Comparative evaluation of six techniques for determining the Michaelis-Menten parameters relating phenytoin dose and steady-state serum concentrations. Using randomly generated data within set error limits, the Michaelis-Menten parameters Dmax and Km relating steady-state serum phenytoin concentrations (Css) and dose (D) were determined by 5 graphical techniques and an iterative computer fit to the hyperbolic equation. The best mean estimates of Dmax and Km were provided by the latter. Assuming the experimental error to be in Css the results indicate that the most reliable graphical technique is that based on the equation Css = Dmax Css/D - Km. However, considering its obvious simplicity and relative reliability the direct linear plot is recommended for clinical use.


Percutaneous absorption: interfacial transfer kinetics. A new rotating diffusion cell is described in which a solute diffuses through a rotating filter. The transport of the solute to both sides of the filter is controlled by the rotation. The filter is filled with an organic phase. The rate of transfer of the solute through the filter is determined by the transport and by the kinetics of the interfacial transfer reactions. Since the transport is controlled the rate constant for the transfer reaction can be measured. Results for eleven different systems are reported and it is found that the rate constants are all smaller than 10(-4) ms-1.


The mechanical strength of film-coated tablets. The mechanical strength of film-coated tablets has been assessed using the diametral compression test. The results show that the influence of the film is more complex than that suggested by Stern (1976). The film may increase the breaking load of the core itself by acting as a padding material during the test and also by filling in surface irregularities. The film may also have enough intrinsic strength and elasticity to hold the core together once it has broken. The maximum breaking load to completely fracture the coated tablet is related to film properties, but the relation is not a simple one.


Improved gas chromatographic method and micro-extraction technique for the measurement of nicotine in biological fluids. A rapid and sensitive method for the measurement of nicotine in plasma, urine, saliva and breast milk is described. An internal standard (quinoline) is added to the samples and these are made alkaline and extracted with diethyl ether. The solvent is evaporated to small bulk and extracted with dilute acid which is then made alkaline. The nicotine is finally extracted into butyl acetate and an aliquot of this extract is injected onto a gas-chromatograph fitted with a nitrogen detector. Quantitation relies on comparison of peak areas and the calibration curve is linear over the concentration range 0.5 to 100 ng ml-1. Nicotine concentrations as low as 0.1 ng ml-1 can be measured. In addition, a micro-method is described which requires only 100 microliter of sample and yields an accurate result in 5 min.


A spectropolarimetric assay of (-)-adrenaline in compendial formulations. A method is described for the determination of (-)-adrenaline in certain formulations containing adrenaline hydrogen tartrate at concentrations down to 0.18 mg ml-1 (1:10 000 adrenaline). The assay is based upon a spectropolarimetric measurement at 249 nm of sample solutions, suitably treated to remove interfering substances. The rotation of the sample solutions is corrected for the rotation of the tartaric acid species which is determined by a difference rotation measurement on equimolar sample solutions at pH 1.1 and pH 5.6. The concentration of (-)-adrenaline in the sample is calculated from the net rotation at 249 nm due to the (-)-adrenaline and the total concentration of adrenaline (+)-and (-)-isomers) determined by a published spectrofluorimetric method. The assay is specific for (-)-adrenaline in the presence of (+)-adrenaline, (+)-tartaric acid, adrenaline sulphonic acid and low levels of adrenochrome.


The application of cryobiology to the microbiological assay of nystatin. Improvements in the reproducibility of nystatin agar diffusion assays have been achieved by the use of liquid nitrogen stored inocula and deep frozen standard stock solutions. The overall percentage variability of the assay has been reduced from over 5% with daily prepared standards and inocula to around 1% with a frozen inocula and to 0.6% with a combination of frozen inocula and standards. The implications of these improvements in the standardization of nystatin assays, and microbiological assays generally are discussed.


Modification of cortical neuron responses to acetylcholine by viloxazine. Viloxazine, an antidepressant with no peripheral antiacetylcholine activity, was capable of reducing responses of single cortical neurons to acetylcholine. Acetylcholine responses could also be potentiated by viloxazine. Both potentiation and reduction by viloxazine were often seen in the same study, reduction of responses invariably preceding potentiation. These results suggest that viloxazine may have selective effects on central cholinergic receptors. Responses of cortical neurons to monoamines could also be potentiated by viloxazine although it has little effect on monoamine uptake. These results are compatible with the idea that potentiation of monoamine responses may occur by a postsynaptic mechanism.


N-o-Methoxyphenylpiperazine: a simple blocker of dopaminergic receptors in the brain. N-o-Methoxyphenylpiperazine (MPP) is a moderately effective in vivo blocker of dopaminergic receptors. Its ability to increase the concentration of rat brain homovanillic acid (HVA) and the resulting time course for HVA were similar to the actions of clozapine. The increased concentration of HVA did not result from decreased outflow from brain because HVA also rapidly decreased after a subsequent injection of pargyline. MPP blocked the circling behaviour caused by apomorphine in mice with a unilateral striatal lesion, and MPP and apomorphine reciprocally blocked the occurrence of stereotypy and increased HVA in rats. Diazepam partially prevented the MPP-induced elevation of HVA. Thus, both biochemical and pharmacological evidence indicate the dopaminergic blocking action of MPP.


Change in brain guanosine 3',5'-monophosphate (cGMP) content by thyrotropin-releasing hormone. Thyrotropin-releasing hormone (TRH) causes a significant increase in rat cerebellar guanosine 3',5'-monophosphate (cGMP) content after parenteral administration. A smaller but still significant increase in cGMP was also observed in brain stem, whereas no significant changes were observed in cGMP in other gross brain regions or in adenosine 3',5'-monophosphate in any brain region. TRH also caused a similar increase in cerebellar cGMP content in hypophysectomized rats indicating that the increase is independent of an intact pituitary. The time course of cGMP elevation in the cerebellum after administration of 10 mg/kg of TRH i.v. showed a peak at 2.5 to 5.0 min followed by a less rapid decrease. The time course of TRH immunoreactivity in the same cerebellar homogenates roughly paralleled these changes. Only those TRH analogs which were previously shown to antagonize pentobarbital sleeping time in mice caused an elevation in cGMP content in the cerebellum. TRH also caused a significant increase in cerebellar cGMP in rats pretreated with phenobarbital and chlordiazepoxide. The TRH-induced increase in cerebellar cGMP was not affected by cerebellar climbing fiber lesions caused by 3-acetylpyridine nor blocked by haloperidol, suggesting that TRH acts by mechanisms different from harmaline or apomorphine in raising cerebellar cGMP.


Quantitative subunit hybridization of drosophila alpha-glycerophosphate dehydrogenase. The dimeric enzyme, alpha-Glycerophosphate dehydrogenase, was purified from eight Drosophila species by the method of Collier et al. (1976). The enzymes were inactivated at high pH and the conditions sufficient for reactivation were established. Electrophoretic patterns of reactivated alpha-glycerophosphate dehydrogenases which were mixed following inactivation of two species' enzymes, demonstrate that high pH dissociates the enzyme into its constituent subunits and reactivation involves subunit reassociation. Twenty interspecific combinations of dissociated enzymes were allowed to reassociate, and the amounts of both heterospecific and homospecific enzyme activity and protein were determined by densitometry. In all 20 tests there were no differences between observed and expected heterospecific:homospecific enzyme ratios. These results are consistent with the very slow rate of evolution of this enzyme in the family Drosophilidae (Collier and MacIntyre, 1977).


Complications of deep puncture wounds of the foot. Eleven cases of deep puncture wounds of the foot and their complications are reviewed. More than half of the patients had foreign materials introduced at the time of the injury which was not completely removed initially. The morbidity with these "simple puncture wounds" may be quite prolonged. The authors conclude that attention to details when the patient is first seen in the emergency room or the physician's office and aggressive treatment of these wounds will prevent serious sequelae in many instances.


Pharmacologic antagonism of beta-adrenergic blockade in dogs. I. Hemodynamic effects of isoproterenol, dopamine, and epinephrine in acute propranolol administration. Hemodynamic effects of isoproterenol, dopamine, and epinephrine were studied before and after acute beta-adrenergic blockade in 16 open-chest, anesthetized mongrel dogs. Beta blockade was induced with 1 mg. per kilogram of intravenous propranolol. Cardiac output measurements were obtained by thermal dilution, and pressure recordings were obtained in the right ventricle, pulmonary artery, left atrium, left ventricle, and aorta. Derived parameters included stroke volume, pulmonary and systemic vascular resistances, and peak left ventricular dP/dt. In the presence of propranolol, epinephrine became a lethal drug in large doses and did not increase cardiac output in standard doses. Dopamine, in 25 to 50 mcg. per kilogram per minute doses, increased arterial pressure and systemic resistance; cardiac output was diminished compared with dopamine, 10 mcg. per kilogram per minute, prior to propranolol, as a result of increased resistance and decreased LV contractility. Isoproterenol, 0.6 to 0.9 mcg. per kilogram per minute, 15 to 20 times standard dosages, had moderately positive inotropic effects and increased cardiac output. Left ventricular systolic pressure with isoproterenol after propranolol was reduced when compared with effects of smaller doses prior to propranolol. These observations suggest that none of the catecholamines studied would be optimal for circulatory support in heart failure in the presence of propranolol. The present results define a pharmacologic basis for design of appropriate drug combinations for circulatory support in beta-blocked animals.


Anatomy of the interstitial tissue.

Anatomy of the interstitial tissue. Aspects on composition and function of the interstitial tissue have been given. The glycosaminoglycans of the interstitum have at physiological pH a net negative charge and are osmotically active. They restrict free diffussion through the interstitium. The ground substance phase can be further subdivided into a colloid-rich subphase and a colloid-poor subphase. The latter seems to constitute the true tissue fluid phase of the interstitium. The functional importance of the interstitium on exchange processes between the vascular and the cellular compartments is discussed. Changes in aggregation and hydration of the ground substance change the physico-chemical properties and the functional characteristics of the interstitium.


[The effect of chenodesoxycholic acid on cholesterol gallstones (author's transl)]. 30 patients with radiolucent gallstones and 2 patients with radioopaque stones recieved chenodesoxycholic acid (CDC). In 12 patients stones were dissolved completely by CDC therapy, in 6 of the patients the size of the stones decreased by 40-70%. Only 1 patient developed severe diarrhea, so therapy had to be stopped. In 5 patients there was a slight and transient increase in SGOT and SGPT, in 2 other patient gammaGT increased; value normalized while treatment was continued. In 23 cases liver biopsies were done before and during treatment: no histological changes could be found in the specimens. 5 of the patients, whose gallstones had been dissolved, received 500 mg CDC/day thereafter, another 5 patients received 500 mg/d every other day. No recurrence of lithiasis was observed in either group. One patient on 500 mg CDC twice a week developed lithiasis after 6 months, another one stopped treatment completely and gallbladder stones reappeared after 8 months. The patients with radioopaque stones did not show any changes during treatment.


