Effect of exercise in the heat on plasma renin and aldosterone with either water or a potassium-rich electrolyte solution. Information concerning the renin-angiotension-aldosterone system during physical exercise in the heat with adequate fluid and/or electrolyte supplement is lacking. The present study was intended to describe the changes in renin activity and serum aldosterone, serum sodium, and serum potassium in subjects receiving water or a potassium-rich electrolyte solution while exercising (50% VO2 max) for 120 min in a warm environment (32 degrees C, 50% relative humidity). This study shows that, in subjects receiving the electrolyte supplement, serum potassium is elevated slightly during the exercise period whereas serum sodium is unchanged from preexercise levels without the electrolyte supplement. Plasma renin and aldosterone levels were significantly reduced in the subjects receiving the electrolyte supplement compared to subjects receiving only water. The ingestion of the electrolyte supplement replaced 42% of the sodium and 100% of the potassium lost by way of sweat and urine while exercising in the heat.


Speech intelligibility through communication headsets for general aviation. Word discrimination was measured on eight general aviation pilots listening alternately through each of three communication headsets and an aircraft loudspeaker in the presence of light aircraft noise. Each subject listened at the speech intensity designated by him as yielding optimal intelligibility. Performance varied directly with the degree of attenuation provided by the headset. Mean intelligibility scores ranged from 73% through the loudspeaker to 92% through two of the headsets, although retesting through the loudspeaker at a higher signal level improved mean scores to 85%. Articulation functions obtained on four normally hearing listeners tested under the same conditions as the pilots revealed that, for situations when little or no attenuation was available (loudspeaker and one headset), greater signal-to-noise ratios were necessary to allow discrimination equivalent to that obtained under conditions of greater noise attenuation (two headsets). Although good intelligibility could be achieved through the loudspeaker given sufficient signal intensity (greater than 100 dB SPL) some pilots preferred lower levels even though discrimination was reduced.


Influence of hyperoxia (1 ATA) on mouse brain GABA, glutamate, and glutamine. Breathing 100% oxygen at ambient pressure induces disorders in glutamate, GABA, and ammonia metabolism in the brain, beginning 30 min after exposure. The steep increase in glutamine content points to an enhanced metabolism of endogenous amino acids and a breakdown of protein, although the glutamate content is scarcely influenced during the first hours of exposure. The graph of glutamine increase proceeds nearly asymptotically after 24 h, which may be related to the permeability of blood brain barrier for glutamine. The initially fast increase in the GABA level attains a half-maximum augmentation after 2-4 h of exposure and a maximum value after 50 h, but then the graph of GABA slopes steeply downwards, and approximately linearly, until 74-76 h and finally, by 103 h, more gradually approaches control values. The increase in GABA level is discussed with regard to the physiological role of GABA as a homeostatic agent that connects oxidative metabolism with neuronal function. Glutamate, the precursor of glutamine as well as GABA, is affected by oxygen breathing with a "loss" of more than 6 micronmol/g wet wt. after 100 h of exposure. Functionally, this diminution may be correlated to the increase of GABA with respect to its anti-excitatory effect and a possible postsynaptic function of glutamine synthetase.


Blood gas tension and development of lung damage in mice exposed to oxygen at 1 ATA. Oxygen and carbon dioxide tension in arterial blood were studied in mice breathing 100% oxygen at ambient pressure. The lungs were simultaneously investigated in order to relate the oxygen-induced pulmonary alterations to the altered pulmonary function. The development of an impairment in pulmonary diffusing capacity is initiated after 30 h of oxygen exposure, at which time the increase in lung weight is associated with beginning lung edema and beginning accumulation of carbon dioxide in the blood. Red spots or areas on the lung surface, which merged together to large streaks or areas after 20 h of exposure, preceded the measurable diffusing impairment noted at 30 h. Light microscope preparations revealed intraalveolar hemorrhagic exudation and proliferative changes in the alveolar walls. After 50 h, the development of severe pulmonary dysfunction is mainly due to an intense parenchymal reaction in the alveolo-capillary region with thickening in the alveolar walls, dystelectasis in the corresponding parenchyma, and further development of pulmonary edema. The resulting impairment in pulmonary diffusing capacity causes a steep decrease in oxygen tension and an accentuated increase in carbon dioxide accumulation. The present results are discussed in relation to the previous findings of oxygen-induced alterations in brain glutamate, GABA, and glutamine concentration.


Effect of clothing insulation beneath an immersion coverall on the rate of body cooling in cold water. Deep body and skin temperatures were measured on nine subjects during a 1 h immersion in water at 2.5 degrees C whilst wearing an RAF Mark 10 immersion coverall. With no additional insulation, mean skin temperature fell 13.1 degrees C and deep body temperature 0.74 degrees C. When a full Acrilan pile suit was worn beneath the coverall mean skin temperature fell 8.3 degrees C and deep body temperature 0.33 degrees C. With insulation covering the trunk and upper limbs alone, mean skin temperature fell 9.9 degrees C and deep body temperature 0.45 degrees C. Conclusions are drawn concerning the effects on body cooling of changes in insulation of aircrew clothing assemblies designed to protect against immersion in cold water.


Postural illusions experienced during Z-axis recumbent rotation and their dependence upon somatosensory stimulation of the body surface. A blindfolded recumbent subject experiences a variety of postural illusions when rotated about his Z axis. Initially, during the acceleratory phase of rotation turning about his Z axis is experienced; but, as rotary velocity increases, a spiraling of the body outward in the direction opposite to true rotation is experienced as well. Above 15-20 rpm, only orbital motion of the body is experienced, with the subject feeling that he is always facing in the same direction. One cycle of the apparent orbit is completed each time the subject actually rotates 360 degrees. The reverse sequence of illusory motion is experienced during deceleration. The illusory motion all subjects experience during Z-axis recumbent rotation is shown to depend upon the touch- and pressure-stimulation of the body surface generated by contact forces of support.


Responses of articular and epiphyseal cartilage zones of developing avian radii to estrone treatment and a 2-G environment. Female chicks at 2 weeks post-hatch were maintained for 2 weeks at earth gravity or 2 G with daily injections of 0.2 or 0.4 mg estrone. Animals were sacrificed following the last injection and radii were fixed in 10% NBF, decalcified in 3% Nitric acid, doubly embedded, sectioned at 4 to 5 micrometer, and routinely processed for histological measurements of the midcoronal height and width of the cartilage zones of the proximal and distal epiphyses. Estrone treatment increased the growth in height and width of the cartilage layers of the proximal epiphyses and inhibited the growth in height of the distal epiphyseal cartilage of earth gravity chicks. Animal exposure to 2 G without estrone treatment resulted in increased width of the cartilage layers  of the proximal epiphyses and inhibition of both height and width growth of the cartilage layers of the distal epiphyses. Growth in height, but not width, of the cartilage layers of both proximal and distal epiphyses was inhibited by combined estrone treatment and animal exposure to the 2 G environment.


Prevention of hypoxia--acceptable compromises. The acceptable degree of hypoxia is a most important factor in the design of pressure cabins and of aircrew oxygen breathing equipment. The studies of the effects of mild hypoxia upon human performance performed since 1960 are reviewed. It is concluded that the hypoxia induced by breathing air at altitudes up to 5000 ft is acceptable for both crew and passengers of combat and passenger aircraft. The magnitude and the effects of the hypoxia induced by rapid decompression are also considered. The results of the experimental investigations are correlated and it is deduced that the minimum acceptable alveolar oxygen tension on rapid decompression is 30 mm Hg.


Treatment of hypertension in aviators: a clinical trial with Aldactazide. Thirty-two USAF aircrewmen with mild or moderate, uncomplicated essential hypertension were treated with Aldactazide (spironolactone and hydrochlorothiazide). The study was designed to determine the efficacy and safety of this drug combination in aircrew subject to the stress of flying high-performance aircraft. All patients were investigated in detail before, and again 6 weeks after, beginning Aldactazide treatment. Adequate blood pressure control was achieved in 94% of patients; 84% were able to return to flying duties. Treatment was associated with a moderate loss of weight and plasma volume, and a slight reduction in renal function. Tolerance to multiple stress tests was unimpaired after treatment. Symptoms attributable to treatment were minimal. We conclude that in the dose used, four tablets or less daily, Aldactazide is a safe and fairly effective secondline treatment for hypertensive aircrewmen.


Effect of ozone variation on disease in Great Britain: I. Skin cancer. Ozone levels were rising during the period 1951 to 1972 and resulted in decreased levels of solar ultraviolet radiation reaching sea level. Analysis of the records of skin cancers for Bristol and Oxford in England showed that during the first decade of this period incidence and mortality for the skin carcinomas, basal cell and squamous cell, fell in line with theory; but both incidence and mortality for melanoma inexplicably rose. Figures for the second decade show that the data were dominated by trends other than those possibly attributable to ozone change.


Medical certification of pilots.

Medical certification of pilots. This paper reviews some of the problems encountered in administering satisfactory medical requirements for professional pilots. The role of these requirements in the context of flight safety is discussed. The control of risk by the imposition of strict requirements is contrasted with that achieved by training designed to contain the risk introduced by incapacitation. The fact that aviation safety is based on acceptable risk levels is pointed out and the role of physician in this regard is discussed. The need for a widely accepted minimum level of fitness required for aviation duties is brought out. Certain operational aspects are touched upon. Medical requirements based on the desire to avoid on-duty incapacitation are contrasted with those designed to ensure adequate performance. The present ICAO cardiovascular requirement is discussed with particular reference to permanent grounding following myocardial infarction. The significance of inflight crew incapacitation training is pointed out and a plea for close cooperation between licensing authorities, airline operators, and pilots is made.


International biosatellite.

International biosatellite. It is not the first time that Soviet satellites are orbited to carry out an international scientific programme. A new and convincing example of active international cooperation in space studies is the Cosmos-936 satellite which accommodates biological objects and scientific apparatus from the USSR, Czechoslovakia, the USA and France.


