[Basic principles of physiotherapy for allergic diseases of the otorhinolaryngologic organs]. Physiotherapy for allergic diseases of otorhinolaryngeal organs is often practiced without taking into consideration the stage of development of the pathologic process, its form and individual peculiarities of its course. This is partly connected with lack of data on the mechanism of the hyposensibilizing effect of physiofactors. In this paper the authors divide the methods of hyposensibilizing physiotherapy into groups according to their prevalent effect on the particular system taking part in the formation of clinical manifestations of the allergic reaction. The authors discuss the expediency of using each group of methods at various stages of the disease according to its form and individual peculiarities of its course.


[Glucose infusions in suspected chronic placental insufficiency caused by gestosis]. In this study glucose load and its possible therapeutical efficiency in chronic nutritive insufficiency of the placenta is investigated. Following a definite regime glucose infusions were applied to the mother prepartually as well as subpartually in order to substitute the carbohydrate metabolism of hypotrophic fetuses. Glucose values and the parameters of the acid-base-balance were taken and calculated. The microblood analyses were performed subpartually on the mother and the fetus and postpartually on the newborn. The results gained are discussed and explained with regard to metabolism. The glucose infusion therapy in the form mentioned is suited to influence favourably the fetal hypoglucosemia.


Susceptibility of Staphylococcus aureus, Streptococcus pyogenes and Diplococcus pneumoniae to antibiotics. Comparison of patterns in Poland and Federal Republic of Germany. One hundred and eighty five strains of Gram-positive cocci were tested for susceptibility to 16 antibiotics, including some newer drugs, by agar dilution technique. Of these, 100 strains (50 each isolated in Poland and Germany) were Staphylococcus aureus, 55 Streptococcus pyogenes, and 30 Diplococcus pneumoniae. Previous investigations of streptococci and pneumococci isolated in Poland and Federal Republic of Grmany, revealed no differences in antibiotic-susceptibility patterns in both countries, which was not the case with staphylococci. Present study demonstrates further evidence for existence of differences in antibiotic-sensitivity of staphylococci, depending of their geographical origin, and presents actual state of susceptibility to antibiotics of Streptococcus pyogenes and Diplococcus pneumoniae.


Sport training and some activities of human polymorphonuclear leukocyte lysosomes. The acid phosphatase and protease, neutral protease, bactericidal and mitogenic activities were determined in the polymorphonuclear leukocyte (PMNL) lysosomes of 16 years old boys. The investigated group consisted of 20 intense sport training persons during the last six years, the control one of the same age boys without any sport training. The significant decrease of hydrolase activity has been observed in the lysosomes of the peripheral blood PMNL's of the sport training boys.


[Enzymatic conversion of tetradecanol in heterogenous phase by yeast-alcohol dehydrogenase]. Alcohol dehydrogenase from yeast converts long-chain primary alcohols not only in the dissolved state, but also at the surface of undissolved particles. Tetradecanol beads with a defined surface can be produced and employed as model substrate. The reaction rate was determined by the proton release accomplished in the reaction. The initial reaction rate depends on the enzyme concentration. The relation is nonlinear (vi = k-[e]0,4); the numerical value of the exponent (n = 0.4) argues in favour of a reaction occurring at the interface. The Lineweaver-Burk plots become linear if the substrate concentrations are based on the molar surface concentrations of the particles. The pH optimum for the reaction at the surface is displaced by 0.25 pH units towards the alkaline region (compared with ethanol as substrate). The activation energy of the reaction with tetradecanol beads as substrate is 30% lower than that for the ethanol oxydation.


[Structure-activity relationships of halogenated phenylethanolamine and phenoxypropanolamine]. 12 compounds from the series of halogenated phenylethanolamines and phenoxypropanolamines were tested at the isolated rabbit jejunum, and the pD2-and pA2-values were determined. All the substances act beta-adrenolytically. Except for 3,4-dichloronoradrenaline, which stimulates the alpha-receptors, all the compounds still have pronounced beta-mimetic effects. The 2,5-dihalogenated phenylethanolamines and phenoxypropanolamines block the beta-receptors at lower concentrations than 2,4-dihalogen derivatives. The weakest beta-adrenolytic effects at the intestine were found with compounds halogenated at the 3,4-position.


The binding of noradrenaline to human erythrocytes. When human erythrocytes are incubated in a suspension medium containing noradrenaline, they take up noradrenaline in a reaction proceeding in two phases. In a rapid first reaction noradrenaline is bound by the cells by adsorption at pH-values above 6.0; this reaction follows Freundlich's isotherms. Subsequently, noradrenaline is taken up much more slowly by transmembranous diffusion into the cells. Neither reaction can be influenced by inhibitors such as N-ethyl maleinimide, ouabain, alpha- or beta-receptor blockers.


[Renal excretion of long term sulfonamides under fluid administration and modification of the urinary pH value]. The renal excretion of sulfaclomide, sulfamerazine and sulfamethoxypyridazine is delayed by increased fluid application in rats. The simultaneous administration of sulfonamides and ammonium chloride or sodium hydrogen carbonate causes, respectively, retardation and acceleration of renal sulfonamide excretion which is consistent with the change in urinary pH value. The retarded renal sulfonamide excretion with increasing diuresis is explained by the ensuing change in the urinary pH value. For clinical uses, a speedy renal excretion of long-time sulfonamides by increased diuresis can be expected only if alkalization of the urine is achieved at the same time.


On the behaviour of murine lymphocytes after in vitro treatment with acid mucoproteins from human serum. Seromucoproteins from human serum were isolated by perchloric acid extraction followed by DEAE-Sephadex A-50 ion exchange chromatography. The in vitro pretreatment of spleen leukocytes with this fraction caused a dose-dependent inhibition of graft-versus-host reaction as well as an increase of their electrophoretic mobility, the viability being maintained. On contrary, the pretreatment of mice (prospective spleen cell donors of recipients of sheep red blood cells) with human seromucoproteins had no effect on the gvh-reaction as well as on the agglutinin formation to sheep red blood cells under the given conditions. It is supposed that the suppressive effect after in vitro pretreatment may be attributed to a coating effect of seromucoproteins. The fact that spleen cells pretreated in vitro with seromucoproteins are lysed in presence of complement and antiseromucoprotein antiserum supports our opinion. These findings as well as data from the literature support the hypothesis that local concentrated mucoproteins in the skin graft bed in cases of protractedly surviving skin grafts, in the placenta, and on neoplastic tissues can influence unspecifically the immune response. We hope that the understanding of this mechanism may open new possibilities in prolonging allograft survival time.


Immunological mechanisms in aspirin hypersensitivity. Studies on the immunogenicity of free aspirin. Anti-aspiryl antibodies were produced in rabbits and guinea pigs by inoculation of aspirin incorporated in complete or incomplete Freund's adjuvant. These antibodies were readily detected by passive haemagglutination using rabbit erythrocytes incubated with aspirin at alkaline pH. Aspiryl conjugates with ovalbumin, human gamma-globulin, bovine gamma-globulin and rabbit serum were also prepared by incubating the proteins with aspirin at alkaline pH. Aspiryl conjugates prepared by this technique behaved, immunologically, identically with the conjugates prepared from aspirin chloride. By contrast, the molar absorbance at 305 nm of the conjugates prepared from aspirin was about 25 times lower than the molar absorbance of the conjugates prepared from aspirin chloride. Since the absorbance of salicylic acid is about eight times greater than that of aspirin, the conclusion is drawn that the aspiryl/salicylyl ratio is significantly higher in the conjugates prepared by incubating proteins with aspirin at alkaline pH than in the conjugates prepared from aspirin chloride. In parallel experiments, salicylic acid did not induce formation of specific antibodies capable of reacting with aspirin- or salicylic acid-treated red cells. Sera giving positive passive haemagglutination with aspirin-treated erythrocytes did not react with erythrocytes treated with salicylic acid or acetic anhydride.


High uptake in the erythrocytes and the spleen of the quaternary dipyridylium salt paraquat injected intravenously in hypotonic solutions. Intravenous injections of the quaternary dipyridlium salt paraquat (14C-labelled) dissolved in solutions of low tonicity result in a high uptake in the erythrocytes and concomitantly also in the spleen (red pulp), the latter being probably due to phagocytosis of paraquat-containing erythrocytes by the reticuloendothelial system. Higher tonicities of the injected solutions result in a low uptake and the same applies to oral, intraperitoneal and subcutaneous injections. Paraquat was present in the erythrocytes in a non-metabolized form without being bound to membranes or proteins. The uptake in the erythrocytes was not influenced by alterations of the pH or by the preparation of a charge-transfer complex with serotonin in the injection solutions. Chemical alterations of the paraquat in the injection solutions could not be detected. In vitro the uptake of paraquat in the erythrocytes was higher in the haemolysed (and then reconstituted by adding sodium chloride) erythrocyte-ghosts than in the non-haemolysed erythrocytes, as shown by incubations at various tonicities. It is proposed that the intravenous injections of paraquat in hypotonic solutions temporarily alter the membranes of the erythrocytes in the blood-stream and make them permeable to paraquat, possibly, as judged from the in vitro experiments, only during a short period of partial haemolysis. The distribution studies also showed a retention of paraquat in the lungs. In addition paraquat was accumulated in the melanin of the tissues.


Morphology and enzyme aktivity in rat small intestinal epithelium 6 and 12 hrs. after an alkylating agent (cyclophosphamide). Six and twelve hours after a single i.p. dose of cyclophosphamide (100 mg/kg body weight) the activity of different "brush border enzymes" (maltase, sucrase lactase, alkaline phosphatase, gamma-glutamyl transferase) and of a lysosomal enzyme (acid phosphatase) did not change. In vivo absorption of galactose was not diminished by the treatment. The pattern of response to cyclophosphamide seems to be different in SPF and GF rats. The response of crypt epithelium (cell number, mitotic number, mitotic frequency) was more pronounced in the SPF rats, whereas the villus height only decreased in the GF rats.


