[Pulmonary function in papain induced emphysema in dogs (author's tranls)]. By intratracheal injection of the protease Papain to experimental animals parenchymal changes in the lung can be induced, that resemble human emphysema. Papain (dosage 26 to 112 mg, 1 to 4 injections) was given intratracheally to 8 bastard dogs, (weighing from 12.5 to 20 kg) during light general anesthesia. Pulmonary function was assessed in weekly intervals and related to morphologic changes in the lung. Static compliance of the lung and FRC measured during respiratory arrest were increased after papain, bronchial resistance, measured while artificially ventilated at constant pressure was also increased. Changes of static lung compliance and FRC were seen after the first administration of papain, but further increased with time of observation and after multiple doses of papain. Increase of resistance was not found before 5 weeks. At quiet breathing resistance was not increased at all. No significant changes were found of arterial pO2 and pCO2, pH, standard and actual bicarbonate, diffusion capacity for O2, tidal volume, minute ventilation and ventilatory rate. Morphological findings confirmed the changes described by others. Pulmonary function appears to be pathological at a time when morphology still seems to be normal. The question is discussed to what extent the model of experimental emphysema induced by proteolytic enzymes can contribute to the understanding of human pulmonary emphysema. Lung function in the course of experimental emphysema is compared with function in different clinical types of emphysema.


The p-hydroxylation of amphetamine and phentermine by rat liver microsomes. 1. The products of p-hydroxylation of amphetamine and phentermine by two different preparations of rat liver microsomes were identified and quantitatively determined. At low concentrations (muM) significant proportions of the substrates were metabolized to the p-hydroxy derivatives by an NADPH-dependent system. The enzyme system was inhibited by higher substrate concentrations (mM) and was not induced by either phenobarbital or 3-methylcholanthrene. 2. The properties of this in vitro system are consistent with reports on in vivo studies of this reaction.


Effect of mineral acids on iron bacteria. The oxidative ability of Thiobacillus ferroxidans in the presence of different concentrations of H2SO4, HC1, HNO3, and their mixtures was investigated. Bacteriological oxidation of FeSO4 is expressed as a function of time and acid concentration. For each acid and for their mixtures lethal concentrations for T. ferroxidans were found experimentally. On the basis of the lethal concentration for each acid separately the lethal concentrations of their mixtures were computed and it was found that they are in good agreement with the experimental data.


[The effect of lumbar peridural anesthesia with catheter on the maternal and fetal acid-base status and the 1 minute apgar score (author's transl)]. Comparison of 650 deliveries with P.A. and of 928 deliveries without P.A. during the same period. PH from the umbilical artery and 1 minute Apgar score were studied in three groups of patients: 1.) All deliveries, 2.) Spontaneous vaginal deliveries without maternal or fetal risk, 3.) Operative vaginal deliveries. The only significant differences were found among the operative vaginal deliveries: The infants of the peridural group showed a higher incidence of pH-values above 7,2 than those of the non peridural group. Analysis of the maternal acid-base status showed less respiratory alcalosis and less metabolic acidosis in the peridural group. The neonates of this group showed a lower post partum metabolic acidosis than those in the non peridural group.


A rare type of low birthweight dwarfism: the Dubowitz syndrome. Two patients with the Dubowitz syndrome are presented. This presumably recessive inherited syndrome was first defined by Grosse et al. (1971). So far 11 patients with this syndrome have been described. Major clinical findings are intrauterine and postnatal growth retardation, considerable microcephaly, mild mental retardation, hyperactivity, hyperextensibility of joints, eczema and a characteristic appearance of the face due to marked epicanthic folds, blepharophimosis, broadening of the bridge and tip of the nose and retrognathia. Minor anomalies as clinodactylyl of the firth digits, cutaneous syndactyly of toes, foot deformity, sacral dimple and cryptorchidism may be seen. The exclusion of the non genetic fetal alcohol syndrome presents serious diagnostic problems.


[Optimized determination and properties of NADPH-dependent glutathione reductase in serum. Studies on serum glutathione reductase, I. (author's transl)]. Reaction conditions were optimized for the determination of serum glutathione reductase, which has not yet been investigated systematically. Imidazole was found to be the most suitable buffer material; the highest glutathione reductase activity in serum was always obtained with imidazole/HCl buffer, which, in contrast to all other tested buffers, also resulted in the maximal enzyme activity without preincubation. In imidazole buffer, the pH-activity curve of serum glutathione reductase shows a broad optimum between pH 6.5 and 6.9. A GSSG concentration of 2 mmol/l and a NADPH concentration of 0.43 mmol/l gave maximal enzyme activity and a linear reaction over 10 min up to 20 U/l test solution. An investigation of serum glutathione reductase activity from 100 clinically healthy probands gave values between 20 and 50 U/l. In the optimized assay system the glutathione reductase in the serum reacts specifically with GSSG and NADPH.


Serum dopamine beta-hydroxylase: assay and enzyme properties. A method for the estimation of dopamine beta-hydroxylase activity in human serum is described, based on a thin layer chromatographic separation of the substrate ([14C]tyramine) from the reaction product ([14C]octopamine). The basic properties of the human serum enzyme, investigated by this method are described.


Serum alpha-N-acetylglucosaminidase: determination, characterization, and corrective activity in Sanifilippo B fibroblasts. Assays for the determination of serum alpha-N-acetylglucosaminidase (EC 3.2.1.50) activity are described employing p-nitrophenyl-N-acetyl-alpha-D-glucosaminide, phenyl-N-acetyl-alpha-D-glucosaminide, and UDP-N-acetylglucosamine as substrates. A log normal distribution of the serum enzyme activity was found. The determination of serum alpha-N-acetylglucosaminidase activity proved to be a valuable tool for the recognition of homozygous and heterozygous carriers of the Sanfilippo B gene.


The effect of heavy metal ions on the rate of decomposition of N-ethyl-N-nitrosourea and other carcinogenic N-nitrosamides. The decomposition of ethylnitrosourea (ENU) in aqueous solution is enhanced by Cu2+ ions. Ni2+ shows a similar, but less pronounced effect. The decomposition rate of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), a compound known to be relatively stable in aqueous solution, is strongly enhanced by the addition of Cu2+ and to a smaller extent also by Ni2+ ions. On the other hand the stability of N-methyl-N-nitrosourethane is not influenced by heavy meatal ions. The influence of Cu2+ ions on the decomposition rate of ENU is similar to that of OH-anions, influencing the reaction kinetics on a molar basis. The increase in decomposition rate of ENU by copper ions is not seen in the presence of blood serum or other complexing agents. The results are discussed in relation to the known enhancement in toxicity and carcinogenicity of ENU by heavy metal salts in animal experiments.


[Gelelectrofocusing of protektin anti AHP from the albumin gland of Helix pomatia (author's transl)]. The protektin anti AHP from the albumine gland of Helix pomatia is a very interesting substance because of its ability to agglutinate erythrocytes of blood group A as well as group C streptococci. Purification is possible by reversible absorption on Sephadex G200. Isoelectric focusing in a sucrose density gradient is difficult, because the protein precipitates at the isoelectric point. The agglutinin, which is homogeneous in disk electrophoresis experiments (in an alkaline gel system as well as in an acidic one), shows around 9 bands in gelelectrofocusing. All components are able to agglutinate group C-streptococci. Complex formation between protein and ampholytes has been excluded by experiments in gels containing 7M urea. The region of the isoelectric points of the components is between pH 6 and pH 8. The inhomogeneity in gelelectrofocusing is caused probably by differences in the subunits of the protein molecule.


[Giant-cell (Takayasu) arteritis as a cause of renovascular hypertension]. In a young female with renovascular hypertension multiple stenoses affecting both renal arteries, abdominal aorta and left axillary artery could be demonstrated. The elevated blood pressure could be normalized by bypass operation of the renal arteries. Histopathologic findings were those of giant cell (Takayasu) arteritis.


[The hatching of the eggs of the liver fluke Fasciola hepatica L. under various CO2-concentrations (author's transl)]. The presupposition for the hatching of the eggs of Fasciola hepatica is the presence of undissociated CO2 with the most effective concentration of 2-10 mMols/l. Higher concentrations show inhibitory effects (Abb. 6). In hatching pH has only importance in dissociation of carbonic acid and so in maintaining free CO2. To provide for sufficient CO2 at higher pH - but below 8.3 - the concentration of carbonic acid must be increased by higher concentrations of metallic ions electrically neutralized by hydrogen carbonate (e.g. in Abb. 1-4). Higher pH is necessary for miracidia surviving. Beside the wellknown hatching factors of exposure to light and cooling, darkening is a new found factor (s. Abb. 7) as well as sufficient increase of CO2 itself. The effect of light stimulation is lasting for at most 3 h with exponential decrease (Abb. 7). At low CO2-pressure the occurrence of hatching is greater without any oxygen (Abb. 5).


Monoxenic and axenic cultivation of carrier and patient strains of Entamoeba histolytica. All of five strains of Entamoeba histolytica, isolated from symptomatic cases of amoebiasis, could be adapted to axenic growth on the TP-S-1 medium of Diamond (1968). Four axenic strains were started from amoeba-Crithidia cultures; one could be axenized directly after isolation from a case of cutaneous amoebiasis. Attempts to monoxenize, resp. axenize strains, isolated from Dutch, asymptomatic carriers, were less successful. Only three out of ten strains could be submitted to bacteria-free growth. These three strains, however, originated probably from a recent case of intestinal amoebiasis. The results, suggesting that highly virulent strains can be easier cultivated bacteria-free than those with low or no virulence, are further discussed. The yield of axenic amoebae per tube fluctuates largely depending on many factors such as the strain, the number of transfers (i.e. degree of establishment), the quality of Panmede liver digest and serum in the TP-S-1 medium, and the care of manipulating the cultures. For optimal growth, a more acid medium was required  in an amoeba-Crithidia culture than in an axenic culture. Multinucleated, giant amoebae were frequently observed in axenic cultures.


Studies on the excystment of trematode metacercariae in vitro. Excystment of metacercariae of Parorchis acanthus, Posthodiplostomoides leonensis, Posthodiplostomum sp. and Clinostomum tilapiae was found to be an active process initiated by the metacercariae when the correct physico-chemical conditions exist in the environment; but in the excystment of Posthodiplostomum nanum the metacercaria seems not to take part in the process. Temperature, osmotic pressure, pH and eH are factors which influence all the five species studied. Fresh ox bile was found not to be an absolute necessity for the excystment of the five species studied but its presence in the medium increased the rate of excystment of three species.


