On the stimulation of gluconeogenesis by L-lysine in isolated rat kidney cortex tubules. 1. L-Lysins (2 mM) stimulates (30-50%) gluconeogenesis in isolated kidney cortex tubules from 24-h-starved rats in the presence of lactate and Krebs cycle intermediates, but not pyruvate and glutamate. The stimulation of renal gluconeogenesis by L-lysine is a short-term effect. The effect is of catalytic nature, but not due to sparing of substrate. L-lysine caused a decrease of lactate/pyruvate ratio. 2. Apart from L-lysine, 1-10 mM NH-4Cl (16-40%) and 2 mM aspartate (66%) were capable to stimulate gluconeogenesis from lactate. Other amino acids tested did not stimulate renal gluconeogenesis, except L-alanine. The stimulation of gluconeogenesis by lysine was not additive to the stimulation by NH-4Cl. Likewise, there was no stimulation of gluconeogenesis from lactate by L-lysine in the presence of glutamate or arnithine. Levels of ammonia, glutamate and aspartate were elevated in the presence of L-lysine, NH-4Cl or glutamate about two-fold, were capable to stimulate gluconeogenesis. 3. The stimulation of gluconeogenesis by L-lysine from malate, succinate and oxoglutarate was abolished in the presence of amino oxy-acetate (0.05 mM), whereas controls were not significantly affected. 4. After 1 h of incubation about 5% of added [U-14C] lysine was recovered as 14-CO-2. The extra ammonia formed in the presence of L-lysine would also correspond with about 5-10% of added lysine being metabolized. 5. 14-CO-2 formation from [1-14C] butyrate and [1-14C] palmitate was inhibited by 20-30% in the presence of 2 mM L-lysine. 6. O-2 uptake and cellular levels of K+ were not significantly affected by L-lysine. 14-CO-2 fixation from pyruvate and 14-CO-2 formation from [1-14C]-pyruvate by isolated, intact rat liver mitochondria remained unchanged by L-lysine. Likewise no direct effect of L-lysine on enzyme activities could be detected. 7. The data seem compatible with the assumption that stimulation of gluconeogenesis in isolated kidney cortex tubules by L-lysine is due to a stimulation of the malate-aspartate shuttle as a consequence of an increased provision of glutamate and aspartate.


Rat pancreas adenylate cyclase. III. Its role in pancreatic secretion assessed by means of choleara toxin. 1. The role of adenylate cyclase in rat pancreas is further investigated by means of cholera toxin, which is known to activate the enzyme in several tissues. 2. Cholera toxin activates rat pancreatic adenylate cyclase in vitro upon preincubation of tissue slices with the toxin for more than 30 min, but not when it is merely present during the enzyme assay. The maximal effect is reached after 90 min pre-incubation. The half-maximally activating concentration is 3.5 mu-g/ml upon pre-incubation for 90 min. 3. After pre-treatment of pancreatic tissue slices with 2 mu-g/ml cholera toxin, further stimulation of adenylate cyclase activity can be obtained by adding pancreozymin-C-octapeptide, secretin, or fluoride to the assay medium, but the final activity with maximally effective concentrations of the hormones is not higher, and with fluoride even less, than that without the toxin pre-treatment. 4. The in vivo effects of the two hormones and of cholera toxin have been studied after cannulation of the pancreas. Pancreozymin-C-octapeptide (intravenously) markedly stimulates both flow rate and rate of protein secretion. Synthetic secretin (intravenously), in addition to its expected effect on flow rate, slightly stimulates protein secretion, which is not due to a wash-out effect. Cholera toxin, topically applied to the cannulated rat pancreas, causes a steady increase of the flow rate after a delay of 20--30 min. The rate of protein secretion is not affected or slightly decreased by the toxin. Pancreozymin-C-octapeptide, given intravenously 1 h after cholera toxin application, causes the same increase in flow rate and rate of protein secretion as would be expected without cholera toxin treatment. 5. The sodium and potassium levels in the pancreatic fluid after administration of secretin or cholera toxin do not change, while the chloride level decreases in both cases. 6. These observations indicate that the rat pancreas adenylate cyclase activity is a rate-limiting factor in the regulation of water and electrolyte secretion. A possible auxiliary role in the regulation of enzyme secretion cannot yet be excluded.


The dependence of glucose formation from lactate on the adenosine triphosphate content in the isolated perfused rat liver. Bilateral intercollicular lesions in the chick abolish or depress notonly calling, but also those phases of behavior when calling would have been occurring. These include: long bouts of excited feeding immediately after food is made available;examining and pecking moving targets and novel objects;  persistent scanning, and inhibitionof other behaviour in a novel environment.  Deaf birds behave precisely like controls,so that possible auditory deficits are not involved.  During calling phases significantvisual stimuli are treated as if they were startling or conspicuous.  Conversely,continuousexamination of a stimulus causes calling to diminish or disappear even though responsecontinues;  a brief period when the stimulus is not seen causes calling to begin againwhen it is once more perceived.  In addition to the increased effectiveness of relevantvisual stimuli, motor facilitation is usual in calling phases, as is inhibition ofirrelevant responses.  Emotioanl behaviour in man and other mammals is composed tocalling phases in the chick


Chondroitin sulphate of calf knee-joint cartilage. Chondroitin sulphate from different layers of calf knee-joint cartilage has been isolated and purified. Analysis for hexosamine, uronic acid, sulphate and relative proportions of the 4- and 6-isomers revealed no differences between the layers. However, an increase in the average molecular weight of the chondroitin sulphate was found to correspond with distance from the articular surface. In particular, the average molecular weight in the epiphyseal cartilage was significantly higher than that in the articular cartilage. The chondroitin sulphate of the 40-mu-mthick articular surface layer was found to have a higher molecular weight than the rest of the articular part of the cartilage and also to be more polydisperse. These results, regarding molecular size, are in agreement with the cetylpyridinium chloride cellulose microcolumn fractionation patterns.


The transfer of galactose from UDP-galactose to endogenous lipid acceptors in liver microsomes. When the microsomal fraction of beef liver is incubated with UDP-[14-C]-galactose in the presence of an inhibitor of nucleotide pyrophosphatase, there is an incorporation of the [14-C]galactose into glycoprotein and into two lipid components, one soluble in chloroform and the other in chloroform/methanol/water (1:1:0.3). Chromatography of the chloroform fraction on DEAE-cellulose or Kieselguhr G gives a single peak with behavior identical to that of dolichol phosphate mannose. Hydrolysis of the chloroform fraction released free galactose. It seems, therefore, that galactose, like glucose, mannose, and N-acetylglucosamine, can be transferred from its respective sugar nucleotide to glycoprotein via dolichol intermediates.


Electrical capacity of black lipid films and of lipid bilayers made from monolayers. Planar bilayer membranes were formed from monolayers of a series of mono-unsaturated monoglycerides and lecithins. The hydrocarbon thickness of these membranes, as calculated from the electrical capacity, increases with the length of the fatty acid chain. The specific capacity of monoolein bilayers was found to be 0.745 muF/cm-2 which is nearly twice that of a monoolein black film made in the presence of decane, but is close to that obtained after freezing out the solvent from the black film. The hydrocarbon thickness of the bilayer, as calculated with a dielectric constant of 2.1, is considerably less than twice the length of the extended hydrocarbon chain of the monoglyceride. The specific capacity (Cm) of bilayers made from monoolein monolayers showed a negligible voltage dependence, whereas the Cm increased significantly at a voltage of 150 mV in the case of Mueller-Rudin-type monoolein films with n-decane as a solvent.


Kinetics of a Ca-2+-triggered membrane aggregation reaction of phospholipid membranes. Ca-2+ and other divalent cations can trigger aggregation of phospholipid vesicles containing phosphatidic acid or phosphatidylserine. The reaction, which can be detected by an increase in light scattering, has a critical dependence on the Ca-2+ concentration, with a threshold near 4 mM Ca-2+. This is the concentration for half-saturation of the polar head groups and for full neutralization of the membrane surface charge. The aggregation proceeds as a "polymerization" reaction, eventually forming such large aggregates that the vesicles precipitate. The stopped-flow rapid mixing technique was used to study the vesicle dimerization reaction which is the first step in the overall aggregation process. Vesicle dimerization resulted in a doubling of light scattering and had a vesicle concentration-dependent time constant (t1/2) which varied between 0.4 and 2.0s under the conditions of the study. Analysis of the dependence of the reaction amplitude and l/t 1/2 on the concentrations of vesicles and Ca-2+ showed that the Ca-2+ binding is fast, and that the dimerization proceeds by a mechanism in which the vesicles first collide to form an encounter complex followed by a slower conversion of the encounter complex to a stable complex. For phosphatidic acid vesicles, about 200-700 collisions are necessary to achieve a stable dimer. The rate-limiting step in the overall reaction is thus the transformation of the encounter complex into a stable complex, requiring 0.5 and 1.0 ms. The above-mentioned results are relatively insensitive insensitive to the type of divalent cation or to the choice of negatively charged lipid (phosphatidic acid or phosphatidylserine). Evidence is given that the stable complex is effected by Ca-2+-mediated salt bridges between the two membranes and that the rate constant of the transformation step derives from the statistics of the distribution and the rate of redistribution of Ca-2+-occupied polar head groups on the membrane surfaces. The relevance of these results to the problem of Ca-2+-induced fusion of biological membranes is discussed.


Solubilization of brush borders of hamster small intestine and fractionation of some of the components. About 90% of the protein of hamster intestinal brush borders was solubilised in 0.25% (w/v) sodium dodecyl sulphate without total loss of biological activity. Detergent-polyacrylamide gel electrophoresis of the solubilised proteins separated 10-15 bands and partially resolved maltase, lactase, sucrase-maltase, trehalase and alkaline phosphatase activities. The disaccharidases, which were associated with the higher molecular weight proteins, were preferentially solubilised with 0.1%. (w/v) Triton X-100, butanol or papain, whereas Tris and NaI extracted only the lower molecular weight proteins, possible derived from the core filaments. Electrophoresis of brush border proteins metabolically labelled with [14-C] glucosamine suggested that many of the membrane-bound enzymes are glycoproteins. However, chromatography of a papain digest on Sephadex G-200 showed that the sucrase-maltase complex can be separated nearly free of carbohydrate without total loss of activity. The importance of characterizing membrane proteins solubilised by a number of techniques is discussed.


