Neurotransmitters increase cyclic nucleotides in postganglionic neurons: immunocytochemical demonstration. Dopamine increases adenosine 3',5'-monophosphate (cyclic AMP) but not guanosine 3',5'-monophosphate (cyclic GMP) in slices of bovine sympathetic ganglion; this increase is localized to the postganglionic neurons. Conversely, acetylcholine increases cyclic GMP but not cycle AMP in the ganglion; this increase also occurs within postganglionic neurons. Thus, different neurotransmitters can selectively alter cyclic nucleotide levels within the same neuronal population.


Effect of anesthetics on the heart.

Effect of anesthetics on the heart. In man, high doses of the "group 1" inhalation anesthetics (diethylether, cyclopropane, and fluroxene) produce relatively minor depression of ventricular function, although it is possible to depress the heart if the dose is great enough. The "group 2" drugs (halothane, methoxyflurane, etc.) produce dose-related depression in cardiac function, but reasonable caridac outputs and blood pressure can be maintained at light anethetic levels. Much the same can also be said for the intravenous barbiturates and other hypnotics. If ventilation is supported and hypovolemia avoided, large doses of the narcotic analgesics appear to produce minimal cardiac effects. The only intravenous drug which stimulates the heart is the dissociative anesthetic ketamine, and this is probably an autonomic, reflex phenomenon (as with group 1 inhalation anesthetics). Regional anesthesia and the neuromuscular blocking drugs appear to have relatively little effect on ventricular function. Most of the work in man on the effect of anesthetics has been in healthy patients or volunteers. The effects on patients with severe heart or other systemic disease may well be different. In fact, low concentrations of fluroxene have been shown to produce significant depression of stroke volume in patients with aortic vavular disease in contrast to the effects on healthy volunteers. All potent central nervous system depressant drugs possess the potential for significant cardiac depression. If such depression is undersirable in a particular patient, the only safe way to administer anesthesia is by careful titration of the dose against the best measurement of cardiac function which is available. At the present time, this would mean measuring at least direct arterial pressure, central venous pressure, and a continuous electrocardiogram. The optimal management would prpbably include recording systolic time intervals, pulmonary capillary wedge pressure, and some measure of cardiac output as well. All the skill and pharmacologic knowledge available connot substitute for vigilant monitoring and carful tiration of drug dose in the clinical situation.


[Occurrence, diagnosis and course of chronic hepatitis in weaned lambs of a flock of Texel sheep (author's transl)]. A disease of weaned lambs is described, which is attributable to chronic hepatitis marked by impaired secretion of cholephils in the acute or early stage and by inadequate growth due to persistent dysfunction of the liver during the subsequent or chronic stage. Regardless of its duration, the disease may be diagnosed in the living animal by determining the SDH and gammaGT activity levels, the total serum protein, the serum iron concentration and the serum iron-binding capacity.


[The use of analgesic and antiphlogistic agents in small animals (author's transl)]. The metabolism of many analgesic and antiphlogistic agents in dogs and cats differs markedly from that in man or other animals. When the known data on the subject are borne in mind, potentially toxic agents such as acetosal, phenylbutazone, ibuprofen and indomethacin may be used without much risk in various indications. It is pointed out that double-blind studies on the clincal effectiveness in patients unfortunately have not yet become available.


Hydro-proteolytic activity in rat's pancreas after irradiation. Investigations were carried out on the problem of hydrolytic ability of rat's pancreas 24 h after whole body irradiation with the single dose of 800 R and after fractionated irradiation (5 x 150 R). Besides kallikrein, enzymes of intracellular digestion (B-glucuronidase, acid phosphatase, cathepsin) and enzymes of intraluminal digestion (amylase, lipase) were chosed for examination. It was stated, that single irradiation evokes rather moderate changes in the activity of examined enzymes causing increase of catheptic and lipolytic activity and decrease in amylase activity accompanied by sharp increase of kallikrein activity in the tissue. Mechanical obstruction of biliopancreatic duct renders trend to decrease of enzymatic activity in almost all enzymes of irradiated group. After fractionated irradiation the general increase of hydroproteolytic activity (with one exception of pancreatic amylase) was stated.


Radiation effects on rat testes. IX. Studies on oxidative enzymes after partial body gamma irradiation. Oxidative enzymes in the rat testes have been studied after gamma irradiation. The role of these enzymes in relation to spermatogenesis and steroidogenesis after radiation injury to testis has been discussed. Loss of succinic dehydrogenase and sorbitol dehydrogenase reflects the losts of germ cell population. Malic enzyme and malic dehydrogenase seem to the related to the deficiency of steroid hormones, whereas increase in glucose-6-phosphate dehydrogenase and NADP isocitric dehydrogenase is due to secondary stimulation of pituitary.


24xi-Methylcholestane-3beta, 5alpha, 6beta, 12beta, 25-pentol 25-monoacetate, a novel polyoxygenated marine sterol. 24xi--Methylcholestane-3beta, 5alpha, 6beta, 12beta, 25-pentol 25-monoacetate has been isolated from an Alyconarian and its structure was established in part through extensive high resolution mass spectral and nmr studies and partly through the nonidentity of one of its degradation products with 24xi-methylcholestane-3beta, 5alpha, 6beta, 12alpha-tetrol synthesized from deoxycholic acid.


Bone marrow transplantation in the busulfan-treated rat. I. Effect of cyclophosphamide and rabbit antirat thymocyte serum as immunosuppression. It was previously shown that lethal doses of busulfan (BU) were not immunosuppressive in the rat. In the present studies the effect of rabbit antirat thymocyte serum (RARTS) and cyclophosphamide (CY) as immunosuppressive preparation for marrow allografts in the rat given supralethal doses of BU was investigated. Lewis or LBNF rats were given RARTS for 4-12 consecutive daily doses. They were given a supralethal dose of BU in addition on the last day of RARTS administration. Ag-B-incompatible (ACI). Ag-B-compatible (F344), or syngeneic marrow was infused 24 hr later. In general, RARTS was not toxic to the marrow graft and permitted engraftment of Ag-B-incompatible and compatible marrow. All animals given Ag-B-incompatible marrow and Ag-B-compatible marrow that survived to day 21 were shown to be chimeric, but all those with incompatible marrow subsequently died from severe graft-versus-host disease (GVHD). In other experiments Lewis or LBNF1 rats were given Ag-B-incompatible (ACI) and compatible (F344) marrow after a supralethal dose of BU and single graded doses of CY. Doses of CY as low as 25-50 mg/kg provided sufficient immunosuppression to allow allogeneic engraftment. Transient chimerism was seen up to doses of 100 mg/kg of CY. Permanent chimerism was seen with doses of CY from 150 to 250 mg/kg. The incidence of lethal GVHD increased in parallel with the percentage of animals that were demonstrated to be chimeric. Mild but transient GVHD was seen with Ag-B-compatible marrow given to Lewis rats.


Chimaerism of immunocompetent cells in allogeneic bone marrow-reconstituted lethally irradiated chickens. Injection of parental bone marrow cells into 12-day-old lethally irradiated F1 hybrid chickens resulted in chimaerism of donor-type graft-versus-host (GVH)-reactive cells and suppression of antisheep red blood cell antibody response. These manifestations of a chronic graft-versus-host reaction were prevented by pretreatment of the donor marrow with specific anti-T cell globulin. In some chimaeras donor-type GVH-reactive cells developed gradually from T cells precursors of donor origin. Transplantation of spleen and marrow cells from sheep red blood cell-primed F1 hybrid donors into lethally irradiated parental recipients resulted in the loss of memory potential within 1-2 weeks of transfer, whereas donor-type IgG allotype synthesis was preserved. Injection of goat antichicken thymocyte serum to recipients 1 day before reconstitution enabled the antibody response of memory cells at 1-2 weeks, although it failed to prevent their rejection by 8-9 weeeks after transplantation. Split chimaerism of donor-type GVH-reactive cells was demonstrated in chickens which had previously rejected the B cells derived from the same graft.


Some aspects of HB Ag in hepatitis in Sri Lanka. Twenty-four out of 72 sera from patients with acute viral hepatitis were positive for HB Ag. HB Ag positive males were more severely ill than HB Ag positive females. The sera of four patients with active chronic hepatitis were negative for HB Ag. Thirteen sera of HB Ag positive cases were tested for anti-nuclear factor, all with negative results. In all four patients with active chronic hepatitis anti-nuclear factor was positive. There was a high incidence of latex fixation reactivity in the HB Ag positive cases (9 out of 13). Arbovirus antibodies were detected in 16 out of 18 HB Ag positive cases and in 19 out of 27 HB Ag negative cases of acture viral hepatitis. Fifty percent of these HB Ag positive cases had titers suggestive of recent infection as against 33% of the HB Ag negative cases. The arbovirus antibody titers were determined in four out of six HB Ag positive cases that did not give a history of parenteral injections and in everyone of them the titers were suggestive of a recent arbovirus infection.


[Study of the mutagenic activity of mazheptil]. Mutagenic activity of the psychotropid drug--majeptil was studied. Majeptil does not induce gene mutations on Salmonella typhimurium and chromosomal aberrations in mice bone marrow cells in vivo. It is shown that majeptil increase the level of chromosome aberrations in the culture of human peripheral blood lymphocytes. It is also active in the dominant lethal test on mice.


Measurement of substrate-induced oxygen uptake during microsomal drug oxidation using a gold micro-electrode. 1. A resin-coated gold micro-electrode has been used for polarographic determination of oxygen concentration in liver microsomal suspensions from phenobarbital-pretreated rats. 2. The rate of oxygen uptake on addition of an NADPH-regenerating system and the rate after addition of various substrates of the mixed function oxidase system were measured. The rate of oxygen uptake was faster in the presence of substrate than in the presence of NADPH alone. 3. Kinetic constants (Km and V max) for biphenyl, hexobarbital, ethylmorphine, naphthalene and SKF 525-A measured by this technique compare favourably with those obtained either by measurements of NADPH oxidation, or chemical measurements of substrate disappearance or product formation. 4. The practical applications of the gold electrode to drug metabolism studies are discussed.


The metabolism of N-ethyl-N-methylaniline by rabbit liver microsomes: the measurement of metabolites by gas-liquid chromatography. 1. A method for the determination of N-ethyl-N-methylaniline and its metabolites by g.l.c. is described. 2. Following incubation in N-ethyl-N-methylaniline with rabbit liver microsomes for 60 min, over 95% of the substrate was accounted for as unchanged compound or metabolites. 3. N-Ethyl-N-methylaniline is metabolized in vitro by rabbit tissues mainly by N-oxidation and N-demethylation and to a lesser extent by N-deethylation and di-dealkylation. 4. Both major routes of metabolism were observed in homogenates prepared from rabbit liver and lung; in addition N-oxidation occurred in kidney and bladder tissue homogenates.


