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PMID:4834 | Biosynthesis of uroporphyrinogens from porphobilinogen: mechanism and the nature of the process. | The enzymic self-polymerization of prophobilinogen gives rise to the cyclic tetrapyrroles uroporphyrinogen III and uroporphyrinogen I. The former is the precursor of all the natural porphyrins and chlorins. The formation of uroporphyrinogen III is catalysed by a dual enzymic system, porphobilinogen deaminase and uroporphyrinogen III cosynthase. Deaminase polymerizes four porphobilinogen units on the enzymic surface, without liberation of free intermediates into the reaction medium, and forms uroporphyrinogen I. Cosynthase enters into association with the deaminase, and acts as a 'specifier protein' of the latter, changing the mode of porphobilinogen condensation on the enzymic surface. The association is independent of the presence of substrate. While deaminase catalyses the head-to-tail condensation of the porphobilinogen units, the association deaminase-cosynthase catalyses the head-to-head condensation of the same units. As a result different enzyme-bound dipyrrylmethanes are formed form the beginning of the process, and this can be demonstrated by using synthetic dipyrrylmethanes and tripyrranes. | Biosynthesis of uroporphyrinogens from porphobilinogen: mechanism and the nature of the process. The enzymic self-polymerization of prophobilinogen gives rise to the cyclic tetrapyrroles uroporphyrinogen III and uroporphyrinogen I. The former is the precursor of all the natural porphyrins and chlorins. The formation of uroporphyrinogen III is catalysed by a dual enzymic system, porphobilinogen deaminase and uroporphyrinogen III cosynthase. Deaminase polymerizes four porphobilinogen units on the enzymic surface, without liberation of free intermediates into the reaction medium, and forms uroporphyrinogen I. Cosynthase enters into association with the deaminase, and acts as a 'specifier protein' of the latter, changing the mode of porphobilinogen condensation on the enzymic surface. The association is independent of the presence of substrate. While deaminase catalyses the head-to-tail condensation of the porphobilinogen units, the association deaminase-cosynthase catalyses the head-to-head condensation of the same units. As a result different enzyme-bound dipyrrylmethanes are formed form the beginning of the process, and this can be demonstrated by using synthetic dipyrrylmethanes and tripyrranes. | [
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PMID:4835 | Biosynthesis of porphyrins and corrins. | Haem, chlorophyll and vitamin B12 are all derived ultimately from four molecules of the pyrrole porphobilinogen (PBG) and the initial enzyme catalysed condensation of PBG leads to the unsymmetrical type III isomer of uroporphyrinogen. On the basis of straightforward chemical considerations the type I isomer should be formed and so the porphyrinogen-forming enzymes of all living systems must catalyse a highly specific rearrangement process. The nature and chemical mechanism of this rearrangement poses one of the most fascinating problems in the porphyrin field and so it is not surprising that over 20 hypothetical schemes have been proposed to account for it. Analysis of the problem suggested that the incorporation of doubly 13C-labelled precursors into the rearranged macrocyclic rings would give valuable new information on the nature of the rearrangement process. In this approach the meso=bridge atoms are of crucial importance, and several unambiguous syntheses of 13C-labelled pyrroles and porphyrins were developed to allow rigorous n.m.r. assignments to be made, and also to provide substrates for enzymic experiments. Studies carried out with enzymes from both avian blood and from Euglena gracilis have revealed the precise nature of the assembly of four PBG molecules into the type-III macrocycle: it is the same in both systems despite their vastly different evolutionary development. Complementary studies are in progress in order to determine the intermediates involved in the conversion of PBG into uroporphyrinogen III. The synthesis of amino methyl pyrromethanes and their interaction in the presence of PBG with the appropriate enzyme systems are described. It is important for the work to be able to separate not only isomeric pyrromethanes but also the four isomeric coproporphyrins. Powerful methods are described which make use of high pressure liquid chromatography for both types of separation process. Once uroporhyrinogen III has been built enzymically, there is a stepwise enzymic decarboxylation of the four acetic acid residues. A heptacarboxylic porphyrin shown to be a type-III porphyrin is isolated from the action of avian blood enzymes on porphobilinogen. Spectroscopic studies with 13C-labelling limit the possible structures to two and total synthesis of these substances shows that the natural product carries its methyl group on ring D. An isomeric heptacarboxylic porphyrin having its methyl group on ring C is of particular interest in relation to the biosynthesis of vitamin B12. This substance is synthesized together with uroporphyrin III, 14C-labelled specifically in ring C. This latter product is used to settle one of the key questions concerning nature's route to vitamin B12 - that is, does the corrin macrocycle arise from uroporphyrinogen III? Incorporation studies and specific degradations prove specific incorporation of uroporphyrinogen III into cobyrinic acid, which is the known precursor of vitamin B12. | Biosynthesis of porphyrins and corrins. Haem, chlorophyll and vitamin B12 are all derived ultimately from four molecules of the pyrrole porphobilinogen (PBG) and the initial enzyme catalysed condensation of PBG leads to the unsymmetrical type III isomer of uroporphyrinogen. On the basis of straightforward chemical considerations the type I isomer should be formed and so the porphyrinogen-forming enzymes of all living systems must catalyse a highly specific rearrangement process. The nature and chemical mechanism of this rearrangement poses one of the most fascinating problems in the porphyrin field and so it is not surprising that over 20 hypothetical schemes have been proposed to account for it. Analysis of the problem suggested that the incorporation of doubly 13C-labelled precursors into the rearranged macrocyclic rings would give valuable new information on the nature of the rearrangement process. In this approach the meso=bridge atoms are of crucial importance, and several unambiguous syntheses of 13C-labelled pyrroles and porphyrins were developed to allow rigorous n.m.r. assignments to be made, and also to provide substrates for enzymic experiments. Studies carried out with enzymes from both avian blood and from Euglena gracilis have revealed the precise nature of the assembly of four PBG molecules into the type-III macrocycle: it is the same in both systems despite their vastly different evolutionary development. Complementary studies are in progress in order to determine the intermediates involved in the conversion of PBG into uroporphyrinogen III. The synthesis of amino methyl pyrromethanes and their interaction in the presence of PBG with the appropriate enzyme systems are described. It is important for the work to be able to separate not only isomeric pyrromethanes but also the four isomeric coproporphyrins. Powerful methods are described which make use of high pressure liquid chromatography for both types of separation process. Once uroporhyrinogen III has been built enzymically, there is a stepwise enzymic decarboxylation of the four acetic acid residues. A heptacarboxylic porphyrin shown to be a type-III porphyrin is isolated from the action of avian blood enzymes on porphobilinogen. Spectroscopic studies with 13C-labelling limit the possible structures to two and total synthesis of these substances shows that the natural product carries its methyl group on ring D. An isomeric heptacarboxylic porphyrin having its methyl group on ring C is of particular interest in relation to the biosynthesis of vitamin B12. This substance is synthesized together with uroporphyrin III, 14C-labelled specifically in ring C. This latter product is used to settle one of the key questions concerning nature's route to vitamin B12 - that is, does the corrin macrocycle arise from uroporphyrinogen III? Incorporation studies and specific degradations prove specific incorporation of uroporphyrinogen III into cobyrinic acid, which is the known precursor of vitamin B12. | [
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PMID:4836 | Synthesis of probable and improbable precursors for porphyrin biosynthesis. | Insights into details of the biomechanism by which porphobilinogen (1) cyclotetramerizes to uroporphyrinogen III (2) as well as promising synthetic applications are provided by investigation of this reaction in vitro. The cyclotetramerization of newly prepared norporphobilinogen (5) proved to be extemely specific due to strong conformation control. Advantage was taken of this finding by preparing a N,N,N,N-tetramethyl-porphyrinogen (13a) for the first time. Protected derivatives of the linear tetramer of porphobilinogen (20c) which is regarded as an intermediate of the cyclotetramerization were gained by total synthesis and their transformations investigated. | Synthesis of probable and improbable precursors for porphyrin biosynthesis. Insights into details of the biomechanism by which porphobilinogen (1) cyclotetramerizes to uroporphyrinogen III (2) as well as promising synthetic applications are provided by investigation of this reaction in vitro. The cyclotetramerization of newly prepared norporphobilinogen (5) proved to be extemely specific due to strong conformation control. Advantage was taken of this finding by preparing a N,N,N,N-tetramethyl-porphyrinogen (13a) for the first time. Protected derivatives of the linear tetramer of porphobilinogen (20c) which is regarded as an intermediate of the cyclotetramerization were gained by total synthesis and their transformations investigated. | [
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PMID:4837 | Macrocyclic intermediates in the biosynthesis of porphyrins. | The hepta-, hexa- and penta-carboxylic porphyrins found in the faeces of rats poisoned with hexachlorobenzene have been separated by high-pressure liquid chromatography and characterized largely by spectroscopie methods. Their structures were confirmed by total synthesis, as part of a programme in which eleven of the fourteen hepta-, hexa- and penta-carboxylic porphyrins derived from uroporphyrin III have now been synthesized as their methyl esters. The four isomeric heptacarboxylic and three of the pentacarboxylic porphyrinogens have been incubated with haemolysates of chicken erythrocytes, and they are all converted into protoporphyrin IX but at different rates. On the basis of this and other evidence we conclude that the decarboxylation of uroporphyrinogen III to coproporphyrinogen III is a stepwise process taking place by a preferred pathway (both in normal and abnormal metabolism); the acetic acid groups are decarboxylated in a sequential clockwise fashion starting with that on the D ring and followed by those on the A, B and C rings. In the poisoned rats the uroporphyrinogen decarboxylase enzyme (or group of enzymes) is probably partially inhibited and the pentacarboxylic porphyrinogen with an acetic acid group on ring C accumulates. The latter is then transformed by a side pathway into dehydroisocoproporphyrinogen and thence into dehydroisocoproporphyrin and its congeners. | Macrocyclic intermediates in the biosynthesis of porphyrins. The hepta-, hexa- and penta-carboxylic porphyrins found in the faeces of rats poisoned with hexachlorobenzene have been separated by high-pressure liquid chromatography and characterized largely by spectroscopie methods. Their structures were confirmed by total synthesis, as part of a programme in which eleven of the fourteen hepta-, hexa- and penta-carboxylic porphyrins derived from uroporphyrin III have now been synthesized as their methyl esters. The four isomeric heptacarboxylic and three of the pentacarboxylic porphyrinogens have been incubated with haemolysates of chicken erythrocytes, and they are all converted into protoporphyrin IX but at different rates. On the basis of this and other evidence we conclude that the decarboxylation of uroporphyrinogen III to coproporphyrinogen III is a stepwise process taking place by a preferred pathway (both in normal and abnormal metabolism); the acetic acid groups are decarboxylated in a sequential clockwise fashion starting with that on the D ring and followed by those on the A, B and C rings. In the poisoned rats the uroporphyrinogen decarboxylase enzyme (or group of enzymes) is probably partially inhibited and the pentacarboxylic porphyrinogen with an acetic acid group on ring C accumulates. The latter is then transformed by a side pathway into dehydroisocoproporphyrinogen and thence into dehydroisocoproporphyrin and its congeners. | [
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PMID:4838 | Neovitamin B12 (cyano-13-epicobalamin). | Beta-Epimerization in the corrinoid system has recently emerged as a complicating factor in the latter stages of the total synthesis of vitamin B12 (Eschenmoser 1971; Woodward 1973). It has also found some application in biosynthetic studies on the origin of the methyl groups in ring C (Scott, Townsend & Cushley 1973; Scott, this Discussion p. 303). This paper sets out to review briefly the beta-epimerization of corrinoid polyamides, with particular reference to our work on the neo-series which provided the first established example of this phenomenon. | Neovitamin B12 (cyano-13-epicobalamin). Beta-Epimerization in the corrinoid system has recently emerged as a complicating factor in the latter stages of the total synthesis of vitamin B12 (Eschenmoser 1971; Woodward 1973). It has also found some application in biosynthetic studies on the origin of the methyl groups in ring C (Scott, Townsend & Cushley 1973; Scott, this Discussion p. 303). This paper sets out to review briefly the beta-epimerization of corrinoid polyamides, with particular reference to our work on the neo-series which provided the first established example of this phenomenon. | [
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PMID:4839 | The biosynthesis of vitamin B12. | The use of 13C-Fourier transform nuclear magnetic resonance (F.t.-n.m.r.) has led to the observation that while 8 molecules of [2-13C]ALA are incorporated into vitamin B12 in P. shermanii, [5-13C]ALA labels only seven of the carbon atoms of cyanocobalamin, i.e. one of the amino methyl groups of ALA is "lost" in the process. It has also been confirmed that seven of the methyl groups of B12 are derived from 13CH3-enriched methionine and further that the chirality of the gemdimethyl grouping at C12 labelled with [13CH3]methionine is R. A soluble enzyme mixture from the 37000 or 100000 g supernatant of disrupted cells of P. shermanii converts both 14 C-labelled ALA and [14C]uro'gen III to cobyrinic acid, the simplest corrinoid material on the pathway to vitamin B12 and the coenzyme, in presence of NADPH, Co2+, Mg2+, S-adenosyl-methionine and glutathione. Multiply-labelled uro'gens (13C, 14C and 3H) have been used to show that incorporation takes place without randomization. A sequence for corrin synthesis from uro'gen III is presented. | The biosynthesis of vitamin B12. The use of 13C-Fourier transform nuclear magnetic resonance (F.t.-n.m.r.) has led to the observation that while 8 molecules of [2-13C]ALA are incorporated into vitamin B12 in P. shermanii, [5-13C]ALA labels only seven of the carbon atoms of cyanocobalamin, i.e. one of the amino methyl groups of ALA is "lost" in the process. It has also been confirmed that seven of the methyl groups of B12 are derived from 13CH3-enriched methionine and further that the chirality of the gemdimethyl grouping at C12 labelled with [13CH3]methionine is R. A soluble enzyme mixture from the 37000 or 100000 g supernatant of disrupted cells of P. shermanii converts both 14 C-labelled ALA and [14C]uro'gen III to cobyrinic acid, the simplest corrinoid material on the pathway to vitamin B12 and the coenzyme, in presence of NADPH, Co2+, Mg2+, S-adenosyl-methionine and glutathione. Multiply-labelled uro'gens (13C, 14C and 3H) have been used to show that incorporation takes place without randomization. A sequence for corrin synthesis from uro'gen III is presented. | [
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PMID:4840 | Synthesis of corrins and related macrocycles based on pyrrolic intermediates. | Intermediate in structure between porphyrins and corrins are the corroles and 1-methyltetradehydrocorrins. These ring systems, like the porphyrins, can be obtained by cyclization of linear tetrapyrrolic compounds, reactions which have been shown to proceed by orbital symmetry-allowed electrocyclic processes, and examples will be quoted. Thermolysis of nickel 1-methyltetradehydrocorrins causes a migration of the methyl group whereas similar treatment of nickel 1,19-dimethyltetradehydrocorrin salts yields porphyrin derivatives; the mechanisms of these transformations have been elucidated. Stepwise hydrogenation of metal tetradehydrocorrin salts (10 double bonds) yields a series of macrocycles containing 9, 8, 7, 6 and 5 double bonds and conditions necessary to obtain corrins have been established. | Synthesis of corrins and related macrocycles based on pyrrolic intermediates. Intermediate in structure between porphyrins and corrins are the corroles and 1-methyltetradehydrocorrins. These ring systems, like the porphyrins, can be obtained by cyclization of linear tetrapyrrolic compounds, reactions which have been shown to proceed by orbital symmetry-allowed electrocyclic processes, and examples will be quoted. Thermolysis of nickel 1-methyltetradehydrocorrins causes a migration of the methyl group whereas similar treatment of nickel 1,19-dimethyltetradehydrocorrin salts yields porphyrin derivatives; the mechanisms of these transformations have been elucidated. Stepwise hydrogenation of metal tetradehydrocorrin salts (10 double bonds) yields a series of macrocycles containing 9, 8, 7, 6 and 5 double bonds and conditions necessary to obtain corrins have been established. | [
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PMID:4841 | Chemical behavior of dicyanocob(III)yrinic acid heptamethyl ester and cob(I)yrinic acid heptamethyl ester in some preparative experiments. | Preparations of C10 acetate, trifluoroacetate, and chloro derivatives of dicyanocobyrinic acid heptamethyl ester ('cobester') are described. The nature and properties of intermediates in the synthesis of the 10-chloro derivative are discussed, and the electronic absorption spectra of the products are presented. | Chemical behavior of dicyanocob(III)yrinic acid heptamethyl ester and cob(I)yrinic acid heptamethyl ester in some preparative experiments. Preparations of C10 acetate, trifluoroacetate, and chloro derivatives of dicyanocobyrinic acid heptamethyl ester ('cobester') are described. The nature and properties of intermediates in the synthesis of the 10-chloro derivative are discussed, and the electronic absorption spectra of the products are presented. | [
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PMID:4842 | Chemical reactivities of tetrapyrrole pigments: a comparison of experimentalbehaviour with the results of s.c.f.-pi-m.o. calculations. | Porphyrins are highly sigma-electron donating bases and very weak pi-acids. Hence they increase the electron density on central metal ions, e.g. iron, which leads to the specific reactivity of haem cytochromes, haemoglobin and oxidizing enzymes. The macrocyclic chlorin ligand behaves similarly but to a lesser degree which explains the comparably low oxidation potential of chlorophyll. Phlorins, oxophlorins, oxa- and aza-orphyrins, tetradehydrocorrins, corrins and biliverdins all produce metal complexes which have a similar geometry to that of metalloporphyrins, but their reactivity patterns are different. In contrast to the metalloporphyrins which undergo many fully reversible reactions, these compounds tend to irreversible addition and cleavage reactions. The tetrapyrrole ligands are stronger pi-acids than porphyrins. Results of some recent experimental work and pi-electron s.c.f. calculations are presented in support of these generalizations. | Chemical reactivities of tetrapyrrole pigments: a comparison of experimentalbehaviour with the results of s.c.f.-pi-m.o. calculations. Porphyrins are highly sigma-electron donating bases and very weak pi-acids. Hence they increase the electron density on central metal ions, e.g. iron, which leads to the specific reactivity of haem cytochromes, haemoglobin and oxidizing enzymes. The macrocyclic chlorin ligand behaves similarly but to a lesser degree which explains the comparably low oxidation potential of chlorophyll. Phlorins, oxophlorins, oxa- and aza-orphyrins, tetradehydrocorrins, corrins and biliverdins all produce metal complexes which have a similar geometry to that of metalloporphyrins, but their reactivity patterns are different. In contrast to the metalloporphyrins which undergo many fully reversible reactions, these compounds tend to irreversible addition and cleavage reactions. The tetrapyrrole ligands are stronger pi-acids than porphyrins. Results of some recent experimental work and pi-electron s.c.f. calculations are presented in support of these generalizations. | [
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PMID:4843 | The structures of some cobalamins in solution. | Nuclear magnetic resonance spectroscopy has been used to examine the conformations of cobalamins in solution. The perturbation of the resonances in the n.m.r. spectra by lanthanide probes provided particularly valuable information. Except for minor details the conformations are the same as those in the crystalline state. The temperature dependence of the conformation has been reassessed. | The structures of some cobalamins in solution. Nuclear magnetic resonance spectroscopy has been used to examine the conformations of cobalamins in solution. The perturbation of the resonances in the n.m.r. spectra by lanthanide probes provided particularly valuable information. Except for minor details the conformations are the same as those in the crystalline state. The temperature dependence of the conformation has been reassessed. | [