Flow of reducing equivalents into isolated intestinal mitochondria. A system of enzymes is required for the transport of reducing equivalents from reduced nicotinamide adenine dinucleotide (NADH) generated in the cytosol into the mitochondria by the substrate cycles. Also, the intestinal mitochondria must be capable of oxidizing the substrates of the cycles. Both substrate cycle enzymes and permeable mitochondria are necessary for the flow of pyruvate derived from glucose into the mitochondria for oxidative decarboxylation and for the efficient production of adenosine 5'-triphosphate (ATP) for the unique intestinal nutrient transport functions. Mitochondria from hamster intestinal mucosa were prepared exhibiting good respiratory control ratios. The isolated intestinal mitochondria would not oxidize NADH unless N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD) was added as a carrier of reducing equivalents. The rates of oxidation of the substrates of the L-glycerol 3-phosphate and the L-malate/1-aspartate substrate cycles were measured with the mitochondria isolated from the small intestinal mucosa. The key enzymes measured in the cytosol and mitochondria from the mucosa were NAD-L-glycerol 3-phosphate dehydrogenase, Fp-L-glycerol 3-phosphate dehydrogenase, L-malate dehydrogenase and L-glutamate-oxaloacetate transaminase. In addition, the substrate cyclase were simulated in vitro by following NADH oxidation by isolated mitochondria in the presence of added cytosolic constituents.


Perhexiline maleate in the treatment of angina pectoris. Five years of personal clinical experience. A five-year personal experience of the use of perhexiline maleate (Pexid) in the treatment of severe angina pectoris is presented. Ninety-four patients, all severely incapacitated by cardiac pain, received perhexiline maleate for an average period of 12.2 months. Perhexiline maleate was used either alone or, more commonly, in conjuction with other antianginal therapy, such as beta-adrenergic receptor blocking agents. The results demonstrate that perhexiline maleate is a very effective agent which appears to be safe for long-term usage. Side effects have been frequent, and occasionally bothersome, but all have been transient and dose-dependent. The possibility that the regimens of treatment may materially improve long-term prognosis is raised.


[Metabolism of carbromal during detoxication with combined hemoperfusion and hemodialysis (author's transl)]. Combined charcoal hemoperfusion and hemodialysis was performed on three occasions in two patients with severe carbromal intoxication. The concentration of carbromal, its organic metabolites and of bromide was determined in arterial blood before and after passage of the charcoal column and behind the dialyzer cartridge. Results show a rapid metabolic degradation of carbromal including cleavage of bromide. Besides carbromal and its main metabolite 2-brome-2-ethylbutyramide (=carbromide) debromised organic metabolites appear to be responsible for the severity of the intoxication. Bromide plays no role in the pathogenesis of acute intoxication. Carbromal and its organic metabolites are eliminated through a large surface dialyzer almost as effectively as with charcoal hemoperfusion. The effectivity of detoxication is enhanced by the combination of both procedures. Free bromide is not adsorbed at charcoal but is readily dialyzable. Values of carbromal, calculated out of bromide levels, do not correspond to directly measured blood levels. Treatment of carbromal intoxication with combined hemoperfusion-hemodialysis should be performed early in all severe, risky or otherwise complicated cases until the patients awakens.


Cytoplasmic malic enzyme from mouse kidneys. NADP+-dependent cytoplasmic malic enzyme was purified to homogeneity from mouse kidneys by a two-step procedure involving 8-(6-aminohexyl)-amino-2', 5'-ADP-Sepharose affinity chromatography and DEAE-Sephadex ion exchange chromatography. The biochemical properties of the purified enzyme from DBA/2J mice were characterized. These include the determination of molecular weight and amino acid compositions, steady-state kinetics, thermal stability and inactivations by iodoacetate and urea. The native enzyme is a tetramer with a molecular weight of 270,000.Km's for NADP+, L-malate, NADPH and pyruvate were determined to be 3.3 micrometer, 50 micrometer, 10.5 micrometer respectively. Similar to the pigeon liver enzyme, the mouse enzyme exhibits an ordered kinetic mechanism proceeding with the binding of coenzyme first. The enzyme is only weakly inhibited by ATP and other cellular metabolites. A remarkable similarity in amino acid compositions was found between the mouse and rat liver malic enzymes.


Kinetic characterization of plasma membrane ATPase from Saccharomyces cerevisiae. 1. Plasma membrane preparations have been isolated from spheroplasts of Saccharomyces cerevisiae, strain R XII, via lysis and subsequent differential centrifugation. These preparations are almost devoid of mitochondrial contamination. 2. The plasma membrane ATPase is fairly stable when refrigerated, but loses activity at 8 degrees C and above. Below pH 5.6 the ATPase is irreversibly inactivated. The enzyme also splits GTP and ITP, although to a lesser extent. 3. Mg2+-ions are essential as part of the reactive substrate, MgATP, and furthermore they activate the ATPase. Optimal conditions depend on substrate concentration. When the concentration of free Mg2+ ions exceeds about 0.1 mM, competitive inhibition occurs. 4. In the range of pH 5.6-9.2 two functional groups dissociate. One, with pKb = 8.1 +/- 0.1 participated in substrate binding and another one with pKb' = 8.1 +/- 0.1 is involved in substrate splitting. 5. The experiments with group-specific inhibitors suggest that an alpha-amino group and a sulfhydryl residue are involved in substrate binding and conversion. Furthermore, imidazole, tryptophan and carboxyl residues may be important for the catalytic process.


Neuropharmacology of sedatives and anxiolytics. Sedative drugs are intended to cause various degrees of drowsiness. Animal experiments indicate that barbiturates induce these effects primarily by depression of the reticular activating system in the rostral brainstem. This in turn potentiates the thalamic recruiting system, thereby inducing 'barbiturate bursts' in the EEG. Anxiolytic drugs are intended to reduce anxiety or tension at doses which do not cause sedation or sleep. Propanediols may depress deactivating centers in the caudal brainstem, thereby releasing the activating centers in the rostral brainstem and depressing the thalamic recruiting response. These drugs may also act on the amygdala. Benzodiazepines have depressant effects on the amydala or hippocampus. These effects may release the reticular formation from inhibition. Enhanced activity of the activating and deactivating centers, to a different extent in different animals, would produce restlessness in some animals and sedation in others, accompanied by a mixture of fast and slow waves in the EEG. Sedative and anxiolytic agents also have central relaxant effects. The barbiturates act directly on the spinal cord, depressing both monosynaptic and polysynaptic reflexes. Propanediols and benzodiazepines act primarily on the descending facilitatory influence of the brainstem. Reduction of this influence depresses spinal polysynaptic but not monosynaptic reflexes. Biochemical studies suggest that barbiturates may act by antagonizing synaptic excitation induced by glutamate. Benzodiazepines may act by enhancing presynaptic inhibition mediated by GABA. The mechanism of action of propanediols is unknown.


[Treatment of bronchitis with cefaclor (Panoral) (author's transl)]. 14 patients from the Allergy Unit of an outpatient clinic suffering from acute exacerbation of chronic bronchitis and 13 outpatients with acute bronchitis were treated with 250 mg cefaclor (Panoral) 3 times daily per os for 5 days. 59% of the organisms isolated from cefaclor-sensitive sputum at the time of prominent clinical symptoms were resistent to tetracycline, 53% of them were resistant to penicillin, and 37% were resistant to ampicillin. 12 out of the 14 patients with acute exacerbation of chronic bronchitis became asymptomatic, and no organisms could be detected in the sputum of 13 out of the same 14 patients two days after cessation of cefaclor treatment. In 12 out of the 13 patients with acute bronchitis, the acute clinical symptoms disappeared and in 11 out of the 13 patients the initial sputum organisms were two days after stopping cefaclor treatment.


Cataleptic and anticataleptic effects of muscimol and gabaculine injected into globus pallidus and substantia nigra, and interactions with haloperidol or benzodiazepines. Intranigral injection of muscimol induced hyperactivity in rats and antagonized haloperidol-induced catalepsy. Intranigral injection of gabaculine, an inhibitor of GABA transaminase, induced similar effects 5h after injection, when the nigral GABA content was increased 7-fold. On the other hand, injections of muscimol (30 ng) into the globus pallidus potentiated the cataleptic effect of haloperidol, and muscimol alone in high doses (100 and 200 ng) induced catalepsy. Gabaculine also induced catalepsy of medium intensity and potentiated the effect of haloperidol 24h after injection, when GABA was increased in the globus pallidus as well as in the substantia nigra. Injections of muscimol into either the globus pallidus or substantia nigra increased striatal HVA and enhanced haloperidol-induced elevation of HVA. Three benzodiazepines, nitrazepam, diazepam and chlordiazepoxide administered orally, potentiated the effect of muscimol (30 ng) injected into the globus pallidus and induced catalepsy. A similar effect was not obtained with phenobarbital. It is suggested that stimulation of GABA receptor or increase of GABA content in the sustantia nigra antagonize haloperidol-induced catalepsy by activation of nigral dopaminergic system, and that enhancement of pallidal GABA function induces catalepsy by non-dopaminergic mechanisms. Potentiation of haloperidol-induced catalepsy by benzodiazepines may be due to enhancement of GABA-ergic transmission within the globus pallidus.


Phosphorylated derivatives of phloretin inhibit cyclic AMP accumulation in neuronal and glial tumor cells in culture. The potencies of polyphloretin phosphate, di-4-phloretin phosphate, 4-phloretin phosphate and phloretin to inhibit the stimulation of cAMP accumulation by prostaglandins, isoproterenol and adenosine were studied in 2 clonal cell lines of CNS origin. The sequence of potency to inhibit PGE1 effects was the same in neuroblastoma (N4TG3) and human astrocytoma cells (1321N1): di-4-phloretin phosphate greater than polyphloretin phosphate greater than phloretin greater than 4-phloretin phosphate. The inhibition of PGE1 stimulated cAMP accumulation by the most prostaglandin-specific inhibitor di-4-phloretin phosphate was rapidly established after its addition, fully reversible after a 30 min preincubation period and independent of the presence of calcium. Kinetic studies of the inhibition of PGE1 effects by di-4-phloretin-phosphate suggest a different type of inhibition in 1321N1 and N4TG3 cells.