Hypertension in end-stage renal disease. The relationship between blood pressure, plasma renin, plasma renin substrate and exchangeable sodium in chronic hemodialysis patients. Blood pressure (BP), plasma renin concentration (PRC), plasma renin substrate concentration (PRSC) and exchangeable sodium (ES) have been studied in 27 patients undergoing regular hemodialysis because of end-stage renal disease. PRC was significantly higher in the hypertensive than in the normotensive patients. The pattern of PRSC was similar in the groups of patients but with a marked individual variation. ES was slightly lower in the hypertensives than in the normotensives but the difference was not statistically significant. Multiple regression analysis demonstrated a significant correlation between mean BP, the natural logarithm of PRC and ES, but the effect of ES was negligible. PRC was negatively correlated to ES in all patients, including the hypertensives. These results strongly suggest that the renin-angiotensin system is the most important factor involved in the pathogenesis of hypertension in end-stage renal disease, when sodium balance is adequately controlled. A clinical application of the predictive value of PRC concerning the effect of bilateral nephrectomy on hypertension is outlined.


A new pattern of multiple endocrine adenomatosis: chemodectoma, bronchial carcinoid, GH-producing pituitary adenoma, and hyperplasia of the parathyroid glands, and antral and duodenal gastrin cells. A female patient was found to have a chemodectoma, a GH-producing pituitary tumour and a bronchial carcinoid combined with hyperplasia of the parathyroids and of antral and duodenal gastrin cells. This combination of endocrine tumours and hyperplasias does not fit with the two multiple endocrine adenomatosis syndromes recognized at present. The case stresses the importance of scanning the patient for other endocrine tumours, once one has been diagnosed.


Multiple endocrine adenomatosis of mixed type. A case of multiple endocrine adenomatosis (MEA) of mixed type is presented. The syndrome, observed in a 65 year-old female, consisted of multiple neurofibroadenomatosis, medullary thyroid carcinoma, multiple adenomata of the parathyroids, adrenal cortical adenoma and small cell anaplastic bronchogenic carcinoma. Thus, it was composed of type 1 as well as of type 2 MEA. On the basis of another seven cases, collected from the literature, the MEA syndrome of mixed type is reviewed with special reference to the phylogenetic origin of the cells of the APUD system.


Current dimensions of the endocrine system. The basic and clinical sciences have become fused in the investigation of relatively new syndromes and their pathogenesis. The measurement of hormone content in serum and tissues and the elucidation of its biologic effect via the membrane and cytoplasmic receptors leads to diagnostic and prognostic accuracy. New breakthrough advances in clinical and cellular phenomena will portend new horizons for more specific diagnoses and modern treatment of present and new endocrinopathies. The dimensions of the neuroendocrine system are expanding; the future perimeters are beyond sight today.


Present state of alpha- and beta-adrenergic drugs I. The adrenergic receptor. The cardiovascular alpha adrenergic receptors evoke vasoconstriction, the cardiovascular beta receptors evoke vasodilation and cardiac stimulation. All blood vessels have both alpha and beta receptors. In some areas, for example skin and kidney, the alpha receptors predominate. In some vascular beds, for example the nutrient vessels in skeletal muscle, beta receptors predominate. In other beds, such as coronary, visceral, and connective tissue both receptors are active. The cardiovascular effects of adrenergic agonists depend on which receptor they act on. Phenylephrine is specific for alpha receptors. Isoproterenol is specific for beta receptors. Epinephrine and norepinephrine act on both. The real value of knowing the receptor specificity of each agonist is that side effects can more easily be predicted. For example, adrenergic cardiac stimulants are antiasthmatics. Therefore, adrenergic antiasthmatics can produce excessive cardiac stimulation. For the future, agonists that are not only receptor-specific but also tissue-specific will be developed. The first of these in the United States is terbutaline. The rest of the world has in addition a similar drug, salbutamol. No one knows if this drug will be approved for use by American physicians.


Juvenile Sandhoff disease: some properties of the residual hexosaminidase in cultured fibroblasts. The residual hexosaminidase isoenzymes in juvenile Sandhoff and infantile Sandhoff disease fibroblasts, have been determined by starch gel electrophoresis and column isoelectric focusing. Hex A and hex S are the major residual isozymes in fibroblasts from the juvenile patient, while hex B is barely detectable. Only hex S could be detected in fibroblasts from infantile Sandhoff patients. These results suggest that the defects in juvenile and infantile Sandhoff disease may be different allelic modifications of the beta subunit common to hex A and hex B.


Effect of sodium depletion on plasma renin concentration before and during adrenergic beta-receptor blockade with propranolol in normotensive man. Plasma renin levels have been used to discriminate between different forms of hypertension, but how to define the normal range of plasma renin levels has not been agreed upon. Sodium depletion stimulates renin release. Evaluation of plasma renin would, therefore seem possible only in relation to sodium balance. Plasma renin concentration and concurrent daily sodium excretion were determined in 33 healthy normotensive subjects (control group) ingesting high, normal and low sodium diets. A well-defined hyperbolic relationship was found between the two variables indicating that the physiologic level of plasma renin concentration depends on the state of sodium balance. An increase in plasma potassium concentration may reduce plasma renin concentration, but this appeared to be overruled by the stimulating effect of sodium depletion. To examine whether beta-adrenergic stimulation contributes to the increase in plasma renin concentration during sodium depletion, the relationship between plasma renin concentration and concurrent sodium excretion was studied during beta-receptor blockade with propranolol. In 20 healthy normotensive subjects in whom beta-receptor blockade was verified by a significant reduction in pulse rate, the same hyperbolic relationship was found between plasma renin concentration and sodium excretion as in the control group showing that sodium depletion stimulates renin release independent of sympathetic nervous activity.


[Etiopathogenesis of necrotizing arteritis (leukocytoclastic vasculitis)]. The small vessel's necrotizing angiitis (necrotizing microangiitis (NMA), leucocytoclastic angiitis) form a continuous spectrum from the exclusively cutaneous forms of Gougreot, to those which seriously affect the viscera, as the very acute and fatal cases of Zeek, passing through a series of intermediate phases, in which Schönlein-Henoch's purpura is found. In all of these clinical forms, the existence of an allergic mechanism has been suggested from their origin itself and in 1964 Alarcón-Segovia and Brown grouped them under the common denominator of allergic angiitis. Later investigations are far from completely confirming this hypothesis. In isolated cases, the clinical sequence corroborates the hypothesis of a bacterian aetiology (local septic focus), but in the Schónlein-Henoch purpura it has not been proven that there is a greater streptococcus beta-haemolytic frequency is the throat nor a greater number of antibodies in the serum than in normal children or those affected by illnesses not related to rheumatic fever. The aetiologic role of drugs and food is very difficult to prove. The anatomopathologic similarity between the Arthus reaction, the serum sickness and the spontaneous human NMA have led to the hypothesis that the NMA are immunocomplex (IC) diseases. In order to try to prove this, basically three techniques have been used: Direct immunofluorescence to show the IC tissue deposits, and mixed cryoglobulinemia and the serum's anti-complementary activity for the circulating IC. Direct immunofluorescence shows, in approximately 50% of the cases, the presence of IgG and C3 in the damaged vessels (also IgM with frequency). But, are these found combined as complexes? Parish, in some cases of presumably post-bacterial angiitis, has shown the simultaneous presence of the bacterian antigen and the Ig. The direct immunofluorescence negativity can be due to: (1) The IC being rapidly eliminated by the neutrophils; (2) the fact that these are nonimmunologic pathologic cases. On the other hand, the IC deposit could be a passive phenomenon in a previously damaged vessel. With great frequency, mixed cryoglobulinemia is associated with systemic conditions of the auto-immune type (collagenosis, etc) or of the malignant lymphoid haemopathy type, and with NMA. With what frequency is mixed cryoglobulinemia found in the NMA? 33% of the 47 cream's cases. What is the pathogenic relationship between processes? Often the cryoglobulin components are found deposited in angiitis lesions, but its presence and intensity does not guard any relationship with the cryoglobulinemia rate. Besides the 33% of the cases with mixed cryoglobulinemia, 13% serum's anti-complementary activity, and the remaining 54% had no indications of circulating IC with the usual techniques. Of 104 cases of Schónlein-Henoch purpura, 75 of which had nephritis, only 10% had hypocomplementemia. In summary, in about 50% of the patients with NMA, no reasonable indication of IC disease was found...


Methodologic problems in plasma renin activity measurements. The influence of pH and angiotensinase inhibitors on the in vitro generation of angiotensin I during PRA measurements has been investigated. PRA values obtained at pH 5.7 are higher than those obtained at pH 7.4. At pH 5.7, values obtained using diisopropylfluorophosphate (DRP 9 mM) as an angiotensinase inhibitor are higher than values obtained with a mixture of dimercaprol (BAL, 1.6 mM) and hydroxyquinoline (8-OHQ, 3 to 4 mM). Since the two methods for inhibiting angiotensinase are completely and equally efficient, it is suggested that these inhibitors might interfere with the renin angiotensinogen reaction. Significant correlations are observed between the PRA values obtained by the different methods which have been studied. Using an incubation pH of 5.7, and BAL and 8-OH quinoline as angiotensinase inhibitors, the distribution of PRA values in a population of 124 hospitalized hypertensive patients ingesting a normal sodium diet had been studied, and it has been demonstrated that the sensitivity of this method of measurement can detect small changes in PRA in patients with low renin activity.


Plasma prorenin: cryoactivation and relationship to renin substrate in normal subjects. We previously demonstrated an inactive form of renin, termed prorenin, in the plasma of normal, hypertensive and anephric patients. Prorenin activity can be determined in plasma from the total renin activity after activation, minus the prior endogenous plasma renin activity. In the present study, conditions for cryoactivation of prorenin have been defined. Plasma prorenin is slowly converted to active renin-like material at -5 degrees C at pH 7.4. Activation takes four days and does not occur at pH 5.0. The degree of activation increases above pH 5 and is greatest between pH 7 and pH 9. Thus, almost no cryoactivation of prorenin occurs at the pH optimum for renin (5.7) in contrast to maximum activation at pH 7.4. No activation has been observed in the frozen state, but it does occur with decreasing rapidity at temperatures from -5 degress to +4 degress C. Since blood samples obtained for the determination of plasma renin activity are routinely chilled upon collection by most laboratories, some activatin of prorenin most likely occurs in all routine renin assays. The pH optimum of the enzymatic reaction of the activated prorenin in plasma is 5.8, the same as for renal renin, and the shape of the pH optimum curve is similar to that of renal renin added to human plasma. In a group of 23 normal subjects with plasma renin activity of 3.5 +/- 2.9 (SD), the activated prorenin increment was found to be significantly higher, 6.3 +/- 5.0 (SD) ng/ml/hour. Unlike plasma renin activity, prorenin activity in these normal subjects was directly related to the concentration of renin substrate (p less than 0.001). When the actual "concentration" of prorenin was calculated using renal renin as the reference standard, a direct relationship was also found between the concentration of prorenin and renin substrate (p less than 0.01). The observed relationship between prorenin and renin substrate concentrations might be a consequence of their regulation by common factors.


