Some aspects of proximal tubular sodium chloride reabsorption in Necturus kidney. Some aspects of proximal tubular sodium chloride reabsorption in Necturus kidney. Renal tubular reabsorption of fluid and sodium was measured by clearance methods in the doubly perfused Necturus kidney in which the bicarbonate concentration was varied between 0 and 60 mEq/liter. The effects of Damox (2.2 times 10-3M), ocubain (10-5M) and ethacrynic acid (10-4M) and of acidosis were also investigated. In addition to clearance experiments, stationary microperfusion experiments were carried out on promimal tubules to measure volume flow and steady-state sodium and chloride concentration differences across the tubular epithelium. In some experiments, the transepithelial electrical potential difference was also measured using an axial electrode system. The following results were obtained: 1) Bicarbonate is not essential to the operation of renal tubular fluid and sodium transport. 2) Total renal and proximal tubular fluid and sodium transport are partially inhibited by Diamox, ouabian and ethacrynic acid. 3) The proximal tubule maintains a significant transepithelial sodium and chloride concentration difference and a significant electrical potential difference (lumen-negative) in the presence of a poorly permeant nonelectrolyte. The direction and magnitude of the electrical polarization fully accounts for the observed chloride concentration difference. The data support the thesis that sodium chloride transport accross the proximal tubular epithelium takes place by active sodium transport and electically coupled passive chloride reabsorption. Important species differences with respect to mammalian transport mechanisms are discussed.


Nature of the acidifying defect after the relief of ureteral obstruction. Nature of the acidifying defect observed after relief of ureteral obstruction. The acidifying capacity of the normal and experimental kidney was studied in rats three hours after release of complete unilateral ureteral obstruction or after unilateral release of unilateral ureteral obstruction,  mean plasma bicarbonate concentration was 23.5 mEq/liter, and plasma pH, 7.45. Urine pH from the postreleased kidney was 7.47 and 6.01 from the control side. Net acid escretion averaged 0.97 muEq/min in the experimental kidney. Fractional excretion of bicarbonate averaged 0.02% in the control and 3.17% in the experimental kidney. In eight animals with unilateral release of bilateral ureteral obstruction, mean plasma bicarbonate was 16.9 mEq/min and plasma pH was7.35. Mean urine pH in the postreleased Kidney was 6.11, net acid excretion averaged 2.01 plus or minus 0.69 muEq/min and fractional bicarbonate excretion averaged 0.84%.


Renal mitochondrial glutamine metabolism and dietary potassium and protein content. Renal mitochondrial glutamine metabolism and dietary potassium and protein content. Glutamine distribution, glutamate accumulation, phosphate-dependent glutaminase (PDG) concentrations and intact mitochondrial ammonia production were studied in renal mitochondria from rats fed low, normal and high potassium diets and in mitochondria from rats fed high or low protein diets. The rats given a low potassium diet were potassium-depleted by 10 to 20% but in none of the groups were there any abnormalities of extracellular acid-base status. Glutamine was present in the outer space of mitochondria but could not be depleted in the matrix space in any group. In both the potassium-depleted and the high protein animals, we found increased matrix -14-C-uptake of glutamine (as -14-C-glutamate), increased intact mitochondrial ammonia production and increased concentrations of PDG. In the K+-depleted group there was a decreased matrix -14C-uptake when -14C-gamma-ketoglutarate of -14C-glutamate was present in the medium. Potassium loading produced no change in mitochondrial glutamine metabolism. Protein loading (compared with protein depletion) and potassium depletion induce an increased uptake of glutamine into the renal mitochondrial matrix space which leads to its increased deamidation. This adaption may explain the increased renal ammonia production seen in these situations when compared to their respective controls.


Arterial blood gas tensions and acid-base status of Wistar rats during thiopental and halothane anesthesia. Arterial blood gas tensions and acid-base status of spontaneously-breathing, unanesthetized Wister rats were compared with values obtained during 4 hr of thiopental and 6 hr of halothane (1%) anesthesia. During thiopental anesthesia, marked respiratory depression occurred (PaCO-2:57.0 plus or minus 10.0 MM Hg, PaO-2:70.4 plus or minus 11.2 MM Hg). Thirty-six percent of the rats died. During inhalation of room air and 1% halothane, PaO-2 decreased also, whereas PaO-2 did not change. Twenty-seven percent of the original number of rats died. Lowered arterial oxygen tension may have caused death; no rats died during inhalation of oxygen and 1% halothane. This technic insured sufficient analgesia for surgical procedures without marked alterations of the acid base status and is recommended for long-term anesthesia of small laboratory animals like rats.


[Loading-stable osteosynthesis of pertrochanteric femoral fractures using a condyle plate]. Also the authors' Department shares SPIER's opinion, according to which the ideal treatment of the proximal femur fractures is the osteosynthesis, with the greatest stability. The aim of surgical treatment of the fracture is the motion-stable and possibly loading-stable osteosynthesis. Since proximal femur fractures occur mostly in aged patients, the survival is considerably augmented by early and efficacious mobilization. If the general state of the patient is suitable, after consultation with the anaesthesiologist and the internist the surgical intervention is carried out. AO-condyle-plate yields further possibility to the loading-stable osteosynthesis of the pertrochanteric fractures.


[Comparative evaluation of various surgical technics in the treatment of dislocated patellar fractures]. From the point of view of the different operative methods 137 patellar fractures operated on in the 3 years' material (1969--1971) of the Central Casualty Rehabilitation Institute have been analysed by the authors. 116 fractures could be re-examined 2--4 years after patients were back at work. If the operation was followed by adequate functional management, satisfactory results were found after all operations. When the patients were back at work, further improvement of the results has been observed. In the time the patients got again to work, the results of partial patellectomy seemed better,--however, after 2--4 years osteosynthesis yielded better final results. Traction loop proved more effective than cerclage. If possible, conservation and exact unionof the patella is of great importance in both juveniles and manual workers. Early functional treatment improves the late results of the operation.


[History of traumatology in Hungary].

[History of traumatology in Hungary]. The history of the Hungarian Traumatology since the 16th century up to the present days is outlined by the author. The most important works--dealing with the treatment of the fractures and with the activity of other areas of the traumatology--are enumerated. Moreover, the factors promoting the development of the Hungarian traumatology are specified and the important surgeons active in the field of traumatology and the war operative surgery are named, who too have contributed to the development of the Hungarian traumatology. The importance of the Hungarian Institute of Traumatology--founded in 1956--is emphasized,--thus, the traumatology became an independent section of the Hungarian public health; and centrally directed and organized function of the traumatology was assured.


[Bilateral shortening of the m. rectus femoris due to complications after injection]. A case of bilateral shortening of the muscle rectus femoris--developed as complication of the injection--is reported. The mechanisms of the development of the alteration and the examination method are described. The possibility of the prevention of the extension knee constractures--developing as complication of the injection--is similarly discussed.


[Current problems in the treatment of open fractures]. The paper evidently does not discuss several important problems of the management of open fractures, but it is confined to the exposition of some fundamental rules of their traitment. Nowadays, the treatment of open fractures is to be decided individually for all cases. A great number of patients with open fracture owe their recovery to the proper first aid care at scence of accident. This is also in respect of the further treatment in the hospital of great importance. Exagerated activity is usually superfluous in the treatment of open fractures. Less and more proper management is often more useful for the injured patient.


[Classification of 557 open fractures of the leg and results of the treatment]. The results of the treatment of 557 open fractures of the leg are discussed from the standpoint of healing of the fractures. According to the severity of the fracture the patients have been ranked into 3 groups. Although in 95,1% of the patients recovery was obtained, in 50% of severe injuries healing occurred only over 20 weeks. The time of recovery was influenced unfavourably by the non stable osteosyntheses. Conservative treatment performed in a great number of patients yielded satisfactory results. The number of the cases treated with stable osteosynthesis is relatively small for comparison with the former groups. In the authors' opinion, the classification of the cases according to the severity of the fracture is of great importance, since it influences the treatment, the recovery time as well as the prognosis.


[Infectious complications of 227 open fractures of the leg]. Out of 557 open fractures of the leg we have analysed 472 cases in respect of recovery. We tried to discrive the relationship between the infection and the severity of the lesion and the methods of treatment resp. We have analysed also the further course of the infect.on. In our material considerable risk of the infections in the case of open leg fractures was found, since the incidence of all infections corresponded--in accordance with the data of the literature--to 16,7% of the appreciable cases. Significant relationship between the occurrence of infections and the severity of the lesion was found. In the material analysed according to the ACD code the incidence of infections is in the severely injured patients three times as much as in the case of slight or moderately severe groups. The occurrence of posttraumatic osteitis corresponds to 9,11%--this latter is similarly in relation with the severity of the lesion. The infection leads to the protraction of the osseous union,--however, no convincing data were found in the authors' material in respect of the relationship between the infection and the methods of treatment. The course and the proportion of healing of the infected cases correspond to the mean values reported in the literature. On the basis of their great material it is stated by the authors that only in the case of lesions with identical or at the least  similar severity comparison of the results of recovery or of the complications is possible and suitable.


Constituents of Ruscus aculeatus.

Constituents of Ruscus aculeatus. A phytochemical investigation of the acidic fraction from an ethanolic extract of the roots of Ruscus aculeatus L. (Liliaceae) has resulted in the isolation and identification of a sterol mixture, a fatty acid mixture, chrysophanic acid, a new compound named euparone and an incompletely characterized phenolic substance.


Medical and surgical management of reflux esophagitis.  A 38-month report of a prospective clinical trial. We compared the surgical and medical managements of reflux esophagitis in a prospective managements of reflux esophagitis in a prospective clinical trial.  Patients wissigned to surgical (15 patients) and medical (16 patients) groups.  A non-randomized medical group (20 patients) was also studied.  Seventy three per cent of the surgical and 19 per cent of the medical group had an excellent to good response.  A fair to poor response was observed in 81 per cent of medical and 27 per cent of surgical patients.  Symptomatic improvement was accompanied by normal findings on acid infusion test and esophagoscopy.  The histologic appearance of the squamous mucosa, however, remained abnormal in all but one patient.  In patients who did well after operation there was improvement in resting lower-esophageal-sphincter pressures and absence of gastroesophageal reflux.  The relative increases in pphincter pressure to graded increases in gastric pressure, however, remained abnormal in all but one patient.


The effect of chronic ammonium chloride ingestion on parathyroid hormone function. The purpose of this study was to examine the effect of ammonium chloride ingestion on the hypercalcemic effect of parathyroid hormone in vivo. Thyroparathyroidectomized rats were given 1.5% ammonium chloride for 5-6 days. Ingestion of ammonium chloride increased serum calcium, but also significantly enhanced the calcium elevating effect of injected parathyroid extract. This result is compatible with a proposed hypothesis that the calcium mobilizing function of the parathyroid hormone may be enhanced by the hormone's own influence on systemic hydrogen ion concentration.


