[The behavior of gamma-glutamyltranspeptidase and other liver enzymes in the plasma during alcohol withdrawal treatments]. 90 chronic alcoholics (55 men and 35 women, aged between 20 and 60 years) were investigated to determine how alcohol withdrawal effects the pattern of enzymes in plasma and if changes in this enzyme pattern could be used as criteria for evaluation of the recovery process. Among the different enzymes tested, gamma-glutamyl-transpeptidase (GGTP) and the transamines seemed the most suitable parameters. At the beginning of the alcohol withdrawal course, 79 out of 90 patients (80%) showed elevated values of one of these enzymes in plasma. GOT was elevated in 31 (34%), GPT in 24 (23%) and GGTP in 79 (88%) of the cases. In 49 patients (54%) GGTP was the only enzyme found to be elevated. The values of GGTP were on the average higher than those of GOT and GPT. GGTP has thereforeto be regarded as the most sensitive enzyme since it was elevated in most of the patients. GGTP reacted with 6.8 times more sensitivity than GOT and 6.3 times that of GPT. After withdrawal of alcohol the three enzymes showed a decline in all 79 patients. The transaminases normalized faster than GGTP. GTP fell into the upper normal limit after only 30 days. Among the 90 alcoholics examined, 14 relapsed during the alcohol withdrawal course. After the new excess of alcohol intake, the GGTP in plasma rose immediately. Alcohol abuse was suspected in 50% of the patients due to the increase in this enzyme and was subsequently confirmed by the patients. Acute alcohol loading in normal volunteers did not lead to an increase in GGTP activity. A comparison of the histology of liver biopsy material showed that neither the transaminases nor the alkaline phosphatase and GGTP served to differentiate the various forms of alcoholic liver damage. However, GGTP represents the most sensitive enzymatic parameter for the detection of alcoholic liver disease. This enzyme is useful in evaluating the success of a course of alcohol deprivation. The decreasing values during such treatment, as well as the prompt increase after a relapse, points to the high sensitivity of this enzyme. A further argument is that in 54% of the patients elevation of GGTP only was present. Since no liver damage could be demonstrated in these patients with the aid of the other liver enzymes, the elevation of GGTP may be related to the alcohol intake through an enzyme induction mechanism such as has been demonstrated for this enzyme with certain drugs.


[Impotence and male sterility].

[Impotence and male sterility]. The causes of sexual impotence, including disturbances of ejaculation, and the methods of treatment are described. In the vast majority of cases male sterility results from a disorder of spermatogenesis. The main factors responsible for infertile semen are discussed: in most cases the causes are unknown. It is to be hoped that progress in research into human reproduction and recent diagnostic advances will provide the groundwork for more successful therapy of male sterility.


Presynaptic facilitation as a mechanism for behavioral sensitization in Aplysia. Sensitization is an elementary form of nonassociative learning, related to behavioral arousal, in which a strong stimulus facilitates a reflex response. Studies of the neural circuit of the gill-withdrawal reflex in the isolated abdominal ganglion on Aplysia indicate that short-term sensitization is due to presynaptic facilitation. The facilitation results in a sudden increase in the amount of neurotransmitter released by the sensory neurons at their synapses with motor neurons.


Recent studies on the identification of proliferative abnormalities and of oncogenic potential of cutaneous cells in individuals at increased risk of colon cancer. This recent study describes the growth characteristics of ACR skin fibroblasts in culture and their differential susceptibility to transformation by Kirsten murine sarcoma virus (Ki-MSV). The SF were derived from normal appearing subepidermoid biopsies of ACR individuals, their progeny and ocntrols. Normal SF were contact-inhibited and grew only in 15% FCS. SF of ACR subjects, and some asymptomatic ACR progeny were not contact inhibited, grew in both 1% and 15% FCS and were considerably more susceptible to transformation by Ki-MSV than were control SF. The virally transformed SF showed a loss of anchorage dependency in methylcellulose and formed tumors in athymic mice. The results suggest the presence of early and previously undetected metabolic lesions in SF from clinically asymptomatic subjects. These phenotype markers are currently evaluated for their utility in the clinical diagnosis of individuals with latent ACR and those at increased risk for colon cancer. SF from ACR individuals have been recently shown to contain significant alterations in the intracellular distribution of actin (R. Pollack and L. Kopelovich, in preparation), and elevated levels of plasminogen activator (L. Kopelovich).


Histamine H2-receptor antagonists in the treatment of duodenal ulcers. A double-blind trial of histamine H2-receptor antagonists and placebo was carried out in 46 patients with endoscopically proven duodenal ulceration. H2-receptor antagonists (metiamide and cimetidine) produced a significantly greater degree of completely healed ulcers and fewer complete failures than placebo. The results of the trial indicate that H2-receptor antagonists promote the healing of ulcers. The action of these compounds would appear to be related to the inhibition of acid secretion. Neither the duration of the illness, rate of recurrence of the ulcers of level of gastric acid secretion materially affected the healing rate in indvidual patients. There were no serious side-effects over the 6-week period of drug administration, but the metiamide was replaced by cimetidine because reports from other centrea indicated that agranulocytosis was associtated with metiamide therapy.


Facts, anecdotes, and new horizons in the medical treatment of duodenal ulcers. There continue to be marked differences of opinion regarding how to manage duodenal ulcer disease. Recent developments in medical management which appear of major importance include the development of antagonists of H2-receptors of histamine, the prostaglandins, and transendoscopic instrumentation. Intractability of duodenal ulcer continues to be an over-used category which disguises situations that are easily remedied. Until we have more long-term and complete evaluations of ulcer treatment, we will continue to base therapy on anecdotes and incomplete data.


Factors influencing the ionization of calcium during major surgical procedures. The existence of a clinically feasible calcium electrode makes it possible to obtain rapid, accurate levels of ionized calcium. It is now possible to study the actual ionization of calcium under normal and abnormal physiologic conditions. The present investigation was directed at changes in ionized calcium during major surgical procedures. The total series of 125 patients was divided into three groups according to the type of plasma volume expander: group 1, whole blood alone; group 2, whole blood plus exogenous albumin, and group 3, albumin alone. Ionized calcium levels dropped significantly, p less than 0.001, in all three groups. Although albumin alone produced a decrease in ionized calcium, the addition of albumin to whole blood did not result in a greater decline than that experienced with whole blood alone. Chelation with the citrate ion of bank blood preservative was the major factor responsible for the decrease in ionized calcium. There was no statistically significant relationship between the extent of the decrease, the total volume of blood, the volume of blood per kilogram of the rate of transfusion in milliliters per kilogram per minute. Although the ionized calcium level fell initially, it increased while blood administration continued. In view of these facts, it is difficult to estimate the acutal level of ionized calcium at any point during the operation. Twenty patients in the series had ionized calcium levels below 1.25 milliequivalents per liter, range of 0.51 to 1.24 milliequivalents per liter. With the possible exception of one patient, no adverse cardiovascular effects could be attributed to the low levels of ionized calcium. The results in this series confirm our previous conclusion that the administration of exogenous calcium is not necessary during massive transfusion, with the possible exception of bypass open heart procedures and exchange transfusions in children.


Effect of nitrazepam and flurazepam on the ventilatory response to carbon dioxide. Ventilatory response to CO2 was measured before and after two different benzodiazepine hypnotics in both chronic bronchitics and patients without chest disease. Flurazepam, but not nitrazepam, produced a significant decrease in CO2 sensitivity, although there was no significant change in FEV1 or mixed venous PCO2. This is the first unequivocal evidence of central depression of respiration by a benzodiazepine and may be the mechanism by which benzodiazepines cause deterioration in patients with respiratory failure.


Comparative studies of the effects of cyclic AMP, various hormones and chloramphenicol on the induction of delta-aminolevulinic acid synthetase and tyrosine aminotransferase in the organ-cultured chick embryo liver. Induction of delta-aminolevulinic acid synthetase by allylisopropylacetamide in organ-cultured chick embryo liver was not appreciably influenced by any of cycli AMP, dibutyryl cyclic AMP, theophylline, glucose, insulin, glucagon, epinephrine, isoproterenol, and hydrocortisone, whereas the activity of tyrosine aminotransferase significantly increased in response to cyclic AMP and some of those hormones. Accumulation of delta-aminolevulinic acid synthetase in the cultured liver cytosol fraction was not appreciably increased by the addition of dibutyryl cyclic AMP or insulin to the incubation medium. Apparently the behaviors of the induction of delta-aminolevulinic acid synthetase in chick embryo liver in ovo and in vitro differ from those in the livers of adult chicken and rat. High concentrations of chloramphenicol suppressed significantly the allylisopropylacetamide-induced increase of delta-aminolevulinic acid synthetase as well as incorporation of 14C-leucine into proteins. The activity of tyrosine aminotransferase, however, was rather increased when relatively low concentrations of chloramphenicol were added to the medium.


Cytotoxicity in graft-versus-host reaction. II. Lysis of target cells of parental genotyppe by F1 hybrid macrophages. Graft-versus-host (GVH) reactions were induced in adult F1 hybrid mice with the i.p. injection of parental strain spleen cells. Peritoneal exudate and spleen cells of the F1 hybrids taken 8 days after the induction of GVH reaction had a nonspecific in vitro cytotoxic effect which was measured by using 51Cr-labeled target cells of parental genotype. The cytotoxic cells in the peritoneal exudates were shown to be macrophages which adhered to plastic surfaces and were sensitive to the toxic action of crystalline silica particles. Moreover, the injection of partially purified syngeneic macrophages into the F1 hybrids undergoing GVH reactions increased the cytotoxic activity of the peritoneal exudate cells obtained from these animals. These results suggest that during GVH reaction host macrophages are activated into a state of nonspecific cytotoxicity.


Cellular and humoral immunity after allogeneic renal transplantation in the rat. V. Appearance of anti-idiotypic antibody and its relationship to cellular immunity after treatment with donor spleen cells and alloantibody. Enhancement of LBN F1 renal allograft survival in Lewis (L) rats is achieved by injecting the recipient i.v. with donor antigen (LBN F1 spleen cells) 1 day before transplantation and antidonor antibody (L anti-BN alloantiserum) at the time of transplantation. Treatment with this combination of antigen and antibody also induces the recipient to make L anti-(L anti-BN) anti-idiotypic antibody that reaches peak titers within 10 days. The degree of graft enhancement achieved was increased greatly by delaying transplantation until the peak of the anti-idiotypic antibody response 10 days after treatment with antigen and antibody. Two in vitro assays for cellular immunity (51Cr release and microcytotoxicity) failed to demonstrate antidonor activity in spleen cells from recipients for which transplantation had been delayed 10 days. The close correlation of enhancement, absence of cellular immunity in vitro, and the kinetics of the anti-idiotypic antibody response suggest that anti-idiotypic antibody may prevent either sensitization and generation of effector T lymphocytes or the destructive potential of sensitized cells.


