the subject in an ad lib satiation context, and either did or did not identify herself as a dieter. Subjects were 86 female undergraduates, split into normally dieting or nondieting subgroups. Number of sandwich quarters consumed ad lib following a small fixed preload was found to vary as a function of (a) model's consumption (b) model's dieter status and (c) subject's dieter status; there were no significant interactions. A subsequent taste-rating assessment of nut consumption, in which the model was present but could neither see nor be seen by the subject, indicated that the three factors which had previously affected sandwich consumption independently combined to affect nut consumption interdependently. The results were interpreted in terms of the effect of the model on the quantity and pattern of consumption, and conclusions were drawn about the dynamics of restrained and unrestrained eating and implications for therapy.


Effects of an observer on eating behavior: the induction of "sensible" eating.

An experiment was conducted to investigate the extent of caloric compensation to differential preloading among normally restrained and unrestrained female subjects. Subjects' eating was either explicitly observed or unobserved by the experimenter. Unrestrained eaters compensated appropriately for the preload, whether or not they were observed. Restrained eaters failed to compensate when unobserved , but compensated strongly when observed. A subsequent unobserved eating task revealed that restrained eaters failed to compensate for prior consumption when the observer was withdrawn. Implications for research and therapy are discussed.


The scientific status of the Rorschach.

Demonstrated that the interpretation of projective test data is semantic, not probabilistic. The clinician does not employ the model of statistical inference in evaluating the meaning of test responses, although he may employ probabilistic rules as guides to interpreation. Procedural rules for interpreting meaning, the nature of clinical diagnosis from psychological tests, and the meaning of prediction as a clinical activity are discussed. It was concluded that clinicians do not make inferences, in the mathematical sense of this term.


The State-Trait Anxiety Inventory A-Trait Scale: dimensions and their generalization.

The State-Trait Anxiety Inventory A-Trait scale was administered to 152 female and 158 male students. Principal-components factor analyses yielded four orthogonal factors for each sex. The findings indicated that factor pattern comparisons should be made prior to pooling data across sex for psychometric investigations. Also, limited support was found for the generalization of dimensions across sex and samples both within and between cultures.


A psychometric investigation of the Eysenck Personality Questionnaire.

The Eysenck Personality Questionnaire was administered to 139 females and 123 males. Scale statistics were obtained and hierachial factor analyses were performed. The P scale was found to have low internal consistency reliabilities and to covary with the L scale in the female subsample. Factor analyses showed recovery of E scale items in a secondary factor, Social Extraversion, without an impulsivity primary factor. No P and N dimensions recovered; rather components of each scale interrelated in two meaningful dimensions at the tertiary level.


Response consistency on the MMPI; the TR Index.

The number of inconsistent responses to the repeated items (the TR Index) on the group booklet form of the MMPI provides important information on a person's test-taking behaviour which received scant attention. Normative data from a variety of populations and an optimal cutting score for the TR Index is provided.


Indirect self-destructive behavior in patients with Buerger's disease.

Patients with Buerger's disease (a circulatory illness) were studied to evaluate indirect self-destructive behavior (ISDB), evidence by neglect in following medical regimen, disregard of suggestions for environmental imporvements (avoidance of undue exposure to cold) and refusal to abstain from smoking. Personality characteristics and behavioral phenomena associated with ISDB were obtained by comparison of the files of 26 uncooperative patients with 26 matched cooperative controls with Buerger's disease and with 25 Buerger's disease patients representing a unselected annual population in a Veterans Administration (VA) hospital. The experimental group was characterized as more often complaining, manipulative, and aggressive. They manifested denial, negligence, and a tendency to minimize their illness. They were more likely to complain of pain and to demand relief. In a second clinical investigation of patients still in the hospital, 12 experimentals were compared with 12 controls using interview data and psychological tests measuring attitudes toward time and toward death. The experimentals did not seem to value time nor to be interested in achievement. They felt that a dull life was worse than death.


Pharmacokinetics and cardiopulmonary effects in dogs of sublingual pirbuterol, a new bronchodilator.

The time course of plasma concentrations of sublingually administered pirbuterol was investigated in anesthetized dogs; there was a dose-related increase in plasma drug concentrations which reached maximum values 1 hr or more after administration. In a second study plasma drug levels were correlated with antagonism of histamine-induced changes in pulmonary compliance and resistance which also reached maximum values 1 hr or more after drug administration, although marked antagonism was apparent at 15 to 30 min; blood pressure was unaltered at any dose level and heart rate was influenced only at the highest dose level. A convenient method for study of the bioavailability of sublingual formulations is described, and the potential usefulness of a sublingual dosage form of pirbuterol is discussed.


The anaerobic metabolism of metronidazole forms N-(2-hydroxyethyl)-oxamic acid.

N-(2-hydroxyethyl)-oxamic acid is formed when metronidazole is reduced either chemically or by the action of the intestinal bacteria. When metronidazole, labeled with carbon-14 in the hydroxyethyl side chain, is administered by gavage to rats in doses of 200 mg/kg, an average of 1.4% of the administered radioactivity is recovered in the urine in the form of N-(2-hydroxyethyl)-oxamic acid. The presence of conjugated N-(2-hydroxyethyl)-oxamic acid in some samples was suggested by the detection of small additional amounts of the free acid after treatment of the urine with beta-glucuronidase. The metabolite is not found in the feces. In contrast N-(2-hydroxyethyl)-oxamic acid is not found in the urine or feces of germfree rats which receive metronidazole. Thus, the finding of N-(2-hydroxyethyl)-oxamic acid in the urine of rats which receive metronidazole appears to depend on the activity of the bacterial flora.


Dopaminergic control of the septal-hippocampal cholinergic pathway.

Apomorphine given subcutaneously is known to decrease the turnover rate of acetylcholine (TR(ACh) in the hippocampus. Blockade of dopaminergic receptors by intraseptal haloperidol or destruction of dopaminergic terminals by intraseptal 6-hydroxydopamine results in an increase in TR(ACh) in the hippocampus. Specific destruction of the dopaminergic neurons projecting to the septum by the injection of 6-hydroxydopamine into the A10 mesencephalic cell group also results in an increased TR(ACh) in the hippocampus. None of the above treatments affects TR(ACh) in the cortex. Thus, it appears that dopaminergic neurons exert a tonic inhibitory effect on the ACh metabolism of the septal-hippocampal pathway, but do not affect that of cholinergic neurons projecting from the septum to the cortex. It can be inferred that this decrease in the rate of metabolism may be associated with a regulation of the rate of neuronal firing.


The specificity of antimorphine and antimeperidine antibodies and their reactivity with opioid peptides.

The specificity of antimorphine and antimeperidine antisera was measured by competitive displacement of immunizing radiolabeled haptens. Antimorphine antisera demonstrated a high degree of specificity for a conformation of the phenylpiperidine moiety contained within the structures of morphine and its congeners of the morphinan and benzomorphan series. Antimeperidine antisera demonstrated a high degree of specificity for a different conformation of the phenylpiperidine moiety represented within the structures of meperidine and its semisynthetic derivatives. The reactivity of methionine- and leucine-enkephalin, several synthetic enkephalin analogs, and alpha- and beta-endorphin with the antibodies was tested using purified immunoglobulin G in order to avoid serum-induced proteolysis. No significant cross-reactivity of antimorphine antibodies with any of the opioid peptides was detected. All of the opioid peptides tested exhibited weak but immunologically specific cross-reactivity with antimeperidine antibodies. These findings suggest that conformations analogous to the phenylpiperidine moiety in morphine as have been proposed for [Tyr1] in opioid peptides do not appear to be present as measured by immunochemical methods. A conformation with weak stereochemical similarity to the phenylpeperidine moiety in meperidine does appear to be present. The possible homologies between [Phe4] of opioid peptides, meperidine and hydrophobic side chains of certain oripavine derivatives are discussed.


Amphetamine- and phenylethylamine-induced alterations in dopamine synthesis regulation in rat brain striatal synaptosomes.

Amphetamine and phenylethylamine stimulate dopamine synthesis in rat brain striatal synaptosomes via a calcium- and tyrosine-dependent mechanism. The similarity of this stimulation to that produced by depolarizing concentrations of veratridine, along with the non-additivity of maximally stimulating concentrations of amphetamine and veratridine, suggests that these treatments may all share a common locus of action. Differences in exact modes of action can be seen, however, in the blockade only of the stimulation of veratridine by tetrodotoxin, and by the lack of effect of amphetamine or phenylethylamine on tyrosine uptake. At high concentrations, amphetamine and phenylethylamine lose their ability to stimulate dopamine synthesis and produce an antagonism of veratridine-induced synthesis stimulation.