Lack of effect of helium breathing on catecholamine levels in the adrenal vein blood of the rabbit. Catecholamine levels were measured in the adrenal vein blood of the chloralose anesthetized rabbit during periods of helium-oxygen breathing (50% He-50% O2) and of air breathing. Blood samples were taken from the T-arm of a venous shunt made by cannulating the renal vein proximally to the orifice of the adrenal vein and connecting the distal end of the cannula to one in the femoral vein. Adrenal vein blood flow varied from 0.09-0.30 g/min in five animals, and catecholamine release from 10-92 ng/min. There were large differences between levels from animal to animal but no significant differences in any one animal between levels measured while breathing helium and levels measured while breathing air. The same held true for respiratory rate, blood pressure, heart rate, and percent change in blood pressure during a simulated valsalva maneuver. Although there were changes seen in catecholamine release during some of these experiments, they could not be related to an effect of gases breathed. It is concluded that if there was an effect of helium breathing on catecholamine release in these anesthetized rabbits it was masked by other conditions with stronger action on the sympatho-adrenal system.


Effects of infrasound on cognitive performance. The cognitive performance of 40 subjects was measured during exposure to infrasound and noise in three experiments. In the first experiment, 12 subjects were exposed for 15 min to each of four experimental conditions while performing a Serial Search Task. The conditions were: 65 dB ambient noise (AN), a low-frequency background noise (BN) at 110 dB, a 7-Hz tone at 125 dB + AN, and the 125 dB tone + BN. The second experiment was the same as the first except a Complex Counting Task was used and the exposure duration was increased from 15 min to 30 min. In the third experiment, the Complex Counting Task was used and the subjects were exposed for 15 min to each of the following four conditions: BN, 125 dB at 7 Hz plus BN, 132 dB at 7 Hz plus BN, and 142 dB at 7 Hz plus BN. No decrements in performance were obtained in any of the three experiments, and there were no subjective reports of dizziness or disorientation as suggested in some of the previous literature. The authors conclude that adverse effects of infrasound have been exaggerated and the current levels of infrasound components as produced by modern jet aircraft are not considered in themselves a practical problem.


Psychological states and aerobic fitness of male and female recruits before and after basic training. Psychological states and aerobic fitness were measured using a battery of psychological tests and a bicycle ergometer work test. A group of approximately two hundred male and female subjects were tested at the beginning of a six week basic training cycle and another group of two hundred were tested at the completion of basic training. A difference in mood, anxiety, self confidence and physical fitness was evident in the groups of male recruits, but not in the female recruits after training. A significant difference existed between males and females in terms of physical work capacity. These differences in work capacity and psychological responses should be considered in the assignment and selection of personnel for high work intensity military occupations.


Ultrasonic effects on mammalian intestinal muscle membrane. The effects of ultrasound on the bioelectric activities of rat intestinal muscle were studied. It was found that low level ultrasound of 1.5 W/cm2 inhibited action potentials of the intestinal smooth muscle. This biophysical action of ultrasound had accumulative effects. The presence of high Ca++ in the medium (3.4 mM or 2 x normal [Ca++]) prevented this action of ultrasound. These data suggested that ultrasound probably acted on the calcium influx mechanism of the cell membrane.


Cosmic radiation exposure in subsonic air transport. This FAA- and NASA-sponsored study of cosmic radiation doses recieved by United States residents flying in commercial jet aircraft is the most extensive to date and combines computer calculations with experimental data. Data derived from 1973 statistics on 2.99 million intercity flights carrying 468 million seats were included in the calculations, yielding a total of 581 billion seat-kilometer. The average flight was 1,084 km in length, was flown at an altitude of 9.47 km, and lasted 1.41 h. The average dose rate was 0.20 mrem/h, resulting in an average passenger dose of 2.82 mrem/year and an average crewmember dose of 160 mrem/year. The average radiation dose to the total U.S. population was 0.47 mrem/person/year. These results are in good agreement with data from several experiments performed by us and others in aircraft at various altitudes and latitudes. The significance of these doses to the population is discussed.


Recurrent atrial fibrillation with nausea and vomiting. Atrial fibrillation occurred twice during episodes of severe nausea and vomiting in a previously healthy 40-year-old male with new onset of Meniere's syndrome (tinnitus, vertigo, deafness). No organic cause was identified to explain the arrhythmia. Holter monitoring, maximal treadmill stress testing, and sinus node recovery times were normal. Intense vagal stimulation, subsequent bradycardia, and dispersion of atrial tissue refractory period is the likely explanation for this arrhythmia.


Helicopter support of North Sea oil exploration. Exploration for oil beneath the North Sea started in the early 1960's with the discovery of natural gas and oil in the southern part between the coasts of East Anglia and the Netherlands. Since then oil exploration has built up considerably, the main effort moving northwards between the Shetland Islands and the Norwegian coasts. The helicopter offered the most direct and rapid contact with off-shore oil rigs and since these early days and immense helicopter operation has been built up round the borders of the North Sea by all the nations involved. Flying conditions in this area, particularly in winter, are at times difficult if not to say hazardous. Nevertheless, a sophisticated helicopter support service has been built up using modern aircraft and equipment which is unique in aviation history. This paper attempts to trace the history of the service, the operational problems involved and the special needs such as survival equipment and clothing. In addition, a co-ordinated air/sea rescue service largely based on helicopters has been built up and provides not only rescue facilities for possible rig disasters but also for shipping emergencies in the area.


Stress and workload in pilots.

Stress and workload in pilots. Several studies have highlighted the increase in physiological activity which occurs in pilots during flight and especially during takeoffs and landings. For example, it has been clearly demonstrated that pilots' heart rates increase during the landing approach to reach a peak at or just before touchdown. These changes have been attributed to workload and to psychological or emotional stress. This paper examines a number of test pilots' heart rate responses recorded during various flight trials involving different types of aircraft. Examples include ramp takeoffs in a VTOL fighter, automatic landings in fog, supersonic flight through monsoon rain, and a sortie in which the pilot developed acute appendicitis. It is concluded that heart rate responses in experienced pilots are influenced almost entirely by workload-related factors and not by emotional stressors, such as risk and anxiety. Because of the emotional overtones of the word "stress," it is suggested that the term workload should be used when referring to the reason for increased cardiovascular activity of pilots.


Systems analysis of an aeromedical evacuation mission. The author applies general systems theory to the analysis of a social system. Through an examination of information processing in an aeromedical evacuation mission, more meaningful levels of coordination evolve. Thus system analysis, as applied here, is an approach used to not only describe an organization but, more importantly, to clearly discern the interrelationships inherent in an activity of major significance such that change or improvement, if needed, may the more readily result.


Radio telemetry system for obtaining body temperature during simulated diving to 1000 FSW. An implantable radio telemetry system for transmitting deep body temperatures from dogs subjected to hyperbaric conditions was designed and tested. The design was adapted from a transmitter described by J. L. Riley, and was successfully tested both in vitro and in vivo to a simulated depth of 1000 FSW. Circuit schematic, printed circuit layout, and component layout are given.


In pursuit of the "spatial gene": a family study. Members of 192 families in the Tel Aviv area were given a battery of eight cognitive tests focusing on spatial measures but sampling verbal, numerical, and perceptual speed domains as well. The patterns of parent-child and sibling correlations gave very weak evidence, if any, for the operation of the X-linked recessive gene postulated by Stafford and others to affect performance on tasks involving spatial visualization. An analysis of male and female score distributions provided results more favorable to the X-linkage hypothesis, at least for the child generation, although suggesting that X linkage does not explain the whole male-female difference in performance on spatial tasks.


Response to 30 generations of selection for open-field activity in laboratory mice. High and low lines resulting from 30 generations of bidirectional selection for open-field activity have nonoverlapping distributions and more than a thirtyfold difference in mean activity. Open-field defecation scores of low-active lines are approximately 7 times higher than those of high-active lines, substantiating earlier reports of a large, negative genetic correlation between these characters. Since the selection experiment is replicated, other variables which are found to be reliably different among the high, control, and low lines are likely to be causally related to open-field activity; thus these selected lines of mice may be of use to other investigators.


Parent-offspring resemblance for specific cognitive abilities in Korea. Regressions of offspring on midparent value for tests of specific cognitive abilities in Korea were considerably higher than those for Americans of Japanese ancestry or Americans of European ancestry tested in Hawaii. This greater parent-offspring resemblance in Korea may be due to the particular method of test administration or to an increased genetic variance resulting from assortative mating. The pattern of parent-child correlations for three relatively pure tests of spatial ability and for the spatial factor did not conform to that of a sex-linked recessive character.


Intrafamilial correlations and heritability estimates for spatial ability in a Minnesota sample. Data collected by university students on their family members showed intrafamilial correlations and heritability estimates for spatial ability similar in magnitude to those reported in three larger samples in Hawaii and Korea.


The Burt controversy: a comparison of Burt's data on IQ with data from other studies. A recent controversy has given reason to examine the place of Burt's data among other behavioral genetic data on IQ. Although Burt's kinship correlations are higher than the average of other studies, his results are generally consistent with other data.


Changes in the lactate dehydrogenase isoenzyme pattern during differentiation of rabbit bone-marrow erythroid cells. 1. Differentiation and maturation of rabbit bone-marrow erythroid cells was accompanied by a 15-fold decrease in lactate dehydrogenase activity from approx. 0.1pmol of NADH utilized/min per cell in basophilic cells to 0.007 pmol of NADH/min per cell in reticulocytes. 2. In early cells, cell division takes place with a corresponding decrease in cell volume, but the concentration of lactate dehydrogenase remains almost constant. 3. When cell division ceases, qualitative as well as quantitative changes in the lactate dehydrogenase isoenzyme pattern become apparent and reticulocytes were found to contain almost exclusively the H4 isoenzyme, whereas early erythroblasts contained also the M4 and hybrid isoenzymes. 4. Extracts from a lysosome-enriched subcellular fraction of bone-marrow erythroid cells specifically degraded the M4 isoenzyme in vitro, but the H4 form was stable. It is suggested that lysosomal enzymes are involved in bringing about the observed changes in lactate dehydrogenase isoenzyme patterns in vivo.


Androgenic regulation of elongation of polyribonucleotide chains on rat ventral-prostate chromatin. The kinetics of polyribonucleotide-chain elongation by rat ventral-prostate RNA polymerase B with homologous chromatin as a template were investigated. Chain elongation was measured under conditions wherein all initiation had occurred, no reinitiation took place and the reaction rate was constant. The kinetic behaviour of prostate RNA polymerase B was consistent with a mathematical model formulated for the multisubstrate enzyme. The addition of each nucleoside triphosphate was independent of the other three. The overall rate of chain elongation was lower when prostate chromatin from castrated rats was used than with prostate chromatin from normal rats. The inclusion of dihydrotestosterone-receptor complexes stimulated the rate of elongation. Androgenic effects did not appear to be directed towards the addition of individual nucleoside triphosphates, but probably towards one of the other major events in RNA-chain elongation, i.e., unwinding of DNA or movement of the enzyme along the template.