The differentiation of N-oxidation and N-dealkylation of N-ethyl-N-methylaniline by rabbit liver microsomes as distinct metabolic routes. 1. N-Oxidation and N-dealkylation were shown to be separate routes of metabolism for N-ethyl-N-methylaniline. 2. N-Dealkylation, but not N-oxidation, is enhanced when NADH is present in addition to the NADPH-regenerating cofactors. 3. Some inhibitors, e.g. p-chloromercuribenzoate, inhibit N-dealkylation to a very much greater extent than they do N-oxidation. 4. N-Dealkylation is affected more by 'ageing' of the microsomal preparation or by the presence of bile salts, than is N-oxidation. 5. N-Oxidation followed by N-O-alpha-carbon migration of oxygen is only implicated to a very minor extent in the N-dealkylation process.


Enzymic N-acetylation of 2,4-toluenediamine by liver cytosols from various species. 1. 2,4-Toluenediamine was incubated with liver cytosol from various species, or cytosol from various tissues of the hamster or rabbit, in the presence of [1-14C]acetyl-CoA. N-Acetylation occurred selectively at the p-amino group of 2,4-toluenediamine and to a much lesser extent on the o-amino group. 2. In hamsters and rabbits the highest N-acetyltransferase activity was present in the liver cytosol, followed by kidney intestinal mucosa and lung cytosols. 3. Hamster liver cytosol had the greatest activity followed by liver cytosols from guinea-pig, rabbit, mouse and rat. With human liver cytosol only a trace of an N-acetyl derivative of 2,4-toluenediamine was found while dog liver cytosol showed no activity. 4. N-Acetyltransferase activity was maximal at pH 7-5 in mouse, pH 6-0 in rat and man, and pH 7-0 in rabbit liver cytosols. 5. There was a slight difference in the levels of N-acetyltransferases in males and females; the female mouse had more enzyme activity than the male, but the male rat had more enzyme activity than the female.


Properties of benzpyrene hydroxylase from human liver and comparison with the rat, rabbit and guinea-pig enzymes. 1. Benzpyrene hydroxylase of human liver biopsies and of livers from four inbred rat strains and from a non-inbred Sprague-Dawley rat strain, rabbit and guinea-pig was studied. 2. The human liver benzpyrene hydroxylase was similar to that of laboratory animals with respect to cofactor requirements, NADPH and O2, microsomal localization and inhibition by CO and N2. 3. Kinetic analysis of human adult benzpyrene hydroxylase indicated the presence of two enzymes, whereas human foetal liver contained only one enzyme hydroxylating 3,4-benzpyrene. Michaelis constants of human liver benzpyrene hydroxylase were slightly higher than Km values of animal liver enzymes. 4. Benzpyrene hydroxylase activity in human liver showed no sex difference, was enhanced by cigarette smoking and was decreased in patients with liver damage. 5. Variation of benzpyrene hydroxylase activity in human liver samples was about 6-fold in the 'control' group and 16-fold when all patients were considered. Variation of benzpyrene hydroxylase activity in inbred rat strains was less than 60% between different individuals and in the non-inbred rat, rabbit and guinea-pig the variation was 2- to 3-fold or less.


[Precursor formation and biosynthesis of the macrolide antibiotic a 6599 (turimycin) by streptomyces hygroscopicus JA 6599]. The possible role of some metabolic systems producing acetyl-CoA, and methylmalonyl-CoA as initial precursors in the biosynthesis of the macrolide antibiotic A 6599 by Streptomyces hygroscopicus JA 6599 was studied. The activities of pyruvate decarboxylase exceeded in two higher producing strains about twofold those found in the mycelium of a lower producing one suggesting that in this organism an enhanced production of acetyl-CoA should be one of the prerequisites necessary for an improved antibiotic biosynthesis. No clear interrelationship was established, however, between the biosynthesis of the secondary metabolite A 6599 on the one hand and the acetate and propionate kinase content on the other hand. In S. hygroscopicus JA 6599 the carboxylation of acetyl-CoA or propionyl-CoA seems to be the major pathway giving malonyl-CoA or methylmalonyl-CoA, respectively. Thus, the activities of acetyl-CoA and propionyl-CoA carboxylases corresponded with both the levels of antibiotic production in several strains and with variations observed in the specific antibiotic production rate during the cultivation. Some other pathways synthesizing these precursors, e.g. via oxaloacetate, are assumed to be negligible since even in the mycelium of the lower producing strain increased activities of phosphoenolpyruvate carboxylase were present.


[Perinatal mortality and asphyxia in premature babies (author's transl)]. The aim of the present investigation was to study the influence of O2-ventilation, blind buffer therapy with Na-bicarbonate, late cord clamping and infusion of low molculare weight dextran on morbidity of Respiratory-Distress-Syndrom (RDS) and mortality during the first week in infants with a birthweight of 2500 g and less. The charts of 536 infants were studied. There were 481 life birth and 55 stillbirth (10.2%). In 185 infants the pH and Base-excess in the umbilical arterial blood was meassured. The infants born in 1969--1971 were compaired with them born in 1972--1973. In 52% of the "premature infants" the pH was 7.25 U and lower and in 90% of the Base-Excess was --4.5 meq/l and more. The perinatal mortality (PM) was 30% and 13% (P less than 0.01) resp. There was a correlation to the birthweight. The decrease of the PM was related to the fall in mortality of infant during the first week: 21% and 4% resp. Here too, there was a correlation to birthweight and gestational age. The morbidity in RDS: 20.6% and 10.0% (P less than 0.01) and mortality following RDS: 79.3% and 35.0% resp. (P less than 0.01) was also low in 1972--1973. The results permit us to conclude that it is of great importance to correct fetal acidosis immediately after birth to prevent irreversible alterations in the lung. It could also be of value to encrease cardiac output and lungperfusion by late cord clamping and injection of dextran 40. The other procedures belong to standard managment in handling an asphyxiated fetus.


[The acidity and peptic activity of gastric juice in healthy children and in children suffering from cystic fibrosis (author's transl)]. The acid concentration and quantity, the pH and the peptic activity of the gastric juice were measured after stimulation with pentagastrin in 10 children with cystic fibrosis between the ages 2 and 12 years and in 20 healthy children of the same age group. Furthermore, the basal, maximal and peak volume outputs (BVO, MVO and PVO), the basal, maximal and peak acid outputs (BAO, MAO and PAO) and the basal, maximal and peak pepsin output (BPO, MPO and PPO) were determined. The statistical calculations were carried out with the help of partial hierarchical analysis of variance, comparison of regression curves, simple analysis of covariance and the t test. After stimulation with pentagastrin, the volume of the gastric juice, the acid quantity and the peptic activity were found to be dependent on age in healthy children as well as in children with cystic fibrosis. The maximal volume of secretion in children with cystic fibrosis is less than that of healthy children; however, the acid quantity and peptic activity show no significant difference in both groups. The volume of the gastric juice, acid quantity and peptic activity in basal and stimulated secretions, expressed in kilograms per body weight or surface area in square meters, are independent of age and show no significant difference between the two groups. In the two groups the curves for the three parameters differ significantly from one to another. There is a significant shift in the time course of the curves that depict the acid secretion and peptic activity. Contrary to the accepted views, the acid and enzyme secretions are not closely interrelated. Based on the acidity and peptic activity, the digestive capacity of the stomach is the same for healthy children and children with cystic fibrosis. In contrast to the pancreas, there is no impairment in the exocrine function of the stomach. The gastric secretions of children with cystic fibrosis are not completely the same as in healthy children.


Studies on the specificities of various anti-H reagents. Four different eel serum samples and the lectins Cytisus sessilifolius and Evonymus europaeus were examined for their capacities to react with a number of preparations which show O(H) blood group-like activity. Some similarities and major differences between the anti-H reagents were observed in experiments where the "H-like" activities of invertebrate extracts and blood group substances were compared. A comparison of the reactivities of eel sera, catfish anti-H sera and 4 anti-H lectins with a number of different "H-like" preparations is summarized. Data obtained from preliminary sugar analyses of preparations isolated from 5 different invertebrate species studied is presented.


The immunochemistry of (L-Ala-D-Glu-L-Lys-D-Ala-Gly)n: II. Rabbit antibodies of restricted heterogeneity. A rabbit antiserum of restricted specificity elicited by the sequential polypeptide, (L-Ala-D-Glu-L-Lys-D-Ala-Gly)n, was purified by column chromatography using Sepharose 4B to which the inhibitor, Gly-L-Ala-D-Glu-Gly, was covalently attached. Approximately 95% of the antibody activity was retained on the immunoabsorbant. After elution, the purified antibody was shown by electrofocusing in a sucrose gradient to be of restricted heterogeneity. The entire antibody fraction was contained within the pH range of 6.9-8.9. The normal immunoglobulin pool from this rabbit, on the other hand, was found by electrofocusing to be distributed throughout the pH range studied (3.6-9.2).


Low molecular weight water-soluble peptidoglycans as adjuvants and immunostimulants. The tetrasaccharide-heptapeptide (TH), when injected with mineral oil, exerted a strong adjuvant effect. It stimulated B and T cells, but did not increase the phagocytic activity of the reticulo-endothelial system. While BCG exerted significant preventive effect on the growth of sarcoma 180, leucosarcomatosis an EHRLICH ascitic tumor, TH, at the doses used, was devoid of such activity.


[A ferredoxin-linked sulfite reductase from Spinacia oleracea (author's transl)]. A sulfite reductase from spinach has been purified 125 fold. Throughout all stages of purification the reduction of sulfite has been found dependent on ferredoxin. Reduced ferredoxin has been provided either by photosynthetic reduction in isolated, broken chloroplasts or by NADPH via the ferredoxin-NADP-oxidoreductase. During the purification procedure ferredoxin as electrondonor has been replaced by reduced methylviologen.


[Michaelis constants of neuraminidases of pathogenic and apathogenic microorganisms (author's transl)]. The Km-values of neuraminidases from different pathogenic and apathogenic microorganisms have been determined on low and high molecular substrates. The substrate specificity and the affinity to the different types of substrates in relation to the pathogenicity of the microorganisms are discussed.


Determination of the isotope effect of the enzymatic oxidation of (R)Carnitine by displacement of the equilibrium via mass action. An isotope effect of the dehydrogenation of (R) Carnitine [(R) 3-hydroxy-4-trimethylaminobutyric acid hydrochloride] catalyzed by (R) carnitine dehydrogenase [(R) carnitine: NAD oxidoreductase E.C. 1.1.1.108] from Pseudomonas aeruginosa was measured at different temperatures. It was found that k1H/k3H does not vary greatly with changes of temperature. The value of 3 for k1H/k3H measured at small initial conversions strongly indicated that the rate limiting step of the oxidation of (R) carnitine is the cleavage of the C-H bond at C3.