A comparative study of the two alternative larval forms of Hymenolepis nana, the dwarf tapeworm, with special reference to the process of excystment. Studies of the cysticercoids of Hymenolepis nana from insects and from mouse villi revealed important differences in cyst structure and function. The insect form resists low pH unless treated with bile salts which render the cyst permeable and reduce infectivity to mice. Bile salts are not essential for scolex activation. Activation is inhibited by pH 2.5 and under and by 1% succinic acid up to pH 4.0. The importance of scolex immobility and energy conservation in relation to cyst impermeability is discussed. The villus cysticercoid has no special insulating layer. It is vulnerable to low pH and cannot infect mice orally. Bile salts are without effect and excystment occurs unaided by external agents. The structural differences between the two forms revealed by the electron microscope may be attributed to changes in the relative rates of development of the various tissues.


[Phospholipase D of cereals (author's transl)]. Phospholipase D containing water insoluble fraction was isolated from mature barley; the enzym preparation only had weak phospholipase B activity. The phospholipase D of barley was activated by Ca2+, diethyl ether and sodium dodecyl sulphate (SDS); EDTA inhibited the enzyme to an extent of 10% of the original activity. Diethyl ether and SDS showed and additive effect. Phospholipase D activated by CaC12, diethyl ether and SDS exhibited a sharp optimum at pH 6.6. Lysophosphatidylcholine was hydrolysed much slower than phosphatidylcholine. Diethyl ether and SDS also increased the breakdown of the lysophosphatidylcholine.


Mitochondrial enzyme pathways and their possible role during curing. The velocity of oxidation of exogenous ferrocytochrome c by nitrite under anaerobic conditions in the presence of skeletal muscle mitochondria is dependent upon pH over at least the range 5.6-6.7, increasing markedly as the pH is lowered. A product of the reaction is the complex formed between nitric oxide and ferricytochrome c. At levels up to 20 mM, nitrite inhibits aerobic cytochrome oxidase action; at higher concentrations, however, a partial resuscitation of the oxidation of ferrocytochrome c occurs, the enhancement of reaction velocity being considerably greater at pH 6.0 than at 6.5. Mitochondrial respiration is also inhibited by nitrite but no similar resurgence was, however, observed and thus the oxidation of ferrocytochrome c by high levels of nitrite is considered to be a direct non-enzymic action. Under anaerobic conditions, the rate of increase of the velocity constant of the oxidation of ferrocytochrome c with nitrite concentration in the presence of muscle mitochondria similarly decreased with rise of pH over the same range. The permeability of the muscle mitochondrion to nitrire has been demonstrated by swelling studies and by the rapid conversion of endogenous ferrocytochrome a3 into its nitrosyl-derivative. Over longer periods of anaerobic incubations of mitochondria with nitrite, oxidation of endogenous cytochromes occurs with the formation of nitrosylferricytochrome c. Above a nitrite concentration of 0.3 mM, the mitochondrial enzyme system probably involved is increasingly inhibited but by a concentration of 30 mM a direct non-enzymic oxidation has intervened. Commercial vacuum packed bacons were examined by electron microscopy. Mitochondria were clearly recognisable although they contained fewer cristae than those observed in fresh meat.


[Contribution to postmortem diagnostics of poisoning due to insulin (author's transl)]. In a case of lethal poisoning due to insulin a significant low level of lactic acid and a corresponding high pH value in the brain tissue were detected. Methods used to determine lactic acid and pH in the brain tissue are recommeded for postmortem diagnostics of insulin poisoning.


[The significance of meconium-containing amniotic fluid at the onset of labor following a normal pregnancy]. The delivery process of 218 gravids admitted after a normal course of pregnancy with meconium containing amniotic fluid are analysed. The higher operative frequency (25,2%) in comparison with the test group (10,9%) and the fact that in 4 fetuses the pH value on admission was under 7,20 confirm the recommendation to make obligatory the admission amnioscopy of all gravids at the beginning of birth. This practice involves continuous medical shift work. The perinatal mortality of the analysed deliveries was 0,46%.


[Determination of bilirubin in the amniotic fluid by means of the chloroform-extraction method]. A reproducible method for the determination of bilirubin in amniotic fluid by measuring the extinction of the the chloroform extract is described. The measurements can be carried out by means of a simple spectrophotometer. In case of extraction of amniotic fluid containing blood informative results are obtained as well. Since the extinction values are equal to the deltaE-values it is possible to determine the degree of morbus haemolyticus fetalis using the schema of Liley.


[Emissions from combustion of indoor dust (author's transl)]. Combustion of dust is an old problem which has gained a new importance since the introduction of electric storage heaters for space heating. Physico-chemical changes caused by heating indoor dust in a model apparatus were investigated. Four dust samples of different origins were heated at three temperatures (200, 400, 600 degrees C) for three residence times (5, 15, 30 min). The higher the temperature, the higher the weight loss expressed as percentage (15 to 75%). The residence time had no effect on the loss. Three dust samples showed pH of about 7 before heated, while the fourth showed pH of about 10. After heating to 200 degrees C, the pH of one of the samples rose from 7 to 10. When heated to 400 and 600 degrees C, all the samples showed pH values between 10 and 11. The residence time had no effect. The pH of the gaseous reaction products did not show uniform pattern at 200 degrees C. At 400 degrees C, the measured pH was between 7.5 and 8.5, while at 600 degrees C no further change was observed. Changes in pH took place during the first fifteen minutes. Chemical analysis of the reaction products with help of detector tubes indicated that dust samples when heated emit carbon monoxide, carbon dioxide, oxides of nitrogen and ammonia.


[Glass fibre HEPA filters. II. Communication: Microbiological and physico-chemical researchs on used and unusued, hydrophilic and hydrophobic filter materials in an air conditioning plant (author's transl)]. Hydrophobic and hydrophilic, used and unused HEPA filters from various manufacturers, inoculated with vegetative bacteria, bacterial and fungal spores, were exposed to clean outside air for up to 17 weeks in an air conditioning plant. With relative humidities up to 60%, an increase in germ count could not be found. The rate of killing the micro-organisms inoculated were different and were generally higher on used filters. The low water content of the filter material was apparently not sufficient for microbial growth. In addition, the increase in electric conductivity and reduction of pH value resulting from deposition of substances from the outside air with an acid reaction ascertained in the aqueous filter extracts had a negative effect on the living conditions of the microorganisms.


[Metabolism of rat liver in the electrostatic field and in the faraday cage before and after hepatectomy (author's transl)]. Investigations were performed with the aim of establishing the influence of various environmental conditions (such as steady field conditions, climatized laboratories, Faraday's cage) on a number of enzymic activities in the rat (including glutamic oxaloacetic tic transaminase, glutamic pyruvic transaminase, lactic dehydrogenase, gamma-glutamyl transpeptidase, acid phosphatase), as well as the serum concentrations of triglycerides, the oxygen consumption of hepatic parenchyma cells, and the influence on the incorporation of 3H-thymidine (following partial hepatectomy). In the steady field, the activities of the cytoplasmic enzymes (GOT, GPT, LDH) were higher then under Faraday conditions. The same applies both to the hepatic oxygen consumption and to the neutral fat serum levels. The control values always remained within the range of the results obtained under steady field or Faraday conditions. In the structure-linked enzymes (gamma-glutamyl transpeptidase, acid phosphatase) the results were not uniform. Following partial hepatectomy, and under steady field conditions, the serum triglyceride concentrations showed a less pronounced drop than they did in the controls. Under selected environmental conditions, the results obtained lie within the physiological range. The present findings, therefore, do not permit definite conclusions to be drawn on favourable or unfavourable effects exerted by the different types of electroclimates.


[Report of "lethal factor" synthetized by Bacillus cereus (author's transl)]. Bacillus cereus growing in nutrition broth produces during logarithmic growth and in stationary phase a lethal factor extremely toxic for rodents. This toxin is only produced in the presence of oxygen and depends on bacterial replication. The highest titers of toxin are obtained using bacteria in a concentration of 10(7) to 10(9) per ml of nutrition broth. During regression phase of Bacillus cereus the titer of toxin declines to zero. Toxicity of the lethal factor becomes not altered in an alcaline or acidic medium. Temperatures exceeding 65 degrees C inactivate the toxin indicating its thermolability. Oral and rectal dispension of large quantities of the lethal factor does not induce toxic symptoms in rodents. However, when applicating toxin containing cultural filtrate of Bacillus cereus as an i.v., i.p., i.n. or s.c. injection it becomes highly toxic for mice, rats, hamsters, guinea pigs and rabbits. All animals injected by the different ways parenterally died.


[Polarographic studies on the peroxidase activity of liganded deuterohemin]. The peroxidase activity of deuterohemin and deuterohemin complexes relative to the substrates pyrogallol and ascorbic acid was studied using d.c. polarography in aqueous solution. Imidazole and pyridine served as complex ligands. In the absence of the ligands, a continual rise in the substrate conversion rate with increasing H2O2 initial concentration is observed. Imidazole or pyridine were found to considerably increase the peroxidase activity of deuterohemin at low H2O2 concentrations. At high H2O2 concentrations, the dependence of the reaction rate on H2O2 concentration shows a bend, the reaction rate being in each case higher than that of free hemin under the same conditions. The reason of this fact is discussed to be a retarded formation of activated H2O2 hemin-ligand complexes at high H2O2 concentrations.


[The effect of the immobilization of hemoglobin on its oxygen binding]. Hemoglobin (Hb) covalently fixed to CM-Sephadex was found to bind oxygen in weakly acidic medium with higher affinity than free Hb. The opposite relation is seen in the alkaline pH region. The alkaline Bohr effect was determined to be -0.2 only. Cooperativity is pH dependent. The sigmoid coefficient at pH 6 is 0.7; at pH 8.7 n was determined to be 1.3. As the reason of these altered binding properties a blockade of the primary amino groups, disturbance of the salt bridges, and restrained cooperative mobility of the Hb-subunits are discussed. The Hill coefficient is additionally lowered by the heterogeneity of the immobilized Hb.


[Characterization of the effect of bradykinin on the smooth muscle with special reference to its latency]. The biological activity of bradykinin on the isolated guinea-pig ileum is evident after a defined period of time - its latency. The latency of a bradykinin induced contraction is not caused by the strong protonization of the polypeptide. Analogues with the same or diminished basicity have a shorter latency than bradykinin. The latency is increased at high hydrogen concentration in comparison with the physiological pH-value. But this phenomenon is also observed at angiotensin, eledoisin, acetylcholine, histamine and barium chloride. The latency is dependent upon the temperature. Exogenous calcium ions are without demonstrable influence on the bradykinin induced latency. The membrane potential is not changed during the latency. The results are discussed in connection with the drug-receptor interactions.


