Stereoscopic subsystems for position in depth and for motion in depth. We describe psychophysical evidence that the human visual system contains information-processing channels for motion in depth in addition to those for position in depth. These motion-in-depth channels include some that are selectively sensitive to the relative velocities of the left and right retinal images. We propose that the visual pathway contains stereoscopic (cyclopean) motion filters that respond to only a narrow range of the directions of motion in depth. Turning to the single-neuron level we report that, in addition to neurons turned to position to depth, cat visual cortex contains neurons that emphasize information about the direction of motion at the expense of positional information. We describe psychophysical evidence for the existence of channels that are sensitive to change size, and are separate from the channels both for motion and for flicker. These changing-size channels respond independently of whether the stimulus is a bright square on a dark ground or a dark square on a bright ground. At the physiological level we report single neurons in cat visual cortex that respond selectively to increasing or to decreasing size independently of the sign of stimulus contrast. Adaptation to a changing-size stimulus produces two separable after-effects: an illusion of changing size, and an illusion of motion in depth. These after-effects have different decay time constants. We propose a psychophysical model in which changing-size filters feed a motion-in-depth stage, and suppose that the motion-in-depth after-effect is due to activity at the motion-in-depth stage, while the changing-size after-effect is due to to activity at the changing-size and more peripheral stages. The motion-in-depth after-effect can be cancelled either by a changing-size test stimulus or by relative motion of the left and right retinal images. Opposition of these two cues can also cancel the impression of motion in depth produced by the adapting stimulus. These findings link the stereoscopic (cyclopean) motion filters and the changing-size filters: both feed the same motion-in-depth stage.


Binocular single vision and perceptual processing. Stimuli with small binocular disparities are seen as single, despite their differing visual directions for the two eyes. Such stimuli also yield stereopsis, but stereopsis and single vision can be dissociated. The occurrence of binocular single vision depends not only on the disparities of individual stimulus elements, but also on the geometrical relation of different parts of the pattern presented to each eye. A pair of vertical bars with opposite binocular disparities is seen as single if the pair is moderately widely spaced but not if it is narrow. Vertical alignment and identity in length of such bars also increase the occurrence of double vision. It is argued that these effects reflect the extraction of features of the monocular patterns, with these detected monocular features determining the binocular percept. Single and double vision of bars differing in orientation can be similarly analysed. The occurrence of relatively elaborate processing of monocular signals does not exclude the possibility that binocular interaction can occur between signals that have not been so processed. Multiple sites or types of binocular interaction are likely.


Mechanism of S-(carboxymethylthio)cysteine cleavage by rat liver cystathionine-gamma-lyase. Rat liver cystathionine-gamma-lyase [L-cystathionine cysteinelyase (deaminating), EC 4.4.1.1] catalyzes the formation of pyruvic acid, ammonia, and carboxymethylhydrodisulfide from S-(carboxymethylthio)cysteine (CMTC). As judged by pyruvic acid production, the optimal pH is 8.3 in tris-HCl buffer and the Km is 2.9 mM. A possible mechanism of CMTC cleavage by cystathionase is proposed.


Subcellular distribution and some properties of alanine aminotransferase in striated muscles of the crayfish, trout, carp, frog, pigeon and rabbit. Subcellular distribution and some physicochemical properties of alanine aminotransferase in striated muscles of the crayfish, trout, carp, frog, pigeon and rabbit were studied. It was established that: (1) Alanine aminotransferase activity in all mentioned animals occurred almost entirely in the cytosolic fraction of the muscles. Total activity and activity per mg protein were highest in crayfish and pigeon muscles and lowest in carp and trout muscles. (2) The pH optimum for the muscles of homoiotherms and poikilotherms ranged from 7.5 to 8, Km values for L-alanine were of the order 10(-3)--10(-2) M and those for alpha-ketoglutarate 10(-4) M. (3) A 10 degree C temperature increase of the incubation medium was accompanied by a 70--90% increase in activity. (4) The higher the alanine aminotransferase activity of the muscles, the relatively higher their alanine production during electrical stimulation. (5) From the above results it is concluded that alanine aminotransferase in striated muscles regulates the rate of glycolysis and energy production under conditions of anaerobiosis through the formation of alanine.


The role of depot neuroleptics in the treatment of schizophrenic patients. Because of the potential importance of prolonged action neuroleptics for the delivery of care to schizophrenic patients, and because of the availability of new, extensive data from clinical trials on the utility of these drugs, a workshop conference was convened by the United States National Institute of Mental Health in collaboration with the Institute of Clinical Psychiatry of the University of Pisa to assess the role of depot neuroleptics in the treatment of schizophrenic patients. This paper summarizes its conclusions.


[Effects of four beta-blocking agents on some psychopharmacological tests in mice (author's transl)]. Common effects of four beta-adrenergic blocking drugs have been investigated in mice using classical and new psychopharmacological tests. Propranolol, alprenolol, practolol and penbutolol reduced the increase in locomotor activity produced by reserpine after MAO inhibition; they produce hypothermia when associated with amphetamine and they increase oxotremorine-induced hypothermia. Regarding these three tests the studied substances ranged themseleves in the same order of potency: penbutolol greater than propranolol greater than alprenolol greater than practolol. Propranolol and penbutolol decreased the toxicity provoked in crowded mice by amphetamine or by the association pargyline-reserpine; alprenolol and practolol did not. Propranolol, penbutolol and alprenolol antagonized the amphetamine-induced increase in motor activity; practolol did not. When used at doses for which d-l propranolol was active, the dextrogyre isomer of propranolol was without effect whatever the test studied. It is suggested that for the selection of a beta-blocking drug, regarding central effects in man, the tests described would deserve consideration.


Etonitazene as a reinforcer for rats: increased etonitazene-reinforced behavior due to food deprivation. Etonitazene-reinforced performance of rats was increased by food deprivation and decreased by food satiation. These changes were not due to general increases in either activity or liquid intake.


Neuroleptic influence on hyperthermia induced by 5-hydroxytryptophan and p-methoxy-amphetamine in MAOI-pretreated rabbits. 5-Hydroxytryptophan (5-HTP) and p-methoxyamphetamine (p-MA) induce dose-dependent, lethal hyperthermia when applied intravenously to monoamine oxidase inhibitor (MAOI) pretreated rabbits. The time course of hyperthermia and the doses required to induce hyperthermia varies between the two substances. Results with alpha-MT and PCPA suggest that 5-HTP hyperthermia depends on 5-HT formation, release of endogenous 5-HT, and the presence of catecholamines, whereas p-MA-induced hyperthermia most likely is a result of indirect 5-HT release. Some neuroleptics (piflutixol, spiroperidol and methiotepine) are extremely potent inhibitors of the induced hyperthermia, Also the 5-HT receptor blocking agent methergoline antagonizes hyperthermia induced by the two substances in rather low doses. On the other hand cis (Z)-flupenthixol is a very weak antagonist of 5-HTP but a more potent inhibitor of p-MA hyperthermia. It is concluded that both 5-HT and catecholamine (dopamine) receptor blockade is required to antagonize 5-HTP hyperthermia and that antagonism of p-MA induced hyperthermia is primarily a result of influence on the 5-HT system.


Antagonism of apomorphine-induced hyperthermia in MAOI-pretreated rabbits as a sensitive model of neuroleptic activity. Apomorphine induced dose-dependent hyperthermia when applied intravenously to rabbits pretreated with a monoamine oxidase inhibitor. Inhibition of the synthesis of catecholamines (by alpha-MT) did not influence on apomorphine-induced hyperthermia, whereas 5-HT synthesis inhibition (by PCPA) completely abolished the hyperthermic response. Some neuroleptics and a 5-HT receptor blocking agent inhibited the hyperthermia in very low doses. A highly significant correlation was registered between the antagonism of apomorphine hyperthermia of 15 neuroleptics and their clinically useful doses. It is concluded that apomorphine-induced hyperthermia most likely is a result of direct stimulation of dopamine receptors and release of 5-HT, and that abolition of this response represents a very sensitive in-vivo model for neuroleptic substances. Antagonism of apomorphine-induced hyperthermia may be achieved by either dopamine or 5-HT receptor blockade.


The effects of psychomotor stimulants on single-spatial alternation behavior in dogs. Dogs were trained to pedal press for drinking water in a noncued, single-spatial alternation task. After the dogs were exhibiting stable performance at or above predetermined criteria levels, they were given three doses of four different drugs (methylphenidate, 0.2, 0.4, and 0.8 mg/kg; d-amphetamine, 0.15, 0.3 and 0.6 mg/kg; cocaine, 0.5, 1, and 2 mg/kg; and phenmetrazine, 0.6, 1.2 and 2.4 mg/kg). In general, all four drugs produced similar changes in performance. The number of correct responses was an especially sensitive indicator of drug effects. All four drugs also produced significant increases in both the average response latency and total session duration, but there were few significant changes in either the total number of responses or number of intertrial interval responses. Relative to d-amphetamine, the potencies of cocaine and phenmetrazine, but not methylphenidate, were generally higher for the measures of single-spatial alternation than for self-administration.


Discriminative stimulus properties of psychomotor stimulants in the cat. Cats were trained to choose between two levels or an operant chamber using interoceptive cues provided by d-amphetamine or saline as the discriminative stimuli. Following training, stimulus generalization was observed to additional doses of d-amphetamine and cocaine. but not to morphine. Clozapine blocked the generalization of the drug discrimination response to d-amphetamine, but had no effect on generalization to cocaine. These data indicate that discriminative stimulus properties of psychomotor stimulants, previously described in rats, are similar in cats.


Comparative effects of trazodone and tricyclic antidepressants on uptake of selected neurotransmitters by isolated rat brain synaptosomes. The effect of trazodone, a new antidepressant agent, on uptake of serotonin (5-HT), norepinephrine (NE), and dopamine (DA) by crude synaptosome preparations from rat hypothalamus was compared with imipramine, desipramine, and clomipramine. Trazodone was determined to be a very selective inhibitor of the 5-HT uptake mechanism with IC50 values of 5.67 X 10(-7), 3.54 X 10(-5), and 5.25 X 10(-5 M, for 5-HT, NE, and DA uptake, respectively. Clomipramine, the only other selective inhibitor of 5-HT uptake studied, had IC50 values of 7.59 X 10(-9), 1.12 X 10(-7), and 2.51 X 10(-7) M, for 5-HT, NE, and DA, respectively. Although less potent, trazodone was 4 +/- 0.6 times more selective than clomipramine in its ability to inhibit synaptosomal uptake of 5-HT with respect to NE. This selectivity for the 5-HT uptake mechanism is consistent with the clinical antidepressant efficacy of trazodone.