Reaction of glutathione with conjugated carbonyls. 1. GSH reacts with conjugated carbonyls according to the equation: GSH+R-CH=CH-COR in equilibrium R-CH(SG)-CH2-COR. The forward reaction follows second order, the reverse reaction first order kinetics. It is assumed that this reaction reflects best the ability of conjugated carbonyls to inactivate SH groups in biological systems. 2. The rate of forward reaction increases with pH approx. parallel with alphaSH. Besides OH- ions also proton donors (e.g. buffers) increase the rate. The catalytic effect of pH and buffer is interpreted in view of the reaction mechanism. 3. The equilibrium constants as well as the rate constants for forward (k1) and reverse reaction show an extreme variation depending on the carbonyl structure. Acrolein and methyl vinyl ketone (k1 = 120 and 32 mol-1 sec-1, resp.) react more rapidly than any other carbonyl to give very stable adducts (half-lives for reverse reaction 4.6 and 60.7 days, resp). Somewhat less reactive are 4-hydroxy-2-alkenals and 4-ketopentenoic acid (k1 between 1 and 3 mol-1 sec-1), but they also form very stable adducts showing half-lives between 3.4 and 19 days. All other carbonyl studied react either very slowly (e.g. citral, ethly crotonate, mesityl oxide, acrylic acid) or form very labile adducts (crotonal, pentenal, hexenal, 3-methyl-butenone). Comparing biological activities of conjugated carbonyls their reactivity towards HS (k1) and the stability of the adducts must be considered.


[Gas chromatographic mass spectrometric analysis of neurtral and acid oligosaccharides from human milk as their trimethylsilyl derivatives (author's transl)]. Gas chromatography and the 20 eV mass spectra of the human milk oligosaccharides fucosido-galactose, fucosido-lactose, di-fucosido-lactose, 3'-N-acetylneuraminyl-lactose, 6'-N-acetylneuraminyl-lactose and of N-acetyllactosamine as pertrimethylsilyl (TMS) ethers are described. The gas chromatographic separation of the L-fucose containing oligosaccharides was performed on Silicone SE 30. The sialic acid containing sugars were separated on DEXSIL 300. The correlations between oligosaccharide structures and mass spectrometric fragmentation patterns are discussed.


[Dissociation and reassociation of poliovirus. I. Effect of urea on the virion]. Poliovirus is dissociated by urea in the presence of mercaptoethanol or dithiothreitol into RNA and protein(s). Differences exist in the sensitivity of poliovirus type I, II or III toward these agents. The decrease in infectivity titer of the virion is in the range of 10(9). After appropriate dissociation no infectious virions are found in urea-treated poliovirus concentrates. The released viral RNA is infectious. Its infectivity (1 times 10(6) PFU/mug RNA) is comparable to that of phenol extracted RNA. Therefore, urea dissociation is a fast and reliable method for the preparation of infectious poliovirus RNA even at the microliter scale. The dissociation of poliovirus is dependent upon the concentration, temperature and pH. The decrease in virion infectivity is time dependent. It is preceded by a lag phase of different lengths for poliovirus type I, II or III. During the lag phase the virion undergoes configurational changes without losing infectivity. From the observed hyperchromic effect is it obvious that the secondary structure of the RNA inside the virion breaks down, giving rise to expanded forms of poliovirus particles. After the lag phase the RNA is released and the empty capsid dissociated into the appropriate polypeptides.


[Synthetic medium for testing of susceptibility. II. Susceptibility of bacteria to sulphonamides (author's transl)]. A comparative study of 9 media for testing the susceptibility of bacteria to 7 sulphonamides has been carried out. The evaluated culture-media included 4 "Mueller Hinton" media (MH), 4 others based on the formula of the "Diagnostic Sensitivity Test" agar base (D.S.T.) and a "Synthetic Medium" (SM) which has been developed in our laboratory. MH and D.S.T. culture-media have been supplied by 4 manufacturing companies in Europe and USA. A total number of 21 bacterial cultures have been employed. The included species belong to the gram negative genera Citrobacter, Escherichia, Klebsiella, Proteus, Salmonella, Serratia and Shigella, and to the gram positive genus Streptococcus. Sulphafurazole, sulphasomidine, sulphamethoxazole, sulphamethoxypyridazine, sulphadimethoxine, sulphaphenazole and sulphamethoxydiazine have been investigated. SM proved to be clearly superior to the other 8 culture-media mentioned above. Just one MH afforded good results. The 3 other MH and 2 D.S.T. media were not quite satisfactory. The two remaining D.S.T. media were unsuitable. Moreover, the activity of the tested sulphonamides was not equally high against the concerned bacteria. The author discussed the significance of the inoculum-size and of competitive and noncompetitive sulphonamide-antagonists in commercial culture-media and the difficulties they raise by the interpretation of the results.


[Long-term toxicity of benorylate].

[Long-term toxicity of benorylate]. A long term study was carried out to determine the possible toxic effects of therapeutic doses of a suspension of benorilate on bone marrow, liver and kidneys in 33 patients with rheumatoid arthritis. 14 were male and 19 femal patients. 11 of the male and 14 of the female patients presented a positive rheumatoid factor. The duration of the treatment was first limited to 6 months. In 20 of the 33 patients duration of treatment was extended to 7 and 91/2 months. Three patients interrupted treatment after respectively 2, 3 and 5 months. Benorilate was given in a daily dosage varying from 6-8-12 g (as a suspension containing 40% benorilate). The following parameters were used to determine the effect of the drug on bone marrow: Hemoglobin, erythrocyte count, leucocyte count, thrombocyte count. Tests were done at regular intervals to determine a possible toxic effect on the kidney: urea nitrogen, uric acid, creatinine and urineanalysis were performed at regular intervals. To determine any possible hepatic toxicity, SGOT, SGPT, alkaline phosphatase and prothrombin time were done at regular intervals. On the basis of the laboratory results, no toxicity could be demonstrated in bone marrow, liver and kidneys when benorilate was given in therapeutic doses for the treatment of rheumatoid arthritis. Rare temporary abnormal laboratory values are not statistically significant and can be considered part of systemic involvement secondary to rheumatoid arthritis. The combination of the two active substances of benorilate decreases to a minimum on the one hand the above mentioned side effects and on the other potentiates the therapeutic and especially the analgetic effect. After resorption, the preparation is hydrolized in the plasma to acetylic salicylic acid and paracetamol. The hydrolysis takes place in the gastrointestinal tract which probably explains why the drug is so well tolerated.


[Toxin production by enteropathogenic colibacilli in adult persons (author's transl)]. Culture filtrates of enteropathogenic strains of E. coli from adult patients with cholera-like diarrhoea produced a rhythm-disturbing effect when injected into isolated sacklets of rabbit ileum. This action was shown to be medium-dependant. It could not be elicited by cultures grown in synthetic medium. Meat extract cultures gave variable results, but the gut movements could be irritated regularly when cultures were grown in a casamino acids - yeast extract medium (table, figure). This activity which was not associated with non-pathogenic strains appeared in the beginning of the stationary phase of growth. The factor responsible for the dysrhythmic effect could be precipitated by ammonium sulphate, was dialysable, withstood boiling for 10 minutes (figure) and treatment with trypsin, chymotrypsin and pancreatin. Antisera prepared against culture filtrates of strain 10407 containing agglutinating and vascular permeability neutralizing antibodies did not neutralize the gut irritating effect efficiently. We conclude that the factor of our assay system is perhaps closely related to the heat-stable enterotoxin described by other authors concerned by E. coli enterotoxins.


[Toxigenesis of Clostridium novyi type A. 2. Communication: Extraction alpha-toxin from the cells by hypertonic buffers (author's transl)]. Great amounts of alpha-toxin produced by Cl. novyi type A and accumulated within the cell can be extracted by 0,2M sodium citrate buffer (pH 7,7) during the course of 2 to 5 days at 37 degrees C. Physiological saline, 0,1 M sodium citrate buffer (pH 7,7) and 0,05 to 0,2 M EDTA-buffers (pH 7,7) were not effective for complete extraction. During the process of extraction the lattice like structure of the peripheral part of the Cl. novyi cell wall was partially destroyed. The lattice is supposed to be a diffusion barrier for the toxin and may be regarded as one reason for the toxin accumulation in Cl. novyi.


[Practical considerations on treatment with antipsychotic preparations]. On the basis of a study of several hundred patients using the method of a double blind control the author showed the possibility of a successful maintenance treatment using intermittent dosage schedules with a marked reduction in the administration of antiparkinsonic agents. It is also demonstrated that patients under the age of 40 currently hospitalized less than 10 years on high doses of chlorpromazine in addition to showing generalized symptom reduction showed significant improvement in areas of social adjustment.


[Rational utilization of the major tranquilizers]. The author examined a group of drug-free patients who during the subsequent period of I month received chlorpromazine. These patients were studied for the chlorpromazine content in the blood, pupilzise, handwriting test, EEG and mental state. The level of chlorpromasine was maximal in the first 2 weeks and then declined. Changes in the peripheral autonomic measures correlated with those in the plasma levels and with an increased liver hydrozylation. Changes in the central measures were inconsistent. A 3-week treatment with phenobarbitone and antiparkinsonic drugs accelerated the metabolism of chlorpromazine. An increased metabolism of chlorpromazine in the intestine and liver may be the cause of the patients' resistanec to chlorpromazine therapy.


Fluorescence of tyrosine residues in the basic trypsin inhibitor from bovine lungs. Fluorescence of 0.02 - 2% water solutions of basic trypsin inhibitor in the temperature range of 5 - 80 degrees C at pH 2.6 and 7.7 has been investigated and changes of the relative emission at 302.5 and 307.5 nm analysed. The observed fluorescent effects were ascribed to individual tyrosine residues in the protein molecule. The temperature-dependent changes of spectra were discussed in terms of possible influence of molecular aggregation in solution at higher protein concentrations.


[Microcalorimetric determination of thermochemical parameters of the phosphofructokinase reaction]. A calorimetric procedure for determining deltaH, deltaG, deltaS and Keq of a bimolecular reaction with two or more products is described. By using this method the thermodynamic parameters of the phosphofructokinase reaction are determined. At pH 7.0 and 25 degrees C a reaction enthalpy of-6.96kcal/mole was found after correction for the neutralization enthalpy of the buffer and of the enthalpy difference of the magnesium complexes of ATP and ADP, respectively. The free energy of the phosphofructokinase reaction has been found under these conditions to be -3.96kcal/mole.


[Studies on bradykinin-binding cell fractions. 1. Characterization of kininase activity of the microsomal and membrane fraction from the rat uterus]. In the membrane fraction of rat uterus, kinin-destroying activity was found and characterized as kininase II by means of several kininase inhibitors. It could be shown that sudies of bradykinin-receptor interactions requires the use of kininase inhibitors like phenanthroline or the use of a stable bradykinin analogue like [8-erythro-alpha-amino-beta-phenylbutyric acid]-bradykinin.