Alpha-N-benzoylarginine-2-naphthylamide hydrolase (cathepsin B1?) from rat skin. I. Preliminary experiments with skin extract. The cathepsin B1-like, alpha-N-benzoyl-DL-arginine-2-naphthylamide (BANA) hydrolyzing activity of rat skin extract was studied. The enzyme was extracted into low ionic strength buffers, and was activated by dithiothreitol, EDTA and KCN. Incubation of the extract at acidic pH resulted in a 3.6-fold increase in its BANA hydrolase activity. The presence of inhibitor(s) of BANA hydrolase in the skin extract was indicated by the non-linearity of the activity/enzyme concentration curve and by Sephadex G-100 gel chromatography, which also caused separation of several other skin proteases.


Properties of the glycoprotein laccase immobilized by two methods. Laccase (p-diphenol:oxygen oxidoreductase; EC 1.10.3.2) from Neurospora crassa has been immobilized by two different procedures: (1) Covalent attachment to Sepharose 4B activated with cyanogen bromide, and (2) Adsorption to Concanavalin A-Sepharose via the carbohydrate moiety. Except for small changes in the Michaelis-Menten constants, no differences were noted in the enzymological properties of the immobilized enzymes when compared to free enzyme. The carbohydrate moiety of laccase involved in the interaction with Concanavalin A does not appear to be closely associated with the active center since binding to the lectin has no effect on the enzymological parameters investigated.


alpha-N-benzoylarginine-2-naphthylamide hydrolase (cathepsin B1 ?) from rat skin. II. Purification of the enzyme and demonstration of two inhibitors in the skin. A thiol-activated, alpha-N-benzoylarginine-2-naph-thylamide (BANA) hydrolyzing enzyme was purified from rat skin by ammonium sulfate precipitation, gel filtration, and DEAE cellulose chromatography. In DEAE cellulose chromatography the enzyme was fractionated into two multiple forms (preparations I and II). The activity of undiluted preparation II, but not that of preparation I, was increased, when the enzyme was preincubated at pH 4, at 55 degrees C. Simultaneously, the isoelectric point of preparation II was shifted to that of preparation I, i.e., from 6.2 to 7.5. Activated preparation II behaved in DEAE cellulose chromatography as preparation I. Molecular weights of the enzymes of both preparations were 27 000, and pH optima were at pH 5.8 and 7.0, for BANA and leucine-2-napthylamide (Leu-NA), respectively. The BANA and Leu-NA hydrolyzing enzymes could not be separated by gel filtration, DEAE, CM, or Amberlite IRC-50 chromatography, isoelectric focusing, or analytical polyacrylamide gel electrophoresis. Two inhibitors of BANA hydrolase were demonstrated by gel filtration in the salt precipitated skin extract. The activities of the BANA hydrolase preparations did not increase linearly with increasing enzyme concentration, with the exceptions of activities of preparation I and acid-activated preparation II. The role of the inhibitors in the nonlinearity of the activity/enzyme concentration curves is discussed.


The effect of artificial cryptorchidism on serum oestrogen and testosterone levels in the adult male rat. Oestrone, oestradiol and testosterone levels were measured by radioimmunoassay in male rats 0.5, 1, 4, 8 and 16 days after rats were either made artifically cryptorchid or sham-operated. Oestradiol levels were not significantly different between cryptorchid and control rats 12 h or 1 day after surgery, but levels in cryptorchid animals fell to 35% of controls on day 4 (P less than 0.05), 31% on day 8, and 29% on day 16 (P less than 0.01). Conversely, oestrone and the total of the two oestrogens was higher in cryptorchid rats at one-half day (P less than 0.05), but did not differ at any other time. Testosterone levels were generally lower in cryptorchid rats than in controls. The minor contribution of oestradiol to total oestrogen levels and the lack of change of total oestrogens in cryptorchid rats led to the conclusion that oestrogens are probably not the tubular regulator of FSH in the male.


[Androgenic treatment with depot mesterolone in dyspermia]. The clinical use of testosterone, and more recently of orally administered mesterolone in disorders of male fertility is of limited therapeutic efficacy, as shown by data found in the literature. On the basis of these considerations, the authors have tested mesterolone cyclopentylproprionate in 15 subjects suffering from sperm disorders. The drug, which is slowly released in the tissues has been parenterally administered at a total dose of 1,200 mg (100 mg per week). During the therapeutic trial the following aspects have been studied: spermiologic and hormonal patterns, general conditions, libido, principal organic functions and the possible side effects. Results are critically evaluated.


[Histochemical evidence of aminotransferases. III. Localization of aminotransferases in the mesencephalon, diencephalon, cortex cerebri and in the peripheral nervous system (author's transl)]. The histochemical distribution of some aminotransferases at various levels through the midbrain and cerebrum and in the peripheral nervous system of the rat has been described. The selective localization of the reaction product in the neurons and the neuropil was the same for the aminotransferases studied. There was a difference in the intensity of the enzyme activity. The white matter was negative, and only the glial cells and the blood vessels exhibit transaminase activity. Some nuclei showed an intensive reaction in the neurons and neuropil: nuel. ruber, substantia nigra, hypothalamic nuclei, Ammon's horn. A high activity was observed in the ganglion cell, and the nerve fibres were negative. There was a great similarity between the pattern of distribution for aminotransferases and that for some dehydrogenases.


[Histochemical evidence of aminotransferases. IV. Histochemical and electrophoretical investigation of aminotransferases in rat organs (author's transl)]. The histochemical localization and isoenzyme profil of some aminotransferases in different organs of the rat has been studied. A positive histochemical reaction with unequal intensity, depending on the aminotransferase investigated, was been observed. The topochemical and cytochemical localization of the aminotransferases was typical for everyone organ. The studied aminotransferases possessed isoenzyme fractions with characteristic number, electrophoretic mobility and intensity in the different organs. The results were discussed in relation with substrate specifity of the aminotransferases.


An optimum pH for the demonstration of chitin in Periplanata americana using Lugol's iodine. Modification of chitosan test of Campbell is suggested with a controlled procedure involving heating with saturated potassium hydroxide at 160 degrees C for a period of 45 min and subsequent washing of the deacetylated chitin in running water and application of Lugol's iodine solution (1:2:300, w/w/v) at a pH range of 1.4 to 4.0, thus replacing the use of dilute sulphuric acid. Consistent results were obtained not only with the cuticle of Periplanata americana but also with the cuticle of Emerita asiatica (crustacea).


Serum cholinesterase activity in burned patients. II: anaesthesia, suxamethonium and hyperkalaemia. The importance of serum cholinesterase activity in burned patients was evaluated in relation to anaesthesia. Anaesthesia included a repeated administration of suxamethonium. Thirty-two patients with an estimated area of burn between 3 and 72% were studied during 39 anaesthetic procedures. A statistically significant inverse correlation was found between serum cholinesterase activity and the apnoea period following intravenous suxamethonium. In patients with very low enzyme activity, apnoea periods of 10 to 25 min were observed. No correlation was found between the changes in serum potassium following suxamethonium and either the serum cholinesterase activity or the changes in Pco2 and pH. The most reliable parameters in predicting a dangerous increase in serum potassium following intravenous suxamethonium were shown to be 1) the time elapsed from burn injury to anesthesia and 2) the degree of burn injury. However, abnormal reactions to suxamethonium were seen as early as 9 days following injury, and rises in serum potassium to over 6 mmol/l were observed even in patients with a total burn surface of around 8%, i.e., less than the surface of one arm.


Anesthesia for cesarean section II: effects of the induction-delivery interval on the respiratory adaptation of the newborn in elective cesarean section. Ten healthy mothers and their infants were studied in connection with elective cesarean section. Anesthesia was induced with 250-300 mg hexobarbitone followed by 100 mg succinylcholine for endotracheal intubation. The surgeon started the operation when the eyelid reflex disappeared, and delivered the baby as quickly as possible. Mean induction-delivery (I-D) interval was 2 min 45 s. Anesthesia was then deepened with further barbiturate, diazepam and methoxyflurane, and alcuronium used as muscle relaxant. The respiratory adaptation of the infant was studied by blood gas and acid-base measurements in repeated arterial samples during the first three hours of life. The mothers were interviewed after 3-12 months. A comparison was made with another barbiturate group with a longer I-D interval (x = 9 min 10 s). The present material showed initially higher PaO2 lower PaCO2, higher pH and less base deficit (BD), which relfected the maternal state at delivery. After 10-30 min, the results approached equivalence, though the babies in the short I-D group showed a tendency toward normalization of metabolic acidosis earlier. At the interviews, two mothers complained of pain during skin incision, and two of nightmares. Anesthesia with barbiturate for cesarean section with the I-D intervals studied in both groups allowed good respiratory adaptation in the infants. There is, neverless, the need for an adequate period of time between induction and the start of the operation in order to minimize the risk for maternal awareness.


Continuous measurement of arterial PO2, PCO2 and pH during autotransplantation of canine hearts. Arterial PO2, PCO2 and pH were measured continuously with electrodes placed in a flow cuvette. Comparison between continuous readings and results of single sample analyses showed practically no discrepancy, and the drifts of the electrodes during time of measurements were negligible. During hypothermic perfusion with a Rygg-Kyvsgård bubble oxygenator, autotransplantation of canine hearts was performed. PO2, PCO2 and pH were measured continuously to check the performance of the heart-lung machine, and to evaluate the therapeutic and diagnostic significance of these blood gas values during cardiac surgery. At the start of perfusion, a steep fall in all three parameters was observed. The average fall in PO2 was 313 mmHg; PCO2 fell by 15 mmHg and pH BY 0.15. PCO2 rapidly returned to normal values, while pH and PO2 increased slowly during the perfusion period. PO2 reached its highest value at the lowest temperature and fell during rewarming. PCO was regulated by the carbon dioxide concentration in the heart-lung machine. pH did not return to normal levels within the time of perfusion. In the transistional period from perfusion, PCO2 increased and pH fell. Alterations in the distribution and direction of blood flow and a low systemic blood pressure are possible explanations of the initial fall in PO2 and the post-perfusion changes in PCO2 and pH. The variations in pH and PCO2 at the start of perfusion were caused by an acid priming fluid with low CO2 content. The post-perfusion changes indicated an unstable circulation, but imminent myocardial failure could not alone be diagnosed by continuous measurement.


Phosphatases in the lingual glands of man and dog. Phosphatase activity was demonstrated in the lingual glands of man and dog. Especially the ducts of the glandular elements of the dog exhibited a peculiar and rather perplexing pattern of activity which does not seem to fit in with any of the prevailing concepts of the function of the duct system. The secretory capillaries (Sekretionscapillaren) in many of the serous acini of the human lingual glands have demonstrated phosphatase activity with all the 17 substrates used. The significance of these phosphatases, expecially ATPase, in the active transport across biological unit membranes has been discussed.