Beta-adrenergic receptor blocking drugs in spontaneous hypertension. Eleven beta-adrenergic receptor blocking agents and derivatives were evaluated for their ability to affect systolic arterial blood pressure and pulse rate in unanesthetized, male spontaneously hypertensive rats (SHRs) and normotensive Wistar Kyoto (WKY) controls. Animals ranged from 7 to 76 weeks of age. The subcutaneous injection of 5 and 45 mg/kg metoprolol in 52 to 64 week old SHRs and 45 mg/kg twice a day to 26 to 29 week old SHRs produced a significant decrease in blooc pressure. The subcutaneous injection of pindolol (0.1 and 1.0 mg/kg) produced a greater and more consistent depressor effect in mature SHRs. The subcutaneous administration of sotalol (100 mg/kg) and alprenolol (20 mg/kg) resulted in a depressor action which was significant 120 minutes after injection of the drug. In the doses used, propranolol, oxprenolol, 4-hydroxypropranolol and K9-1366 produced pressor effect in SHRs. Propranolol did not cause this pressor effect in prehypertensive (seven week old) SHRs. Practolol, dextro-propranolol and KO-1313 had no effect on blood pressure in the doses used. Propranolol, pindolol, metoprolol, dextro-propranolol, 4-hydroxypropranolol, practolol, oxprenolol, KO-1366 and KO-1313 produced no significant effects on blood pressure in normotensive WKY controls in the doses tested. Placing oral doses of 160 mg/kg/day of metoprolol in the drinking water for seven days significantly lowered blood pressure in 14 week old SHRs previously exposed to ineffective doses of 77 mg/kg/day for 24 days. The administration of oral doses of oxprenolol (40 mg/kg/day) in drinking water for three weeks had a slight but insignificant pressor effect. Smaller doses of metoprolol (15 and 39 mg/kg/day for three to four weeks) and practolol (70 to 85 mg/kg/day for two weeks) had no effect on 52 week old SHRs. Oral doses of pindolol, metoprolol, practolol and oxprenolol had no significant effect on blood pressure in WKY controls. There was no clear relationship between the effects of the drugs on blood pressure and their ability to affect the pulse rate. Similarly, there did not appear to be any consistent relationship between the potency of the beta-blocking drug and the blood pressure lowering action. In addition, neither cardioselective beta-blockade nor sympathomimetic properties allowed the prediction of blood pressure responses to the administration of those agents possessing these features. Although SHRs provide a valuable model of human essential hypertension, the variable effects reported here and elsewhere in the literature require caution as to the applicability and usefulness of testing and evaluating beta-adrenergic blocking drugs for theri potential anti-hypertensive effects in this particular form of experimental hypertension.


Modern system for treating high blood pressure based on renin profiling and vasoconstriction-volume analysis: a primary role for beta blocking drugs such as propranolol. A new system is proposed for treating the spectrum of patients with high blood pressure. It is based on studies of the renin axis using renin profiling, pharmacologic probes and our bipolar vasoconstriction-volume hypothesis. The new system does not require renin profiling, pharmacologic testing or a vasoconstriction-volume analysis for widespread application. But these procedures, whenever available, will make treatment more efficient and more certain, and at the same time provide better base line definition.  In the new system, all patients, except the elderly and those with congestive heart failure, bradycardia or a history of asthma, are treated first with propranolol alone, a procedure which will diminish or normalize blood pressure in many patients with high and noraml renin levels. For nonresponders, diuretic therapy is then superimposed. Subsequently, a propranolol subtraction trial picks out the low-renin patients who will usually respond to a diuretic alone. This program is likely to be fully effective in possible up to 85 per cent of patients. For the residual smaller fraction, drugs such as hydralazine, methyl DOPA, clonidine, reserpine or guanethidine are then added in traditional trial and error fashion. The proposed system has the theoretic attraction for long-term commitment, implicit in antihypertensive therapy, of achieving blood pressure control in large fractions with one drug instead of two or with two drugs instead of three or more. Moreover, the large groups who respond to therapy with propranolol alone (most high-renin and normal-renin patients) or to diuretics alone (most low-renin patients) gain the advantage of simple, more specific, long-term (i.e., antirenin or antivolume) therapy. The use of propranolol alone has practical and theoretic advantages over diuretics. Control may be achieved with even fewer side effects and without hypokalemia and chronic dehydration with its possibly adverse consequences (hyperuricemia, azotemia, hyperlipidemia, hyperreninemia, increased blood viscosity). Also, propranolol provides more direct control of the increased peripheral resistance and of neurogenically-induced swings in blood pressure. At the same time, the new system efficiently exploits the long-term use of diuretic therapy alone in low-renin patients in whom volume excess seems a causal factor. And it tends to avoid the use of diuretics in high-renin patients and of beta-blockers in low-renin patients in whom these drug types may be contraindicated.


Controlled trial of fetal intensive care. A fetal intensive care unit was formed at the Queen Victoria Memorial Hospital in 1972. Because of some doubt concerning the value of fetal intensive care, a controlled clinical trial including all high-risk patients was performed. The trial clearly showed that intensive care is associated with improved neurologic and biochemical status of the neonate; however, it is possible that this improvement results from the use of fetal diagnostic tests or some other factor associated with intensive care. Sufficient evidence was gathered to warrant the continuation of fetal intensive care in this hospital, but in other contries, where funding is difficult to obtain, a controlled trial would appear justified.


Other hydrophilic lens environments: pH. Although hydrophilic contact lenses are specifically designed for compatibility with the eye environment, i.e., the tears, they will, with the exception of continuous wear types, spend a significant fraction of their daily cycle in other solutions. This investigation explores the pH characteristics of certain of those alternative media.


Participation of H1 and H2 histamine receptors in physiological vasodilator responses. Histamine causes vasodilation in the dog by activation of H1 and H2 receptors blocked by mepyramine and metiamide, respectively. Experiments were conducted in anesthetized dogs to determine the participation of H1 and H2 receptors in several forms of physiological dilatation. Mepyramine attenuated both histamine-induced and active-reflex dilatation in the hindlimb. Metiamide caused a further reduction in both sets of dilatation. Neither single nor combined antihistamines reduced dilatation due to exercise or after temporary occlusion of the circulation in the hindlimb. Poststimulation dilatation in the gracilis muscle was partially attenuated by metiamide or mepyramine. Neither dilatation caused by sympathetic nerve stimulation in the hindpaw nor dilatation in the gracilis muscle caused by compound 48/80 was reduced by mepyramine. Following combined H1- and H2-receptor blockade, portions of both types of dilatation were reduced. These data provide evidence for the participation of both types of histamine receptor in active reflex dilatation, low-frequency neurogenic dilatation, dilatation caused by compound 48/80, and poststimulation dilatation. Neither type of histamine receptor appears to be involved in reactive hyperemia or dilatation caused by exercise.


Maleate-induced bicarbonaturia in the dog: a carbonic anhydrase-independene effect. Studies were performed to characterize the renal effects of maleate in anesthetized dogs. Following the intravenous administration of maleate or maleic acid (50 mg/kg), mean fractional bicarbonate excretion (CHCO3/GFR) rose to as high as 26%. Na, K, and phosphate excretion also increased markedly, whereas C1 excretion remained low. An initial transient fall in urinary pH from 6.53 to 6.13 contrasted sharply with the rapid alkalinization of the urine induced by acetazolamide administration. During saline expansion CHCO3/GFR rose from 4 to 37% after maleate administration, whereas Cl excretion did not change significantly. During continuous carbonic anhydrase inhibition with acetazolamide, maleate administration resulted in a further rise in CHCO3/GFR from 22 to 35%. Whereas CPO4/GFR increased only from 1 to 3% during acetazolamide administration, this ratio reached 75% following the addition of maleate. Fumarate, the transisomer of maleate, and malonate, a well-known inhibitor of Krebs cycle, failed to affect bicarbonate excretion. This study demonstrates that maleate inhibits the fraction of bicarbonate reabsorption uncatalyzed by carbonic anhydrase. Impaired anionic reabsorption of bicarbonate or accelerated passive backflux of this ion into proximal tubular lumen are the two mechanisms that best explain the bicarbonaturia induced by maleate.


Tetanic hyperpolarization of single medullated nerve fibers in sodium and lithium. Repetitive stimulation of a single medullated nerve fiber of Xenopus yields a succession of postspike voltage-time curves which are nearly coincident until attainment of a voltage that corresponds to that of the maximum attained by the normal postspike undershoot. Initially the interspike potential returns toward a resting level after this brief phase of hyperpolarization. However, as tetanization proceeds, a pattern of hyperpolarization develops with the result that, in the tetanic steady state, there exists a progressive hyperpolarization throughout each interspike interval. Extent of postspike hyperpolarization in terms of a deviation deltaVm from the resting level of membrane potential is approximated by the variation deltaVm = delta[MNa + MK]/[GNa + GK] where MNa and MK are current densities associated with active pumping of sodium and potassium ions and GNa and GK are corresponding time-dependent leak conductances. Tetanic hyperpolarization is reversibly abolished by cyanide and by exposure to lithium Ringer. Eventual reappearance of tetanic hyperpolarization in the presence of lithium Ringer suggests lithium pumping.


Glutamine synthetase and glutamyltransferase in the kidney of man, dog, and rat. Glutamine synthetase (GS) is known to exist in the kidney of the rat, guinea pig, rabbit, and sheep but not in that of the dog, pig, cat, or pigeon. No data is available in man. Assay of histologically normal renal tissue obtained in human subjects during surgery for abdominal vascular disease failed to demonstrate significant GS activity. In addition, L-glutamine gamma-glutamyltransferase (GT) activity was also very low. The same results were observed in the dog, in which both GS and GT activities did not exceed 15% of those found in the kidney of the normal rat. In the latter animal both GS and GT activities are higher in the outer medulla (312 and 1,165 mumol/h per g wet wt, respectively) than in the cortex (230 and 844, respectively). During metabolic acidosis, GT activity did not change but GS activity decreased in the outer medulla by 40%. When renal cortex slices from normal rats were incubated in the presence of ammonia, glutamate, and octanoate (as a source of ATP), net synthesis of glutamine was readily demonstrated in contrast to slices from normal DOGS. The present studies demonstrate that the kidney of man, like that of the dog, is devoid of significant glutamine synthetase and glutamine gamma-glutamyltransferase activities. In the rat, we have confirmed the functional significance of GS activity in the kidney. We have also shown that renal GT activity is ammoniagenic in vitro in this animal, but the contribution of this system to total ammonia production in vivo remains to be demonstrated.