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PMID:4844 | Control of 5-aminolaevulinate synthetase activity in Rhodopseudomonas spheroides. | Rhodopseudomonas spheroides can grow in a defined medium with either light or oxygen as an energy source. Cells grown anaerobically or at very low oxygen tensions are rich in the photosynthetic pigment bacteriochlorophyll, whereas this pigment is virtually absent in cells grown under high oxygen tensions. Aminolaevulinate synthetase, the first enzyme on the pathway to bacteriochlorophyll, appears to play an important role in the control of bacteriochlorophyll synthesis. Thus, the enzyme has a high activity in extracts of pigmented cells and a low activity in extracts of non-pigmented cells. Further, oxygenation of a pigmented culture causes immediate cessation of pigment synthesis and produces a rapid fall in the activity of aminolaevulinate synthetase. This loss of activity appears to be due to the loss of an endogenous activator of the enzyme. Thus, pigmented cells contain cystine trisulphide, which at muM concentrations is an activator of aminolaevulinate synthetase, while oxygenation causes a rapid fall in the cellular content of this trisulphide. Cystathionase (EC 4.2.1.15) extracted from pigmented cells can catalyse the formation of cystine trisulphide from cystine, while rhodanese (EC 2.8.1.1) extracted from the same cells can catalyse the degradation of cystine trisulphide in the presence of sulphite to form cystine and thiosulphate. It is proposed that the cellular content of cystine trisulphide is controlled by changes in the levels of substrates for cystathionase and possibly rhodanese rather than changes in the amounts of these enzymes. Cystine trisulphide controls the activity of aminolaevulinate synthetase by converting a low-activity form of the enzyme (b-form) into a high-activity form (a-form). The fall in aminolaevulinate synthetase activity on oxygenation appears to be the result of cessation of conversion of b-form into a-form, along with a conversion of a-form into b-form. Factors affecting the equilibrium between the forms and the possible mechanisms for their interconversion are discussed. | Control of 5-aminolaevulinate synthetase activity in Rhodopseudomonas spheroides. Rhodopseudomonas spheroides can grow in a defined medium with either light or oxygen as an energy source. Cells grown anaerobically or at very low oxygen tensions are rich in the photosynthetic pigment bacteriochlorophyll, whereas this pigment is virtually absent in cells grown under high oxygen tensions. Aminolaevulinate synthetase, the first enzyme on the pathway to bacteriochlorophyll, appears to play an important role in the control of bacteriochlorophyll synthesis. Thus, the enzyme has a high activity in extracts of pigmented cells and a low activity in extracts of non-pigmented cells. Further, oxygenation of a pigmented culture causes immediate cessation of pigment synthesis and produces a rapid fall in the activity of aminolaevulinate synthetase. This loss of activity appears to be due to the loss of an endogenous activator of the enzyme. Thus, pigmented cells contain cystine trisulphide, which at muM concentrations is an activator of aminolaevulinate synthetase, while oxygenation causes a rapid fall in the cellular content of this trisulphide. Cystathionase (EC 4.2.1.15) extracted from pigmented cells can catalyse the formation of cystine trisulphide from cystine, while rhodanese (EC 2.8.1.1) extracted from the same cells can catalyse the degradation of cystine trisulphide in the presence of sulphite to form cystine and thiosulphate. It is proposed that the cellular content of cystine trisulphide is controlled by changes in the levels of substrates for cystathionase and possibly rhodanese rather than changes in the amounts of these enzymes. Cystine trisulphide controls the activity of aminolaevulinate synthetase by converting a low-activity form of the enzyme (b-form) into a high-activity form (a-form). The fall in aminolaevulinate synthetase activity on oxygenation appears to be the result of cessation of conversion of b-form into a-form, along with a conversion of a-form into b-form. Factors affecting the equilibrium between the forms and the possible mechanisms for their interconversion are discussed. | [
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PMID:4847 | The structural subunit of glucose-6-phosphate dehydrogenase (baker's yeast). | The subunit molecular weight of glucose-6-phosphate dehydrogenase (G6PD) from baker's yeast has been evaluated. The subunit molecular weight value is shown to be 25,500 daltons by analytical ultracentrifugation, SDS-polyacrylamide gel electrophoresis, and the number of peptides produced by CNBr cleavage. The number of NADP binding sites was determined to be one per 25,500 dalton unit. | The structural subunit of glucose-6-phosphate dehydrogenase (baker's yeast). The subunit molecular weight of glucose-6-phosphate dehydrogenase (G6PD) from baker's yeast has been evaluated. The subunit molecular weight value is shown to be 25,500 daltons by analytical ultracentrifugation, SDS-polyacrylamide gel electrophoresis, and the number of peptides produced by CNBr cleavage. The number of NADP binding sites was determined to be one per 25,500 dalton unit. | [
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PMID:4848 | Study of cystinaminopeptidase heterogeneity in animal sera by the isoelectric focusing method. | Study of the quantitative distribution of cystinaminopeptidase activity in the serum of pregnant and control animals (cow, sheep and rat) by the isoelectric focusing method showed heterogeneity of the cystinaminopeptidase activity of the animals' serum enzymatic system, which was well pronounced in the cow and rat and less pronounced in the sheep. The authors assume from their results that the principal difference between the pregnant and control animals is not the total increase in the level of activity of the enzyme in question, but the shift in its incidence, or the increase in activity at a given pH. It is possible that pregnancy, in man and animals, produces in the serum cystinaminopeptidase system (which is evidently heterogeneous even under normal, physiological conditions) given changes, i.e. the formation of new fractions with a different pI from the controls; other fractions disappear, or their activity diminishes. | Study of cystinaminopeptidase heterogeneity in animal sera by the isoelectric focusing method. Study of the quantitative distribution of cystinaminopeptidase activity in the serum of pregnant and control animals (cow, sheep and rat) by the isoelectric focusing method showed heterogeneity of the cystinaminopeptidase activity of the animals' serum enzymatic system, which was well pronounced in the cow and rat and less pronounced in the sheep. The authors assume from their results that the principal difference between the pregnant and control animals is not the total increase in the level of activity of the enzyme in question, but the shift in its incidence, or the increase in activity at a given pH. It is possible that pregnancy, in man and animals, produces in the serum cystinaminopeptidase system (which is evidently heterogeneous even under normal, physiological conditions) given changes, i.e. the formation of new fractions with a different pI from the controls; other fractions disappear, or their activity diminishes. | [
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PMID:4849 | Thiopental anaesthesia and the acid-base balance in the blood of experimental dogs. | An analysis of basic parameters representative of the acid-base balance was made in arterial blood samples from 140 clinically healthy dogs, under a general intravenous Thiopental anaesthesia. The following mean values +/- S.E.M. were obtained: pH = 7.33 +/- 0.01; pCO2 = 47.16 +/- 0.95; base excess = -2.12 +/- 0.27; buffer base = 46.63 +/- 0.37. The results showed a prevalent trend of lower values of pH, base excess and buffer base and higher values of pCO2 than those found commonly in human clinical practice. Special attention was paid to the respiratory component of the acid-base balance (ABB) revealing certain undesirable side effect of Thiopental anaesthesia. | Thiopental anaesthesia and the acid-base balance in the blood of experimental dogs. An analysis of basic parameters representative of the acid-base balance was made in arterial blood samples from 140 clinically healthy dogs, under a general intravenous Thiopental anaesthesia. The following mean values +/- S.E.M. were obtained: pH = 7.33 +/- 0.01; pCO2 = 47.16 +/- 0.95; base excess = -2.12 +/- 0.27; buffer base = 46.63 +/- 0.37. The results showed a prevalent trend of lower values of pH, base excess and buffer base and higher values of pCO2 than those found commonly in human clinical practice. Special attention was paid to the respiratory component of the acid-base balance (ABB) revealing certain undesirable side effect of Thiopental anaesthesia. | [
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PMID:4853 | Fast neutron and x-ray induced single strand DNA breaks in cultured mammalian cells. | The relative biologic effectiveness (RBE) of fast neutrons in the production of single strand DNA breaks is 1.6 as compared to that of 250 kVp x rays. Monolayers of L-929 cells were treated with dinitrophenol during irradiation to prevent the DNA strands from rejoining; the extent of DNA damage was measured by the alkaline sucrose sedimentation method. The RBE for DNA damage is essentially the same as the RBE measured by cell survival methods. | Fast neutron and x-ray induced single strand DNA breaks in cultured mammalian cells. The relative biologic effectiveness (RBE) of fast neutrons in the production of single strand DNA breaks is 1.6 as compared to that of 250 kVp x rays. Monolayers of L-929 cells were treated with dinitrophenol during irradiation to prevent the DNA strands from rejoining; the extent of DNA damage was measured by the alkaline sucrose sedimentation method. The RBE for DNA damage is essentially the same as the RBE measured by cell survival methods. | [
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PMID:4854 | Inhibition of prostaglandin biosynthesis by sulphasalazine and its metabolites. | Sulphasalazine (SZ) inhibits prostaglandin (PG) biosynthesis in vitro with a potency comparable to that of aceylsalicylate. The metabolites of SZ, sulphapyridine and 5-aminosalicylic acid, were of considerably lower potency as inhibitors of PG biosynthesis in the synthetase preparations used. Th inhibition of prostaglandin production by SZ could at least partly account for the clinical utility of sulphasalazine in ulcerative colitis. Sulphapyridine may help to maintain inhibitory concentrations of SZ by restraining bacterial breakdown of the active drug. | Inhibition of prostaglandin biosynthesis by sulphasalazine and its metabolites. Sulphasalazine (SZ) inhibits prostaglandin (PG) biosynthesis in vitro with a potency comparable to that of aceylsalicylate. The metabolites of SZ, sulphapyridine and 5-aminosalicylic acid, were of considerably lower potency as inhibitors of PG biosynthesis in the synthetase preparations used. Th inhibition of prostaglandin production by SZ could at least partly account for the clinical utility of sulphasalazine in ulcerative colitis. Sulphapyridine may help to maintain inhibitory concentrations of SZ by restraining bacterial breakdown of the active drug. | [
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PMID:4855 | Partial characterization of prostaglandin synthetase in the reproductive tract of the male house cricket, Acheta domesticus. | An active prostaglandin (PG) synthetase was found in the 12100 g pellet of reproductive tract homogenates of the male house cricket, Acheta domesticus. Comparatively, the 12100 g supernatant and the microsomal fractions were inactive. The PG synthetase in the pellet fraction was characterized in terms of cofactor, temperature, pH, and incubation time requirements. Indomethacin, a known inhibitor of mammalian PG synthetase, was not inhibitory to the cricket synthetase. The procedure and findings are relevant to PG synthetase studies of any organism or tissue. | Partial characterization of prostaglandin synthetase in the reproductive tract of the male house cricket, Acheta domesticus. An active prostaglandin (PG) synthetase was found in the 12100 g pellet of reproductive tract homogenates of the male house cricket, Acheta domesticus. Comparatively, the 12100 g supernatant and the microsomal fractions were inactive. The PG synthetase in the pellet fraction was characterized in terms of cofactor, temperature, pH, and incubation time requirements. Indomethacin, a known inhibitor of mammalian PG synthetase, was not inhibitory to the cricket synthetase. The procedure and findings are relevant to PG synthetase studies of any organism or tissue. | [
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PMID:4857 | Hydroxyzine hydrochloride: possible adverse cardiac interactions. | Hydroxyzine hydrochloride may produce abnormal ventricular repolarization when given in substratial doses or to susceptible individuals. Phenothiazines, such as thioridazine, tricyclic antidepressants, or antiparkinson drugs, any of which may be given concurrently to psychiatric patients, may augment this effect as well as atropine, quinidine or procainamide. Such EKG abnormalities may increase the likelihood of dysrhythmias and sudden death. | Hydroxyzine hydrochloride: possible adverse cardiac interactions. Hydroxyzine hydrochloride may produce abnormal ventricular repolarization when given in substratial doses or to susceptible individuals. Phenothiazines, such as thioridazine, tricyclic antidepressants, or antiparkinson drugs, any of which may be given concurrently to psychiatric patients, may augment this effect as well as atropine, quinidine or procainamide. Such EKG abnormalities may increase the likelihood of dysrhythmias and sudden death. | [
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PMID:4858 | Assessment of antipsychotic activity of an unique agent: SU-23397. | SU-23397 is a unique new hybrid molecule, the animal profile being characteristic of neuroleptic activity. Although the trial was uncontrolled, there appears to be no doubt that SU-23397 exerts antipsychotic activity between 20 mg and 250 mg daily in severely ill schizophrenic patients. Seven of the ten subjects required at least transient antiparkinson medication. Two patients demonstrated premature ventricular contractions. One patient had infrequent PVCs at baseline which increased in frequency with rising dosage. The other patient developed frequent premature ventricular contractions only after active and medication was initiated and was subsequently withdrawn from the study. | Assessment of antipsychotic activity of an unique agent: SU-23397. SU-23397 is a unique new hybrid molecule, the animal profile being characteristic of neuroleptic activity. Although the trial was uncontrolled, there appears to be no doubt that SU-23397 exerts antipsychotic activity between 20 mg and 250 mg daily in severely ill schizophrenic patients. Seven of the ten subjects required at least transient antiparkinson medication. Two patients demonstrated premature ventricular contractions. One patient had infrequent PVCs at baseline which increased in frequency with rising dosage. The other patient developed frequent premature ventricular contractions only after active and medication was initiated and was subsequently withdrawn from the study. | [
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PMID:4859 | The effect of various chlorpromazine derivatives on the apomorphine-elicited inhibition of synaptosomal tyrosine hydroxylase activity. | The effects of chlorpromazine and of some metabolites of chlorpromazine on the apomorphine-elicited inhibition of synaptosomal tyrosine hydroxylase activity were investigated. Chlorpromazine, nor1-chlorpromazine and 7-hydroxychlorpromazine reverse the apomorphine-elicited inhibition of tyrosine hydroxylase activity while nor1-chlorpromazine sulfoxide and nor2-chlorpromazine sulfoxide have no effect on this inhibition. 6-Hydroxychlorpromazine and promethazine also reverse the enzyme inhibition by apomorphine but are less potent than chlorpromazine or 7-hydroxychlorpromazine. These results show that chlorpromazine and its metabolites with antipsychotic activity are more effective in reversing the apomorphine-elicited inhibition of tyrosine hydroxylase than those metabolites which are devoid of antipsychotic activity. | The effect of various chlorpromazine derivatives on the apomorphine-elicited inhibition of synaptosomal tyrosine hydroxylase activity. The effects of chlorpromazine and of some metabolites of chlorpromazine on the apomorphine-elicited inhibition of synaptosomal tyrosine hydroxylase activity were investigated. Chlorpromazine, nor1-chlorpromazine and 7-hydroxychlorpromazine reverse the apomorphine-elicited inhibition of tyrosine hydroxylase activity while nor1-chlorpromazine sulfoxide and nor2-chlorpromazine sulfoxide have no effect on this inhibition. 6-Hydroxychlorpromazine and promethazine also reverse the enzyme inhibition by apomorphine but are less potent than chlorpromazine or 7-hydroxychlorpromazine. These results show that chlorpromazine and its metabolites with antipsychotic activity are more effective in reversing the apomorphine-elicited inhibition of tyrosine hydroxylase than those metabolites which are devoid of antipsychotic activity. | [
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PMID:4860 | Effects of benzodiazepines on the binding of tryptophan in serum. Consequences on 5-hydroxyindoles concentrations in the rat brain. | Benzodiazepines (diazepam, oxazepam, chlordiazepoxide) inhibited competitively the binding of tryptophan onto rat serum albumin. As a result, in vivo treatment with one of these compounds (chlordiazepoxide for instance) induced a significant increase in the concentration of free tryptophan in serum. These observations suggest that the high levels of both 5-hydroxyindoles and tryptophan which occurred in the rat brain after any benzodiazepine administration could be at least partly the consequence of its effect on tryptophan binding in blood. | Effects of benzodiazepines on the binding of tryptophan in serum. Consequences on 5-hydroxyindoles concentrations in the rat brain. Benzodiazepines (diazepam, oxazepam, chlordiazepoxide) inhibited competitively the binding of tryptophan onto rat serum albumin. As a result, in vivo treatment with one of these compounds (chlordiazepoxide for instance) induced a significant increase in the concentration of free tryptophan in serum. These observations suggest that the high levels of both 5-hydroxyindoles and tryptophan which occurred in the rat brain after any benzodiazepine administration could be at least partly the consequence of its effect on tryptophan binding in blood. | [
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PMID:4861 | The search for the dopamine receptor: tribulations. | In an attempt to identify specific binding to dopamine receptors the binding of 3H-pimozide to preparations of brain and to an artificial cellulose membrane was examined. Binding occurred rapidly, was pH and temperature dependent, and was displaceable by other neuroleptics. Displaceable binding was saturable at 5 X 10(-8) M pimozide. A weak correlation between IC50's for displacement of binding by drugs and their clinical potencies was observed. Displaceable binding of 3H-pimozide in different brain areas did not correlate with dopamine levels. The similarity of binding properties to brain and to artificial membrane suggests that these effects are a function of the physical-chemical properties of these drugs, and that these properties may be related to their clinical effect. | The search for the dopamine receptor: tribulations. In an attempt to identify specific binding to dopamine receptors the binding of 3H-pimozide to preparations of brain and to an artificial cellulose membrane was examined. Binding occurred rapidly, was pH and temperature dependent, and was displaceable by other neuroleptics. Displaceable binding was saturable at 5 X 10(-8) M pimozide. A weak correlation between IC50's for displacement of binding by drugs and their clinical potencies was observed. Displaceable binding of 3H-pimozide in different brain areas did not correlate with dopamine levels. The similarity of binding properties to brain and to artificial membrane suggests that these effects are a function of the physical-chemical properties of these drugs, and that these properties may be related to their clinical effect. | [
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PMID:4862 | Functional heterogeneity within neurotransmitter systems. | This paper reviews experiments that have revealed distinct differences between the dorsal and median raphe nuclei in the rat midbrain. The raphe nuclei appear to be hetrogeneous with respect to their anatomical projections to the forebrain, their relevance to specific behaviors, and their pharmacological responses. Startle response measures are useful indicators of the functional state of serotonergic system originating in the median raphe. As a way to study individual cells within the various raphe nuclei, microspectroflurimetric techniques are promising. | Functional heterogeneity within neurotransmitter systems. This paper reviews experiments that have revealed distinct differences between the dorsal and median raphe nuclei in the rat midbrain. The raphe nuclei appear to be hetrogeneous with respect to their anatomical projections to the forebrain, their relevance to specific behaviors, and their pharmacological responses. Startle response measures are useful indicators of the functional state of serotonergic system originating in the median raphe. As a way to study individual cells within the various raphe nuclei, microspectroflurimetric techniques are promising. | [
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PMID:4863 | Benzodiazepines and reproduction of swiss-webster mice. | Chronic dietary administration of 6 different benzodiazepine tranquilizers (chlordiazepoxide, diazepam, oxazepam, prazepam, flurazepam, and nitrazepam) to breeding pairs of Swiss-Webster mice resulted in alterations of the normal patterns of reproductive behavior and fetal growth. Significant decreases in mating performance were seen among mice given diets containing 0.15% chlordiazepoxide, 0.05% diazepam, 0.05 and 0.15% oxazepam, 0.02 and 0.10% prazepam, 0.10% flurazepam, and 0.025% nitrazepam. Offspring in all drug treatments showed significantly depressed body weights at birth. | Benzodiazepines and reproduction of swiss-webster mice. Chronic dietary administration of 6 different benzodiazepine tranquilizers (chlordiazepoxide, diazepam, oxazepam, prazepam, flurazepam, and nitrazepam) to breeding pairs of Swiss-Webster mice resulted in alterations of the normal patterns of reproductive behavior and fetal growth. Significant decreases in mating performance were seen among mice given diets containing 0.15% chlordiazepoxide, 0.05% diazepam, 0.05 and 0.15% oxazepam, 0.02 and 0.10% prazepam, 0.10% flurazepam, and 0.025% nitrazepam. Offspring in all drug treatments showed significantly depressed body weights at birth. | [
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PMID:4864 | In vitro and in vivo studies of (1-sarcosine, 8-threonine) angiotensin II. | The capacity of (1-Sarcosine, 8-Threonine) angiotensin II to block the contractile and pressor effects of exogenous and endogenous angiotensin II was examined. In isolated rabbit aorta, the pA2 value (from pA2 plots) for the analog was 8.75 +/- 0.11. Both the maximum response and the slope of the dose-response curve to angiotensin II were unchanged by the analog. In ganglion-blocked vagotomized rats, infusion of the analog produced a dose-dependent blockage of the angiotensin II pressor effect. In these rats, the analog displayed less agonistic activity than that of (1-Sarcosine, 8-Isoleucine) and (1-Sarcosine, 8-Alanine) angiotensin II. In two-kidney hypertensive rats, the angiotensin II antagonist significantly reduced the arterial blood pressure. The results indicate that (1-Sar, 8-Thr) angiotensin II is a potent antagonist of angiotensin II with less inherent agonistic activity than previously reported analogs. | In vitro and in vivo studies of (1-sarcosine, 8-threonine) angiotensin II. The capacity of (1-Sarcosine, 8-Threonine) angiotensin II to block the contractile and pressor effects of exogenous and endogenous angiotensin II was examined. In isolated rabbit aorta, the pA2 value (from pA2 plots) for the analog was 8.75 +/- 0.11. Both the maximum response and the slope of the dose-response curve to angiotensin II were unchanged by the analog. In ganglion-blocked vagotomized rats, infusion of the analog produced a dose-dependent blockage of the angiotensin II pressor effect. In these rats, the analog displayed less agonistic activity than that of (1-Sarcosine, 8-Isoleucine) and (1-Sarcosine, 8-Alanine) angiotensin II. In two-kidney hypertensive rats, the angiotensin II antagonist significantly reduced the arterial blood pressure. The results indicate that (1-Sar, 8-Thr) angiotensin II is a potent antagonist of angiotensin II with less inherent agonistic activity than previously reported analogs. | [
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PMID:4865 | The effect of mercuric chloride intoxication on urinary psi-glutamyl transpeptidase excretion in the sheep. | The activity of the enzyme psi-glutamyl transpeptidase (psi-GT) was measured in the urine of sheep. In clinically normal animals the mean value was 6-3+/-0-6 mU/ml. In sheep with kidney damage induced by the administration of mercuric chloride there were marked increases in urinary concentrations of psi-GT, in some cases values in excess of 1000 mU/ml were recorded. This enzyme may be of value in the diagnosis of certain forms of renal disease. | The effect of mercuric chloride intoxication on urinary psi-glutamyl transpeptidase excretion in the sheep. The activity of the enzyme psi-glutamyl transpeptidase (psi-GT) was measured in the urine of sheep. In clinically normal animals the mean value was 6-3+/-0-6 mU/ml. In sheep with kidney damage induced by the administration of mercuric chloride there were marked increases in urinary concentrations of psi-GT, in some cases values in excess of 1000 mU/ml were recorded. This enzyme may be of value in the diagnosis of certain forms of renal disease. | [