The use of sulthiame- in myoclonic epilepsy of childhood and adolescence. Sulthiame has been used by most investigators in psychomotor seizures, other focal seizures and grand-mal, usually in conjuction with other anticonvulsants. Reports on its use in myoclonic epilepsy and as a sole anti-convulsant are few and inconclusive. The present report presents the results of a study carried out on the use of sulthiame in 54 cases of myoclonic epilepsies originating in infancy, childhood and adolescence. The different types of myoclonic epilepsy are defined. An illustrative case report is included. Results indicated that sulthiame is the drug of choice, often as the sole anti-convulsive agent, in cases of "juvenile myoclonic epilepsy". In the myoclonic encephalopathies of childhood (the so-called "minor motor epilepsy" or Lennox-Gastaut syndrome), which are notoriously refractory to therapy, sulthiame appears to be an efficacious adjunct to currently-used agents, including benzodiazepines, succinimides, dipropyl acetate, steriods and a ketogenic diet.


Bilateral keratopathy and tyrosinosis.

Bilateral keratopathy and tyrosinosis. A case of tyrosinosis due to lack of soluble tyrosine aminotransferase is described. The first clinical sign of this disorder may be bilateral keratopathy. Treatment is diet with restriction of phenylalanine and tyrosine. The disorder is rare and must be differentiated from other conditions of tyrosinosis.


Survival after massive pulmonary haemorrhage in the neonatal period. 4 babies with massive pulmonary haemorrhage were seen in an 18 month period. 2 had severe rhesus maemolytic disease, and the other 2 severe respiratory problems. There was evidence of a profound respiratory acidosis and hypoxia prior to the onset of the haemorrhage. 2 babies survived the episode and subsequently developed normally. Adequate ventilation and attendance to the treatment of blood coagulation disorders may have been a factor in their survival.


Metabolic characteristics of fibre types in human skeletal muscle. Muscle biopsy samples were obtained from healthy subjects in order to evaluate quantitative differences in single fibres of substrate (glycogen and triglyceride) and ion concentrations (Na+ and K+) as well as enzyme activity levels (succinate-dehydrogenase, SDH; phosphofructokinase, PFK; 3-hydroxyacyl-CoA-dehydrogenase, HAD; myosin ATPase) between human skeletal muscle fibre types. After freeze drying of the muscle specimen fragments of single fibres were dissected out and stained for myofibrillar-ATPase with preincubations at pH's of 10.3, 4.6, 4.35. Type I ("red") and II A,B, and C ("white") fibres could then be identified. Glycogen content was the same in different fibres, whereas triglyceride content was highest in Type I fibres (2-3 X Type II). No significant differences were observed for Na+ and K+ between fibre types. The activity for the enzymes studied were quite different in the fibre types (SDH and HAD, Type I is approximately 1.5 X Type II; PFK Type I is approximately 0.5 X Type II, Myosin ATPase Type I is approxiamtely 0.4 X Type II). The subgroups of Type II fibres were distinguished by differences in both SDH and PFK activities (SDH, Type II C is greater than A is greater than B; PFK, Type II B is greater than A is approximately C). It is concluded that contractile and metabolic characteristics of human skeletal fibres are very similar to many other species. One difference, however, appears to be than no Type II fibres have an oxidative potential higher than Type I fibres.


Inhibition of induced pinocytosis in Amoeba proteus by membrane stabilizing drugs. The effect of membrane stabilizing drugs on cation induced pinocytosis was studied in Amoeba proteus. Initially the presence of local anesthetic drugs during a pinocytosis cycle had a stimulating effect on channel formation, however, the capacity to develop pinocytotic channels was reversibly inhibited after a period of treatment with these drugs. Imipramine, vinblastine and the phenothiazines had effects similar to local anaesthetics. The local anesthetics inhibited pinocytosis in the following order: dibucaine greater than tetracaine greater than bupivacaine greater than lidocaine greater than procaine, and the phenothiazines: thioridazine greater than prochlorperazine greater chlorpromazine greater than prometazine. Pinocytosis, when induced by Na+ or tris, was more affected by the drugs and by calcium binding agents than pinocytosis induced by K+. After pretreatment with inhibitory concentration of dibucaine (3 x 10(-4) M) the depolarization of the membrane and the conductance increase during pinocytosis were normal, while the increase of oxygen uptake during the pincoytosis cycle was abolished. Addition of Ca++ before, during or after dibucaine treatment decreased the effect of the drug. Conversely, in dibucaine-treated cells, cation induced pinocytosis was less inhibited by Ca++ than pinocytosis in normal cells. Addition of EGTA to the inducing solutions potentiated the inhibitory effect of the drug. It is suggested that these drugs release Ca++ from the cell surface and at higher concentration or after prolonged incubation time interfere with a Ca++ mechanism which couples the membrane and contractile systems in the cytoplasm.


L-asparaginase activity of Mycobacterium phlei under various growth conditions. Seven Mycobacterium strains were grown statically on salts-glycerol-asparagine (Sauton) or on salts-glucose-glutamate (Sym) media. At desired time of incubation, the bacteria were washed with water, disintegrated with powdered corundum and in resulting cell-free extracts L-asparaginase activity was determined by the Conway method. The majority of experiments were performed on M. phlei which exhibited considerable rise in L-asparaginase activity with increasing age of the culture. This change did not occur on Sym medium because of Zn2+, which proved to abolish the effect of the enzyme induction in vivo but did not inhibit the activity in vitro. Addition of rifampicin to Sauton culture media resulted in a low enzyme level. Exogenous asparagine and glycerol were not indispensable for the enzyme synthesis and could be replaced by glutamate and glucose, respectively.


The effect of microorganisms on phytotoxicity of herbicides. III. Interaction of Bacillus sp. 72 with Venzar. Interactions between Venzar and some metabolites of Bacillus ps. 72 were studied. This strain was found to produce flavonoids increasing the phytotoxicity of Venzar. Venzar action was also increased by NH4+ ions released aboundantly by the bacterial strain.


Influence of amino acids on the activity of cellulolytic enzymes obtained from spent medium of Fusarium cultures and on the "Cellulase S" Novo. Comparative studies on the influence of 4 amino acids (cysteine, cystine, methionine and alanine) on the activity of enzymatic preparation were carried out. The action of the amino acids was shown to depend on pH, incubation time and the temperature of incubation. Attempts were made to find a correlation between the amino acids introduced and redox potential (Eh), pH and the activity of the cellulolytic enzymes. It was found that the addition of some amino acids to the reaction mixtures at different pH values affected the value of Eh -- which enhanced the cellulase activity.


Behavioral analysis of the effects and mechanisms of action of benzodiazepines. Conflict behavior is a powerful tool to reveal relevant pharmacologic correlates of the therapeutically desirable properties of benzodiazepine antianxiety compounds. The predictability of its clinical effectiveness in psychoneuroses is very high, and important quantitative and qualitative differences between compounds in this chemical class can be shown using such a behavioral technique. It is important to take these differences into account when studying biochemical correlates or mechanisms of action within the benzodiazepine class. Conflict behavior has been used to evaluate several biochemical hypotheses concerning the mechanism of action for the antianxiety properties of benzodiazepines. These studies found that inhibition of cyclic AMP phosphodiesterase did not seem to be a relevant factor. Similarly, experiments with AOAA did not provide evidence to support the involvement of GABA with benzodiazepines' antianxiety properties, nor did glycine receptor affinities correlate significantly with anticonflict effects. Thus, while it is reasonable at present to associate either GABA or glycine with the muscle-relaxant or anticonvulsant properties of benzodiazepines, no support was provided in the conflict procedure for their involvement in the anxiolytic effects. Partial support was provided for the proposal that serotonin is involved in the benzodiazepines' anxiolytic activity. This was determined in studies with the serotonin antagonists cinanserin and methysergide, which had anti-conflict activity, as well as in studies of monoamine turnover after initial chlordiazepoxide treatments to previously undrugged, conflict-trained rats.


Possible involvement of GABA in the central actions of benzodiazepines. The effects of several benzodiazepines on a variety of nervous activities known or presumed to depend on GABA are presented and compared with those of agents that deplete or increase the level of endogenous GABA: antagonism of various convulsant agents in mice, enhancement of presynaptic inhibition in the spinal cord and the cuneate nucleus of cats, decrease of the spontaneous firing rate of cerebellar Purkinje cells in cats and rats, antagonism of bicuculine-induced depression of the strio-nigral-evoked potential in the cat, potentiation of haloperidol-induced catalepsy in rats, GABA-mimetic actions on drug-induced PGO-waves in cats and on eserine-induced circling in guinea pigs. Diazepam slightly increased the GABA level in the cat spinal cord and in the total brain of mice and rats; this increase does not seem to be due to an increase of GABA synthesis. It is concluded that benzodiazepines probably enhance presynaptic inhibition at all levels of the neuraxis and that this effect requires not only the presence of GABA but is also dependent on an activity of GABA-ergic neurons. Benzodiazepines also appear to enhance postsynaptic inhibition where this is mediated by GABA. Many actions of benzodiazepines can be tentatively explained by a stimulus-bound enhancement of GABA effects.


Modulators of cyclic AMP systems.

Modulators of cyclic AMP systems. On the basis of the data reported here, one may conclude that although many agents that act in the central nervous system are modulators of the action of cyclic AMP, it is difficult to establish a direct connection between the pharmacologic activity and the levels of cyclic AMP in the brain. This lack of interrelation applies to the benzodiazepines as well as to the pyrazolopyridines. The data for members of the latter group are somewhat frustrating in this regard, since an excellent correlation has been shown to exist between the potency of inhibition of PDE and activity in the antianxiety test. In measurements of steroidogenesis in the isolated adrenal cell, the correlation between activity in vito and the conflict assay is even better. The data presented here and reported elsewhere (Shimizu et al., 1974; Kelly et al., 1974; Mayer and King, 1974; King and Mayer, 1974) provide evidence that agents that act as inhibitors of PDE in cell-free systems exert their influence on cyclic AMP in tissue slices of the brain of guinea pigs by mechanisms that seem not to be related to an effect on PDE. Papaverine, and possibly chlordiazepoxide, may act by releasing agonists that, in turn, stimulate the accumulation of cyclic AMP. This activity is blocked bo other inhibitors of PDE, such as theophyline. Results obtained by the use of platelets are refreshingly clear. Inhibition of aggregation has been shown to occur when the level of cyclic AMP is raised, and a suggestive exists that the most potent inhibitors of platelet PDE are the best potentiators of the action of PGE1 in blocking aggregation. The study utilizing drugs collected from a large number of therapeutic classes makes clear that it is difficult to attribute the mechanism of action for any of the classes studied to modulation of cyclic AMP. An unexpected finding of this study, however, was the fact that pharmacologic agents include an unusually large number of inhibitors of PDE as compared with agents chosen at random. This finding provides a powerful tool for the biochemical pharmacologist who is examining large numbers of compounds in the search for potential drugs.