Vocalization response to close-arterial injection of bradykinin and other algesic agents in guinea pigs and its application to quantitative assessment of analgesic agents.

A method for determining the vocalization response to algesic agents in conscious guinea pigs is described. Retrograde injection of small amounts of algesic agents into the femoral artery caused transient but obvious vocalization response in a dose-dependent manner. The vocal sound was converted into electrical signals and the envelope of the sound obtained by a peak detector circuit was recorded on an ink-writing oscillograph. The area of the vocalization response circumscribed by a base line and the envelope tracing of the vocal sound was also recorded. Bradykinin, kallidin, acetylcholine (ACh) and nicotine caused the vocalization response, while substance P, histamine, bethanechol, methacholine, serotonin, kallikrein and prostaglandins E1 and E2 caused no or little response. No detectable tachyphylaxis to bradykinin, ACh and nicotine was observed. The pretreatment with hexamethonium abolished the response induced by ACh or nicotine but not the response induced by bradykinin. These results suggest that the paravascular pain receptor of the femoral artery excited by ACh is nicotinic in character. Subcutaneous injection of morphine, pentazocine, diclofenac and aminopyrine inhibited the vocalization response induced by bradykinin in a dose-dependent manner.


SC 25152: a potent mineralocorticoid antagonist with decreased antiandrogenic activity relative to spironolactone.

The widely used mineralocorticoid antagonist spironolactone has antiandrogenic activity that may contribute to its side effects of decreased libido, impotence and gynecomastia. We have therefore sought a less antiandrogenic analog of spironolactone that may exhibit reduced endocrine side effects. The analog SC 25152 was chosen for pharmacological testing because of the previous observation that it has considerably reduced affinity for the androgen receptor of both man and rat but exhibits an affinity for the mineralocorticoid receptor similar to that of spironolactone. Bioassays in the rat  show that SC 25152 has a 60% decrease in antiandrogenicity, and a 4-fold increase in antimineralocorticoid activity compared to spironolactone, resulting in an overall reduction of antiandrogenic activity to one-tenth that of spironolactone at doses giving equal antimineralocorticoid activity. These studies demonstrate that the antiandrogenic and antimineralocorticoid activities of spironolactone analogs can be dissociated and illustrates the utility of measurements of drug-receptor interaction to identify a compound with desired pharmacological properties.


Ryanodine: its alterations of cat papillary muscle contractile state and responsiveness to inotropic interventions and a suggested mechanism of action.

Cat right ventricular papillary muscles responded biphasically to cumulative additions of ryanodine. A progressive and pronounced negative inotropic effect was observed with low to intermediate ryanodine concentrations (5 nM-1 muM) while a rebound or reversal of these initial changes back toward pre-drug values was obtained as the ryanodine concentration was further increased to 100 muM. Active force development (DF), the rate of force development (dF/dt), as well as the rate of relaxation all exhibited these bidirectional changes. In contrast, time to peak force underwent only a progressive prolongation over the entire concentration range tested. This response pattern was observed with both normal and K+-depolarized (isoproterenol- or dibutyryl cAMP-restored) preparations. The response to a single addition of 100 muM ryanodine, in the presence of 2.5 mM Ca++ mimicked both the qualitative and quantitative aspects of the cumulative concentration response curve. In the presence of 5.0 mM Ca++ the high concentration of ryanodine no longer caused depression but instead caused only a slowly developing, monophasic increase in DF. Ryanodine also changed the response of ventricular muscle to other inotropic interventions. Ryanodine (1 muM; 2.5 mM Ca++) abolished the normal increase in dF/dt following either paired electrical stimulation (PES) or 50 mOsM mannitol, but not that in response to a doubling of the stimulation rate (0.2--0.4 Hz). After ryanodine exposure, the potentiation of developed force by PES was shifted from the first (regular) to the second (premature) contraction, producing a summation-like waveform. Prior addition of the calcium channel antagonist D600 (1 muM) did not alter ryanodine-induced changes in PES. Caffeine (1 mM) produced alterations in the responses to PES and hyperosmolarity which were similar to those observed with ryanodine. In the presence of high concentrations of both ryanodine (100 muM) and calcium (5 mM) both the transient and steady-state responses to a doubling of the stimulation rate (0.2--0.4 Hz) were markedly depressed, whereas the decrease in DF or dF/dt normally accompanying a reduction in the rate of stimulation was attenuated. The data obtained in the present study are consistent with a functional inhibition of sarcoplasmic reticular calcium release by ryanodine.


Effects of sodium nitroprusside, isosorbide dinitrate, isoproterenol, phentolamine and prazosin on hepatic venous responses to sympathetic nerve stimulation in the cat.

Hepatic blood volume was recorded by a plethysmographic technique in cats anesthetized with pentobarbital. The effects of three doses of each vasodilator drug were measured on arterial and portal pressures, hepatic blood volume in the denervated liver and on the portal pressure and hepatic venous responses to sympathetic nerve stimulation. Isosorbide dinitrate caused a small reduction in basal hepatic venous tone increasing hepatic blood volume by up to 15%; it had no effect on the responses to sympathetic nerve stimulation. Isoproterenol increased hepatic venous tone perhaps by stimulation of angiotensin formation and the responses to stimulation of the hepatic nerves were reduced because of this increased basal tone. Sodium nitroprusside produced a small decrease in basal venous tone and only large doses produced any reduction in the venous responses to hepatic nerve stimulation. The evidence that nitroprusside is a venodilator requires reexamination. Phentolamine had no effect on basal venous tone but markedly reduced the responses to sympathetic nerve stimulatiqn. When compared to phentolamine, prazosin produced comparable effects on arterial pressure but much less reduction in the hepatic venous responses to sympathetic stimulation. It is suggested that the alpha receptor blocking action of prazosin is selective for arterioles and this may explain the minor incidence of postural hypotension during clinical use.


Mossy and climbing fibre mediated responses evoked in the cerebellar cortex of the cat by trigeminal afferent stimulation.

1. The trigeminal input to the cerebellar cortex was studied by recording mass and unitary resonses evoked by electrical stimulation of individual trigeminal cutaneous and muscle nerve branches, in cats lightly anaesthetized with sodium thiopentone. 2. The trigeminal projection area of the cerebellar cortex comprised essentially lobule HVI, but included adjacent folia of lobules HV and HVIIA. 3. Each trigeminal branch had a 'patchy' representation throughout the projection area and there was extensive convergence of individual afferents at each site. Exact combinations of convergent inputs varied between loci, the projection from the muscle nerve being weaker. No other differential representation of individual trigeminal branches was evident. 4. Responses were evoked by stimulation of both ipsi- and contralateral trigeminal afferents but contralateral projections were present at fewer sites. 5. Mass responses to stimulation of individual trigeminal branches comprised mossy fibre and climbing fibre-mediated potentials, although both components were not always present. Latencies for mossy and climbing fibre responses, evoked by ipsilateral nerve stimulation, were in the ranges 5--8 msec and 11--29 msec respectively. 6. Unitary responses of Purkinje cells activiated by trigeminal inputs also revealed convergence from individual ipsilateral afferent sources (28% influenced by one ipsilateral trigeminal branch, 48% by two branches, 17% by three branches and 7% by four branches). 7. Response patterns comprised one or more of the following: short latency (3--8 msec) simple, mossy fibre-mediated spikes, 'delayed' (10--25 msec) simple spikes and climbing fibre-mediated multiple spike bursts (9--35 msec).


The effect of carbon dioxide upon myocardial contractile performance, blood flow and oxygen consumption.

