[Lymphogenic osteomyelitis of the foot (author's transl)]. The special way of infection of the lymphogenic osteomyelitis caused by trivial trauma is demonstrated in 4 cases. Germ ascension is done by lymphatics or fissures in the tissue, as it is well known in the panaritium ossale. The treatment consists in removing the focus of infection, irrigation-suction drainage and specific antibiotic therapy. Trivial trauma of the lower extremity should be treated according to the principles of asepsis.


Effect of cholera enterotoxin preparations on cutaneous response in rabbit under varied conditions. Enterotoxic activity of two preparations obtained from Vibrio cholerae, B-53-6 Inaba and B-53-10 Ogawa was tested in ligated ileal loops of rabbit. The biologically active enterotoxic preparations were further used to study the permeability reaction in rabbit skin. Cutaneous response tended to be linear only with higher concentrations of the toxin and showed maximum blueing intensity between 16 and 24 hrs of intracutaneous inoculation. Exposure of enterotoxin preparations to elevated temperatures greatly reduced the cutaneous response and the activity was completely lost at 100 degrees C. Change in pH towards alkaline side lowered the permeability activity to lesser extent as compared to a shift on acidic side. However, a residual activity could still be detected when pH of the enterotoxins was lowered to 3 at 30 degrees C for 4 hrs.


Pyruvate metabolism in rat brain mitochondria. 1. Oxidation of pyruvate by rat brain mitochondria was stimulated in state 3 by malate or succinate up to 250 nmoles O2/mg protein/min. Oxidation of malate, succinate, 2-oxoglutarate or glutamate as the sole substrates, was 1/4 - 1/5 that observed with pyruvate. 2. Maximum oxygen consumption in state 3 was observed at pH 6.90 - 7.20, whereas in state 4 it was not affected by changes in pH. 3. In state 4, in the absence of exogenous acceptor or acetyl residues, acetate was the main oxidation product, corresponding to about 80% of the amount of pyruvate utilized. Malate did not affect the rate of pyruvate utilization but lowered acetate concentration and raised concentration of citrate and 2-oxoglutarate. 4. In state 3, pyruvate and malate were converted mainly to 2-oxoglutarate, its concentration being three times as high as that of citrate. 5. Formation of citrate, 2-oxoglutarate and acetate from pyruvate in brain is considered as a function of availability of the acceptor of acetyl residues and the energy state of mitochondrion.


Purification and properties of two protease inhibitors from rat skin inhibiting papain and other SH-proteases. Two papain inhibitors, I1 and I2, from rat skin extract were purified by affinity chromatography on KSCN-modified papain-agarose gel and by gel filtration on Sephadex G-100. I1 had a molecular weight of 74 000, a pI of 4.6, and it contained 4% of carbohydrates. I1 inhibited papain, ficin, bromelain, rat skin benzoylarginine-2-naphthylamide hydrolase, and to a minor extent, rat skin cathepsin C and bovine trypsin. Bovine chymotrypsin or rat skin cathepsin D were not inhibited and benzoylarginine-2-naphthylamide hydrolase was inhibited only at alkaline pH. An inhibitor corresponding to I1 was present in various rat tissues and also in serum. A similar inhibitor was present in the skin of cat, rabbit, guinea pig, and man. I2 had a molecular weight of 13 400, a pI of 4.9 and it contained no carbohydrates. I2 inhibited all thiol proteases tested, but not trypsin, chymotrypsin, or rat skin cathepsin D. I2 formed an equimolar complex with papain and benzoylarginine-2-naphthylamide hydrolase. I2 was present in rat skin, muscle, lung, and small intestine, but not in kidney, liver, or serum. A similar inhibitor was found in skin extracts of cat, rabbit, guinea pig, and man.


Histochemical studies on the mucins of the vertebrate tongues. VII. Histochemical analysis of mucosubstances in the tongues of some fishes. The tongues of three fishes were investigated histochemically to determine the distribution and nature of mucosubstances by employing recent techniques and the results were considered comparatively with the lingual mucosubstances of other vertebrates. A heterogenous distribution of neutral mucosubstances, sulfomucins and sialomucins in various lingual sites was noted. The taste buds and/or free nerve endings were found to be restricted in the areas containing abundance of goblet cells. In non-gustatory areas of tongue, the goblet cells were very few or absent. Importance of lingual histology in establishing phylogenetic relationships and the possible functional significance of the mucosubstances in the physiology of gustation is discussed in detail.


Histochemistry of Centroorhynchus falconis (Das, 1950). With a view to augment the understanding of the animal mucosubstances in general and Acanthocephalan mucosubstances in particular, Acanthocephalan worms of (Centrorhynchus falconis, Das, 1950) were investigated histochemically by employing recent techniques. Variations in the intensity of histochemical reactions in different tissues revealed a heterogenous distribution of mucosubstances. The cuticle contained a mixture of periodate reactive neutral mucosubstances and sulfomucins, whereas the subcuticle contained only glycogen. Retractor muscles contained glycogen together with some acidic mucosubstances which exhibited alcianophilia only at high pH. Cement glands elaborated a mixture of glycogen and galactogen. Histochemical methods revealed two types of acanthors: Some contained only glycogen, whereas others contained glycogen and galactogen.


Intramuscular premedication with lorazepam. Lorazepam is recognized as a tranquillizer. It is presented for intramuscular and intravenous injection. In a study of this drug's possible effects in premedication, its action was studied systematically when it was used for preoperative premedication. The drug has no side-effects other than drowsiness, which occurs in almost all cases. It produces very good premedication, sometimes with anterograde amnesia in the doses used. This anterograde amnesia is dependent on the dosage used but it is always accompanied by profound drowsiness, from which the patient can be roused verbally. The dose will be selected in relation to whether amnesia is desired or not. However, whatever the dose administered (over 2.5 mg), the tranquillizing effect is always of high quality.


The amnesic action of diazepam, flunitrazepam and lorazepam in man. Studies in man show that it is possible to reliably study the incidence, degree and duration of amnesia produced by drugs by showing patients 10 postcards and testing their ability to recall or recognise them six hours later. Using this method of study it was found that 1 mg flunitrazepam produced a comparable degree of amnesia to 10 mg diazepam, although its action was slightly longer. This difference was more marked when double doses were studied. The onset of the amnesic action of both drugs occurred within 2 minutes of their intravenous injection and rarely persisted for more than 10-15 minutes. In contrast, with 4 mg lorazepam the onset of amnesia was slower and persisted for up to 270 minutes. This was accompanied by a moderate but not excessive amount of drowsiness. Possible clinical uses for such a drug deserve serious consideration.


Comparative evaluation of neuromuscular blockade and reversibility of AH 8165 and pancuronium bromide in man. The neuromuscular properties of AH 8165 were compared to those of pancuronium bromide in 66 patients during analgesic anesthesia procedures. Administration of 0.5 mg/kg AH 8165 and 0.04 mg/kg pancuronium bromide produced very similar degrees of non-depolarizing block. AH 8165 acted quicker and therefore gave better conditions for intubation. Spontaneous recovery of muscle twitch tension was slightly shorter for AH 8165 than for pancuronium bromide, whether small or larger amounts of drugs were used. Administration of neostigmine caused rapid and complete return of muscle twitch tension, well-maintained tetanus and insignificant posttetanic potentiation within 20 minutes, with a similar efficiency of competitive neuromuscular block reversal for both drugs.


Turku sugar studies XX. Microbiological findings and plaque index values in relation to 1-year use of xylitol chewing gum. The aim was to study possible alterations in the microbial flora of plaque and saliva in relation to partial substitution of dietary sucrose with xylitol. The development of plaque index values was observed simultaneously. These observations were carried out during a 1-year clinical trial, the effects of sucrose (S) and xylitol (X) chewing gum on the incidence of dental caries being observed in 100 young adults. Paraffin-stimulated saliva samples were diluted stepwise and cultivated on Rogosa S.L. agar and Sabouraud agar aerobically. Lyophilized dental plaque samples were cultivated on phenol red agar under anaerobic and aerobic conditions. The pH-values were measured after incubating the mixed plaque flora for 1 and 7 days in the presence of various sugars. Both the arithmetic and geometric means of the total CFU values on Rogosa S.L. agar decreased in the S-group at the 6-month phase but returned to the starting level after one year, whereas in the X-group they decreased or remained on the starting level. At the 6-month phase the difference between the groups was significant (U-test, p = 0.0013) and almost significant (U-test, p = 0.0569) at the end of the study. No significant differences or changes could be seen between or within the groups on Sabouraud agar. The geometric mean values of S. sanguis and S. mutans as well as the total CFU values on phenol red agar decreased considerably in both the S- and X-groups, but no significant differences could be detected in any of the streptococcal counts between the groups. The pH of the carbohydrate-containing culture media infected with mixed dental plaque significantly decreased, with the exception of the xylitol containing ones in which the pH values were not lowered even after 7 days' incubation. A significant decrease in plaque formation in relation of chewing per se was demonstrable. The difference in the plaque index values equalling or exceeding 2 was significant between the S- and X-groups. No bacterial adaptation to utilize xylitol occurred during the trial.


Turku sugar studies XXI. Xylitol, sorbitol-, fructose- and sucrose-induced physico-chemical changes in saliva. The aim was to study eventual physico-chemical changes occurring in whole saliva due to sweetened and unsweetened stimulators. The assay was carried out in 10 female subjects with regard to changes of pH, buffering capacity and electrolytes in saliva as influenced by chewing of fructose, sucrose, sorbitol and xylitol gum, gum base and paraffin. The flow rate of saliva was measured in relation to use of xylitol and sucrose chewing gum and unsweetened gum base. These sweeteners increased significantly the salivary flow rate in comparison to the unsweetened gum base. Generally, xylitol and sorbitol on one hand, and sucrose and fructose on the other, behaved in an almost similar way. Increased buffering capacity and elevation of pH saliva was found in the presence of the polyols tested.