Induction of cadmium-thionein in isolated rat liver cells. The uptake of cadmium by isolated liver cells was linearly related to the cadmium concentration to which the cells were exposed in the medium. Cadmium-treated cells synthesized proteins de novo with the characteristics of cadmium-thionein induced in the liver of cadmium-treated animals. Thionein from liver cells incorporated cadmium and [35S]cysteine, had a Ve/Vo (Sephadex G-50) of 1.8-1.9, and was separated into two subfractions by DEAE-cellulose ion-exchange chromatography. Cycloheximide and actinomycin D when added after a cadmium exposure prevented the synthesis of thionein. However, addition of actinomycin D after synthesis had started only decreased the total amount of thionein synthesized. The concentration of cadmium to which the cells were exposed affected the amount of cadmium-thionein synthesized in 6h. The maximum response occurred when cells were exposed to 0.5 microgram of cadmium/ml; at higher metal concentrations the total amount of cadmium-thionein synthesized declined. The system described in the present paper can be used to study the mode of metal toxicity and the mechanism of cadmium-thionein synthesis.


Metabolic effects of pent-4-enoate in isolated perfused rat heart. The metabolic effects of the hypoglycaemic agent pent-4-enoate were studied in isolated, beating or potassium-arrested rat hearts. The addition of 0.8mM-pent-4-enoate to the perfusion fluid increased O2 consumption by 76% in the arrested heart and by 14% in the beating heart; the concentration ratio of phosphocreatine/creatine increase concomitantly by 47% and 27% respectively. Perfusion of the heart with pent-4-enoate resulted in a 30-fold increase in the concentration of the pool of tricarboxylic acid-cycle intermediates in the tissue, about 90% of this increase being due to malate. The sum of the concentrations of the myocardial free amino acids remained virtually unchanged during the accumulation of the tricarboxylic acid-cycle intermediates. It was concluded that pent-4-enoate can be effectively metabolized in the myocardium and that its metabolism probably proceeds via propionyl-CoA, since pent-4-enoate reproduces many of the metabolic characteristics of propionate in the cardiac muscle. The accumulation of the tricarboxylic acid-cycle intermediates is probably due to carboxylation of propionyl-CoA. The response pattern of the metabolite concentrations in the cardiac muscle is quite different from that in the liver, in which decrease of the concentrations of the tricarboxylic acid-cycle intermediates has been observed previously [Williamson, Rostand & Peterson (1970) J. Biol. Chem. 245, 3242-3251].


Effect of potassium deficiency on mouse kidney lysosomal enzymes. Mice of inbred strains A/J, C57BL/6J and C57BL/6J beige were kept on a K+-deficient diet for up to 40 days to determine the magnitude and mechanism of changes in tissue lysosomal enzymes. From days 10 to 40 glucuronidase activity increased 3-fold in kidney of K+-deficient mice, but there was little effect on beta-galactosidase or acid phosphatase activity. Similar increases in kidney glucuronidase activity occurred in inbred strains known to have genetically altered control of the synthesis (A/J) and secretion (C57BL/6J beige) of glucuronidase in kidney proximal-tubule cells. Deprivation of K+ did not affect glucuronidase activity in liver, spleen, lung and brain, but there was a 2-3-FOld increase in glucuronidase activity in heart in the C57BL/6J and C57BL/6J beige strains. As shown by specific antibody titration, increased glucuronidase activity in kidney of K+-deficient mice was accompanied by accumulation of enzyme molecules. Likewise in kidney of deficient mice there was an increased rate of synthesis of glucuronidase as measured by incorporation of labelled leucine into immunoprecipitable glucuronidase. In kidney of K+-deficient mice the elevated glucuronidase activity was found in both collecting-tubule and interstitial cells of the medulla. It is probable therefore that a significant fraction of the increased kidney lysosomal synthesis and enzyme activity is due to infiltrating cells.


The metabolism of shikimate in the rat.

The metabolism of shikimate in the rat. In the rat, shikimate was metabolized and excreted as hippurate, hexahydrohippurate, 3,4,5,6-tetrahydrohippurate, t-3,t-4-dihydroxycyclohexane-r-1-carboxylate and c-3,t-4-dihydroxycyclophexane-r-1-carboxylate, conjugates of catechol and CO2. The metabolism was entirely dependent on various initial microbial transformations in the gut, metabolite formation being suppressed in animals pretreated with antibiotics. Shikimate was not metabolized by mammalian tissues, and products of microbial metabolism were excreted either unchanged or after further biotransformation in the animal tissues.


Uptake and metabolism of adenosine by pig aortic endothelial and smooth-muscle cells in culture. 1. Adenosine, a potent vasodilator, is transported very efficiently by pig aortic endothelium in monolayer culture (approx. 50pmol/min per 10(6) cells at 2 micrometer). Uptake proceeds by diffusion at high (millimolar) substrate concentrations, and by two discrete transport processes (Km approx. 3 micrometer and 250 micrometer) at lower concentrations. Over 90% of the adenosine taken up at 10 micrometer or 100 micrometer is rapidly converted into adenine nucleotides (mainly ATP). 2. The high-affinity process is selectively inhibited by dipyridamole and by nitrobenzylthioinosine. Adenine preferentially inhibits the lower-affinity process, papapaverine inhibits both transport processes, and inosine has no significant effect. 3. Pig aortic smooth-muscle cells in culture show no high-affinity transport system for adenosine; uptake is much slower at low concentrations than that by endothelium (approx. 5pmol/min per 10(6) cells at 2 micrometer). Over 80% of the incorporated adenosine at 10 micrometer or 100 micrometer is rapidly converted into adenine nucleotides. 4. The uptake of adenosine by smooth-muscle cells is powerfully inhibited by adenine, but dipyridamole is much less potent than in endothelium. 5. We conclude that endothelial cells are mainly responsible for the removal of circulating adenosine.


Lipid oxidation by heart mitochondria from young adult and senescent rats. 1. State-3 (i.e. ADP-stimulated) rates of O(2) uptake with palmitoylcarnitine, palmitoyl-CoA plus carnitine, pyruvate plus malonate plus carnitine and octanoate as respiratory substrate were all diminished in heart mitochondria isolated from senescent (24-month-old) rats compared with mitochondria from young adults (6 months old). By contrast, State-3 rates of O(2) uptake with pyruvate plus malate or glutamate plus malate were the same for mitochondria from each age group. 2. Measurements of enzyme activities in disrupted mitochondria showed a decline with senescence in the activity of acyl-CoA synthetase (EC 6.2.1.2 and 6.2.1.3), carnitine acetyltransferase (EC 2.3.1.7) and 3-hydroxy-acyl-CoA dehydrogenase (EC 1.1.1.35), but no change in the activity of carnitine palmitoyltransferase (EC 2.3.1.21) or acyl-CoA dehydrogenase (EC 1.3.99.3). 3. Measurement of dl-[(3)H]carnitine (in)/acetyl-l-carnitine (out) exchange in intact mitochondria showed decreased rates when the animals used were senescent. However, this followed from a decreased intramitochondrial pool of exchangeable carnitine, such that calculated first-order rate constants for exchange were identical in mitochondria from the two age groups. 4. The decline in acyl-CoA synthetase activity is thought to be the reason for the diminished rate of O(2) uptake with octanoate in senescence. The decline in carnitine acetyltransferase activity is considered to be the cause of the diminished rate of O(2) uptake with acetylcarnitine or with pyruvate plus malonate plus carnitine as substrate. The mechanism of the diminished rate of O(2) uptake with palmitoylcarnitine in senescence is discussed.


The mechanism of haem catabolism. Bilirubin formation in living rats by [18O]oxygen labelling. 1. The pathway of haem breakdown in living rats was studied by using 18O in the oxygen that the animals consumed. By cannulation of the common bile duct and collection of bile, labelled bilirubin was isolated and its mass spectrum determined. One set of results was obtained for a rat to which haemoglobin had been intravenously administered and another set obtained for a rat that was not given exogenous haem. Isomerization of bilirubin IXalpha to the XIIIalpha and IIIalpha isomers did not occur to any significant extent. The 18O-labelling pattern obtained in the bilirubin was consistent with a Two-Molecule Mechanism, whereby the terminal lactam oxygen atoms of bilirubin are derived from different oxygen molecules. The consequences of this mechanism are discussed in terms of the possible intermediates of the catabolic pathway. 2. 18O-labelled bilirubin appeared in the bile in less than 10 min after exposure of the animals to labelled oxygen. This result suggests that all of the chemical transformations involving production of biliverdin, reduction to bilirubin and conjugation of the bilirubin are fast processes. 3. The quantitative recovery of label obtained in the experiments suggests that there is little or no exchange of newly synthesized bilirubin with existing bilirubin pools in the animal.


Inter-organ relationships between glucose, lactate and amino acids in rats fed on high-carbohydrate or high-protein diets. 1. Inter-organ relationships between glucose, lactate and amino acids were studied by determination of plasma concentrations in different blood vessels of anaesthetized rats fed on either a high-carbohydrate diet [13% (w/w) casein, 79% (w/w) starch] or a high-protein diet [50% (w/w) casein, 42% (w/w) starch]. The period of food intake was limited (09:00-17:00h), and blood was collected 4h after the start of this period (13:00h). 2. Glucose absorption was considerable only in rats fed on a high-carbohydrate diet. Portal-vein-artery differences in plasma lactate concentration were higher in rats fed on this diet, but not proportional to glucose absorption. Aspartate, glutamate and glutamine were apparently converted into alanine, but when dietary protein intake was high, a net absorption of glutamine occurred. 3. The liver removed glucose from the blood in rats fed on a high-carbohydrate diet, but glucose was released into the blood in rats fed on the high-protein diet, probably as a result of gluconeogenesis. Lactate uptake was very low when amino acid availability was high. 4. In rats on a high-protein diet, increased uptake of amino acids, except for ornithine, was associated with a rise in portal-vein plasma concentrations, and in many cases with a decrease in hepatic concentrations. 5. Hepatic concentrations of pyruvate and 2-oxo-glutarate decreased without a concomitant change in the concentrations of lactate and malate in rats fed on the high-protein diet, in spite of an increased supply of pyruvate precursors (e.g. alanine, serine, glycine), suggesting increased pyruvate transport into mitochondria. 6. High postprandial concentrations of plasma glucose and lactate resulted in high uptakes of these metabolites in peripheral tissues of rats on both diets. Glutamine was released peripherally in both cases, whereas alanine was taken up in rats fed on a high-carbohydrate diet, but released when the amino acid supply increased. 7. It is concluded that: the small intestine is the main site of lactate production, and the peripheral tissues are the main site for lactate utilization; during increased ureogenesis in fed rats, lactate is poorly utilized by the liver; the gut is the main site of alanine production in rats fed on a high-carbohydrate diet and the liver utilizes most of the alanine introduced into the portal-vein plasma in both cases.