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PMID:4880 | Nucleotide pyrophosphatase and phosphodiesterase I. Demonstration of activity in normal serum, and an increase in cholestatic liver disease. | Nucleotide pyrophosphatase activity with uridine diphosphoglucose and dephospho-CoA as substrates was demonstrated in normal human serum. The enzyme has a pH-optimum of about 9.6 and is inhibited by EDTA. Phosphodiesterase I (hydrolysis of thymidine-5'-monophospho-p-nitrophenylester) was also found in normal human serum, with a pH-optimum of about 9.8 and a Km of 0.20-0.25 mM. Probably both activities should be attributed to one enzyme. Different isoenzymes may exist, however. The activity of nucleotide pyrophosphatase/phosphodiesterase I in normal serum in many respects resembles an enzyme previously isolated from liver plasma membranes. Phosphodiesterase I activity was increased in normal pregnancy, in primary biliary cirrhosis, and in patients with bone lesions, but not in acute viral hepatitis or active chronic hepatitis. In primary biliary cirrhosis, the activity of phosphodiesterase I paralleled an increase of alkaline phosphatases. | Nucleotide pyrophosphatase and phosphodiesterase I. Demonstration of activity in normal serum, and an increase in cholestatic liver disease. Nucleotide pyrophosphatase activity with uridine diphosphoglucose and dephospho-CoA as substrates was demonstrated in normal human serum. The enzyme has a pH-optimum of about 9.6 and is inhibited by EDTA. Phosphodiesterase I (hydrolysis of thymidine-5'-monophospho-p-nitrophenylester) was also found in normal human serum, with a pH-optimum of about 9.8 and a Km of 0.20-0.25 mM. Probably both activities should be attributed to one enzyme. Different isoenzymes may exist, however. The activity of nucleotide pyrophosphatase/phosphodiesterase I in normal serum in many respects resembles an enzyme previously isolated from liver plasma membranes. Phosphodiesterase I activity was increased in normal pregnancy, in primary biliary cirrhosis, and in patients with bone lesions, but not in acute viral hepatitis or active chronic hepatitis. In primary biliary cirrhosis, the activity of phosphodiesterase I paralleled an increase of alkaline phosphatases. | [
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PMID:4881 | [The value of renin determination in the diagnosis of hypertension]. | Primary aldosteronism and renovascular hypertension are two different diseases in which renin determinations are necessary for establishment of diagnosis or therapeutic procedure. Low renin values which are not stimulated by acute stimuli combined with elevated plasma aldosterone concentrations confirm the diagnosis of primary aldosteronism. When in a patient with proven renal artery stenosis a significant difference in renal venous renin activity is observed between the two kidneys, a connection between hypertension and renal artery stenosis is likely when in addition the renin secretion of the unaffected kidney is suppressed. A favourable outcome for surgery can be predicted when the individual clinical picture in such a case is also considered. A similar view also holds for the connection between hypertension and unilateral small kidney not due to renal artery stenosis. In essential hypertension the plasma renin level makes it possible to a certain extent to predict whether a patient will benefit from diuretics or from beta-blocking agents. Despite this experience, however, renin determinations are not indicated in every case of essential hypertension. It has not been proven that the prognosis of this disease is improved by renin oriented monotherapy rather than by effective treatment with other antihypertensive agents. | [The value of renin determination in the diagnosis of hypertension]. Primary aldosteronism and renovascular hypertension are two different diseases in which renin determinations are necessary for establishment of diagnosis or therapeutic procedure. Low renin values which are not stimulated by acute stimuli combined with elevated plasma aldosterone concentrations confirm the diagnosis of primary aldosteronism. When in a patient with proven renal artery stenosis a significant difference in renal venous renin activity is observed between the two kidneys, a connection between hypertension and renal artery stenosis is likely when in addition the renin secretion of the unaffected kidney is suppressed. A favourable outcome for surgery can be predicted when the individual clinical picture in such a case is also considered. A similar view also holds for the connection between hypertension and unilateral small kidney not due to renal artery stenosis. In essential hypertension the plasma renin level makes it possible to a certain extent to predict whether a patient will benefit from diuretics or from beta-blocking agents. Despite this experience, however, renin determinations are not indicated in every case of essential hypertension. It has not been proven that the prognosis of this disease is improved by renin oriented monotherapy rather than by effective treatment with other antihypertensive agents. | [
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PMID:4894 | Alpha-adrenergic receptor identification by (3H)dihydroergocryptine binding. | A radioactively labeled alpha-adrenergic antagonist, [3H]dihydroergocryptine, binds specifically to a site on rabbit uterine membranes. Binding is rapid, reaching equilibrium in less than 17 minutes at 25 degrees C. Adrenergic agonists compete for this binding site with an order of affinities identical to the pharmacological potency order of these agents as alpha-adrenergic agonists (epinephrine greater than norepinephrine greater than isoprotereonl). The (-) stereoisomers of epinephrine and norepinephrine are 30 times more potent in competing for the site than the corresponding (+) stereoisomers. alpha-Adrenergic antagonists, such as phentolamine and phenoxybenzamine, potently compete for the binding sites while the beta-adrenergic antagonist propranolol does not. Structural analogs of catecholamines that are devoid of alpha-adrenergic physiological activity do not compete for [3H]dihydroergocryptine binding sites. These data suggest that alpha-adrenergic receptors can be directly identified and studied by [3H]dihydroergocryptine binding. | Alpha-adrenergic receptor identification by (3H)dihydroergocryptine binding. A radioactively labeled alpha-adrenergic antagonist, [3H]dihydroergocryptine, binds specifically to a site on rabbit uterine membranes. Binding is rapid, reaching equilibrium in less than 17 minutes at 25 degrees C. Adrenergic agonists compete for this binding site with an order of affinities identical to the pharmacological potency order of these agents as alpha-adrenergic agonists (epinephrine greater than norepinephrine greater than isoprotereonl). The (-) stereoisomers of epinephrine and norepinephrine are 30 times more potent in competing for the site than the corresponding (+) stereoisomers. alpha-Adrenergic antagonists, such as phentolamine and phenoxybenzamine, potently compete for the binding sites while the beta-adrenergic antagonist propranolol does not. Structural analogs of catecholamines that are devoid of alpha-adrenergic physiological activity do not compete for [3H]dihydroergocryptine binding sites. These data suggest that alpha-adrenergic receptors can be directly identified and studied by [3H]dihydroergocryptine binding. | [
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PMID:4895 | Aspartate: distinct receptors on Aplysia neurons. | Aplysia neurons have specific aspartate receptors that are distinct from those to glutamate. In some cells, asparate selectively increases the membrane permeability to chloride, giving rise to a hyperpolarization, while on other cells it increases the permeability to sodium, causing a depolarization. There are also specific receptors for L-glutamate which mediate sodium, chloride, or potassium conductance increases, and another class of receptors activated by both glutamate and aspartate. | Aspartate: distinct receptors on Aplysia neurons. Aplysia neurons have specific aspartate receptors that are distinct from those to glutamate. In some cells, asparate selectively increases the membrane permeability to chloride, giving rise to a hyperpolarization, while on other cells it increases the permeability to sodium, causing a depolarization. There are also specific receptors for L-glutamate which mediate sodium, chloride, or potassium conductance increases, and another class of receptors activated by both glutamate and aspartate. | [
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PMID:4896 | Reduction in myocardial infarct size: prevention of heart cell death. | The course of myocardial necrosis, the clinical syndrome, and methods of treatment are presented. Heart cell death may be prevented by maintaining the balance between myocardial oxygen and energy supply and consumption. New technics of improving this balance by reducing myocardial energy demand, altering metabolism, increasing myocardial substrate supply, and protecting cellular integrity are discussed. | Reduction in myocardial infarct size: prevention of heart cell death. The course of myocardial necrosis, the clinical syndrome, and methods of treatment are presented. Heart cell death may be prevented by maintaining the balance between myocardial oxygen and energy supply and consumption. New technics of improving this balance by reducing myocardial energy demand, altering metabolism, increasing myocardial substrate supply, and protecting cellular integrity are discussed. | [
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PMID:4897 | Hypo-acidity of gastric juice in chronic gastric ulceration caused by neutralisation. | Samples of gastric juice were aspirated every 15 minutes from 54 normal subjects and 31 patients with chronic gastric ulcers during a maximal histamine infusion test. The known tendency of patients with gastric ulcers to secrete a less acid gastric juice than that of normal subjects was confirmed. However, the hypo-acidity was related to the extent by which the total ionic concentration was less than the isotonic value of 328 mEq/l. On the assumption that such hypo-acidity was produced by the neutralisation of hydrogen ions by bicarbonate ions refluxing into the stomach from the duodenum, the data were corrected and resulted in a normal estimate of the hydrogen ion concentration in the gastric ulcer group. Independent corrections, according to the sodium content of refluxed duodenal juice, yielded similar results for the volume of gastric juice aspirated. It is concluded that while back-diffusion can explain the hypo-acidity of gastric juice in patients with gastric ulcers, duodenal reflux can explain both the hypo-acidity and the hypotonicity, and is therefore more likely to be the correct explanation. | Hypo-acidity of gastric juice in chronic gastric ulceration caused by neutralisation. Samples of gastric juice were aspirated every 15 minutes from 54 normal subjects and 31 patients with chronic gastric ulcers during a maximal histamine infusion test. The known tendency of patients with gastric ulcers to secrete a less acid gastric juice than that of normal subjects was confirmed. However, the hypo-acidity was related to the extent by which the total ionic concentration was less than the isotonic value of 328 mEq/l. On the assumption that such hypo-acidity was produced by the neutralisation of hydrogen ions by bicarbonate ions refluxing into the stomach from the duodenum, the data were corrected and resulted in a normal estimate of the hydrogen ion concentration in the gastric ulcer group. Independent corrections, according to the sodium content of refluxed duodenal juice, yielded similar results for the volume of gastric juice aspirated. It is concluded that while back-diffusion can explain the hypo-acidity of gastric juice in patients with gastric ulcers, duodenal reflux can explain both the hypo-acidity and the hypotonicity, and is therefore more likely to be the correct explanation. | [
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PMID:4898 | Antihypertensive therapy with timolol and alpha-methyldopa. A double-blind trial in patients with moderately severe hypertension. | After 24 moderately severe hypertensive patients had been treated for 4 weeks with a placebo for timolol, alpha-methyldopa was added and titrated until control of the blood pressure or a total daily dose of 2 500 mg was achieved. At the 9th week, the dose of alpha-methyldopa was halved and either timolol or its placebo was titrated in double-blind fashion. Titration over a period of 4 weeks was followed by a further 5 weeks of stabilisation. In 22 patients whose responses were accepted for analysis, alpha-methyldopa caused a significant lowering of blood pressure, with a greater reduction in the upright posture and a reduction in pulse rate. The addition of timolol caused a highly significant further reduction in pulse rate and a significant reduction in blood pressure in 8 of 10 patients. Apart from a statistically significant increase in serum urea and creatinine with, however, retention of normal renal function, no other side-effects were attributable to timolol. | Antihypertensive therapy with timolol and alpha-methyldopa. A double-blind trial in patients with moderately severe hypertension. After 24 moderately severe hypertensive patients had been treated for 4 weeks with a placebo for timolol, alpha-methyldopa was added and titrated until control of the blood pressure or a total daily dose of 2 500 mg was achieved. At the 9th week, the dose of alpha-methyldopa was halved and either timolol or its placebo was titrated in double-blind fashion. Titration over a period of 4 weeks was followed by a further 5 weeks of stabilisation. In 22 patients whose responses were accepted for analysis, alpha-methyldopa caused a significant lowering of blood pressure, with a greater reduction in the upright posture and a reduction in pulse rate. The addition of timolol caused a highly significant further reduction in pulse rate and a significant reduction in blood pressure in 8 of 10 patients. Apart from a statistically significant increase in serum urea and creatinine with, however, retention of normal renal function, no other side-effects were attributable to timolol. | [
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PMID:4900 | Iatrogenic cryptorchidism resulting from hernia repair. | Nine children have been examined for iatrogenic cryptorchidism during a four year period. Wound infection and testicular retractility appear to be factors predisposing to this complication. Routine testicular palpation for position at the completion of hernia repair and the use of orchidopexy in selected patients should aid in the prevention of this problem. | Iatrogenic cryptorchidism resulting from hernia repair. Nine children have been examined for iatrogenic cryptorchidism during a four year period. Wound infection and testicular retractility appear to be factors predisposing to this complication. Routine testicular palpation for position at the completion of hernia repair and the use of orchidopexy in selected patients should aid in the prevention of this problem. | [
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PMID:4901 | The effect of antihistamines on experimental posttraumatic edema of the spinal cord. | The present experiments were designed to test the effect of antihistamines on the formation of post-traumatic edema of the spinal cord. Ten rhesus monkeys received 600 gm cm injuries to the T10 level of the spinal cord. Five animals received antihistamine treatment and five animals acted as untreated controls. Posttraumatic edema was estimated using radio-active tagged serum albumin. A significant increase in radioactivity of the injured segment was demonstrated in both groups when compared to noninjured issue, but no difference was demonstrated in the radioactivity of the injured segment in the treated versus the nontreated group. | The effect of antihistamines on experimental posttraumatic edema of the spinal cord. The present experiments were designed to test the effect of antihistamines on the formation of post-traumatic edema of the spinal cord. Ten rhesus monkeys received 600 gm cm injuries to the T10 level of the spinal cord. Five animals received antihistamine treatment and five animals acted as untreated controls. Posttraumatic edema was estimated using radio-active tagged serum albumin. A significant increase in radioactivity of the injured segment was demonstrated in both groups when compared to noninjured issue, but no difference was demonstrated in the radioactivity of the injured segment in the treated versus the nontreated group. | [
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PMID:4904 | Chemical studies of marine invertebrates. XVI. Structure and absolute configuration of lobosterol, a novel polyoxygenated sterol from the alcyonacean Lobophytum pauciflorum (clelenterata, octocorallia). | Lobosterol [(24S)-24-methylcholestane-3beta,4beta,5beta,25-tetrol-6-one 25 monoacetate] has been isolated from the Alcyonacean Lobophytum pauciflorum. The structural elucidation of this novel polyoxygenated sterol was achieved by chemical and spectroscopic evidence, and by X-ray diffraction analysis. | Chemical studies of marine invertebrates. XVI. Structure and absolute configuration of lobosterol, a novel polyoxygenated sterol from the alcyonacean Lobophytum pauciflorum (clelenterata, octocorallia). Lobosterol [(24S)-24-methylcholestane-3beta,4beta,5beta,25-tetrol-6-one 25 monoacetate] has been isolated from the Alcyonacean Lobophytum pauciflorum. The structural elucidation of this novel polyoxygenated sterol was achieved by chemical and spectroscopic evidence, and by X-ray diffraction analysis. | [
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PMID:4905 | Irreversible protein binding of norethisterone (norethindrone) epoxide. | 14,15-3H-Norethisterone-4 beta, 5 beta-epoxide, a metabolite of norethisterone, was incubated with several proteins and nucleic acids. After 30 min incubation 0.19 nmol of the epoxide were irreversibly bound per mg albumin which contains free sulfhydryl groups; proteins without SH-groups, such as concanavalin A, gamma-globulin, DNA and RNA, did not irreversibly bind norethisterone epoxide. A superoxide (O2) generating enzyme system comprised of xanthine oxidase and hypoxanthine was capable of catalyzing the irreversible binding of the parent compound, norethisterone, to albumin, indicating that an oxidation product was formed which reacted with the protein. When norethisterone epoxide was incubated for 60 min with hepatic microsomes of rats in absence of NADPH, about 2.0 nmol of the epoxide were irreversibly incorporated per mg microsomal protein. This binding was increased to 5.2 nmol by addition of a NADPH regenerating system. Addition of glutathione and cytosol decreased only the NADPH-dependent protein binding; phenobarbital pretreatment of rats induced this NADPH-dependent binding of norethisterone epoxide to microsomal protein by a factor of 2. In presence of NADPH, binding of the epoxide to microsomal protein depended on substrate concentration used. The results indicate that norethisterone epoxide is able to chemically react with proteins. In addition, hepatic microsomal enzymes convert the epoxide to another metabolite which also can react with proteins. | Irreversible protein binding of norethisterone (norethindrone) epoxide. 14,15-3H-Norethisterone-4 beta, 5 beta-epoxide, a metabolite of norethisterone, was incubated with several proteins and nucleic acids. After 30 min incubation 0.19 nmol of the epoxide were irreversibly bound per mg albumin which contains free sulfhydryl groups; proteins without SH-groups, such as concanavalin A, gamma-globulin, DNA and RNA, did not irreversibly bind norethisterone epoxide. A superoxide (O2) generating enzyme system comprised of xanthine oxidase and hypoxanthine was capable of catalyzing the irreversible binding of the parent compound, norethisterone, to albumin, indicating that an oxidation product was formed which reacted with the protein. When norethisterone epoxide was incubated for 60 min with hepatic microsomes of rats in absence of NADPH, about 2.0 nmol of the epoxide were irreversibly incorporated per mg microsomal protein. This binding was increased to 5.2 nmol by addition of a NADPH regenerating system. Addition of glutathione and cytosol decreased only the NADPH-dependent protein binding; phenobarbital pretreatment of rats induced this NADPH-dependent binding of norethisterone epoxide to microsomal protein by a factor of 2. In presence of NADPH, binding of the epoxide to microsomal protein depended on substrate concentration used. The results indicate that norethisterone epoxide is able to chemically react with proteins. In addition, hepatic microsomal enzymes convert the epoxide to another metabolite which also can react with proteins. | [
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PMID:4906 | Hydroxyapatite - a reagent for the separation of free and antibody-bound steroid during the radioimmunoassay. | The use of hydroxyapatite to absorb antibody-bound steroid and thus separate free and antibody-bound steroid during radioimmunoassay has been examined using three steroid antisera (to testosterone, to 17-hydroxyprogesterone and to estradiol-17beta). For all three antisera studied the separation was shown to be independent of length of time in contact with hydroxyapatite (up to 1h); temperature variations from 4 degrees -37 degrees and pH over the range 4.9-8.0. The presence of protein affected the absorption of antibody-bound steroid but this effect could be overcome by the addition of increasing amounts of hydroxyapatite. Further increase in the amount of hydroxyapatite added had no effect on the separation of free and bound steroid. Sodium phosphate buffers of molarity greater than 0.01M eluted antibody-bount steroid from hydroxyapatite, but Tris-HC1 buffers up to molarities of 0.1 M had no effect. Hydroxyapatite when used as a dry powder had the same effects as suspensions. No effect on the cross-reactivities of the antisera used could be demonstrated when hydroxyapatite was used and plasma testosterone assays on 22 plasma samples using hydroxyapatite gave essentially the same results as assays on the plasma using a coated-tube assay. Hydroxyapatite can also be successfully pumped along small bore plastic tubing without settling and can thus be used in automated immunoassay systems. | Hydroxyapatite - a reagent for the separation of free and antibody-bound steroid during the radioimmunoassay. The use of hydroxyapatite to absorb antibody-bound steroid and thus separate free and antibody-bound steroid during radioimmunoassay has been examined using three steroid antisera (to testosterone, to 17-hydroxyprogesterone and to estradiol-17beta). For all three antisera studied the separation was shown to be independent of length of time in contact with hydroxyapatite (up to 1h); temperature variations from 4 degrees -37 degrees and pH over the range 4.9-8.0. The presence of protein affected the absorption of antibody-bound steroid but this effect could be overcome by the addition of increasing amounts of hydroxyapatite. Further increase in the amount of hydroxyapatite added had no effect on the separation of free and bound steroid. Sodium phosphate buffers of molarity greater than 0.01M eluted antibody-bount steroid from hydroxyapatite, but Tris-HC1 buffers up to molarities of 0.1 M had no effect. Hydroxyapatite when used as a dry powder had the same effects as suspensions. No effect on the cross-reactivities of the antisera used could be demonstrated when hydroxyapatite was used and plasma testosterone assays on 22 plasma samples using hydroxyapatite gave essentially the same results as assays on the plasma using a coated-tube assay. Hydroxyapatite can also be successfully pumped along small bore plastic tubing without settling and can thus be used in automated immunoassay systems. | [