Drug overdoses: Is one stomach washing enough? Naso-gastric tube aspirates were taken from patients with drug overdoses who had been given a gastric lavage and admitted to the resuscitation ward. Although care was taken to conduct thorough washouts, it was found that these were not always efficient. In several cases an amount equivalent to a therapeutic dose of drug was recovered in later aspirates. There was no correlation between the amount of drug recovered in the initial stomach washings and that found in the aspirates. It was concluded that routine aspiration of gastric contents at hourly intervals after admission was of considerable value in removing any residual drugs.


Edema of the pulmonary interstitium in infants and children. Ten infants and children with respiratory failure, receiving standard maintenance water requirements, were treated on 13 occasions with intravenously given furosemide (1 to 2 mg/kg) because of continued impairment of oxygenation despite conventional therapy. Pulmonary auscultation and radiographs were normal or typical of the primary diagnosis. After a five-fold increase in urine output the mean Po2 rose from 61 mm Hg at a mean FiO2 of 0.7 to 140 mm Hg at an FiO2 of 0.65. The Pco2 decreased from 46 to 38 mm Hg. Interstitial pulmonary edema in these patients can be related to both their lung disease and impaired water tolerance during ventilatory therapy.


The muscular membrane and calcium activation of the contractile system of a lamellibranch smooth muscle (ABRM). 1. Thin bundles of fresh ABRM treated by EDTA solution or Triton x-100 0.1% can be brought like glycerol-extracted fibres through contraction-relaxation cycles by changing the free Ca2+ level of the bathing medium for 10-6 M to 10-9 M. The kinetics of isometric force development and relaxation has been studied in the two conditions i.e ionic strength 0.06 pH 6.5 and ionic strength 0.28, pH 7.0 which are known to induce the catch-state in glycerol extracted fibres. When the low Ca-2+ solution (10-9M) is substituted for the high Ca-2+ solution (10-6M) immediately after the maximal force has been developed, relaxation occurs at a higher rate at ionic strength 0928 and pH 6.5. In this last condition, no tension redevelops after a quick release applied during the slow relaxation. 2. During the plateau, in presence of Ca-2+ 10-6 M. a quick release applied at any time is followed by a large redevelopment of tension at ionic strength 0.06 and pH 6.5. At ionic strength 0.28 and pH 7.0, the tension redevelops only during the decreased from 10-6 to 10-9 M without any change in the time course of the tension maintained. 3. These results suggest that in EDTA and Triton X-100 treated fibres of Abrm, the catch-state is spontaneously induced after the activation of the contractile mechanism under the same conditions of ionic strengh and pH as in glycerol extracted fibres. However, in the EDTA and Triton treated fibres, the presence of a high free Ca-2+ level is not necessary to maintain the tension in the catch-state induced at ionic strength 0.28 and pH 7.0.


The control mechanism of relaxation in molluscan catch-muscle (ABRM). The relaxing effects of 5-hydroxytryptamine (5-HT) have been tested on glycerol-extracted and chemically treated fibres (EDTA and Triton X-100 at two ionic strengths (0.06 and 0.28) and two pH's (6.5 and 7.0). The resistance to stretch of the two muscle preparations has been studied in the low Ca2+ medium i.e. without contractile activity in presence and in absence of 5-HT. The presence of 5-HT reduces significantly the resistance to stretch of chemically treated fibers in conditions of ionic strength 0.28 and 7.0, but has no effect on glycerol extracted fibres. 2. After the maximal tension has been developed in a high Ca2+ solution (10-6 M) the rate of relaxation of chemically treated fibres, induced by a low Ca2+ solution (10-9 M) at ionic strength 0.28 and pH 7.0 is increased by the addition of 5-HT. No effect is observed in glycerol extreacted fibres. 3. Chemically treated fibres in catch-state induced at ionic strength 0.28 and pH 6.5. 4. Cyclic AMP (c-AMP) induces the same relaxing effects at 5-HT on chemically treated fibres in the same conditions of ionic strength, pH and Ca2+ concentration. 5. The results are in disagreement with the hypothesis that the catch-state in ABRM is due to a lowering of the intracellular strength and pH; they suggest that the intracellular physiological conditions are rather near ionic strength 0.28 and pH 7.0 even in catch-state. We suppose that the relaxing effect of 5-HT, is not be due to a decrease of the intracellular free Ca2+ level but rather to an increase of the rate of Ca2+ release from the contractile proteins, and that it is mediated through c-AMP and intracellular relaxing mediator.


Purification of S1 muclease from Takadiastase by affinity chromatography on single-stranded DNA-acrylamide columns. When S1 nuclease from Takadiastase was partially purified according to previously reported methods, it showed a 10 to 15 fold increase in specificactivity. Although such preparations were highly active on single-stranded DNA, they had traces of activity on native DNA and were contaminated by T1-RNase. The S1 enzyme was further purified by a single step of affinity chromatography on single-stranded DNA-acrylamide column to a final purification of 275-fold. This preparation was free of T1-RNase and had an absolute specificity for single-stranded DNA.


A rapid assay technique for RNA ribose methylases. A rapid technique for quantitative separation of ribose-methylated nucleosides from base-methylated and non-methylated nucleosides by chromatography on DEAE-cellulose paper in the presence of borate is described. The method has been used as an assay for tRNA ribose methylases from yeast, using under methylated Escherichia coli tRNA as substrate. The main product formed with a partly purified yeast enzyme was characterized as 2'-O-methylcytidine.


Short-term effects of sodium pentobarbital on blood gases and chemistry in young chickens. Sodium pentobarbital, in its commercially prepared propylene glycol-ethanol-saline vehicle, was given intravenously to 8-week-old male and female Athens Randombred chickens, and either the vehicle alone or 0.8% saline was given to similar groups. One minute after injection, blood samples were taken for blood pH, pCO2, HCO3 minus, corticosterone, total protein, or cholesterol levels. The pO2 was significantly lower in the pentobarbital-anaesthetized birds than in those given saline or the vehicle only. Plasma glucose of birds given the vehicle was elevated over that of those given pentobarbital or saline. Triglycerides were significantly higher in plasma of birds given pentobarbital or the vehicle. This increase appeared related to the presence of the glycol moiety in the vehicle.


Utilization of L-cystine by the gamma-glutamyl transpeptidase-gamma-glutamyl cyclotransferase pathway. Cystine is a good acceptor of the gamma-glutamyl group of gamma-glutamyl donors in the reaction catalyzed by gamma-glutamyl transpeptidase. The product of the enzymatic reaction and an authentic sample of gamma-glutamylcystine were shown to exhibit identical chromatographic and electrophoretic behaviors; acid hydrolysis gave equimolar amounts of cystine and glutamate. In studies with two gamma-glutamyl donors, apparent Km values in the neighborhood of 0.3 mM were found for L-cystine; these values are not far from the concentrations of L-cystine in mammalian blood plasma. At an amino-acid acceptor concentration of about 0.5 mM, L-cystine is somewhat more active than L-glutamine, and much more active than L-cystein. L-gamma-Glutamyl-L-cystine was found to be a good substrate of gamma-glutamyl cyclotransferase. These observations thus indicate that L-cystine is a very active substrate of the gamma-glutamyl transpeptidase-gamma-glutamyl cyclotransferase pathway. In relation to the hypothesis that the gamma-glutamyl cycle functions in animo-acid transport, it may be significant that glutathione (which is the most abundant intracellular form) is a much better gamma-glutamyl donor than glutathione disulfide, while the predominant extracellular form-cystine-is a much better gamma-glutamyl acceptor substrate than cystein.


Kinetics of steroid induction and deinduction of tyrosine aminotransferase synthesis in cultured hepatoma cells. The specific rate of synthesis of tyrosine aminotransferase (EC 2.6.1.5; L-tyrosine:2-oxoglutarate aminotransferase) is used as a measure of the level of functional, cytoplasmic, tyrosine aminotransferase-specific mRNA in cultured rat hepatoma cells. An analysis of the kinetics of change in this rate after the addition or withdrawal of glucocorticosteroids sets an upper limit on the half-life of the enzyme-specific mRNA of 1-1.5 hr, whether or not steroid is present. The inactivation rate of the enzyme mRNA is independent of the growth condition of the cells, occuring equally rapidly in the presence or absence of serum or insulin, both of which induce tyrosine aminotransferase in these cells. The implications of these results for the mechanism of steroid induction are discussed.


Brdicka currents observed with bovine serum albumin and completely reduced bovine serum albumin in the presence of urea. In ammonia buffers of varying composition and pH, native bovine serum albumin and completely reduced bovine serum albumin, denoted by p(SH)35, yield quite different Brdicka current-voltage (i-E) curves, but they are identical in the presence of 5 mM calcium chloride. This means that in the presence of calcium, bovine serum albumin becomes completely reduced to p(SH)35. In 8 M urea and ammonia buffers the Brdicka i-E patterns of serum albumin and p(SH)35 are identical even in the absence of calcium, the effect of calcium on the first wave being negligible while calcium slightly increases the second wave. The maximum polarographic effect is attained at urea concentrations of about 5-6 M. Quite generally, the appearance of a second Brdicka wave is attributed to complexation of Co(II) with S- and a group of ligands that is different on the second than on the first wave. The effect of calcium on Brdicka currents of bovine serum albumin in the absence of urea is attributed to an orientation of the protein on the surface of the electrode such that all disulfide groups are reduced and with other ligands can complex with Co(ii). Denaturation of bovine serum albumin in buffers with a pH less than 10.5, and which are 8 M in area, is (polarographically) completely reversible if dilution is made within 15 minutes after preparation. Changes in Brdlcka I-E patterns upon longer aging at varying pH are attributed-in part at least-to dimerization of the denatured protein by interaction of pS- in one molecule with -S-S-in another.


Changes in cyclic nucleotide metabolism in aorta and heart of neurogenically hypertensive rats: possible trigger mechanism of hypertension. Changes in cyclic nucleotide metabolism similar to those characteristic of the chronic forms of hypertension were observed in an acute neurogenic form of hypertension in rats produced by electrolytic lesions of the nucleus tractus solitarii. These changes that were evident 2 hr after the lesions were made included decreased cyclic AMP levels in the heart, increased cGMP:cAMP ratio, cAMP phosphodiesterase (3':5'-cAMP 5'-nucleotidohydrolase, EC 3.1.4.17) and guanylyl cyclase (GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2) activities in the aorta and decreased snesitivity of adenylyl cyclase (ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1) in both the aorta and heart to stimulation by the beta-adrenergic stimulant isoproterenol. These changes appear to depend on catecholamine release and are not due to mechanical distortion secondary to the increased arterial pressure. These studies provide biochemical support to the concept that the sympathetic nervous system may play a critical role in the initiation of the hypertensive syndrome and that chronic hypertension could result from the fixation of the biochemical effects of increased sympathetic activity.