Comparison of methods to wash liquid-stored red blood cells and red blood cells frozen with high or low concentrations of glycerol. The efficiency of washing liquid-stored red blood cells and red blood cells frozen with high or low glycerol concentrations was evaluated by measuring the recovery of red blood cells in vitro, supernatant hemoglobin, extracellular potassium and red blood cell potassium levels, supernatant osmolality, residual 125I albumin, glycerol, hypoxanthine, and di-2-ethylhexyl phthalate (DEHP) levels. Four commercial washing systems were studied, three which used sodium chloride solutions with serial or continuous-flow centrifugation and one which used sugar solutions and dilution/agglomeration. Washing was most efficient using sodium chloride solutions in the IBM Blood Processor, an automated serial centrifugation procedure and in the Fenwal Elutramatic, a continuous-flow centrifugation procedure. Less efficient washing was achieved in the Haemonetics Processor 15, a continuous-flow centrifugation procedure and the least efficient washing occurred using the original and modified dilution/agglomeration procedures. To achieve the most efficient washing, three principles must be utilized: concentration of the red blood cells to hematocrit values of 90 per cent, prior to washing or freezing. Liquid-stored red blood cells concentrated to hematocrit values of 90V per cent should be diluted with hypertonic sodium chloride solutions prior to recovery and washing. Red blood cells containing 20 per cent or 40 per cent W/V glycerol should be diluted with hypertonic sodium chloride solutions before recovery and washing. Finally, on-line dilution should be achieved in the washing systems that use continuous-flow centrifugation.


Absence of specific mixed leukocyte culture reactivity during graft-versus-host disease and following bone marrow transplant rejection. Retrospective mixed leukocyte culture studies were performed in eight patients who had either rejected their marrow grafts or experienced graft-versus-host disease and in seven patients with successful marrow engraftment. In tests of pre-and post-transplant lymphocytes we found no evidence that rejection or graft-versus-host disease was caused by antigens that stimulate in the mixed lymphocyte culture assay.


Metabolic changes during platelet storage. Platelet concentrates (PC) were stored in plastic bags with continuous shaking at 4, 22, and 37 C. Various metabolic parameters were examined over a 72-hour period. At 22 C, the pH and PO2 declined over 72 hours while the PCO2 and lactate increased. Hypotonic shock declined to 70 per cent. This differed from the small amounts of CO2 and lactate found at 4 C and the marked accumulation of metabolites and almost complete loss of shock response at 37 C. Aggregation was always better maintained with 4 C storage. The toxic effect of the accumulation of metabolites on the platelets was tested by adding lactate to fresh PC at zero time. This was effective in lowering the initial pH, markedly inhibiting the response to aggregation and decreasing the total accumulation of lactate during storage, but did not produce an inhibition of hypotonic shock response. The effect of accumulation of toxic metabolites was further investigated by using 72-hour plasma and platelets and recombining each of them with fresh preparations. Platelets were tested under degassed conditions to outline the requirements for oxygen and gasious exchange. Surprisingly, there was less accumulation of lactate and CO2 and better hypotonic shock response. These experiments have detected various changes in viability markers in platelets that are stored under actual blood bank conditions and indicate that the accumulation of lactate is not totally responsible for the toxic inhibition of platelet performance that is found upon storage at 22 C.


Freezing and deglycerolizing sickle-trait red blood cells. Sickle-trait red blood cells respond to freezing and thawing like normal cells, but during deglycerolization by centrifugal methods, they pack and hemolyze. This appears to be the result of changes in surface characteristics with suspension in hyperosmotic saline and even modest increases in osmolality result in packing with centrifugation. Modifications to permit deglycerolization of sickle-trait cells have been designed for use with both the Haemonetics and the IBM cell washing systems. Sickle-trait cells do not agglomerate satisfactorily but we were unable to devise a modification of this deglycerolizing system that would accommodate sickle-trait cells.


Long survival and immunologic reconstitution following transplantation with syngeneic or allogeneic fetal liver and neonatal spleen cells. (1)Spleen cells from newborn syngeneic and allogeneic mice that lack fully differentiated T lymphocytes can be used as a hematopoietic source to reconstitute both hematopoietic and lymphoid systems of lethally irradiated mice without producing a GVHR. (2) Fetal liver cells from syngeneic and allogeneic mice that lack postthymic T lymphocytes can also be used for hematopoietic and immunologic reconstitution of lethally irradiated mice without producing GVHR. (3) Immunologic deficiency is observed in some experiments in mice given supralethal irradiation (1000 R) and fetal liver as reconstituting hematopoietic tissue. (4) The findings suggest that Tcells, at an early stage of differentiation, are more susceptible to tolerance induction than are T lymphocytes at later stages of differentiation and do not, in general, produce GVHR. (5) It is postulated that hematopoietic cells, free of postthymic lymphoid cells, can be used for hematopoietic or immunologic reconstituting and cellular engineering without producing GVHD.


Graft-versus-leukemia for AKR spontaneous leukemia-lymphoma. Adoptive immunotherapy in the form of a transient graft of mismatched DBA/2 BM + LN cells was used in combination with several chemoradiotherapy regimens to treat AKR mice bearing advanced SLL. Leukemic mice treated in this manner had a significant prolongation of their MST and significantly higher survival rates 60 and 90 days posttreatment than corresponding control groups. Syngeneic- or allogeneic-matched cells did not provide substantial GVL effect. An inverse relationship that influenced survival was observed between the radiation dose and the dose of GVL effector cells used to treat leukemic AKR mice in the treatment model. Recurrence leukemia remains a major problem.


Renal complications of drug addiction.

Renal complications of drug addiction. The kidney is one of the target organs involved as a consequence of the systemic complications seen in drug abusers. This may manifest itself in one of the following forms: acute hepatitis with modest proteinuria (less than 2 Gm. per day); bacterial endocarditis with hematuria, azotemia, and a focal or diffuse glomerulonephritis; the nephrotic syndrome with focal mesangial sclerosis and diffuse interstitial nephritis often pursuing a fulminant course terminating in uremia; acute renal failure secondary to rhabdomyolysis and myoglobinuria; polyarteritis nodosa with renal involvement; and obstructive uropathy secondary to fungus ball in the urinary tract.


Spontaneous renal hemorrhage.

Spontaneous renal hemorrhage. This report of 9 cases of spontaneous renal hemorrhage illustrates the wide variety of responsible conditions that may be found in a small series and the tendency for some of these conditions to coexist. In particular, all 3 patients with a bleeding diathesis had an associated anatomic lesion, and it was concluded that this group of patients required aggressive radiologic investigation. Three main clinical presentations were identified: sudden severe flank pain, symptomless hypertension, and a palpable mass with few or no symptoms. The radiologic signs are reviewed with emphasis on a recently described sign of streaky retroperitoneal fat. Treatment is discussed briefly.


[Effect of glutamic acid on the interrelationship of the effects of different activators of cerebral glutaminase]. When phosphate and tyroxine (activators of brain glutaminase) are used in small amounts, a potentiation of their stimulatory effect is observed. Higher concentrations exhibit an opposite effect. Glutamic acid has a strong inhibitory effect on all the activators of glutaminase given separately. The inhibitory effect of glutamate increases on lowering the pH. On the other hand the potentiation observed on adding two stimulators is increased greatly in the presence of glutamate. On the addition of tyroxine to other stimulators a greater potentiation and rise of glutaminase activity are observed. The potentiation, which occurs on the joint addition of phosphate and tyroxine, is raised with the increase of the amount of glutamic acid, while on the contrary on joining phosphate with other stimulators potentiation is reduced. Potentiation is variable and depends on the pH. Preincubation of brain mitochondrial fraction with guanidine chloride inhibits markedly the stimulatory effect of all the stimulators used, but their joint addition almost abolishes the potentiating effect. In the presence of glutamic acid, due to the increase of the cooperative effect between the two stimulators, glutaminase activity is greatly increased and sometimes its inhibitory effect is not even observed. The data obtained indicate that in brain glutamic acid in the presence of phosphate+thyroxine cannot be considered as an inhibitor of glutaminase and that the important factor here is not so much the absolute levels of the activators as their favorable combinations.


Comparative studies on the N-oxidation of aniline and N,N-dimethylaniline by rabbit liver microsomes. 1. Rate studies of N-oxidation of aniline and N,N-dimethylaniline by rabbit liver microsomal preparations were performed at different pH values. The apparent pKs of the free functional groups were 7-2 and 6-9, respectively, at 26 degrees. The apparent heats of ionization of these groups varied from 26-8 to 31-8 kJ mol-1. 2. Photo-oxidation of the microsomal mixed function oxidase resulted in rapid loss of N-oxygenating activity. The enzyme was markedly protected from inactivation by the presence of aniline or N,N-dimethylaniline. The apparent KD values for protection were close to the Km and KS values for the individual arylamines. The pH profiles of the initial rates of photo-inactivation resembled the titration curves of groups with an apparent pKa between 6-0 and 6-2. 3. The N-oxidase was strongly inhibited by diethyl pyrocarbonate at pH 6-2. 3. The N-oxidase was strongly inhibited by diethyl pyrocarbonate at pH 6-0. Catalytic capacity was partially restored by treatment with neutral hydroxylamine. Pyridine protected the enzyme from acylation. 4. A close relationship exists between the N-hydroxylation of aniline and the N-oxide formation from N,N-dimethylaniline with respect to sensitivity to photo-oxidation, reactivity to protective substrates and susceptibility to carbethoxylation.


Azo- and nitro-reductases of the cestode Moniezia expansa. Substrate specificity, reaction products and the effects of flavins and other compounds. 1. The effects of various inhibitors and activators on the azo- and nitro-reductases of Moniezia expansa have been studied. Both reductions were partially inhibited by FAD, FMN, riboflavin, allopurinol, dicoumarol, 5-nitro-2-furaldehyde, azide and cyanide at 1 mM. Both reactions were stimulated by hypoxanthine. Menadione, nitrofurantoin, SKF 525-A (2-diethylaminoethyl 2,2-diphenylvalerate) and fluoride were without effect. 2. Xanthine- and aldehyde-oxidase activities were not detected in the enzyme preparation. 3. The substrate specificity of the azo- and nitro-reductases were determined. Azobenzene, 4-dimethylamino-azobenzene and 1,2-dimethyl-4-(4-carboxyphenylazo)-5-hydroxybenzene, nitrobenzene, 4-nitrohippuric acid and the isomers of nitrophenol, nitroanisole, nitrobenzoic acid, nitrobenzaldehyde and nitrobenzyl alcohol were reduced. Nitrobenzaldehyde isomers were not reduced to the alcohols and the coumaric acids were not reduced to the phenylpropionic acids. 4. The products of azo- and nitro-reduction were the corresponding amines; hydroxylamino- and hydrazo-compounds were not detected. 5. The pH optima and cofactor requirements were the same for both azo- and nitro-reduction. Neither reaction was inhibited by oxygen.