1. Mongrel dogs were anaesthetized with chloralose, paralysed, ventilated and vagotomized and given a beta-blocking drug, sotalol, in sufficient doses to block the effects of 5 microgram of adrenaline. 2. Changes in inspired CO2 concentration were produced, causing increases of arterial PCO2 up to 120 mmHg. The effects on myocardial blood flow were measured with radioactive microspheres. Coronary sinus and arterial blood was sampled. 3. In the absence of beta-blockade, an increase in arterial PCO2 produced variable effects. In some dogs coronary blood flow increased, while in others there was no change. There was a mean increase in coronary blood flow at arterial PCO2 values above 85 mmHg which was abolished by beta-blockade. 4. In the presence of beta-blockade, an increase of arterial PCO2 produced depression of left ventricular performance, i.e. a fall of maximum rate of rise of left ventricular pressure and a rise of left ventricular end-diastolic pressure. 5. In the presence of beta-blockade, there were no consistent changes in myocardial blood flow, left ventricular pressure or cardiac output. 6. In the absence of beta-blockade, coronary arterial minus venous ocygen content was reduced by hypercapnia. In the presence of beta-blockade, the changes were small and not statistically significant. The direct coronary vasodilator effect was therfore negligible. 7. It is concluded that the previously reported hypercapnic vasodilatation was mainly an effect of sympatho-adrenergic stimulation by hypercapnia. 8. In the presence of beta-blockade, coronary sinus PO2 increased markedly, with little change in coronary sinus oxygen content; this was consistent with a shift to the right of the oxy-haemoglobin dissociation curve. Under circumstances of hypercapnia, a rise in coronary sinus (and presumably tissue) PO2 failed to produce vasoconstriction. 9. It is argued that the vasodilator effect of hydrogen ions and the vasoconstrictor effect of oxygen probably cancel one another when the arterial PCO2 is raised.


The relation between net calcium, alkali cation and chloride movements in red cells exposed to salicylate.

1. From a 150 mM-NH4 salicylate medium salicylate enters human red cells with a rate constant of 1.9 min-1 at 0 degrees C. 2. Salicylate increases the red cell permeability for Ca2+ (and Mg2+). There is no saturation of the Ca2+ transfer with respect to salicylate up to 150 mM and with respect to external Ca2+ up to 30 mM. 3. Ca2+ entering from salicylate media activates the Ca-sensitive K channel present in human but not in adult ruminant red cells. 4. The increase in K permeability which ensues hyperpolarizes the membrane in Na salicylate media, accelerating further Ca2+ entry and Mg2+ entry and favouring Cl- loss (see Fig. 8). The Ca2+ inward movement is in agreement with the constant field equation if the membrane potential is assumed to equal the K equilibrium potential and if two charges are attributed to the mobile species. 5. The effect of salicylate on Ca2+ permeability and hence its sequelae are reversible upon washing the cells. 6. 3-OH-benzoic acid and 4-OH-benzoic acid do not exert the effect salicylate has on Ca2+ permeability. 7. In 150 mM-Na salicylate media the Cl--salicylate exchange is virtually nil at 0 degrees C. The exchange seen at 19 degrees C is obviously not across the anion exchange mechanism and proceeds at a rate comparable to that for Cl- movement in the nonexchange-restricted mode given by Hunter (1971, 1977) for cells in a normal medium. 8. Ca2+ seems to increase the Cl- permeability seen under these conditions. 9. The possibility that salicylate acts as an ionophore for Ca2+ is discussed.


Relationship between spatial frequency selectivity and receptive field profile of simple cells.

1. Receptive fields of simple cells in area 17 of the cat were mapped with stationary stimuli. Spatial frequency selectivities of the same cells were measured with drifting sinusoidal gratings. 2. The reconstructed field profile (inverse Fourier transform of selectivity curve) shows qualitative agreement with the mapped profile, and suggests the existence of additional side-lobes in the field. The side-lobes may correspond to the 'unresponsive regions' investigated by Maffei & Fiorentini (1976). 3. Our data suggest that the simple cell may perform approximately linear spatial summation of inputs to the visual system. However, the output of the simple cell is generally non-linear as reflected in its truncated responses to gratings.


Sympathetic control of lower oesophageal sphincter motility in the cat.

1. The action of adrenaline, noradrenaline and efferent sympathetic fibres on the smooth muscle of the lower oesophageal sphincter (l.o.s.) was studied in vivo on the anaesthetized cat and in vitro with the sucrose gap method. 2. Adrenaline and noradrenaline produce a marked depolarization of the circular muscle of the l.o.s. This effect is suppressed by dihydroergotamine or phentolamine, and greatly reduced by atropine; it remains unaltered by hexamethonium. 3. Sympathetic fibres are excitatory for the l.o.s. They come from the stellate ganglion or run along the splanchnic nerve: the fibres arising from the stellate ganglion (mainly by the cardiac branch of the ganglion) join the vagus nerve at the thoracic level; the fibres running along the splanchnic nerve pass through the coeliac ganglion without synapsing; their cellular bodies lie probably in the ganglia of the sympathetic chain. 4. Repetitive stimulation (20--40 Hz) of these fibres induce, with a latency of 5--8 sec, a sustained or rhythmic contraction of the l.o.s. This response is suppressed by dihydroergotamine, and greatly reduced by atropine, while hexamethonium has no effect. 5. Stimulation of sympathetic fibres induces a facilitation of the vagal excitatory responses and an inhibition of the vagal inhibitory responses of the l.o.s. 6. Our data show that the sympathetic response of the l.o.s. results from the stimulation of adrenergic receptors which are located not only on muscular fibres but also, and chiefly, on intrinsic neurones. Thus, the sympathetic control of the l.o.s. is mainly exerted through cholinergic myenteric neurones which could be excited either directly or indirectly by inhibition of inhibitory intrinsic neurones.


Graded changes in central chemoceptor input by local temperature changes on the ventral surface of medulla.

1. In cats under pentobarbitone anaesthesia the effects of focal temperature changes of the ;chemoceptive' areas on the ventral surface of medulla, described by Loeschcke and his associates, were studied with respect to tidal volume, V(T), tidal variation in efferent phrenic activity, Phr(T), and respiratory rate. The cats were either paralysed and ventilated at various constant P(A,CO2) and P(a,O2) levels, or breathing spontaneously.2. It was confirmed that focal bilateral cooling of the intermediate, ;I((S))', areas caused rapid depression of respiration even at constant artificial ventilation. In normocapnic and normoxic conditions apnoea usually ensued at brain surface temperatures of 20-22 degrees C.3. The effects were graded along continuous temperature-response curves with enhancements of ventilation above and depression below normal body temperature.4. The strongest effects on V(T) and Phr(T) were obtained from the I((S)) areas with no or only small effects on inspiratory or expiratory timing in the vagotomized animal. The Hering-Breuer inflation reflex and its effects on timing and amplitudes were not affected by cooling this area.5. Focal cooling of the caudal or the rostral ;chemoceptive' areas, ;C((L))' and ;R((M))' areas, caused smaller effects on V(T) and Phr(T) but produced significant effects on respiratory rate even after vagotomy.6. The effects of focal cooling of these areas could be mimicked by topical application of procaine solution which has been shown not to penetrate deeper than 100 mum from the surface.7. Moderate focal cooling of area I((S)) to temperatures above 28-30 degrees C caused a parallel shift in the CO(2)-response (V(T), Phr(T)) curves to the right with little change in slope. The P(CO2) thresholds for apnoea were correspondingly raised. These focal temperature effects could be compensated by changes in P(CO2) with, on the average, 2.7 torr/ degrees C. Focal temperatures below 28 degrees C usually caused some decrease in slope of the CO(2)-response curves in addition to further shifts.8. Added hypoxic stimulus or electrical stimulation of the carotid sinus nerves caused an almost parallel increase of Phr(T) at all P(CO2) levels and all focal temperatures suggesting an additive type of interaction between the input from the peripheral chemoreceptors and that from the central (CO(2), H(+)) sensing structures whether the latter was altered by changing P(CO2) or by focal temperature changes on the I((S)) areas.9. In contrast to these effects of hypoxia and stimulation of the carotid sinus nerves the reflex increase of inspiratory activity caused by lung deflation or by electrical stimulation of the glossopharyngeal nerve distal to the carotid sinus nerves was CO(2) dependent. These reflex effects decreased with focal cooling of the I((S)) areas as with hypocapnia, suggesting a mainly multiplicative or ;gain-changing' type of interaction with the central chemoceptive drive.10. The close similarities in effect of focal cooling and of hypocapnia on the different respiratory parameters even during constant artificial ventilation indicate that focal temperature changes of the I((S)) areas intervene effectively with the normal ventilatory response to CO(2) without changing the chemical or physical environment of those neural structures in the brain stem which set respiratory pattern.


End-plate currents and acetylcholine noise at normal and myasthenic human end-plates.