Effects of benzodiazepines on central serotonergic mechanisms. If the rat conflict test were a valid animal model of anxiety neurosis, evidence which implicates serotonin systems in the anxiety-reducing actions of benzodiazepine tranquilizers could be summarized as follows: (1) The punishment-lessening effects of benzodiazepines in the conflict test are mimicked by serotonin antagonists (methysergide, cinanserin, bromolysergic acid), serotonin synthesis inhibition (PCPA), and serotonin nerve terminal damage (5,6-dihydroxytryptamine). (2) Punishment effects may be intensified by the serotonin precursor, 5-hydroxytryptophan (in combination with a monoamine oxidase inhibitor), serotonin agonists (alpha-methyltryptamine), or intraventricular injections of serotonin itself. Intraventricularly administered serotonin also antagonizes the punishment-lessening effects of benzodiazepines. (3) Stimulation of the serotonergic cell bodies in the dorsal raphe nucleus by local application of crystalline carbachol causes intense suppression of behavior. The suppressive effects of raphe stimulation are antagonized by systemic administration of benzodiazepines. (4) In biochemical experiments, the decrease in norepinephrine turnover induced by oxazepam rapidly undergoes tolerance, whereas the decrease induced in serotonin turnover is maintained over repeated doses. These results parallel findings in the conflict test which indicate that the depressant action of oxazepam rapidly undergoes tolerance, whereas the anxiety-reducing action is maintained over repeated doses. Although central serotonin neurons are thus implicated in the therapeutic actions of benzodiazepine tranquilizers, it is quite possible that the drugs actually act indirectly to reduce serotonin activity. The concept that benzodiazepines may exert a primary action on GABA-containing neurons, which in turn regulate serotonergic transmission, was supported by preliminary psychopharmacological evidence. The GABA-antagonist picrotoxin, at doses that do not disrupt unpunished behavior, fully antagonizes the punishment-lessening effects of benzodiazepines in the conflict test.


The possible involvement of GABA mechanisms in the action of benzodiazepines on central catecholamine neurons. With the use of quantitative microspectrofluorometry, it has been shown that diazepam (10 mg/kg) and chlordiazepoxide (10 mg/kg) reduce DA turnover in the tuberculum olfactorium, nuc. accumbens, the DA islands of the entorhinal cortex, and caput of nuc. caudatus, whereas DA turnover is increased in the lateral external layer of the median eminence after 10 mg/kg of diazepam. It is of considerable interest that with a dose of 1 mg/kg of diazepam a reduction of DA turnover can still be observed in the tuberculum olfactorium and nuc. accumbens but not in the nuc. caudatus, due to a high variability of the response in this area. A similar trend is also found with chlordiazepoxide. Thus, changes in limbic DA turnover are observed in doses close to the minimal effective dose (0.6 mg/kg) needed to release punished behavior and to cause anticonvulsive effects, and may therefore be related to these actions of diazepam. For various reasons it is speculated that an increased GABA receptor activity on the DA cell bodies and their dendrites could mainly be involved in causing the reduction of DA turnover observed after benzodiazepines by diminishing the firing rate in the ascending DA pathways, particularly the mesolimbic DA pathways. Evidence for a change of GABA turnover by diazepam has also been found. It is also suggested that the reduction of cortical NE turnover found after benzodiazepines can partly involve an increased GABA receptor activity on the locus ceruleus cells, although the activation of E receptors on these cells cannot be excluded. These effects on locus ceruleus may be partly responsible for the sedation found after benzodiazepines. Diazepam (1 mg/kg) mimics both clonidine and GABA-ergic drugs in reducing blood pressure and slowing respiration rate, but the effects are blocked by picrotoxin but not by piperoxane, an E receptor-blocking agent. In agreement with the view that blockade of the stress-induced increases of NE turnover by benzodiazepines may be related to their antianxiety actions, it was found that the increase in NE turnover elicited by yohimbine, a drug that causes anxiety in man, is blocked by diazepam.


Antihypertensive beta blocking action as related to renin and age: a pharmacologic tool to identify pathogenetic mechanisms in essential hypertension. Three hundred fifteen patients with essential hypertension were classified according to low (18 percent), normal (59 percent) or high (23 percent) renin-sodium index. The proportion of patients with low renin hypertension progressively increased with increasing age and blood pressure, there being no difference between the sexes. Two high renin groups emerged: a younger group with early moderate hypertension, and an older group with severe hypertension consequent to possibly ischemic renal disease. Long-term beta blocking monotherapy in 137 patients resulted in a reduction of idastolic pressure to 95 mm Hg or less in 65 percent: 85 percent in those with high and 73 percent in those with normal renin activity; pressure was reduced to this level in only 1 of 24 patients (4 percent) with a low renin index. Antihypertensive efficacy was also related to age, since diastolic pressure was normalized in 80 percent of patients under age 40 years, in 50 percent of those aged 40 to 60 years, but in only 20 percent of those over age 60 years. Age may heolp in patient selection but is no substitute for the more reliable renin index, especially in patients over age 40 years, or with high pressure. Using studiew with propranolol as a standard, similar renin responses were obtained with two cardioselective beta1 type blocking drugs, atenolol and metoprolol, as well as with two nonselective beta2+1 receptor antagonists, LL21945 exhibiting prolonged receptor affinity and oxprenolol in slow release form. These long-acting drugs, which proved effective in single daily doses, could be of value in improving patient compliance...


Hemodynamic lesions in hypertension.

Hemodynamic lesions in hypertension. Essential hypertension is increasingly recognized as a nonhomogenous disorder by various methods of study. The hemodynamic approach, coupled with clinical determination of the range and lability of blood pressure, has resulted in the description of several subgroups: labile hypertension with normal or elevated cardiac output, fixed or established hypertension with varying cardiac output and advanced hypertension with normal or low cardiac output. There is a tendency to postulate that these categories are stages of one disorder, but this remains to be proved. Still other patients have been described who may be further set off by exceptionally labile or hyperkinetic features. In some hypertensive patients, the peripheral resistance is normal; however, regardless of its numerical value, it is now considered to be increased if it fails to decrease normally in the presence of elevated cardiac output. Because an elevated cardiac output is the hemodynamic function that differentiates these groups, and renovascular hypertension as well, it is the focus of much current work. New interest in the central blood volume, the peripheral veins, and the portal veins and splanchnic circulation is focused on their connection with cardiac out-put. Newly appreciated, too, is the existence of parasympathetic inhibition in hypertension, which not only contributes to elevations of heart rate, cardiac output and possibly renin secretion, but also depresses baroreflex responses. Thus far, hemodynamic and endocrine mechanisms of hypertension have not been studied together, except possibly through the blood volume, which remains a highly controversial topic. In this paper, some recent work in the above areas is reviewed and emphasis is given to studies in man.


Abnormal forms of bacteria produced by antibiotics. Subinhibitory concentrations of antibiotics can produce in vitro aberrant forms of bacteria that are similar to those observed in specimens and cultures from patients being treated with antibacterial agents. Eight species of bacteria were grown on membranes placed on agar containing subinhibitory concentrations of nine antibiotics. The resulting organisms were examined by Gram stain and electron microscopy. Gram stains showed filamentous and granular forms of enterobacteria with bipolar staining, giant staphylococci, and rodlike pneumococci. Electron micrographs showed changes in the number and distribution of ribosomes in enterobacteria and septum abnormalities in cocci. Such abnormal forms can occasionally simulate the appearance of quite different species, and they may indicate the presence of a subinhibitory antibiotic concentration at the site of infection as a result of prior antibacterial therapy.


Gastric secretion, gastroesophageal reflux and esophagitis. Neither gastroesophageal reflux nor esophagitis were found to have a clear-cut relationship with gastric secretory output. Patients with esophagitis had significantly longer periods of reflux than those without esophagitis. It is concluded that the important factor in the genesis of esophagitis is the duration of contact between the esophageal mucosa with gastric contents rather than gastric secretory output.


Effect of lactulose on rabbits fed on a low residue diet. The effect of lactulose (Duphalac) was tested for four months on six rabbits on a low residue diet representative of the diet ingested by the peoples of western civilization. A control group of six rabbits simply had the low residue diet and they developed a very low fecal output, with a mean wet fecal weight measured at monthly intervals varying between 2 and 4.6 gm.; increased transit times of 48 hours and intracolonic pressures which increased over four months from a colonic motility index (CMI) of 12,261 to a CMI of 28,084 in response to neostigmine. The rabbits on diet and lactulose did not develop diarrhea but produced three times the wet fecal weight of the rabbits on diet alone, with a range of mean values from 9.4-12.4 gm.; transit times remained at 24 hours which is normal transit time for rabbits on regular laboratory diet; intracolonic pressures in response to neostigmine rose only from a CMI of 11,652 to a CMI of 14,263 during the four months on diet with lactulose.


Physicochemical stability of a preanesthetic mixture of hydroxyzine hydrochloride and atropine sulfate. The stability of a combination of hydroxyzine hydrochloride and atropine sulfate stored in syringes was studied. Syringes containing the two drugs were stored at 25 C and 3 C for ten days and analyzed at specific time intervals. Absorption spectra, chromatographic characteristics and pH were determined. Results showed the admixture to be stable for ten days at room temperature or under refrigeration. The technique used would probably not detect any significant degradation of atropine sulfate unless the reaction occurred with the hydroxyzine hydrochloride.


Stability of parenteral solutions of tobramycin sulfate. The stability and physical compatibility of tobramycin sulfate in commonly used intravenous fluids were evaluated; in addition, pH values were obtained on 1 mg/ml tobramycin solutions, and microbiological potencies were obtained on 1 mg/ml and 0.2 mg/ml concentrations for 24- and 48-hour periods at 25 C. Most solutions were stable for 48 hours at room temperature. However, it is recommended that solutions of tobramycin sulfate be discarded after 24 hours to minimize the potential for inadvertent introduction of microorganisms during manipulations in the hospital environment.


Hematological findings in acute infections and septicemias. This paper is a report on twelve cases of septicemia, the diagnosis made possible by medical technologists observing the degenerative morphological findings in the peripheral blood smears. This led to the finding of microorganisms, prior to the bacteriological confirmation, in an active emergency department. It also includes four case reports in which the organism was identified: a meningococcus, a pneumonococcus, an Escherichia coli, and a clostridium perfringens (welchii).


Morphologic features of spleen allografts in rats. Graft rejection, acceptance, or lethal graft-versus-host disease in the same donor-recipient pairing. The structural changes in serial biopsies of spleen allografts in inbred histoincompatible rats are described. Three experimental procedures in the same donor-recipient pairing (PVG to AGUS) were employed and resulted in spleen graft rejection (Group I, no pretreatment), spleen graft acceptance (Group II, hosts pretreated with donor cells), and lethal GVH disease (Group III, donors pretreated with host cells). Striking features in the three groups were the variation of involvement of the periarterial lymphatic sheaths (PALS) shortly after grafting, and a substantial increase in hemopoiesis, particularly erythropoiesis, in the red pulp. The very "quiet" cellular reaction in the PALS of the host spleens in Group II corresponded with permanent graft acceptance. In Group III the previously sensitized allografts behaved rather like Group I host spleens and, by causing fatal GVH disease, demonstrated their immunologic superiority.


