Immunological response to experimental echnococcosis in Meriones unguiculatus. Varying doses of protoscolices of Echinococcus granulosus were injected intraperitoneally into Mongolian jirds, Swiss mice, and golden hamsters. After 4 months the animals were killed and the numbers of developing cysts counted. Jirds were by far the most susceptible hosts. Doses of 500 protoscolices produced 100% infection rates in both weanlings and adults. Comparable infection rates in weanling mice required inocula of 5,000 protoscolices, but even at this dose hamsters were refractory to infection. Three of 5 jirds developed pulmonary cysts after intravenous administration of 500 protoscolices. Serologic responses in infected jirds were followed using the indirect hemagglutination tests and a purified fraction of hydatid cyst fluid (HCF) as antigen. Titers reached a plateau after 15 weeks and were maintained for several months. Much brisker serologic responses occurred in animals sensitized with the antigenic fraction in various adjuvant vehicles. At no time during infection did jirds show any evidence of immediate hypersensitivity to HCF in direct skin tests, passive cutaneous anaphylactic tests, or after intravenous challenge with antigen. After artificial immunization with hapten-conjugated antigens or HCF, jirds underwent a fatal shock following intravenous challenge with antigen. HCF provoked the appearance of circulating antibodies which were capable of sensitizing normal recipients for passive systemic anaphylaxis after a latent period of 72 hr. It is concluded that the failure of the infected  jird to develop immediate hypersensitivity responses to E. granulosus represents a marked deviation from the parrern of the immune response in echinococcosis in man and domestic animals and must be considered in the future use of this animal in experimental studies on the host-parasite relationship.


Eucyathostomum webbi sp. n. (Strongyloidea: Cloacinidae) from white-tailed deer (Odocoileus virginianus). The new species is described from white-tailed deer of McIntosh County, Georgia, and Pushmataha County, Oklahoma. Eucyathostomum webbi sp. n. differs from E. longesubulatum (type) in possessing more internal leaf crown elements, unbarbed spiculte tips, variability in the configuration of the dorsal ray of the male bursa, and shorter vagina and ovejectors; from E. copulatum in being much larger and not having males and females permanently united; from E. spinulosum in the origin of the externo-dorsal ray of the male bursa; and from E. dentatum in having more internal leaf crown elements, shorter spicules, a distinct cephalic vesicle, no dorsal gutter, and a pectinated flange posterior to the vulva. Problems in the taxonomy of the genus Eucyathostomum are discussed. Specimens previously identified as E. longesubulatum from southeastern white-tailed deer were reexamined and found to be conspecific with E. webbi.


Post-labial sensory structures on the cecal worm, Heterakis gallinarum. Sense organs that lie just posterior to the lips on the sides of the body of Heterakis gallinarum have been examined by scanning and transmission electron microscopy. The sense organs appear externally as a short peg surrounded by a collarlike elevation of cuticle. Each sense organ contains the endings of 2 sensory dendrites; 1 extending to the tip of the peg is probably chemosensitive, while the other ending just within the cuticular cylinder that projects internally from the peg, is probably mechanosensitive.


A simple method for collecting infective larvae of Litomosoides carinii. A method is described whereby substantial quantities of infective larvae of Litomosoides carinii can be obtained with relative ease. In each of 2 separate experiments, over 5,000 infective larvae were recovered by soaking the pelts of 5 or 7 Mongolian jirds (Meriones unguiculatus) that had been exposed for 6 or 7 hr to infected tropical rat mites (Ornithonyssus bacoti). The mites had been infected either 7 to 8 or 9 to 10 days earlier by exposure to jirds with patent infections. Ninety-four percent of the total number of infective larvae recovered and migrated out of the pelts within 2 1/2 hr. Jirds inoculated subcutaneously with infective larvae collected in this manner exhibited high mean percent recoveries at necropsy, i.e. 79 and 60 at 5 and 29 days postinoculation, respectively. In addition, the ranges in worm recoveries were narrow.


Cruorifilaria tuberocauda gen. et sp. n. (Nematoda: Filarioidea) from the capybara, Hydrochoerus hydrochaeris in colombia. Cruorifilaria tuberocauda gen. et sp. n. is described from blood vessels of the kidney, heart, and lungs of the capybara, Hyrochoerus hydrochaeris, in Colombia, S.A. The adult worms are robust, of moderate size (females approximately 42 mm long, males about 27 mm long), and tapered at both ends. The males have unequal, dissimilar spicules, lack a gubernaculum and possess both pre- and postanal papillae. The unsheathed microfilaria is found in the peripheral blood. Even though a severe tissue response is seen in the walls of the blood vessels occupied by the adult worms, it appears to be a common parasite in the population of capybaras surveyed.


Studies on resistance in snails. 7. Evidence of interference with the defense reaction in Biomphalaria glabrata by trematode larvae. Echinostoma lindoense sporocysts that develop from irradiated miracidia normally are destroyed by amebocyte capsules in the ventricle of Biomphalaria glabrata within 10 days postexposure. The survival period of these ventricular sporocysts was considerably longer in snails that also harbored normal sporocysts of E. lindoense, Paryphostomum segregatum, or Schistosoma mansoni. Protection of irradiated E. lindoense sporocysts by the same of different trematode species is presumed to be the result of an active process by which normal sporocysts interfere with capsule formation and protect themselves and other trematode larvae from encapsulation. Homologous protection was stronger than heterologous.


New Oncomelania hupensis foci on Taiwan. Six new areas for Oncomelania hupensis were found on Taiwan: three in Nan-tou, and 1 each in Chia-i, Hua-lien and Tai-tung counties. Most of the new habitats, unlike previously known areas, are not in alluvial plains, but are at higher elevations. The Nan-shan-chi colony in Nan-tou county is located at the altitude of 740 m, which is the highest of all known Oncomelania localities on the island. Oncomelania has now been found in 9 out of 15 counties on Taiwan. Shell features of the newly-discovered snails resemble those of Oncomelania hupensis formosana but further study will be required for final subspecies designation. Nearly 60,000 oncomelanids from both old and new localities were examined for schistosome infection with negative results.


Cystobranchus meyeri sp. n. (Hirudinea: Piscicolidae) from Catostomus commersoni Lacépède in North America. Cystobranchus meyeri sp. n. (Hirudinea: Piscicolidae) is described from the white sucker, Catostomus commersoni Lacépède (Osteichthyes: Catostomidae) from the Mohawk River drainage of eastern New York. Size, details of internal anatomy, and the presence of 8 ocelli on the posterior sucker distinguish it from the 3 other species in North America. A table compares the members of this genus and a key to the species is included. Problems of classification, host records, and host specificity are discussed.


Winter ecology of ectoparasites collected from hibernating Myotis velifer (Allen) in southwestern Oklahoma (Chiroptera: Vespertilionidae. During the winter of 1971-72, Trichobius major, T, corynorhini, Mydopsylla collinsi, Macronyssus crosbyi, M. unidens, Paraspinturnix globosus, Spinturnix carloshoffmani, Ornithodoros sp., Albeckia senase, Nycteriglyphus sp. A, and Olabidocarpus sp. were quantitatively collected from hibernating Myotis velifer, Plecotus townsendii, and Pipistrellus subflavus. Significantly greater numbers of S.  carloshoffmani and M. crosbyi were found on female M. velifer, while greater numbers of P. globosus were found on males. With the exception of T. major and P. globosus which were radomly distributed, all ectoparasites exhibited a contagious distribution on M. velifer. Only T. major and S. carloshoffmani had a 1:1 sex ratio, the remaining species had significantly fewer males. M. unidens, M. crosbyi, and N. species A were positively associated, while M. collinsi was negatively associated with both Macronyssus; the remaining species were not signficantly associated. With the exception of T. major and P. globosus, ectoparasite densities decreased during the winter.


Prognostic factors in neuroblastic tumors. Data of 101 patients with neuroblastic tumors from 1950 to1974 at The Johns Hopkins Hospital have been abstracted onto specially designed summary sheets, and subjected to multifactorial analysis. One-third of the 21 benign ganglioneuromas showed evidence for spontaneous maturation. The overall cure rate among the malignant tumors was 39%. Cures were higher with an extraabdominal primary, with more  mature histologic differentiation, and if excision, even partial, was carried out. Neither radiotherapy nor evolving modalities of chemotherapy appear to have had benefit over this 25-yr period. An age at diagnosis less than 2 yr, and a less extensive clinical stage both were independent predictors of survival. The apparent effects of a favorable site of tumor origin, or more mature histologic differentiation were not of major impact in and of themselves, but correlated better with clinical stage. Two prognostic schemata, based on stage plus age, and stage plus histologic differentiation plus age respectively, proved to be 95% accurate in  our experience. With more extensive evaluation and experience, either or both may be helpful in the management of malignant neuroblastic tumors, and assessment of therapeutic regimens.


Esophageal atresia and associated anomalies. One hundred and two patients with esophageal  atresia possessed 237 additional anomalies. Risk grouping of these patients was useful and showed a direct relationship between the increased incidence of anomalies, low birth weight, and nonsurvival. Fifty-seven per cent of the patients with additional anomalies possessed multiple anomalies, most frequently occurring in the gastrointestinal, cardiovascular, and musculosketetal organ systems. Fifty-five per cent of the deaths appeared to result from the coexistent severe anomaly, while the remaining 45% of the deaths appeared to occur as a result of the presence of esophageal atresia. It is our suspicion that the insult producing esophageal atresia with a high incidence of associated anomalies occurs at a more critical time in organogenesis than that event that produces the esophageal atresis alone or with one moderate anomaly.


Continuous dynamic monitoring of pressure and flow patterns during assisted ventilation. A system for continuous, dynamic monitoring of children requiring ventilatory assistance  has been developed and used in a critical care setting. Breath by breath airway pressure changes are measured on a specially adapted meter with high-and low-pressure limit alarms, and are displayed graphically on a bedside oscilloscope. This system has proved to be beneficial in detecting ventilator system malfunction; in adjusting ventilator settings, such as inspiratory/expiratory ratios, end-expiratory pressure, and phase duration and flow  ratios; in assessing compliance of a child requiring ventilatory assistance and his capability for spontaneous breathing; and in the early recognition of potentially harmful problems attendant upon assisted ventilation. The system provides additional educational benefit for the I.C.U. personnel, who become more knowledgeable regarding ventilatory problems, and more apt to discover them promptly. The simplicity of the system, compatibility with other I.C.U. monitoring equipment, capability for continuous, dynamic monitoring, and broad scope recommended it for infants and children requiring assisted ventilation.


