Influence of morphine on protein synthesis in synaptic plasma membranes of the rat brain. The effects of acute and chronic morphine treatment on the incorporation of 3H-lysine into synaptic proteins were studied. No changes related to tolerance development were observed in the total incorporation of 3H-lysine into cortical or subcortical synaptic plasma membrane (SPM) or synaptic soluble proteins. Two populations of subcortical SPM were prepared, one from light (L) and one from heavy (H) nerve ending particles. When the labeled SPM-L proteins were separated by means of sodium dodecyl sulfate disc gel electrophoresis, an increased amount of label was found in the high molecular weight region of the gel. This increase depended on the rate of tolerance development. In contrast to the results found in the SPM-L gels, chronic morphinization significantly decreased the amount of high molecular weight labeled protein recovered from SPM-H gels.


Inhibition of the metabolism of cocaine by SKF-525A. In vitro and in vivo studies in rats indicate cocaine to be metabolized primarily in the liver to form benzoylecgonine and norcocaine. The formation of these metabolites was significantly hindered by SKF-525A, a microsomal enzyme inhibitor. In in vivo studies, pretreatment of rats with SKF-525A prior to receiving cocaine resulted in increased amounts of unchanged cocaine in the brain. No accompanying increase in spontaneous motor activity was observed for these animals, indicating a possible role for metabolites in the stimulant action of cocaine.


Possible significance of clozapine-induced increase in brain dopamine. Clozapine elevates the concentration of dopamine in the brains of mice injected with doses of 5-20 mg/kg while a 40 mg/kg dose has no effect. This biphasic change in dopamine content is seen in both the striatum and olfactory tubercle. The elevated dopamine concentration is dose-dependently antagonized by apomorphine, while a corresponding clozapine-induced reduction in norepinephrine concentrations is unaffected by apomorphine. These results suggest that part of the action of clozapine may be to reduce the release of dopamine.


The effects of methaqualone on the temperature regulation of mice. Methaqualone produces dose and time dependent changes in the rectal temperature of mice. More specifically, the drug produces poikilothermia. This effect appears to be produced by methaqualone itself rather than a liver metabolite since SKF525A, a compound known to block drug metabolizing enzymes in the liver, does not abolish the phenomenon. Tolerance to the temperature altering effects of methaqualone is also shown.


Penetration of some O-and/or N-methylated norepinephrine derivatives through the rat blood brain barrier. Methods for the determination of a number of O and/or N-methylated derivatives of norepinephrine were developed. The IP injection of these compounds into rats shows quick absorption and short half-lives in plasma, liver and brain. Most compounds do not cross the Blood-Brain-Barrier (BBB) due to low lipid solubility. However, lipid solubility is not a sole determinant. Compounds which have at least one of the 2 phenolic hydroxyl groups methylated and possess a tertiary amino group do cross the BBB readily.


Effect of pretreatment with antiinflammatory agents on paraquat toxicity in the rat. Aspirin (ASA), indomethacin (IND), hydrocortisone (HYC) or 0.25% agar (control) were administered (p.o.) daily to rats for 5 days. Following drug pretreatments, the activities of cytosolic superoxide dismutase (SOD), glutathione peroxidase (GP) and glutathione reductase (GR) were elevated 30-70%, 5-25% and 8-25%, respectively. In a second experiment, rats pretreated as above were injected (ip) on the 5th day with paraquat (PQ) (29 mg/kg). Rats in each group expired more ethane 2 hours after PQ injection. After 22 hours, expired ethane returned to zero time levels. All control rats died within 48 hours after PQ injection. At the end of 48 hours, rats pretreated with ASA, IND, or HYC demonstrated survival rates of 13%, 31%, and 47%, respectively. PQ injection produces marked elevations of SOD (82%), GP (328%), and GR (36%) in the lungs of PQ-injected controls rats over non-PQ injected controls. Elevation of these enzymes were also noted in drug-treated rats after PQ injection but at values less than PQ-injected controls. Anti-inflammatory drugs were tested in rat liver homogenates for their ability to inhibit thiobarbituric acid (TBA) reactive product formation. Only the addition of HYC resulted in a decrease formation of TBA-reactive products. Thus in vitro studies suggest that the antiinflammatory drugs tested, other than HYC, may have other mechanisms of actions in addition to inhibition of lipid peroxides.


Effects of monoamine oxidase inhibitors on the borohydride stabilizable binding of serotonin and tryptamine in brain. The in vivo and in vitro effects of various monoamine oxidase inhibitors (MAOI) on the borohydride stabilizable finding of serotonin (5-HT) or tryptamine in brain was investigated. A significant correlation between the extent of Mao inhibition and the amount of stabilized binding of the indolealkylamines was demonstrated. All hydrazine-type MAOI and harmine, a reversible nonhydrazine-type MAOI, employed in vitro, were shown to decrease the binding. beta-Phenylisopropylhydrazine apparently blocks the receptor carbonyl groups in the brain in vitro as well as in vivo.


3,4,3',4'-tetrachloroazobenzene: a potential environmental toxicant. 3,4,3',4'-tetrachloroazobenzene (TCAB), a potential environmental toxicant formed in the industrial manufacturing and the microbial degradation of chloroanilide herbicides, has been prepared in 87% yield by an improved procedure. In vitro experiments with C3H/10T1/2 cells have shown that TCAB is toxic to mammalian cells, which may be correlated with observable cytological changes. TCAB has also been found to be weakly mutagenic by the Salmonella/microsome test. In addition, C3H/10T1/2 cells are transformed following a ten day incubation with TCAB. These data suggest the potential health hazard associated with the environmental occurrence of TCAB.


Effects of lead and cadmium on adrenal and thyroid functions in rats. Seventy sexually mature male rats were injected with lead (50 and 250 mcg), cadmium, (50 and 250 mcg) and a mixture of lead (25 mcg) and cadmium (25 mcg) for 70 days. TSR results show that 250 mcg cadmium had a stimulating effect but 1/10 of the dose of cadmium plus 25 mcg lead had the opposite effect. Plasma thyroid hormones indicated that 50 mcg lead had a stimulating effect on T4 but cadmium and a mixture of lead and cadmium had a suppressing effect on both T4 and T3. Plasma corticosterone and adrenal cortical histology showed increased adrenal function in animals treated with 50 mcg lead, 50 mcg and 250 mcg cadmium and a mixture of lead and cadmium. The data indicated that cadmium had more deleterious effects on thyroid and adrenal function than lead.


Toxic interactions of stimulants, narcotics and narcotic antagonists. This study examines the lethality of combinations of central nervous system stimulants, narcotics and narcotic antagonists in rodents housed individually. The lethality of mice and rats from d-amphetamine was potentiated by methadone, cyclazocine and morphine, in that order of potency. Naloxone did not enhance lethality from d-amphetamine in mice, whereas it did antagonize lethality from morphine-d-amphetamine interactions. Naloxone did slightly enhance lethality from d-amphetamine in rats, but at a higher dose than those found to antagonize the lethality from morphine-d-amphetamine combinations. Methadone also enhanced the lethality from cocaine. These results have important implications for drug abusers and for patients being treated for narcotic addiction with either a methadone maintenance program or a cyclazocine administration program.


Induction by carbon tetrachloride of a lipid peroxidation inhibitor (LPI) present in rat liver soluble fraction. Oral administration of an adequate amount of carbon tetrachloride to rats resulted in an increase in the ability of the soluble fraction to inhibit microsomal NADPH-dependent lipid peroxidation. Aso, feeding of a fat-free, high carbohydrate diet to rats led an increase in the ability of the soluble fraction to prevent lipid peroxidation. Partial purification of the soluble factor inhibiting lipid peroxidation (LPI) by means of polyethylene glycol 6,000 (PEG) fractionation and hydroxylapatite column chromatography indicated that LPI is not glutathion peroxidase.


Deficiency of vitamin B6 in women taking contraceptive formulations. The specific activities (S.A.) of the glutamic oxaloacetic transaminase from erythrocytes (EGOT) of 75 women taking 16 diversified contraceptive formulations were determined by the principle (CAS) of unsaturation and saturation of receptors of the Coenzyme-Apoenzyme-System with the coenzyme, pyridoxal 5'-phosphate. 52 women were not taking pyridoxine; 20 were taking 1-5 mg; 3 were taking 25-100 mg. The mean basal S.A. of the 52 women without pyridoxine was lower (p less than 0.01) than for the 20 on  1-5 mg. The mean basal S.A. for the women on 25-100 mg was higher (p less than 0.01) than for the women without pyridoxine. The mean % deficiency for the women on 25-100 mg was negligible and lower (p less than 0.01) than 18+/-8 for the 52 women, and 14+/-6 for the 20 women. These data indicate that 1-5 mg of pyridoxine is inadequate for women on contraceptives. The requisite daily dosage is projected at 50-100 mg. Other data indicate that 5-12 weeks of supplementation with pyridoxine can be required to reach a stable "ceiling" of S.A. of EGOT. This period indicates some regulatory mechanism by diminished levels of the apoenzyme upon gene expression to bring about normal levels of the transaminase.


Penicillamine effects on enzyme efflux from skeletal and heart muscle. We have previously shown that pretreatment of mice with diethylstilbestrol (DES) or prednisolone (Pr) lowered enzyme efflux from isolated mouse skeletal muscle. These same agents also lowered the high serum enzyme activities in boys with Duchenne's muscular dystrophy (DMD). In a continuing search for other agents with similar effects, the influence of penicillamine (Pe) on enzyme efflux from isolated muscle was assessed, because it lowered the high plasma creatine phosphokinase (CPK) and produce beneficial effects in avian muscular dystrophy. Three groups of mice received 0, 1, or 10 mg Pe daily for 14 days. All mice were given supplementary pyridoxine. The egress of CPK and lactate dehydrogenase from the isolated left gastrocnemius and heart was determined over a 5 hour period. Pe produced more modest effects than did DES or Pr. The 10 mg dose reduced enzyme efflux from the gastrocnemius by 10%. In contrast, heart enzyme efflux was augmented by 20%. Similar dose-related disparate effects on enzyme efflux from skeletal muscle and heart have been previously noted for DES and Pr. Pe is the third agent found to lower the high serum enzyme activities in muscular dystrophy and reduce gastrocnemius enzyme efflux from isolated mouse skeletal muscle. This further establishes the usefulness of the mouse assay for identifying agents that lower the high serum enzyme activities in muscular dystrophy.