Reduced inactivation of tyrosine aminotransferase in the prefused rat liver in the presence of ethanol. The mode of action whereby alpha-methyltyrosine (alpha-MT) potentiates the behavioural effects induced by catecholamine receptor blocking antipsychotic drugs was investigated in rats trained to lever-press for food on a fixed-ratio 40 schedule of reinforcement. It was found that alpha-MT (20 mg/kg intraperitoneally -- 4 hrs potentiates the effects induced by pimozide (0.04 mg/kg intraperitoneally -- 6 hrs) which preferentially blocks central dopamine (DA) receptors, but not the effects induced by phenoxybenzamine (0.5 mg/kg intraperitoneally -- 30 min.) which blocks central noradrenaline (NA) receptors. Furthermore, the behavioural suppression induced by chlorpromazine (0.5 mg/kg intraperitoneally -- 15 min.), thioridazine (1.5 mg/kg intraperitoneally -- 15 min.), or haloperidol (0.02 mg/kg intraperitoneally -- 15 min.) were not potentiated by the administration of the inhibitor of DA-beta-hydroxylase, bis-(4-methyl-1-homopiperazinylthiocarbonyl) disulfide (FLA-63) 4 mg/kg subcutaneously -- 1 hr). The potentiation by alpha-MT of the clinical effects of antipsychotic drugs and of their behavioural effects in animal experiments is in all probability due to a blockade by alpha-MT of a feed-back mediated compensatory increase in the catecholamine synthesis as a result of a blockade of central NA and/or DA receptors by the antipsychotic drugs. Since, in the present experiments, the behavioural effects induced by drugs which block central DA but not NA receptors were potentiated by the simultaneous administration of alpha-MT, it seemed probable that the disruption of conditioned behaviours by antipsychotic drugs is due to a blockade of central DA receptors. In view of the fact that the ability to selectively disrupt conditioned behaviours is shared by a wide range of antipsychotic drugs differing in chemical structure and also in their mode of action, it is possible that a blockade of DA neurotransmission is also of primary importance for the clinical effects induced by antipsychotic drugs.


Potentiation by alpha-methyltyrosine of the suppression of food-reinforced lever-pressing behaviour induced by antipsychotic drugs. The mode of action whereby alpha-methyltyrosine (alpha-MT) potentiates the behavioural effects induced by catecholamine receptor blocking antipsychotic drugs was investigated in rats trained to lever-press for food on a fixed-ratio 40 schedule of reinforcement. It was found that alpha-MT (20 mg/kg intraperitoneally - 4 hrs potentiates the effects induced by pimace, causing an alteration of the neuronal function.


Characterization of the adrenergic beta-receptor in the urinary bladder of man and cat. The corpus-fundus of the urinary bladder of man and cat was studied in vitro with respect to type of beta-adrenergic receptors. In both species beta-adrenergic stimulation produced marked relaxation but species differences were apparent. In the cat bladder only beta1-receptors were found. In the human bladder the beta-receptors had neither beta1- nor beta2-characteristics. It is suggested that the beta-adrenergic receptors in the corpus-fundus of the human bladder are of a third type.


Cholinergic mechanisms in the learning and memory facilitating effect of caffeine. Experiments are made to train rats in a maze involving memory tests 24 hours and 14 days after training. As it was established in previous studies of the authors, caffeine introduced in low doses (5 mg/kg) 5 min before training facilitates learning and memory. Applied immediately after training, caffeine even in higher doses (20 mg/kg) also improves the memory indices 24 hours and 14 days after the experiment. The anticholinergic agents spasmolytine and scopolamine in higher doses (20 and 2 mg/kg respectively) have a markedly deteriorating effect on learning, while scopolamine deteriorates retention as well. Introduced after training, both drugs deteriorate memory even in smaller doses - 2 and 0,25 mg/kg, respectively. On the background of the anticholinergic agents (especially in the higher doses), the learning and memory facilitating effects of caffeine are not manifested in any of the experimental setups (administration before and after train. The results obtained show that cholinergic mechanisms play an important role in the learning and memory facilitating effect of caffeine. A necessary condition for the manifestation of this effect is the optimum functional level of these cholinergic mechanisms in the central nervous system.


Amylase, hepatic enzymes and bilirubin in serum of chronic alcoholics. The serum concentration of bilirubin and the activities of aspartate aminotransferase (ASAT, GOT), alanine aminotransferase (ALAT, GPT), gamma-glutamyltransferase (GT), total amylase and pancreatic isoamylase have been determined in serum of 182 male chronic alcoholics. Twelve per cent had abnormally high levels of bilirubin, 73% increased activity of S-ASAT, 50% increased S-ALAT, and 69% increased S-GT. The highest values were often found after 5-20 years of well documented alcoholism. Some patients with alcoholism of more than 20 years' duration displayed a slight tendency towards normalization of the activities. For all parameters the scatter around the mean was greater in the patients than in the controls. Patients who had had attacks of delirium showed slightly higher S-ASAT and S-ALAT than other alcoholics. Determination of S-ALAT and S-bilirubin did not add to the cases with abnormal laboratory tests demonstrated by the combination of S-ASAT and S-GT. In 14 patients the above mentioned parameters were within normal limits, even though severe alcoholism had lasted for many years. Isoamylase determination disclosed 20% to have decreased activity of pancreatic isoamylases in serum, whereas only 6% had low total serum amylase activity.


Oxygen transport and hemodynamics of stroma-free hemoglobin solutions. The intravascular persistence of hb-W is significantly longer than of pyridoxylated hb (hb-PLP), however, no significant differences in BV were observed after isovolemic exchange of 20 ml/kg b.w. Even though the oxygen affinity of hb-PLP in vitro was reduced when compared to the affinity of hb-W significant differences in vivo were lacking. The development of hypovolemia and thus the lack of an adequate increase in cardiac output have been recognized as the most relevant causes to explain the changes observed. Neither of the solutions is yet to be recommended for clinical blood replacement therapy.


Problems in determination of oxygen dissociation of avian blood. No appreciable errors are expected in determination of blood gas values and pH using classical techniques provided time of anaerobic storage is kept small and is, if unavoidable performed on ice. In particular, dissociation curves may safely be analyzed with the Van Slyke technique which is in disagreement with the conclusions of Lutz et al. (1973). For measurement of PO2 and PCO2, delay time is mainly dictated by response time of the electrodes; measurements may have to be corrected for metabolism, particularly in high PO2 range.


A theoretical model of the respiratory function of blood. The model of the respiratory function of blood as outlined here is judged to be a powerful tool for the evaluation of the potential effects of changes in blood as well as tissue parameters upon the supply of oxygen to tissue. The erythrocyte-plasma disequilibria in lung and systemic capillaries which is a consequence of the slowness of plasma CO2 hydrolysis are not significant in terms of the delivery of oxygen to tissue, but result in slightly lower unloading of CO2 in the lungs compared to that which might occur at full equilibration. However, the effects might be of greater interest when relating pH values measured by in vivo sampling to actual values prevailing within the capillaries. The physiological importances of hyperventilation and elevated DPG levels in anemia cannot as yet be clarified. If anything, it appears that increased DPG is a compensatory mechanism to restore proper O2-Hb affinity in alkalosis, while the purpose for an alkalosis is not obvious.


Control of prolactin secretion by the hypothalamic catecholamines. The neuroendocrine control of prolactin secretion is very complex. Even though the hypothalamus exerts a profound inhibitory influence upon the secretion of this hormone, the mechanism(s) involved is poorly understood. The cerebrospinal fluid seems to be becoming increasingly important as regards neuroendocrine regulatory mechanisms involving prolactin. Pharmacological agents such as apomorphine and many of the ergot alkaloids are very effective inhibitors of the secretion of prolactin. Still other pharmacological agents such as DMPEA, alpha-methyldopa, reserpine, and certain of the phenothiazines are very effective in causing a stimulation of prolactin secretion.


[Immunologic relations between cattle and ticks, specifically between cattle and Boophilus microplus]. In the present investigation, it has been demonstrated that cattle become resistant to ticks after several heavy infestations, particularly with B. microplus. During development of the infestations, antibodies against salivary glands of B. microplus were detected using 2 techniques: indirect immunofluorescence and immunoelectrophoresis. There is a positive causal relationship between antibody titer and resistance development. Two precipitating systems against B. microplus in infested cattle and 7 systems in immunized rabbits were studied. The systems 1 and 2 are similar in cattle and rabbits, but system 2 does not show any specificity, as it has been detected in cattle completely lacking tick infestations. Two one-day calves were treated with the antigen of B. microplus by injection of salivary glands and repeated infestations with a small number of larvae. They developed a pronounced resistance to the usual subsequent infestations by the ticks of the same species. Specific antibodies were found before the first usual infestation. This suggests that they might be responsible for resistance.


The occurrence of an intraerythrocytic microorganism Neitziella rezendei gen. nov. sp. nov. (Microtatobiotes, Rickettsiales) of poultry in Brazil. An extremely polymorphous intraerythrocytic microorganism occurring in naturally infected turkeys, ducks and fowls has been discovered in the states of Minas Gerais, Rio de Janeiro and Espirito Santo. 2. Studies on the morphology and biology have shown that it is a hitherto undescribed heteroxenous parasite for which the name Neitziella rezendei gen. nov., sp. nov. is proposed. 3. Its morphological features permit its inclusion in the class Microtatobiotes and order Rickettsiales. 4. Microscopical examination of blood films have shown that the parasitic carrier state in turkeys persists for more than 200 days (endpoint not determined). 5. The natural mode of transmission needs to be determined. 6. The suspicion that the parasite may cause illthrift and deaths in poultry requires confirmation.


Protease activity in female Ornithodoros tholozani ticks. The protease activity in guts of Ornithodoros tholozani females was studied in vitro. The intracellular protease in Ornithodoros tholozani guts has a pH optimum of about 3.0. Hemoglobin is the preferred substrate, and bovine serum albumin is digested very slowly. In this respect the protease resembles cathepsin D. Unfed ticks contain a small amount of protease in the gut. After feeding the level of protease increases gradually for several days until peak protease activity is attained. The level of gut protease activity depends on the size of the blood meal taken and on the interval after feeding. After a period of peak protease activity, the level of protease declines. The level of gut protease in unmated females (kept at 27 degrees C) did not reach prefeeding levels within 100 days. The level of gut proteolytic activity, as determined by in vitro protease assays, does not reflect the degree of blood digestion which takes place in vivo. After a period of rapid digestion, lasting for about two weeks, the undigested part of the blood meal remains unchanged in the lumen of the gut. At that time the gut tissue contains considerable levels of protease, which can be demonstrated by in vitro assays. Presumably, the protease remains active inside the gut cells, although the uptake of hemoglobin from the gut lumen has ceased. The results are compared to those obtained in other tick species.