Studies on 17 beta-hydroxysteroid dehydrogenase in human endometrium and endometrial carcinoma. III. Partial purification and characterization of the microsomal enzyme. Microsomal 17 beta-hydroxysteroid dehydrogenase obtained from the human secretory endometrium (17 beta-HSD) was solubilized with triton X-100. A 4-fold purification was achieved by ammonium sulphate precipitation and isoelectric focusing. In the presence of glycerol the partially purified enzyme was stable at 4 degrees C for at least 48 h. Using crude microsomes, the conversion of oestradiol to oestrone was linear with time and with the concentration of protein. The optimum temperature was approximately 40 degrees C and the optimum pH 9.4. For the reduction of oestrone the optimum pH was 6.5. With NAD, oestradiol was oxidized approximately three times more rapidly than with NADP. Km-values for oestradiol were nearly the same in endometrial carcinoma and in proliferative and secretory endometrium (i.e. approximately 3 X 10(-6) M). The maximal velocity was highest in secretory endometrium. Testosterone and androstenedione could also serve as substrates but they were interconverted more slowly than oestradiol and oestrone. Sulphhydryl groups were shown to be essential for catalysis.


Evaluation of a new method for the intragastric titration of gastric juice. A new method for the intragastric titration of hydrochloric acid with a pH sensitive telemetric antimone electrode connected via a receiver to an electronic trigger, which regulates a pump for the inflow of 1 M KHCO3 solution, was evaluated in 22 achlorhydric patients by a series of intragastric instillations of 0.1 N HCl. In vitro this procedure presented a high precision (r = 0.99). Under in vivo conditions a significant correlationship (r = 0.84, p = 0.001) between the input of hydrochloric acid and bicarbonate in a range from 1.4 to 16.7 mEq/30 min could be established in non-operated subjects. The average coefficient of variation was 34%. In subjects with partial gastrectomy (Billroth II) overtitration of 100% (y = 2.1 x -1.7, r = 0.78, p = 0.001) was recorded, suggesting an increased loss of bicarbonate related to the accelerated gastric evacuation.


[Histochemical evidence of aminotransferases. II. Localization of aminotransferases in the medulla spinalis and metencephalon of the rat (author's transl)]. The cytochemical and topochemical localization of 10 aminotransferases have been studied in a serial slices through the spinal cord, medulla oblongata, pons and cerebellum of the rat. In the gray matter a high enzyme activity was observed. The reaction product was localized in the cells and the surrounding neuropil. The cell nuclei were found negativ. In some nuclei aminotransferase activity was higher in the neurons than in the neuropil. In the other nuclei there were no recognizable differences in staining intensity between the neurons and the neuropil. The nerve cells of spinal cord and reticular formation, nuclei n. hypoglossi and n. facialis, nucl. vestibularis lateralis and the Purkinje cells exhibited particularly high aminotransferase activity.


[The mucous secretion anisotropy of the sublingual gland of the guinea-pig by means of topo-optical histochemical reaction (author's transl)]. The authors study the mucous secretion of sublingual gland of the guinea-pig by means of topo-optical histochemical reactions with polarized light. They show a "paracristalline" organization of glucidic and protidic portion of these macromolecules. The results are discussed and compared with those of the literature.


[Histochemical investigations in the experimental unilateral cryptorchism of the dog after HCG-treatment (author's transl)]. The behavior of various enzymes in the orthotopic and dystopic dog testis was examined under the conditions of experimental unilateral cryptorchism after HCG-treatment over a period of 3 months. The following findings could be obtained: 1. Under the HCG-application the orthotopic impuberal testis there was a change of behavior of the enzyme in the tubuli and Leydig-cells in comparison with test animals. A loss of LDH of the epithelium of the tubuli can be avoided through HCG-treatment. 2. In the dystopic testis of the impuberal animal, HCG cannot avoid this loss of LDH in the epithelium of the tubuli. In the Leydig cell complexes the Glucose-6-Phosphate-Dehydrogenase shows an increase of activity. 3. In the Leydig cell complexes of the impuberal testis an apparent loss of LDH is noticeable in the epithelium of the tubuli, while the non-specific esterase, SDH and the Glucose-6-Phosphate Dehydrogenase increases in activity. The activity of the Leydig cell complexes shows the expected stimulation. The present results prove that under a large dose of HCG-treatment can lead to different changes in the enzymes of the orthotopic testis of dogs.


Relationship between pycnotic indec Qp as a result of oxygen supply and similar indices as a result of in vitro offer of cytochrome c and NADP in psychiatry. The authors follow up on their previous studies of morphological changes in the properties of white blood cells represented by the oxygen pycnotic index Qp in patients with the schizophrenic syndrome. Several years of research made it obvious to them that this index remains generally unaffected by drugs administered during the treatment although the patient does show a pronounced clinical change. They decided to substitute the offer of oxygen by adding a supply of cytochrome c and NADP, i.e. by substances that give a boost to the oxidoreduction processes within the cell. They found the pycnotic quotient, based on cytochrome c, and - to an even greater degree - the NADP-based quotient to be more responsive to differences in the seriousness of the disease than the oxygen quotient.


Cardiovascular effects of benzquinamide in man. Benzquinamide HCl, a new antiemetic agent, was studied in twelve healthy volunteers. Each subject received intravenously both benzquinamide (0.7 mg/kg) and placebo in a randomized, double-blind crossover manner. Cardiac output and arterial pressure, arterial blood gases, respiration (tidal volume and rate), and oxygen consumption were measured twice before drug administration and at 5, 10, 20 and 30 min after injection. Intra-arterial pressure increased significantly (P less than 0.005) at 5 min (12.6%) and 10 min (8.6%) following benzquinamide. Likewise, peripheral vascular resistance increased significantly (P less than 0.005) at 5 min (14.3%) and 10 min (8.8%) post-injection. Cardiac output, stroke volume and heart rate remained essentially unchanged. A significant increase (P less than 0.025) in respiratory rate was observed at 10 min (8.7%) and 20 min (12.6%) following benzquinamide. Values for the arterial Po2, Pco2, and pH showed no significant changes. It is considered that the effect of benzquinamide in increasing intra-arterial pressure is due to the increased peripheral vascular resistance.


Effects of hypothermia and hyperthermia on brain energy metabolism. The influence of elevated and reduced body temperatures upon the metabolic state of the brain was evaluated from the tissue concentrations of phosphocreatine (PCr) ATP, ADP and AMP and from the concentrations of glucose, lactate and pyruvate in immobilized and artificially ventilated rats anesthetized with 70% N2O. The results were compared to the results obtained in normothermic animals. It was found that rats with body temperatures of 32 degrees and 22 degrees C had the same brain tissue concentrations of high energy phosphates and the same adenylate energy charge as the controls, but hypothermia led to a progressive decrease of both cerebral and arterial lactate and pyruvate concentrations. A metabolic acidosis but no excess lactate appeared in the blood. At a body temperature of 42 degrees C, the metabolic pattern in the brain agreed with a state of hypoxia at a time when there was no sign of substrate depletion. Arterial blood showed excess lactate which may indicate an inadequacy of the oxygen supply also to other tissues.


Pulmonary and circulatory reactions during total hip replacement surgery. The pulmonary and circulatory reactions to insertion of the acetabular and of the femoral prosthesis were studied during total hip replacement surgery in 22 patients with osteoarthrosis. The patients were given lumbar epidural analgesia and were divided into two groups. One group of 15 awake patients breathed air spontaneously (group A). The other group of seven patinets received additional anaesthesia with controlled ventilation with air (group B). This permitted an evaluation of the influence of the ventilatory pattern on the pulmonary and circulatory reactions to the surgical events. The greatest alterations were observed following impaction of the femoral prosthesis. This event caused the following statistically significant changes in both groups: An increase in total pulmonary venous admixture (from a mean value of 6.8 to 12.2% in group A and from 8.2 to 10.5% in group B) and a decrease in arterial oxygen tension (group A: 80.3 to 71.5 mmHg; group B: 82.6 to 76.9 mmHg); an increase in pulmonary vascular resistance (group A: 122 to 155 dyn -s- cm-5; group B: 129 to 164 dyn -s- cm-5) and an increase in mean pulmonary arterial pressure (group A: 17.3 to 19.0 mmHg; group B: 21.8 to 24.4 mmHg). Furtheremore, within the first 2 min after impaction a distinct transient rise in mean pulmonary arterial pressure by 2-4 mmHg was noted in a few patients, and in many patients the mean systemic arterial pressure decreased by 5 mmHg or more. No significant changes were found in cardiac output, pulmonary capillary wedge pressure, oxygen uptake, mixed venous oxygen tension, acid-base values, ratio of total dead space to tidal volume, or total airway resistance. The above findings indicate a tendency to pulmonary vascular and peripheral airway constriction leading to transient ventilation/perfusion disturbances and a decrease in arterial oxygen tension, and peripheral vasodilatation leading to a transient decrease in systemic arterial pressure.


The effect of controlled halothane anaesthesia on splanchnic oxygen consumption in the dog. The influence of halothane ansesthesia on splanchnic oxygen flow and oxygen uptake was studied in seven dogs. Mean oxygen supply to the liver and the portally-drained tissues decreased significantly to 44% and 53% of control values, respectively, while mena oxygen consumption diminished insignificantly to 68% and 82% of control values, respectively. There was a fall in the oxygen flow/oxygen consumption ratio in all animals following halothane. The relatively unimpaired oxygen uptake, in spite of a diminished oxygen supply, led to an increased extraction of oxygen by the tissues. Some factors affecting oxygen utilisation during halothane anaesthesia are discussed.


Etidocaine in intercostal nerve block for pain relief after thoracotomy; a comparison with bupivacaine. For pain relief after thoracotomy, intercostal nerve block with etidocaine 1% and bupivacaine 0.5%, both containing adrenaline 5 mug/ml, was used. Duration of skin analgesia for sharp pain was around 11 hours for both solutions. Post-operative pain was noted 6 and 5 hours after injection for etidocaine and bupivacaine respectively. No pathological changes in acid-base balance or ventilation were observed. Peak expiratory flow decreased to 35-40% of the pre-operative values and remained at this level for about 12 hours. Arterial and venous blood levels of the local anaesthetics were low and no signs of toxicity were noted. All patients experienced a certain pain relief from the blocks. Because of shoulder pain in some patients intercostal nerve block alone does not seem to be a perfect post-operative method for pain relief after thoracotomies.