A new metabolic pathway of bromazepam involving attachment of a methylthio group. 1. The structures of three hitherto unidentified metabolites of bromazepam in the rat were elucidated using u.v., mass, n.m.r. and i.r. spectrometry. 2. All three metabolites contained a methylthio or corresponding oxidized group at the C-6' position of the pyridyl moiety. 3. Quantitative analysis of the metabolites determined after administration of [14C]bromazepam to rat revealed that the three metabolites together comprised about 6% of the total radioactivity excreted in the 24-h urine, or about 1% of the dose.


[Incidence of stress ulcer and secretion of gastric juice following truncal and selective vagotomy]. In rats development of stress ulcers by immobilization is accompanied by elevated pH, reduced amount of gastric juice, and by this with decreased amount of acid. Consequently, the acid factor has no primary importance for the development of stress ulcer. Truncal vagotomy, selective proximal vagotomy, and selective antral vagotomy result in reducing the acid secretion at elevated pH value and increased juice amount, and in a decreased ulcer rate. Greatest certainty to prevent stress ulcer gives the truncal vagotomy, whereas there is a poor effect after antral vagotomy.


Influence of alpha-adrenergic block and beta-adrenergic stimulation on distribution of cardiac output after cardiopulmonary bypass. Organ and tissue damage restricts total cardiopulmonary bypass to a few hours in patients. The cause might be the disturbance of tissue flow in which the sympatho-adrenal hyper-activity plays a decisive role. In dogs, killed 30 min after cardiopulmonary bypass was stopped, we studied the tissue distribution of cardiac output with the method of Sapirstein. In one group the alpha-adrenergic blocker, in the other one the beta-adrenergic stimulator was continuously applied during the whole operation-period. Compared to a control group the per cent of cardiac output as well as the regional tissue flow after alpha-adrenergic block increased in the liver, ileum, adrenals, testes, kidney and in the skin and decreased in the spleen and thyroid gland. After beta-adrenergic stimulation the per cent of cardiac output increased in the heart muscle, lungs, liver, ileum, adrenals and m. soleus and decreased in the spleen and thyroid gland. The absolute values of organ tissue flow increased in ileum and decreased in the spleen, thyroid gland and in the kidney.


[On the effect of particulate airborne substances on various micro-organisms (author's transl)]. Experimental studies on the reaction of micro-organisms on fine-dust filters (type C) and high-efficiency particulate air filters (type R and S) have shown no evidence of a growth of microorganisms. Therefore efforts were aimed at detecting antimicrobial factors which were supposed to exist in the precipitated acidic continental aerosol. With this in mind, air filters from different locations and with service times were extracted in water and the extract was tested for its antimicrobial effects. Die-off rates are used to demonstrate the influence of such extracts with varying concentrations of substances and pH values on bacteria.


[On the enzymatics of the microbial breakdown of pyrazone (author's transl)]. From samples of earth taken in different parts of the world bacteria were isolated which grow on pyrazone as the only source of carbon. When these bacteria are grown in a pyrazone mineral salt medium, four compounds are excreted into the medium. The structures of these compounds furnish information on the catabolic route of pyrazone. Since the suggested scheme of breakdown was incomplete, enzymatic tests were carried out to clarify the matter. It was possible to carry out the first steps of breakdown also in the cell-free extract of the pyrazone-degrading bacteria. For the second step of pyrazone breakdown, 2 different enzymes of the same catalytic activity were identified. For the oxidative cleavage of the pyrocatechole derivative 2 different enzymes were found: an ortho- and a meta-clearing enzyme. The 2-hydroxy muconic acid decarboxylase was identified as a further enzyme. The importance of this enzyme is discussed in connection with the further breakdown.


[Determination of the toxicity of industrial waste by means of a bacterial test (author's transl)]. The decision on whether industrial waste should be deposited on general or special dumps depends upon the toxicity of the waste and thus upon the risk of ground-water pollution and the killing off of micro-organisms responsible for breaking down waste products. Since chemical analyses that are to provide information on toxicity are frequently very costly, an attempt was made to determine the toxicity of solid or semi-solid waste with the aid of a bacterial test. As in the perforated-plate test, here, too, the formation and size of inhibition zones were used to determine the toxicity after diffusion of substances contained in industrial waste. About 30 different types of industrial waste were examined with this method. For almost all substances a positive correlation of the (known) constituents of waste to the formation of inhibition zones was found to exist. The influence exercised by solubility and diffusibility and other problems are dealt with.


[The effect of pH value and temperature on the stability of L-aminoacidoxidase from the venom of the sand viper]. The stability of highly purified L-amino acid oxidase from the sand viper venom remains practically unaffected by the pH-value at 4degreesC between pH 5 and 8, whereas a sharp activity fall was observed on both sides of this range. At temperatures above 30 degreesC the enzyme is stable only at pH 5.0--5.5. The inactivation pH values above 5.5 follows a first-order rate equation with characteristic changes in the absorption and emission spectra of the enzyme. The stability of the enzyme is dependent on the temperature of storage. At pH 7.5 there is a stability minimum at --10 degrees and -- 30 degreesC. At -- 72 degreesC the enzyme is stable practically for an unlimited period of time; temperatures exceeding 50 degrees C rapidly lead to complete inactivation. Also in the cold, the L-amino acid oxidase is most stable at pH 5.5. There are characteristic changes in absorption and emission spectra in the temperature-stability minimum (--15 degreesC) and at temperatures above 30degreesC. The inactivations follow a first-order rate equation. The cold inactivation is reversible. The stability of the enzyme is diminished by some anions and cations at 37 degreesC. The cold inactivation is promoted by several inorganic anions; organic anions and ammonium sulfate prevent cold inactivation.


Retransfusion acidosis after brief haemorrhagic hypotension in the dog. Dogs under chloralose anasthesia were bled at a rate of 50 ml/min to a total of 25 ml/kg body weight and 2 minutes later a quick reinfusion of adequate volumes of blood, dextran, or Locke's solution was done. Within 2 minutes after reinfusion, the pH of arterial blood fell by 0.074--0.127; concurrently, PaCO2 rose by 9.2-12.9 mm Hg. A close correlation was demonstrated between these changes. After retransfusion, PaO2 and the arterial lactic acid level did not change significantly. Thus retransfusion acidosis in the dog appears after a brief hypotensive period, too, but cannot be attributed to a "washout" of lactate from the tissues.


[Gamma-glutamyl-transpeptidase in alcoholic liver diseases]. In well defined liver diseases in 69 alcoholics and in 71 patients without history of alcoholism the enzymatic findings were compared. Also a group of 43 alcoholics with praedelirium or delirium tremens were examined. In steatosis due to alcohol, the average of GGTP (145 U/l) attains values two times higher than in comparable cases of non-alcoholic origin (73 U/l). In cirrhotics with alcoholism, the average GGTP levels (477 U/l) exceed those obtained in patients with cirrhosis of other origin (110 U/l), four times more. Similar or higher GGTP values were found only in primary biliary cirrhosis. After a period of at least 3 months of abstinence, GGTP values had decreased (to 68 U/l) in the average). The highest values of GGTP were found in acute alcoholic hepatitis and in chronic alcoholics with praedelirium or delirium tremens. GGTP accords diagnostic hints in comparison with other enzymes, as shown by a quotient of GGTP-GPT. GGTP is very helpful for differentiation and long time observation of alcoholic liver disease, especially with regards controlling abstinence of alcohol.


Hepatic blood flow and cardiac output during Fluoromar anaesthesia. An animal study. Related values of cardiac output and hepatic blood flow were measured in eight premedicated (pethidine 10 mg/kg b.w.) dogs under varying depths of fluoromar anaesthesia. The measurements were first taken under basis anaesthesia with barbiturate (mebumal natrium 25 mg/kg b.w.) gallamine (80 mg)-N2O-O-O2 (ratio 2 to 1) with controlled normoventilation, and then under increasing depths of fluoromar anaesthesia: increasing stepwise to 1 1/2-3 and 6% inspiratory concentrations. Finally the measurements were repeated after the fluoromar had been discontinued. Using the basis anaesthesia as a reference, it was found that 6% fluoromar gave a reduction in cardiac output (34%), heart rate (11%) and mean pressure in the aorta (18%). The peripheral resistance was simultaneously increased by 22%. The effect on the splanchnic blood flow was far less and without significant changes from one step in the anaesthesia to the next. Using 6% fluoromar it was found that there was a maximum reduction in blood flow of 20% of the initial value. There was unchanged splanchnic resistance during the whole of the investigation. After discontinuation of the fluoromar for 15 min and continued controlled ventilation (O2-N2O), rising heart rate and blood pressure were observed; however, cardiac output and splanchnic blood flow were unchanged. Corresponding to this, an additional increase in peripheral resistance of 10% and an insignificant increase of 5% in the splanchnic resistance were observed.


Regulation of the cyclic guanosine 3'-5' monophosphate system in human brain tumors. Several reports have suggested that cylcic guanosine 3'-5' monophosphate (cGMP) and cyclic 3'-5' adenosine monophosphate (cAMP) are involved in the regulation of cellular proliferation. Following our previous reports on the cAMP system in human brain tumors, we decided to investigate the cGMP system in the same pathological tissues by studying the activity of guanylate cyclase and cGMP-phosphodiesterase (cGMP-PDE). We found that the activity of both enzymes is lower in neurinomas and glioblastomas than in meningiomas or in normal cerebral cortex. Furthermore, the subcellular distribution of guanylate cyclase in human cerebral cortex differs from that of neurinomas and glioblastomas. On the basis of such observations we have discussed the possibility that the regulatory mechanism of the enzymes related to the cyclic nucleotide metabolism is altered in brain tumors.