Studies on secretion and endocytosis of macromolecules by cultivated skin fibroblasts. Effects of anti-microtubular agents on secretion and endocytosis of lysosomal hydrolases and of sulphated glycosaminoglycans. Fibroblasts were incubated in the presence of the anti-microtubular drugs colchicine, vinblastine and vincristine. In concentrations between 10nm and 1 mM these drugs stimulated the secretion of beta-N-acetylglucosaminidase, alpha-N-acetylglucosaminidase and beta-glucuronidase, but not of beta-galactosidase. The endocytosis of beta-N-acetylhexosaminidase and alpha-N-acetylglucosaminidase, but not of beta-glucuronidase, was inhibited at drug concentrations higher than 0.1 micrometer. Formation, secretion and association with the cell membrane of sulphated proteoglycans were not affected by anti-microtubular drugs. Endocytosis of sulphated proteoglycans and their subsequent degradation was inhibited by drug concentrations above 0.1 micrometer. The inhibition of intracellular glycosaminoglycan degradation led to a moderate storage of these compounds. These results suggest that microtubules participate in the control of secretion and endocytosis of lysosomal enzymes, and in the endocytosis and degradation of lysosomal substrates such as sulphated proteoglycans.


Oestrogen induction of riboflavin-binding protein in immature chicks. Nature of the secretory protein. The riboflavin-binding protein isolated from sera of oestrogen-treated male chicks as well as that synthesized and secreted in vitro by the chicken liver have the same molecular size as that of the egg-yolk protein. Functionally the serum and yolk proteins are similar. This is in contrast with the hormone-induced synthesis, secretion and deposition of phosvitin and lipovitellin in the ovary.


The effects of hypoglycin on glucose metabolism in the rat. A kinetic study in vivo and [U-14C,2-3H]glucose. 1. The kinetics of glucose metabolism were evaluated in rats deprived of food 15-21 h after the administration of hypoglycaemic doses of hypoglycin (100 mg/kg body wt.) by following changes in the specific radioactivities of 14C and 3H in blood glucose after an intravenous dose of [U-14C,2-3H]glucose [Katz, Rostami & Dunn (1974) Biochem. J. 142, 161-170]. 2. During this time, recycling of glucose through the Cori cycle was virtually abolished, the rate of irreversible disposal of glucose and its total body mass were both decreased by about 70%, whereas there was little effect on the mean transit time for glucose. 3. It was concluded that hypoglycaemia is due to inhibition of gluconeogenesis.


Evidence from mycelial studies for differences in the sterol biosynthetic pathway of Rhizoctonia solani and Phytophthora cinnamomi. Phytophthora cinnamomi, a member of the Pythiacease, does not synthesize sterols. Small amounts of squalene, but no squalene epoxide or sterol, were isolated from the dried mycelium of this fungus after growth in sterol-free medium. The dried mycelium of Rhizoctonia solani, a sterol-synthesizing fungus grown under the same conditions, contained small amounts of squalene and squalene epoxide and large amounts of ergosterol. When the two organisms were grown in the presence of [14C]acetate, only labelled geraniol, farnesol and squalene were recovered from the P. cinnamomi mycelium, whereas labelled geraniol, farnesol, squalene, squalene epoxide and ergosterol were recovered from the R. solani mycelium. Similar results were obtained when the organisms were incubated in the presence of [2(-14)C]mevalonate; in this case, labelled lanosterol was also detected in the R. solani mycelium. Both organisms, when incubated in the presence of unlabelled squalene, squalene epoxide or lanosterol, incorporated these compounds into their mycelia; however, only the R. solani mycelium was able to convert these substrates into products further along the sterol pathway. It appears that squalene is the terminal compound in the sterol biosynthetic pathway of P. cinnamomi.


Evidence from cell-free systems for differences in the sterol biosynthetic pathway of Rhizoctonia solani and Phytophthora cinnamomi. Cell-free preparations of both Rhizoctonia solani, a sterol-synthesizing fungus, and Phytophthora cinnamomi, a non-sterol-synthesizing fungus, incubated in the presence of [2(-14)C]mevalonate and iodacetamide, converted the mevalonate into labelled mevalonate 5-phosphate, mevalonate 5-pyrophosphate and isopentenyl pyrophosphate. In the absence of iodoacetamide, but under anaerobic conditions, the same preparations converted the mevalonate into labelled geraniol, farnesol and squalene, the first two compounds presumably as their pyrophosphates. When cell-free preparations of both organisms were incubated aerobically in the presence of [1(-14)C]isopentenyl pyrophosphate, only labelled geraniol, farnesol and squalene were recovered from the P. cinnamomi reaction mixture, whereas labelled geraniol, farnesol, squalene, squalene epoxide, lanosterol and ergosterol were present in the R. solani reaction mixture. When these same preparations were incubated in the presence of 14C-labelled squalene, labelled squalene epoxide, lanosterol and ergosterol were recovered from the R. solani reaction mixture. In contrast, the P. cinnamomi preparation was unable to convert the squalene into products further along the sterol pathway; instead, a portion of the labelled squalene was converted into water-soluble products, indicating the possible existence of a squalene-degradation process in this organism. It appears that the block in the sterol biosynthetic pathway of P. cinnamomi occurs at the level of squalene epoxidation.


Interrelations between ureogenesis and gluconeogenesis in isolated hepatocytes. The role of antion transport and the competition for energy. 1. Glucose synthesis from lactate plus pyruvate and from lactate plus alanine was measured in the presence or absence of 1mM-oleate or 2mM-octanoate at low (2mM) or high (8mM) concentrations of NH4Cl. 2. Both fatty acids alone or with 2mM-NH4Cl doubled glucose production from lactate plus pyruvate. Glucose synthesis from lactate plus alanine, in the presence of oleate, was decreased 16% by 2mM-NH4Cl. 3. In the presence of fatty acids, 8mM-NH4Cl decreased gluconeogenesis by 60-65% from both lactate plus pyruvate and lactate plus alanine. This inhibition was correlated with a high accumulation of aspartate and a drastic decrease in 2-oxoglutarate and malate in the cells. 4. In the presence of 2mM- or 8 mM-NH4Cl, oleate and glucogenic precursors, the addition of 2.5mM-ornithine stimulated urea synthesis. 5. This was paralleled by a decrease of 16% in glucose synthesis from lactate plus pyruvate in the presence of 2mM-NH4Cl and had no effect at 8mM-NH4Cl. In the system producing glucose from lactate plus alanine, ornithine completely reversed the inhibition caused by 2mM-NH4Cl and only partly that by 8mM-NH4Cl. 6. Gluconeogenesis from pyruvate was also inhibited by 2mM-NH4Cl in the presence of oleate or ethanol. This way due to the decrease of malate, which is the C4 precursor of glucose in this system. 7. The limitation of gluconeogenesis by 2-oxoglutarate and malate concentrations in the liver cell and the competition for energy between glucose and urea synthesis is discussed.


Synthesis of ophthalmic acid in liver and kidney in vivo. The synthesis of ophthalmic acid, an analogue of glutathione, was studied in vivo in mouse liver and kidney after administration of either L-alpha-aminobutyrate or L-gamma-glutamyl-L-alpha-aminobutyrate as precursor. L-alpha-aminobutyrate accumulated to a much greater extent, and induced a much greater synthesis of ophthalmic acid in the liver than in the kidney. In contrast, L-gamma-glutamyl-L-alpha-aminobutyrate initiated a large and more rapid synthesis of ophthalmic acid in the kidney than in the liver. Experiments with L-gamma-[G(-14)C]glutamyl-L-alpha-aminobutyrate showed that, although part of the dipeptide is degraded to its constituent amino acids, a significant proportion is directly incorporated into kidney ophthalmic acid. In contrast L-gamma-glutamyl-L-alpha-aminobutyrate serves poorly as a direct precursor of liver ophthalmic acid. The present results show that kidney gamma-glutamyl tripeptide synthesis can proceed directly from an exogenous gamma-glutamyl dipeptide precursor.


Transformation of arachidonate into 6-oxoprostaglandin F1 alpha, thromboxane B2 and prostaglandin E2 by sheep lung microsomal fraction. In the presence of haemoglobin and isoproterenol, the microsomal fraction of sheep lung catalysed the conversion of arachidonate predominantly into thromboxane B2 and to a lesser extent into 6-oxoprostaglandin F1alpha. Very little prostaglandin E2 and prostaglandin F2alpha were formed. If reduced glutathione was added in combination with haemoglobin and isoproterenol, the synthesis of prostaglandin E2 was favoured over that of thromboxane B2 and 6-oxoprostaglandin F1alpha. The identities of these products were confirmed by t.l.c. and by combined g.l.c.-mass spectrometry. These results indicate that microsomal fraction of sheep lung possesses active prostaglandin synthase, prostacyclin synthase and thromboxane synthase activities.


Calcitonin-mediated changes in plasma tryptophan and brain 5-hydroxytryptamine and acetylcholinesterase activity in rats. After a single injection of calcitonin (20 M.R.C. units/kg body wt.) marked decreases in both Ca2+ and free tryptophan in plasma were observed, during the initial period of the treatment (up to 1 h). However, 5-hydrotryptamine contents of the whole brain and the cerebral acetylcholinesterase activity were greatly enhanced. The cerebellar acetylcholinesterase activity was not influenced by calcitonin.


Normal distribution of acetylation phenotypes in systemic lupus erythematosus. Previous reports have indicated that idiopathic systemic lupus erythematosus (SLE), like drug-induced lupus, is more frequent in "slow" hepatic acetylators. Using dapsone acetylation rate to determine phenotypes, we found that of the 18 SLE patients studied, 9 were fast acetylators, 8 were slow, and 1 was indeterminate. This result (53% fast) is similar to acetylator phenotypes in our normal controls (50% fast) and in the population at large (52%).