Ultrasonographic demonstration of undescended testes. Twelve cryptorchid patients had sonographic evaluation of the inguinal region prior to surgical orchiopexy. When the testis was within the inguinal canal, the gonad was localized preoperatively by sonography in eight of nine patients. One patient had an associated inguinal hernia in which loops of bowel concealed the gonad. There were no false positive cases. The authors were not able to show abdominal or pelvic maldescended testes.


Effect of mercaptoethanol in the radioactive thin layer chromatography assay of NAD+-15-hydroxyprostaglandin in dehydrogenase. The use of mercaptoethanol in the assay of rat kidney 15-hydroxyprostaglandin dehydrogenase (PGDH) was found to have minimal effect on activity assayed with the spectrophotometric and substrate loss assays. However, mercaptoethanol appeared to inhibit PGDH when assayed by thin-layer chromatography, based upon conversion of 3H-PGE1 to 15-keto-3H-PGE1. Mercaptoethanol reacted with 15-keto-PGE1 to alter its chromatographic mobility and to suppress the U.V. absorption spectrum of 15-keto-PGE1. The implication of the use of ME in radiometric assays is discussed.


Physician's assistants in primary care practices: delegation of tasks and physician supervision. Little information is available on factors influencing physicians (MDs) to delegate health care tasks to physician's assistants (PAs). Information about assignment of tasks to PAs was sought from 19 MDs engaged in practice in primary care settings in Iowa. These MDs employed 28 PAs. Tasks assigned to PAs appeared to be those that MDs judged to require little or no supervision. Tasks that could be performed efficiently by other non-MD personnel were not asigned to PAs. However, PAs were observed at the practice sites to perform tasks which the MDs had indicated could be appropriately assigned to PAs, as well as some tasks that could be performed by other non-MD personnel. The MDs provided health care to 126 (13.6 percent) of the 925 patients seen by PAs for whom the sequences of patient-provider contact were recorded. In these settings, the PAs functioned with a high degree of autonomy in providing health care. These findings have implications for educators and potential employers of PAs.


[Preconcentration of trace chalcophile elements by a zincon--loaded resin and its application to neutron activation analysis (author's transl)]. A chelating agent-loaded resin consisting of an anion exchange resin and zincon which has widely been employed as a specific reagent for zinc(II) and copper(II) in spectrophotometry was prepared. The adsorption behavior of some chalcophile elements was studied in detail, with respect to pH, flow rate and exchange capacity. From the results, it was confirmed that the zincon-loaded resin reacts selectively with copper(II), zinc(II), mercury(II) and lead(II) at lower pH region, and the above reaction is stoichiometric as in the case of the reaction of zincon with metal ions in aqueous solution. Furthermore, the zincon-loaded resin was applied to the selective concentration of trace amounts of chalcophile elements in natural water samples prior to neutron activation analysis. Water samples taken from the Watarase River were filtered and the pH of each filtrate was adjusted to ca. 5.5. After preconcentration was made by the column method (zincon-loaded resin: 2 x 10-4 mol/g resin, 1.0 g, 7 mm phi x 35 mm), the resin in the column was washed and dried in a desiccator. The standard material was also prepared according to the above mentioned scheme. The sample and the standard materials packed in polyethylene vials were irradiated for 40 min by a neutron flux of 5 x 10(13 n.cm-2.sec-1 in the JRR-4 of the Japan Atomic Energy Research Institute. After cooling the materials, activity measurements were made. The results were 53 ppb for copper, 0.25 ppb for mercury.


[Polyarteritis nodosa: evolution of the angiographic findings and uncommon localizations (author's transl)]. A series of 10 patients with polyarteritis nodosa have been studied by means of angiographic investigations with selective arteriography of the different visceral districts. The attention is focused on some unusual localizations of the typical lesions such as aneurysms of the supra-renal artery of the coronary artery and of the femoral artery. Up to now these localizations have been described only in post mortem examinations. Such localizations should be considered as a demonstration of the multicentric spread of the disease, independently from its degree of development. On the other hand a correlation seems to exist between the evolution of the disease in the increase in size of the aneurysmatic lesions as well as with the simultaneous presence of all the angiographic signs.


[Radiological study of panarteritis nodosa with renal localization. Considerations on 9 cases]. The pathologic lesions in panarteritis nodosa with renal involvement are of two types: macroscopic and microscopic. The diagnosis of the macroscopic form is made with angiography when it discloses diffuse aneurysms. The angiographic features of the microscopic form are not distinguished from those of other renal parenchymal diseases. Plain films of the abdomen and urography are insufficient for diagnosis but they can be useful in the follow up of the panarteritis nodosa.


Selenium and gamma-glutamyl transferase activity in the serum of thoroughbreds. Selenium and gamma-glutamyl transferase activity has been measured in the serum of clinically health thoroughbreds. The thoroughbreds, whose performance was reported to be unsatisfactory, had consistently low concentrations of selenium and high activity of gamma-glutamyl transferase in the serum when compared with those whose performance was as expected. Vitamin E levels in the serum showed no such difference. The only other biochemical and haematological abnormality was lower serum phosphate concentrations in the unsatisfactory group. These results suggest that low concentrations of selenium in the serum may be associated with subclinical hepatic insufficiency in the thoroughbred.


Pathophysiology of dehydromonocrotaline-induced pulmonary fibrosis in the beagle. The purpose of this study was to characterize the sequential hemodynamic alterations and pulmonary vascular lesions produced by a single pulmonary artery injection of the vasotoxic pyrrolic alkaloid dehydromonocrotaline in the young beagle. Normotensive pulmonary pressure was replaced by hypertension 21 days after injection. By 28 days, the pulmonary pressure and total pulmonary vascualr resistance of the experimental animals were significantly greater than the controls (p less than 0.01). Right ventricular work increased from a baseline mean of 0.58 to 1.40 kg . m/min. Morphological and morphometrical analyses revealed alveolar edema, increased numbers of alveolar macrophages, cellular hyperplasia in the alveolar septa, and a progressive interstitial fibrosis. The precise mechansims by which dehydromonocrotaline injection initiates and promotes pulmonary hypertension and pulmonary fibrosis still needs clarification; however, our data indicate that the fraction of air space is reduced relative to the fraction of tissue space, and this change occurs with concurrent fibrosis in the alveolar septa and an increased pulmonary arterial pressure although hypoxia was not clinically detectable.


Bronchial reactivity in asthma to inhaled histamine during treatment with ketotifen. A 12-week open trial using varying dosages of ketotifen, an oral drug with a prophylactic anti-asthmatic effect, was carried out in 20 patients with stable chronic bronchial asthma (age 20--50 years, no steroid treatment) to determine whether the frequency of asthma attacks and bronchodilator consumption could be reduced, and whether pulmonary function would improve. The protective action of ketoifen against a histamine inhalation test was measured at the beginning of the trial and at regular intervals during the trial. The patients experienced a significant improvement in their asthma and a significant decrease in the number of asthma attacks during the trial. Concomitantly, the need for other anti-asthma agents was reduced. Pulmonary function tests improved before and following histamine inhalation after 4, 8 and 12 weeks of treatment. In some patients cromoglycate was successfully replaced by ketotifen. Efficacy was rated as very good or good in 17 patients and moderate in 3 patients. Tolerance was good in all patients, no serious side-effects were observed. Summing up, it may be stated that ketotifen is a compound which by virtue of its activity profile and route of administration offers a new approach to the prophylactic treatment of bronchial asthma.


Acid-base balance of pleural liquid in dogs. Acid-base balance and electrolyte concentrations were measured in dogs on small artificial hydrothoraces and in vitro on bicarbonate buffered Ringer solution on serosal and interstitial side of specimens of parietal pleura. Under steady conditions, pleural liquid PCO 2 was similar to and pH higher (delta = 0.022 +/- 0.006 SE) than that in mixed venous blood. Computed pleural liquid [HCO-3] was similar to that in venous plasma and hence less than that set by the Donnan effect, with which Na+ and Cl- approximately complied. In vitro, pH, [Na+], [Cl-], and computed [HCO-3] were significantly lower (delta = 0.030 +/- 0.004; -2.6 +/- 0.5; -1.2 +/- 0.5 and -1.7 +/- 0.2 meq/L, respectively) on the serosal than on interstitial side of pleural specimens, PCO2 being 42 mm Hg on both sides . HCO-3 and Na+ were not distributed according to transpleural potential (-0.4 +/- 0.1 mV on serosal side), suggesting an active transport of Na+ and HCO-3 from pleural liquid to blood. This, however, does not seem to add to the absorption pressure of plasma proteins in setting pleural liquid pressure.


Successful treatment with prednisone and graft-versus-host disease in an allogeneic bone-marrow transplant recipient. A 51-year-old patient with aplastic anaemia in whom a successful allogeneic bone-marrow transplantation had been performed developed acute graft-versus-host disease in spite of prophylactic administration of methotrexate. There was severe liver injury but no involvement of the skin or intestines. When prednisone therapy was introduced the fever and the eosinophilia disappeared and liver damage was rapidly reversed. There was no haematological impairment. It would seem warranted to consider a wider use of prednisone in the treatment of acute GVHD in human recipients of allogeneic bone-marrow.


[Physiopathological and clinical aspects of Parkinson disease. Current problems]. Some interpretative hypotheses of the most important symptoms of Parkinson's disease are formulated, on the ground of acquired neurohistopathologic elements and in the light of new observations of experimental neuro-physiology. The possible role of the inferior olivary body in the genesis of parkinsonian tremor is pointed out. The psycho-behavioural disorders and among these the severe weakness of pulsional control and the scanty elaboration of the affective-emotional motivation would be in relation, according to the Authors, to the involvement of the pallido-habenular pathways and the habenuloreticular midbrain outflow (limbic midbrain area).


Antipsychotic drug action in schizophrenic patients: effect on cortical dopamine metabolism after long-term treatment. In the brains of deceased schizophrenics who underwent long-term treatment with antipsychotic drugs, the concentration of homovanillic acid (a dopamine metabolite) was significantly increased in the orbital frontal, cingulate, and temporal tip areas of the cortex, but not in the putamen or the nucleus accumbens. The concentration of homovanillic acid was normal in the brains of schizophrenics who were not treated with drugs.