A rapid sensitive radioassay for serum native and denatured DNA. A radioassay for human serum DNA using 3H-actinomycin D was developed and evaluated. The assay was found to be technically simple, precise, sensitive and specific for DNA. Both native and denatured DNA levels could be measured using a nuclease specific for sDNA, since denatured DNA reproducibly bound 3H-actinomycin D under the assay conditions. Analysis of human sera yielded results in accord with those previously reported for man.


Simultaneous assay of the methylxanthine metabolites of caffeine in plasma by high performance liquid chromatography. A fast and sensitive method by high performance liquid chromatography for the quantification of the methylxanthine metabolites of caffeine in human plasma is described. Plasma is extracted with 20% isopropanol in chloroform and the evaporated residue is redissolved and chromatographed on silica gel using dichloromethane containing 2.2% of a solution of methanol-ammonium formateformic acid (100:0.02:0.017). The method is suitable for metabolic and pharmacokinetic studies of all mono- and dimethylxanthines in plasma. The limits of quantification, with C.V. of 10% or less are 40 ng/ml for the dimethylxanthines, 100 ng/ml for 3- and 7-methylxanthine and 500 ng/ml for 1-methylxanthine.


Dietary selenium status and pyrrolizidine alkaloid metabolism in vitro by rat liver microsomes. The effect of dietary selenium status on the metabolism of pyrrolizidine alkaloids (monocrotaline, and mixed pyrrolizidine alkaloid from Senecio jacobaea) by rat liver microsomes in vitro was studied. In two experiments, there was no difference in the rate of metabolism of alkaloid by microsomes from selenium deficient or selenium supplemented rats. Selenium deficiency was confirmed by measurement of erythrocyte glutathione peroxidase. Administration of excess selenium by i.p. injection did not affect alkaloid metabolism. It was concluded that dietary selenium status was unlikely to influence the metabolism of pyrrolizidine alkaloids.


Dependence of gel-filtered guinea pig hepatic microsomes on a soluble factor for maximum mono-oxygenase activities. Guinea pig hepatic microsomes were prepared by gel filtration on Sepharose 2B. A second, peak containing protein and hemoproteins (Hp) markedly increased mono-oxygenase activities when added to the microsomes. Gel filtration of guinea pig microsomes prepared by differential centrifugation revealed possible dissociation during elution from the Sepharose column. Parallel experiments with rat liver were negative.


Urinary excretion of phenolic metabolites of N-(n-propyl)amphetamine in man. In vivo metabolism of (+)-N-(n-propyl)amphetamine (NPA) in man (2 subjects) produced, among other products, two conjugated phenolic metabolites which are identified as 1-(4-hydroxyphenyl)-2-(n-propylamino)propane and 1-(4-hydroxy-3-methoxyphenyl)-2-n-propylamino)propane. In a 24 hr urine sample (pH uncontrolled), 13.4% of the NPA administered was excreted as the former, and 3.5% as the latter metabolite.


Some observations on the antihistamine activity in the guinea pig of aliphatic 2,4-diketones, a new class of physiological tissue components. Eight saturated aliphatic 2,4-diketones, ranging in chain length from C7 to C21 were examined for their potency in counteracting the effects of histamine anaphylaxis in guinea pigs. A 0.2% suspension of the mixed C15, C17, C19 and C21 diketones was more effective than a 1% phenylephrine solution when these were administered as aerosols. Of the individual diketones, 2,4-nonadecanedione was the most potent in vivo. ED50 data for the antihistamine activity of the C7, C9, and C13 homologues in the in vitro guinea pig ileum bioassay indicated that, on a weight basis, the activity increased with increasing molecular weight. The antiallergic activity of tissue and of urine extracts has been attributed to the presence of 2,4-diketones.


Biochemical changes in fowl serum during infection with strains of Newcastle disease virus of differing virulence. Changes in serum proteins, uric acid, lipids and electrolytes. Chickens aged five to six weeks were inoculated with three strains of Newcastle disease virus of differing pathogenicity. The serum level of the metabolites: total protein, albumin, globulin, uric acid, total lipids, cholesterol and electrolytes: calcium, magnesium, sodium and potassium were determined. The changes in serum levels of metabolites were as follows: velogenic infection was accompanied by decrease in total protein and albumin, reduction of lipids and cholesterol and increase in uric acid. No significant changes were found in the values of these metabolites in the serum of chickens infected with mesogenic strain. Lentogenic strain caused elevation of uric acid and cholesterol. All three strains caused decrease of the level of potassium in serum.


Radiosulphate: its metabolism and use in measurement of extracellular fluid volume in calves. Radiosulphate injected intravenously into calves under 14 days of age equilibrated, by 30 min, with a mean fluid volume of 311 ml/kg body weight. During the equilibration period 3-7 per cent of the injected dose was excreted in the urine. The volume of distribution of radiosulphate increased for at least 4-5 h after equilibration suggesting that it penetrated beyond the readily miscible water of the extracellular fluid.


Age changes in Alcian blue staining of glycosaminoglycans in sheep articular cartilage. Alcian blue staining of glycosaminoglycans in sheep articular cartilage is described and discussed. Chodrocytes contain mainly low molecular weight chondroitin sulphate in the outer layers but keratan sulphate increases with depth. Protein-polysaccharide interaction increases with age but the cellular staining decreases in intensity with age. Lacunar capsules contain material of higher molecular weight, much of which is chondroitin sulphate, but no protein-polysaccharide interaction occurs. The matrix of the outer layers is deeply stained while that of the inner layer is pale and consists mainly of keratan sulphate. When stained in high salt concentrations (greater than 0-7 M) the matrix of the middle layer shows two zones; hyaluronidase treatment allows these zones to be differentiated at lower salt concentrations.


Faecal thiaminase in clinically normal sheep associated with outbreaks of polioencephalomalacia. Three flocks in which in with one of more sheep had succumbed to polioencephalomalacia (cerebrocortical necrosis) were used for faecal thiaminase studies. Up to one third of the clinically normal animals in these flocks to be excreting thiaminase on any one day and over half the  flock could be thiaminase excretors at some time during an outbreak. The possible detrimental effects of sub-clinical thiamine antagonism in sheep are therefore worthy of consideration. Thiaminase excretion by individual animals was variable and sometimes intermittent. It was unaffected by changes in diet, pasture or enviroment. In two of the flocks multiple cases of polioencephalomalacia followed the administration of the anthelmintics, levamisole hydrochloride and thiabendazole. This aspect merits further investigation in view of the widespread use of anthelmintics of this type, especially as the profuse diarrhoea which can be associated with outbreaks of polioencephalomalacia may be wrongly attributed to gastro-intestinal parasitism.


The competition of molybdate and sulphate ions for a transport system in the ovine small intestine. The transport of molybdate and sulphate by segments of ovine small intestine in vitro was examined and kinetic constants derived for the late ileum where transport was highest. Sulphate inhibited the uptake of molybdate, probably by competition for sites on a common transport system. The significance of the results with respect to the problem of molybdate toxicity in animals is discussed, and related to the known protective effect of sulphate.


Anti-larval antibodies in the serum and abomasal mucus of sheep hyperinfected with Haemonchus contortus. A radioimmunoassay technique was used to follow the anti-larval antibody response in the serum of sheep subjected to repeated dosing with Haemonchus contortus. The response was found to develop slowly and seemed to decline as soon as the sheep stopped receiving larvae. No immunological memory was observed after the sheep were challenged with 4000 larvae nine weeks after daily dosing was stopped. Examination of abomasal mucus collected from the sheep at slaughter revealed the presence of IgA and IgG antibodies. It is suggested that most of this mucus IgG was derived from blood whereas the IgA was locally produced.


Intestinal absorption of palmitate and 2-aminoisobutyric acid in piglets infected with Strongyloides ransomi. Piglets were infected with 5000 or 15,000 third stage larvae of Strongyloides ransomi/kg of body weight. On the 15th day post infection absorption of the amino acid 14C alpha-amino-isobutyric acid (AIB) and the fatty acid 3H palmitic acid were studied. It was found that the onset of absorption of amino and fatty acids was delayed in the infected animals. Defective absorption of the amino acid was found in heavily infected piglets, whereas in moderate infection there was no failure of absorption from the entire small intestine. There was no difference in the rates of absorption of 3H-palmitic acid between infected and control piglets.


Biochemical and physiological effects of catecholamine administration in the horse. Adrenaline was given intramuscularly to resting horses. It increased heart rate, sweating, blood levels of lactic dehydrogenase, aldolase, creatine kinase, glucose, lactate, free fatty acids and glycerol. Responses to isoprenaline, to noradenaline and to adrenaline after pretreatment with propranolol indicated that beta receptors were involved in stimulation of tachycardia, sweating, lipolysis and muscle glycogenolysis, and alpha receptors in stimulation of liver glycogenolysis and leakage of intracellular enzymes. The time course and relative magnitude of the effects on different enzymes was not identical to that produced by exercise.


Haematological changes in fowls infested with black flies (Simulium griseicolle). The effect of Simulium griseicolle on the blood of growing and laying birds was studied for periods of 10 and eight weeks respectively. The red cell counts and the haemoglobin concentrations were reduced but the mean corpuscular volume was increased. The packed cell volume and the mean corpuscular haemoglobin concentration were only slightly changed. The macrocytic normochromic anaemia thus observed in the infested birds might have been due to nutritional factors rather than to blood loss caused by the feeding insects. Morphological changes were observed in the erythrocytes of the infested birds and these suggest presence of in vivo haemolysis, probably caused by some haemolysing agents in the saliva of the insects.


A technique for chronic intermittent bile collection from the rat. A technique is described for inserting into the bile duct, a re-entrant cannula with a sampling arm to allow intermittent collections of bile from unanaesthetised, minimally restrained rats, for a period of 30 days or more. The flow rate of bile (5.38+/-0-25 cm3/h/kg) was higher than that previously reported when using simple or re-entrant cannulas. This higher flow rate may be a result of allowing a minimum of 10 days post-operative recovery period before starting collection of bile and of avoiding anaesthesia and other stresses at the time of collection.


Altered absorption and regulation of iron in chicks with acute Salmonella gallinarum infection. Chicks aged 15 days were infected orally with Salmonella gallinarum. During the six-day period immediately following infection the absorption of 59Fe from the gut fell progressively to be eventually about half that in noninfected chicks. This reduced uptake was accompanied by a shift in the distribution of the 59Fe absorbed, more occurring in the spleen and less in the liver and blood. During the eight-day period that immediately followed infection in another experiment, serum iron concentration on day 4 and 6 in infected chicks was significantly lower than that in noninfected birds. In the infected chicks also the transferrin saturation was significantly lower and the unsaturated ironbinding capacity higher, on days 4, 6, and 8 after infection. These findings show that there is a major disturbance in iron regulation in acute systemic bacterial infection in the immature fowl and suggest that the mild anaemia which occurs in chicks during acute S gallinarum infection a shortage of iron in the body.