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PMID:4907 | Influence of adrenergic receptor blockade on circulatory and metabolic effects of disordered neurotransmitter function in stroke patients. | Cerebral hemispheric blood flow and metabolism were measured before and after therapy with intracarotid infusion of combined PBZ and PPL in 15 patients with recent cerebral infarction. HBF was unaltered despite decrease in cerebral perfusion pressure. Cerebral hemispheric oxygen comsumption and carbon dioxide production decreased while cerebral hemispheric lactate production increased. Biphasic cerebral uptake of tyrosine was observed during and immediately after PBZ and PPL infusion. CSF HVA increased, indicating altered DA turnover. CSF 5HIAA levels also increased, suggesting altered 5HT turnover after PBZ and PPL. Release of cyclic AMP from ischemic brain into cerebral venous blood seen in the steady state was abolished after therapy. Cerebral hemodynamic studies suggest a functional balance between monaminergic neurogenic influences in the control of cerebral circulation. Imbalance of such controlling factors in ischemic brain may lead to paradoxical vascular responses to induced hypertension and hypotension. PBZ and PPL enhance such responses perhaps by increasing central neurotransmitter turnover and release. Further shift toward cerebral anaerobic metabolism may occur in ischemic brain following the use of phenoxybenzamine and propranolol. Worsening of neurological deficit occurred in four cases. Combined therapy with PBZ and PPL does not appear beneficial in the therapy of patients with recent stroke. | Influence of adrenergic receptor blockade on circulatory and metabolic effects of disordered neurotransmitter function in stroke patients. Cerebral hemispheric blood flow and metabolism were measured before and after therapy with intracarotid infusion of combined PBZ and PPL in 15 patients with recent cerebral infarction. HBF was unaltered despite decrease in cerebral perfusion pressure. Cerebral hemispheric oxygen comsumption and carbon dioxide production decreased while cerebral hemispheric lactate production increased. Biphasic cerebral uptake of tyrosine was observed during and immediately after PBZ and PPL infusion. CSF HVA increased, indicating altered DA turnover. CSF 5HIAA levels also increased, suggesting altered 5HT turnover after PBZ and PPL. Release of cyclic AMP from ischemic brain into cerebral venous blood seen in the steady state was abolished after therapy. Cerebral hemodynamic studies suggest a functional balance between monaminergic neurogenic influences in the control of cerebral circulation. Imbalance of such controlling factors in ischemic brain may lead to paradoxical vascular responses to induced hypertension and hypotension. PBZ and PPL enhance such responses perhaps by increasing central neurotransmitter turnover and release. Further shift toward cerebral anaerobic metabolism may occur in ischemic brain following the use of phenoxybenzamine and propranolol. Worsening of neurological deficit occurred in four cases. Combined therapy with PBZ and PPL does not appear beneficial in the therapy of patients with recent stroke. | [
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PMID:4913 | Action of beta-adrenergic blocking agents on the urethral pressure profile. | The action of beta-adrenergic blocking agents on the urethral pressure profile was studied. Sotalol, 20 mg, and inderal, 7 mg, were administered intravenously. Whereas the alpha-adrenergic blocking drug phentolamine, as already known, changed the maximum value of the pressure profile with an average decrease of 33%, the beta-adrenergic blocking drugs did not show any action at all. There was no difference between the results obtained with Sotalol and Inderal. | Action of beta-adrenergic blocking agents on the urethral pressure profile. The action of beta-adrenergic blocking agents on the urethral pressure profile was studied. Sotalol, 20 mg, and inderal, 7 mg, were administered intravenously. Whereas the alpha-adrenergic blocking drug phentolamine, as already known, changed the maximum value of the pressure profile with an average decrease of 33%, the beta-adrenergic blocking drugs did not show any action at all. There was no difference between the results obtained with Sotalol and Inderal. | [
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PMID:4914 | [Urodynamic measurements in enuretics]. | Distal urethral stenosis in girls as well as meatal and bulbar narrowed urethral segments in boys are still subjects of discussion about their pathologic value in the literature. The urodynamic findings in enuretic children by urethral pressure profile and cystometry frequently point to a outflow resistance. Calibration with bougies à boule, urethroscopy and permictional cysturethrography disclose such urethral narrowing. The survey of our own 107 enuritic children shows that urethrotomy has given good results relative to urodynamic data. The effect of methantheline medications consists in suppressing the hyperactivity of the detrusor. | [Urodynamic measurements in enuretics]. Distal urethral stenosis in girls as well as meatal and bulbar narrowed urethral segments in boys are still subjects of discussion about their pathologic value in the literature. The urodynamic findings in enuretic children by urethral pressure profile and cystometry frequently point to a outflow resistance. Calibration with bougies à boule, urethroscopy and permictional cysturethrography disclose such urethral narrowing. The survey of our own 107 enuritic children shows that urethrotomy has given good results relative to urodynamic data. The effect of methantheline medications consists in suppressing the hyperactivity of the detrusor. | [
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] |
PMID:4915 | Conservative bladder treatment in myelodysplasia. Differentiation of patients by cystomanometry. | Urodynamic evaluation was performed in 75 patients with congenital neuropathic bladder. Concerning treatment the most important parameters were detrusor tone, detrusor activity and bladder outlet resistance. Based on these findings individual conservative therapy was applied. Reflux or dilatation of the upper urinary tract found in 26 children could be controlled by drugs or transurethral operations in 20, urinary diversion had to be done only 4 times. 26 children were selected for intensive treatment of incontinence; in about 50% satisfying urinary control was achieved. These results still need long-term observation. The main interest, however, was to postpone irreversible surgery and to gain time for possible better treatment in the future. | Conservative bladder treatment in myelodysplasia. Differentiation of patients by cystomanometry. Urodynamic evaluation was performed in 75 patients with congenital neuropathic bladder. Concerning treatment the most important parameters were detrusor tone, detrusor activity and bladder outlet resistance. Based on these findings individual conservative therapy was applied. Reflux or dilatation of the upper urinary tract found in 26 children could be controlled by drugs or transurethral operations in 20, urinary diversion had to be done only 4 times. 26 children were selected for intensive treatment of incontinence; in about 50% satisfying urinary control was achieved. These results still need long-term observation. The main interest, however, was to postpone irreversible surgery and to gain time for possible better treatment in the future. | [
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PMID:4929 | [Treatment of hypertonus in diabetes mellitus]. | When pathophysiological and pathogenetic aspects of hypertension are taken into consideration with special regard to diabetes mellitus the exhaustion of the "insulin enhancement" within the cerebrovisceral functional systems (Baumann) are discussed and the authors enter possible connections of diabetes mellitus to the renin-angiotensin-aldosterone system. After explanation of the diabetogenic and antidiabetogenic pharmacodynamic qualities of the antihypertensive drugs adequate therapeutic recommendations are proposed summarized in a figure. The authors conclude that for the present antihypertensive therapy in diabetics taking into consideration the references reported on there are sufficient possibilities of treatment for all degrees of severity of hypertension. Such preparations as Rausedan, Disotat, Dopegyt appear as particularly suitable; moreover, the beta receptor blockers, Haemiton, Depressan as well as Guanitil and Pargylin prove to be possible or without disadvantage, respectively. Especially when diuretics are described an exact control of the metabolism should be carried out. | [Treatment of hypertonus in diabetes mellitus]. When pathophysiological and pathogenetic aspects of hypertension are taken into consideration with special regard to diabetes mellitus the exhaustion of the "insulin enhancement" within the cerebrovisceral functional systems (Baumann) are discussed and the authors enter possible connections of diabetes mellitus to the renin-angiotensin-aldosterone system. After explanation of the diabetogenic and antidiabetogenic pharmacodynamic qualities of the antihypertensive drugs adequate therapeutic recommendations are proposed summarized in a figure. The authors conclude that for the present antihypertensive therapy in diabetics taking into consideration the references reported on there are sufficient possibilities of treatment for all degrees of severity of hypertension. Such preparations as Rausedan, Disotat, Dopegyt appear as particularly suitable; moreover, the beta receptor blockers, Haemiton, Depressan as well as Guanitil and Pargylin prove to be possible or without disadvantage, respectively. Especially when diuretics are described an exact control of the metabolism should be carried out. | [
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PMID:4930 | [The reaction of chorion epitheliums of human placentae to beta-sympathocomimetics (author's transl)]. | The enzyme histochemical response of chorionic epithelium after treatment with Dilatel has been examined on 50 placentae of classified eutrophic premature and full-term births. In relation to the degree of damage to trophoblasts at the start of treatment and to dosage the response is mobilisation and further differentiation of Langhans cells and their transformation into mature plasmodium. The relevance of these results for metabolic transport and hormonal synthesis in the feto- maternal metabolic barrier and for the chance of therapeutic effects on insufficiency of the placenta is discussed. | [The reaction of chorion epitheliums of human placentae to beta-sympathocomimetics (author's transl)]. The enzyme histochemical response of chorionic epithelium after treatment with Dilatel has been examined on 50 placentae of classified eutrophic premature and full-term births. In relation to the degree of damage to trophoblasts at the start of treatment and to dosage the response is mobilisation and further differentiation of Langhans cells and their transformation into mature plasmodium. The relevance of these results for metabolic transport and hormonal synthesis in the feto- maternal metabolic barrier and for the chance of therapeutic effects on insufficiency of the placenta is discussed. | [
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PMID:4932 | [PH-static pectin esterase analysis in sweet cherries (author's transl)]. | For the analysis of pectin esterase (PE) activities in sweet cherries some methods, as described in literature, were tested as to their usefulness in this specific range of application. The PE activities in dependence of the methods of extraction, the pH-value and the temperature were examined and a suitable procedure was achieved. With this method the PE activities in deposited sweet cherries were analyzed. | [PH-static pectin esterase analysis in sweet cherries (author's transl)]. For the analysis of pectin esterase (PE) activities in sweet cherries some methods, as described in literature, were tested as to their usefulness in this specific range of application. The PE activities in dependence of the methods of extraction, the pH-value and the temperature were examined and a suitable procedure was achieved. With this method the PE activities in deposited sweet cherries were analyzed. | [
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PMID:4933 | [Phospholipase D - a review (author's transl)]. | Phospholipase D (phosphatidylcholine-phosphatidohydrolase, EC 3.1.4.4) hydrolyses lecithin into phosphatidic acid and choline. A review is given on the properties of phospholipase D described in the literature; it deals with the occurrence and distribution of phospholipase D in higher plants, with it's pH and temperature, substrate specifity, activators, inhibitors and with occurrence and properties of bacterial phospholipase D. | [Phospholipase D - a review (author's transl)]. Phospholipase D (phosphatidylcholine-phosphatidohydrolase, EC 3.1.4.4) hydrolyses lecithin into phosphatidic acid and choline. A review is given on the properties of phospholipase D described in the literature; it deals with the occurrence and distribution of phospholipase D in higher plants, with it's pH and temperature, substrate specifity, activators, inhibitors and with occurrence and properties of bacterial phospholipase D. | [
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PMID:4938 | [Differential pharmacotherapy of neurotic conditions (comparative effectiveness of benzodiazepine derivatives)]. | The effectiveness in treating borderline states to a certain degree depends upon the pole (sthenic or asthenic) of the corresponding disturbance. Tranquilizers are the preparations of choice in the treatment of disorders of an asthenic pole (psychopathy of the asthenic range, neurotic states). In borderline conditions of a sthenic pole the effectiveness of tranquilizers is equal or sometimes is even less than in therapy with small doses of neuroleptics. In treating neurotic conditions tranquilizers of the benzodiazepine group can be ranged in the following succession: nitrazepam, chlordiazepoxide, medazepam, oxazepam, diazepam, lorazepam. This preparation is a continuun of an increasing psychotropic activity. | [Differential pharmacotherapy of neurotic conditions (comparative effectiveness of benzodiazepine derivatives)]. The effectiveness in treating borderline states to a certain degree depends upon the pole (sthenic or asthenic) of the corresponding disturbance. Tranquilizers are the preparations of choice in the treatment of disorders of an asthenic pole (psychopathy of the asthenic range, neurotic states). In borderline conditions of a sthenic pole the effectiveness of tranquilizers is equal or sometimes is even less than in therapy with small doses of neuroleptics. In treating neurotic conditions tranquilizers of the benzodiazepine group can be ranged in the following succession: nitrazepam, chlordiazepoxide, medazepam, oxazepam, diazepam, lorazepam. This preparation is a continuun of an increasing psychotropic activity. | [
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PMID:4939 | [The relationship between the state of the pulmonary circulation and indices of cerebral gas exchange in patients with acquired heart defects]. | The author studied the state of hemeostasis in normals and in patients with acquired heart insufficiency. By means of bloody methods of triple probe samples of the blood inflow and outflow from the brain, and by biochemical methods they also studied 22 normals and 100 patients with acquired heart insufficiency for interrelations between the gas metabolism indices and acid-base equilibrium of the central pulmonary hemodynamics. As a results it was established that the brain blood flux in patients with acquired heart insufficiency in different degrees of pulmonary hypertension is adequate to the metabolic requirement of the brain in oxygen and corresponds to identical indices in normals. There was no relation between the state of pulmonary circulation and brain circulation. | [The relationship between the state of the pulmonary circulation and indices of cerebral gas exchange in patients with acquired heart defects]. The author studied the state of hemeostasis in normals and in patients with acquired heart insufficiency. By means of bloody methods of triple probe samples of the blood inflow and outflow from the brain, and by biochemical methods they also studied 22 normals and 100 patients with acquired heart insufficiency for interrelations between the gas metabolism indices and acid-base equilibrium of the central pulmonary hemodynamics. As a results it was established that the brain blood flux in patients with acquired heart insufficiency in different degrees of pulmonary hypertension is adequate to the metabolic requirement of the brain in oxygen and corresponds to identical indices in normals. There was no relation between the state of pulmonary circulation and brain circulation. | [
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PMID:4941 | Effect of laser irradiation and immunosuppressive treatment on survival of mouse skin allotransplants. | The effect of laser beam on the survival of skin allotransplants has been studied. Irradiation of the donor skin and of the recipient graft bed improved the survival of the graft. The graft protecting effect of anti-thymocyte serum was considerably enhanced by laser irradiation. | Effect of laser irradiation and immunosuppressive treatment on survival of mouse skin allotransplants. The effect of laser beam on the survival of skin allotransplants has been studied. Irradiation of the donor skin and of the recipient graft bed improved the survival of the graft. The graft protecting effect of anti-thymocyte serum was considerably enhanced by laser irradiation. | [
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PMID:4947 | Anesthesia for cesarean section III: effects of epidural analgesia on the respiratory adaptation of the newborn in elective cesarean section. | A rise in fetal Paco2 was observed after elective cesarean section in patients anesthetized both with a barbiturate and with nitrous oxide/oxygen. Epidural analgesia seemed to be a good alternative in order to attain better blood gas values in the newborn infant. Fourteen healthy mothers and their infants were studied in connection with elective cesarean section. Epidural analgesia with plain bupivacaine 0.75% was used. Doses varied between 90 and 120 mg. The time between the epidural injection and delivery was around 50 min. In six cases the fetal heart rate was registered continuously. Most of the mothers were sedated with diazepam intravenously or fully anesthetized, after delivery. The mothers were interviewed later. The respiratory adaptation of the infants was studied by blood gas and acid-base measurements in repeated arterial samples during the first 3 hours of life. A comparison was made with a group previously studied, where general anesthesia with a barbiturate, nitrous oxide/oxygen was the method used. The present material showed no differences concerning Pao2 and Paco2 but clearly indicated a tendency towards an earlier normalization of the initial metabolic acidosis. Mothers showed a respiratory alkalosis which was overcompensated by the metabolic component. Maternal blood pressure falls were observed in four cases, and fetal effects could be detected. Although epidural analgesia has a more favorable effect upon the newborn's metabolic component, both the compared methods allow good respiratory adaptation provided they are used correctly. Mothers can be given the opportunity to choose between being conscious or asleep when their child is delivered. | Anesthesia for cesarean section III: effects of epidural analgesia on the respiratory adaptation of the newborn in elective cesarean section. A rise in fetal Paco2 was observed after elective cesarean section in patients anesthetized both with a barbiturate and with nitrous oxide/oxygen. Epidural analgesia seemed to be a good alternative in order to attain better blood gas values in the newborn infant. Fourteen healthy mothers and their infants were studied in connection with elective cesarean section. Epidural analgesia with plain bupivacaine 0.75% was used. Doses varied between 90 and 120 mg. The time between the epidural injection and delivery was around 50 min. In six cases the fetal heart rate was registered continuously. Most of the mothers were sedated with diazepam intravenously or fully anesthetized, after delivery. The mothers were interviewed later. The respiratory adaptation of the infants was studied by blood gas and acid-base measurements in repeated arterial samples during the first 3 hours of life. A comparison was made with a group previously studied, where general anesthesia with a barbiturate, nitrous oxide/oxygen was the method used. The present material showed no differences concerning Pao2 and Paco2 but clearly indicated a tendency towards an earlier normalization of the initial metabolic acidosis. Mothers showed a respiratory alkalosis which was overcompensated by the metabolic component. Maternal blood pressure falls were observed in four cases, and fetal effects could be detected. Although epidural analgesia has a more favorable effect upon the newborn's metabolic component, both the compared methods allow good respiratory adaptation provided they are used correctly. Mothers can be given the opportunity to choose between being conscious or asleep when their child is delivered. | [
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PMID:4948 | The effect of halothane anaesthesia upon cerebral oxygen consumption in the rat. | The influence of halothane (0.6 and 2%) upon cerebral (cortical) blood flow (CBF) and cerebral metabolic rate for oxygen (CMRo2) was studied in artificially ventilated rats, using a modified technique of Kety & Schmidt (1948). The values obtained in halothane anaesthesia were compared to those recorded in nitrous oxide anaesthesia, or to those measured in unanesthetized animals given an analgesic drug (fentanyl citrate). Although it could be confirmed that halothane induces vasodilatation in the brain, there were relatively small differences in CBF between the groups. The results demonstrate that, in the rat, halothane depresses CMRo2 in a dose-dependent way. With 0.6% halothane, CMRo2 was reduced by 20-30% and, with 2% halothane, CMRo2 was reduced by about 50%. Thus, in the rat the effect of 2% halothane upon metabolic rate is comparable to that observed in barbiturate anaesthesia. | The effect of halothane anaesthesia upon cerebral oxygen consumption in the rat. The influence of halothane (0.6 and 2%) upon cerebral (cortical) blood flow (CBF) and cerebral metabolic rate for oxygen (CMRo2) was studied in artificially ventilated rats, using a modified technique of Kety & Schmidt (1948). The values obtained in halothane anaesthesia were compared to those recorded in nitrous oxide anaesthesia, or to those measured in unanesthetized animals given an analgesic drug (fentanyl citrate). Although it could be confirmed that halothane induces vasodilatation in the brain, there were relatively small differences in CBF between the groups. The results demonstrate that, in the rat, halothane depresses CMRo2 in a dose-dependent way. With 0.6% halothane, CMRo2 was reduced by 20-30% and, with 2% halothane, CMRo2 was reduced by about 50%. Thus, in the rat the effect of 2% halothane upon metabolic rate is comparable to that observed in barbiturate anaesthesia. | [
