Supratentorial extracerebral cysts in infants and children. Twelve cases of supratentorial extracerebral cysts in infants and children are reported. Eight were located in the Sylvian fissure, two in the interhemispheric fissue, and two over the convexity of the cerebral hemispheres. Irrespective of their precise location these cysts, in their common, uncomplicated form, give rise to a clinical syndrome different from that recorded in older patients, with a symmetrical macrocrania of a severe degree unassociated with any neurological signs or abnormalities in psychomotor development. Extensive unilateral transillumination of the skull is common (six cases). These features, in association with specific angiographic and pneumoencephalographic findings, make a preoperative diagnosis possible. Extracerebral cysts (either arachnoidal or histologically more complex) should be distinguished from intracerebral cavities which may closely mimic them, even at surgery. The natural history of infatile cysts is studied and serial head-measurements (pre-and postoperative) are presented in five cases. Insufficient knowledge of the spontaneous course and incidence of complications prevents definite statements on the necessity and type of therapy.


Auditory affective agnosia. Disturbed comprehension of affective speech. Hughlings Jackson noted that, although some aphasic patients were unable to use propositional speech, affective speech appeared to be spared. The purpose of this experiment was to study patients with unilateral hemispheric disease in order to ascertain if there are hemispheric asymmetries in the comprehension of affective speech. Six subjects had right temporoparietal lesions (left unilateral neglect) and six subjects had left temporoparietal lesions (fluent aphasias). These subjects were presented with 32 tape recorded sentences. In 16 trials the patients were asked to judge the emotional mood of the speaker (happy, sad, angry, indifferent) and in 16 trials the patients were asked to judge the content. Line drawings containing facial expressions of the four emotions or line drawings corresponding with the four basic contents were displayed with each sentence and the patient responded by pointing. All 12 subjects made perfect scores on the content portion of the test. On the emotional portion the right hemispheric patients scored a mean of 4-17 and the left hemispheric group scored a mean 10-17. The difference between these means is significantly (P less than 0-01) and suggests that patients with right hemispheric dysfunction and neglect have a defect in the comprehension of affective speech.


Arterial blood pressure in patients with Parkinson's disease. The casual arterial blood pressure of 411 patients with Parkinson's disease was compared with that of a representative sample of the general population. The patients were also divided into various sub-groups, and comparisons of blood pressure were made between them. The results provided no support for the widely held belief that blood pressure tends to be low in patients with Parkinson's disease.


Regional cerebral blood flow changes after bilateral external carotid artery ligation in acute experimental infarction. Regional cerebral blood flow (rCBF) was measured in baboons by intracarotid injection of 133Xe and a gamma camera after acute cerebral infarction was induced by occlusion of the middle cerebral artery (MCA). A steady state of rCBF was measured four hour after MCA occlusion and was followed by bilateral ligation of the external cartoid arteries (ECA). Subsequent rCBF measurements were obtained at 30, 60, and 120 minutes. After bilateral ECA ligation, flow in ischaemic and non-ischaemic areas was greatly enhanced and flow in the hyperaemic areas significantly reduced, presumably since they had provided collateral circulation to the ischaemic zone with a favourable redistribution.


Spontaneous spinal epidural haemorrhage: good results after early treatment. Extravasation of blood in the spinal epidural space is an uncommon but often disastrous problem. Severe trauma, anticoagulants, bleeding diatheses, and intraspinal vascular malformations have been associated with such haemorrhage, but occasionally it occurs without apparent cause. It may then be confused with transverse myelopathy or vascular occlusion. Early diagnosis by myelography and treatment by surgery can result in good recovery, as illustrated by two cases.


Sub-clinical entrapment neuropathy in man. Twelve median and 12 ulnar nerves were obtained at routine autopsies from patients without known disease of the peripheral nervous system.  Enlargement of cross-sectional area due to an increase in connective tissue elements was commonly present in the ulnar nerve at the elbow and in the median nerve under the flexor retinaculum. Renaut bodies were also prominent at these two sites.  The connective tissue changes did not appear to be related to the presence or absence of nerve fibre damage. When nerve fibres were teased apart and examined individually, localised changes were found at the elbow in 5 ulnar nerves and under the flexor retinaculum in 5 median nerves.  The changes were mild and transverse sections at the same levels showed few abnormalities. However, the changes were similar in character to those described previously in experimental animals with entrapment syndromes. They are therefore considered to be valid evidence of sub-clinical entrapment in apparently unaffected human subjects.


A pressure vessel model for nerve compression. This paper suggests that compression block in nerve can be better interpreted in terms of a pressure vessel model for nerve fiber distension that the more common models based upon tubes with more or less rigid walls. In this model resistance to compression is due to the elasticity of the cell membrane at locations where displaced intracellular fluid tends to distend it.  Because the stresses in pressure vessels increase with the size of the vessel, the theory predicts that the percentage deformation should be larger in larger diameter fibers.


Vesicular disruption of myelin in autoimmune demyelination. A pattern of autoimmune demyelination in EAE and EAN has been described which was encountered consistently and was sometimes more common than the better known phenomenon of active stripping of myelin by macrophages. This pattern involved the rapid dissolution of myelin into a vesicular network which was later degraded by macrophages. It occurred early in the disease, was not accentuated perivascularly, and was usually associated with the presence of macrophases. The underlying mechanisms are not known but several alternatives have been discussed, viz., activity of locally released antibody, cytotoxic factors, or hydrolytic enzymes.


Hyperthyroid myopathy. Intracellular electrophysiological measurements in biopsied human intercostal muscle. Morphological and electrophysiological studies were performed on intercostal muscle biopsies from 2 thyrotoxic patients. The diseased fibers had numerous areas of subsarcolemmal glyogen accumulations and abnormal membranous projections. Both Type I and Type II muscle fibers were atrophied.  Diseased fibers were substantially depolarized and when artifically hyperpolarized showed earlier inactivation of the sodium conductance as a function of membrane potential, and a critical depolarization potential more depolarized than in normal fibers. When stimulated at 20 pulses/sec, or faster, the diseased fibers could not generate normal action potentials due to membrane depolarization and the appearance of a marked after-hyperpolarization. Muscle weakness associated with hyperthyroidism is attributed to the reduced membrane excitability.


Recurrent experimental allergic neuritis. An electron microscope study. Experimental allergic neuritis has been induced in 52 guinea pigs by the inoculation of rabbit peripheral nerve in Freund's adjuvant. The majority  of the animals developed an acute monophasic illness after a mean interval of 16 days and, if they survived, recovered fully after an average period of 52 days. Two animals displayed a more chronic course and 1 animal relapsed spontaneously after clinical recovery had occurred. Twenty-three animals that recovered were re-inoculated when recovery was complete and in 4 a relapse was induced. In the remainder, no clinical response was observed, even after repeated reinoculations. The ultrastructural appearances in the animals with a monophasic illness were similar to those previously reported. The appearances differed markedly in those animals that were induced to relapse and were similar to those in the animal that relapsed spontaneously. The findings indicated persistent demyelination and remyelination with striking hypertrophic changes (onion bulb neuropathy). The possible reasons for the differences between the two groups are discussed.


Adenyl cyclase activity in Duchenne dystrophic muscle. Adenyl cyclase activity in normal and Duchenne dystrophic muscle was assayed using a radiochemical method. In dystrophic muscle, the enzyme activity is reduced. The reduced enzyme activity and its adverse effects on energy metabolism in dystrophic patients are discussed.


Single fibre electromyography in various processes affecting the anterior horn cell. SFEMG recordings were carried out in patients with amyotrophic lateral sclerosis, progressive muscular atrophy, familial spinal muscular atrophy and syringomyelia. The fibre density was increased in all conditions, especially in progressive muscular atrophy indicating marked collateral sprouting. The duration of the action potential was increased indicating a mixture of hypertrophic and atrophic fibres and slowly conducting newly formed nerve sprouts. The action potentials were unstable with varying degree of impulse blocking especially in the more progressive cases (ALS), representing recent re-innervation. The SFEMG method is used to characterize the functional status of the motor unit and helps in diagnosis and in predicting prognosis. In addition, SFEMG recordings reveal abnormalities in clinically and electromyographically normal muscles.


Neurotoxicity of hexachlorophene: new pathological and biochemical observations. Twenty female rats with nursing litters were fed a diet containing 500 p.p.m. of hexachlorophene (HCP). The blood concentrations of hexachlorophene in mother rats were 4.7-6.0 mug/ml and in infant rats 2.0-2.5 mug/ml. Fifty percent of mother rats and 75% of infant rats died. Most of the surviving animals were asymptomatic apart from imparied visual function. Ten adult and 20 infant rats were killed by perfusion. Light- and electron-microscopic studies showed vacuolation of myelin in the central and peripheral nervous system and axonal degeneration which was especially severe in the optic nerves. After withdrawal of HCP hydrocephalus ex vacuo was present in the chronically intoxicated infant rats and the optic nerves showed marked atrophy and gliosis. Studies with liver mitochondria prepared from lactating hexachlorophene-fed rats showed a 50-75% inhibition of respiration with succinate as substrate.


Some observations on the skeletal musculature of aged rats. Part 2. Fine morphology of diseased muscle fibres. The ultrastructural changes seen in muscle fibres of aged rats have been studied and described in relation to the degree of fibre atrophy and to the involvement of the different fibre types. The ultrastructural abnormalities were classified into four different categories: (1) diffuse dilatation of sarcoplasmic reticulum, (2) streaming of Z-bands, (3) so-called myofibrillar degeneration, and (4) myofibrillar "homogenization". These are all, except (1), abnormalities which affect principally the contractile elements of the muscle fibre. The ultrastructural changes represent a chronic process. The abnormality most often encountered and hence the most important is myofibrillar degeneration. Of these four types of change, myofibrillar degeneration and myofibrillar "homogenization" may be degenerative in nature and lead eventually to the total dissolution of the muscle fibres involved. Smudging of Z-bands and diffuse dilatation of the sarcoplasmic reticulum, although occasionally diffuse and massive, were often found in otherwise normal muscle fibres and were rarely observed in severely atrophic ones. We therefore conclude that these latter two types of change are probably reactive in nature and are not ultimately lethal to the muscle fibres involved. Longitudinal sections of affected muscle fibres clearly showed that the morbid process involves a muscle fibre unevenly and not simultaneously over its entire length. Various stages of myofibrillar degeneration, for example, could be observed at the same time in different portions of one and the same muscle fibre. Streaming of Z-bands was observed exclusively in what appeared to be red fibres, while myofibrillar degeneration was observed predominantly in white or intermediate fibres. However some of these muscle fibres with myofibrillar degeneration could have been red fibres which had lost their mitochondrial population. Myofibrillar "homogenization" occurred in both red and white fibres. Other miscellaneous changes within muscle fibres are briefly described and discussed. Although the findings observed are in general non-specific in nature, the importance of neurogenic mechanisms is inferred. The occurrence of age-related ultrastructural alterations may have important implications in the study of muscle in general.