Serum gastrin concentrations in infants with short gut syndrome. Seven babies with 100 cm or less remaining small bowel have been evaluated for evidence of gastric hyperacidity and/or hypergastrinemia. Two babies were also studied after feeding. No patient demonstrated hyperacidity or hypergastrinemia. This infant data is discussed in regards to reported contradictory data in adult studies.


Intestinal stricture in necrotizing enterocolitis. In a 3-yr period, eight infants among 43 survivors of acute NEC developed intestinal stricture. Four infants developed multiple stricture after proximal diversion procedures, and four had single strictures after medical therapy. Nineteen cases of intestinal stricture after NEC were collected from the literature. Radiographic examinations at the time of the acute disease were not predictive of the risk of subsequent stricture. Histologic examination showed various stages of wound healing, most prominently in the submucosa. Stricture should be considered as the cause of intestinal malfunction in any child who survives acute NEC.


Primary subacute pyogenic osteomyelitis in long bones of children. Ten cases of primary subacute osteomyelitis illustrate its clinical resemblance to various bone neoplasms. Diagnosis was established by open biopsy. Treatment with curettage, cast immobilization, and antibiotics, when indicated, resulted in radiographic healing and resolution of symptoms.


Primary surgical management of the deeply burned hand in children. Primary burn excision with immediate wound closure by skin grafting was used as the initial definitive treatment for deep burns of the hand in 30 consecutive  children. The results are compared with an additional group of 30 children whose burns were treated with AgNO3 alone. There is a significant difference in all categories examined between the excised and the nonexcised group. Hand deformities, secondary reconstructive procedures, and morbidity  were significantly reduced in the excised group. Excision provided improved functional and cosmetic results.


Wringer arm injuries.

Wringer arm injuries. During a 20-yr period, 483 children 16 yr of age or under were hospitalized for management of a wringer arm injury. Although the majority were indigent, black males, such trauma was frequently sustained by all classes and races as well as by both sexes. Principles of treatment consisted of cleansing the abrasion wound, application of a pressure dressing from axilla to finger tips, elevation, and close observation. With the exception of a destroyed brachial vein in one patien, significant vascular injuries  did not occur despite a "medical fixation" on evidences of impaired circulation. Likewise, no fractures were noted even though all patients had x-rays of the full extremity. However, there were six metacarpophalangeal dislocations, five instances of neuropathy, and one traumatic amputation. Major skin sloughs occurred in 18 children, yet only 11 of them required a skin graft.


Modified Duhamel procedure for treatment of total aganglionic colon in childhood. Based on this series of six patients with aganglionosis  of the entire colon we conclude: (1) Radiographic findings of a shortened colon of normal caliber or the presence of "jejunalization" of the colon suggest total colonic aganglionosis in patients with a suggestive history. (2) All infants with persistent obstipation, distention, and poor weight gain should have a punch biopsy of the rectum even if the barium enema is normal. (3) The Martin modification of Duhamel's operation gives functional results comparable to those achievable in children with short-segment Hirschsprung's disease. (4) The use of a stapling device to divide the septum between aganglionic colon and pulled-through  ileum is less satisfactory than using crushing clamps.


Jejunoileal atresia: a proposed classification. An experience with 59 infants with jejunal and ileal atresia is presented along with a proposed classification based on a combination of morphology and clinical characteristics. It would appear that the characteristics of each type are sufficiently distinct as to render this worthwhile classification.


Ruptured appendicitis in children: continuing controversy over antibiotic combinations. A prospective study has been made of 36 children with ruptured appendicitis. Alternate patients were managed with a standard protocol of therapy differing only in the antibiotics used. One group received a combination of penicillin/streptomycin/sulfadiazine while the other children were treated with cephalothin (Keflin) and cephalexin (Keflex). No major infections complications occurred in the P/S/S study group but there were four in the C/C patients. No serious adverse reactions due to the antibiotics occurred in either group.


Are hemisplenectomy and/or primary splenic repair feasible? Following splenectomy, infant rats are at risk when challenged with pneumococcus. Mortality was 85% in splenectomized rats and 6.6% in controls. Rats subjected to a standardized splenic trauma had a 16% mortality when left untreated and a zero mortality with operative therapy by splenectomy, hemisplenectomy, or primary splenic repair. Hemisplenectomy and primary splenic repair are indeed feasible in rats with resultant splenic tissue showing a normal histologic appearance. Hemisplenectomized infant rats, when subjected to pneumococcal challenge, had a 15% mortality compared to 85% for splenectomized infant rats. This suggests that the repaired spleen retains its very important immunologic abiltiy to resist infection. Despite differences in species and organ sizes and shapes, these data suggest that partial splenectomy and primary splenic repair may be attractive alternatives to splenectomy in instances of trauma and  inadvertant operative injury.


Repair of laryngotracheoesophageal cleft using interposition of a strap muscle. Two  children with laryngotracheoesophageal clefts were operated with success. In one case the cleft resulted from trauma. The second case was of  congenital origin and had been operated twice previously. Interposition of the sternohyoid muscle was an important adjuct contributing to success in repair.


Endoscopic resection of obstructing airway lesions in children. In the past 8 yrs, 14 children were treated with obstructing lesions of the larynx, some of then acquired from prolonged intubation. Endoscopic resection of the obstructions proved feasible in selected cases. The use of a wire stylette of fine needle within a small ureteral catheter sheath provides a  readily available and accurate means for dealing with some  of these lesions.


Clinical technique and success of the esophageal stent to prevent corrosive strictures. The Reyes technique for the management of severe, acute  corrosive injuries of the esophagus has been modified and successfully applied to two children and one adult whose cases are reported. None developed stricture and two were uncomplicated. Esophagomegaly, motility dysfunction, upper gastrointestinal bleeding, and pneumonitis complicated the hospitalization of one child whose subsequent course has been asymptomatic. Until more experience can be recorded, widespread use is not yet recommended.


Changes in appearance of amniotic fluid during pregnancy - the macroscore. During the first two trimesters of pregnancy the amniotic fluid is clear and yellow; during the third trimester the amniotic fluid becomes colourless; then, approximately from the 33rd-34rd week on, cloudiness and flocculation occur, at first very slowly, after the 36th-37th week steadily faster (Tab. I). At term, the amniotic fluid is moderately cloudy and contains a moderate number of flakes of vernix. The appearance of the amniotic fluid depending on the degree of cloudiness and on the number of flakes, has been expressed by means of a score system, the socalled macroscore (Tab. II). Relationships were observed: a) between the disappearance of the yellow colour (bilirubin) and the initial occurrence of cloudiness and flocculation; b) between the duration of pregnancy and the macroscore; from the 32nd-36th week of pregnancy the mean macroscore increases until the second half of the 40th week; then in the 41 st week there is a drop in the mean macroscore, after which a new increase occurs (Fig. 1,2 and 3). c) between the total gestation period at birth and the progression of the macroscore (Fig. 5); when birth takes place earlier (later), the macroscore will increase earlier (later). d) between the total duration of gestation at birth and the macroscore at the end of pregnancy; with an earlier (later) birth, the macroscore is lower (higher) (Fig. 5 and 6). With the macroscore it is possible to determine the duration of pregnancy (b) and the time before birth even more accurately (c). The fairly large standard deviation of the macroscore per pregnancy week (Fig. 1) also in case of a given duration of gestation at birth (Fig. 7) points to a fairly large interindividual variation in the appearance of the amniotic fluid at a certain duration of pregnancy. The macroscore is determined by elements originating from the fetal skin; the cloudiness and flocculation are caused by release of vernix and the flaking off of cells from the stratum corneum. Hence the macroscore reflects changes in the function of the fetal skin and is an indicator of the functional maturation of the fetal skin. The considerable variation of the macroscore at a given duration of pregnancy indicates a great variation of fetal maturation. The fetus that is maturing faster, will be delivered earlier; the fetus that  is maturing slower, later (c). This points to a correlation between the degree of fetal maturation and the start of labour. The higher macroscore during the last days before birth in pregnancies of longer duration (d) (Fig. 5 and 6) may be explained by a less sensitive uterus, requiring a greater maturity of the fetus for delivery to start. The drop of the mean macroscore in the 41 st week of pregnancy is due to a sudden increase of lower scores in this week (Fig. 4). A lower score at a given stage of pregnancy means a later birth (Tab. VI and VII). Thus in the 41 st week of pregnancy a considerable group of pregnant women appears, that has a total duration of gestation that is, on the average, two weeks longer than normally...


Problems in using linear ultrasound parameters for the determination of fetal weight. We have developed three formulas for the calculation of fetal weight by means of ultrasound which have proved clinically useful   (Formula I for normal size fetuses, Formula II for very small fetuses, and Formula III as a control). From 621 controlled calculations of the fetal weight and the general experience from our ultrasound clinic (over 20,000 examinations) we discuss the inherent problems. We used the Vidoson apparatus manufactured by Siemens (West Germany) which is a rapid imaging B-scan. We have learned from many years of studying means of calculating fetal weight that a regression equation from linear fetal measurements can be used: namely the biparietelllll skull diameter, the sagittal and the transverse thoracic diameter and the length of the trunk (Tab. I)...