Release and uptake of haemoglobin and ions in red blood cells induced by dielectric breakdown. External electric field strengths of the order of 10-3 minus10-4 v-cm-minus1 induce potassium release and concomitant sodium uptake in human and bovine red blood cells, as demonstrated in an electrolytic discharge chamber. The reversible increase of the membrane permeability once the critical membrane potential is reached is caused by dielectric breakdown of the membrane. The values of the critical membrane potential differences calculated from the potassium release and sodium uptake curves are close to those which were calculated from dielectric breakdown measurements in a hydrodynamic focussing Coulter Counter using the Laplace equation. With bovine red blood cells, the potassium release and the concomitant sodium uptake is coupled with haemoglobin release from the cells, while with human red blood cells much higher external electric field strengths are required for haemoglobin release. The external electric field strength required for solute release and uptake in bovine and human red blood cells depends on the pulse length, particularly below a value of about 10 mus, when a strong increase in the field strength occurs with decreasing pulse lengths. At 50-100 mus pulse lengths an asymptotic value of the critical electrical field strength of 2.6 kV-cm-minus1 for the modal volume of human red blood cells and 2.8 kV-cm-minus1 for the modal volume of bovine red blood cells is reached, corresponding to a critical membrane potential difference of about 1.1 V for both species. This value is close to that measured directly for dielectric breakdown of the membranes of Valonia utricularis (0.85 V, 20 degrees C). The increase in electric field strength with decreasing pulse length can be explained by the capacitance of the membrane, which becomes the rate limiting step for the temporal build-up of the electric potential across the membrane. The time constant of this process was determined to be approx. 10 mus. The critical membrane potential difference for breakdown is therefore pulse-length independent. The breakdown of the membrane can be interpreted by an electromechanical collapse of the membrane material. Numerical considerations of the dynamics of this membrane collapse predict that the breakdown time is a very rapid process.


Influence on fetal carbohydrate and fat metabolism and on acid-base balance of glucose administration to the mother during labour. Parturients during normal labour were given glucose. The maternal-fetal difference of glucose increased with increasing maternal glucose level. Glucose load caused a rapid early response of maternal insulin release. A parallel rise in plasma lactate and pyruvate occurred in both fetus and mother. The basal maternal hydroxybutyrate and glycerol concentrations decreased significantly during glucose load. The study demonstrated that at term, components of lipid metabolism in fetal and maternal plasma-in contrast to glucose -vary independently. No major disturbances of the fetal acid-base balance were found.


Changes in cellular growth in newborn rats and rabbits exposed to photoirradiation. Effects of photoirradiation from lamps currently used in phototherapy on growth in newborn rats and rabbits were studied. The newborn animals subjected to 96 h of phototherapy were found to be smaller than comparable nonirradiated animals. Mean organ weight of the brain, liver, heart and kidney was lower in the photoirradiated groups than in the nonirradiated group. DNA, protein content, protein/DNA ratio, cell number and cell size were also significantly reduced (p= less than 0.01) in the photoirradiated groups when compared to the nonirradiated group. The degree of growth retardation was more pronounced in rats subjected to continuous photoirradiation than intermittent photoirradiation (12 h on and 12 h off).


Some physical and biochemical parameters during normal labour. A statistical study of parameters of uterine contraction, fetal heart rate, acid-base balance and glycaemia has been made in 30 patients during spontaneous and clinically normal labour for each 2 cm of cervical dilatation. The study of uterine contractility gives the mean values and 95% limits of parameters of uterine contraction as labour progresses. The fetal heart rate is stable during dilation, on the other hand, during the expulsive phase, alterations of fetal heart rate appear, modifications which give evidence of trial that expulsive phase is for the fetus. The study of fetal and maternal acid-base balance shows little change during cervical dilatation, changes towards acidosis during expulsive phase, as importance of feto-maternal relationships. These relationships meet again on the study of glycaemia.


Characterization and quantitation of the five major plasma protein fractions in seven-day-old piglets. Cellulose acetate electrophoresis was applied to resolve, characterize and quantitate the five major plasma protein fractions of 7-day-old pigs. Purified Cohn fractions were added to the piglets plasma and the individual fractions characterized by similarities in mobilities. All mobilities were expressed relative to albumin. Relative percentages and concentrations of the electrophoretically separated plasma proteins were also calculated. The respective mean values for the plasma concentration of albumin, alpha-, beta, gamma-globulin and fibrinogen obtained from 45 piglets were 1.98, 0.93, 0.27, 0.60 and 1.49 g/100 ml, respectively.


Maximum thermogenic response to cold in relation to the proportion of brown adipose tissue and skeletal muscle in the body and to other parameters in young lambs. No relationship was apparent between the maximum thermogenic response of lambs to cold (summit metabolism) and the dissectable brown adipose tissue content, or the chemically extractable lipid content of the whole animal or the weight of various skeletal muscles. Correlations of summit metabolism with other parameters also suggested that the level of glucose, FFA and glycerol in the circulation, and the glycogen stores in liver and muscle, did not limit summit metabolism. However, significant correlations of summit metabolism with cardiac output and arteriovenous differences in oxygen content of blood focused attention on the possible role of the cardiovascular system and on the metabolic capability of the thermogenic tissues in determining summit metabolism.


Quantity and calculated oxygen consumption during summit metabolism of brown adipose tissue in new-born lambs. Macroscopic dissection of new-born lambs of several breeds revealed that brown adipose tissue comprised approximately 1.5% of the body weight. The perirenal-abdominal and prescapular-cervical depots were by far the largest, and the overall distribution was largely consistent with that reported for other species, although there was no significant interscapular depot. The oxygen consumption of the brown adipose tissue in lambs was calculated to reach 70 ml/(g-h), which is consistent with published data for rabbit brown adipose tissue, in vivo, but 35 times higher than that for the same tissue in vitro. It was also calculated that a substantial portion, perhaps two thirds, of the lipid available for metabolism was stored outside the adipose tissue. The study also made it possible to examine the validity of methods of estimating blood flow through brown adipose tissue. Untenable venous blood oxygen saturations were calculated from results obtained using 86-Rb, but saturation calculated from results with the radio-active microsphere method were entirely plausible.


Experimental intrauterine growth retardation. The effects of experimental intrauterine growth retardation on subsequent fetal development, especially with respect to brain development, were studied in a new animal model. The rabbit was chosen since it has a perinatal pattern of brain development similar to that of the human. Experimental ischemia was induced during the last trimester by ligation of spiral arterioles and the differential effects on fetal development at term (30th gestational day) are reported. Specific brain regions were examined for wet weight, total cell number (DNA) and total protein content. Highly significant decreases in all these parameters were found in both the cortex and cerebellum following experimental intrauterine growth retardation; these two organs were differentially affected. The prospects and advantages of using this animal model for the study of the postnatal "catch-up growth" are discussed.


Estimation of red blood cell volume in premature infants with and without respiratory distress syndrome. Red blood cell volume was estimated indirectly from plasma volume and venous hematocrit measurements in 262 consecutively delivered premature infants of less than 37 weeks' gestation. Infants with respiratory distress syndrome averaged lower red cell volumes (P0.02) than those without. Fatal cases had the lowest volumes. There was a 10.3% mortality from RDS (respiratory distress syndrome) among the one third of infants with the smallest red cell volumes, and only a 2.3% mortality among the one third with the largest volumes. Red cell volume was shown to be a direct correlate of time of cord clamping and thereby of the amount of placental transfusion, both in infants with and without RDS. From this study it is probable that delayed cord clamping, by allowing placental transfusion, decreases the risk of death from RDS in premature infants. Delay in clamping the umbilical cord for 1-1.5 min is advised in premature births.


Studies on normal and precocious appearance of jejunal sucrase in suckling rats. Some of the cellular and molecular events involved in the normal and precocious appearance of sucrase in jejunum of infant rats have been studied. Actinomycin D has been shown to inhibit (by 79%) the rise in sucrase activity usually seen after administration of hydrocortisone to 9-day-old rats. The precocious appearance of sucrase has also been studied with respect to the cytological localization of enzyme activity in the intestinal mucosa. Tissue was sectioned in a cryostat (transverse to the villi) and sucrase was assayed in homogenates prepared from the sections. By 24 h after administration of hydrocortisone to 9-day-old animals, sucrase was detectable only at the bases of the villi. During the subsequent 72 h the enzyme activity increased and spread along the villi at a rate consistent with that of cell migration. These data have lead to the conclusion that the action of glucocorticoids on enterocytes can occur only when the cells are in their proliferative phase. An ontogenic study of the ability of hydrocortisone to elicit jejunal sucrase showed that the tissue becomes increasingly responsive to the hormone with increasing age through the first and second postnatal weeks. Various hypotheses to explain this increase have been examined.


Quantitative evaluation of the maternal-fetal transfer of free fatty acids in the rat. On the 21st day of pregnancy the amount of fatty acids transferred from the mother to the fetuses was determined using the tracer technique and a mathematical model. The present study showed that 0.19 mu-mol fatty acids/min pass into the fetuses from the maternal circulation. The amount of fatty acids required for the growth and development of the rat fetuses amounts to 0.25 mu-mol fatty acids/min. From these data one can conclude that the maternal circulation is an even more important source of fetal fatty acids than the fatty acid synthesis in fetal tissue.


Identification of alkaloids; the condensation products of biogenic amines with formaldehyde, enzymatically formed from 5-methyltetrahydrofolic acid. The use of thin-layer chromatography has demonstrated that incubations of indoleamines with 5-methyl[14-C]tetrahydrofolic acid and an enzyme previously described as an N-methyltransferase, do not yield Nw, N1, or O-methylated products. Further elucidation by thin-layer chromatography, gas chromatography, mass spectrometry and selected ion monitoring enabled us to identify the reaction products as tetrahydroisoquinolines and tetrahydro-beta-carbolines in mixtures incubated respectively with catecholamines and indoleamines in the presence of 5-methyl[14-C]tetrahydrofolic acid and enzyme. The alkaloids have been shown to originate from a spontaneous condensation of the corresponding amines with formaldehyde, this latter being formed in the first stage of the reaction by enzymatic conversion from 5-methyltetrahydrofolic acid.