Effects of alkylation of phosphodiesters and of bases of infectivity and stability of tobacco mosaic virus RNA. Upon ethyl nitrosourea treatment of RNA of tobacco mosaic virus, up to four phosphodiester groups may be alkylated per molecule without chain breakage, as shown be sucrose gradient centrifugation. This indicates that ribophosphotriesters are quite stable. However, when this alkylation reaction is of longer duration and 6 to 10 triesters are formed, then an average of 1 to 2 breaks occurs and little or no intact RNA can be isolated. Methyl nitrosourea is less effective in forming triesters (about 25% of total alkyl groups compared to about 65% for ethyl nitrosourea), and a greater number of alkyl groups can, therefore, be introduced before breaks occur. Diethyl sulfate and dimethyl sulfate, which alkylate almost only the bases of nucleic acids, do not cause significant degradation of RNA of tobacco mosaic virus, even when as many as 70 alkyl groups are bound. All types of alkylation cause similar losses in viral infectivity at low levels of alkylation. Thus, an average of two chemical events leads to one lethal event, regardless of the nature of the alkylating reaction, which, for example, is with dimethyl sulfate about 65% on the N-7 guanine while with ethyl nitrosourea it is about 65% on phosphodiesters. It is thus concluded that all alkyl groups, whether on the base or on the phosphate, have the same potential to cause inactivation and that inactivation of RNA can result from phosphotriester formation per se.


Dissociation of bovine 6S procarboxypeptidase A by reversible condensation with 2,3-dimethyl maleic anhydride: application to the partial characterization of subunit III. Bovine 6S procarboxypeptidase A can be dissociated into its three subunits by acylation with dimethyl maleic anhydride. The deacylated subunits are obtained in a largely native form due to instability of the bonds to dimethyl maleate at pH values near neutrality. The seven first residues of subunit III are identical to residues 18-24 of bovine chymotrypsinogen B and very similar with the same residues in bovine chymotrypsinogen A and C (subunit II) and also in proelastase A of the African lungfish. Therefore, this subunit is likely to be a chymotrypsinogen or proelastase-A-like zymogen which has lost the ability to be activated on account of a deletion of the N-terminal residues from half-cystine 1 to valine 17. Like other pancreatic zymogens, subunit III appears to possess a weakly functional active site.


Interaction of hemoglobin with three ligans: organic phosphates and the Bohr effect. The assumption that the Bohy coefficient (less than log p 50)/(less than pH) is equal to the haldane coefficient (less than h minus plus) of hemoglobin is shown to be incorrect in the presence of allosteric effectors such as 2,3-diphosphoglycerate. The theoretical relation between the two coefficients in the presence of 2.3-diphosphoglycerate as derived. Experimental data on the variation of both coefficients with diphosphoglycerate concentration are presented and shown to be in agreement with prediction.


Polyarteritis Nodosa "mimicking" eosinophilic gastroenteritis. This case of a 71-year-old man with persistent eosinophilia (33-54%), intermittent abdominal pain, and transient pulmonary infiltrates illustrates how polyarteritis nodosa may mimic eosinophilic gastroenteritis. The radiographic manifestations and clinical findings of both are similar.


Kinetic study of neutrophil and inflammatory fluid beta glucuronidase. Beta glucuronidase obtained from rat inflammatory fluid and granulocytes was studied kinetically. Linear increases in activity occurred with time and enzyme concentration. No evidence of enzyme degradation during incubation was obtained. Supernatant and granulocyte enzyme activity was identical in relation to Km, and pH optima and resistance to high NaCl concentration. Minimal contributions to supernatant activity occur from plasma and red cells.


Effects of experimental bilateral cryptorchidism and castration on the plasma gonadotropins in male rats during sexual maturation. The effect of bilateral cryptorchidism and castration on serum LH and FSH was assessed in rats throughout their sexual maturation. After short time (4 days) castration marked elevations of FSH and increases of LH in plasma are recorded in all developmental stages. Bilateral cryptorchidism caused after 4 days in different age groups elevations of LH regardless of the sexual maturation. FSH was elevated in these cryptorchid animals only in more mature animals.


Degrees of saturation with respect to apatites in fruit juices and acidic drinks. Some fruit juices and carbonated acidic drinks, recognized as agents causing dental erosions, were analyzed for calcium, phosphate, fluoride and pH. Ionic activity/concentration products for hydroxyapatite and fluorapatite were calculated. It was found that all liquids analyzed were unsaturated with respect to both apatites, which explains their erosive effect.


Degrees of saturation with respect to apatites in parotid saliva at various ph values. The purpose of the present work was to investigate the degrees of saturation with respect to hydroxyapatite and fluorapatite in saliva at various pH's. The data of ionic activities in parotid saliva were collected from the literature and the degrees of saturation with respect to hydroxyapatite and fluorapatite were calculated. It was found that parotid saliva was supersaturated with respect to both apatites above pH 5.5, unsaturated with respect to hydroxyapatite and concurrently supersaturated with respect to fluorapatite in the pH range 5.5-4.5, while it was unsaturated with respect to both apatities below pH 4.5. In the laboratory it has been found that when enamel is exposed to a liquid unsaturated with respect to hydroxyapatite and supersaturated with respect to fluorapatite, a caries-like lesion is developed. A liquid unsaturated with respect to both apatites leads to an erosion-like injury. It is concluded that the two chemical conditions leading to the two types of enamel lesions may both occur in the oral cavity.


In vivo studies on the neutralizing effect of antacids using the Heidelberg capsule. The effects on gastric pH of various forms of administration of antacids have been studied in healthy volunteers. Gastric pH was recorded using a radiotelemetric technique (Heidelberg Capsules). In one series of experiments the Heidelberg Capsules were compared with a conventional aspiration method of measuring gastric pHqt lower pH-levels (pH smaller than 2) the Heidelberg Capsules recorded lower values than what was found with the aspiration technique. However, when the pH-response to an antacid dose was studied the two techniques gave concordant results. In another series of experiments, four antacids with the same acid-neutralizing capacity in vitro were compared in fasting subjects, using a crossover design. A liquid preparation and a chewable tablet gave almost equal results with a short latency time and a duration of action of more than one hour (mean 69 minutes and 82 minutes, respectively, with pH above the basal level). Two other tablet antacids designed to be swallowed whole gave less prompt effects and a shorter duration of action (mean 45 minutes for both, with pH above the basal level).


Genetic control of the in vitro responses of rat blood lymphocytes. I. Comparison of in vitro and in vivo responses. Nielsen, H. E. & Koch, C. Genetic Control of the In Vitro Responses of Rat Blood Lymphocytes. I. Comparison of In Vitro and In Vivo Responses, Scand. J. Immunol. 4, 31-36, 1975. In vitro DNA synthetic responses of blood lymphocytes from the inbred rat strains BN, Lewis, and AS were compared with each other after stimulation with allogeneic lymphocytes, human lymphocytes, phytohemagglutinin, and anti-Ig antibodies. BN lymphocytes responded less well than AS and Lewis lymphocytes regardless of the stimulus used. The responses of the congenic strains Lewis and Lewis. BN were identical, suggesting that H-1 (Ag-B)-linked loci do not determine in vitro responsiveness in these strains. In vivo, AS and BN rats were equally able to reject third-party skin grafts and to induce graft-versus-host reactions in F1 hybrids. We conclude that the interstrain differences found in vitro reflect genetically determined differences in in vitro kinetics, possibly related to the fraction of short-lived lymphocytes present rather than to demonstrable differences in the frequency of reactive lymphocytes.


Local graft-versus-host-reaction in mice specifically inhibited by anti-receptor antibodies. The local graft-versus-host (GVH) reaction provoked by parental spleen cells in F1 mice was shown to be T-cell-dependent. GVH reactions were suppressed in F1 hybrid mice immunized with parental T lymphocytes of the same genotype, but not in F1 mice immunized with parental B cells. In some cases this immunity could be passively transferred by serum into normal F1 mice. The specific activity of such sera could be removed by absorption with either parental T or B cells. Some of the F1 antisera were specificlly cytotoxic for parental GVH-reactive lymphocytes.


[Cerebral sclerosis. Diagnostic criteria and differential diagnostic consideration in practice]. In"cerebral arteriosclerosis" the diffuse sclerotic involvement of the cerebral vessels may produce acute softening of cerebral tissue. However this paper concentrates mainly on the clinical symptomatology which, in the absence of major vascular accidents, is characterized from the psychopathologic viewpoint by acute confusional states, aggressive behaviour, fluctuating loss of memory, disturbances of concentration and finally dementia. The chief neurologic symptoms are motor disturbance with short-stepping gait, stooped position of the body, pseudobulbar symptoms with dysarthric speech and disturbances of swallowing, and increased perioral reflexes. A complete case history and a thorough neurologic and psychopathologic examination are the most important factors in diagnosis, while ancillary methods are of value only for differential diagnosis. Prophylaxis and therapy (cardiotherapy, treatment of diabetes and hypertension, lowering of serum cholesterol and sedation) are discussed. In the differential diagnosis of dementia in the elderly patient consideration should be given to chronic vascular diseases, degenerative cerebral atrophies, brain tumors, low pressure hydrocephalus, progressive paralysis and some other rare brain conditions.


Practical problems in the treatment of pain. According to modern pain concepts, "pain" is the result of multifactorial influences. Planning of therapy therefore requires the diagnostic evaluation of a number of factors including delineation of an organic lesion, evaluation of the influence of pain on the individual's psychological development, situational anxiety, psychological coping style etc. The understanding and management of psychological factors is crucial in every pain syndrome as the idea the pain is either psychogenic or organic is outdated. For the treatment of mild pain salicylic acid is still unsurpassed. The rationale of its combination with a tranquillizer, and with codeine or benzomorphane for moderately severe pain, can be understood on the basis of modern pain concepts. Before strong narcotics are used a trial with combination of a phenothiazine with a tricyclic antidepressant drug is warranted. Methadone seems to have advantages over morphine for very distressing pain treated with narcotics. Biofeedback for pain due to muscle spasms, electrical stimulation of the dorsal column for intense chronic pain due to a well-delineated organic lesion, and operant conditioning applied by a well-trained team of physicians and staff are promising new treatments for pain. The place of acupuncture in future pain therapy cannot yet be judged. It must first be freed of cult-type opinions and evaluated further by studies meeting modern western standards of pain research.