Calcium uptake by subcellular fractions of human umbilical artery. Two different mechanisms for the active accumulation of Ca2+ by subcellular fractions of human umbilical artery are described. One, located in the mitochondrial fraction, was induced by exogenous ATP or respiratory substrates (ADP and succinate) and was inhibited by azide. The other, located in the microsomal fraction, was induced by ATP and potentiated by oxalate, but not inhibited by azide. Increasing ATP concentrations up to 4-5 mM increased microsomal Ca2+ accumulation, whereas increasing ATP concentration above 2-3 mM caused inhibition of mitochondrial Ca2+ uptake. Although changing pH from 7.4 to 7.2 had no effect on mitochondrial Ca2+ accumulation, it doubled microsomal uptake. Neither adenosine 3',5'-monophosphate nor guanosine 3',5'-monophosphate in the presence or absence of protein kinase and kinase modulator affected Ca2+ uptake by or phosphorylation of the subcellular fractions. Partially purified protein kinases from umbilical and beef skeletal muscle contained a component(s) distinguishable from the kinase on the basis of its heat stability that enhanced ATP-induced Ca2+ uptake by mitochondrial fractions from the umbilical artery. It is suggested that alterations in Ca2+ sequestration induced by changes in ATP concentration and intracellular pH in mitochondrial and microsomal fractions, respectively, could play a role in the control of arterial patency and closure with changes in PO2.


Intrarenal blood flow distribution in the desert quail following salt loading. The total-kidney glomerular filtration rate (GFR) falls when birds are salt loaded. This fall in GFR is caused by glomerular intermittency. The nephrons that stop filtering are small, surface nephrons without loops of Henle. Larger nephrons with loops of Henle in the deeper regions of the kidney continue to filter during salt loading. Microfil casts were made of the renal microvasculature of the desert quail, Lophortyx gambelii, in an attempt to determine at what points intrarenal blood flow is regulated to cause glomerular intermittency. Casts of the renal vasculature were made in quail that were hydrated and in quail that were salt loaded. The results indicate that the small, surface nephrons stop filtering during salt loading because of a vasoconstriction at the level of the afferent arterioles of these nephrons. At the same time, blood flow is maintained to the large nephrons with loops of Henle. Reducing GFR at the expenses of excreting wastes can be viewed as a mechanism to conserve body water during periods of water deprivation.


Inhibition of inotropic effect of hyperosmotic mannitol by lactate in vitro. Isolated, isometrically contracting cat papillary muscles were used to evaluate the inotropic interactions of lactic acidosis, hypercarbic acidosis, and lactate ion with hypertonic mannitol. These studies have documented that both lactic acidosis (pH less than 7.0) and lactate ion at a normal pH inhibit the inotropic effect of hyperosmotic mannitol in vitro. In contrast, hypercarbic acidosis does not prevent the inotropic effect of mannitol. Inhibition by lactic acid of mannitol's effects on contractility persists in the presence of beta-receptor blockade. The results suggest that inhibition by severe lactic acidosis of the direct inotropic effect of hyperosmolality in isolated cardiac muscle is mediated by lactate ion rather than acidosis per se.


Renal hydrogen ion secretion after release of unilateral ureteral obstruction. The effect of 24 h of unilateral ureteral obstruction on HCO3 reabsroption and urinary acidification was studied in dogs. The postobstructed kidney (EK) had a significantly lower glomerular filtration rate and renal plasma flow than the contralateral kidney (CK). Urinary pH prior to HCO3 loading was significantly higher in the EK as was maximal HCO3 reabsorption. Saline loading depressed HCO3 reabsorption to the same degree in both kidneys. Urinary PCO2, during HCO3 loading, and during phosphate infusion, was significantly lower in the EK than the CK. Fractional Na excretion was significantly higher in the EK than the CK after deoxycorticosterone acetate administration. Na2SO4 administration enhanced acid excretion only in the CK. K excretion was significantly lower in the EK than the CK both during HCO3 loading and Na2SO4 administration. There was redistribution of cortical blood flow from the outer cortex toward the inner cortex in the EK as compared to the CK. There was no difference in plasma renin activity from both renal veins. These data demonstrate enhanced proximal H+ secretion (which is abolished by volume expansion) and impaired distal H+ secretion by the postobstructed kidney. The distal defect is likely an effect of a generalized disorder of distal transport in that both K secretion and steroid-responsive Na reabsorption were impaired in the postobstructed kidney.


Effects of increased O2 and CO2 on acid secretion by dogfish gastric mucosa in vitro. The gastric mucosa of the dogfish (Squalus acanthias), as usually prepared for in vitro chambered experiments, shows a secretory rate (JH) of about 2 mueq/cm2-h, but a potential difference (PD) of zero. Raising PCO2 from 0.05 to 0.1 atm increases JH by 40% and causes the development of a PD of about 2 mV, mucosal surface positive. Increasing PO2 from 0.9 to 1.9 atm in a hyperbaric chamber (at constant PCO2 = 0.1 atm) doubles JH and increases PD to 5 mV. Transepithelial resistance falls by 20% at high PO2. It appears that the dogfish gastric mucosa, like that of the frog, is rate limited by CO2 diffusion into the tissue from the usual 5% mixture and is also rate limited by the usual O2 levels (unlike the frog), presumably due to its thicker structure and higher O2 consumption. The mucosal-positive PD, which is reversed from all other mucosae studied, is readily explained by separate electrogenic H+ and Cl- pumps, but less readily by schemes embodying a neutral HCl pump. It is not yet known whether the hyperbaric conditions are sufficient to ensure O2 sufficiency.


Depression and the reintegration phase of acute schizophrenia. The authors found moderate to severe depression in 60% of a group of schizophrenic patients experiencing acute decompensations (N=30). The course of the depression was followed over an 8-week period8,during which patients were treated with depot fluphenazines. There was a statistically significant reduction in depression that closely paralleled the correction of the cognitive disorder. The authors discuss problems in identifying and quantifying depression during acute schizophrenic decompensation and suggest that the Hamilton scale anxiety/depression factor and the BRPS depression factor may be useful diagnositc tools.


Self-induced depersonalization syndrome. The author reports two cases in which depersonalization occurred during the waking consciousness of individuals who had engaged in meditative techniques designed to alter consciousness. Psychiatrists should be aware of this phenomenon, as the number organizations in the "consciousness movement" is increasing, and should ask people manifesting depersonalization about any involvement in activities leading to altered states of consciousness. In some cases it might be appropriate to refer such patients to responsible groups that teach altered consciousness by meditation as an egosyntonic desirable state. The author cautions against the use of phenothiazines in cases where depersonalization is a prominent feature.


Generic and trade-name antipsychotic drugs: clinical equivalence. The clinical inequivalence of generic versus trade-name drugs has been reported for nonpsychiatric drugs but rarely for psychotropic drugs. Recent expiration of patents on some psychotropic drugs has made the evaluation of the clinical equivalence of generic versus trade-name drugs a matter of interest from methodological, sociopolitical, and economic aspects. The authors discuss these points, with emphasis on methodology, in their report of a double-blind study of the efficacy of chlorpromazine and Thorazine in the treatment of 54 acute schizophrenic patients. An analysis designed to infer the maximum possible advantage of Thorazine over generic chlorpromazine indicated that differences between the two were clinically insignificant.


Coffee consumption among psychiatric inpatients. Of 135 patients on an acute psychiatric ward, 34 were "high users" of coffee. The high users tended to be older, single, and have diagnoses of psychosis. They showed significantly more state anxiety than other patients, but there were no differences in trait anxiety or MMPI scores. Further research is suggested to determine whether high caffeine consumption among inpatients may be related to staff coffee-drinking behavior and/or treatment with anticholinergic drugs.


Catatonialike symptomatology and withdrawal dyskinesias. The authors describes a patient who presented catatonialike symptoms and dyskinesias associated with glutethimide discontinuance and antihistamine use. He hypothesizes that altered dopamine metabolism may produce some of the unusual neuropsychiatric characteristics of glutethimide withdrawal. Drug-withdrawal catatonia may be an additional entity in the differential diagnosis of catatonialike states of organic etiology.


Formal presentation at a scientific meeting. The giving of a ten minute scientific communication is an art form peculiar to researchers who frequently fail to research the technology required for the performance. Careful selection of the scientific material to be included, the audio-visual aids to support it, and adequate rehearsal before presentation to a critical audience are vital to the success of the presentation.


Intravenous flunitrazepam as an anesthetic induction agent. The effects of the fluorinated benzodiazepine compound flunitrazepam were studied in eighty patients. The drug was administered intravenously in a standard dose of 2 mg, 3 mg, or 4 mg to supplement lumbar epidural analgesia. Induction was smooth and pleasant. The sleep onset time was dose related and exceeded one minute in the majority of patients. Sleep was invariably produced in patients receiving 4 mg but at lower dosage some patients failed to become unconscious. Pain in the arm during injection was a common feature. The respiratory rate was slightly increased, but in two patients apnoea occurred at induction. The cardiovascular system was minimally depressed with a small decrease in systolic blood pressure and pulse rate. Recovery from sleep was slow but sequelae were minimal. The sedative and amnesic properties contributed significantly to the high rate of patient acceptance.


In vitro effects of certain neurohumors on ultrastructural change of the chick embryonic thyroid gland. In vitro effects of certain neurohumors, on ultrastructure of 14 days old chick embryonic thyroid gland, has been studied. When the chick embryonic thyroid gland was cultivated in vitro, in the medium containing neurohumors like acetylcholine, adrenaline and histamine for a definite period in a particular sequence and dose, has resulted almost similar ultrastructural changes as seen in the hyperactive thyroid gland.


Histological response of various endocrine glands after administration of certain neurohumors in chicks. Histological response of various endocrine glands like pituitary, adrenal, testes and pancreas after administration of certain neurohumors like acetylcholine, adrenaline and histamine in a particular dose and sequence, has been carried out in white leghorn chicks. Result of this study revealed that administration of these neurohumors produced definite changes in various endocrines. Histological changes are more prominent in pituitary and adrenal glands, whereas, pancreas and testes did not reveal much influence of these neurohumors.