Prospective and retrospective examination of an easily applicable score to predict the probability of premature birth defined by weight. An easily applicable score to predict the risk of prematurity (Tab. I) (defined by weight) is examined prospectively (scoring during 6 th month of pregnancy) in 431 and retrospectively (obtained after delivery) in 1183 pregnancies. In the prospective study (Tab. II) 71.4% of all pregnancies resulting in babies below 2501 g exceed the proposed 50 points risk probabilty limit whereas only 18.7% of pregnancies with babies of more than 3000 g do so. Excluding pregnancies with 20 or more risk points and excellent prenatal care (8 or more consultations) - which should change the outcome of risk-pregnancies - the percentages are 77.8% and 12.2% respectively (Tab. III). Pregnancies resulting in babies with birth weight of 2501 g -2750 g exceeded the limit in 38.9% and those with babies of 2751 g-3000 g in 20.7%. If 60 risk points are used as the limit the percentages for more than 3000 g until less than 2501 g would be 8.2%, 6.9%, 33.3% and 66.7%. In the resrospective study (Tab. V) 14.7% of all pregnancies with babies above 3000 g exceeded the 50 risk points limit compared with 57.2 of those with babies below 2501 g. Excluding pregnancies with 20 or more risk points and excellent prental care the percentages are 7.6 and 59.4 respectively. In the retrospective study the influence of the quality of prenatal care by the number of consultations (3-4; 5-7; 8 or more) is clearly demonstrable: Pregnancies with more than 50 risk points resulted in 80.7%, 57.1% and 19.8% depending on the quality of care in babies below 2501 g. Pregnancies with 31-50 risk points did so in 47.2%, 20.4% and 11.8%. In 334 women the score could be applied twice, in the 6th month and at delivery. Comparing both scores it was found that only 1.8% of these women exceeded the 50 risk points limit by events occurring after the 6th month scoring (Tab. IV). The score, simple enough to be applied by nurses and midwives, seems to be able to select 77.8% of pregnancies resulting in babies below 2501 g already during the 6th month of pregnancy, i.e. early enough for preventive measures to be taken that decrease the frequency of underweight births by three quarters.


Fetal paroxysaml supraventricular tachycardia recorded by intrauterine scalp electrocardiography. Fetal and neonatal paroxysmal supraventricular tachycardia (PST) requires attention because it may be associated with cardiac pathology and neonatal demise. Continuous monitoring of fetal heart rate and the ability to record clearly interpretable electrocardiograms from fetal scalp electrodes makes discovery and diagnoses of these fetal arrhythmias relatively simple. This report describes the discovery of this arrhythmia during routine DOPPLER ultrasound fetal monitoring and its documentation as PST by fetal scalp electrocardiography. (Fig. 1) The fetal heart rate during PST was 300 BPM, higher than previously reported. In contrast to previous reports, it did not appear post-natally and no pathology was found. Although the significance of transient fetal PST is not known, prudence indicates close observation of the neonate. This case demonstrates the value of fetal monitoring for the discovery, diagnosis and documentation of fetal arrhythmias during labor.


Perceptual development on the Rorschach. The Rorschach was given to 60 school children in two designs: CA and MA orthogonal (9 and 12 years) and CA =MA (for 6, 9 and 12 years). Responses were scored for Form Accuracy, Complexity, Movement, and Friedman's Developmental Level (DL) Scoring System. There were significant MA effects independent of CA on Form Accuracy, Complexity and DL, and significant CA effects on Complexity and Movement. Form Accuracy was highly correlated with the DL score and correlated with MA at a slightly higher level than DL with MA. The Complexity score provided some additional information about development. Movement decreased with age but was higher in intelligent subjects. The results suggested that the DL system does assess MA independently of CA, but this is accounted for primarily by Form Accuracy.


The relationship between behavioral indices of aggression and hostile content on the TAT. The role played by fantasy in mitigating the overt expression of aggression was investigated by examining the relationship between aggressive behavior and aggressive story content on the Thematic Apperception Test. A rating scale, checklist, and offense scale were used to measure the aggressive behavior of 76 juvenile offenders. While only one measure correlated significantly with hostile content on the TAT, all three correlations were negative, suggesting an inverse relationship between measure of aggression and aggressive content on the TAT.


Interrelationships of psychopathology and adience-abience on the HABGT. Using two distinctively different populations, 40 hospitalized schizophrenics and 100 outpatient therapy cases, the interrelationships of two measures based on the HABGT, one of psychopathology and the other of perceptual adience-abience, were investigated. The relationships of each of these measures with sex, age, and educational level were examined. Both measures significantly differentiate the psychotic from the non-psychotic population. Although there is a statistically significant correlation between the two measures in each population, it is shown that the commonality between them varies from a considerable degree of commonality in the schizophrenic group to only a limited degree in the outpatient group. Both measures are uncorrelated with sex, age, and level of educational attainment. The study offers additional evidence of the values of these two measures.


Anxiety and defense against anxiety as reflected in percept-genetic formations. Two percept-genetic methods, the Meta-Contrast Technique (MCT) and the Serial Afterimage Test (AI), were used to study adaptive aspects of perception in a group of 37 subjects suffering from manifest anxiety. The perceptual processes laid bare by these methods reflected not only anxiety but also defensive formations. MCT and AI correlated with each other in these respects and, when combined, correlated with rated symptoms. In accordance with the theory behind percept-genetic methods, anxiety signs appearing late in the test serials were more likely to correspond to manifest symptoms than signs which appeared early. The AI test scores seemed to reflect a difference between anxiety experienced as an inherent quality of life and anxiety as a foreign force struggling for dominance.


Associative elaboration and integration scales for evaluating TAT protocols. An Associative Elaboration Scale and an Integration Scale were constructed for evaluating Thematic Apperception Test (TAT) protocols. Interrater reliabilities and the correlation between the two scales were determined for a selection of TAT cards. The Integration Scale was dropped from further analyses, because its interrater reliabilities were low and it correlated highly with the Associative Elaboration Scale. The relation between the Associative Elaboration Scale and age was then investigated for randomly selected patients aged 7, 9, 11, 13, and 15. There tended to be a rapid increase in Associative Elaboration scores up to age 11 and then little or no increase in scores. There was no significant relation between Associative Elaboration and IQ.


Decisiveness and psychological adjustment. Decisiveness, defined as the ability of the individual to engage in the decision-making process, was examined in relation to a number of parameters of psychological adjustment. Six decisiveness instruments, a series of adjustment measures, and peer rating assessments were obtained for 228 volunteer subjects. The pattern of relationships between the decisiveness measures suggested that decisiveness is not a monolithic trait, but rather is multidimensional. The relationship between the decisiveness and adjustment, with the impressionistic, global measures of decisiveness showing a stronger relationship to adjustment than the behavioral, objective ones. However, contamination of the data due to methods factors was observed, and sex was seen to be a factor in the interaction between decisiveness and adjustment. Methodological improvements and suggestions for further research are offered.


Correlates of risky decision-making.

Correlates of risky decision-making. The purpose of this investigation was to develop a personality pattern which could be used for both the explication and prediction of risky behavior in a variety of decision-making situations. Two months after the completion of a battery of psychological examinations, 240 randomly selected subjects responded to three problems adapted from the Kogan and Wallach Choice Dilemma Problems. Analyses of the data (correlational, factor analytic, and stepwise multiple regression) revealed a stable personality index representative of individuals exhibiting riskiness in decision-making. Variables contributing to this pattern characterized a dynamic task oriented individual. The results of this study should prove useful to future decision-making research by providing a framework for prediction.


An evaluation of an MMPI response consistency measure. Response inconsistency as an index for invalidating MMPI protocols was investigated by measuring the number of inconsistent responses given to 14 pairs of identical items by brain-damaged and nonbrain-damaged schizophrenic, alcoholic, neurotic and normal patients (n = 22 in each of the 8 groups). In addition the patient's number of inconsistent responses were correlated with the usual MMPI validity measures (?, L, F and K). Although all the response consistency scores of the groups were high it was found that the brain-damaged were more response inconsistent than the nonbrain-damaged patients (regardless of psychiatric diagnoses). The correlations between response inconsistency and the MMPI validity measures were significant but low. Because of the over-all high level of response consistency found for all the groups, it was concluded that MMPI protocol validity should be based on the validity scale measures, rather than upon response inconsistency.


An objective measure of fear of success: construction and validation. A 27-item Fear of Success Scale (FOSS) was developed to assess individual differences in the motive to avoid success. Females scored significantly higher on the FOSS than did males; the FOSS was positively related to Horner's projective measure of fear of success, and negatively related to Mehrabian's measure of achievement motivation; subjects (both males and females) with high scores on the FOSS (a) performed less well on an anagram test, (b) attributed success more to external factors, and (c) attributed failure more to internal factors than subjects with low scores on the FOSS. These results supported the validity of the FOSS with regard to its use in future research.


The Stanford Preschool Internal-External Scale: extension to kindergarteners. To investigate whether the characteristics of the recently developed Stanford Preschool Internal-External Scale (SPIES; Mischel, Zeiss, & Zeiss, 1974) would remain stable for older children of apparently different socioeconomic status than the normative sample, the SPIES was administered to 104 kindergarteners of essentially middle class background in an ordinary elementary school. The findings indicate that the SPIES may be useful in research on perceived locus of control in kindergarteners as well as preschool children.


Kinesthetic aftereffect and personality: a case study of issues involved in construct validation. Kinesthetic Aftereffect (KAE), once a promising personality index, has been abandoned by many investigators because of poor retest reliability and intermittent validity. In challenging this current consensus, we argue that (a) first-session KAE is valid; (b) poor retest reliability simply reflects later-session bias; (c) hence, multisession studies should not be used to assess validity without taking this bias into account. Those recent studies which failed to support KAE validity were each multisession in design. If our bias contention is correct, these studies should be ignored, and the claim of intermittent validity is thus rebutted. Reanalysis of the most recent major multisession, nonsupportive validity study indicates (a) Session 1 validity, (b) later-session bias, and (c) later-session valdiity when multisession scores are combined to avoid bias. Thus, KAE validly measures personality.


Stability of adult personality traits: fact or fable? Theoretical positions for and against a stability model for adult personality traits are examined. Results of a sequential study of 19 personality factors over a 7-year period and with participants ranging in age from 22 to 84 years suggest that stability within generations appears to be the rule, albeit combined with many differences between successive population cohorts and subject to transient secular trends. A typology of 13 possible models is offered to account for the different developmental trends observed for the various personality factors.


The experience of crowding: a two-factor theory. It was proposed that the experience of crowding occurs in a two-step process: First, the individual becomes aroused by violations of his personal space, and then he attributes the cause of this arousal to other people in his environment. Based on this model it was predicted that violations of personal space rather than simple density is the spatial variable associated with crowding. Further, it was predicted that the experience of crowding can be alleviated if the individual is distracted from making the attribution that his arousal is caused by other people. In order to test these prediction, interaction distance (close and far) and density (high and low) were varied separately. In addition, for half of the conditions, pictures (attribution inhibitors) were placed on the walls of the experimental room, and in the other half, the walls were bare. Subjects worked on two tasks and were then questioned about their experience of crowding. The results showed that interaction distance was more closely related to crowding than was density and that the addition of pictures reduced the experience of crowding only in the close interaction conditions. The results were interpreted as supporting the attribution analysis of crowding.