Amino acid composition of proteins: Selection against the genetic code. Distribution of amino acids in 68 representative proteins is compared with their distribution among 61 codons of the genetic code. Average amounts of lysine, aspartic acid, glutamic acid, and alanine are above the levels anticipated from the genetic code, and arginine, serine, leucine, cysteine, proline, and histidine are below such levels. Arginine plus lysine account for 11.0 percent of codons and aspartic acid plus glutamic acid account for 11.3 percent; thus the average charge is roughly neutral.


The drug management of acute behavioural disturbances. Some aspects of drug management of acute behavioural disorder are discussed. Drug management aims at the amelioration of the patient's ineraction with his environment; it is used as a diagnostic procedure, and to facilitate further definitive diagnosis and investigation, as a form of psychotherapeutic contact, to facilitate further psychotherapy, and to initiate a treatment programme aimed at returning the patient to being a useful and health member of society. Some methods of rapid tranquillisation are described and the drug management of the following specific behavioural disturbances are discussed: schizophrenic distrubance, acute mania, depressive behavioural disturbance, acute anxiety states, acting-out psychopathic behaviour, toxic states, epileptic furore and dyscontrol syndrome, behavioural disturbances of the elderly, and behavioural disturbances in organic conditions.


Total body potassium, acid-base status and serum electrolytes in acute diarrhoeal disease. Total body potassium (TBK), acid-base status and serum electrolyte concentrations were measured in 49 children suffering from acute diarrhoeal disease, on admission and after rehydration. The TBK was usually low and the lowest values were found in those with the lowest pH. There was no relationship between TBK and serum sodium or potassium concentrations. Hyponatraemia was common as would be expected in a series containing many underweight children.


Treatment of hypertension with the aid of beta-adrenergic blocking drugs. Beta-adrenergic blocking drugs have become a recognized addition to the hypotensive agents. This article reviews the current beta-blocking agents, with regard to their usage, side-effects and role in the treatment of hypertension.


Anxiety: its nature and treatment.

Anxiety: its nature and treatment. Anxiety is an unpleasant, diffuse emotion, directed towards the future and associated with feelings of threat to the individual. Clinical anxiety occurs when a patient suffers from anxiety which is more frequent, more severe or more persistent than he is used to and can tolerate. Almost a third of the adult population will admit to some symptoms of anxiety. Drug therapy, in particular the benzodiazepines, is the mainstay of treatment, but care must be taken to avoid overprescription.


Nitrogen sparing by carbohydrate in man: Intermittent or continuous enteral compared with continuous parenteral glucose. To test whether oral carbohydrate would provide greater conservation of body protein than would intravenous carbohydrate, healthy normal human subjects were infused with high doses of glucose either continuously intravenously or by nasogastric tube in both continuous and intermittent regimes. Metabolic responses to high calorie, nitrogen-free infusions in normal man were documented in the blood hormone and substrate changes, and protein sparing was assessed by urinary nitrogen excretion. Continuous glucose produced a lower urinary "nitrogen floor" than did the intermittent regime, and intravenous glucose was more effective than was oral glucose. The insulin responses to continuous nasogastric and continuous intravenous glucose were similar, and nitrogen excretion did not differ between those two groups. The increased insulin levels seen with intermittent glucose were not accompanied by greater protein sparing.


Scanning electron microscopic and electrophoretic observations on barium sulphate used to absorb clotting factors. Electron microscopy and particle electrophoresis were found to be complementary techniques with which to complete the physical data from an earlier study on barium sulphates used to absorb clotting factors from serum. The differences revealed by scanning electron microscopy (S. E. M) in the physical shape of low and high density grades of barium sulphate particles appear to be of greater significance than charge as expressed by electrophoretic mobility, in determining whether or not precursor or performed factor Xa is eluted. This conclusion was based on the finding that at pH values close to 7, where the adsorption from serum occurs, all samples with the exception of natural barytes were uncharged. However as the high-density, or soil-grade, was found by S. E. M. to consist of large solid crystals it was suggested that this shape might induce activiation of factor X as a result of partial denaturation and consequent unfolding of the adsorbed protein. In contrast, uptake of protein into the centre of the porous aggregates revealed by S. E. M. pictures of low-density or X-ray grade barium sulphate may afford protection against denaturation and exposure of the enzyme site. The porous nature of particles of low-density barium sulphate compared with the solid crystalline forms of other grades accounts not only for its lower bulk density but also for its greater surface/gram ratio which is reflected by an ability to adsorb more protein from serum. Neither technique produced evidence from any of the samples to indicate the presence of stabilising agents sometimes used to coat particles in barium meals.


The significance of malate dehydrogenase isoenzymes in human blood platelets. Two MDH isoenzymes were detected in the homogenate of normal human blood platelets. According to their properties the cationic isoenzyme is compartmentalized in the mitochondria, the anionic one belongs to the cytoplasma. In spite of the few mitochondria in human blood platelets the proportion of the cationic enzyme is relatively high. Both of these enzymes could belong to a transfer system for malate transport across the mitochondrial membrane. As human blood platelets do not contain creatine phosphate a system like that could be of significance for platelet function.


Radiocurability of a transplantable murine sarcoma as influenced by immune competence of the host and adjuvant active specific immunotherapy. The immunization induced in CBA mice by allogenic transplantation of sarcoma J was evaluated through the rejection rate of a subsequent isologous tumour graft. Female animals appear to be significantly much more competent at various stages of sarcoma growth as after their definite cure by radiation or surgery. A difference of response according to the sex is also present with regard to the auto-immune reaction evoked by tumour irradiation. A marked discrepancy in radiotherapy efficiency is linked to the disparity of immune behaviour, emphasizing the fact that an immunologically competent host constitutes an important factor of tumour radiocurability. In male recipients, an adjuvant active specific immunotherapy potentiates tumour response to a single dose of radiations. On the contrary, the adjunct treatment may display a detrimental effect in animals which already possess a high degree of anti-tumour immunization.


Effect of antithymocyte globulin pretreatment on immunological reconstitution of lethally irradiated animals. Clinical and experimental studies have shown that antithymocyte globulin pretreatment will reduce the severity of the graft-versus-host reaction after allogeneic bone marrow transplantation. To determine whether this was attributable to a persisting cytotoxic factor in the recipients' sera or a result of the "masking" of foreign antigens by the antihymocyte globulin, an experimental schema utilizing a syngeneic transfer of immunocompetent cells was devised. Lethally irradiated mice that had been pretreated with rabbit antimouse thymocyte globulin (RAMTG) were injected with syngeneic spleen or bone marrow cells and their immunological competence was measured by the response to a test antigen, sheep red blood cells. It was found that such pretreatment had an adverse effect on the immunological potential of the infused cells. Thus, the plaque-forming cell response to sheep red blood cell antigen in RAMTG-pretreated recipients injected with spleen cells was reduced when compared to the saline or normal rabbit globulin-treated controls. The immunological recovery of lethally irradiated animals protected with syngeneic bone marrow was also delayed, but not permanently impaired, when the recipients had been pretreated with RAMTG. These effects were evident although the spleen or bone marrow cells had been injected into the RAMTG-pretreated recipients at a time when their sera were devoid of any cytotoxic antibodies. It is speculated that two mechanisms may contribute to this alteration in immune function of the infused cells: (1) that RAMTG exists in the serum in amounts sufficient to attach to receptor sites on lymphocytes or their precursors but insufficient to kill the cells, interfering with the antigen recognition mechanism or migration and homing patterns, or (2) that the RAMTG treatment creates a temporary defect in the microenvironment of the spleen and other hemopoietic tissues, thereby affecting the transplantation and proliferation kinetics of the infused cells.


Transplantation of autoimmune potential. II. Glomerulonephritis in lethally irradiated DBA/2 recipients of NZB bone marrow cells. Lethally irradiated (850 rads) DBA/2 mice which had been transplanted 10 months previously with 2 times 10-6 bone marrow cells from 3-week-old donors of the H-2-histocompatible NZB, BALB/c and DBA/2 strains were examined for manifestations of autoimmune disease. Also studied were lethally irradiated (950 rads) NZB mice grafted with NZB marrow. Strongly positive antinuclear antibody responses were present in all NZB and DBA/2 recipients of NZB marrow, but absent in DBA/2 mice grafted with BALB/c and DBA/2 marrow cells. The antinuclear antibody-positive animals had glomerulonephritis with the deposition of globulin in or along the basement membranes. These observations support the view that the potential for autoantibody formation and subsequent autoimmune disease development is inherent to the NZB hemopoietic stem cell and their progeny.


Stimulation of rat graft-versus-host reactions by polyinosinic-polycytidylic acid. The effect of polyinosinic-polycytidylic acid (poly I:C) treatment on the rat graft-versus-host reaction (GVHR) initiated in parental to F1 hybrid strain combinations differing at either major or minor histocompatibility determinants were studied in three different protocols. 1 A GVHR initiated in juvenile (LBN)F1 recipients and treated concurrently with poly I:C alone produced neither splenomegaly nor dermatitis in these juvenile rats. (2) Pretreatment of L donors with a single injection of poly I:C 3 days before initiation of the GVHR enhanced resultant splenomegaly in the newborn (LBN)F1 recipients. A high poly I:C dose was inhibitory. (3) Newborn recipients which received lymphocytes from L donors and which were concurrently treated with poly I:C developed dermatitis at an accelerated rate. However, poly I:C alone given to newborns mimicked the GVHR by induction of a syndrome characterized by splenomegaly, dermatitis, thymic involution, and body growth retardation. The parental L and (LF)F1 hybrid strain combination differing only at a minor histocompatibility determinant or in an isogenic hybrid combination (LBN)F1 leads to (LBN)F(1) developed no GVHR when recipients were treated with poly I:C. We conclude that poly I:C can stimulate a rat GVHR initiated with unsensitized donor cells differing at a major histocompatibility locus.


Retransplantation of human bone marrow. Two immunosuppressive drug regimens. A 15-year-old boy with aplastic anemia was successfully retransplanted with matched sibling bone marrow after failure of a first transplant from the same donor. Cyclophosphamide was used as immunosuppression for the first transplant, and cyclophosphamide plus procarbazine plus antithymocyte globulin were used for the second transplant. Laboratory studies of peripheral blood and bone marrow karyotypes and T and B lymphocytes supported the conclusion that immunosuppression was inadequate for the first transplant, but adequate for the second transplant.