Beta-D-glucosidase in fractions from rat brain. Beta-Glucosidase activity has been determined in homogenate and in centrifugation fractions of 7-day-old and adult rat brain; maximum activity was found at pH 4 and pH 5. Of the adult brain, more than 50% of the activity was concentrated in the 800-g sediment fraction (P1), while in the brain of 7-day-old rat about 20% was found in the corresponding fraction. The activity maximum in all fractions after a 2% Triton X-100 treatment occurs at pH 5. Addition of Triton to adult brain homogenate enhances the activity, but this stimulation is less than the sum of the activities observed at pH 4 and pH 5 in the absence of Triton. Triton addition to brain homogenate of 7-day-old rat results in a fall in activity at pH 4 and in a maximum at pH 5. In rat brain homogenate subjected to sonication, a loss of activity is observed at pH 4, scarcely at pH 5; the activity loss is completely abolished and turned into an increase under the influence of Triton. This increase equals the level obtained when Triton is added to an untreated brain homogenate. Sonication of rat brain homogenate leads to changes in the distribution pattern; about 25% of the activity of the adult brain is found in the P1 fraction compared to 50% in the corresponding fraction of the untreated brain. Fractionation of a sonicated brain homogenate from adult rat reveals that at pH 4 most activity (52%) is concentrated in the 20,000-g pellet (P2), 23% in supernatant fluid (S2); at pH 5 the opposite is observed; most activity (49%) is found in the 20,000-g supernatant (S2) and 23% in the 20,000-g pellet (P2). In the presence of Triton the activity of the sonicated brain homogenate of adult rat increases; this stimulation roughly equals the sum of the corresponding activities measured at pH 4 and pH 5 in the absence of Triton.


Phenylethanolamine N-methyltransferase from the brain and adrenal medulla of the rat: a comparison of their properties. Two different molecular forms of phenylethanolamine N-methyltransferase (PNMT, EC 2.1.1) have been isolated from the brain and adrenal glands of the rat as indicated by certain of their physicochemical properties, such as: molecular weight estimated on the basis of gel chromatography of Sephadex G-100; pH optima; electrophoretic mobility on acrylamide gel; and steady-state kinetic parameters. The high Km value for the brain PNMT has been assumed to be responsible for the low methylation ratio between norepinephrine and epinephrine in the CNS.


d-Amphetamine binding to brain lipid.

d-Amphetamine binding to brain lipid. The interaction of d-amphetamine with several brain tissue components has been investigated. A brain lipid extract and a number of individual phospholipids were found to bind d-amphetamine when measured by means of a hexane-buffer partition coefficient technique. Phosphatidylserine showed the greatest binding and phosphatidylethanolamine and dipalmitoyllecithin were also effective. Phospholipid binding of d-amphetamine was shown to be related to fatty acid composition. Cholesterol and ganglioside did not bind. It is suggested that phospholipid binding of d-amphetamine may play a role in the pharmacological action of this drug.


Alpha blockade and surgical intervention of pheochromocytoma in pregnancy. The antepartum diagnosis of pheochromocytoma concurrent with pregnancy has been reported in 42 cases. These cases were analyzed for the effect of preoperative alpha blockade and of the timing of surgical intervention. Alpha blockade, when performed promptly in all pregnant patients in whom the diagnosis of pheochromocytoma was made, reduced fetal mortality regardless of the gestational age. In addition, when the diagnosis of pheochromocytoma was made in the third trimester of pregnancy and alpha blockade was adequately maintained, a combined procedure of cesarean section and tumor resection was best. If the tumor could not be located during a combined procedure, delivery followed by delayed resection was not associated with any greater maternal mortality. The surgical approach required for patients diagnosed in the first or second trimester was less clear. Although alpha blockade is indicated in such early patients, it cannot yet be determined if a delay in the tumor excision will subject the mother and fetus to a greater risk  than the accepted practice of early resection with delayed delivery.


[Effect of chest physiotherapy on pO2 and pCO2 in premature and mature babies with respiratory distress syndrome (author's transl)]. pH, pCO2, pO2 and where possible DAaO2 determinations were done before, immediately after and 30 minutes after chest physiotherapy in 4 groups (respiratory adaptation disturbance, pneumonia, hyaline membrane disease--controlled ventilation and RDS--nasal-CPAP) of mature and premature infants and in a group of healthy infants. The most striking alterations of the parameters investigated were found in infants treated with nasal-CPAP and controlled ventilation where especially a decrease of pH and increase of pCO2 was observed. After small increases of paO2 immediately after physiotherapy the paO2 values and concomitantly DAaO2 values 30 minutes after chest physiotherapy fell below the levels before physiotherapy. There was no significant change from pretreatment values in any group of infants. A physiotherapist experienced in the care of infants with respiratory diseases is most important for achieving satisfactory results.


[Comparative evaluation of pH, pCO2 and pO2 from arterial and capillary blood samples during the first two weeks of life (author's transl)]. 193 determinations of pH, pCO2 and pO2 have been performed simultaneously on arterial and capillary blood samples in 22 mature and premature infants 1 to 2 weeks old. Despite good agreement of arterial and capillary pH and pCO2 values no such results could be found in pO2 values. In cases of oxygen therapy especially if positive endexspiratory pressures are used control of oxygen tension should be done exclusively from arterial and not from capillary blood samples.


Plasmodium knowlesi in the marmoset (Callithrix jacchus). Common marmosets were shown to be susceptible to Plasmodium knowlesi malaria. The morphology of the parasite was indistinguishable from the observed in the natural host (Macaca fascicularis) and the common laboratory model (Macaca mulatta). A differential susceptibility to P. knowlesi was observed in the 8 marmosets studied. Multiplication rates of parasites were variable over 24 h periods. Five animals died of a fulminating infection within 12--17 days after challenge. Three animals recovered spontaneously from infection and were subsequently resistant to challenge with homologous and heterologous variants and strains of P. knowlesi. This resistance was maintained for intervals up to 100 days between challenge infections.


Blood gas measurements.

Blood gas measurements. pH and blood gas measurements are used to detect and monitor ventilation, oxygenation, and acid-base disturbances. The blood sample must be drawn anaerobically and transported in ice water to the laboratory. Partial pressure of carbon dioxide in arterial blood (PaCO2) reflects alveolar ventilation; partial pressure of oxygen in arterial blood (PaO2) reflects oxygen loading. The alveolar-arterial PO2 gradient (PA-aO2) distinguishes hypoxemia due to hypoventilation from that due to inefficent pulmonary gas exchange. The demand status of the cardiovascular system and the hemoglobin value reflect oxygen delivery to tissues. The relationship among pH, PaCO2, and bicarbonate concentration, when interpreted in the light of clinical findings, specifies the type and duration of acid-base disturbance.


The influence of neuroleptics on the behavioural effect of 5-hydroxytryptophan. The antagonism of neuroleptics of various groups (chlorpromazine, chlorprothixene, clopenthixol, clozapine, flupenthixol, fluphenazine, haloperidol, levomepromazine, mepazine, perazine, perphenazine, pimozide, prochlorperazine, promazine, spiperone, thiopromazine, thioridazine, trifluperazine, trifluperidol, triflupromazine) towards L-5-hydroxytryptophan (5-HTP) was assessed on the basis of inhibition of characteristic head-twitches. ED50 was assayed in mice and rats. The results indicate that all investigated neuroleptics inhibit the action of 5-HTP and their ED50 values are, as a rule, lower than the values of ED50 for catalepsy. That action is for the majority of neuroleptics more pronounced in mice than in rats. The present paper disucsses possible serotonergic, dopaminergic and also noradrenergic mechanism of action of neuroleptics in the 5-HTP test.


The effect of baclofen and aminoxyacetic acid on catalepsy in the rat. Gabaergic compounds, baclofen and aminoxyacetic acid (AOAA) potentiate the catalepsy induced by neuroleptics. This effect indicates their functional antagonism towards the central dopaminergic system. Both compounds exert a central antiserotonin effect. Baclofen, but not AOAA, also shows weak cholinolytic properties. However, the potentiation of cataleptogenic action of neuroleptics by baclofen and AOAA is not related to their effect on the central serotonergic or cholinergic systems.


Preventing portal systemic encephalopathy in the patient with cirrhosis. Portal systemic encephalopathy is a serious complication of cirrhosis. It can be prevented if the patient avoids the contributing factors--ingestion of alcohol, inappropriate diet, infection, stress, hepatotoxic agents--and if other complications are treated promptly.


Studies on the mechanisms of central action of alpha-adrenergic receptor blocking agents. The article summarizes the results of experiments, partly published, on the central action of alpha-adrenergic receptor blocking drugs given systemically in rats. Phenoxybenzamine, phentolamine and aceperone increase utilization of noradrenaline (NA in whole brain and antagonise NA--stimulated formation of cyclic AMP in brain cortical slices. They also counteracts locomotor hyperactivity and flexor reflex stimulation induced by NA receptor agonists. The investigated alpha-adrenolytics do not antagonize brain dopamine (DA) or acetycholine (ACh) receptor stimulation, although they weakly reduce the effects of central serotonin (5-HT) system activation. It is concluded, that phenoxybenzamine, phentolamine and aceperone block directly central NA receptors. They do not block DA or ACh receptors in the brain but they are weak antagonists of 5-HT system stimulation. The investigated compounds decelerate utilization of DA and increase those of ACh in the brain, these effects seem to be secondary to NA system hypofunction.


[The influence of sedation with diazepam and flunitrazepam during regional anaesthesia upon postoperative pulmonary performance (author's transl)]. In 32 patients between 53 and 86 years of age, undergoing transurethral prostatectomy, the influence of intraoperative sedation with Diazepam (5-10 mg) and Flunitrazepam (0,4-0,8 mg) on postoperative forced vital capacity, forced exspiratory volume (1 sec.) and peakflow, were measured, compared to placebo. We could not find a depression of these ventilatory parameters, in the three groups except peak-flow after sedation with Flunitrazepam in the evening after operation (p less than or equal to 0,05). We conclude that sedation during regional anesthesia does not impair the most important advantage of local anesthesia, the minor effect on ventilation, compared with general anesthesia.


The effect of alpha-adrenergic receptor stimulant drugs on amphetamine or apomorphine-induced stereotypy in rats. Clonidine, xylometazoline and naphazoline given ip cause a transition from sniffing to licking or gnawing stereotypy induced by amphetamine or apomorphine. Methoxamine, phenylephrine and in a lesser degree noradrenaline (all given ivc) inhibit licking and gnawing stereotyped behavior. Biochemical results correlate with the depressant action of clonidine and naphazoline on central noradrenergic neurotransmission and also with the stimulant action of methoxamine and phenylephrine on noradrenergic system. The both groups of alpha-adrenergic agonists seem to modify both the central dopaminergic and noradrenergic system activity in the same direction. It is suggested that this action can play a role in observed modification by alpha-sympathomimetic drugs of responses to dopamine agonists. However, the influence of alpha-sympathomimetics on other brain systems must be also taken into consideration.