Acetaminophen: potentially toxic metabolite formed by human fetal and adult liver microsomes and isolated fetal liver cells. A reactive metabolite of acetaminophen is hepatotoxic in humans when the drug is ingested in large overdoses. The ability of the human fetal and adult liver to oxidize acetaminophen by trapping the potentially toxic metabolite as a glutathione conjugate has been measured. Oxidation by fetal liver was approximately ten times slower than by adult liver. However, there was a definite increase in acetaminophen oxidation with fetal age. Isolated human fetal liver cells conjugated acetaminophen with sulfate but not with glucuronic acid. The results indicate that the human fetal liver is able to detoxify acetaminophen by conjugation. However, it also catalyzes the formation of an active metabolite of acetaminophen through oxidation. Hence the fetus remains at risk should a large dose of the drug cross into the fetal circulation.


[Therapeutical study in patients admitted to an emergency unit (author's transl)]. In an emergency Unit tiaprid has been used in: acute alcoholism and delirium or pre-delirium states. Good results have been obtained with 200 mg (IV) possibly repeated every twenty minutes.


[The treatment of essential cramp muscular (author's transl)]. The cramp in usual practice of practitioner are to difficult treatment such their appeared of different origin. The tiapride that we have used to the dose of 200 to 400 milligrams of 24 hours. We have seemed to have a very clean activity on the cramp ask essential, which are very frequent in practice of practitioner.


[Kinetics of action of Vectarion. Ventilatory chemo-stimulant (author's transl)]. Vectarion has a powerful respiratory stimulant effect in animals and in man which is manifested by a significant and lasting increase in ventilation, as shown by a marked lowering of arterial P. CO2 and an increase in blood pH. This activity is maintained in dogs with experimental alkalosis or acidosis as well as during morphine or oxygen-induced respiratory depression. This respiratory stimulating action originates at the level of the aortic and carotid chemo-receptors: this explains why Vectarion is devoid of any epileptogenic risk. The aim of the present study was to demonstrate the peak of activity and duration of action of an intravenous perfusion of Vectarion, in such a way as to be able to plan administration all through the day and night.


Duodenal ulcer in the new-born (author's transl). A new-born baby was found to have a duodenal ulcer after developing a severe hematemesis 24 hours after birth. The diagnosis was established by fibroscopic examination, which was also used to follow progress in this case, in which operation for a secondary hypertrophic stenosis of the pylorus led to a favourable outcome. The role of "stress" and, more particularly, gastric hyperacidity in the neonatal period are discussed. Once the critical period is passed, during which hemorrhage and perforation are the cause of the high mortality, recovery is complete.


[New therapeutics import in clinical manifestations on alcoholism (author's transl)]. The nutritional and neurologic manifestations of alcoholism can be corrected by neutralizing the topic effects of the alcoholemia on neurologic centers and the resultant metabolic excesses. Tiapride has obtained its preferencial action on the mesolimbic region, interesting therapeutic results in the different clinical forms of this type of intoxication.


[Therapeutical trial in recovery room (author's transl)]. During a limited period of time, the authors have systematically administered tiapride to all patients in the immediate post-operative phase presenting with: nausea, vomiting, pain. Intravenous injection of a single dose of 400 mg of tiapride produces: a strong anti-emetic action; an inconstant analgesic action, but very interesting for it is not accompanied with adverse effects.


[Advances on prolactin (author's transl)]. Prolactin has been lately singled-out among the pituitary hormones, and as such the object of considerable research in the past 15 years. The frequency of prolactin secreting adenomes is established now. The responsability of iatrogenic factors (neuroleptics, oral contraceptives) in some hyperprolactineamias is a known fact. The study of the inhibiting dopaminergic system was a landmark in the treatment of hyperprolactinaemia. During the recent Nice Congress, some issues remained unsettled on the physiological activities of prolactin. The matter is clearer when its comes to prolactin secretion. In equilibrium between inhibiting and stimulant factors, the secretion is controlled by the CNS, influenced by the hormonal environment, and its timing is the object of a retrocontrol. This is a very instructive pattern in endocrinology.


Strategies for using and evaluating physician assistants and family nurse practitioners. New health practitioners are no longer new on the medical scene, but they still present a radical innovation in the provision of medical care. As such, they pose both rational and emotional threats to physicians, nurses, and administrators. Two pivotal questions related to their acceptance and use will be discussed in this presentation: (1) How can new health practitioners best be introduced to office and hospital health workers? (2) How much responsibility can these new health workers be allowed? Strategies and tactics for the introduction and honest evaluation of these new health workers will be provided.


[Abnormal movements and shaking in geriatrics (author's transl)]. The authors have experimented tiapride in 37 cases of abnormal movements and 20 cases of shaking anxio depresive origin. The best indication of tiapride corresponds to lingual buccal an facial dyskinesia caused by neuroleptics and senile trembling increased by alcoholism. On the other hand its anxiolytic and anti shaking properties are more limited. Finally in the case of degenerative senile trembling its action is less effective. Tolerance to tiapride seemed to be excellent even at high dose.


[Recurrent attacks of facial neuralgia (author's transl)]. The author reports one case of sedation by tiapride of severe and recurrent attacks of facial neuralgia. Knowing the rather poor therapeutic means for this disease, it is suggested to extend the use of this recent neurotropic drug to this purpose.


Influence of long-term citro-soda ingestion on acid-base balance and blood gases. Citro-Soda (Abbott), 4 gram every 6 hours, was administered orally over a period of 8 weeks to 20 healthy female volunteers, and its influence on acid-base, urinary pH and other biochemical parameters was assessed. The mean urinary pH increased from a basal value of 6,0 to 7,4 after 7 days, and to 7,7 after 8 weeks. Blood pH increased significantly during the first 2 weeks only, and then returned to basal values. Likewise, the base excess and standard bicarbonate values increased significantly during the first 2 weeks only. The PO2 and PCO2 remained within normal limits for the duration of the trial. Electrolyte values and liver and kidney function showed no abnormality. Thus, in subjects with normal renal function, Citro-Soda appears to be safe for long-term use in a dosage adequate for sustained urinary alkalinization.


The MEA-I syndrome: an all or none phenomenon? Studies of two kindreds with the MEA-I syndrome prompted us to challenge the long-standing concept that endocrine involvement in this syndrome may be limited to one or two endocrine glands. Evaluation of medical histories, autopsies, or biochemical screening of 72 family members from five generations suggests that individuals inheriting the trait will develop endocrinopathy in all three endocrine systems characteristically involved in this syndrome, i.e., parathyroids, islets of Langerhans, and pituitary. Thirty-six surgical procedures have been performed on 21 family members. Gastrointestinal bleeding was the cause of death in 10 of 11 affected individuals. Only two individuals who inherited the trait have lived beyond 54 years, one with a total gastrectomy and one taking Cimetidine. In each instance, when tissue from one of the three endocrine systems was obtained (surgery or autopsy), abnormalities were documented. A search of the English-language literature (1953 to 1978) for reports of complete autopsies of MEA-I-affected individuals indicated pathology in all three endocrine systems in 29 of 32 cases. Medical and surgical management of this inherited disorder should be based on the concept that pathological changes will develop in the parathyroids, pancreatic islets, and the pituitary.


Physical studies on isolated human prothrombin fragment-2. Comparisons with human prothrombin fragment-1. Variation of pH strongly affects the fluorescence intensity of human prothrombin fragment-1 in a manner suggesting contributions from a number of protropic equilibria including groups with apparent pKa values near 3.0. These results suggest a structural role for pK1a of gamma-carboxyglutamic acid noieties. Added calcium ions (9 mM calcium chloride) quench the fluorescence titration curve uniformly above pH 4. Below pH 4, however, the titration curve in the presence of calcium ions suggests that calcium-ion-dependent processes leading to fluorescence quenching are pH-dependent. Upon back titration of human fragment-1, from pH 9, hysteresis is observed. Human prothrombin fragment-2 fluorescence titration curves are relatively broad at low pH suggesting the titration of normal carboxyl groups. The titration curves of fragment-2 are not affected by the presence of calcium ions, and hysteresis occurs upon back titration from low pH values. Circular dichroism (CD) Cotton effects appear at 232 nm and 280 nm and a trough appears at 203 nm in the CD spectrum of human prothrombin fragment-2. The Cotton effects in the region from 230 nm to 300 nm are sensitive to pH, ellipticity values at 232 nm increasing from approximately 300 at pH 2.5 to 1300 (degree-cm/decimole) at neutral pH and finally become negative at high pH values. In contrast to fragment-1, at neutral pH the fragment-2 Cotton effect at 232 nm is insensitive to the presence of 8 mM calcium chloride.


Destructive corneal disease in the connective tissue disorders. Comparison with an experimental animal model. The corneo-scleral changes described are highly characteristic and may be the first signs of an underlying systemic disorder so that otherwise healthy patients who present with limbal guttering and scleral disease must be continuously monitored with this association in mind. The clinical and histological features of limbal guttering in connective tissue disorders strongly suggest that a local antigen-antibody reaction triggers off a number of biochemical and cellular responses which combine to produce lysis of scleral and corneal collagen, although immune complexes have not so far been demonstrated in these eyes. Modes of therapy aimed at one particular chain of events have varying degrees of success, as indeed does more blunderbuss treatment with steroids, anti-inflammatory drugs, or cytotoxic agents. The early stages of the ocular lesion in the rabbit are now being studied, as is the immunological basis for its production. It is hoped that further work with the animal model will lead to a deeper understanding of the pathogenesis of these conditions, which will turn provide both ophthalmologists and rheumatologists with more scientific guidelines for treatment.


Hydrogen ion excretion and urine osmolality in patients with obstructive uropathy secondary to Schistosoma haematobium. Sixty-one patients with urinary schistosomiasis were studied to determine the effects of obstruction and bacteriuria on renal function. 39 (12 with bacteriuria) had demonstrable obstruction and 22 (5 with bacteriuria) had no obstruction. Total hydrogen ion excretion (T.H.+) for obstructed patients with sterile urine did not differ from that in controls; patients with bacteriuria with and without obstruction had a significantly lower T.H.+ (all P values less than 0.05). Obstructed patients (with or without bacteriuria) had significant impairment of maximal (U max) and minimal (U min) urine osmolality. Patients with bilateral obstruction and bacteriuria had a significantly lower U max (P less than 0.01 than obstructed patients without bacteriuria. The T.H.+ is mainly associated with bacteriuria but that the effects of unilateral or bilateral obstruction and bacteriuria on urine osmolality are additive. These abnormalities are usually corrected after therapy.