Role-taking standpoint and adolescent usage of Kohlberg's conventional stages of moral reasoning. By taking into account a respondent's role-taking standpoint, this study proposes that moral judgments coded at Kohlberg's conventional stages can be expected to vary depending upon (a) the identity of the protagonist implicated in the moral dilemma and (b) the nature of the issues raised by the moral dilemmas used. Different groups of respondents were asked to answer three versions of Kohlberg's moral judgment questionnaire. One version implicated strangers in the dilemmas used (fictitious-other questionnaire), while the other two versions implicated respondents' best friends or mothers (primary-other questionnaires). A comparison of these questionnaire treatments indicates that Stage 3 response rate significantly increases and Stage 4 response rate significantly decreases when respondents answer primary-other questionnaires. It is suggested that this finding casts doubt on the adequacy of the displacement view of moral stage acquisition. The displacement perspective argues that as more cognitively complex structures are acquired, earlier acquired structures are displaced. In contrast, the present study proposes that a "nondisplacement" view of stage acquisition is required in order to explain variation observed at Stage 3 when it may be assumed that a Stage 4 reasoning capability has been acquired.


Vicarious eyelid conditioning.

Vicarious eyelid conditioning. This study attempted to demonstrate that elicited electromyographic (EMG) reactions in observers may become conditioned to environmental events during the observation of a modeling sequence. Observers were shown a videotape of a model in a simulated direct eyelid discriminative conditioning situation involving adaptation, acquisition, and extinction trials. Various EMG measures were obtained in order to determine the occurrence of vicarious instigation and conditioning. The results demonstrated vicarious EMG eyelid responses. Also, the motor reactions were found to be localized to specific muscular activity rather than a result of general arousal. Some theoretical and clinical implications of these findings are discussed.


Nonlinear pharmacokinetic model of intravenous anesthesia. A nonlinear pharmacokinetic model was constructed to describe the body distribution of intravenous anesthetics, using the physiological modeling approach for drug distribution kinetics. The model considers the physiological parameters of tissue volumes and blood flow rates for the standard four phases of blood, viscera, lean tissue, and adipose tissue and also the associated drug parameters known to influence drug distribution. A simple ramp function having a characteristic time (volume per flow rate) is used to describe the rate of approach to equilibrium conditions for each tissue phase. The model was evaluated for the distribution of methohexital and thiopental by comparing calculated values to experimental drug concentrations taken from the literature. The physiological alteration of obesity also was programmed into the model to evaluate its capability for predicting the influence of body alterations on drug distribution. The results indicated that a preliminary mathematical model of relatively simple design is capable of at least a semiquantitative prediction of intravenous anesthetic drug concentrations in body tissues and has the potential of accounting for differences in drug distribution in the presence of selected physiological alterations.


Anticonvulsant activity and inhibition of cellular respiratory activity by substituted imidazolocarbamides. Several 1-(1-aryl-2-mercaptoacetylimidazole)-3-alkylcarbamides were synthesized and characterized by their sharp melting points, elemental analyses, and IR spectra. These substituted imidazolocarbamides possessed anticonvulsant activity, which was reflected by the 20-80% protection observed with these compounds against pentylenetetrazol-induced convulsions in mice. These substituted imidazolocarbamides selectively inhibited the in vitro oxidation of nicotinamide adenine dinucleotide (NAD)-dependent oxidations of pyruvate, alpha-ketoglutarate, beta-hydroxybutyrate, and NADH by rat brain homogenates. However, NAD-independent oxidation of succinate was not affected. The anticonvulsant activity possessed by 1-(1-aryl-2-mercaptoacetylimidazole)-3-alkylcarbamides had no relationship to their ability to inhibit cellular respiratory activity.


Quantum chemical studies on drug action V: Involvement of structure-activity, quantum chemical, and hydrophobicity factors in thrombocyte uptake of 5-hydroxytryptamine. Inhibition of the uptake of 5-hydroxytryptamine (serotonin) in the thrombocyte by various tryptamine derivatives was investigated. The activity depended on the nature and position of the substituent. This activity was correlated with the total orbital energy and hydrophobicity factors. Other quantum parameters, such as the highest occupied molecular orbital energy and the lowest empty molecular orbital energy, failed to correlate. The possible involvement of two receptor sites that are sterically and electronically dissimilar is postulated because compounds fell into two distinct groups. The hydrophobicity factor was important in only one group of compounds, while the electronic factor was important in both.


Coumarins XIV: high-resolution mass spectra of 3',4'-disubstituted 3',4'-dihydroseselins. High-resolution mass spectra of 14 3',4'-disubstituted 3',4'-dihydroseselins were examined. The nature of the substituents determinines the mode of fragmentation. Compounds having one or two acyloxy substituents fragment mainly by a pathway leading to the stable coumarinopyrilium ion. Coumarins with alkoxy or hydroxy substituents proceed by way of fission of the chroman ring, accompanied by the loss of two ring carbon atoms. Several generalizations are formulated which will aid in the interpretation of the mass spectra of this class of coumarins from a structural standpoint.


Pharmacokinetic studies of pentylenetetrazol in dogs. Pharmacokinetic profiles of pentylenetetrazol in the dog were studied following rapid intravenous and oral administrations of a convulsant dose (15-20 mg/kg). Plasma level-time curves after a rapid intravenous injection showed biexponential decline, indicating that the disposition of this drug in the dog follows a two-compartment body model. Pharmacokinetic parameters were calculated from the intravenous data. After oral administration of the solution dose, the peak plasma level appeared at about 30 min postdose, indicating that the absorption occurs rapidly. Areas under the oral plasma level-time curves s howed that the drug was absorbed completely and that the first-pass metabolism effect was minimal. The ligation studies of the kidney and the liver suggested that the main elimination pathway of this drug was biotransformation in the liver. The average plasma half-life was 1.4 hr. At steady state, the volume of distribution was approximately equivalent to the volume of the total body water.


Model systems for dissolution of finely divided (multisized) drug powders. Several reports have dealt with model systems for the dissolution of log-normally distributed powders. A numerical solution is presented for the previously published Higuchi-Hiestand equations for a log-normal particle-size distribution. This solution was realized via an application of the System 360 Continuous System Modeling Program (CSMP). The resulting computer-aided calculations were utilized in the comparisons between the Higuchi-Hiestand model and other existing models. These comparisons provided a basis for the development of an adaptation of the Nielsen moving sphere model for log-normally distributed powders. The adaptation of the Nielsen equation for multisized particle systems is suggested as being potentially useful for treating experimental data where hydrodynamic effects must be considered.


Binding characteristics of drugs to synthetic levodopa melanin. To define binding characteristics of drugs, levodopa melanin was prepared with the aid of mushroom tyrosinase. The binding of radiolabeled substances was studied with increasing concentrations of melanin in a fixed volume of potassium phosphate buffer (pH 7.4) at 37 degrees. The affinity and capacity of the drug binding were calculated according to Langmuir's adsorption isotherm. The affinity constant of various sympathomimetic amines such as (-)-amphetamine, (+)-amphetamine, (-)-ephedrine, (+/-)-octopamine, and (+)-norepinephrine ranged from 1.1 to 2.8 X 10(5) M-1. The binding capacity for the amines ranged from 1.4 to 3.2 X 10(-9) mole/mg. Although the capacity of (+/-)-cocaine for binding was similar to that of the amines, the affinity was slightly higher, 8.9 X 10(5) M-1. The binding of atropine to the synthetic melanin appeared to be a saturable process with the affinity and capacity values of 0.2 X 10(5) M-1 and 7.6 X 10(-9) mole/mg, respectively. Although the binding lacks stereoselectivity, the drugs vary in their capacity and affinity to bind with melanin. The observed differential pharmacological and toxicologic properties of drugs in the pigmented tissues may in part be related to their differential bi binding characteristics.


Hermetic packaging of drugs: optimized sealing of foil pouches. Factors affecting the sealing of foil packages were studied in the sealing of foil packages were studied in three laboratories. The relationship of sealing temperature (with machine speed and pressure kept constant) to the incidence of defective packages was determined. The maximum acceptable limit for defective pouches was 1%. Three tests were employed to detect defects: vacuum-dye, seal strength, and pressurized ammonia vapor. Only the last was sensitive enough to determine the optimum sealing conditions. This test also was capable of detecting leakage sites. Replacement of the cellophane layer of the foil laminate with polyvinylidene chloride-coated polyester improved the barrier properties of the package.


Comparison of observed and predicted first-pass metabolism of imipramine in humans. The first-pass metabolism of imipramine was calculated based on the dose, hepatic blood flow, and total area under the plasma-time curve after oral administration of 0.71 +/- 0.03 mg/kg of imipramine to four individuals suffering from mild depression. The predicted values of first-pass metabolism ranged from 37 to 68%, consistent with experimentally derived estimates.


High-pressure liquid chromatographic determination of acetaminophen in biological fluids. A method for the rapid estimation of free acetaminophen in biological fluids is described. The assay involves either extraction and high-pressure liquid chromatographic analysis on a 10-mum particle-size silica gel column, using a mobile phase of 10% chloroform in tetrahydrofuran. The procedure was used to determine acetaminophen levels in urine from two healthy volunteers who ingested 650 mg of 14C-acetaminophen (20 muCi), and the accuracy of the method was compared with the carbon-14 determination. The limit of detectability for acetaminophen is 1 mug/ml.


GLC determination of doxepin plasma levels. A procedure is described for extracting doxepin, a tricyclic antidepressant, from plasma and subsequently measuring its concentration by GLC. The developed technique permits the resolution and quantitative determination of the cis- and trans-isomers of doxepin as well as its desmethyl metabolite. The method allows precise, reliable measurement of the drug and one of its metabolities in concentrations as low as 10 ng/ml of plasma.


Calibration of a horizontal pendulum-type tablet breaking strength tester. A rapid, simplified method of checking the calibration of a new motorized pendulum type of tablet hardness tester and the accuracy and precision of three testers were determined. Two force gauges were calibrated, and both gauges were used by two operators to determine the accuracy of the new testers. The calibration method using the force gauge was reliable for checking the accuracy. The results show the various new testers to be in calibration and to give reproducible results.