[The sedative and amnesic effects of flunitrazepam during regional anaesthesia (author's transl)]. The sedative, hypnotic and amnesic effects of flunitrazepam, a new benzodiazepine, were tested in doses of 0 (placebo), 0,4 mg and 0,8 mg. These doses were sufficient to produce a satisfying sedative effect on patients, being operated on in regional anaesthesia. In few cases we found undesirable effects. Positive and negative aspects of amnesia will be discussed.


Direct phosphorylation of brain tyrosine hydroxylase by cyclic AMP-dependent protein kinase: mechanism of enzyme activation. Tyrosine hydroxylase [tyrosine monooxygenase, L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2] was highly purified from rat caudate nuclei. When the pure hydroxylase was phosphorylated by incubation with cyclic AMP-dependent protein kinase and [32P]ATP, 32P and tyrosine hydroxylase activity were detected after polyacrylamide gel electrophoresis in a single protein band. After sodium dodecyl sulfate gel electrophoresis, 32P was detected only in a probably active subunit of tyrosine hydroxylase of molecular weight 62,000. Phosphorylation of the hydroxylase increased its activity by 2-fold, and was associated with an increase in Vm without any change in Km for either substrate or cofactor. We propose that the pool of native tyrosine hydroxylase is composed of a mixture of enzyme molecules in both active and probably inactive forms, that the active form is phosphorylated, and that phosphorylation produces an active form of the enzyme at the expense of an inactive one.


Serine-borate complex as a transition-state inhibitor of gamma-glutamyl transpeptidase. gamma-Glutamyl transpeptidase, a membrane-bound enzyme, functions in the gamma-glutamyl cycle to catalyze utilization of glutathione. It has been postulated that the amino-acid-stimulated utilization of glutathione by gamma-glutamyl transpeptidase reflects an aspect of amino acid translocation. As one approach to the effective in vivo inhibition of this enzyme, the inhibition of the enzyme by L-serine in the presence of borate buffers [Revel, J.P. & Ball, E.G. (1959) J. Biol. Chem. 234, 577-582] was reinvestigated. Inhibition by L-serine, D-serine, and alpha-methyl-DL-serine in the presence of borate is competitive with respect to gamma-glutamyl substrate and such inhibition is parallel to the activity of transpeptidase toward L-gamma-glutamyl, D-gamma-glutamyl, and L-gamma-(alpha-methyl)glutamyl derivatives. L-Serine and borate effectively protect against inactivation of the enzyme by the gamma-glutamyl analogs, 6-diazo-5-oxonorleucine and azaserine, which bind to the gamma-glutamyl site of the enzyme. These studies, kinetic investigations, equilibrium dialysis experiments, and other data support the view that inhibition is produced by formation of serine-borate complex which binds at the gamma-glutamyl binding site of the light subunit of gamma-glutamyl transpeptidase. The data indicate that serine-borate complex is a transition state inhibitor of gamma-glutamyl transpeptidase.


Iron, an essential element for biosynthesis of aromatic compounds. Homogeneous preparations of 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase [7-phospho-2-keto-3-deoxy-D-arabino-heptonate D-erythrose-4-phosphate lyase (pyruvate phosphorylating), EC 4.1.2.15] isolated as the enzyme-phosphoenolpyruvate complex from Escherichia coli are shown by atomic absorption analysis to contain approximately one mole of iron per mole of native enzyme. No cobalt was found, in contrast to suggestions of earlier workers. Pure enzyme preparations show a unique absorption maximum around 350 nm with an epsilon value of about 3500 M-1cm-1. The 350-nm band as well as the enzyme activity is lost when the enzyme is denatured with guanidine-hydrochloride, or when phosphoenolpyruvate, the first substrate to bind to the enzyme, is totally removed from the enzyme by incubation with an excess of erythrose 4-phosphate, the second substrate to bind to the enzyme. The iron remains bound to the enzyme when phosphoenolpyruvate is removed from the enzyme-phosphoenolpyruvate complex.


Sanfilippo syndrome type C: deficiency of acetyl-CoA:alpha-glucosaminide N-acetyltransferase in skin fibroblasts. Removal of N-sulfated glucosamine residues during degradation of heparan sulfate is accomplished by the sequential action of three enzymes. Action of sulfamidase results in the formation of alpha-glucosaminide residues. Removal of these groups requires conversion to alpha-N-acetylglucosaminide by the action of an acetyltransferase in the presence of acetyl-CoA, followed by hydrolysis by alpha-N-acetylglucosaminidase. In fibroblast homogenates from three patients with Sanfilippo syndrome type C (mucopolysaccharidosis III C), a biochemical variant of the Sanfilippo syndrome, complete deficiency of the acetyl-CoA:alpha-glucosaminide N-acetyltransferase activity was detected. Activities of all lysosomal hydrolases known so far to degrade mucopolysaccharides, including those of sulfamidase and alpha-N-acetylglucosaminidase, were in the range of controls. Acetyl-CoA:alpha-glucosaminide N-acetyltransferase activity was normal in fibroblasts of patients with other genetic mucopolysaccharidoses, including Sanfilippo syndrome A and B.


Evidence that catecholamine transport into chromaffin vesicles is coupled to vesicle membrane potential. The effects of ATP, Mg(2+), and various agents on pH gradient, membrane potential, and catecholamine transport across membranes of intact bovine chromaffin vesicles were investigated. Methylamine and thiocyanate (SCN(-)) distributions across the vesicle membrane were used to estimate the H(+) concentration gradient and membrane potential, respectively. The H(+) concentration ratio (intravesiculanmedium) equals 16 when the medium pH is 6.9 and is unaltered by ATP and Mg(2+). In the absence of ATP and Mg(2+), the steady-state intravesicular S(14)CN(-) concentration is lower than the medium concentration. ATP and Mg(2+) cause an increased influx and a decreased efflux of SCN(-) that results in SCN(-) being concentrated in the vesicles 6- to 8-fold over the medium. The findings are consistent with an ATP,Mg(2+)-induced potential of approximately 50 mV (intravesicular side positive). Carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP), a H(+) translocater, and N-ethylmaleimide (NEM), a sulfhydryl reagent, decrease the SCN(-) ratio and, thus, the membrane potential in the presence of ATP and Mg(2+). They have no effect on the H(+) concentration gradient. The rate of catecholamine uptake into vesicles is increased 4- to 6-fold by ATP and Mg(2+). The ATP,Mg(2+)-stimulated uptake is inhibited by FCCP and NEM over the same concentration ranges that reduce the SCN(-) distribution (membrane potential). FCCP increases and NEM decreases vesicular membrane ATPase activity. Thus, catecholamine uptake is correlated to an inside-positive membrane potential, and not to ATPase activity. If catecholamine uptake is coupled to membrane potential, then a charged species must be involved in the transport mechanism. Reserpine and rotenone inhibit catecholamine influx but have no effect on the H(+) electrochemical gradient; they probably act at a step before coupling to the membrane potential (or the H(+) electrochemical gradient). Atractyloside, an inhibitor of nucleotide transport, has no effects on catecholamine transport or the H(+) electrochemical gradient.


A re-examination of curare action at the motor endplate. Recent evidence indicates that curare, in addition to its competitive' interference with endplate receptors, can block open ionic channels by a 'non-competitive' action on the activated acetylcholine-receptor complex. These findings called for further study of the kinetic behaviour of endplate channels and their modification by curare. Examining impulse-evoked endplate currents and acetylcholine-induced current fluctuations, it is found that the lifetime of the open channel is shortened by relatively high concentrations of curare (greater than 5 micrometer), an effect which shows up most strikingly at hyperpolarized levels of membrane potential (-130 mV and above). No shortening of this kind is observed when a neuromuscular block of equal or greater intensity is produced by a dose of alpha-bungarotoxin. Two other neuromuscular blocking agents, gallamine and pancuronium are shown to have an action on channel kinetics which cannot be explained by competitive receptor binding, but conforms to the hypothesis of rapidly repeated blocking and unblocking of individual ion channels, which had been proposed originally to account for the endplate action of local anaesthetics.


Morphology and molecular composition of isolated postsynaptic junctional structures. The solubilization of isolated brain synaptosomal plasma membranes by various detergents was studied and in each case found to depend upon detergent concentration. By using conditions sufficient to extract maximally protein and phospholipid from the membranes, postsynaptic junctional particles were isolated with each of four detergents and their ultrastructural appearances and protein contents compared. Two basic structural forms were identified. One, isolated with Triton X-100, consists of a planar array of dense-staining particles ca. 20 nm in diameter. It resembles the postsynaptic density seen in undigested synaptosomal plasma membranes. The other, isolated with sodium deoxycholate, contains less protein. It has the same overall shape and dimensions as the postsynaptic density, but consists of a branching network of short 5 nm fibres (the postsynaptic junctional lattice) making up an array of contiguous polygons, each ca. 20 nm across. The interior of these polygonal elements seems to be hydrophobic since it cannot be penetrated by metallic salts used for negative staining. It is suggested that the dense-staining 20 nm subunits observed at the postsynaptic junctional site may be composed of hydrophobic proteins inserted into the hollow cores of the lattice polygons. Electrophoretic analysis of the proteins present in the various postsynaptic junctional preparations identified two major common components with molecular masses of 275000 and 47500. The latter is tentatively identified as actin. Components comigrating respectively with alpha- and beta-tubulin are present, and the relation of the lattice structure to subjacent microtubules is discussed.


The position of regenerating cambia: auxin/sucrose ratio and the gradient induction hypothesis. To account for the positions in which vascular cambia regenerate in wound callus, a gradient induction hypothesis was proposed in 1961 in terms of gradients in 'some factor as yet unknown'. It now seems likely that the gradient is based on morphogen diffusion between source and sink on opposite sides of existing cambia, with morphogen diffusing into the adjoining wound callus. It is specifically proposed that there are two morphogens, auxin diffusing centrifugally and sucrose diffusing centripetally. The cambium then regenerates along a path where the ratio of auxin to sucrose concentration is similar to that at the original cambium, and its orientation (as regards xylem and phloem formation) is determined by the direction of the gradient in this ratio. These proposals are supported by published evidence on auxin and sucrose concentration gradients across the cambium, and on their sources, movements, and known effects on vascular differentiation. Simulations of the proposed positional control system predict patterns of cambial regeneration and orientation corresponding to those observed in four different types of wound and graft.