Human sleeping sickness in the Gboko endemic area of Nigeria. Human infection with Trypanosoma gambiense in the Gboko endemic area was first reported in May, 1974 although T. gambiense sleeping sickness had been present there since the turn of the century. The disease is associated with the presence of the tsetse Glossina tachinoides and Glossina palpalis which is plentiful and widespread throughout the division as well as in thickets along the streams in the area. No successful attempt has been made to control the tsetse vector in the Division. The incidence and geographical distribution of cases of T. gambiense sleeping sickness in the Gboko area are described in this report. Cases were treated with Antrypol Tryparsamide mixture and Mel B. The highest number of cases of infection is usually picked up just before the start of the rains in early April. It is suggested that, for meaningful control of the disease a quick method should be devised to rid the area of the insect vector.


Mel B toxicity in human trypanosomiasis in the Gboko endemic area of Nigeria. Nine cases of Mel B (a melaminyl arsenical used in treating sleeping sickness patients who have developed central nervous system involvement) treated patients who developed reactions to the drug are described. They all developed high temperatures, pyrexia, diarrhoea, vomitting or itching and some had convulsions. Three of the nine described patients died. It is recommended that extra care and caution is needed while treating patients with Mel B.


Principles of complementation interaction of ts mutants of orthomyxoviruses. The possibility of complementation between ts mutants of fowl plague virus (FPV) belonging to 5 different complementation groups was studied using various time intervals between inoculation of the cells with two complementation partners. The structural proteins of virions formed on complementation of individual ts mutants with wild virus were analysed by polyacrylamide gel electrophoresis after amino acid pulse label followed by pulse chase. The features of complementation interactions between the mutants are discussed.


Influence of host cell type on the density of herpes simplex virus particles. The densities of purified herpes simplex virus (HSV) particles prepared from infected rabbit lung (ZP) and baby hamster kidney (BHK-21) cells were investigated in potassium tartrate (PT) and potassium citrate (PC) density gradients. Virions obtained from ZP cells exhibited a higher density than those from BHK-21 cells. In PT and PC gradients, the former banded at densities of 1.226 and 1.267, while tha latter at 1.194 and 1.233, respectively. Deenveloped viral particles prepared by Nonidet P-40 treatment from purified virions of either origin were found in PT and PC gradients at the densities of 1.263 and 1.320, respectively. The possible causes of the density change of virions propagated in different hosts are discussed.


Reversible inhibition of interferon-induced antiviral state by deoxyadenosine. Deoxyadenosine reversibly inhibited the development of antiviral state (AVS) in chick embryo fibroblasts stimulated by interferon. Studies on cellular macromolecular syntheses in deoxyadenosine-treated cells suggested that the inhibition was related to nucleolar RNA synthesis. Reference experiments with actinomycin D and cordycepin (3'deoxyadenosine) also implied causal- or interrelation between AVS development and nucleolar RNA synthesis.


Study of the priming effect of interferon in L cells. I. The primed interferon response and the kinetics of development of priming. Interferon was detected one hour earlier, its production followed an enhanced pattern and became resistant to actinomycin D 30 minutes sooner in cultures primed by interferon pretreatment before stimulation by polyriboinosinic-polyribocytidylic acid than in unprimed cultures. The kinetics of development of the primed state was found to be a time and dose dependent phenomenon. The continuous presence of interferon during the pretreatment period was not required for the development of the primed state.


Phenothiazine-induced alterations of immune response in experimental tick-borne encephalitis: morphological model analysis of events. The depressive effect of trifluoperazine (TFP), a phenothiazine derivative, on the morphology of the development of immune response (IR) (humoral and cell-mediated component) was studied in mice given tick-borne encephalitis (TBE) virus, sheep red blood cells (SRBC) or the BCG vaccine. This effect was manifested by a decrease in the mitotic activity of lymphocytes and in the number of blastic transformations after antigenic stimulation. In virus-infected and TFP-given mice, lowered levels of specific virus neutralizing antibody (VNA), together with a pronounced reduction of the inflammatory response in the brain were found. No signs of cytotoxicity following administration of the drug were observed. The mechanism of the immunodepressive action of TFP are discussed.


Influence of temperatures corresponding to those of the host animals on Tahyna virus. The influence of temperature of 36.5 and 39.2 degrees C on uncloned low passage Tahyna virus in chick embryo cell cultures was studied in the course of 10 passages. At a high multiplicity of infection, the virus titres showed a considerable variability, especially at 39.2 degrees C. The cytopathic effect (CPE) apparent at both temperatures started later and was of lower intensity at 39.2 degrees C than at 36.5 degrees C. The temperature of 39.2 degrees C intensified the thermostable character of the virus. Changes in plaque size and virulence were connected mainly with the cultivation substrate of the virus.


Influence of temperature corresponding to that of the vector on Tahyna virus. The behaviour of uncloned, low-passage Tahyna virus in an Aedes albopictus (AA) cell line at 28 and 20 degrees C was studied in the course of 10 passages. The virus multiplied at both temperatures without any apparent effect on the host cell. At 28 and 20 degrees C reduction of plaque size, decrease of peripheral virulence and weakening of thermostability were observed. Differences between both temperatures were only in the intensity of these changes.


Cultivation of Lednice (Yaba 1) virus in goose, duck, and chick embryo cells. Lednice (Yaba 1) virus was found to multiply in primary cultures of goose, duck and chick embryo cells. The size of inoculum and age of embryos used for preparation of primary cultures was decisive for the amount of multiplied virus. One strain (110) of Lednice virus showed reduced ability to induce a cytopathic effect in the first passage in chick embryo cells. Virus multiplication in all three kinds of cells was confirmed by immunofluorescence.


Systematic management of the anxious patient. The patient usually consults his family physician because of the physical symptoms of anxiety, usually cardiorespiratory, but often gastrointestinal or musculoskeletal. An organized, systematic approach includes these steps: an invitation to talk; identifying the problem; understanding the patient's wishes; choosing an appropriate drug (if necessary); involving the family, and behavioral modification techniques.


Observations of plasma secretin levels by radioimmunoassay in response to duodenal acidification and to a meat meal in humans. The endogenous release of secretin in healthy human subjects was studied by measuring plasma secretin levels by radioimmunoassay (RIA) before, during, and following duodenal acidification and eating a meal. The sensitivity of our RIA was assessed by measuring plasma secretin levels during constant intravenous infusions of 4 graded doses of secretin. Our RIA detected significant increases (P less than 0.001) in plasma secretin with each dose, including a low dose of 0.125 U (41.3 ng)/kg hr. Intraduodenal infusion of 0.1 N HCl resulted in marked increases (P less than 0.001) in plasma secretin levels whenever pH in the second portion of the duodenum was reduced to less than 3.5. In contrast, following a meal, pH in the second portion of the duodenum remained consistently greater than 4.5 and plasma secretin levels showed no changes from basal levels. These studies confirm that endogenous release of secretin depends on an acidic pH of the duodenum, and insigificant changes in the plasma secretin level following ingestion of a meal suggest that endogenous release of secretin in the postprandial period is probably to small in quantity to be detected by the present radioimmunoassay method.


Lower esophageal sphincter pressure and serum motilin levels. The gastrointestinal hormone motilin has recently been proposed as having a physiological role in the determination of lower esophageal sphincter (LES) strength. The present study was performed to evaluate the effect of gastric alkalinization of LES pressure and serum motilin levels. Instillation of 0.1N NaHCO3 into the stomach resulted in a significant increase in LES pressure (P less than 0.01) without affecting serum motilin levels. No correlation was found between fasting serum motilin levels and resting LES pressure (r = -0.31). These observations do not support the theory that LES pressure increases during gastric alkalinization are mediated through motilin release.


Imminent shock; a useful diagnosis in drug pathology. A research has been carried out on a total of 121 persons with survival post-drug shock (DS), which registered 192 DS. Mention should be made of their predominance in the feminine sex (85 per cent) and their maximum frequency between the ages of 21-50 (average age 34). DS was the first adverse reaction to drugs in 71 per cent of the cases. Therefore DS unpredictability is very frequent. A retrospective study suggested the role of risk factors which should help the doctor to prevent DS (personal allergic antecedents, antecedents of adverse reactions to drugs, neuroses, disorders of endocrine glands, feminine sex, etc.). In 1970, the clinical concept of shock imminence (SI) was formulated and it is applied to various etiologies (drugs, insect stings, food). The existence of SI was identified in the case history of 14 per cent of the persons with DS. SI is a syndrome which includes all clinical manifestations with imminent potential of transformation into shock condition, and represents the stage precursory to the setting up of shock. The utility of SI diagnosis is maximum if it also includes the causal factor (e.g. SI by penicillin or aspirin). The clinical image of SI may vary from the monosymptomatic aspect (urticaria, vomiting, diarrhoea, headaches, etc.) to the one with complex symptomatology (mixed form). Usually the symptoms are dramatic and depend on the administration of a certain drug (often in SI of allergic origin) or of various drugs (mainly on non-immunologic form). The absence of vascular collapse differentiates SI from shock. Differential diagnosis is more difficult in border cases with a slight diminution of blood pressure. SI can be diagnosed especially in several circumstances: when the first adverse drug reaction is dramatic; when the first allergic-type reaction to a drug occurs; when the repetition of drug reactions is amplified in intensity or frequency; when it occurs in persons with risk factors. The differential diagnosis of SI is made with a crude or minimum shock and with pre-shock condition. The advantages of SI diagnosis are the institution of efficient treatment with rapid recoverability and the prevention of subsequent shock to the respective drug.


Effect of methylated PGE2 analogs given orally on pancreatic response to secretin in man. The effect of two methylated PGE2 analogs given orally on the pancreatic response to intravenous secretin has been studied in 8 healthy subjects. The secretion of bicarbonate was not changed by these PGE2 analogs. The secretion of enzymes during infusion of PGE2 analogs was significantly greater than in the control.


Renal proximal tubular dysfunction and paroxysmal nocturnal hemoglobinuria. A patient with paroxysmal nocturnal hemoglobinuria, who required many blood transfusions for hemolytic episodes, had a persistent hyperchloremic metabolic acidosis. Bicarbonate infusion demonstrated a large fractional excretion of bicarbonate (28.6 per cent at a plasma bicarbonate level of 23 meq/liter) which was consistent with proximal renal tubular acidosis. Generalized aminoaciduria and decreased tubular reabsorption of phosphate were also present. Marked deposition of iron in renal proximal tubules was associated with these functional abnormalities. We believe that, as systemic acidosis can promote hemolysis in patients with paroxysmal nocturnal hemoglobinuria, hemolysis can lead, by way of iron deposition in renal tubules, to further acidosis. This cycle should be interrupted with appropriate doses of bicarbonate.