[Anaphylactic shock to pentothal induction]. In a patient who had been anaesthetised twice with penthiobarbitone, who had contracted a localised then a generalised eczema, collapse appeared during a third anaesthetic induction, 30 minutes after the injection of penthiobarbitone which was revealed by Shelley's test to be the most positive product.


[Anaphylactoid complications of iodide contrast media in arteriography of the lower extremities during general anesthesia]. The authors studied the manifestations of intolerance to certain iodide contrast products injected by the arterial route, under general anaesthesia. The study covers 385 arteriographies of the lower limbs which were divided into two groups, depending on whether a cortisone premedication had been administrated or not. In the premedicated group, no incidents were noted. In the other group, 13 p. 100 of subjects had cutaneous manifestations with Radioselectan. General anaesthesia did not avoid the accidents which depend on the nature and the quantity of the product injected. Corticosteroids prevent these reactions.


[Complications of local anesthetics].

[Complications of local anesthetics]. With reference to two personal cases of accidents due to local anaesthetics, the authors deal with the clinical symptomatology of these accidents, whether they be toxic or truly allargic, and look at the treatment.


[Clinical observations of per- and post-anesthetic anaphylactoid complications. Results of an a posteriori survey]. After enquiry in seven French anaesthetic departments, 66 cases of anaphylactic accidents during and after anaesthesia were grouped together. The following are successively described, the clinical symptomatology, the products incriminated, the treatment and course. The immuno-allergological tests were not always carried out.


[Bronchial mediators and receptors: current data]. This is a very precise study of the mechanisms which intervene in bronchial motility. It is apparent that the most important recent acquisitions in the realm of bronchial mediators, over these last 10 years remains: the demonstration in the animal and in man of the duality between adrenergic bronchoconstriction of alpha nature and adrenergic bronchoconstriction of beta-2 nature, the duality of the effects of prostaglandins (PGF2 alpha broncho-constrictive, and PGE2 bronchodilator), and the role of cyclic AMP at the junction of the action of numerous substances which are active on the bronchial musculature.


[Allergy and anesthesia: environment and psychological factors]. The assessment of so-called risk "carriers" is difficult from the standpoint of true allergy and consideration must be given to the following:- the psychology and environment of the patient to be anaesthesia, with regard to any warning signs. -also, though, the psychology and environment of the anaesthetist; himself alerted in the presence of a presumptive allergy. Such an attitude will lead to more rapid assessment of the true nature of the complication occurring. In most instances, acquired presumptions can only lead to widened prevention. A formal anaesthetic consultation, including a careful history, will aid in the detection of problems. It is also of significant value from a legal standpoint, at the same time ensuring application by the anaesthetist of appropriate therapy as early as possible.


[Pre-anesthesia survey].

[Pre-anesthesia survey]. The pre-anaesthesia enquiry reposes essentially on a detailed interrogation, with respects to the risks of anaphylactic accident. Two types of information must be obtained: the presence of risk factors (related to an allergic background, to the pre-existence of a drug allergy, to a spasmophilic background) on the one hand; knowledge of anaesthetic substances and adjuvants already used, on the other hand.


[What prevents the diagnosis of spasmphilia]. The frequency of spasmophilia in subjects who had had anaphylactic reactions during anaesthesia (80 p. 100 in our statistics, as opposed to 10 p. 100 in a normal population) must make one consider this condition as a risk factor. It must be looked for in the history, on clinical examination, on the electromyogram, and by laboratory assays. Therapeutic orientations are indicated.


[Skin tests for 48/80 and histamine].

[Skin tests for 48/80 and histamine]. The variability in time of the cutaneous response, resulting from morbid and specially from therapeutic physiological interferences, restrains the credibility of cutaneous allergological investigations. The authors present the first results, established on control population considered as normal, of an approach to cutaneous reactivity by means of a non-specific histamine liberation, induced by a tween: 48/80 coupled with appreciation of the reactivity to histamine injected by the intra-dermal route. The study objectively demonstrates the variability in the response in terms of the doses injected, age, and especially in terms of drug interferences which usually, go in the direction of a hyporeactivity. On the contrary, hyper-reactivity is frequently observed in certain morbid conditions, in particular in spasmophilia. In conclusion, before including the 48/80 and histamine tests in the battery of allergological investigations, it seems indispensable to specify the limits in normal subjects and to better aprehend interferences which modify its expression.


[Determination of serum IgE].

[Determination of serum IgE]. After recalling the properties of IgE antibodies responsible for allergic reactions, the author looks at the methods of assay by the techniques of radial immunodiffusion and radio-immunology. The total serum IgE of 13 subjects who had had an anaphylactic accident during anaesthesia, were assayed according to the latter technique. Elevated values were found in patient with an atopic background. The assay of IgE could be of value in the assessment of the allergic risk in anaesthesia.


[2 cases of anaphylactic-type reaction to alphadione (Alfatesine, Althesin, CT 13.41)]. Two cases of anaphylactic-type reaction to alfadione were referred to our Department for immuno-allergic enquiry. From the clinical standpoint, the pictures obtained were rather similar, dominated by dramatic collapse of abrupt onset associated with an erythemato-oedematous cervico-facial rash, however with a favourable course under respiratory and circulatory emergency resuscitation. The immunological enquiry carried out in both cases did not enable one to attribute the responsibility for the accident to alfadione or to cremophor EL nor to be able to put it down to a direct pharmacological histamine-liberation, or to a specific histamine-liberation due to an antigen-antibody reaction.


[2 cases of anaphylactic-type reaction related to anesthesia]. Two cases of anaphylactic shock during anaesthesia are presented, in which the etiology is confirmed by the lymphoblastic transformation test. In one case, the responsability was due to Pentothal, in the other to the combination of Pentothal-succinylcholine.


[In tolerance reactions to Rheomacrodes. Apropos of 3 cases]. Three cases of reactions of intolerance to Rheomacrodex were observed during these last four years in our Department, and this led us to attempt to sum up their exact nature and in particular the possibility of an immuno-allergic orgin. From the clinical standpoint, the symptomatology is dominated by the combination of abrupt collapse associated with Quincke's edema in two cases, and with bronchospasm in the third. The course was rapidly favourable under respiratory and circulatory emergency resuscitation. The immuno-allergic enquiry carried out in one case, did not enable one to demonstrate the responsibility of an antigen-antibody reaction. Analysis of the different works appeared on this subject, in particular those of the Swedish school, of W. RICHTER et col., did not enable one to pick out with any certainty the responsibility of an antigen-antibody conflict in the genesis of these reactions.


[Does anesthesia have an immunosuppressive effect?]. Immune depression occurs after general anaesthesia. It is related to depression of serum factors after anesthesia with ether or chloroform, or secondary to depression of antibody-producing cells after anaesthesia with halothane, nitrous oxyde or Pentothal. This immune depression augments proneness to bacterial and viral infection and to malignant disease.


[Does local regional anesthesia exert an immunosuppressive effect?]. Lignocaine in very high doses exhibits immunodepressant properties in vitro. In vivo, in surgical patients submitted to spinal anaesthesia, lymphocyte transformation is diminished for one week. This inhibition is, however, less marked than after general anaesthesia.


[Diagnosis of drug allergies related to anesthesia and surgery]. Drug allergies are increasingly common. They may occur in 5-10 p. 100 of patients treated with drugs. From a diagnostic standpoint, the problem is a complex one, many aspects of which are still poorly understood. This is particularly true with regard to the nature of the antigenic determinants and their vectors. Allergic reactions in patients submitted to anaesthesia and surgery represent a very particular case of the situation. A study of the immune status of such patients was undertaken and revealed that T lymphocyte depression, lasting from one to three weeks, often occurs. It is important to take this concept into account when choosing laboratory tests designed to substantiate the diagnosis. Several examples are presented and discussed.


[Immunobiological means of identifying hypersensitivity to anesthetics and adjuvants]. The diagnosis of hypersensitivity to anesthetics and adjuvants is based chiefly on immunobiological tests which involve:-sensitized lymphocytes; -IgE or IgG antibodies; -sensitized target cells; -determination of chemical mediators. Comparison between these different methods is only possible for techniques involving the sensitized lymphocyte, such as the LTT and EA rosettes for examples, or T.D.B.H. and liberation of histamine. Comparison between the LTT and RAST is difficult, since the first technique investigates the sensitized lymphocyte while the second involves radio-immune antibody assay. An attempt to establish a correlation between these two types of methods is difficult but they can, however, complement each other.


[A study of allergy to local anesthetics using the lymphoblast transformation test]. The lymphocyte transformation test (LTT) confirms the classical concept that Novocain is three times as potent as Xylocaine as a sensitizing agent. This sensitization to Novocaine is more common in patients with an allergic constitution and in those treated with several drugs. The LTT made it possible to identify the responsible drug, which was not always a local anesthetic, but sometimes Penicillin G and aspirin.


[Allergic characteristics of halothane hepatitis. Apropos of a case report]. The authors report a case of postoperative jaundice occurring within 30 days in a patient anesthetized three times with halothane. The responsibility of the anesthetic is discussed in view of the positivity of the lymphocyte transformation test and the absence of Australia antigen. It is suggested that this case of hepatitis may be related to a delayed hypersensitivity phenomen.


[Experimental study of the sensitizing properties of halothane]. The sensitizing properties of halothane were investigated experimentally in guinea pigs using two different techniques. The first method, derived from that of DRAIZE, included a sensitizing phase in which the product was administered by inhalation, while the second method, derived from that of MAGNUSSON and KLIGMAN, used guinea pigs sensitized to FREUND's adjuvant and which were sensitized to halothane administered subcutaneously. The results obtained in these two series of experiments appeared concordant. They showed that effective sensitization occurred in 60 to 80 p. 100 of the animals treated. This places halothane between level 3 (moderate potency) and level 4 (high potency) on the classical drug scale of "allergenic potencies".


[Experimental study of conjugates of a catabolite common to halothane, enflurane and fluroxene in guinea pigs]. The authors sensitized guinea pigs to a halothane catabolite, trifluoroacetic acid, combined with guinea pig albumin. They then exposed the animals to halothane. There was no correlation between the presence of humoral and cell-mediated immune reactions obtained with the catabolite and the incidence of liver necrosis.


[Immunologic study of viral hepatitis].