1. The amplitudes and time courses of miniature end-plate currents (m.e.p.c.s) have been compared at normal and myasthenic (MG) human end-plates studied under voltage clamp. The m.e.p.c. amplitude at MG end-plates is reduced to about one third normal; mean m.e.p.c. (normal) = 2.6 +/- 0.2 nA, mean m.e.p.c. (MG) = 1.0 +/- 0.1 nA. The decay time constant of m.e.p.c.s (tau m.e.p.c.) is very similar at normal and MG end-plates; tau m.e.p.c. (normal) = 1.70 +/- 0.1 msec, tau m.e.p.c. (MG) = 1.80 +/- 0.13 msec (Vm = - 80 mV. T = 23 degrees C). 2. The equilibrium potential of the end-plate current (e.p.c.) at normal and myasthenic human end-plates is close to 0 mV. 3. Decay time constants tau e.p.c. and tau m.e.p.c. increase exponentially with membrane hyperpolarization. The voltage sensitivity of the time constants was similar at normal and MG end-plates. 4. Both normal and myasthenic e.p.c.s are greatly prolonged in the presence of neostigmine (10(-6) g/ml.). At the same time the voltage sensitivity of tau e.p.c. is slightly reduced. 5. In response to steady ionophoretically applied ACh the mean membrane currents obtained at MG end-plates were smaller than the normal under similar conditions. 6. Analysis of end-plate current noise obtained during the steady application of acetylcholine (ACh) to voltage clamped normal and MG human end-plates showed that the amplitude of the elementary current event (gamma) and the average channel life-fime (tau noise) was similar at the two sites: tau noise (normal) - 1.54 +/- 0.04 msec, tau noise (MG) = 1.60 +/- 0.11 msec; gamma(normal) - 22.3 +/- 1.57 PS, gamma (MG) = 20.25 +/- 1.93 pS (Vm = - 80 mV, T = 23 degrees C). The voltage sensitivity of the channel life time, measured from end-plate current noise, was similar at normal and MG end-plates. 7. At normal human end-plates a packet of transmitter opens about 1500 channels whereas at MG end-plates a packet opens only about 600 channels. It is calculated that the size of the transmitter packets released from MG-terminals is at least as large as the packet of the ACh released from normal human nerve terminals.


Photoresponses of a sensitive extraretinal photoreceptor in Aplysia.

1. The light-evoked membrane current, photo-current, of an extraretinal photo-receptor, the ventral photoresponsive neurone (v.p.n.), in the abdominal ganglion of Aplysia californica, was studied using the voltage clamp method. Flashes and steps of monochromatic light were used as stimuli. 2. Flashes of light 100 msec in duration elicit slowly developing outward currents which peak at 5--10 sec and then return to dark levels within 30--60 sec. 3. The peak of the action spectrum of v.p.n. is at 470 nm and is similar to the peak for R2, another photoresponsive extraretinal Aplysia neurone, and to the peak of absorption spectra of molluscan rhodopsins. V.p.n. also contains membrane-bound cytoplasmic pigmented granules similar to those found in R2, and these are thought to mediate the light response. 4. Photo-current is associated with an increase in membrane conductance. In normal sea water photo-current has a reversal potential at the K equilibrium potential, EK and the reversal potential has a Nernstian relationship with external K concentration. The current--voltage relationships for peak and steady-state photo-current are fitted by the same constant field equation; currents measured when voltage was changed in steps at peak photo-current also have a similar relationship with voltage. The results are similar when saturating or non-saturating light intensities were used. Thus it appears that the light-activated K+ conductance is neither time nor voltage dependent. 5. Minimally detectable responses occurred at flash photon densities of 10(12) photons cm-2 which is 10(-3) that for R2. This value is comparable to those reported for retinal photoreceptors of Pecten irradians, a scallop, and Salpa democratica, a pelagic tunicate, and is lower than values reported for extraretinal photoreceptors such as the pineal photoreceptors of Salmo gairdnerii irideus, the rainbow trout, and the caudal photoreceptor in the sixth abdominal ganglion of Procambarus clarkii, a crayfish. 6. V.p.n. has a linear amplitude response range for low intensities of light and a non-linear range that saturates at high intensities. In the accompanying paper the response wave form and its temperature dependence are interpreted according to a diffusion-based model.


The role of diffusion in the photoresponse of an extraretinal photoreceptor of Aplysia.

1. Membrane currents produced by flashes and steps of light (photo-current) were recorded from the ventral photoresponsive neurone of Aplysia californica. The effects of background illumination and changes in temperature were also examined. 2. The falling phase of the response wave form may be separated into two components with time constants of 10--12 sec and 50 sec. 3. Background illumination reduced the response amplitude to light impulses without appreciably altering the response wave form. 4. Lowering the temperature greatly reduced the amplitude of the photo-current with a Q10 of 2.91 (25--15 degrees C) and greatly prolonged the duration of the response. 5. Because of the relatively large distance between the plasma membrane and the pigmented cytoplasmic lipochondria where light is absorbed, a diffusion-based model with Ca as the internal-transmitter (Andresen & Brown, 1979) was developed. 6. In this model diffusion of Ca2+ released from the lipochondria upon photon absorption is slowed by the reversible uptake of Ca2+ at cytoplasmic binding sites. Ca2+ interacts with sites at the plasma membrane to increase GK and Ca2+ levels are subsequently restored by irreversible uptake processes. Ca2+ release and its adsorption and desorption from the more numerous plasma membrane binding sites were assumed to be instantaneous with respect to the duration of the light-evoked response. 7. The linearized model equations adequately predict the experimental response wave forms, the effects of temperature, and saturation of the steady-state amplitude--stimulus relationship. Aside from amplitude scaling, no curve-fitting was used. 8. The model also gives realistic values for the cytoplasmic diffusion coefficient of Ca and the net rate of Ca efflux required to restore dark Ca activity.


Phosphate efflux and oxygen consumption in small non-myelinated nerve fibres at rest and during activity.

1. The oxygen consumption and the movements of labelled phosphate were measured in garfish olfactory nerve at rest and during activity.2. In solutions with 2.5 mM-K and 0.2 mM-phosphate the resting oxygen consumption was 0.206 m-mole/kg.min; activity at 2 sec(-1) produced an extra oxygen consumption of 2.46 mumole/kg.impulse. The extra oxygen consumption declined exponentially with a time constant of 2.62 min at 22-26 degrees C.3. The phosphate efflux, measured simultaneously, had a resting efflux rate constant of 1.24 x 10(-3) min(-1); activity at 2 sec(-1) produced an extra fractional loss of 9.38 x 10(-6) impulse(-1). The increase in phosphate efflux followed almost the same time course as the increase in oxygen consumption.4. Increasing the frequency of stimulation from 2 sec(-1) to 3 or 5 sec(-1) decreased both the extra oxygen consumption and the extra fractional loss of phosphate. When the frequency was decreased to 0.5 or 1 sec(-1) the extra oxygen consumption per impulse increased, while the extra phosphate liberation was lowered.5. Changing the phosphate concentration did not much affect the extra oxygen consumption; on the other hand, lowering or increasing the phosphate from the standard 0.2 mM decreased both the resting and the stimulated phosphate efflux.6. Lowering the K from the standard 2.5 mM did not affect the extra oxygen consumption, but increased both the resting and the extra loss of phosphate. At higher K concentrations the extra oxygen consumption and the extra fractional loss of phosphate decreased without much change in the resting phosphate efflux.7. Application of 1-20 muM-strophanthidin produced a transient decrease in the resting phosphate efflux without much change in resting oxygen consumption. With 10 or 20 muM-strophanthidin the extra fractional loss of phosphate and the extra oxygen consumption were both lowered in approximately the same proportions.8. The findings are consistent with the hypothesis that the increase in intracellular inorganic phosphate that results from increased break-down of ATP after activity, is the main cause for the increased phosphate efflux. A fraction of the increase in intracellular phosphate only appears to be liberated to the outside, the value of the fraction depending on the resting phosphate efflux before activity.9. The initial increase in intracellular inorganic phosphate after an impulse, estimated from the oxygen consumption or the phosphate fluxes, appears to be about 12-19 mumole/kg nerve, remarkably close to the value known from chemical analysis.


Motor unit organization of human medial gastrocnemius.

1. The properties of fifty-seven motor units in human medial gastrocnemius have been studied using controlled intramuscular microstimulation, glycogen depletion and muscle biopsy. 2. Motor units could be divided into three classes on the basis of their mechanical properties. Type S units were slow, small and fatigue resistant. Type FR units were fast, intermediate in size, and fatigue resistant. Type FF units were fast, large and fatigable. 3. Glycogen depletion of a number of type S and FF units revealed them to be composed of type 1 and type 2b muscle fibres respectively. 4. The results suggest that during slowly increasing voluntary contractions where units are recruited in order of size, type 1 and 2a muscle fibres would be employed at low force levels followed by type 2b muscle fibres in stronger contractions.


