[Positive end-exspiratory pressure for the treatment of respiratory distress syndrome with indirect increase of pressure. Clinical experience with the Pulmarca box (author's transl)]. Harrison could demonstrate the benefit of exspiratory grunting in respiratory distress syndrome. Probably it delays alveolar collapse and promotes gasexchange. Since the publication of Gregory different methods for therapeutic use were practised. Our report deals with own investigations with continous negative chest wall pressure (CNP). Effect, indication and complications are discussed especially.


[Disturbances of cardiac rhythm in neonates and infants (author's transl)]. The authors report on the kinds and frequency of cardiac rhythm disturbances observed in neonates and young infants at the University Children's Hospital of Innsbruck within the past 3 years. Four children who were already in utero suspected to have arrhythmia are dealt with in greater detail. The etiology and pathogenesis of rhythm disturbances are briefly outlined and the therapeutic measures summarized.


[The plasma-protein-binding of Clindamycin Cephazolin and Cephradin in neonates and adults (author's transl)]. In pooled serum of 12 healthy adults and 12 neonates (blood taken from the umbilical cord) the free and protein-bound parts of Cephazolin, Cephradin and Clindamycin were tested by equilibrium dialysis in relation to the concentration of the antibiotic. In the serum of adults at a concentration of  36 mcg/ml the free part of Cephazolin amounted to 16%, at a concentration of 35 mcg/ml the free Cephradin was 87%, at a concentration of 97 mcg/ml the free Clindamycin was 16%. The binding constant k of Cephazolin was 12.0 (rise-constant 0.58), of Cephradin 0.26 and of Clindamycin 15.8 (rise-constant 0.58). When concentration of antibiotics rose, the free part of Clindamycin and Cephazolin increased more than with Cephradin. At a concentration of 30--42 mcg/ml the differences between the sera of adults and neonates were 26.4% with Cephazolin, 3.7% with Cephradin and 3.1% with Clindamycin (concentration 92--97 mcg/ml). In neonates the free part of Cephazolin was 43%, of Clindamycin 19% and of Cephradin 90%. The lower ablumin content in serum of neonates (3.7 g%) does not altogether explain the reduced protein-binding. In neonates a different affinity for binding has to be assumed.


[Congenital defect of the scalp in 4 generations (author's transl)]. In the parietal region of a newborn male child, two skin lesions are found. An according sceletal defect could not be proved. These skin lesions are well known in the family of the mother. In the last three generations one member of the family showed those defects. A survey of literature gives more than 20 reports concerning these lesions in families, reporting cases where brothers and sisters are concerned up to three generations, and several cases where the underlying bone is concerned too.


[The differential diagnosis of the Meckel syndrome and the Ellis-van-Creveld syndrome with encephalocele (author's transl)]. The differential diagnosis of Meckel's syndrome and Ellis-van-Creveld's syndrome with encephalocele is summarized utilizing two own observations. Radiographic criteria are of special importance. In EvCS typical signs of chondrodysplasia are present whereas in MS we found pelvic changes similar to Down's syndrome and striking rhomboid deformities of the tibiae. Clinically relevant is ectodermal dyplasia in EvCS, especially, when cystic kidneys in MS are not palpable.


[Allergic alveolitis due to inhalation of avian proteins (author's transl)]. Allergic alveolitis is the immunologic response of the alveolar wall and the interstitial spaces of lung to inhalation of different organic, antigenic substances. This paper presents the case of a 12 1/2-year old girl with a pulmonary disease caused by inhalation of protein contained in the excrement dust from budgerigars. In the paat few years several reports already described this disease in breeders of pigeons and budgerigars. During some years our patient had recurrent episodes of a subacute illness with severe cough, dysponea, cyanosis of lips, tachycardia, and weakness. Auscultation showed only discrete crepitant rales at both lung bases. In contrast the chest roentgenogram demonstrated marked changes with soft fine patchy densities and reticulation dispersed through the lung parenchyma. The histological examination of lung biopsy showed a thickening of alveolar walls and of interstitial spaces with lymphocytic infiltration, fibrosis, and multinuclear giant cells. In accordance with this findings pulmonary function tests revealed a restriction and a decrease in diffusing capacity; furthermore there was a middle-grade obstruction. The presence of precipitating antibodies in the serum against extracts of excrements from budgerigars confirmed the relation between pulmonary disease and domestic allergen. Our experience indicates that perferential therapy is the avoidance of contact with birds.


[Osteopoikilia with dermofibrosis lenticularis disseminata (Buschke-Ollendorf syndrome) (author's transl)]. In a family, we have observed through 3 generations a Buschke-Ollendorf syndrome. All 12 children and grandchildren, descendants from actually 59 year old grandmother were examined. 8 probands had a osteopoikilia, 5 of them as the grandmother had a dermatofibrosis lentcularis disseminata. The Buschke-Ollendorf syndrome is not really a syndrome in his strong sense, rather a variant of osteopoikilia with participation of skin.


[Treatment and results in necrotizing enterocolitis in infancy (author's transl)]. 29 children aged between 1 day and 22 months were treated for enteritis with complications. 2 children were cured conservatively. In 27 cases surgery was needed; of these 13 children survived. In 19 patients bacteria were found in the stools. Operation was indicated when there was diffuse peritonitis or when perforation could be shown radiologically. In cases of intestinal perforation the following technique was used in the last few years: 1. resection of the segment involved and ileoor colostomy. 2. Anastomosis and closure of colostomy 4--6 weeks later. Among 29 children with necrotizing enterocolitis there were 12 who also had malformations of the heart and lungs. This made worse a prognosis which was bad anyway.


[The serum level of ionized calcium, total calcium, and magnesium in neonates (author's transl)]. In the first three days of life ionized and total calcium and magnesium were determined in the serum and compared with perinatal parameters in a heterogenous groups of newborn infants (n equals 33). The findings allow the following conclusions: 1. There is a relative good correlation between ionized and total calcium. 2. There is no statisticly proven correlation between magnesium and ionized or total calcium. 3. There is a close relation between APGAR-score and the levels of calcium in the first hours of life. But apparently there is no relation between the gestational age or the weight of birth and magnesium, between the gestational age or the weight of birth and ionized or total calcium there is no close correlation.


[Sialadenosis as secondary organ manifestation of anorexia nervosa (author's transl)]. In a 13-year-old boy the occurence of a sialadenosis of the submaxillary glands was observed in association with anorexia nervosa (a.n.). The non-inflammatory salivary gland enlargement became apparent after the boy had suffered a progressive weight loss of 5 kilograms during a period of three years prior to admission. The psychogenic origin of the disorder could be confirmed by 1. the history of the patient being almost identical compared to the few observations of a.n. in males, 2. the absence of any other organ involvement, and 3. follow up over a period of two years during which time the boy regained normal weight, and the salivary gland enlargement disappeared spontaneously. The diagnosis of sialadenosis was based on histological examination.


[Hereditary deficiency of isomaltase and saccharase responsible for a malabsorption syndrone (author's transl)]. Among 135 infants and children with a supposed malabsorption syndrome, a deficiency of isomaltase-saccharase of the duodenal mucosa was detected in 5 cases by measuring the disaccharidases directly in the mucosa homogenate. In one instance a deficiency of lactase was found in addition. In all patients the villi were of normal length, with an increased cell infiltration of the stroma detected in two cases. The loading tests with xylose-sucrose yielded a diminuished rise in the blood glucose level. Three of the patients were dwarfish, but only one showed an increased growth after the reduction of sucrose in the supplied diet. As a result of adaptation difficulties in the change of diet, one patient had to be treated with an additional saccharase substitution.


[The acute crisis of blood pressure and its treatment in childhood (authors transl)]. Hypertension emergencies in childhood occur mainly in end-stage renal disease. In the management the intravenous administration of diazoxide (3--5 mg/kg) is of special importance. Diazoxide results in an immediate and prolonged effect in lowering the blood pressure in 15 children. Serious side effects were not observed. The experiences with the use of diazoxide in the treatment of hypertensive emergencies is discussed.


[Cyclic agranulocytosis (author's transl)]. Report about cyclic agranulocytosis in a 10 1/2 years old girls, having stomatitis, sore throat and fever up to 39 degrees C in the interval of approximately 3 weeks since the age of 6 months. By the prophylactic treatment with pulverized tetracyclin, which is already given 2 days prior to the expected decrease of the neutrophils, the patient stays clinically asymptomatic since 7 months.


Dichlorvos effects on estrous cycle onset in the rat. Continuous exposure to dichlorvos (DDVP) vapors from birth in rats caused a statistically significant mean delay of 10 da in the onset of the first estrous cycle. DDVP, BUT NOT ITS PRIMARY METABOLITE (DES-METHYL DDVP), could be readily isolated from blood and ovarian tissue, and occassionally in minute quantities from the kidney and adrenal tissues. DDVP was recovered only once in 40 brain tissue samples examined.


Ultrastructural features of viral leukoencephalomyelitis of goats. Ultrastructural studies were made of the central nervous system of three goats during the early stages of viral leukoencephalomyelitis of goats and of one goat 3 years after onset of the disease. In both early and late lesions, the following features were recognized: loss of myelin from normal axons, separation of the myelin sheath from the axon by cell processes, pronounced astrocytosis with numerous cell processes packed with heavy fibrils, paucity of oligodendrocytes, normal capillaries, and normal cellular elements in the adjacent gray matter. Early lesions also had many cells of the lymphoid series infiltrating perivascular spaces, within lesions, and, particularly, along axons undergoing demyelination. Although viral particles were extensively sought, only one suspect structure, with a tubular nucleocapsid-like configuration, was seen. Individual tubules of this particle measured 22 nm. in diameter. The ultrastructural features of demyelination in viral leukoencephalomyelitis of goats were compared with those described for demyelination that occurs in multiple sclerosis, experimental allergic encephalomyelitis, canine distemper encephalomyelitis, and that produced by diphtheria toxin.


The PSRO hospital review system.