Lactic acidemia in baboons after transfusion of red blood cells with improved oxygen transport function and exposure to severe arterial hypoxemia. Baboons were bled one-third of their blood volume and then transfused with an equivalent volume of compatible donor red blood cells with 160 per cent of normal 2,3-diphosphoglycerate (2,3-DPG) levels and improved capacity to release oxygen to tissue. The mixture of baboon donor-recipient red blood cells in the circulation had a 2,3-DPG level of 130 per cent of normal. After transfusion, the baboon's inspired oxygen was first lowered from 21 to 10 per cent to produce severe arterial hypoxemia with a PO2 tension of less than 40 mm Hg for two hours and then restored to 21 per cent. Lactic acidemia occurred when the alveolar oxygen tension was reduced so as to produce an arterial oxygen tension of less than 40 mm Hg, even though oxygen consumption was maintained. The data suggest that when red blood cells with normal or improved oxygen delivering capacity are transfused to patients, the alveolar oxygen tension should be sufficient to maintain an arterial oxygen tension of greater than 40 mm Hg.


[Activation of plasminogen with immobilized trypsin]. Human plasminogen isolated from the placenta serum fraction by means of affinity chromatography was activated by trypsin being in covalent bond with sepharose. The activation is studied as dependent on pH, temperature and the proenzyme-activator ratio in the presence of 25% glycerol as a stabilizing agent and without it. Utilization of the immobilized trypsin as a plasminogen activator makes it possible to transform completely the proenzyme to plasmin varying the plasminogen-trypsin ratio and time of activation when it is conducted under optimal conditions: in the presence of 25% glycerol at pH 7.0-7.1 and the temperature of 30 degrees C.


[Properties of immobilized complexes of Streptomyces griseus proteases on different carriers]. A complex of Str. griseus proteases was obtained. The proteases were immobilized on Sephadex G-200 and agarose by the bromo-cyanogen method and on the microcrystalline cellulose by means of TiCl3. The enzymic complex immobilized on different carriers possesses the proteolytic activity of a wide specificity. Due to addition to different carriers the activity of certain enzymes producing the complex varies. The immobilized complex is shown to be more stable in the alkaline zone. The immobilized complex is shown to be more stable in the alkaline zone. The temperature optimum of the activity of the immobilized forms is higher than in the initial enzyme and is 70--75 degrees C. Under multiple application of the immobilized forms of the protease complex the preparation obtained on Sephadix G-200 by the bromo-cyanogen method is most stable: it retains 70% of initial activity after 10-repeated applications.


[The influence of uric acid on the calcium oxalate stone formation (author's transl)]. Statistic analysis of data from 209 calcium oxalate stone patients and 42 stone-free patients pertinent to the concentration and excretion of uric acid in urine and of uric acid levels in the serum yielded no significant difference between the two groups. Only 17% of the calcium oxalate stone patients suffered from hyperuricuria and hyperuricemia was found only in 15% of these patients. Based on these findings, our in-vitro experiments as to the influence of uric acid on calcium oxalate stone formation yielded the following results: firstly, precipitates in urine form only at uric acid concentrations which in-vivo are rate exceptions humans, and secondly, the precipitates at pH 5.5--6.0 always contain uric acid, and a precipitation of calcium oxalate only is never observed. From the experiments one has to conclude that there exists no "salting-out effect" of uric acid on calcium oxalate in urine but rather that precipitate formation reflects the individual solution- and crystallization characteristics of the precipitating compounds.


[Immobilization of aspergillus oryzae aminopeptidase on organic and inorganic carriers]. The process of Asp. oryzae aminopeptidase immobilization on organic (AE-cellulose, sepharose 4B, Sephadex G-200) and inorganic (SCh-2, SCh-3 sylochromes and KCK N 1 silicagel) carriers was studied. Aminopeptidase immobilized on Sephadex G-200 contains the largest amount of protein (80 mg per 1 g of carrier) and is the most active of all other preparations. The immobilized preparations retain the temperature optimum, like the soluble form, at 60 degrees C, except the preparation immobilized on AE-cellulose (50 degrees C). At temperatures of 70, 80 degrees C the obtained preparations are more thermostable than the initial enzyme. The pH-stability zone for the preparations immobilized by means of sylochrome-3 and Sephadex G-200 is wider to some extent as compared to the soluble enzyme. When studying the substrate specificity it is established that leucyl-glycyl-glycine is the best substrate for both the soluble form and the immobilized preparations. Multiple application of the immobilized aminopeptidase is shown to be possible.


In vitro study of phenothiazine effects on urinary bladder. Clinical observations suggest that long-term phenothiazine therapy can cause urinary retention and stress incontinence. The phenothiazines, chlorpromazine and perchlorperazine, depress bladder smooth muscle activity in vitro by depressing bladder smooth muscle activity directly and by a peripheral cholinergic blocking action.


[Immobilization of Penicillium vitale glucose-oxidase on aminosilochrome and properties of immobilized enzyme]. Penicillium vitale glucose-oxidase modified by means of the carbohydrate component oxidation is added covalently to aminoorganosylochrome. The activity of the immobilized preparations is 20-38% depending on the protein-carrier ration in immobilization. Comparison of some properties of native and immobilized glucose-oxidase showed that the rH optimum of the immobilized glucose-oxidase is slightly widened towards the alkaline regions; the immobilized glucose-oxidase possesses a considerably higher pH-stability at pH alkaline values; the immobilized glucose-oxidase preparations are characterized by a significantly greater thermostability: their thermoinactivation constant at 65 degrees C is 8-10 times lower than that of the native enzyme.


[Properties of amylase immobilized on aerosil derivatives]. The properties of three preparations of alpha-amylase immobilized on aminoaerosil by 2,4-toluylenediisocyanate and N,N'-dicyclohexylcarbodiimide as well as on carboxyaerosil by N,N'-dicyclohexylcarbodiimide were compared with the properties of soluble enzyme. Under immobilization the pH-effect and pH-stability zones of amylase are 0.5--1.0 pH units shifted towards the alkaline region. The preparations in which the enzyme is bound with the matrix through the amine groups on carboxyaerosil by N,N'-dicyclohexylcarbodiimide and on aminoaerosil by 2,4 toluylenediisocyanate are the most stable at 50 degrees C and to the EDTA effect. The preparation obtained by means of 2,4-toluylenediisocyanate contains a greater amount of the bound protein, is more active and stable.


Formaldehyde-fluorescamine-induced fluorescence as a property of carcinoma cells. Fluorescamine is a sensitive cytochemical probe for primary amino groups and produces an intense general fluorescence in unfixed tissue sections reflecting the ubiquitous occurrence of such groups. Following treatment with formaldehyde, most primary amino groups react to form derivatives unable to yield fluorescence with fluorescamine. Certain cell systems, however, contain amino groups which do not react with formaldehyde but display strong reactivity with fluorescamine. In formaldehyde- and fluorescamine-treated specimens such cell systems display an intense fluorescence, whereas the majority of tissue constituents are non-fluorescent. Fluorescent cell systems include certain protein- and peptide-secreting cells and a large number of different types of carcinoma cells. In some cases it appears that neoplastic transformation is necessary before the cells display formaldehyde-fluorescamine-induced fluorescence. Available data indicate that the reactive substance(s) are peptide in nature and that the production of such substance(s) may be a general property of carcinoma cells.


Histochemical studies on carbohydrate metabolism in rat liver after galactosamine administration. The development of hepatitis, induced in 48 rats by the administration of galactosamine (GalN) in varying doses, was studied with the use of substrate and enzyme histochemical techniques. The so-called atypical glycogen, which is at first highly resistant to diastase, was shown to be digestible after deamination. The increasing accumulation of atypical glycogen during the course of GalN-hepatitis conceals the loss of normal glycogen when the PAS-reaction is used. Nevertheless glycogenolysis could also be demonstrated by the increasing activity of phosphorylase. The acid phosphatase activity was progressively diminished, which was interpreted as signifying early lysosomal damage. G6Pase activity remained nearly constant but SDH showed a decrease in activity after 12 h. These histochemical results are considered to provide deeper insight into the pathological mechanism of GalN-hepatitis.


Ultrastructural localization of apo-b and apo-c binding to very low density lipoproteins in rat liver. Hepatic synthesis of apo-B and apo-C and their binding to nascent very low density lipoproteins (VLDL) have been studied in fat-fed rats. Apolipoproteins were located in hepatocyte organelles by light and electron microscopy after immunoenzymatic staining using peroxidase-conjugated antibodies. Our results indicate that apo-B and apo-C are synthesized by membrane-bound ribosomes. Both apoproteins seem to be adsorbed simultaneously to the lipid core of VLDL in the lumen of the endoplasmic reticulum channels, at the junction zone between rough and smooth endoplasmic reticulum. Some additional protein presumably binds nascent VLDL in the Golgi apparatus as judged by the strong positive reaction of lipoprotein particles with peroxidase-labeled antibodies. Finally our data show that significant amounts of apo-B and apo-C are bound to the sinusoidal plasma membrane in fed rat livers which probably represent remnants of lipoprotein of intestinal origin since membrane-bound apolipoproteins virtually disappeared 24 h after lymphatic duct cannulation. It is suggested that nascent VLDL (apo-C poor) could be enriched in apo-C from lipoprotein remnants at the space of Disse.


Experimental study of follicle formation in suppressed parathyroid glands of Mongolian gerbils. Parathyroid follicle formation was studied in Mongolian gerbils subjected to different concentrations of calcium in vivo and in vitro, using light and electron microscopic methods, including the potassium pyroantimonate technique and x-ray microanalysis for identification of cations. Follicles were frequent at high calcium concentration, but sparse at intermediate and low levels of calcium. Two main types of follicle were differentiated: "degenerative follicles" containing cellular debris and lined by smooth-surfaced epithelium which occasionally showed degenerative changes; and "secretory follicles" characterized by amorphous and granular contents, and an epithelium possessing microvilli and cytoplasmic projections. Amorphous masses were also seen in dilated intercellular spaces and in dilated cisterns of rough endoplasmic reticulum in the follicle epithelium. Calcium-containing precipitates were found in degenerating chief cells, and between degenerating cells and follicles. Parathyroid follicles are believed to be formed by degeneration of suppressed chief cells (degenerative follicles), and by secretion of hormonal and/or other substances into dilated intercellular spaces which progressively increase in size to form follicular cavities (secretory follicles), thereby possibly reducing the level of metabolically active parathyroid hormone. Functional suppression is believed to underlie the development of parathyroid follicles.


Occurence and cytodifferentiation of mucopolysaccharide secreting cells in the pancreas of children with nesidioblastosis. Large numbers of mucopolysaccharide secreting cells were found in the pancreatic tissue of children with nesidioblastosis. Ultrastructural studies showed that mucus cells contained secretion granules and a characteristic smooth endoplasmic reticulum composed of an array of anastomosed tubules. The periodic acid - thiocarbohydrazide - silver reaction demonstrated the presence of glycogen in the hyaloplasm and of polysaccharides in secretion granules, the Golgi apparatus and in vesicles. A hypothesis is proposed, according to which mucus cells differentiate from a pancreatic stem cell common to both endocrine and exocrine tissues, through a mitochondria-rich intermediate cell stage.