Antimicrobial agents: synthesis and antimicrobial activity of new aryloxyalkyl esters of p-hydroxybenzoic acid. Several new aryloxyalkyl esters of p-hydroxybenzoic acid were synthesized and screened for in vitro antimicrobial activity. Although a few compounds showed low antifungal activity, many possessed appreciable in vitro antibacterial activity. However, none of these compounds was active against Mycobacterium tuberculosis (H37Rv).


Anti-inflammatory and antiproteolytic properties of 1-(1-naphthylacetyl)-3-substituted carbamides. Several 1-(1-naphthylacetyl)-3-substituted carbamides were synthesized, characterized, and evaluated for anti-inflammatory and antiproteolytic activity. The protection afforded by most of these carbamides against carrageenan-induced edema in rats at a dose of 100 mg/kg ranged from 4.4 to 50%. Some of these carbamides, which showed higher protection against carrageenan-induced edema, were further evaluated for their antigranulation effect against cotton pellet-induced granuloma formation in rats. All carbamides showed a poor degree of protection against granuloma formation. The antiproteolytic activity of these carbamides, as reflected by their ability to inhibit trypsin-induced hydrolysis of the bovine serum albumin, was of a low order and was unrelated to their anti-inflammatory activity.


Isolation of cannabisativine, an alkaloid, from Cannabis sativa L. root. An ethanol extract of the root of a Mexican variant of Cannabis sativa L.(marijuana) afforded, after partitioning and chromatography, the new spermidine alkaloid cannabisativine.


Synthesis and antibacterial and antifungal activities of alkyl and polyhalophenyl esters of benzo[b]-3-methyl-2-furancarbamic acid. Several alkyl and polyhalophenyl esters of benzo[b]-3-methyl-2-furancarbamic acid were prepared and tested for antifungal activity against Candida albicans, Penicillium notatum, and Aspergillus niger. The pentachlorophenyl ester was the most active substance and the only compound to show antibacterial activity against Staphylococcus aureus.


Simultaneous analysis of hydrocortisone and hydrocortisone phosphate by high-pressure liquid chromatography: reversed-phase, ion-pairing approach. The reversed-phase, ion-pairing approach to high-pressure liquid chromatography was applied to the simultaneous analysis of hydrocortisone and its phosphate ester in laboratory-prepared samples and injectable solutions. Results of this technique were evaluated and compared with results of the official procedure.


High-pressure liquid chromatographic determination of thiothixene in pharmaceutical formulations. A method was developed for the quantitative determination of thiothixene in pharmaceutical formulations by high-pressure liquid chromatography after dissolution of the sample in methanol.


Structural features and protective activity of dexamethasone and pregnenolone-16 alpha-carbonitrile. Pretreatment with dexamethasone acetate or pregnenolone-16 alpha-carbonitrile markedly diminished the pharmacological effect of zoxazolamine in rats. This prophylactic action was associated with significantly decreased plasma drug levels, which, in turn, were correlated with enhanced hepatic drug biotransformation, induced by the steroids. Dexamethasone proved to be more active than pregnenolone-16 alpha-carbonitrile in this respect. The A-ring conformation as well as the distances of O-3-O-11, O-11-O-17, and the O-3-mean plane C-5-C-17 may be key factors in glucocorticoid activity, and the longer the distances, the greater the potency. These characteristics have no bearing on catatoxic activity for which the 16 alpha-substituent appears to be a structural prerequisite.


Stability of vitamin C (ascorbic acid) in tablets. Stability of ascorbic acid (vitamin C) in various tablet formulations and the nature and extent of formation of decomposition products (dehydroascorbic acid, diketogulonic acid, and oxalic acid) were determined under normal conditions of storage and in simulated use tests. IR spectrophotometric, colorimetric, fluorometric, titrimetric, polarographic, and chromatographic methods were applied. Recent implications concerning the instability of ascorbic acid in tablets and the potentially harmful nature of the breakdown products are shown to be unfounded. Under normal storage conditions, commerical-type ascorbic acid tablets are stable for over 5 years (greater than 95% potency retention). The amounts of all three breakdown products formed under the various storage conditions constitute a small percentage of the ascorbic acid content and pose no dietary hazard. IR spectroscopy was inadequate as a quantitative method for evaluating ascorbic acid potency in tablet formulations. The official titration methods and TLC, colorimetric, and polarographic determinations correlate well and define accurately the stability of ascorbic acid in these dosage forms.


Combined assays for vitamins A, D (ergocalciferol), and E in multivitamin preparations with separation by reversed-phase partition chromatography. A rapid method was developed whereby vitamins A, D (ergocalciferol), and E in multivitamin products are measured in a common assay sample. The method depends on reversed-phase partition chromatography by which the vitamin alcohols are eluted in separate fractions from a column. Vitamins A and E are then determined by their UV absorption, while vitamin D is measured colorimetrically with an antimony trichloride reagent. The column consists of diatomaceous earth impregnated with dimethyl polysiloxane, with n-heptane as the immobile solvent, and 90% methanol followed by 95% methanol as the mobile solvents. Vitamins A and D elute in that order in the 90% methanol, and finally vitamin E elutes in the 95% methanol fraction. The method is widely applicable to various types of multivitamin and vitamin-mineral products including oil-based, water-based, and dry formulations.


Effect of inorganic additives on solutions of nonionic surfactants III: CMC's and surface properties. Continuing work on the interaction of inorganic additives with nonionic surfactants in aqueous solution dealt with their effect on the CMC and surface tension. The surfactants were octoxynol and polyoxyethylated oleyl alcohol, containing an average of 9.5 and 10 ethylene oxide units, respectively. Their CMC values were lowered by most electrolytes studied, representing salting out of the surfactants. The steepest reductions in the CMC were produced by the nitrates of sodium and potassium, which had been found to lower the cloud points of nonionic surfactants, salting them out because of the inability of their cations to form complexes with the ether oxygen linkages of the polyoxyethylene moieties. However, even electrolytes with cations such as hydrogen, lithium, calcium, nickel, lead, and aluminum capable of forming complexes with the ether oxygens, thereby increasing the cloud points of the surfactants, lowered their CMC values. In the presence of increasing concentrations of the latter electrolytes, the CMC values frequently went through minima and approached the CMC of the surfactant in the absence of additives. Increases in the CMC over the entire range of additive concentrations investigated were produced by cadmium nitrate for octoxynol, urea for polyoxyethylated oleyl alcohol, and magnesium nitrate for both. Net increases in the plateau or micellar surface tension of polyoxyethylated oleyl alcohol, i.e., in the constant surface tension of surfactant solutions above the CMC, were brought about by the nitrates of cadmium, aluminum, and magnesium at low concentrations only and by urea at all concentrations. This increase is interpreted as salting in. The area per surfactant molecule adsorbed at the air-water interface was reduced by all added electrolytes. Urea caused no such reduction.


Effect of inorganic additives on solutions of nonionic surfactants IV: Krafft points. Two polydisperse polyoxyethylated nonionic surfactants were found to possess Krafft points as well as cloud points. The significance of the Krafft point and the reason why it is rarely observed in nonionic surfactants are discussed. The values of the Krafft and cloud points of the two surfactants underwent only small changes as a function of surfactant concentration in the range of 0.5-7.5% (w/w). All electrolytes investigated, as well as urea, raised the Krafft points by between 1 and 4 degrees in the concentration range of 0.5-4 molal. Included were salting-in electrolytes, which raised the cloud points, as well as salting-out electrolytes, which lowered them. Electrolytes that salt out nonionic surfactants strongly may depress the cloud point to the Krafft point temperature, rendering a water-soluble surfactant insoluble in salt solutions at all temperatures.


Interactions of adenine, thymine, and uracil with epinephrine: UV studies. Based upon UV absorption studies, charge transfer complex formations by the nucleic acid bases adenine, thymine, and uracil with epinephrine were demonstrated. The pertient equilibrium constants were calculated by assuming 1:1 complexes using the Benesi-Hildebrand equation and were found to decrease in the following order: uracil-epinephrine greater than thymine-epinephrine greater than adenine-epinephrine. The values of delta G degrees, delta H degrees, and delta S degrees were calculated for the various interactions. Theoretical arguments are presented as to the possible stoichiometries of the various complexes existing in aqueous solutions. The electron-donating or electron-accepting abilities of the interacting molecular species are discussed.


Analysis of alkaloid mixtures by charge-transfer complexation. Binary mixtures of weak and strong UV-absorbing alkaloids were analyzed by a charge-transfer spectrophotometric method, utilizing iodine in ethylene dichloride as the acceptor. In the uncomplexed form, the strong absorbing alkaloid (papaverine, quinine, ergotamine, or reserpine) was measured at a wavelength where there was no interference from weak absorbers (at 335, 332, 315, or 300 nm, respectively). The weak absorbing alkaloid (ephedrine, codeine, atropine, or homatropine methylbromide) was determined by computing its contribution to the total charge-transfer band at 295 nm where absorbance was linearly additive for mixtures. The greater increase in the original epsilon-values of the weak absorbers upon complexation with iodine relative to the corresponding increase in the epsilon-values of the strong absorbers led to good recoveries even at the low dose ratios of the weakly absorbing, and often more potent, alkaloids.


Physical aspects of wet granulations I: distribution kinetics of water. The kinetics of wetting during the process of making tablet granulations were studied; the process progresses through an intermediate (overwetted) nonequilibrium granule to a final, equilibrated granule. In systematic formulation changes, there is an optimum composition from the point of view of hardness and content of equilibrium granules.


Comparative serum prednisone and prednisolone concentrations following prednisone or prednisolone administration to beagle dogs. The relative serum prednisone and prednisolone concentrations were determined following the administration of prednisone or prednisolone as 5-mg tablets to male beagle dogs. Serum prednisone concentrations were significantly greater following prednisone administration than they were following prednisolone administration. Serum prednisolone concentrations were significantly greater following treatment with prednisolone than with prednisone. The combined prednisone and prednisolone areas under the serum concentration-time curves were similar for the two treatments.