Intestinal uptake and transport of proteins in the adult rat. The transport of immunoglobulin and ferritin across the intestinal mucosa of adult rats provides an excellent model for transcellular protein transport study. Intestinal uptake and transcellular transport have been extensively studied in the neonatal rat, but not to such an extent in the adult rat. The transport of 125I labelled bovine immunoglobulin G and ferritin was studied in 100 days old rats using intestinally administered proteins. Antigen was estimated in the tissues by reacting extracts against specific immune antiserum prepared in rats, and visualization studies were carried out by fluorescence microscopy and direct deposition autoradiography at electron microscopic level. From these studies, it can be seen that these proteins are taken up by the intestinal cells and transported, antigenically intact, across the barriers to the body organs.


Observations on the vegetation of northeastern Mato Grosso II. Forests and soils of the Rio Suiá--Missu area. The vegetation of the well drained soils along the Suiá--Missu road in the Serra do Roncador region of NE Mato Grosso is Evergreen Seasonal forest of Amazonian type. The area lies close to the meeting place of the Amazonian forest (the hylaea) and the cerrado (savanna) formation of Central Brazil. The structure of the forest is simple: the canopy is at about 18--23 m, and is exceeded by a few scattered emergents; no recognizable strata can be distinguished among the understorey trees and the shrub and herb layers are sparse. Table 1 lists the most important species and gives information on stratification and general distribution. Most of the species appear to have a hylaean centre of distribution but extend into other vegetation types. The forest differs from related communities which lie closer to the cerrado/forest boundary in its greater height and luxuriance, the presence of additional tall tree species, and the great reduction in abundance of a cerrado floristic element. A survey on the Xavantina--São Felix road allowed us to extend previous observations on the distance to which the cerrado tree Pterodon pubescens extends into the forest. The results obtained indicate a considerable extension of forest into cerrado during the life of an individual tree. A characteristic low forest occurs in the flood plain of the Rio Suiá--Missu while Swampy Gallery forests occur on permanently waterlogged soils around the headwaters of streams. The well drained soils of the Suiá--Missu forest are very uniform, deep latosols (oxisols) of very dystrophic nature with pH (in water) between 4.0 and 5.0 (see table 2, p. 203).


The coding of sound pressure and frequency in cochlear hair cells of the terrapin. Intracellular recordings have been made from single hair cells in the cochlea of the terrapin, and the site of recording has been verified by injection of a fluorescent dye through the recording electrode. A hair cell gives periodic voltage responses graded with the intensity and frequency of the sound stimulus, and produces the largest response at its characteristic frequency. When small current steps are injected through the recording electrode, the voltage response of the cell exhibits damped oscillations at its characteristic frequency. The results are consistent with the idea that the cochlear frequency selectivity arises in two stages and it is suggested that the second stage resides within the hair cell itself.


Synaptic vesicles and microtubules in frog motor endplates. Motor endplates of the cutaneous pectoris skeletal muscle of the frog have been examined by electron microscopy using a new technique. This involves pretreatment with an albumin solution, followed by fixation with 4% unbuffered tetroxide. A small proportion of the endplate axonal ramifications show microtubules clothed in synaptic vesicles and focused on the presynaptic membrane, in particular on the active zones. The microtubules run in the presynaptic cytoplasm either parallel to or across the active zones. These two sets of microtubules cross each other at the active zones, which lie opposite the dips in the post-junctional folds. The possibility that the microtubules are involved in the translocation of synaptic vesicles to the active zone is discussed.


Kinetic studies in isolated organs: tools to design analgesic peptides and to analyze their receptor effects. The opioid activities of peptide and non-peptide narcotics were studied in longitudinal muscle strip of guinea pig ileum (GPI) and in mouse vas deferens (MVD). The comparison of agonist activities of peptides found in GPI and MVD offered the opportunity to predict the presence but not the magnitude of potential analgesic activity. The kinetics of the antagonism between naltrexone and different types of agonists were also determined in these systems. Using C-6 epimers of naltrexone, it was found that the site of opiate receptors recognizing the information provided by the C-6 substituent of naltrexone are different in GPI and MVD.


[Dopamine-receptor stimulators and neuroleptic-induced dyskinesia (author's transl)]. We have examined bromocriptine, levodopa and trihexyphenydil ins ingle-blind design in 16 chronic productive schizophrenics having the same degree of tardive dyskinesias. Treatment time for each patient was 60 days: Bromocriptine was given in mean daily doses of 32 mg, levodopa 3,2 g and trihexyphenydil 27 mg. Bromocriptine and trihexyphenydil allowed the continued use of neuroleptics, without necessitating an increase in dosage. On the other hand, with levodopa 25% of the patients deteriorated, and this could not be prevented by increasing the dose of neuroleptics. Bromocriptine and trihexyphenydil permitted treatment of tardive dyskinesias, whereby bromocriptione was clinically (and statistically) superior to trihexyphenydil. Trihexyphenydil had only a slight effect on tremor, whilst treatment with levodopa was ineffective.


CNS effects of the antihistamines diphenhydramine and terfenadine (RMI 9918). The quantitative EEG profile of a putative antihistaminic drug, terfenadine, was determined in a crossover comparison with diphenhydramine in normal male volunteers. Terfenadine failed to elicit the characteristic EEG or behavioral effects of sedative antihistaminics, and was distinguishable from diphenhydramine. The EEG profile confirmed the lack of CNS effect observed in preclinical and clinical trials.


Chemical modification of the surfaces of bacterial cell walls. The surfaces of the isolated cell walls of four bacterial species were studied by microelectrophoresis following chemical treatments intended to remove specific charged groups. Acid-base titrations of the walls were used to assess specificity and extent of the modifications. Carboxyl groups were specifically and completely modified by activation with a water-soluble carbodiimide and subsequent reaction with a nucleophile, such as glycinamide, to give an uncharged pH-stable product. Aqueous media and mild reaction conditions make the method suitable for modifying carboxyl groups on cell surfaces too labile to withstand the harsh conditions required for conventional esterification reactions. Use of the carbodiimide-mediated reaction for discharging carboxyl groups, along with fluorodinitrobenzene for discharging amino groups and extraction procedures for removing constituents carrying phosphoester groups (teichoic acids), made it possible to obtain information about the spatial arrangement of charged groups on the wall surfaces. Removal of the exterior negative charge dominating wall surfaces allowed underlying amino groups to become electrokinetically effective and, in the case of E. coli, also revealed a lipophilic region with an affinity for a cationic surfactant.


Stability and kinetic behavior of carboxymethylated horse muscle acylphosphatase. Horse muscle acylphosphatase consists of a main chain S-S bound to glutathione. It was found that removal of the glutathione by reduction and successive carboxymethylation of the only cysteine of the main chain affects the stability of the enzyme, mainly with respect to thermal inactivation. On the other hand, the kinetic properties of the enzyme are affected very little.


Management of compound injuries of the lower extremity. The reconstructive surgeon experienced in the use of rotated or free muscle and myocutaneous flaps, skilled in microvascular surgery, and interested in lower extremity trauma, may favorably alter the course of management of these historically difficult problems. It can be of great advantage to the patient if this surgeon is involved in the primary evaluation, so that all initial therapy can be performed with the future reconstructive goals in mind.


[Clinical study and development of a revealing case of phlebitis]. This article deals with a case of pleural metastases of an adenocarcinoma starting at an unknown point in a 59-year-old patient without notable circulatory antecedents, shown by a recurrent phlebitis having several sites over two months and a hemothorax.


Temperature and blood acid-base status in the blue crab, Callinectes sapidus. The blood acid-base status of blue crabs. Callinectes sapidus, was assessed at temperatures ranging from 10 to 30 degrees C. Blood pH varied inversely with temperature, with a slope (dpH/tT) of - 0.012. The PaCO rose only slightly between 10 and 27 degrees C, from 2.09 torr to 2.91 torr, with the result that the total dissolved CO2 actually fell slightly due to the decrease in solubility. In vitro the blood behaved like a conventional Rosenthal system, with a rise in PCO2 at constant CT which was much greater than the observed in vivo increase. I vivo the CT of the blood decreased significantly in order to maintain the OH/H ratio. The ratio of ventilation to oxygen consumption (and presumably carbon dioxide production) was not significantly different at 10 and 27 degrees C, indicating that ventilation is not participating in the acid-base adjustment to temperature. The principal acid-base regulating mechanisms in the crab are probably ionic exchanges in the gills rather than ventilatory control of PaCO2.


Regulation of oxygen affinity in blood of fetal, newborn and adult mouse. Oxygen half saturation pressure (P50) of blood and the role of 2,3 diphosphoglycerate (DPG), adenosine-triphosphate and red cell pH regulating oxygen affinity were examined in fetuses (16,5-18,5 days of gestational age), neonatal (1-22 days post partum) and adult mice (Balb/c). The high oxygen affinity of fetal blood (P50 = 29 Torr at 37 degrees C, pH 7.4 and Pco2 = 40 Torr) decreases to an average adult value of 41 Torr within two weeks after birth, accompanied by an increase of DPG-concentration from 0.2 M/MHb4 to the average of 1.5 M/MHb4. At a constant pHe of 7.4 red cell pH decreases from pH 7.3 to 7.18 from 18.5 days of gestational age to ten days post partum. Electrophoretic mobility and functional characteristics of purified fetal and adult hemoglobin were identical. Changes in oxygen affinity occur only due to organic phosphate concentration variations. A rapid replacement of large size fetal red cells by smaller adult cells after birth fairly coincides with the increase of the 2,3-DPG concentration.


[Evaluation of antacids "in vitro"].

[Evaluation of antacids "in vitro"]. Five different antacids were compared "in vitro" through titration with NaOH 0.5 N to observe their neutralising power towards HCl 1.0 N. Eight pH measurements were done for each antacid. The neutralising capacity of the antacid was calculated with a specific formula for each pH measure reading, with this information statistical calculation were made to compare the antacids among themselves, with suggest that the method can be useful in the valuation of newly produced antacid before their clinical application.


[Late chronic dyskinesia from neuroleptic drugs (CSF and pharmacological data) (author's transl)]. CSF values of dopamine and serotonine metabolites (homovanillic acid and 5-hydroxy-indoleacetic acid) have been studied in 4 patients suffering from late dyskinesia due to neuroleptics. Trazodone (which acts on all monoaminergic systems, namely noradrenergic, dopaminergic and serotoninergic) induced a marked clinical improvement associated with CSF HVA increase and 5-HIAA decrease. The Authors suggest that involuntary movements could be due to an impairment of 5-HT e DA link.