Exposure to drugs and other possibly harmful factors during the first trimester of pregnancy. Comparison of two prospective studies performed in Sweden 10 years apart. 474 women in mid-pregnancy, interviewed at ten different hospitals in Sweden, were questioned on a number of social and medical items: e.g., drug use, contraceptive technique used before pregnancy, exposure to possibly deleterious factors in the environment. The study, compared with a similar study made ten years earlier in Sweden, showed little or no difference in the use of iron and/or vitamin preparations, analgesic drugs, antibiotics, or endocrine drugs; but a drastic reduction is noted in the use of psychotropic drugs and of antihistaminic drugs. A marked decrease in frequency of first trimester X-ray exposures can be found, but no marked changes in smoking habits. Appr. 18% of the women used contraceptive pills within 6 months of becoming pregnant---3 had used them during early pregnancy. About 4% (18 women) had used IUD---one became pregnant with a Cu-UID (intra-uterine device inpregnated with copper).This type of study can provide some information on the prevalence of relatively common factors, but it must be considerably extended in order to permit an analysis of rare events, e.g., use of most drugs.


Correlation of maternal physical fitness during pregnancy with maternal and fetal pH and lactic acid at delivery. The physical fitness of 120 healthy primigravidae was determined two weeks before term using first the standardized three-stage submaximal work test on the following day the voluntarily maximal pulse-conducted work test on a bicycle ergometer. After the first test the level of lactic acid in the capillary circulation of 115 mothers was examined. Immediately after delivery the pH and the level of lactic acid in the maternal artery, umbilical vein and umbilical artery were determined. The level of lactic acid after the work test was negatively correlated with the physical performance of the mother. The level of lactic acid in the mother after the work test and the levels of lactic acid in the umbilical vessels were positively correlated. The mean pH value in physically fit women after delivery was almost significantly higher than in the women of below average performance. The pH level in the umbilical artery was also almost significantly higher in the mothers with above average performance. The physically fit women appear to work more during delivery than the less fit mothers, as the level of lactic acid after the delivery was as high as or higher than in mothers with a physical performance below average. The physical fitness of six mothers, who delivered an asphyxiated baby, was almost significantly lower than the performance of the mothers. Five mothers with an exceptionally high pH after delivery had a significantly higher performance than the other mothers.


Serum gamma-glutamyl transpeptidase activity and urinary D-glucaric acid excretion in newborns in the first week of life. Effects of phenobarbital and nicethamide combination. High serum gamma-glutamyl transpeptidase activity was found in cord blood of newborn boys. This activity decreased to lower values on the 4th and 7th days. In newborns treated for 3 days following the birth with a combination of phenobarbital and nicethamide an increase of gamma-glutamyl transpeptidase activity occurred from the 4th to the 7th days. The 7th day levels were significantly higher when compared with the controls. Simultaneous determination of urinary glucaric acid excretion confirmed the induction of hepatic microsomal enzymes in glucuronic acid pathway. This could also be demonstrated by a pronounced decrease of serum bilirubin levels in groups receiving the enzyme inducers whether phenobarbital was administered intramuscularly or orally as sodium salt solution.


Enzyme histochemical study on fat-storing cells (so-called Ito's cell) of liver. Inorder to gain a foothold in clarifying the functional significance of fatstoring cells, an enzyme histochemical study on these cells was carried out. Fat-storing cells showed no alkaline phosphatase, acid phosphatase or esterase activity but demonstrated a marked gamma-glutamyl transpeptidase activity suggesting the possibility of its participation in the synthesis of fiber protein. This possibility was further heightened by its remarkable activity noted at the site of progressive fibrosis. Fat-storing cells under a normal condition partake in the formation of fibers supporting the sinusoidal wall, and under an abnormal condition gradually change their shape with loss of fat droplets and then transform into fibroblast-like cells closely related to the progress of fibrosis.


A simple procedure for the purification of staphylococcal alpha-toxin. Staphylococcal alpha-toxin was produced in a fluid medium based on acid hydrolysed casein using strain Wood 46. alpha-Toxin and several other proteins were precipitated from bacteria-free culture supernatants by heating at 60 degrees C for 20 min. The process was influenced by the pH of the solution. The toxin was completely inactivated and the precipitate contained a number of proteins if the pH of the solution was adjusted to 4.0-5.0. Heat precipitation of solutions having a pH of 6.0-7.0 resulted in a partial inactivation of alpha-toxin. The precipitates at this pH contained less of the additional proteins and had higher relative amounts of alpha-toxin than precipitates formed at a lower pH. The precipitate was dissolved in 8 M urea with the resultant activation of the haemolysin. Pure alpha-toxin with a molecular weight of 39,000 was obtained by electrophoresis in 8 M urea at pH 8.6 in ordinary tubes for polyacrylamide electrophoresis. The separation time was 45 min. The minor component of alpha-toxin with a pI of 7.4 could be demonstrated by the same method. A non-haemolytic protein with a molecular weight of 27,500 which existed in at least two charged forms, was shown to have an antigenic relationship to the toxin with a molecular weight of 39,000.


Some physicochemical properties of human leucocyte migration inhibitory factor (LIF). Leucocyte migration inhibitory factor (LIF) obtained from human lymphocytes stimulated with concanavalin A was consistently and irreversibly blocked by the serine-esterase inhibitor phenyl-methyl sulphonylfuoride (PMSF). This effect was not due to fluoride ions, hydrolysis products of PMSF or to impurities. PMSF pulse treatment of human buffy coat cells did not affect cell migration under agarose. LIF was also irreversibly destroyed by treatment with L-cysteine and 2-mercapto-ethanol, suggesting that the molecule contains disulphide linkage groups decisive for its configuration and biological activity. Di-sodium EDTA completely inhibited LIF activity but only if present during the entire migration period. Removal of EDTA before LIF assay restored LIF activity. Leucotye migration was neighter influenced by L-cysteine nor by EDTA. LIF activity was slightly diminished after treatment at 56 degrees C for 1 h and completely lost at 80 degrees C for 1/2 h. Furthermore, LIF appeared rather stable when treated at pH values between 4 and 11. These findings suggest, but do not prove, an esterase or a protease nature of human LIF.


A study of the relationship between the electrocardiogram and hemodynamics in the fetal lamb during asphyxia. Progressive changes in the S-T interval of the fetal ECG were studied in 22 lamb fetuses, acutely exteriorized and submitted to graded hypoxia. The ECG changes were studied in order to correlate them with cardiovascular function, as measured by heart rate, mean arterial pressure, end diastolic pressure and combined cardiac output, estimated by the thermodilution method, as well as with blood gases and acid-base status. Close correlations were obtained between PaO2, pH and base deficit and the severity of ECG changes, graded according to a scoring system. Alterations in the ECG pattern consistently preceeded signs of failing cardiovascular function. Our previous findings indicated that the hypoxic ECG changes could be regarded as a sign of myocardial glycolysis. Accordingly, similar progressive ECG changes could be induced by isoprenaline injections. It is concluded that progressive changes of the S-T interval of the fetal ECG contains information about fetal hypoxic stress before signs of failing cardiovascular function are seen.


Non-pharmacological factors in drug treatment of anxiety states. Forty-six outpatients with anxiety tension states took part in a study on the effects of anxiolytic drugs. After the first interview the subjects also filled in a questionnaire as to their expectations of treatment outcome (n=41) and their experience of the first consultation (n=42), and the doctors made a prognostic evaluation (n=46). The relations between these three factors and background variables as well as initial ratings and outcome as rated by the doctors at follow-up examinations after 2, 4, and 8 weeks were investigated. Expectations, experience, and prognosis were not related to each other. Less hopeful patients more often considered conflicts to be the exclusive cause of their disorder and they were rated higher on signs and on the variable difficulties in being with people. Patients with less favourable experience more often considered practical and economic difficulties to be a cause of their disorder. Single or divorced patients were more often judged to have a less favourable prognosis. More positive expectations and a favourable prognosis. More positive expectations and a favourable prognosis were to some extent related to a better outcome after 2 and 4 weeks and a favourable experience was to some extent related to a better outcome after 4 and 8 weeks.


A comparison of drug use among Houston and lower Rio Grande valley secondary students. The authors conducted a study of drug use among students of a predominantly Mexican-American population and compared their findings with a similar study that was done in a large urban setting. They suggest that drug use among Mexican-American secondary students is less than among Anglo secondary students, which is opposite to popular lay notions.


Chlorination, decarboxylation and bactericidal activity mediated by the MPO-H2O2-C1- system. 1. MPO, H2O2 and C1- form a complex that undergoes intramolecular rearrangement yielding the chlorinium ion. 2. The chlorinium ion can interact with MPO, bacteria and amino acids. 3. The reaction can occur at a wide range of pH, H2O2 concentration and C1- concentration. 4. The chlorinium ion can attack different protein molecules to cause structural changes. 5. Preincubation of MPO with bacteria results in greater bactericidal activity. 6. Diffusible bactericidal agents are also produced by the MPO-H2O2-C1- system.


Antagonism of arachidonic acid hydroperoxide on isolated gastrointestinal tissues as a measure of the inhibition of prostaglandin biosynthesis. Arachidonic acid hydroperoxide (AAP)-induced contractions of the isolated guinea pig ileum and rat stomach fundus are inhibited by suprofen [alpha-methyl-4-(2-thienylcarbonyl) benzeneacetic acid], indomethacin, phenylbutazone, and acetylsalicyclic acid in descending order of activity. This effect is highly specific, since prostaglandins (PG) and various agonists of gastrointestinal smooth muscle are not, or only weakly antagonized by these four compounds, whereas various compounds, including narcotic analgesics, are inactive versus AAP. The antagonism of AAP-induced contractions of the isolated rat stomach fundus is a valuable test system for inhibitors of PG biosynthesis.


Splenomegaly in Northern Nigeria.