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PMID:4950 | Treatment of comatose patients by mechanical hyperventilation. | In case of cranial trauma, early respiratory troubles either of central or peripheral origin often accelerate the deterioration of the neurological situation. The different values of PCO2, PO2, pH and alcaline reserve measured on samples of CSF in comatose patients prove the central acidosis related to metabolic and vascular disorders in the damaged areas. Our results confirm the correlation between the importance of this disturbances and the severity of the trauma. It is thus necessary to insure patients of satisfactory respiration conditions. The tracheobronchial cleansing is applicable to intubated or tracheotomized patients by an instillation of 5ml of simple or bicarbonated physiological serum 4 to 6 times a day, followed by repeated aspirations and associated to a preventive endotracheal instillation of 80 mg of Gentamycin 4 times a day. Moreover we use controlled respiration which does not modify the gazometric parameters in the CSF but which assures patients a normoxia and moderate hypocapnia with a decrease of intracranial hypertension. Treatment by controlled hyperventilation must be precocious, because the recuperation at the level of the damaged zones is very slow. | Treatment of comatose patients by mechanical hyperventilation. In case of cranial trauma, early respiratory troubles either of central or peripheral origin often accelerate the deterioration of the neurological situation. The different values of PCO2, PO2, pH and alcaline reserve measured on samples of CSF in comatose patients prove the central acidosis related to metabolic and vascular disorders in the damaged areas. Our results confirm the correlation between the importance of this disturbances and the severity of the trauma. It is thus necessary to insure patients of satisfactory respiration conditions. The tracheobronchial cleansing is applicable to intubated or tracheotomized patients by an instillation of 5ml of simple or bicarbonated physiological serum 4 to 6 times a day, followed by repeated aspirations and associated to a preventive endotracheal instillation of 80 mg of Gentamycin 4 times a day. Moreover we use controlled respiration which does not modify the gazometric parameters in the CSF but which assures patients a normoxia and moderate hypocapnia with a decrease of intracranial hypertension. Treatment by controlled hyperventilation must be precocious, because the recuperation at the level of the damaged zones is very slow. | [
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PMID:4952 | Resistant transitory epilepsy in children. | Three case histories are presented which are characterized by progressive, severe symptoms of mental and epileptic nature with EEG abnormalities of increasing severity culminating in "hypsarhythmia". The seizures were resistant to any treatment over a period of several months. Apparently spontaneous cures followed, and the patients remained healthy during follow-up, which ranged from 10 to 12 years. The observations confirm Lennox's remark that a miraculous cure may occasionally be expected in even severe, probably symptomatic, epilepsy. Some exogenous (infectious?) cause is suspected. | Resistant transitory epilepsy in children. Three case histories are presented which are characterized by progressive, severe symptoms of mental and epileptic nature with EEG abnormalities of increasing severity culminating in "hypsarhythmia". The seizures were resistant to any treatment over a period of several months. Apparently spontaneous cures followed, and the patients remained healthy during follow-up, which ranged from 10 to 12 years. The observations confirm Lennox's remark that a miraculous cure may occasionally be expected in even severe, probably symptomatic, epilepsy. Some exogenous (infectious?) cause is suspected. | [
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PMID:4951 | A comparison of the cardiovascular effects of enflurane, halothane, methoxyflurane and fluroxene during open cardiac surgery. | During open heart surgery hemodynamic changes due to 1.5% enflurane, 0.75% halothane, 0.18% methoxyflurane and 3.4% fluroxene have been compared. The following parameters have been measured: arterial pressure, heart rate, cardiac output, right and left atrial pressure, left ventricular pressure and dp/dt. The strongest effects were found with enflurane and halothane. Marked reduction in cardiac index, stroke index, left ventricular dp/dt as well as reduction of peripheral resistance caused severe systemic hypotension. Because of its slow uptake methoxyflurane was followed by small hemodynamic changes in this study. The rapid acting fluroxene had caused only minor reductions of cardiac output, stroke volume and dp/dt. There was no decrease in peripheral resistance. | A comparison of the cardiovascular effects of enflurane, halothane, methoxyflurane and fluroxene during open cardiac surgery. During open heart surgery hemodynamic changes due to 1.5% enflurane, 0.75% halothane, 0.18% methoxyflurane and 3.4% fluroxene have been compared. The following parameters have been measured: arterial pressure, heart rate, cardiac output, right and left atrial pressure, left ventricular pressure and dp/dt. The strongest effects were found with enflurane and halothane. Marked reduction in cardiac index, stroke index, left ventricular dp/dt as well as reduction of peripheral resistance caused severe systemic hypotension. Because of its slow uptake methoxyflurane was followed by small hemodynamic changes in this study. The rapid acting fluroxene had caused only minor reductions of cardiac output, stroke volume and dp/dt. There was no decrease in peripheral resistance. | [
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PMID:4956 | Long-term hypotensive effect of atenolol (ICI 66.082), a new beta-adrenergic blocking agent. | A report is given from an on-going multicenter trial in Sweden, in which 117 hypertensive patients have been treated with a new cardioselective beta-adrenergic blocking agent, atenolol (ICI 66.082, Tenormin) for an average of six months (range 2-21). Statistically significant reductions of BP were observed, recumbent by 29/19 mmHg (p less than 0.0001) and standing by 28/18 mmHg (p less than 0.0001). Few and comparatively mild side-effects were seen. | Long-term hypotensive effect of atenolol (ICI 66.082), a new beta-adrenergic blocking agent. A report is given from an on-going multicenter trial in Sweden, in which 117 hypertensive patients have been treated with a new cardioselective beta-adrenergic blocking agent, atenolol (ICI 66.082, Tenormin) for an average of six months (range 2-21). Statistically significant reductions of BP were observed, recumbent by 29/19 mmHg (p less than 0.0001) and standing by 28/18 mmHg (p less than 0.0001). Few and comparatively mild side-effects were seen. | [
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PMID:4953 | Bacteremia after tonsillectomy and adenectomy. | 40% of negative hemocultures become positive immediately after tonsillectomies and/or adenectomies. This bacteremia is asymptomatic and remains no longer than one hour. | Bacteremia after tonsillectomy and adenectomy. 40% of negative hemocultures become positive immediately after tonsillectomies and/or adenectomies. This bacteremia is asymptomatic and remains no longer than one hour. | [
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PMID:4957 | Hemodynamic long-term effects of timolol at rest and during exercise in essential hypertension. | Sixteen men with previously untreated essential hypertension in WHO stage I have been studied as out-patients. Oxygen consumption, heart rate (HR), cardiac output (Q) (Cardiogreen) and intraarterial brachial pressure were recorded at rest in supine and sitting position and during steady state work at 300, 600 and 900 kpm/min. The subjects were treated with timolol as the sole drug for one year and the hemodynamic study was repeated. BP was reduced approximately 18% at rest and 14% during exercise, HR approximately 26% and the cardiac index 28% at rest supine and 32% at rest sitting. During exercise the reductions in Q were 25-30%. The calculated total peripheral resistance was significantly increased at rest as well as during exercise. The product of mean arterial pressure and HR was reduced about 40%. No severe side-effects were seen. | Hemodynamic long-term effects of timolol at rest and during exercise in essential hypertension. Sixteen men with previously untreated essential hypertension in WHO stage I have been studied as out-patients. Oxygen consumption, heart rate (HR), cardiac output (Q) (Cardiogreen) and intraarterial brachial pressure were recorded at rest in supine and sitting position and during steady state work at 300, 600 and 900 kpm/min. The subjects were treated with timolol as the sole drug for one year and the hemodynamic study was repeated. BP was reduced approximately 18% at rest and 14% during exercise, HR approximately 26% and the cardiac index 28% at rest supine and 32% at rest sitting. During exercise the reductions in Q were 25-30%. The calculated total peripheral resistance was significantly increased at rest as well as during exercise. The product of mean arterial pressure and HR was reduced about 40%. No severe side-effects were seen. | [
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PMID:4958 | [Energy state of the cerebral cortex of the cat during hyperventilation (author's transl)]. | Average Po2 and Pco2, local blood flow and pH values in the cerebral cortex of the cat were measured during passive hyperventilation (arterial Pco2 below 19 mm Hg). At defined intervals tissue samples were taken for metabolite analysis. The object of the study was to correlate the data obtained on the brain surface with metabolic responses. Immediately after the start of hyperventilation blood flow decreased, average cortical tissue pressures of O2 and CO2 fell, and there was a simultaneous rise in cortical pH. At a later stage in the experiment the local blood supply reverted to its resting level. Despite a fivefold rise in tissue lactate level during hyperventilation and a decrease in local O2 pressure on the brain surface to 5-10 mm Hg the degree of phosphorylation of energy rich phosphates was not less than under normal conditions of oxygenation. Our investigations showed no evidence of energy lack in cerebral cortex cells during hyperventilation. Cellular hypoxia and its characteristics are defined. The possible causes of raised tissue lactate levels during hyperventilation despite the lack of evidence of cellular hypoxia are discussed. | [Energy state of the cerebral cortex of the cat during hyperventilation (author's transl)]. Average Po2 and Pco2, local blood flow and pH values in the cerebral cortex of the cat were measured during passive hyperventilation (arterial Pco2 below 19 mm Hg). At defined intervals tissue samples were taken for metabolite analysis. The object of the study was to correlate the data obtained on the brain surface with metabolic responses. Immediately after the start of hyperventilation blood flow decreased, average cortical tissue pressures of O2 and CO2 fell, and there was a simultaneous rise in cortical pH. At a later stage in the experiment the local blood supply reverted to its resting level. Despite a fivefold rise in tissue lactate level during hyperventilation and a decrease in local O2 pressure on the brain surface to 5-10 mm Hg the degree of phosphorylation of energy rich phosphates was not less than under normal conditions of oxygenation. Our investigations showed no evidence of energy lack in cerebral cortex cells during hyperventilation. Cellular hypoxia and its characteristics are defined. The possible causes of raised tissue lactate levels during hyperventilation despite the lack of evidence of cellular hypoxia are discussed. | [
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PMID:4959 | [Postoperative mental blocking in a continuous reaction task. With supplementary results showing the influence of age (author's transl)]. | By means of a four colour device for measuring continuous reaction sequences the mental blockings of brain damaged patients in comparison with patients suffering from skin disease were determined. Differences due to age were also investigated. The analysis of frequency distribution of reaction times (dissection method according to Daeves and Beckel) yielded the following results: a) Brain damaged patients show a higher percentage of blockings (23%) than patients suffering from skin-disease (10%). "Normal" reaction times as well as "blockings" are not prolonged significantly. b) Older patients show prolonged normal reaction times and prolonged blockings without increase in the percentage of blockings. c) Patients with left hemisphere lesions show longer normal reaction times than those who undergo right hemisphere operations. The results are discussed with regard to their significance for theory and practice (road accidents). | [Postoperative mental blocking in a continuous reaction task. With supplementary results showing the influence of age (author's transl)]. By means of a four colour device for measuring continuous reaction sequences the mental blockings of brain damaged patients in comparison with patients suffering from skin disease were determined. Differences due to age were also investigated. The analysis of frequency distribution of reaction times (dissection method according to Daeves and Beckel) yielded the following results: a) Brain damaged patients show a higher percentage of blockings (23%) than patients suffering from skin-disease (10%). "Normal" reaction times as well as "blockings" are not prolonged significantly. b) Older patients show prolonged normal reaction times and prolonged blockings without increase in the percentage of blockings. c) Patients with left hemisphere lesions show longer normal reaction times than those who undergo right hemisphere operations. The results are discussed with regard to their significance for theory and practice (road accidents). | [
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PMID:4963 | Immunosuppression by fetal liver as a model for tolerance to self. | The embryonic liver chimera system was used as a model to study the development of tolerance to self antigens. It was found that the permanent tolerant state which was induced in (C3H/eb x C57BL/6)F1 irradiated hosts following reconstitution with parental C57BL liver cells could be due to the development of suppressor cells within the liver cell inoculum, which specifically prevent reactivity of immunocompetent cells. General suppressor activity could be found in embryonic liver cells at early stages of gestation. However, the differentiation of such cells into specific suppressor of "self" antigens is dependent on the presence of the thymus. | Immunosuppression by fetal liver as a model for tolerance to self. The embryonic liver chimera system was used as a model to study the development of tolerance to self antigens. It was found that the permanent tolerant state which was induced in (C3H/eb x C57BL/6)F1 irradiated hosts following reconstitution with parental C57BL liver cells could be due to the development of suppressor cells within the liver cell inoculum, which specifically prevent reactivity of immunocompetent cells. General suppressor activity could be found in embryonic liver cells at early stages of gestation. However, the differentiation of such cells into specific suppressor of "self" antigens is dependent on the presence of the thymus. | [
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PMID:4964 | Suppressor cells in the embryonic thymus mediate allograft tolerance. | Thymus cells from non-immunized young chickens suppress the allograft rejection in lightly irradiated syngeneic or allogeneic recipients and mediate longlasting skingraft survival in a significant proportion of recipients across a strong histocompatibility difference. Suppressive activity of this kind is already found in the embryonic thymus and is therefore believed to mediate also self tolerance and neonatal allograft tolerance. | Suppressor cells in the embryonic thymus mediate allograft tolerance. Thymus cells from non-immunized young chickens suppress the allograft rejection in lightly irradiated syngeneic or allogeneic recipients and mediate longlasting skingraft survival in a significant proportion of recipients across a strong histocompatibility difference. Suppressive activity of this kind is already found in the embryonic thymus and is therefore believed to mediate also self tolerance and neonatal allograft tolerance. | [
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PMID:4970 | Internal mammary artery bypass graft in reoperative myocardioal revascularization. | Thirty-two consecutive patients who earlier received indirect or direct myocardial revascularization underwent reoperation with one or more internal mammary artery grafts either alone or in combination with saphenous vein grafts. The main indication for reoperation was graft closure or progression of coronary atherosclerosis in nongrafted vessels, or both. Graft construction was performed under normothermic perfusion and anoxic arrest with interrupted suture technique. No intraoperative infarctions or hospital deaths occurred. All patients are alive after an average follow-up period of 20 months, and two thirds are asymptomatic. Arteriography after reoperation in nine patients revealed patency of eight of nine internal mammary artery and five of five secondary vein grafts. When angiographic and symptomatic indications for reoperation exist, the internal mammary artery bypass graft has become a valuable alternative, particularly for patients with small coronary vessels or previous vein graft failure. | Internal mammary artery bypass graft in reoperative myocardioal revascularization. Thirty-two consecutive patients who earlier received indirect or direct myocardial revascularization underwent reoperation with one or more internal mammary artery grafts either alone or in combination with saphenous vein grafts. The main indication for reoperation was graft closure or progression of coronary atherosclerosis in nongrafted vessels, or both. Graft construction was performed under normothermic perfusion and anoxic arrest with interrupted suture technique. No intraoperative infarctions or hospital deaths occurred. All patients are alive after an average follow-up period of 20 months, and two thirds are asymptomatic. Arteriography after reoperation in nine patients revealed patency of eight of nine internal mammary artery and five of five secondary vein grafts. When angiographic and symptomatic indications for reoperation exist, the internal mammary artery bypass graft has become a valuable alternative, particularly for patients with small coronary vessels or previous vein graft failure. | [
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PMID:4972 | Evaluation of a 5-mum stainless steel filter as an intravenous inline filter or prefilter. | The suitability of a 5-mum stainless steel filter as an inline filter or a protective prefilter during simulated i.v. therapy was evaluated using flow rate measurements of two routinely used i.v. fluids and parenteral nutrition fluid. As an inline i.v. filter, the 5-mum stainless steel filter was capable of maintaining suitable flow rates. The addition of antibiotic additives decreased the flow rates slightly but not below the range required for i.v. therapy. Flow rate profiles, however, when compared to a 0.45-mum membrane filter suggest that antibiotic additives contain high numbers of particles in the less than 5-mum range. Consequently many of the particles, especially those in the less than 3-mum range will pass the 5-mum filter. As a protective prefilter, the 5-mum filter device in combination with a 0.45-mum membrane filter provided more uniform flow rates over longer periods of time when additives were employed. Using the aspiration device as a prefilter for adding antibiotics to the infusion fluid resulted in improved flow rates through a 0.45-mum membrane filter for lactated Ringer's containing cephalothin sodium, while for solutions containing ampicillin or oxytetracycline, prefilteration did not change the flow rate profiles. | Evaluation of a 5-mum stainless steel filter as an intravenous inline filter or prefilter. The suitability of a 5-mum stainless steel filter as an inline filter or a protective prefilter during simulated i.v. therapy was evaluated using flow rate measurements of two routinely used i.v. fluids and parenteral nutrition fluid. As an inline i.v. filter, the 5-mum stainless steel filter was capable of maintaining suitable flow rates. The addition of antibiotic additives decreased the flow rates slightly but not below the range required for i.v. therapy. Flow rate profiles, however, when compared to a 0.45-mum membrane filter suggest that antibiotic additives contain high numbers of particles in the less than 5-mum range. Consequently many of the particles, especially those in the less than 3-mum range will pass the 5-mum filter. As a protective prefilter, the 5-mum filter device in combination with a 0.45-mum membrane filter provided more uniform flow rates over longer periods of time when additives were employed. Using the aspiration device as a prefilter for adding antibiotics to the infusion fluid resulted in improved flow rates through a 0.45-mum membrane filter for lactated Ringer's containing cephalothin sodium, while for solutions containing ampicillin or oxytetracycline, prefilteration did not change the flow rate profiles. | [
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PMID:4973 | Hyperactive children and the efficacy of psychoactive drugs as a treatment intervention. | Characteristics of hyperactive children, including speculation in regard to etiology, are reviewed. Drug effects studies and drug treatment of hyperactive behavior are examined, and unresolved issues are discussed. Conclusions indicate that individual differences in hyperative children should form the basis for treatment planning, rather than simply treating groups of children under the rubric "hyperactivity." | Hyperactive children and the efficacy of psychoactive drugs as a treatment intervention. Characteristics of hyperactive children, including speculation in regard to etiology, are reviewed. Drug effects studies and drug treatment of hyperactive behavior are examined, and unresolved issues are discussed. Conclusions indicate that individual differences in hyperative children should form the basis for treatment planning, rather than simply treating groups of children under the rubric "hyperactivity." | [
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] |