Therapeutic studies in NZB/NZW mice. VI. Age-dependent effects of concanavalin A stimulated spleen cell supernate. Spleen cells from normal mice were cultured with Concanavalin A to produce an immunosuppressive supernate. This supernate was used to treat the lupus-like autoimmune disease of NZB/NZW mice. Such treated mice lived significantly longer than did controls, but only if treatment was initiated early in the course of the illness.


Hand structure and function in an industrial setting. The influence of patterns of usage on the structure and function of the hands was formally tested. Three groups of female textile workers, each employed in a distinct and defined, atraumatic, repetitive, stereotyped manual task for at least 20 years, were identified in a single rural mill. Replicate data were obtained for the following measures of structure and function: range of motion, a score for the degree of radiographic degenerative changes at each hand joint, malalignment at digital joints determined radiographically, and a quantitative measure of osteophyte formation. Significant and consistent differences in the right hand when compared to the left were detected. Furthermore, highly significant task-related differences were demonstrated. These task-related differences in the structure and function of the hands were consistent with the pattern of usage. Therefore these three patterns of usage influence hand structure and function in the population studied.


Carpal tunnel syndrome with polymyalgia rheumatica. Association of carpal tunnel syndrome with systemic diseases is well established. Carpal tunnel syndrome preceded or existed simultaneously in 5 patients with polymyalgia rheumatica. It is probably related to tenosynovitis resulting in increase in the volume of the contents of the tunnel.


Psychosocial factors in juvenile rheumatoid arthritis. A detailed survey of 88 children with juvenile rheumatoid arthritis (JRA) was made in an attempt to elucidate characteristics that may participate in the etiologic mechanism. Data from a random pediatric population from the same geographic area were also included for comparisons. The most striking findings were psychosocial factors. Children whose parents were unmarried as a result of divorce, separation, or death comprised 28.4% of the JRA population, compared to 10.6% of the comparison group. In addition, adoption occurred three times more often in the JRA population. Fifty-one percent of these events (divorce, separation, death, or adoption) occurred near the date of onset of the disease.


Quantitative sacroiliac scintigraphy in patients with Crohn's disease. Sixty patients with Crohn's disease have been assessed radiologically and by quantitative sacroiliac scintigraphy for evidence of sacroilitis and/or ankylosing spondylitis. The incidence of radiologic sacroiliitis (11%) and ankylosing spondylitis (5%) was no greater in our series than previously reported. However, the incidence of increased uptake of radiotracer at the sacroiliac joints was 52%. There was no correlation in the group as a whole between radiologic and/or scintigraphic evidence of sacroiliitis and the tissue antigen HLA-B27.


Demonstration of anticollagen antibodies in rheumatoid arthritis synovial fluids by 14C-radioimmunoassay. Twenty-seven synovial fluids from rheumatoid arthritis (RA) patients and 17 synovial fluids from controls were investigated in a new radioimmunoassay for anticollagen antibodies. In vitro labeled human 14C-collagen of type I in native or denatured state was used as antigen. Passive hemagglutination was used in comparison. Parameters for defining positive results in radioimmunoassay were evaluated on the basis of control synovial fluids. Synovial fluids from 20 RA patients (74%) showed antibodies to denatured collagen; synovial fluids from 8 RA patients (30%) also demonstrated antibodies to native collagen. Control fluids of posttraumatic effusions were negative; among the other controls synovial fluid from 1 psoriatic arthritis patient reacted positively. Inhibition experiments showed that antibodies to denatured collagen cross-reacted with native collagen. Inhibition with human denatured type III collagen displayed strong cross-reactivity of anti-type I collagen antibodies with type III collagen.


Multiple myeloma complicating the course of seronegative systemic lupus erythematosus. A patient with a 20-year history of clinical systemic lupus erythematosus (SLE) who later developed multiple myeloma is described. SLE was diagnosed on the basis of a butterfly rash, photosensitivity, nondeforming arthritis, pleuropericarditis, and alopecia. However, the patient has never had LE cells, antinuclear antibody, or depressed complement. The patient was treated with intermittent courses of corticosteroids over a 20-year period with good results. Multiple myeloma, diagnosed by bone marrow biopsy, has responded favorably to therapy with L-phenylalanine mustard and prednisone.


Sensitization following Hymenoptera whole body extract therapy. Treatment of an insect-sensitive patient with Hymenoptera whole body extracts (WBE) led, on five occasions, to a serum sickness--like syndrome which did not recur after therapy was stopped. The patient was found to be sensitive by skin test, histamine release, and radioallergosorbent test (RAST) to both venom and WBE as well as to venomless bee body preparations. Subsequent therapy with honeybee and yellow jacket venoms was without sequelae, and after treatment the patient did not react to a sting. In order to assess the frequency of sensitivity to irrelevant body proteins in patients treated with WBE we carried out WBE RASTs on sera from 15 such patients and compared them with those from 15 nontreated insect-allergic patients who had similar venom-specific IgE antibody levels. None of the patients allergic to insects who had not been treated with WBE had detectable IgE anti-WBE antibodies, while about 50% of those treated with WBE had developed IgE antibodies against these proteins. It appears that sensitization to nonvenom WBE proteins in terms of the development of IgE antibody is a common result of this therapy, and, rarely, repeated challenge with this complex antigenic mixture can also lead to clinical illness.


Thymidine rescue of high-dose methotrexate in humans. Thymidine rescue was administered following 63 courses of high-dose methotrexate in 20 patients. In the first part of this study, the methotrexate was given as a 24-hr infusion and the dose was escalated from 0.14 to 8.54 g/sq m; in the second part, methotrexate was infused to maintain a serum concentration of 15 micrometer for 30, 36, or 40 hr. Thymidine rescue was started immediately after the end of the methotrexate infusions, and consisted of 8 g/sq m/day for 3 days or until serum methotrexate was below a toxic level. Mucositis and myelosuppression were the major toxicities. Neither was dose related. Serum methotrexate levels were proportional to the logarithm of the methotrexate dose. There was a mean 6-fold increase in thymidine concentration during rescue. However, thymidine levels prior to and during rescue were not related to the incidence of subsequent toxicity. Recovery of DNA synthesis in bone marrow cells was evident by nucleoside precursor incorporation at 24 hr after the start of rescue. Two of 16 evaluable patients achieved partial responses. This study indicates that thymidine is an effective rescue agent for high-dose methotrexate in humans.


Hypersensitivity lung disease: early diagnosis. The early diagnosis of hypersensitivity lung disease (HLD) is important because of its progressive morbidity. It is often difficult to establish the diagnosis in the early stages because of the absence of defined symptoms. Case histories of 2 patients with pigeon breeder's HLD are reported. Both patients presented with unusual manifestations of the disease: one patient was asymptomatic but had an abnormal chest radiograph; the other patient had a normal chest radiograph but experienced occasional symptoms of exertional dyspnea. Both patients had abnormal pulmonary function and precipitin bands against pigeon serum. Following inhalation challenge with pigeon serum both patients developed fever and leukocytosis, but no significant pulmonary function response was observed. In both patients pulmonary function tests returned to near normal levels after corticosteroid therapy. Early detection of HLD may prevent progressive irreversible pulmonary damage. This requires a high index of clinical suspicion and appropriate screening tests. Inhalation challenge procedures are useful in establishing the diagnosis.


Panic-fear in asthma: rehospitalization following intensive long-term treatment. The panic-fear personality scale related to rehospitalization rates of asthmatics during two successive 6-month periods following intensive long-term treatment. High and Low Panic-Fear patients were nearly twice as likely as Moderates to be rehospitalized. Neither longitudinal pulmonary function measurements, physicians' judgments about the medical severity of the asthma during treatment, nor the presence or absence of maintenance oral corticosteroids at discharge were related to rehospitalization. The available information suggests that High Panic-Fear patients react to asthma with symptom exaggeration and helplessness, while Low Panic-Fear patients employ an equally maladaptive strategy best characterized as symptom minimization and denial. It is possible that both of these extreme response styles may affect adherence to prescribed medical regimens and are equally detrimental as indicated by rehospitalization following intensive long-term treatment.


Bilateral optic system aplasia with relatively normal eyes. An infant with extensive CNS malformations and aplasia of the optic system in association with grossly normal-appearing eyes was studied. The neural malformations included partial agenesis of the medulla, pons, and cerebellum and striking maldevelopment of the telencephalon and diencephalon, with lissencephaly, complete arrhinencephaly, and agenesis of the optic system. Because the optic vesicles are outgrowths from the diencephalon, the absence of some structures derived from them is not surprising.


Amniotic fluid cell mosaicism for presumptive trisomy 20. Trisomy for an F-like chromosome with banding characteristics of chromosome 20 was observed, respectively, in 25 and 8% of amniotic fluid cell clones in two cases of prenatal diagnosis for advanced maternal age. No such aneuploidy was found upon examination of fetal or postnatal tissues. In both instances there were no detectable malformation. It is suggested that propensity to nondisjunction for an F-like chromosome, not unlike tetraploidy, might be another characteristic of amniotic fluid cells in culture.


sn-Glycerol-3-phosphate dehydrogenase and its interaction with nitrate reductase in wild-type and hem mutant strains of Staphylococcus aureus. Staphylococcus aureus has membrane-associated sn-glycerol-3-phosphate dehydrogenase activity that is strongly activated by detergents. The enzyme can be measured spectrophotometrically in intact cells in assay systems containing lauryldimethylamine oxide (Ammonyx LO). The dehydrogenase activity was located exclusively in the membrane fraction of cells grown with glycerol under aerobic conditions or under anaerobic conditions with the addition of nitrate; there was no evidence of multiple forms. Development of sn-glycerol-3-phosphate dehydrogenase activity was studied with suspensions of cells grown previously under semianaerobic conditions with glucose and nitrate. The wild-type strain rapidly formed the enzyme when incubated with glycerol under aerobic conditions or under semianaerobic conditions in the presence of nitrate. Under similar conditions, suspensions of hem mutant H-14 required the addition of hemin. Induction of the enzyme was strongly repressed by glucose with both organisms. A procedure was established to obtain cells of mutant H-14 with sn-glycerol-3-phosphate dehydrogenase and nitrate reductase activities, but which could not link the systems unless supplemented with hemin. The coupled activity could also be reconstructed in vitro by the addition of hemin to the depleted membranes.