Bacterial flora in relation to cataract extraction. I. Material, methods and preoperative flora. The conjunctival flora of 499 patients was studied the day before cataract extraction, no antibiotics or chemotherapeutical agents had been used before admission. Staphylococcus albus was by far the most common micro-organism (95.4%), followed by corynebacteria (44%), Staphylococcus aureus (14.9%), gram-negative bacilli (7.8%) and pneumo-streptococci (4.4%). Corynebacteria was isolated more frequently in the presence of S. albus, while S. aureus and gram-negative bacilli were found more frequently in the absence of S. albus. No relationship could be demonstrated between the occurrence of pneumo-streptococci and S. albus. The flora of the nose and skin of the face were studied and compared with the conjunctival flora, and a similarity could be observed. Furthermore, strains of S. aureus isolated at the same time from the two or three regions, in most cases, showed the same bacterio-phage type complex. The conjunctival flora was further correlated with sex, age, season, and number of polymorphonuclear neutrophils recovered from the conjunctival fluid. The incidence of corynebacteria and gram-negative bacilli was found to be higher in males, while corynebacteria was the only organism to show seasonal variation, i.e. was isolated more frequently in the second and third quarters of the year. No correlation could be found between age or number of neutrophils.


Bacterial flora in relation to cataract extraction. II. Peroperative flora. The peroperative flora of 499 patients undergoing cataract extraction was studied with local bacterial cultures taken at the beginning and end of surgery and compared with the preoperative flora examined previously (Fahmy et al. 1975 b) on admission the day prior to surgery. The local application of a single dose of oxytetracycline - polymyxin B, approximately 18 hours before surgery, significantly reduced the incidence of bacteria at the time of surgery. However, 92% of the conjunctivas examined immediately before operation proved to harbour one or more kinds of microorganisms. Futhermore, 61% of the wound sites were found to be contaminated with bacteria at the conclusion of surgery. The reasons are discussed. The origin of Staphylococcus aureus isolated peroperatively from the conjunctiva and wound site was studied. The great majority of strains could be traced to the patient's own conjunctiva preoperatively. In a few cases S. aureus was traced to the patient's own nose, skin of face or to the surgeon's nose. The air of the wards and operating theatre as well as the hands and gloves of surgeons and assistant nurses apparently did not play any role as a source of S. aureus infection.


Histochemical demonstration of an LNA-splitting enzyme in the cerebellum of the rat. A aminopeptidase-like reaction localized selectively in the granular layer with acid pH optimum. Histochemical investigations of leucine aminopeptidase using LNA (L-leucyl-beta-napthylamide) as a substrate reveals a marked enzyme activity selectively localized to the granular layer with inconspicuous reaction in the stratum moleculare and the Purkinje cells in the rat cerebellum. The LNA-splitting enzyme differs from the well-known leucine aminopeptidase (LAP) by its optimum at pH 5.5. The necessary long incubation period used in the present study, and its focal precipitation of the enzyme reaction product in the same place, like acid phosphatases, in the granular layer, suggest a lysosomal localization. The functional role of the LNA-splitting enzyme has been discussed; it is considered that it is involved not only in the protein transformation for synaptic function, but may perhaps also play an important pathogenic role in necrosis, atrophy or even autolysis.


On histochemical enzyme changes in association with canalicular activity of alkaline phosphatase in human liver. 56 human liver biopsy specimens with insignificant or no histological changes, but with abnormally strong canalicular alkaline phosphatase activity, were studied histochemically for other enzyme changes. In comparison with normal specimens, more extensive and increased canalicular activity of gamma-glutamyl transferase, and increase of canalicular leucine aminopeptidase, was found, while the sinusoidal activity of the latter enzyme was decreased. Staining for adenosine triphosphatase regularly desclosed the normal pattern of sinusoidal and canalicular activity. The lysosomal enzymes, acid phosphatase and beta-glucuronidase, stained more intensely than ordinarily, while the reactions for enzymes present in the cytosol (lactic dehydrogenase), in the mitochondria (succinic dehydrogenase, imonoamine oxidase) and in the endoplasmic reticulum (glucose-6-phosphatase) were normal.


The effect of Ca++, Mg++ and H+ on the capillary permeability of the rete mirabile of the eel, Anguilla vulgaris L. The effects of EDTA, and of varying pH on the capillary permeability in the rete mirabile have been investigated: EDTA had to be added to the perfusate in excess to the total content of Ca++ and Mg++ in plasma in order to elicit changes in the permeability. When exposed to sufficient amounts of EDTA, the capillary permeability to hydrophilic molecules increased several fold whereas the permeability to THO and lipid-soluble molecules remained unchanged. The increase in the permeability to high-molecular dextrans was delayed. When the EDTA-effect was maximal the mutual relationship between the permeabilities of THO and the lipid-insoluble molecules became close to the ratio between the corresponding free diffusion coefficients in water. During exposure to EDTA the content of K+ and Na+ of the rete tissue (mostly endothelial cells) became very similar to that of plasma. Similar effects were obtained when the rete was perfused with plasma having a pH below 4 or above 9. The EDTA-effect was reversible during its initial stage. Perfusions with plasma in which Ca and Mg had been removed by dialysis at pH 3.5 were performed. When an EDTA-effect had been induced with this type of perfusates, it could be reversed by addition of equimolar amounts of either Ca++ or Mg++. This indicates Ca++ and Mg++ to be equally important in order to assure normal permeability properties of the capillary membrane.


Cardiovascular responses to changes in carotid sinus transmural pressure in man. To study the relative importance of cardiac and peripheral effector mechanisms in the carotid sinus baro-reflex in man cardiovascular responses to equal changes of the carotid sinus transmural pressure (Ptm) in either direction of the normal were recorded and compared in eight physically well-trained young male volunteers. In both the supine and the 70 degrees head-up position, a decrease in Ptm produced a more potent reflex response of the systemic arterial pressure than did a similar increase in Ptm. Whereas the arterial pressure response to increased Ptm was due solely to a reduction in vascular resistance, a significant increase in cardiac output contributed to the more potent pressor response to a decrease in Ptm and thus to the predominantly antihypotensive properties that characterize the carotid sinus baroreceptor control system in man. However, since combined beta-adrenergic and parasympathetic blockade abolished the effect of reduced Ptm on cardiac output without greatly impairing the blood pressure response, it is concluded that adjustments in cardiac output are not of critical importance in the buffering function of the carotid sinus baroreceptors. Autonomic cardiac blockade exaggerated the fall in cardiac output on head-up tilt, the arterial pressure remaining unaffected due to a compensatory increase in systemic vascular resistance.


Stimulation of adrenergic nerve fibres to the urinary bladder of the rat. The contraction of the rat detrusor muscle caused by electrical stimulation of the hypogastric or pelvic nerves was followed by relaxation when the nerves were stimulated for a short period. The relaxation was more pronounced when the initial contraction was reduced by atropine. It was found to be mediated by adrenergic fibres acting on inhibitory beta2-receptors. Stimulation of the hypogastric or pelvic nerves at high frequencies increased the contractile response probably via adrenergic fibres activating excitatory alpha-receptors.


Potentiation by prostaglandins e1, e2, and f2alpha of the contraction response to transmural stimulation in the bovine iris sphincter muscle. The contraction response to transmural stimulation in the bovine iris sphincter muscle was abolished by atropine but was left virtually unchanged by hexamethonium, and by adrenergic neuron and receptor blockers, indicating activation of postganglionic cholinergic nerve fibres. Low doses of prostaglandins e1, e2 and F2alpha (0.1-5.3 ng/ml) consistently and apparently in a dose-dependent manner enhanced the contraction response to transmural stimulation. Prostaglandins E1 and E2 were equipotent while F2alpha was at least 10 times less active. Within the same dose range the prostaglandins also enhanced the contraction response to exogenous acetylcholine, indicating that part of the enhancing effect of the prostaglandins on neuromuscular transmission was due to a postjunctional action. A spontaneous increase in tone of the preparation commonly occurred about 1 h after the beginning of the experiment. SC 19220, a potent antagonist of prostaglandin action, reduced the tone and the contraction responses as well as the enhancing effect of the prostaglandins. It is concluded that prostaglandins might serve the function of controlling neuroeffector transmission and muscular tone in the sphincter muscle of the bovine iris.


Influence of amino acids, thiourea and hydroquinone on cellulolytic activity in some Fusarium strains. Studies were carried out on the influence of various amino acids: cysteine, cystine, methionine, alanine, serine, tryptophan, and of thiourea and hydroquinone on the activity of cellulase synthesized by four strains of Fusarium. It follows from the results obtained that the addition of amino acids, thiourea or hydroquinone to the culture media stimulates or inhibits the activity of the enzyme studied. The effect of this action depended both on the compound and the strain studied.


The influence of glucose on simazine decomposition. Glucose added to soil and to the culture medium of Penicillium citrinum stimulated simazine decomposition. Differences in the rate of simazine decomposition depended on the dose of glucose. Both in soil and in the medium the rate of simazine decomposition was connected with the intensity of development of microorganisms.


Effect of the concentration of available carbon compounds on the microbial reduction of sulphates. A change of the concentration of available carbon compounds in the reaction medium affecting the carbon to sulphur ratio (C/S) affects the reduction degree of sulphates. The time interval between the initial and the log phase of the process (to) also varies depending on the concentration of carbon compounds. It was demonstrated that optimal reduction conditions for the strain Desulfovibrio desulphuricans used exist in media of C/S = 1.84 +/- 0.2. Kinetic data for the reduction process are presented.


Effect of chronic alcohol consumption on ethanol and acetaldehyde metabolism. Hepatic metabolism of ethanol to acetaldehyde by the alcohol dehydrogenase (ADH) pathway is associated with the generation of reducing equivalents as NADH. Conversely, reducing equivalents are consumed when ethanol oxidation is catalyzed by the NADPH dependent microsomal ethanol oxidizing system (MEOS). Since the major fraction of ethanol metabolism proceeds via ADH and since the oxidation of acetaldehyde also generates NADH, an excess of reducing equivalents is produced. This explains a variety of effects following acute ethanol administration, including hyperlactacidemia, hyperuricemia, enhanced lipogenesis and depressed lipid oxidation. To the extent that ethanol is oxidized by the alternate MEOS pathway, it slows the metabolism of other microsomal substrates. Following chronic ethanol consumption, adaptive microsomal changes prevail, which include enhanced ethanol and drug metabolism, and increased lipoprotein production. Eventually, injury develops with alterations of the rough endoplasmic reticulum and structural and functional abnormalities of the mitochondria.


Phosphopyridoxal complexes with histamine and histidine. (2) The influence of presumed complex on histidine decarboxylase activity in rat gastric mucosa. It was found that in vitro, histidine and histamine form a complex compound with pyridoxal-5'-phosphate (PLP). The purpose of the present experiments was to find whether formation of this complex can influence histidine decarboxylase activity. It was found that excess PLP inhibits rat's gastric mucosa histidine decarboxylase activity in vitro. The inhibitory action of PLP depends on the histidine concentration and is independent on the amount of crude enzyme preparation. The histidine-PLP complex did not influence enzyme activity. The possible mechanisms of the inhibitory action of PLP on histidine decarboxylase activity are discussed.