Specific inhibition of the graft-versus-host reaction in fetal or neonatal liver chimeras. The fetal liver chimera system was used as a model to study the nature of transplantation tolerance in radiation chimeras. A permanent state of tolerance was induced in (C3H/eb times C57BL/6)F1 irradiated mice after reconstitution with parental C57BL/6 fetal or neonatal liver cells. It was found that although enough host hemopoietic cells were present in such chimeras to provide antigenic stimulation, subsequent inoculation of these chimeras with C57BL/6 immunocompetent cells syngeneic to liver donor cells specifically abolished their response against the host. In addition, cells obtained from liver chimeras after their challenge with C57BL cells were unable to produce a graft-versus-host response upon transfer to (C3H/eb times C57BL/6)F1 newborn mice. Transfer of serum of these mice could not prevent immune reactivity of syngeneic C57BL/6 cells neither in the graft-versus-host nor in the mixed lymphocyte culture assays. These observations are compatible with the hypothesis that suppressor cells may differentiate within the fetal liver, which specifically inhibits the immune reactivity of syngeneic cells, and thus leads to the establishment of tolerance.


Human immunity to rat antigens.

Human immunity to rat antigens. A test has been devised with the object of assaying immune responsiveness in normal and immunodepressed persons. It has been based on the graft-versus-host model of Ford et al. (Transplantation 10: 258, 1970) and employs rat antigens as the immunological stimuli. Peripheral blood lymphocytes were injected into the hind feet of young Wistar rats, and 7 days later the popliteal lymph nodes were removed and weighed. It was found that the unwanted host-versus-graft activity could be suppressed in the rats by total body irradiation. Inactivated lymphocytes were injected into the right hind foot as a control and the result was expressed as a ratio: weight of left node to weight of right node. Lymphocytes from 45 healthy individuals were examined in this way. The response was readily suppressed by administering daily injections of steroid or antilymphocyte globulin to the rats, but was not influenced by the presence or absence of antirat antibodies in these individuals.


[Karyosphere in oogenesis].

[Karyosphere in oogenesis]. The purpose of this review is to draw attention to the peculiar phenomenon during gametogenesis: the formation of the karyosphere. This phenomenon is characterized by concentration of all chromosomes in the limited area of the nucleus and may be considered as alternative of the genome in the state of lumpbrush chromosomes. The formation of the karyosphere is a widely spread phenomenon during oogenesis of different animal classes. The karyosphere can be developed during different stages of oogenesis in different organisms; but as a rule the chromosomes of diploten stage of meiosis take part in its formation. As to functional identity of the karyosphere in different species, special investigations are to be done, but contemporary knowledge of the karyosphere formation reveals some common feature:1) in the karyosphere the chromosomes are in a relatively spiral state as demonstrated by the positive Feulgen reaction; 2) there is a low level of RNA synthesis or the absence of it in the karyosphere; 3) during the karyosphere formation the nucleus is enriched by the acid proteins and a lot of protein granules and structures appearing in a close contact with the karysphere. The more typical examples of the karyosphere formation can be observed in the insect oocytes belonging to the nutrimentary type of oogenesis. In the oocytes of some animals the peculiar protein substances are formed around the chromosome knot and appear as a fibrillar zone. Such karyosphere appears to be a kind of capsule inside the nucleus. The capsules are developed as a result of complex interaction between the main nuclear structures; chromosomes, nucleoli, and nuclear membrane as it is manifested by the analysis of some recent ultrastructural date obtained in some insect and amphibian oocytes. The function of the karyosphere capsule and the role of the nuclear structure (sinaptonemal complex, extrachromosomal DNA, and nuclear membrane) in formation of the capsule, are discussed as well as the ultrastructural and cytochemical similarity between the karyosphere capsule of oocytes and nuclear bodies of somatic cells.


[Effect of thymocytes on the quantity of polypotent hematopoietic mast cells in the spleen of sublethally irradiated mice]. With the aid of Till and McCulloch's method, 5 times 10(-6) thymic cells were found to cause an increase in the number of hemopoietic endogenous spleen colonies in syngeneic donor-recipient combination. Thymic cells of C57BL mice had no effect on the number of endogenous colonies in the spleen. 40 times 10(-6) thymic cells administered 24 hr after sublethal irradiation caused an increase in the number of colony forming units in the spleen within 14 days. Possible ways of the thymus effect on hemopoiesis are discussed.


Effect of human chorionic gonadotrophin on the dog seminiferous tubule, with and without experimental unilateral cryptorchism. The effect on human chorionic gonadotrophin (HCG) on the testes of pubertal and postpubertal Beagle dogs was studied, in the one instance in bilaterally normotopic testes and in the other on the still scrotally located gonad of dogs which had been subjected to unilateral experimental cryptorchism. The area of the cross-sectioned seminiferous tubules served as a parameter for evaluating the effect of HCG. Administration of therapeutic doses of HCG produced, in animals with bilaterally normotopic testes, a marked diminution of the area of the seminiferous canals. This means that HCG application at normal dosage impairs the seminiferous tubules in the dog. In animals with unilateral cryptorchism, HCG application produced no significant change in the tubule area of the scrotally located testis beyond that which is ascertainable anyway on the orthotopic testis following translocation of the contralateral gonad to within the abdominal cavity. Hence, HCG does not influence the degenerative change in the orthotopic testis in experimental unilateral cryptorchism. Rather, an adverse effect of HCG on the seminiferous tubule is evident, independently of the hitherto published reports of successfully attained descent.


[Ornithine transcarbamylase in Clostridium perfingens]. Five strains of A type Cl. perfringens of different titres of toxicity (BP6K, SR-12, 2836, 2910, 1) possessed a distinct activity of ornithine transcarbamylase. In cells the maximal activity of the enzyme was observed within 3-5 hrs of growth of the culture. The enzyme was partially purified and some of its physico-chemical properties were studied. Ornithine transcarbamylase was termostable. Monoiodine acetate, p-chloromercurybenzoate, semicarbazide, Hg-2+, Cu-2+ and Fe-3+ inhibited the enzymatic activity, but Mg-2+ and Ca-2+ activated the enzyme. Ornithine transcarbamylase was shown to be active in wide region of pH: from pH 6.0 to pH 9.0 and higher. Two peaks of the enzyme activity were observed: the first (a more distinct one) at pH 8.6-8.9 and the second, smaller,--at pH 6.5-6.7.


[Acid-base balance in the cerebrospinal fluid of normal subjects. Comparison of cisternal and lumbar CSF (author's transl)]. 1. An investigation was carried out on 40 normal subjects of the acid-base balance in arterialized capillary blood and in the CSF (17 cisternal and 23 lumbar samples). The pH value was 7.324 in the cisternal CSF and 7.317 in the lumbar CSF, giving a difference of 0.007. The respective pCO2 values were 45.0 mm Hg and 45.9 mm Hg. The HCO3-minus value was 21.8 mMol/l, both in the cisternal and the lumbar CSF. 2. A comparison of the cisternal and lumbar CSF samples by means of the Wilcoxon-Mann-Whitney Test did not show any significant differences. 3. Neither of the groups showed a statistically significant dependence on age or sex. 4. Comparative studies by several authors of the acid-base balance in the cisternal and lumbar CSF are mentioned and discussed with reference to the present results.


Changes in systolic time intervals during stepwise increasing hypoxia. Determinations of the reciprocal value of the square of the pre-ejection period (1/PEP-2) and the pre-ejection period/left ventricular ejection time-ratio (PEP/LVET-ratio) during stepwise increasing hypoxia showed in seven mongrel dogs in a decrease in PEP/LVET-ratio and an increase in 1/PEP-2 as an expression of a stimulation of the cardiac function. Significant changes were not observed before the arterial oxygen tension (Pao2) was below 40 mmHg. During severe hypoxia (Pao2 15-20 mmHg), some deterioration in the systolic time intervals occurs with time, but a stimulation persists at the time of death compared to the prehypoxic values.


Effects of general anaesthetics on the pH of gastric contents in man during surgery: a survey of halothane, fluoroxene and cyclopropane anesthesia. The effect of premedication and three general anaesthetics on gastric content pH was investigated. Neither premedication with pentobarbital-atropine nor morphine-scopolamine given 1-2 h prior to anaesthesia appeared to affect the acidity of the gastric contents. Halothane invaribly increased the pH of the gastric contents; none of the seven patients studied had a gastric pH of less than 2.5 (mean 5.1) after 1 h of anesthesia. Cyclopropane uniformly maintained the acidity of the gastric contents; only one out of seven patients had a gastric content pH above 2.5 (mean 1.7) after 1 h of anaesthesia. This effect of cyclopropane in maintaining the pH of gastric contents was unaffected by the use of premedication and induction with thiopental. Fluorexene affected the pH of the gastric contents much less uniformly. Although the pH for the group as a whole gradually increased (after one hour from 1.7 plus or minus 0.2 (s.e. mean) to 3.1 plus or minus 0.7), some of the seven patients studied reacted to fluroxene with a constant low gastric content pH. The findings are discussed, and it is concluded that the risk of pulmonary complications in case of vomiting and aspiration upon emergence from anaesthesia is greater if the anaesthetic agent is cyclopropane or fluoroxene, than if it is halothane.


Prostaglandin F2 alfa infusion and halothane anaesthesia. The cardiovascular reaction to infusion of prostaglandin F2 alfa was examined in seven patients during N2O-jalothane anaesthesia. As in the non-anaesthetized individual, no changes in blood pressure, pulse rate, CVP or ECG occurred during anaesthesia, but a great reflux of enteric juice to the ventricle was noticed only 2-3 min after the beginning of the hormone infusion. It is concluded that prostaglandin F2 alfa may be safely given to patients who are going to be anaesthetized, but the patients must be considered as having a full stomach and therefore treated as such.


Cardiac function during halothane anf fluroxene anesthesia expressed by systolic time intervals. A non-invasive method of measuring the systolic time intervals (STI) during anesthesia is described. Using the ratio between the pre-ejection period and the left ventricular ejection time (PEP/LVET-ratio) as an expression of cardiac function, it is shown in 39 patients that thiopentone exerted a marked depression on the heart (increase in PEP/LVET-ratio). This depression was further aggravated by halothane, while fluroxene caused an improvement of PEP/LVET-ratio. In the immediate post-anesthetic period PEP/LVET-ratio almost reached control value after discontinuation of fluroxene in contrast to halothane, where an increased PEP/LVET-ratio (25%) still persisted. The changes were mainly due to a prolongation of PEP without any specific change in LVET. During the study, PEP/LVET-ratio showed a close correlation to the reciprocal value of the square of the pre-ejection period (1/PEP-2). STI form 27 volunteers were measured and compared to the values from the patients before anesthesia was induced. PEP and PEP/LVET-ratio were significantly shorter in the patient group.