Splenomegaly in Northern Nigeria. Seventy five patients with large spleens were investigated in order to establish the causes of splenomegaly in Northern Nigeria, to define further the diagnostic criteria of tropical splenomegaly syndrome (TSS), and to study its pathogenesis. Investigations included examination of liver biopsy, bone marrow cytology, lymphocyte response to phytohaemagglutinin (PHA), serum immunoglobulins and complement, and the presence of immunoglobulin and complement fixed in Kupffer cells. Thirty patients had TSS, five chronic lymphatic leukaemia (CLL), four a syndrome of gross lymphoid hyperplasia (GLH) distinct from TSS, CLL and the lymphomas, and twenty three miscellaneous conventional diseases. In thirteen cases no definite diagnosis could be established. TSS was found to be predominantly a disease of female Fulani cattle herders. Its essential characteristics were splenomegaly in the presence of acquired immunity to malaria, a grossly raised serum IgM, a lowered serum complement, and the presence of IgM fixed in Kupffer cells. There was lymphoid hyperplasia in bone marrow, hepatic sinusoids and often blood which may be indistinguishable from that in CLL. Lymphocytes undergo normal blastogenesis to PHA. There was clinical and haematological response to proguanil therapy. Reticuloendothelial phagocytosis of IgM, probably as a complex, seems to be the essential feature of the condition. As it was impossible to identify early cases of TSS it is unclear whether IgM overproduction or phagocytosis of IgM complexes is the first stage of the disease. The precise nature of the association with malaria remains obscure. The diagnosis of CLL demanded the demonstration of an abnormally low immunoglobulin level and impaired lymphocyte responsiveness to PHA by blast transformation or 3H-thymidine incorporation, in addition to the usual haematological findings. The syndrome GLH occurred in multiparous Hausa women. It was characterised by intense lymphocytosis with active, PHA-responsive cells, and normal immunoglobulin levels. Patients responded to proguanil therapy. It is suggested that these patients have a depressed immune response to malaria, perhaps through repeated pregnancies, and to a leukaemogenic agent, both of which stimulate lymphocytosis. Antimalarial treatment at this stage may prevent the development of frank leukaemia or lymphoma. The usefulness of the various investigative procedures and the problem of managing the large number of undiagnosed cases are discussed.


Rheumatic fever and rheumatic heart disease among 56,8000 inhabitants in southeast Teheran from 1972-1974. A study of the incidence of R. fever in an area in southeast Teheran during the period 1972-1974 revealed 92 cases. The crude annual incidence of R. fever ranged from a high of 58 cases to a low of 51 cases per 100,000 population. The age and sex specific rates revealed the incidence to be strikingly higher in the 5-19 year age group, reaching roughly 80/100,000. There was an approximately similar number of males and females with R. fever. Among the R. fever patients, there were 6 cases of chorea, 5 girls and 1 boy. From 92 R. fever cases, 49 (53%) developed carditis. Among these patients, 35 (71%) were female in contrast to 14 (29%) male cases. Overall there were 59 cases (62%) which were initial attacks and 33 cases (38%) which were recurrences. During the trial there were also 7 recurrences of R fever and 4 deaths. The seasonal pattern showed that the majority of cases occurred during the winter and spring months. From the R. fever/R.H.D. patients, 63 (70%) and from cases with carditis alone, 24 (40%) were hospitalized.


Incidence of and beliefs about trypanosomiasis in the Senegal River Basin. A survey was conducted for trypanosomiasis of 10,875 persons living in 56 villages in the Senegal River Basin in Mali. The incidence of the disease was found to be 137.9/100,000. An interview survey was simultaneously undertaken in order to elucidate local beliefs about the disease. Although trypanosomiasis is recognized as a distinct disease entity once the late stage has developed, there is no knowledge of its relationship to tsetse flies. It is common knowledge that hunters who frequent riverine forest galleries and forested savanna often contract the disease. Their frequent and intense exposure to Glossina sp. is not viewed as having any relationship to their contracting the disease.


[Toxoplasmosis in the Republic of Mali. An epidemiologic approach]. 1664- sera from children and adults were collected in rural and urban areas of Mali and were tested in Toxoplasmosis serology. Immunofluorescent antibody tests and direct agglutination test have been used for this purpose. 65 per cent of adults from urban area and 56 to 58 per cent of adults from rural area gave positive results. Before the age sixteen, only 33 to 40 percent of children are positive in urban area while 51 to 53 per cent are so in rural area. The study of hundreds of sera collected from various animals allows to explain the different ages of the serological changes. In rural area children have been infected very early after catching birds, reptiles and above all, rodents and eating them not cooked enough. In urban area the infection occurs all along the life and, particularly, in adults, after consuming grilled meat. The recent description of three cases of congenital toxoplasmosis demonstrates the interest of such an epidemiological study.


[Changes in the blood pictureof the red goat of Maradi as a function of its gastrointestinal parasitism]. Numerous "chèvres de Maradi" are bred in Republique du Niger (cap. Niamey), 2 - 10(+6) numbered in 1973. This rustic ruminant is often very parasitized by intestinal nematodes and sporozoa. The most frequent genera are Bunostomum (55%), Trichostrongylus (40%), Strongyloides (27%), Oesophagostomum and Haemonchus (20%), sometimes Moniezia or Stilesia, coccidiosis being endemic and very pathogenic, Eimeria (70%). Polyparasitism is a "modus vivendi" between the host and these various parasites. All modification of the number or the kind of parasites (prevalence of one or two genera) involves a variation of the differential leucocyte count (anthelmintic cure for example). When the normal leucocyte count is 18 to 22 - 10(+3) per mm3, whose neutrophils: 40.73%; acidophils: 2%; basophils: 0.28%; monocytes: 11.28%; lymphocytes (small and big forms): 45.71%, a tapeworm parasitism by adults (Moniezia or Stilesia) or by peritoneal larvae (Cysticercus sp.) involves a light eosinophilia (8%), in morbid cases of coccidiosis, neutrophilia prevails (70%), and a polyparasitism with nematodes and Eimeria is characterized by monocytosis and neutrophilia, the polynuclear eosinophils being very rare. These observations show the necessity to elaborate simultaneously two cures: the first with an anthelmintic product, the second against coccidia, to avoid an uncertain Eimeria proliferation after the nematode destruction. In African breeding conditions, where polyparasitism is very frequent, such a therapeutic schedule is recommended.


[Distribution and ecology of Ixodes trianguliceps (Birula, 1895) (Acarina, Ixodoidea) in France, particularly in the South-East]. Ixodes trianguliceps, parasite of insectivores and rodent mammals seems to be distributed throughout France, except in the mediterranean low altitude areas. This tick which does not manifest any parasitic specificty, has meanwhile preferred hosts (Clethrionomys glareolus, especially). At low altitudes, it likes forests, hedge-rows and heaths and at higher altitudes (Subalpine and alpine), opened area may be densely inhabited. The authors study the numerous concerned vegetal associations and precise the tick's phenology, particularly in the Bas-Dauphiné. They also discuss the many hypothesis concerning the still unknown ecology of I. trianguliceps free instars.


Buoyant density of some togaviruses in sucrose density gradient and capacity of their haemagglutinin fractions to interact with antibody. The buoyant densities of Western equine encephalomyelitis virus (an Alphavirus) and tick-borne encephalitis (TBE) virus (a Flavivirus) antigens prepared by different methods were studied. Sucrose density centrifugation revealed a heterogeneity in the density of the virions. The sedimentation pattern and height of peaks of the haemagglutinating activities and infectivity, other conditions being equal, depended both on the virus species and properties of its strains and on the mode of preparation and treatment of the virus-containing material. Different haemagglutinating antigen fractions differed in their capacity to interact with specific antibody. It was suggested that the kinetics of a serological reaction and its result depend on the functional activity of the antigen preparation and, in particular, on the proportion in the reaction mixture of virus particles with a dissimilar antigenic structure.


The opposite temperature-sensitivity character (ts) in two attenuated flaviviruses, used for human immunization: 17D yellow fever and E5"14" (Langat) viruses. A reappraisal of thoughts. For the reproduction of the man-attenuated E5"14" clone of the Langat virus (tick-borne encephalitis complex) in pig kidney epithelial cells, the temperature of 39 degrees C was shown as restrictive, whereas it was permissive for the 17D strain of yellow fever virus and three virulent strains of tick-borne encephalitis (western subtype) virus. The temperature of 36 degrees C permitted the reproduction of all viruses studied. The implication of genetic marker studies in the assessment of human neuropathogenicity of flaviviruses is discussed.


Studies on the characteristics of Poliovirus type 3. III. Strain characteristics after passage in man. The markers d, IST, EA1(OH)3 and rct at sub- and supraoptimal temperatures as well as neurovirulence (PMic) for monkeys was determined for strains isolated from children vaccinated with Leon 12a1b vaccine, their contacts and from paralytic cases. The strains were isolated at early and late phases of excretion. The changes concerned mainly rct determined at supraoptimal temperatures, d and PMic markers, especially in strains isolated at the late phase of excretion. The passage through the human alimentary tract did not change such markers as IST and EA1(OH)3. Some degree of correlation was observed between the rct 40.3, d and PMic markers.


Effect of methyl glyoxal on infectivity and antigenicity of foot-and-mouth disease virus. The inactivating effect of methyl glyoxal on foot-and-mouth disease (FMD) virus was studied. The rate of inactivation depended upon the drug concentration, incubation temperature and pH of the medium. RNA recovered from the inactivated virus was not infectious. The complement-fixing activity of the virus was not reduced by methyl glyoxal treatment. The antigenicity of inactivated virus preparations determined by levels of virus neutralizing antibody in the blood sera of immunized white rats and rabbits was not inferior to that of the initial uninactivated virus.


Some immunological mechanisms of the influenza virus antitumour effect. Vaccine strains of influenza A virus inhibited the growth of ascitic tumour cells and outbred rats or inbred mice. The infected tumour bearers had an enhanced immune response to viral and specific tumour antigens. These phenomena are apparently due to the formation of complexes of both antigens on cell membranes and increased immunogenicity of such complexes.


In vitro studies on cell-mediated immune response to tick-borne encephalitis virus: findings in convalescents and human subclinical infections. Peripheral blood leukocytes from tick-borne encephalitis (TBE) convelescents (manifest and inapparent forms) working with TBE virus-containing material and from individuals without specific serum virus neutralizing antibodies (VNA) were studied in capillary tube leukocyte migration experiments. Partially purified TBE virus preparations were used as antigen. Under standardized conditions a strong inhibitory reaction was observed in convalescents with significantly higher values in persons recovered from an abortive form of infection only. These results differed markedly from values recorded in persons without specific VNA. Significance of correlation between humoral VNA titres and the intensity of the cell-mediated component of the immune response (CM IR), as indicated by leukocyte migration inhibition (LMI) values, was less than P equals 0.25.


Computer evaluation of antiviral activities of some thiosemicarbazones in experiments in vivo. A new mathematical method based on 3-, 4- or 6-point parallel-line assays was applied for working out a computer programme used to evaluate the activity of some new isatin-beta-thiosemicarbazone derivatives against vaccinia virus, studied in vivo.


Quantitative assay of influenza virus soluble antigen by complement-fixation micromethod. A modified micromethod of complement fixation (CF) reaction for quantitive assay of Influenzavirus soluble (s) antigen was elaborated. The method makes it possible to determine microquantities of s-antigen with an accuracy of +/- 15%. The accuracy of the method was checked by theoretical calculations.