The PSRO hospital review system. The 1972 Social Security amendments contained the landmark Professional Standards Review Organization (PSRO) provisions as well as several sections upgrading existing utilization review (UR) requirements under Medicare and Medicaid. With issuance of the PSRO Program Manual and the recent publication of the new UR regulations, HEW for the first time has brought Medicare and Medicaid hospital review requirements into conformity and made them compatible with and supportive of the PSRO program. This article defines the PSRO hospital review system, describes how the three major components-concurrent review, medical care evaluation studies, and profile analysis-interrelate and provides examples of each of these components. Under utilization review requirements or PSRO, hospitals will be required to implement an integrated system of review designed to assure appropriate utilization practices and improve the quality of care. These aims are to be accomplished through the application of concepts of peer review, the use of norms, criteria, and standards, the identification of deficiencies in the quality, administration, or appropriateness of health care services, and their correction through linkage with programs of continuing medical education. Although PSROs are initially responsible for review in hospitals, they will likely provide the locus for a community-wide system of peer review for all services provided under National Health Insurance.


Ossiculotympanic transplantation.

Ossiculotympanic transplantation. Continued investigations into current tympanoplasty problems have been carried out in the Eye and Ear Clinic, Royal Victoria Hospital, Belfast. Retrospective studies have been helpful in identifying some of the main problems responsible for many of our unsatisfactory results, both in the irradication of disease and the restoration of aural function. Prospective studies into the behavior of grafting materials for tympanic reconstruction in the experimental animal have led us to an overwhelming preference for natural materials as opposed to plastics or stainless steel. Both homologous and autologous bone and cartilage appear to offer good prospects in ossicular replacement techniques. The most satisfactory material we have used for repair of tympanic membrane defects continues to be either autologous or homologous temporalis fascia. The long-term success of these materials in functional restoration is utterly dependent on continued aeration of the tubotympanic cleft.


[Serologic diagnosis of coxsackie virus infections in the newborn period using acetate foil electrophoresis]. 150 sera from newborn infants were examined by means of counter current electrophoresis for precipitating antibodies against Coxsackie virus Group B and Group A, Type 9 to detect pre- or perinatal Coxsackie virus infections. Fresh Coxsackie virus infections were observed in 16 sera, more than 50% of these sera showed an abnormally high level of IgM.


Prolactin release in dairy heifers relative to duration of teat stimulation. Experiments have shown that the prolactin response specific to sustained teat stimulation is strictly dependent upon the duration of stimulation. There is some evidence for assuming two principally different patterns of prolactin response, namely high sensitivity to the stimulus with an initial maximal response, and poor sensitivity to the stimulus with a gradually intensifying response. Hyperstimulation of teats results in relative refractoriness of neural receptors for specific prolactin impulses. Refractoriness of one teat leads to a reduction in the release of prolactin which can be overcome by the stimulation of another as yet unstimulated teat.


Acute effects of ovariectomy and sham ovariectomy on pituitary-ovarian phenomena in the mouse. Four- and 5-day cyclic mice housed with and without males, respectively, were autopsied at 10 a.m. on proestrus (P) or estrus (E) after no treatment, or after ovariectomy (Ovax) or sham Ovax at 10 a.m. or 4 p.m. on one of the preceding 3 days. Results indicate the ovarian must be in situ between 4 p.m. the day before P and 10 a.m. the day of P for a normal proestrous uterine weight increase to occur in both 4- and 5-day cyclic mice. For estrous cornification to occur, ovaries must be in situ between 10 a.m. and 4 p.m. on diestrus (D) in 4-day cyclic mice, and between 4 p.m. on D-I and 10 a.m. on D-II in 5-day cyclic mice. Sham Ovax tended to inhibit ovulation in both 4- and 5-day cyclic mice. The effects of both Ovax and sham Ovax on proestrous and estrous pituitary LH values were variable. ttiming of the feedback relationship between ovary and hypothalamus-pituitary in mice may be imprecise, leading to easy disruption of the estrous cycle in this species.


Spinal cord infarction due to minor trauma in children. In two children, ages 22 months and 4 years, after slight trauma, flaccid weakness of both arms developed, followed by flaccid quadriplegia with sphincter involvement. No vertebral fracture or dislocation was found, myelograms were negative, and diagnosis was made only after the full clinical syndrome developed. Pathologic studies revealed ischemic infarction involving the cervical cord and low medulla in one patient, and central gray matter of low cervical cord in the other, without hematomyelia or external compressive lesions. The pattern of infarction may be related to spasm of distal branches of the central sulcal arteries in a terminal arterial bed.


Mechanisms underlying spinal cord damage in decompression sickness. Decompression sickness, which damaged the spinal cord, was produced in anesthetized dogs using a compression chamber. Cerebrospinal fluid pressure and several intravascular and intracardiac pressures were monitored during the course of the simulated dives. Manometric responses to forcible lung inflation and abdominal compression were measured both predive and postdive after signs of spinal cord damage were evident. Cinevenography of the epidural vertebral venous system was performed both predive and postdive. Histopathologic  studies of the brains and cords of both predive and postdive. Histopathologic studies of the brains and cords of paretic animals were carried out. The results indicate that the epidural vertebral venous system becomes obstructed during spinal cord damaging decompression sickness and strongly suggests that spinal cord infarction in decompression sickness is caused by obstruction of cord venous drainage at the level of the epidural vertebral venous system.


Edrophonium infrared optokinetic nystagmography in the diagnosis of myasthenia gravis. Horizontal optokinetic nystagmus was measured by an infrared eye movement recording technique before and after the administration of intravenous edrophonium chloride in 16 patients wtih proved myasthenia gravis. All the patients, even those without clinically apparent ophthalmoparesis, demonstrated an increased amplitude of optokinetic nystagmus after administration of the drug. None of 12 control patients, many with ophthalmoparesis, showed increased optokinetic nystagmographic amplitude. The superiority of infrared recording techniques to electro-ocuography was discussed. Edrophonium infrared optokinetic nystagmography proved to be a sensitive and specific test of myasthenic weakness in extraocular muscles.


Associative visual agnosia without alexia. A brain-damaged man was unable to appreciate the nature of objects and meaningful nonverbal symbols presented visually, although he could see, draw, describe, and match these stimuli. He had no difficulty understanding visually presented words. Auditory and tactile recognition of both verbal and nonverbal stimuli were normal. Our findings provide evidence that two neuropsychologic mechanisms were responsible for this disorder. One was an interhemispheric visual-verbal disconnection; the other was a specific categorization defect for visual, nonverba, meaningful stimuli. Neither mechanism alone was sufficient; both were necessary.


Behavioral assessment of peripheral nerve function. Behavioral psychophysical techniques were used to obtain strength-duration curves for the ulnar nerve at both threshold and suprathreshold levels. The functions well match those obtained with electrophysiologic procedures, but overcome many of the difficulities associated with traditional electrodiagnosis. An alternate means of presenting the data provides a parameter, the critical duration, that describes the ability of the stimulated nerve to integrate or summate energy over time. The very brief criticial duration for normal ulnar nerve and the similar functions at threshold and suprathreshold levels suggest possible mechanisms for the transduction and coding of percutaneous electrical stimuli.


Routine use of hysterography in endometrial carcinoma and postmenopausal bleeding. Unexpected hysterographic findings were encountered in 42 of 105 patients with postmenopausal bleeding or endometrial carcinoma. These included the extent and location of tumor, size and position of the uterus, uterine perforations or fistulas, and undetected myomas, congenital defects, or adnexal pathology. The findings proved of sufficient value in clinical management that hysterography, using water soluble medium, has been adopted as a routine procedure in such cases, especially if radium or cesium packing is employed. There was no statistically significant correlation between the histologic grade of the tumor and the hysterographic appearance of well-circumscribed or diffusely infiltrating lesions. Intravasation of contrast media occurred in 9 patients, lymphatic uptake was observed in 8, and peritoneal spillage of dye in 31 patients. There was no significant morbidity, and results to date show no evidence of tumor spread from the procedure.


Congenital malformations due to anticonvulsive drugs. A retrospective study of congenital malformations in the offspring of 20 women who received antiepileptic drugs during pregnancy is presented. Of 56 births, 9 children (16%) were born with malformations. Four children were born dead or died shortly after delivery. Congenital heart disease, cleft lip with or without cleft palate, neural tube defects, and skeletal abnormalities were the commonest anomalies found. One child had a recognizable pattern of multiple malformations. The increased perinatal mortality was mainly due to congenital malformations and spontaneous hemorrhage. The teratogenic activity of anticonvulsant drugs is mediated by interference with folic acid metabolism, and such activity might be influenced by hereditary and environmental factors. Bearing in mind the importance of anticonvulsant therapy in epilepsy, there is certainly need for an investigation of the problem in a larger and more representative birth population than that described.


Hydrocele of the canal of nuck. A report of five cases. Because of lack of information in the gynecologic literature on the subject of hydrocele of the canal of Nuck, 5 cases are reported here. The condition is reviewed, and the pathogenesis, clinical features, differential diagnosis, and management are discussed.


Primary hyperparathyroidism during the third trimester of pregnancy. Primary hyperparathyroidism during pregnancy has been reported in 36 women; 1 new case is reported here. Screening by determining serum calcium levels is a valuable method of diagnosing the disease. Radioimmunoassay of serum parathyroid hormone (PTH) greatly aids in the diagnosis. Amniotic fluid PTH values are discussed. Hyperparathyroidism has a high association with progressive renal insufficiency, renal calculi, hypertension, and bone disease. During pregnancy, there is an increased incidence of stillborns, premature labor, and neonatal tetany. Acute hyperparathyroid crisis may result in maternal death. This is the first reported case surgically treated during the third trimester of pregnancy. Surgery should be considered when the diagnosis is made late in pregnancy, as this may protect the infant from neonatal tetany.


[Validity of simple X-ray-techniques in misdiagnosed anorectal malformations (author's transl)]. One particular form of an anorectal malformation--the anterior perineal anus--is frequently overlooked in the neonate period because defecation is easy at this age. However, with the change of diet, this malformation as a rule leads to chronic constipation. The lateral view at the beginning of an irrigoscopy usually shows a characteristic picture of a horizontal caudal limitation of the rectum, a dorsal pouch, a beakshaped fistula and an elevation of the anorectal transition. These findings contribute essentially to the clinical diagnosis and permit early operation.


Maze learning by adult rats after inhibition of neuronal multiplication in utero. Rats whose mothers received hydroxyurea (HU, 1 or 2 g/kg) at 14 days of gestation had a 30% deficit in both brain and body weight at birth, when compared with controls. Number of brain cells at birth (mainly neurons) was reduced by 33-34%. A severe reduction in postnatal whole brain growth (31-33% in adulthood) was observed, but the cerebellum was relatively spared. In the Hebb-Williams maze text in adulthood HU animals made 28% more errors than controls over 12 problems. The differences were much more marked on certain problems and for HU animals with particularly small brains. In a T-maze spatial discrimination test in adulthood HU rats learned the initial response normally but, when required to reverse this response, showed a significant tendency to make more perseverative errors than controls.