Effects of respiratory acidosis on the arrhythmia threshold during fluroxene and halothane anesthesia. Hypercarbia was induced in 12 patients anesthetized with either halothane or fluroxene in an inspired concentration of approximately 1.3 MAC (1% halothane and 4-5% fluroxene). The six patients receiving halothane anesthesia responded to hypercarbia with a pronounced tachycardia, an increased arterial pressure and an electrocardiographically monitored threshold level for ventricular arrhythmias at a Paco2 level averaging 98 mmHg. The six patients receiving fluroxene anesthesia responded to hypercarbia with both tachycardia and hypertension, but in spite of an average Paco2 level of 109 mmHg, no ventricular arrhythmias could be provoked. It is therefore suggested that within the non-narcotic level of hypercarbia a threshold level for cardiac arrhythmias does not exist under fluroxene anesthesia.


The influence of arterial carbon dioxide tension on the cerebrovascular response to arterial hypoxia and to haemodilution. Cerebral blood flow (CBF) measurements and blood gas analyses were performed on anaesthetized and artifically ventilated dogs during arterial hypoxia or haemodilution in different ranges of arterial carbon dioxide tension. Arterial hypoxia as well as haemodilution produced a flow increase in all ranges of ventilation. However, this flow increase was elicited at a cerebrovenous oxygen tension which rose with the arterial carbon dioxide tension, but which tended to be maintained by the flow increase during continued decrease of the arterial oxygen content. On the assumption that the cerebrovenous oxygen tension reflects the oxygen tension of the brain tissue, it is suggested that the arterial carbon dioxide tension influences the ability of the brain tissue to maintain the aerobic metabolism during reduced tissue oxygen tension. This means that tissue hypoxia, in the sense of utilisation of anaerobic metabolism, occurs at a tissue oxygen tension which is lower the lower the arterial carbon dioxide tension is.


Acid-base and electrolyte balance in infants of diabetic mothers. Vaginal delivery versus caesarean section. The acid-base and electrolyte balance of 30 women studied at delivery and in their infants during the first 48 h. 18 women were diabetics, 10 of these were delivered vaginally (DMvag) and 8 by elective caesarean section (DMcs). 12 healthy women were vaginally delivered (HMvag). The infants of diabetic mothers (IDM) received active infusion therapy. At birth the DMvag and their infants (IDMvag) had a more pronounced metabolic acidosis than the DMcs and their babies (IDMcs). The largest metabolic acidosis occurred, however, in the group of HMvag and their infants (IHMvag). After birth no significant differences were obtained in the acid-base and electrolyte balance between IDMvag and IDMcs. The plasma potassium level remained lower in IDM than in IHM. The study stress the importance of adequate management of diabetes in pregnancy in combination with active intravenous therapy during delivery and to the infant in the immediate neonatal period. The slightly larger metabolic acidosis seen in combination with vaginal delivery suggests that this mode of delivery should not be attempted uncritically in diabetic women.


Correlation between blood gases, glycolytic enzymes and EEG during electroconvulsive treatment in relaxation. Twenty-three psychiatric patients were investigated during electroconvulsive treatment in relaxation. The blood gases, pH and serum bicarbonate levels in blood samples from the internal jugular vein and the femoral artery were measured radiometrically. The LDH fractions were separated electrophoretically and their activity, along with the activity of aldolase, was then determined on test materials. EEG recordings were made during the seizure and also during postconvulsive restitution. The following conclusions were drawn: (1) There was no evidence of anoxic anoxia in the brain during and after seizures. (2) A close relationship was found between the corresponding phases of electrical activity and brain metabolism as indicated by the blood gas changes during postconvulsive restitution. (3) On the basis of the increased glycolytic activity in the sera it is probable that glucose metabolism was shifted in the anaerobic direction during postconvulsive restitution of the brain tissues.


The automated assessment of the effect of flurazepam and nitrazepam on mood state. Some further results on the effects of the two hypnotic drugs, nitrazepam and flurazepam monohydrochloride, on mood state are described. An automated assessment and scoring system, Computer Assisted Psychometric System (C.A.P.S.), was used to assess mood state and showed that both hypnotics had a mild euphoriant effect even when administered to healthy volunteers during the daytime. This was most marked in the case of nitrazepam. It is argued that such euphoriant side effects should be further investigated as they can occur when hypnotics are administered on a long-term nightly basis, and there may therefore be a dependency aspect for those patients who habitually take such hypnotic drugs. The broad scope of the C.A.P.S. system is also discussed.


Hemodynamic effects of slow and rapid defibrination with defibrizyme, the thrombin-like enzyme from venom of the timber rattlesnake. The hemodynamic response to slow and rapid defibrination was sutdied in anesthetized beagle dogs, with the following results: 1. Slow defibrination was a benign procedure that had little or no effect on the hemodynamic variables studied. 2. Rapid defibrination induced statistically significant decreases in cardiac output, stroke volume, and mean aortic arterial pressure. 3. Bradycardia, a drop in mean left v"ntricular pressure, cardiac and minute work indices, an increase in pulmonary artery pressure, and a drastic rise in pulmonary and systemic vascular resistances were also observed. Although physiologically apparent, these changes were not statistically significantly different from control levels. 4. Pulmonary capillary wedge pressure, left ventricular end-disatolic pressure, arterial pH, and blood gases were not altered by rapid defibrination. 5. In view of the similarities between the hemodynamic changes observed after rapid defibrination and acute myocardial ischemia, the role of decreasing fibrinogen concentrations and blood viscosity in aucte myocardial infarction and the sudden death syndrome is questioned.


In line final filters for removing particles from amphotericin B infusions. The feasibility of using membrane filters to remove particles from intravenous infusions of amphotericin B in dextrose 5% (a colloidal solution) was studied. Six types of commercial membrane filters, ranging in pore size from 0.45-1.0 mum, were used. Because of the effect of pH on the particle size of colloidal solutions, each filter was tested at solution pH 4.7, 5.6 and 6.5. Samples of filtrate were analyzed spectrophotometrically for amphotericin content. All filters of pore size 0.22 mum removed amphotericin B from solution and were inappropriate for use with this product. Solutions at pH 4.7 were turbid, filtered slowly and were generally unacceptable for clinical use. At pH 5.6, only filters with pore sizes of 1.0 mum or greater showed acceptable results. At pH 6.5, filters with pore sizes of 0.45 mum or greater gave acceptable results; the use of a filter with a pore size of not less than 1.0 mum would provide a margin for error to compensate for variations in the colloidal particle size of amphotericin B.


Drug therapy in terminally ill patients. The drug treatment of terminally ill patients is reviewed. The treatment of the major discomforting symptoms of degenerative diseases--pain, anxiety, nausea, vomiting and depression--is reviewed. The use of phenothiazines, anticholinergic drugs and corticosteroids is discussed. To help patients keep track of their drugs, use of a medication schedule card is recommended.


Clinical neuromuscular pharmacology of AH 8165 D, an azobis-arylimidazo-pyridinium-compound. The neuromuscular blocking properties of AH 8165 D (1,1'azobis-(3-methyl-2-phenyl-1H-imidazo-1,2a-pyridinium)dibromide) were quantitatively studied in 50 patients, undergoing extra-abdominal surgery and anaesthetized with barbiturates, nitrous oxide, fentanyl and droperidol, by means of mechanograms of the hand muscles obtained by ulnar nerve stimulation. AH 8165 D is a rapid-acting nondepolarizing agent (full effect within 1--2 min) providing good intubation conditions similar to those obtained with suxamethonium. AH 8165 D may be considered to be indicated for emergency intubation in patients with full stomach when the risk of regurgitation is high. The duration of action of clinically useful doses (0.4-0.8 mg/kg body weight) is shorter than that of equi-effective doses of other nondepolarizing muscle relaxants. Repeated doses show a cumulative effect. The neuromuscular blockade can easily be reversed by an anticholinesterase drug. AH 8165 D-induced muscle relaxation is always accompanied by a dose-dependent tachycardia limiting the clinical usefulness of this new drug.


Light- and electron microscopic investigations of pulmonary tissue after high-frequency positive-pressure ventilation (HFPPV). Narcotisized dogs were artificially ventilated for periods of two to five hours with HFPPV. During this time the blood gases, pH and bases were controlled. In spite of sufficient oxygenation and CO2-elimination, a metabolic acidosis developed which could not be fully compensated by the addition of buffer solutions. In light and electron microscopy these lungs did not differ significantly from control lungs. Haemorrhages or atelectases were never observed. Type I cells as well as Type II cells in the alveoli are unchanged, i.e. the Type II cells were not depleted but contained numerous typical lamellar bodies with a diameter of 0.4-1 mu. The blood gas barrier was not widened and was ca. 3000 A wide. The alveolar surface was coated by an often fragmented electron-dense film (monolayer of the surfactant).


Transmission of hog hog cholera virus by mosquitoes. Mosquitoes trapped during an epizootic of hog cholera (HC) in Maryland in 1969 were prepared into 40 pools which were inoculated in pigs. Hog cholera virus was confirmed in pigs inoculated with 8 of 40 pools of mosquitoes. Generally, the pigs contracting HC developed chronic infections with persistent viremia that lasted 30 or more days. Two pigs seemed healthy when euthatized 62 and 80 days after inoculation, yet viremia of high titer was detected in each. Experimental studies were performed with 2 laboratory strains of mosquitoes, Aedes aegypti and Culex tarsalis, to determine if biological and mechanical transmission occur. Biological transmission was not confirmed, but HC virus was retained in A aegypti for 3 days. Mechanical transmission was confirmed with A aegypti in 2 of 9 experiments.


Exit of Anaplasma marginale from bovine red blood cells. Incubation of Anaplasma marginale-infected bovine red blood cells in a flow culture system resulted in a decrease of observable marginal bodies. The decrease was twice the degree of hemolysis, indicating that marginal bodies may leave red blood cells without concomitant lysis of the host cell.


Experimentally induced intestinal obstruction in sheep: paradoxical aciduria in metabolic alkalosis. Ewes with surgically prepared obstruction of the duodenum were used as a model in the study of ruminant metabolic alkalosis and paradoxical aciduria. Metabolic alkalosis occurred as a result of irreversible chloride loss, presumably into the abomasum and forestomachs. Analysis of data on serum and urinary electrolye concentrations provided limited support for the explanation of paradoxical aciduria in terms of chloride and potassium deficiencies. The accumulation undetermined anions in the serum indicated that the decreased urinary pH was due to the excretion of titratable acid.