Stable erythrocyte diagnostic preparation for passive haemagglutination test with herpes simplex virus antigen. A method for the preparation of stable suspensions of erythrocytes sensitized with herpes simplex virus (HSV) antigen and for their use in the passive haemagglutination test (PHAT) was developed. Formolized sheep erythrocytes were treated with tannin and sensitized with HSV antigen prepared from infected chick embryo cell culture by ultrasonication and virus extraction with alkaline glycine buffer. Antibody titres determined in the PHAT were higher than titres of neutralizing antibody. The specificity of the results was checked by the passive haemagglutination-inhibition test (PHAIT). The sensitized erythrocytes retained their activity for 5 months (the observation period) and gave reproducible results. The availability of stable erythrocyte diagnostic preparations simplifies the detection of herpesvirus antibody and makes the method widely applicable.


Uptake of labelled tobacco mosaic virus by tobacco protoplasts in the presence of metabolic inhibitors and at low temperature. In the presence of inhibitors of protein synthesis and energy metabolism, tobacco protoplasts were shown to retain 14C-labelled tobacco mosaic virus (14C-TMV) with the same intensity as in control. At 2 degrees C, the protoplasts retained 14C-TMV at approximately the same rate as at 25 degrees C. In protoplasts inocculated at different temperatures, approximately equal amounts of infectious virus were produced, this being possibly indicative of a non-physiological nature of the first stages of virus penetration into the protoplast.


Present state of alpha and beta adrenergic drugs. II. The adrenergic blocking agents. There are selective blocking agents (antagonists) for alpha receptors and beta receptors. These blocking agents prevent the response to injected agonists and neurogenically released norepinephrine. The principal cardiovascular response to alpha blockade is postural hypotension with reflexly induced cardiac stimulation. If neurogenic vasoconstriction is present, this will be removed. The principal cardiovascular response to beta blockade is bradycardia. If fast arrhythmias are present, these will be slowed. Beta blockade tends to increase peripheral resistance. Unless circulation is previously impaired this vasoconstrictive effect is insignificant.


The binding of the components of mixed micelle to dietary fiber. Bile acid conjugates are adsorbed to cereal fiber. Bile acid conjugates incorporated into micelles with cholesterol are reversibly adsorbed as micelles on to the fiber. Incorporating bile acid conjugates into micelles with monoglycerides somewhat depresses adsorption of bile acid conjugate. If fatty acids, monoglycerides, and bile acid conjugate mixed micelles are exposed to cereal fiber, then adsorption of bile acids to the fiber is diminished. The extent to which the adsorption is diminished is affected by the fatty acid concentration, chain length, and unsaturation. This suggests that bile acid conjugates are minimally adsorbed to fiber in the jejunum but deconjugation and dehydroxylation as in the cecum favors adsorption.


Anti-inflammatory drug treatment in Crohn's disease. In a prospective evaluation of all patients with Crohn's disease treated by us since 1970, 62 have completed at least one year, or required bowel resection after at least three months, of anti-inflammatory drug treatment. Sulfasalazine alone was used in 24 patients, steroids alone were used in four patients, both drugs were used together in 29 patients and azathioprine was added to the drug regimen of five patients. The initial choice of drug followed a set design but the regimens ultimately arrived at depended upon patient responses. Favorable complete or partial clinical responses were obtained in 54 patients, while 37 patients showed objective radiographic improvement or regression. No radiographic improvement was found in the eight patients with clinical treatment failure as well as in 11 patients with clinical improvement. Six clinically improved patients had not yet been re-examined radiographically. The study provides objective evidence that the majority of patients with Crohn's disease can be successfully treated by means of anti-inflammatory drugs.


A filtration model for study of leukocyte transit in the microcirculation. In order to study characteristics of leukocytes which would be important determinants of their flow in the microcirculation, a model system was tested which utilizes in vitro filtration of leukocytes. Normal human peripheral blood leukocytes (85-90% granulocytes) were studied with filters with uniform 8 mum pore size. Studies were performed to determine the effects of EDTA, temperature, hydrostatic pressure, pH, and osmolarity on filtration. Filterability was optimal at 0.2% EDTA, 10 cm hydrostatic pressure, neutral pH, isotonicity, and at room temperature. Filtration was slowed greatly at leukocyte concentrations exceeding 25 X 10(9)/liter. When leukocyte membranes were altered by formalin fixation, filtration slowed greatly, indicating that deformability is an important determinant of flow through small orifices. When mixtures of erythrocytes and leukocytes were filtered, there was a paradoxically enhanced transit of leukocytes compared to filtration of leukocytes alone, indicating interactions between these cells which alter flow. These studies serve to characterize this model system which can be used to study the contribution to flow in the microcirculation of both normal and pathological leukocytes.


Pharmacology and therapeutic use of antihistamines. The classes of antihistaminic agents, their pharmacology and therapeutic uses, adverse effects, drug interactions, toxic overdoses and abuse are reviewed. It is concluded that antihistamines are valuable drugs for treating a number of conditions and diseases (e.g. allergic rhinitis, motion sickness and parkinsonism), but proof of efficacy has not been established for the treatment of cardiac arrhythmias, peptic ulcers, insomnia and headaches. Because responses to antihistamines may vary, titration of each patient's dose is recommended.


Hemolysis of erythrocytes by primary pharmacologic agents, part 2: influence of the vehicle. The hemolytic activity in vitro of chlorpromazine hydrochloride, chlordiazepoxide hydrochloride and brompheniramine maleate was examined using various intravenous solutions as the vehicle. Fresh human blood was employed in the investigation which used a colorimetric method for the determination of hemolysis. Prior to the examination of the hemolytic activity of each drug in the various vehicles, the vehicles themselves were examined for their ability to protect erythrocytes from hemolysis. Little to no hemolysis occurred in normal saline solution (the standard), dextrose 2.5% in normal saline, dextrose 5% in normal saline, dextrose 10% in normal saline, and lactated Ringer's injection. Low levels of hemolysis occurred in dextrose 5% in water, invert sugar 10% in water, and M/6 sodium lactate in water. High levels of hemolysis occurred when red blood cells were suspended in dextrose 2.5% in water. Invert sugar 10% in normal saline and fructose 10% in water caused red cell denaturation resulting in brown cells and hemolysate rather than the characteristic red color. This denaturation was attributed to the hydrogen ion concentration of these two solutions, both having pH values less than 4.0. Vehicles of dextrose in saline, dextrose in water, lactated Ringer's, and invert sugar in water reduced the level of drug-induced hemolysis for the drugs tested compared to that which occurred in normal saline solution. The reduction of hemolysis was greater as the tonicity of the vehicle used was increased. It was concluded that the pharmaceutical vehicles examined have an influence on the cellular effects of drugs which only affects the erythrocyte but which could potentially affect the drugs' distribution from the blood to the sites of their action.


Beta blockers in hypertension: a review. The mechanisms of action, clinical use and untoward reactions of the beta-adrenergic blocking drugs, with particular attention to the role of these agents in the treatment of hypertension, are reviewed. Specific topics covered include the effect of beta-adrenergic blockade on the heart, renin secretion and the central nervous system; the efficacy and pharmacokinetics of beta-blocking agents; combinations with other drugs; patient acceptance and advantages; and toxicity and side effects. It is concluded that, with proper dosage titration, most hypertensive patients could probably be controlled on beta blockers alone or in combination with a diuretic.


Effect of orange juice consumption on urinary pH. The effect of orange juice consumption on urinary pH was studied in seven adult male subjects, each of whom served as his own control. The diet of the subjects was standardized during the work-day. The effects of two regimens of orange juice were studied: 1500 ml divided into five 300-ml portions during the day, and 300 ml once in the morning. Urine was collected, its pH recorded, and titrated with HCl to determine the mEq of base excreted per unit time. The consumption of 300 ml of orange juice did not significantly alter urinary pH. The consumption of 1500 of orange juice changed the urinary pH by an average of one pH unit. A change of this magnitude could cause clinically significant variation in the overall excretion pattern of acidic or basic drugs.


Prevention of prematurity.

Prevention of prematurity. Although only about 8 per cent of pregnancies end prematurely, as much as 75 per cent of perinatal deaths are due to prematurity. Since it is difficult to identify the predisposing factors in individual cases and to prevent the premature onset of labor, it is necessary to try to arrest such labor when it occurs. A theoretical scheme for the mechanism of labor in the human subject is presented. This permits the identification of four possible points of attack: (1) replacement of progesterone to reduce the myometrial sensitivity to oxytocin, (2) administration of beta-mimetic agents to relax the uterus and make it unresponsive to stimuli, (3) administration of ethanol to block oxytocin secretion, and (4) administration of anti-inflammatory drugs to inhibit prostaglandin synthesis. Results obtained with ritodrine, a beta-mimetic agent, and with ethanol are presented as illustration. Ritodrine gave somewhat better results than ethanol, possibly because the treatment was continued after discharge of the patients.


Effect of ritodrine on uterine activity, heart rate, and blood pressure in the pregnant sheep: combined use of alpha or beta blockade. Ritodrine hydrochloride was administered parenterally to pregnant ewes during spontaneous or oxytocin-induced uterine activity. The effects of ritodrine on the uterus and cardiovasculature were assessed both with and without simultaneous administration of either alpha or beta blockade. Ritodrine was found to be an effective inhibitor of both spontaneous and induced uterine activity. Ritodrine did cause maternal tachycardia but no significant hypotension. Alpha-adrenergic blockade did not influence the effects of ritodrine. Beta blockade with propranolol reversed the uterine and cardiovascular effects of ritodrine, whereas beta blockade with practolol reversed the cardiovascular effects without interfering with the inhibition of uterine activity produced by ritodrine.


Effect of propranolol infusion on the umbilical and uterine circulations of pregnant sheep. Propranolol was infused intravenously for 60 minutes to five ewes (4 mug per kilogram per minute) or five fetal sheep (10 mug per kilogram per minute). The umbilical blood flow was significantly decreased by 18 per cent from control at 60 minutes with either maternal or fetal propranolol infusion. Uterine blood flow and maternal and fetal mean arterial pressure did not significantly change. Maternal and fetal heart rates decreased 18 and 9 per cent from control, respectively, during maternal propranolol infusion. With propranolol to the fetus, fetal heart rate decreased 15 per cent and maternal heart rate did not change. During all infusion, maternal and fetal arterial pH, PCO2 and PO2 remained within normal physiologic limits.