Comparative studies of porphyrin production in Propionibacterium acnes and Propionibacterium granulosum. Porphyrin production by Propionibacterium acnes and that by Propionibacterium granulosum were compared. Porphyrin synthesized by both organisms was identified as coproporphyrin III on the bases of absorption and fluorescence spectra and behavior on paper chromatography and thin-layer chromatography. Quantitative, rather than qualitative, differences in production were found between these organisms. In general, P. granulosum produced significantly greater amounts (P less than 0.001) of porphyrin than did P. acnes. delta-Aminolevulinic acid synthetase appeared to be the rate-limiting enzyme of the heme biosynthetic pathway in both organisms. The increased porphyrin production in P. granulosum is apparently associated with increased delta-aminolevulinic acid synthetase activity.


The role of memory in the age decline in digit-symbol substitution performance. Adult age differences in the Digit Symbol Test were investigated in three separate experiments. All experiments incorporated a manipulation of the number of digit-symbol pairs in modified versions of the test forms to determine whether the age differences would be reduced with decreased memory requirements. The results of all three experiments indicated that, as the number of digit-symbol pairs was reduced, the age difference was reduced in absolute terms, but not in relative terms. Older subjects decreased their times by greater absolute amounts, but by the same relative amounts when the number of digit-symbol pairs was decreased from nine to one. Independent results supported the interpretation that memory factors play a very small role in contributing to the age decline in digit-symbol performance.


Logical, epistemological and statistical aspects of nature-nurture data interpretation. In this paper the nature of the reasoning processes applied to the nature-nurture question is discussed in general and with particular reference to mental and behavioral traits. The nature of data analysis and analysis of variance is discussed. Necessarily, the nature of causation is considered. The notion that mere data analysis can establish "real" causation is attacked. Logic of quantitative genetic theory is reviewed briefly. The idea that heritability is meaningful in the human mental and behavioral arena is attacked. The conclusion is that the heredity-IQ controversy has been a "tale full of sound and fury, signifying nothing". To suppose that one can establish effects of an intervention process when it does not occur in the data is plainly ludicrous. Mere observational studies can easily lead to stupidities, and it is suggested that this has happened in the heredity-IQ arena. The idea that there are racial-genetic differences in mental abilities and behavioral traits of humans is, at best, no more than idle speculation.


Correction for loss of CO2 from blood during measurement of osmotic pressure. During osmolality measurement by the vapor pressure method, exposure of the blood sample to air lowers the blood CO2 content and hence osmolality. A modification of the sample holder of a vapor pressure osmometer is described allowing exposure of the blood sample to a gas mixture with known concentration of CO2 and O2 while inside the closed sample chamber. This restores its CO2 content and hence osmolality. Data are presented comparing the unmodified and modified vapor pressure method with the freezing point depression method. A table was prepared for further correction of osmolality in case the blood's PCO2 differs from that of the gas mixture.


Clinical experience with trisomies 18 and 13. The clinical, cytogenetic, dermatoglyphic, and postmortem observations of the 29 cases of trisomy 18 and 19 cases of trisomy 13 seen in the Department of Medical Genetics from 1963-76 are summarised. Chromosomes were studied in all and 30 were banded. One patient had tertiary trisomy 18 and 8 had translocations of chromosome 13. The features of these patients are described and the syndromes compared with each other and summaries found in the literature.


Radionuclide imaging of metastases from renal-cell carcinoma by 131I-labeled antitumor antibody. On immunofluorescence assay, goat antisera reacted with renal-cell carcinomas from 20 patients, but not with adult normal human tissues (including patient's normal kidney). After in travenous injection, the 131I-labeled antibody localized preferentially in metastatic renal carcinoma in 6 consecutive patients. Labeled antitumor antibodies may have the specificity for tumor imagining which current radiopharmaceuticals lack.


[Distribution of association fibers impinging upon the middle suprasylvian sulcus area (MSs area) in the cat (author's transl)]. Following lesions of various cortical areas of altogether 13 adult cats, the distribution of degenerating fibers in the cortical area surrounding the middle suprasylvian sulcus (MSs area) has been studied with the method of Fink and Heimer. Association fibers from the visual cortex mostly end in the vicinity of fundus of the medial wall of the MSs area and a fair number of fibers do in the fundus area of the posterior portion of its lateral wall. Most of the fibers terminate in layers III-V. Fibers from the auditory cortex terminante in the lip of the lateral wall, while few fibers end in the fundus and the medial wall. The fibers from the somatosensory cortex chiefly end in the vicinity of the fundus terminate in layers III-V. The "association cortex" sends a good amount of fibers to the lip region and the upper area of the media wall and lesser amount to the posterior part of the lateral wall of the MSs. The fibers terminant in layer III. From the present and the previous findings, it has become evident that inputs of different kinds of sensory modalities converge upon th elayers III-IV of the MSs area from the various cortical functional areas, and that the MSs area also sends fibers back to the sensory cortical areas. In addition, it has reciprocal connections with some thalamic nuclear groups, e.g., the "pulvinar posterior" system. Based upon the findings of neuronal connections, it can be suggested that the MSs area may play an important role with regard to the "integration of sensory inputs" in the cat cerebral cortex.


[Metastatic breast carcinoma in the pituitary gland (author's transl)]. Metastatic carcinoma was found in 9 pituitary glands (24%) of 37 patients undergoing transphenoidal hypophysectomy for diffuselly metastatic breast carcinoma. In all cases the preoperative neurological examination was negative, as were neuroradiological studies, including skull X-ray, tomograms of the sells turcicabrain scan, and angiography. Diabetes insipidus, however, was seen more frequently in patients with pituitary metastasis preoperatively (3 of 9) and postoperatively (8 of 9). Four of the nine patients with pituitary metastasis developed severe diabetes insipidus, which continued more than one month, while similar severe disease was seen in three of twenty-seven cases with no pathological evidence of pituitary metastasis. The prognosis in patients with pituitary metastasis was poor, with seven of the nine dying with an average survival of eighteen months. Pathological studies disclosed metastatic lesions in the anterior lobe (78%), posterior lobe (44%), and stalk (11%). The study emphasized that pituitary metastases, usually considered to be rare, occurred in 24% of patients with diffusely metastatic breast carcinoma. Such metastases correlate with the development of severe diabetes insipidus and with poor prognosis.


[Malignant choroid plexus papilloma. An autopsy case report (author's transl)]. Malignant choroid plexus papilloma is a rare disease. The autopsy case of malignant choroid plexus papilloma being suggestive of the youngest in Japan, was reported. This 8-months-old baby had normal delivery history, and the development and growth were not eventful. The patient admitted to the University hospital because of projecting vomiting and meningeal irritating signs at 7.5 months in age, and septic meningitis was most suspected. He died 2 weeks afte the admission. At autopsy, a large papillary tumor with marked necrosis and hemorrhage was seen in the right lateral ventricle. The right lateral ventricle was almost replaced by the tumor. The metastasis to the brain base and the sheeding to the subarachinoidal space of the cerebellum were noted.


Severe stenosis occurring in antibiotic sterilised homograft valves. This paper describes 3 patients who developed late severe stenosis in fresh antibiotics sterilised homograft valves. Two were in the aortic position and one in the mitral. All 3 patients underwent successful reoperation. This complication has not been previously reported in valves prepared by this method.


Overdrive suppression of implanted pacemakers in patients with AV block. Patients being permanently paced for symptomatic AV block were studied by overdrive suppression of the QRS-inhibited pacemaker, in order to observe the underlying heart rhythm. The chest wall stimulation method was used. In complete AV block the escape rhythm recovery time proved highly reproducible on repeated testing on the same day, and in many patients remained so over months or years. Occasionally, a doubling of the escape rhythm recovery time was seen, suggesting initial exit block of the escape focus. Resetting of the escape rhythm usually followed an exponential curve until stabilisation after about 3 minutes. An early escape rhythm with a recovery time of less than 4 seconds was found on every occasion in 21 of 58 patients with complete AV block, and inconstantly in 23 more; in 14 it was never observed. Accidental pacing failure was seen in 15 patients. The overdrive suppression test was helpful in selecting pacemaker dependent patients.


Use of subclavian vein for permanent cardiac pacing. The subclavian vein has been used to implant permanent pacing catheters in 40 patients with symptomatic heart block. Though the cephalic and external jugular veins are usually preferred for this purpose in Britain, the use of these veins has certain disadvantages. In this study subclavian venepuncture by the infraclavicular approach was performed without diffculty and found to be a safe procedure. Three months after implantation, 7.5 per cent of patients had developed catheter tip dislocation and 87.5 per cent of patients were entirely free of complications.


Noninvasive assessment of pressure drop in mitral stenosis by Doppler ultrasound. A noninvasive method is described for measuring the pressure drop across the mitral valve in mitral stensois by Doppler ultrasound. A maximum frequency estimator was used to record maximum velocity in the Doppler signal from the mitral jet. Provided the angle between the ultrasound beam and the maximum velocity is close to zero the pressure drop can be calculated directly. Good correlation was found between Doppler measurements and simultaneous pressure recordings during heart catheterisation in 10 patients. No false negative or false positive diagnoses of mitral stenosis were made among 55 patients (35 patients with mitral stenosis and 20 patients with other valve lesions). The measurements were easy to perform in most patients and the method seems well suited both to diagnose and to follow patients with mitral stenosis.


Coronary thrombosis in pathogenesis of acute myocardial infarction. Histopathological study of coronary arteries in 108 necropsied cases using serial section. An extensive histopathological study was carried out on the hearts of 108 patients with electrocardiographically proven acute myocardial infarction dying after admission to a coronary care unit. The occluded or the narrowest segments of the coronary arteries were examined at intervals of 100 mu using serial sections. Serial sectioning is important in such a study because the pathology of the lumen can vary considerably within a 2 to 3 mm segment. A high incidence (80.3%) of thrombus formation corresponding to the site of infarction was observed. These thrombi occluded the vessel lumen, were usually found proximally in the coronary arteries, and were associated with a ruptured atheromatous plaque in 90.8 per cent of cases. It is postulated that an increase of intraplaque pressure resulting from a honeycomb-like accumulation of foam cells, cholesterol clefts, and blood infiltration through the injured endothelial cells is the cause of rupture of the atheromatous plaque. This rupture into the vessel lumen may precede, and be responsible for, formation of thrombus and the onset of acute myocardial infarction.


A score for prescribing digoxin.