Impact of physician's assistants on patient visits in ambulatory care practices. The addition of a physician's assistant to an ambulatory care practice increases the practice's productivity. Practices using physician's assistants (medexes) had a 12% increase in the number of patient visits during the first year of training and 1 3/4 years later had an average increase of 37%. The medex by himself provided care to 28% of the patients and, in company with the physician, to another 10%. No consistent changes across practices were noted in patient waiting times or time physicians spend with patients.


Cephalothin and cephaloridine therapy for bacterial meningitis. The efficacy of cephalothin and cephaloridine in the treatment of bacterial meningitis was evaluated from a review of 106 cases reported in the literature. Fifty-nine percent of 34 patients treated with intravenous cephalothin responded suboptimally; those receiving daily doses of 12 g or more fared significantly better (P less than 0.025). In contrast, 74% of 72 patients treated with cephaloridine responded favorably; those who received concomitant intrathecal cephaloridine responded significantly better (P less than 0.005). These findings indicate that cephalosporin therapy for bacterial meningitis, without concomitant intrathecal medication, is unreliable and that this is probably due to inadequate penetration of the antibiotics into cerebrospinal fluid. In penicillin-allergic patients with pneumococcal, meningococcal, and hemophilus meningitis, chloramphenicol is the agent of choice. For staphylococcal meningitis, intravenous cephalothin at doses of 12 g/day with additional intrathecal cephaloridine at doses of 12.5 to 50 mg/day should be administered concomitantly.


Theophylline-induced seizures in adults. Correlation with serum concentrations. Eight patients developed grand mal seizures during intravenous theophylline therapy. None had a history of neurologic disorder, and all were acutely ill with severe pulmonary or cardiovascular disease, or both. Serum theophylline concentrations obtained within 1 hour of the seizure ranged from 25 mug/ml to 70mug/ml, with a mean value (53 plus or minus 4.8 mug/ml) more than twice the upper limit of the recommended therapeutic concentration. This serum theophylline concentration was greater than the concentration found in a group  of patients with less severe drug-related symptoms (35 plus or minus 1.8 mug/ml, P less than 0.01). A third group of patients without drug-related symptoms had a mean theophylline serum concentration of 19 plus or minus 2.0 mug/ml, which was less than that found in either group with toxicity symptoms (P less than 0.05). Factors predisposing to the high serum concentrations in the patients with seizures were both higher drug dosage, compared with the other groups (P less than 0.01), and hepatic dysfunction, which was more common in both groups with drug-related symptoms.


Lactic acidosis from carboxyhemoglobinemia after smoke inhalation. Tissue hypoxia as a result of a wide variety of clinical situations had frequently been implicated as a cause of systemic acidosis due to the accumulation of lactic acid. Four patients suffering from smoke inhalation had lactic acidosis in association with carboxyhemoglobinemia. There was no evidence of decreased tissue perfusion, hypotension, arterial hypoxemia, or anemia. The following were tested in all patients: arterial pH (7.25 to 7.40), Pco-2 (19 to 27 mm Hg), Po (63 to 116 mm Hg), HCO-2- (11 to 19 meq/litre), carboxyhemoglobin (13% to 37%), and lactic acid (5.1 to 9.3 meq/litre). After therapy with oxygen and intravenous corticosteroids, there was prompt return of lactic acid levels, carboxyhemoglobin values, and arterial pH to normal. It is concluded that the cause of lactic acidosis in the presence of carboxyhemoglobinemia during smoke inhalation is tissue hypoxia. This tissue hypoxia is due to the reduction of the oxygen-carrying capacity of the blood and the concomitant shift of the oxyhemoglobin dissociation curve to the left, both known to result from carboxyhemoglobinemia.


Bicycle and moped spoke injuries in children. Analysis of 103 consecutive cases. The series consists of 60 boys and 43 girls, aged from 1 to 14 years, mean 4.95 years, whose right (42) or left (61) foot was caught between the bicycle (97) or moped (6) spokes. The skin was involved with ankle sprain, with fracture or without other injuries in 97 children; lateral aspect of the ankle and foot in 65 and heel in 21 patients. The X-rays revealed 10 tibial fractures, 4 fractures of the tibia and fibula, one fracture of the medial malleolus, one of the lateral malleolus and one bimalleolar fracture. Hence an X-ray of the leg should always be taken. Twenty-six patients were treated on the ward, 77 as outpatients. The mean total time of healing in the group as a whole was 25 days and 44 days in patients having a fracture. Heel avulsion injuries caused by the spokes need special attention. The vitality of the crushed and dirty, caudally or medially based skin flap is minimal and very often yields a marginal or total necrosis if primary suture is done.


[Extraction of rifamycin B from native and aqueous solutions]. Optimal conditions for extraction of rifamycin B from aqueous solutions and fermentation broth filtrates at pH values within 2.0-7.0 were determined. When the antibiotic was extracted from the aqueous solutions, the highest yield was obtained at pH 2.0. When the antibiotic was extracted from the fermentation broth filtrates, it was found that chloroform was the most selective solvent with respect to rifamycin B, the chloroform selectivity being increased at pH 3.5-4.0. It was shown that rifamicin B passed from the buffer solutions with a concentration of 3-20 mg/ml to chloroform in amounts of 6-7 mg/ml and to ethylacetate and butanol in amounts of 20 mg/ml. Such conditions of chloroform and butanol (9 : 1) increased the rifamycin B contents in the extract up to 40 mg/ml.


[Action of migillin on its own producer, Asp. fumigatus]. Addition of migillin to the nutrient medium at early stages of the fungus development induced at one hand inhibition of the fungus growth during the first 24-48 hours and stimulation of the biomass accumulation during the following hours of the development and on the other hand it induced inactivation of migillin added and inhibition of production of the "own" antibiotic. The migillin effect was accompanied by a delay in liberation of the substance with adsorption at 260nm from the mycelium.


Activity of pure streptovaricins and fractionated streptovaricin complex against Friend virus. Chromatographic fractionation of streptovaricin complex yields two stable components enriched (4- to 16-fold) in activity directed against the polycythemic strain of Friend virus; both components apparently contain no streptovaricins. When compared with their unfractionated parent streptovaricin complex, eight individual intact streptovaricins (A through G and J) show at least a 30-fold reduction in antiviral activity. These results further support the conclusion that the diversified biological properties of streptovaricin complex probably reside in different molecular structures.


Management of chemical cyanosis by oxygen saturation readings. Chemical cyanosis is an oxygen transport deficiency produced by exposure to aromatic nitro- or animo-compounds. Evaluation of its severity by methemoglobin determinations defines the problem incompletely and is time consuming. Twenty-nine patients were studied over a five-year period by both methemoglobin level using classical laboratory methods and oxygen saturation level, using a reflection oximeter. The two results were found to bear an inverse linear relationship. Oxygen saturation may be determined easily and rapidly by the reflection oximeter method, and may be used safely as a guide to treatment of chemical cyanosis. No changes would have been made in medical management of any of the patients if the decisions had been made on the basis of the oxygen saturation level of less than 90% rather than the methemoglobin percentage of 10% or more.


Lymphocyte proliferation to artery antigen as a positive diagnostic test in polymyalgia rheumatica. The transformation response of peripheral blood lymphocytes in vitro to human arterial and muscle antigen has been studied in patients with polymyalgia rheumatica, polymyositis, rheumatoid arthritis, and polyarteritis, and polyarteritis nodosa and in unrelated controls. Lymphocytes from patients with polymyalgia rheumatica showed transformation responses significantly higher to artery antigen than those in the other disease and control groups. The highest responses were found in patients with evidence of the most active clinical disease at the time of testing. It is suggested that the transformation response to arterial antigen might aid the diagnosis of polymyalgia rheumatica.


A double blind trial to assess the value of alclofenac compared with phenylbutazone in the management of rheumatoid arthritis. A double-blind cross-over study using a double placebo technique was employed to compare the effectiveness of daily alclofenac 3 g and phenylbutazone 300 mg in rheumatoid arthritis. (2) Thirty-one patients with classical or definite rheumatoid arthritis entered the trial. Twenty-three patients completed the trial; eight patients were withdrawn while on alclofenac, six developing a rash and two having inadequate analgesia. (3) Relief of pain on both drugs was comparable. (4) When questioned at the end of the trial, sixteen patients preferred phenylbutazone, four preferred alclofenac. (5) No significant changes in laboratory values were found, apart from a slight mean fall in haemoglobin on phenylbutazone. (6) There were significantly more side effects on alclofenac and rashes were particularly prominent.


Functional changes in platelets during extracorporeal circulation. An in vitro trauma test was conducted to determine the effects of extracorporeal circulation on platelet count and function. Fresh human blood was circulated in two identical in vitro circuits for six hours at a rate of 500 ml per minute (500 recirculations). One circuit included a G.E.--Peirce membrane lung and the other was a control. Platelet aggregation induced by adenosine diphosphate (ADP), epinephrine, or collagen was studied before and after six hours of perfusion. No important drop in platelet count occurred in the control circuit (Control-C) following bypass, but there was a 20% drop for the lung circuit (Lung-C). Platelet aggregation was reduced by about 30% for the control circuit and 65% for the lung circuit. The large decrease in platelet function accompanied by only a moderate decrease in platelet count is discussed in terms of loss of the youngest and most active platelets, platelet inhibition due to ADP released by red blood cell lysis, and platelet trauma.


Continuous percutaneous monitoring of muscle pH and oxygen pressure. A new technique for in vivo use. Newly developed all solid state catheter oxygen pressure (PO2)  and pH electrodes were evaluated in dogs in respiratory acidosis and hemorrhagic shock. The electrodes were inserted into the blood vessels and thigh muscle by a percutaneous puncture technique. In animals with respiratory acidosis, arterial, venous, and intramuscular pH decreased in parallel as arterial carbon dioxide pressure (PCO2) increased. During severe acidosis, arterial and venous PO2 did not change appreciably, but intramuscular PO2 decreased moderately, indicating decreased tissue perfusion. In animals with hemorrhagic shock, intramuscular PO2 decreased in proportion to the blood loss, whereas the reduction in intramuscular pH and blood pressure lagged behind blood loss. A similar finding was observed during reinfusion of shed blood in surviving animals. In the animals that died, intramuscular PO2 AND PH remained low after the reinfusion of all shed blood, although arterial blood pressure did return to base line levels.


Hydrochloric acid in the correction of metabolic alkalosis. Intravenous infusion of hydrochloric acid was used as a safe, effective, and quantitative method for correction of metabolic alkalosis in two patients. The first shows the risks of intravenously administered ammonium chloride, the currently available alternative to hydrochloric acid therapy. The second shows the efficacy of intravenously administered hydrochloric acid. While breathing spontaneously throughout the period of severe alkalosis, this patient showed compensatory hypoventilation with conspicuous increase in arterial carbon dioxide pressure. Normal spontaneous ventilation returned with correction of the metabolic alkalosis.