Exudative retinal detachment and scleritis in polyarteritis. A 64-year-old white man, treated with systemic corticosteroids for five years, developed polyarteritis. He then developed a severe scleritis with an exudative retinal detachment in the right eye, which became blind and painful and was enucleated 23 months after onset of the scleritis. Histopathologic examination of the enucleated eye revealed granulomatous scleritis, chronic nongranulomatous uveitis, exudative retinal detachment, and perivasculitis of intrascleral, iris, ciliary body, and retinal blood vessels. Systemic findings were minimal and limited to elevated sedimentation rate, weight loss, mild anemia, and microscopic hematuria. Respiratory disease, severe kidney disease, hypertension, and arthritis were notably absent. A muscle biopsy established the diagnosis.


The stability of ten antibiotics in artificial tear solutions. We determined the relative potencies of penicillin G, carbenicillin, oxacillin, cephalothin, cephaloridine, gentamicin, kanamycin, neomycin, vancomycin, and bacitracin after their addition to three commercially available 0.5% hydroxypropyl methylcellulose artificial tear solutions in plastic squeeze bottles. We found no significant loss of antibiotic activity at room temperature over a period of seven days for all antibiotics except penicillin G, cephalothin, and cephaloridine. Three of the antibiotics were insoluble in one or more of the artificial tear solutions.


The closed eye environement: pH.

The closed eye environement: pH. Earlier observations showed that unbuffered bathing media held by a closed chamber against the eye would become progressively more acid over a few minutes. Such shifts, however, when examined for the naturally closed eye, even for prolonged periods, were found to be within 1 pH unit of the open-eye measured average.


Effect of virus infection on the inflammatory response. Depression of macrophage accumulation in influenza-infected mice. To better define the mechanisms by which viruses depress immune function, the effect of influenza infection on the ability of macrophages to accumulate at sites of inflammation was determined. Mice were inoculated with virus, and their inflammatory response measured in vivo by counting the number of leukocytes which accumulated in the peritoneal cavity 2 days after an intraperitoneal injection of phytohemagglutinin. Mice infected with influenza had a 57% and 65% depression of total leukocyte and macrophage accumulation, respectively, as compared to the response of uninfected mice. In contrast, bacterial pneumonia did not produce a decrease in the macrophage response. This indicated that the depression was produced by the virus infection rather than being a nonspecific phenomenon accompanying any inflammatory focus in the lung. The in vitro chemotactic responsiveness of normal peritoneal macrophages incubated with infectious influenza virus was 53% of normal. These experiments suggest that influenza infection may depress a host's ability to mobilize macrophages to inflammatory sites in vivo by inhibiting their chemotactic responsiveness.


Formation of slow-reacting substance by guinea pig immunoglobulins. The capacity of guinea pig antibodies to mediate the antigen-induced release of slow-reacting substance (SRS) in the rat peritoneal cavity is restricted to IgG2 and, to a lesser extent, to IgG1 populations of immunoglobulin. IgM and homocytotropic antibody of the reaginic type lacked this activity. The process was partially blocked by previous decomplementation of the rats, was not affected by previous reduction of the circulating leukocytes, and was partially suppressed by previous depletion of circulating platelets with an antiserum to rat platelets.


Interaction of chemical carcinogens and drug-metabolizing enzymes in primary cultures of hepatic cells from the rat. The experiments described in this paper have demonstrated that hepatocytes cultured on floating collagen membranes for periods of 10 days retain their ability to respond to the inducers of drug-metabolizing enzymes, phenobarbital and methylcholanthrene, by increases in cytochromes of the cytochrome P-450 complex. Since the regulation of these cytochromes is the rate-controlling factor in the metabolism of drugs and carcinogens in hepatocytes, such experiments indicate that hepatocytes cultured on floating collagen membranes retain those functions of the liver cell responsible for the metabolism and "activation" of carcinogenic substances. The data support this hypothesis and further indicate that this system may have potential application both in the investigation of hepatocarcinogenesis by chemicals in vitro and as a screening system for the detection of substances truly carcinogenic for the mammalian organism.


Properties of toad skin Na-K-ATPase with special reference to effect of temperature. The NA-K-ATPase of toad skin was characteristically sensitive to Na, K, and ATP. It was not affected by amiloride, vasopressin, cAMP, and thyroxine, but stimulated by insulin. Ouabain, a potent inhibitor at 37 degrees C, did not inhibit the enzyme activity significantly at 23 degrees C. The optimal pH for the enzyme activity increased as temperature decreased. However, the optimal OH-/H+ ratio of the medium remained constant at 16 regardless of temperature. The Km for ATP remained unchanged between 37 and 8 degrees C if the OH-/H+ ratio was held constant at 16, but increased as temperature decreased if the pH of the medium was held constant at 7.4. The enzyme activity showed no appreciable variation between 37 and 20 degrees C with a constant OH-/H+ ratio of 16, whereas it decreased logarithmically at a constant pH of 7.4 over the same temperature range. These results indicate the presence of a typical Na-K-ATPase system in toad skin and that the enzyme is in the most active catalytic state at a fixed level of OH-/H+ ratio in the medium regardless of incubation temperature.


Extracranial angiographic findings in giant cell (temporal) arteritis. Angiograms of 10 patients with giant cell arteritis who had large-artery and aortic abnormalities were reviewed. The affected arteries had multiple stenotic areas, and occlusions were relatively common, usually located at the end of tapered stenotic segments. Bridging collateral arteries usually refilled the distal portion of the occluded artery. The laterations were seen most frequently in the subclavian, axillary, and brachial arters, and the arteriographic lesions reflected the clinical findings. Such arteriographic abnormalities are suggestive of giant cell arteritis in a patient over the age of 50. The differential diagnosis includes Takayasu's disease, arteriosclerosis, thoracic outlet syndrome, and ergotism.


Analysis of body height in 829 patients with different forms of testicular pathology. Analysis of body height was performed in the control group of 500 well-fertile men and in 829 patients with various forms of testicular pathology such as hypoplasia of testicles, unilateral and bilateral cryptorchism, hypogonadotrophic eunuchodism, and Klinefelter's syndrome. A statistically greater average height was found in bilateral cryptorchids, unilateral cryptorchids with an adequate spermiogenesis, hypogonadotrophic eunuchoids and chromatin-positive men. The greatest difference, when compared with the control group, was found in patients with a Klinefelter's syndrome. The authors hold the view that the plasmatic testosterone values are not the only factor conditioning the termination of the process of growth into height in males. Importance must also be given to the lowered sensibility of epiphysial growth zones to male sex hormone; this reduced sensibility is especially to be seen in chromatin-positive men.


Cutaneous necrotizing vasculitis and related disorders. Leukocytoclastic vasculitis of the skin comprises several distinct clinical syndromes, each with immune complex deposition and some form of complement activation. Necrotizing vasculitides of larger blood vessels also produce skin lesions. These can be distinguished morphologically from those of small vessel vasculitis. Analysis of the features of these lesions is discussed.


[Anesthesia for resections-anastomoses of the trachea and the tracheal bifurcation]. Resection and anastomosis of the trachea or the tracheal bifurcation, raises numerous problems, which will be discussed in a series of 81 patients: -there is more or less marked ventilatory insufficiency related to the degree of the stenosis, and difficulties of expectoration responsible for retention of sputum; -per-operative ventilation. One must choose between an intubation catheter of small caliber in order to overcome the stenosis, or a large catheter to remain above it. The problem is all the more delicate to solve when the stenosis is tighter and higher; -during the period when the trachea is open, the surgeon must intubate the central part of the trachea with a sterile catheter. If the division is low, it is necessary to intubate the main bronchi or one only, and then create a marked shunt effect which would be ill-supported by the patient; -It is advisable to remove the catheter at the end of the operation. Awakening should be perfect in order to cough to be immediately efficacious in a patient who often has to remain with his head flexed forwards.


[Note on the care of tracheotomized patients]. After considering the indications for tracheotomy on his intensive care unit, the author describes the risks of this operation and the means of avoiding them. Out of 1940 patients admitted over a period of 5 years on the intensive care unit of the Royal Victoria Infirmary, Newcastle-on-Tyne, 175 were tracheotomised, inclusing 133 who were submitted to intermittent positive pressure ventilation. Only three patients had complications linked to the tracheotomy, complications which were the cause of the death of two of them.


[Present role of selective intubation sounds in thoracic surgery]. After the indications for selective bronchial intubation, the methods of bronchial control by various techniques, together with their advantages and disadvantages, are discussed. A Advantages: -the right and left lungs are completely separated and if the tube is correctly placed in position, it will avoid any loss of secretions towards the healthy lung; -the lungs may be ventilated together or separately; -there is perfect water tightness within the traches and bronchi; -rapid deflation or inflation of each may be obtained without modifying the position of the tube. B Disadvantages: -there is an increased resistance to the air flow if only one lung is ventilated; -alone, a small diameter aspiration catheter may be used; -the catheters are costly, they may be difficult to introduce in small size subjects.


[Benign esophagotracheobronchial fistulas in adults]. Oeso-tracheal-bronchial fistulas are rare in adults and their precise etiology is often difficult to determine, apart from the traumatic causes. Their diagnosis, based on symptoms, is confirmed by tracheal, bronchial and esophageal endoscopy, esophageal opacification and esophageal cineradiography. Treatment should permit one to avoid progressive pulmonary deterioration. Fatal accidents of bronchial inudation are rare but have been observed, especially in tracheotomised subjects. Surgical cure is possible and should be carried out under conditions of security which are defined here. In cases of irreversible pulmonary damage, one should carry out during the same stage, resection of part of the lung. Whereas the prognosis of fistulas after tracheotomy or intubation is always reserved, that of primary fistulas is good, providing the surgical cure is carried out early.


[Role of peridural anesthesia in thoracic surgery]. Periduralaneaesthesia by the cervical route (C6-C7 or C7-D1) or by the upper lumbar route with an ascending catheter, permit thoracic surgery in all its applications. The reduction in operative bleeding is an appreciable advantage of the method, and automatic nervous stability is remarkable. On the other hand, keeping the patient in the waking state is a definite disadvantage, especially in removal of one lung. As far as the anaesthetist is concerned he will be faced with difficulties of ventilation and bronchial aspiration. On the other hand, combined with slight general anaesthesia and tracheal intubation, peridural anaesthesia is definitely of interest. Furthermore, during the post-operative period, it is precious permitting a cough without pain and, in this respect, the comparison with anaesthesia of the inter-costal nerves, is worth discussins, each technique having special advantages.


[Anesthesia for lung grafts].

[Anesthesia for lung grafts]. The problems of anaesthesia for pulmonary transplantation are discussed from the theoretical and practical points of view. The problems of elimination of carbon dioxide and adequate oxygenation of the arterial blood, and protection of the transplanted lung, are considered. In the phase immediately after transplantation, the efficacy of gas exchanges are determined by reciprocal values of the resistance of the pulmonary artery, the resistance of the airways and the compliance of the transplanted and non-transplanted lung.