Phosphopyridoxal complexes with histamine and histidine. (3) The influence of presumed complex on activity of rat intestinal histaminase. Histamine in high concentration inhibits the rat intestinal histaminase (diamine oxidase E.C. 1.4.3.6.). The apparent Km is approximately 4.2 X 10(-5) M. This inhibition can be reversed by an addition of PLP. It was also found that excess of PLP inhibits enzyme activity. It is competitive inhibition. Histamine and other amines which were associated with enzyme inhibition form spectrophotometricaly demonstrable complex with PLP. The possible mechanism of the inhibitory action of PLP and complex with histamine and other amines on rat intestinal histaminase activity are discussed.


Purification and separation of enveloped and unenveloped herpes simplex virus particles. Enveloped and unenveloped forms of herpes simplex virus (HSV) occurring in infected rabbit lung (ZP line) cells were purified by differential and discontinuous Ficoll density gradient centrifugation. Then the viral particles were separated in a sucrose-D2O density gradient. In the course of the procedures, both virus preparations were freed of Mg2+-dependent Na+ plus K+-stimulated adenosine triphosphatase (ATPase), 5'-nucleotidase, and glucose-6-phosphatase activities. However, Mg2+ -activated ATPase was shown to be firmly associated with purified virions. The recovery of infectious virus was 50-60 percent. The specific infectivities (TCID50/mg protein) of the purified enveloped and unenveloped viral particles were 1-2 times 10(10) and 2-5 times 10(6), respectively. The infectivity of the unenveloped viral particles was discussed.


Heterogeneity of A/Singapore/1/57 (H2N2) influenza virus. The population of A/Singapore/1/57 (H2N2) influenza virus was found to contain two types of infectious particle. "Normal" virions with a diameter from 100-130 nm, a buoyant density in sucrose of 1.21 g/cm3 and a sedimentation coefficient 770 S represented about 90 percent of the population. In addition, a considerable amount of larger particles (up to 1000 nm) with a buoyant density in sucrose of 1.18 g/cm3 and a sedimentation coefficient of over 1000 S were present.


Reproduction in unadapted and adapted cells at 40 degrees C of herpes simplex virus type 1 and type 2 strains. Differences in the reproduction of infectious virus in unadapted and adapted rabbit lung cells at 40 degrees C were observed among 8 strains of herpes simplex virus (HSV) type 1 and 6 strains of HSV type 2. The adapted cells represented a permissive system for some strains of both types at supraoptimal temperature. Reproduction of HSV type 2 was not demonstrated in unadapted cells at 40 degrees C. Strains of HSV type 1 reproduced to different titres in unadapted cells grown at 40 degrees C.


Marek's disease virus (Kekava strain) replication in chickens, chick embryos and cell cultures. In the course of 12 passages of Marek's disease virus (MDV) strain Kekava (MDV-Kekava) in chickens, the morbidity varied greatly (from 23 to 50 percent). MDV-Kekava produced plaques in cultures of chick embryo kidney and adult chicken kidney cells and chick embryo fibroblasts (CEF). The virus adaptation to the cultures was very slow. MDV-Kekava induced the formation of pocks on the chorioallantoic membranes (CAM) of chick embryos but the proportion of embryos with CAM lesions did not exceed 24 percent. Serial passaging of the virus in chick embryos beyond the 5th passage was unsuccessful. The results of virus isolation in chickens, cell cultures and chick embryos indicate the possibility of a long-term latent virus carrier state in chickens without development of tumours.


The mutagenic effect of measles virus on cell cultures of different origin. Differences between strains of measles virus in their mutagenic effect on cells of different animals and man were found. The mutagenic activity of measles virus strains was species-specific. In the process of spontaneous transformation the sensitivity of cells to the mutagen changed.


Morphological differences in the central nervous system and organs of monkeys inoculated intracerebrally with virulent and attenuated strains of mumps virus. The degree of attenuation of mumps virus was studied in intracerebrally inoculated Macaca mulatta monkeys. The virulent Leningrad-3 strain and its attenuated variant as well as the attenuated Sophia-6 strain were used. The nature of pathological alterations in the neurons pointed to neurotropism of only the virulent strain. Morphological changes caused by attenuated and virulent strains in the brain structures, in the epithelium and glandular structures of the salivary glands differed considerably and may be used as a kind of markers of neurovirulence and the degree of attenuation of mumps virus strains.


Streptovirudins -- new antibiotics with antiviral activity. The antiviral spectrum and inhibition of Newcastle disease virus in cell cultures. Streptovirudins are new antibiotics isolated as a mixture of several structurally related compounds from fermentations of Streptomyces griseoflavus (Krainsky) Waksman et Henrici var. thuringensis JA 10124. They possess antiviral activity against RNA and DNA viruses cultivated in chick embryo cells, namely Sindbis, fowl plague, Newcastle disease (NDV), pseudorabies, vaccinia and sheep abortion viruses. The naturally formed streptovirudin complex, in concentrations of 20-2.5 mug/ml inhibited the viral cytopathic effect and caused 100 percent plaque reduction. Mengo, Coxsackie B1-B5, ECHO 30 and 33, and polio (wild and attenuated types 1, 2, and 3) viruses grown in FL cells were not sensitive in the agar-diffusion plaque-inhibition test. The antibiotics failed to show a direct virucidal effect on the NDV virion itself or to influence virus adsorption and penetration processes. Addition of streptovirudin complex during a one-step growth cycle of NDV from 0-4 hours after virus adsorption resulted in complete suppression of virus yield. The antibiotic complex consists of two main groups: I - A1, B1, C1, D1, E1 and II - A2, B2, C2, D2, E2, each of which possess antiviral activity.


Selection for plaque variants of two California group arboviruses (Jamestown canyon and La Crosse) by passage in natural vertebrate hosts. The plaque size and distribution of prototype La Crosse (LAC) and Jamestown Canyon (JC) viruses were investigated in Vero cell cultures. The effect of serial passage of the viruses in their natural vertebrate hosts - the chipmunk and grey squirrel for LAC and the white-tailed deer for JC virus - was studied. Prototype JC virus was predominately a pinpoint plaque type (about 0.3 mm in diameter). A large plaque variant (about 1.0 mm in diameter), which was only 1 percent of prototype JC virus, increased to over 80 percent of the resultant virus after one passage in white-tailed deer. The large plaque type (about 1.0 mm in diameter) also predominated in JC isolates from mosquitoes, biting flies, and a white-tailed deer in Wisconsin. Prototype LAC virus consisted of a variety of plaque sizes, ranging in diameter from 0.3 mm to 3.0 mm. Passage through chipmunks increased the mean plaque diameter almost twofold, whereas passage in the grey squirrel resulted in a more uniform small plaque population practically eliminating the largest plaques. Preliminary results suggest that the resultant viruses are antigenically different. If these selective processes occur in nature, they man explain how four serologically related California group arboviruses with distinct vector-host cycles in nature could have evolved and have sympatric distribution.


Growth of Tahyna virus at low temperatures. Replication of two Tahyna virus strains in the Aedes albopictus mosquito cell line was studied in the temperature range from 6 to 28 degrees C. The virus grew in this temperature range; its replication rate was related to the temperature of incubation. At lower temperatures the virus titres increased more slowly and did not reach as high maximum values as at higher temperatures. Short increase in incubation temperature resulted in a short increase in the titre of virus previously incubated at 10 degrees C, but not of virus previously incubated at 15 degrees C. At 10 and 15 degrees C, the released virus was demonstrated for more than 300 days past infection (p.i.).


Influence of early passages on the character of freshly isolated strains of Tahyna virus. The plaque size, thermostability, virulence, and average lethal time of uncloned freshly isolated strains of Tahyna virus were studied in the course of 3 passages in suckling mice. All of the 10 strains were in the 1st passage thermostable (indices 4 degrees/50 degrees C less than 1.0 log10) and highly virulent (indices ic/sc less than 1.0 log10). They differed significantly in plaque size only. The effect of 3 passages in suckling mice was manifested by titre increase and plaque size reduction. The differences in thermostability and virulence were too small as to be distinctly significant, but at least they indicated the heterogeneity of the strains. The variability in behaviour of uncloned strains and significance of changes observed during passages are discussed.


Experiences with the adaptation of crimean hemorrhagic fever virus to the CV-1 monkey cell line. Of several cell lines tested, the CV-1 monkey cell line proved to be the most suitable system for propagation of Crimean hemorrhagic fever (CHF) virus. Two CHF strains could be adapted to this cell line by serial passaging. The viral progeny from these passages was specifically cytocidal and produced plaques in CV-1 cells, which could be used in serological diagnosis of CHF. After adaptation of CHF virus to CV-1 cells, the rate of virus synthesis was more rapid, but the yield of virus produced by these cells did not substantially increase. Data reported on cultivation of CHF-Congo viruses are discussed in comparison with the present findings.


Virus neutralizing antibodies to arboviruses in birds of the order Anseriformes in Czechoslovakia. Sera from birds of the order Anseriformes in Czechoslovakia were examined for virus neutralizing (VN) antibodies to arboviruses. VN antibodies to Sindbis, Calovo and Tahyna viruses were found in 15, 5 and 6 out of 106 greylag goose (Anser anser) sera. Out of 38 ducks, 6 mallards (Anas platyrhynchos) and 1 garganey (Anas querquedula) contained VN antibodies to Sindbis virus, 6 mallards to Calovo virus, 4 mallards and 1 garganey to Tahyna virus, 2 mallards and 1 garganey to tick-borne encephalitis (TE) virus and 1 mallard to West Nile (WN) virus.


Development of sensitive methods for detection of latent Kilham virus infection of rats. The developed system of procedures, including preliminary selection of rats according to the presence of 19 S antibody in the blood serum, and the use of the most sensitive methods has increased considerably the incidence of detection of Kilham virus (KV) in organs of latently infected rats. To isolate and establish KV strains from the organs of rats in which the specific antigen was detected by immunofluorescence, at least 5-9 passages in rat embryo cell cultures or in newborn Syrian hamsters were required.


Phase II to phase I conversion of Coxiella burneti in immunosuppressed mice. Coxiella burneti strains 48 and Nine Mile, serologically in phase II, changed their antigenic properties and virulence for guinea pigs and mice upon passaging in immunosuppressed mice. Conversion to phase I of these strains in a system lacking antibody response throws doubt on the importance of specific antibodies in phase variation of C. burneti.


Morphological methods of Kilham virus detection. Morphological investigations on organs from Kilham virus (KV)-infected Syrian hamsters revealed acute glomerulonephritis with a clear-cut haemorrhagic syndrome. No pathological changes were found in internal organs from KV-infected rats.


Electron microscopic demonstration of Crimean hemorrhagic fever virus in CV-1 cells. Crimean hemorrhagic fever (CHF) virus was detected by electron microscopy in ultrathin sections of CV-1 cells. The virus particles appeared spherical or oval and occurred both intra- and extracellularly. Based on their size and density of their contents, two types of virions, probably representing different phases of the reproduction cycle of CHF virus, could be distinguished.