Studies of glucose turnover and renal function in an unusual case of hereditary fructose intolerance. Examination of glucose kinetics, pancreatic alpha and beta cell function, plasma lipids, urinary acidification and calcium excretion has been undertaken in a patient with hereditary fructose intolerance. This case was unusual as it was associated with insulin-requiring diabetes, type IV hyperlipemia, hypercalciuria and renal calculi. He also demonstrated the previously described fructose-induced defect of urine acidification. Glucagon and C-peptide assays showed that the pancreatic alpha cells were stimulated by fructose and that the beta cells did not respond to fructose. It is not known whether the latter was due to his diabetes or to the lack of a beta cell response to this sugar. Primed 14C-glucose infusions were used for the first time to study nonsteady state glucose kinetics in man. They showed that, 24 hours after the last insulin injection and under basal conditions, the glucose concentrations increased because glucose production exceeded glucose utilization. However, after the administration of sorbitol the plasma glucose concentration decreased because glucose production decreased. After the administration of sorbitol there was no change in the metabolic clearance of glucose. This reflects the lack of a peripheral insulin effect and is consistent with the lack of any measurable C-peptide. Glucose utilization also decreased, but this decrease was less than the decrease in glucose production. Because the metabolic clearance of glucose remained unchanged, it was concluded that the change in glucose utilization was solely due to the decrease in glucose concentration. The absence of C-peptide in the plasma indicated that changes in glucose turnover were not related to any changes in endogenous plasma insulin. Furthermore, the plasma glucagon concentration increased and, hence, changes in this hormone could not account for the decrease in glucose production. Therefore, it was concluded that the sorbitol-induced decline in glucose production was due to a direct effect on hepatic metabolism.


Evaluation of success in treatment of threatening premature labor by betamimetic drugs. For prevention of premature labor the betasympathicomimetic drugs buphenin, fenoterol, and ritodrine were administered to 135 patients intravenously for 1 week and afterward orally up to the end of week 37 of gestation. No satisfactory evaluation of success could be obtained by analyzing only the time gained by the treatment. Two supplemental parameters were needed. In addition to the previously introduced Tocolysis Index (TI) which describes the obstetric situation at the beginning of the treatment, a Prolongation Index (PI) was defined transforming the lag time gained by the treatment into a relative measure. By means of this PI, extremely differing cases could be compared, though the gestational ages at the start of treatment and the lag times between admission and delivery showed wide variation. In addition, satisfactory statistical correlations between the PI and the clinical signs as well as the neonatal outcome could be computed, indicating the PI to be a suitable parameter for the estimation of success.


Fetal breathing and adaptation to maternal hemorrhage in the sheep. The effect of maternal hemorrhage in chronic preparations was studied on fetal lambs in the last month of gestation. Fourteen to 20 per cent of maternal blood was estimated to have been removed within 30 minutes, which resulted in a drop of 30 per cent of mean maternal arterial pressure. A fetal bradycardia started 28 +/- 13 minutes after the beginning of maternal hemorrhage. It lasted 30 +/- 15 minutes and was concomitant with a rise in fetal arterial pressure. It was followed by a long-lasting fetal tachycardia of 130 +/- 38 minutes and was corrected only by reinfusion of blood to the mother. The fetal blood gases demonstrated a mild asphyxia with a persistent metabolic acidemia until reinfusion of blood to the mother. Maternal and fetal plasma cortisol levels rose significantly at the end of the hemorrhage. Tracheal fluid flow did not change. Fetal breathing recorded 20 hours before and 24 hours after the experiment did not show consistent changes, but during fetal bradycardia there was no fetal breathing. Recent clinical investigations in this field have been made in the human fetus to estimate standards of fetal well being. These peculiar animal experiments do not show any significant improvement by recording fetal breathing over the recording of prelabor fetal heart rate.


Secretory surface area and phosphatase activity of frog gastric mucosa. Gastric mucosae were isolated from the European frog, R. temporaria, and after 5-7 h, stimulated with histamine (10(-4) M) and theophylline (5 mM). Acid secretion increased about fourfold, and this was accompanied by a threefold increase in secretory surface of the oxyntic cells, as determined in electron micrographs with conventional morphometric techniques. At the same time phosphatase activity of the secretory surface increased. Other experiments showed that the latter was due to an acid phosphatase, with pH optimum near 3. It appears that the increase in surface phosphatase with stimulation can be attributed to a diminished local pH and not to the increase in surface area demonstrated in this study.


HCO3 transport in rat jejunum: relationship to NaCl and H2O transport in vivo. HCO3- absorption and its association with Na+ absorption has been studied in the rat jejunum in vivo, using a single-pass perfusion technique. The method of disequilibrium pH, the only valid way of demonstrating jejunal H+ secretion, was used to distinguish between an HCO3- pump and H+ secretion as the mechanism of HCO3- absorption. HCO3- stimulated Na+ absorption; Na+ deletion inhibited HCO3 absorption, decreased luminal acidification, and decreased the level of luminal PCO2. These results confirmed an Na+:H+ cation exchange, the possible mechanism of which is discussed in terms of results using other tissues. Na+-dependent HCO3-absorption made up a larger part of total HCO3-absorption as the luminal HCO3-concentrations diminished, although the precise degree of Na+-dependency could not be determined because of the unstirred layer effect. The mechanism of Na+-independent HCO3-absorption was not established, but it was not affected by PD, Cl-, or H2O movements. Glucose-stimulated and HCO3-stimulated Na+ absorption were less than additive. The physiological importance of HCO3-stimulated Na+ absorption in the acidic postprandial jejunum is probably due entirely to the effect of free CO2 in the lumen.


Vitamin K1 intestinal absorption in vivo: influence of luminal contents on transport. Intestinal absorption of [3H]phylloquinone was investigated in the unanesthetized rat by the use of a technique of recirculating perfused isolated intestinal segments. Apparent saturation kinetics were found as the concentration of the vitamin in the perfusate was increased in a stepwise fashion from 15 nM to 300 muM. Alkalinization of the perfusate or the addition of 2.5 mM linoleic acid to the perfusate caused a significant (P less than 0.05) decrease in the absorption rate of phylloquinone. Modifications in the perfusate concentration of sodium taurocholate, the substitution of a nonionic detergent (Pluronic F-68) for sodium taurocholate, the addition of medium- and long-chain saturated fatty acids, or the addition of vitamins K2 and K3 to the perfusate did not alter the absorption rate of the vitamin. Decreasing the thickness of the unstirred water layer by increasing the perfusion rate caused a significant increase in phylloquinone absorption rate. In vivo absorption of vitamin K1 appears to be mediated by an energy requiring saturable transport mechanism. The composition of the perfusate, its pH, and its rate of flow are all important determinants of vitamin K1 absorption rate.


Fluoride absorption from the rat urinary bladder: a pH-dependent event. Urinary bladder absorption of stable and radiofluoride was studied as a function of pH in anesthetized rats to further evaluate the influence of pH gradients on fluoride transport. Buffered pH values and stable fluoride concentrations ranged from 1.85 to 7.90 and from 0.012 to 8.81 mM, respectively. [14c]inulin served as a marker for solute concentration changes due to water migration or dilution. The results indicate that bladder fluoride absorption is inversely related to pH over the 1.85-5.50 range. Mean, 15-min radiofluoride absorption values of 70% at pH 1,85, 37% at pH 3.95, and 5% at pH 5.50 WERE OBSERVED. These fractional absorption values were not significantly influenced by carrier fluoride concentration, the buffers used, or the presence of urine. Above pH 5.50, pH-independent absorption occurs to a slight extent. The results are consistent with a first-order absorptive process which occurs by the nonionic diffusion of hydrogen fluoride.


Effect of autonomic blockade on the hemodynamic findings in acute cardiac tamponade. Twenty-three closed-chest, alpha-chloralose-anesthetized, volume-expanded, alpha- and beta-adrenergic-blockaded dogs with rate fixed by atrial pacing had 30-90 ml of saline at 37 degrees C infused into the pericardial sac a) with vagus intact, b) after vagotomy, and c) with vagus intact but with systolic pressure augmented with a balloon. A significant reduction in left ventricular (LV) systolic pressure (SP), and cardiac output (CO) occurred at a pericardial volume of 30-60 ml, when LV end-diastolic (ED) and right atrial (RA) pressures were not increased. Whereas the percentage decline of CO, LVSP, maximum negative and maximum positive dP/dt was greater in group A (vagus intact) than in group B (vagus cut), significant residual depressed performance was demonstrated only in group B. In four paced, atropinized, beta-blockaded dogs, response to tamponade was similar to that in intact dogs; vagotomy at 90 ml in these dogs resulted in a fall in CO, a rise of LVSP and a significant elevation in LVED and RA pressures. Thus, in the early phases of cardiac tamponade a sympathetic neurohumoral response supports cardiac performance while the vagus nerve exerts a myocardial protective effect. Vagal afferents appear to modulate this response.


Action of histamine and H1 and H2 blockers on the cardiopulmonary circulation. Systemic and pulmonary hemodynamic responses to histamine were investigated inchronically instrumented unanesthetized nonpregnant ewes. Histamine was administered intravenously and into the pulmonary artery. The effects of the same doses of histamine were assessed following H1 and H2 receptor blockade. The effects ocular changes were also monitored. Results indicate that intravenous histamine produces tachycardia, systemic hypotension, pulmonary hypertension, and reduced cardiac output. The pulmonary response could be modified significantly by pentobarbital anesthesia. When injected directly into the pulmonary artery histamine failed to elicit any circulatory response. Blockade of H1 and H2 receptors, as well as autonomic ganglia, resulted in a comparable attentuation of the histamine circulatory response. It is concluded that a) central hemodynamic responses do not seem to be mediated through specific H1 and H2 receptors; b) histamine-induced pulmonary vasoconstriction can be reversed by pentobarbital anesthesia, and c) the absence of circulatory response to intrapulmonary histamine administration suggests that whatever receptors that may exist in the pulmonary vascular bed are not necessary for the central hemodynamic effects.


Physiologic effects of normal-or low-oxygen-affinity red cells in hypoxic baboons. Baboons were bled one-third their red cell mass and were given homologous transfusions of red blood cells to restore the red cell volume. One group of baboons received red blood cells with a normal 2,3-diphosphoglycerate 2,3-DPG) level and normal affinity for oxygen, and in this group the 2,3-DPG level after transfusion was normal. The other group received red blood cells with a 160% of normal 2,3-DPG level and decreased affinity for oxygen, and in this group the 2,3-DPG level after transfusion was 125% of normal. In both groups of baboons, the inspired oxygen concentration was lowered and arterial PO2 tension was maintained at 55-60 mmHg for 2 h after transfusion. During the hypoxic state, systemic oxygen extraction was similar in the two groups, whereas oxygen saturation was lower in the high 2,3-DPG group than in the control animals. Cardiac output was significantly reduced 30 min after the arterial PO2 was restored to normal. These data indicate that red blood cells with decreased affinity for oxygen maintained satisfactory oxygen delivery to tissue during hypoxia.