Organization of the nervous control of urethral sphincter. A study in the anaesthetized cat with intact central nervous system. The electromyographic response of the striated urethral sphincter has been evoked following stimulation of its motor nerve, the pudic nerve. Stimulation of the intact nerve fires the muscular fibres directly with a latency of approximately 1.2 msec and also in a reflex manner via the ipsilateral and contralateral pathways. The two paths transmit the reflex responses with a minimal latency of 8--10 msec (chloralose). During Halothane anaesthesia the reflex appears with a longer latency (up to 26 msec). The variability of this latency and the central delay of around 5 msec agree well with a polysynaptic central pathway. The reflex response is generally composed of an early wave of large amplitude followed by an afterdischarge lasting (between 30--60 msec) and of higher threshold. This response is triggered by the fastest afferents in the pudic nerve. The excitability of the motoneurones controlling the sphincter was tested by the double shock method and was shown to be analogous to other somatic motoneurones. The electrically evoked reflex response is slightly inhibited by bladder distension. A more powerful type of inhibition of the sphincter activity is associated with activation of the bladder motor centre.


Behaviour of the urethral striated sphincter and of the bladder in the chronic spinal cat. Implications at the Central Nervous System Level. Nine cats were spinalized at the thoraco-lumbar junction (T12-L7) and the subsequent behaviour of the bladder and urethral striated sphincter was observed during periods of up to 27 days after spinalization by means of bladder manometry and of urethral electromyography. On the day following operation, the urethral sphincter responds to stimulation of its intact motor nerve, the pudic nerve by reflex (R) and direct (M) responses analogous to those of the intact animal anaesthetized with chloralose. The ratio R/M lies between 1 and 0.6 in the chronic spinal cat whereas it is generally less than 0.5 in the intact chloralose-anaesthetized cat. The tonic activity of the sphincter is weak or not present. The continence, however, is well maintained. The bladder activity appears only 4 to 8 days after spinalization. The bladder can thus void urine during brief contractions. These micturitions are always incomplete. The urethral reflex activity, either spontaneous or triggered by stimulation of the pudic nerve, may be inhibited, i: to a moderate degree by passive bladder distension; ii: almost completely by activation of vesicomotor neurones which provoke the bladder contraction. The first inhibition is seen the day after spinalization and is probably a protective reflex against vesical hypertension. The second inhibition develops progressively and in parallel to the functional recovery of vesical preganglionic neurones. It takes place on a background of antagnostic equilibrium of bladder and of urethral sphincter activities during micturition.


Post-tetanic changes in the discharge pattern of the extensor alpha motoneurones. The after effects of orthodromic tetanization on the discharge pattern of gastrocnemius motoneurones were investigated in decerebrate and spinalized cats. tduring stimulation of intact gastrocnemius nerves at 20 Hz, small motoneurones showed ttion for 8 sec, large motoneurones followed the 20 Hz stimulation in 1:1 order, whereas small motoneurones became silent for about 37 sec. Thereafter, the impulse rate of large motoneurone decreased while that of small motoneurone increased, progressively reaching the pre-tetanic values in about 72 sec. When gastrocnemius nerves were tetanized for 20 sec, potentiation of large motoneurones and depression of small motoneurones lasted for about 120 sec. Post-tetanic potentiation of large motoneurone was still observed during stimulation with 40 Hz but not with 80 Hx. Inhibition of a small tonic motoneurone during repetitive activity of a large motoneurone was observed during stimulation of Group I + II afferents following injection of 0.025 mg/kg strychnine. Another strychnine injection of the same dose reduced this inhibition. It was concluded that large-phasic motoneurones may be highly susceptible to post-tetanic potentiation; and that small-tonic motoneurones may be inhibited by large motoneurones through a recurrent circuit.


Antagonistic effects of vasopressin and hypervolemia on osmotic reactivity of the thirst mechanism in dogs. The reactivity of the thirst mechanism to osmotic stimuli was examined in conscious dogs 1. under control conditions, 2. after raising the plasma vasopressin (PADH) level to about 30 muU/ml by intravenous infusion of the hormone, 3. after expansion of the blood volume by 15% by an intravenous infusion of dextran solution, and 4. after a simultaneous increase of PADH and blood-volume expansion. The osmotic thirst threshold was significantly lowered by the elevation of PADH and augmented by an expansion of blood volume, whereas no significant changes were observed when the increase in PADH and expansion of blood volume were applied simultaneously. The interactions between body-fluid osmolarity, blood volume, and vasopressin in regulation of water intake are discussed.


The central arterial pulses. Experiments on a hybrid model of the heart and the arterial system. In order to examine the contours of central aortic and coronary flow pulses as well as those of pressure and flow pulses along the aorta, a hybrid model of the arterial system and the heart was designed. The digitally programmed model of the aortic system is an inhomogeneous transmission line with adjustable reflection factors at the end and at three intermediate locations. For the reflection factor at the entrance different values may be chosen for the ejection time and the diastole. The influence of a stenosis and of frequency-independent damping may be examined. The model of the ventricle is the analog solution of a system consisting of an internal isometric pressure source and an internal resistance and capacitance. The model of the coronary artery is the analog solution of a windkessel model of the system. The digital and analog models are interlocked by AD and DA converters. All programs can be executed in real time. The characteristic contour of the aortic flow is determined by the relation between the internal impedance of the ventricle and the magnitude of the characteristic impedance of the aorta. Furthermore, the influence of reflections within the arterial system is shown to be quite remarkable. Natural pressue pulses can be simulated by the model under normal and pathological conditions including aortic coarctation. The contour of the left coronary artery flow is determined on the one hand by the fraction of the ventricular pressure which acts as a counterpressure at the site of the peripheral resistance, and by the time constant of the coronary windkessel on the other hand.


Quantitative aspects of autoregulation in the canine kidney. Autoregulatory changes in series connected vascular resistances were studied in the normal canine kidney. Two sets of observations were made: a) ureter pressure was increased by ureteral obstruction and b) arterial pressure was decreased by aortic clamping. It was assumed that in both experimental panels the decrement in intrarenal resistance is solely due to dilatation of the preglomerular vessels. Proximal tubular pressure is thought to equal deep venous (wedged) pressure under free flow and ureteral pressure under stop flow conditions. Calculation of the glomerular filtration coefficient yielded the same value in both sets of observations: k similar to 2 ml/min/100 g per 1 mm Hg effective filtration pressure. Glomerular capillary pressure rises steeply and roughly parallels arterial pressue below the autoregulatory range (about 40-80 mm Hg), whereas in the autoregulatory range (about 90-150 mm Hg) its value is stabilized at 74 plus or minus 1 (S.E.)mm Hg. Afferent resistance is negligible in the hypotensive range and increases progressively in the normotensive range. Changes in efferent and venular resistance are insignificant in the whole pressure range considered, i.e. 40 to 150 mm Hg.


Static and dynamic activity of warm receptors in Boa constrictor. Afferent impulses from multi- and single-fiber preparations of the trigeminal nerve in Boa constrictor were recorded during exactly controlled thermal stimulation of the receptive field in the labial region. At constant temperatures in the range between 18 and 37 degrees C, multi-fiber preparations showed a continuous discharge with a maximum around 30 degrees C. Dynamic warming caused a high increase of the discharge, whereas dynamic cooling led to a complete inhibition. No cold-sensitive fivers have been found. Mechanical stimulation elicited large spikes from specific mechanoreceptors. Single-fiber preparations from labial warm receptors did not respond to mechanical stimulation. Their discharge was always regular at constant temperatures. The average frequency of a warm receptor population was zero at about 18 degrees C, reached a maximum of 13 sec-1 at 30 degrees C and fell again to zero at 37 degrees C. In addition, a few warm receptors increased their static discharge with temperature up to 36 degrees C, the highest frequency being 38 sec-1. Stepwise warming by delta T = + 5 degrees C caused a marked overshoot in frequency, after which the discharge usually fell to a minimum and then rose again to a new static level. Stepwise cooling by delta T = MINUS 5 DEGREES C led to a transient inhibition of activity followed by an increase until the new static level was reached. In the first group of warm receptors the height of the dynamic overshoot varied with the adapting temperature, the largest average overshoot of 160 sec-1 occurring at an adapting temperature of 30 degrees C. These receptors have their static maximum as well as their highest dynamic sensitivity in the temperature range of the natural tropical habitat of Boidae.


Regeneration in grafts of normal and denervated rat muscles. Contractile properties. The soleus or extensor digitorum longus muscles of young rats were freely garfted into the bed of the corresponding contralateral muscle. The grafts were of normal muscle or muscles which had been denervated for 14 days. Grafts of normal muscle were characterized by little or no contractile activity for the first 2-4 days after transplantation. In contrast, denervated grafts contracted weakly, but consistently, throughout this early period. The patterns of contraction were complex. In early transplants, the contractions were due entirely to surviving muscle fibers in the graft, and the contractile characteristics were those of denervated muscle fibers. After the first week, contractions of newly regenerating muscle fibers within the grafts were superimposed upon and later took over those from the fibers that survived the original transplantation. The contraction times approached those of the normal soleus or extensor muscles during the second month after grafting, and the grafts contracted like fast or slow muscles.


Cycloleucine (1-amino-cyclopentane carboxylic acid): tubular reabsorption and inhibitory effect on amino acid transport in the rat kidney. (Microperfusion experiments). Renal tubular reabsorption of cycloleucine (1-amino-cyclopentane carboxylic acid) was studied in vivo et situ by continuous microperfusion of single proximal tubules of the rat. The results show: a) cycloleucine is reabsorbed rapidly compared with other amino acids b) this reabsorption is saturable and can be inhibited by oligomycin c) cycloleucine inhibits tubular reabsorption of L-arginine, glycine, and of L-phenylalanine. Mutual reciprocal inhibition occurs only with L-phenylalanine (and perhaps also with glycine). A maximal possible permeability coefficient for cycloleucine (less than 6 times 10--5 cm times sec--1) was calculated. Assuming simple 2-parameter kinetics, Vmax and Km for tubular reabsorption of cycloleucine were estimated. It can be concluded from the present results that cycloleucine is reabsorbed by a mechanism that transports L-phenylalanine, but not by the system shared by dibasic amino acids.