A reproducible gas chromatographic mass spectrometric assay for low levels of methylphenidate and ritalinic acid in blood and urine. A rapid, sensitive method of analysis for methylphenidate and ritalinic acid in blood and urine has been developed using gas chromatography mass spectrometry and selected ion monitoring for separation and detection. The methylphenidate is isolated by solvent extraction into chloroform and the ritalinic acid is isolated by salting out into isopropyl alcohol, followed by methylation and subsequent solvent extraction. The method has been applied to the study of methylphenidate metabolism and excretion in adults and hyperactive children undergoing treatment with methylphenidate.


The rapid identification of a new metabolite of warfarin via a chemical ionization mass spectrometry ion doublet technique. An ion doublet chemical ionization mass spectrometry technique was utilized for the rapid detection and elucidation of the structure of a new hydroxylated metabolite of the oral anticoagulant warfarin. This technique involves the use of a 50:50 mixture of stable isotope labeled and unlabeled drug. With this procedure ions found in the mass spectrum which are associated with the administered drug can be identified unambiguously. The unknown metabolite from rat liver microsomal preparations was identified as benzylic hydroxywarfarin by reincubating the microsomes with warfarin specifically labeled in the benzylic position and observing the subsequent loss of label in the product. The ion doublet technique was also employed in a single human study, and benzylic hydroxywarfarin was detected and identified.


The application of quadrupole mass filters in field desorption mass spectrometry. The advantages and limitations which quadrupole mass filters afford to the field desorption technique with respect to use for routine work are discussed and experimentally confirmed by the analyses of some drugs using a field desorption quadrupole mass spectrometer. The possibility of fast identification of drug intoxication is demonstrated by the analysis of the chloroform extract of urine in a case of overdose of hypnotics.


The mass spectra of permethylated oligosaccharides. The electron impact mass spectra of permethyl ethers of twenty-five highly purified oligosaccharides, containing first, aldohexose units only and second, at least one fructose unite, have been determined. It is concluded that spectra of these derivatives can yield considerable structural information, especially in relation to the detection of fructose units, the pyranose/furanose ratio and the position of the glycosidic linkage, and are to be preferred from this point of view to the mass spectra of trimethylsilyl ethers.


Isolation and mass spectral identification of blood metabolites of cyclophosphamide: evidence for phosphoramide mustard as the biologically active metabolite. Thin-layer chromatography and mass spectrometry were used to isolate and identify cyclophosphamide metabolites present in blood of mice. Blood was removed 5, 15, 30 and 45 minutes after intraperitoneal administration and extracted with chloroform followed by methanol. Thin-layer chromatography of the two extracts and the residual solid with or without prior methylation, collection of resulting alkylating components, determination of radioactivity and mass spectral analysis, served to identify cyclophosphamide, 4-ketocyclophosphamide, alcophosphamide, N-dechloroethylcyclophosphamide, carboxyphosphamide, phosphoramide mustard and nor-HN2. The absence of detectable levels of 4-hydroxycyclophosphamide or aldophosphamide in the blood of cyclophosphamide-treated mice suggests that cyclophosphamide is converted rapidly in the liver to carboxyphosphamide, 4-ketocyclophosphamide, phosphoramide mustard and nor-HN2. Direct administration of synthetic 4-hydroxycyclophosphamide to mice and extraction of blood with chloroform demonstrated the recovery of this metabolite in vivo. Analysis of extracts of blood from mice treated with phosphoramide mustard indicated the presence of nor-HN2, 3-(2-chloroethyl)-1,3-oxazolidin-2-one and unchanged drug. Consideration of blood levels, cytotoxicity and alkylating activity of metabolites identified, in or inferred from, this study, implicates phosphoramide mustard as a leading condidate for the biologically active form of cyclophosphamide.


Species differences in the metabolism of alpha-1-trans-4-dimethylaminotetrahydro-3-furyl-cyclohexanephenylglycolate, an experimental anticholinergic agent. Metabolism studies in the rat, dog and cat have demonstrated a definite species difference in biotransformation and elimination of alpha-1-trans-4-dimethylaminotetrahydro-3-furylcyclohexanephenylglycolate (Lilly 82537), an experimental anticholinergic agent. Separation and identification of urinary and biliary metabolites by gas chromatographic mass spectrometric analysis has shown three mechanisms to be involved in the metabolism of Lilly 82537 in these species; N-demethylation, aliphatic hydroxylation ahd ester hydrolysis. A major portion of the drug administered was eliminated unaltered in the cat and dog, while only trace quantities of parent drug were observed in the urine and bile of rats. These metabolic differences may be responsible for observed species differences in the pharmacologic activity of Lilly 82537.


Plasma amino acid analysis by isotope ratio gas chromatography mass spectrometry computer techniques. A routine analysis for micro samples of plasma amino acids by a gas chromatography mass spectrometry computer system has been developed. Isotope ratio determination was used as the quantitating technique via multiple internal standards. The speed of the analysis is increased by omitting the ion exchange purification step and its flexibility is maximized by using repetitive scanning rather than selective ion monitoring. This procedure yields excellent precision and accuracy, as demonstrated by the analysis of a known amino acid mixture and of neonatal plasma.


Gamma heavy chain disease: rapid, sustained response to cyclophosphamide and prednisone. A patient, CAL, with gamma heavy chain disease is presented who has had a complete remission lasting over 2 yr with combination chemotherapy consisting of pulsatile cyclophosphamide and prednisone. The patient exhibited many features of an atuoimmune process including a vasculitis, low serum complement levels, a positive antiglobulin (Coombs) test, Raynaud's phenomenon, and keratoconjunctivitis sicca. The CAL paraprotein was found to have several previously undescribed characteristics. It reacted with antisera to Fd, Fab, and Fab', suggesting that most of the Fd portion of the molecule was intace. CAL protein consists of two polypeptide chains of molecular weight 49,000 covalently linked to form a dimer of 95,000 molecular weight. The covalent linkage suggests that the hinge region of this gamma heavy chain is intact.


Ethnic variation in red cell glutathione peroxidase activity. Glutathione peroxidase activity was measured in blood and cultured fibroblasts from healthy persons of several different population groups. Individuals of Jewish ancestry and others of Mediterranean origin were found to manifest a decrease of red cell but not of leukocyte or fibroblast enzyme activity. Oriental populations differed in that the scatter in red cell enzyme activity was significantly lower than in Occidental populations. The erythrocyte enzyme of individuals with low activity was found to be less stable to heating than was the enzyme from persons with high activity. As a possible explanation for these data, a provisional genetic model is presented: a low GSH Px allele with a frequency of 0.556 in the Jewish population and of only 0.181 in the United States-Northern European population. Our results suggest that an association between GSH Px deficiency and hemolytic anemia need not represent a cause-and-effect relationship.


Active transport of GSSG from reconstituted erythrocyte ghosts. Human erythrocyte ghosts were loaded with 35S-labeled GSSG and with a sucrose marker, and the transport of GSSG to the suspending medium was studied. GSSG transport from ghosts occurred only when ATP was also present in the ghosts, proceeded against a concentration gradient, and was inhibited by fluoride. The rate of transport was dependent upon the intracellular concentration of GSSG. The relationship between GSSG concentration and rate of transport was sigmoidal. Half-maximal transport was observed at a GSSG concentration of approximately 9.6mM. The maximal velocity was estimated to be in the range of 0.27 umole GSSG per ml of ghosts per hr. These data suggest that the rate of GSSG transport a physiologic concentrations of GSSG is not sufficiently rapid to account for the turnover of glutathione by red cells. It seems more likely that the GSSG transport system serves an emergency function of erythrocytes.


Content and thrombin-induced release of acid hydrolases in gel-filtered platelets from patients with storage pool disease. The levels of four acid hydrolases, beta-N-acetyl glucosaminidase, beta-glucuronidase, beta-galactosidase, and acid phosphatase, and the extent of their release (release II) by thrombin was determined in platelets from nine normal subjects, nine patients with storage pool disease, and in normal platelets which had been exposed to aspirin. The levels of all four hydrolases were normal in patients with SPD. However, release of three of these hydrolases (acid phosphatase was an exception) by low concentrations of thrombin (0.015 and 0.04 U/ml) was decreased in the patients as a group, although considerable variation in the extent of release of each enzyme was noted. In contrast, aspirin failed to inhibit release II in normal platelets (except for a slight impairment in the release of beta-N-acetyl glucosaminidase), although release I (serotonin, ATP and ADP) was inhibited. All release defects could be overcome by using higher concentrations of thrombin (0.2 U/ml). The normal levels of acid hydrolases in the platelets of patients with SPD (who are deficient in the platelet dense granules) suggest that these enzymes are not normally stored in the dense granules, but rather in alpha-granules. The findings also support the conclusions of previous studies that the release reaction is impaired in SPD. This release defect appears to be different from that seen in normal platelets after exposure to aspirin.


Metal ion contents of gel-filtered platelets from patients with storage pool disease. Platelets from nine patients with storage pool disease (SPD) and from ten control subjects were isolated by gel filtration into a suspension medium permitting the direct determination of platelet Mg-2+, Ca-2+, and K+ levels. The total intracellular levels of ATP and ADP, as well as the incorporation patterns of 14-C-adenine into the metabolic nucleotide pool, were also determined in these platelet suspensions. The gel-filtered platelets (GFP) from SPD patients exhibited slightly lowered levels of ATP and substantially reduced amounts of ADP, in agreement with previous studies using PRP suspensions. Diminished aggregation responses to ADP, epinephrine, and to collagen in particular, similar to those observed previously in PRP, were obtained in GFP from SPD patients. However, GFP from the patients exhibited more variable aggregation responses to addition of ADP and epinephrine than did GFP from the control subjects. Increases in the extent of radioactive hypoxanthine formation, observed previously in normal platelets as a result of isolation into the suspension medium used in these studies, were significantly reduced in the GFP from SPD patients. The levels of platelet Mg-2+ and K+ determined in GFP from the patients were not significantly different from the levels of these ions in GFP from control subjects. However, substantial reductions in platelet Ca-2+ were found in the SPD platelets. A strong correlation was obtained between this reduction in platelet Ca-2+ and the reduction in ADP in these platelets. No such correlation was apparent between the ATP and Ca-2+ deficiencies. These results suggest that a major portion of platelet Ca-2+ may be located in the dense granules and support previous hypotheses that granular ADP and/or Ca-2+ may play a role in the release reaction. The finding of normal levels of platelet Mg-2+ and K+ in SPD platelets, however, suggests that these latter ions are not located in the dense granules.