The transfer of Newcastle serum antibody from the laying hen to the egg and the chick. Four spaced injections of Newcastle disease virus were given to laying fowls. A state of hyperimmunity was reached at the 42nd day and was maintained up to the 91st day when haemagglutination inhibition antibody titre started to fall. Haemagglutination inhibition antibody produced by the hen could be detected both in egg yolks and chicks although to a lower titre than in the serum of the hen. Fuctuation of antibody transmitted by the individual hens was observed.


Electrolyte concentrations in sheep cerebrospinal fluid. Cerebrospinal fluid (csf) of sheep was obtained by acute lumbar puncture and from chronic cannulations of the lateral cerebral ventricle. The concentrations of ions in the csf including chloride which had previously been reported to be very high, were found to be similar to those of other mammals and were not greatly affected by changes in plasma electrolyte composition associated with adrenalectomy.


The estimation of fibrinogen levels in animal plasmas by a simple refractometric method. A comparison with a biuret method. A comparison was made between a biuret (reference) method and a simple refractometric (test) method for measuring fibrinogen levels in 84 animal plasmas. Although the correlation between the two methods was high (4=0.90 P less than 0-001) there was considerable random variation in the refractometric results in relation to the biuret results. This was thought to be due in part to the fact that refractometric results could only be expressed in multiples of 2.4 g/litre. In spite of this limitation, the refractometric method, on the grounds of speen and simplicity, is considered to have worthwhile application for fibrinogen determinations in practice laboratory.


Mycobacterium avium infection in freeliving hedgehogs (Erinaceus europaeus L). Mesenteric lymph nodes were examined from five hedgehogs captured on the Berkshire Downs. The single culture obtained was identified as Mycobacterium avium type 2.


The effect of niclosamide on Echinococcus granulosus, Taenia hydatigena and Taenia ovis infections in dogs. The effect of niclosamide (particle size 1 micron m) and its piperazine salt (particle size 5-10 micron m) on Echinococcus granulosus and Taenia hydatigena has been investigated. The piperazine salt of niclosamide was also tested for activity against Taenia ovis. These trials involved 326 dogs. Irrespective of particle size, the drug was found to be virtually inactive against 28-day-old E granulosus. Some evidence was found indicating that there may be a low degree of activity against 70-day-old worms. The drug was found to be effective at 32 mg/kg and 64 mg/kg against T hydatigena and 50 mg/kg against T ovis. Some evidence was obtained that milk decrease the efficiency of the piperazine salt against T hydatigena at the lower dose rates. Micronisation of the drug did not increase the efficiency against this parasite. Vomiting and diarrhoea were common sequelae.


The effect of micronised nitroscanate on Echinococcus granulosus and Taenia hydatigena infections in dogs. Trials with micronised nitroscanate carried out on 170 dogs infected with either Echinococcus granulosus or Taenia hydatigena indicated that a single treatment at 62-5 mg/kg and 16 mg/kg respectively significantly reduced the proportion of dogs infected with tapeworms. Some evidence is presented that micronisation may give a fourfold increase in the efficiency of nitroscanate in worm removal without increasing the toxic effects to the dog.


Plasma zinc levels in sheep in the peri-parturient period. No consistent pattern of plasma zinc concentrations was observed in the peri-parturient period in 17 ewes, although large transitory depressions of plasma zinc levels were recorded in five ewes including one non-pregnant control. Sheep with dystocia did not exhibit a fall in plasma zinc similar to that recorded in cattle.


Human nasal mucosal function at controlled temperatures. We exposed 16 healthy human volunteers to air temperatures ranging from 7 to 39 degrees C and measured nasal mucus flow, nasal airflow resistance, forced vital capacity, rectal and body surface temperature, and air temperature within the nasal passage. A moderate fall in nasal mucus flow rate in the anterior and middle parts of the nose was observed with temperature above or below 23 degrees C. The nasal airflow resistance decreased in warm air and tended to increase in cold air. No significant changes in forced vital capacities or rectal temperature were observed. Nasopharyngeal end inspiratory air temperatures at 23 degrees C averaged 32.6 degrees C. At environmental temperatures of 15 and 31 degrees C they average 28.1 and 32.8 degrees C, respectively. Although we found alterations in upper airway function associated with altered inspired air temperature, over the range of 32 degrees C studied these changes were of minor physiological significance.


Respiratory control of body temperature: a theoretical model. The two-compartment model of a ventilatory CO2 chemostat of Grodins et al. (1954) is modified to describe a ventilatory thermostat fitting the requirements of panting. Allowance for the extra heat production during panting leads to a second order third degree differential equation which by introducing the ventilation/perfusion ratio can be reduced to the second degree. From the steady-state solutions calculated for dogs using experimentally determined constants it is concluded that: (1) the ventilation/perfusion ratio has no influence; (2) the ambient temperature leads to a marked panting only above 30 degree C; (3) the relative humidity of the air increases the panting; (4) due to the oxygen cost of panting, the regulation of the body temperature is possible only within limits. The limitation depends upon the energy requirements of the respiratory muscles, upon the set-point temperature and the controller gain. The unsteady-state solution is given by approximation. The ventilatory reaction to the heat stress appears to be slow with a half-time of about 15 min for a 20 kg dog. All properties of the model are mainly determined by the high specific heat of tissues relative to expired air.


Diffusion of water vapor in binary and ternary gas mixtures at increased pressures. Diffusion of water vapor was measured at 25 degrees C in the binary systems water vapor-He and water vapor-N2 at approximately 1, 4 10, 20 and 50 atm. Diffusion was also measured in the ternary system water vapor-He-O2 in both 2%O2-98%He, and at 1 and 20 atm. At 1 atm, comparison of binary diffusion coefficients (delta) shows that water vapor diffuses 3.3 times more readily in He than in N2. Values of delta at elevated pressures were reduced in proportion to 1/p, the absolute pressure, in qualitative agreement with Chapman-Enskog theory. However, the reduction in Delta was less than predicted at pressure above 4 atm in water vapor-N2 and above 20 atm in water vapor-He. The deviations from theory are more pronounced in N2 than in He, and become larger at higher pressures. When 26% O2 is present in the ternary system water vapor-He-O2, diffusion of water vapor is reduced to about 60% of its rate in pure He. In contrast, 2% O2 in He has little effect on diffusion of water vapor.


Effects of uneven elastic loads on breathing pattern of anesthetized and conscious men. In anesthetized subjects rib cage strapping (RCS) did not change tidal volume (VT) and increased ventilation (V), whereas abdomen strapping (AS) markedly decreased VT and V. Both kinds of strapping decreased expiratory duration (TE), but did not change inspiratory duration (TI) and breathing rate. RCS and AS decreased lung volume by about 200 ml and increased the elastance of the repiratory system by 12 cm H2O/1 and 9 CM H20/l, repectively. The changes produced are mainly due to mechanical factors, although reflexes also seem to be operating in some cases. In conscious subjects RCS decreased VT, TI, TE and did not change V, whereas AS did not change these parameters. The different changes in conscious and anesthetized subjects show the effects of cortical influences, which also partly explain the differen effects elicited in conscious subjects by RCS and AS. The effects produced by RCS are mainly due to the sensation of hindrance to rib cage expansion, rather than to that of rib cage squeezing, as shown by experiments of RCS without reduction of rib cage volume.


Hypoxic ventilatory response of cats at high altitude: an interpretation of 'blunting'. Cats acclimatized to a simulated altitude of 5500 m developed attenuated ventilatory response in the hypoxic test range of PAO2 = 60-45 torr, but their CO2 response remained normal, although the curve was shifted to a lower PACO2 range. The acclimatized cats a high respiratory frequency and maintained hyperventilation under normoxia. Cats from 3100 m altitude had hypoxic reponses which were, on the average, slightly below sea level standards, but the difference was not statistically significant. Two cats raised at 4640 m had a normal hypoxic ventilatory response even though the frequency response was 'blunted'. These data suggest the possibility of hypoxic 'threshold' near 5500 m to produce an attenuation effect. Another series of cats acclimatized to 5500 m were tested with more severe hypoxia, and they exhibited brisk ventilatory response in range PAO2, 40-25 torr, although they showed typical 'blunting' in the range PAO2, 60-45 torr. These results suggested that the phenomenon of attenuated hypoxic response at high altitude was a reflection of shift of hypoxic set point to a lower PAO2. Finally, it was shown that the hypoxic responses of 'blunted' animals were restored to normal after mid-collicular decerebration; and that decortication resulted in a typical hyperexcitability of the hypoxic response. These results are discussed in terms of hypothesized suprapontine modulating influences on the control of breathing, and possiblities for a contribution of these mechanisms in pathogenesis of hypoxic 'blunting' are raised.


Respiration and circulation during swimming activity in the dogfish Scyliorhinus stellaris. A number of respiratory and circulatory parameters was measured in the Larger Spotted Dogfish Scyliorhinus stellaris before, during and after periods of spontaneous swimming. During swimming the gill ventilation was increased, mainly due to increased ventilatory stroke volume, the respiratory frequency showing a small rise only, and the cardiac output was increased at only slightly elevated cardiac frequency. Coordination between cardiac, ventilatory or locomotor (tail-beat) rhythms was not observed. The decrease in utilization of inspired water O2 during swimming was attributable to diffusion limitation in branchial O2 transfer. A considerable fraction of the total net amount of O2 required for swimming was taken up during the recovery phase. From the observations that (1) the decrease in gill ventilatory flow after cessation of swimming revealed a very rapid component (followed by a slow component), and that (2) changes in swimming speed were reflected by immediate changes in momentary ventilatory flow, it is concluded that the increased ventilation during swimming was in part mechanical-passive and/or due to nervous coupling between respiratory and locomotor centers.


Mixing in flowing gas.

Mixing in flowing gas. We used a mass spectrometer to analyze continuously from a flow stream after changeover of one gas to a mixture of other gases. At the end of a straight cylinder (length = 100 cm, inner diameter = 1/2 inch), light-weight gases appeared later but reached full-scale deflection earlier than heavy gases. Apparently gases with high molecular diffusivity tended to diffuse radially so that they were not carried forward axially in rapidly moving streams. This blunting of the profile of mean concentration vs distance as fresh gas move down a tube, plus spreading of a gradient region of transition between fresh gas and stale gas, are the fundamental processes of diffusion/convection interactions in the lung. Turbulence and molecular diffusion are similar in that they limit the penetration of inspired gases that could occur if laminar flow were the only process acting. However, turbulence and molecular diffusion cause true irreversible mixing of fresh and stale gases, whereas dispersion by laminar flow does not.