Temperature-sensitive ascending neurons in the spinal cord of pigeons. Ascending neuronal activity in the lateral funiculus of the spinal cord of pigeons (spinalized at about C4, recordings at about C6) has been studied with regard to effects of temperature changes with a thermode in the vertebral canal between Th4 and C8. 2. Both warm-sensitive (35) and cold-sensitive (14) neurons were found. According to the change in impulse frequency during steplike thermal stimuli, different reaction types could be distinguished. Twenty-four warm-sensitive and seven cold-sensitive units showed a proportional frequency change without any dynamic reaction. Three other warm-sensitive neurons had an additional dynamic reaction (excitatory overshoot during warming, inhibition during cooling). Five warm-sensitive and three cold-sensitive units showed no static sensitivity but responded with outstanding dynamic frequency changes during rising or falling temperature. The activity of some neurons stopped suddenly above (4) or below (3) a critical temperature, which was always near the normal spinal temperature (about 41 degrees C). Altogether the reaction to rapid temperature changes was consistently greatest near the normal body temperature. 3. The mean static sensitivity of 17 warm-sensitive units was + 4.2 plus or minus 1.3 imp./sec. degrees C (mean value and s. d.) and that of three cold-sensitive ones minus 2.3 plus or minus 0.3 imp./sec. degrees C in the range 35 degrees minus 45 degrees C (vertebral canal temperature). The temperature coefficient (Q10) which was calculated for the same neurons showed great variations with mean values of about 5 for both warm- and cold-sensitive units.


CD studies of conformational changes of DNA upon photosensitized UV-irradiation at 313 nm. The role of thymine dimerization for previously reported U.V. induced conformational changes has been proved using acetophenone as sensitizer for the specific thymine dimerization upon irradiation at 313 nm. CD results demonstrate that formation of pyrimidine dimers cause typical conformational changes of the DNA B helix as observed on irradiation at 254 nm. Thus the primary role of adenine photoproducts may be excluded.


Reassociation kinetics of three satellite components of calf thymus DNA. Using absorption measurements the reassociation kinetics of three satellite DNA components isolated from calf thymus was studied under various conditions. A different method using CsC1 density gradient determinations particularly suited for kinetic analysis of mixtures was also used and shown to give similar results. Reassociation rate constants were corrected for mismatching during strand reassociation using data obtained by kinetic analysis of fractions of the 1.714 g/cm-3 satellite component. The values of corrected as well as uncorrected complexities were calculated and compared with results of other methods. They were shown to be compatible with the concept of sequence repetition at various levels.


Alterations in the growth rate and metabolism of Chinese hamster cells in vitro (38530). Chinese hamster (Don) lung cells undergo a gradual decline in proliferation (Phase III) during their lifespan in culture.  In addition, cells in Phase III utilize more glucose per 10-4 cells and produce more lactic acid per 10-4 cells than do Phase II cell cultures.


Narcotic antagonist activity of several metabolites of naloxone and naltrexone tested in morphine dependent mice (38558). A rabbit liver enzyme system was used to produce the 6beta-OH reduced metabolites of naloxone and naltrexone. GC analysis indicated the presence of some 6alpha-OH metabolite in these samples. The narcotic antagonist activity of these 6beta-OH metabolite samples were compared to naloxone, naltrexone and standard 6alpha-OH naltrexone (EN-2260A) using the jumping response of morphine pellet implanted mice. For the naloxone series, the potencies were: Naloxone greater than EN 2265A greater than 6 beta-OH maloxone. For the naltrexone series: Naltrexone greater than EN 2260A greater than beta-OH naltrexone. The low potency of the reduced metabolites the rapid onset of action of the parent compounds militate against the formation of these metabolites contributing substantially to the overall narcotic antagonist action of the parent compounds.


Dengue virus plaque formation on microplate cultures and its application to virus neutralization (38564). Dengue virus plaque formation on BHK-21 cell microplate cultures was described.  The clear plaques were visible usually 5 days after incubation in a CO-2 incubator at 37 degrees.  The cells cultured in a 3-oz bottle were sufficient to prepare two microculture plates which were usually ready for use after 1-2 days of cultivation in the CO-2 incubator at 37 degrees.  The overall procedures were easy and of economic advantage.


Androgens in the bovine fetus and dam (38567). Umbilical arterial and venous blood, and fetal testes were taken from 38 bovine fetuses at 90, 180 or 260 days of gestation. Concurrently blood also was taken from the jugular, and from the uterine artery and vein of the dams. Testosterone and androstenedione were determined by radioimmunoassays. Fetal testicular homogenates had 0.96 and 0.35 mug/g of testosterone and 0.39 and 0.50 mug/g of androstenedione at 180 and 260 days of gestation, respectively. Males had five to tenfold more serum testosterone and about twofold more androstenedione than female fetuses at each trimester of gestation. Male fetal blood testosterone decreased (P less than 0.01) from 2.7 to 0.3 ng/ml between 90 and 260 days of gestation. But, maternal testosterone and androstenedione increased (P less than 0.05) during gestation in cows with males, but not in cows with female fetuses. Testosterone was higher (P less 0.05) in cows carrying males than in cows with female fetuses. Androstenedione was higher in blood leaving the placenta on both the maternal and on the vetal sides suggesting placental synthesis of androstenedione.


Formation of colonies in soft agar medium by regenerating liver cells (38591). The culture of actively regenerating liver tissue in soft agar reveals the presence of a cell population, not previously described, which includes (a) cells capable of forming hematopoietic colonies and (b) additional cells producing colonies with epithelioid characteristics.


Morphine analgesia in grouped and isolated rats. The effects of long-term isolation of young adult male rats on the analgesic effects of morphine were investigated. Isolated rats developed altered patterns of behavior, including muricidal behavior in some animals. Analgesic activity of morphine was assessed with both the tail compression and the hot plate methods. The results indicate that chronically isolated rats, whether developing muricidal behavior or not, show no alteration in either pain thresholds or in their response to morphine-induced analgesia.


Dependence to morphine in differentially housed rats. Although the effects of differential housing, particularly isolation, on the action of several classes of pharmacological agents have been studied, little attention has been given to this factor in regard to narcotics. The present study involves the effects of long-term social isolation on dependence to morphine produced by pellet implants in rats. When abstinence was precipitated with naloxone, isolated rats demonstrated less jumping and less diarrhea then grouped rats. No differences were found in other signs. In addition, the differences were seen both in isolates developing muricidal behavior and those not developing this behavioral pattern.


Brain acetylcholine in morphine pellet implanted rats given naloxone. Adult male rats were implanted with intraventricular (ivt.) brain cannulae for injection of 5 mug of acetylseco-hemicholinium-3 (acetylseco HC-3) as a means of studying acetylcholine (ACh) utilization during morphine withdrawal. Animals were made dependent by implanting s.c. two 75 mg morphine base pellets 24 hrs apart. On the 4th day animals were given 10 mg/kg of naloxone i.p. and/or 5 mug acetylseco HC-3 ivt. and sacrificed by decapitation at various times. The brains were removed and assayed for ACH using a pyrolysis gas chromatographic procedure. Total brain ACh before or after acetylseco-HC-3 was not altered at 5, 30, 60 and 120 but was decreased at 10 min after naloxone. These results are in sharp contrast to our previous data of enhanced brain ACh utilization in withdrawn rats made dependent to morphine by several weeks of twice daily injections. It is apparent that short term morphine pellet administration does not produce the marked neurochemical and behavioral changes of long term morphine injections.


Consequences of social conflict on plasma testosterone levels in rhesus monkeys. Four adult male rhesus monkeys formed a new social group with 13 adult females. The male who became dominant [alpha] showed a progressive increase in plasma testosterone. The male who became subordinate to the other three males showed an 80% fall in testosterone from baseline levels. After 7 weeks, this group was introduced to a well-established breeding group, and all four males became subordinate to all members of the breeding group. All four males evidenced a fall in testosterone during the first week after introduction, and within 6 weeks their levels were approximately--80% of pre-introduction values. The alpha male of the breeding group showed a large increase in testosterone [238%] 24 hr after he successfully defended his group and became the dominant animal of the larger, newly-formed group. Thus, plasma testosterone levels appear to be significantly influenced by the outcome of conflict attendant to alterations in status of rhesus monkeys living in social groups.


Development of a radioimmunoassay for etorphine (preliminary communication). A radioimmunoassay for etorphine has been developed using antibodies raised in a rabbit against an etorphine-3-hemisuccinate-bovine serum albumin conjugate. Using tritiated etorphine as the label, the antiserum could be used at a final dilution of 1:4 and had an avidity of 1.8 times 10-9 L.M.-1. The sensitivity of the assay was 0.88 plus or minus 0.04 ng etorphine per ml of serum and there was no cross-reactivity with any of the six opiate alkaloids examined over the range 0-100 ng/ml.


Radioimmunoassay for dieldrin and aldrin. A radioimmunoassay for dieldrin and aldrin has been developed which can detect picomole levels of either compound. The specificity of the antibodies, determined with respect to several other organochlorine insecticides, indicates that most of the binding energy is directed to the polychlorinated bicyclic ring system. DDT, 2,4,5-T, dechachlorobiphenyl (a PCB standard), and several other insecticides which may be found in samples containing dieldrin and aldrin should not interfere with the radioimmunoassay.


Secretin snuff: evaluation of the action on pentagastrin-stimulated gastric acid secretion and on pancreatic bicarbonate production. In an informative qualitative study 75 U (near the range of 1 U/kg) secretin given as a snuff resulted in a weak but significant stimulation of pancreatic bicarbonate output in 8 volunteers studied. The result further indicated that this dose would slightly inhibit pentagastrin-stimulated gastric acid secretion. This was confirmed in a quantitative study at the dose of 150 U (similar to 2 U/kg), and the mean amount of inhibition of MAO was 30% in the 10 subjects studied. A supramaximal dose of 1 mg (approximatively 54 U/kg) of synthetic secretin given to one volunteer resulted in a transient block of near maximally pentagastrin-stimulated gastric acid secretion. The amount of acid inhibition as compared to a control experiment was 45% in the first and 52% in the two post-secretin hours. These results indicate that secretin given as a snuff at dose levels that would induce maximal pancreatic secretion when given as an i.v. injection results only in a weak inhibition of  stimulated gastric acid secretion and evokes only a little stimulation of pancreatic bicarbonate secretion. Supramaximal secretin snuff doses have, however, a potent effect on both gastric and pancreatic secretion that is of similar order to that achieved by intravenous secretin. Owing to the obviously incomplete absorption of secretin through the nasal mucosa, secretin snuff is unlikely to solve the therapeutic problem of duodenal ulcer disease. If, however, an active fragment of the peptide could be synthetized at a reasonable price, the greater convenience of pernasal application might compensate for the partial loss of action.