Modulation of murine granulocyte proliferation in diffusion chamber cultures. Normal mouse marrow cells were cultured in Millipore diffusion chambers for long periods of time and at a variety of cell concentrations. All cultures showed a pattern of granulocyte proliferation characterized by logarithmic growth followed by prolonged stabilization of cell number starting a 7 days thereafter. The height of this "plateau" varied in relationship to the level of cell input and characteristically was far lower than the maximum cell density that can be maintained in this culture system. Additional studies showed that the plateau represented a steady state of granulocyte turnover and was not due to alterations in the diffusion chambers or the host mice. Regulatory mechanisms intrinsic to the cultured cell population appeared to play a primary role in maintaining this stable plateau. Modulation of granulocyte proliferation was partly due to increasing cell density; particularly with high input concentrations. In addition, differential cell counts suggested that critical changes in the relationship between immature and mature granulocytes partially accounted for this apparent autoregulation of cell growth. The plateau period in diffusion chamber cultures in many ways resembles granulocyte proliferation in normal mouse bone marrow and is a useful model for the study of regulatory functions in granulocytopoiesis.


The effect of azathioprine (Imuran) on the kinetics of monocytes and macrophages during the normal steady state and an acute inflammatory reaction. The effect of azathioprine on the kinetics of peripheral blood monocytes and peritoneal macrophages was studied in normal mice and in mice in which an inflammatory reaction was provoked. Two dosage levels were used: a high dose of 200mg/kg which is the maximum tolerated daily dose in mice, and low dose of 3 mg/kg which is about equivalent to a nontoxic, immunosuppressive, anti-inflammatory dose in man. The number of peripheral blood monocytes decreases gradually during azathioprine treatment of normal mice, the extent and duration being dependent on the dose and duration of administered over a period of 9 days  gives an almost complete reduction, and a low dose (3 mg/kg) given for the same period results in a reduction of about 50%. This effect seems to be reversible, because when treatment is stopped the number of monocytes starts to increase 24-48 hr later. The number of peritoneal macrophages is only affected when a high dose (200 mg/kg) is given over a long period; a low dose has virtually no effect. In mice in which an inflammatory reaction was prevoked in the peritoneal cavity, the normally occurring increase in the numbers of both peripheral blood monocytes and peritoneal macrophages was suppressed, the extent being dependent on the dose of azathioprine administered. Labeling studies with 3H-thymidine indicated that the reduction of peripheral blood monocytes and peritoneal macrophages in the inflammatory exudate is due to a diminished monocyte production.


The relative spatial distributions of CFUs and CFUc in the normal mouse femur. Femoral bone marrow was divided longitudinally into two groups of cells of varying size. By assaying CFU and CFU in the two zones of the marrow, their distributions across the diameter of the femur was determined. It is shown that the concentration of CFU increases from the femoral axis (15 CFU/105 bone marrow cells) to the bone surface (44 CFU/105 cells), obeying approximately a square-law relationship. The CFU concentration, on the other hand, increases from the femoral axis (32CFU/105 cells) to a peak value (260 CFU/105 cells) at about 330 um from the axis and thence falls off against to the bone surface (77 CFU/105 cells). Selective kinning cells in DNA synthesis using the tritiated thymidine suicide technique, in vivo, showed that CFU, near the bone surface are proliferating at a faster rate than those more distant from bone, but that CFU have a fast proliferation rate irrespective of their position in the distribution. Thus, bone marrow cell populations are shown to conform to a well-defined spatial organization corresponding to the chronologic relationships between marrow cells.


The factors controlling stem cell recirculation. i. Migration of hemopoietic stem cells in adrenalectomized mice. The influence of bilateral adrenalectomy on hemopoietic stem cell (CFU) migration in mice has been studied. Formation of endogenous spleen colonies in lethally irradiated, leg-shielded mice was sharply increased by prior adrenalectomy, and this increase was not dependent on the volume of shielded bone marrow. Adrenalectomy was shown to increase endogenous spleen colony formation in sublethally irradiated mice as well. However, it had no affect on formation of spleen colonies in lethally irradiated mice injected with syngeneic bone marrow. The CFU content of murine bone marrow decreased acutely after removal of the adrenals, and this decrease was accompanied by a concomitant increase in the peripheral blood and splenic CFU. Thus, adrenalectomy appeared to have no affect on the splenic plating efficiency or proliferative rate of hemopoietic stem cells, but it did result in increased migration of stem cells from the bone marrow to the blood, and thence to the spleen. It is concluded that the adrenal steroids may be of physiologic importance in the regulation of ehmopoietic stem cell migration.


In vitro production of erythropoietin by mouse fetal liver. Mouse fetal liver tissue has been cultured and shown to produce and release into the culture medium an erythropoietically active substance for up to 30 days of culture. Since this substance can be completely neutralized by an antiserum to erythropoietin and shows a dose--response relationship in the plethoric mouse assay, it is suggested that the culture medium contains erythropoietin, a hormone important in the regulation of erythropoiesis. Using this procedure, we have obtained the equivalent of about 20.7 unites of erythropoietin from five T-flasks (75 sq cm) over the 30-day culture period.


A feeding study with the herbicide, Kerb (N-(1, 1 dimethylpropynyl)-3,5-dichlorobenzamide, in the dairy cow. The herbicide, Kerb ((N-(1,1 dimethylpropynyl)-3,5-dichlorobezamide) was fed to a lactating cow at a concentration of 5 ppm in the ration for four days. Excretion of residues of equivalent herbicide in milk, urine and feces were found to be, respectively, 0.19, 44.38 and 4.46% of the total dose.


The non-teratogenicity of 2,4,5-trichlorophenoxyacetic acid in the rhesus monkey (Macaca mulatta). The herbicide 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) containing 0.05 ppm of tetrachlorodibenzo-p-dioxin, was administered to pregnant rhesus monkeys daily from Day 22 through Day 38 of gestation. At the dose levels administered, 0.05 mg/kg, 1 mg/kg, and 10 mg/kg, no evidence of toxicity was seen in the mother and no evidence of teratogenicity was seen in any of the offspring. Observations of the infants for 1 year following birth indicated that there was no toxicity due to the 2,4,5-T.


Avoidance of fenitrothion by goldfish (Carassius auratus). Goldfish (Carassius auratus) avoided water containing the pesticide fenitrothion. The response was graded over the tested concentration range of 5 orders of magnitude, with a threshold around 10 mug/1, equivalent to 3.5 times 10-minus 8 M.


Diurnal variation in logical reasoning.

Diurnal variation in logical reasoning. Subjects performed two tests of logical reasoning at each of six different times of day. In terms of speed, preformance on both tests was found to improve markedly from 08.00 to 14.00 and then to fall off fairly rapidly. Accuracy was found to decrease fairly linearly over the day. The results are interpreted as indicating that the different functions relating performance efficiency to time of day found by previous workers are due to differences in task demands rather than to individual differences. It is suggested that the larger the short-term memory component of a task the earlier in the day performance peaks.


Temporal numerosity discrimination: intermodal comparisons revisited. Temporal numerosity discrimination was investigated for visual, auditory and tactile senses. Trains of two to nine signals (flashes, clicks, taps) were presented at rates of from 3 per sec. to 8 per se. The subjects were instructed specifically to report only the number of signals counted. Significant modality differences were obtained. Auditory counts were almost perfectly accurate inder all conditions. Visual judgement of number, which were consistently the least accurate, were underestimated. The error increased appreciably as the rate increased from 3 per sec. to 6 per sec. but decreased with rates of 7 per sec. and 8 per sec. Tactile reports also underestimated the actual number of signals, the underestimation increasing linearly as a function of rate.


Extraversion, neuroticism, and verbal reasoning ability as determinants of paired-associates learning. Predictions based on theories of verbal learning proposed by Spence and Eysenck were compared by using a non-competitive list of paired-associates formed from seven synonym pairs, and a competitive list formed by pairing each of the seven S words with a R word with which it was not synonymous. Each list was presented in a 2x2x2 design to groups of primary school children differing in extraversion, neuroticism, and verbal reasoning ability. Performance on both lists was related to ability level and extraversion, and these relationships did not interact with the stage of learning. It is concluded in support of Eysenck's theory that differences in extraversion are of importance in determining performance on such tasks.


Handedness and controlled movement.

Handedness and controlled movement. Subjects classified according to degree of hand perference were tested with both hands on two tasks of controlled movement. Strongly lateralized subjects (both left- and right-handers) showed greater skill with their better hand than ambilaterals on a visually controlled aiming test (faster speed and equal errors), but there was no marked differences between groups with the other hand. Between-hand differences were also greater in lateralized subjects. On a ballistic rhythmical tapping test, no marked differences in speed were found, but ambilaterals made slightly fewer errors with the better hand. It is argued (i) that for ballistic movements the hands are equipotential, and skill is a direct function of practice, (ii) that the essential dexterity difference between the preferred and non-preferred hands is in the sensory or feedback control of movements rather than in motor function per se, and (iii) ambilaterals, especially those with very mixed preferences, have virtually two non-preferred hands in continuously controlled movement tasks, and may therefore reply on ballistic movements more than do pronounced sinistrals and dextrals.


The effects of noise and incentives upon attention in short-term memory. Recent work concerned with task performance under conditions of high arousal has emphasized the changes that appear to occur in the allocation of attention to different components of the task. Hockey (1970 a, b), for example, has shown that loud noise, which may be considered to raise arousal level (Broadbent, 1971; Davies, 1968; Hockey, 1969), biases attention towards high-priority task components and away from low-prioposed that an increase in arousal level brings about a restriction of the range of cues trity ones. This result agrees with a suggestion made by Easterbrook (1959), who proposed that an increase in arousal level brings about a restriction of the range of cues that a subject utilizes in performing a task. Easterbrook arg ued that when arousal level is low, selectivity in the utilization of cues is also low, and irrelevant cues may be accepted uncritically. As arousal level increases, so does selectivity, and attention is diverted away from irrelevant task components. Further increases in arousal diminish still further the range of usable cues, so that eventually some relevant cues are no longer utilized and task performance deteriorates.