Histamine H1- and H2-receptors in pulmonary and systemic vasculature of the dog. This study was conducted to identify and clarify the actions of pulmonary and systemic H1- and H2-receptors by utilizing specific histamine receptor antagonists. Histamine was infused in anesthetized dogs during control conditions, after H2-receptor blockade with metiamide, after H1-receptor blockade with chlorpheniramine, and after combined H1- and H2-receptor blockade. Histamine infusion, alone, induced marked systemic vasodilatation, pulmonary vasoconstriction, and transient increases in cardiac output and heart rate. H2-receptor blockade prevented the systemic vasocilatation and potentiated the pulmonary vasoconstriction induced by histamine. H1-receptor blockade augmented the systemic vasodilatation, prevented the pulmonary vasoconstriction, and increased the cardiac output and heart rate responses induced by histamine. Thus, H2-receptors appear to mediate the vasocilatation, tachycardia, and increased cardiac output induced by histamine, whereas H1-receptors appear to mediate the vasoconstrictor and the minimal cardiac depressent actions of histamine. Histamine stimulates only H1- and H2-receptors, since combined H1- and H2-receptor antagonism prevented almost all of the cardiovascular actions of histamine.


Metabolic and respiratory responses during Helox-induced hypothermia in the white rat. Unanesthetized and unrestrained rats, chronically cannulated in the carotid artery, were exposed to normal air (NA) and Helox (21% O2, 79% He) at ambient temperatures (Ta) of 22 and -10 degrees C. In Helox at Ta = 22 degrees C, the Vo2 was 1.39 ml O2/g-h and the Vco2 0.98 ml CO2/g-h, 145 and 126%, respectively, of the values in NA at Ta = 22 degrees C. The arterial Pao2, Paco2, and pH were comparable in Helox and NA at Ta = 22 degrees C. In Helox at Ta = -10 degrees C, rats invariably became hypothermic after exposure of 0.75 to 1.5 h. During the induction of hypothermia the decrease of Vo2 and Vco2 was oscillatory, Pao2 and pH increased, and Paco2 decreased significatnly (P less than 0.05). Minimum Vo2 and Vco2 during hypothermia averaged 0.71 ml O2/g-h and 0.50 ml CO2/g-h, 23 and 22%, respectively, of the values in normothermic animals at Ta = -10 degrees C. Minimum body temperature during hypothermia was clamped at 21.7 +/- 0.3 degrees C (X +/- SE) by increasing Ta to 19 degrees C. When Helox was replaced by NA, hypothermic rats rewarmed spontaneously, returning to normothermia within 4 h. The data suggest that hypothermia induced by Helox plus cold does not seem to be due to respiratory failure, as systemic hypoxia or hypercapnia were not observed. The controlled hypothermia cycle reported here provides a model for dynamic studies of thermogenic mechanisms both at the normothermic and hypothermic states without the interference of drugs and other nonphysiological treatments.


Extrahepatic manifestations of viral hepatitis. Recent evidence indicates that viral hepatitis is sometimes associated with the production of extrahepatic tissue injury. Hepatitis B virus (HBV) infection is most commonly incriminated but non-type B hepatitis may also be involved. Three types of syndromes have been recognized. First, a serum sickness-like prodrome consisting of skin eruptions, urticaria  and polyarthralgias or arthritis may occur from one to six weeks prior to the onset of hepatitis in 15 to 20 per cent of patients and usually disappears by the time the patient becomes jaundiced. There is extensive evidence that circulating immune complexes are responsible for these symptoms. Second, about 30 to 40 per cent of patients with typical polyarteritis nodosa have persistent hepatitis B surface antigenemia (HBs Ag). Circulating immune complexes composed of HBs Ag, antibody, and complement have been demonstrated together with deposits of immune complexes at sites of vascular injury. Third, an immune complex type of glomerulonephritis may occur following hepatitis B virus infection, usually in association with chronic active hepatitis. Thus there is impressive evidence that hepatitis viruses, especially HBV, may produce a variety of extrahepatic manifestations in which the mechanism of pathogenesis involves an immunologic process rather than direct viral invasion and cytopathogenicity.


Adrenergic mechanisms in canine gastric circulation. The effects of adrenergic stimulation and blockade on the gastric circulation were studied in anesthetized dogs. Blood flow through the right and left gastric artery was measured electromagnetically. Norepinephrine and isoproterenol were injected intra-arterially and intravenously before and after alpha- and beta-adrenergic blockade. Isoproterenol caused vasodilation of both right and left gastric circulations and this effect was attenuated by beta blockade. Epinephrine and norepinephrine induced constriction followed by dilation in both circulations. The constrictor components were attenuated or abolished by alpha-adrenergic blockade and the dilator components were attenuated by beta-adrenergic blockade. The right and left gastric vascular beds demonstrated quantitatively different responses to the same dose of each adrenergic amine. The left gastric circulation had a greater vasodilator response than did the right gastric circulation. These data support the classical concepts that epinephrine and norepinephrine are "mixed" adrenergic agonists and isoproterenol is a "pure" beta-adrenerigic agonist. The data further suggest that there is a differential in beta-adrenergic receptor distribution with the left gastric vasculature demonstrating greater dilator responses than the right.


Effect of volatile fatty acids on water and ion absorption from the goat colon. The absorption of volatile fatty acids (VFA) and the influence of VFA on the net transport of inorganic electrolytes and water were examined in the temporarily isolated colon of the conscious goat. Perfusion of the colon with a solution similar in content to that normally present in the cecal outflow showed that the net absorption of VFA was more rapid than that of any other ion present in the solution. When the VFA were replaced with Cl, the net absorption of Na and water was reduced nearly twofold. Increasing the pH of the solution from 6.0 to 7.4 in the presence of VFA also resulted in a twofold decreased in the net transport of Na and water. Perfusion of the colon with a hypertonic solution resulted in approximately zero net water transport; however, the net absorption of Na and VFA continued at similar rates as before. These results support the concept that the colon primarily conserves solute followed by the passive movement of water. They also demonstrate that VFA are rapidly absorbed from the goat colon and indicate a striking influence of VFA on the net transport of Na and water. The presence of VFA in the large intestine may be important for normal absorptive function.


Lactate, pyruvate, and excess lactate during ether and halothane anesthesia in infants and children. Arterial blood lactate, pyruvate, and excess lactate (XL) were measured and calculated in 33 patients aged 7 months to 6 years over a period of 2 hours during repair of harelip or cleft palate. When the anesthetic was diethyl ether, lactate and pyruvate levels rose significantly 60 minutes after induction of anesthesia but did not rise thereafter. Excess lactate appeared 60 minutes after induction of ether anesthesia, but it, too, showed no further increase. When the anesthetic was halothane there was no significant change in lactate, pyruvate, or XL. Changes with ether were not age-related, nor could they be correlated with changes in rectal or skin temperature. The responses of lactate, pyruvate and XL to ether anesthesia in the present study were not significantly different from those found by others in adults.


Hypocapnic bronchoconstriction and inhalation anesthetics. The effects of halothane, enflurane, and methoxyflurane on hypocapnic bronchoconstriction (increased airway resistance and decreased compliance of the lung) were studied in vivo in the isolated left lower lobe of the canine lung. Hypocapnic bronchoconstriction, induced by altering the concentration of CO2 in gas ventilating the lobe, was repeated in the presence and absence of various concentrations of anesthetic gases (halothane: 0.5, 1.0, and 3.0 per cent; enflurane: 1.0, 3.0, and 5.0 per cent; methoxyflurane: 0.25, 0.50, and 1.0 per cent). In the higher concentrations, all three drugs blocked the bronchoconstrictor effect produced when the inspired CO2 was decreased from 5 to 0 per cent. In lower concentrations, halothane was the most effective blocking drug. Propranolol did not affect the ability of the three anesthetics to block hypocapnic bronchoconstriction, nor did the beta-receptor blocking drug sotalol affect the blocking effects of halothane. The ability of these anesthetics to block hypocapnic bronchoconstriction probably is mediated not through an adrenergic mechanism but by one that is nonspecific. (Key words: Lung, bronchoconstriction; Carbon dioxide, hypocarbia; Anesthetics, volatile, halothane; Anesthetics, volatile, enflurane; Anesthetics, volatile, methoxyflurane.)


The ineffectiveness of steroid therapy for treatment of fresh-water near-drowning. The authors evaluated the efficacy of continuous positive-pressure ventilation (CPPV) and methylprenisolone alone and in combination as therapy for near-drowning in 80 dogs that had aspirated distilled water (22 ml/kg or 44 ml/kg). Forty dogs were treated with mechanical ventilation for one hour and 40 for 24 hours. Blood-gas tensions, pH, cardiac output and intrapulmonary shunt (Qs/Qt) were measured frequently for 24 hours. Blood-gas tensions and pH were again measured 48 and 72 hours and seven days later in survivors. Arterial oxygen tension (PaO2) decreased and Qs/Qt increased in all animals following aspiration and before therapy. Forty dogs received methylprednisolone intravenously (30 mg/kg) (20 breathed spontaneously and 20 had CPPV). There was a significant increase in PaO2 and decrease in pulmonary shunt in dogs that were ventilated mechanically compared with animals that breathed spontaneously. Treatment with methylprednisolone made no difference in blood gases, pulmonary shunt, or survival rates. Thus, no evidence to support the use of methylprednisolone in the treatment of the pulmonary lesion of fresh-water near-drowning was found. (Key words: Drowning, fresh-water; Hormones, adrenal, methylprednisolone.)


[Semiautomatic method of measurement of serum 5'nucleotidase activity]. A semi-automated method for determining the 5'-nucleotidase activity in human serum for use with the Technicon Autoanalyzer I is described. Based upon the manual method of Persijn and Van Der Slik, adenosine formed by hydrolysis of 5'-AMP is deamined enzymatically and ammonia determined with the Berthelot reaction. The non specific alkaline phosphatases are inhibited by phenylphosphate. Concentrations of 5'-AMP and phenylphosphate are discussed. Nucleotidase activity is determined without dilution up to a value of 210 UI/liter. The precision is better than other manual or semi-automated methods in current use.