A score for prescribing digoxin. A simple method of selecting a maintenance dose of digoxin, suitable for an adult patient, was derived from data on 129 patients taking digoxin. Eight items of readily available information are required for entry into the prescribing aid: out/inpatient status, sex, age (less/not less than 70 years), weight (allocated to one of four ranges), whether or not chronically house/chair bound, cardiac rhythm (sinus/other), serum creatinine concentration (allocated to one of four ranges), and diuretic therapy (prescribed/not prescribed). The recommended dose is given in terms of size and number of tablets to be prescribed. Using this method 72.3 per cent of patients are expected to achieve mean steady state serum digoxin concentrations within the therapeutic range, 6.5 per cent above and 21.2 per cent below. This performance would be considerably better than that expected from the use of other prescribing aids. If available, routine measurement of the serum digoxin concentration during follow-up is recommended to detect those who might benefit from a change, usually an increase, in dose.


Pericardial effusions in patients with end-stage renal disease. Echocardiography has greatly increased the accurate recognition of pericardial effusion. Echocardiograms were performed prospectively on the total group of 35 stable asymptomatic patients on chronic haemodialysis to determine the incidence of pericardial effusion. Effusions were shown in 11 per cent (4/35); only 6 per cent (2/35) were estimated as greater than 100 ml. For comparison, records were reviewed retrospectively from 41 haemodialysis patients referred during a 27-month period for echocardiographic assessment of suspected pericardial effusion. These 41 patients came from a total group of 108 patients treated with chronic dialysis over this interval. Of 41 examined, 21 (51%) or 21 of 108 (19%) of the population at risk had an effusion. Of 21 with echocardiographic effusions, 15 (71%), or 15 of 41 (37%) of those with clinically suspected effusion, had more than 100 ml fluid. Gross (greater than 100 ml) pericardial effusions are infrequent in stable, asymptomatic patients with end-stage renal disease. When clinical findings suggest pericardial disease, the echocardiographic demonstration of over 100 ml pericardial fluid is indicative of new effusion, rather than coincidental pre-existing effusion.


Isolated acquired pulmonary valve regurgitation. Report of long-term follow-up. A patient is reported with isolated pulmonary valvular regurgitation acquired probably as a result of endocarditis at age 22 years. The patents remained essentially asymptomatic with physical findings compatible with haemodynamically significant pulmonary regurgitation until death at age 85 years. A necropsy confirmed the presence of isolated severe pulmonary valvular destruction. This long-term follow-up lends further support to the concept that significant volume overload of the right ventricle from pulmonary regurgitation is well tolerated and usually does not require surgical intervention.


Right atrial myxoma: an echocardiographic study. A case of right atrial myxoma is reported in a 29-year-old man. Though it was a large tumour, the diagnosis remained unsuspected for a long time. Multiple echo recordings strongly contributed to the diagnosis. After surgical removal, the post-operative course was uneventful.


Transposition of the great arteries. New technique for anatomical correction. We describe a new technique for the correction of transposition of the great arteries by "detransposition". An aortopulmonary window is created and a patch placed over this and the coronary ostia so that the coronary arteries arisen from the new aorta. Thus, direct surgery on the coronary arteries is avoided with all the complications which may result from this in neonates and infants. A 4.2 kg infant, with transposition and ventricular septal defect, was successfully operated on using this technique. We discuss the indications for this type of operation and conclude that, until we have more experience, it should be used only in children with a left ventricular pressure at least half systemic.


Histopathology of the ductus arteriosus after prostaglandin E1 administration in ductus dependent cardiac anomalies. The histology of the ductus arteriosus was studied after prostaglandin E1 (PGE1) administration in 4 infants with ductus dependent cardiac malformations. Pronounced pathological changes were found in each instance. The changes consisted of oedema of the media with separation of medial components by clear spaces, pathological interruptions of the internal elastic lamina, and intimal lacerations, some of which extended into the media. The findings suggest that PGE1 administration has a profound weakening effect on the structure of the wall of the ductus arteriosus, rendering the vessel prone to laceration.


Treatment of patients with transposition of great arteries and pulmonary vascular obstructive disease. Twenty-two patients with transposition of the great arteries with or without ventricular septal defect and one with double outlet right ventricle, d-malposition, and severe pulmonary vascular obstructive disease were treated surgically. All were cyanosed and had very limited exercise tolerance. Preoperatively, systemic arterial oxygen saturation (SaO2) varied from 45 to 79% (mean 65), haemoglobin was 13 to 23 g/dl (mean 19). Pulmonary arteriolar resistance was 6.4 to 35 units m2 (mean 17). In the patients with a ventricular septal defect the Mustard operation was done without closure of the ventricular septal defect, and in the 3 patients with intact ventricular septum the Mustard operation was combined with creation of a ventricular septal defect. All patients survived the operation and improved. Postoperative SaO2 ranged from 75 to 96% (mean 89) and haemoglobin from 10.6 to 17.8 g/dl (mean 14.0). This improvement was significant (P less than 0.05). Five patients have had a postoperative cardiac catheterisation. The pulmonary arteriolar resistance remains high in all. Postoperative follow-up varies from 4 to 40 months (mean 14 months). So far there have been no late deaths and all patients remain improved.


99mTc-imidodiphosphonate: a superior radio-pharmaceutical for in vivo positive myocardial infarct imaging. I: Experimental data. 99mTc-Imidodiphosphonate (99mTc-IDP) was investigated as an agent for nuclear medicine imaging of acute myocardial infarctions. For this purpose a suitable animal model was found. After coronary artery ligation reproducible myocardial infarcts were obtained with 80% of surviving animals. Scans of the myocardial infarcts were recorded with a high resolution gamma camera and good quality images were obtained. 99mTc-IDP ratios for normal and infarcted tissue were calculated and compared with similar data available from other 99mTc-labelled phosphates. With an infarct/normal ratio of 21:1, 99mTc-IDP is so far the best radiopharmaceutical for nuclear medicine imaging of necrosed heart muscle. Images of the myocardial infarcts have been recorded as early as 6 hours after infarction.


99mTc-imidodiphosphonate: a superior radio-pharmaceutical for in vivo positive myocardial infarct imaging. II: Clinical data. 99mTc-Imidodiphosphonate was investigated as a new myocardial infarct imaging agent. In the acute phase, 50 patients admitted to the coronary care unit were serially scanned over a period of 7 days. A mobile gamma camera linked on line to a remote data processor was used. Because of higher uptake in infarcted myocardium and faster blood clearance, superior images than those recorded with 99mTc-pyrophosphate were obtained. Its ease of preparation, low cost, and favourable dosimetry (because of its label with conventional 99mTc) transforms this agent into the present radiopharmaceutical of choice for acute infarct imaging in particular if sizing and follow-up is intended versus time and type of treatment. In this series, no false positive cases were seen. The sensitivity of the method in the detection of full thickness myocardial infarction was 95%. It dropped to 70% in the detection of subendocardial infarction. However, some of these apparent false negative cases may reflect severe ischaemia without infarction. It is postulated that this discrimination may not always be realistic.


Clinical assessment of calibrated jugular pulse recording. Calibrated jugular pulse tracings and cardiac catheterisation were performed on 50 consecutive patients with organic heart disease. Twenty normal adults had calibrated jugular pulse tracings and served as controls. The height of the jugular 'A' and 'V' waves was quantified as a percentage of a known displacement, rendering measurements independent of the amplification used in recording technique. A close correlation existed between the size of the calibrated jugular 'A' and 'V' waves and the actual magnitude of the right intra-atrial pressure changes (A wave, r = 0.72; V wave, r = 0.80). Patients who were free of pulmonary hypertension or tricuspid disease had calibrated 'A' and 'V' waves similar in height to the control population. An enlarged 'A' wave was usually associated with conditions restricting flow into the right ventricle. An enlarged 'V' wave generally indicated tricuspid regurgitation. These changes are often subtle and are not apparent in conventional venous tracings or at the bedside. We conclude that the calibrated jugular pulse tracings can accurately separate normal from abnormal venous waves and expand the diagnostic potential of the jugular pulse.


Effects of atrial fibrillation on prognosis of acute myocardial infarction. Nine hundred and sixty-nine coronary care patients with acute myocardial infarction were followed for one year. Atrial fibrillation was documented in 107 patients. Compared with patients without atrial fibrillation, those with this arrhythmia were older, had clinically more severe infarction, and had a higher frequency of ventricular fibrillation or tachycardia, and right bundle-branch block. They had similar past histories of ischaemic heart disease and coronary risk factors. Patients with atrial fibrillation had a higher total mortality at 3 months and 12 months. The presence of atrial fibrillation was not associated with any significant increase in mortality within any decade of age or within any subgroup of clinical severity of infarction. The frequency of atrial fibrillation was similar in anterior and inferior infarction. Multiple episodes of atrial fibrillation occurred in 52 patients and episodes usually lasted for over 1 hour. In 50% of patients with single episode of atrial fibrillation the initial ventricular rate was greater than 120 beats per minute.


Secondary leiomyosarcoma of the right ventricle. A surgical report. A 48-year-old woman developed symptoms related to a tumour attached to the outflow tract of the right ventricle. Eleven years earlier she had undergone hysterectomy for leiomyosarcoma, and 4 years later a retroperitoneal mass was removed. One year later a further retroperitoneal mass was removed, and after a further 4 years a cutaneous tumour was removed from her back. Histologically these three tumours were identical with the leiomyosarcoma removed with the uterus at the primary operation. A confident preoperative diagnosis of recurrent leiomyosarcoma within the pericardium was made, and it was possible to remove this tumour using cardiopulmonary bypass with relief of symptoms. The patient remains well 15 months after surgery.


Intracardiac heterotopia--mesenchymal and endodermal. A case is reported of an intracardiac 'epithelial heterotopia' with a predominant mesenchymal component. This is thought to have resulted from the differentiation of aberrant primitive cell(s) displaced into the heart during its development. Though microscopically resembling a myxoma, this lesion is clearly distinguished by the presence of glandular structures. The myxoid component exhibited a startling invasiveness which resulted in occlusion of the superior vena cava, causing symptoms very early in life and death at the age of 6 months.


Effect of cyclopropane on pulmonary vascular resistance and hypoxic pulmonary vasoconstriction in the isolated perfused cat lung. Cyclopropane was found to produce no significant changes in pulmonary vascular resistance or the pulmonary vasoconstrictor response to alveolar hypoxia in isolated cat lungs perfused at constant flow.