Effect of iodide-deficiency on rat mammary gland. When rats are kept iodide-deficient, atrophy and necrosis takes place in the mammary gland and areas of dysplasia and atypia are seen. Administration of estradiol to iodide-deficient rats stimulates cell division in the gland and leads to the formation of alveoli. Continued stimulation by estradiol produces changes in the newly-formed alveolar cells. Their nucleoli are altered and show a separation of components. Ribosomes and lipid droplets increase and the cells synthesize large vacuoles containing protein. The secretion of great quantities of this material into areas of the tissue where regressive changes have occurred undoubtedly contributes to the formation of cysts within the gland. The present findings indicate that iodide-deficiency alters the structure and function of mammary gland alveolar cells and makes them highly sensitive to stimulation by estradiol.


A model for the study of epithelial migration in wound healing. A model is described which enables the detailed study of epithelial regeneration in experimentally produced lesions in the common bile duct of the rabbit. The circular on slightly oval defect of 1 mm diameter produced by a specially developed apparatus has a perfectly smooth base. Epithelial migration in this model has been investigated using light microscopy of transverse sections and scanning electron microscopy of whole preparations. Typical changes in the border cells, characterised by the formation of tapered protusions, can be observed as early as two hours after the lesion has been made. Later the cells in the flattened edge of the moving border also show various types of protrusion which rest on the substratum. Mitotic activity in the surface epithelium and crypts in the surrounding region only increases after closure of the lesion, which usually takes place within 16--24 h.


Surface configuration of mesothelial cells in effusions. A comparative light microscopic and scanning electron microscopic study. Surface configuration of mesothelial cells identified by light microscopy (LM) has been studied by scanning electron microscopy (SEM). It has been shown that mesothelial cells may have a variable SEM appearance. The surfaces of a small proportion of mesothelial cells are covered by regular microvilli (MV) and show openings of the pinocytotic vesicles. The surfaces of the majority of these cells are covered by vesicles or blebs. An intermediate population of mesothelial cells, i.e., cells  displaying side-by-side blebs and MV, has also been observed. The latter cells no longer display pinocytotic vesicles. Occasional mesothelial cells have smooth surfaces. It has been shown by LM and transmission electron microscopy that cells with blebs are viable and capable of mitotic activity. It is concluded that mesothelial cells, detached from their epithelial setting, lose microvilli and pinocytotic vesicles and acquire surface blebs. The possible relationship between mesothelial cells and macrophages based on surface features has been discussed.


[Use of aerosils in activating plasma prekallikrein]. Activation of prekallikreine from human blood plasma was studied using silica (airsiles), which carried functional groups with acidic and alkaline properties on the surface. Prekallikrein was similarly activated by amino- and carboxyairsiles, possessing positive and negative electric charges, respectively, at neutral pH value in a medium. Lysozyme, ribonuclease and spermidine inhibited partially the prekallikreine activation; spermine inhibited it completely.


The effects of cytochrome P-450-448 inhibitors on the binding of benzo(a)pyrene and derivatives to DNA upon microsomal activation. 1. [3H]Benzo(a)pyrene and 6-substituted derivatives of [3H]benzo(a)pyrene are covalently bound to calf thymus DNA upon reaction with microsomal preparations from rats pretreated with 3-methylcholanthrene in the presence of NADPH. Two different types of cytochrome P-450-448 inhibitors, alpha-naphthoflavone and 1-benzylimidazole, show greater than 80% inhibition of the binding of benzo(a)pyrene to DNA. 2. In the presence of these inhibitors, 6-hydroxymethylbenzo(a)pyrene, 6-methylbenzo(a)pyrene and 6-formylbenzo(a)pyrene show varying degrees of inhibition of binding to DNA depending upon the inhibitor employed. 3. Polyguanylic acid is the most effective substrate for the binding of each activated polynuclear aromatic hydrocarbon; polyadenylic acid and DNA show essentially equivalent binding.


[Diagnosis of histidinemia through using the determination of urocanic acid in the sweat by an enzymatic method]. A diagnosis of histidinemia was confirmed by estimation of urokaninic acid in sweat using highly purified preparation of urokaninase from rat liver tissue. The content of urokaninic acid was estimated by the method developed and by means of a known chemical method, which involved reduction of urokaninic acid with zinc in a medium containing HCL; seven children with histidinemia and ten healthy children were examined. The diagnosis of histidinemia was confirmed since the content of urokaninic acid was distinctly decreased in sweat of the imparied children as compared with the control group. The method developed was highly sensitive, reproducible and accurate.


[New viewpoints in the pathogenesis and therapy of bronchial asthma]. The bronchial asthma is a polyetiologic syndrome with increased bronchomotoric excitability. The most important forms are the allergic asthma, the infection-conditioned one, the asthma conditioned by analgetics, the exertion and the irritation asthma. Apart from the direct affections on the smooth musculature and other target cells reflectorical mechanisms play an essential part. The first above all operate in the smaller respiratory tracts and stand in the foreground in the allergic bronchial asthma. The latter have above all an influence on the larger bronchi and are to be found in a typical way in irritation asthma. However, the transitions are fluent. The differentiation of the responsible mechanisms and the localisation of the bronchial obstruction give the possibility of a more aimed treatment. An essential improvement of the -- symptomatic -- treatment might be achieved, when the factors of the increasing bronchomotoric excitability are better known.


Ultrastructural peculiarities of the chemical transmission of the nerve impulse in the gravity receptors of some invertebrates. Electron microscopic and cytochemical studies of the synapses of the gravity receptors in Coelenterata, Ctenophora, Annelids and Molluscs has shown the mediators both of cholinergic and adrenergic systems. As a rule, the two mediatros were connected with different receptor systems (Ctenophora) or with the synaptic structures of various parts of the chain: receptor--neuron--effector (Medusa, Annelids). The synaptic transmission in the gravity receptor of studied molluscs classes is carried out by means of either cholinergic or adrenergic systems.


[Relationship between interhemispheric irradiation of excitation and the individual characteristics of the animal]. The changes in irradiation coefficient (the ratio between the value of secretion resulting from interhemispheric irradiation of secretion and the main one secreted on the side of excitation evaluated in per cent) were studied in norm and under different functional loads in dogs with exposed symmetrical parts of the tongue following the method of K. S. Abuladse. It is shown that dogs with low and mean level of irradiation of excitation have good mobility of nervous processes and rapid excitation in homonomous structures whereas dogs with high coefficient of irradiation demonstrated inert nervous processes and were not able to show a clear one-way reaction during interhemispheric interaction. A group of dogs with sharply pronounced asymmetry in coefficient of irradiation to the right and to the left is described. This description permitted an assumption about functional heterogeneity of the hemispheres. The obtained data showed that the character of interhemispheric irradiation is determined by individual characteristics of animals.


Factors affecting the microbial and chemical composition of silage. IV. Effect of wilting on maize silage. The effect of wilting on the microbial and chemical composition of ensiled maize plants was studied. Wilting stimulated high densities of lactic acid bacteria, with the decrease in counts of undesirable flora, i.e., yeasts, moulds, proteolytic and saccharolytic anaerobes, causing spoilage of silage. Moreover, wilting decreased the losses of dry matter, total acidity, and butyric acid content of silage. Accordingly, wilting proved to be a favourable treatment for the production of good quality silage from maize plants.


[Metabolism of ammonium compounds by Azotobacter chroococcum (author's transl)]. A study on the metabolism of ammonium sulphate, amino acids, peptides, and nutrient broth by Azotobacter chroococcum is presented in this paper. Some of the amino acids studied lowered the pH of the medium while others alkalinized it. After prolonged incubation desamination could be observed. Peptides were hydrolyzed in some cases, although glycyl-glycyl-glycin was not degraded. A certain amount of growth could be observed with peptone as a sole source of carbon. Both nitrogen fixation and growth were stimulated by nutrient broth, but the medium was alkalinized when a higher concentration of nutrient broth was used, due to the production of ammonia.


Production of cellulase (Cx) by different species of Erwinia. The tested isolates of Erwinia chrysanthemi (corn pathotype) and E. carotovora constitutively produce high levels of cellulase(s) (Cx) in presence or absence of carboxymethyl-cellulose (CMC) as substrate in the medium. The tested isolates of E. atroseptica produced high levels of cellulase when grown in presence of both carboxymethyl-cellulose (CMC) and sucrose, low levels in presence of carboxymethyl-cellulose alone, and traces of cellulase(s) in presence of sucrose alone. The activity of cellulase(s), present in culture supernatants of E. chrysanthemi (corn pathotype) and E. carotovora, occurred in a broad range of pH value (2.2--9) with an optimum pH ranging from pH 4 to 7. However, the activity of cellulase(s), present in culture supernatant of E. atroseptica, occurred in a narrow range of pH value (3--7) with an optimum of about pH 5.


[Freeze fracture study of vesicle attachment sites during mediator liberation in spinal motoneuron synapses]. Freeze-fractured appearances of vesicle attachement sites (VAS) in presynaptic active zone were studied in the spinal cord of 4-aminopyridine (4-AP) treated and nembutalized rats. The VAS were classified into: type 1 containing no intramembranous particles, type 2 with particles around the edge of openings, type 3 containing several particles within the VAS. The application of 4-AP, which is known to enhance transmitter release, affected strikingly the total number of VAS (p less than 0.001) but not the proportion of the three types. The predominance of type 3 outside the active zone and its similarity to particle-loaded indentations possibly corresponding to coated vesicle formation, suggested that type 3 may represent endocytosis. It is likely that the remaining two types represent exocytosis.


[Evolution of neuronal connecting mechanisms: electrical, mixed and chemical synapses]. Investigation of the mechanisms of junctional transmission in the isolated spinal cord in cyclostomes, amphibians, reptilia and mammals reveals the decrease in the number of electrical synapses during evolution from primitive to more advanced vertebrates. Electrical transmission is lacking in reptilian and mammalian cord. On the basis of these data, the analysis of the unitary EPSPs evoked in motoneurons of the lamprey and frog by intracellular stimulation of reticulospinal axons and primary afferent fibers and dendrodendritic interaction between motoneurons, a hypothesis is advanced that neurons of similar type may communicate through pure electrical junctions, whereas successive synaptic articulations between different functional groups of neurons are formed by mixed or chemical synapses. The cellular mechanisms controlling interneuronal communications are discussed.