Cardiopulmonary readjustments during graded immersion in water at 35 degrees C. Six normal male volunteers, aged 25 to 34, suspended vertically in a harness that allowed them to completely relax their postural muscles, were studied in four randomly ordered conditions, namely in air at 28 degrees C, and immersed in water at 35 degrees C to the level of the hips, the xiphoid, or the chin. In each situation, several variables were measured by noninvasive techniques. Cardiac output rose from 5.11 min-1 (air) to 8.31-min-1 (chin), the increase in each of the three steps being significant at the 0.001 level. Heart rate dropped from 76 to 68 min-1 (P less than 0.001) from air to xiphoid immersion, but appeared to rise again (P less than 0.02) during chest immersion. Functional residual capacity decreased marginally during lower limb submergence, and considerably in each of the following stages. Pulmonary capillary blood volume rose significantly only during abdomen immersion. The arterial-endtidal PCO2 difference was minimally reduced as water reached hip level and then remained steady. Mixed venous PO2 increased during abdomen submergence, and PVCO2, was unaltered throughout. Analysis of the step-to-step changes demonstrates  that some variables are set by a combination of processes which may counteract each other, and explains the difference between results obtained by previous investigators.


Cardiorespiratory and metabolic responses to positive, negative and minimum-load dynamic leg exercise. Cardiorespiratory and metabolic responses to steady-state dynamic leg exercise were studied in seven male subjects who performed positive and negative work on a modified Krogh cycle ergometer at loads of 0, 16, 33, 49, 98, and 147 W with a pedalling rate of 60 rpm. In positive work, O2 uptake increased with the ergometric load in a parabolic fashion. Net O2 uptake averaged averaged 220 ml-min-1 at 0 W (loadless pedalling), and was 75 ml-min-1 lower at the point of physiological minimum load which occurred in negative work at approximately 9 W. The O2 cost of loadless pedalling is for one-third attributed to the work of overcoming elastic and viscous resistance, the remaining part being due mainly to the work of antagonistic muscle contraction in the moving legs. Although at a given VO2, work rate was much higher in negative than in positive work, corresponding values for VE were similar, suggesting that the mechanical tension in working muscles is of little or no importance in the control of ventilation in steady-state exercise. Heart rate increased linearly with VO2 in both positive and negative work, with a steeper slope in negative work. Evidence is presented that none of the current definitions of muscular efficiency yields the true efficiency of muscular contraction in cycle ergometry, net efficiency calculation resulting in too low estimates, and work and delta efficiency calculations in overestimated values in the low-intensity work range, and in underestimated values in the high-intensity range.


Heart rate response to breath holding at 18.6 ATA. The heart rate (HR) responses to breath-holding (BH) with the without face immersion (FI) in 31 or 27 degrees C water was studied in 1 ATA air and hyperbaric He-O2 environments in 4 male subjects during a dry saturation dive to simulated depth of 580 ft (18.6 ATA). When a 60 sec BH or FI was performed while leaning forward, there was a significant linear correlation between the maximal bradycardial response (delta HRmax) and ambient pressure for simple BH (r-0.08, P less than 0.05) and 31 degrees C FI (r = 0.91, P less than 0.01), but not for 27 degrees C FI. A similar trend was seen during 30 sec BH's while seated erect. The facial cold-dependent component of the FI bradycardia was not significantly altered by pressure. In general, there were significant correlations between the initial HR and the initial thoracic conductive volume (TCV; measured by the four-electrode Minnesota impedance cardiograph), and between the initial TCV and delta HRmax observed during seated erect BH's. Since the TCV was generally higher at depth, it is suggested that a mechanical effect due to increased TCV at depth, possibly related to increased gas density, is at least partly responsible for the pressure dependence of BH bradycardia.


Pressure-flow relationships and power output of breathing. The pressure-flow relationship obtained by Agostoni and Fenn (1960) during maximal inspiratory efforts against various external resistances contains information from which inferences regarding the power output, and the internal impedance of the breathing system can be made. Similar inferences can be made from measurements obtained with submaximal but constant inspiratory efforts. An analysis is presented to reconcile the observed linear pressure-flow relationships with the usually observed hyperbolic force-velocity relationship of muscle.


Oxygen uptake transients at the onset and offset of arm and leg work. The halftimes (t1/2) of the VO2 on-and off-responses have been determined on 4 moderately active subjects (1) in arm cranking (VO2 congruent to 1 1/min). (2) in leg pedaling at 4 graded submaximal (VO2 congruent to 0.8 to 2.51/min) work loads, and (3) when superimposing arm cranking on preexisting leg pedaling, both in the supine and in the upright position. In supine experiments the mean t1/2 of the VO2 on-response was longer for arm cranking than for leg pedaling (64 vs 44-49 sec) at equal VO2; however, at the same percentage of arm and leg VO2 max the respective t1/2 were similar. In sitting experiments all t1/2 of the VO2 on-response were shorter than when supine, but the t1/2 for the arms were still slightly longer than those for the legs. When arm cranking was superimposed on preexisting leg pedaling, the t1/4 for arms was reduced both in supine (from 64 to 35-38 sec) and in the sitting position (from 44 to 40 sec). The halftime of the VO2 off-response were much shorter (20-32 sec) than those of the on-response and similar in all experiments. In all conditions the O2 deficits at work onset were considerably larger than the fast component of the corresponding O2 debts during the first minutes of recovery. The difference was totally accounted for by anaerobic glycolysis occurring early during the VO2 on-response, particularly in arm exercise. It is concluded that at submaximal work loads the O2 deficit is accounted for the fast component of the O2 debt plus the O2 equivalent of the early lactate production.


Measurement of cardiac output using improved chromatographic analysis of sulfur hexafluoride (SF6). A constant current variable frequency pulsed electron capture detector has been incorporated into the gas chromatographic analysis of trace amounts of sulfur hexafluoride (SF6) in water and blood. The resulting system offers a broader effective operating range than more conventional electron capture units and has been utilized for measurements of cardiac output employing constant-rate infusion of dissolved SF6. The SF6 technique has been validated against direct volumetric measurements of cardiac output in a canine right-heart bypass preparation and used subsequently for rapidly repeated measurements in conscious animals and man.


Characterization of the cobalamins attached to transcobalamin I and transcobalamin II in human plasma. Insolubilized antibody to transcobalamin I was used to separate transcobalamin I and transcobalamin II. By bioautography of the extracted cobalamins it was shown that transcobalamin II bound more deoxyadenosylcobalamin than did transcobalamin I, and that methylcobalamin accounts for most of the cobalamins attached to transcobalamin I. This finding may indicate that transcobalamin I has a function in the metabolism of methylcobalamin in man.


Vitamin B12 metabolism in myelomatosis.

Vitamin B12 metabolism in myelomatosis. In 38 patients with myelomatosis the serum cobalamin varied from 34 pmol/1 to 404 pmol/1, median 181.5 pmol/1, which is significantly lower than the levels in 22 control persons with range 173-535 pmol/1, median 265 pmol/1. In spite of low serum cobalamin no symptoms of vitamin B12 deficiency could be demonstrated in any of the patients, except for the one patient who had a serum cobalamin of 34 pmol/1. Mean values for Hb, MCV, PCV, serum lactate-dehydrogenase, adjested red cell folate and nucleated neutrophil count were similar in a group of patients with a serum cobalamin below 160 pmol/1 and a group of patients with higher serum cobalamin values. The decrease in serum cobalamin is due in part to a reduction in the major cobalamin binder (TC-I) in serum. Measuring serum cobalamin in relationship to gastric acis secretion, we found a significantly higher frequency of hypo- and achlorhydria in patients with serum cobalamin below 160 pmol/1 although the intestinal absorption of vitamin B12 was normal by a Schilling test. Although our finding of low saturation of TC-I in serum seems to demonstrate decreased vitamin B12 content in the body in myelomatosis, the lack of evidence for a functional vitamin B12 deficiency speaks against giving a supplement to patients with myelomatosis.


Comparison of biochemical properties of human serum B12 binders derived from sephadex and DEAE-cellulose chromatography. Vitamin B12 binding proteins were separated into 2 peaks corresponding to small (TCS) and large (TCL) molecular weight fractions by gel-filtration of Sephadex G-200 using 0.005 M-sodium phosphate buffer, pH 7.4 containing 1 M-NaC1. Each peak, after dialysis and concentration, was chromatographed on DEAE-cellulose. 3 peaks of radioactivity were recovered from both TCS and TCL. Peaks from TCS had an apparent mol. wt. of about 40,000 and those from TCL about 110,000, as determined by gel-filtration on Sephadex G-200. On electrophoresis, peaks eluted with 0.06 M-phosphate buffer, pH 5.85 from both TCS and TCL moved as beta-globulins; those eluted with 0.1 M buffer, pH 5.8 between beta- and alpha 2-globulin and those eluted with 0.25 M buffer, pH 5.4 between alpha 1-globulin. In our assay system, TCS delivered 57CoB12 to L-1210 leukaemic lymphoblasts while TCL had no such activity. Of the 6 binders from DEAE-cellulose, only peaks eluted with 0.06 M and 0.1 M buffers from TCS delivered labelled B12 to these cells. Antisera prepared against TC II B12 reacted only with TC II B12 from serum, TCS, and fractions D and E obtained from TCS which were eluted with 0.06 and 0.1 M buffers, respectively.


Ph1-negative eosinophilic leukaemia with trisomy 8. Case report and review of cytogenetic studies. A case of eosinophilic leukaemia of the mature cell type in a 73-year-old man is described. Bone marrow chromosomes were studied in direct preparations on 3 occasions. With the G- and Q-banding techniques an extra chromosome number 8 was observed in all metaphases. There was no Ph1-chromosome. Therapy with vincristine and prednisone produced remissions but the course of the disease was accelerated. Review of the literature and study of the present case suggests that eosinophilic leukaemia like CGL may be divided into a Ph1-positive and a Ph1-negative group. In both groups karyotype abnormalities may be present and might herald a downhill course.


Resistance to activated F IX concentrate (FEIBA). A 10-year-old haemophiliac with an inhibitor to Factor VIII was treated by repeated infusion of an activated Factor IX concentrate (FEIBA). During therapy the patient was monitored with extensive coagulation studies, and the initial effect of FEIBA on the whole blood coagulation time was seen to disappear in spite of increased doses of concentrate. A fall in Factor IX activity and a rise of antithrombin III and anti-Factor Xa was recorded, while the titer of anti-F VIII remained unchanged. The exact nature of this FEIBA-resistant state was not revealed, however, it was speculated that a rise of natural inhibitors of the coagulation system could explain the findings.