Tetrachlorodibenzodioxin:  an accidental poisoning episode in horse arenas. Tetrachlorodibenzodioxin was identified as the apparent cause of an outbreak of poisoning in humans, horses, and other animals.  Exposure was related to the  spraying of contaminated waste oil on riding arenas for dust control.  The contamination resulted from improper disposal of a toxic industrial waste.  The pathologic effects and chemical identification of tetrachlorodibenzodioxin are described.


Diurnal rhythms of cell reproduction and of some morphometric indices in the thyroid gland of young rats. Monophasic diurnal rhythms of mitosis and DNA synthesis are characteristic of the thyroid gland epithelium of young rats (unlike adults). It is postulated that the diurnal rhythm of mitotic activity is under the influence of a mechanism synchronizing the cell population before mitosis. With an increase in thyrocyte differentiation the number of mitoses and of DNA-synthesizing cells falls. Diurnal changes in the duration of mitosis affect the dynamics of the diurnal rhythm of mitotic activity. Changes in the height of the follicular cells during the 24-hour period are evidence of a diurnal rhythm of thyroid function in young rats.


Content of DNA and dry weight of the nuclei of neurons of the external geniculate body and retina of the eye in guinea pigs. The amount of DNA and the dry weight of the nuclei of cells of the external geniculate body, as well as the photoreceptor, bipolar, and ganglionic cells of the retina of the eye, were studied at the early stages of postnatal development of guinea pigs by the methods of cytospectrophotometry and interferometry on prints of the tissue. In the photoreceptor and bipolar cells of the retina, a stable, diploid amount of DNA is detected. In the ganglionic cells and nerve cells of the external geniculate body, in addition to the diploid cells a small group of tetraploid cells was detected. The dry weight of the nuclei of the external geniculate body and retina increased appreciably on the third day of postnatal development.


Auscultatory features of hypertrophic obstructive cardiomyopathy. A study of 90 patients. The auscultatory signs in 90 subjects with hypertrophic obstructive cardiomyopathy are described. The late-onset ejection systolic murmur and its responses to vaso-active manoeuvres reflect a volume-dependent outflow tract obstruction. Late vibrations of the systolic murmur, not uncommonly recorded at the apex, are due to associated mitral incompetence. Non-ejection systolic clicks may occur, and the likely explanation is inequality of the functional length of the mitral chordae tendineae secondary to asymmetrical myocardial hypertrophy. The second heart sound is often abnormal, usually with delay in the aortic component. Some correlation was demonstrated between the relative degrees of left and right ventricular outflow obstruction and the pattern of splitting of the second heart sound. Reversed or partially reversed splitting is usually associated with a more severe left ventricular outflow obstruction. Ejection systolic clicks and early diastolic murmurs occur infrequently, but are not incompatible with the diagnosis of hypertrophic obstructive cardiomyopathy.


[Effect of phagocytosis in vitro on Paracoccidioides brasiliensis]. Peripheral leukocytes from 17 patients with paracoccidioidomycosis were mixed with yeast cells from Paracoccidioides brasiliensis and Rhodotorula sp. to ascertain their phagocytic and lytic capacities. The role of circulating antibodies in the process was also investigated by the use of autologous serum. The phagocytic capacity of the leukocytes was found to be normal for both types of yeasts. However, in the presence of the patient's serum, the percentage of P. brasiliensis cells ingested was increased (P smaller than or equql to 0.02). Furthermore, in 70-5% of the cases the lytic process was increased and more P. brasiliensis cells were killed when such a serum was employed (P smaller than or equal to 0.0013). This increased effect was not recorded for Rhodotorula sp. cells, thus indicating specificity. The peripheral leukocytes from patients with paracoccidioidomycosis are not defective. However, the success of the phagocytic process is aided by the opsonic action of the specific antibodies in the patient's serum.


Tinea nigra palmaris from South India.

Tinea nigra palmaris from South India. A middle aged woman was diagnosed as a case of tinea nigra palmaris in a Pondicherry hospital. Ascraping from a dark patch on her palm yielded Cladosporium werneckii. This is the first report of mycologically confirmed tinea nigra palmaris from India.


Basidiobolomycosis with lymph node involvement. Two cases of Basidiobolomycosis caused by species of the order Entomophthorales are discussed with the report on lymph node involvement by B. haptosphorus. A clearer aetiological classification of the diseases caused by various agents belonging to the class Phycomycetes is preferred in view of the distinct clinical entities produced by them. Involvement of the lymph nodes is also an evidence that the disease produced by B. haptosporus is not restricted to subcutaneous tissue. A routine lymph node biopsy with mycological studies of the node is suggested in such cases.


An analysis of skin prick test reactions in 656 asthmatic patients. Of 656 asthmatic patients referred specifically for allergy assessments, 544 (84 percent) gave positive immediate skin prick tests to at least one of 22 common allergens used routinely. Comparison of these skin test positive patients with the 102 (16 percent) who were skin test negative showed a number of significant differences. The majority of the skin test positive patients (52 percent) were less than 10 years old at the time of onset of the asthma, whereas, of the skin test negative patients, 56 percent were aged over 30 years at the time of onset. Seventy per cent report rhinitis compared with 48 per cent of the skin test negative patients, and 29 per cent reported infantile eczema compared with 9 per cent. Symptoms attributed to house dust, pollens, and animals were noted two to three times more frequently by the skin test positive patients, while corticosteroid drugs had been used more commonly by the skin test negative patients (45 percent compared with 35 percent). No significant differences were observed with the other factors studied, namely, history of urticaria or angio-oedema, family history of "allergic" disease, and awareness of sensitivity to foods, aspirin or penicillin. Prick test reactions in the skin test positive patients were most commonly seen to house dust or the acarine mite, Dermatophagoides farinae (82 percent), followed by pollens (66 percent), animal danders (38 percent), foods (16 percent), Aspergillus fumigatus (16 percent), and other moulds (21 percent). There was a highly significant association of positive history with positive prick test for all allergens studied.


Cad antigen: comparative study of 50 samples. 50 Cad (+) blood samples were tested using various anti-Cad reagents. Results demonstrated a wide Cad antigenic expression, even among the members of one family. In particular experimental procedures, almost all Cad (+) cells were polyagglutinable.


A cold auto-agglutinin of anti-B specificity in an A1B patient. A high titre cold auto-agglutinin with anti-B activity was found in the serum of an A1B group individual. The B/anti-B reaction was thermodynamically investigated and quantitative analysis of the patient's B antigen revealed no abnormality.


Effect of modification of amino groups of human erythrocytes on M, N and NVg blood group specificities. Modification of amino groups on the surface of human erythrocytes by acetic anhydride and trinitrobenzenesulfonic acid caused loss of agglutinability by human and rabbit anti-M and anti-N sera, was without any effect on agglutinability of N red cells by Vicia graminea agglutinin, and made M cells agglutinable by the same agglutinin. Modification of amino groups had no effect on agglutinability of red cells by anti-H and anti-A lectins and only slightly decreased agglutinability by human anti-H, anti-A and anti-I sera. The results suggest that the difference between M and N receptors is not determined by the structure of oligosaccharide chains.


[Inhibiting effect and mechanism of action of 5'-deoxy-5'-fluorothymidine on vaccinia virus reproduction]. 5'-deoxy-5'-fluorothymidine in concentrations 2.5 times 10-4 to 2 times 10-3 M was found capable of inhibiting vaccinia virus reproduction in tissue culture. Its inhibiting effect was associated with the primary capacity to inhibit biosynthesis of thymidylic nucleotides in the stage of TDP and TTP synthesis which appears to be the consequence of inhibition of thydidylate kinase activity. Under these conditions accumulation of TMP is observed. The data obtained permit to consider 5'-deoxy-5'-fluorothymidine to be an "early" inhibitor of vaccinia virus reporduction, and its mechanism of action to be a new type of directed interference with vaccinia virus reproduction.


Pre-operative localization of parathyroid tissue by selective neck vein catheterization and radioimmunoassay of parathyroid hormone. Preoperative localization of parathyroid tissue by selective neck vein catheterization and radiommunoassay of parathyroid hormone (PTH) was used in 18 patients with primary hyperparathyroidism (PHPT), 9 or whom had earlier been subjected to surgical neck exploration. Sampling from large and small neck veins provided localizing data in 11 of 15 patients with parathyroid adenomas. In 3 other patients, diffuse parathyroid hyperplasia was also correctly predicted preoperatively. In 3 patients hyperplasia was found, the surgical procedure was not influenced in a negative way by the failures. Large vein sampling was less helpful then selective small vein sampling. The results show that selective venous sampling from the neck and radioimmunoassay of PTH are valuable preoperative adjuncts to surgical exploration, escpecially in patients who have had previous neck surgery. Since the catheterization procedure is uncomfortable to the patient and difficult for the investigator, its use should be restricted to patients with previous neck surgery, Neck vein catheterization can probably not be used to establish the diagnosis of PHPT in uncertain cases.


[Effect of pyrimidine amino acid derivatives on vaccinia virus in tissue culture]. The results of the study of antiviral properties of 9 derivatives of pyrimidine amino acids showed only N-(2-chloro-5-bromopyrimidil-4)-1-leucin to possess marked antiviral properties manifested in the capacity of this compound to inhibit the vaccinia virus DNA synthesis in chick embryo fibroblast culture and, consequently, to reduce the infections activity of the virus. All the other derivatives of this class have no marked antiviral properties.


[Activity and properties of RNA-dependent RNA polymerase induced in cell cultures infected with Venezuelan equine encephalomyelitis virus]. The activity and properties of RNA-dependent RNA-polymerase in cells infected with Venezuelan equine encephalomyelitis virus were studied. The maximum activity of the enzyme was found 4-5 hours after infection. The effect of two synthetic drugs (rimantadine and diacetylaminocyclohexenon) with antiviral activity against some viruses on RNA-polymerase was studied. Rimantadine was shown to have no effect on the synthesis and activity of the enzyme. Diacetylaminocyclohexenon added into the growth medium was found to inhibit production of RNA-polymerase by 35-40% without reducing the activity of the enzyme in vitro.