PMID:4969 | Experiments on the role of virus infections in the pathogenesis of bronchial asthma. The role of innate or acquired insufficiency or ergotropic adaptation in the mechanism of genesis of bronchial asthma. | The wide mosaic of congruent clinical and experimental observations led to the postulation that the cause of the pharmacological abnormality of the asthmatic patient, i.e. the immensely increased reactivity of the bronchial smooth muscles, is to be sought in an insufficiency of the beta-adrenergic receptor system. It is to be assumed that the so-called asthma diatheses is based inter alia on a genetically determined defect of the adenyl cyclase system. The role of previous infections of the respiratory tract in asthmagenesis should lie--following this working theory--not in a sensitization in the sense of an allergic reaction of the immediate type, but in the formation of a defective beta-adrenergic substance or in a blockade of the beta-receptor. A genetically determined innate defect of the beta-adrenergic receptors, or a defect acquired through infections of the respiratory tract, is hence likely to be the cause of the pathologically potentiated reactivity of the bronchia. It is likely that the infective stimuli--quite apart from this preparatory role--are later capable of triggering asthmatic paroxysms when the vegetative homeostasis is impaired. We know from the experiments of many authors that a blockade of the beta-receptors produced by chemical blocker substances, or by pertussis vaccine or various bacterial substances, results in a significant increase in bronchial reactivity towards histamine, serotonin, acetylcholine and other stimuli. We have shown in our experiments that heat-inactivated adeno viruses and influenza viruses also increase the anaphylactic shock reactivity and the histamine reactivity of the organism. On the basis of this working hypothesis, the pathomechanism of the asthmatic process is as follows in individual asthma forms: 1) In the 'purely" allergic asthma form, the antigen-antibody reaction that occurs after sensitization (i.e. formation of skin-sensitizing allergic antibodies of the class IgE) results in re-formation and release of slow-reacting-substances. spasm of the bronchial muscles, asthmatic paroxysm. The expulsion of catecholamines that follows the release of slow-reacting-substances makes a decisive contribution to the reestablishment of the impaired homeostatic balance. It is to be assumed that this form of asthma both symptomatically and causally--using specific desensitization--can be influenced more easily than other forms of asthma with a more complicated pathogenic background. 2) In the second allergically determined form of asthma, we are confronted by the genetically fixed or acquired insufficiency of the beta-receptors in addition to the immunological mechanism. As a result of the innate or acquired blockade of the beta-receptive substance, or the relative dominance of the alpha-receptors, the catecholamines (that physiologically serve to maintain homeostasis) contribute to a protraction, intensification and perpetuation of the bronchial obstruction. In this way the asthmatic circulus vitiosus is complete... | Experiments on the role of virus infections in the pathogenesis of bronchial asthma. The role of innate or acquired insufficiency or ergotropic adaptation in the mechanism of genesis of bronchial asthma. The wide mosaic of congruent clinical and experimental observations led to the postulation that the cause of the pharmacological abnormality of the asthmatic patient, i.e. the immensely increased reactivity of the bronchial smooth muscles, is to be sought in an insufficiency of the beta-adrenergic receptor system. It is to be assumed that the so-called asthma diatheses is based inter alia on a genetically determined defect of the adenyl cyclase system. The role of previous infections of the respiratory tract in asthmagenesis should lie--following this working theory--not in a sensitization in the sense of an allergic reaction of the immediate type, but in the formation of a defective beta-adrenergic substance or in a blockade of the beta-receptor. A genetically determined innate defect of the beta-adrenergic receptors, or a defect acquired through infections of the respiratory tract, is hence likely to be the cause of the pathologically potentiated reactivity of the bronchia. It is likely that the infective stimuli--quite apart from this preparatory role--are later capable of triggering asthmatic paroxysms when the vegetative homeostasis is impaired. We know from the experiments of many authors that a blockade of the beta-receptors produced by chemical blocker substances, or by pertussis vaccine or various bacterial substances, results in a significant increase in bronchial reactivity towards histamine, serotonin, acetylcholine and other stimuli. We have shown in our experiments that heat-inactivated adeno viruses and influenza viruses also increase the anaphylactic shock reactivity and the histamine reactivity of the organism. On the basis of this working hypothesis, the pathomechanism of the asthmatic process is as follows in individual asthma forms: 1) In the 'purely" allergic asthma form, the antigen-antibody reaction that occurs after sensitization (i.e. formation of skin-sensitizing allergic antibodies of the class IgE) results in re-formation and release of slow-reacting-substances. spasm of the bronchial muscles, asthmatic paroxysm. The expulsion of catecholamines that follows the release of slow-reacting-substances makes a decisive contribution to the reestablishment of the impaired homeostatic balance. It is to be assumed that this form of asthma both symptomatically and causally--using specific desensitization--can be influenced more easily than other forms of asthma with a more complicated pathogenic background. 2) In the second allergically determined form of asthma, we are confronted by the genetically fixed or acquired insufficiency of the beta-receptors in addition to the immunological mechanism. As a result of the innate or acquired blockade of the beta-receptive substance, or the relative dominance of the alpha-receptors, the catecholamines (that physiologically serve to maintain homeostasis) contribute to a protraction, intensification and perpetuation of the bronchial obstruction. In this way the asthmatic circulus vitiosus is complete... | [
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PMID:4974 | Ventilatory response to hypercapnia in the larger spotted dogfish Scyliorhinus stellaris. | Dogfish were exposed to sudden changes of Pco2 in inspired seawater. During hypercapnia breathing frequency remained constant, but gill ventilation was transiently increased to about 140% of control levels in the 1st h. O2 uptake was significantly increased also, but returned to the initial level before nomalization of gill ventilation. In contrast to the transient rise in gill ventilation and O2 uptake, arterial Po2 was increased for the whole period of hypercapnia. Hypercapnia results in a marked fall in pHa which returned to the initial value in 4-5 h even though hypercapnia is maintained. This rise in pHa with little change in PaCO2 was associated with an increase in plasma bicarbonate concentration. The increase of plasma bicarbonate was in part due to compensatory bicarbonate uptake from the seawater across the gills and in part was effected by transfer between intracellular tissue compartments and extracellular spaces. The compensatory bicarbonate exchange mechanism in the gills seems to have a delay both after onset and termination of hypercapnia. | Ventilatory response to hypercapnia in the larger spotted dogfish Scyliorhinus stellaris. Dogfish were exposed to sudden changes of Pco2 in inspired seawater. During hypercapnia breathing frequency remained constant, but gill ventilation was transiently increased to about 140% of control levels in the 1st h. O2 uptake was significantly increased also, but returned to the initial level before nomalization of gill ventilation. In contrast to the transient rise in gill ventilation and O2 uptake, arterial Po2 was increased for the whole period of hypercapnia. Hypercapnia results in a marked fall in pHa which returned to the initial value in 4-5 h even though hypercapnia is maintained. This rise in pHa with little change in PaCO2 was associated with an increase in plasma bicarbonate concentration. The increase of plasma bicarbonate was in part due to compensatory bicarbonate uptake from the seawater across the gills and in part was effected by transfer between intracellular tissue compartments and extracellular spaces. The compensatory bicarbonate exchange mechanism in the gills seems to have a delay both after onset and termination of hypercapnia. | [
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PMID:4975 | Does hyperinsulinemia in ob/ob mice cause an insulin-stimulated adipose tissue? | After a 1-h preincubation to remove endogenous insulin, adipose tissue of obese mice (C57BL/L4 ob/ob) had a lower rate of glucose metabolism than tissue which was not preincubated. In contrast, preincubation did not change the metabolism of adipose tissue from lean mice (C57B1/6J +/+). The preincubation effect was abolished in obese mice which had had their serum insulin levels lowered toward normal by streptozotocin treatment. Injection of anti-insulin serum to obese mice caused adipose tissue removed 15 min after the injection to display a rate of glucose metabolsim lower than that of tissue removed before the injection. No such effect was seen in lean mice. These data are consistent with the hypothesis that hyperinsulinemia in the obese mice causes a chronic state of insulin stimulation of their adipose tissue, possibly contributing to their high rates of lipogenesis and their obesity. Several lipogenic enzymes were measured in adipose tissue of both lean and obese mice, and no single enzymatic abnormality was detected which might explain the hyperlipogenesis. Pyruvate dehydrogenase and acetyl-CoA carboxylase were both insulin-sensitive enzymes in lean and obese mice. | Does hyperinsulinemia in ob/ob mice cause an insulin-stimulated adipose tissue? After a 1-h preincubation to remove endogenous insulin, adipose tissue of obese mice (C57BL/L4 ob/ob) had a lower rate of glucose metabolism than tissue which was not preincubated. In contrast, preincubation did not change the metabolism of adipose tissue from lean mice (C57B1/6J +/+). The preincubation effect was abolished in obese mice which had had their serum insulin levels lowered toward normal by streptozotocin treatment. Injection of anti-insulin serum to obese mice caused adipose tissue removed 15 min after the injection to display a rate of glucose metabolsim lower than that of tissue removed before the injection. No such effect was seen in lean mice. These data are consistent with the hypothesis that hyperinsulinemia in the obese mice causes a chronic state of insulin stimulation of their adipose tissue, possibly contributing to their high rates of lipogenesis and their obesity. Several lipogenic enzymes were measured in adipose tissue of both lean and obese mice, and no single enzymatic abnormality was detected which might explain the hyperlipogenesis. Pyruvate dehydrogenase and acetyl-CoA carboxylase were both insulin-sensitive enzymes in lean and obese mice. | [
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PMID:4976 | Importance of pulmonary ventilation in respiratory control in the bullfrog. | Pulmonary and cutaneous O2 consumption (Vo2) and CO2 production (Vco2) were measured simultaneously in bullfrogs Rana catesbeiana at 20 degrees C. The lungs were responsible for 77.3-91.0% of the total Vo2 and 28.5-74.9% of the total VCO2. The distribution of the total exchange between the lungs and skin depended on metabolic rate; frogs with higher rates relied more heavily on the pulmonary mode for both Vo2 and Vco2. When prevented from ventilating their lungs in an O2-rich environment, bullfrogs developed severe respiratory acidosis, demonstrating the importance of lung exchange in normal acid-base balance. When frogs were totally submerged in an O2-saturated medium, skin Vco2 increased linearly to a steady-state value which approximated the preapneic total Vco2. In these same animals, arterial Pco2 increased proportionately to the increase in skin Vco2, indicating that skin diffusion capacity for CO2 was unaffected. We conclude that the control of breathing in the bullfrog in response to changes in metabolic rate relies predominantly on changes in lung ventilation while the skin plays a more passive role. | Importance of pulmonary ventilation in respiratory control in the bullfrog. Pulmonary and cutaneous O2 consumption (Vo2) and CO2 production (Vco2) were measured simultaneously in bullfrogs Rana catesbeiana at 20 degrees C. The lungs were responsible for 77.3-91.0% of the total Vo2 and 28.5-74.9% of the total VCO2. The distribution of the total exchange between the lungs and skin depended on metabolic rate; frogs with higher rates relied more heavily on the pulmonary mode for both Vo2 and Vco2. When prevented from ventilating their lungs in an O2-rich environment, bullfrogs developed severe respiratory acidosis, demonstrating the importance of lung exchange in normal acid-base balance. When frogs were totally submerged in an O2-saturated medium, skin Vco2 increased linearly to a steady-state value which approximated the preapneic total Vco2. In these same animals, arterial Pco2 increased proportionately to the increase in skin Vco2, indicating that skin diffusion capacity for CO2 was unaffected. We conclude that the control of breathing in the bullfrog in response to changes in metabolic rate relies predominantly on changes in lung ventilation while the skin plays a more passive role. | [
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PMID:4977 | Electromyographic response of respiratory muscles during elastic loading. | The response of respiratory motor neurons to graded elastic loading was assessed in anesthetized dogs by recording the electromyogram (EMG) from the diaphragm (ED) and the intercostal muscle (EIC). Elastic loads were applied for 1-20 breaths. The effects of changes in PCO2 on respiratory motor neuron output was assessed by applying loads during the course of CO2 rebreathing. On the first loaded breath, ED and EIC increased reflexly due chiefly to prolongation of inspiration. Vagotomy or vagal cooling to block the Hering-Breuer reflex eliminated the increase in ED and diminished the increase in EIC. During the second to fifth breath, the level of EMG activity was disproportionately high for the level of PCO2, suggesting an additional reflex component over and above the reflex activity present on the first loaded breath. | Electromyographic response of respiratory muscles during elastic loading. The response of respiratory motor neurons to graded elastic loading was assessed in anesthetized dogs by recording the electromyogram (EMG) from the diaphragm (ED) and the intercostal muscle (EIC). Elastic loads were applied for 1-20 breaths. The effects of changes in PCO2 on respiratory motor neuron output was assessed by applying loads during the course of CO2 rebreathing. On the first loaded breath, ED and EIC increased reflexly due chiefly to prolongation of inspiration. Vagotomy or vagal cooling to block the Hering-Breuer reflex eliminated the increase in ED and diminished the increase in EIC. During the second to fifth breath, the level of EMG activity was disproportionately high for the level of PCO2, suggesting an additional reflex component over and above the reflex activity present on the first loaded breath. | [
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PMID:4978 | Plasma secretin and gastrin responses to a meat meal and duodenal acidification in dogs. | In five conscious dogs with gastric fistula and two duodenal cannulas, plasma RIA secretin and gastrin levels were determined in response to 1) infusion of 0.1 N HCl in the proximal duodenal cannula, 2) ingestion of a meal, and 3) intraduodenal infusion of 0.1 N HCl following ingestion of a meal. Significant increases in plasma RIA secretin levels occurred during duodenal acidification. However, no significant change occurred in the secretin levels after ingestion of a meal, whereas significant increase in plasma gastrin level was observed. Postprandial duodenal pH remained above 4.5 for 3 h. | Plasma secretin and gastrin responses to a meat meal and duodenal acidification in dogs. In five conscious dogs with gastric fistula and two duodenal cannulas, plasma RIA secretin and gastrin levels were determined in response to 1) infusion of 0.1 N HCl in the proximal duodenal cannula, 2) ingestion of a meal, and 3) intraduodenal infusion of 0.1 N HCl following ingestion of a meal. Significant increases in plasma RIA secretin levels occurred during duodenal acidification. However, no significant change occurred in the secretin levels after ingestion of a meal, whereas significant increase in plasma gastrin level was observed. Postprandial duodenal pH remained above 4.5 for 3 h. | [
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PMID:4979 | Intracellular pH of brain: alterations in acute respiratory acidosis and alkalosis. | To evaluate the metabolic adaptations of the brain to acute respiratory acid-base disturbances, a method was developed to measure intracellular pH (pHi) in the brain of dogs under conditions in which arterial pH is rapidly altered. Brain pHi was determined by measuring the distribution of 14C-labeled dimethadione (DMO) in brain relative to cortical CSF. Brain extracellular space (ECS) was evaluated as the 35SO4 = space relative to cortical CSF, and arterial Po2 was maintained at 82-110 mmHg. In normal dogs, brain (cerebral cortex) pHi was 7.05, and after 1 h of hypercapnia (arterial pH = 7.07) it fell to 6.93. However, after 3 h with arterial Pco2 maintained at 85 mmHg brain pHi was normal (7.06), and during this time brain bicarbonate had risen from 11.3 to 24.4 meq/kg H2O. These changes were not prevented by intravenous doses of acetazolamide, | Intracellular pH of brain: alterations in acute respiratory acidosis and alkalosis. To evaluate the metabolic adaptations of the brain to acute respiratory acid-base disturbances, a method was developed to measure intracellular pH (pHi) in the brain of dogs under conditions in which arterial pH is rapidly altered. Brain pHi was determined by measuring the distribution of 14C-labeled dimethadione (DMO) in brain relative to cortical CSF. Brain extracellular space (ECS) was evaluated as the 35SO4 = space relative to cortical CSF, and arterial Po2 was maintained at 82-110 mmHg. In normal dogs, brain (cerebral cortex) pHi was 7.05, and after 1 h of hypercapnia (arterial pH = 7.07) it fell to 6.93. However, after 3 h with arterial Pco2 maintained at 85 mmHg brain pHi was normal (7.06), and during this time brain bicarbonate had risen from 11.3 to 24.4 meq/kg H2O. These changes were not prevented by intravenous doses of acetazolamide, | [
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PMID:4980 | Myocardial CO2 buffering: role of transmembrane transport of H+ or HCO3-ions. | Isolated rabbit hearts were perfused with rabbit red cells suspended in Ringer solution. A small volume of perfusate was recirculated for 10 min at Pco2 of 33.4 +/- 0.9 or 150.8 +/- 7.5 mmHg. Hypercapnia resulted in an increase in perfusate HCO3- concentration that was smaller than that observed when isolated perfusate was equilibrated in vitro with the same CO2 tensions (delta HCO-3e = 1.6 mM, P less than 0.01). This difference is consistent with a net movement of HCO3- into or H+ out of the mycardial cell, and cannot be accounted for by dilution of HCO3- in the myocardial interstitium. Recirculation of perfusate through the coronary circulation at normal Pco2 for two consecutive 10-min periods was not followed by changes in perfusate HCO3- concentration. A high degree of correlation (r = 0.81) was observed between intracellular HCO-3e concentration and the corresponding delta HCO-3e in individual experiments. The results suggest that transmembrane exchange of H+ or HCO3- is a buffer mechanism for CO2 in the myocardial cell. | Myocardial CO2 buffering: role of transmembrane transport of H+ or HCO3-ions. Isolated rabbit hearts were perfused with rabbit red cells suspended in Ringer solution. A small volume of perfusate was recirculated for 10 min at Pco2 of 33.4 +/- 0.9 or 150.8 +/- 7.5 mmHg. Hypercapnia resulted in an increase in perfusate HCO3- concentration that was smaller than that observed when isolated perfusate was equilibrated in vitro with the same CO2 tensions (delta HCO-3e = 1.6 mM, P less than 0.01). This difference is consistent with a net movement of HCO3- into or H+ out of the mycardial cell, and cannot be accounted for by dilution of HCO3- in the myocardial interstitium. Recirculation of perfusate through the coronary circulation at normal Pco2 for two consecutive 10-min periods was not followed by changes in perfusate HCO3- concentration. A high degree of correlation (r = 0.81) was observed between intracellular HCO-3e concentration and the corresponding delta HCO-3e in individual experiments. The results suggest that transmembrane exchange of H+ or HCO3- is a buffer mechanism for CO2 in the myocardial cell. | [
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PMID:4981 | Cardiovascular effects of cerebroventricular ouabain perfusion in the adult dog. | Cerebroventricular perfusion with artificial cerebrospinal fluid containing 10(-5) M ouabain was performed in adult dogs in order to describe the time course of the cardiovascular effect of intraventricular ouabain and to evaluate treatments to eliminate the cardiovascular effect. The central effect of ouabain caused a 56% increase in blood pressure above control values and a 35% increase in heart rate with various cardiac arrhythmias. Both alpha- and beta-adrenergic blocking drugs given intravenously.altered the pressure and rate effects ou ouabain, whereas vagotomy attenuated the effect. | Cardiovascular effects of cerebroventricular ouabain perfusion in the adult dog. Cerebroventricular perfusion with artificial cerebrospinal fluid containing 10(-5) M ouabain was performed in adult dogs in order to describe the time course of the cardiovascular effect of intraventricular ouabain and to evaluate treatments to eliminate the cardiovascular effect. The central effect of ouabain caused a 56% increase in blood pressure above control values and a 35% increase in heart rate with various cardiac arrhythmias. Both alpha- and beta-adrenergic blocking drugs given intravenously.altered the pressure and rate effects ou ouabain, whereas vagotomy attenuated the effect. | [
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PMID:4982 | Effect of beta-adrenoreceptor blockade on rat cardiac and skeletal muscle pH. | The effect of catecholamines on the intracellular pH of rat cardiac and skeletal muscle during varying extracellular acid-base states was determined. Intracellualr pH (pHi) was calculated from the distribution of [14C]DMO. Acid-base disturbances were produced by placing the animals in an environmental chamber containing 10 or 20% CO2 or by administering HCL or NaHCO3. Two hours later the animals were anesthetized with sodium pentobarbital and blood and tissue samples obtained. In one series of animals, the effects of catecholamines were attenuated by administering the beta-adrenoreceptor antagonist MJ 1999 (Sotalol). In animals breathing 20% CO2, cardiac muscle pH was lower in beta-blocked than unblocked animals (6.69 vs. 6.78). During metabolic acidosis, cardiac muscle pH of beta-blocked animals was lower than that of unblocked animals (6.75 vs. 6.84). The same relationship was observed for skeletal muscle during metabolic acidosis-beta blockade pHi, 6.66; unblocked pHi, 6.77. The pHi of beta-blocked versus unblocked animals was not significantly different under normal acid-base conditions or metabolic alkalosis for cardiac or skeletal muscle. The effective buffer value of both tissue over the normal acidotic range was decreased by the beta-blocking agent. These results indicate that catecholamine release accompanying acidosis attenuates the change in pHI and increases the effective buffer value of cardiac and skeletal muscle. | Effect of beta-adrenoreceptor blockade on rat cardiac and skeletal muscle pH. The effect of catecholamines on the intracellular pH of rat cardiac and skeletal muscle during varying extracellular acid-base states was determined. Intracellualr pH (pHi) was calculated from the distribution of [14C]DMO. Acid-base disturbances were produced by placing the animals in an environmental chamber containing 10 or 20% CO2 or by administering HCL or NaHCO3. Two hours later the animals were anesthetized with sodium pentobarbital and blood and tissue samples obtained. In one series of animals, the effects of catecholamines were attenuated by administering the beta-adrenoreceptor antagonist MJ 1999 (Sotalol). In animals breathing 20% CO2, cardiac muscle pH was lower in beta-blocked than unblocked animals (6.69 vs. 6.78). During metabolic acidosis, cardiac muscle pH of beta-blocked animals was lower than that of unblocked animals (6.75 vs. 6.84). The same relationship was observed for skeletal muscle during metabolic acidosis-beta blockade pHi, 6.66; unblocked pHi, 6.77. The pHi of beta-blocked versus unblocked animals was not significantly different under normal acid-base conditions or metabolic alkalosis for cardiac or skeletal muscle. The effective buffer value of both tissue over the normal acidotic range was decreased by the beta-blocking agent. These results indicate that catecholamine release accompanying acidosis attenuates the change in pHI and increases the effective buffer value of cardiac and skeletal muscle. | [