[Changes in alkaline and acid proteins in a chronic epileptiform focus]. The acid and alkaline proteins were studied histochemically in neurons of the mirror epileptiform focus (frontal-parietal cortex of rats) on the 11th and 63rd days following cobalt implantation. A specific localization of such proteins was established. During experiments alkaline proteins demonstrated more marked changes than acid ones. The conclusion is made that alkaline proteins play an important role in the protein metabolism of neurons in an epileptiform focus.


[Neuromediators and neuromodulators. Evolution of compounds and the evolution of hypotheses]. Probable peculiarities of evolution of neurotransmitters (NM) and neuromodulators (NR) of various types are discussed. The hypothesis of higher evolutionary rate of peptide NM and NR, and of more diverse possibilities of the formation of this type of NM and NR is suggested. Monomolecular MN and NR are presumably more conservative, although they exhibit some advantage with respect to strict differentiation of the systems of synthesis and degradation. Probably, the most ancient NM and NR are presented by such compounds as peptides, some amino acids, and ATP.


Degradation of low-density lipoproteins (LDL) and LDL - protamine complexes by lysosomal protease. Native LDL are degraded by the protease of the lysosomal extract but they are not sensitive to isolated cathepsin D. Protamine increases the sensitivity of LDL to the effect of lysosomal protease and makes them sensitive to the effect of cathepsin D. Degradation of LDL by lysosomal protease is most intensive between pH 4.0 and 4.5 but in case of LDL bound with protamine it is most intensive at pH 4.5--5.0.


[Primary excitatory rhythms in locomotor activity of scyphomedusae]. Periodic organization of autorhythmic motor activity which is typical of ontogenetically earlier stages of development of the nervous functions in vertebrates has been found in larval scyphomedusae. In hydromedusae which exhibit less complex nervous system, periodic organization of excitation persists also in adult individuals. It is suggested that already at the level of scyphomedusae, periodic form of organization of autorhythmic excitation in the nervous system was transformed in a category of recapitulating characters and in this quality passed along all phylogenetic pathways.


[Superfusion technique for studying the in vitro release of putative neurotransmitters from brain structures]. The superfusion technique described enables a stimulus synchronous observation of release mechanisms by reason of the size of the perfusion chamber and by the arrangement of the medium supply. The presentation of the results allows a quantitative comparison of releasing activity also in case of different chemical or electrical stimulation conditions.


Neurotransmitter regulation of arginine vasotocin release from rat pineal glands in vitro. Studies were performed to determine the effects of neurotransmitters on arginine vasotocin (AVT) release in vitro. Rat pineal glands were incubated with 10(-8)M or 10(-6)M norepinephrine (NE), dopamine (DA), serotonin (5HT), and acetylcholine (ACH) for eight h after which the concentrations of AVT in the media were determined by radioimmunoassay. With the exception of ACH, none of the neurotransmitters had a significant effect on AVT release. ACH significantly (P less than 0.05) elevated AVT release in vitro at the 10(-6)M concentration but not at the 10(-8)M concentration. The data indicate that ACH may play a role in the regulation of rat pineal gland secretion of AVT in vitro.


Comparative study of cardiovascular, neurological and metabolic side effects of 8 narcotics in dogs. Pethidine, piritramide, morphine, phenoperidine, fentanyl, R 39 209, sufentanil, R 34 995. III. Comparative study of the acute metabolic toxicity of the narcotics used in high and massive doses in curarised and mechanically ventilated dogs. The I.V. administration in dogs of high and massive doses of narcotics produced an acute rise in CO2 consumption, a rise of plasma catecholamines and other slight biochemical and metabolic perturbances. A general trend towards metabolic acidosis and hypermetabolism was noticed but important differences appeared according the drugs and doses chosen. The safety margin for metabolic toxicity (ratio between IV doses producing severe metabolic side-effects and doses necessary for deep surgical analgesia) were calculated for each narcotic and found as follows: 1 for pethidine, 3.3 for piritramide, 13 for morphine and phenoperidine, 12.5 for R 39 209, 60 for fentanyl, 800 for sufentanil and 4 000 for R 34 995. Drug associations may decrease or increase the metabolic safety margin of the narcotics. Beneficial associations with morphinomimetics are found with droperidol, etomidate and flunitrazepam.


Histofluorescence study on monoamine entry into the brain before and after opening of the blood-brain barrier by various mechanisms. The relationship between exogenous, circulating monoamines to the wall of cerebral microvessels, and the entrance of these amines into the cerebral parenchyma was studied by the formaldehyde histofluorescence technique in rats. No monoamine fluorescence could be detected in the wall tissue of the microvessels (pericytes and andothelial cells) unless either MAO or COMT were inhibited; these are integral to the blood-brain barrier mechanisms to monoamines. After transient opening of the morphologic blood-brain barrier by either a hypertonic of hypertensive insult, the amine fluorescence in the walls of the microvessels was intensified compared to that which was noted after monoamine oxidase inhibition by itself. Following opening of the structural blood-brain barrier, the circulating amines also passed through into the neuropil where they were concentrated within neurons, as demonstrated by prior depletion of endogenous monoamine transmitters by reserpine. Thus, both enzymatic and morphologic mechanisms in the blood-brain barrier ar involved in impeding the passage of monoamines into the cerebral parenchyma.


The long-term hypotensive effect of timolol maleate compared with the effect of pilocarpine in simple and capsular glaucoma. The long-term intraocular pressure (IOP) lowering effect of a beta-adrenergic blocking agent, timolol maleate, in topical administration was compared with the effect of pilocarpine on simple and capsular glaucoma by means of diurnal pressure curves during a six-month follow-up. In simple glaucoma timolol was more effective than pilocarpine in lowering IOP. In the follow-up a significant but not marked increase of the IOP was observed. In capsular glaucoma timolol was not effective enough, but when it was co-administered with miotics the IOP lowering effect was better than with either substance alone. Timolol induced no accomodative myopia, miosis, reduction of tear flow or other side effects. It increased the outflow facility in simple glaucoma but not in capsular glaucoma. During the trial, the anterior chamber depth increased while the corneal thickness remained unchanged. Four out of the six eyes included in a previous report of secondary glaucoma due to chronic uveitis are still, after one year of therapy, controlled with timolol.


Effects of 4-aminopyridine on statistical parameters of transmitter release at the neuromuscular junction. 4-Aminopyridine (4-AP) potentiates transmitter release from motor nerve terminals by increasing the quantum content (m) of endplate potentials. Estimates of the binomial parameters of transmitter release shows that 4-AP enhances m by increasing n and not p.


Acute effects of temazepam and nitrazepam on psychomotor skills and memory. Twelve pretrained students ingested temazepam, nitrazepam, and placebo, each double blind at one-week intervals in randomized order. Reactive and co-ordinative skills and critical flicker fusion were measured before each drug intake and 1, 2, 3, 6 and 8 hours after it. Short-term memory and paired association learning were measured at 1, 3 and 8 hours. The psychomotor responses to drugs were modified by a sequence effect (not at zero tests) which effect varied depending on the drug and parameter. In multivariance analysis it was included to reveal drug effects. Nitrazepam 10 mg increased reaction and co-ordination errors and also impaired learning and memory. Temazepam 10 mg impaired co-ordinative skills; on a whole it differed from nitrazepam but hardly from placebo. Temazepam 20 mg impaired co-ordination, and learning and memory. Both temazepam 20 mg and nitrazepam were experienced sedative. All drug effects were clearest during the first 3 hours, nitrazepam also impaired learning at 8 hours. Temazepam 20 mg seems suitable as a hypnotic.


Pharmacological investigation on the neurohumoral transmission of the vasomotor regulation. Renal efferent sympathetic activity and its changes due to stimulation of the central stump of the vagal, sciatic and ulnar nerves were investigated. In addition, the effect on basal activity and sympathetic reflexes of drugs with well defined site of action was studied (diazepam, tofizopam, phentolamine, dihydroergotamine, chlorpromazine, reserpine, clonidine, atropine, methysergide and phenindamine). The sympathetic efferent activity and the changes in sympathetic reflexes allowed conclusions to be drawn as to the functional state of the vasomotor centre. Neither methysergide nor phenindamine inhibited efferent sympathetic activity or influenced sympathetic reflexes. These findings exclude the possibility of serotonin or histamine being the transmitter substance in the vasomotor neurone. Experiments with atropine revealed that the muscarinic action of acetylcholine does not figure in the sympathetic inhibitory or excitatory reflex processes. Of the drugs investigated only diazepam and clonidine inhibited efferent sympathetic activity. Clonidine was more selective and acted in much lower doses (20 micrograms/kg) than diazepam (0.5--1 mg/kg). The alpha blocking agents inhibited the viscero-sympathetic inhibitory reflex arch more intensely than the somato-sympathetic inhibitory one. The transmitter is presumably noradrenaline. The sympathetic excitatory reflexes were decreased by diazepam and tofizopam and increased by clonidine and phentolamine. The other substances were ineffective. As to the transmitter substance figuring in the sympathetic excitatory reflexes no unequivocal answer could be obtained in the present experiments.


Diabetes-induced alterations of autonomic nerve function in the cat. The susceptibility to competitive ganglionic blocking agents such as hexamethonium (C6), tetraethylammonium bromide (TEAB), mecamylamine and d-tubocurarine (d-TC), of the superior cervical ganglion in cats with pancreatectomy and spontaneous diabetes or in animals treated with contrainsular drugs such as cortisone or dihydrochlorothiazide, was found to be decreased as compared to the reactivity of normal controls. The increased tolerance to ganglioplegics was not correlated with the elevation of the blood sugar level, and proved to be resistant to an acute administration of insulin. The results could not be explained by a decrease in the specific cholinesterase activity of the ganglionic tissue due to diabetes. Alteration of the peripheral autonomic synaptic transmission may be an early sign of diabetic neuropathy.


Inhibitory effect on gastric motility of chloroquine and mepacrine. Measured on isolated rat-stomach fundus strips, the isolated cervical sympathetic trunk, and on the superior cervical ganglion, chloroquine and mepacrine have parasympatholytic, spasmolytic, ganglionic blocking and local anaesthetic effects. On rising the doses these manifest themselves in a given sequence. On the basis of this fact it is concluded that the inhibition of gastric motility by chloroquine and mepacrine in the rat, is based on the parasympatholytic property of the drugs in question.