[Neutralization of Venezuelan equine encephalomyelitis virus by anticellular serums]. The results of the study of host antigens in Venezuelan equine encephalomyelitis virus by means of neutralization test in tissue culture using sera containing antibody for the species-specific antigens, Forssman antigen and group A and B antigens are presented. They show the inhibiting effect of the sera to be not uniform. The greatest neutralizing effect on the virus was exerted by immune sera to chick embryo fibroblasts and their fractions (by 0.5-3.9 lg PFU/ML). The lack of the virus neutralizing effect in sera for the Forssman antigen and for group A antigen appears to depend upon their deeper localization in the structure of virion.


Cerebrovascular ultrastructural alterations after intra-arterial infusions of ouabain, scilla-glycosides, heparin and histamine. Cardiac glycosides which inhibit Na/K-ATPase (ouabain, scilliroside, scillirosidin) as well as heparin and histamine were infused into a cannulated branch of the middle cerebral artery or by isolated head perfusion in cats and dogs. Ouabain permeating the blood-brain barrier (BBB) caused the same selective swelling of astrocytes and of certain presynaptic elements as after direct application to the brain tissue. The other cellular elements of brain tissue and the vascular endothelium did not react, although the latter was exposed to the highest drug concentrations (about 10-3 M ouabain). By the swelling about one third of the capillaries became more or less constricted accompanied by an increase in endothelial vesiculation and in the number of osmiophilic inclusions in all cells of the vascular wall and of the pericapillary tissue. Osmiophilic material resembling plasma proteins occured in widened intercellular clefts indicating an increased BBB permeability after survival times (40 min). In contrast to the capillaries some terminal vessels are dilated which may correspond to shunt vessels causing an inhomogeneous, even increased cerebral blood flow after ouabain. Scilliroside and scillirosidin cause essentially the same changes as ouabain, but of smaller intensity and extent. In the present study, neither histamine nor heparin caused any structural change of the vessels or brain tissue.


The role of interferon in interference and auto-interference elicited by Newcastle disease virus. Newcastle disease virus (NDV) strains interfere in different degree with the growth of the velogenic NDV strain Texas GB (homologous interference) and Sindbis virus (heterologous interference) in chick embryo fibroblast cells. Homologous interference was elicited by interferon-producing live or UV-inactivated strains and non-interferon-producing live or beta-propiolactone-inactivated strains and it was not influenced by actinomycin D. Thus, interferon had apparently no role in homologous interference of NDV. The growth of Sindbis virus was, however, much more inhibited by interferon-producing live or UV-inactivated NDV strains than with non-inducing ones and the interference was reversible by actinomycin D. Thus heterologous interference is apparently mediated by interferon. In chicken cells infected with the mesogenic NDV strain H, virus yields were 50 to 100 times lower at multiplicities of infection above 0.1 p.f.u./cell than below it. The interferon formed during infection played no role in auto-interference, but may well be held responsible for the mild cytopathic effect observed.


[Peripheral blood lymphocytes in female mice during successive phases of the sexual cycle]. The authors determined the lymphocyte count, nucleo-cytoplasmic ratio, nuclear diameter, and the number of nucleoli and their morphology in peripheral blood of female mice. The results indicate that lymphocyte count remains unchanged during the sexual cycle but changes occur in the nucleocytoplasmic ratio, nuclear diameter, the number and morphology of lymphocyte nucleoli and are synchronized with the cycle. The observations suggest that changes in the maturity and activity of lymphocytes depend on the phase of the sexual cycle.


Microbiological degradation of diazepam. In studying the transformation of diazepam (7-chloro-1-methyl-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one) by fungi isolated from soil. N1-demethylation and cleavage of the diazepine ring were observed. Three metabolites: 7-chloro-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one, 2-acetamido-2"-benzoyl-4"-chloroacetanilide and 2-acetamido-2"-benzoyl-4"-chloro-N-methylacetanilide were isolated and identified.


Family crisis.

Family crisis. Various family crises confront the busy family physician on almost a daily basis. He must recognize the existence of a family crisis and assess the situation adequately and thoroughly. This includes being impartial and unbiased, being aware of countertransferential feelings and asking all necessary questions to obtain adequate information. The family physician must become the objective clarifier and definer of the situation for the family and assume the role of consultant-strategist.


Managing infections of the prostate gland. Each year members of a different well-known medical faculty prepare articles for "Practical Therapeutics." This is the eighth in a series from the University of Arkansas School of Medicine.


Diagnostic echocardiography.

Diagnostic echocardiography. Ultrasound has become an important diagnostic tool for a variety of cardiac problems. It has the advantage of being noninvasive and, in certain conditions, quite accurate. It has been used for the assessment of mitral stenosis and for the diagnosis of cardiac tumors, mitral valve prolapse, asymmetric thickening of the interventricular septum, atrial septal defect and pericardial effusion.


Neonatal risk following late gestational genital herpesvirus hominis infection. Five women developed genital herpesvirus hominis (herpes simplex virus) infection beyond 32 week's gestation. Two of the women had fresh vesicular lesions at parturition. The five infants were delivered per vaginum at term and escaped subsequent overt herpesvirus hominis infection, although a scalp lesion in one infant was dismissed as inconsequential and disappeared without virologic study. Examination of the infants two months to four years after birth failed to detect sequelae of possible subclinical infection.


The effect of cirrhosis on the disposition and elimination of clindamycin. This study assessed the effect of alcoholic cirrhosis in man and of experimental liver injury in rats on the disposition and elimination of clindamycin. In 7 cirrhotics a statistically significant, although modest, prolongation of clindamycin half-life (T1/2beta) was observed as compared to values in 7 age-matched normal contrals (mean plus or minus SD: 4.46 plus or minus 0.93 hr vs 3.42 plus or minus 0.45 hr, P equals 0.02). This was primarily due to a decrease in clindamycin serum clearance in the cirrhotics, since the volume of distribution of the drug was similar in both groups (P more than 0.05). Serum protein binding of clindamycin was of the order of 79% and was comparable in both groups (P more than 0.05). There was a significant correlation between the T1/2beta of the drug and both total serum bilirubin and SGOT. The T1/2beta of clindamycin was also prolonged in rats with acute hepatic necrosis induced by administration of carbon tetrachloride and those with acute cholestasis caused by common bile duct ligation. These data suggest that liver damage, both chronic and acute, impairs the elimination of clindamycin but that this effect is small.


Torsion of the wandering spleen.

Torsion of the wandering spleen. We report 2 cases of torsion of the wandering spleen that illustrate the roentgenologic features of this unusual condition. These are an abdominal mass, usually in the left flank of pelvis; absence of the splenic shadow beneath the left diaphragm; extrinsic compression of the colon at the level of the phrenicocoloc ligaments by the elongated splenic pedicle; and evidence of splenic vein occlusion, as indicated by gastric varices in the absence of esophageal varices. A combination of these findings should permit diagnosis or lead to angiographic or isotopic studies to confirm the presence of a wandering spleen.


Alice strain live attenuated influenza (H3N2) vaccin in an elderly population. The clinical and antibody responses to Alice strain (AS) live attenuated influenza A (H3N2) vaccine and killed parenteral (KP) bivalent influenza vaccine were compared in a randomly allocated group of 150 elderly volunteers. AS recipients experienced more symptoms but these were mild and short in duration. Rhinitis occurred in 45% and pain at injection site in 25% of the AS and KP groups, respectively. Influenza A (H3N2) serum hemmaglutination inhibition titer responses were significantly higher in KP vaccinees; 95% of KP AND 60% OF AS recipients with initial titers smaller than or equal to 1:16 had fourfold or greater titer rises. KP induced significantly higher nasal neutralization titers but the proportion with fourfold or greater responses was not significantly different. Previous studies have shown poor correlations between antibody levels induced by live influenza vaccines and protection. Natural and/or challenge studies are needed before efficacy of influenza vaccines can be established.


Institutional control of prescription blanks. A system designed to eliminate the illegal use of hospital prescription blanks to obtain Schedule II drugs is described. Several community pharmacies had reported receiving forged prescriptions for Schedule II drugs on hospital prescription blanks. The system places controls on prescription blanks for Schedule II drugs. Hospital physicians may prescribe these drugs using only special prescription blanks which are sequentially numbered. The blanks must be obtained by the physician in person from the pharmacy. Community pharmacists in the area are alerted in cases of lost or stolen prescription blanks.


Rational use of psychotropic drugs. IV. Antidepressants. Rational use of tricyclic antidepressant drugs is discussed. Before using antidepressant drug therapy, the clinician should determine the disease subtype of the depressive syndrome. Response to antidepressants is most favorable in cases of "endogenous" depression and less favorable in cases of situational (reactive) depression. The following considerations regarding tricyclic antidepressant therapy are discussed: dosage schedules, onset  of action, anticholinergic effects, cardiac toxicity and drug interactions. Patients who fail to respond to antidepressant drug therapy should be considered candidates for electroconvulsive therapy.


Photocoagulation of active and inactive lesions of presumed ocular histoplasmosis. Argon laser photocoagulation was employed in 27 eyes with presumed ocular histoplasmosis. Thirteen eyes with active macular lesions had stable or improved visual results (72%).


Computer content analysis of schizophrenic speech: a preliminary report. Computer analysis significantly differtiated the thermatic content of the free speech of 10 schizophrenic patients from that of 10 nonschizophrenic patients and from the content of transcripts of dream material from 10 normal subjects. Schizophrenic patients used the thematic categories in factor 1 (the "schizophrenic factor") 3 times more frequently than the nonschizophrenics and 10 times more frequently than the normal subjects (p smaller than 01). In general, the language content of the schizophrenic patient mirrored an almost agitated attempt to locate oneself in time and space and to defend against internal discomfort and confusion. The authors discuss the implications of this study for future research.


Granular cells in the juxtaglomerular apparatus in perinatal rats. Granular cell indices (GCI; Dunihue and Robertson, '57) in kidneys of fetal and newborn rats were determined by examining sections stained with Bowie's technique. Some fetuses were delivered prematurely by Caesarean section a day earlier than the expected delivery, and were then nursed by a foster mother. Similarly, postmature Caesarean newborn rats were obtained; retention one day beyond the normal gestation was induced by maternal progesterone injections. The GCI was strikingly increased within a day after birth, followed by an immediate decrease therafter. This was also observed in both premature and postmature rats. It seems that this temporary increase of the GCI is not attributable solely to the age of rat, but follows only the separation from the maternal environment.