Changes in creatine kinase and its isoenzymes in human fetal muscle during development. The total creatine kinase activity and its isoenzyme patterns were investigated in the skeletal muscle of 87 fetuses, of which 80 were presumed normal, 5 were anencephalic and 2 were "at risk" for Duchenne muscular dystrophy (DMD). No differences, either in total enzyme activity or in the isoenzyme distributions, were found between the anencephalic fetuses or those at risk for DMD, when compared to normal fetuses of similar gestation. Creatine kinase activity was found to rise steadily throughout embryonic life. During fetal development, the isoenzyme pattern in skeletal muscle was observed to change from the initial prevalence of the brain (BB) type, to the predominance of the muscle (MM) form. The most pronounced change occurred between the 6th and the 16th week of gestation, a period characterized by the rapid fusion of myoblasts to form myotubes and the concomitant production of myofibrils. It is proposed that there is a close association between the creatine kinase isoenzymes spectrum and the stage of muscle development.


X-linked spinal and bulbar muscular atrophy of late onset. A separate type of motor neuron disease? The clinical, electrophysiological and muscle biopsy findings of 7 cases with a peculiar form of X-linked hereditary degenerative motor neuron disease are presented. It is suggested that the disease might be a separate clinical entity with the following characteristics: (1) sex-linked recessive inheritance, (2) unusual but not invariable late onset, (3) slow progression, (4) facial-bulbar and proximal spinal muscle involvement, (5) consistent fasciculations, sometimes massive and more pronounced about the lips, chin and tongue, (6) fine tremor of the hands, (7) muscle cramps usually preceding the other symptoms, and (8) gynaecomastia as a frequent but not a constant feature.


Transmission of multiple sclerosis by blood transfusion? A survey of 14,000 multiple sclerosis patients revealed 289 blood donors; 65 of them had already shown clinical manifestations at the time of blood donation. In view of current immunological and virological hypotheses on multiple sclerosis, such patients should not be accepted as blood donors. An effort is being made to determine whether multiple sclerosis has been transmitted to the recipients of this blood.


The fine structure of the cervical spinal cord, ventral root and brachial nerves in the wobbler (wr) mouse. Much indirect evidence supports the prevailing concept that the wobbler mouse represents an inherited form of lower motor neuron degeneration, with resultant neurogenic muscular atrophy, due to an autosomal recessive gene (wr). This report, which emphasizes the fine structural changes in the wobbler mouse cervical spinal cord, ventral root and brachial nerves, both extends and modifies previously published data concerning the ultrastructural changes in this disorder. In addition to the more obvious neuronal cytoplasmic vacuolization known to occur, studies extended to a broader age range of wobbler mice have revealed neuronal alterations such as nonvacuolar dissolution of granular endoplasmic reticulum, proliferation of cytoplasmic microtubules and neurofilaments, proliferation of branched tubules resembling smooth endoplasmic reticulum, development of lipid droplets, and increased numbers of pleomorphic dense and lamellar cytoplasmic bodies. The spectrum of pathological changes in this murine form of motor neuron disease thus appears more complex and varied than has hitherto been appreciated, and may be relevant to the formulation of pathogenetic hypotheses.


Retinal tumor induction by ocular inoculation of human adneovirus in 3-day-old rats. A direct causal relationship between a human DNA virus, adeno serotype 12, and malignant transformation in target cells (sensory retinal neuronal precursors) was suggested by the development of a remarkably uniform retinoblastoma-like neoplasm in rats. In order to focus upon incipient photoreceptor differentiation, 27 3-day-old CD rats were selected for intraocular virus inoculation. A single injection of 0.03 ml of the virus fluid, 104.5 TCID50 HeLa cells/0.1 ml was given in the left eye. Within 73 to 167 days after the virus inoculation, 12 rats (44.4%) developed retinal tumors in the left eye. Although retinal tumors mimicking human retinoblastoma with true rosettes were anticipated, the highly uniform histopathologic appearance of all 12 eyes was virtually indistinguishable from that of 0-day-old rats. However, multiple foci of malignant cells fusing with the inner segment of relatively well-differentiated retinal layers were found haphazardly throughout the cases; such retinal remnants were not detectable in tumors of 0-day-old rats. Electron microscopy revealed poorly differentiated tumor cells that possessed a single cilium consisting of a typical ring of nine doublets with no axial pair (a 9 plus 0 pattern). Advenovirus-specific T-antigens detected in vivo by the immunofluorescein microscopic procedure in abortively infected or transformed cells clearly indicated that some neuronal precursors destined for part of the ganglioneuronic layer are selectively susceptible to viral oncogenesis. No preferential involvement of the photoreceptor cells was observed. No control animals developed retinal neoplasms.


Dermatomyostis of childhood, ultrastructural alteratious of muscle and intramuscular blood vessels. Muscle biopsies from 8 children with dermatomysotis and from 4 normal children and 4 children and adults with other primary diseases of muscle were studied by ultrastructural techniques. The major abnormalities in dermatomyositis of childhood were in the walls of the intramuscular blood vessels, more specifically in the endothelial cells of capillaries, arterioles, and veins. Endothelial cells were observed in various stages of degeneration and regeneration. In a single plane of section, inclusions consisting of tubular aggregates were found within the cytoplasm of 76 to 98% of all intramuscular blood vessels. The angiopathy resulted in multiple thrombus formation and infarction of muscle. Three factors were of particular importance in the genesis of these events: separations at the cell junctions in the regenerating endothelium; the necrosis of endothelium with subsequent retraction, distortion and cell loss; and endothelial hyperplasia. These observations provide strong support for the concept that dermatomyositis of childhood is a unique disease, the fundamental lesion of which is in the walls of the intramuscular blood vessels.


Effects of mannitol and steroid therapy on intracranial volume-pressure relationships in patients. The intracranial volume-pressure response was measured in 61 patients undergoing continous monitoring of intraventicular pressure. This test, which determlnes the increase in intracranial pressure induced by an addition of 1 ml in ventricular CSF volume in 1 sencond, yields information concerning spatial compensation in patients with intracranial space-occupying processes. On the basis of variability tests, a change in volume-pressure response of 2 mm Hg/ml was accepted as significant. Pronounced enlargement of the ventricles interferes with the test. In patients with intracranial hypertension, intravenous mannitol (0.5gm/kg) and intramuscular betamethasone (26 mg) both reduce the volume-pressure response significantly more than they reduce intracranial pressure. This suggests that these agents favorably alter the configuration of the volume-pressure curve.


Increase in cerebral perfusion pressure by arterial hypertension in brain swelling. A mathematical model of the volume-pressure relationship. Brain swelling was produced in monkeys and cats by the inflation af an epidural balloon against the parietal lobe. Resulting changes in intracranial pressure (ICP) were correlated to variation in systemic arterial pressure (SAP). Intracranial perfusion pressure (ICPP) defined as the difference between SAP and ICP, was found to vary with the degree of arterial hyper-and hypotension. The relationship between SAP and ICP can be explained by an existing equilibrium between extramural pressure and vessel wall circumferential tension. A positive perfusion pressure can exist in brain swelling as long as vessel wall tension is preserved and the degree of expanding brain tissue volume is held below certain limits.


Distribution of activity in spinal pathways evoked by experimental dorsal column stimulation. Experiments were performed in rhesus monkeys to determine the distribution of activity evoked in spinal pathways by dorsal column stimulation. It was shown that many pathways in both the dorsal and ventral quadrants of the cord can be activated either directly or transsynaptically by stimulation with electrodes of the type implanted clinically. Moreover, the transsynaptically evoked responses recorded in each quadrant had somewhat different characteristics. Therefore, since the activation of each group of pathways may have differing effects in modifying the preception of noxious stimuli, the authors believe that changes in electrode position and stimulus parameters may be important in obtaining the therapeutic value of spinal cord stimulation for relief of pain.


Supraspinal interactions resulting from experimental dorsal column stimulation. Experiments were performed on rhesus monkeys to examine the hypothesis that stimulation with dorsal column electrodes of the type implanted clinically could alter the responses evoked in supraspinal nuclei through pathways in the ventral quadrant of the spinal cord. Dorsal column stimulation did produce changes in responses evoked in supraspinal nuclei; this effect could not be ascribed to a conduction block in ascending pathways. These results suggest that the mechanism of action of the dorsal column stimulator need not be dependent on interactions in the dorsal horn.


Phantom limb pain. Treatment with dorsal column stimulation. Good to excellent relief of phantom pain is reported in 5 of 6 patients by the use of dorsal column stimulation. Follow-up periods are 7 to 25 months. One failure occurred despite excellent pain relief; this patient could not tolerate application of the DCS apparatus to his chest wall. The authors review the physiology involved and some less successful series reported by others.


Relief of pain by transcutaneous stimulation. A series of 198 patients with chronic pain of diverse etiology was carefully analyzed for epidemiologic and descriptive factors which might influence the response to transcutaneous stimulation. The overall series included 12 1/2% with long-term success, and 68% with partial or short-term relief. There were no consistent specific diagnoses, or epidemiologic or descriptive factors that made good results from stimulation predictable. Stimulation of the painful area itself was not always necessary for pain relief. Favorable responses to transcutaneous stimulation were usually correlated with the continued existence of significant sensory input from the painful region. The authors conclude that transcutaneous stimulation is a valuable therapeutic modality for some patients with chronic pain.