A comparison between the Grid Test of Schizophrenic Thought Disorder and diagnostic psychological testing. Bannister and Fransella's Grid Test of Schizophrenic Thought Disorder based on  Personal Construct Theory and the concept of "loosened construing", as measurable in the scores of Intensity and Consistency between intercorrelations, has been applied to a Scandinavian sample of psychiatric patients. The validity of the test was illustrated, and a significant difference was found between a group of schizophrenics and schizophrenic borderline states and a group without schizophrenic thought disorders. The Grid Test scores were found to agree with thought disorder manifestations as evaluated in qualitative terms on the basis of cognitive and projective tests, but they did not differentiate between developmental levels of thinking corresponding to concreteness in organic impairment versus diffuseness in schizophrenia. Thus, the concept of "loosened construing" as applied in this thought disorder test seems too unspecific.


The effect of amphetamine and L-dopa on tetrabenazine-induced suppression of intracranial self-stimulation in the rat. The administration of d-amphetamine sulphate resulted in a restoration of intracranial self-stimulation (ICSS) suppressed by tetrabenazine (TBZ). A dose-dependent increase in the rate of ICSS was seen after L-dopa in animals pretreated with TBZ. d-Amhetamine is believed to act by facilitating the nerve-impulse induced release of central catecholamines (CA) whereas the blockage of the granular uptake-storage mechanism by TBZ will prevent the storage of CA formed from the administrated L-dopa and thereby interfere with their release by nerve-impulses. Thus, in the latter case, an activation of central CA receptors in all probability will be due to a dose-dependent diffusion of CA from nerve terminals. It is suggested that the failure to completely antagonize the TBZ-induced suppression of behaviour by L-dopa is due to the fact that a direct activation, independent of the nerve-impulse flow, of central CA receptors easily results in an overstimulation and a reduced specificity in behaviour.


Emotion and cognition in vicarious instigation research. It is argued that the vicarious instigation research would benefit from integrating phenomena and distinctions acknowledged within emotion psychology and cognitive psychology. In particular, suggestions are made which aim at increasing the specificity of terminological, methodological, and interpretational aspects of vicarious instigation research.


[Clinical experiences with prostaglandin E 2 and F 2 alpha in the termination of pregnancy and labor induction in intrauterine fetal death]. In 34 cases of therapeutic termination of pregnancy in the second trimester and in 26 cases of fetal death in utero up to the 43rd week of pregnancy, expulsion of the uterine contents was achieved by means of transabdominal-intraamniotic and intravenous administration of prostaglandin (PG) E2 and PGF2lalpha. The average expulsion time was 14 1/2-16h. The following respective doses were needed: for intraamniotic use, 5-25 mg PGE2 and 40-120 mg PGF2alpha, and for intravenous use 5.8-7.3 mg PGE2 and 43.3-52.3 mg PGF2alpha. Two patients required treatment for side effects. These results are compared with existing data from the literature and the clinical application of various prostaglandins is discussed.


[Study of vitamin D deficiencies in the aged]. Plasma levels of 25-hydroxycalciferol (25-OH-D) and the biological parameters of phosphocalcium metabolism were determined in 55 patients institutionalized in a geriatric hospital in Geneva. They were compared with two control groups, one of the same age and the other younger. The mean plasma 25-OH-D level of the hospitalized patients was 22.7 +/- SD 13.6 microgram/l, which is significantly lower (p less than 0.001) than the mean level obtained from both the control group of the same age (46.2 +/- SD 20.1 microgram/1 25-OH-D) and the control group of young subjects (48.6 +/- SD 16.8 microgram 25-OH-D/1). Among the 55 hospitalized patients, 27 (49%) had a deficient 25-OH-D plasma level lower than 20 microgram/1. Compared to the control group of the same age, the group of hospitalized subjects had lower mean plasma level of inorganic phosphate (27.1 +/- SD 4.34 mg/1; p less than 0.01) and an elevated mean plasma level of alkaline phosphatase (46.9 +/- SD 16.5 UI/1; p less than 0.005). For those 27 patients deficient in 25-OH-D, a positive correlation exists between the plasma values of 25-OH-D and the total calcium (r = 0.584). The high incidence of biological indicators of osteomalacia found in the group of hospitalized patients suggests that vitamin D deficiency is a current problem of the elderly in Switzerland necessitating a review of the prophylactic measures now in use.


[Epidemiology of hepatitis--Canton of Zurich and environs, 1976]. 338 consecutive patients with acute viral  hepatitis occurring in 1976 were analyzed and the data compared with similar studies from 1973 and 1974. 56% of the patients suffered from hepatitis B and the others had "non B" hepatitis. 44% were between 15 and 29 years old and 47% were women. In 43% of patients "administration and consumption of medical measures" were thought to be responsible for the viral transmission and in 24% foreign travel, while in 16% contact with hepatitis patients was suspected to be relevant. Clusters of hepatitis (more than 3 linked cases) occurred in only 3 instances (common travel abraod) involving 16 patients. While 73% of the patients with hepatitis thought to be the consequence of medical measures had hepatitis B, this was the case only in 13% of individuals in whom the disease occurred after trips to southern countries. 146 patients under hemodialysis and 78 staff members of five different hemodilaysis centers were tested for HBS-antigen and corresponding antibodies at intervals of 1-2 months. 57 individuals had signs of ongoing or past infection with hepatitis virus B at the beginning of 1976 while another 52 individuals were newly infected in the course of the year. The estimated risk of acquiring hepatitis was highest for drug addicts (15 per 1000 per year), followed by surgical staff (3-5) and travellers to "high risk" countries (4). Reasonable prophylactic measures to limit the circulation of hepatitis virus in the surveyed population are discussed.


[Result of an antifibrinolytic treatment using tranexamic acid for the reduction of blood-loss during and after tonsillectomy]. Blood loss during and after tonsillectomy was assessed in 80 patients, 40 of whom were treated with tranexamic acid. A statistically significant reduction of blood loss (28%) was observed in this group during operation. Later bleedings occurred only in 27.5% (control: 67.5%) and stopped after 2 h (mean of control: 5.6h). Bleedings in the tranexamic acid group were mild and scarcely required other hemostyptic treatment, while in the control group some patients had to be treated with etamsylate or fibrogen for a longer period to stop bleeding. Tranexamic acid appears to be an effective and well-tolerated agent for reduction of blood loss caused by local hyperfibrinolysis.


[Atypical spermatogonias as precancerous conditions]. Atypical spermatogonia are relatively frequent in the vicinity of testicular teratomas or seminomas. These voluminous cells are seminoma-like, showing broad and clear cytoplasm borders, big nuclei and peculiarly enlarged nucleoli. Atypical spermatogonia usually line the tubules and displace the remaining Sertoli cells towards the middle of the tubules. Recently, such atypical spermatogonia have been described in testicular biopsies performed for fertility disturbances. Two patients showing atypical spermatogonia developed, years later, malignant testicular tumors. Therefore, were checked all of our histological specimens from testicular biopsies over the period 1950-1976 for atypical spermatogonia. They originated from 1935 adult patients in whom biopsy had been performed, in general bilaterally, for fertility disturbances. In fact, atypical spermatogonia were found in the specimens of 9 patients, that is, 0.55%. Five of these patients developed malignant testicular tumours within periods ranging from months to six years, viz. three seminomas, one teratoma and one combined tumor, i.e. a teratoma and seminoma. The remaining four patients with atypical spermatogonia have shown no sign of tumor to date. As the results of our investigation show, atypical spermatogonia in testicular biopsies should not be taken lightly. We therefore strongly advise checks at short intervals on such patients in view of the high risk of their developing malignant testicular tumors.


[Cheyne-Stokes respiration in chronic heart insufficiency]. 1.26 of 340 patients with chronic heart failure (aortic-valve or mitral-valve disease, congestive cardiomyopathy) showed Cheyne-Stokes respiration in supine position. 2. The incidence of Cheyne-Stokes respiration in males is more than twice as high as in females with similar hemodynamic conditions. 3. Lung volumes and airway resistance did not appreciably deviate from the predicted values and are therefore of no etiologic significance. 4. Delay of the feedback between changes in the alveolar gas tensions and respiratory center caused by a prolonged circulation time (decreased cardiac index and increased central blood volume) is the predominant cause of Cheyne-Stokes breathing in patients with chronic heart failure. 5. Metabolic alkalosis (e.g. after diuretics) favors Cheyne-Stokes respiration in patients with congestive heart failure and low cardiac output, by lessening respiratory changes in pH of blood and cerebrospinal fluid.


[Buffering capacity and cost of fluid antacids in 1977]. The 12 liquid antacids most frequently used in Switzerland underwent in vitro determination of their buffering capacity, which was then related to their price. There was a twentyfold difference in buffering capacity between the most potent and the weakest antacid, and a 36-fold difference in price between the most expensive and the cheapest preparation. Based on these results and on the literature the guiding principles and effectiveness of antacid therapy in medical practice are discussed.


Pharmacokinetics of heparin after a single intravenous or subcutaneous injection. In 2 groups of 4 probands the pharmacokinetics of heparin were investigated by a physiologic method (factor Xa inhibition) and an isotope method (35S-heparin) following a single intravenous injection of 5000 IU heparin and a single subcutaneous injection of 10000 IU heparin respectively. Following intravenous administration the anticoagulant effect and radioactivity fall exponentially. The half-life is about 50 min and the distribution volume 3000 ml (factor Xa inhibition) and 3800 ml (radioactivity). With subcutaneous injection peak concentrations above 0.2 IR heparin/ml were measured by both methods 2-4 h after administration; 9 h after administration, no further factor Xa inhibition was detectable in 2 probands. In the light of these and previously published results, some practical aspects of the conduct of therapy and prophylaxis of thromboembolism with heparin are discussed.


[Traumatic paramediastinal air cysts].

[Traumatic paramediastinal air cysts]. A case of double paramediastinal air cyst is described. The diagnosis is easy if the identity is known. Spontaneous regression was always the outcome in the cases published so far. No treatment is necessary. Radiologic examination should include only films of the chest and baryum swallow. The lesion must be recognised in order to avoid unnecessary diagnostic and therapeutic measures.


