A long-lasting change in ocular dominance of kitten striate neurons induced by reversible unilateral blockade of tonic retinal discharges. The effect of reversible blockade of tonic retinal discharges upon the excitability of binocular visual cortical neurons was studied in kittens during the "critical period". Following the direct application of a small amount of blocking agent to the unilateral optic nerve, the responsiveness of single cortical neurons to ipsilateral eye (non-blocked side) stimulation was enhanced while that to contralateral stimulation was suppressed. Changes started soon after blocking and were long lasting, over 1 hour, compared with the duration blocking (7 min) as measured at the level of the later geniculate nucleus. This effect was found to be age-dependent: in older kittens which were out of the critical period, results were ambiguous and in young adult cats the same treatment induced no obvious changes. The results favor the idea of binocular competition at postsynaptic sites of the geniculo-cortical projection during the critical period. Furthermore, tonic afferent activity in the visual system is proposed as one of the primary carriers of effects of the environmental manipulation of visual inputs in the developing visual cortex. This is consistent with the previous notion that tonic afferent activity is indispensable for maintenance of existing synaptic contacts in the matured brain.


Studies on the effect of long-term exposure to nitrogen dioxide on serum and liver proteins level and enzyme activity in guinea pigs. Forty male guinea pigs were exposed to nitrogen dioxide in a concentration of 2 mg/m3, 8 hours daily for a period of 180 days. Forty male animals were used as a control group. The following changes were found in intoxicated animals: the decrease of total protein and seromucoid concentration in blood serum and the decrease of total protein, perchloric acid-soluble proteins, protein-bound hexosamines and sialic acids content, in liver tissue. Electrophoretic examination of the serum proteins showed the increase of alpha 1- and beta 2-globulins and the decrease of albumin concentration. Changes in the level of glycoproteins fractions and protein-bound carbohydrates in blood serum were described also. Estimation of enzymes activity showed the decrease of alanine and aspartate transaminase activity in blood serum caused by the strong decrease of the cytoplasmic fraction of these enzymes. However the simultaneous increase of the mitochondrial fraction of transaminases activity was observed. The decrease of the activity of choline esterase was found also. Similar changes of enzymes activity were found in liver tissue. Histopathological studies were done for the further clearing the influenze of nitrogen dioxide on serum and liver proteins concentration and enzymes activity. It was found that after long-term exposure to nitrogen dioxide the destruction processes may be observed in the liver. The possible mechanism of the nitrogen dioxide-induced damage of protein metabolism is discussed.


Proprioceptive effects on evoked responses to sounds in the cat auditory cortex. With a view to analyse the influence of neck proprioceptors on directional hearing, evoked potentials (EPs) to dichotically or monaurally presented clicks were recorded from the auditory cortex of cats under deep Nembutal anaesthesia with their head pointing to the front, and then to the right or to the left side at 45 degrees. The change in the head position produced considerable changes in the amplitude of the two primary EP components and in their thresholds. The changes were of two kinds: either decrease or increase of the amplitude. At symmetrical points of the auditory cortex they went in the same direction. The also appeared in the associative zone with the same sign. With monaurally presented clicks, the change of the side of stimulation for the most part resulted in a reversal of the sign of the proprioceptive effect. Similar proprioceptive influences were recorded when the clicks were presented not through earphones but in an open acoustic field.


Integration in descending motor pathways controlling the forelimb in the cat. 1. Pyramidal effects on motoneurones. Stimulation of the contralateral pyramid and intracellular recording from forelimb motoneurones was used to investigate corticimotoneuronal pathways in the cat. A train of pyramidal volleys evokes short-latency EPSPS in flexor motoneurones and in many extensor motoneurones. The latency for the onset after the effective pyramidal volley-usually the third - strongly indicates a disynaptic linkage. These disynaptic EPSPs were common in triceps motoneurones to fast heads but rare in those to slow heads. Pyramidal IPSPs with a slightly longer latency, suggesting a trisynaptic linkage, were found in both flexor and extensor motoneurones. They were common in motoneurones to slow heads of triceps. Disynaptic pyramidal IPSPs were found only occasionally. In addition pyramidal volleys may evoke late large EPSPs and/or IPSPs in any combination with the short-latency PSPs.