Plasma levels of diazepam and mood ratings. Ten subjects received 10 and 20-mg. doses of diazepam intravenously. The plasma levels of the drug and its major metabolite, desmethyl-diazepam were measured and coordinated with answers to a subjective questionnaire. After initial rapid decline of the diazepam level, the level and shape of the remaining part of individual plasma curves showed considerable variance. Increases in diazepam levels were minute (0.04 plus or minus 0.03 mcg./ml.). Desmethyl-diazepam levels continued to build up until the end of sampling. Contrary to some previous reports, no recurrent drowsiness was evident after initial recovery. Correlation between plasma levels of diazepam and some of the subject's moods was significant. Nevertheless, further studies are needed to determine whether plasma levels can be meaningfully related to various cerebral effects of the drug.


The effect of levodopa on halothane anesthetic requirements. Acute and chronic levodopa (L-dopa) administration alters halothane minimum alveolar concentration (MAC) in dogs. L-dopa 5, 10, and 25 mg./kg. intravenously (I.V.) reduced halothane MAC 15, 20, and 25 percent, respectively, 1 hour after injection, with return toward normal after 3 hours. Fifty mg./kg. increased halothane MAC 40 percent at 1 hour, but produced at 30 percent decrease from control MAC at 3 hours. Two groups of 4 dogs each given oral L-dopa in doses increasing from 50 mg./kg. daily the 1st week to 300 mg./kg. daily the 5th week, decreased MAC an insignificant 9.5 plus or minus 25.2 percent at 4 hours after the last dose and increased MAC 3.5 plus or minus 7.3 percent at 12 hours after the last dose. A small, insignificant decrease of 9 percent in MAC was measured in 4 dogs given I.V. L-dopa 25 mg./kg. q.i.d for 4 days.


Missionary anesthesia.

Missionary anesthesia. Missionary anesthesiologists are needed for developing areas around the world. Missionary work has both rewarding and frustrating aspects. The rewards include adventures in living and medicine and the chance to aid less fortunate people. The frustrations include separation from family, uncomfortable living conditions, language barriers, and inability to change medical practices that seem improper.


Further studies of the neural mechanisms of ketamine-induced anesthesia in the rhesus monkey. Bipolar stimulation of tooth pulp was used to elicit evoked potentials in the cortex, thalamus, and midbrain reticular formation (MBRF) of 4 monkeys. Averaged evoked potentials in MBRF and medial thalamic nuclei were either completely obliterated or markedly reduced in amplitude by anesthetic dosages of ketamine. In contrast, little effect was observed upon the primary response elicited in the ventrobasal complex of the thalamus. These results suggest that anesthetic doses of ketamine block afferent signals concerned with the affective-emotional components of pain perception, but conduction of signals related to the localization of somatic stimuli in time and space may be relatively unimpaired.


The influence of enflurane anesthesia on intraocular pressure in youths. In a group of 19 patients aged 6 to 19, intraocular pressure was found to be moderately decreased in 84 percent during general anesthesia with enflurane.


Myotonia dystrophica--an anesthetic hazard: two case reports. The cluster of abnormalities characteristic of myotonia dystrophica makes anesthesia a hazardous procedure. A thorough history and physical examination are essential, anesthetic agents must be selected with care, and ventilation requires meticulous attention.


Patient refusal of surgery following Innovar premedication. Of 1438 patients premedicated with Innovar, 10 refused to undergo surgery. During the same period, there were no refusals by 2107 patients not premedicated with Innovar. This apparent difference suggests that a prospective study of Innovar and droperidol be made to determine whether there are changes in patient attitude that lead to refusal of surgery.


A volumetric system for monitoring minimal respiration in man. A microvolumetric noninvasive sensor is described for the monitoring of minimal respiration in adults, children, and infants. The monitor, designated a diaphragm sensor, has been applied since 1965 in the clinical management of optimal ventilation and relaxant drug administration. As an inspiratory monitor in the curarized patient, the sensor responds quantitatively to persisting spontaneous tidal volumes of 1 ml. or more. This minimal respiration is observed between controlled lung inflations. The monitor also indicates small outboard circuit leaks and responds to cardiac pulsations when respiratory deflections disappear after succinylcholine administration or hyperventilation. Applications include easy maintenance of ventilation near or below the patient's carbon dioxide (CO2) apneic threshold despite curarization and the assessment of diaphragm paralysis when the CO2 drive is maintained slightly above threshold. In continuous routine use, the diaphragm sensor provides the anesthesiologist with a quantitative monitor of persisting spontaneous respiratory activity.


The lower limits of flammability of halothane, enflurane, and isoflurane. Halothane, enflurane, and isoflurane, generally regarded as nonflammable, can be ignited under laboratory conditions. Attainment of similar conditions during clinical anesthesia is most unlikely. Nevertheless, early in the course of anesthesia while the concentration of the agent is still high, electrosurgery is best avoided if nitrous oxide is part of the anesthetic mixture and the operative field is exposed directly to the inflowing gases (as during certain laryngeal procedures).


Cytotoxic testing and leucocyte increase as an index to food sensitivity. II. Coffee and tobacco. Cytotoxic testing has been used to identify and evaluate potential sensitizers among three adult age groups. Coffee and toabacco were used as single sensitizers to further illustrate the vivo WBC response technique, as an independent test for corroborating was advanced outlining a possible explanation of the cytotoxic test results. This theoretical approach might be used to study clinical problems where allergic etiologies are suspected.


Propagation of bovine viral diarrhea viruses in bovine fetal lung cell cultures. A procedure to prepare and maintain bovine fetal lung (BFL) cell cultures was established. These cell cultures grew abundantly and readily and were easy to handle. Monolayers could be kept in satisfactory condition in maintenance medium for 14 days. The yield from the lungs of one fetus was 15 to 30 primary culture Roux bottles, and 40,000 5th-generation test tubes. The BFL cells were satisfactorily kept at minus 70 C with the addition of dimethyl sulfoxide (DMSO). When the BFL cell cultures were infected with cytopathic bovine viral diarrhea (BVD) viral strains, the cytopathic effect (CPE) was clear and distinct and was first seen on postinoculation (PI) day 1. The end points for viral titrations and serum-neutralization (SN) tests were readily determined. The BFL cells were satisfactory for supporting replication of the BVD viral strains. The titer of the virus propagated in the cells was 10-7.0 to 10-8.0 median tissue culture infective doses (TCID50)/1ML. Growth curves of the BVD viruses are reported.


Use of ketamine in pediatric dentistry.

Use of ketamine in pediatric dentistry. Intramuscular ketamine, in a dose of 3 to 5 mg./kg. of body weight, associated with succinylcholine or halothane when necessary, was found to provide satisfactory anesthetic and operating conditions for dental extractions or surgery in 92 mentally or physically handicapped pediatric outpatients.


Photocoagulation in diabetic retinopathy: focal treatment or partial retinal ablation? Diabetic retinopathies treated by two different techniques were followed photographically and fluoro-angiographically. With the argon laser we treated the fluoro-angiographical lesions (210 eyes, follow-up 6 to 29 months) and with the xenon arc we made a barrage around the posterior pole without treating the lesions specifically (54 eyes, follow-up 12 to 36 months). In fact, we compared two different techniques and not two types of photocoagulators. After reviewing our results we may conclude that widespread coagulation (indirect method) is better than the topical treatment alone, but the combination of both techniques is the most suitable method.


Bupivacaine compared with etidocaine for vaginal delivery. A comparison of 0.5 percent etidocaine with 0.25 and 0.5 percent bupivacaine, using continuous (intermittent) caudal block in 60 vaginal deliveries, showed the latter two solutions to be the agents of choice. All solutions contained a final concentration of 1:2000,000 epihephrine. In 40 parturients given either 0.25 or 0.5 percent bupivacaine, all had pain relief after the initial dose, while 5 of 20 given etidocaine required a refill dose within 30 to 50 minutes for complete pain relief. The duration of action of the initial dose with both concentrations of bupivacaine was longer than that of etidocaine. The degree of motor blockade with 0.5 percent etidocaine was greater than with 0.5 percent bupivacaine, and with 0.5 percent concentrations of either etidocaine or bupivacaine was greater than with 0.25 percent bupivacaine. The duration of motor blockade of 0.5 percent etidocaine and bupivacaine was comparable. The duration of motor blockade of the 0.25 percent concentration of bupivacaine was shorter than with the 0.5 percent concentration of both etidocaine and bupivacaine; and with both bupivacaine concentrations the duration of sensory anesthesia in the extremities was longer than motor blockade; with etidocaine, the opposite occurred.


Regulation of predation by prey density: the protozoan-Rhizobium relationship. Tetramitus rostratus and strains of Hartmanella, Naegleria, and Vahlkampfia consumed large numbers of Rhizobium meliloti cells in a salt solution, but protozoan multiplication and the bacterial decline stopped when the prey density fell to about 10-6 to 10-7 cells/ml. At higher prey densities, the maximum numbers of Hartmanella sp. and Naegleria sp. were proportional to the quantity of R. meliloti initially provided to the amoebas. When supplemental rhizobia were supplied to Hartmanella sp. or Naegleria sp. after their active feeding had terminated, presumably because the remaining 10-6 or 10-7 bacteria/ml could not be captured, replication of the protozoa was initiated. The rate of elimination of rhizobia present in large populations was proportional to the initial abundance of Naegleria sp., but the final numbers of amoebas and surviving R. meliloti cells were independent of initial numbers of predators. The surviving bacteria were not intrinsically resistant to attack because 98% of the survivors, when concentrated, were consumed. It is suggested that large populations of bacteria in nature may be reduced in size by predatory protozoa, but many of the prey cells will not be eliminated.


Mycotoxin-producing potential of mold flora of dried beans. To evaluate the potential for mycotoxin production by molds in dried beans, the mold flora of 114 samples was determined both before and after surface disinfection of the beans with 5% NaOCl. Surface disinfection substantially reduced mold incidence, indicating that contamination was mainly on the surface. The flora, both before and after disinfection, was dominated by species of the Aspergillus glaucus group, the toxicogenic species A ochracues, Penicillium cyclopium, and P. viridicatum, and species of Alternaria, Cladosporium, and Fusarium. The toxicogenic species Aspergillus flavis, A. versicolor, Penicillium Citrinum, P. expansum, P. islandicum, and P. urticae were encountered less frequently. Of 209 species of Aspergillus and Penicillium screened for mycotoxin production on sterile rice substrate, 114 produced one or more of the following mycotoxins: A. flavus, aflatoxins; A. ochraceus, ochratoxins; A. nidulans, A. unguis, and A. versicolor, sterigmatocystin; P. cyclopium, penicillic acid; P. citrinum and P. viridicatum, citrinin; P. urticae, patulin and griseofulvin. Sterigmatocystin production by A. unguis is reported for the first time.