[Anesthesia and the postoperative period in non-urgent tracheal surgery. Apropos of 36 patients]. The authors report 36 cases of resection and suture for stenosis or tumour of the trachea and give details of their technique of anaesthesia, the post-operative follow-up and their results. The development of fiber endoscopy and simplification of intubation, increases the security of the patient, facilitates the task of the anaesthetist and thus improves greatly the operative conditions and post-operative period.


Lorazepam premedication: lack of recall and relief of anxiety. Premedication with lorazepam (4 mg), diazepam (10 mg), and a placebo was compared in a randomized, double-blind study of 95 adult surgical patients. Comparisons were made of recall of a memory card and events of the operative day, relief of anxiety, degree of somnolence, effects on blood pressure and heart rate, and incidence of side effects. Lorazepam produced a significant lack of recall (antegrade amnesia) compared to the other agents. Lorazepam produced a greater antianxiety effect than placebo and a greater degree of somnolence than diazepam or placebo. Since no adverse effects on blood pressure or heart rate occurred, lorazepam appears to show promise as a premedicant.


[Technic of pleural drainage (emergency pleural drainage)]. Pleural effusion is still often poorly drained: - incorrect introduction of the drain into the thorax, - ill-chosen position of the drain. Simple drainage, a minima, is considered here, that which requires no broad surgical incision and which, in cases of effusion with compression of the lung, is often a life saving procedure which any doctor should be able to carry out, especially if he deals with emergencies. The surest technique consists of placing a No. 30 drain, using a pleurotomy trocart, type Monod or Coquelet, under local anaesthesia. Introduction of the drain using a forceps after an incision with the scalpel blade is only justified if one has no trocart available. So-called disposable drains, mounted on a pointed bevelled needle prepared in advance, are practical but dangerous. Capillary drainages are methods of second choice. They are often excluded within short delays. The efficacy of the drainage depends on its position.


[Tracheobronchial ruptures seen in emergencies. Viewpoint of the anesthesiologist]. At the Marie Lannelongue surgical centre between 1964 and 1975, out of 278 patients with trauma of the thorax, we noted only 10 cases of tracheal-bronchial rupture admitted as an emergency = 9 ruptures due to closed trauma of the thorax, one with division of the lower part of the trachea. Analysis of these cases showed in particular:-the notion of violent trauma in -young subjects (average age: 20 years). In these thoracic injuries suspected of tracheal-bronchial rupture, the anaesthetist intervenes in four early stages: 1) arrival of the injured patient 2) bronchoscopy-diagnosis 3) surgical operation, the anaesthetic problems are linked to various factors, the most important of which are the very precarious cardio-respiratory condition, the lack of information and, sometimes, the lack of time. 4) Post-operative respiratory resuscitation.


[Emergency treatment of tracheal and bronchial foreign bodies]. Basing their report on personal experience of more than 300 tracheal or bronchial foreign bodies, the authors emphasize: -the difficulty of extraction, even in very expert hands. -the absolute necessity of a fully trained operator, and experienced anaesthetist and appropriate material. Apart from acute respiratory distress, they consider preferable to defer operation for a few hours, under strict supervision, in order to make available all these optimal conditions.


[Extraction of intrabronchial foreign bodies in young patients in a surgical unit]. The authors report a study of 35 cases of intra-bronchial foreign bodies in young subjects (average age 6 years). This shows that, more than the age of the child, or the duration of the presence of the object, its nature, has an influence on the possibilities of extraction by bronchoscopy or by thoracotomy. Whatever the nature of the foreign body, the authors emphasize the importance of the quality of the team formed by the endoscopist and the anaesthetist, repeated attempts at bronchoscopy compromise success and may lead to tracheotomy.


Glucose and insulin responses in sheep subjected to a second episode of hemorrhagic shock. These studies indicated that the responses of the sheep beta cell parallel mnay of those seen in man. Regulation by pH, potassium, and epinephrine and suggested, as is the existence of a two-pool system for insulin synthesis and release which is responsive to glucose. Differences in glucose and insulin responses following a second episode of shock are noted. It is shown that the addition of hypertonic glucose to a resuscitation regimen is associated with a response to a second episode of shock that is more nearly like that to a first episode of shock.


Chemical mediation in Coelenterata.

Chemical mediation in Coelenterata. This paper reports the results of a pharmacological survey of drug action on muscle preparations of the anthozoan Bunodosoma caissarum. A critical review of previous results of drug action on Coelenterate neuromuscular junction is also given. The preparations responded only to body wall homogenates and acetylcholine. Sympathomimeticamines (adrenaline and nor-adrenaline), indolalkylamines (tryptamine, serotonin) and other drugs (tyramine, histamine, 1-glutamate and GABA) showed no action. The view that the Coelenterates do not employ acetylcholine as a neurotransmitter is discussed.


Studies on the carbohydrate metabolism in psoriatic epidermis. Enzymic activities and cofactor levels in the epidermis are reviewed with special regard to psoriasis and the papulosquamous disorders lichen simplex and lichen planus. The metabolism of nicotinamide adenine dinucleotide phosphate and its dependent pathways seems to deviate in psoriasis from that in the contrasted dermatoses, in normal skin in health and in skin during the process of wound healing. The mitochondrial function also differs between psoriatic and normal skin. In some conditions in psoriasis this function cannot be seen to deviate from normality, however. The regulation and control of mitochondrial function in psoriasis might be another area in which future investigations may yield significant information on the pathophysiology in this skin disease.


[Carbohydrate and pyruvic acid degradation pathways in Fusidium coccineum strains with varying levels of antibiotic synthesis]. A number of enzymes and reactions of glycolysis, pentose-phosphate cycle and degradation of pyruvic acid in strains of F. coccineum with various levels of antibiotic production was studied comparatively. The experiments showed that highly productive strains were characterized by higher activity of the NADP-deficient enzymes of the pentoze-phosphate cycle as compared to the low active strains. The activity levels of glycolytic enzymes, such as fructose-diphosphate-aldolase and 3-phosphoglycerolaldehydehydrogenase did not practically differ. Significant differences were found in the reactions of puryvic acid degradation: the activity of cytoplasmic pyruvatedecarboxylase in the mutant with high antibiotic production level was lower than that in the low productive strain, while oxidation of the pyruvate of the mitochondrial fraction was on the contrary more intensive than in the highly productive strain. Therefore, metabilism in the strains studied was characterized by ever-increasing biochemical changes with an increase in their antibiotic productivity. Lowering of the growth rate of the mutants as their capacity for antibiotic supersynthesis increased and subsequently the anabolic processes became more intensive was accompanied by increasing derepression of the key enzymes of carbohydrate metabolism and in particular NADR-deficient dehydrogenase of the pentose cycle and pyruvatedehydrogenase, significant for fusidin biosynthesis and providing production of the antibiotic of steroid nature by cofactor NADP-H and acetyl-KoA, the primary precursor.


[Dependence of erythromycin biosynthesis on the active acidity of the medium]. Dependence of erythromycin biosynthesis on the medium active acidity was studied by the following methods: by changing pH of the initial medium, by changing the concentration of the medium components determining the active acidity of the culture, by using buffer mixtures by automatic control of pH. It was found that pH of the initial medium within 5.7-8.1 had no effect on the culture growth. Biosynthesis of erythromycin markedly decreased at pH 6.3 or lower. The values of pH within 6.6-7.5 (optimal values 6.7-6.9) were favourable for the antibiotic biosynthesis. At pH 6.2-6.3 the antibiotic accumulation was equal to 5-10 per cent of the control.


[Determination of rifamycin B activity in culture liquids and in preparations with varying degrees of purity]. A possibility of using the biological method of rifamycin B activity determination in the fermentation broth and dry preparations of various purity levels was studied. It was found that the biological method was useful only for determination of rifamycin B activity in preparations containing not less than 850 gamma/mg of the main product. When the activity of rifamycin B was determined in the fermentation broth and crude preparations containing less than 800 gamma/mg of the main product, the results of the biological assay were always higher as compared to those of spectrophotometrical estimation. It was accounted for the effect of other rifamycin types possessing high biological activity.


[Stability of 6-beta-[(hexahydro-1H-azepin-l-yl)methyleneamino]-penicillanic acid in aqueous solutions]. Stability of acqueous solutions of 6-beta-[(hexahydro-IH-azepin-I-yl)methylenamino] penicillanic acid at various values of pH and temperature was studied. It was found that inactivation of the antibiotic in both the acid and the alkaline medium proceeded according to the equation of the 1st order. At pH 1.3 and a temperature of 35 degrees the half life of the antibiotic was 7 hours. The activation energy calculated according to the Arrenius equation was 13.5 kcal/mol at pH 1.3 and 22.2 kcal/mol at pH 10.5. The antibiotic was inactivated in glycol and phosphate buffers. Its qualitative analysis was performed according to an improved iodometric method.


[Interaction of morphocycline with beryllium ions]. Behaviour of morphocycline (H5R) and its complex with beryllium ions in acqueous solutions was studied fluorimetrically. The ionization constants of H5R were estimated at pH 1.5-15 according to the data of fluorimetric determination with respect to OH-group: pK1 6.40, pK2 8.25, pK3 10.65, pK4 11.30. Two constants characterizing the deprotonization process with respect to the carbonylic group and nitrogen were also estimated: pK01--1.0 (greater than C = 0) and pK02 4.75 (--N=). Formation of an intensively fluorescing compound less than [Be3(OH)3(H2O2)5]2HR greater than 2+ was observed at pH 6.0-7.0. The cause of such intensive fluorescence was deformation of ion [Be3(OH)3(H2O)6]3+ because of its exclusion from the coordinating sphere of one molecule of water during the complex formation and decreasing of level H comes from II as compared to the morphocycline level II comes from n. A procedure for detecting morphocycline in the blood of humans and animals was developed.


[Dependence of the mutagenic effect of N-nitroso-N-methylbiuret on the pH index]. The mutagenic effect of nitrosocompounds is known to be dependent on pH. The effect of N-nitrozo-N-methylbiuret on the conidia of Penicillium chrysogenum was studied within the ranges of pH from 5.0 to 7.0, the role of the buffer and distilled water being also considered. It was found that survival, morphological variation and induction of biochemical mutants depended on the value of pH. The optimal conditions for the culture treatment at the exposures tested were provided at pH 6.0 with the use of a phosphate buffer mixture as a substrate.