[Immunologic study of viral hepatitis]. The author discusses the various immunological methods used to demonstrate antigen in serum hepatitis. This antigen is made up of three main types of particles: a spherical particle, a tub-like structure and a second larger spherical particle with a hexagonal centre, described by DANE. The centre of DANE's particle is immunologically distinct from its surface. The immune complexes thus formed by antibody links between surface antigens play a major role in extrahepatic manifestations of serum hepatitis. The various subtypes of antigen can be used as a basis for geographical and epidemiological study of the disease. The centre of DANE's particle is considered to be the virus itself. It cannot be cultured with current methods but it can be transmitted to chimpanzees. The antibody reacting with the surface antigen is protective. In conclusion, the author observed that an increase in serum transaminases in anesthetized patients occurred only after halothane. This suggests that liver damage after administration of halothane may be due to a direct effect of the product or its metabolites.


[Antigenicity of drugs used in anesthesiology]. The authors studies the factors involved in the antigenicity of the principal medications used in anaesthetics, including general anaesthesia, local anaesthetics and muscle relaxants. Any attempt at establishing a correlation between the chemical properties of these medications and their haptenic power would seem difficult by virtue of the fact that the complications seen in clinical practice are characterised by their rarity. The latter may be explained either on the basis of a low haptenic power of the substances or by the fact of their administration which is rarely repeated after a short time interval. Finally, the difficulties of this correlation are even further increased by the fact that the haptenic power is not always due to the medication itself, but sometimes to one of its metabolites.


[Technics for the experimental study of delayed hypersensitivity]. The author reviews the principal experimental methods proposed for the study of the sensitising power of medications. All these methods involve delayed hypersensitivity (Type IV) and fall into the same broad category, with a sensitisation phase, a rest phase and a stimulating phase. A critical review of these various phases is made; together with the interpretation of the results and their significance.


[Biological rhythms and chronopharmacology]. After defining the various factors of chronobiology (chronophysiology, chronopathology, chronotoxicology and chronopharmacology), the authors describe the various methods available for the study of biological rhythms; which leads to the concept of "time structure".


[Plasma level of the thiocyanate ion in sodium nitroprusside perfusion]. 24 subjects were selected at random out of a group of 80 patients undergoing surgery under a hypotensive anaesthetic technique by means of nitroprusside perfusion; the variation of one of the metabolites, the thiocyanide ion, were assayed. Hypotension was of 30 to 380 minutes duration and mean dosage of 12,44 mg (1,99 mug/kg/min). SCN- assays were performed by means of an original technique, which is described in this publication, before any perfusion of nitroprusside, every 30 minutes during perfusion and 30 and 60 minutes after ending the perfusion. Results show that SCN- concentration is increasing during perfusion but not as much as compared with the toxic concentration. Major increase takes place 30 minutes after starting the perfusion (1,27 10(-4) M/l). Increase slows down then and remains on a plateau level until the end of the perfusion where it decreases. Those results allow to reject a toxicity risk related to an increase of SCN- during nitroprusside perfusion. However, the accidents reported after high dosage of NPS and probably related to cyanogenic ion accumulation combined with lactic acidosis as shown in this publication, led the authors to advise a dosage not over 10 mug/kg/min in a maximum of 2 hours time.


[Electromyography and AH/8165 in man].

[Electromyography and AH/8165 in man]. This article concerns the electromyographical study of a synthetic curare derived from Azobis Arylimidazo (1-2a) Pyridinium (AH/8165) with a simultaneous recording of the spontaneous diaphragmatic activity and "testing" of the neuro-muscular transmission at the level of a peripheral muscle. This study shows that AH/8165 is a powerful non-depolirizing curarimimetic drug that quickly induces a neuro-muscular block at the level of the diaphragm and the peripheric muscles that can be reversed by anticholinesterasic drugs. Its reaction time is short (about 1 mn). There are importante individual variations in the duration of the neuromuscular blockage. Towards the end of the experience, tetanizing stimulations reveal a muscular fatigability in all the cases. No ill side-effects could be observed upon the cardiovascular system or any side-effects ascribable to a histaminergic mechanism.


[Epidurography in the continuous peridural anesthesia technic in geriatric surgery]. The radiographic opacification of the peridural space was carried out prior to any injection of anaesthetic solution, both in the interest of security and to maximize the chances of success, on a homogeneous series of patients of more than 75 years of age, benefiting from continuous peridural analgesia. The following observations are made: - the direction of the catheter is ascending in 94 p. 100 of the cases, - the frequency of malpositions seems to increase with the lenght of the catheter introduced into the space, - the images obtained by injections of the radio-opaque agent are sufficiently specific to allow verification of the extra-dural situation of the apex of the catheter, - the permeability of the intervertebral foramina is found in 36 p. 100 of the cases, - the unilateral blocks appear to be exceptional, the technical difficulties inherent in the effects of aging on the vertebral system being compensated for by the constant success whenever the peridural space is reached.


[Involvement or non-involvement of intracranial pressure with arterial pressure]. In this experiment carried out on dogs, the authors demonstrate with the aid of very expressive illustrations that rapid variations in arterial pressure are accompanied by variations of the intracranial pressure. The latter may be, depending on the case, either in the same direction or inverse, according to the local cerebral vasomotor response accompanying the systemic arterial hypertension.


[PLACEMENT OF AN INTRACAVITARY PROBE WITH RESPECT TO THE TRANSPORT OF CARDIAC PATIENTS UNDERGOING ELECTROSTIMULATION. Apropos of 11 cases at the Toulouse Emergency Medical Assistance Service]. In connection with the secondary transportation of cardiac patients, the medicine doctors at the SAMU in Toulouse placed endocavitary probes in 11 patients for purposes of electrosystolic releasing. The subjects exhibited auriculo-ventricular blocks resistant to isoprenaline and accompanied by syncopes. The evacuations were carried out in this fashion without any accident and with no negative effects in 10 out of the 11 cases. In light of this result, the indications and techniques of the process are discussed.


[Amiodarone hydrochloride and anesthesia in heart surgery. Use of an injectable form in the correction of peroperative rhythm disorders]. The amiodarone is studied in the context of cardiac surgery to evaluate its anti-arrythmic properties in its injectable form and possible interference with the anaesthetic drugs. Two groups of patients were established: - the first group of 10 patients received the amiodarone per-os in the immediate pre-operative period, - the second group of 19 patients received injectable amiodarone either by direct intraveinous injection at a dose of 5 mg/kg or in I.V. drip for rhytmic irregulatities during surgery. The anti-arrythmic property of the product is confirmed. No incompatibility with the anaesthetics employed (neuroleptanalgesia) was observed. Howerer, a potentialization of the sympatholytic alpha-effects by the anaesthesia is observed. The fall in arterial pressure, when it is measureable, is of the order of a third of the initial value, with a return to the previous level within about ten minutes.


[Prevention of stress ulcer by vitamin A. Experimental study in rats]. 71 male rats (Whitstar strain) are submitted to restraint. 37 of them were receiving twice an injection of 10 000 I.U. of vitamin A in order to protect them against the occurence of stress ulcer. Untreated animals are used as controls. Incidence of obtained ulcer is compared with the variation of vitamin A serum concentration, classicaly decreased in stress. Analysis of individual results shows that, if parenteral administration was followed either by restitution of the initial serum concentration, or by its increase, the treatment was efficient in 64 p. 100 of the cases.


[Stress ulcer and acute postoperative renal insufficiency. An attempt at preventive treatment with Solcoseryl and proglumide]. The study grouped 68 patients treated for severe post-operative or post-traumatic renal insufficiency, having survived over 7 days after being admitted into the Reanimation Department. A group of 32 patients were given systematic preventive treatment for nervous ulcers witch Solcoseryl and Proglumide. A control group of 36 patients received no specific treatment. Nervous ulcerations (showing up in gastrocopy) are found in three patients in the group receiving treatment, as compared with seven in the control group. This preventive treatment appears to be of interest, especially as other local or neuroleptic treatments are difficult to use in the group of patients concerned here.


[Clinical evaluation of Trivé 1000 in surgery]. Trials with Trive 1000 allow to confirm its perfect tolerance and its real interest in N sparing effect provided a minimum of 1500 ml, or even better 2000 ml are perfused with an adequate caloric carboyhdrate complement. However, in severe cases such as septicemia, one may expect a positive N balance only with much more important supply of N and calories. Since there is almost no change in parameters refleting fat metabolism, one may suppose a normal utilisation of injected fat.


[Technics and indications of general anesthesia for tonsillectomy and adenoidectomy. Apropos of an experience using anesthetic perfusion and cold loop technic]. The authors present the results of an enquiry carried out in University and regional hospitals in France and recall the interest of general anaesthesia with tracheal intubation during tonsillectomy. This makes possible, even in young children, the use of the technique of cold loop dissection. Its main advantage is in the absolute control of the airways which permits the operator to carry out careful hemostasis. Propanidide used in perfusion, allows these patients to wake up rapidly and the awakening is of good quality; this is essential in this type of operation.


[General anesthesia for multiple dental extractions]. Between 1970 and 1975, 528 sessions of teeth extractions were carried out under general anaesthesia at the Ambroise Paré Hospital in Boulogne. The distribution was as follows: -70 multiple dental extractions in cardiac patients, mostly sent up by cardiology units outside the establishment. -458 multiple dental extractions for orthodontic treatment, germectomies, removal of included or supernumerary teeth, contra-indication or refusal of local anaesthetic. Since 1972, all patients for whom a surgical decision was considered were examined at the Anaesthetic out-patients and the advantages appear obvious. The type of premedication, the choice of the anesthetic technique were classical in the vast majority of cases and, in particular, intubation was carried out as a routine.


[General anesthesia in major cancer surgery of the upper respiratory and digestive tracts. Significance of a fentanyl-thiamine combination]. Synaptanalgesia uses a polysynaptic inhibitor: thiamine and a powerful analgesic drug with or without nitrous oxide. This type of vigil or sub-vigil anesthesia used in major cancer surgery of the upper digestive tract and the airway, permits one to obtain: -efficacious protection of the autonomic nervous system, in spite of manipulations of highly reflexogenic areas, -a marked reduction in bleeding. The technique used is derived from that of other authors: DE CASTRO, MUNDELEER, VALENI, MAZZONI, GASPARETTO, adapting it to this type of surgery and attempting to simplify it.