[Difference in the sensitivity of the hamster and the rat to the effects of long-term administration of ethylenethiourea]. Rats and hamsters were fed ETU at levels of 0, 5, 17, 60, 200 mg/kg in the diet. Body weights, food consumption, seric enzyme activities (GPT, alkaline phosphatase), hepatic enzyme activities (GPT, alkaline phosphatase G6PDH), cholesterolemia, thyroid weight and others organs, histology were the criteria studied. ETU was found causing hypercholesterolemia for the 2 species at 5 mg/kg dietary levels. Thyroid impairement is predominant in rat and hepatic impairment is predominant in hamster. ETU was found to be not carcinogenic for hamsters even at 200 mg/kg level and carcinogenic for rats at 60 mg/kg level for males and 200 mg/kg level for females.


[Toxicity of oxythioquinox (Morestan) administered in a lipid solution]. Administered to rats by stomach tubing oxythioquinox (Morestan) toxicity is very strongly increased after solubilisation in olive oil. The oxythioquinox DL50, in this case, is 500 mg/kg although we can reach 2.8 g/kg in aqueous suspensions. When it is administered (1 g/kg) in aqueous suspension, the decrease in body weight is the same as these observed with a 5 fold lower dose in oil. Conversion rate feed and weight of differents organs decrease when animals are daily submitted to oxythioquinox in oil, during 16 days, compared with animals treated with an equivalent dose in aqueous suspension. Potentiation, in oil solutions, of the decrease of oxythioquinox intestinal transit, promoting its absorption, could explain the increase of oxythioquinox toxicity in oil solution.


Tyrosine hydroxylation in the rat striatum after fentanyl and droperidol in vivo. The effects of fentanyl, droperidol, and morphine on tyrosine hydroxylation in the rat striatum was measured after inhibition of aromatic amino acid decarboxylase with R04-4602. Any direct change in the product of hydroxylation (i.e.dopa) was supposed to reflect a change in enzyme activity. Fentanyl (0.1 mg/kg intraperitoneally) first (10 min) appears to slightly depress, and later (30 min) significantly activate tyrosine hydroxylation. Morphine (10 mg/kg i.p.) activates tyrosine hydroxylation to a much lesser degree than fentanyl. Droperidol (3 mg/kg i.p.) only slightly activates the in vivo activity of the enzyme.


[Acute poisoning of an infant by cutaneous application of a local counterirritant and pulmonary antiseptic salve]. The case of acute poisoning reported here raises the question of the harmlessness of preparations destined for cutaneous application in infants. After describing the method perfected for the identification and estimation of camphor, menthol and thymol in biological material, the authors present the toxicological, clinical and biological arguments in favour of the notion that the cutaneous resorption of these substances was responsible for this acute intoxication in an infant. Particular attention should be paid to poisoning which may result, in the newborn and infant, from the cutaneous application of active substances.


The sensitivity of rat spinal interneurones and renshaw cells to L-glutamate and L-aspartate. L-Glutamate and L-aspartate were administered electrophoretically near spinal interneurones and Renshaw cells of pentobarbitone-annaesthetized rats. Other spinal interneurones were consistently more sensitive to L-glutamate than to L-aspartate. Renshaw cells, however, showed no consistent difference in their sensitivity to these two amino acids. The results, which are compared with those reported previously in the cat, support the hypothesis that L-glutamate could be a transmitter at spinal primary afferent terminals.