[The determination of salivary pH by contact pH meter in individuals receiving psychotropic therapy. Study of pH on the tongue and at the orifice of Wharton's and Stenon's ducts (author's transl)]. The authors studied salivary pH at different sites in 172 patients receiving psychotropic therapy in hospital. For statistical purposes, the study was limited to individuals receiving a "moderate" dose of: --a benzodiazepine derivative --a neuroleptic and benzodiazepine --antidepressant, neuroleptic and benzodiazepine. Regardless of the type of psychotropic therapy and of the site of measurement, acidification of salivary pH which was statistically significant in comparison with values found in healthy subjects was noted. This acidification was particularly marked with regard to "lingual" pH. In addition, regardless of the site of measurement, a higher degree of acidification of salivary pH was seen in individuals receiving a combination of psychotropic agents. This acidification was particularly striking with regard to salivary pH in patients given a combination of antidepressant, neuroleptic and a benzodiazepine derivative. The cause of this acidification is not definitely known. A number of hypotheses may be put forward: decrease in salivary volume (Laudenbach, 6, and Vermeil, 7), excretion of acid metabolites by the salivary glands, effect of psychotropic agents upon the action itself of the salivary glands.


Hydrolysis of long-chain fatty acyl-CoA in homogenates of human blood platelets: the existence of a platelet palmitoyl-CoA hydrolase. The existence of a very active long-chain fatty acyl-CoA hydrolase in homogenates of human blood platelets is reported. The highest activity was found with palmitoyl-CoA as the substrate. Palmitoyl-CoA hydrolase activity was not found in intact platelets indicating that the enzyme is localized within the platelet membrane. No palmitoyl-CoA hydrolase activity was found in fasting plasma. Mg2+, Mn2+, Ca2+ and Triton X-100 inhibited the palmitoyl-CoA hydrolase activity. Sulphydryl reagents had no effect, whereas high concentrations of D- and L-carnitine inhibited the activity. Carnitine palmitoyltransferase did not interfere with the assay of palmitoyl-CoA hydrolysis as the activity of carnitine-palmitoyl hydrolase was less than 1% of the palmitoyl-CoA hydrolase activity.


Counterimmunoelectrophoresis of sputum and blood for the diagnosis of chest infections caused by pneumococci or Haemophilus influenzae. In 107 patients with lower respiratory tract infections, counterimmunoelectrophoresis (CIE) of blood and sputum, bacterial cultures of blood, sputum and nasopharyngeal secretion, and enzyme-linked immunosorbent assay (ELISA) for antibody determination were performed, with special reference to pneumococci and Haemophilus influenzae. For pneumococci CIE of sputum was superior to culture especially in antibiotic-treated patients. The clinical significance of a positive CIE of sputum was supported by close correlation to significant antibody increase. The usefulness of CIE regarding H. influenzae was more difficult to evaluate.


Polyglycolic acid (Dexon) sutures in Escherichia coli infected urine. The tensile strength, knot strength and stretch of polyglycolic acid (Dexon) was studied after emersion in physiological saline, sterile urine and infected urine. Tests were made each day under controlled conditions over a 10 day period. The results are compared with those of other earlier studies. Tensile strength, knot strength and stretch were found to be fully acceptable in all studies, and there are no grounds to advise against the use of Dexon when urine is infected.


Urodynamic studies in prune belly syndrome. A case report. Urodynamic studies were carried out in a 14-year-old boy with Prune Belly Syndrome and terminal renal failure prior and after successful renal transplantation. Increased bladder capacity, nonprovocative detrusor instability and a high compliance were the most characteristic findings during the filling phase of the bladder. During the voiding phase an increased detrusor pressure was demonstrated. Outflow resistance and maximum urinary flow rate were within normal range before and after transplantation. In contrast to the findings before renal transplantation, however, micturition was imbalanced after transplantation (residual urine 100 ml). Urodynamics revealed that the bulging of the posterior urethra, observed in the early voiding phase, was due to a congenital insufficiency of the posterior urethral musculature (megalourethra) and not caused by mechanical obstruction leading to urethral dilatation. It is suggested that detrusor-bladder-neck-dyssynergia is the primary cause of the imbalanced micturition and its consequences (bladder distention, reflux, urinary tract infection, hydronephrosis, pyelonephritis) in patients with Prune Belly Syndrome. The findings of a normal, respectively increased detrusor activity are in contrast to the observations of some authors, describing attenutation and absence of detrusor muscle fibres. The indications and effects of transurethral resection and internal urethrotomy, proposed by some authors, are discussed.


[The treatment with tiparide of the agitation and aggressivity of oligophrenic patients (author's transl)]. Tiapride, which is an original medication for the treatment of agitation and psychomotor excitation, was studied in mentally retarded patients; 9 severe and 3 moderate, suffering from bouts of agitation and excitation and aged from 18 to 40 years. The dosage was 4 ampoules (400 mg) daily by IM injection in acute agitation (2 cases), 6 tablets (600 mg) daily in moderately severe cases, and 4 tablets (400 mg) daily in milder cases (4). Very good results were obtained in 3 patients, and good results in 6 others, while no effect was noted in 3 patients (in spite of a reduction in dosage of the other medications). Tolerance was excellent in all cases. Tiapride should fill the therapeutic gap which exists today in the treatment of the agitation and aggressivity of oligophrenia.


[Bucco-linquo-facial and choriform hyperkinesies (author's transl)]. These bucco-linguo-facial and choriform hyperkinesies still remain all too frequent in many neurological diseases. The authors study exclusively the dyskinesies of essential origin or iatrogenous including the post neuroleptic and post dopatherapy dyskinesies. All the neuroleptics can be involved at different stages of the treatment, giving rise to difficulties in the diagnosis. Dopatherapy in the Parkinson disease is also responsable of many dyskinesias. Time of appearance after the drug's taking, significance and treatment are discussed. The idiopathic dyskinesis are more unusual either with the some only facial involvement, or in association with another abnormal movements. The physiopathology is doubtful, so the treatment is often very difficult.


Metronidazole in the prophylaxis and treatment of anaerobic infection. The influence of prophylactic metronidazole on vaginal carriage rates of anaerobes and the development of postoperative anaerobic infection was studied in 104 women who underwent abdominal hysterectomy. Metronidazole prophylaxis in 54 patients led to a decrease in the anaerobe vaginal carriage rate from 65% pre-operatively to 17% and 28% on the 3rd and 7th postoperative days respectively. In the control group (50 patients) no significant decrease in anaerobe yield was noted, corresponding percentages being 72%, 64%, and 74%. Postoperative infection occurred in 36 patients (28 controls; 8 on prophylactic metronidazole). Wound swabs from all 8 patients in the latter group yielded aerobes, and in 1 patient mixed infection (aerobes/anaerobes) occurred. In 7 of these patients (including the patient with mixed infection), the infection resolved spontaneously, while the 8th patient responded to therapy with metronidazole, kanamycin and ampicillin. In the control patients, 21 cases of postoperative wound infection and 4 of vault infection were seen; wound swabs from patients in the former group yielded aerobes in only 6 cases, and mixed growth of aerobes/anaerobes in 10 cases. Postoperative wound/vault infections in control patients cleared spontaneously in 18 cases and responded to imidazole therapy, with or without ampicillin and kanamycin, in 7 cases.


Anaesthetic induction of caesarean section with thiopentone, methohexitone and ketamine. Thiopentone (3,5 mg/kg) was compared with methohexitone (1 mg/kg) and 'low-dose' ketamine (1 mg/kg) for induction of obstetric anaesthesia. Anaesthesia was maintained with gas, oxygen, muscle relaxant and 0.6% enflurane. Fetal oxygenation was superior with thiopentone, but blood gas/acid base status was otherwise comparable among the different agents. Methohexitone and low-dose ketamine appear to offer reasonable alternatives to thiopentone for anaesthetic induction at caesarean section.


[Interest of the use of pain drug in hyperalgic ophthalmic herpes zoster (author's transl)]. In ophthalmic herpes, very frequent residual pain may be the cause of severe facial neuralgia which may persist for many years. These cases of neuralgia often occur in the elderly and raise difficult therapeutic problems. Tiapride which is a neuro-visceral mediator of the substituted benzamide family gave excellent results in 3 cases of ophthalmic herpes zoster in the elderly. The dosage was 200 to 300 mg daily by the intramuscular route, then by the oral route. Tolerance was excellent.


[Qualitative and quantitative determination of amino-2 benzimidazole in aqueous medium by polarography (author's transl)]. Amino-2 Benzimidazole, a residue of the decomposition of some fungicides (Benomyl, Carbendazine, Thiophanate, Methylthiophanate), is measured by polarography in aqueous medium, with a platinium rotating electrode, for the exploration in potentials from +0.5 v to 1.4 v. The best conditions for the quantitative determination are investigated, the study according to pH is performed and the standard curve is given for concentrations from 10(-5) to 10(-3) M/l. The interaction of elementts found in tap water and in aquarium water is also investigated.


[Urine elimination of gamma-glutamyl transferase with repeated injections of mercuric chloride in the rat (author's transl)]. Daily intraperitoneal injection of HgCl2 (2.5 mu-mole Hg/kg) induces an early and important increase of urine gamma-glutamyl transferase, This enzyme is a good test of the evolution of the toxic lesion in the live animal.


[Evaluation of results of therapy with cast removable partial prosthesis. I. Significance of the residual teeth]. On the basis of results from follow-up examinations in patients with removable cast partial prostheses, the author points to injuries to the remaining teeth which are attributable above all to errors of indication, insufficient preliminary measures, and inadequate metaphylaxis.


Eperythrozoon ovis. III. The effect of infection on blood pH, concentrations of pyruvate, lactate and glucose in blood, haematology, and on concurrent and superimposed trypanosoma vivax infection in sheep. Infections of sheep with Eperythrozoon ovis has been shown to increase pyruvate and lactate concentrations in blood and to reduce blood pH over a period of 10-14 days post-inoculation. There was no effect on the concentration of blood glucose. However, if care is not taken to inhibit glycolysis, the concentration of blood glucose in samples of blood taken for analysis falls markedly. Rapid destruction of erythrocytes started about 10 days post-inoculation and was progressive. Superimposition of Trypanosoma vivax infection on E. ovis infection did not appear to affect the growth of either parasite.


Role of microsurgery in orchiopexy.

Role of microsurgery in orchiopexy. Intra-abdominal tests cannot be completely brought down into the scrotum by conventional methods. Four intra-abdominal testes in 3 patients underwent successful orchiopexy by dividing the spermatic artery and vein near their origin and anastomosing these vessels to the inferior epigastric vessels with the use of microsurgical technique.


The destruction of pig helminth ova and larvae in a slurry treatment process. It was established that a thermophilic system for the treatment of pig slurry at 55 degrees C rapidly killed the free living stages of three common pig parasites. This treatment could be beneficially incorporated in any pig slurry recycling process, whether to land or to animals.