[Current aspects of ambulatory anesthesia for otorhinolaryngologic and stomatologic surgery in France]. Ambulatory anaesthesia is becoming more popular in France for several reasons: -for humanitory reasons and greater comfort, -for reasons of economy in hospital, -professional responsibility and insurance. This change has been made possible by: -techniques of anaesthesia using drugs which are eliminated rapidly without any rebound phenomenon, -medical attitudes, such as prior examination of the patient by an anesthetist; this is much better than a rapid examination at night or in the morning on admission of the patient, thus precise control of awakening by tests of psychomotor activity. -changes in hospital structure, e.g. post-anaesthetic awakening wards with specialised personnel. Anonymous questionnaires were sent out to O.R.L. surgeons and French oral surgeons, we received 38.5% replies: -51.75% never used ambulatory anaesthesia, -48.25% used ambulatory anaesthesia almost always in hospital with a recovery room and anaesthetic consultation. Admission to hospital for one day seems rarer. It thus appears that ambulatory anaesthesia is becoming common in France and that more than 50% of surgeons remain opposed to this technique.


[Trials of controlled hypotension with sodium nitroprusside in ORL surgery. Resistance and tachyphylaxis]. Sodium nitropusside has been used to lower blood pressure during surgical operations on the ear, nose and throat when an operative field without bleeding was desired, e.g. surgery of the inner ear under microscope in particular. In our experience, with the preparation used, sodium nitropusside proved to be a powerful hypotensive agent, the effect of which comes on early but it is difficult to use owing to frequent tachyphylaxis, the possible causes of which are considered. No undesirable side-effects were noted on the main functions. From this limited personal experience, the efficacy of this technique of per-operative hypotension did not appear greater in the surgical field under consideration to those of the anaesthetic techniques used commonly, e.g. neuroleptanalgesia under artificial ventilation, which proved sufficient for reduction in operative bleeding and which had already caused the authors to abandon, some time ago, the use of hypotensive ganglioplegic drugs.


[Use of ventilation by oxygen injection in laryngeal microsurgery]. Thirty patients with a laryngeal polyp or other tumour, were operated on under the microscope. During the operation, which lasted from 10 to 30 minutes, ventilation was ensured by injection of oxygen at 3 to 4 atmospheric pressures through a naso-tracheal catheter. Anaesthesia was obtained by an association of propanidide, small doses of analgesic and succinycholine, constant rate syringes were used for maintenance of narcosis and curarisation. In 23 patients, blood gases were analysed at various stages of the operation permitting one to assess the quality of the ventilation carried out. In a few patients, it was also possible to record pressure curves in the trachea. The results were excellent, both concerning the quality of the ventilation and that of the anaesthesia together with the operative conditions. After recalling the main characteristics of this mode of ventilation which uses Venturi's principle, the authors expose the other methods which are variants compared with their technique of use of this procedure for laryngeal micro-surgery.


[Significance of Alfatesine in anesthesia for multiple dental extractions before major cardiac surgery]. This technique of anaesthesia used for oral surgical operations such as, multiple dental extractions, apical resection, carried out in cardiac patients before major cardiac surgery under extra-corporeal circulation, for insertion of valvular prostheses or aorto-coronary by-pass operations, has passed by various stages. The present technique associating phenoperidine-alfatesine-suxame-thonium-N2o-o2, was used in the last 58 cases. It presents a certain number of advantages compared with previous techniques: -very stable level of anaesthesia whatever the duration of the operation, -satisfactory cardio-vascular stability, -almost constant absence of hypo-excitability of the myocardium even in patients in poor cardiac condition before the operation with uninterrupted treatment with digitalis and diuretics, -good quality of awakening.


[Treatment of respiratory distress caused by laryngeal obstruction]. Respiratory distress due to laryngeal obstruction produces a more or less dramatic syndrome depending on the cause of the obstruction and its evolution in time. Treatment should be immediate in order to avoid death or cerebral and cardiac sequelae. It consists, above all, of restoring the patency of the respiratory tract, the short-circuit obtained by intubation or tracheotomy should, in no case, leave any laryngeal sequelae. The authors present their personal series based on a study of respiratory distress due to laryngeal obstruction in the child. These observations were obtained from a large series of 480 cases of laryngeal dyspnea observed over the last 5 years on the E.N.T. unit of the Edouard Herriot Hospital in Lyons. They contrast a very small number of sub-glottic laryngitis cases requiring intubation or tracheotomy to a very large number of cases of subglottic laryngitis, even with respiratory distress, which recovered with well designed medical treatment. Foreign bodies, of which they report eleven cases, all required emergency surgery. They emphasize the severity of this cause. As far as papillomas and angiomas are concerned, they require emergency treatment, either straightaway or after a trial of medical treatment.


[Anesthesia and resuscitation in emergency maxillofacial surgery]. A series of 290 cases of maxillo facial trauma permitted the authors to draw up the indications for resuscitation and surgery. Restoration of the permeability of the airways is most often obtained by oral intubation under non-depressor pharmcological agents. The difficulties encountered during intubation were usually linked to pain, but sometimes had a mainly mechanical origin, particularly during zygomatic and malar bone fractures. Tracheotomy was exceptional. Hemorrhage was often the major obstacle and, in certain cases, could only be controlled by immobilisation of the fragments. The anaesthetic technique is very similar to that used in neurosurgery.


[Anesthesia and pre- and postoperative resuscitation in massive maxillofacial destruction]. Severe facial injuries are becoming more and more common, -either facial injuries alone or associated with other injuries, -or facial deformities due to cancer which has required radical surgical operation. The authors analyse the cases of 26 patients with trauma and 24 with neoplastic radical surgical modifications. In the first group, pre-operative resuscitation is often an emergency, e.g. tracheotomy to restore or maintain vital respiratory functions. In the second group, the patients are often elderly and undernourished and they require intensive care before operation. In both groups there are common problems: -feeding by gastric catheter is generally required, -many re-operations with their problems: -avoid nutritional disorders, -and avoid morphine addiction.


[Massive facial destruction. Management, resuscitation, anesthesia, surgery (experience at the Henri-Mondor University Hospital Center)]. Anaylsing 67 cases of facial injury treated at the Henri Mondor Hospital in Créteil, the authors consider the various problems raised by these injured patients. -first aid, -methods of protection of the airway, -surgical management, -anaesthetic management and resuscitation, -problems of post-operative supervision, -methods of feeding. Owing to the localisation of these lesions, and the surgical methods, these are high risk injured patients who raise complex problems in the pre, per and post-operative periods, dominated by maintenance of the permeability of the airway. A specialised multidisciplinary team ensures coordination of the various acts.


[Problems presented by closed laryngeal-tracheal injuries]. The authors consider the problems raised by severe closed laryngotracheal trauma and report 4 cases. -the immediate tisk to life is due to direct involvement of the respiratory tract requiring emergency measures including cardiorespiratory resuscitation in cases of acute asphyxia. -the origin of the initial respiratory distress, if not obvious from the start, may be suspected in view of the difficulties or impossibility of tracheal intubation, which is also liable to aggravate lesions due to trauma. It is one of these rare cases of resuscitation where emergency tracheotomy is essential. It permits also early, precise surgical exploration. -in cases of fracture of the larynx, a wound of the trachea or rupture and separation of the trachea, the reconstruction must be constructiononstruction must be considered within the first 48 hours. Provision of food and resting of the larynx may be conciliated by installing an esophageal catheter or performing a gastrostomy. Benign trauma, such as contusion or laryngeal commotion, requires close supervision association with medical treatment designed to prevent the onset of lesional oedema.


[Laryngeo-tracheal contusion caused by a seat belt]. The authors report cases of laryngo-tracheal rupture due to seat belts. They analyse the mechanisms, the clinical and radiological signs of these lesions. Although these lesions are rare, they should be recognised by medical teams when called to treat injured patients. It is, in fact, at this level that emergency treatment must be carried out, although difficult, this alone permits one to save a certain number of injured patients from asphyxia.


[Problems presented to the surgeon, anesthetist and resuscitation personnel by fractures of the malar bone (study of 100 cases)]. The authors emphasize the difficulties encountered with fractures of the zygomatic bone, both from the technical operative points of view and conditions of anaesthesia and intensive care. They distinguish in both fields, the so-called simple zygomatic fractures from fractures associated with multiple injuries of the face or skull. After recalling the surgical techniques, they consider routine management, from diagnosis to recovery from the anaesthetic, emphasizing the problem of the time of the operation, of the method ensuring freedom of the airways and anaesthetic indications used together with problems of intensive care.


[Surgery of cancer of the larynx. The patient in the pre-, per-, and postoperative period]. Surgery of tumours of the larynx requires two main types of operation: -Extensive laryngeal surgery including: -the full pre-operative assessment and preparation of the patient's general condition which is always poor, e.g. due to alcoholism or respiratory failure. -variable techniques, adapted to the lesion, for the control of the patency of the upper airway. -operative risks, such as: reventilation shock, reflex cardiac arrest, disorders of cardiac rythm and gas embolism. -Its complications: -may be immediate and poorly specific, especially respiratory, neurological and infective. -secondary and more specific e.g. Pharyngostoma, and tracheal stenosis. -late complications due to spread of a malignant process. -Laryngeal surgery limited to one vocal cord for which local anaesthetic, improved by neuroleptanalgesia, such as Diethazine-Diparcol, best meets the surgeon and the interest of the patient.


[Personal experience with anesthesia of ambulatory patients operated on in odontostomatological offices]. The authors report their experience of anaesthesia of ambulatory patients operated on in dental surgeries; the authors review safety factors, specially, choice of material, drugs and techniques which seem to them essential. They expose in detail their personal techniques, in particular, nasotracheal intubation and open circuit, association of a powerful analgesic drug with a short duration of activity and a mild antiemetic neuroleptic drug completed by inhalation of a mixture of Ethrane and oxygen. The various problems which may occur are considered together with their solutions.


[CT 1341 in continuous administration in 75 cases of prolonged general anesthesia in odontostomatology (constant flow assured by a double-lumen venous catheter and electric perfuser)]. The authors used during 75 prolonged general anaesthesia in maxillo-facial surgery CT. 1341 (Alfatesine) administered pure at constant flow rate through a double lumen venous cannula and electric perfuser. Four series of patients were thus distinguished depending on their use or not of N2O as the only analgesic and of gallamine. We do not agree with the classical assertion that CT. 1341 has a cumulative effect on some EEG results. The technique is quite inocuous and the authors propose a technique using CT. 1341 at a dose of 0.1 ml/kg for induction of anaesthesia with, later, 1 mg/kg of gallamine. Under a mixture of oxygen and nitrous oxide at 60 p. 100, the maintenance dose advised in 6.17 microliters per kilo, per minute of CT. 1341.