Acid-base balance and plasma composition in the aestivating lungfish (Protopterus). Upon entering into aestivation, Protopterus aethiopicus develops a respiratory acidosis. A slow compensatory increase in plasma bicarbonate suffices only to partially restore arterial pH toward normal. The cessation of water intake from the start of aestivation results in hemoconcentration and marked oliguria. The concentrations of most plasma constituents continue to increase progressively, and the electrolyte ratios change. The increase in urea concentration is disproportionately high for the degree of dehydration and constitutes an increasing fraction of total plasma osmolality. Acid-base and electrolyte balance do not reach a new equilibrium within 1 yr in the cocoon.


Secretory state of gastric mucosa and resistance to injury by exogenous acid. The capacity of the stomach to resist the effects of highly acid solutions was assessed by comparing the effects of such solutions on spontaneously secreting, stimulated, and inhibited gastric mucosae of rabbits in vivo and frogs in vitro. Exposure of unstimulated resting mucosa to HC1, 120 mM, for 60 minutes produced superficial erosions in all rabbits, whereas such lesions were observed in only one of ten animals stimulated with histamine. Metiamide obviated the protective effect of histamine against ulcerations even though it did not reduce H+ secretion to zero. Exposure of inhibited isolated frog fundic mucosa to HC1 resulted in significant deterioration of electrical parameters, suggesting impairment of active transport processes and increased tissue permeability. These data are consistent with the hypothesis that actively secreting gastric mucosae from two species resist injury to exogenous acid more effectively than do resting or inhibited tissues, perhaps in part as a result of a greater alkaline tide.


Effects of chronic hypoxia on canine gastric secretion. Interdigestive gastirc acid output and acid secretory response to histamine, insulin  and pentagastrin were studied in five dogs before and after creation of a right to left extracardiac vascular shunt. The arterial PO2 decreased from 81.5 +/- 5.5 mm Hg to 39.8 +/- 6.0 mm Hg postoperatively with no change in arterial pH or PaCO2. Basal (interdigestive) acid output increased from 1.19 +/- 0.26 mEq/hr to 4.97 +/- 0.81 mEq/hr postoperatively. Acid secretory response to insulin was increased after the induction of chronic hypoxia. Increased sensitivity to pentagastric was also observed although parietal cell mass (maximum histamine-stimulated output) was unchanged postoperatively. Changes in acid secretory response and PaO2 were present at one week and were sustained through twelve weeks after shunting. Chronic hypoxia resulted in gastric acid hypersecretion secondary to enhanced sensitivity of the parietal cell to a combination of neural and humoral stimuli.


The redox state of the glutathione in the bovine corneal epithelium. In the corneal epithelium the levels of the oxidized and reduced glutathione, the oxidized and reduced triphosphopyridine nucleotide, the glucose-6-phosphate and the 6-phosphogluconate were investigated. The in vivo steady state levels were defined by preparation procedures and by the energy state of the adenosine phosphate system. The ratios of the levels of the metabolites involved suggested that the reactions of the glucose-6-phosphate dehydrogenase and of the glutathione reductase operate dependent on the redox state of the triphosphopyridine nucleotides.


Acid-base balance and blood gases changes and "lactate excess" in acute respiratory alkalosis during general anaesthesia. In 40 young males aged 18-20 years operated on for inguinal hernioplasty acute respiratory alkalosis was obtained in the 45th minute of general anaesthesia. The values of basic acid-base balance parameters, blood gases, pyruvate and lactate levels and "lactate excess" were determined before and after hyperventilation. Shifts in the concentrations of hydrogen and bicarbonate ions were found which are both typical of acute respiratory alkalosis. No changes were observed in the oxygenation of capillary blood and the values of "lactate excess" were normal which rules out tissue hypoxia during acute respiratory alkalosis. Passive hyperventilation being a less dangerous alternative of hypoventilation is a frequent occurrence during general anaesthesia and it causes transient respiratory alkalosis.


The effect of adrenergic receptor blocking agents on arrhythmia caused by trauma. Experiments on animals have shown that blunt trauma to the anterior chest wall causes arrhythmia and conduction disturbances. In most cases nodal rhythm and ST segment elevation were observed. Microscopic examination disclosed myocardial damage in the vicinity of the atrioventricular node. Administration of alpha or beta adrenergic receptor blocking agents immediately before trauma failed to prevent arrhythmia and conduction disturbances, on the contrary, they became even more pronounced.


General anesthetics and regional hypoxic pulmonary vasoconstriction. Administration of N2O, fluroxene and isoflurane to the left lower lobe (LLL) of dogs anesthetized with pentobarbital was previously shown to inhibit LLL hypoxic pulmonary vasoconstriction (HPV). Using the same experimental model, the present study examined the effect of whole-lung administration of N2O, fluroxene, isoflurane, halothane, and enflurane on left-lower-lobe HPV. Selective ventilation of the LLL with N2 alone caused blood flow to the lobe to decrease 53.3 +/- 3.0 per cent. Responses to LLL hypoxia were remeasured during administration of inhalation anesthetics at 1 and 2 MAC to both the LLL and the rest of the lung. Isoflurane and fluroxene progressively inhibited and at 2 MAC halved lobar HPV. N2O (one third MAC) caused slight but significant inhibition, while halothane and enflurane caused slight and nonsignificant changes in lobar HPV. These effects of whole-lung administration of anesthetics on HPV were almost identical to those obtained when the administration was confined to the test lobe alone. It is concluded that N2O, isoflurane, and fluroxene locally inhibit regional HPV and via this mechanism increase total venous admixture, while halothane and enflurane do not have this effect.


Control of breathing using an extracorporeal membrane lung. Various amounts of carbon dioxide were removed through an extracorporeal membrane lung in spontaneously breathing lambs. The decrease in alveolar ventilation was proportional to the fraction of total carbon dioxide removed by the membrane lung. When extracorporeal CO2 removal approximated CO2 production (VCO2), alveolar ventilation almost ceased. Pulmonary ventilation can be controlled by extracorporeal carbon dioxide removal.


Kinetic analysis of the AH8165-receptor interaction at the mammalian neuromuscular junction. The effect of a new neuromuscular blocking agent, AH8165, on carbachol-induced end-plate depolarization was measured in isolated guinea pig lumbrical muscles. The results showed that the kinetics were competitive (parallel shift of dose-response curves to the right and a slope of Schild plot of 1.09 +/- 0.07) and the AH8165-receptor dissociation constant was estimated as 0.337 +/- 0.008 muM. Once the dissociation constant was known, the fraction of receptors occupied by any given concentration of AH8165 could be determined. This fractional receptor occupancy was then compared with the indirect twitch response in an isolated guinea pig nerve-lumbrical muscle preparation. These measurements of the effect of AH8165 on the margin of safety of neuromuscular transmission gave values comparable to those obtained with d-tubocurarine, i.e., the twitch remained normal until 75-80 per cent of the receptors were blocked and was abolished when 90-95 per cent of the receptors were occluded. Thus, the neuromuscular blocking action of AH8165 appears to be consistent with a simple postsynaptic competitive interaction with the transmitter.


Comparison of THAM and sodium bicarbonate in resuscitation of the heart after ventricular fibrillation in dogs. Tris (hydroxymethyl) aminomethane (tromethamine or THAM) has been suggested as an effective substitute for sodium bicarbonate (NaHCO3) in the treatment of metabolic acidosis accompanying cardiac arrest. Even though several reports on its appraisal have been published, there is still no clear agreement on its therapeutic value. A double-blind study was therefore lndertaken to compare in 36 dogs the effectiveness of 0.6 M THAM, 0.3 M THAM, and NaHCO3 (0.892 mEq/ml) to correct metabolic acidosis produced during 3 minutes of cardiac fibrillation, followed by a 3-minute period of cardiac compression. The dogs were then defibrillated and observed for 45 minutes. One group of 8 dogs was treated with 0.9 percent NaCl infusion. Compared with 0.9 percent NaCl, both THAM and NaHCO3 were equally effective in correcting metabolic acidosis (p less than 0.05). Initially, 0.6 M THAM produced a more pronounced (p less than 0.05) elevation of blood pH, but this effect was not sustained during the later postdefibrillation period. There was little difference in the effect of either of these drugs on mean aortic pressure and total peripheral vascular resistance. It is concluded that adequate ventilation and effective cardiac compression are still the chief criteria on which the final outcome of cardiac resuscitation depends. Correction of metabolic acidosis is important supportive therapy, but either THAM or NaHCO3 can be used with comparatively equivalent effect.


[Drugs combined with neuroleptics in anesthesia]. The neuroleptics are characterised by the large number of pharmacological effects they develop. When they are associated with other substances, it is frequent for the latter to have with neuroleptics one or several common sites of action. At this level, they develop phenomena of drug interaction, for example, synergy with depressors of the central nervous system or, in the periphery, with alpha-adrenolytic or parasympatholytic drugs. This type of interaction is used in anesthesia to obtain more intense effects with lesser doses of each component and also avoid the toxic effects of efficacious doses of general anesthetics used alone. However, although certain interactions are useful, others may prove harmful. This is in particular the case where neuroleptic drugs are administered after ingestion of alcohol. Various mechanisms, central and peripheral, explain the marked depression of the central nervous system which results. Potentialisation of the effects of tricyclic antidepressor drugs by neuroleptics raises a difficult problem for the anesthetist, the elimination of tricyclic antidepressor drugs is slow and requires several weeks after stopping treatment. During this period, the tissue and plasma concentrations become reduced gradually. They are pharmacologically insufficient, but are potentialised by injection of neuroleptic drugs, and may become active again, and even toxic. It seems to us advisable to avoid the use of neuroleptic drugs in patients treated with tricyclic antidepressor drugs and, if necessary, to use another method of anesthesia.


[The origin and success of neuroleptics]. The authors retrace the origin and the development of the idea of neurolepsy in anesthesiology, first under the influence of Laborit, and in psychiatry, under the influence of Delay and Deniker, during the early 1950's. In these two fields, neuroleptic drugs were considered contrary to ideas and practice at that time and disturbed current ideas.