Characteristics of Sendai virus RNA transcriptive complex formed in the cytoplasm of infected ascites cells. Virus-specific structures with sedimentation coefficients of 250-300, 200 and 150 S were isolated from the polysome fraction of Sendai virus-infected Ahrlich ascitic carcinoma cells treated with cycloheximide, at early stages of infection (1.5 to 2 hours after inoculation). All these 3 types of structure contained both parental and newly synthesized viral RNA. RNA extracted from these structures consisted of 2 components sedimenting in sucrose density gradients in the zones of 50-70 and 35-40 S. Both components contained parental and newly synthesized RNA and were partially resistant to ribonuclease. RNA extracted from rapidly sedimenting structures (250-300 S) contained mainly the 50-70 S component; RNA recovered from 200 S structures contained the 35-40 S component. By analogy with reported data, the isolated forms of RNA have been characterized as transcriptive intermediates.


Purification of togavirus haemagglutinins by chromatography on controlled pore glass. Purified preparations of haemagglutinins from Sindbis, West Nile and tick-borne encephalitis (TBE) viruses could be obtained from infected mouse brains by alkaline extraction, precipitation with protamine and chromatography on polyethylene glycol-coated controlled pore glass with 242 A pore diameter.


The effect of temperature and urea on virulent and attenuated strains of pseudoabies virus. Out of 10 virulent strains of pseudorabies virus (PRV), 9 proved to be resistant and 3 out of 4 attenuated strains were sensitive to the temperature of 53 degrees C. No differences were found between attenuated and virulent strains of PRV in their rate of inactivation of 2 M urea; its inactivating effect was enhanced by increasing the temperature. The t (effect of temperature) and u (effect of urea) markers proved unsuitable for a sufficient characterization of PRV strains.


Physico-chemical characteristics of interferons induced by human adenovirus in chick fibroblasts and leucocytes. The physico-chemical characteristics of interferons with different anti-viral activities produced in chick fibroblast cells and leucocytes in response to the human adenovirus type 12 were investigated. The molecular weights of interferons produced by chick fibroblasts and leucocytes were similar: the main anti-viral activity was found at 27000 and 32000 and a low-titered shoulder at 28000 and 23000 respectively. Under our experimental conditions no oligomeric structure of interferons could be detected. The isoelectric pattern of leucocyte interferon was slightly different from that of the fibroblast interferon.


Herpesvirus-induced availability of host DNA to exogenous endonuclease. Deoxyribonuclease I penetrates herpesvirus-infected L cells and degrades host DNA without interfering with viral multiplication. The DNA of uninfected control monolayers of L cells, disrupted by scraping, is similarly attacked. In contrast, undisturbed L cells are not affected. This suggests that altered cell membrane permeability allows the nuclease to enter the cell, thereby permitting access of exogenous deoxyribonuclease to cellular DNA.


Polymorphism of human blood groups and incidence of influenza A/Hong Kong (H3N2). During three epidemics of influenza A/Hong Kong (H3N2) and experimentally in vaccines, the relation between influenza infection and ABo, Rh and MN blood groups was studied. Examinations of 2760 patients with laboratory-confirmed diagnosis of influenza and 749 persons vaccinated with live influenza vaccine showed that individuals of blood groups O and B were susceptible to influenza 1.67 and 1.20 times more, respectively, than individuals of blood group A. The difference in incidence was most manifested in first attacks and decreased in subsequent epidemics. The increased incidence in individuals of blood groups O and B as compared to those of blood group A was not associated with factors of specific (antibody) and nonspecific (interferon) resistance to influenza but was related to a greater capacity of leukocytes from these individuals to adsorb the virus. No relation between blood groups Ph and MN and incidence of influenza A/Hong Kong (H3N2) was established.


Diagnosis of rhinovirus-infections by virological and immunofluorescent methods. In January--May, 1971, detection of rhinoviurs infections among ambulatory patients with respiratory diseases in Moscow was carried out in parallel by virological and immunofluorescent methods. Rhinovirus infections were virologically confirmed in 13% out of 238 patients. By the indirect immunofluorescence technique, rhinovirus antigens of serotype 17 were detected in 2.2% out of 220 patients, of type 1B in 4.3% out of 183 patients, of type 48 in 5.6% out of 123 patients and of type 7 in 4.6% out of 86 patients. The use of immunofluorescence supplemented the results of virological examinations and increase the effectiveness of aetiological diagnosis of rhinovirus infections.


Phagocytosis of Coxiella burneti by macrophages. Live or killed purified phase I and phase II Coxiella burneti organisms were phagocytized to a similar extent by mouse or guinea pig peritoneal macrophages and polymorphonuclear leukocytes (PMN); phase II was much more susceptible to phagocytosis than phase I. Phagocytosis of phase I was enhanced only by immune sera containing phase I antibodies. Increased in vivo phagocytosis of phase I organisms by macrophages from animals immunized with live phase I C. burneti was lost following their in vitro cultivation and washing.


Use of duck embryo cell cultures for the study of arbovirus reproduction. Duck embryo cell (DEC) cultures were used for the study of arbovirus reproduction. High sensitivity of DEC cultures to Japanese encephalitis, West Nile, Tyuleniy, Sakhalin and Baku viruses was established. DEC cultures are recommended for investigation of arbovirus reproduction.


Some properties of clover blotch virus.

Some properties of clover blotch virus. Clover blotch virus (CBV) was purified by differential centrifugation or precipitation with polyethylene glycol 6000 or 20000. Analytical centrifugation of purified CBV preparations revealed 2 components, the proportions of the lighter (96 S) nad heavier (112 S) being 88 and 12%, respectively. RNA isolated from purified CBV represented a micture of several RNA species of different molecular weight and its infectivity was by about 2 log units lower than that of the original nucleoprotein. CBV virions are isometric with a diameter of 28 nm. CBV is tentatively included into the Cucumovirus group.


Isolation of spotted fever group and Wolbachia-like agents from field-collected materials by means of plaque formation in mammalian and mosquito cells. Three isolations from ticks (Dermacentor occidentalis) of a rickettsia of the spotted fever group and 5 isolations from chipmunk (Eutamias rugicaudus) blood of a Wolbachia-like agent were obtained from plaques formed in Singh's Aedes albopictus (mosquito) and Vero (African green monkey kidney) cell cultures. These organisms could not be isolated by injection of the infected ticks or blood into embryonated chicken eggs, guinea pigs, or voles (Microtus pennsylvanicus), but fluid cultures of Grace's Antheraea eucalypti (moth1 and Singh's A. albopictus cells inoculated with the bloods yielded the Wolbachia-like agent.


A rapid method for the determination of fluoride in vegetation. An analytical procedure for the determination of fluroide in vegetation has been developed to aid in environmental studies. The method involves leaching the vegetation with a hot solution of strong base and then determining the fluoride in an acidified solution directly with a fluoride selective ion electrode.


Removal of cyanoacrylate vapor from work spaces by activated carbon. The purpose of this research program was to evaluate several gas sorbents for methyl-2-cyanoacrylate vapor collection efficiency and service life in portable, recirculating room air filters. Two acid carbons were found to be effective and are recommended for further evaluation under actual field conditions.


Thin layer chromatographic identification of phenothiazines in urine specimens. Two newly developed, thin layer chromatographic (TLC) solvent systems are presented to separate and identify commonly used phenothiazines in the presence of other drugs in urine specimens. These solvent systems are 1) ethyl acetate: n-butanol: concentrated ammonium hydroxide (89:10:1.5) and 2) ethyl acetate: O-dichlorobenzene: concentrated ammonium hydroxide (90:9:1.4). The phenothiazines are identified on the TLC plates both by Rf values and by colors produced with ethanolic sulfuric acid and palladium chloride sprays. With this method 0.025 mug/ml levels of unchanged phenothiazines can be detected in urine specimens.


The effect of increased maternal PaO2 upon the fetus during labor. The effect of increased maternal PaO2 upon the fetus during labor was studied in 36 subhuman primates. The animals were divided into two groups, one in which the fetus was not asphyxiated and showed no evidence of fetal distress (Group I) and another in which the fetus was acidotic, hypoxic, and exhibited the pattern of late deceleration of the heart rate (Group II). One hundred per cent oxygen was administered to the mothers for a period of 30 minutes. Elevation of maternal PaO2 to 430 mm. Hg increased fetal oxygen levels in Group I. and in most instances in Group II, without significant changes in the acid-base state. In Group II, maternal hyperoxemia also abolished or reduced the frequency of late deceleration of the fetal heart in most animals but had little or no effect on fetal blood pressure. Termination of high-concentration oxygen to the mother resulted in a fall in maternal and fetal oxygen levels to their original values and the reappearance of late fetal heart decelerations. Thus, administration of high-concentration oxygen to the mother for the treatment of fetal distress may be of some benefit. The problems of fetal acidosis and hypotension are not cured, however, and may still progress if there is placental insufficiency or cord compression. Therefore, this treatment should be regarded as a temporary supportive measure only.


Pharmacologic control of uterine contractility. In vitro human and in vivo monkey studies. The exact cause and mechanism of the onset of labor are unknown but the theories are many. There is considerable evidence that prostaglandins are potent stimulants of uterine activity and may play a role in the onset of labor. Prostaglandin release may be the natural mediator of uterine contractions during labor. A group of anti-inflammatory compounds (aspirin-like compounds) that inhibit prostaglandin synthesis include indomethacin and fenoprofen. Inhibition of prostaglandin production is a reasonable approach to inhibiting premature labor. An excised muscle strip technique was used as a screening procedure for pharmacologic depression of human uterine activity in vitro, testing isoxsuprine, mesuprine, Alupent, ritodrine, indomethacin, and fenoprofen. The prostaglandin antagonists indomethacin and fenoprofen exhibited marked depressant activity. These drugs were further tested in an in vivo rhesus monkey preparation measuring uterine activity, maternal blood pressure, uterine blood flow, fetal heart rate, fetal blood pressure, and blood gases. Fenoprofen is effective in reducing uterine contractility without serious maternal or fetal side effects and shows promise as a clinically effective agent for pharmacologic control of premature labor.


Secondary ocular bacterial infection in hypovitaminosis a xerophthalmia. Extraocular bacterial culture was performed in 100 patients with hypovitaminosis A xerophthalmia. There was corneal ulceration in 29 cases and corneal perforation in 22 cases. Eighty-six percent of the patients harbored frankly pathogenic bacteria (46 patients) and potentially pathogenic bacteria (40 patients). All but two patients with either cornal ulceration or perforation harbored potentially pathogenic or frankly pathogenic bacteria. Pseudomonas aeruginosa, Diplococcus pneumoniae, and Moraxella species were isolated in 37% (19 patients) of cases with corneal ulceration and perforation. I cultured P. aeruginosa from 36% (eight patients) of cases with corneal perforation. The many ocular secondary bacterial infections in the early stages of xerophthalmia seem to suggest that bacterial action plays a major role in causing the corneal ulceration and perforation in hypovitaminosis A xerophthalmia.