Pulmonary arterial wedge pressures: blood gas tensions and pH in the resting horse. Blood pressure recordings were made from right atrium, right ventricle, pulmonary trunk, and pulmonary arterial "wedge" positions in the standing, resting, adult horse. Similarly, comparisons were made of blood samples collected from these vascular positions, as well as from jugular vein and carotid artery. A consistently lower partial pressure of carbon dioxide and a greater partial pressure of oxygen and pH were found in blood samples from pulmonary arterial wedge than from carotid artery. A technique for safe and rapid collection of pulmonary trunk and pulmonary arterial wedge blood gases, pH, and pressure data, using a balloon-tipped flow-directed catheter, is described in the nonsedated, nontranquilized, resting, adult horse.


Cardiopulmonary effects of positive end-expiratory pressure in anesthetized horses. The cardiopulmonary effects of 0, 5, 10, and 15 cm of H2O positive end-expiratory pressures (PEEP) were determined in anesthetized, spontaneously breathing horses, using a 4 by 4 Latin-square design with one repetition. Cardiac output, alveolar-arterial oxygen tension difference, alveolar ventilation, dead space/tidal volume ratio, and carbon dioxide elimination were not significantly altered by the procedure. As PEEP was increased, alveolar and arterial oxygen tensions, respiratory exchange ratio, and pH decreased, whereas arterial carbon dioxide tension and oxygen consumption increased. These results indicate PEEP is contraindicated in laterally recumbent spontaneously ventilating anesthetized horses breathing air, because it causes alveolar hypoventilation and does not improve pulmonary gas exchange.


Mammalian erythrocyte glutathione reductase: kinetic constants and saturation with cofactor. Glutathione reductase (GR) was studied in erythrocytes of horses, cats, dogs, and man. Glutathione reductase activity was measured in hemolysates with and without preincubation of hemolysates with flavinadenine dinucleotide. The percentage saturation of GR apoenzyme with cofactor (flavin-adenine dinucleotide) was lower in cats and dogs than in horses or man. The greatest amount of inactive apoenzyme was in feline erythrocytes. Total GR activity listed in order by species is cat greater than man greater than dog greater than horse. Kinetic constants for oxidized glutathione and reduced nicotinamide-adenine dinucleotide phosphate were determined in each species. Although kinetic constant (reduced nicotinamide-adenine dinucleotide phosphate) values for GR were similar, considerable species variation was observed in the kinetic constant (oxidized glutathione) for GR. The kinetic constant (oxidized glutathione) for equine GR was approximately 3 times that for human GR, with intermediate values determined for feline and canine GR.


Hemodynamic and metabolic alterations in peripheral tissue during hemorrhagic shock. In dogs subjected to hypovolemic shock (modified Wiggers model) severe enough to decrease the arterial flow in an isolated hind limb by two-thirds, a marked hyperglycemia (three times control) and an increase in blood glucose AV difference (ten times control) occur. Despite the decreased arterial flow, glucose uptake by peripheral tissues increased by a factor of three within one-half hour of hemorrhage and remained elevated for several hours. Presumably, the increased glucose uptake reflects the need for more energy substrate during the hypoxic conditions of the decreased peripheral blood flow.


Utilization of Fe3+ by the inshore colorless marine dinoflagellate Crypthecodinium cohnii. A Puerto Rican isolate of the colorless dinoflagellate Crypthecodinium cohnii was grown in a defined marine medium. Fe was added as Fe(NH4)2(SO3)2 - 6H2O (2.0 mg%), FeCl3 - 6H2O (1.0 mg%) or a particulate slurry prepared from FeCl3 + KOH, along with varying concentrations of several chelators. Heavy growth at pH 7.5-7.7 occurred with salicylhydroxamic acid, aurintricarboxylic acid, EDTA, NTA, and humic acid; and at pH 7.9-8.1 with SHAM and ATA. Moderate growth occurred at pH 7.5-7.7 with sulfosalicylic acid, dipicolinic acid, pyrocatecholdisulfonic acid, hexanohydroxamic acid, L-histidine, and at pH 7.9-8.1 with 1-naphthohydroxamic acid, EDTA, NTA. Slight growth occurred at pH 7.5-7.7 with benzohydroxamic acid, 1-naphohydroxamic acid, 2.6-dipicolinic acid N-oxide, salicylic acid, rhodotorulic acid, Na oxalate, EDDHA, sorbohydroxamic acid, gamma-pyrone-2, 6-decarboxylic acid, and at pH 7.9-8.1 with hexanohydroxamic acid, benzohydroxamic acid. Some ecological and physiological implications are discussed.


[Complex rearrangement of chromosomes 3 and 5 in an adolescent with multiple abnormalities]. Cytogenetic studies were performed on a severely mentally retarded adolescent with multiple congenital abnormalities (congenital heart disease, cryptorchidism and infantilism, rocker bottom feet and eye abnormalities). He had a complex rearrangement as a result of three breaks of chromosome 3 and two breaks of chromosome 5, and haphazard reunion of the fragments. This complex rearrangement appears balanced. The loss of very small chromosome fragments is perhaps the cause of the dysmorphia. The possibility of position effect is discussed.


Acid alpha-glucosidase: a new polymorphism in man demonstrable by 'affinity' electrophoresis. 1. A new polymorphism of the enzyme acid alpha-glucosidase is described. The three phenotypes, 1, 2-1 and 2, appear to be determined by two alleles alpha-GLU1 and alpha-GLU2 at an autosomal locus. The allele frequencies in Europeans are approximately alpha-GLU1 = 0-97 and alpha-GLU2 = 0-03. 2. The polymorphism is not detectable after electrophoresis on other support media (cellogel and agarose) and evidence is presented that the separation is effected by a difference in binding of the isozyme products of the two alleles to the support medium starch, which contains alpha-1-4 and alpha-1-6 linked glucose units. We have called this type of separation affinity electrophoresis. 3. No difference in the kinetic properties of the two enzymes could be demonstrated using 4-methyl umbelliferyl alpha-D-glucopyranoside and maltose as substrates or maltose and turanose as inhibitors, but it is possible that differences might exist when macromolecular substrates are used. 4. One individual with the rare homozygous genotype has been found. There is at present no indication that this genotype is associated with a pathological condition.


Production and property of beta-lactamases in Streptomyces. The production of beta-lactamases by 100 strains of Streptomyces was studied. About one-half of the strains produced more than 2.3 U of beta-lactamase per ml, and another half produced less than 1.4 U/ml. The amounts of beta-lactamases produced by two strains were in the order of those produced by Bacillus cereus 569/H and Bacillus licheniformis 749/C. These Streptomyces enzymes function primarily as penicillinases rather than cephalosporinases. Properties such as pH optimum, substrate specificity, and heat stability suggest that these Streptomyces beta-lactamases are closely related to each other. In contrast to bacterial beta-lactamases, Streptomyces beta-lactamases were insusceptible to inactivation by N-bromosuccinimide and only slightly susceptible to iodine. This suggests that the construction mode of the active site would be different from other beta-lactamases. Studies on the minimum inhibitory concentrations of benzylpenicillin to seven Streptomyces strains and on their maximum beta-lactamase production indicate that the susceptibility of Streptomyces to penicillin is not directly related to the beta-lactamase production.


Mechanism of benzoic acid uptake by Saccharomyces cerevisiae. A fast uptake of the preservative benzoic acid was observed in Saccharomyces cerevisiae, reaching saturation in about two min and then remaining constant at this level. The strong dependence of benzoic acid uptake on pH was due to the relative distribution of molecular and ionic forms in solution and not to the pH itself. The molecular form was the only one taken up by the cells. The specificity of the uptake mechanism was evidenced by the pattern of irreversible heat inactivation of the uptake system resembling protein denaturation by heat. Furthermore, the effect of temperature on the uptake was similar to that observed in enzymic reactions, whereas the kinetic data of uptake conformed to the Michaelis-Menten curve of saturation with a Km of 1.54 X 10(-2) M and Vmax of 3 X 10(-3) M/10s. The evidence presented in this paper indicates that compounds of protein nature are involved in the uptake of this preservative.


Purification and characterization of extracellular proteinases of Aspergillus oryzae. The extracellular proteinases of Aspergillus oryzae EI 212 were separated into two active fractions by (NH4)2SO4 and ethanol fractionation followed by diethylaminoethyl-Sephadex A-50 and hydroxyapatite chromatography. The molecular weight was estimated by gel filtration to be about 70,000 and 35,000 for proteinases I and II, respectively. Optimum pH for casein and hemoglobin hydrolysis was 6.5 at 60 C for proteinase I and 10.0 at 45 C for proteinase II, and for gelatin hydrolysis it was 6.5 at 45 C for both enzymes. The enzymes were stable over the pH range 6 to 8 at 30 C for 60 min. The enzyme activity for both the proteinases was accelerated by Cu2+ and inhibited by Fe2+, Fe3+, Hg2+, and Ag+. Halogenators (e.g., N-chlorosuccinimide) and diisopropyl fluorophosphate inhibited proteinase II. Sulfhydryl reagents such as p-chloromercuribenzoate and iodoacetate inhibited proteinase I. Sulfhydryl compounds accelerated the action of both enzymes.


Microbial metabolism of a parathion-xylene pesticide formulation. A mixed bacterial culture was adapted to growth on a mixed carbon substrate consisting of the pesticide parathion and its xylene-based formulation. The environmental growth parameters of temperature, pH, and  dissolved oxygen concentration were optimized to obtain complete metabolism of parathion from this mixed carbon substrate. This adapted culture grew rapidly (mu = 0.7 per h) on the pesticide formulation at high parathion suspensions (3,000 mg/liter). Carbon utilization from this mixed substrate was strongly dependent on pH. At slightly acidic pH, xylene was preferentially metabolized, whereas at slightly alkaline pH, parathion was preferentially metabolized. Diethylthiophosphoric acid, a metabolite from parathion, and toluic acid, a metabolite from xylene, also influenced the selection of the primary carbon source.


Effects of adrenergic stimulating and blocking agents on the eccrine sweat secretion in atopic dermatitis and psoriasis. Quantitative measurements of eccrine sweat secretion following stimulation with adrenaline and terbutaline sulphate, a beta-stimulator, have been performed in patients with atopic dermatitis and psoriasis by means of the electrolytic water analyzer, "Meeco". Seasonal variations were demonstrated, the values being lower in the late autumn. The response to adrenaline could be blocked by phentolamine, an alpha-inhibitor, while propranolol, a beta inhibitor, had no effect.--The response to terbutaline was blocked by atropine and partly by practolol, a beta-inhibitor. Terbutaline induced a larger sweat response than isoprenaline, another beta-stimulator. A beta-receptor mechanism, in some way related to cholinergic receptors, is suggested.


Nucleation of monosodium urate crystals. (1) Calcium greatly increased crystallization of monosodium urate in otherwise pure water, by enhancing both nucleation and growth. (2) Acid accelerated urate nucleation, both by its direct action and indirectly by increasing the free calcium in physiological fluids. (3) Synovial fluid from one gouty patient accelerated urate nucleation, while that from one rheumatoid patient inhibited nucleation. (4) X-rays, collagen, ethyl alcohol, cupric ion, and potassium ion all had negligible influence on urate nucleation. (5) Mechanical shock greatly increased urate nucleation.