[Adjuvant chemotherapy of the colonic and rectal carcinoma: concepts and uptodate results]. The aim of adjuvant chemotherapy is the destruction of micrometastases after surgical removal of a malignant tumor. This treatment modality is gaining in importance in the light of experimental data and lcinical success in pediatric tumors. Results of ongoing studies in colo-rectal cancer show a marginal effect of prophylactic treatment with 5-fluorouracil. The treatment benefits in trials with historical controls are much greater than in studies with simultaneous controls. Use of historical controls is therefore of doubtful value. Ongoing trials use the combination of 5-fluorouracil and methyl-CCNU, which has been shown to double the remission rate in advanced gastrointestinal cancer. Adjuvant chemotherapy of colo-rectal cancer is still experimental and justified only in the framework of clinical trials.


[Crisis and crisis intervention in modern psychiatry]. After discussion of the definition, concept and theory of psychic crisis, the modern techniques of crisis intervention are presented in the light of the literature and the author's personal experience, illustrated by case histories. Finally, the organizational place of crisis intervention in a modern psychiatric care system is discussed, with emphasis on the advantage of using socio-psychiatric half-way institutions for rehabilitation between hospital and ambulatory services for crisis intervention as well.


[Surgical therapy of severe chronic constipation]. Primary chronic constipation is an ailment of modern civilisation. Severe forms can seldom be treated satisfactorily by conservative methods, and in these cases surgical intervention must be considered. This consists of subtotal colectomy with ileosigmoidostomy. Partial resection and hemicolectomy do not afford the desired result. A report is presented on 28 patients who had subtotal colectomy for chronic constipation during the period 1959 to 1976. Immediate and long-term results have proved to be surprisingly good. Unsatisfactory conditions are to be expected in patients with strong complementary psychoneurotic symptoms. Preoperative investigations must be carried out with precision, morphological changes accurately identified and treated by differentiated surgical methods. The indication for colectomy in cases of chronic constipation must be strictly established, if possible in collaboration with a gastroenterologist.


[VP 16-213 in combination with endoxan, methotrexate and oncovin as polychemotherapy for bronchogenic carcinoma]. Thirty patients with bronchogenic carcinoma underwent an 8 week course of induction therapy consisting of cyclophosphamide, methotrexate, vincristine, and VP 16-213 (NSC 141 540). Those who achieved objective remission or tumor stabilization were then placed on an intermittent treatment schedule with the same drugs. Of the 30 patients, 17 had an objective response, 5 were unchanged and 8 progressed. Responses were more frequent in anaplastic carcinoma (13/19) than epidermoid or adenocarcinoma (4/11). The toxicity mainly consisted of leukopenia, thrombopenia, alopecia, nausea and vomiting. The implications of these findings in the planning of further chemotherapeutic programs are discussed.


Ammonia in the human airways: neutralization of inspired acid sulfate aerosols. In the human being, expired ammonia concentrations from 7 to 520 micrograms per cubic meter are controlled by the last airway segment traversed by the air, and such concentrations are higher in the mouth than nose. Inspired submicrometric sulfuric acid aerosol at a mass concentration of 600 +/- 100 micrograms per cubic meter was found to be an ammonium salt with an average ammonium to sulfate molar ratio of greater than or equal to 1, when sampled  within 0.5 second after exhalation.


The cytoplasmic differentiation of jumelle Stylonychia. Jumelle Stylonychia with oppositely oriented peristomes, which we obtained by artificial operations, carried on not only asexual reproduction and generation, but sexual reproduction and encystment as well, and seemingly tended to form a new species [7-10]. Our recent experimental analysis revealed that the sinister grew more and more dependent on its dextral sister organism, losing the ability of independent existence. Once cut off from the dexter, the organelles of the sinister ceased to regenerate, and the sinister died. But, if, when cutting, a portion is left connected to the dexter, the sinister will then be able to regenerate, and all its organelles become completely revealed. This indicates that dependence on the dexter weakened the metabolic functions of the sinister, primarily influencing the cytoplasm, which is manifested by the formation and development of its organelles. This, in effect, is a phenomenon of cytoplasmic differentiation induced by co-existence of the jumeaux.


Clomid or nafoxidine administered to neonatal rats causes reproductive tract abnormalities. A single injection of either Clomid or Nafoxidine in neonatal rats causes multiple abnormalities of the reproductive tract of the adult female animal. These anomalies include cystic ovaries, ovarian hypoplasia, hilus cell tumors, oviductal hyperplasia, pyometra, epithelial metaplasia, uterine cystic hyperplasia, and tumors of the uterus.


Adriamycin: the role of lipid peroxidation in cardiac toxicity and tumor response. The antitumor antibiotic, adriamycin, induces severe cardiac toxicity associated with peroxidation of cardiac lipids in mice. Both this lipid peroxidation and cardiac toxicity of adriamycin are reduced by prior treatment of the animals with the free radical scavenger tocopherol. Such treatment with tocopherol does not, however, alter the magnitude or duration of the adriamycin-induced suppression of DNA synthesis in P388 ascites tumor, nor does it diminish the antitumor responsiveness of P388 ascites tumor. These results suggest that adriamycin has at least two mechanisms of tissue damage: one, which involves lipid peroxidation, is blocked by tocopherol and results in cardiac toxicity; the other, which involves binding to DNA, is not antagonized by tocopherol and is responsible for tumor response.


Transport interaction of cystine and dibasic amino acids in renal brush border vesicles. The uptake of cystine by vesicles prepared from rat kidney brush borders occurs by two distinct transport systems. The higher affinity system is inhibited by the dibasic amino acids lysine, arginine, and ornithine. The lower affinity system, unaffected by dibasic amino acids, appears to correspond to that observed by studying uptake of cystine by kidney slices.


Angiotensin: physiological role in water-deprivation-induced thirst of rats. Cerebroventricular infusion of P-113, the blocking agent of angiotensin II, into rats for 75 minutes prior to their being allowed to drink, significantly attenuated their water intake when they had been deprived of water for 30 hours. However, a similar infusion had no effect on the food intake in rats fasted for 30 hours. The results indicate a physiological role for angiotensin II in the drinking response of rats deprived of water.


Siamese cats: abnormal responses of retinal ganglion cells. Comparison of optic tract recordings in Siamese and ordinary cats reveals that Siamese cats have a significantly lower percentage of Y-cells than of X-cells. In addition, Siamese cats show depressed responses to a contrast-reversal stimulus, a result that supports the lower spatial contrast sensitivity demonstrated behaviorally by these animals. Both physiological findings suggest neurophysiological anomalies in the Siamese retina.


Fragile sites on human chromosomes: demonstration of their dependence on the type of tissue culture medium. The observation of heritable fragile sites on human chromosomes prepared for lymphocyte cultures has been shown to depend on the type of tissue culture medium in which the lymphocytes are grown. The sites are observed at a much greater frequency when medium 199 is used than when RPMI 1640, Ham's F10, Eagle's (basal), and CMRL 1969 are used. One site on the X chromosome is of clinical significance in that it is a marker for X-linked mental retardation.


Induction of acetylcholinesterase activity by beta-ecdysone in a Drosophila cell line. When cells of the Drosophila Kc-H line are treated with larger than or equal to 10(-8) molar beta-ecdysone, they extend long processes and acquire acetylcholinesterase activity. Thus, this permanent line, derived originally from embryol cultures, may be composed of cells having some neural or glial characteristics.


Proton-induced x-ray emission analysis of single human hair roots. Collimated beams of 3.75 million electron volt protons were used to examine a 2-millimeter length of the root end of human hair; the concentrations of some hair root elements were correlated with the results of standard clinical assays of blood samples. The technique should be useful for the analysis of micro amounts of biological tissue.


Binocular differences in cortical receptive fields of kittens after rotationally disparate binocular experience. Kittens were afforded visual experience only while wearing goggles fitted with prisms that rotated the inputs to the two eyes equally but in opposite directions about the visual axes (16 degrees for experimental subjects, 0 degrees for control subjects). Subsequently, receptive-field organization of the visual cortex was studied, special attention being given to the preferred orientation centered about the prism rotation experienced during early development. Thus, for moderate amounts of relative rotation, the development of interocular matching of orientation specificity in binocular cells of the visual cortex reflects the correspondence of early visual input between the two eyes.


Fatty acids and their prostaglandin derivatives: inhibitors of proliferation in aortic smooth muscle cells. Prostaglandins are synthesized from eicosa-8,11,14-trienoic acid and eicosa-5,8,11-14-tetraenoic acid by smooth muscle cell cultures from guinea pig aorta. Production is inhibited by indomethacin. The precursor fatty acids and their prostaglandin derivatives inhibit proliferation of the cell cultures. The relative availability of fatty acids for prostaglandin biosynthesis may represent a control mechanism for cell proliferation.


Antibody-induced antigen redistribution and shedding from human breast cancer cells. Cell surface antigens of human breast cancer cells undergo a rapid redistribution when bound by antibodies from cancer patients. The subsequent shedding of these antigen-antibody complexes and free antigen may be instrumental in tumor survival.


Stimulation by immune complexes of mucus release from goblet cells of the rat small intestine. Immune complexes (bovine serum albumin with rat antibodies to bovine serum albumin) formed in twofold antibody excess were injected into the duodenum of normal rats. In comparison to controls injected with antigen only, there was a marked increase in the percentage of disrupted goblet cells (an index of mucus release) in segments from the intestine of rats exposed for 3 hours to immune complexes in vivo. Similarly, there was a significant increase in 35S-labeled mucus recovered by filtration of intestinal wash, rinse, and mucosal homogenate fluids from rats exposed to immune complexes compared to those from rats exposed to bovine serum albumin or purified rat antiserum to bovine serum albumin alone. These findings suggest that certain immune complexes can stimulate mucus release from intact rat small intestine; enhanced mucus release may have a role in clearing the surface of complexes.


Formation of a serine enzyme in the presence of bovine factor VIII (antihemophilic factor) and thrombin. Factor VIII is present in plasma in a precursor or inactive form. When bovine factor VIII that has been purified approximately 10,000-fold is incubated with thrombin, an activated product is formed which participates in the conversion of factor X to factor Xa in the presence of factor IXa, calcium ions, and phospholipid. This activated product, which has been tentatively identified as activated factor XIII, was stable when formed in the presence of 0.25M CaCl2 but was rapidly inactivated in the absence of CaCl2. It was inhibited by diisopropyl phosphorofluoridate and antithrombin III, suggesting that it is a serine enzyme. The exact role of this serine enzyme in the intrinsic pathway of coagulation remains to be established.