[Laryngo-tracheal injuries in hangings (apropos of 359 cases)]. Hanging is a relatively frequent method of suicide, and strangulation (accidental or volontary) may cause direct laryngeal or tracheal trauma and various lesions which may express themselves clinically either: -early, was severe from the start, e.g. fracture of the larynx, with major ventilatory distress, -or delayed, simple trauma without fracture, becoming manifest only after a few hours with severe dyspnea. In any case, early and late complications of these traumas require, even when they are apparently benign, admission to hospital on a specialised unit able to carry out rapidly respiratory intensive care.


[Anesthesia and emergencies in otorhinolaryngology]. In this paper are considered the etiology, the clinical findings and the management of anaesthesia for a certain number of ENT emergencies, situations of respiratory distress which may lead rapidly to death, or be the cause of severe complications, e.g. -haemorrhage (epistaxis or tonsilar haemorrhage, haemorrhage from carcinoma..), -dyspnea of the adult, neonatal dyspnea and dyspnea of infants and children, -foreign bodies, burns and perforations of the esophagus.


Lack of a significant protective effect of augmented circulating glucose on the ischemic myocardium. This was a 60 year old woman, with a very large retro-pharyngeal tumour, mainly situated on the right, revealed by chronic decompensated respiratory failure. Admission to hospital was justified by deep coma with cyanosis of the face and extremities. She had taken 50 mg of Oxazepam the day before admission to hospital. This coma was due to chronic respiratory failure decompensated, as suggested by clinical and laboratory examination after elimination of any traumatic, neurological, endocrine or metabolic disorder. Intubation, rendered difficult by the retro-pharyngeal tumour and assisted ventilation permitted recovery of normal consciousness within 48 hours. This bi-lobed and encapsulated tumor was completely removed after full radiological assessment which showed the absence of any bony lesions. Histology suggested that this was a  benign lipoma. The course was very rapidly favourable with a definite improvement in respiratory function one year after the surgical operation.


Cardiopulmonary effects of the combination of neuroleptic azaperone and hypnotic metomidate in swine. Cardiopulmonary measurements were made at given intervals up to 120 minutes on 6 awake, unanesthetized pigs given azaperone and metomidate. Decreases from control values occurred in arterial blood pressure (deltaBPart = 30 mm of Hg), heart rate (deltaHR = 30 to 35 beats/minute), and cardiac index (deltaCI = 1.5 L/minute/m2). Blood gas and pH measurements indicated no severe impairment of pulmonary function or arterial acidosis. Although the drugs led to decreases in the various functions, cardiopulmonary function remained stable and uncompromised.


Propoxyphene napsylate.

Propoxyphene napsylate. Propoxyphene napsylate differs from the hydrochloride salt in several ways. It is much less soluble and bitter and poses few stability problems when capsulated or tableted with aspirin. There is some evidence in several animal species that the pattern and severity of poisoning may be different with the two salts. Equimolar doses of the two salts are probably interchangeable in the relief of pain. The role of propoxyphene in clinical medicine and the questions of propoxyphene abuse and propoxyphene-related fatalities are discussed.


Medical problems of surgical patients. Hypertension and ischaemic heart disease. Pre-existing disease in the form of hypertension or ischaemic heart disease may increase morbidity and mortality in patients presenting for anaesthesia and surgery. The interaction of these two cardiovascular conditions in relation to anaesthesia has been studied in a series of 115 patients. The results did not support the view that antihypertensive drugs and beta-receptor blocking agents should be withdrawn before anaesthesia and surgery. The main cause for concern in providing anaesthesia for these patients is that sympathetic nervous activation induced either by anaesthetic manoeuvres or by surgical stimulation may lead to reflex cardiovascular responses which, by increasing myocardial oxygen demand, lead to episodes of myocardial ischaemia. In this respect beta-receptor blocking drugs appear to have a protective effect on the ischaemic myocardium.


Effect of organic mercurials and sulfhydryl compounds on the urease activity of Proteus: inhibition by urine and ascorbic acid. Meralluride, mercaptomerin, ethacrynic acid, and penicillamine inhibited urease activity of Proteus mirabilis. The activity of the organic mercurials and ethacrynic acid was markedly inhibited by human and dog urine. Antiurease activity could not be detected in the urine of a human and a dog given meralluride by injection. Urine from patients receiving penicillamine also failed to inhibit urease activity. Ascorbic acid inhibited, whereas dehydroascorbic acid enhanced, the activity of the mercurials, but neither agent altered the inhibitory effect of urine. The lethal effect of meralluride against Proteus occurred at the same concentration at which urease activity was inhibited, but penicillamine inhibited the enzymatic activity without affecting viability of the organism. The data suggest that these sulfhydryl-reactive compounds will not be useful against Proteus infections of the urinary tract.


In vitro study of netilmicin compared with other aminoglycosides. Netilmicin (Sch 20569) is an ethyl derivative of gentamicin C(1a) that is active against most Enterobacteriaceae, Pseudomonas aeruginosa, and Staphylococcus aureus isolates. Among 342 clinical isolates tested, all staphylococci; 92% of Escherichia coli, 93% of Klebsiella pneumoniae, and 92% of Enterobacter were inhibited by 0.8 mug or less of netilmicin per ml, but only 78% of P. aeruginosa were inhibited by 3.1 mug or less per ml. Most clinical isolates of enterococci, Serratia marcescens, and Providencia were not inhibited by 3.1 mug of netilmicin per ml. Like other aminoglycosides, the netilmicin in vitro activity was markedly influenced by the growth medium used, with activity decreased by sodium, calcium, and magnesium. Netilmicin was more active at alkaline pH. Addition of magnesium to Pseudomonas or Serratia pretreated with netilmicin produced inhibition of killing. Netilmicin was more active than gentamicin, sisomicin, tobramycin, or amikacin against E. coli and K. pneumoniae. Netilmicin inhibited growth of all gentamicin-resistant isolates of Klebsiella and Citrobacter tested, but only 73% of E. coli; Pseudomonas and Providencia were resistant to netilmicin. Most Serratia (95%) and indole-positive Proteus (83%) isolates were resistant to netilmicin but were inhibited by amikacin.


Growth of Physarum gyrosum on agar plates and in liquid culture. The physical and nutritional requirements of the antibiotic-producing slime mold Physarum gyrosum were examined to develop a liquid medium for this myxomycete. Liquid culture is desired to expedite a useful scale of production of antibiotic materials for ease of isolation and structure study. Culture conditions were selected to favor antibiotic production rather than maximum growth. The medium devised consisted of 0.010 M potassium phosphate buffer (pH 6.0), 2% bakers' yeast, and 0.2% glucose and was supplemented with either 10(-7) M hemoglobin (preferred) or 2.0 ml of live Escherichia coli per 100 ml of culture medium grown to a steady-state population in nutrient broth. The slime mold, which contained some E. coli carried along with the inoculum, was allowed to grow as a surface plasmodium at 20 degrees C in the dark with weekly subculturing for stocks or for 10 days for antibiotic production. P. gyrosum produced the same antibiotic materials when grown in liquid medium as it did when grown on agar plates. A seeded plate disk assay against Bacillus cereus was employed to follow antibiotic activity.


Suppression of the lytic and bactericidal effects of cell wallinhibitory antibiotics. The bacteriolytic effect of beta-lactam antibiotics on Bacillus subtilis and on Streptococcus pneumoniae was found to be a function of the pH; lysis was suppressed if the pH of the pneumococcal culture was below 6.0 during penicillin treatment. In the case of B. subtilis, growth at pH 6.6 prevented penicillin-induced lysis. In pneumococci, the addition of trypsin to the growth medium also protected against lysis. The pH-dependent protection phenomenon resembled in several respects the antibiotic "tolerance" of pneumococci with a defective autolytic system. (i) At the pH nonpermissive for lysis, the bacteria retained their normal sensitivity to beta-lactam and to other cell wall inhibitors; however, instead of lysis, the drug-treated bacteria simply stopped growing. Loss of viability of the cells was also greatly reduced. (ii) Protection against lysis was independent of the dose and chemical nature of the cell wall inhibitors. (iii) The protection effect was reversible; lysis and loss of viability could be triggered by a postincubation of the drug-treated bacteria at the pH permissive for lysis.


Starch degradation by the mould Trichoderma viride. I. The mechanism of starch degradation. The mechanism of starch degradation by the fungus Trichoderma viride was studied in strain CBS 354.44, which utilizes glucose, starch and dextrins but is unable to assimilate maltose. It was shown that the amylolytic enzyme system is completely extracellular, equally well induced by starch, amylose or amylopectin and that it consists mainly of enzymes of the glucoamylase type which yield glucose as the main product of starch hydrolysis. Small amounts of alpha-amylase are produced also. The enzymes produced in starch cultures degrade starch, amylose and amylopectin equally well. Enzyme synthesis in starch media takes place to a considerable extent after exhaustion of the carbon source when maximum growth has been attained. Low-molecular dextrins are degraded by extracellular enzymes of the glucoamylase type. These enzymes are produced in media containing starch or dextrins. Maltotriose is consumed for only one third leaving maltose in the culture filtrate. Maltose is hardly attacked and hardly induces any amylolytic enzyme activity. No stable alpha-glucosidase appears to be produced.


Synthesis of chitin by particulate preparations from Aspergillus flavus. Cell-free extracts from Aspergillus flavus catalyzed the synthesis of chitin from UDP-GlcNAc. Most of the activity was associated with membrane-rich fractions whereas no activity was detected in the cell walls. Chitin synthetase was activated by fungal acid proteases; animal and plant proteases destroyed it. Upon incubation at 0 C and 28 C chitin synthetase was inactivated, probably by the action of proteases present in the particulate preparations. Maximal activity was obtained at pH 6.6-7.1 and 15 C. Arrhenius plot showed a biphasic curve with the transition at 7 C. E values were 3300 Kcal/mole above this temperature and 15500 Kcal/mole below it. The enzyme was activated by GlcNAc and required a divalent metal, the most active being Mg++. By plotting v vs UDP-GlcNAc concentration a sigmoidal curve was obtained. Km calculated at high substrate concentrations was 20 mM. Chitin synthetase was competitively inhibited by polyoxin D (Ki 6.5 muM) and (Ki 1.35 mM), the latter giving complex kinetics.