[Neuroplegia: results of an interdisciplinary approach to its physiopathology]. Neuroplegia was born from a physiopathological study of states of shock and research on inhibition of the autonomic reaction to aggression. Over the last 25 years, the experimental facts have become accumulated in favour of the first theory of H. Laborit, i.e. that this so-called defence reaction defended our lives only through conservation of motor activity in the environment. When this motor activity is inefficacious or useless, the neuroendocrine reaction may lead, during the acute phase, to states of shock and to chronic psychosomatic pathology. On this general theme, inhibition of this reaction by neuroplegic drugs, among which the phenothiazine derivatives have played a very important role, has led in numerous surgical and medical disciplines, to basic research and therapeutic consequences. Thus, in anesthetics, it was at the origin of potentialised anesthesia, then neuroleptanalgesia. In general intensive care, it is used in various ways in the study and treatment of states of shock. In psychiatry, it has initiated neuro-psychopharmacology and the neuro-physiological and biochemical study of the nervous system in its response to the psycho-social environment. It has found its place in anesthesia and in obstetric pathology. But above all, has led pharmacologists to the study of metabolic and biochemical activities. The result of an interdisciplinary approach, neuroplegia has on the contrary, often been the origin of an interdisciplinary development of our physiological and physiopathological knowledge. Today this development seems to better understand its mode of action at various levels of organisation of living systems. One may thus say that neuroplegia, apart from its therapeutic interest, has been a good working instrument and led to better understanding of numerous biological disciplines.


[Neurophysiologic justification of the place of neuroleptics in neuroleptanalgesia]. We studied the action of drugs on the cortical and systemic hemodynamic responses to reticular stimulation and somatic nociceptive stimulation. Central analgesics, even in high dosage, do not suppress the awakening reaction and the attack of hypertension produced by sciatic stimulation in curarised cats. The addition of a neuroplegic, such as Droperidol or Ethrane in low dosage, abolishes completely the response to painful stimulation. The action of pure analgesic anesthesia seems to be situated, above all, at spinal level.


[Endocrine effects of neuroleptics].

[Endocrine effects of neuroleptics]. The neuroleptic drugs used in anesthetics belong to the group of phenothiazines or butyrophenones. The endocrine response to their intravenous administration is still ill-known and usually only concerns the association of anesthetics and neuroleptics. However, as far as the catecholamines are concerned, it is known that neuroleptic drugs do not prevent either their secretion nor their liberation but, depending on their dosage, they block the dopaminergic receptors and the alpha-receptors and induce disturbances in the metabolism of the mono-amines. The injection of neuroleptics associated with analgesics, raises the blood levels of catecholamines, does not induce a rise in ACTH and cortisol levels in the absence of stress, but does not totally prevent their rise in cases of aggression. As far as growth hormone is concerned, the effects are variable depending on the association studied. There is a rise with droperidol + pethidine or pentazocine, no change with chloroprotixene-dextromoramide. In both cases, the blood sugar rises. As far as STH, or growth hormone, free fatty acids and insulin are concerned, one may note a rise with associations containing droperidol even in the absence of any stress and stability with  a mixture of chlorprotixene and dextromoramide. With none of these well known associations was there any variation either in levels of pituitary thyreo-stimulin, nor in thyroxine levels. Testosterone becomes reduced with the association of droperidol + analgesics but this effect does not seem to be specific to droperidol. These responses are frequently disturbed in case of additional stress.


[Sympathetic-adrenergic and hypophysial response to different anesthesia-analgesia technics]. The authors used techniques of pure anesthesia analgesia with Fentathienyl-Pavulon, or anesthesia and analgesia potentialised with Fentathienyl-Flunitrazepam, or Pentothal-Fentathienyl-Pavulon on various series of patients. The study was oriented on changes in the sympathetico-adrenalin pituitary response, and the use of glucose under the effect of these techniques. There was noted a fall in plasma cortisol levels, a fall in urinary excretion of catecholamines, an increase in growth hormone and better peripheral use of glucose. A comparative study was carried out with similar techniques using morphine, pentazocine or fentanyl.


[Limits of pure analgesic anesthesia].

[Limits of pure analgesic anesthesia]. Before dealing with this subject, the author believes that it is useful to give a definition of this technique and justify it. He then recalls the results which he obtained with various analgesic drugs, few products permit this technique, either because of too low analgesic power, or because of the appearance in high dosage, of troublesome or dangerous side-effects. At present, in this type of anesthetic, one may use either morphine or fentanyl or fentathienyl. Analgesic anesthesia with morphine. This technique presents advantages and disadvantages. The author has no personal experience of high doses of morphine and can only report that of other authors who have studied this problem. Anesthesia analgesia with fentanyl and fentathienyl. The author believes that this technique presents advantages over the previous technique, he has personally studied the clinical pharmacology of high doses of fentanyl and he believes that this drug used by the intravenous route, at a dose of 0.05 mg/kg associated with a curare derivative, possesses favourable cardiovascular and respiratory metabolic effects during the surgical operation, but one must recognize that +/-20 p. 100 of cases, fentanyl associated only with curare is not sufficient to give a stable anesthetic. At present, the author has replaced, in his technique, fentanyl by fentathienyl which is a morphine derivative 6 to 7 times more powerful. He found with this drug most of the properties of high doses of fentanyl but the analgesia obtained is deeper, one does not find more than 20 p. 100 of resistant cases. However, the author noted the fairly frequent appearance of tachycardia for which there was no valid explanation. In conclusion. The author believes that in the reproaches which are made to analgesic anesthesia, some are justified, others are less so. It requires prolonged post-operative supervision, but the latter would be advisable for any other type of anesthesia. It dose not always permit one, in its pure form, to obtain stable anesthesia, but this is less and less true with the appearance of more and more powerful derivatives. The use of analgesic anesthesia as a routine technique is only possible in the form of sequential analgesic anesthesia, a technique which uses an antimorphine drug to awaken the patient. In this field, various new products are presented are discussed.


[Definition of the antineurotic, antipsychotic, neuroplegic and neuroleptic properties of psychotropic substances used in anesthesia and resuscitation]. There is a great deal of evidences (pharmacological, experimental and clinical, therapeutic, biological, biochemical, metabolic, toxicological and neurophysiological) which permits one to characterise among the psychotropic substances, the antineurotic or antipsychotic properties of certain psycholeptic drugs.  They authorize also the differentiation in the sub-group of "antipsychotics" of substances with a dominant neuroplegic or neuroleptic activity and others, such as lithium, which do not have this activity. This revision of the terminology avoids the confusion maintained by the use of terms "tranquillisers" and "neuroleptics" in the classification of psychotropic drugs.


Bone marrow transplantation with intensive combination chemotherapy/radiation therapy (SCARI) in acute leukemia. Fifteen patients with acute leukemia resistant to standard chemotherapy were treated by bone marrow transplantation from HLA-matched siblings after conditioning with a new combination chemotherapy/radiation therapy regimen--SCARI. SCARI consists of 5 days of high-dose cytosine arabinoside and 6-thioguanine followed by 3 days of daunorubicin. After a rest period, cyclophosphamide and total-body irradiation are given sequentially. This regimen had acceptable morbidity. Median survival was 169 days. Overall survival and disease-free survival was 27% at over 11 months. Relapse rate was 13% of the entire group and 30% by actuarial projection. Relapses were late and initially extramedullary. Deaths from causes other than leukemia occurred early secondary to fungal infection and late secondary to interstitial pneumonia (frequently cytomegalovirus). Graft-versus-host disease and graft rejection were not causes of mortality. In these patients conditioned with SCARI, leukemic recurrences were infrequent but infectious complications were a major hazard.


Effect of sera from immunologically altered mice on phytohemagglutinin-induced mouse lymphocyte transformation. The DNA-synthetic response of mouse spleen cells to phytohemagglutinin in vitro is depressed by the addition of normal mouse serum. The effects of sera from mice that had been modified immunologically were examined. Increased depressive activity was found in sera from nude mice and from mice recently treated with anti-thymocyte globulin, but no change was found in sera from thymectomized, irradiated, bone marrow-reconstituted mice, nor from lethally or sublethally irradiated or cyclophosphamide-treated mice. Base line DNA synthesis was, however, less inhibited by sera from irradiated or cyclophosphamide-treated mice. Increased depressive activity was found in sera from mice with graft-versus-host reaction and from mice injected with Salmonella enteritidis 11RX, in which macrophage stimulation occurred. Increased depressive activity was also found in the sera of mice injected with sheep erythrocytes. T cells do not appear to be a source of depressive activity but B cells, macrophages and nonlymphoid cells may be sources.


[Feeding and growth of elvers of anguilla Anguilla L. (eel-like teleosten fish) experimentally reared at various temperatures in the laboratory]. In France, there are few researches carried out on the eel's elvers rearing. So, we have undertaken to do, in a first time, a study of their alimentation and growth, in relation to the temperature, at laboratory. The structure of european eels' elvers population, drawn in its natural environment, shows a polymodal frequency distribution of individual weights. The temperature has a direct effect on general metabolism of animals and consequently on their growth. For temperatures included between 10 degrees C and 25 degrees C, any increase of this factor induced an individual activity more important. The quantity of ingested food and its rapidity of utilization, the precocity of alimentary behaviour, are in relation with temperature. The best growth is obtained at 25 degrees C. It seems that this temperature permits to have a very low mortality. From 10 degrees C and below, growth is inhibited, the individual activity and the alimentary taking are very low or non-existent. However, if temperature is elevated, from 11,5 degrees C, growth can start off again, animals are very active and an alimentary behavious is observed. At least, rearing of the european eels' elvers is possible with a salt water (salinity : 32 p. 1000); this system permits suppress in totality fungi desease (saprolegnia).


Measurement of ionised calcium in body fluids-a review. This paper reviews the techniques available to the clinical biochemist for measuring ionised calcium concentrations in biological fluids with particular reference to serum. At present ionised calcium may be measured colorimetrically, using tetramethyl murexide, or potentiometrically, using a calcium ion-selective electrode. These techniques compare favourably in terms of precision with existing methods for measuring total calcium. Advantages of measuring ionised calcium in preference to total calcium are (a) that there is no effect of venous occlusion or change of posture on the ionised fraction of the effect on total calcium, (b) that ionised calcium is the physiologically active form of the element, and (c) that the ionised calcium concentration is a more reliable indicator of the calcium status of patients in certain clinical conditions. The main problem in the measurement of ionised calcium is the marked dependence of the ionised fraction of the pH of the sample. Extreme care must be taken to avoid loss of CO2 or build-up of acid during the handling of the blood sample.