Rectification in the smooth muscle cell membrane of rabbit aorta. 1. The current-voltage relation of the smooth muscle cell membrane of rabbit aorta was determined by the partition method. 2. No anomalous rectification was observed in any of the following solutions: normal Krebs, Na free choline, Na sulphate, and high K-Na free sulphate. 3. Delayed rectification was seen on application of depolarizing current in both normal Krebs solution and Na free choline solution. 4. High concentration of K made the steady-state current-voltage relation almost linear in a voltage range of about 0 to -20mV. This effect, and steady-state cathodal rectification which was seen in physiological solution, could be explained qualitatively by constant field theory without involving channels capable of anomalous rectification. 5. A slow decrease in K conductance, during application of large and long-lasting hyperpolarizing currents, which occurs in skeletal muscle and is attributed to the tubule system, was never observed in the arteries either in Krebs, Na-free choline, or Na sulphate solution.


A quantitative description of end-plate currents in the presence of two lidocaine derivatives. 1. Possible ways in which local anaesthetics may act to produce their characteristic alterations of end-plate current (e.p.c.s) are considered. 2. Following Magleby & Stevens (1972b), it is proposed that when acetylcholine (ACh) binds to its end-plate receptor it induces a conformational change which causes an increased ionic permeability and, thus, the measured e.p.c.; the reverse conformational change which returns the permeability to its resting state is postulated to be the rate-limiting event for e.p.c. decay whether or not local anaesthetics are present. Moreover, it is proposed that the ACh receptor had multiple binding sites and the local anaesthetics can bind to one or more of these sites thereby altering the conformational changes induced when ACh binds to remaining sites. 3. Equations based on this proposal are developed and are shown to provide an accurate description of the entire e.p.c. time couse as modified by eith QX-222 or QX-314. 4. Other models are also discussed; models in which local anaesthetic molecules bind only after receptor activation appear to be ruled out.


Analysis of spontaneous activity of auditory neurones in the spiral ganglion of the guinea-pig cochlea. 1. Spontaneous activity of single afferent neurones in the cochlea of the guinea-pig was studied by measurement of mean rates and computation of interspike interval histograms. 2. The shapes of interval histograms agreed with those found in cat cochlear nerve fibres. Modes of the histograms were less than 7 msec for all cells with mean rates ranging from 20 to 150 spikes/sec. 3. The distribution of mean rates showed higher maximum rates than those found in cat. Cells from animals with abnormally high thresholds showed lower mean rates than those from sensitive animals. 4. No correlation was found between mean spontaneous rate and sensitivity to acoustic stimulation. No discrete populations of cells could be discerned on any of the criteria used. 5. The simultaneous effects of hypoxia on cell thresholds, mean spontaneous rate and scala media potentials are reported. These and other results are discussed in relation to possible sites of generation of spontaneous activity in primary auditory afferents.


Vasodepressor effects obtained by drugs acting on the ventral surface of the brain stem. 1. In cats anaesthetized with I.P. pentobarbitone sodium and atropinized with intravenous atropine methyl nitrate, the effects on arterial blood pressure were examined of nicotine, physostigmine, carbachol, glycine and pentobarbitone sodium applied to the exposed ventral surface of the brain stem by means of paired Perspex rings placed across the medulla. The drugs were placed inside each ring in a volume of 10mul. 2. Nicotine (0-5-6mg/ml.) produced a fall in blood pressure when the upper limit of the areas covered by the rings was about 5-6 mm caudal, but not when it was just caudal to the trapezoid bodies. The depressor effect was obtained both on bilateral and unilateral application. After application the nicotine sensitive area became for several minutes insensitive to its renewed application. 3. The depressor effect of nicotine was sensitive to hexamethonium (50 mg/ml.) but resistant to atropine (50 mg/ml.) similarly applied. 4. When the nicotine sensitive areas had become insensitive to nicotine, bilateral carotid occulusion produced its normal sustained pressor response. 5. By applying the nicotine through a single Perspex ring which could be moved stepwise along and across the medulla, the nicotine sensitive area was localized and the highest sensitivity was found in a region around and a little caudal to the rootlets of the XIIth cranial nerve. 6. Physostigmine (25 and 50 mg/ml.) and carbachol (6 mg/ml.) produced a fall in blood pressure when the uppermost limits of the areas covered by the paired rings were 5-6 mm caudal to and also when they were just caudal to the trapezoid bodies. From both regions the effects were obtained on bilateral and unilateral application. Their depressor effects were sensitive to atropine but resistant to hexamethonium similarly applied. 7. Glycine (200 mg/ml.) and pentobarbitone sodium (100 mg/ml.) produced scarcely any blood pressure effects when applied bilaterally to the nicotine sensitive areas but produced strong depressor effects on more rostral application, i.e. when the uppermost limit of the areas covered by the rings were just caudal to the trapezoid bodies. 8. It is concluded that the ventral surface of the medulla contains at least two bilateral areas from which vasodepressor effects are obtained on topical application of drugs: a more caudally situated one which is sensitive to nicotine, but insensitive to glycine and pentobarbitone sodium; a more rostrally situated one which is insensitive to nicotine but sensitive to glycine and pentobarbitone sodium; and both areas are sensitive to carbachol and physostigmine.


The effect of temperature on potassium chloride contracture in cat myocardium. 1. Contracture was induced in cat myocardium by exposure to 140 mM-KC1 In isotonic Tyrode solution. Force of contracture expressed as mg/mm2 (muscle cross-sectional area) falls with increasing cross-sectional area. 2. The effect of temperature on isometric force developed during contracture was evaluated both in normal (untreated) atrial and ventricular muscle and following treatment with sympatholytic drugs. 3. The force of contracture was not significantly affected by sympatholytic drugs at 36 degrees C. 4. In normal atrial and ventricular muscle, force of contracture decreased when the muscle was cooled from 36 to either 29 or 20 degrees C. 5. In atrial muscle, the effect of temperature was not changed by sympatholytic drugs. In contrast, exposure to sympatholytic drugs increased contracture force developed by ventricular muscle at 20 degrees C. Also, contracture force was significantly greater at 20 than at 36 degrees C in ventricular muscle from reserpine-pretreated cats. 6. It is suggested that ventricular muscle becomes more sensitive to the relaxing effects of endogenous catecholamines at temperature is lowered. 7. The differences shown between atrial and ventricular muscle with respect to the effect of temperature and sympatholytic drugs on contracture force may result from the differing amounts of sarcoplasmic reticulum found in these types of cardiac muscle and also from different mechanisms of "excitation-contracture" coupling in atrial and ventricular muscle.


Active sodium uptake by the skin of foetal sheep and pigs. 1. Simultaneous measurements of unidirectional sodium fluxes across foetal skin incubated in vitro with identical solutions ([Na] = 150 mM) bathing either side showed a flux ratio (influx/efflux) of 1-40+/-0-08 in twenty-seven sheep skins, which was significantly different from unity (P less than 0-001). The gestational ages ranged from 47 to 98 days (term = 147 days). Similar experiments on eight foetal pig skins at 58 days gestation (term = 114-118 days) gave a mean flux ratio of 1-10 +/- 0-03 (P less than 0-02). 2. Unidirectional sodium fluxes measured with dilute Ringer solution on the outside (mucosal) surface ([Na]0 = 100mM) gave influx to efflux ratios of 0-86 +/- 0-09 in seventeen sheep (P less than 0-05) and 1-07 +/- 0-26 in five foetal pigs; the value predicted for passive movement was 0-67. 3. Incubation with inhibitors, ouabain (10-4 M) or dinitrophenol (DNP) (10-4 M) gave a flux ratio for sodium which was not significantly different from unity in the absence of a gradient, or from 0-67 when the concentration gradient was applied. 4. Sequential measurement of unidirectional diffusional fluxes of tritiated water across foetal skin gave flux ratios of 0-98 +/- 0-02 in six sheep skins and 1-06 +/- 0-11 for four pig skins in control conditions. When the outside solution was diluted to give an osmotic gradient of 100 m-osmole. kg-1 across the skin a flux ratio of 0-95 +/- 0-07 was obtained for seven sheep and was not measured in pig skin. Hormones and inhibitors had no effect on the diffusional flux ratio for water in the presence or absence of an osmotic gradient. 5. Lysine vasopressin (ADH) (200 mu./ml.) increased influx and efflux of water in the presence and, to a lesser extent in the absence of an osmotic gradient in sheep skin. In pig skin prolactin (1 u./ml.) increased both influx and efflux, but ADH had no effect on diffusional water fluxes. 6. ADH increased sodium influx in sheep skin slightly but vasotocin (5-5 mu./ml.) was more potent, particularly in the presence of an opposing diffusion gradient. Vasotocin (55 mu./ml.) reduced sodium influx in pig skin ADH had no effect on influx or efflux and prolactin reduced sodium influx and efflux. Ouabain and DNP generally reduced permeability to both sodium and water in sheep skin but had no effect in pig skin.


The effect of hormones and of an osmotic gradient on the structure and properties of mammalian foetal urinary bladder in vitro. 1. Water and isotope fluxes were measured by incubating urinary bladders of foetal pigs and sheep in vitro in the presence and absence of a concentration and osmotic gradient. The structure of the urinary bladder of foetal pigs under various conditions was studied by electron microscopy. Its ultrastructure was found to be closely similar to that of foetal sheep. 2. Antidiuretic hormone (ADH) (0-2 U. ml-1) enhanced the enlargement of intercellular spaces caused by dilute mucosal medium in pig bladders; prolactin (1 u. ml-1) prevented osmotic dilatation of the intercellular spaces. 3. The hydraulic conductivity, Lp, was estimated to be 0-5 X 10 (-7) cm.s-1atm-1 in sheep and pigs at about 100 days gestation; the ratio of osomotic to diffusional permeability, (LpRT/VW)/PD, in the presence and absence of ADH, was 2-1 and 1-6 respectively. These are similar to the values found in fish gills. 4. Prolactin reduced bulk flow of water to zero in seven out of eight bladders investigated. Incubation with ADH or vasotocin (55 mu. ml-1) in the presence of prolactin restored water flux to 22% and 45% of control values respectively. 5. There was no significant net flux of sodium from mucosa to serosa in pig bladder except in the presence of prolactin. No net flux of sodium occurred from mucosal to serosal side of pig or sheep bladders in the presence of an adverse electrochemical gradient, although in sheep the permeability ratio was significantly greater than one. 6. The diffusional flux ratio for water remained unity under all conditions; vasotocin increased unidirectional fluxes and prolactin reduced them. The flux ratios were unaffected by the direction of bulk fluid flow, probably because diffusion was rapid compared to flow: the ratio of diffusional flux to volume flow was between 11 and 18.