Extraversion and variety-seeking in a monotonous task. It is hypothesized on the basis of Eysenck's theory of extraversion that extraverts should build more variety into their performance at a monotonous task than introverts. The performance of a group of extravets (n = 16) and a group of introverts (n = 16) on a simple repetitive task was compared. Comparisons were made on two measures of response variety: firstly, a simple measure of number of alternations among possible responses and, secondly, a measure of variety taken from information theory-the average entropy of the set of responses made. The hypothesis was confirmed on both measures. The results are interpreted as adding further support to Eysenck's work linking differences in extraversion to differences in arousal.


Effect of length, density, and angel between arms of Gestalt grouping. In three experiments, subjects viewed two lines (arms) of dots in which one dot was shared by both arms, then judged with which arm the shared dot appeared to group. Length of an arm, density of the dots in the arm, and angle between arms were manipulated. Increasing the density of an arm increased grouping with that arm regardless of the angle between arms. Increasing the length of an arm however, increased grouping when arms met at 30 degree but not at 180 degree; intermediate angles produced intermediate effects. Advantage of the present method's simplification of the stimulus display are discussed.


Evaluation of acetabular anteversion following total hip arthroplasty: necessity of proper centring. To assess accurately the degree of anteversion of the acetabular component following total hip arthroplasty, the radiologist must obtain a view with the central ray directed over the hip, and not rely solely on frontal views of the pelvis.


Optimum photon energies for the measurement of bone mineral and fat fractions. Relative error functions have been calculated for the various single and double photon energy techniques used for the measurement of linear bone mineral and fat mass in vivo. By considering only those errors arising from statistical fluctuations in photon counting useful information for guidance in the most efficient operation of the method is obtained. The results indicate that statistically the single energy method is always significantly better than the double energy method for measurement of both bone and fat fractions in soft tissue at total thicknesses up to 15 g/cm-2. In those circumstances where it may be necessary to use the double-photon energy technique there is an optimum sample thickness of 5 g/cm-2 for minimum error. Values of photon energy which permit measurement with the maximum precision in the minimum count time are deduced for a wide range of practical conditions and are presented along with a table of potentially suitable radioisotopes.


Kidney position and the measurement of relative uptake of 131-I Hippuran in renography. The distribution of kidney position in the sitting posture has been determined in a series of patients presenting for renography, using radiographic and ultrasonic techniques. Both the craniocaudal distribution of kidney centre positions and the distribution of the differences in depth below the posterior skin surface of the two kidney centres have been found to have a significant standard deviation. The effect of these distributions on the measurement of relative effective renal plasma flow by 131-I Hippuran probe renography has been calculated for the situation in which no kidney localizing techniques are used. The resulting error distribution has an SD of 21.7 per cent in the case of equally divided function.


Kidney depth measurements using a double isotope technique. Differences in kidney depth, particularly between the two kidneys of an individual patient, may lead to distortions of the renogram owing to attenuation and geometrical factors. A method of assessing the magnitude of these variations was developed. A double isotope technique was used, employing 125-I and 131-I Hippuran, the kidney depth being a function of the ratio of the count-rates from the two isotopes. It was necessary to apply a correction for extrarenal activity, based on a third detector and doubly labelled human serum albumin. The average kidney depth observed was 7.3 cm; in only two cases out of 13 did the difference in depth of the two kidneys exceed 1 cm. It is concluded that when 131-I Hippuran is used the consequent distortion of the renogram is acceptable. With 125-I the distortion may be excessive, even though the contribution of extrarenal activity is then reduced. There was frequently an apparent increase in the depth of activity during the renogram attributable to intrarenal translocation of the tracer.


A simple after-loading technique for the treatment of cancer of the cervix. A simple manual after-loading system for the treatment of carcinoma of the cervix has been developed. Radiochemical Centre J-type caesium sources are used made up in PVC tubes which can be inserted into PVC uterine tubes or rubber ovoids after these have been packed in position in the patient. Radiation exposure to theatre staff has been reduced by a factor of about four.


Protection problems in radionuclide therapy: the patient as a gamma-radiation source. Estimates have been made of the rate of uptake, metabolism and excretion of radioiodine given in treatments of patients with hyperthyroidism or thyroid carcinoma. Average values for the exposures to be expected at a given distance from such patients, and the variability of such exposures, are derived from these data. The mean exposure of a patient in an adjacent bed, at 2.5 m bed spacing, following typical therapeutic doses of 131-I in the treatment of hyperthyroidism or thyroid carcinoma, is estimated to be about 0.02 or 0.08 R respectively. Variations in the metabolic parameters would increase these exposures to about 0.03 and 0.14 R, at the 90 percentile values. Exposures following treatments with 100 mCi of 198-Au, or of 300 mg days of -226Ra would be about 0.2 and 0.6 R.


The staging of renal parenchymal tumours. The relation between the anatomical features in the development of renal parenchymal tumours and the prognosis are analysed. It is suggested that the clinical and anatomical classification must be revised.


Conservative renal surgery for adenocarcinoma. The place of bench surgery. A brief review of reported cases of tumours in solitary kidneys and of bilateral simultaneously occurring tumours is reported. 1 case of bilateral simultaneously occurring tumour ana 3 cases of tumour occurring in solitary kidneys are reported. The treatment of these cases by simple partial nephrectomy under regional hypothermia is described. The palce of ex vivo "Bench Surgery" for this condition is discussed.


Ultrasound in the staging of bladder tumours. The ultrasonic features of 162 bladder tumours are described. Comparing clinical staging by the TNM system and the ultrasonic appearances, there is a high degree of accuracy in staging by ultrasound. The use of this painless non-invasive technique is assessed and should be used in staging bladder tumours only in conjunction with other established methods, and not in isolation.


A critical review of the management of bladder neoplasia using a modified form of Helmstein's pressure therapy. 30 patients with proven bladder malignant disease have been treated by Helmstein's hydrostatic pressure technique. Massive necrosis of tumour tissue has been shown to occur at cystoscopy, cytologically and on histological examination. Double contrast cystography can indicate reduction in tumour size within 2 weeks of treatment Haematuria is usually stopped with diminution of frequency and dysuria. This treatment is suitable for large bulky T1 tumours and advanced T4 growths where palliation is the only treatment possible but not for TI and T3 growths. Elderly and ill patients can tolerate this therapy easily and there were no serious side-effects in this series.


A study of the bladder blood flow during distension in rabbits. This study has shown that there is a linear relationship between bladder blood flow and bladder pressure. At a bladder pressure of 80 mm Hg (blood pressure in rabbits varying from 90/60-100/70 mm Hg) the blood flow in the bladder is minimal. It is suggested that bladder distension at 80 mm Hg in rabbits leads to hypoxia in the bladder wall as a result of the reduced blood flow. Prolonged bladder wall hypoxia occurring as a result of prolonged bladder distension may be responsible for selective necrosis of bladder tumours.


Is urography necessary for patients with acute retention of urine before prostatectomy? In 180 urograms performed on 203 patients admitted to hospital with acute or acute-on-chronic retention of urine 38 abnormalities were noted, most of them being related to upper tract obstruction. Of 4 diverticula detected only one needed treatment. Waiting for the urogram imposed an extra delay of more than 3 days between admission and operation and an equal prolongation of the whole hospital stay. There appears to be no justification for routine urography prior to prostatectomy in the patient admitted with urinary retention.


Identification of a prostate in female praomys (Mastomys) natalensis using 3-H steroids. The female of the species Praomys (Mastomys) Natalensis has a ventral prostate similar both in position and in histological appearance to the ventral lobe of the male prostate. The hormonal uptake of this female prostate has been investigated using (3-H) testosterone and (3-H) oestradiol. The results showed that the uptake of these steroid hormones by the prostate was identically to our findings in the male prostate. The potential value of a female prostate in prostatic research is discussed.


The diagnostic and prognostic significance of delayed hypersensitivity skin testing in patients with urological cancer. The responses to several skin test antigens of patients with bladder or prostatic cancer has been compared with responses of normal controls. All of the controls and all of the patients with prostatic cancer (irrespective of the stage of the tumour or the method of treatment) showed responses to dinitrochlorbenzene. 80% of all patients with bladder cancer responded to DNCB, but a highly significant number of patients with advanced disease showed no response. This test appears especially useful in predicting the prognosis in patients with bladder tumours and its routine use is recommended. Response to candida extract, streptokinase/streptodornase (SKSD) and purified protein derivative (PPD) were also studied. No conclusion could be drawn as to their value as a prognostic index.


The importance of environmental conditions, especially temperature, in the operating room and intensive care ward. Although most patients are essentially well enough to be able to resist or to adapt to unfavourable ambient conditions, this may not be so with an ill patient or one who is having or has had a serious operation. The climatic conditions necessary in the operating room to give an optimal environment are discussed. These are second in importance only to control of infectivity. Air-conditioning in operating suites should be obligatory; there is even official acceptance of this. Earlier recommendations that the operating room should be heated to up to 80 degree F (27-9 degree C) are obsolete. The temperature most favoured by surgeons is 18-5-21 degree C; some prefer a range of 21-22 degre C. The critical ambient temperature desirable is 21 degree C. For infants and children this may be increased up to 24 degree C. It is difficult or impossible to achieve climatic conditions in the operating room that are acceptable to all. The needs of the patient are of special importance and are largely neglected; he alone is unable to speak for himself. The disposition of air inlets in the operating room is fully discussed. Climatic conditions in the intensive care unit are of great importance and are discussed. The need for full air-conditioning is absolute although this is often ignored. The delivery of conditioned air within the intensive care unit is also fully presented, especially the need to avoid direct chilling of the patient. The advantages of horizontal laminar air flow are presented.