Chemical and morphological studies of rat myocardium after application of a necrogenic dose of isoproterenol. In male Wistar rats myocardial necroses were produced by application of 80 mg of isoproterenol per kg of body weight. 2 and 48 hours after isoproterenol administration the Na+ and K+ contents were determined. At these times Na+ presented increases of 128 and 83% respectively, and K+ of 13 and 8% respectively as compared to the controls. These results were related to the morphological changes appearing at the same time, and were discussed with references to the literature. Taking edema and vasodilatation into account, the degree of cell damage can be estimated on the basis of the chemical data available.


Ultrastructural changes in the myocardium due to acute uremic syndrome. The acute uremic syndrome caused by bilateral ligation of the ureters leads to ultrastructural changes in the myocardium after 12 hours. They are characterized by dilatation of the tubules of the endoplasmic reticulum and by the focal disintegration of mitochondria. After 24 hours, besides damaged mitochondria the glycogen granules were reduced and the number of pinocytic vesicles in endothelial cells increased. After 48 hours advanced changes of mitochondria associated with myelin structure and dense bodies could be observed. The myofibrils were fragmented. Sometimes contraction rings occurred. After 72 hours all myocardial structures were strongly damaged, especially in the subendocardial and subepicardial regions. In this period the hyperhydration of the myocardium led to dissociation of the myofibrillar structures.


The action of a single toxic dose of 2-acetylaminofluorene or allylic alcohol on the adrenals. I. Behaviour of organ weight and mitotic activity of the adrenocortical cells. In male Sprague-Dawley rats the relative organ weight and mitotic activity of the adrenal cortex were investigated after intoxication by a single dose of 200 mg/kg b.w. of 2-acetylaminofluorene (AAF) or 20 mg/kg b.w. of allylic alcohol (ALL). 36, 42, 48 and 72 hours after application a significant enhancement of the mitotic rate of the adrenocortical cells was produced by AAF in comparison with that following ALL administration. Interrelations of organ weight and proliferative activity could not be found.


An experimental model for inducing fetal hypotrophy in the rabbit. Intravenous injection of a saponin-collargol solution into pregnant rabbits induced, in addition to haemolysis and decrease in body weight of the gravid animals, a dose-dependent intrauterine deficient development of the fetuses accompanied by pronounced general reduction in body weight and disproportionate growth of fetal organs. Brain, heart, lungs, and the kidneys to a lesser degree, were found to be comparatively heavier when compared to the total body weight. The reasons discussed are hypoxia-dependent deficiency in glycogen and glucose, nutritional factors resulting from malnutrition, intoxication, and placental insufficiency due to infarctions, particularly for groups II and III.


Transmission and scanning electron microscopy of experimentally induced thyroid tumors in rats. Irradiation of the neck region of 10 days old Wistar rats with 300 rads X-rays and their subsequent treatment with MTU leads to the development of thyroid tumors. The ultrastructure of the thyroid tumors induced was studied by transmission (TEM) and scanning electron microscopy (SEM). In follicular carcinomas, cylindrical or high columnar cells with abundant microvilli, well-developed ergastoplasmic reticulum and a hypertrophied Golgi complex predominate. The cytoplasm of the tumor cells of papillary carcinomas was composed of large pleomorphic cisternae, irregular in shape mitochondria, dense bodies, phagolysosomes and lamellar or multivesicular structures. Scanning electron microscopy revealed in the control animals a regular pattern of thyroid follicles tied to each other by tissue bridges and covered by set of blood and lymph vessels. The relief of the follicular carcinomas was irregular indicating follicles different in size and shape. The internal surface of the neoplastic follicles was also irregular as result of deep invaginations and intrafollicular cell growth. The apical region of the normal and neoplastic thyroid follicular cells was covered with abundant microvilli protruding into the colloid.


Differential uptake of platinum-uracil by human peripheral lymphocytes. Human peripheral blood lymphocytes (PBL) obtained from healthy individuals and cancer patients were stained with platinum-uracil and processed for electron-microscopic inspection According to their staining behaviour with platinum-uracil human PBL may be divided into two populations. Electron-dense patches at the plasma membrane could also be observed.