Inactivation of African horse-sickness virus by betapropiolactone and by pH. The inactivation of several types of African horse sickness virus (AHSV) by pH and by betapropiolactone (BPL) was studied. At 19 degrees - 22 degrees C the virus was stable between pH 6.0 and 10.4, whether suspended in mouse brain or in serumfree buffer. Below pH 5.6 and above pH 10.9, more than 99 per cent of infectivity was inactivated within 15 minutes. The addition of 50 per cent serum did not influence pH stability. Disinfection in the presence of citric acid and caustic soda is briefly discussed. Inactivation by BPL was complete within 30 minutes at 37 degrees C, yet incomplete after 15 hours at 4 degrees C. Types 3 and 9 virus grown in suckling mouse brain and types 1, 3 and 9 produced in pig kidney cells were equally susceptible to 0.1 per cent BPL, more than 99.9 per cent being inactivated. The effectiveness of BPL was reduced at least 10-fold by the addition of 50 per cent serum. No infective virus was detected following incubation of either tissue culture virus with 0.2 per cent BPL or of mouse brain virus with 0.3 per cent BPL. Virus suspensions exposed to 0.3 per cent BPL required buffering with Tris of at least 0.05 molar strength in order to maintain the pH within an acceptable range. Inactivated antigens prepared with 0.4 per cent or lower concentrations of BPL were immunogenic in guinea pigs.


A primate model for testing anticonvulsant drugs. Senegalese baboons (Papio papio), with a natural syndrome of photosensitive epilepsy, consistently show generalized myoclonic jerks if stimulated stroboscopically at hourly intervals, two to eight hours after the intravenous administration of allylglycine, 200 mg/kg. This provides a model for testing the acute antiepileptic effects of established or new drugs. The relationship between concentration of drug, antiepileptic action, and acute neurological toxic effects can be studied. Pnehobarbital (15 mg/kg) and diazepam (0;5 to 1.5 mg/kg) were highly effective in the absence of signs of toxic reaction (plasma levels: phenobarbital sodium, 0.7 to 1.7 mg/100 ml; diazepam, greater than 0.5 mug/ml). After administration of carbamazepine (30 to 40 mg/kg) and diphenylhydantoin sodium (40 to 50 mg/kg), antiepileptic action was seen, but was accompanied by severe toxic signs (nystagmus and ataxia). Sulthiame (20 to 125 mg/kg) and ethosuximide (50 to 100 mg/kg) had little antiepileptic activity and no acute toxic effects. This primate model may aid the identification of new drugs that are active against grand mal seizures and status epilepticus.


Plasma albumin concentration and diphenylhydantoin binding in man. The plasma protein binding of diphenylhydantoin sodium was determined in 26 patients who had been taking diphenylhydantoin regularly for more than two weeks. The free (unbound) diphenylhydantoin level was found to vary from 5.8% to 12.6% of the total drug concentration. This range of variation may be clinically important, if it can be established that the binding of diphenylhydantoin to plasma proteins limits entry of the drug into the brain. The binding of diphenylhydantoin was directly proportional to the plasma albumin concentration, which thus appeared to be the most important determinant of diphenylhydantoin binding. Diphenylhydantoin binding was independent of the plasma concentration of the drug in the usual therapeutic range. In vitro studies showed little effect by phenobarbital sodium or penicillin G; therapeutic levels of acetylsalicylic acid, however, increased free diphenylhydantoin by nearly 50%.


Ocular anti-inflammatory effect of fenoprofen. Dose-response study. An experimental rabbit uveitis model was used to establish a dose response range for topical administration of fenoprofen (dl-2(3-phenoxyphenyl) propionic acid. The 0.3% concentrate group was not distinguishable from the untreated group, and 3% concentrate proved highly irritating. Fenoprofen 1%, pH 6.4, proved most efficacious and had an effect comparable to dexamethasone phosphate 0.1%, seen in a previous study.


Fibre in nutrition.

Fibre in nutrition. The physical properties and the chemical variety of the substances which make up the plant cell wall are inadequately described by any one term such as "fibre". It would seem that an understanding of the role of the unavailable carbohydrates and lignin in the diet in the functioning of the gastro-intestinal tract and on possible pathological process must be based on a better knowledge of the chemical and physical properties of these substances as they occur in foods than is at present available. It is suggested that this knowledge can come from a synthesis of the findings of the plant anatomists, plant biochemists and structural organic chemists and the application of this synthesis to studies in man.


[Myocardial metabolism under intravenous infusion of glucagon (author's transl)]. In 7 healthy-hearted probands the arterial-coronary-venous oxygen difference for glucose, K+, lactate, pO2, pCO2 and pH during a glucagon infusion was determined and compared with the values before and 10 minutes after infusion. Contradictory to the unchanged myocardial lactate extraction and the positively or negatively influenced K+-uptake recorded in the literature, in this contingent there was a statistically significant myocardial lactate production and an unchanged potassium uptake. The respiratory quotient of the heart increased. These changes are regarded as the result of a direct hormonal influence on the myocardial metabolism and have nothing to do with the change of an aerobic into an anaerobic metabolic state.


Carbamyl phosphate synthesis in Bacillus subtilis. In vitro and "in situ" assays have been developed to test the carbamyl phosphate synthetase (CPSase) activity of a series of pyrimidine-requiring mutants of Bacillus subtilis. The enzyme has been shown to be highly unstable, and was successfully extracted only in the presence of 10% glycerol and 1 mM dithiothreitol (Cleland's reagent). It loses activity rapidly when sonicated or when treated with lysozyme. Genetic studies, using mutants, indicate that B. subtilis may possess two CPSases. This possibility and its physiological consequences were probed enzymatically. CPSase activity has been shown to undergo inhibition by both uridine triphosphate and dihydroorotate; activation has been demonstrated in response to phosphoribosyl pyrophosphate (PRPP) and (to a lesser extent) ornithine.


The effect of carbon dioxide on the neuromuscular and haemodunamic effects of AH 8265, a new non-depolarizing muscle relaxant. The influence of carbon dioxide on the neuromuscular and haemodynamic effects of AH 8165, a new non-depolarizing muscle relaxant, was determined in nine healthy patients before the onset of minor elective surgery. Five patients (hypocapnic, group I) were maintained at an arterial Pco2 ranging from 25 to 31  mm Hg; four patients (hypercapnic, group II) at a Cco2 from 54 to 57 mm Hg. AH 8165 0.25 MG/KG (one-quarter of the dose required for intubation) was given by rapid central venous injection. Haemodynamic responses were similar in the two groups; there were increases in heart rate ranging from 45 to 60 per cent, increases in mean arterial pressure of 17 - 20 percent, and increases in cardiac output of 22-32 per cent. The intensity of neuromuscular blockade of the forearm muscles after AH 8165 was similar in the two groups, and there was no significant difference in recovery rates; group I patients were 80 percent recovered in 36.6 min. group II patients in 47.3 min. It was concluded that the activity of AH 8165 was not influenced by moderate changes in respiratory acid base status.


Maternal arterial oxygen tension during intermittent inhalation analgesia. In mothers nursed in a semi-recumbent position, arterial oxygen tension was measured at the beginning and END OF AN an intermittent period of inhalation, Lasting for six contractions, during the first stage of labour. Ten mothers had methoxyflurane 0.35 per cent and air, followed by methoxyflurane 0.35 per cent with approximately 50 per cent oxygen. Another 10 mothers had 50 per cent nitrous oxide and 50 per cent oxygen (Entonox). The mean values of PaO2 at the beginning of periods of inhalation in those who received methoxyflurane in air, methoxyflurane in 50 per cent oxygen, and nitrous oxide in oxygen were 109, 120 and 106 mm Hg respectively. The mean increases in PaO2 by the ends of periods of inhalation were 18, 43 and 63 mm Hg respectively. On average, increasing the inspired concentration of oxygen to 50 per cent significantly and substantially increased maternal PsO2 with both agents by the emd pf inhalation. There would therefore be some increase in available oxygen during the phase of higher blood flow following a uterine contraction. However, the lowest maternal PaO2 measured was 72 mm Hg; therefore additional oxygen is unlikely to offer much advantage except in patients with respiratory or cardiac deficiencies. In the intervals between inhalations of the analgesic mixture the PaO2 decreased to about the level found during air breathing. Consequently it would be necessary to breather additional oxygen continuously, between as well as during contractions, to ensure an increased maternal PaO2 throughout labour.


The use of a small endotracheal tube in bronchoscopy. The use of the standard 4-mm cuffed endotracheal tube to deliver manually or mechanically interrupted jets of oxygen or nitrous oxide and oxygen into the trachea allowed bronchoscopy and other related procedures to be performed with advantage to the patient, the surgeon and the anawsthetist. This paper describes the equipment used and the advantages obtained.


[Parenteral nutrition in critically ill newborns]. In nine critically ill newborns, five of them with intractable diarrhea and four surgical patients, we administered a 5% crystalline aminoacids solution (AA) and glucose in sufficient amount to provide 120 cal times kg. in 24 hours. Six of them recovered after receiving parenteral alimentation for 3 to 15 days, gained weight during or after treatment and were discharged from the hospital in good conditions. Three died, one of them presented septicemia and two pneumonia and pulmonary infarcts. The solution used generated few metabolic alterations, the acid-base status remained within normal range and there were not important changes in the sodium and potassium serum concentrations. On the contrary, children with hyponatremia and hypokalemia at the beginning of the treatment, normalized these constants within the first hours, as diarrhea ceased. The most frequent complications were infiltrations and reaction of the surrounding tissue of the catheterized vein and local skin infection. Only one patient died of septicemia, possibly caused by this proceeding. In summary, parenteral alimentation though not free from risk, seems to be a useful proceeding when oral feeding is impossible or inadvisable. The utmost danger is septicemia. Metabolic changes are minimal and they do not mean a risk for child's life; nevertheless, there is a need for long term studies to bring up definite conclusions. The solutions in actual use are probably not the most physiological for the newborn. It is necessary to adequate them according to the new advances made on child nourishment during his first days of life.


The effect of seven vasopressors of halothane MAC in dogs. We evaluated the effects of ephedrine, mephentermine, metaraminol, phenylephrine, methoxamine, noradrenaline and adrenaline on halothane anaesthetic requirement (MAC) in dogs. MAC increased significantly only during ephedrine infusion (50%) although significance was approached with mephentermine (21%). Phenylephrine, metaraminol, methoxamine, noradrenaline and adrenaline did not change MAC. Arterial pressure was increased 50-100% with all agents. Our results support the hypothesis that anaesthetic requirement may be related, in part, to release of brain noradrenaline.