Some observations on peripheral venous pressure using a non-invasive technique: a preliminary report. Observations are presented which suggest that peripheral venous pressure can be measured indirectly by a non-invasive technique at the bedside, using a portable Doppler ultrasound flowmeter. The pressure at which the audio signals are heard over veins on release of the occluding cuff seems to be a measure of peripheral venous pressure. This is supported by showing a correlation between the method and conditions in which raised venous pressure in the lower limb are known to exist. The results of a few direct venous pressure measurements are reported which appear to give added support. It is suggested that this simple non-invasive technique may be of value in detecting certain cases of deep vein thrombosis of the lower extremities.


Report of a family with inherited medullary carcinoma of the thyroid and phaeochromocytoma. A family in which several members have medullary carcinoma and phaeochromocytoma is described. Four of the 5 patients in this family who had a phaeochromocytoma have died; in one of these the medullary carcinoma may have contributed to death but in general the thyroid cancers were slow growing. In our experience successful diagnosis and treatment of the phaeochromocytomas have presented the greatest challenge. The welfare of future generations with this syndrome would seem to depend upon regular clinical and biochemical surveillance of the individuals and expeditious diagnosis and treatment of their tumours, particularly the phaeochromocytomas.


Neoplastic change in duplications of the alimentary tract. Two cases of adenocarcinoma arising in sequestrated duplications of the bowel in adults are reported. The literature is reviewed and a tendency for duplications to present in early childhood is noted. Although relatively few of these anomalies persist into adult life 8 cases of neoplastic change have now been reported. The histological features of many of the duplications undergoing malignant degeneration suggest the presence of underlying epithelial instability in this condition. It is postulated that duplications of the large bowel have malignant potential.


Operative biopsy of the pancreas.

Operative biopsy of the pancreas. A review has been undertaken of the 47 patients who have had open pancreatic biopsy performed at the Royal Free Hospital between 1967 and 1972. It is concluded that not only is the procedure safe when using the technique described but also it is a valuable and accurate diagnostic procedure.


Bacteria in flower vase water: incidence and significance in general ward practice. Culture of flower vase water from wards in the David Lewis Northern Hospital, Liverpool, revealed large numbers of potentially pathogenic bacteria. The types of organisms isolated may reflect the particular ecology of this hospital as they differed in some ways from those reported from other centres. The incidence of wound infections during the period of study was low (5-2 per cent) despite the regular overgrowth of bacteria in flower vases, and there did not appear to be any definite correlation between the types of bacteria isolated from flower vase water and those responsible for wound infections. The addition of hydrogen peroxide to flower vases proved a very effective antiseptic and is recommended for general use as a precautionary measure.


Analgesic abuse in urological practice.

Analgesic abuse in urological practice. Thirty-three patients seen in a urological department had taken large doses of analgesic for prolonged periods of time. In 9 cases a diagnosis of pyramidal necrosis was established, while 4 other had pyelographic evidence of pyelonephritis, and analgesic abuse was probably an important aetiological factor in their renal condition. Analgesic nephropathy is easily overlooked unless patients are questioned routinely regarding their intake of analgesic. It is important to identify the group of patients without evidence of serious renal disease who are taking excessive quantities of analgesic and to urge them to abandon the practice.


Subphrenic abscess in children.

Subphrenic abscess in children. Nineteen consecutive cases of subphrenic abscess which were treated in the Royal Hospital for Sick Children, Glasgow, from 1962 to 1972 are analyzed. This complication of intra-abdominal suppuration of surgery still carries a grave prognosis. Four of the patients died (21 per cent); 2 deaths were related to the subphrenic abscess while the remaining 2 were not directly related to the abscess. The mean hospital stay of the survivors was 59 days (range 30-122 days). The changing patterns of aetiology and presentation which have recently been emphasized in general surgical practice are not reflected in this paediatric series.


The cause and treatment of postvagotomy diarrhoea. Six patients with watery postvagotomy diarrhoea and 4 patients with intractable diabetic diarrhoea were treated with cholestyramine. The diarrhoea responded completely to therapy, during which the stool content of water, sodium, postassium and magnesium fell. Two of the patients, while receiving cholestyramine, had a rise in faecal fat, but this was not accompanied by diarrhoea, the stools being well formed. Evidence is presented which suggests that the mechanism of diarrhoea is similar in both disorders and is due to division or neuropathy of the hepatic fibres of the vagus nerve. This results is distension of the gallbladder, contraction of which expels increased quantities of bile salts, which swamp the reabsorptive capacity of the small intestine and induce diarrhoea by direct action on the colon. If this theory is valid, cholecystectomy, by preventing large quantities of concentrated bile salts from suddenly entering the gut, may result in improvement of postvagotomy and diabetic diarrhoea.


The cholecystokinin test: an assessment. A cholecystokinin (CCK) test was performed on 13 female patients who were thought to be having attacks of gallbladder pain and in whom at least one cholecystogram had been normal. In 10 of these patients the CCK test was performed during the course of a repeat cholecystogram in order to assess the effect of CCK on gallbladder contraction. There was no constant relationship between a positive test and gallbladder contraction as measured radiographically. Cholecystectomy was undertaken in 9 patients and of these, 4 had been CCK positive, 4 had been CCK negative and 1 had reacted equivocally. None of the CCK positive patients had stones at operation, whereas 2 of the CCK negative patients had one or two small stones. In this small series cholecystectomy relieved both the CCK negative and CCK positive patients of pain with equal frequency. It is concluded that a negative CCK test by no means excludes the presence of symptomatic gallstones in patients with X-ray negative gallbladder pain.


Intra-abdominal symptoms arising from spinal osteophytes. A case of abdominal pain caused by irritation of a segment of jejunum and another due to irritation of the ureter are reported. In both cases the cause of the irritation was established to be osteophytic growth from the 4th lumbar vertebra. After its excision the symptoms disappeared in both cases. To the best of our knowledge, osteophytes have not been reported before to be the cause of intestinal and ureteric pain, and its is therefore urged that in cases of intractable pain these must be considered as a possible cause.


Tuberculous peripheral lymphadenitis in the Igbos of Nigeria. Peripheral lymphadenitis is a leading manifestation of tuberculosis. Among the Igbos, who constitute one of the largest ethnic groups in Nigeria, it presents most commonly in the neck, as in other parts of the world. An inguinal presentation, however, is also common. The nodes are often of considerable size. The maximal incidence occurs in the 10-29-year age group, males outnumbering females slightly. It is only the 40-59-year range that tuberculosis is less common than lymphoma or carcinoma of the peripheral lymph nodes.


Gynaecomastia.

Gynaecomastia. There are two different types of male breast enlargement-gynaecomastia and mammaplasia. A series of 53 consecutive patients with one of these conditions is presented. In the younger age group treatment has usually been conservative, surgery only being advocated when the diagnosis was in doubt or for cosmetic reasons. In the older age group the diagnostic must be confirmed histologically. The incidence of underlying conditions is much higher in this series than in any previously reported.


Cavernous haemangioma of the frontal bone: case report. A rare of haemangioma of the frontal bone is presented together with a review of the literature. Carotid angiography was found to be a useful diagnostic aid to differentiate if from other lesions of the frontal bone. The best treatment is to excise both tables containing the haemangioma together with a rim of healthy bone in one block.


Psychosocial effects of disaster: birth rate in Aberfan. An increased birth rate occurred in Aberfan during the five years after the disaster there in 1966. It was not confined to the bereaved parents.


Clinical trial of mebendazole, a broad-spectrum anthelminthic. Eighty-five children aged 5-14 years who were infested with worms were treated with mebendazole 100 mg twice daily for three days. The percentage cure rates were ascaris 100%, trichuris 94%, hookworm 82%, and hymenolepis 39%. The drug was well tolerated and with its broad activity should be very useful in treating those with multiple infestations.


Electrical requirements for ventricular defibrillation. Most deaths from ischaemic heart disease are sudden, occur outside hospital, and result from ventricular fibrillation. But defibrillators have only limited availability because of their size and weight. A miniature defibrillator has been developed. A singe low-energy shock succeeded in removing ventricular fibrillation in 73 out of 82 episodes, and a further shock was successful in seven more episodes. Primary ventricular fibrillation probably always responds to low-energy electrical shocks, which challenges the conventional view that correction of ventricular fibrillation requires high-energy direct-current shock. Thus even smaller and lighter defibrillators are possible. Furthermore low-energy shocks cause less myocardial damage.


Necropsy rates in the United Birmingham Hospitals. The necropsy rate in the United Birmingham Hospital has fallen from 74-4% in 1958 to 46-0% in 1972. In the Birmingham region as a whole the rate is 27-3%, approximately equal to the national rate. Most clinicians in the group who replied to a standard questionary considered that the necropsy still has an important part to play in their own practice and in undergraduate training, and they viewed the declining rate as a matter for concern. Some measure of disagreement was found between the ante-mortem and post-mortem diagnoses of patients in the two largest hospitals in the group. This suggests that the necropsy has a role to play in medical audit and that attempts to reverse the declining trend should be encouraged.


Fibrillation of head of radius as one cause of tennis elbow. Twenty-five patients with resistant tennis elbow were treated by exploration of the radio-humeral joint. Twenty cases showed abnormalities of the cartilage of the head of the radius. Division of the orbicular ligament and excision of the abnormal cartilage gave good results in 19 to 20 cases seen recently. We believe fibrillation of the head of the radius is an important cause of tennis elbow, and the arguments to support this theory are enumerated.


Fibrinolytic capacity of arm and leg veins after femoral shaft fracture and acute myocardial infarction. The local fibrinolytic activity generated in the leg and arm veins during venous occlusion (fibrinolytic capacity) and the systemic fibrinolytic activity were measured at intervals in 11 patients after fracture of the femoral shaft and in 11 patients after acute myocardial infarction. In both groups the fibrinolytic capacity of the leg veins and the systemic fibrinolytic activity were significantly reduced two days after the onset of tissue injury. The fibrinolytic capacity of the arm veins was not altered. These results provide a possible explanation for the predilection of venous thrombosis for the leg veins after accidental trauma and acute myocardial infarction.


Doppler ultrasound and fetal activity.