Massive Ringer's lactate infusion: comparison with dextrose 5% and whole blood. The objectives of this study were to compare in dogs the effects of massive infusion of Ringer's lactate, 5% dextrose in water, and whole blood. Special interest centered upon lung function, central venous pressure, and dilutional effects upon the blood components. Three groups of 5 healthy dogs each received respectively Ringer's lactate, 5% dextrose, or whole blood over 60 minutes in the amount of 135 ml/kg. Arterial blood gases and pH, right atrial and systemic arterial pressures, hemoglobin and hematocrit values, and plasma sodium, chloride, potassium and protein levels were determined. Coagulograms and serum osmolality were examined in the early experiments. The purpose of the whole blood infusion was primarily to serve for comparison in the study of dilutional effects upon blood components. There was no statistically significant change in the arterial blood gas values or pH following Ringer's lactate infusion. The infusion of 5% dextrose in water produced moderate decline in arterial Pco2 and a temporary, slight fall in blood pH. Ringer's lactate infusion produced a prompt and statistically significant rise in central venous pressure. The infusion of 5% dextrose was followed by a late moderate decline in arterial blood pressure, possibly due to marked dilution of plasma sodium, chloride and potassium. It is concluded that massive Ringer's lactate infusion is capable of increasing right atrial pressure and presumably cardiac output. In healthy dogs, lung function was not impaired sufficiently to alter arterial blood gas values. However, where other previous or concomitant factors have diminished pulmonary reserve, fluid overload may impose a serious additional burden upon cardiopulmonary function.


The pathophysiology of smoke inhalation injury. The consequences of near-lethal smoke inhalation in dogs were studied for a 72-hour period following injury. Progressive hypoxemia and decrease in compliance developed. Severe respiratory distress and frank pulmonary edema were not encountered. Respiratory insufficiecy was related more to alterations in ventilation perfusion ratios than to alveolar destruction. These data were related to clinical observations made by others. No deterioration of lung function was seen with crystalloid overload imposed upon smoke inhalation. The presence of bacterial infection in dogs surviving beyond 24 hours appears pathogenically significant.


A comparison in vivo dacron wool (Swank) and polyester mesh (Pall) micropore blood transfusion filters in the prevention of pulmonary microembolism associated with massive transfusion. Experiments were performed to compare the effectiveness in vivo of the two most widely used micropore blood transfusion filters in preventing detrimental physiologic changes associated with transfusion of microaggregate-containing blood. Exchange transfusion with stored blood having an elevated screen filtration pressure (SFP) through polyester mesh (Pall) filters (Group PM) was followed by decreases in arterial blood pH and O2 consumption, increases in arterial blood pyruvate and lactate concentrations, and a decrease in pulmonary DO2. The lungs of 5 of 6 animals revealed emboli far out in the pulmonary microcirculation. These changes did not occur in animals transfused through dacron wool (Swank) filters (Group DW). Even though an increase after transfusion in pulmonary Qs/Qt in Group PM did not achieve statistical significance when compared to pretransfusion Qs/Qt, it was significantly higher than that in animals in Group DW. Both filters removed considerable quantities of microaggregates; however, the polyester mesh (Pall) filters permitted passage of small microaggregates and development of ditrimental physiologic changes. Dacron wool (Swank) filters completely removed measurable microaggregates and detrimental changes did not occur.


Postoperative arterial blood gas measurement in obese patients: effect of position on gas exchange. The effect of position change on blood gas exchange was studied in 22 markedly obese, otherwise healthy, women both preoperatively and postoperatively. There was a statistically significant decrease in arterial oxygen tension and a simultaneous reduction both in the arterial carbon dioxide tension and the base excess with the assumption of the supine versus the semirecumbent position on postoperative days one and two. However, no positional difference was demonstrable in any variable by the third postoperative day. This study indicates that in obese patients during the first 48 hours after abdominal surgery, assumption and maintenance of the semirecumbent posture is a valuable therapeutic adjunct to improve arterial oxygenation.


On the narcotic cuing action of fentanyl and other narcotic analgesic drugs. Using a food-reinforced two-levers operant procedure, rats could be trained to discriminate fentanyl (1.25 mg/kg, p.o., t-60') from solvent (1 ml/100 g B.W., p.o.,t60)treatment. The administration of the other narcotic analgesics bezitramide, dextromoramide, methadone and morphine produced a dose-related stimulus generalization with the standard fentanyl treatment. The results further evidence the validity of the narcotic cue.


The effects of three benzodiazepines and of meprobamate on the action of smooth muscle stimulants on the guinea-pig ileum. The benzodiazepines chlorodiazepoxide, diazepam and flurazepam and meprobamate depress the response of the guinea-pig ileum to acetylcholine, histamine and 5-hydroxytryptamine. As compared to the benzodiazepines the action of meprobamate is very weak. Chlorodiazepoxide has a weaker anti-acetylcholine activity than diazepam and flurazepam. On the other hand chlorodiazepoxide possesses a realtively strong anti-histamine activity. The three benzodiazeptines tested are about equally effective in reducing the contraction of the guinea-pig ileum caused by 5-hydroxytryptamine. The potency of diazepam and flurazepam in blocking the effect of the three smooth muscle stimulants appears to be rather similar.


Pharmacological characteristics of the responses of rabbit oviduct to transmural stimulation. The nature of the response of oestrogen dominant rabbit oviduct to transmural stimulation has been investigated. Both ampulla and isthmus responded to transmural stimulation with a single maintained response. This response was abolished by phentolamine, guanethidine, tetradotoxin and 6-hydroxydopamine showing that it resulted from the release of noradrenaline from adrenergic nerves and an action on alpha receptors. Propranolol had no effect on the responses of circular isthmic muscle suggesting that the beta receptors were relatively unimportant in determining the magnitude of the response. Cocaine failed to potentiate the magnitude of the response to field stimulation but did prolong the duration of the response. UO521, an inhibitor of COMT, had no effect on the responses of circular isthmus to transmural.


Cinnarizine and flunarizine, potent inhibitors of anaphylactic shock in guinea-pigs. Histamine-induced paw oedema and anaphylactic shock were studied simultaneously in ovalbumin-sensitized guinea-pigs and cinnarizine and flunarizine were evaluated quantitatively with regard to protection from the two types of challenge. Both compounds were markedly more active in preventing lethal anaphylaxis (ED50's of 0.67 and 0.53 mg/kg OR) than in reducing histamine oedema (ED50's of 2.77 and 1.54 mg/kg OR). The high anti-anaphylactic potency after oral administration may be an important finding in view of the therapeutic applications of cinnarizine and flunarizine.


The role of the central nervous system in the cardiovascular responses to yohimbine. Yohimbine injected intravenously or intracerebroventricularly in conscious dogs produced behavioural excitation accompanied by a rise in blood pressure and heart rate. The cardiovascular effects were reduced or abolished by hexamethonium, phenoxybenzamine and reserpine. In conscious cats intravenously administered yohimbine was depressor but intracerebroventricular administration in these animals caused a rise in blood pressure accompanied by behavioural depression. In anaesthetized or decerebrate cats yohimbine was always depressor. Yohimbine injected intracerebroventricularly produced a rise in blood pressure and heart rate in both conscious and anaesthetized rats. When administered intravenously to these animals there was a fall in blood pressure. It was concluded that the pressor action of yohimbine in conscious dogs was central in origin via the sympathetic nervous system. The different pattern of cardiovascular responses in the dog, cat and rat may be related to differences in the balance between medullary effects and effects on higher brain centres of the three species.


The role of bronchoconstrictors in evaluating smooth muscle relaxant activity. Several bronchoconstrictor and smooth muscle relaxant agents were studied in a dog preparation (in vivo) and on guinea pig tracheal strips (in vitro). Isoproterenol, isoetharine and N-t-butylnorepinephrine, individually, had similar dose-response curves and ED50 values when tested as antagonists of histamine and carbamylcholine-induced bronchoconstriction in dogs. Diphenhydramine, cyproheptadine, thenyldiamine, atropine and suloxifen each exhibited more selective antagonism. A ratio of anticholinergic and antihistamine ED50s was obtained in dogs and on guinea pig tracheal strips. The rank order correlation coefficient of this ratio for each drug in the two species (rs = 0.93) was highly significant. Dose-responses to smooth muscle relaxant effects of isoproterenol were obtained with several different constrictors and experimental conditions on guinea pig tracheal strips. The choice of a constrictor and experimental conditions was found to affect EC50 values. The influence of resting tension, temperature, season, dibenamine-pretreatment and manner of performing the dose-response was evaluated. Both Ba and carbamylcholine were found to be suitable constricting agents under various conditions, whereas histamine, serotonin, potassium and rubidium had more limitations and eight other inorganic ions were not suitable.


Effect of temperature, salts, pH, and other factors on the development of peritrichous flagella in Vibrio alginolyticus. The development of peritrichous flagella and, consequently, swarming of Vibrio alginolyticus depend on a complex relationship between temperature, salt concentrations and pH. At temperatures above 28 degrees C V. alginolyticus did not develop peritrichous flagella unless certain minimal concentrations of NaCl are present: the higher the temperature, the higher the NaCl concentrations required for peritrichous flagella synthesis. This requirement for NaCl at high temperatures is much more pronounced at pH 9 than at pH 6. High temperatures and low concentrations of NaCl also inhibited swarming of cells already armed with peritrichous flagella. Other cations, such as Li+, K+ and Mg2+. replaced NaCl only at temperatures below 28 degrees C.


Observations on enzymes of ammonia assimilation in two different strains of Cyanidium caldarium. Two strains of Cyanidium caldarium, one able to utilize nitrate as a substrate, and the other not, were tested for the presence of enzymes of ammonia assimilation. The nitrate-assimilating strain exhibits glutamate dehydrogenase activity. By contrast, the other strain lacks glutamate dehydrogenase; it possesses high alanine dehydrogenase and L-alanine aminotransferase activities which suggest that this strain may incorporate ammonia through reductive amination of pyruvate and may form glutamate from 2-ketoglutarate by a transamination reaction with alanine. Neither strain reveals glutamate synthase activity. Both strains contain similar levels of glutamine synthetase.


The nitrate-reducing enzyme system of Chlamydomonas reinhardii. In Chlamydomonas reinhardii the reduction of nitrate to ammonia occurs in two independent enzymatic steps: 1. the two-electrons reduction of nitrate to nitrite catalyzed by NADH-nitrate reductase, and, 2. the six-electrons reduction of nitrite to ammonia catalyzed by ferredoxin-nitrite reductase. Both enzymes have been purified and characterized, and some of their properties have been studied.