Value of gas myelography in early management of acute cervical spinal cord injuries. Gas myelography was carried out in 22 patients with acute cervical spinal cord injuries in whom oily contrast media seemed contraindicated. The authors believe this technique makes a valuable contribution to the basic decision regarding the surgical versus medical treatment of a specific patient with a cervical cord injury. They emphasize the importance of visualizing cord compression due to disc herniation in these cases and conclude that gases are the optimal contrast agents for visualization of the entire circumference of the spinal cord.


Effect of alpha-retinyl acetate on growth of hamsters fed vitamin A-deficient diets. The capacity of the alpha-isomer of retinyl acetate to support growth in hamsters fed a vitamin A-deficient diet was assessed over a 40-fold dose range. Although decreased relative potency of the alpha isomer, as compared with the beta isomer, was found, sustained weight gain and survival for 6 months were achieved with a weekly intraperitoneal dose of 300 mug of the alpha isomer. An intraperitoneal dosage of alpha-retinyl acetate resulted in greater activity than an oral dosage.


Selenium content of food consumed by Canadians. Four composite diets from three cities, each representing the daily per capita consumption of foods in Canada, contained on analysis 191, 220, 113, and 150 mug selenium. Cereals provided the most selenium (62-112 mug) followed by meat, poultry, and fish (25-90 mug) and dairy products (5-25 mug). The average daily intake of selenium in Canada was also calculated from published analytical data and the per capita disappearance of unprepared foods. The total intake was 197 mug/day, and the major sources were wheat flour (98 mug), pork (21 mug), poultry products (24 mug), and fish (17 mug). Because the average diet is rich in selenium, the possibility of a deficiency in the adult is considered to be remote. Milk is relatively low in selenium, and thus the greatest deprivation in humans would occur during infancy.


Fat deficiency in rats during development of the central nervous system and susceptibility to experimental allergic encephalomyelitis. On day 14 of gestation, Sprague-Dawley rats were assigned to a diet adequate in fat (C), a fat-deficient diet (FD), or a fat-deficient diet supplemented with ethyl linoleate (FD-S). The same diets were continued during lactation. On weaning, the offspring were fed the same diets as their mothers. Rats were killed at 21 and 33 days, and the lipid compositions of brain, brain myelin, and spinal cord myelin were determined. Experimental allergic encephalomyelitis (EAE) was induced in animals from each group at 54 days of age. Acute EAE occurred after 13 days, and on day 14 (day 68 of age), the rats were killed. Body, brain, and brain myelin developments were slower in the FD and FD-S rats during early life. At 68 days, brain myelin from all groups reached mature composition, although body and brain weights of FD and FD-S rats remained lower than those of controls. With the exception of a slightly lower plasmalogen content at 33 and 68 days, the composition of spinal cord myelin from FD and FD-S rats was similar to that of C rats throughout the period of study. The plasmalogen content at 33 and 68 days, the composition of spinal cord myelin from FD and FD-S rats was similar to that of EAE occurred in animals from the FD group. The incidence of the disease in FD-S rats was similar to that in the controls. A reduction in total brain protein occurred in FD-EAE rats and in C-EAE and FD-EAE cerebrosides. Myelin from brain and spinal cord of EAE rats did not differ appreciably in protein content or lipid composition from myelin of controls. It was concluded that fat deficiency during development leads to increased susceptibility to EAE, and that a supplement of a source of linoleic acid has a marked protective effect against EAE.


Determination of carnitine turnover in choline-deficient and cold-exposed rats. Two experimetns were conducted to study the body pool size and turnover rate of carnitine in rats. The turnover of carnitine was determined by injection of a tracer dose of L-[methyl-14C] carnitine. In experiment 1, carnitine body pool size and turnover in rats fed a choline-deficient basal diet were compared with values obtained from rats fed the basal diet supplemented with choline. These rats were maintained at 22degrees. In experiment 2, carnitine body pool size and turnover were determined in cold-exposed (2degrees) rats fed the choline-deficient basal diet. Carnitine body pool sizes of rats maintained 22degrees and fed the choline-deficient basal diet and the choline-supplemented diet were 35.6 and 41.8 mumoles/100 g body weight, respectively. Carnitine body pool size of rats maintained at 2degrees and fed a choline-deficient basal diet were 6.6 and 56.1 days, for rats fed a choline-supplemented diet, 6.7 and 40.2 days, and for rats maintained at 2degrees and fed a choline-deficient diet, 2.9 and 36.4 days, respectively. Carnitine turnover times obtained with DL-[14C]carnitine in our previous study longer than turnover times obtained with DL-[14C]carnitine in our previous study (j. nutr. 104, 782-792). These observations suggest that D-carnitine is not metabolized the same way as L-carnitine, and that D-carnitine is not cleared from the body within 2 days after injection. The results also suggest that carnitine metabolism can be influenced by the amount of choline in the diet and by cold exposure.


Hyperglycemic effect of amino compounds structurally related to caproate in rats. The chronic feeding of small amounts (0.3-3% of diet weight) of certain amino derivatives of caproate resulted in hyperglycemia, an elevated glucose tolerance curve and, occasionally, glucosuria. Effective compounds included norleucine, norvaline, glutamate, epsilon-aminocaproate, methionine, and leucine.


Feeding studies in rats with high protein fungus grown on natural gas. Preliminary feeding studies were conducted with a high protein fungus (Graphium sp.) grown on natural gas. The biomass, containing approximately 50% protein, is considered a potential source of single cell protein. In short-term (1-week) experiments, rats gained weight when fed semisynthetic diets containing up to 40% of the biomass, although growth was depressed at the higher levels. Rats lost weight but survived for this length of time when fed biomass alone. Chronic toxicity was tested in a 5-month study with diets in which the casein (20% by weight) of the semisynthetic diet was either partially or entirely replaced by the proteinaceous biomass. Rats fed these diets grew more slowly but appeared normal and healthy, and no pathological changes were observed at autopsy. Some of these rats were fed a standard laboratory diet for an additional 10-month observation period, and at autopsy, one cortical adenoma of the kidney was found in a rat originally fed the lower level of Graphium biomass.


Effect of hydrogen peroxide treatment on the nutritional quality of rapeseed flour fed to weanling rats. The effect of treating rapeseed flours with hydrogen peroxide on the glucosinolate content and nutritional value of the protein was examined. Four flours were prepared from Target variety rapeseed (Brassica napus) by dehulling and defatting the seed (sample RF), by heat treating and water washing the dehulled seed prior to defatting (sample WWRF), and by treating a part of samples RF and WWRF with solutions of 7 and 3% hydrogen peroxide, respectively. Chemical analysis showed that the hydrogen peroxide treatment lowered the glucosinolate content of the flour but was not as effective as the water extraction. The hydrogen peroxide treatment also oxidized methionine to its sulfoxide and sulfone and cysteine to cysteic acid. In the first experiment, weanling rats were fed for 3 weeks diets in which casein or each of the flour preparations provided 5, 10, or 20% protein. Rats fed the high glucosinolate-containing flour (sample RF) at the 10 to 20% protein level died, while those fed 5% survived but lost weight. Those fed the hydrogen peroxide-treated flours survived, but weight gains and food consumption were low compared with the values of the caseinor WWRF-fed groups. Rats fed sample RF exhibited enlarged thyroids. Those fed the peroxide-treated samples had high plasma levels of methionine sulfoxide and sulfone. In the second experiment, additions of 0.15 or 0.30% methionine to the 10% protein diets resulted in increased weight gains of the groups fed the peroxide-treated flours. It was concluded that the hydrogen peroxide treatment was effective in reducing the glucosinolate content of the rapeseed flour. However, the production of the oxidized sulfur amino acids, in particular methionine sulfone, reduced considerably the nutritional value of the protein.


Comparative metabolism of L-methionine and N-acetylated derivatives of methionine. These experiments compared the metabolism of the N-acetylated derivatives of D- or L-methionine to that of L-methionine. Spargue-Dawley rats were orally or intraperitoneally dosed with N-[1-14C]acetyl-L-methionine, N-[1-14C]acetyl-D-methionine, or sodium [1-14C]acetate. 14CO2 was collected at intervals over 24 hours. In addition, groups of rats were orally dosed with either 35S-labeled N-acetyl-L-methionine or L-methionine. The animals were killed 3, 24, and 168 hours after dosing. Urine and feces were collected, and tissues were excised for 35S determinations. With either route of dosing, N-[1-14C]acetyl-L-methionine yielded the same amount of 14CO2 as sodium [1-14C]acetate over a 24-hour period. The acetate moiety of N-[1-14C]acetyl-D-methionine is not readily metabolized to 14CO2. Within each time period after dosing, the tissue distribution of 35S from 35S-labeled N-acetyl-L-methionine and L-methionine was similar. Protein specific activities for the two isotopes were also the same. After 168 hours, 30% of both isotopes of 35S appeared in the urine and feces, and the two isotopes were similarly distributed in the organic -S and inorganic -S fractions of urine. The studies show that L-methionine from N-acetyl-L-methionine is metabolically equivalent to free L-methionine. This conclusion is consistent with rat feeding studies showing that N-acetyl-L-methionine is nutritionally equivalent to L-methionine.


Developmental and postdevelopmental uptake of dietary organic and inorganic selenium into the molar teeth of rats. The mechanism for the uptake of dietary inorganic and organic selenium by the fully developed, mature molar teeth of mother rats and the developing molar teeth of their pups was studied. Pregnant rats received drinking solutions containing either 0.2 ppm Na2SiO3 plus 0.043 muCi Na2-75SeO3 per ml from day 10 of pregnancy until parturition. Thirteen days postpartum, the uptake of dietary 75Se into developing molar teeth was more extensive than the postdevelopmental uptake onto mature teeth. Developing molar teeth incorporated more 75Se from dietary selenomethionine than from selenite, as did many hard and soft tissues studied. The major portion of 75Se in enamel and dentine was located in the protein fraction of these dental tissues. Dialysis experiments showed that the selenium in enamel and dentine existed in at least three forms: loosely bound selenium, proteinaceous selenotrisulfides, and proteinaceous stable selenium. These data and the results of a previous study (J. Nutr. 103, 553-559) provide evidence that selenium incorporated into developing proteins as selenotrisulfides or selenoamino acids may be responsible for the increases in dental caries reported in man and experimental animals ingesting somewhat increased amounts of dietary selenium.