Location of stretch receptors in the trachea and bronchi of the dog. 1. Using single fibre vagal afferent recording techniques, we have investigated the longitudinal and circumferential location of slowly adapting stretch receptors in a functionally isolated, in situ segment of the trachea in dogs. 2. We have also studied the depth of these receptors within the airway wall and their response to reflex and drug induced contraction of the airway smooth muscle. 3. Thirty-four per cent of the receptors studied were in the extrathoracic trachea; calculations indicate that about 17-1% of all airway stretch receptors lie outside the thorax. 4. All the receptors were located in the membranous posterior wall of the trachea, and those tested responded more to transverse than to longitudinal stretching of the wall. 5. Receptors in the extrathoracic trachea continued to function after the regional mucosa had been widely resected; subsequent removal of histolocially proven smooth muscle tissue caused the abrupt cessation of receptor discharge. 6. Contraction of airway smooth muscle brought about an increase in receptor discharge frequency. 7. Similar results were found for a smaller number of stretch receptors located in the mainstem and lobar bronchi. 8. These findings procided evidence that stretch receptors are anatomically located within the smooth muscle layer of the airways and are functionally aranged in series with the muscle fibres.


Transduction properties of tracheal stretch receptors. 1. Using single fibre vagal afferent recording, we have studied the behavior of slowly adapting stretch receptors located in an isolated, in situ, segment of the trachea in dogs. Responses to positive and negative steady and oscillating transmural pressures were investigated. 2. Seventy-eight per cent of the receptors studied were tonically active at resting tracheal volume. Ninety per cent showed a more pronounced response to positive than to negative transmural pressures. 3. During pressure oscillations the majority of the receptors had a higher discharge frequency at any given pressure during the ascending phase of the pressure wave than at the same pressure under static conditions. During most of the ensuing descent of pressure toward zero the discharge frequency led transmural pressure. 4. With increasing frequency of oscillation the differences from the static responses increased (dP/dt sensitivity), especially during the ascending limb of the pressure oscillation (rectifying behavior). 5. In a small number of receptors, discharge frequency lagged behind transmural pressure or was in phase with it ("no loop" pattern). 6. In three cases the same receptor exhibited dP/dt sensitivity during positive pressure oscillations, whereas discharge frequency lagged behind pressure during negative pressure oscillations. This indicates that the lack of dP/dt sensitivity exhibited under negative pressure conditions does not represent an intrinsic property of these receptors, but reflects some aspect of their mechanical arrangement within the airway wall. 7. THESE PATTERNS OF RESPONSE ARE DISCUSSed in terms of intrinsic and extrinsic characteristics of the receptors. 8. The physiological implications  of stretch receptor behaviour are also considered.


Release of peptide hydrolases during incubation of intact intestinal segments in vitro. 1. Rat intestinal segments have been incubated in isotonic saline in vitro and release of peptide hydrolase enzymes into the incubation media examined over a 90 min study period. 2. Chemical assay data, as well as analysis of electrophoretic mobilities of release enzymes on starch gel, indicate that peptide hydrolase enzymes in the incubation media originate predominantly from the cytoplasm of the mucosal cells. 3. Peptide hydrolases were released rapidly from intact intestinal segments. Release occurred from the start of the in vitro incubations and was not affected by temperature and shaking. 4. It is concluded that compared to the in vivo situation, cytoplasmic peptide hydrolases are released from intestinal tissue very rapidly in vitro. Caution is therefore required when comparing results of in vivo and in vitro peptide absorption experiments.


Sites of autoregulatory escape of blood flow in the mesenteric vascular bed. 1. Stimulation of the sympathetic nerves to the intestinal vascular bed results in an initial decrease in blood flow followed by a recovery towards the control level. This recovery was termed autoregulatory escape by Folkow and his co-workers and they suggested it was associated with a redistribution of blood flow within the intestinal wall. This theory has been examined in cats anaesthetized with pentobarbitone sodium. 2. The sympathetic nerves to the intestinal vascular bed were stimulated for 4 min periods at a submaximal frequency (4 Hz). The blood flows to individual parts of the superior mesenteric arterial bed (whole intestine, mucosal and submucosal layer, muscle layer of intestine, mesentery and lymph nodes, appendix and colon) were measured using radioactive microspheres before, at the peak of the vasoconstriction (30 sec), after autoregulatory escape had occurred (3-5 min) and during the hyperaemia after cessation of nerve stimulation. 3. All parts of the mesenteric vascular bed showed a significant initial vasoconstriction followed by a recovery in the flow to a level not significantly different from the pre-stimulation control flow. All parts showed a significant hyperaemia after cessation of stimulation. The distribution of the superior mesenteric flow at the peak of the vasoconstriction, after autoregulatory escape had occurred and during the hyperaemia after cessation of nerve stimulation was not significantly different from that during the control period. 4. It is concluded that all parts of the mesenteric vascular bed show autoregulatory escape and that this phenomenon is not associated with a redistribution of blood flow within the intestinal wall. Autoregulatory escape must involve relaxation of the same vessels which were originally constricted and various theories on the mechanism of the escape are discussed.


Functional and structural changes in mammalian sympathetic neurones following colchicine application to post-ganglionic nerves. 1. The effects of post-ganglionic colchicine application on neurones of the guinea-pig superior cervical ganglion were studied with intracellular recording and electron microscopy. 2. Local colchicine application for 30 min to one of the major post-ganglionic nerves caused several electrophysiological changes after 4-7 days in many neurones whose axons run in this nerve. These changes include: (a) a reduction in the amplitude of synaptic potentials elicited by supramaximal preganglionic stimulation; (b) a decrease in the number of preganglionic fibres innervating individual neurones; (c) the development of regenerative responses in dendrites; and (d) the failure of antidromic action potentials to fully invade the neuronal soma. These functional changes occurred in the absence of impaired impulse conduction or axon degeneration, and were not observed in nearby neurones whose axons ran in an untreated post-ganglionic nerve. The effects of colchicine are similar to the changes produced by axotomy. 3. Counts of synapses in thin sections from the region of the ganglion where the affected neurones were located showed a reduction, compared to the number of synapses in other regions of the colchicine treated ganglia, or normal control ganglia. This finding indicates that synaptic depression after colchicine treatment, like that after axotomy, is due primarily to a loss of synaptic contacts from the dendrites of affected nerve cells. Unusual profiles containing numerous vesicular and tubular organelles frequently seen after interruption of the axons were also observed in thin sections after colchicine treatment. 4. The similarity of the electrophysiological and ultrastructural effects of colchicine treatment and axon interruption offers further support for the view that synaptic contacts on sympathetic neurones are normally regulated by an interaction of the neuronal soma with its axonal extension to the periphery.


Activation of two types of fibres in rat extraocular muscles. 1. The contractile responses of the inferior rectus, one of the extraocular muscles of the rat, to a depolarization induced by an elevation of the potassium concentration in the external medium ([K]O) have been studied 'in vitro'. 2. The elevation of [K]O to 20 and 30 mM-K produced contractures that consisted of a sustained or tonic tension. When [K]O was increased to 50 mM or more a well-defined transient or phasic tension appeared before the tonic response. The increment of [K]O above 50 mM enhanced the phasic component and depressed the tonic tension. The maximal tonic tension, usually evoked by 50 mM-K, is about 50% of the tetanic tension, shows a gradual decline with time and lasts for hours. Control experiments performed in diaphragm showed that this muscle only responds with phasic tensions. 3. The difference in the repriming of the phasic and tonic responses when tensions were induced with salines containing low or normal [Cl] suggests that the muscle fibres responsible for the tonic tension are poorly permeable to Cl-. 4. The amplitude of the tonic tension was reduced by Ca deprivation and by an elevation of [Ca] in the saline to 10 mM. 5. It is concluded that in rat extraocular muscles, an increase in [K]O activates two types of muscle fibres: singly and multiply innervated. These appear to be functionally equivalent to the twitch and slow fibres of amphibian and avian muscle and would give rise to the phasic and tonic components of the contracture, respectively.


Regulation of cerebrospinal fluid potassium by the cat choroid plexus. 1. The regulation of cerebrospinal fluid (c.s.f.) potassium concentration was studied using the cat choroid plexus isolated in a chamber in situ. 2. Hyperkalaemia (plasma potassium concentration greater than 6 m-equiv/l.) caused relatively small increases in c.s.f. potassium concentration. 3. Alterations in c.s.f. potassium concentration (c.s.f. K = 0-15 or 6-56 m-equiv/l.) were countered by changes in potassium concentration of the produced fluid or in the rate of potassium transport which returned c.s.f. potassium towards normal. 4. The data indicate that potassium concentration in c.s.f. secreted by the choroid plexus is actively regulated by the plexus whether the primary alteration in potassium occurs in plasma or c.s.f.


Reflex activation of sympathetic pathways to vesical smooth muscle and parasympathetic ganglia by electrical stimulation of vesical afferents. 1. Activation of the sympathetic input to the urinary bladder by electrical stimulation of afferent fibres in the pelvic nerve evoked three responses: (1) an initial transient rise in intravesical pressure, (2) an inhibition of neurally evoked bladder contractions and (3) an inhibition of transmission in vesical parasympathetic ganglia. Similar responses were elicited by stimulation of the hypogastric nerve. 2. The reflex responses were observed in acute spinal preparations (T10-T12) and in cats with intact spinal cords, but were abolished by bilateral transection of the hypogastric nerves. 3. The inhibition of bladder contractions was antagonized by the administration of propranolol (200-400 mug, I.A.), a beta-adrenergic blocking agent. The inhibition of ganglionic transmission was antagonized by dihydroergotamine (30-75 mug, I.A.), an alpha-adrenergic blocking agent. The initial rise in intravesical pressure was not antagonized by either agent. 4. Electrical stimulation of other afferents (carotid sinus nerve and sciatic nerve) did not consistently elicit responses in the urinary bladder. However, stimulation of these afferents as well as pelvic nerve afferents evoked reflex firing in nerve filaments on the surface of the urinary bladder. The firing was abolished by transection of the ipsilateral hypogastric nerve. 5. It is concluded that stimulation of vesical afferents activates a spinal sympathetic reflex which results in closing of the internal urethral sphincter and a depression of bladder activity. The latter occurs by a direct depression of detrusor smooth muscle as well as a block of the neural input to the bladder. This vesico-sympathetic reflex represents a negative feed-back mechanism which may have an important role in the maintenance of urinary continence.