New Genetic marker in human parotid saliva (pm). In 195 parotid saliva samples collected at random from a Japanese population, two phenotypes were observed by electrophoresis in acid-urea starch gels. The protein showing polymorphisms was detected in the middle zone between Pa and Pb, and was tentatively designated Pm. Inheritance was controlled by a dominant allele at an autosomal locus. The frequencies of the genes determining these phenotypes were, for the Japanese population studied, Pm+=.38+/-.03, Pm-=.62+/-.03.


North American egg parasite successfully controls a different host genus in South America. Telenomus alsophilae, a parasite of the eggs of the geometrid Alsophila pometaria in North America, was introduced into Columbia, South America, for the biological control of a pest host in another genus, Oxydia trychiata. Successful results were obtained with this unorthodox procedure to control a forest insect.


Adipose tissue regeneration following lipectomy. Surgical removal of subcutaneous fat depots in weanling rats leads to a regenerative response. If the rats are fed a diet high in fat, adipose mass and adipocyte number are precisely restored within 7 months of surgery. Thus, under appropriate experimental circumstances, compensatory hyperplasia will occur in adipose tissues of the rat.


Surgical removal of adipose tissue alters feeding behavior and the development of obesity in rats. Lipectomized and sham-operated rats were fed a high-fat diet to induce hyperphagia and rapid fat accumulation. Lipectomized rats with 25% fewer adipocytes were less hyperphagic and accumulated less fat, but their adipocytes remained equal in size to adipocytes of controls. A role for adipocyte size in fat storage regulation and food intake control is postulated.


A critical period for acoustic trauma in the hamster and its relation to cochlear development. Young hamsters pass through a developmental stage during which they are unusually susceptible to acoustic trauma. This sensitive period occurs after apparent structural and functional maturation of the ear and appears to be dependent on unidentified developmental changes within the cochlea.


Suprachiasmatic nuclear lesions do not abolish food-shifted circadian adrenal and temperature rhythmicity. Daytime restriction of food and water availability in nocturnal animals phase shifts the circadian periodicity of plasma corticosteroid concentrations and body temperature. These shifted rhythms persist in animals with lesions of the suprachiasmatic nuclei who are arrhythmic under normal conditions. These findings suggest the existence of an additional "clock" that may be involved in the generation of the rhythm.


The development of language-like  communication without a language model. Deaf children who are unable to acquire oral language naturally and who are not exposed to a standard manual language can spontaneously develop a structured sign system that has many of the properties of natural spoken language. This communication system appears to be largely the invention of the child himself rather than of the caretakers.


Pesticide uptake into membranes measured by fluorescence quenching. Pesticides that contain chlorine have been shown to quench the fluorescence of carbazole-labeled phospholipids. Incorporation of these carbazole-labeled phospholipds into model membranes provides a system that allows the rapid determination of the uptake rates of chlorinated hydrocarbons into model membranes. This technique can be used in the determination of diffusion rates and partition coefficients of chlorine-containing organic compounds in model membrane systems, and hence may provide a method by which the bioaccumulation potential of synthetic chlorine-containing compounds can be estimated.


L-dopa: selective toxicity for melanoma cells in vitro. In a study of the effect of L-dopa, an intermediate in the biosynthesis of the pigment melanin, on the growth of human and murine melanoma cells a highly selective inhibition of growth was observed for pigmented cell lines (S91A and human melanoma) as compared to the nonpigmented control cells (amelanotic melanoma S91B, mouse fibroblast L929, and Chinese hamster ovary). There was a correlation between toxicity and the extent of incorporation of radioactively labeled L-dopa by each line.


Inhibition of a lymphocyte membrane enzyme by delta9-tetrahydrocannabinol in vitro. Delta-9-tetrahydrocannabinol (delta9-THC) inhibited the activity of lysolecithin acyl transferase, a membrane-bound lymphocyte enzyme, at concentrations above 1.3 muM. Stimulation of acyl transferase activity by concanavalin A, an early response in lymphocyte activation, was entirely abolished in the presence of delta9-THC.


Perilla ketone: a potent lung toxin from the mint plant, Perilla frutescens Britton. Perilla ketone, from the essential oil of Perilla frutescens, is a potent pulmonary edemagenic agent for laboratory animals and livestock. This finding would account for reported effects of the plant on grazing cattle. The use of perilla in oriental foods and medicinal preparations suggests possible hazards to human health as well.


Quantitation of cytoplasmic tubulin by radioimmunoassay. A radioimmunoassay has been developed for the quantitation of crytoplasmic tubulin. It measures tubulin between 20 and 1500 nanograms and does so independently of decay in colchicine-binding activity. In addition, the state of tubulin as subunit or polymer does not alter the measurement.


Event-related brain potentials: comparison between children and adults. Event-related brain potentials in response to tachistoscopically presented stimuli were recorded from adults and children. Rare, nontarget stimuli (both novel and easily recognized) elicited different brain potentials in children and adults, while equally rare, target stimuli elicited similar potentials in children and adults.


Dopamine receptor binding enhancement accompanies lesion-induced behavioral supersensitivity. The binding of [3H]haloperidol to rat striatal dopamine receptors increases after lesion (made by injection of 6-hydroxydopamine) of the nigrostriatal dopamine pathway in those rats which are behaviorally supersensitive, as reflected by apomorphine-induced contralateral rotations. The enhanced binding is associated with an increased number of receptor sites with no change in their affinity.


Catechol estrogens: presence in brain and endocrine tissues. Catechol estrogens have been identified and measured in rat brain and various endocrine tissues with the use of a sensitive radioenzymatic assay. The specificity of this assay was confirmed by thin-layer chromatography and mass spectral analysis of the reaction products. The concentration of catechol estrogens in the hypothalamus and pituitary are at least ten times higher than reported previously for the parent estrogens. Catechol estrogens have potent endocrine effects and, because of their normal occurrence in the hypothalamic-pituitary axis, they have an important role in neuroendocrine regulation.


Porphyrin induction: equivalent effects of 5alphaH and 5betaH steroids in chick embryo liver cells. The 5alphaH (A : B trans) and 5betaH (A : B cis) steroids are equipotent in inducing delta-aminolevulinic acid synthetase and porphyrin accumulation in chick embryo liver cells maintained in serum-free culture medium. Thus there is no specific steric requirement for porphyrin-inducing activity in steroids.


Hydrodynamic evidence in support of spacer regions in chromatin. Quasi-elastic light scattering and sedimentation velocity methods were used to study the hydrodynamic properties of purified dimer subunits obtained from partial digestion of chicken erythrocyte chromatin with staphylococcal nuclease. The experimental value of 1.87 +/- 0.08 X 10(-7) gram per second for the friction factor of these dimer subunits in low ionic strength buffer cannot be reasonably interpreted in terms of a contiguous sphere model. Analysis by means of an equivalent dimer method suggests that the spacer region accounts for a maximum of 19 percent of the friction properties of the dimer.


Phenylketonuria: a new method for the simultaneous determination of plasma phenylalanine and tyrosine. This quantitative spectrophotometric method is based on the conversion of phenylalanine and tyrosine by phenylalanine ammonia-lyase to trans-cinnamic acid and trans-coumaric acid, respectively. Neither deproteinization nor prior incubation of the sample is required, and the entire procedure can be performed in 20 minutes. The method is sensitive to 1-micromolar concentrations of the two compounds, and only 20 microliters of plasma or serum is required to determine both phenylalanine and tyrosine simultaneously. These amino acids were determined between molar ratios (phenylalanine to tyrosine) of 0.1 to 40 in the serum or plasma of healthy individuals and plasma of phenylketonuric patients.


Hepatic binding protein: the protective role of its sialic acid residues. Removal of sialic acid from a specific hepatic binding protein virtually abolishes its capacity to bind certain asialoglycoproteins. The loss of this capacity is the result of competition for the binding sites by galactosyl residues, of hepatic binding protein, that become terminal after desialylation.


Structure of a molluscan cardioexcitatory neuropeptide. A cardioexcitatory substance from ganglia of the clam Macrocallista nimbosa, formerly designated peak C, is the tetrapeptide amide Phe-Met-Arg-Phe-NH2. Its structure was determined by the combined use of Edman dansyl degradation and tryptic digestion. The structure was confirmed by synthesis. This neuropeptide is active at about 10(-8)M when assayed on molluscan muscle.


DNA strand scission by benzo[a]pyrene diol epoxides. Syn-and anti-benzo[a]pyrene diol epoxides elicit a concentration-dependent nicking of superhelical Col E1 DNA in an in vitro reaction monitored by agarose gel electrophoresis and electron microscopy. This strand scission represents less than 1 percent of the DNA modification by diol epoxide. Kinetic analysis implicates the formation of unstable phosphotriesters, hydrolysis of which nick the DNA.


Interferon: an inducer of macrophage activation by polyanions. Purified mouse fibroblast interferon (IF) directly rendered resting macrophages tumoricidal. The physicochemical properties and species specificity of the stimulatory agent fall within the present definition of IF. Since a number of polyanions induce macrophage IF, the antitumor and antimicrobial activities may result from the ability of newly released IF to modify macrophage activity.


Toxicity of mild prenatal carbon monoxide exposure. Rats prenatally exposed to a low concentration of carbon monoxide which results in carboxyhemoglobin levels equivalent to those maintained by human cigarette smokers, show reduced birth weight and decreased weight gain. Neuro-behavioral and biochemical testing of the offspring reveals lower behavioral activity levels through the preweaning period, altered central catecholamine activity, and reduction in total brain protein at birth.


Cerebral lateralization of haptic perception: interaction of responses to Braille and music reveals a functional basis. Normally, haptic perception of the left hand surpasses that of the right. But simultaneously playing music into the left (but not the right) ear reverses this superiority. This suggests that the left cerebral hemisphere has full haptic perceptual capability, which is subject to right hemisphere interference unless the latter's attentional mechanisms are engaged by contralateral peripheral stimulation.


A developmental theory of environmental enrichment. The differential brain development induced by sensory enrichment or deprivation is most apparent in rats with low brain weights. These differences are hypothesized to represent the retarded development of environment-dependent neurons in the isolated animals.


Planning for ambulatory care: simple methods for improving patient flow. A combined patient flow and work sampling study was done at the Ambulatory Pediatric Service of the Medical University of South Carolina. The biggest problem was that almost two thirds of the patient's time was spent waiting to see the doctor. Reasons for delay included too few examining rooms, the single block appointment system, and design of the facility.