Doppler ultrasound and fetal activity. The possibility that Doppler ultrasound, as used in routine fetal monitoring by external cardiotocography, might stimulate fetal activity was investigated. A mean increase in fetal activity of over 90% was found, as judged by the fetal movement count.


Accumulation of storage iron in patients treated for iron-deficiency anaemia. The repletion of iron stores after treatment was studied in 38 patients with uncomplicated iron-deficiency anaemia. The serum ferritin concentration rose significantly when oral treatment was continued for two months after the attainment of a normal haemoglobin concentration. Patients treated with a total-dose infusion of iron dextran had thehighest final serum levels, which were significantly greater than in patients given Ferro-Gradumet. Oral ferrous sulphate was almost as effective as parenteral iron in producing iron stores.


Analgesic abuse, ureteric obstruction, and retroperitoneal fibrosis. We report two cases of unusual ureteric obstruction in patients with an excessive consumption of analgesics. In a retrospective survey of seven cases of non-malignant retroperitoneal fibrosis seen in the last 15 years it was found that four had taken excessive amounts of analgesics. A careful drug history should be taken in all patients with restroperitoneal fibrosis and ureteric obstruction.


The medical student as behavioural psychotherapist. A group of medical students were randomly selected from a larger group to carry out behaviour therapy under supervision. Ten patients with phobic disorders and two with obsessive-compulsive neurosis were treated, and the results, assessed by ratings of proved reliability, compared favourably with other studies in which psychiatrists or nurses acted as therapists. A questionnaire survey showed that students involved in therapy had a more favourable opinion about this kind of treatment than those receiving only theoretical instruction. The results suggested not only that medical students make good behavioural psychotherapists but also that the subject is a worthwhile training experience which warrants inclusion in the curriculum.


Behaviour of the dying patient.

Behaviour of the dying patient. One hundred and ten dying patients were studied during the 24 hours before death and 250 patients during the weeks before death: 60% were well orientated in time and space 24 hours before death and 26% at 15 minutes before death. A control group of patients with serious, but not fatal, illness were also studied. There was a contrast in attitude to death between the dying patients and the ill but not dying controls. The dying were resigned to their approaching death, experienced little or no fear, and did not wish to know about their illness, whereas the control patients wanted information about their condition and feared death, though few thought they would actually die. The relief of physical symptoms in the dying is important. There was often a brief improvement in condition, with reduced need for analgesic, shortly before death.


Maintenance of labour.

Maintenance of labour. In 160 women large but variable amounts of intravenous oxytocin were needed to induce labour within a reasonable time interval to 5 cm cervical dilatation. Thereafter 7 mU of oxytocin/min would maintain progress. Since large maintenance doses may cause obstetric problems it is recommended that a maintenance regimen should be used once labour has progressed to this stage.


Recovery from Goodpasture's syndrome after immunosuppressive treatment and plasmapheresis. A patient with Goodpasture's syndrome has recovered after treatment with immunosuppressive drugs (cyclophosphamide and prednisolone) and removal of circulating antibodies by plasma exchange. This was performed on seven occasions and seems to have hastened the decline in circulating antibody levels. Undertaken early in the course of the disease plasmapheresis could prove a useful addition to its therapy.


Microcephaly following baby battering and shaking. Three cases of microcephaly following the rough handling of babies are described. If detailed social and psychiatric information had not been available, these three children would have become part of the large proportion of individuals in subnormality hospitals who have unsatisfactory and incomplete diagnoses.


Reorganization of a nutrition unit in Papua New Guinea. Adequate nutrition is a medical priority. It has been estimated that more than half the children in the Chimbu District of Papua New Guinea are malnourished. A practical scheme combat poor nutrition there was based on emphasizing the value of breast-feeding and of locally grown foods. The daily menu given was the same, with three meals each day. The scheme's underlying principles can be adapted for any developing country or for migrant and other minority groups in a developed country.


Aspirin and coronary heart disease: findings of a prospective study. Over 1 000 000 men and women answered a confidential questionnaire and were traced for up to six years afterwards. Among other questions each person was asked how often he or she took aspirin-"never", "seldom," or "often." Coronary heart disease death rates were no lower among people who took aspirin often than among those who did not do so.


Disappearing diabetes.

Disappearing diabetes. For five years a nurse was treated for diabetes mellitus. She was found to have tampered with her blood and urine tests and later was believed to have fabricated her condition from the outset.


Cost-benefit analysis of long-term haemodialysis for chronic renal failure. A cost-benefit analysis of long-term maintenance haemodialysis indicates that there is a large gulf between the cost of the service and "economic" benefit. The difference may be considered to represent one estimate of the price society is prepared to pay to maintain life. Using "best estimates" from available data we found the implicit social value of maintaining a patient on haemodialysis to be approximately pounds 4720 per annum in hospital or pounds 2600 at home. The analysis would suggest that society must look carefully at alternative uses for health expenditure before extending indiscriminately to large sections of the population these treatment programmes or other similarly expensive.


Individual differences in selecting patients for regular haemodialysis. Eight clinicians in a renal dialysis unit were asked to classify the suitability of 100 cases (some real, some simulated) for regulat haemodialysis. Seven categories were used, ranging from "excellent prospect: accept without reservation" to "unequivocal rejection," based on 18 items of information previously agreed on as sufficient for the purpose. The ways in which they classified the cases different considerably; only six cases were placed in the same category by all eight clinicians, and this was the "unequivocal rejection" category. Analysis of the extent to which they made effective use of the items showed that between three and nine items were used to a sufficient extent to reach significance for the 100 cases.


Reduced secretory antibody response to live attenuated measles and poliovirus vaccines in malnourished children. Serum and nasopharyngeal IgA antibody levels were estimated in 20 malnourished children and 20 matched healthy controls after immunization with a single dose of live attenuated measles or poliovirus vaccine. Seroconversion and serum neutralizing antibody titres were comparable in the two groups. Secretory IgA antibody was detected significantly less often in undernourished children; the time of its first appearance was delayed-and its maximum level was significantly lower. Impaired secretory antibody response in malnourished children may contribute to slow inadequate recovery from viral and enterobacterial infections and predispose to lifethreatening complications.


Cardiovascular control in diabetes mellitus. Heart rate variability and the changes in heart rate and blood pressure which occur on standing were measured in 21 diabetics. These simple measures distinguished four groups of patients, with loss of parasympathetic activity being commoner than loss of sympathetic activity.


Vagal impairment of gastric secretion in diabetic autonomic neuropathy. Gastric acid output in response to insulin-induced hypoglycaemia and pentagastrin was measured in 18 diabetic patients with symptoms of autonomic neuropathy. Two patients had achlorhydria but the rest responded normally to pentagastrin. The acid output evoked by insulin-induced hypoglycaemia was low in 10 of the 16 patients who secreted acid in response to pentagastrin. These changes suggest that vagal impairment is common in diabetics with autonomic symptoms, which might explain the infrequency of duodenal ulcer in diabetics.


Localized avascular necrosis of lesser curve of stomach complicating highly selective vagotomy. The fourth case of localized avascular necrosis of the lesser curve of the stomach after highly selective vagotomy is reported. The pathogeneses was probably related to the relative poverty of the submucosal blood supply along the lesser curve. This complication may be prevented by peritonealizing the lesser curve before closing the abdominal wall.


Protein-losing enteropathy and malabsorption in acute measles enteritis. Gastrointestinal protein loss and xylose and lactose absorption were both abnormal in underweight children with acute measles and diarrhoea. The protein loss was equivalent to a mean absolute albumin loss of 1.68 plus or minus 0.21 g/day, while the mean one-hour blood xylose level was 0.93 plus or minus 0.38 mmol/l (14.0 plus or minus 5.7 mg/100 ml) in the acute stage and 1.71 plus or minus 0.43 mmol/l (25.6 plus or minus 6.5 mg/100 ml) after recovery (P less than 0.01). Lactose intolerance was found in four children out of 17 tested. Thus faecal protein loss and malabsorption may contribute significantly to the development of malnutrition after measles.


Interaction of phenytoin and primidone.

Interaction of phenytoin and primidone. The ratio of derived phenobarbitone to unmetabolized primidone in the serum was significantly higher in 50 epileptic patients on a combination of primidone and phenytoin than in 12 patients on primidone alone, though the dose and serum levels of primidone were similar in the two groups. Out of 253 patients attending a seizure clinic 47% were taking a combination of these two anticonvulsants. The effect of phenytoin on the metabolism of primidone may have clinical implications in view of the frequency of their combined use.


Cardiac tamponade and central venous catheters. An analysis of the reports on 16 patients who developed cardiac tamponade, complicating the use of central venous catheters, showed that 14 died. The two survivors were treated by removal of the catheter and needle aspiration of the pericardial fluid. Some patients complained of warning symptoms such as nausea, pain, and dyspnoea, and the combination of tachycardia, hypotension, and raised venous pressure was common. We suggest that awareness of the hazard, radiographic visualization of the catheter tip, and expeditious treatment would reduce the mortality.


Comparison of use of the Dalkon Shield in Dublin and Southampton. The results of fitting Dalkon Shield I.U.D.s in Southampton and Dublin were compared. At 12 months the continuation rates were 77.4% and 93.4% respectively. There were also differences between the two cities in the major complication rates associated with the use of the device. At 12 months these rates for Southampton and Dublin were: pregnancy 5.6% and 1.4%, expulsion 4.0% and 0.9%, and removal for pain and/or bleeding 12.1% and 3.0%, respectively. Possible reasons for the difference in performance may include the older average age of the users in Dublin, and the greater number and more varied experience of the medical staff responsible for fitting in Southampton. We recommend that population factors be taken into account when comparing data relating to fertility regulation.


Screening for hypothyroidism in elderly inpatients. Routine biochemical screening for hypothyroidism in 2000 geriatric inpatients proved valuable and practicable and yielded 46 cases (2.3%). A non-specific clinical picture was particularly common, with less than a third of the cases showing "typical" signs and symptoms. Psychiatric manifestations, especially depression, were important and frequent and responded well to thyroxine. There was a preponderance of female cases of hypothyroidism and a strong association with other autoimmune diseases, notably pernicious anaemia and rheumatoid arthritis.