Some properties of the excitatory junction potentials recorded from saphenous arteries of rabbits.

1. Excitatory junction potentials (e.j.p.s) were recorded from smooth muscle cells of the saphenous arteries of young rabbits. 2. The amplitudes of e.j.p.s recorded from different preparations, in response to a single maximal stimulus, were small and variable (5--14 mV). They decayed exponentially with a time constant of about 200 msec. 3. At frequencies greater than 1 Hz the shape of those e.j.p.s which exceeded 12--15 mV in amplitude was changed. The early part of the e.j.p.s became faster in time course. 4. Trains of up to five stimuli, at frequencies greater than 4 Hz, caused summation of e.j.p.s; 'active responses' were superimposed on this depolarization. Peak amplitude of the response to repetitive stimulation was 50 mV. 5. In normal solution, contraction appeared to be associated with a change in the configuration of e.j.p.s. 6. No action potentials resembling those recorded from most visceral smooth muscles were observed in normal solutions although these could be evoked in the presence of TEA (2.5--10 mM). 7. The method of Abe & Tomita (1968) was used to determine the values of the length constant (lambda) and time constant (tau) of the smooth muscle of intact arteries. The value of lambda (0.6 mm) was about half that found for circular strips cut from larger arteries. 8. The time constant of decay of single e.j.p.s of less than 12 mV in amplitude was indistinguishable from the membrane time constant. 9. Noradrenaline caused contraction of the artery in the absence of a change in membrane potential. 10. It is tentatively suggested that there may be two different populations of receptors in this smooth muscle membrane.


Movements of monosaccharides between blood and tissues of vascularly perfused small intestine.

1. A method involving the analysis of pulse transients of the vascular concentrations of test sugar and extracellular marker has been used to study the movements of non-metabolized sugars between the cells and vascular fluid of the vascularly perfused small intestine of R. ridibunda. Reasons are given for supposing that the method does properly measure the net entry of sugars into a cellular compartment that includes at least the epithelium. 2. It is found that while the glucose analogues, 3-O-methyl-D-glucose (3MG) and 2-deoxy-D-glucose (2)DG) are able to enter a cellular compartment when they are added to the vascular bed, alpha-methyl-D-glucoside (alpha MG) is able to enter the compartment only at a very slow rate from the vascular bed. In contrast, 3MG and alaph MG are well absorbed from the lumen whereas the inward permeability of 2DG across the lumen face of the epithelium is very low and, unlike 3MG and alpha MG, is not influenced by the presence in the lumen of other transported sugars. 3. The presence of phlorizin in the intestinal lumen increases the flux of alpha MG and of 3MG in the direction vascular bed--bulk phase of lumen. Reasons are given for supposing that the movement of sugars from the vascular bed into the lumen may involve a cellular route but occurs, at least in part, through a paracellular, extracellular route. 4. The exit of monosaccharides that have been loaded previously into the epithelium either from the lumen or from the vascular bed has been investigated. 3MG washes out rapidly into the vascular bed and the exit is stimulated by the addition of D-glucose to the intestinal lumen and by the addition of 2DG, but not alpha MG, to the arterial infusate. In contrast, alpha MG, loaded into the epithelium from the lumen, washes out of the cells only slowly into the vascular bed, so that even with high rates of vascular perfusion alpha MG accumulates within the tissue. The sustained accumulation of alpha MG implies that not only is the permeability for exit into the blood restricted for this sugar, but also the permeability is low across the brush border in an outward direction, cell to lumen ('lobster pot effect'). The wash-out of 3MG into the vascular effluent is sufficently rapid that only in the absence of vascular perfusion is 3MG accumulated within the tissue. 5. The contrasting properties of the monosaccharide transport systems accessible from the intestinal lumen and the vascular bed respectively are discussed in relation to the problems of epithelial transport of monosaccharide.


The effects of histamine, acetylcholine and 5-hydroxytryptamine on lung mechanics and irritant receptors in the dog.

1. The ability of histamine, acetylcholine, acetylcholine (ACh) and 5-hydroxytryptamine (5-HT) given I.V. and by aerosol to induce reflex bronchoconstriction and to activate lung irritant receptors has been studied in dogs anaesthetized with chloralose. 2. Histamine (four breaths of an aerosol from 0.0625%, 0.125% and 0.25% solutions and 5, 10 and 20 microgram kg-1 I.V.), 5-HT (four breaths of an aerosol from 0.5% or 1.0% solutions and 10, 20 and 40 microgram kg-1 I.V.) produced significant relex changes in RL (total lung resistance). The changes in RL produced by ACh (four breaths of an aerosol from 0.25%, 0.5% and 1.0% solutions, of 5, 10, 20 and 40 microgram kg-1 I.V.) were unaffected by vagal cooling. 3. The falls in Cdyn (dynamic compliance) produced by ACh given by aerosol or I.V. were unaffected by vagal cooling. The falls in Cdyn produced by histamine (10 microgram kg-1 and 40 microgram kg-1 I.V.) and 5-HT (four breaths of an aerosol generated from a 0.5% solution and 20 microgram kg-1 and 40 microgram kg-1 I.V.) were significantly reduced by vagal cooling. 4. Histamine, 5-HT and ACh given by aerosol and I.V. increased lung irritant receptor discharge. Irrespective of the route of administration, for a given change in RL histamine produced a greater increase in irritant receptor discharge than did ACh or 5-HT, which produced similar increases. 5. For a given change in RL, histamine, ACh and 5-HT were more effective in activating lung irritant receptors when given I.V. than by aerosol. 6. The mechanisms of irritant receptor activation by histamine, ACh and 5-HT and the relationship between irritant receptor discharge and reflex bronchoconstriction are discussed.


Functional relationships between the hippocampus and the cerebellum: an electrophysiological study of the cat.

1. Functional interrelationships between the hippocampus and the cerebellum have been investigated in the anaesthetized cat. Plots of the stimulating and recording sites as well as the latency range of the responses indicated the extent of ascending and descending lines of operation between these two structures. 2. Stimulation of the fastigial nucleus evoked the discharge of single hippocampal units on both sides of the brain. Early responses had a mean latency of 12 msec and late responses had a mean latency of 21 msec. Increasing the intensity of the stimulus had little effect on the patterns of discharge. 3. There was no topographical organization within the hippocampus. On the other hand, the activity evoked by a cutaneous stimulus was shown to be greatly depressed by a preceding cerebellar stimulus, particularly at intervals 30--40 msec between the two stimuli. 4. Cerebellar responses evoked by stimulating the hippocampus were found mainly in lobule VI of the posterior lobe. Early and late responses were frequently recorded in the same trace, ipsilateral stimulation yielding the shortest latencies. Increasing the intensity of the stimulus increased the likelihood of there being a response and increased the number of spikes in each discharge. Hippocampal stimulation also had a profound influence on resting cerebellar discharges. 5. Symmetrical points in the two hippocampi were chosen for conditioning and testing sequences. The conditioning stimulus had a long-lasting inhibitory effect on the test response followed by a slow recovery. 6. The location and extent of hippocampal influences on the cerebellum were determined by plotting the presence or absence of a response at each stimulated site. The results indicated the existence of bilateral descending projections containing fast and slow components in conformity with the known conduction properties of mossy fibre and climbing fibre inputs. 7. The physiological significance of interrelationship between the hippocampus and the cerebellum is discussed. It seems that there are many similarities as well as fundamental differences in the cerebellar control of movement under normal circumstances and in conditions of stress.


Cation transport across the guinea-pig placenta perfused in situ.