Effect of different levels of gossypol on transaminase activity, on nonessential to essential amino acid ratio, and on iron and nitrogen retention in rats. Metabolic experiments with rats fed rations containing varying levels of free gossypol (from 3 to 109 mg/100 g) showed that nitrogen retention was not affected by gossypol while iron absorption decreased as the levels of gossypol in the ration increased. This in turn resulted in lower hematocrit and hemoglobin values and lower levels of iron in the liver. The levels of glutamic-oxaloacetic and glutamic-pyruvic transaminases, an indication of liver necrosis, increased in blood serum and decreased in liver when gossypol was fed. The ratio of nonessential to essential amino acids in both serum and liver increased with increasing levels of gossypol in the diet showing that, in spite of an equalized available lysine intake, the cottonseed pigment was capable of binding this and/or other essential amino acids. In all cases, weight gain was adversely affected by the level of gossypol used.


An asparagine requirement in young rats fed the dietary combinations of aspartic acid, glutamine, and glutamic acid. The effect of dietary asparagine on rat growth was investigated. Diets were formulated with L-amino acids so as to contain asparagine, aspartic acid, glutamine and/or glutamic acid in all possible combinations and then fed to weanling rats for 3 weeks. Of the four, only asparagine was found to be essential for optimal growth, and it was essential regardless of the presence or absence of any dietary combination of these related amino acids. In selected dietary groups, the unbound asparagine levels were measured in various tissues over an 8-day period. Muscle asparagine levels were reduced for asparagine-deprived animals over the entire period studied; brain levels were decreased only after 7 days of dietary depletion, while hepatic levels were unaffected by dietary asparagine deprivation. In a related series, animals were more drastically depleted of asparagine by combining dietary deprivation with asparaginase treatment, causing a rapid decrease in cellular concentration of asparagine, which affected protein and DNA synthesis for those organs undergoing hyperplastic growth. Thus, asparagine may be rate limiting to protein synthesis for this extreme case as well as during dietary asparagine deprivation, which also decreased intracellular levels of unbound asparagine and led to irreversible deficits in development.


Studies on the formation of lipid peroxides and on some enzymic activities in the liver of vitamin E-deficient rats. Rats were fed a 5 or 20% casein diet that causes liver necrosis unless supplemented with vitamin E or selenite. The following activities were studied in liver subcellar fractions: enzymic formation of lipid peroxides, NADPH-cytochrome c reductase, oxidative demethylation of aminopyrine, and incorporation of [14C]leucine into protein (with microsomes); xanthine oxidase (with soluble supernatant); and RNA polymerases I and II (with nuclei). Formation of lipid peroxides was higher in rats fed diets without vitamin E and was not reduced significantly by dietary selenite. The activity of xanthine oxidase was higher in animals fed the 20% casein than in those fed the 5% casein diet; however, a higher activity was observed in the rats fed the latter diet without vitamin E or selenite than in those receiving these supplements. The activity of RNA polymerase I was higher in rats fed the low casein diet. Other activities examined were not affected significantly by the level of dietary casein or by vitamin E or selenits.


Effects of substitution of methionine, leucine, phenylalanine, or valine by their alpha-hydroxy analogs in the diet of rats. Weanling male rats were fed diets containing essential amino acids as the sole source of nitrogen at a level of either 6 or 15% by weight of the diet. When L-valine was replaced isonitrogenously by calcium L-alpha-hydroxyisovalerate in the 15% amino acid diet, growth ceased and urea excretion increased; urea clearance was unaffected. When L-leucine was replaced isonitrogenously by calcium L-alpha-hydroxyisocaproate in this diet, growth and feed efficiency fell approximately 60% and urea excretion rose, but urea clearance doubled. L-Phenylalanine was replaced both isonitrogenously and without supplemental glutamate by calcium L-phenyllactate in both the 6 and 15% amino acid diets and was also added in twice equimolar quantities to the 6% amino acid diet. When the 15% amino acid diet was fed, growth was severly reduced, but when the 6% diet was fed, the double dose of phenyllactate reduced growth and feed efficiency only 25%. Urea clearance was not consistently altered. When D,L-methionine was replaced by calcium K,L-alpha-hydroxy-gamma-thiobutyrate in the 15% amino acid diet, growth and feed efficiency improved whether or not glutamate was added to make diets isonitrogenous, and also whether or not 0.1% neomycin was included. Urea clearance did not differ among these groups but was significantly higher in rats receiving the hydroxy analog or D,L-methionine than that in controls receiving L-methionine. Thus, the ability of these hydroxy analogs to replace the corresponding amino acids in the diet of rats varies from complete (methionine) to partial (leucine and phenylalanine) or virtually nonexistent (valine).


Gluconeogenesis from L-cysteine in the perfused rat liver. The effects of dietary and hormonal treatments on the rate of gluconeogenesis from L-cysteine have been investigated in the perfused rat liver in situ. In order to demonstrate gluconeogenesis from L-cysteine, rats were fed either a 90% casein diet, or this diet with 2 or 4% cysteine, added in place of casein, and perfused in the fed state; or fed stock diet and starved 48 or 72 hours; or fasted and injected with cortisol. The net rate of gluconeogenesis (in mumoles/min/g liver) from cysteine in rats fed 4%cysteine was 0.24; in 48-hour starved rats it was 0.10; in 72-hour starved rats it was 0.16; and in the cortisol injected rats it was 0.23. When [U-14C]cysteine plus carrier cysteine (10 mM) was added as the substrate for gluconeogenesis in 72-hour starved rats; 3.9% of the label appeared in glucose. The above dietary and hormonal treatments stimulated gluconeogenesis from L-cysteine.


Paratenuisentis gen. n. for Tanaorhamphus ambiguus Van Cleave 1921 (Acanthocephala), with a reconsideration of the Tenuisentidae. Paratenuisentis gen. n. (Tenuisentidae) is characterized by quincuncially arranged proboscis hooks, numerous giant nuclei in the subcuticula and cement glands, and a prominent muscular sling around the proboscis receptacle. P. ambiguus (Van Cleave, 1921) is redescribed following study of a long series of mature males and females. On the basis of the typical pattern of giant nuclei distribution, it is concluded that Tanaorhamphus and Microsentis, previously included in the Tenuisentidae, belong in the Neoechinrhynchidae.


Ultrastructural changes in Ascaris suum intestine after mebendazole treatment in vivo. The effect of in vivo treatment with mebendazole on the ultrastructural morphology of Ascaris suum intestine was investigated. Pigs, infected with A. suum, were fed ad libitum a medicated food containing mebendazole at a concentration of 30 ppm. Control and treated animals were killed 6, 9, 15, and 24 hr after the onset of feeding. The parasites were quickly collected from the pig intestinal tract and prepared for ultrastructural and cytochemical examination. Absence of secretory granules in the terminal web, accumulation of secretory granules in the Golgi region, formation of autophagic vacuoles in the apical cell part, and loss of glycogen were the characteristic changes observed after 6 and 9 hr of treatment. Degenerative changes were very pronounced after 15 and 24 hr and involved almost the entire cytoplasm. Microvilli were decreased in number and appeared swollen in the majority of absorptive cells. Some more severely altered cells were completely devoid of microvilli. Cytochemistry revealed that the accumulated secretory granules in the Golgi area contained glycoproteins or polysaccharides. Microvilli, lysosomes, and Golgi apparatus were reactive for acid phosphatase in the control intestinal cells. After treatment, the enzyme activity was localized in numerous autophagic vacuoles, whereas the secretory granules remained unstained. The acid phosphatase activity in the microvilli decreased or was completely absent. The possible significance of these modifications in view of mebendazole's anthelmintic activity is discussed.


Trypanosomes in horse flies and deer flies in central New York State. Tabanids were collected during 2 consecutive summers from 3 counties in New York using a canopy trap and insect net. Twenty-seven per cent of all fly specimens (N equals 641) representing 69% of the species collected (N equals 36) were infected with flagellates. Tabanid intestines harbored amastigote, choanomastigote, and epimastigote forms. Epimastigotes were frequently found, and trypomastigotes and choanomastigotes rarely found in cultures of tabanid intestinal flagellates. Epimastigote and trypomastigote forms closely resembled Trypanosoma theileri-like trypanosomes reported from ruminants.


Two new species of the genus Caminacarus (Acarina: Cloacaridae) from turtles in Louisiana. Caminacarus chrysemys sp. n. and Caminacarus terrapenae sp. n. are described from the cloaca of Chrysemys scripta elegans and Terrapene carolina in Louisiana. The former species is very similar to Caminacarus deirochelys but differs in the form of the dorsal shield which has longer lateral elongations and the median dorsal elongation does not extend to the genital sclerite, structure of the anterodorsal wall of the gnathosomal base which is closed forming a ringlike apodeme, and structure of the tarsal setae as well as the presence of one additional seta on the dorsal surface of tarsus III. Caminacarus terrapenae differs from the above species by the form of the dorsal shield which extends more anteriorly but lacks anterior winglike elongations and has rounded anterolateral margins, the posteriorly concave shape of the genital sclerite and more sclerotized vaginal wall, the anterodorsal wall of the gnathosomal base which is not ringlike but open with lateral sclerotizations and interior punctations in this species, and structure of the tarsal setae with the presence of smaller heavier setae. The host specificity and biology of these species are discussed in relation to other members of the Cloacaridae.


Trypanosoma cervi sp. n. from elk (Cervus canadensis) in Wyoming. Trypanosoma cervi sp. n. is described from 22 trypomastigote syntypes from the blood of elk, Cervus canadensis, in North America (type locality: Wyoming). The blood trypomatigotes of T. cervi are compared with various culture forms: epimastigotes in 22 to 25 C NNN cultures; trypomastigotes in 37 C NNN cultures; and trypomastigotes from CAM chick embryo (10-day) cultures. Trypanosoma cervi is differentiated on morphological grounds from the cosmopolitan bovine species, T. theileri, and from T. ingens and T. mazamarum. Transmission of T. cervi to cattle was attempted using infected elk blood. No trypanosomal stages were recovered when recipients were examined by blood culture. The findings support the morphological data that T. cervi is distinct from T. theileri.