Cardiac performance during prolonged halothane anaesthesia in the cat. Isolated heart muscle study. The contractile response of papillary muscles, isolated from normal cats, to prolonged administration of halothane at minimum alveolar anaesthetic concentration (MAC) was studied. Average values of maximal velocity of shortening (Vmax) and maximal developed force (Fm) obtained in 12 muscles during the 1st, 2nd and 3rd hour of exposure to halothane anaesthesia were significantly less than those obtained during the control period and after recovery from halothane. There were no significant differences in values over a 3-h period. When post-extra-systolic potentiation was induced by paired electric stimulation, average values of Vmax and Fm increased significantly. We conclude that prolonged administration of halothane at a constant concentration resulted in a sustained depression of myocardial contractility without tissue tolerance. The myocardium depressed by halothane, however, still retains the ability to respond to additional inotropic stimulation.


Simultaneous trace analysis of nitrous oxide and halothane in air. A gas chromatographic method for the simultaneous analysis of halothane and nitrous oxide in operating theatre atmospheres has been developed and evaluated. The flame ionization detector is suitable for the quantitative analysis of halothane in concentrations approaching one part per million. The frequency-modulated electron capture detector is highly sensitive to nitrous oxide but we have found it to be non-linear over the range 25--1000 p.p.m. The overall reproducibility of the gas chromatographic method based on the dynamic technique of standard preparation is approximately 4%. Effective exposure of personnel to pollutant anaesthetics is assessed by the analysis of end-expired gas.


Failure to replicate negative effects of trace anaesthetics on mental performance. Twenty-four male subjects individually undertook a selection of cognitive tasks during each of two different 2-h sessions in a climatic chamber. Twelve subjects breathed a mixture of air, nitrous oxide 1600 p.p.m. (v/v) and halothane 16 p.p.m. (v/v) during the first session, and air alone during the second session 1 week later. For the other 12 subjects the order was reversed. The tests comprised learning a list of word-number pairs, solving a set of anagram problems, recognizing words and numbers, recalling word-number pairs and performing a four-choice audiovisual reaction time task. Testing was commenced after 45 min of exposure to the atmospheric conditions. A strong learning effect both within and between sessions was observed on the audiovisual task. None of the tasks, however, reflected any adverse effect of the trace anaesthetics.


Plasma concentrations of pancuronium during predetermined intensities of neuromuscular blockade. The plasma concentrations of pancuronium were monitored during i.v. infusions of the relaxant in dogs. Pancuronium was administered at rates which maintained the degree of neuromuscular blockade at three predetermined levels. The concentrations of the drug in the blood were consistent for any one animal but showed considerable overlap for the three levels of paralysis between animals. Concentrations obtained during infusion and which maintained the twitch response at 20% and 80% of control were compared, in the same dogs, with concentrations obtained during recovery from a bolus injection of pancuronium. When the infusion maintained the twitch response at 20% of the control value, the mean plasma concentration of pancuronium was 0.152 microgram ml-1. That measured after the bolus injection was 0.156 microgram ml-1. The concentrations at 80% of control were 0.094 microgram ml-1 and 0.083 microgram ml-1 respectively. The agreement between these results suggests a relationship between the plasma concentration of the relaxant and its effect during the termination of the action after a large bolus injection of the drug. As this occurs chiefly during the postdistribution equilibrium, the relatively slow decrease in plasma concentration would appear to become the rate-limiting factor in recovery from paralysis.


Porcine malignant hyperthermia. VI: the effects of bilateral adrenalectomy and pretreatment with bretylium on the halothane-induced response. The effects of bilateral adrenalectomy, together with the i.v. administration of bretylium tosylate 20 mg kg-1 on halothane-induced malignant hyperthermia (MH), were investigated in six Pietrain pigs. All six animals survived the halothane challenge, and failed to show any signs of increased muscle metabolism. Bilateral adrenalectomy alone prevented halothane-induced MH in three out of four Pietrain pigs, whereas the i.v. administration of bretylium alone protected only one pig out of an additional four animals studied. The results show that complete adrenergic blockade inhibits the susceptibility of Pietrain skeletal muscle to halothane and that the adrenal medulla makes an important contribution to this response.


A low pass filter with amplifier for measurement of active and passive tensions of skeletal muscle in vitro. When displaying and measuring passive and active twitch tensions developed by skeletal muscle in vitro, the problems of amplification may be resolved by recording two traces. One, recorded at relatively low gain, is used for measurements of twitch tension amplitude. The other, recorded simultaneously, is a modified version of the first trace, in which the voltage signals are passed through a suitably constructed low pass filter, amplified and displayed. This second trace, recorded at relatively high gain, is used for measurements of changes in passive tension and contracture responses of relatively small amplitude.


Impairment of oxygen transfer in the lung by increasing oxygen concentration during halothane and trichloroethylene anaesthesia. Two groups of 10 patients were studied during artificial ventilation with a mixture of oxygen, nitrogen and either halothane or trichloroethylene. Arterial blood and respiratory gas smapling was performed at FIO2 values of 0.33, 0.5 and 0.75. The efficiency of oxygen transfer, expressed as the difference between pulmonary end-capillary and arterial oxygen content, was found to decrease progressively in most patients as the alveolar partial pressure of oxygen increased. This pattern of response may be explained by the effect of oxygen on regulatory reflexes in the lung.


Placental blood flow during caesarean section under lumbar extradural analgesia. The effect on intervillous blood flow of lumbar extradural analgesia for Caesarean section was studied in nine healthy women using xenon-133. Extradural anaesthesia was performed with lignocaine 1 1/2% 16--20 ml with adrenaline 5 microgram ml-1. Impairment of placental blood flow during the block was observed in seven patients, but the mean decrease (13% from the control value) was not statistically significant. The most notable decrease in intervillous blood flow occurred in two patients with simulateous arterial hypotension.


The action of commonly used antiemetics on the lower oesophageal sphincter. The effects of five antiemetic drugs on the lower oesophageal sphincter (LOS) were studied in five groups, each comprising eight healthy volunteers. Cyclizine, prochlorperazine and metoclopramide have a desirable functional effect on LOS, while promethazine and droperidol were associated with evidence of increased gastro-oesophageal reflux.


Methaemoglobinaemia induced by mafenide acetate in children. A report of two cases. The local application of mafenide acetate (Sulfamylon, Winthrop) applied to extensive burn areas resulted in acute methaemoglobinaemia.


Monocytes and macrophages in malignant melanoma. II. Lysis of antibody-coated human erythrocytes as an assay of monocyte function. Peripheral blood mononuclear cells will lyse antibody-treated human erythrocytes. Using Group A red cells and a hyperimmune anti-A1 serum, we have devised a microassay for the cytolytic capacity of mononuclear cell suspensions. The effector cells responsible for red-cell lysis are mononuclear, adherent and phagocytic, and their activity is blocked by aggregated IgG. Their presence correlates well with non-specific esterase-containing cells and we conclude that they are monocytes. Dose-response curves of red-cell lysis plotted against numbers of monocytes were used to derive a simple parameter expressing the number of monocytes needed to lyse 15% of the 51Cr-labelled red cells. The assay was applied to a group of 27 normal controls and 36 patients with a histologically proven diagnosis of malignant melanoma. The results indicate that monocytes from patients show significantly greater lytic activity than those from the controls. These data suggest that monocytes from cancer patients are in some way activated, and that other defects in monocyte function which have been detected in cancer patients (defective chemotaxis and maturation) may be associated with monocyte "activation".


Studies with a spontaneous mouse tumor. I. Growth in normal mice and response to Corynebacterium parvum. Growth of isogeneic transplants of a spontaneous murine adenocarcinoma, which is virtually devoid of tumour-specific transplantation antigens, is inhibited by i.v. injection of C. parvum 3 days after tumour inoculation, or by mixing a small dose of C. parvum with the tumour inoculum. Moreover, the therapeutic effect of cyclophosphamide, followed by i.v. or i.p. injection of C. parvum 5 days later, on established transplants of the same tumour is greater than that of cyclophosphamide alone. These findings are consistent with the hypothesis that in both situations (i.e. before the appearance of a palpable tumour and after reduction of an established tumour transplant with cyclophosphamide) the effect of C. parvum is largely due to activation of macrophages or macrophage precursors. They have the important practical implication that adjuvant therapy with C. parvum may be of value, even with tumours which are devoid of TSTA.


Extrapulmonary colony formation after intravenous injection of tumour cells into heparin-treated animals. Recent data on extrapulmonary colony formation after heparin administration are inconclusive. A systematic study of this topic was undertaken with 4 experimental tumour systems and 2 distinct periods of reduced clotting capacity in rats and mice. I.v. injection of various numbers of tumour cells into i.p. heparinized animals leads to: (1) Significant reduction in the number of lung colonies. The effect after 9 h anti-coagulation is equal to or probably greater than after 2 h. (2) The reduction in the number of lung colonies caused by heparin is independent of the number of cells injected. (3) The number of extrapulmonary extrathoracic colonies is significantly increased by heparin in 3 of the 4 tumour systems. (4) The number of extrapulmonary intrathoracic colonies is probably unaffected. (5) The increase in extrapulmonary extrathoracic colony formation is not related to the degree of reduction in lung colonies. These data lead to the conclusion that the capacity of the lung capillaries to trap tumour cells can be decreased by heparin-induced alterations in fibrin formation. This results in a lodgement of tumour cells throughout the body which is far more pronounced than in animals with normal clotting capacity.


Responses of proliferating and non-proliferating Chinese hamster cells to cytotoxic agents. The effects of various cytotoxic chemicals, as measured by viable cell counts, colony-forming ability and proliferative capacity, have been studied using Chinese hamster cells in exponential and plateau (stationary) phases of growth. The proliferating cells were altogether more sensitive to the action of the drugs than non-proliferating cells. However, imuran (azathioprine) a purine antimetabolite, was more effective against the plateau-phase cells. The observed response of cells to imuran could be detected at a wide range of concentrations (1-100 microgram/ml). These findings are discussed in view of the possible ability of imuran to interfere with active metabolic processes in non-proliferating cells.


Different esterase activities of exponential and plateau phases of EMT6 cells monitored by flow cytofluorimetry. The reaction rates of enzymes hydrolysing fluorescein diacetate have been studied in populations of intact tissue-culture EMT6, cells using flow cytofluorimetric techniques. It was found that the activity of these enzymes increased in plateau phases and that this correlated inversely with plating efficiency. Highly abnormal substrate-dependent reaction velocity kinetics were found in 14-, 21-, 28- and 35-day cultures.