1. The guinea-pig placenta perfused in situ via the umbilical circulation has been used to measure unidirectional fluxes of Na from mother to fetus, and in the reverse direction, with 24Na and 22Na. There was no significant difference between the two fluxes, each being 22 mumole.min-1. 2. Ouabain 10(-5) M in the perfusion fluid had no detectable effect on radioisotopic movements of Na in either direction. 3. Unidirectional fluxes of 42K in both directions were approximately equal at 1.7 mumole.min-1 mother fetus and 1.8 mumole.min-1 in the reverse direction, despite a K concentration of 3.4 mM on the maternal side and 5.0 mM on the fetal side of the placenta. 4. Extraction of 42K and 86Rb from the perfusion fluid was inhibited by 43% by 10(-5) M-ouabain in the fluid. This effect was largely due to a reduction of isotope uptake by the placental tissue. 5. The relative permeabilities of the placenta, mother to fetus, were Rb approximately K (3.2) greater than Na (1.0) greater than Li (0.55). 6. Under the experimental conditions, the electrical potential difference between perfusion fluid and maternal blood was 6 mV (fetus negative). It was shifted towards the positive by a low Na fluid. 7. The results suggest the presence of a dominant Na-K pump (active component towards mother) sited at the maternal-facing membrane of the syncytiotrophoblast together with a subsidiary pump oriented in the opposite direction and probably sited together with a subsidiary pump oriented in the opposite direction and probably sited at the fetal-facing membrane of the syncytiotrophoblast. 8. A high proportion of Na movement particularly towards the fetus is probably passive, occurring through water-filled spaces, whilst K movement is more dependent on active transport.


Left ventricular inotropic responses to stimulation of carotid body chemoreceptors in anaesthetized dogs.

1. Dogs were anaesthetized with chloralose and artificially ventilated. The regions of both carotid bifurcations were vascularly isolated and perfused at constant pressure with arterial blood or with venous or hypoxic blood. 2. Inotropic responses were assessed by measuring the maximum rate of change of left ventricular pressure (dP/dtmax) with aortic pressure and heart rate held constant. 3. Stimulation of the chemoreceptors with venous blood from the inferior vena cava resulted in a decrease in dP/dtmax from 510 +/- 27 kPa.s-1 to 418 +/- 21 kPa.s-1 (mean +/- S.E.): a change of 17.9 +/- 1.0% 4. In experiments in which the oxygen tension of the blood perfusing the carotid chemoreceptors was decreased in steps between 10 and 3 kPa, by use of an oxygenator, graded responses of dP/dtmax were obtained at each step. 5. The inotropic responses to chemoreceptor stimulation were abolished by raising carotid pressure. 6. The inotropic responses were abolished either by crushing both carotid bodies or both ansae subclaviae, indicating that the reflex originates from the carotid bodies and that the efferent pathway is in the cardiac sympathetic nerves.


Differential alteration by hypercapnia and hypoxia of the apneustic respiratory pattern in decerebrate cats.

1. A combination of bilateral lesions within the nucleus parabrachialis medialis complex (n.p.b.m.) and bilateral vagotomy typically resulted in an apneustic respiratory pattern in decerebrate and paralysed cats. Integrated efferent phrenic nerve activity was recorded as an index of the respiratory rhythm.2. Changes in components of this apneustic breathing cycle were evaluated in response to steady-state hypercapnia and hypoxia. The components evaluated were (a) the period of phrenic discharge (inspiratory time, T(I)), (b) the period of no detectable phrenic activity (expiratory time, T(E)), (c) the total duration of the apneustic respiratory cycle (T(TOT), the sum of T(I) and T(E)), and (d) the average height of the integrated phrenic nerve activity (apneustic depth).3. Elevations of P(A, CO2) from values below 45 torr to 50-60 torr, under both hyperoxic and normoxic conditions, resulted in significant elevations of T(I), T(E), T(TOT) and depth. Further P(A, CO2) elevations to approximately 70 torr caused no change, or frequently, a decrease in T(I), T(E) and T(TOT); the apneustic depth increased in most animals.4. Diminutions in P(A, O2) from normoxic to hypoxic levels at isocapnia typically caused an increase in apneustic depth and, concomitantly, significant decreases in T(I), T(E) and T(TOT).5. Pharmacological stimulation of the carotid chemoreceptors by intracarotid administration of 1.0-20 mug NaCN produced a premature onset of phrenic nerve activity if delivered during the expiratory period. Such NaCN administrations, delivered during the inspiratory phase, resulted in an augmentation of the integrated phrenic discharge and a premature termination of phrenic activity. Carotid sinus nerve section eliminated the response to NaCN administration.6. In experimental animals having bilateral carotid sinus nerve section, normoxic hypercapnia caused similar changes in the apneustic breathing pattern to those recorded in cats having intact carotid chemoreceptors. However, isocapnic hypoxia induced time-dependent changes in the pattern of phrenic discharge including diminutions in depth, an onset of gasping-type activity, or expiratory apnea.7. In a few animals, bilateral n.p.b.m. lesions and bilateral vagotomy resulted in expiratory apnea which was continuous as long as ventilation with air was maintained. This expiratory apnea was replaced by an apneustic breathing pattern following diminutions of P(A, O2) below 90 torr. This establishment of an apneustic breathing pattern by hypoxia was observed both in animals having intact, as well as sectioned, carotid sinus nerves. This expiratory apnea could also be terminated by a single apneustic inspiration following general somatic stimulation or, in cats having intact carotid chemoreceptors, following intracarotid NaCN administration.8. It is concluded that hypercapnia and hypoxia produce differential alterations of the apneustic breathing pattern in decerebrate cats. Further, the hypoxia-induced changes are considered to represent the net result of carotid chemoreceptor stimulation and brain stem depression. The results of this study are considered in the context of proposed mechanisms for phase-switching of the respiratory cycle.


The heat sensitization of polymodal nociceptors in the rabbit and its independence of the local blood flow.

1. The firing frequency of polymodal nociceptor units with C-fibre axons was found to increase exponentially with skin temperature as the latter was raised linearly at 1 degree C/sec. Q10 values ranged from 3.6 to 120. 2. Following skin heating to 54--64 degrees C, average firing thresholds fell substantially. This sensitization was accompanied by a 46% increase in interval by interval variability of firing during heat stimulation. 3. Stopping the blood flow to the saphenous area by ligaturing the femoral or saphenous arteries had no significant effect on heat thresholds, on firing patterns during heat stimulation or on variability of firing in sensitized units. There were no changes in continuous, background firing during periods of arterial ligation. 4. It is concluded that if the maintenance of nociceptor heat sensitization depends on the continuous local production of chemical substances, these substances must either be rapidly broken down locally or able to move only slowly into blood vessels.


The nature of the receptor mediating stimulant effects of histamine on rapidly adapting vagal afferents in the lungs.

1. The effects of histamine H1- and H2-agonists on these airway sensory receptors were also examined. 2. Neither I.V. infusion of metiamide (5 mg/kg, min for 35 min) in seven experiments, nor I.V. bolus injection of burimamide (15 mg/kg) in six other experiments, both substances being H2-antagonists, altered the response of rapidly adapting receptors to aerosols of histamine (from 0.1 or 1.0% solutions). 3. Chlorpheniramine (H1-antagonist), 2--5 mg/kg, I.V., completely abolished responses of rapidly adapting receptors to histamine in seven experiments in which metiamide had been given previously and in seven other preparations in which it had not, but had no effect on responses to prostaglandin F2 alpha. Chlorpheniramine itself caused a brief stimulation of rapidly adapting receptors. 4. The H2-agonist S-[3-(N,N-dimethylamino) propyl] isothiourea (Dimaprit), given as aerosol (1% solution for 2 min) or I.V. (2 mg/kg), was without effect on activity of four airway rapidly adapting receptors. These receptors were stimulated, however, by the H1-agonist 2,(2 pyridylethylamine) dihydrochloride (PEA), administered both as aerosol (from a 10% solution) and I.V. (0.4--2 mg/kg). These stimulant effects were abolished by chlorpheniramine. 5. The results indicate that stimulation of airway rapidly adapting receptors by histamine is mediated by histamine H1-receptors.


Effects of central administation of probenecid on fevers produced by leukocytic pyrogen and PGE2 in the rabbit.