On the cultivation of Trypanosoma vivax: a tale of two visits in Nigeria. A new method is presented for obtaining in vitro development of the insect cycle of Trypanosoma vivax. Bloodstream trypanosomes from infected sheep were inoculated to tsete fly organ cultures in a modified Eagle's medium with 20% sheep serum, and incubated at 28 C. The organisms multiplied first as elongate spiral trypomastigotes. In successful cultures these transformed to epimastigotes. The epimastigotes multiplied extensively to form dense layers attached to formed structures, especially to pieces of peritrophic membrane. In older cultures transitional forms appeared, including some approaching the morphology of metacyclic trypanosomes.


Four new species of Gyrodactylus from fishes of Alabama. Four new species of Gyrodactylus are described from fishes of Alabama. Gyrodactylus dorosomae was collected from Dorosoma cepedianum (Le Sueur) and D. petenense (Gunther); G. parvicirrus from Notropis atherinoides Raf; G. lythruri from Notropis b. bellus Hay and N. atrapiculus Snelson; and G. nigrum from Etheostoma nigrum Raf.


Activity of commerical fasciolicides in small laboratory mammals. The activity is reported of 6 commerical fasciolicides and disophenol administered at doses of effective in sheep, against 6- and 12-week-old Fasciola hepatica in rats and rabbits and 6-week-old flukes in guinea pigs. Tests in rats and rabbits do not give a reliable indication of the activity of fasciolicides in sheep, but results with guinea pigs were closer to those in sheep. A comparison of the effective dose in rats and sheep indicates that tests in rats usually underestimate activity in sheep. The use of a simple egg count procedure in sheep to provide information on potential fasciolicides is described.


The life cycle of Echinoparyphium ralphaudyi sp. n. (Trematoda: Echinostomatidae). The life cycel and morphology of Echinoparyphium ralphaudyi sp. n. is described. Natural infections were found in Bulinus truncatus from Egypt, Ethiopia, and the Yemen Arab Republic, and later in B. forskalii and B. sericinus from Ethiopia. Sporocysts develop near the places of miracidial entry into the snail (the head-foot region, mantle edge, pseudobranch, and antennae). Rediae occur mainly in the ovotestis and in tissues anterior to the liver. The first cercariae are released 24 days postexposure. Metacercariae encyst in various freshwater snails and are localized in the pericardial sac and the posterior part of the kidney. Adult worms live in the small intestine of a variety of experimental animals: hamsters, rats, mice, chicks, ducklings, pigeons, and finches.


Identification of sex in Schistosoma mansoni cercariae. A simple method for determining the sex of larval stages of Schistosoma mansoni involved cytological demonstration of sex chromatin (heterochromatin) in the interphase and prophase nuclei of cercariae. Cerariae from unimiracidial infections were fixed, and permanent slides were stained with thionin, Giemsa, or fuchsin. On examination, a given cercaria showed either 1 or 2 sex chromatin bodies in the nuclei, the female with 1 and the male with 2 bodies. The results of observation on the sex of cercariae from the slides were matched with those of worms obtained from mice injected with the corresponding batch of cercariae. The accuracy of cytologic sex identification was greater than 80% in these experiments. The sex chromatin in both adult and larval stages was in the form of large, dark purplish bodies usually situated towards the periphery of the nuclei and could be easily distinguished from the other chromatin granules present in the nuclei.


Fine structure of possible photoreceptor in cercariae of Schistosoma mansoni. Two structures near the anterior end of cercariae of Schistosoma mansoni are interpreted as possible photoreceptors. Each appears to be ovoid and is composed of a thin cytoplasmic wall surrounding a cavity which contains lamellae. The lamellae are extensions of modified cilia which arise from the inner wall of the cavity.


Superinfection of Biomphalaria glabrata with Schistosoma mansoni. Biomphalaria glabrata 2 to 12 mm in diameter were exposed to 1 miracidium of Schistosoma mansoni and after 15, 30, or 60 days were reexposed to the homologous strain. The criterion of superinfection was the subsequent escape of cercariae of both sexes. Opposite sex superinfection was acquired by 45 of 106 snails of various sizes, all of which were in the group reexposed at 30 days. The observations confirm those of Kagan and Geiger and suggest that in the schistosomes a maximizing of the number of intermediate hosts with larval populations of both sexes may be an adaptation having a high species survival value.


Ammonia formation and amino acid excretion by Gyrocotyle fimbriata (Cestoidea). Gyrocotyle fimbriata isolated from the spiral valve of Hydrolagus colliei were washed, then held in a filtered seawater-penicillin-Tris buffer medium. Ammonia and urea release to the medium declined together and ammonia production was minimal when the urea concentration was below detectable limits. Alanine and smaller amounts of glycine were released to the medium at a more constant rate. After 12 hr the alanine-glycine excretion was more than 20 times the ammonia excretion. L-arginine, L-serine, L-histidine, and urea were most effective in stimulating ammonia production by whole worms; other L-amino acids were essentially ineffective. L-glutamate dehydrogenase, L-amino acid oxidase, uricase, and ornithine transcarbamylase were below detectable levels. L-serine dehydrase, L-arginase, L-histidase, and urease were detected in tissue homogenates and probably account for most of the endogenous ammonia production. L-arginase has a molecular weight of 28,000 by Sehpadex gel filtration. The high levels of glutamate-pyruvate transaminase and lower levels of glutamate-oxalacetate transaminase correlate with the high level of alanine excretion. It is concluded that (1) ammonia production is not strongly linked to the overall energy metabolism of Gyrocotyle and is probably a result of a series of unrelated enzymatic reactions such as the action of urease of urea from the tissue of the rat fish, and (2) alanine and glycine are the major nitrogen excretory products and their production is linked to the energy metabolism of Gyrocotyle.


Three new species of Echeneibothrium (Cestoda: Tetraphyllidea) from the skate, Raja chilensis Guichenot, 1848, with comments on mode of attachment and host specificity. Echeneibothrium multiloculatum sp. n., E. williamsi sp. n., and E. megalosoma sp. n. are described from the spiral valve of 90 specimens of Raja chilensis collected off central Chile. In Echeneibothrium infections, attachment sites and host infectivity are indicated as at least a partial function of hold-fast type, mucosal pattern, and first worms established. This is the first report of the genus Echeneibothrium from South American waters.


Two new species of Echeneibothrium (Cestoda: Tetraphyllidea) from skates in the western North Atlantic. Echeneibothrium bathyphilum sp. n. is described from the deep-sea skate, Raja bathyphila Holt and Byrne. Echeneibothrium sobrinum sp. n., a parasite in the spiral intestine of the skates Raja ocellata Mitchill and Raja erinacea Mitchill, is described from Vineyard Sound near Woods Hole, Massachusetts. Additional data are given for E. vernetae Euzet, 1956, from living and fixed specimens obtained from the type host in the type locality. Morphology of the strobilae and bothridia, testes numbers, and cirrus pouch dimensions clearly distinguish the new species from all others.


Giant-cell tumors and aneurysmal bone cysts of ribs in childhood. Cystic or solid lesions of ribs containing giant cells are rarely seen in children. Three cases are presented which are uncommon with regard to the age of the patients (5-14 yr old) as well as the site. These lesions were diagnosed late and exclusively by X-ray. Radiographically it was impossible to distinguish between a giant cell tumor and an aneurysmal bone cyst. Although the distinction of aneurysmal bone cysts and giant cell tumors sensu strictiori is justified from a clinical point of view, the two may be variants of the same pathologic growth process, i.e. growth of angiogribous tissue with giant cells in excess of that generally observed in the course of a "reactive" process.


Testicular tumors in childhood.

Testicular tumors in childhood. Tumors of the testis are uncommon in childhood comprising only about 2% of all malignant tumors. Twenty-five children with testicular tumors seen in the last 25 yr had 11 orchioblastomas, nine differentiated teratomas, three paratesticular sarcomas, one seminoma, and one dermoid cyst. It must be stressed that, contrary to popular opinion, the prognosis for orchioblastoma is favorable today, eight of the 11 children with this condition have survived for more than 2 yr. Orchiectomy should be followed by rigorous treatment with anticancer chemotherapy for 1 yr. Excision of the para-aortic glands and radiotherapy are not beneficial in prophylaxis. Lymphadenectomy is indicated only if metastases are demonstrated by lymphangiogram. Patients who have survived for more than 2 yr should, in general, be regarded as cured.


Hemangiomatosis of the liver in infants. Seven patients with hemangiomatosis of the liver are presented together with 100 cases reported in the literature. Six of seven patients survived; four with supportive treatment only. Follow-up is from 2 to 11 yr. Hepatomegaly, heart failure, and cutaneous angiomas constitute the classical clinical triad. Arteriography is the best method for diagnosis; biopsy should be avoided. Clinical features and histologic examination of these benign vascular tumors seem to confirm the theory that hemangioendothelioma and hemangioma represent only different developmental stages of one disease. These lesions can regress spontaneously if left alone. Despite contrary prevailing opinion, the authors recommend nonoperative treatment as the first choice of the clinician.


Major hepatic resections in children.

Major hepatic resections in children. An experience with 31 hepatic resections in children has demonstrated that mortality and morbidity are primarily determined by percentage of normally functioning liver retained as well as by the experitse of both intraoperative and postoperative care. Criteria for resectability in neoplasia  and trauma can readily be established. Early peripheral hypovolemia due to splanchnic pooling was observed frequently, while drains appeared to favor significantly the development of intra-abdominal spesis. Bleeding diatheses did not occur. An inability of the patient to maintain blood glucose and serum albumin were the sole metabolic derangements necessitating replacement therapy. The over-all mortality rate was 13%, with survival of two of four children subjected to 90% resections.


Intestinal smooth muscle response to chronic obstruction : possible applications in jejunoileal atresia. Hyperplasia is the main change occurring in intestinal smooth muscle above a chronic obstruction and explains the functional obstruction seen in the proximal bowel of a jejunoileal atresia. With an experimental model in dogs, this hyperplasia has been shown to be reversible. However, changes are extreme in atresia, and experiments in animals with induced atresia will best evaluate various kinds of treatment.