Cytotoxicity of the pyrrolizidine alkaloid fulvine to pancreatic acinar cells in the rat. Light microscopic, histochemical and ultrastructural studies. Veno-occlusive disease of the liver is caused by the hepatotoxic pyrrolizidine alkaloid fulvine which is found in the plant Crotolaria fulva. Histological, histochemical and electronmicroscopic studies carried out in Wistar rats showed that an aqueous solution of fulvine produced an acute pancreatopathy with interstitial oedema and secondary hypoxic dystrophy of the acinar cells, when administered at doses of 10 and 20 mg/kg body weight.


[Research on heterocyclic compounds. III. Imidazo/1,2-a/pyrimidin-2-acetic acid and correlated compounds]. The preparation of imidazo [1,2-a] pyrimidin-2-acetic acid by two different synthetic methods is reported. A structure is tentatively proposed for a side product.


2- and 5- substituted 5-amino-2,6,6-trimethyltetrahydropyrans. Reaction of N,N-disubstituted 2-carboxyamido-2,6,6-trimethyltetrahydropyran-5-carboxylic acids with diphenyl phosphorazide in the presence of triethylamine and benzyl alcohol gave N,N-disubstituted 5-benzyloxycarbonylamino-2-carboxyamido-2,6,6-trimethyltetrahydr-pyrans, which in turn yielded N,-disubstituted 2-aminomethyl-5-methylamino-2,6,6-trimethyltetrahydropyrans by LiA1H4 reduction. 5-Benzyloxycarbonylamino-2-carboxypyrrolidino-2,6,6-trimethyltetrahydropyran gave 5-amino-2,6,6-trimethyl-2--pyrrolidinomethyltetrahydropyran by hydrogenolysis followed by LiA1H4 reduction. Among the amides prepared from the latter, the diphenylacetic acid amide showed antiarrhythmic and local-anesthetic activity.


[N-acylindoline with phytotoxic activity. I]. A series of N-acyl derivatives of indoline (A) was prepared and tested for phytotoxic activity. The substances studied (Tables I leads to III, substances I leads to XXVIII) were prepared by reaction of indoline with suitable acylating agents and were mainly new compounds. The biological tests consisted in pre- and post-emergence treatment in doses of 6 kg/ha or lower doses on five common weeds; one substance (XXV) was tested also on other species of economic importance (Table III). The results show that of the three classes studied the N-carbamoyl- and N-thiocarbamoyl derivatives of indoline have wide spectrum phytotoxic activity especialy on absorption via the foliage. The highest phytotoxic activity in both pre- and post-emergence tests was shown by N-(methylcarbamoyl)indoline (XIII) and N-(dimethylcarbamoyl(indoline (XXIII).


Radiopaque contrast media. XXXIX - Metabolism of iopronic acid by rat liver microsomes: characterization and identification of the metabolites. The metabolism of iopronic acid, 2(2[(3-acetamido-2,4,6-triiodophenoxy)ethoxy]methyl)butyric acid, was studied in vitro using rat liver microsomes as enzyme source. By means of solvent extraction, T.L.C., H.P.L.C. and mass spectrometry, the hydroxyethyl (3-acetamido-2,4,6-triiodophenyl) ether and the 3-acetamido-2,4,6-triiodophenoxyacetic acid have been identified as the metabolities of the parent drug. No deiodinated metabolites were found. The probable mechanism of the in vitro formation of the metabolites is discussed.


Prostaglandins XI. alpha-Halo-alpha,beta-unsaturated ketones: a synthetic approach to 13-dehydroprostaglandins. Synthesis of alpha-halo-alpha,beta-unsaturated ketones from aldehydes as a synthetic approach to prostaglandins is investigated.


Synthesis of N-acetylcysteine compounds. The preparation of some anilides, esters and amides of N-acetyl and N,S-diacetyl-cysteine is described. Of the compounds synthesized, particular interest was aroused by the p-hydroxyanilide derivatives of N-acetyl and N,S-diacetyl-L-cysteine owing to their analgesic, antiinflammatory and antipyretic activity.