[Effect of physical and chemical factors on the antigenic activity of the cell walls of Brucella abortus 99]. Studied was the effect of some physical and chemical factors--heating, acidity, treatment with ultraviolet rays, and enzyme treatment--on the activity of the Brucella abortus 99 cell wall antigen. The activity of the antigen was determined through the microreaction of complement-fixing after Kolmer. It was found that the antigen was most sensitive to acid treatment and treatment with ultraviolet rays, and was more slightly sensitive to the effect of alkaline agents and pronase. Besides, the antigen proved heat-resistant and did not lose its activity after treatment with trypsin and alph- and beta-amylase. The chemical nature of the epitopes (the determinant groups), substantiating the activity of the antigen is briefly discussed.


Arthritis and hepatitis.

Arthritis and hepatitis. The evidence relating four clinically distinct rheumatologic syndromes to infection by the hepatitis B virus is reviewed. Acute hepatitis B is not infrequently heralded by a prodromal rash and rheumatoidlike polyarthritis. Chronic active hepatitis B more rarely is associated with transient arthritis or arthralgias. Polyarteritis nodosa may be a manifestation of hepatitis B infection in as many as 40 percent of cases, and recently the syndrome of "essential" mixed cryoglobulinemia has also been linked to infection with this virus. The finding of immune complexes of varying composition, sometimes with the viral antigen or its antibody (or both) contained in both the serum and synovial fluid suggests that these four syndromes are clinical manifestations of immune complex disease resulting from hepatitis B infection.


[Influence of pirenzepin on healing of gastric ulcer. A double blind study in in-patients (author's transl)]. In a double-blind study the influence of Pirenzepin on ulcer healing was studied in 28 in-patients with gastric ulcer under endoscopic control. The ulcer size was reduced by Pirenzepin significantly quicker, and the number of ulcers healed after three weeks treatment with Pirenzepin was significantly higher than under placebo. As to accompanying symptoms appetite stimulation was significantly more frequent with Pirenzepin compared to placebo. No patient complained of dryness of the mouth.


[Clinical studies on acidosis morbidity (author's transl)]. Basing on the pH values of the umbilical artery of a total of 3,421 births in 1977 and in the first half of 1978, the acidosis morbidity associated with the various methods of delivery and dependent upon the weight at birth is determined, and compared with the Apgar score. The results are discussed with reference to literature. It is concluded from this study that electronic monitoring should be intensified, that indication for abdominal Caesarean section should be considered on a relatively liberal scale, and that the quota of underweight children should be reduced further.


[The reaction of lung mast cells to acute barbiturate and bromureide poisoning (author's transl)]. Guinea pigs were poisoned by large oral doses of hypnotics in order to study the effect of bromureides on the mast cell contents of the lungs in comparison to the influence of barbiturate intoxication. The dose of the hypnotics chosen was thus, that all animals died within the first three hours after the beginning of feeding. Then the degranulation of mast cells with decrease of the mast cell number in the lung tissue was merely small in the barbiturate poisoned animals, but very extensive in the animals intoxicated by bromureides. The difference is highly significant. The possible influence of this effect upon the different clinical course of both kinds of intoxication is discussed.


The effect of beta-adrenoceptor blocking drugs on free fatty acid and glucose utilization of the isolated canine heart with normal and restricted flow in the presence and absence of noradrenaline. Effect of adrenergic beta-receptor blockade on the myocardial utilization of the main substrates by the isolated fibrillating dog heart perfused with constant volume of blood from a donor animal was studied at normal and restricted flow, and in the presence of noradrenaline. A direct metabolic action of the beta-blockade by increasing glucose uptake in the normal and reducing it in the ischemic heart, furthermore moderating the ischemic diminution of the lactate uptake could be shown. The intervention reduced elevated serum free fatty acid level and increased myocardial free fatty acid uptake observed in the presence of noradrenaline.


Effects of prostaglandins, calcium, and bradykinin on guanylate cyclase in different organs. The effects of prostaglandins and bradykinin on the activity of guanylate cyclase in plasma membranes from rat uterus and duodenum have been found strongly dependent on calcium content.


Studies of the TSH radioreceptor assay.

Studies of the TSH radioreceptor assay. We have examined several variables in the reagents and procedures used in the TSH radioreceptor assay, the binding of iodinated TSH to its thyroidal receptor. We found that iodinated bovine TSH (S.A. 30 U/mg) was more effectively bound to receptor than iodinated human TSH (S.A. 7.3 U/mg). Iodination of TSH was the Bolton-Hunter acylation method apparently prevented binding to TSH receptor. Surgically removed human thyroid tissue specifically bound 10.3 +/- 1.0 (mean +/- SEM) of added [125I]TSH, but post-mortem human thyroid bound only 3.9 +/- 0.4% of [125I]TSH (p less than 0.001). Maximal binding of [125I]TSH was found at pH 5.8. Many tissue preparations contained activity, possibly due to proteases, which inactivated TSH, and inclusion of a protease inhibitor, aprotinin, significantly increased specific binding.


Bone marrow transplantation for acute leukemia using a histocompatible paternal donor. A bone marrow transplantation from an HLA-identical, MLC nonreactive paternal donor has been performed in a patient with acute lymphoblastic leukemia resistant to drug treatment. Prompt engraftment was documented; however, the patient died of interstitial pneumonitis due to cytomegalovirus 65 days after transplant. Clinical manifestation of graft-versus-host reaction was mild. Recurrence or persistence of leukemia was found at the time of death using cytogenetic markers and determination of the leukemic marker enzyme terminal deoxynucleotidyl transferase.


Acid-base balance during laparoscopy. The effects of intraperitoneal insufflation of carbon dioxide and nitrous oxide on acid-base balance during controlled ventilation. During laparoscopy the carbon dioxide used to achieve a pneumoperitoneum is absorbed from the peritoneal cavity into the blood. The object of the present study was to clarify certain aspects concerned with  anesthetic and ventilatory techniques, mostly in connection with the comparison between the effects of insufflation of either carbon dioxide or nitrous oxide. Anesthesia included ventilation with a volume controlled ventilator in curarised patients. Respiratory volumes were calculated according to the patient's body area. The results show a  sharp rise in PaCO2 and a fall in pH after intraperitoneal insufflation with carbon dioxide, while no changes were observed when nitrous oxide was used. The clinical consequences of these findings are discussed.


Increase in bilirubin binding to albumin with correction of neonatal acidosis. Twenty-six serial measurements of free bilirubin concentration and apparent association constant of bilirubin for albumin (Ka) at a bilirubin: albumin molar ratio of 0.8 were performed and compared with baseline values in 11 newborn infants with acidosis before treatment and during recovery from acidosis. When arterial pH was corrected from 7.12 +/- 0.02 (Mean +/- S.EM.) to 7.34 +/- 0.02, there was a significant decrease in serum free bilirubin concentration and a significant increase in the Ka at molar ratio 0.8. The data offer in vivo evidence that correction of acidosis in the neonate results in an improvement of the apparent bilirubin binding affinity of albumin.


Electron microscopy of nephropathia epidemica cell nuclei in kidney biopsies. Ultrastructural changes in cell nuclei were studied in kidney biopsies from 18 patients suffering from Nephropathia epidemica. Three patients showed small nuclear particles in a large aggregate in a few cells of  the distal tubule. The particles had a diameter of about 30 nm and their occurrence was not associated with intravenous glucose infusions. Large light nuclear bodies were numerous in the nuclei of both interstitial and tubular cells. Many showed strands of darker material about 35 nm in diameter at their center. Nuclear vesicles with varying amounts of membrane debris were seen in both tubular and interstitial cells. Occasional interstitial lymphocytes showed abnormal margination of chromatin. Of the changes observed the small nuclear particles are not found in kidney biopsies in other conditions and it is possible that they are aggregates of viral protein.


Nervous control of pancreatic exocrine secretion in pigs. The pancreatic secretion of fluid, bicarbonate and protein in response to electrical stimulation of the vagus and splanchnic nerves, to exogenous and endogenous secretin and to various pharmacological agents was studied in anesthetized young pigs (21 kg). Vagal stimulation increased flow, bicarbonate output and protein output in a frequency dependent manner; the half maximal effective frequency was 2--4 Hz and the maximal effective frequency 12 Hz. The secretory response to vagal stimulation was potentiated by physiological elevations of the arterial concentration of secretin brought about by injection of secretin or by acidification of the duodenal bulb. Simultaneous stimulation of the splanchnic nerves strongly inhibited the response to vagal stimulation; splanchnic nerve stimulation alone had no demonstrable effect. The flow and bicarbonate response to vagal stimulation was unaffected by atropine, but abolished by hexamethonium. Protein output was strongly inhibited by both agents. The response to intraarterial infusion of acetylcholine resembled that elicited by vagal stimulation but it was smaller and it was completely abolished by atropine and unaffected by hexamethonium. Alpha- and beta-adrenergic blockade stimulated rather than inhibited the secretory response to vagal stimulation. The portal vein plasma concentration of secretin was not affected by vagal stimulation. The results indicate that the protein response, and the flow and bicarbonate response to vagal stimulation are not brought about by the same mechanism. An increased release of secretin is not involved. Peptidergic (VIP-containing) nerves may contribute.


Effect of proteolytic activation on intraocular hydrodynamics the pressure of O2, CO2 and pH in the aqueous humor. The effect of proteolytic activation on the tonographic indices and secretion of the aqueous humor was studied. It was found that active peptides rise the secretion of intraocular fluids increasing the permeability of capillary plexuses and decreasing the metabolic processes in the structures secreting the aqueous. They may perticipate in haemodynamic and hydrodynamic intraocular autoregulation.


A phenomenologic evaluation of CO2-diffusion restriction in kidney tubules studied in an artificial membrane system. The chemical course in a multi-membrane system with interacting H+ and HCO3 ions has been described phenomenologically as an analogy of the neutralisation reaction between secreted H+ and filtered HCO-3 ions in the proximal tubules of the kidney. It was shown that the produced CO2 gave the highest PCO2 in the asymmetrically placed reaction centre, which favours a build-up of a high intratubular PCO2. The CO2 transport was dependent on the rate-limiting permeation of the reacting ions, and the permeation could be increased by the influence of solutions of macromolecules such as carbonic anhydrase, albumin and dextran.


PCO2 of the proximal tubular fluid and the efferent arteriolar blood in the rat kidney. Recordings in vivo of the carbon dioxide tension of the proximal tubular fluid and of the efferent arteriolar blood were performed with PCO2 microelectrodes in the rat kidney. The buffer lines of the efferent arteriolar blood and systemic arterial blood were determined with an ultramicro equilibration system and the acid-base status of the systemic arterial blood was measured. The intratubular PCO2 was significantly higher than the PCO2 of the arterial blood, and the PCO2 of the efferent arteriolar blood was significantly lower than that of the arterial blood. The buffer capacity was higher and the bicarbonate concentration slightly lower for the efferent arteriolar blood than for the arterial blood. It is concluded that a PCO2 difference exists across the tubular wall and that the high intratubular PCO2 favours a chemical equilibrium of the carbonic acid-bicarbonate system in the proximal tubular fluid. It is supposed that the slightly lowered bicarbonate concentration in the efferent arteriolar blood is an effect of the glomerular ultrafiltration process.