Pilot evaluation of teaching strategies in ambulatory pediatrics. Creating an effective learning experience for medical students in ambulatory pediatrics can be a problem. In a pilot study several strategies to improve learning were tested on 51 students during their eight-week basic pediatric clerkship. Each student spent half of this clerkship in the outpatient area. Thirty-six received a detailed list of cognitive and skill objectives at the beginning of their outpatient experience, and 18 of these also had structured individual teaching sessions with a staff pediatrician. The individual teaching sessions tended to improve performance in patient evaluation skills, but neither approach improved the attainment of factual knowledge or the students' evaluations of their outpatient experiences. Further study of the qualitative and quantitative aspects of various teaching technics is needed.


Acetaminophen and hepatic dysfunction in infectious mononucleosis. Two family members developed severe hepatitic dysfunction in association with infectious mononucleosis and acetaminophen administration. Since severe hepatitis is an extremely rare complication of infectious mononucleosis, we postulate that the hepatic dysfunction was induced by acetaminophen.


Management of open fractures of the tibial shaft. In a retrospective study of 98 open fractures of the tibial shaft, the end result was found to be most closely correlated with the severity of the initial injury. Comparison of six different forms of treatment (external immobilization, external immobilization with early weight bearing, pins and plaster immobilization, intramedullary fixation, multiple screw fixation and plate and screw fixation) did not indicate a superiority of any one method of management.


Spinal epidural abscess.

Spinal epidural abscess. This paper describes problems in the diagnosis and management of six patients with spinal epidural abscess. Since the clinical findings in this disease process are frequently misinterpreted, one must be careful to exclude this diagnosis in any patient with fever, leukocytosis, back pain and recent infection or back trauma. Alcoholic patients, in particular, seem at high risk for missed diagnosis since the clinical findings are frequently misinterpreted to be complications of alcoholism. Suspicion of spinal epidural abscess should lead to immediate lumbar puncture with manometrics as well as myelography. Once the diagnosis is established surgery should be immediate. Gram stains and cultures taken at the time of lumbar puncture or at operation will dictate appropriate antibiotic therapy. The cause of infection can be fairly well determined by the location of the abscess and a knowledge of the pathogenesis. Prognosis seems directly dependent on the preoperative neurologic status of the patient.


Childhood poisoning: a community hospital experience. We reviewed medical records of 53 children who ingested poison and were treated as inpatients and 107 who were treated as outpatients in a Southeastern community hospital. Findings included a much higher incidence of petroleum distillate poisoning than is found nationally, and a low frequency of aspirin ingestions. Data on packaging of the poisons indicate that one third was stored in food containers. Of the products encountered, 33% currently require safety packaging but were found in obsolete containers.


Experience with deep hypothermia and elective circulatory arrest for cardiac surgery in infants. During hypothermic circulatory arrest (19 C nasal) averaging 55 minutes in 25 infants, the mean increase in base deficit was only --3.95 mEq/liter, when arterial gases before circulatory arrest were compared with samples ten minutes after perfusion had been resumed. Few significant arrhythmias occurred, and all survivors appeared neurologically normal at discharge.


Current status of total knee replacement. Correction of deformity and relief of pain in advanced arthritis of the knee joint can be obtained by implantation of a total knee prosthesis. For the painful, mildly damaged knee, the Charnley prosthesis may be used, while in the more moderately damaged knee, the geometric prosthesis may be indicated. For the unstable, severely damaged knee, a constrained prosthesis may be implanted. These knee prostheses can be used to treat knees which previously were not amenable to surgical correction, except by arthrodesis.


The efficacy of percutaneous liver biopsy in the initial staging of patients with lymphoma. To evaluate the usefulness of percutaneous needle liver biopsy in the initial staging of lymphoma patients, 115 patients presenting to M. D. Anderson Hospital between Sept 1, 1972, and Aug 31, 1975, and having either percutaneous (45) or celiotomy (70) liver biopsy were identified. Sixty-six patients had Hodgkin's disease, 49 non-Hodgkin's lymphoma. Overall, results of 13 biopsies were positive--six by percutaneous biopsy, seven by celiotomy. Results showed little difference in yield between percutaneous and celiotomy biopsy. Positivity increased with increasing clinical stage, increasing age (Hodgkin's patients), and increasing number of abnormal liver function tests. It is concluded that percutaneous liver biopsy is useful in lymphoma staging, especially in patients with at least one abnormal liver function test, and in patients with Hodgkin's disease, mixed cell type. The early identification of otherwise unrecognized stage IV disease can spare many patients the morbidity of staging celiotomy.


Recurrence patterns and survival after combined radical mastectomy and postoperative irradiation: a retrospective analysis. Recurrence patterns were analyzed in 323 patients treated by radical mastectomy, 219 of whom received postoperative irradiation. Thirty-five patients with inner quadrant lesions and negative axillary nodes received postoperative regional node irradiation; 33 of these 35 patients are alive without recurrence from 2 to 22 years later. Six of 219 patients receiving postoperative regional lymph node irradiation developed recurrence in the treated area. In patients with positive axillary nodes, 27% of all recurrence developed initially in the chest wall region, and an additional 10% of patients developed distant metastases in addition to chest wall recurrence. The high incidence of chest wall recurrence in patients with four or more positive nodes, and in patients with two or three positive nodes and primary lesions over 3 cm in diameter who did not receive chest wall irradiation, suggests that the maximal benefit from postoperative irradiation would not be realized in prospective, randomized studies without the use of chest wall irradiation postoperatively in these categories of patients.


Removal of foreign bodies: the flexible fiberoptic endoscope. Three foreign bodies were successfully removed from the upper gastrointestinal tract with a fiberoptic endoscope. They included a food bolus lodged above an esophageal stricture, a metallic nebulizer tip impacted in the mid-esophagus, and a spoon lodged in the stomach. A razor blade could not be removed from the duodenum. Many foreign bodies, including large or elongated objects, can be removed from the upper gastrointestinal tract with flexible fiberoptic endoscopes.


Traumatic spinal cord injuries due to automobile accidents. Of the 1,164 patients with traumatic spinal cord injury admitted to the Texas Institute for Rehabilitation and Research from February 1959 through December 1975, 389 were injured in automobile accidents. The patients with spinal cord injury were predominantly male, and the average age was in the late 20s. Two thirds of the accidents involved a single automobile and occurred less than 50 miles from the residence. The driver's seat was the most common seating position. Seat belts were not worn in over 90% of the cases; many of the other victims wore their seat belts improperly. Some of the patients were probably injured because of structural defects of the automobile.


Squamous carcinoma of the lower lip in patients under 40 years of age. In a series of 1,308 squamous carcinomas of the lower lip, 97 (7%) occurred in patients under 40. Among the 56 followed up for at least five years, there were 12 deaths due to disease for a determinate mortality of 21%. In five of these patients (41%) the tumor persisted more than three years from the time of initial treatment and in four others (33%), for more than five years. Of all 97 patients, 15 (15%) developed additional primary tumors. Most second lesions were squamous or basal cell carcinomas of the skin; however, four patients developed second primary lesions with considerable malignant potential (one melanoma and three visceral cancers). Three of these patients died of their second tumors, raising the overall mortality to 26%. Squamous carcinoma of the lower lip appears to have a worse prognosis in younger patients. A significant fraction of these patients succumb to their disease more than five years after initial treatment. This, coupled with a tendency to develop significant second primaries, suggests that a protracted period of close clinical follow-up is essential.


Emotional factors in inflammatory bowel disease. Inflammatory bowel diseases are not caused by emotional conflicts, but emotional factors influence both the pathogenesis and the course of the illness. Establishing a trusting physician-patient relationship is important in helping the patient to (1) avoid denial of illness or chronic illness behavior, (2) understand symptoms and diagnostic and treatment procedures, and (3) cope with loss of a key person or the threat of lessened self-control.


Prognostic value of carcinoembryonic antigen in patients with breast cancer. Carcinoembryonic antigen (CEA) levels were followed in 18 patients with a history of breast cancer to determine the prognostic value of serial determinations in predicting either the development of clinically evident metastatic disease or the progression of previously stable metastatic disease. In patients with local disease, values were in the normal range initially and tended to remain so for the duration of the study, correlating with clinical quiescence. Patients with nodal or extranodal involvement tended to have higher values, but changes could not be consistently correlated with clinical deterioration. Exceptions to these general trends were found in each group. This study suggests that the assay of CEA is of limited predictive value in an individual patient with a history of breast cancer.


Median nerve injuries and their management. Injuries of the median nerve cause two major syndromes. Interosseous nerve injury as it branches from the median just below the elbow produces a characteristic deformity. Treatment involves neurolysis, or primary or secondary repair. Various tendon transfers can be used to compensate for lost function. The other syndrome is produced by median nerve injury at the wrist and consists of thenar muscle paralysis and a sensory deficit on the radial aspect of the palm and radial 3 1/2 digits. The carpal tunnel syndrome is the most common cause. Treatment consists of incising the volar carpal ligament. Lacerations at this level should be repaired primarily if possible. Several types of opponensplasties are available to restore thumb opposition. Median nerve injuries impair the ability to pinch and should be carefully evaluated and treated.


Significant hematuria secondary to sickle cell trait in a white family. A 21-year-old blond, white woman was evaluated for recurrent episodes of significant painless gross hematuria. She was found to have sickle cell trait, and hematologic evaluation made through four generations isolated the trait to the paternal side.


Chronic active hepatitis and cirrhosis in Wilson's disease. A 32-year-old woman was found to have chronic active hepatitis and cirrhosis after exploratory celiotomy resulted in hepatic decompensation. Subsequent investigation confirmed the diagnosis of Wilson's disease. This case demonstrates that Wilson's disease may manifest itself as chronic active hepatitis as late as the fourth decade of life without neurologic symptoms or findings. Wilson's disease should be actively considered in patients with chronic active hepatitis or cirrhosis, even in older age groups and despite the absence of central nervous system manifestations.


Transient megacolon after gastroscopy.

Transient megacolon after gastroscopy. A 38-year-old man who developed abdominal distention and pain following fiberoptic gastroscopy is described. The patient had had an upper gastrointestinal roentgenographic series earlier, and the dilatation of the colon was thought to be due to entrapment of air in the proximal colon secondary to inspissated barium in the descending colon. Premedication with meperidine hydrochloride and atropine also may have been contributory. A saline enema relieved the patient's symptoms and a barium enema examination later showed a normal colon.


Echocardiographic diagnosis of supravalvular aortic stenosis. The echocardiographic features of supravalvular aortic stenosis seen in a patient with valvular aortic and multiple pulmonary branch stenosis are described. Since patterns of valvular, discrete subvalvular, and supravalvular aortic stenosis can be recognized by echocardiography, it is now possible to screen close relatives of patients having supravalvular aortic stenosis and pulmonary branch stenosis by this non-invasive technic.