Comparative in vitro activity of piribenicillin, ticarcillin, and carbenicillin against Pseudomonas aeruginosa. Pirbenicillin, a semisynthetic penicillin, showed greater in vitro activity against 68 recent isolates of Pseudomonas aeruginosa than did ticarcillin or carbenicillin. The median minimum inhibitory concentration of each of these three compounds, respectively, was 3.1, 12.5, and 25 mug/ml when a 10(-4) dilution of an overnight culture (about 10(5) colony-forming units [CFU]/ml) was used as inoculum, but these differences were less striking when larger inocula were used: at 10(7) CFU/ml these values were 6.25, 12.5, and 50 mug/ml, and at 10(8) to 10(9) CFU/ml these values were 50, 50, and 100 mug/ml. All three compounds showed greater inhibitory activity at pH 6 than at pH 8. This pH effect was greatest with pirbenicillin, for 6.25 mug of pirbenicillin per ml inhibited 7, 11, and 57% of the strains at pH 6, 7, and 8, respectively; these values were 4, 4, and 11% with ticarcillin and 0, 0, and 7% with carbenicillin. At sufficient inhibitory concentrations, the rates of bacterial killing of the three compounds were similar. The observed differences in anti-pseudomonad activity were not due to differences in stability to pseudomonad beta-lactamases, but all three compounds were more stable than were cefazolin, cephaloridine, and benzylpenicillin.


Beta-Lactamase activity in strains of Bacteroides melaninogenicus and Bacteroides oralis. beta-Lactamase from strains of Bacteroides melaninogenicus and Bacteroides oralis hydrolyzed penicillin more rapidly than ampicillin or carbenicillin. Cephalothin and a chromogenic cephalosporin (87/312) were also hydrolyzed by the enzyme. Activity was found only in beta-lactam-resistant strains, but there was considerable variation in activity among strains having the same minimal inhibitory concentrations of antibiotic. beta-Lactamase activity was cell bound and appeared to be tightly associated with the cell envelope since detergents were required to elute this activity.


Purification and properties of an NADP+-specific isocitrate dehydrogenase from Rhizobium meliloti. An NADP+-specific isocitrate dehydrogenase has been purified and characterized from Rhizobium meliloti. The enzyme showed Mn++ or Mg++ requirement. The apparent Km values were 2.00 x 10(-5) M and 1.51 x 10(-5) M for DL-isocitrate and NADP+, respectively. The enzyme was inhibited by ATP, to a lesser extent by ADP and AMP. alpha-Ketoglutarate also inhibited the enzyme activity. Oxalacetate and glyoxylate together inhibited the enzyme activity. The inhibition was competitive. Studies with thiol inhibitors suggested that the enzyme contained a sulfhydryl group at or near the active site. The enzyme has an approximate molecular weight of 60,000. Fluorescence studies suggested that the enzyme contained tryptophan.


Significance of gamma-glutamyl transferase (GGT) activity measurements in alcohol-induced hepatic injury. Experimental evidence is presented that the determination of gamma-glutamyl transferase (GGT) activity in serum is useful in the assessment of alcohol-induced liver disease and for demonstrating to patients the toxic effects of their drinking habits on the liver. Serial measurements of GGT activity in serum have also proved valuable in monitoring the progress of therapy as well as alleged abstention from alcohol in the known alcoholic.


Mating reaction in Saccharomyces cerevisiae. X. Agglutinability-inactivating factor: a factor which destroys sexual agglutinability of a mating-type cells. From cells of Saccharomyces cerevisiae a factor has been extracted that destroys the agglutinability of a mating-type cells specifically. It was found in the cell extracts of diploid and tetraploid strains as well as haploid strains of a and alpha mating types. It is heat-labile and the molecular weight is about 50,000. It is adsorbed by neither a cells nor alpha cells. Its biological activity is dependent on the incubation temperature and the pH, and is completely inhibited by phenylmethylsulfonyl fluoride, a potent inhibitor of the serine proteases. All the results described in this paper indicate that this factor is a proteolytic enzyme.


Hydrolysis of lactose by immobilized microorganisms. Cells of Lactobacillus bulgaricus, Escherichia coli, and Kluyveromyces (Saccharomyces) lactis immobilized in polyacrylamide gel beads retained 27 to 61% of the beta-galactosidase activity of intact cells. Optimum temperature and pH and thermostability of these microbial beta-galactosidases were negligibly affected by the immobilization. Km values of beta-galactosidase in immobilized cells of L. bulgaricus, E. coli, and K. lactis toward lactose were 4.2, 5.4, and 30 mM, respectively. Neither inhibition nor activation of beta-galactosidase in immobilized L. bulgaricus and E. coli appeared in the presence of galactose, but remarkable inhibition by galactose was detected in the case of the enzyme of immobilized K. lactis. Glucose inhibited noncompetitively the activity of three species of immobilized microbial cells. These kinetic properties were almost the same as those of free beta-galactosidase extracted from individual microorganisms. The activity of immobilized K. lactis was fairly stable during repeated runs, but those of E. coli and L. bulgaricus decreased gradually. These immobilized microbial cells, when introduced into skim milk, demonstrated high activity for converting lactose to monosaccharides. The flavor of skim milk was hardly affected by treatment with these immobilized cells, although the degree of sweetness was raised considerably.


Deconjugation of bile acids by intestinal lactobacilli. Lactobacillus species normally found in the intestinal tract of humans varied in the ability to deconjugate bile acids, whereas laboratory strains of Lactobacillus acidophilus deconjugated both glycocholate and taurocholate. All isolates of L. acidophilus from human feces deconjugated taurocholate, whereas only one of six deconjugated glycocholate. None of 13 isolates identified as L. casei deconjugated taurocholate, whereas 9 deconjugated glycocholate. The deconjugating system of L. acidophilus appeared to be constitutive, required low oxidation-reduction potential, and was most active at pH 6. No degradation beyond deconjugation was detected.


Aggregation of poliovirus and reovirus by dilution in water. Poliovirus and reovirus were found to aggregate into clumps of up to several hundred particles when diluted 10-fold into distilled water from a stock preparation of minimal aggregation in 0.05 M phosphate buffer, pH 7.2, plus 22 to 30% sucrose. Reovirus was also found to aggregate when diluted into phosphate-buffered saline. The aggregation was concentration dependent and did not occur when either virus was diluted into water 100-fold or greater. The aggregation of poliovirus was reversible by further addition of saline and produced a dispersed preparation of virus. Reovirus aggregation was not reversible. Both viruses aggregated when diluted into buffers at pH 5 and 3, and poliovirus aggregated at pH 6, and this aggregation of both viruses was reversible when returned to pH 7. Aggregation did not occur at alkaline pH values. Aggregation at low pH could be caused aggregation of either virus at pH 7. Calcium ions, however, were found to aggregate both viruses at a concentration of 0.01 M.


Ionic bonding, the mechanism of viral uptake by shellfish mucus. An investigation was conducted to determine the processes involved in the contamination of shellfish by viruses. Results of binding-release studies show that the process involves the attachment of viruses to mucus secreted, and then ingested, by shellfish during feeding. Analysis of the mucus-virus bond involved selective degradation of the mucus and use of chemical agents to block carboxyl and sulfate groups on the mucus. Results obtained indicate that the attachment of virus to mucus is primarily ionic and involves the binding of viral particles to sulfate radicals on the mucopolysaccharide moiety of shellfish mucus.


Fermentation of L-aspartate by a saccharolytic strain of Bacteroides melaninogenicus. Resting cells of Bacteroides melaninogenicus fermented L-[14C]aspartate as a single substrate. The 14C-labeled products included succinate, acetate, CO2, oxaloacetate, formate, malate, glycine, alanine, and fumarate in the relative percentages 68, 15, 9.9, 2.7, 1.8, 1.0, 0.7, 0.5, and 0.06, respectively, based on the total counts per minute of the L-[14C]aspartate fermented. Ammonia was produced in high amounts, indicating that 96% of the L-aspartate fermented was deaminated. These data suggest that L-aspartate is mainly being reduced through a number of intermediate reactions involving enzymes of the tricarboxylic acid cycle to succinate. L-[14C]asparagine was also fermented by resting cells of B. melaninogenicus to form L-aspartate, which was subsequently, but less actively, fermented.


Sanitation in self-service automatic washers. The potential for microbial transfer in self-service laundry washing machines was investigated by obtaining swab samples from the interior surfaces of commercial machines and wash water samples before and after disinfectant treatment. Three disinfectants (chlorine, a quaternary ammonium product, and a phenolic disinfectant) were used. Four self-service laundry facilities were sampled, with 10 replications of the procedure for each treatment at each location. Although washers were set on a warmwater setting, the wash water temperatures ranged from 24 to 51 degrees C. The quaternary ammonium product seemed most effective, averaging a 97% microbial kill; chlorine was the second most effective, with a 58% kill, and the phenolic disinfectant was least effective, with only a 25% kill. The efficacies of the chlorine and phenolic disinfectants were reduced at low water temperatures commonly experienced in self-service laundries. Interfamily cross-contamination in self-service facilities is a potential public health problem, which is aggravated by environmental conditions, such as water temperature and the practices of the previous users of the equipment. Procedural changes in laundering are recommended, including the use of a disinfectant to maintain adequate levels of sanitation.


Solar uticaria. Photoallergen in a patient's serum. A 45-year-old man had solar urticaria that was activated by visible light. Passive transfer of the reactivity with the patient's serum to the skin of normal recipients was accomplished. Results of reverse passive transfer studies were negative. The patient developed an urticarial wheal at the site of injection of his own serum that had been previously exposed to light in vitro. The experimental data suggested that his condition was attributable to an allergic response. Systemic administration of reserpine was of some therapeutic value, and increasing exposure to natural sunlight was associated with substantial in crease in his tolerance to sunlight. Unfortunately, the possible loss of reactivity that may occur in the natural course of the disease makes substantiation of the therapeutic effects difficult.


Some aspects of the persistence and fate of acrolein herbicide in water. Experimental data for the decay of acrolein approximated first order kinetics. The reaction continued to completion in local waters but in buffered solution (pH 5.1-8.6) an equilibrium was reached after reaction of about 92% of the acrolein. It is proposed that data presented on the effects of pH on decay of acrolein may be used as a conservative estimate of dissipation rates in water where non-target organisms are at risk. In flowing water in two channels the 8 to 10 fold discrepancy between observed and predicted rates of dissipation was attributed to major losses in volatilization and adsorption. A relatively non-volatile reaction product (which gave a positive reaction with dinitrophenylhydrazine) accumulated initially but dissipated rapidly, probably by microbiological processes, when acrolein concentrations fell below about 2 to 3 ppm.