Specificity of cultured anterior pituitary cells in detecting corticotropin releasing factor(s): the effect of biologically active peptides and neurotransmitter substances on ACTH release in pituitary cell cultures. Biologically active peptides and neurotransmitter substances were added to anterior pituitary cell cultures to examine the presence of corticotropin releasing factor (CRF)-like activity. Hypothalamic extract (HE) induced significant dose-related increase of ACTH, and the lowest effective dose was 0.01 HE/ml. Other tested substances including luteinizing hormone-releasing hormone, thyrotropin releasing hormone, melanocyte stimulating hormone release inhibiting factor, somatostatin, substance P, neurotensin, beta-endorphin. leu-enkephalin, met-enkephalin, bradykinin, norepinephrine, dopamine, serotonin, acetylcholine, histamine, gamma-amino butyric acid or gamma-hydroxy butyric acid showed no CRF-like activity. Relatively high doses of lysine vasopressin, arginine vasopressin and angiotensin II increased the release of ACTH in pituitary cell cultures, but the maximal ACTH response was markedly less than with HE. These results indicate that cultured anterior pituitary cells are sensitive and fairly specific in detecting CRF(s) comparing with other detecting procedures.


Characterization of RNA polymerases from Rous sarcoma virus-induced mouse ascites sarcoma cells. RNA polymerase was extracted from the Schmidt-Ruppin strain of Rous sarcoma virus (SR-RSV)-induced C3H/He mouse ascites sarcoma cells (SR-C3H). RNA polymerase was separated into RNA polymerases I and II by DEAE-Sephadex chromatography. RNA polymerase I was separated into Ia and Ib fractions by phospho-cellulose chromatography. In SR-C3H cells RNA polymerase Ib was the main component of RNA polymerase I. At 0.05--0.1 M ammonium sulphate RNA polymerase I transcribed native DNA most actively, and RNA polymerase II transcribed denatured DNA most actively. Partial digestion of DNA by DNAase I enhanced RNA synthesis by RNA polymerases I and II. At ionic strength over 0.2 M ammonium sulphate, the initiation reaction of RNA polymerases I and II was inhibited. The initiation complexes of RNA polymerases I and II with native DNA were more stable against high salt concentration than with denatured DNA.


Neurotransmitters and neuromodulators and their mediation by cyclic nucleotides. An effort has been made here to devise criteria allowing discrimination between neurotransmitters, modulators and mediators. However, after consideration of several technical pitfalls in studies of these criteria, and examination of the properties of two examples of neuroactive agents (norepinephrine and endorphins) often referred to as "modulators", it is still difficult to classify these agents in all cases. Thus, in most central targets where NE-fibers are known to terminate, the synaptic actions of NE appear to have properties of both a neuromodulator and a neurotransmitter. Although much more research needs to be pursued, the opioid peptides may be neuromodulators for some neurons (spinal cord neurons) and neurotransmitters for others (myenteric plexus and spinal cord neurons). It may be that classification of such peptide agonists will need to be done on a cell-by-cell basis, with the endogenous peptides subserving a multi-faceted role in central and peripheral neuronal communication. As more and more endogenous ligands and transmitter-like substances are extracted from brain, it begins to appear that the language of neuronal communication is much richer than originally imagined from responses of spinal neurons to the fast-acting classical neurotransmitters. Indeed, it may evolve that the "deviant" forms of communication or transmission are more the rule than the exception. In the final analysis, each neurotransmitter may possess its own "fingerprint" of holistic actions attesting to the unique individuality of neuron types and their neurotransmitters. Such individualities might be expected to accomplish more sophisticated integrative operations, and hence behaviors, than could simple rapid "yes" or "no" messages.


Detection of experimental bacteremia and fungemia by examination of buffy coat prepared by a micromethod. Rabbits received intravenous injections of bacteria or fungi, and a comparison was made of the abilities of broth cultures, plating after dilution either in saline solution or in distilled water containing Triton X-100, and buffy coat examinations to detect the organisms in heart blood. The most sensitive method was broth culture. By microscopy or subculture of buffy coat cells prepared by centrifugation of blood in microhematocrit tubes, organisms were rapidly and regularly detected when their viable counts increased to 300--1,000/ml as detected by plating. By micromodification, buffy coat examination is technically easy to perform, and the method is only slightly less sensitive than when a larger amount of blood is used. Thus, it would be ideal for rapid provisional diagnosis of sepsis in patients, e.g., neonates, when the use of only a small blood sample is preferred.


Efficacy of ketotifen in bronchial asthma. Ketotifen was administered orally during a period of three months to 30 patients suffering from bronchial asthma. It proved to be a strong antiasthmatic agent and the results obtained were positive, i.e.: Excellent in 21 patients (70%), very good in 3 patients (10%), Good in 1 patient (4%), Poor in 5 patients (16%), The drug was very well tolerated and no signs of drug toxicity were observed. It is concluded that ketotifen is a very effective and safe drug for the prevention of bronchial asthma.


Effect of lactulose, neomycin and antacid on colonic pH recorded continuously with an implanted electrode. Colonic pH was continuously monitored by a pH electrode implanted in the transverse colon of rats over a 24-hour period. Lactulose significantly reduced the colonic pH to 5.37 +/- .39 from a fasting value of 6.77 +/- .75. Pretreatment with neomycin or concomitant use of a nonabsorbable antacid prevented lactulose-induced reduction in the colonic pH. The clinical implication of the study is that combined use of lactulose with neomycin or high doses of non-absorbable antacids in the treatment of chronic portasystemic encephalopathy may be undesirable.


Bicarbonate-buffered peritoneal dialysis. An effective adjunct in the treatment of lactic acidosis. Severe lactic acidosis is associated with poor prognosis. Usually, the patient is treated with massive amounts of intravenous sodium bicarbonate, which in itself carries many undesirable consequences such as fluid overload and hypernatremia. We have successfully used peritoneal dialysis with a bicarbonate-buffered dialysate in the management of severe acidosis. Bicarbonate-buffered peritoneal dialysis provided an unlimited supply of physiologic buffer over a prolonged period without causing hypervolemia or hypernatremia. Furthermore, significant amounts of lactate were removed by dialysis. We, therefore, recommend the use of bicarbonate-buffered peritoneal dialysis as an adjunct in the treatment of severe lactic acidosis.


Fetal blood and tissue pH with moderate bradycardia. Eleven patients with moderate fetal bradycardia in labor were studied by fetal scalp blood pH, continuous tissue pH, and umbilical arterty pH at delivery. The neonatal outcomes and biochemical data demonstrated that moderate fetal brdycardia does not indicate fetal distress.


Regional cerebral blood flow changes during severe fetal asphyxia produced by slow partial umbilical cord compression. We studied the effects of severe partial asphyxia on regional cerebral blood flow and arterial blood pressure in the unanesthetized, physiologically stable fetal lamb. Cerebral blood flow was measured by the microsphere technique before and during partial umbilical cord compression. Asphyxia sufficient to decrease pH from 7.40 to 7.04 and reduce oxygen saturation from 50% to 19% increased cerebral blood flow to all areas of the brain with the largest increases going to the brain stem (275% of control) and deep cerebral structures (240% of control). Fetal arterial blood pressures increased from a mean of 58 mm Hg to a mean of 71 mm. Hg during asphyxia. The blood pressure increases correlated closely with the regional cerebral blood flow increases. There was a poor correlation between cerebral blood flow increases and changes in Paco2' pH, or oxygen saturation. We conclude that during severe fetal asphyxia arterial blood pressure is the critical factor in determining cerebral blood flow.


Breathing movements before death in the primate fetus (Macaca mulatta). The incidence and character of fetal breathing movements (FBMs) were determined by analysis of continuous tracheal pressure recordings in a 48 hour period preceeding fetal death in utero in 7 chronic pregnant monkey preparations (Macaca mulatta). All fetuses were judged normal by blood gas tensions, pH, and fetal heart rate within 48 hours of death. In the normal fetus breathing movements were periodic and a circadian distribution in the incidence of FBMs was observed. Four distinct patterns of FBMs were observed in the normal fetuses. In five fetuses death occurred in the intrapartum period; all five fetuses were breathing at the onset of labor. A progressive fall in the incidence of FBMs was observed in labor coincident with the development of fetal acidemia. In the remaining two fetuses death occurred before labor. Apnea and gasping were observed in all fetuses before death. The duration of apnea and gasping appeared dependent upon the nature of the lethal insult.


Adrenergic innervation of the human uterus. Disappearance of the transmitter and transmitter-forming enzymes during pregnancy. The uterine adrenergic transmitter is in many animal species dramatically reduced during pregnancy, probably leading to a functional denervation near term. In order to clarify whether similar changes also occur in the human uterus, the adrenergic innervation of the isthmic myometrium during nonpregnant and pregnant conditions was analyzed by fluorescence histochemistry for demonstration of adrenergic nerves, and by quantitative measurements of norepinephrine and its synthesizing enzymes, tyrosine hydroxylase and dopa decarboxylase. At term pregnancy all fluorescent adrenergic nerves in the myometrium had disappeared, and the norepinephrine concentration had been reduced to almost zero. Parallel to this the activities of tyrosine hydroxylase and dopa decarboxylase were markedly reduced. By contrast, the activity of the acetylcholine-synthesizing enzyme, choline acetyltransferase, was unchanged, indicating that the adrenergic system was selectively affected. The results confirm that the adrenergic nerves in the human uterus, like those in uterine horns of laboratory animals, undergo fundamental changes in the course of pregnancy. This probably reflects entirely different conditions for a sympathetic influence on the myometrium during the last two trimesters of pregnancy compared to the non-pregnant situation.


The influence of scalp sampling on the cesarean section rate for fetal distress. One year's obstetric experience at Los Angeles County-University of Southern California Medical Center was reviewed and compared with previous years. The incidence of cesarean section for fetal distress is low and has remained constant over the past 7 years. Periodic changes and decreased baseline variability of the fetal heart rate accounted for 39% of the diagnoses of fetal distress in this group. Scalp sampling clarified the diagnosis of fetal distress and prevented unnecessary cesarean section. Compromised perinatal outcome in the greater than 2,500 gram weight group was confined to those who were monitored, had indications for monitoring, or had identifiable prospective risk factors, with rare exceptions.