1. Single intracerebroventricular (I.C.V.) injections of probenecid (PBCD, 0.125--0.5 mg) enhanced and prolonged fever caused by I.V. administration of leukocytic pyrogen (LP) in rabbits resting in neutral (23 degrees C), cold (10 degrees C) and hot (30 degrees C) environments. Similar effects were produced by single I.C.V. injections of PBCD given before PGE2 (0.5 microgram) was injected I.C.V. in the three ambient temperatures. 2. Fever produced by IV. LP was also prolonged by infusion and by multiple injections of PBCD. 3. PBCD given I.P. (100 mg/kg) enhanced and prolonged fever caused by I.V. injection of Salmonella typhosa endotoxin. 4. Hyperthermia produced by I.C.V. PGE2 was not augmented by subsequent PBCD infusion. However, pre-treatment with PBCD followed by PGE2 injection and PBCD infusion caused hyperthermia that was very high and prolonged, and, in some cases, lethal. 5. Acetaminophen (2 mg, I.C.V.) and indomethacin (10 mg/kg, I.V.) lowered body temperature when given during fever induced by LP and prolonged by PBCD infusion. 6. The concentration of PGE in cerebrospinal fluid (c.s.f.) samples taken from the third or lateral ventricles rose or stabilized during PBCD infusions made during LP fever. However, similar changes in PGE concentration also occurred during control infusions when body temperature was low. 7. We conclude that termination of the actions of both central endogenous pyrogen and centrally administered PGE2, and the subsequent reduction of fevers produced by them, require a PBCD-sensitive facilitated transport system. The reduction of PBCD-prolonged PL fevers by antipyretics which block PGE synthesis suggests that prolongation by PBCD of LP fever is not due to blockade of PGE transport in a subsequent step in fever mediation per se, but is due to inhibition of transport of LP itself, or of other mediators associated with it.


The origin of the hind limb vasodilatation evoked by stimulation of the motor cortex in the cat.

In cats under Althesin anaesthesia, the hind limb area of the motor cortex has been stimulated by means of monopolar, semi-micro-electrodes with careful experimental control so as to avoid reflex effects evoked through stimulation of meningeal afferent fibres or stimulus spread to non-cortical structures. 2. Localized cortical stimulation which elicited muscle contractions in the contralateral hind limb also elicited vasodilation in the same limb: the stimulus threshold was the same for both effects, and the magnitude of the dilatation was related to the strength of contraction. 3. Reduction of the somatic motor response, caused by lesions in the medullary pyramidal tract, was accompanied by a parallel reduction of the vascular response. 4. Prevention of the motor response by gallamine or by spinal cord section at L4--L5 (which leaves the sympathetic outflow to the hind limbs intact) led to abolition of the vascular response. During recovery from gallamine, contraction and vasodilatation returned in parallel. 5. The muscle vasodilatation was insensitive to atropine or guanethidine. 6. It is concluded that the hind limb vasodilatation observed on stimulation of the motor cortex is simply a post-contraction hyperaemia, and that it is independent of the sympathic nervous system. Previous conclusions of a sympathetically mediated vasodilatation probably resulted from inadequate control of the stimulus or a failure to recognize weak muscle contractions.


The effects of a disulphonic stilbene on chloride and bicarbonate transport in the turtle bladder.

1. In turtle bladders bathed by Na-free media containing Cl and HCO3, the mucosa is electropositive to the serosa. Serosally applied 4-acetamido-4'-isothiocyano-2,2'-disulphonic stilbene (SITS) reduces the p.d. and Isc by 100%, and reduces the rate of net Cl reabsorption in some bladders but not in others. 2. In the absence of exogenous HCO2 (Cl present), SITS reduces the p.d. and Isc by 100%, and reduces the rate of mucosal acidification by 80%; net Cl reabsorption is not detectable under these HCO3-free bathing conditions. 3. In the absence of exogenous Cl (HCO3, present), the mucosa is also electropositive to the serosa and serosally applied SITS reverses the orientation of the p.d. and Isc so that the mucosa becomes electronegative to the serosa. 4. This constitutes sufficient evidence for the active, electrogenic secretion of an anion, probably HCO3. These data are explained by an analogue of discrete, electrogenic pumps and paths for the reabsorption of Na, Cl, and HCO3, and the secretion of HCO3.


Extraversion, neuroticism, and date of birth: a Southern hemisphere study.

The aim of this study was to determine whether variations in Eysenck Personality Inventory (EPI) scoring among zodiacal birth groups follow a similar pattern for Ss born in the Southern hemisphere to that which has been reported for Northern hemisphere Ss. EPI and birth data were obtained from 450 adult Ss, of whom 338 were New Zealand born. Results for Extraversion significantly matched British findings (p less than .01). Results for Neuroticism were ambiguous. It is concluded that seasonal and climatic influences are unlikely to explain the Extraversion differences between birth groups.


Anxiety level as an indicator of academic performance during first semester of graduate work.

This article presents the results of an empirically based research study that examines the use of the trait and state anxiety level of first semester graduate students as a potential indicator of academic performance (N = 63 males and females. The findings reveal that the higher the student's Graduate Record Examination (GRE) score, the greater his chances of achieving a higher grade point average (GPA) at the end of his first semester of graduate work. Moreover, the lower his A-Trait anxiety score at the time of admission, the greater his likelihood of earning a higher first semester GPA.


Reported physiological and psychological symptoms of tobacco smoke pollution in nonsmoking and smoking college students.

A 147-item questionnaire concerning the relevance of the nonsmokers' right movement to college and university campuses was administered to 307 University of New Hampshire undergraduates. The fourth section of the questionnaire consisted of 28 questions on symptoms caused by smoke pollution. Responses to these questions were given on a five-category frequency of occurrence scale. Frequencies, descriptive statistics, and t tests contrasting current smokers from nonsmokers were presented. Generally sizable percentages of nonsmokers reported adverse physiological and psychological symptoms from tobacco smoke pollution. Smokers reported a similar pattern of responding but at lower frequencies of occurrence.


The effects of day care on young children: an environmental psychology approach.

The present paper presents a framework for characterizing the emotional impact of day care  environments and for predicting the consequent effects on child emotional reactions to day care and to separation, extent of active involvement in day care, and long-term effects of day care on cognitive and intellectual development. The physical and social environment of day care is characterized in terms of its emotional impact with use of three orthogonal dimensions: pleasure-displeasure, arousal-nonarousal, and dominance-submissiveness. Approach toward, or preference for, any setting is then predicted in terms of its emotional impact. Finally, day care settings are ordered in terms of their beneficial-detrimental effects by simply considering children's preference levels (approach) for the settings.


Construct validation of children's behavior problem dimensions: relationship to activity level, impulsivity, and soft neurological signs.

A construct validation study of dimensions of children's behavior problems was carried out with use of multiple linear regression. The Ss were 76 latency-aged boys in residential treatment. The dimensions involved were Conduct Disorder and Inadequacy-Immaturity. The predictor variables were activity level, impulsivity, and soft signs of neurological damage. Results indicated that Conduct Disorder was significantly predicted by activity level, in combination with impulsivity. Inadequacy-Immaturity was significantly predicted by activity level and soft signs. A third dimension, Personality Disorder, was found to be uncorrelated with the three predictor variables.


Termination locus of palmar main line A of the left hand in relation to mental pathology.

A ridge originating at digital triradius point a (palmar main line A) was measured from photographs in three groups of Ss, each composed of 36 males: 1) chronic, hospitalized schizophrenics; 2) chronic, hospitalized patients classified as nonpsychotic; 3) business and professional men who were members of a service club. Seven naive judges measured the point of exit of main line A at the ulnar edge of the left palm in each of the 108 SS. Results were as follows: (a) Range of scores in units used was 5.00 to 7.75; total variance, .26 (N = 756). (b) Means of the two control groups were identical, but schizophrenic and control group difference failed to meet the .05 level of significance. (c) Very significant differences were found among judges' means. (d) Median interjudge r = about + .69.


Relationship between attitudes toward feminism and levels of dogmatism, achievement, and anxiety.

More than 1,500 American women from a wide range of age, socioeconomic, and educational backgrounds were administered measures of dogmatism, anxiety, achievement, and feminism. One hundred nine Ss who scored above the 75 percentile on the Attitudes Toward Women Scale (high supporters of the feminist movement) were matched with 109 Ss who scored below the 25 percentile on the Scale (low supporters of feminism). Statistical analyses showed that women who strongly supported women's equality were (a) less close-minded; (b) more goal oriented toward nontraditional roles (vocational, educational, etc.); and (c) no different from the low supporter group in anxiety level or ego strength on four out of five dimensions. These results support the notion that feminist supporters as a group are as well adjusted as their nonfeminist counterparts on these specific traits.


[Diagnostic value of scanning in post-splenectomy left subphrenic abscess. A report on 5 cases (author's transl)].

Diagnosis of a left subphrenic abscess after splenectomy is often difficult. C.T. scanning was used to establish the diagnosis in 5 patients with subphrenic abscesses. The examination is simple and gives valid results. Needle aspirations, controlled by scanning, can confirm the diagnosis or be used for drainage of the abscess.


[Juvenile polyposis. A report on two cases (author's transl)].