[Bacteriological examination of sputum (author's transl)]. The AA., emphasizing the importance of ascertain the bronchial source of microorganisms recoverable from sputum, recommend for this purpose the use of properly collected sputum specimens and the application of washing treatment for mucopurulent materials. The aim of the present study has been to verify the effectiveness of mechanical apparatus to homogenize sputum without affecting the viability of resident microorganisms and the usefulness of prior microscopical examination to establish the rate of dilute inocula for the culture.


[Study on the viscolytic activity of the sputum (author's transl)]. Several mucolytic agents were evaluated on sputum for testing their viscolytic activity and the bacterial tollerance to each of them. Proteolytic enzymes (trypsin, pepsin, papain, pancreatin), KJ, and dithiothreitol (or its derivatives) were better tollerated by common respiratory pathogens (H. influenzae, D. pneumoniae, Klebsiella, etc.) than other mucolytic agents, as acetil-cysteine, cisteamine-HCl, tension active substances, mercaptoethanol, and others. The dithiothreitol showed also one of the strongest viscolytic effect and therefore it was selected for the routinary sputum digestion at the concentration 0.1% in PBS pH 7.2. Such a solution was added to sputum specimen in different proportions according to the macroscopic "apparent" viscosity of each specimen. However researches on the comparative viscolytic activity of all the agents hereinafter considered are still in progress.


[Aerobic flora examination of sputum (author's transl)]. The routine bacteriological test of expectorate, except for mycobacteria, is usually unsatisfactory. There is a need of standardization which results in the present paper from a comparison between the data obtained by two different laboratories on the same samples. It is possible to achieve reasonable and uniform results establishing a uniformity of some procedures, namely; collection of specimens, homogenization, number and type of media, interpretation of data and so on.


[Resistance to antibiotics of bacteria involved in respiratory infections (author's transl)]. The present status of resistance to antibiotics of bacteria involved in respiratory infections is reviewed. Schematically it can outlined as follows. Streptococcus B-haemolyticus as well as Pneumococcus did not change their sensitivity to penicillin, but some strains are now resistant to tetracycline. Streptococcus viridans, Enterococcus and H. influenzae did not change substantially their sensitivity to antibiotics. Staphylococcus aureus is the bacterial species that always poses some problems with regard to antibiotic resistance. Due to the selection of strains penicillinase-producing because of the large use of penicillin, the most part of clinical isolates of staphylococci is now resistant to penicillin. In addition an increased number of strains resistant to the other antibiotics has been registered as soon as they has been introduced in therapy. The resistant strains spread in a particularly rapid way in hospital. The introduction in therapy of penicillinase-resistant penicillins constituted a remarkable advance in therapy of staphylococcal infection. However, there is now a growing number of indications about the emergence of methicillin resistant strains of staphylococci. On the other hand it must be recalled that since 1960 a marked reduction of incidence and mortality in severe staphylococcal infections has been noted. Incidence and mortality of respiratory infections due to Gram-negative bacilli is augmented particularly in connection with a larger use of immunosuppressive and antineoplastic therapies, of particular surgical or reanimation procedures, of intensive courses of antibiotic therapy etc. Emergence of Pseudomonas, Proteus, Serratia, Providencia, etc. infections poses many difficult problems of chemotherapy since these species are scarcely sensitive to antibiotics. Carbenicillin, cephalosporins, sisomicin, tobramycin, amikacin are the more recent drugs that alone or in combination may offer some chances of success in this field.


Treatment of hemorrhagic gastritis by antacid. A simple and safe method of nonsurgical treatment for the control of massive acute gastric mucosal hemorrhage is described. The procedure was developed from experimental and clinical observations that the presence of gastric hydrocloric acid played an important part in the development and perpetuation of the entity. The treatment consists of complete neutralization of gastric acid with antacid to a pH of 7. The antacid is intermittently added and aspirate at 7. In a retrospective analysis, the hemorrhage was controlled in 44 of 49 patients (89%). Five patients who continued to bleed underwent surgery (10%). Three patients had vagotomy and pyloroplasty and their bleeding ceased without recurrence. Two patients underwent partial gastrectomy, but they developed recurrent bleeding and died. One patient whose bleeding has been controlled by vagotomy and pyloroplasty died without hemorrhage 10 days after operation. Of the 44 patients whose bleeding had been controlled by antacid, 11 patients died without hemorrhage one or more weeks later. These results of 89% control of hemorrhage compare favorably with those in the literature.


Patterns of gastroesophageal reflux in health and disease. Twenty-four pH monitoring the distal esophagus quantitates gastroesophageal reflux in a near physiologic setting by measuring the frequency and duration of acid exposure to the esophageal mucosa. Fifteen asymptomatic volunteers were studies with 24-hour pH and esophageal manometry. The normal cardia was more competent supine than in the upright position. Physiologic reflux was unaffected by age, rarely occurred during slumber, and was the rule after alimentation. One hundred symptomatic pateitns with an abnormal 24-hour pH record (2 S.D. above the mean of controls) could be divided into three patterns of pathological reflux: those who refluxed only in the upright position (9), only in the supine position (37), and in both positions (54). Upright differed from supine refluxers by excessive aerophagia causing reflux episodes by repetitive belching. Compared to controls, they had excessive post-prandial reflux, lower DES pressure, and less DES exposed to the positive pressure of the abdomen. Supine differed from upright refluxers by having a higher incidence of esophagitis and an inability to clear the esophagus of acid after a supine reflux episode. Compared to controls, they had only a lower DES pressure. Combined refluxers had a higher incidence of esophagitis than supine refluxers. Stricture (15%) was seen only in this group. They were similar to supine refluxers in their inability to clear a supine reflux episode. Compared to controls, they had a lower DES pressure and less DES exposed to the positive pressure of the abdomen. Forty of the 100 patients had an antireflux procedure (4 upright, 8 supine, 28 combined). The most severe postoperative flatus and abdominal distention was seen in the upright refluxers. It is concluded that minimal reflux is physiological. Patients with pathological reflux all have lower DES pressure. Patients with upright reflux have less of their DES exposed to the positive pressure environment of the abdomen. Patients with supine reflux have an inability to clear the esophagus of reflux acid and are prone to develop esophagitis. Patients with both upright and supine reflux have the most severe disease and are at risk in developing strictures. In patients with only upright reflux, aerophagia and delayed gastric emptying may be an important etiological factor.


Long-term follow-up of internal mammary artery myocardial implantation. A study was made of 100 patients who had undergone internal mammary artery myocardial implantation 7 to 10 years previously. Forty-two patients had single implantation with or without a free omental graft, and 54 received double implantations. Four patients had a single internal mammary artery implant plus a single aortocoronary bypass graft. Eleven patients died at operation or within the first month, and 17 died from 1 to 7 years following operation. Two were lost to follow-up, and 15 refused follow-up angiograms. From 7 to 10 years postoperatively, angiographic studies were performed on 55 patients with 73 internal mammary artery implants. Of these 73 implants, 17 (23%) were occluded; 10 (14%) were patent but did not show myocardial filling; 15 (21%) showed myocardial blush or filling of small vessels; and 31 (42%) showed filling of a major coronary artery. The patency rate correlated well with the amount of coronary disease and slightly with the amount of symptomatic improvement. This study shows that the Vineberg operation is physiologically sound; however, the ideal candidates are those patients with coronary arteries of adequate size who could benefit more by direct perfusion.


Inhibition of prostaglandin biosynthesis by non-narcotic analgesic drugs. The existence of a relationship between inhibition of prostaglandin biosynthesis and analgesic or anti-inflammatory activity was investigated in the case of the non-narcotic analgesics glafenine, floctafenine and clometacine, in comparison to indomethacin and acetylsalicylic acid. These compounds inhibit prostaglandin biosynthesis from arachidonic acid in a guinea-pig lung homogenate as strongly as indomethacin. On its biosynthesis in rat epididymal tissue stimulated by noradrenaline, glafenine equals indomethacin inhibitory potency, whereas floctafenine and clometacine are less active. Acetylsalicylic acid is the least active in both preparations. In vivo, prostaglandin biosynthesis induced in rat peritoneal fluid by injection of acetic acid is inhibited by the 5 drugs, ranked as follows: floctafenine greater than indomethacin greater than glafenine greater than clometacine greater than acetylsalicylic acid. The pharmacological profile of glafenine, floctafenine and clometacine is characterized by a relatively strong effect on acetic acid writhing and a relatively weak effect on carrageenin oedema, U.V. erythema and adjuvant arthritis. The inhibition of prostaglandin biosynthesis seems better correlated with their analgesic activity than with their anti-inflammatory effects. The results show that prostaglandins could play an important role in the genesis of tissulary pain in animals.


Selectivity of clenbuterol (NAB 365) in guinea-pig isolated tissues containing beta-adrenoceptors. The effects of clenbuterol (ANB 365), an aminohalogen substituted phenylethanolamine, have been examined on isolated tissue preparations from guinea-pigs. Clenbuterol produced concentration (or dose)-dependent relaxations of tracheal chains, decreases in perfusion pressure of hind limb blood vessels, inhibitions of acetylcholine-induced contractions of the uterus, increases in atrial rate and inhibitions of electrically-induced contractions of the ileum. These responses were blocked by propranolol. Clenbuterol was similar in potency to isoprenaline on the trachea (carbachol-contracted), hind limb and uterus (beta2-adrenoceptors) but was significantly less potent than isoprenaline on the atria and the ileum (beta1-adrenoceptors). Clenbuterol produced marked relaxation of intrinsic tone tracheal preparations in concentrations up to 3000 times less than were required on carbachol-contracted preparations, whereas for isoprenaline the concentrations required on intrinsic tone preparations were only 55 fold less. It is concluded that clenbuterol is a beta-adrenoceptor agonist and that it is a partial agonist on the carbachol-stimulated trachea, on the atria and on hind limb blood vessels. It shows beta2-selectivity in that its potency, relative to that of isoprenaline, on the preparations containing beta2-adrenoceptors was much higher than on those with beta1-adrenoceptors. On intrinsic tone tracheal preparations it may produce an additional relaxant effect responsible for its high potency on that preparation.