Gastric bypass for morbid obesity in children and adolescents. This report reviews 25 patients 20 yr of age or younger who were treated for morbid obesity by gastric bypass or gastroplasty. Eighteen genetically normal obese adolescents averaged 15% body weight loss 6 mo after operation and 25% weight loss 36 mo postoperatively; the eight males lost more weight than did the ten females. Seven younger children had Prader-Willi syndrome; six of them lost weight postoperatively although not so dramatically as the genetically normal obese patients. Four patients required later revisions to reduce the size of the gastric pouch or stoma. These operations were performed with acceptable morbidity and no mortality. Growth in height was not interrupted and no metabolic problems were encountered postoperatively. Gastric bypass is a safe and effective method of controlling body weight in morbidly obese children and adolescents.


Immunological studies in the postsplenectomy syndrome. Variations in the serial immunoglobulins of 52 children splenectomized for a variety of indications were studied and compared with two groups of children, one postoperative and one without operation. The most significant finding was the constant decrease in Ig M in every instance. Our series of splenectomized children seems to confirm the facts noted by other authors. The incidence of serious infections has been clearly significant and is clearly postsplenectomy sepsis. The age of the patients has a great influence on the seriousness of the septic process, these being more severe on younger children. The influence has also been revealed of the cause which motivated the operation, this corresponding in the first place to thalassemia and in the second place through spherocytosis and pseudohormones. It is evident that the immunologic role of the spleen during early childhood, especially under the age of 5 yr is important. The greatest risk or postsplenectomy sepsis is in the first 2 yr of life. Splenectomy should be delayed until after the age of 5 if clinical circumstances permit. If not, prophylactic chemotherapy should be carried out during the first 18 mo after splenectomy.


Experience with choledocal cyst.

Experience with choledocal cyst. In a series of ten children operated upon for congenital choledocal cyst, it was noted that the diagnosis had often been delayed because of intermittent or moderate symptoms during the first year of life. We favor resection of the cyst, advocated by many authors recently, but it should be emphasized that this procedure is not without risk and may be quite a difficult undertaking. Late results were satisfactory on the whole, even in one child with severe portal hypertension. However, the moderate fibrosis found at operative biopsy and the still slightly enlarged liver at follow-up examination are reasons for long-term observation of these patients.


Hiatus hernia in infants and children: a long-term follow-up of medical therapy. The follow-up of 75 patients over a period of 1-12 yr demonstrates that at least 70% of these--if infants--may be permanently free of symptoms, when placed on medical therapy. If an infant becomes free of symptoms under 14 days, it may be expected that medical therapy will be definitely successful. Therefore, it seems to us that every infant ought to be given medical therapy for a period of at least 14 days. Medical therapy does not give rise to stenosis of the esophagus. Hiatus hernia is a diagnosis which should be made at the earlies possible moment. Only on this basis can medical therapy be successful and stenosis of the esophagus may be prevented.


Individual differences in coalitional behavior. Individual differences in coalitional behavior were investigated in an experimental setting. Variables representing the choice of partner and bargaining on payoff were correlated with one another and with some personality variables. The findings indicate that partner power preference is significantly related to initial bargaining demands and bargaining endurance. The bargaining variables of initial demands, final demands, concessions, and endurance were found to be significantly related to one another. The findings indicate that the personality variable of external control is significantly related to partner power preference and bargaining concessions. The results suggest that differences in coalitional behavior that occur independently of situational variation have a significant systematic component. The findings indicate that an analysis of these differences could enhance prediction of coalitional behavior. Prediction linkages between variables are proposed.


Evaluation of an interviewer as a function of interviewer gaze, reinforcement of subject gaze, and interviewer attractiveness. Male subjects were interviewed by female interviewers who gazed constantly, intermittently, or not at all. Experimental subjects were reinforced with green light feedback whenever they gazed at the interviewers and were punished with red light feedback when they averted gaze for more than 6 seconds. Control subjects received noncontingent green and red light feedback. Although gaze of experimental subjects toward the interviewers was increased significantly, their attitudes toward the interviewers remained the same. This was probably because the subjects did not discriminate that their gazing behavior had changed. Subjects gave the most unfavorable reactions to the nongazing interviewers, rating them as least attractive, giving them the shortest answers, and sitting farthest from them during the debriefing session. Subjects did not discriminate between high and low attractive interviewers, except that the latter were rated disproportionately low on attentiveness if they did not gaze. Interviewers with high rates of talking were preferred over interviewers with low rates of talking. It was concluded that interpersonal attraction is related to gaze and physical attractiveness through a number of mediating variables which will have to be isolated more specifically in future research.


Cross-modal effects of anticipatory bogus heart rate feedback in a negative emotional context. The goal of the present investigation was to examine the effect of altering the perceptions of one's own physiological arousal on the elicitation of emotional behavior as defined by galvanic skin response, the nonspecific galvanic skin response, and verbal report measures of discomfort and unpleasantness. After an initial three-minute rest period, 48 subjects were exposed to 10 successive slides of people who died violently and continuous auditory tones. Results showed that the groups simultaneously exposed to the noxious slides and tones labeled as bogus heart rate feedback responded to the slides with increased electrodermal activity as compared to subjects exposed to the identical auditory feedback labeled as extraneous noise. An increase in bogus heart rate tended to elicit the most pronounced electrodermal responses. As expected, bogus heart rate conditions resulted in greater self reports of discomfort and slide unpleasantness as compared to the noise conditions. These findings were explained as a function of a cyclic cognitive-visceral link.


Influence of locus of control on interpersonal attraction and affective reactions in situations involving reward and punishment. Ninety-six subjects with either high or low I-E Scale scores participated in individual discussions with an experimental who either (a) rewarded and then punished, (b) punished and then rewarded, or (c) gave no evaluative feedback after the subject's responses. Because previous research has suggested that internally controlled subjects attend primarily to rewards while externally controlled subjects attend primarily to punishments, it was hypothesized (a) that the internally controlled subjects, as compared to externally controlled subjects, would be more attracted to the experimenter in the conditions involving rewards and punishments regardless of the sequencing and (b) that the reverse would be true in the nonevaluative control condition. The prediction was consistently supported and subjects' feelings of anger and anxiety during the discussions generally complemented the attention and attraction hypotheses. The results indicate that individual differences influence attraction in situations involving rewards and punishments and they offer a prescription for developing interpersonal attraction and minimizing anger: Offer rewards to internally controlled persons and remain neutral with externally controlled persons.


Conditioned autonomic responses as bidirectional indicators of racial attitude. Present physiological techniques of attitude measurement tap attitude intensity but not attitude direction. An alternative physiological technique, based upon the phenomenon of semantic generalization of conditioned autonomic responses, was tested to determine whether it would provide a bidirectional indicator of attitude. Subjects with favorable or unfavorable self-reported attitudes toward blacks were conditioned to statements having no racial content which they had previously evaluated as "bad." Subsequently, they were presented with statements with racial content; the latter were sentences which would be differentially evaluated as "good" or "bad" by persons with dissimilar racial attitudes. It was hypothesized that racial attitude would predict conditioned autonomic responses elicited by the generalization statements. It was found that groups differing in racial attitude could be distinguished on the basis of their conditioned responses to the race-related generalization statements. Unresolved problems of interpretation are discussed.


Effects of stress and commonality of fate on helping behavior. An experiment was performed in order to examine the joint effects of stress and commonality of fate on helping behavior. In a 2 times 2 factorial design, subjects were randomly assigned to one of four conditions in which (a) the subject and a confederate are both awaiting an experiment involving electric shock (high stress-common fate); (b) the subject is awaiting an experiment involving electric shock while the confederate is awaiting an innocuous word association experiment (high stress-dissimilar fate); (c) the subject is awaiting the word association experiment while the confederate awaits shock (low stress-dissimilar fate); and (d) the subject and the confederate are both awaiting an innocuous word association experiment (low stress-common fate). As predicted, a significant interaction, p less than .01, was obtained, indicating that high stress, as compared to low stress, facilitates helping if the potential recipient is in the same stressful situation but inhibits helping if the potential recipient is in a dissimilar and less stressful situation.


Escalation of aggression: experimental studies. A finding commonly obtained in research using the Buss "aggression machine" is a main effect for trail blocks, indicating an escalation in shock intensity over trails. Theoretical explanations for this effect were tested in a modified verbal operant-conditioning situation. In Experiment 1, subjects could administer any of 10 levels of positive reinforcement to a "learner" for correct verbal responses or any of 10 levels of negative reinforcement to a learner for incorrect responses. Half of the subjects were required to begin with weak, half with strong, reinforcements. Results indicated that, regardless of condition, subjects gave more intense reinforcements as the learning trails progressed. Those who administered negative reinforcements devalued the learner relative to those who administered positive reinforcements. In Experiment 2, a role-playing procedure was used in which subjects administered either positive or negative reinforcements to a learner whose performance either did or did not improve over trials. Again, in all experimental groups, subjects administered increasingly intense reinforcements over trials. The results are interpreted as supporting a disinhibition theory of anti- and prosocial behavior.


Childbirth as crisis: a test of Janis's theory of communication and stress resolution. The relationship between expectation and subjective outcome in childbirth was investigated. Sixty primigravidae responded to a questionnaire before and after labor and delivery. The evaluation of childbirth as favorable or unfavorable was related to whether the experience was rated better or worse than expectation. Anticipation of labor and delivery was positively related to a woman's perception of her mother's experience in childbirth, but was not related to the woman's evaluation of her actual delivery experience. Women receiving extreme communications or no information from their mother reported poorer outcomes than women who received moderate communications. Anxiety, as measured by the Taylor Manifest Anxiety Scale, and denial, as measured by the Self-Criticism Scale of the Tennessee Self-Concept Scale, were not related to anticipation or subjective outcome measures. Results were interpreted within Janis's theory of psychological stress.


Effects of viewed violence and aggression: stimulation and catharsis. Tests of the catharsis hypothesis involving viewed violence have led to conflicting results. It was suggested that the inconsistencies were due in part to the use of two different types of response measures, aggressive responses and hostile responses. This study involved a direct comparison of the two types of responses under conditions of instigation versus no instigation and aggressive versus neutral film. It was hypothesized that viewing an aggressive film would lead to a decrease in hostile responses (catharsis) and an increase in aggressive responses (stimulation) when compared with a neutral film condition. It was also hypothesized that both stimulation and catharsis effects would be enhanced under instigation conditions. A main effect of instigation was found with subjects in the instigation condition having higher scores than those in the noninstigated condition. A main effect of film was found with subjects having lower scores in the aggressive film condition than in the neutral film condition. A significant Film times Response Outlet interaction was found which offered support for the predicted catharsis effect on the hostility measure. There was no support for the predicted stimulation effect on the aggression measure. The results of the study offer support for the main thesis that in examining the effects of viewed violence, separation of hostile responses and aggressive responses is necessary for full understanding.