Method for sampling meat surfaces.

Method for sampling meat surfaces. A new method for sampling meat surfaces was developed. Bacterial counts of beef carcasses by the cotton swab technique and by the new method showed that the latter gave higher counts. These counts were closely correlated with data obtained by using the swab method. Advantages of the new method are its simplicity, rapidity, and adaptability to routine use on any type of carcass.


Thyroid function during exchange transfusion. The changes in plasma thyroid hormone concentration were studied during exchange transfusion performed for haemolytic disease. 24 transfusions were performed using blood preserved with acid-citrate and dextrose and in 11 cases 10 or 50 mug glucagon was added to the donor blood. Plasma tri-iodothyronine (T3), thyroxine (T4), thyrotropin (TSH), thyroid hormone binding capacity, and free thyroxine index were measured in the donor blood and in the infant at the start and at intervals during the transfusion. Before transfusion the plasma TSH levels of the infants fell as postnatal age indreased and plasma T3 and T4 were correlated with one another. In 20 transfusions the mean infant/donor ratio of TSH was approximately 10, of T4 3, and of T3 2. During these transfusions there was a progressive fall in the infant's plasms TSH, T4, and T3 concentration. In 3 transfusions in which the donor plasma TSH was greater than that of the infant, plasma TSH levels rose during the transfusion and in 2 cases this was associated with a late rise in plasma T3 levels. The addition of glucagon to donor blood had no effect on thyroid hormone levels. It is concluded that erythroblastotic infants have normal thyroid function and that they became biochemically hypothyroid during transfusion. Acute changes in plasma thyroid hormone and glucagon concentration do not induce TSH responses by the neonatal pituitary during the period of the exchange transfusion.


Unusual clinical course in a child with cystic fibrosis treated with fat emulsion. A child diagnosed as having cystic fibrosis by customary criteria has been given regular parenteral soya oil emulsion from near birht. Sweat tests have improved, pancreatic achylia was relieved, and the child at present remains entirely well. Correction of the essential fatty acid deficiency found in cystic fibrosis may prevent some of the manifestations of the disease.


Alzheimer II astrocytosis following methionine sulfoximine. A light microscopic study was performed during the preictal period following the administration of methionine sulfoximine (MSO) to adult rats. The principal morphologic observation was the development of Alzheimer II astrocytes in gray matter, suggesting that the metabolic abnormality induced by MSO is initially confined to the astrocyte. In view of the association of the Aizheimer II astrocyte with hyperammonemic states, the drug toxicity may be secondary to the presence of ammonia. A possible mechanism involves astrocytes in the development of seizures produced by MSO.


The diagnosis of fetal hydronephrosis, megaureter and urethral obstruction by ultrasonic echography. Two cases of fetal urethral obstruction, one with megaureter and obvious hydronephrosis, were diagnosed by two-dimensional ultrasonic echography. With good quality echograms it should be possible to make the diagnosis early in pregnancy.


The renal clearance of oestriol in late human pregnancy. The renal clearance of unconjugated oestriol, oestriol glucosiduronate and oestriol sulphate by the kidney in late human pregnancy has been compared with simultaneous measurements of inulin clearance. The results for the fractions not bound to protein indicate that after glomerular filtration, unconjugated oestriol is completely reabsorbed, oestriol glucosiduronate is both filtered and excreted actively by the tubules, and that oestriol sulphate is filtered but not excreted or absorbed by the tubules; the administration of probenecid confirms these observations on tubular handling. The possibility of using endogenous oestril sulphate as a means of measuring the glomerular filtration rate in pregnancy is suggested.


Assessment of thyroid function during pregnancy. Serum levels of thyroid stimulating hormone and of the two thyroid hormones were compared in pregnant women and in non-pregnant control subjects. Circulating levels of thyroid stimulating hormone did not alter significantly throughout pregnancy. Total thyroxine and triiodothyronine concentrations increased markedly during the first and second trimesters, associated with a progressive increase in the thyroid binding capacity of serum proteins. Urinary triiodothyronine and thyroxine excretion during the third trimester of pregnancy was comparable to that found in non-pregnant euthyroid females and, it is concluded, provides the simplest method of assessing thyroid function during pregnancy.


Pneumothorax and surgical emphysema in a newborn baby caused by amniocentesis. A report is presented of a newborn baby who developed a pneumothorax and extensive surgical emphysema after being delivered by Caesarean section for fetal distress soon after the mother had an amniocentesis.


An evaluation of human placental lactogen levels in hypertension of pregnancy. Maternal plasma levels of human placental lactogen (HPL) are decreased in hypertensive pregnancies and the concentration is related to the severity of the condition. Of infants who had HPL concentrations in the fetal danger zone (more than 2 SD's below normal mean) 75 per cent developed fetal distress, neonatal asphyxia or were light for dates. Patients who are identified in this way have lighter infants and placentae than their unidentified counterparts with normal HPL levels.


The reaction of bovine thrombin with N-butyrylimidazole. Two different reactions resulting in the inhibition of catalytic activity. N-Butyrylimidazole has been found to be a potent inhibitor of purified bovine thrombin. The rate and extent of inhibition of thrombin by N-butyrylimidazole could be reduced by the presence of benzamidine, a competitive inhibitor, or by the ester substrate, p-tosyl-L-arginine methyl ester. Spectral studies of the reaction of N-butyrylimidazole with thrombin demonstrated the modification of approximately 1 mol of tyrosine/mol of enzyme at maximum inhibition. In addition to the reaction with tyrosine, N-butyrylimidazole also appears to react with a residue at the "active site" as judged by a decrease in the number of active sites available in the modified enzyme for titration with p-nitrophenyl-p'-guanidinobenzoate. The time course of ester hydrolysis by butyrylated thrombin showed a distinct lag phase suggesting partial reactivation of the enzyme under assay conditions. Partial reactivation of the modified enzyme also occurred spontaneously upon standing in 0.5 M NaCl but was much faster in presence of imidazole (0.03 M, pH 7.6). It is suggested that, in addition to reaction with tyrosine, there is a reaction of N-butyrylimidazole with either the histidine and/or serine residue at the active site of thrombin resulting in a derivative unstable under esterase assay conditions such as that described for the reaciton of N-acetylimidazole with trypsin (L. L. Houston and K. A. Walsh (1970), Biochemistry 9, 156).


Histone-histone associations within chromatin. Cross-linking studies using tetranitromethane. Treatment of chromatin with the protein cross-linker tetranitromethane (TNM) results in a product identified as an F2a1-F2b dimer. The same product appears after treatment with TNM of HeLa cells growing in culture. Furthermore acid-extracted histones which have been fractionated into the five separate species can be recombined and mixed with DNA to produce a nucleohistone preparation which is also cross-linked by TNM to give the F2a1-F2b dimer. F1 and F3 can be excluded from the reconstitution mixture without effect on the dimer production. In contrast, the presence of F2a2 is essential to the proper reconstitution of F2a1 and F2b with DNA. The specificity of TNM and the characteristics of the reaction suggest that F2a1 and F2b are cross-linked at their specific binding sites. These results provide evidence that F2a1, F2a2, and F2b interact specifically in chromatin.


Polyadenylated RNA complementary to repetitive DNA in mouse L-cells. Complementary DNA, synthesized with L-cell polyadenylated RNA as template, renatured with total L-cell DNA to about 70%. About 30% complementary to unique sequence DNA and another 10 and 30% corresponded to sequences about 20- and 500-fold repetitive. Complementary DNA was fractionated after partial hybridization with total polyadenylated RNA to obtain preparations enriched or impoverished in complements of the most frequent polyadenylated RNA. Renaturation of these complementary DNA fractions with L-cell DNA revealed that most frequent RNAs are transcribed from repetitive DNA sequences, Complementary DNA, density labeled with bromodeoxyuridine, was fractionated by renaturation with L-cell DNA to yield fractions enriched in repetitive and unique sequence DNA. The denisty labeled complementary DNA was purified by equilibrium centrifiguation in an alkaline Cs2SO4 gradient. The complementary DNA representing mainly repetitive DNA sequences hybridized preferentially to frequent polyadenylated RNA.


Interaction of histone f2al fragments with deoxyribonucleic acid. Circular dichroism and thermal denaturation studies. The glycine-arginine-rich histone, f2al (IV) (102 amino acids), from calf thymus was cleaved at residue 84 with cyanogen bromide. Complexes containing homologous DNA and each f2al fragment were reconstituted by means of Gdn-HC1 gradient dialysis. The circular dichroic (CD) spectra of these complexes were all examined in 0.14 M NaC1. The CD spectra of the DNA-f2al fragment complexes did not differ appreciably from that of DNA alone in the wavelength region above 240 nm. However, intact f2al-DNA complexes yield CD spectra which differ significantly (enhanced, blue-shifted, 273-nm band) from that of native DNA (Shih and Fasman, 1971). The small C-terminal fragment (85-102) was bound weakly to DNA under the conditions used. However, the large basic N-terminal fragment (1-83) was bound as well to DNA as was whole f2al, but produced no CD distortion. The conformation of the N-terminal fragment, unlike intact f2al, was not changed upon increasing the ionic strength to 0.14 M NaF. These results complement previous studies on f2al and its N-terminal CNBr fragment (Ziccardi and Schumaker, 1973). Thermal denaturation of the complexes in 2.5 X 10(-4) M EDTA was monitored simultaneously by changes in the absorption and CD spectra. All complexes showed a thermal transition at 45 degrees (Tml), attributable to the melting of free, double-stranded DNA. In addition, f2al-DNA and N fragment-DNA complexes displayed melting phenomena at 88 and 78 degrees (Tm2), respectively, caused by the denaturation of the histone-bound DNA. This difference in Tm2 constitutes further evidence that loss of the 18-amino-acid carboxyl end segment of f2al prohibits the unique type of interaction which occurs between DNA and the intact histone.