The discovery of multiple polypi in a small child does not necessarily indicate that this is a case of familial adenomatosis. Two cases of juvenile polyposis were confirmed by histological examinations, and their clinical and, more particularly, their radiological characteristics were studied. The only way to explore the full extent of the lesions in a satisfactory manner is by double-contrast examination of the whole colon. The authors stress the value of radiological examinations, though the frequency with which they should be carried out is open to discussion. Review of the published literature reveals that the association of true familial polyposis or adenocarcinomatosis exists in the same family or even in the same patient. Diagnostic difficulties are usually due to the fortuitons co-existence of a lymphoid hyperplasia, the significance of which is still not known.


[Pancreatic pseudocysts simulating a mass in the left kidney. A report on 4 cases (author's transl)].

Pancreatic pseudocysts were observed to simulate a mass in the upper pole of the left kidney in 4 patients. Urographic investigation of these pseudocysts revealed deformities similar in all respects to those produced by a cyst, though in two cases the mass was surrounded by a thick wall. A better definition of the parenchymatous deformity was obtained by the use of true trunk profile nephrotomograms. The value of ultrasonography, using the grey scale, and of transparietal puncture with measurement of amylase levels, is stressed. The authors discuss the problem of establishing the precise location--anterior to, surrounding, or within the kidney--of these pseudocysts.


[Intestinal obstruction with feces (meconium ileus equivalent) in the course of mucoviscidosis. Radiographic diagnosis (author's transl].

Meconium ileus equivalent is a late intestinal occlusion occurring in patients suffering from mucoviscidosis. Three cases are reported in children aged, respectively, 3 years, 6 years and 10 years. In one of the observations (three year old girl), the intestinal obstruction with feces was first manifestation of a mucoviscidosis that was previously undetected. The radiological signs are identical to those found in cases of neonatal meconium ileus: intestinal obstruction and accumulation of closely spaced matter in a distended ileum (terminal part). As in cases of meconium ileus without complications, treatment consisted of enemas with water-soluble products. The high osmotic pressure of these products made it possible to remove the obstruction.


[Thoracic and retroperitoneal cystic lymphangiomyomatosis. Value of lymphography].

Standard radiological examinations in a woman of 40 years of age with a pneumothorax and chylothorax revealed the presence of a posterior mediastinal mass compressing the oesophagus, and an interstitial syndrome. Retroperitoneal and mediastinal cystic lymphangiomas were found on lymphography. These findings are in accordance with the lymphangiomyomatosis described by Cornog and Enterline in 1966. The similarity between this disease and tuberculous sclerosis is underlined in present-day publications.


[Tomographic incidence of the petrous bone by the controlateral suboccipital approach, in the plane of the ear-drum and in line with the general axis of the ossicules (author's transl)].

Definition and technique of the Dulac 7 incidence. Diagrams 1 and 2 give details of the anatomical orientations which define this incidence. It is:--centered on the head of the malleus,--orientated in the plane of the ossicules or in the neighbouring plane of the ear-drum,--parallel to the general axis of the ossicules,--close to the perpendicular to the tegment tympani. This incidence is easy to obtain with our technique, using a fixed intracranial centering point, The transversal linear scanning is very effective and can be completed in a very short period. It should be noted, however, that in obese subjects with short necks, the entry point of the incidence is difficult to obtain as there is interposition of the neck muscles. Under these conditions, one should try to be as close to this entry point as possible, knowing that the results are still valid. Tomographic anatomy. A close examination of the text of figures 6, 7, and 8 will familiarize the reader with the tomographic anatomy of this incidence. To summarize the important information obtained from the Dulac 7 incidence we should note that in tomographies of normal petrous bones:--the attic is always perfectly visible, expecially its internal and external walls throughout their total length, and more especially the anterior wall;--the ossicles (head of the malleus, body of the incus, and their articulation) are always perfectly visible and distinct;--the inferior processes of the malleus and incus are always visible;--the external wall of the attic is visible throughout its length, more especially the anterior and posterior portions;--the anterior and posterior contours of the external auditory canal are particularly well-defined. Finally, this incidence also gives clear images of the temporo-mandibular joint, the antral region, the superior canal, and the internal auditory canal. A large experience of this incidence is required before interpreting the image of the foramen ovale. Tomographic pathognomonic signs. The texts of figures 9 to 24 are sufficiently demonstrative of the richness of the pathological data obtained from this incidence, without needing to repeat them here. We would only add that the degree of calcification of the ossicles and the anterior wall of the attic can be precisely determined. This incidence, therefore, gives valuable information in almost all middle ear affections. It is also necessary in order to study the external auditory canal.


[Computerized tomography of craniopharyngiomas. Therapeutic consequences].

An analysis was made of the results of C.T. scanning in 43 patients with craniopharyngiomas. Filling of the suprasellar cisternae was observed in most cases, together with dilatation of the lateral ventricles. The appearances of the tumor before and after intravenous injection of the contrast medium are described and the frequency with wich calcification, cysts, and lipid densities were noted is reported. Regular C.T. scanning can define operative indications for craniopharyngiomas as a function of the results obtained.


[Unilateral dysplasia of the circle of Willis with multiple distal stenoses (author's transl)].

Neurological and clinical examinations were found to be normal in a woman aged 40 years who had had a single generalized epileptic seizure. Rediological examinations demonstrated a spiral-shaped calcification above and laterally to the left sella turcica. This corresponded to changes in the C 1 segment of the left carotid sinus, which was partly stenosed distally, with left unilateral abnormalities of the circle of Willis and multiple distal stenoses of the left sylvian and vertebro-basilar arteries. Scanning demonstrated that these had been present for a long time, but it is not possible to establish the diagnosis on an etiological basis as no similar radiological findings have been published.


[A case of pseudocyst of adrenal gland (author's transl)].

A case of pseudocyst of adrenal gland is reported. The first findings have been acute pain and falling hematocrit. Then hepatomegaly is present. All the investigations--ultrasonography, radionuclidescan, arteriography--failed to demonstrate the origin and saided liver cyst. The diagnosis is operative. The pseudocyst hemorrhagic are 32% of adrenal cysts. We think the computer tomography will be an important contribution for the diagnosis of false hepatomegaly.


[Success rate of ultrasonic exploration of the pancreas. Results of 266 followed-up cases].

In two series amounting to 266 cases, the overall success rate of ultrasonic diagnosis, in pancreatic lesions was 94%. Since most of pancreatic lesions, when clinical symptoms are present, are already rather large, imaging improvements did not enhance accurary, except for small lesions. The tenative analysis of small abnormalities can be responsible, with last generation machines, for an increase of false positive diagnoses.


Inhibition of uptake of catecholamines by benzylamine derivatives.

Eight benzylamine analogues of bretylium were synthesized, including N-(2-chloroethyl)-N-ethyl-2-methylbenzylamine (5), and evaluated as inhibitors of accumulation of norepinephrine and dopamine in rat brain homogenates. All compounds gave an I50 value (concentration of inhibitor that causes 50% reduction in control accumulation) considerably lower against norepinephrine in cortex that against dopamine in striatum. High potency (low I50) and high specificity (preference for inhibition of norepinephrine transport compared to dopamine transport) are associated with a (2-chloroethyl) moiety, tertiary amino center, and ortho substitution of the aromatic function in the benzylamino group. 5 also inhibited the uptake of norepinephrine in rabbit aorta, indicating its effect against the uptake process in general. Cocaine protects against the effects of 5 in coincubation studies when compared to the appropriate controls, indicating that 5 acts at or close to the site of action of cocaine which is thought to be the uptake carrier site.


Quantitative structure-activity relationships for biguanides, carbamimidates, and bisbiguanides as inhibitors of Streptococcus mutans No. 6715.

Thirty-seven compounds, including 17 biguanides, 6 carbamimidates, and 14 bisbiguanides, were evaluated for potential antiplaque activity by measuring their minimum inhibitory concentrations [MIC (M)] against Streptococcus mutans no. 6715. Linear regression analysis was conducted with the log 1/MIC (M) values and log P, pi, sigma, and MR. The best correlation for the biguanides (r2 = 0.92) was obtained with log P and (log P)2. When the biguanides were included with the carbamimidates, essentially the same correlation (r2 = 0.91) was obtained with log P and (log P)2. The best correlation for the bisbiguanides (r2 = 0.70) was also obtained with log P and (log P)2. Use of an indicator variable (I) for the bisgiguanides allowed all three groups to be included in one equation, which accounted for over 87% of the variance in the data for inhibition of bacterial growth. These results from the classical parabolic model were also compared with those from the recently developed bilinear model.