Reactions to male and female success and failure in sex-linked occupations: impressions of personality, causal attributions, and perceived likelihood of different consequences. Female subjects responded to three short verbal cues in which either a male or female character succeeded or failed in an examination qualifying the male (or female) for entry into an occupation. Three occupations were involved varying in masculine dominance (medicine, teaching, and nursing). In responding to each cue, subjects first rated the character in the cue on semantic differential scales to provide impressions of personality, then rated the importance of different possible causes of the outcome (causal attribution), and finally rated the likelihood that each of a set of possible consequences might follow the outcome. Results indicated a fairly pervasive tendency for the female subjects to upgrade successful males in relation to unsuccessful males but to downgrade successful females in relation to unsuccessful females. Results were discussed in relation to sex roles in society as they relate to permissible achievements for males and females.


Time perception and stimulus preference as a function of stimulus complexity. The present research joins previous efforts to define more clearly the phenomenon of perceived time as an important social-psychological dimension. In this study, time was considered a socially existential variable that can most meaningfully be measured by comparing two or more subjectively experienced durations, each with the other(s). Combining this view of time judgment with the adaptation level/optimal arousal principle, two hypotheses were tested: (a) that test stimuli differing in degree of complexity elicit from the individual differential degrees of affect, and (b) that intervals during which the individual is exposed to either overly simple or overly complex stimuli are judged as comparatively longer than objectively equal durations filled with moderately complex stimuli. Both hypotheses were affirmed.


Differential self-concept in American Indian children as a function of language and examiner. The hypothesis that minority self-concept may vary as a function of implicit ethnic and nonethnic evaluative criteria was investigated by testing 40 Mikasuki Seminole Indian children in their native language (Mikasuki) with Indian examiners and in English with Anglo examiners. Two reservation groups, matched for age and sex, received four administration of a personal (Piers-Harris) and an Indian self-concept scale, in a repeated measures counterbalanced design, varying language and order. Significant tes-retest correlations indicated response stability across languages and time. Results, homogeneous for all subgroups, showed significantly higher personal self-concept in Mikasuki, significantly higher Indian self-concept in English. It was suggested that minority testing may involve culturally patterned and context-bound response tendencies.


Humorous laughter in children.

Humorous laughter in children. This experiment examines the notion that the sharing of humor enhances overt expressive responses (laughter and smiling) and humor ratings. Independent groups of seven- to eight-year-old children listened on headphones to amusing material. They were tested alone or in dyads or triads with confederates of the same sex. In triads, duration of laughter and smiling was inversely related to the amount that confederates looked at one another; this was the case whether confederates were thought to be listening to the same or different recordings. Laughter and smiling scores support the notion that sharing the social situation is crucial in the facilitation of "humorous laughter." A  theory of socially facilitated laughter is proposed which draws upon social-facilitation drive theory and the tension-reduction aspects of humor theory.


To comply or not comply: testing the self-perception explanation of the "foot-in-the-door" phenomenon. A field experiment was conducted to test the self-perception explanation of the "foot-in-the-door" phenomenon of increased compliance with a substantial request after prior compliance with a smaller demand. In this study, some subjects were first approached with a small request (answer 8 questions in a telephone survey)  the size of which was virtually certain to guarantee compliance. Other subjects were first approached with a request sufficiently large to guarantee noncompliance (answer 50 questions). Subjects in both of these conditions were subsequently approached with a moderately sized request (30 questions sponsored by a different public service organization). As predicted by self-perception theory, subjects in the small-initial-request condition showed a higher rate of compliance to the second request (.519), whereas subjects in the large-initial-request condition showed a lower rate of compliance (.219) than subjects in the no-initial-request control condition (.333).


Effects of "mere exposure" on learning and affect. The mediating role of learning in the relationship between repeated exposure and affect was explored and supported in three experiments involving a total of 229 undergraduate participants. It was found that both learning and affect measures behaved in essentially the same way as a function of exposure duration (Experiments 1 and 3), serial position (Experiments 1 and 2), rating delay (Experiment 1) and stimulus properties (Experiment 1). These results suggest learning may be intrinsically rewarding and clarify one of the mechanisms involved in the relationship between exposure frequency and affect, extending Berlyne's two-factor theory of the effects of stimulus familiarity.


The treatment of ethylene glycol toxicosis with pyrazole. Rats and dogs were protected from the effects of lethal doses of ingested ethylene glycol (EG) with pyrazole (P), an inhibitor of liver alcohol dehydrogenase. Rats given 1.35 ml/100 g of EG followed by 2.2 mmol/kg of P i.p. at 6 and 30 hours postingestion survived. Untreated control animals died. Dogs were given either 10.0 or 12.5 ml/kg of EG and treatment was begun 6 hours later. The control treatment consised of NaHC03 administered i.v. according to the calculated base deficit, B-complex vitamins with ascorbic acid, hydrocortisone, and 5 per cent glucose in water. The addition postexposure to this treatment of 0.9 mmol/kg of P and 0.5 mmol/kg of P at 6 and 30 hours, respectively, constituted the experimental therapy. In summary: with 10 ml/kg of EG, no P, 2 of 5 dogs survived; 12.5 ml/kg of EG, no P, 0/1; 10 ml/kg of EG plus P, 9/11; 12.5 ml/kg of EG plus P, 12/22. Dogs that succumbed had large numbers of oxalate crystals in their kidneys at necropsy. The surviving dogs had few oxalate crystals in their kidneys at the time of unilateral nephrectomy (2 weeks postexposure) or necropsy (30 days postexposure). Several clinical factors were identified as useful prognostic indicators in the treatment of EG poisoning. The results suggested that pyrazole, despite its marked toxicity, may be of clinically significant value in the treatment of ethylene glycol poisoning when therapy is initiated withing 6 hours of exposure.


An extracorporeal complexing hemodialysis system for the treatment of methylmercury poisoning.  I.  In vitro studies of the effects of four complexing agents on the distribution and dialyzability of methylmercury in human blood. Almost all of the methylmercury (MM) in human blood is protein bound, primarily to sulfhydryl ligands.  Sulfhydryl agents such as penicillamine, N-acetylpenicillamine, cysteine and N-acetyleysteine are capable of reversing the protein binding of MM when they are added to whole human blood.  The magnitude of the protein binding reversal was similar for each compound as predicted by the determination of their relative affinities for MM in vitro.  Concentration-dependent reversals of protein binding of MM in blood was observed at increasing sulfhydryl concentrations from 10-4 to 10-2 M.  At 10-2 M, a 55- to 60-fold increase in non-protein-bound plasma MM was observed, when compared to blood with no added sulfhydryl agent.  Both the complexing agent and the MM complex formed in blood were readily dialyzable using a Travenol 145 twin coil hemodialyzer.  At cysteine concentrations of 10-2 M in whole blood, up to 44 percent of whole blood MM was dialyzed on a single pass at a dialyzer blood flow rate of 55 ml/min.  Under the same conditions, up 50 94 percent of plasma cysteine was dialyzed.  A system is presented for use in vivo on experimental animals.  The potential advantages of this method over existing therapeutic regimens for MM poisoning are discussed.


Effect of narcotic drugs on ribonucleic acid and nucleotide metabolism in mouse brain. Mice either were administered 10, 30 or 100 mg/kg of morphine sulfate acutely or were chronically implanted with pellets containing morphine, naloxone or pentazocine. They were then injected intraperitoneally or intracerebroventricularly with [5-3H] uridine or [5-3H] orotic acid either 30 minutes, 24 hours of 48 hours before sacrifice. The incorporation of the 3H into brain total homogenate, ribonucleic acid (RNA) and uridine nucleotides was measured. The RNA content of brain and liver was also assayed. When [3H] uridine was injected. i.p. 30 minutes before sacrifice, acute injection of 30 or 100 mg/kg of morphine sulfate or chronic implantation of morphine pellets decreased the incorporation of the [3H] uridine into brain RNA. However, neither the acute administration of 10 mg/kg of morphine sulfate, nor the chronic administration of naloxone or pentazocine, altered the amount of radioactivity incorporated into RNA. Chronic morphine treatment decreased the incorporation of 3H into uridine nucleotides and nucleotide sugars due partially to increased catabolism of the [3H] uridine. The brain and liver RNA concentration was unchanged by chronic morphine administration. Thus, chronic morphine treatment alters the metabolism of uridine nucleotides but does not appear to alter the net synthesis of the total brain RNA.


Application of principles of steady-state kinetics to the in vivo estimation of acetylcholine turnover rate in mouse brain. The rate of metabolism of acetylcholine (ACh) in mouse brain in vivo has been estimated utilizing a radio gas chromatographic approach and pulse labeling with radioactive phosphorylcholine.  A kinetic model describing the change with time of the plasma choline (Ch), brain Ch and ACh specific radioactivities as interdependent variables is postulated.  The experimental results are analyzed kinetically according to this model using two methods: the finite difference method described by Neff et al. (J. Pharmacol. Exp. Ther. 176: 701-710, 1971) and a simple graphic method based on the transformation of the data in terms of the decline of plasma Ch radioactivity described in this paper.  The accuracy of the latter is evaluated by the classic method of the least mean squares.  Calculations with the two methods yield comparable results.  This method is simple and can be used to study drug effects on brain ACh turnover rate.  ACh turnover rate in mouse brain has been calculated to be 0.36 mumol/g/hr with the latter method, whereas the finite difference method yields slightly lower values.  Because of the compartmentalization of brain Ch and the inherent assumptions, the new method can be used only for data collected during the exponential decline of plasma radioactive choline.