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PMID:4983 | Biliary secretion in elasmobranchs. I. Bile collection and composition. | Bile composition and secretion were studied in tow elasmobranch species, Squalus acanthias (spiny dogfish shark) and Raja erinacea (small skate), after ligation of the common duct and insertion of cannulas into the gallbladder lumen. Fish were then allowed to swim freely in large pools and bile was collected in balloons attached to the externalized cannulas. Both species secreted bile for periods of 4-7 days at a maximum rate of 1.77 +/- .89 ml/kg per 24 h in Squalus acanthias and 2.66 +/- .89 ml/kg per 24 h in Raja erinacea. Comparison of the composition of cannula and gallbladder bile indicated that hepatic bile could be collected by this technique in both species without effective contact with gallbladder epithelium. The low concentrations of HCO3- and CL- and the gigh bile salt levels in dogfish gallbladder bile indicate that mechanisms for concentration and acidification of bile in the gallbladder developed early in vertebrate evolution. These results indicate that gallbladder cannulation in free-swimming elasmobranchs is a useful technique for the study of bile secretory and excretory function in marine species. | Biliary secretion in elasmobranchs. I. Bile collection and composition. Bile composition and secretion were studied in tow elasmobranch species, Squalus acanthias (spiny dogfish shark) and Raja erinacea (small skate), after ligation of the common duct and insertion of cannulas into the gallbladder lumen. Fish were then allowed to swim freely in large pools and bile was collected in balloons attached to the externalized cannulas. Both species secreted bile for periods of 4-7 days at a maximum rate of 1.77 +/- .89 ml/kg per 24 h in Squalus acanthias and 2.66 +/- .89 ml/kg per 24 h in Raja erinacea. Comparison of the composition of cannula and gallbladder bile indicated that hepatic bile could be collected by this technique in both species without effective contact with gallbladder epithelium. The low concentrations of HCO3- and CL- and the gigh bile salt levels in dogfish gallbladder bile indicate that mechanisms for concentration and acidification of bile in the gallbladder developed early in vertebrate evolution. These results indicate that gallbladder cannulation in free-swimming elasmobranchs is a useful technique for the study of bile secretory and excretory function in marine species. | [
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PMID:4984 | Film screening by physician assistants in diagnostic radiology. | Data are presented which indicate that specially selected ART students can be trained to evaluate radiographs as to the presence or absence of significant pathology with an accuracy equivalent to that of experienced staff radiologists. The methods employed in this training program-namely, stressing perceptual recognition of normal and abnormal findings-may be beneficial in the early months of training of diagnostic radiology residents to hasten achievement of an acceptable perceptual performance. Test films, used in this study as an evaluation technique, may also be useful to assess residents' progress. | Film screening by physician assistants in diagnostic radiology. Data are presented which indicate that specially selected ART students can be trained to evaluate radiographs as to the presence or absence of significant pathology with an accuracy equivalent to that of experienced staff radiologists. The methods employed in this training program-namely, stressing perceptual recognition of normal and abnormal findings-may be beneficial in the early months of training of diagnostic radiology residents to hasten achievement of an acceptable perceptual performance. Test films, used in this study as an evaluation technique, may also be useful to assess residents' progress. | [
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PMID:4985 | Use of physician's assistants in a general surgical practice. | A study has been made of three PAS employed in a rural, small town, general surgical practice during a four year period. Their work was equally divided among three areas: minor trauma, obtaining and recording data for history and physical examinations, and assisting at routine surgical procedures and endoscopies. This resulted in a significant saving of time for each surgeon who was thus freed for more time in the care of the more critically ill or injured patients. | Use of physician's assistants in a general surgical practice. A study has been made of three PAS employed in a rural, small town, general surgical practice during a four year period. Their work was equally divided among three areas: minor trauma, obtaining and recording data for history and physical examinations, and assisting at routine surgical procedures and endoscopies. This resulted in a significant saving of time for each surgeon who was thus freed for more time in the care of the more critically ill or injured patients. | [
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PMID:4989 | [The influence of PaCO2 on oxygen consumption during extracorporeal circulation in hypothermia (author's transl)]. | Hypocapnia during extracorporeal circulation in hypothermia increases oxygen consumption. Po2 in mixed venous blood decreases. This probably reflects a decrease in tissue oxygen tension. Hyperventilation will therefore increase the risk of hypoxia in critically perfused tissues. Therefore we recommend to keep PaCO2 (T) constant at 40 mm Hg during hypothermia. | [The influence of PaCO2 on oxygen consumption during extracorporeal circulation in hypothermia (author's transl)]. Hypocapnia during extracorporeal circulation in hypothermia increases oxygen consumption. Po2 in mixed venous blood decreases. This probably reflects a decrease in tissue oxygen tension. Hyperventilation will therefore increase the risk of hypoxia in critically perfused tissues. Therefore we recommend to keep PaCO2 (T) constant at 40 mm Hg during hypothermia. | [
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PMID:4990 | [Clinical studies on the use of ketalar in obstetric anesthesia (author's transl)]. | 26 healthy pregnant women at term were divided into 2 groups and anaesthetized with either 1 mg/kh or 2 mg/kg ketamine - N20/02 - for primary caesarean section. Maternal venous ketamine plasma levels, neonatal ketamine plasma levels (umbilical artery and umbilical vein) and blood gases were measured. Maternal venous ketamine plasma levels in group I exceeded those in group II by 2.8 (30-60 sec after injection) and 2.0 (at the time of delivery) respectively. Independent of the dose used, the plasma levels of ketamine in the umbilical artery or the umbilical vein were found to be identical in the two groups of newborn infants. Neonatal blood gases and acid base parameters did not significantly differ between the two groups, except for the oxygen tension in group II which slightly exceeded the PO2 values in group I 15, 60 and 120 min after delivery. pH and standard bicarbonate values were found to be higher (1 and 5 min) in both groups, compared to pH and standard bicarbonate levels in a group of newborns delivered spontaneously.--The results of this study show: 1. Independent of a low or high ketamine dosage, neonatal blood concentration of the drug remain low, probably due to a placental barrier effect.--2. The post partum recovery of the newborns was neither influenced by the ketamine anesthesia itself nor by different drug doses. | [Clinical studies on the use of ketalar in obstetric anesthesia (author's transl)]. 26 healthy pregnant women at term were divided into 2 groups and anaesthetized with either 1 mg/kh or 2 mg/kg ketamine - N20/02 - for primary caesarean section. Maternal venous ketamine plasma levels, neonatal ketamine plasma levels (umbilical artery and umbilical vein) and blood gases were measured. Maternal venous ketamine plasma levels in group I exceeded those in group II by 2.8 (30-60 sec after injection) and 2.0 (at the time of delivery) respectively. Independent of the dose used, the plasma levels of ketamine in the umbilical artery or the umbilical vein were found to be identical in the two groups of newborn infants. Neonatal blood gases and acid base parameters did not significantly differ between the two groups, except for the oxygen tension in group II which slightly exceeded the PO2 values in group I 15, 60 and 120 min after delivery. pH and standard bicarbonate values were found to be higher (1 and 5 min) in both groups, compared to pH and standard bicarbonate levels in a group of newborns delivered spontaneously.--The results of this study show: 1. Independent of a low or high ketamine dosage, neonatal blood concentration of the drug remain low, probably due to a placental barrier effect.--2. The post partum recovery of the newborns was neither influenced by the ketamine anesthesia itself nor by different drug doses. | [
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PMID:4998 | Effect of abdominal compression on minute ventilation of patients with chronic obstructive lung disease and bronchial asthma. | The effects of manual compression of the upper lateral abdomen (C) of 73 cases of obstructive airway disease were studied in respect to the change in minute ventilation (V) 10 minutes after the procedure was performed. A mean decrease of 13% in V was found in the majority of 15 cases of bronchial asthma or chronic bronchitis and 43 patients with chronic obstructive lung disease. The use of manual compression as a therapeutic measure depends largely on the abrupt reduction of lung volume in cases of obstructive airway disease in which over-inflation of the lung is present as an acute or chronic disorder. The degree and duration of clinical benefit, i.e., relief of dyspnea, depends on such factors as the volume of air trapped in the lungs, broncho-constriction through pathologic change or bronchospasm and impairment of elastic recoil of the pulmonary parenchyma. The lowered V recorded 10 minutes after C is performed suggests that decrease in dyspnea is associated with enhanced efficiency of ventilation in some subjects with obstructive airway disease, including those with bronchial asthma as well as COLD. A brief description is presented of 10 patients with COLD in whom manual compression and other features of a rehabilitation program were employed. Mean length of life of five living subjects is 12.6 years after beginning of therapy. The mean length of life of five who died was 10.2 years after beginning of treatment. | Effect of abdominal compression on minute ventilation of patients with chronic obstructive lung disease and bronchial asthma. The effects of manual compression of the upper lateral abdomen (C) of 73 cases of obstructive airway disease were studied in respect to the change in minute ventilation (V) 10 minutes after the procedure was performed. A mean decrease of 13% in V was found in the majority of 15 cases of bronchial asthma or chronic bronchitis and 43 patients with chronic obstructive lung disease. The use of manual compression as a therapeutic measure depends largely on the abrupt reduction of lung volume in cases of obstructive airway disease in which over-inflation of the lung is present as an acute or chronic disorder. The degree and duration of clinical benefit, i.e., relief of dyspnea, depends on such factors as the volume of air trapped in the lungs, broncho-constriction through pathologic change or bronchospasm and impairment of elastic recoil of the pulmonary parenchyma. The lowered V recorded 10 minutes after C is performed suggests that decrease in dyspnea is associated with enhanced efficiency of ventilation in some subjects with obstructive airway disease, including those with bronchial asthma as well as COLD. A brief description is presented of 10 patients with COLD in whom manual compression and other features of a rehabilitation program were employed. Mean length of life of five living subjects is 12.6 years after beginning of therapy. The mean length of life of five who died was 10.2 years after beginning of treatment. | [
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PMID:5005 | [Accidental peroperative hypothermia during rapid transfusion]. | Six cases of grave hypothermias are reported, having arisen during surgical interventions which necessitated a rapid and abundant transfusion of badly warmed blood. The role of favouring factors, surrounding cold due to the air-conditioning, anaesthesia, extent of the area of operation, seems important. The symptomatology permits the individualization of a hypothermic syndrom neighbouring the picture described in toxic accidental hypothermias. Accidents during the warming process associate collapse and disturbances in coagulation. It is therefore necessary to consider certain signs of alarm as important and generalize the conditions for prevention of thermolysis in the operating theatre. | [Accidental peroperative hypothermia during rapid transfusion]. Six cases of grave hypothermias are reported, having arisen during surgical interventions which necessitated a rapid and abundant transfusion of badly warmed blood. The role of favouring factors, surrounding cold due to the air-conditioning, anaesthesia, extent of the area of operation, seems important. The symptomatology permits the individualization of a hypothermic syndrom neighbouring the picture described in toxic accidental hypothermias. Accidents during the warming process associate collapse and disturbances in coagulation. It is therefore necessary to consider certain signs of alarm as important and generalize the conditions for prevention of thermolysis in the operating theatre. | [
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PMID:5006 | [Information science in intensive care medicine. Examples of the European approach]. | The modern treatment of patients in a precarious state requires the use of technical appliances which become more complex and more numerous day by day. The data generated by these appliances, together with the conventional measurements of physiological parameters carried out by the nursing ataff during care, with the results of laboratory examinations and with medical physical examinations, represent a raw material of information which tends to increase each year. The repetitive and hand-written consigning of these data, likewise their traditional laborious consultation, no longer guarantees today the taking of rapid decisions concerning the patients. Now, this rapid decision-making is at the centre of the functioning of present-day intensive medicine, of the surveillance and optimal treatment of the patients, of the functional organization of the intensive care unit, and of the "economic" efficiency of the exploitation. It seems locigal, therefore, to wish to avail of the resources provided by information science to resolve these problems. The United States, Japan and certain European countries have done so. Our purpose is to give some examples of the European approach. | [Information science in intensive care medicine. Examples of the European approach]. The modern treatment of patients in a precarious state requires the use of technical appliances which become more complex and more numerous day by day. The data generated by these appliances, together with the conventional measurements of physiological parameters carried out by the nursing ataff during care, with the results of laboratory examinations and with medical physical examinations, represent a raw material of information which tends to increase each year. The repetitive and hand-written consigning of these data, likewise their traditional laborious consultation, no longer guarantees today the taking of rapid decisions concerning the patients. Now, this rapid decision-making is at the centre of the functioning of present-day intensive medicine, of the surveillance and optimal treatment of the patients, of the functional organization of the intensive care unit, and of the "economic" efficiency of the exploitation. It seems locigal, therefore, to wish to avail of the resources provided by information science to resolve these problems. The United States, Japan and certain European countries have done so. Our purpose is to give some examples of the European approach. | [
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PMID:5007 | [Iskedyl and general anesthesia. Measurement of the systolic ejection volume and peripheral resistance using the arterial pressure curves]. | ISKEDYL (PF 50), which is sold as a vasoregulator of cerebral irrigation, consists of a mixture of dihydroergocristine and raubasine. This work aims at determining possible interactions between this product and certain drugs used in anesthesia from the cardiovascular point of view. ISKEDYL does not seem to be a contraindication to anesthesia of the "neuroleptic" type, when injected in pre-, per- or post-operative period. A slight temporary and spontaneously reversible fall in arterial blood pressure, affecting both maximum and minimum pressure, together with a decrease in stroke volume and peripheral resistances, estimated by the study of the arterial blood pressure curve, seem to indicate that this product has peripheral vaso-dilatory properties. | [Iskedyl and general anesthesia. Measurement of the systolic ejection volume and peripheral resistance using the arterial pressure curves]. ISKEDYL (PF 50), which is sold as a vasoregulator of cerebral irrigation, consists of a mixture of dihydroergocristine and raubasine. This work aims at determining possible interactions between this product and certain drugs used in anesthesia from the cardiovascular point of view. ISKEDYL does not seem to be a contraindication to anesthesia of the "neuroleptic" type, when injected in pre-, per- or post-operative period. A slight temporary and spontaneously reversible fall in arterial blood pressure, affecting both maximum and minimum pressure, together with a decrease in stroke volume and peripheral resistances, estimated by the study of the arterial blood pressure curve, seem to indicate that this product has peripheral vaso-dilatory properties. | [
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PMID:5008 | [Continuous peridural anesthesia in traumatological and reparative surgery of the lower extremities]. | The authors give an account of their experience of peridural anaesthesia in 250 cases at the Centre for traumatological and reparative surgery. They demonstrate the advantages derived from this type of anaesthesia: in elderly subjects manifesting an organic defect, and in emergency cases with "full stomach". | [Continuous peridural anesthesia in traumatological and reparative surgery of the lower extremities]. The authors give an account of their experience of peridural anaesthesia in 250 cases at the Centre for traumatological and reparative surgery. They demonstrate the advantages derived from this type of anaesthesia: in elderly subjects manifesting an organic defect, and in emergency cases with "full stomach". | [
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PMID:5004 | [Disorders of body temperature regulation. 1. Physiopathological study]. | In this work, disorders of thermo-regulation are first studied in a synthetic manner from the angle of cellular and haemodynamic disturbances. Then the particular physiopathological aspects concerning hypothermia and hyperthermia are looked at in succession. In his next work, the author will view the clinical and therapeutic study of these phenomena. Extensive bibliography. | [Disorders of body temperature regulation. 1. Physiopathological study]. In this work, disorders of thermo-regulation are first studied in a synthetic manner from the angle of cellular and haemodynamic disturbances. Then the particular physiopathological aspects concerning hypothermia and hyperthermia are looked at in succession. In his next work, the author will view the clinical and therapeutic study of these phenomena. Extensive bibliography. | [
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] |
PMID:5014 | [Physico-chemical characteristics, absorption and elimination kinetics and technics of use of enflurane]. | Physical-chemical properties, uptake und elemination of enflurane are described with particular references to halothane. The ratio potency/vapor pressure, the blood and tissues solubility of this agent provide a good flexibility of uptake and elemination in response to changes in alveolar ventilation. When used with nitrous oxide, the enflurane may provide good clinical results at inspired concentration 1-2 p. 100. | [Physico-chemical characteristics, absorption and elimination kinetics and technics of use of enflurane]. Physical-chemical properties, uptake und elemination of enflurane are described with particular references to halothane. The ratio potency/vapor pressure, the blood and tissues solubility of this agent provide a good flexibility of uptake and elemination in response to changes in alveolar ventilation. When used with nitrous oxide, the enflurane may provide good clinical results at inspired concentration 1-2 p. 100. | [
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PMID:5009 | [Impact of alfatesine anesthesia on cerebrospinal fluid pressure in man]. | The variations in pressure of the cerebrospinal fluid was studied in 20 patients before and after induction of anesthesia with alfatesine (0.1 ml/Kg). 14 patients received no other complementary drug (group 1); in the six other cases, 1 g. of acetylsalicylic acid was administered as an analgesic complement (group II). All of the patients spontnaeously ventilated an O2 - N2O 50 p. 100 mixture. The C.S.F. pressure fell by 39 p. 100 on the average (p. less than 0.001) in group I and did not vary in group II. This fall is essentially related to cerebral vasoconstriction, therefore to the fall in cerebral blood flow caused by Alfatesine. In group II hypercapnia was noted in all of the patients; it abolishes the cerebral vasoconstriction due to Alfatesine; the cerebral blood flow did not fall neither did the C.S.F. pressure. | [Impact of alfatesine anesthesia on cerebrospinal fluid pressure in man]. The variations in pressure of the cerebrospinal fluid was studied in 20 patients before and after induction of anesthesia with alfatesine (0.1 ml/Kg). 14 patients received no other complementary drug (group 1); in the six other cases, 1 g. of acetylsalicylic acid was administered as an analgesic complement (group II). All of the patients spontnaeously ventilated an O2 - N2O 50 p. 100 mixture. The C.S.F. pressure fell by 39 p. 100 on the average (p. less than 0.001) in group I and did not vary in group II. This fall is essentially related to cerebral vasoconstriction, therefore to the fall in cerebral blood flow caused by Alfatesine. In group II hypercapnia was noted in all of the patients; it abolishes the cerebral vasoconstriction due to Alfatesine; the cerebral blood flow did not fall neither did the C.S.F. pressure. | [
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PMID:5010 | [Transformation of sorbitol to mannitol when used in parenteral administration]. | This was shown by the unexpected discovery of the urinary excretion of mannitol when urinary sorbitol levels were being measured in connection with the surveillance of patients suffering from malnutrition and head injury and receiving total parenteral nutrition: glucose, sorbitol, amino-acids, soya oil. The presence of mannitol in the urine would appear to result from a secondary catabolic through physiological pathway for the fructose produced by the metabolism of sortibol not metabolised during glycolysis. | [Transformation of sorbitol to mannitol when used in parenteral administration]. This was shown by the unexpected discovery of the urinary excretion of mannitol when urinary sorbitol levels were being measured in connection with the surveillance of patients suffering from malnutrition and head injury and receiving total parenteral nutrition: glucose, sorbitol, amino-acids, soya oil. The presence of mannitol in the urine would appear to result from a secondary catabolic through physiological pathway for the fructose produced by the metabolism of sortibol not metabolised during glycolysis. | [