Dynamic properties of the responses of single neurones in the cochlear nucleus of the rat. 1. The dynamic properties of unit responses to amplitude-modulated tones were studied using modulation with pseudorandom noise and described by cross-covariance and integrated cross-covariance functions between the discharge rate and the modulation. Under the experimental conditions used, these two functions are valid approximations of the system's impulse and step response functions respectively. 2. On the basis of their impulse response functions units could be classified into two groups, Type I with a low adaptation and Type II with a large degree of adaptation as well as a damped oscillation in their impulse response functions. 3. The response pattern of the Type II units is most likely the result of a negative feed-back striving to keep the discharge rate at a nearly constant level. 4. The cross-covariance functions are shown to remain unchanged during long duration recordings from the same unit.


Evidence for genetic control of glycine uptake in cultured cells, regulated by the amino acid concentration of the growth medium. 1. Cultured cells were grown in various concentrations of amino acids for periods up to 3 days and the characteristics of the glycine transport system measured under fixed experimental conditions. During this time, the effect of enucleation, using cytochalasin B, and the effects of protein synthesis inhibitors (cycloheximide and actinomycin D) were investigated. 2. Glycine influx is regulated by the prior growth concentration of similarly transported amino acids. 3. The modification in transport involves primarily a change in Vmax (but also a change in Km in HeLa cells) and is effected within 2-10 hr after media change. Increased transport activity is calculated to be sufficient to compensate for the reduction in extracellular amino acid concentration, so that nearly normal influx values from media are maintained. Regulation over the range of concentrations studied is shown to be very accurate. 4. The nucleus is essential for the regulatory mechanism to function. It seems probable that mRNA synthesis is required for acquisition of increased transport activity and mRNA translation required for maintenance of normal activity. 5. The controlling factor in the regulatory mechanism appears unlikely to be intracellular pool size. Other possible signals are discussed.


Sensitivity of renin secretion to volume depletion in the anaesthetized dog: comparison between urinary drainage and slow haemorrhage. 1. An experimental technique utilizing 'denervation diuresis' from one kidney with measurement of renin release from the contralateral innervated kidney was developed to study the sensitivity of renin secretion to volume depletion. 2. With urine excretion, release of renin increased progressively from the innervated kidney. The increase was significant at a sodium deficit of 0-23 mole.kg-1. At a sodium deficit of 0-6 m-mole.kg-1 renin release had doubled. 3. Bilateral vagotomy did not alter this response. 4. Precise replacement of sodium loss with isotonic saline but without replacement of other urinary components returned renin release to control levels. 5. Slow haemorrhage causing a rate of volume and sodium loss equivalent to urinary drainage did not alter the rate of renin release. 6. With a single denervated kidney and contralateral nephrectomy, renin release fell progressively to minimal levels despite sodium deficits up to 2-6 m-mole.kg-1. 7. It is concluded that renin secretion is sensitive to at most a 0-5% change in body fluid volume and should be considered a primary response to volume depletion. The sensitivity of the response depends upon normal renal innervation but is not mediated via vascular volume receptors nor via receptors innervated by the vagus. 8. It is proposed that the extreme sensitivity of the renin-secreting system in these experiments results from the combination of volume depletion and slight hypotonicity of extracellular fluid acting on the renal afferent arteriole without the mediation of the macula densa,


Relationships between the spike components and the delayed depolarization in cat spinal neurones. 1. Changes in the delayed depolarization (DD) following composite (IS-SD) intracellular spikes in motoneurones and neurones of the ventral spinocerebellar tract were recorded in a variety of experimental conditions. Cell activation was either antidromic or by direct intracellular stimulation. 2. It was observed that under all conditions in which IS-SD coupling changes took place (as a consequence of spontaneous fluctuations, membrane conductance variations, variations of direct-stimulation parameters, changes in steady membrane polarization), SD spike delays were always accompanied by a progressive concomitant reduction of the DD depolarizing hump amplitude. 3. Under the same conditions the latency of the DD peak from the stimulus artifact remained constant. Accordingly, any increase of the SD delay was accompanied by a reciprocal reduction of the time interval between the SD spike and the DD peak. This variability of temporal relationships between SD spike and DD would appear to contradict the hypothesis that the DD might represent the image of the excitation spreading from the soma to the dendrites (Kernell, 1964; Nelson & Burke, 1967). 4. as the gradual reduction of the DD hump progressed, the time course of the decay phase of the afterhyperpotential more and more closely approximated the decay phase of the IS spike. As an alternative hypothesis it is suggested that the DD might originate from the current which generates the IS spike.


Unit responses in the medulla oblongata of rabbit to changes in local and cutaneous temperature. 1. In anaesthetized rabbits which were stereotaxically implanted with a thermode following decerebellation, thermal sensitivity of neurones in the medulla oblongata to local temperature changes was examined systematically. The medullary temperature was changed by circulating water at various temperatures through the thermode. 2. Eighty-seven temperature-responsive neurones were found in the medulla, especially in the medullary reticular formation. Out of these eighty-seven, forty-eight neurones were cold-responsive neurones, while the rest were warm-responsive. Both types of neurones included not only neurones with linear or continuous relations between discharge rate and local temperature but also neurones with non-linear or discontinuous thermoresponse curves. 3. In the medulla a few of the temperature-responsive neurones showed a dynamic reaction with static discharge rate changes to changes of local temperature. 4. Seven neurones out of the fifteen respiratory neurones encountered during the exploration had thermal sensitivity to respiratory alteration of the discharge. 5. with thermal stimulation of a limited area of the skin, over 50% of the temperature-responsive neurones recorded in the medulla responded positively or negatively to changes in the skin temperature.


Strain sensitivity and directionality in cat atrial mechanoreceptors in vitro. 1. Afferent discharges from single atrial mechanoreceptors were studied in vitro in isolated, perfused cat hearts, by balloon inflation and by localized endocardial stretching with step and ramp wave forms. 2. Receptor excitability could be maintained for several hours with perfusion, but failed reversibly within a half hour without it. 3. Responses to pure step stimuli were purely phasic, adapting within a few seconds as negative fractional powers of time. Ramp responses showed corresponding behaviour; 4. Median discharge sensitivities were 12 Hz ml.-1 for step balloon inflation and 110 Hz strain-1 for step local stretching, so that 1 ml. balloon expansion was equivalent to 10% local stretch. 5. Ramp stimulation indicated two distinct receptor groups, a 'high-pass latency' (HPL) group for which threshold decreased with increasing ramp velocity, and a larger 'low-pass latency' (LPL) group with the opposite behaviour. 6. The endocardial deformation due to local stretching comprised about half simple extension and half shear, so that half the effective lineal stretch would occur in end filaments oriented within 20 degrees of the stretch axis. 7. Of five receptors tested for directionality by local stretching in two perpendicular directions, four showed significant directionality in step sensitivity and/or ramp response latency, indicating the capability of receptive fields to encode changes in endocardial shape.


An octopus toxin, maculotoxin, selectively blocks sodium current in squid axons. 1. A low molecular weight, stable, cationic neurotoxin (maculotoxin, MTX) extracted from the posterior salivary glands of the octopus Hapalochlaena maculosa, blocked sodium current in voltage-clamped squid axons without affecting potassium current. 2. The effectiveness of MTX was increased by repetitive, brief, depolarizing pulses but not by a single prolonged depolarization. 3. The potency of MTX decreased at pHs from 8 to 9. Effectiveness could be restored be restored by lowering the pH to 7-1 again. It was concluded that MTX is active in its cationic form. 4. MTX affected sodium conductance kinetics, slowing the turn-on of sodium current. This effect was most noticeable with small deploarizations but became progressively less with larger depolarizations. Neither the turn-off of sodium current nor sodium inactivation kinetics were affected by the toxin. 5. MTX inhibited sodium current without inhibiting sodium gating current. 6. The effectiveness of MTX was not detectably changed when calcium concentration was varied from 50 to 10 mM, or sodium concentration was varied from 225 to 750 mM.


The dark adaptation curve of rods measured by their after-image. 1. The common dark adaptation curve exhibits two branches; the course of the rod branch cannot normally be measured at early times since it lies above the observed cone thresholds. In this paper we measure it. 2. this is done by observing the negative after-image against a uniform background critically adjusted in luminance. 3. adjacent to the bleached area to be studied is a second area more strongly bleached. If the background intensity is below threshold for the less bleached area it will not be seen there; but if the background is above that threshold, this area will be seen brighter than the other. 4. the dark adapted threshold on the less bleached area is therefore the background luminance which just permits the two areas to be distinguished in the after-image. 5. after 5 min cones have quite recovered, and thus have no after-image to contaminate the rod image. 6. the rod curve measured by after-image is traced over 5 units of log threshold: it is an exponential with half life of 4.5 min, and coincides with the time course of regeneration of rhodopsin in man.


Inhibition of food intake in the rat following complete absorption of glucose delivered into the stomach, intestine or liver. 1. Solutions of glucose or other carbohydrates were administered during the dark or light period of the circadian cycle to rats which had been only briefly deprived of food. 2. food was restored to the animals at various times after administration of a glucose load by stomach tube. With delays between loading and access to food of up to 3 hr by night and 2 hr by day, subsequent food intake was less than intake after non-nutritive loads. 3. measurement of the glucose content of the gastrointestinal tract at various times after glucose loading showed that this depression of intake was still apparent even when the rat was offered food some time after complete absorption of the stomach load. 4. infusion of a glucose solution into the duodenum or the hepatic protal vein also inhibited subsequent food intake. 5. in all cases, the inhibition of food intake was expressed as a decrease in the size of the first meal after restoring access to food. 6. these results provide the first demonstration that the entry of normal amounts of carbohydrate into the body by the physiological route is followed by depression of food intake which lasts until after absorption is complete.