Structure-activity relationships between meta-substituted N-ethylamphetamines and locomotor activity in mice. The effects of N-ethylamphetamines substituted at the meta position of the phenyl ring with H, F, Cl, Br, I, CF3, CH3O, NO2 or OH were examined on locomotor activity in mice.  With the exception of meta-CF3-N-ethylamphetamine (fenfluramine), all compounds stimulated locomotor activity to varying amounts as determined in dose-activity curves that included doses which were ineffective through doses which either decreased activity relative to lower doses or were lethal.  Multiple linear regression analyses indicated that the extent to which these compounds increased locomotor activity was inversely related to meta-substituent steric effects (size, r equal to 0.90), whereas hydrophobic and electronic substituent effects did not contribute significantly to this relationship.  In mice pretreated with pargyline (100 mg/kg, 4 hours), the stimulant effects of these compounds were potentiated and again were inversely related only to substituent size (r equal to 0.77).  In reserpine-pretreated mice (5 mg/kg, 24 hours), no relationship was obtained with size, hydrophobic or electronic effects individually or together.  Reserpine pretreatment eliminated the rate-increasing effects of the iodinated and hydroxylated derivatives but not those of the other compounds.  Pretreatment with alpha-methyl-para-tyrosine (100 or 320 mg/kg, 1 hour) caused a dose-related abolition of N-ethylamphetamine-induced increases in acitivity. These data suggest that the amphetamine derivatives of the present study act indirectly, probably through release of catecholamines.


Structure-activity relationships between meta-substituted N-ethylamphetamines and isolated guinea-pig atrial rate. The effects of N-ethylamphetamines (NEAs) substituted at the meta position of the phenyl ring with H, F, Cl, Br, I, CF3, CH3O, NO2, or OH were examined on the rate of spontaneously beating isolated guinea-pig atria. All compounds, with the exception of meta-iodo NEA and meta-trifluoromethyl NEA (fenfluramine), increased atrial rate to varying degrees, as determined in cumulative concentration-response curves that included concentrations which were ineffective through those which decreased rate. Multiple linear regression analyses indicated that the respective maximum increases in atrial rate produced by these compounds were inversely related to the meta-substituted steric factor (size); neither hydrophobic nor electronic substituent effects contributed significantly to the relationship. In atria obtained from guinea pigs pretreated with the monoamine oxidase inhibitor, pargyline (100 mg/kg, 4 hours pretreatment), the stimulant effects of these compounds were markedly potentiated and were again inversely related only to substituent size. In addition, after pargyline, meta-iodo NEA and fenfluramine greatly stimulated the atria. In atria. In atria obtained from guinea pigs which had been administered reserpine (5 mg/kg, 24 hours pretreatment), none of the compounds except meta-hydroxy NEA increased atrial rate. The interactions of pargyline and reserpine pretreatment with the actions of these NEA congeners suggest that all are indirectly acting sympathomimetic amines, except the hydroxylated compound, which is mixed-acting.


Brain concentration of propranolol in relation to hypotensive effect in the rabbit with observations on brain propranolol levels in man. Intracerebroventricular (ICV) injection of propranolol in the dog, cat and rabbit produces a significant fall in arterial pressure.  In the following experiments, regional brain propranolol concentrations and changes in mean arterial pressure (MAP) have been measured in the rabbit after central and peripheral administration of the drug and the results compared to human brain/plasma levels.  In the conscious rabbit, ICV injection of l-propranolol (500 mug) produced a prolonged fall in MAP, maximal at 105 minutes (16.8 plus or minus 5.9 mm Hg below base line).  The regional brain propranolol concentrations after ICV injection of 14C-dl-propranolol (530 mug) were determined and the levels compared to those achieved following i.v. infusion of the unlabeled drug (1.0 and 2.0 mg/kg/hr).  The propranolol concentrations in the hypothalamus, medulla pons and midbrain after i.v. infusion were similar to the propranolol content in these areas at 60 and 120 minutes after ICV injection.  Intravenous infusion of propranolol also resulted in significant falls in MAP between 60 and 120 minutes.  In control studies, infusions of d-propranolol (1.0, 2.0 and 4.0 mg/kg/hr), which is virtually devoid of beta adrenoceptor blocking activity, produced only slight reductions in MAP.  Postmortem studies in patients treated with prolonged i.v. infusions of d-propranolol as part of the treatment of paraquat poisoning indicate that the brain/plasma concentration of propranolol in man is similar to that observed in the rabbit.  Propranolol is therefore highly concentrated in human brain tissue and comparable brain levels in the rabbit result in a hypotensive response.


Inhibition of the sympathetic nervous system by 5,6-dihydroxy-2-dimethylamino tetralin (M-7), apomorphine and dopamine. M-7, in doses of 1 mug/kg, reduces the resting heart rate of anesthetized dogs and cats.  In similar dose ranges, M-7 blocks reflex activation of the sympathetic nervous system.  Experimental procedures included bilateral carotid occlusion in the dog and central stimulation of vagi and right sciatic nerves in the cat.  M-7 inhibits the response to postganglionic stimulation of the right cardioaccelerator nerve if the frequency of stimulation is 2 Hz; no inhibition is observed with a frequency of 18Hz.  The inhibitory action of M-7 is antagonized by haloperidol, 50 mug/kg, or chlorpromazine, 150 mug/kg.  Similar inhibitory actions and frequency specificity were observed in vitro using the right atrium of the cat and nerve stimulation.  In cats, nerve stimulation was inhibited by apomorphine.  Dopamine, in the presence of cocaine, also inhibited low-frequency nerve stimulation.  It is postulated that prejunctional sympathetic nerves innervating the heart have dopamine receptors that serve as inhibitory role in transmission.


On the mechanism of release of norepinephrine from cat spleen slices by sodium deprivation and calcium pretreatment. Endogenous norepinephrine (NE) content of cat spleen slices was markedly depleted by incubating them in a sodium-free solution for 2 hours at 37 degrees C. Dopamine beta-hydroxylase (DBH) activity was not changed by this treatment.  During incubation of the slices in sodium-free solution for 30 minutes at 37 degrees C, there was a marked release of NE into the medium without a concomitant release of DBH.  Incubation of the slices in a potassium-rich solution (140 mM) resulted in the release of both NE and DBH into the medium.  In control slices, the soluble form of DBH accounted for nearly 30 percent of the total DBH activity.  The proportion of soluble DBH was not appreciably affected when slices were incubated in sodium-free medium for 2 hours at 37 degrees C.  It is concluded that release of NE from sympathetic nerves by sodium deprivation probably occurs by a process other than exocytosis.  Additional information is presented concerning the DBH levels in spleen slices which were depleted by their endogenous NE content by preincubation in calcium-rich solution and then in normal Krebs' solution or by a simultaneous inhibition of both glycolytic and oxidative metabolism.


Effect of magnesium on isoproterenol-induced alpha and beta receptor responses of vascular smooth muscle. The presence of 1.2 mM magnesium in normal Ringer's solution decreased the sensitivity (increased ED50) and increased the maximum tension of rabbit aortic strips developed in response to dl-isoproterenol.  Magnesium in the medium enhanced the degree of reserpine-induced supersensitivity to isoproterenol in whole aortic strips.  On the other hand, in adventitia-free aortae, supersensitivity to isoproterenol was absent in the presence of magnesium.  Isoproterenol-induced relaxation responses mediated by beta receptors were not modified by magnesium.  However, maximum contractile responses mediated by alpha receptors were increased in the presence of magnesium.  The decrease in sensitivity to isoproterenol in the presence of magnesium might be the result of its effect on calcium  movements at the membrane and/or at intracellular calcium binding sites.  The potentiating effect on the contractile tension responses to isoproterenol by magnesium might be a result of an increase in the amount of available calcium or to conformational changes produced on the membrane leading to a change in the contractility of the cells.


Altered resting membrane potential in the supersensitive vas deferens of the guinea pig. Microelectrodes have been used to obtain evidence for cellular changes associated with postjunctional supersensitivity in the vas deferens.  Chronic decentralization or denervation caused a partial depolarization.  A study of the time course of this depolarization in decentralized vasa deferentia indicated that the phenomenon appeared and reached a plateau between the 2nd and 4th postoperative day, i. e., at the same time as postjunctional supersensitivity develops in this tissue.  Junction potentials induced by transmural stimulation and measured in impaled cells were not significantly different in control and decentralized cells.  The results are discussed in relation to existing theories of supersensitivity and information in the literature regarding other cellular changes, especially of calcium.  It is hypothesized that postjunctional supersensitivity is due, at least in part, to a reduction in resting membrane potential associated with a decrease in calcium bound to the cell membrane.


Antagonism of the uterotonic action of oxytocin in vitro. Cumulative concentration-effect curves of oxytocin alone and with various antagonists were obtained in vitro on uteri from estrogen-treated rats.  Graded concentrations of salbutamol, isoproterenol, papaverine, theophylline, thioglycollate, and MgCl2 produced a decrease in the maximal effect of oxytocin and a shift of the concentration-effect curves to the right.  Salbutamol and isoproterenol appeared to act as functional antagonists of oxytocin in which agonist and antagonist each interacted with its own specific receptor to produce a decreased combined effect on a common effector.  Antagonism by papaverine or theophylline was increased by prior or simultaneous treatment with salbutamol, isoproterenol, epinephrine, or norepinephrine.  The potentiation had a rapid onset, was partially blocked by propranolol, persisted for at least 85 minutes following washout of salbutamol, and was not due to a residual effect of salbutamol.  This interaction could result from phosphodiesterase inhibition by papaverine and the accumulation of higher levels of cyclic 3',5'-adenosine monophosphate brought about by adenyl cyclase activation with the sympathomimetic amines.


Interaction between halothane and propranolol on oxytocin-induced uterine contractions. Halothane and other volatile anesthetics were found to relax uteri maximally contracted by oxytocin and to enhance the relaxant effect of propranolol and other agents (tetracaine, quinidine and chlorpromazine) with local anesthetic properties.  Concentration-effect curves for inhibition by propranolol or tetracaine were shifted to the left by halothane.  Methoxyflurane, chloroform and diethyl ether also increased the effect of propranolol.  The tissue/medium ratio for propranolol was increased by halothane.  The uptake of propranolol was saturable and was decreased at 2.5 degrees C, suggesting an active transport mechanism.  The increased uptake of propranolol in the presence of halothane was probably insufficient to account for the synergism noted.  Inhibition by propranolol and tetracaine was inversely related to the concentration of calcium in the medium.  The inhibitory effect of propranolol, tetracaine, quinidine and chlorpromazine appeared to be related to their ability to inhibit calcium transport.