Hepatotoxicity of vinyl chloride and 1,1-dichloroethylene. Role of mixed function oxidase system. Vinyl chloride, an occupational carcinogen, produces acute liver injury in rats pretreated with phenobarbital or Aroclor 1254. Injury appears related to morphologic changes in the endoplasmic reticulum. The degree of injury, as indicated by elevation of serum enzymes derived from the liver, correlates with the magnitude of induction of cytochrome P-450 and its reduction by NADPH. Hepatic injury following 1,1-dichloroethylene exposure differs strikingly from that caused by vinyl chloride and appears to involve plasma membranes, mitochondria, and chromatin and spares endoplasmic reticulum. Induction of cytochrome P-450 appears to protect against 1,1-dichloroethylene but not vinyl chloride.


[Blood-pressure regulating drugs and intraocular pressure in animal experiments (author's transl)]. Electromanometric measurements of blood pressure and intraocular pressure, carried out in rabbits after the intravenous administration of Norphen, Peripherin, Sympatol, Hydergin, Tropodil, Complamin, Euphyllin and Vasculat showed that the changes in the pressure curves were largely in the same sense. Apart from a "passive" correlation of the intraocular pressure with the blood pressure, the local effects of pharmaceuticals administered are also discussed. The results obtained provide both general medicine and ophthalmology with insights into the mode of action of drugs, some of which are frequently administered. In addition, they serve both to provide information on the desirable curative effects of the drugs and to help prevent damage being done to the organ of sight.


Hyperventilation in neurosurgery.

Hyperventilation in neurosurgery. An outline of the nature and varieties of hyperventilation is presented together with a discussion on the role of artificial hyperventilation in the management of neurosurgical patients. Attention is called to the value of gasometric investigations in the ventricular cerebrospinal fluid for evaluation of disturbances in pH of the intracranial environment and possible effectiveness of hyperventilation. The results of our measurements of cerebrospinal fluid pressure are presented in 21 cases of supratentorial cerebral tumours in which controlled ventilation with hyperventilation was conducted. In 19 cases, the cerebrospinal fluid pressure fell by a mean of 44.3% with a simultaneous fall of PaCO2 by 29.3%. In the conclusions the authors stress the role of hyperventilation in the lowering of raised cerebrospinal fluid pressure and prevention of cerebral oedema.


Reversal of lorazepam delirium by physostigmine. Two adult patients suffered postoperative delirium following administration of lorazepam, a new benzodiazepine sedative. Physostigmine was found effective in reversing all untoward central nervous system effects.


[Cardiovascular effects of Rohypnol used as an agent to induce anesthesia]. The study involved 34 surgical patients in whom anaesthesia was induced by the intravenous injection of an average dose of 2.5 mg of flunitrazepam (Rohypnol or Ro-5-4200). The induction of anaesthetic sleep was obtained in 50 to 60 seconds and the duration of the anaesthetic effect 15 to 20 minutes. The patients continued to show hypnosedative effects for several hours postoperatively. The cardiovascular parameters studied - radial BP, ECG and pulmonary arterial pressure - were recorded directly whilst cardiac output was measured by thermodilution using a Swan-Ganz catheter. The decrease in systolic and diastolic pressures in relation to pre-anaesthetic values was 21 p. 100 and 16 p. 100 respectively, whilst pulmonary artery pressure fell by 13 p. 100. Cardiac output fell in a non-significant fashion and the same applied to systolic ejection volume for a given constant heart rate. There was a significant (18 p. 100) decrease in total peripheral resistance but alterations in central venous pressure were negligeable. The decrease in peripheral vascular and pulmonary artery resistances suggest that the product has a peripheral circulatory action and it is possible to correct the alterations seen.


[Comparative study of post-anesthesia awakening and behavior following alfatesine and pentothal]. A study of behaviour during the awakening of subjects which had been anaesthetized with a single dose of Alfatesine or of Pentothal was undertaken. This comparison between two anaesthetic drugs offers the opportunity to make, firstly, a critical analysis of the methods of exploration of anaesthetic awakening which are habitually used. An attempt at the definition of this period and a review of the literature on the subject are given, as well as the possible approaches to this period, insisting principally on psychomotor tests. A list of variables which enter into consideration in this type of study completes the account of the methodology. Next, the procedure for the experimental study properly speaking is given. Seven psychomotor tests were chosen, completed by a clinical study. The timetable, the anaesthetic conditions and the process of collecting the information are explained. The clinical results and the results obtained from the tests show extensive perturbations of behaviour lasting for up to one-and-a-half hours following the injection of one or the other product. However, the intensity and the duration of the disturbances recorded are definitely greater with Pentothal. In addition, the state of anxiety before operation could be shown objectively through certain tests. A study of this type poses a certain number of problems and perspectives which are envisaged.


[Intrathoracic gas effusions of iatrogenic origin in neonatal reanimation]. Intra-thoracic gaseous collections, pneumodiastinum and pneumothorax, have become more common since the use of positive expiratory pressure, either with spontaneous ventilation or in association with artificial ventilation. In our experience, the occurence rate of such collections has increased from 7 p. 100 in 1970 to 19 p. 100 in 1974, related to the use of continuous positive pressure of long duration in the treatment of idiopathic respiratory distress or hyaline membrane disease. These gaseous collections were initially associated with a high mortality (50 p. 100) which is now practically nil. Improved knowledge of the clinical and radiological signs and the insertion of thoracic drains in the presence of the slightest doubt represent the explanation of this reduced mortality.


[Perforation of the cervical esophagus during tracheal intubation. Apropos of a personal case]. On the occasion of a personal case of perforation of the cervical oesophagus by laborious tracheal intubation which had necessitated the use of a rigid stilet, we found seven similar cases in the literature since 1971 which can be added to the 16 collected by DUBOST in 1971. We analyse the etiological circumstances, the clinical picture the course and action taken in these eight cases. From this we draw practical conclusions which are imperative during anesthesia.


[Evaluation of 1200 venous catheterizations in reanimation]. The authors present a series of 1247 venous catheterizations during resuscitation, the latter being carried out under particularly strict aseptic conditions. This series contains especially: - 364 internal jugular catheterizations; - 223 subclavian catheterizations; - 130 femoral catheterizations. The total number of days of infusion is 6300, of which 3,619 were of prolonged parenteral feeding. 79.5 p. 100 of the catheters cultured proved to be sterile; in the case of those cultures which were positive, 6.5 p. 100 were due to pathogenic organisms, 13.9 p. 100 were due to saprophytes. On the whole, 7 septicemies of venous origin (0.56 p. 100 of all of the catheterizations) were observed. The détailed study of each route shows that the frequency of cultures of pathogen positive catheters is practically the same in all cases. On the other hand, the frequency of cultures of catheters positive with saprophytes is evidently higher for the internal jugular vein; this being particularly true in the male where the role of the beard as a contaminating factor is evoked. The importance of asepsis in the procedure of putting venous catheters in place and in their maintenance seems to be welle demonstrated by the results presented.


[Automatic dosage of uric acid by urate oxydase. Comparison with Praetorius' methods]. The authors describe an automatic method of estimation of uric acid based on the colour obtained in the presence of Gaiac resin and peroxidase, and the hydrogen peroxide produced by the action of urate oxidase on uric acid.


[Value of Soludactone in cardiac surgery in adults]. The use of potassium canrenoate (Soludactone) in the post-operative period in 31 patients who had undergone open-heart surgery, in comparison with a control batch of patients, led to a more rapid and easier regression of myocardial hyperexcitability, the maintenance of kaliemia at values near normal, a reduction in kaliuresis, a rapid elevation of the urinary Na/K ratio and the maintenance of satisfactory diuresis. But the majority of these effects appear progressively during the first 3 days of treatment, so potassium canrenoate should be prescribed 3 days before the intervention so that the beneficial effects may be manifested from the day of the intervention itself.


[Auricular adynamia due to hyperkalemia]. Auricular asystoly (A.A.) was the electrocardiographic pattern of 6 patients admitted for electrolytic disorders secondary to either renal failure or inadequate treatment. A rapid increase of blood potassium was the unique commun abnormality found to explain the dysrhytmia. Bradycardia (between 25 and 55 beats/mn) was present in each case with or without clinical symptoms. Temporary prophylactic pace maker insertion was performed in 4/7 patients. Recovery appeared after dialysis treatment in 6 cases, medical treatment in one, sinus rhythm being present in 6 and chronic atrial fibrillation in one. Prognosis of A.A. due to hyperkaliemia is good when hydroelectrolytic disorders are rapidly corrected. Follow up of blood electrolytes and electrocardiogram must be regular to prevent reccurencies.


[Measurement of differences in oxygen between arteries and veins. Application to the study of cerebral metabolism]. The cerebral metabolic exploration requires a precises measurement of the arterio-venous differences and this, for each metabolite. As far as oxygen is concerned, there are many techniques to measure the blood contents (CaO2 - CvO2). Direct methods give accurate results but their high technicality makes it difficult to adapt them to the increasing medical demand. The authors report the principle and the technique of the indirect method based upon the measurement of the total hemoglobin concentration and the saturation in oxygen. They recall the possible causes of errors, the main of which - induced by an insufficient homogenization of the sample - is (by the way) to be found in both groups of methods although to a lesser degree in the indirect method. Therefore, the latter, that all normally equipped laboratories can carry into practice, seems quite adapted to the "hospital demand" and its validity confirmed by an experience that now belongs to the past.


The defined antigen substrate spheres (DASS) system and some of its applications. A quantitative immunofluorescent technique based on the covalent coupling of protein to Sepharose beads, the so-called defined antigen substrate spheres (DASS) system is described, and the main technical aspects are discussed. The method proved to be reproducible and has a lower detection limit equivalent to the amount of antigen, present per bead, that can bind 1 pg fluorescent labeled antibody. The DASS system has many applications, and some of them are discussed, such as the quantitation of antibodies and antigens with Sepharose-coupled antigens or antibodies. Not only antigen-antibody interactions but also any reaction that results in a stable complex can be studied, provided antisera against one of the constituents are available. An example is given by the complement fixation to Sepharose-coupled IgG. For the quantitation of hydrophobic antigens, hydrophobic Sepharise can be used.


[Possibility of the intrauterine sensitization to benzylpenicillin and ampicillin in Syrian hamsters]. Immunization of Syrian female hamsters with benzylpenicillin and ampicillin resulted in positive skin reactions of the retarded type and decreased titers of the blood antihistamine factor (AHF) in a part of the posterity. Penicillin allergy was in particular observed in the posterity of the female hamsters immunited before the pregnancy. The state of allergy to penicillins was found in the posterity of the female hamsters with both the positive and negative skin reactions on immunization during the 2nd half of the pregnancy.