Pathology of acute graft-versus-host disease in the dog. An autopsy study of ninety-five dogs. The morphology of graft-versus-host disease (GVHD) in canine radiation chimeras was studied by examination of autopsy tissue from 95 dogs including: 1) 13 healthy, untreated dogs; 2) 9 dogs given 1200 R total body irradiation and no marrow infusion; 3) 17 dogs given 1200 R and autologous marrow infusion; 4) 25 dogs given 1200 R and hemopoietic cells from dog-leukocyte-antigen (DLA)--identical littermates; and 5) 31 dogs given 1200 R and nonidentical DLA hemopoietic cells. Some of the dogs in Groups 3--5 received a postgrafting methotrexate (MTX) regimen of 0.25--0.5 mg/kg body weight on Days 1, 3, 6, and 11 and once weekly until Day 102. Prominent lesions were found in the small and large intestines, skin, and liver of dogs with allogeneic grafts. Skin lesions consisted of lymphocytic infiltrates of epidermis with necrosis of basal epidermal cells progressing to denudation. Gut lesions consisted of mucosal destruction progressing from crypt abscess formation to denudation. Liver lesions consisted of portal triaditis, plasmacytic and lymphocytic infiltrates, necorsis and atypia of small bile ducts, and scattered individual hepatocyte necrosis. These lesions were differentiated from changes caused by irradiation and MTX and were deemed characteristic of GVHD. The overall severity of GVHD lesions was less in the identical DLA group than in the nonidentical DLA group, and also less in dogs treated with MTX than in those not given MTX. The degree of lymphoid depletion in the lymph nodes, spleen, and intestinal lymphoid tissue was very similar in dogs with autologous and allogeneic grafts at comparable survival times. No specific evidence of pancreatic or renal involvement in GVHD was discovered.


Mechanical properties and functions of the myoepithelium in the eccrine sweat gland. Contractile properties of an isolated segment of the secretory coil of the monkey palm eccrine sweat gland were studied in vitro with a transducer. Contraction of up to 10 mgf was induced with acetylcholine but not with alpha or beta adrenergic agonists, caffeine, prostaglandin E1, or by a calcium ionophore A23187. Other features included K+ contracture, staircase effect, poor extensibility, length-tension relationship with a peak tensile response at 115--120% of the resting length, and requirement of Ca2+. The function of myoepithelium is unlikely to expulse the preformed sweat because the amount of preformed sweat is small, K+-contracture failed to expulse sweat, and because myoepithelial contraction was not induced by such stimulants of sweat secretion as A23187, phenylephrine, isoproterenol, and prostaglandin E1. The maximal transverse tension of 20 mgf during acetylcholine stimulation under resting tension was calculated to support the luminal hydrostatic pressure of approximately 500 mmHg. Thus the function of the myoepithelium may be to render structural support for the secretory epithelium.


pH regulation in barnacle muscle fibers: dependence on intracellular and extracellular pH. Intracellular pH (pHi) regulation was studied in acid-loaded barnacle muscle fibers by monitoring recovery of pHi with a pH-sensitive microelectrode. By multiplying the rate of pHi recovery by total intracellular buffering power, the acid extrusion rate was obtained. The acid extrusion rate was greatest at low values of pHi, and declined toward zero as pHi approached normal levels. It increased as the extracellular pH (pHo) was raised either by increasing external [HCO3] ([HCO3]o) at constant PCO2 or by decreasing PCO2 at constant [HCO3]o, but more so in the former case than in the latter. These observations suggest that pHo per se is an important determinant of the acid extrusion rate, but that raising [HCO3]o by itself also stimulates acid extrusion. This would be expected if acid extrusion involves the inward movement of HCO3. When fibers were exposed to HCO3-containing solutions at very low or very high pHo, pHi drifted downward or upward, respectively; thbe drifts were inhibited by 4-acetamido-4' isothiocyanostilbene-2,2' disulfonic acid (SITS). Our results are discussed in terms of possible mechanisms of acid extrusion.


Status of psychotropic drug blood level assays and other biochemical measurements in clinical practice. Assays of drug levels in blood and of other biochemical characteristics of psychiatric patients are being proposed for clinical application, although their utility in practice remains uncertain. Exceptions are the assay of blood levels of anticonvulsants and of lithium ion. Assays of antidepressant drugs may be especially helpful in the evaluation of unexpected responses or in the avoidance of unwanted toxic effects and promise to permit more efficient predictions of individual requirements. Assays of platelet MAO activity or urinary MHPG excretion remain clinically less useful. Attempts to correlate blood levels of antipsychotic agents with clinical effects have been disappointing, although newer assay methods may prove more useful.


Effects of ketotifen and clemastine on passive transfer of reaginic reaction. Passive transfer (PK) tests were performed with a reaginic serum on a recipient reacting with an immediate and a more prolonged reaction when specificity challenged. Both reactions are thought to be mediated by IgE immunology. Ketotifen, a cycloheptathiophene derivative, and clemastine, given to the recipient in maximal clinical doses for 3 days, inhibited the immediate reaction. Ketotifen had a very slight effect also on the prolonged reaction. The results indicate that the in vivo effects of ketotifen in the human system are due not so much to mast cell inhibitory mechanisms, but more to post-release antihistaminic and some anti-inflammatory properties.


The protective effect of a new agent, ketotifen syrup, in the treatment of childhood asthma. Twenty-two children with perennial extrinsic allergic asthma participated in a double-blinded, controlled, cross-over study of Ketotifen syrup during a 2 x 6-week period. The placebo was identical with the active drug in taste, colour, and consistency. The dosage level was, on weight basis, a little higher than the standard dosage for adults. The double-blinded investigation was supplemented with a 1 2-week open study of the tolerance for Ketotifen. This study also involved 22 patients, 12 new ones, and 10 from the double-blind study. The study showed Ketotifen to have no effect on changes in lung function (peak flow), on reduction in frequency of asthmatic attacks, or on consumption of additional medicine. The tolerance for Ketotifen was good, but physicians are advised to watch for increases in weight and decreases in blood pressure during tests on children which involve higher dosage levels.


Ventilatory pattern following diazepam and lorazepam. The effect of intravenous diazepam (10 mg) or lorazepam (2 mg) on the ventilatory pattern has been studied in two groups of ten patients prior to elective surgery. Injection of lorazepam was followed by a periodic pattern of ventilation in nine patients.


Volume and pH of gastric contents following anticholinergic premedication. The effects of anticholinergic premedication with 1.0 mg atropine, 0.5 mg hyoscine and 0.2 mg glycopyrronium on volume and pH of gastric contents were studied and compared with a group receiving no anticholinergic premedication. The antisialogogue effects were also compared. Though the groups receiving atropine and glycopyrronium had the lowest mean aspirated volume and the highest mean pH respectively there was no essential difference between the various groups receiving anticholinergic premedication. However, the pH values were above 2.5 in the majority of these patients in comparison with the control group. The antisialogogue effects of the three anticholinergic drugs were similar.


[Hemodynamic effects of a new antidepolarizing agent: fazadinium bromide]. Studies concerning the hemodynamic effects of this new antidepolarizing agent are scarce and difficult to interpret because of drug interactions, and of an accentuation of vagal tonus related to the use of morphinomimetic analgesics. For a better approach of the effects proper to fazadinium, we have tried to perform a study freed, to a maximum, from any drug interference. We studied the hemodynamic effects to a single dose of 1 mg.kg-1 of fazadinium bromide during 35 minutes in coronary patients normal hemodynamically or rhythmically, non-premedicated, ventilated with 50 p. 100 nitrous oxide in oxygen, and bebore any surgical procedure. All hemodynamic modifications are moderate and maximal 10 minutes after injection. The stroke index decreases 16 p. 100, heart rate increases 6 p. 100 and cardiac index falls 10 p. 100. Total peripheral resistance remains unchanged and mean arterial pressure drops 10 p. 100. Finally pulmonary wedge pressure decreases slightly. None of these modifications are statistically significant. One may, therefore, conclude that fazadinium tolerance, when the drug is freed from any drug interference, in coronary patients normal hemodynamically and free from rhythm disorders is excellent from a hemodynamic and rhythmic point of view. However, other isolated observations of hypovolemic subjects, or patients with atrial fibrillation receiving fazadinium and studied hemodynamically suggest a poorer tolerance in these cases.


The relationship between the arterial level of angiotensin-converting enzymes and arterial gas tension in bronchial asthma. To study the mechanism which causes a lowered serum level of angiotensin-converting enzyme (ACE) in asthma patients, the changes in serum ACE in arterial blood gas tension was measured. Serum ACE was also determined in patients with chronic obstructive lung disease (COLD) and fibrosing lung disease (FLD). A reduced level of serum ACE was found in some patients with COLD, similar to that in patients with asthma. A significant relationship existed between the lowered serum ACE level and the degree of arterial hypoxia, especially in asthmatic patients and some patients with COLD. The significance of lowered serum ACE is discussed in relation to the pathogenesis and the mechanism of hypoxemia in patients with asthma, COLD and FLD.


[Use of frozen hypertonic saline in the treatment of pain]. Fifteen cases of patients referred for treatment of acute and chronic pain problems are reported. The results show that both epidural and peripheric hypertonic frozen saline 5 p. 100 injections were effective, as far as three months afterwards. The possible mechanism of action of frozen saline is discussed.


[Neuromuscular inhibition of new aminoglycoside antibiotics]. The curarizing effect of three new aminoglucosidic antibiotics (amikacine, dibékacine and sisomicine) is compared to that the streptomycin. The experiment was carried out on mice. In the first group of experiments, the curare-like action of increasing doses of the antibiotics is studied on a diaphragm-phrenic nerve preparation. In the second group, the dosage of each antibiotic necessary to induce apnea is sought. The results show that all the antibiotics have a curarizing activity, variable according to the product, and which increases with the doses used. The relationship between the therapeutic doses and the curarizing doses had a greater margin of security with the three antibiotics than with streptomycin.


[Precurarization using pancuronium in male subjects. Evaluation of certain clinical effects]. The authors studied certain effects in the male subject of precurarisation using different doses of pancuronium. The results obtained show that the maximum doses used, corresponding to 0.01 Omg/kg of pancuronium, were associated with subjective symptoms which were well tolerated by the conscious patient, a decreases in the incidence of fasciculations, antagonistic effects against succinylcholine and a decreases in postoperative myalgia. In their conclusion, the authors confirm that the maximum doses of pancuronium used require an increase in doses of succinylcholine in order to avoid the antagonism phenomenon, and that doses ranging from 0.010 to 0.020 mg/kg of pancuronium could be used in order to completely eliminate postoperative myalgia related to succinylcholine.


[Effects of diazepam on oxygen consumption]. Oxygen consumption (VO2) was measured in ten patients before and after the administration of 0.28 mg.kg-1 of diazepam, using a spirometer placed in the circuit of an MA1 respirator functioning on a closed circuit basis. The results showed a significant decrease in VO2 OF 8 p. 100. The differences seen in comparison with previous studies may be explained by differences in the methods of study used. It would appear that this hypometabolic effect is not an intrinsic property of diazepam but rather a consequence of the neurodepressive properties of the drug, on the gamma system in particular.