Chlormethiazole in treatment of status epilepticus. Chlormethiazole (Heminevrin) was successful in controlling fits in seven out of nine episodes of intractable status epilepticus. It was administered as a constant intravenous injection at rates of up to 0.7g/h. No serious side effects were encountered, and the drug deserves wider recognition as a useful therapeutic agent in the management of status epilepticus.


Improvement of oral glucose tolerance in gestational diabetes by pyridoxine. Fourteen pregnant women were shown by the oral glucose tolerance test to have gestational diabetes. In 13 an increased urinary xanthurenic-acid excretion after an oral load of L-tryptophan indicated a relative pyridoxine deficiency. All patients were treated with vitamin B6 (pyridoxine) 100 mg/day for 14 days by mouth, after which the pyridoxine deficiency disappeared and the oral glucose tolerance improved considerably. Only two patients then had sufficiently impaired glucose tolerance to justify the diagnosis of gestational diabetes; Our results substantiated our hypothesis that increased xanthurenic-acid synthesis during pregnancy may cause gestational diabetes. Treatment with vitamin B6 makes the production of xanthurenic-acid normal by restoring tryptophan metabolism and improves the oral glucose tolerance in patients with gestational diabetes.


Defective innervation of heart in diabetic autonomic neuropathy. Heart rate responses to autonomic stimulation and inhibition were studied in 13 diabetic autonomic neuropathy. Parasympathetic function was impaired in all patients and sympathetic function in most. One patient's heart appeared to be totally denervated. The consequences of cardiac denervation include tachycardia, a fixed heart rate, and a possible tendency to cardiac dysrhythmias, which caused spontaneous cardiac arrests in three patients.


Cellular immunity in cancer: comparison of delayed hypersensitivity skin tests in three common cancers. Cellular immunity was studied in three homogenous groups of patients with cancer to determine whether the pattern of depression of immune competence varied between solid tumours with different patterns of clinical behaviour. Delayed hypersensitivity skin responses were measured in patients with carcinoma of the breast, stomach, and colon and matched controls. Response to 2,4-dinitrochlorobenzene (DNCB) was used as an indication of primary responses and the Mantoux reaction as an index of recall responses. Responses were diminished in all three cancer groups, but there were significant differences between each type of cancer and even between different control groups. Cellular immunity was lost earliest and to the greatest extent in patients with colonic cancers and tended to be retained until a late stage in breast cancer, with gastric cancer occupying an intermediate position. Thus, while there was some degree of correlation between depressed immunity and prognosis our results gave no evidence that general host immune competence could explain the worse prognosis of gastric than colonic cancer. Paradoxical findings in patients with breast cancer suggested a great complexity in the host tumour interaction. Assessments of immune competence in cancer patients must be related to specific types of neoplasms with appropriate control groups if the results are to be meaningful.


Needle aspiration of breast cysts.

Needle aspiration of breast cysts. A total of 149 breast cysts have been treated with primary aspiration. Findings were abnormal in 36 patients, 30 of whom underwent excision of the breast cyst with cancer being found in four. Careful examination of the breast after aspiration and follow-up are necessary, but, provided these precautions are observed, this type of treatment is simple, safe, and cheap besides often giving the patient relief at the first consultation.


Approach to rapid problem solving in clinical medicine. Problem-orientated flow charts have been developed to teach paramedical workers the skills of making diagnoses in outpatient clinics in Tanzania. The charts give high levels of repeatability, accuracy, and rapidity and their use may lead to improved standards of medical care.


Very early termination of pregnancy (menstrual extraction). Very early termination of pregnancy was performed on 424 women in three London teaching hospitals. Altogether 90% of the women were no more than 14 days overdue, and 67% of these had histological evidence of pregnancy. The procedure differed little in technique or its acceptability to the patient from termination done later in the first trimester. The similar incidence of complications suggested that it is not an alternative to conventional contraception. The response of patients, general practitioners, and referral agencies, however, indicated that there is a definite need in the community for a very early termination service.


Schistosomiasis of the urinary bladder. A case report. The case is reported of a man with schistosomiasis of the bladder which gave rise to non-gonococcal urethritis. Diagnosis was confirmed by finding the characteristic terminal-spined Schistosoma haematobium ova in the urine deposit. The cystoscopic appearances further confirmed the disease and its stage. The patient responded satisfactorily to treatment although the follow-up period was short.


Syphilitic balanitis of Follmann developing after the appearance of the primary chancre. A case report. A case of primary syphilitic chancre of the coronal sulcus with subsequent development of syphilitic balanitis of Follmann is described. The histopathological picture and preponderantly intraepidermal localization of T. pallidum in the lesions is discussed.


Syphilitic myositis.

Syphilitic myositis. A case of myositis associated with secondary syphilis is described. Complete recovery occurred after antisyphilitic treatment.


Changes in regional blood flow and cardiodynamics associated with electrically and chemically induced epilepsy in cat. Changes in cardiodynamics and regional blood flow were examined in chronically prepared paralyzed cats during seizures induced electrically by transcerebral or direct cortical stimulation or by administration of flurothyl ether (Indoklon) or pentylenetetrazol (Metrazol). Transcerebral and chemical stimuli produced the greatest vascular responses. During seizures there was an abrupt elevation of arterial pressure unassociated with consistent changes in heart rate. Vascular resistance was increased in femoral, renal and mesenteric arteries with variable reductions in blood flow. Resistance was decreased and flow passively increased in the common carotid artery reflecting the loss of cerebral autoregulation. Cardiac output was unchanged. With seizures associated with large elevations of arterial pressure, the central venous and left ventricular end-diastolic pressures were markedly increased indicating incipient congestive failure. The pressor response was blocked by alpha-adrenergic blockade with phentolamine. Increased regional vascular resistance was abolished by regional sympathectomy. While either adrenalectomy or treatment with 6-hydroxydopamine alone failed to abolish the pressor response, combined, they did. Such treatment unmasked an atropine-sensitive bradycardia. The pressor response with seizures is a consequence of increased vascular resistance in viscera and muscles due to widespread activation of sympathetic neurons and release of adrenomedullary catecholamines. Co-activation of cardiovagal and cardiosympathetic neurons may underlie some associated arrhythmias. Cardiovascular events may severe, by redistribution of the cardiac output, to assure increased availability of oxygen and nutrients to brain to meet the metabolic demands of convulsions.


Visual discrimination of flux-equated figures by cats with brain lesions. Cats with various brain lesions were compared in their abilities to learn or relearn for food reward to a strict performance criterion a simple dark--light discrimination and 3 sets of discriminations between pairs of triangle equated for overall luminous flux. The results revealed a spectrum of deficits in visual learning by cats with different lesions and indicate: (1) cats with bilateral lesions of the superior colliculus-pretectum can learn dark-light and geometric figure discriminations in approximately the same number of training trials as unoperated cats or as cats with bilateral lesions of the lateral-posterolateral and splenial gyri; (2) cats with bilateral lesions of the superior colliculus-pretectum can learn to discriminate from a distance between geometric figures equated for overall luminous flux; (3) cats with bilateral lesions of the suprasylvian and ectosylvian gyri in addition to the lateral-posterolateral and splenial gyri require more training to learn both types of visual discriminations than unoperated cats or cats with lesions either of the superior colliculus-pretectum or of the lateral-posterolateral and splenial gyri; (4) cats require either an intact superior colliculus-pretectum or intact lateral-posterolateral and splenial gyri in order to discriminate between geometric figures; (5) cats with bilateral lesions of the posterior two-thirds--three-fourths of the neocortex and most of the superior colliculus-pretectum can learn a simple dark-light discrimination after prolonged training.


A conditioned eyeblink obtained by using electrical stimulation of the facial nerve as the unconditioned stimulus. Cats acquired a conditioned eyeblink (CR) in a situation where the conditioned stimulus (CS) was a click and the unconditioned stimulus (US) was unilateral electrical stimulation of the zygomatic orbital branch of the facial nerve, which is a motor nerve. In a discrimitive training program, cats received both a click paired with a nerve stimulation and an interspersed unpaired hiss delivered randomly; these cats developed a CR only to the click. No CR developed in cats trained with random presentation of both click and nerve stimulation. Of those cases in which a CR was present, as measured electromyographically, this CR was distinguishable from background noise unilaterally approximately 50% of the time and was bilaterally distinguishable the remained of the time. This CR could be extinguished and easily relearned and was specific for blink musculature. Acquisition rates for the CR were somewhat, but not significantly, slower than rates for cats trained with glabella tap US. Cats with a trigeminal rhizotomy on the side for facial stimulation developed a CR, indicating that inadvertent stimulation of trigeminal afferents cannot account for CR development. Experiments on cats with both Vth and VIIth nerves cut unilaterally indicated that other possible afferents were unlikely to be involved. Thus, the sensory excitation ordninarily produced by the US appears to be unnecessary in this case, and firing of facial motoneurons at a suitable interval after the click CS is a sufficient condition for development of this CR.


The release of [3-H]gamma-aminobutyric acid and neurophysin from the isolated rat posterior pituitary. The efflux of [3-H]GABA from glial cells in the rat posterior pituitary was followed in isolated glands incubated in the presence of 10-minus 5 M aminooxyacetic acid which is known to inhibit GABA metabolism. Electrical stimulation of the pituitary stalk evoked an increase in the rate of efflux of [3-H]GABA as did elevation of the extracellular potassium concentration. The release of neurophysin from nerve terminals in the gland was also increased by electrical stimulation. The increase in [3-H]GABA efflux appeared to be independent of frequency at 2, 5, or 25 HZ if the number of pulses delivered was kept constant, although stimulation at 10 HZ was more effective than either 2 or 25 HZ. The efflux of [3-H]GABA evoked by 56 mM K+ was inhibited by 50% when calcium was removed from the washing fluid and 3 mM EGTA added, while the response evoked by electrical stimulation was unaffected by this procedure. The electrically induced efflux of [3-H]GABA was inhibited by 50% when choline chloride was substituted for sodium chloride in the washing medium, although it was unaffected by tetrodotoxin (0.8 times 10-minus 6 g/ml). The release of exogenous GABA from the pituicyte glia is compared with that of neurophysin from the nerve terminals in the posterior pituitary, and the results are discussed with reference to possible mechanisms of the glial release process.