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PMID:5015 | [Clinical evaluation of the new anesthetic "Ethrane"]. | Seventy-four patients aged 14 months to 71 years, classified as ASA I and II were anesthetised with Ethrane for surgical interventions of mean duration 117 minutes. With the exception of 5 patients who were directly anesthetised with Ethrane, the others received Ethrane after induction with Penthiobarbitone. Maintenance of anesthesia was ensured with 1 to 4p. 100 concentrations of Ethrane and 33p. 100 oxygen and 66p. 100 nitrous oxide. Tracheal intubation was facilitated by injection of 1 mg/kg of succinylcholine. Induction with enflurane is rapid with no phenomena of excitation or irritation of the ear passages. The cardiovascular apparatus is stable with no arrythmia but an increase in heart rate of 11 to 50p. 100 is noted and in 41p. 100 of the cases hypotension of 35p. 100 of the intitial value. During spontaneous ventilation, a type of rapid and superficial respiration is observed with a flow volume of 5.3 ml/kg for an average frequency of 25/min. The arterial blood gases show slight hypercapnia. Myorelaxation is significant and better than that obtained with halothane. Coming round poses few problems apart from agitation in adolescents. Response to simple orders appears at 13 minutes. Trembling and rigidity occur in 41p. 100 of the cases for 5 to 30 minutes. From the hepatic point of view, no lastin enzyme changes were noted and no renal toxicity was demonstrated. Ethrane appears to be a good anesthetic agent but the few advantages mentioned means that it does not fulfil ideal conditions. | [Clinical evaluation of the new anesthetic "Ethrane"]. Seventy-four patients aged 14 months to 71 years, classified as ASA I and II were anesthetised with Ethrane for surgical interventions of mean duration 117 minutes. With the exception of 5 patients who were directly anesthetised with Ethrane, the others received Ethrane after induction with Penthiobarbitone. Maintenance of anesthesia was ensured with 1 to 4p. 100 concentrations of Ethrane and 33p. 100 oxygen and 66p. 100 nitrous oxide. Tracheal intubation was facilitated by injection of 1 mg/kg of succinylcholine. Induction with enflurane is rapid with no phenomena of excitation or irritation of the ear passages. The cardiovascular apparatus is stable with no arrythmia but an increase in heart rate of 11 to 50p. 100 is noted and in 41p. 100 of the cases hypotension of 35p. 100 of the intitial value. During spontaneous ventilation, a type of rapid and superficial respiration is observed with a flow volume of 5.3 ml/kg for an average frequency of 25/min. The arterial blood gases show slight hypercapnia. Myorelaxation is significant and better than that obtained with halothane. Coming round poses few problems apart from agitation in adolescents. Response to simple orders appears at 13 minutes. Trembling and rigidity occur in 41p. 100 of the cases for 5 to 30 minutes. From the hepatic point of view, no lastin enzyme changes were noted and no renal toxicity was demonstrated. Ethrane appears to be a good anesthetic agent but the few advantages mentioned means that it does not fulfil ideal conditions. | [
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PMID:5011 | [A case of acute tobacco poisoning by enema]. | The authors report the case of a 5 month old child intoxicated with nicotine through an enema. A mother who wished to treat her infant for constipation had administered to him as an enema a decoction of green tobacco leaves; 15 to 20 minutes after the enema, the child showed diarrhoea and respiratory disturbances. The authors treated the respiratory disturbances by assisted respiration and bradycardia and the diarrhoea with atropine. They also caused a force diuresis using a 10 p. 100 glucose solution and Furosemide. | [A case of acute tobacco poisoning by enema]. The authors report the case of a 5 month old child intoxicated with nicotine through an enema. A mother who wished to treat her infant for constipation had administered to him as an enema a decoction of green tobacco leaves; 15 to 20 minutes after the enema, the child showed diarrhoea and respiratory disturbances. The authors treated the respiratory disturbances by assisted respiration and bradycardia and the diarrhoea with atropine. They also caused a force diuresis using a 10 p. 100 glucose solution and Furosemide. | [
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PMID:5016 | [Hemodynamic effect of enflurane in man]. | The following hemodynamic parameters: cardiac frequency, peripheral arterial pressure, pulmonary pressure and cardiac output were measured by direct catheterisation, as the total peripheral vascular resistance and the systolic ejection volume were calculated from the registered results. The cardiac frequency and the pulmonary arterial pressure were practically not modified in our patients, though we have observed a statistically significant decrease of systolic (-30p. 100) and diastolic (-27p. 100) arterial pressure. The total peripheral vascular resistance shows a marked diminution (-20p. 100) after giving Ethrane? for ten minutes. If it is possible that one part, surely important, of the cardiac output, is preserved under Ethrane anesthesia by a significant decrease of the total peripheral vascular resistance, a myocardial depression might be questionned, the decrease of cardiac output at 30 minutes being more important than the decrease of the total peripheral vascular resistance. | [Hemodynamic effect of enflurane in man]. The following hemodynamic parameters: cardiac frequency, peripheral arterial pressure, pulmonary pressure and cardiac output were measured by direct catheterisation, as the total peripheral vascular resistance and the systolic ejection volume were calculated from the registered results. The cardiac frequency and the pulmonary arterial pressure were practically not modified in our patients, though we have observed a statistically significant decrease of systolic (-30p. 100) and diastolic (-27p. 100) arterial pressure. The total peripheral vascular resistance shows a marked diminution (-20p. 100) after giving Ethrane? for ten minutes. If it is possible that one part, surely important, of the cardiac output, is preserved under Ethrane anesthesia by a significant decrease of the total peripheral vascular resistance, a myocardial depression might be questionned, the decrease of cardiac output at 30 minutes being more important than the decrease of the total peripheral vascular resistance. | [
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PMID:5017 | [Postoperative circulatory arrest (apropos of 37 cases)]. | Within five years, the authors received 37 patients who had presented a post-operative cardiac arrest. Most of them came from the Bordeaux district (from the hospital as well as the public sector) although they did not represent the totality of such accidents. The study bears first of all upon the data concerning the patients, then upon the surgical intervention, the mode of anaesthesia and ventilation, the posture and finally the treatment. In 10 cases. it was noted, as early as the admission, that the blood volume feel short of the theoretical total blood volume by one liter or more. The authors take into account how traces of previous affections, the localization in O.R.L., and, in ophthalmology, an important number of mistakes in anaesthesia, favour the progress of the genesis of the accident. | [Postoperative circulatory arrest (apropos of 37 cases)]. Within five years, the authors received 37 patients who had presented a post-operative cardiac arrest. Most of them came from the Bordeaux district (from the hospital as well as the public sector) although they did not represent the totality of such accidents. The study bears first of all upon the data concerning the patients, then upon the surgical intervention, the mode of anaesthesia and ventilation, the posture and finally the treatment. In 10 cases. it was noted, as early as the admission, that the blood volume feel short of the theoretical total blood volume by one liter or more. The authors take into account how traces of previous affections, the localization in O.R.L., and, in ophthalmology, an important number of mistakes in anaesthesia, favour the progress of the genesis of the accident. | [
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PMID:5018 | [New ventilation technic in anesthesia for direct suspension laryngoscopy]. | The authors bring not only the results of their experience but a solution of the respiratory problems during anaesthesia in suspension laryngoscopy, thanks to the devising of a new intubation probe and a pre-set automatic insufflator with varying volum flow. | [New ventilation technic in anesthesia for direct suspension laryngoscopy]. The authors bring not only the results of their experience but a solution of the respiratory problems during anaesthesia in suspension laryngoscopy, thanks to the devising of a new intubation probe and a pre-set automatic insufflator with varying volum flow. | [
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PMID:5019 | [The second electromyographic study of surgical curarization with AH.8165, a new pachycurare derivative of azobis-arylimidazo(1-2a) pyridinium]. | This second electromyographic study of AH-8165, a product derived from azobis-arymilidazo-(1-2a) pyridinium, carried out with a special apparatus which both stimulates and records, specifies the characteristics of the neuro-muscular block induced by this new non-depolarizing type curarizing substance while taking into account the usual factors of the curarimimetic variability of action. After an initial dose of 1 mg per kg of bodyweight, we notice particularly: -the lapse of time required for a complete block (90 s), its intensity and duration (normally total during at least one hour) -the morphology of the electromyogram during the curarization and the decurarization either spontaneous or induced by Neostigmin with in particular -the muscular fatigability after repeated stimulation following curarization and chiefly during decurarization, chronological data und electro-myographic aspects which are found as well after a reinjection of AH-8165 equivalent to the half of the previous one. | [The second electromyographic study of surgical curarization with AH.8165, a new pachycurare derivative of azobis-arylimidazo(1-2a) pyridinium]. This second electromyographic study of AH-8165, a product derived from azobis-arymilidazo-(1-2a) pyridinium, carried out with a special apparatus which both stimulates and records, specifies the characteristics of the neuro-muscular block induced by this new non-depolarizing type curarizing substance while taking into account the usual factors of the curarimimetic variability of action. After an initial dose of 1 mg per kg of bodyweight, we notice particularly: -the lapse of time required for a complete block (90 s), its intensity and duration (normally total during at least one hour) -the morphology of the electromyogram during the curarization and the decurarization either spontaneous or induced by Neostigmin with in particular -the muscular fatigability after repeated stimulation following curarization and chiefly during decurarization, chronological data und electro-myographic aspects which are found as well after a reinjection of AH-8165 equivalent to the half of the previous one. | [
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PMID:5020 | [Contribution to the study of Trive 1000]. | A glucid-lipid and protein compound nutriment: Trive 1000 was administered to 53 patients during the first three postoperative days in varying doses: -1.000 ml per day to a first group -1.500 ml per day to a second group. The local tolerance was quite good. However, a few accidents of a general character were noted: they were due to a great extent to a non-observance of the rules of preservation. A study of the glucides, in Sorbitol form, showed a good assimilation of the substratum. Glycemia remaining within normal, no glycosuria or ketonuria could be observed. The assimilation of the proteins seemed on the whole satisfactory. No important rise in the blood urea was noted. Nitrogen balances showed that, thanks to this nutriment, almost half of them were positive during the post-aggressive period. The more important the dose of Trive 1000, the more positive the nitrogen balances were. The administration of lipids did not reveal any significant change in the total lipids, triglycerides or cholesterol. A study of the graphic record of lipid levels showed chylomicrons twice. On the opposite, lipoproteins were hardly modified apart from a significant in pre-beta lipoproteins. The quantitative analysis of amino-acids proved interesting. A comparative study of amino-acids both in blood and urine before and after the administration of Trive 1000 showed very little variations in connection with essential amino-acids. If the proportions in the blood of non-essential amino-acids were comparatively but little modified before and after the treatment, on the oppostie, the urinary clearance rate of the same amino-acids after treatment was far more variable and often quite important as far as certain amino-acids were concerned. | [Contribution to the study of Trive 1000]. A glucid-lipid and protein compound nutriment: Trive 1000 was administered to 53 patients during the first three postoperative days in varying doses: -1.000 ml per day to a first group -1.500 ml per day to a second group. The local tolerance was quite good. However, a few accidents of a general character were noted: they were due to a great extent to a non-observance of the rules of preservation. A study of the glucides, in Sorbitol form, showed a good assimilation of the substratum. Glycemia remaining within normal, no glycosuria or ketonuria could be observed. The assimilation of the proteins seemed on the whole satisfactory. No important rise in the blood urea was noted. Nitrogen balances showed that, thanks to this nutriment, almost half of them were positive during the post-aggressive period. The more important the dose of Trive 1000, the more positive the nitrogen balances were. The administration of lipids did not reveal any significant change in the total lipids, triglycerides or cholesterol. A study of the graphic record of lipid levels showed chylomicrons twice. On the opposite, lipoproteins were hardly modified apart from a significant in pre-beta lipoproteins. The quantitative analysis of amino-acids proved interesting. A comparative study of amino-acids both in blood and urine before and after the administration of Trive 1000 showed very little variations in connection with essential amino-acids. If the proportions in the blood of non-essential amino-acids were comparatively but little modified before and after the treatment, on the oppostie, the urinary clearance rate of the same amino-acids after treatment was far more variable and often quite important as far as certain amino-acids were concerned. | [
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PMID:5021 | [Comparative study of nitrogen savings during enteral and parenteral feeding (Trive 1000)]. | Through a study of Nitrogen balances, the authors compare the effectiveness of a proteinic intake carried out per os or by intravenous route. The study involved 22 different carcinoma carriers and lasted for 9 days during which the Nitrogen intake was effected either by the digestive tract or by intravenous route supplemented by a sufficient caloric ration. In the latter case, the aminoacid intake was supplied by Trive 1000 combined with glucides and lipids which were then quantitatively deducted from the enteral intake. A study of the results showed that the assimilation of the Nitrogen injected intravenously was very similar to the one obtained by enteral route. | [Comparative study of nitrogen savings during enteral and parenteral feeding (Trive 1000)]. Through a study of Nitrogen balances, the authors compare the effectiveness of a proteinic intake carried out per os or by intravenous route. The study involved 22 different carcinoma carriers and lasted for 9 days during which the Nitrogen intake was effected either by the digestive tract or by intravenous route supplemented by a sufficient caloric ration. In the latter case, the aminoacid intake was supplied by Trive 1000 combined with glucides and lipids which were then quantitatively deducted from the enteral intake. A study of the results showed that the assimilation of the Nitrogen injected intravenously was very similar to the one obtained by enteral route. | [
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PMID:5022 | [The utilization of EB 51 in parenteral feeding. Clinical, biological and anatomopathological control. Statistical study on 30 patients]. | Two groups of patients (comas of central origin and serious digestive undernourished) were submitted to an exclusive or a supplementary parenteral feeding for a short or a long period of time totaling over 500 days. The catheter was placed (in 80 p. cent of the cases) in a deep vein and was tunnellized. EB 51 (Trivemil) used in those 30 patients gives amino-acids, lipids and glucides. The caloric intake was completed by 30 p. cent glucose solutes. If the average caloric intake was 3.000 calories per day, it was often above that figure since the feeding was combined with a nutri-pump enteral feeding for 60 p. cent of the days. The clinical tolerance was quite good. On a biological level, in addition to classic investigations, 40 analytic graphic records of lipid levels were made, as well as a quantitative analysis of serous triglycerides and lipurias, a study of sorbitol and 500 nitrogen balances combined with 150 chromatographies on the acidaminuria column. An hepatic biological control was also made (amnoniemia, transaminases) as well as a quantitative analysis of lactates, pyruvates and minerals: iron-phosphorus-magnesium. Some of the results were checked by statistical studies. No serious anomaly was detected. Lung and hepatic biopsies carried out upon 9 patients did not apparently reveal any lipidic overloading. The clinical and the biological investigation show that this complete nutriment is perfectly tolerated and assimilated. | [The utilization of EB 51 in parenteral feeding. Clinical, biological and anatomopathological control. Statistical study on 30 patients]. Two groups of patients (comas of central origin and serious digestive undernourished) were submitted to an exclusive or a supplementary parenteral feeding for a short or a long period of time totaling over 500 days. The catheter was placed (in 80 p. cent of the cases) in a deep vein and was tunnellized. EB 51 (Trivemil) used in those 30 patients gives amino-acids, lipids and glucides. The caloric intake was completed by 30 p. cent glucose solutes. If the average caloric intake was 3.000 calories per day, it was often above that figure since the feeding was combined with a nutri-pump enteral feeding for 60 p. cent of the days. The clinical tolerance was quite good. On a biological level, in addition to classic investigations, 40 analytic graphic records of lipid levels were made, as well as a quantitative analysis of serous triglycerides and lipurias, a study of sorbitol and 500 nitrogen balances combined with 150 chromatographies on the acidaminuria column. An hepatic biological control was also made (amnoniemia, transaminases) as well as a quantitative analysis of lactates, pyruvates and minerals: iron-phosphorus-magnesium. Some of the results were checked by statistical studies. No serious anomaly was detected. Lung and hepatic biopsies carried out upon 9 patients did not apparently reveal any lipidic overloading. The clinical and the biological investigation show that this complete nutriment is perfectly tolerated and assimilated. | [
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PMID:5026 | [Effect of increasing doses of dopamine on the left ventricular function in the dog]. | A study on eleven dogs of the effects of increasing doses of dopamine on the left ventricular function. A description of the method which consists of a venous shunt connected to an extra-corporeal circuit and which allows modification simply and rapidly of the state of vascular refilling of the animal. The results differ according to the pressure-level of the refilling of the left ventricule. At low pressure, the dopamine increases the arterial pressure, the cardiac output and the systolic activity of the left ventricle for a reduced tachycardic effect. At higher pressure, the average aortic pressure is only slightly increased and the systolic activity is elevated without increase in cardiac output. These facts indicate dopamine in states of shock with a low pressure of refilling. | [Effect of increasing doses of dopamine on the left ventricular function in the dog]. A study on eleven dogs of the effects of increasing doses of dopamine on the left ventricular function. A description of the method which consists of a venous shunt connected to an extra-corporeal circuit and which allows modification simply and rapidly of the state of vascular refilling of the animal. The results differ according to the pressure-level of the refilling of the left ventricule. At low pressure, the dopamine increases the arterial pressure, the cardiac output and the systolic activity of the left ventricle for a reduced tachycardic effect. At higher pressure, the average aortic pressure is only slightly increased and the systolic activity is elevated without increase in cardiac output. These facts indicate dopamine in states of shock with a low pressure of refilling. | [
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PMID:5027 | [The effect of intravenous dopamine on the hemodynamics of the heart]. | The pharmacological study of dopamine was conducted on 14 patients: eleven normal patients and three with incipient myocardiopathies. The dosages used were 3, 6 and 12 mug/kg/min. The "pump" function, the peripheral resistances, the contractility and the ventricular compliance were studied. Dopamine is a positive inotropic agent without chronotropic action at doses of 6 and 12 mug/kg/min. It acts by increasing the contractility and the venous return and by decreasing the peripheral resistances; this effect disappears with strong dosages. | [The effect of intravenous dopamine on the hemodynamics of the heart]. The pharmacological study of dopamine was conducted on 14 patients: eleven normal patients and three with incipient myocardiopathies. The dosages used were 3, 6 and 12 mug/kg/min. The "pump" function, the peripheral resistances, the contractility and the ventricular compliance were studied. Dopamine is a positive inotropic agent without chronotropic action at doses of 6 and 12 mug/kg/min. It acts by increasing the contractility and the venous return and by decreasing the peripheral resistances; this effect disappears with strong dosages. | [
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PMID:5028 | [Hemodynamic study of dopamine used in chronic heart failures and in cardiogenic shock as a complication of acute myocardial infarct]. | The object of this study is to examine the properties of dopamine at the hemodynamic and renal level in 16 patients with decompensated chronic cardiopathies or very serious cardiogenic shock due to myocardial infarction. The results show an increase in the cardiac index in 75 p. 100 of the cases with a favourable diminution of the arterio-venous difference in O2 and of the pulmonary arterial resistances. The most noticeable and the most constant effect is the recovery and increase of the diuresis. Positive chronotropic and bathmotropic effects were observed which necessitated the limitation of prescription of dopamine in those subjects showing signs of disturbances in ventricular excitability. | [Hemodynamic study of dopamine used in chronic heart failures and in cardiogenic shock as a complication of acute myocardial infarct]. The object of this study is to examine the properties of dopamine at the hemodynamic and renal level in 16 patients with decompensated chronic cardiopathies or very serious cardiogenic shock due to myocardial infarction. The results show an increase in the cardiac index in 75 p. 100 of the cases with a favourable diminution of the arterio-venous difference in O2 and of the pulmonary arterial resistances. The most noticeable and the most constant effect is the recovery and increase of the diuresis. Positive chronotropic and bathmotropic effects were observed which necessitated the limitation of prescription of dopamine in those subjects showing signs of disturbances in ventricular excitability. | [
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