CO2 along the proximal tubules in the rat kidney. The proximal intratubular pH of the rat kidney was measured in vivo with an antimony electrode system. PCO2 and bicarbonate concentration of the proximal tubular fluid were determined with an ultramicro equilibration system. The tubular fluid to plasma inulin concentration ratio was evaluated by a microscope fluorometric method. The acid-base parameters and the inulin concentrations were determined under control conditions and during acetazolamide treatment. The intratubular PCO2 was higher than the PCO2 of the systemic arterial blood under control conditions and the difference in PCO2 was increased during acetazolamide treatment. In acetazolamide treated rats the rate of fractional bicarbonate reabsorption was decreased in the early part of the proximal tubule, while it was of about the same in the middle and late parts as compared with control rats. The total bicarbonate reabsorption in the proximal tubule was reduced by 50% due to the carbonic anhydrase inhibition. It seems possible that the bicarbonate is still reabsorbed as CO2 after carbonic anhydrase inhibition, as hydrogen ion secretion is not totally stopped by this treatment. The increase in intratubular PCO2 after acetazolamide treatment is assumed to be due to an inhibition of the carbonic anhydrase facilitating effect on outward diffusion of CO2 from the tubular lumen across the cell wall.


ECG-changes in the fetal lamb during asphyxia in relation to beta-adrenoceptor stimulation and blockade. Progressive changes in the S-T interval of the fetal electrocardiogram (FECG) were studied in 14 lamb fetuses, acutely exteriorized and subjected to graded hypoxia. The aims of the study were to investigate whether beta-adrenoceptor stimulation and hypoxia exerted additive or potentiating effects on the FECG and several cardiovascular parameters and whether the hypoxic changes of the FECG could be blocked by beta-adrenoceptor blocking agents. The FECG changes were studied in order to correlate them with cardiovascular function, as measured by heart rate, mean arterial pressure, end diastolic pressure, maximum dP/dt and combined cardiac output, estimated by the thermodilution method, as well as with blood gases, acid base status, blood lactate and glucose. Injections of small doses (0.02 to 0.4 microg kg-1 min-1) of isoprenaline induced the same pattern of changes in the FECG as we have previously recorded during hypoxia. By increasing the isoprenaline dose an increase in the duration of the FECG changes and amplitude of the T-wave changes was obtained. Propranolol was found to completely abolish the FECG changes induced by isoprenaline, as well as by mild hypoxia. During severe hypoxia the FECG changes could not be abolished by propranolol. Our previous findings indicated that the hypoxic changes could be regarded as a sign of myocardial glycolysis. Thus, the present finding that even small doses of isoprenaline given to the fetus, initiates the same pattern of FECG changes corroborate this hypothesis.


Simulated discharge system of prescription and long-term drug treatment in a psychiatric hospital. The drug sheets of patients resident in a psychiatric hospital for more than 1 year were reviewed. The simulated discharge system involving the re-writing of drug sheets every 12 weeks was in operation, but there was only a slight increase in prescription changes at the time of renewal; 35.4% of prescriptions had been unchanged for 1 year and 4.3% for 5 years. A high proportion of long-term prescriptions were for purgatives, hypnotics and neuroleptics.


Psychopharmacological treatment of psychotic children. A survey. Controlled investigations on the psychopharmacological treatment of psychotic children are reviewed. Children with infantile autism might benefit from psychopharmacological medication when they grow older, e.g. above the age of 7 years. Learning might be facilitated when the psychoactive medication is able to inhibit psychotic preoccupations and idiosyncratic reactions. Schizophrenic and manic-depressive psychoses are rarely seen in childhood. A subgroup of the children with infantile autism might develop schizophrenic symptoms. Schizophrenia and manic-depressive psychosis in children are treated as in adults. Special caution must be paid to the toxic effects of imipramine.


Assay and properties of IgA protease of Streptococcus sanguis. An assay procedure for streptococcal IgA protease is described which uses isotopically labelled human serum IgA as substrate. Enzyme activity was monitored by the radioactive counts in the Fab alpha product, which was separated from other components in the digestion mixture by electrophoresis. Cleavage of IgA was linear with respect to time using catalytic amounts of the enzyme. Km was calculated to be 5.5 X 10(-6)M, pH optimum 6.0-7.0 at 37 degrees C, and the enzyme was fully inactivated at low concentrations of the metal chelator ethylenediaminetetraacetic acid.


Effect of growth conditions on the antigenic components of Streptococcus mutans and lactobacilli. 1) The release of LTA from chemostat-grown cultures of S. mutans and L. fermentum is dependent on the generation time and pH. 2) The growth rate affects the immunogenicity of LTA and the wall polysaccharide of L. fermentum. 3) The growth of L. plantarum under glucose limitation influences the glucose content of the wall teichoic acid. The composition of the wall polysaccharide of S. mutans Ingbritt may also be changed under these conditions. 4) The conditions of autoclaving used to release cell wall antigens can hydrolyse the covalent linkage between polysaccharide and peptidoglycan.


Genetic alterations of Streptococcus mutans' virulence. The use of mutants defective in caries-associated traits has enabled the genetic dissociation of agglutination from adhesion, the demonstration of serotype-specific contributions of IPS to virulence, the importance of glucanohydrolase to virulence to a greater degree than to plaque formation, and the apparent lack of importance of agglutination to virulence. We have also been able to demonstrate the ability of plaque formation-defective mutants and other variants both to infect and to emerge, yet not to cause disease. Additional mutants, currently under study in our laboratory include fructanase, invertase, and sucrose permease-defectives. Ultimately, the identification of key, probably surface-associated virulence factors will offer more potent and specific antigens for directed immune responses by the host.


Penicillin-insensitive pneumococci. Case report and review. Infections due to pneumococci with decreased susceptibility (or resistance) to penicillin have been infrequently recognized. Our experience and that of others suggest that (1) penicillin susceptibility testing of significant pneumococcal isolates should become routine; (2) penicillin may not be adequate therapy for CNS infections due to pneumococci whose penicillin minimal inhibitory concentration is greater than 0.1 microgram/ml; and (3) long-term penicillin "prophylaxis" may be inappropriate in the splenectomized patient in areas where these organisms are prevalent.


Hemolysis during salicylazosulfapyridine therapy. In 36 unselected patients with ulcerative colitis or Crohn's disease taking 4.5-6 gm. salicylazosulfapyridine per day the incidence of hemolysis and its relation to the serum level of salicylazosulfapyridine (Salazopyrin, Azulfidline, SASP), free sulfapyridine (SP) and acetyl sulfapyridine (ac-SP) was investigated. In 19 patients hemolysis was present. Serum levels of free SP were significantly higher in these patients (P less than 0.001). All patients with a serum SP level higher than 37 microgram./ml. had hemolysis as compared to only four of 21 patients with a serum SP level below 37 microgram./ml. Four patients had evidence of hemolytic anemia. In these patients the serum SP level was higher than 55 microgram./ml. Eighteen of the 19 patients with hemolysis were slow acetylators while six of the 17 patients without hemolysis belonged to the slow acetylator phenotype.


Protection against fatal endotoxin shock in mice by antihistamines. Protection against endotoxin shock by antihistamines and similar pharmacologic agents has been reported in the literature. The authors tested the validity of this form of treatment by animal experiments which were conducted in three phases. During the first phase, 10 mice each were treated intravenously with various doses of gram negative endotoxin to determine the dose of endotoxin which would kill 80% of the animals (LD80). This dose was determined to be 36 mg/kg bodyweight. During the second phase, 10 mice each were pretreated with various doses of either diphenhydramine (Benadryl) or of hydroxyzine HCI (Atarax) one hour prior to the administration of the LD80 of endotoxin. It appeared that high doses of diphenhydramine as well as of hydroxyzine were highly fatal to most animals by causing severe convulsions within 3 to 6 hours at doses of 40 or 50 mg/kg. Doses of less than 1 mg/kg appeared to have no protective effect, while doses of 2.5 and of 5 mg/kg, given one hour prior to the LD80 of endotoxin, had some protective value. In the case of diphenhydramine, 60% of the animals survived with 5 mg/kg pretreatment. Hydroxyzine hydrochloride protected 100% of the 10 animals so treated during the initial experiment and 90% during a subsequent experiment, if given 1 hour before the endotoxin. The third phase of this experiment was designed to determine the optimal time at which hydroxyzine needs to be given to protect against fatal endotoxin shock. Given 6 hours before endotoxin, hydroxyzine appeared to protect half of the animals, 1 hour prior to endotoxin, 5 mg/kg of hydroxyzine protected 90% of animals; if given simultaneously, it protected all animals. When hydroxyzine was given 1 hour after endotoxin there was a 70% survival and, if given 3 hours after endotoxin, a 40% survival.


[The heart of the old hemiplegic patient (author's transl)]. The heart of the old hemiplegic patient is examined as follows: 1. The preapoplectic situation of the heart which often induces in a conclusive manner the beginning of a stroke, 2. the occurrence of heart troubles with the stroke itself and 3. the influence of rehabilitation measures and the heart function. Preexistent heart troubles are very frequent (in ca. 80%). Thereby the hypertension with a left ventricular hypertrophy and later with heart failure play an important role. The stroke itself especially in subarachnoidal bleedings can cause severe electrocardiographic anomalies. The telemetric controlled heart shows specially while rehabilitation more extrasystoles and alterations of repolarisation but usually do not impair the rehabilitation. With a systematic rehabilitation (training) the heart is most favourably influenced.


[Follow up and treatment of pacemaker-patients in advanced age (author's transl)]. Most of the pacemaker-patients are in the eight decade of life. The continuous follow ups of the patient with a pacemaker system have to reguard the often advanced age, the cardiac basic disease, other concomitant diseases and futhermore technical details of the device, the date of implantation and the expected longevity of the power source. The risk of the patient by pacemaker failure in the underlying rhythm disturbance can be estimated by short extinguish of the pacing activity. The additional medical treatment is determined by the findings and must be adapted to the mentioned circumstances.


[Peculiarities of diagnosis and treatment in hypertension of the aged (author's transl)]. It can be noted, a consequently discovered and treated hypertension is one of the most important achievements of modern medicine within the last 20 years. The earlier treatment begins, the better it success of treatment in avoiding complications on the basis of arterio sclerosis and expectation of life. For elderly hypertensives it is particularly important, what is good in younger decades too - but in higher age the acute threat of life by hypertension is much more pronounced.