[Research on heterocyclic compounds. IV. Imidezopyrimidine acetic acids]. A group of ethyl imidazo (1,2-a) and imidazo (1,2-c)pyrimidin-2-acetates was prepared, starting respectively from 2-amino- and 4-aminopyrimidines, by reaction with ethyl 4-bromoacetoacetate. From these esters the corresponding acids were prepared and their antiinflammatory activity was evaluated.


[Reaction between 2-nitrobenzoylaminomalonate and acrylic aldehyde for the synthesis of compounds with the pyrrolo/2,1-ch h 1,4/benzodiazepine structure]. The synthesis of 5,11-dioxo-1,2,3,10,11,11a-hexahydro-5H-pyrrolo (2,1-c) (1,4)benzodiazepine and 2-bromo-5,11-dioxo-1,10,11,11a-tetrahydro-5H-pyrrolo (2,1-c) (1,4)benzodiazepin-11a-ethylcarboxylate, structurally related to anthramycin and tomaymycin, was achieved by forming in situ the pyrrolidine nucleus instead of using proline or its derivatives. The most important intermediate was 1-(2-nitrobenzoyl)-delta4-pyrrolin-2,2-dicarboxylate which was then easily transformed into the above-mentioned tricyclic systems, starting with catalytic reduction or bromination.


Dimeric hydrazones of 3-formylrifamycin SV:synthesis, antibacterial activity and other biological properties. The synthesis of some dimeric hydrazones of 3-formylrifamycin SV is described. The chemical and physical characteristics, the antibacterial activity and other biolgoical properties of the new derivatives are reported.


[Synthesis and biological activity of 1,2,3-triazol-1,8-naphthyridines]. The reaction of 2-methyl-5-azido-1,8-naphthyridine with active methylene compounds was investigated. Several naphthyridines which possess the 1,2,3-triazole ring as a substituent were obtained. Among these compounds (IV o) showed an analgesic activity twice that of phenylbutazone.


Platelet aggregation inhibitors. II - N-heterocyclic aldoxime methiodides (1). On the basis of an hypothesis according to which suitable nucleophilic agents may convert adenosine diphosphate (ADP) into adenosine monophosphate (AMP) and adenosine, well known inhibitors of ADP-induced platelet aggregation, some N-heterocyclic aldoxime methiodides were tested as inhibitors of ADP-induced rabbit platelet aggregation. Several 1-aryl-2-hydroxyiminomethly-3-methylimidazolium iodides significantly inhibit in vitro and in vivo-in vitro ADP-induced rabbit platelet aggregation.


[Complexes of pteridines with phenothiazine and phenoxazine derivatives]. Folic acid and pteroylaspartic acid form solid complexes with N-dialkylaminoalylphenothiazines and with N-dialkylaminoalkylphenoxazines. Folic acid forms 1:2 solid complexes with derivatives having the amine nitrogen in gamma position to heterocyclic nitrogen; the complexes are not formed with those derivatives in which the amine nitrogen is in the beta position to the heterocyclic nitrogen. Pteroylaspartic acid forms 1: 1 solid complexes with classes of compounds having aminic nitrogen in both gamma or beta position to the heterocyclic nitrogen.


[Correlative analysis of chemical structure - biological activity using Hansch's method: principles and development of the method]. The basic principles and developments on which the Hansch multiple parameter approach depends are described. A correlation analysis on the antibacterial activity of 2-Y-4-(X-phenyl)-3H-1,5-benzodiazepines is discussed. The use of indicator varioables is shown to greatly increase one's ability to formulate quantitative structure-activity relationships. This approach allows one to carry out objective studies of massive amounts of chemical and biological data.


[Chemical and pharmacological research on pyran derivatives. VI. 2-Dialkylamino-4-oxo-4H-naphto/1,2-b/pyrans and derivatives]. The 2-dialkylamino-4-oxo-4H-naphtho [1,2-b]pyrans are obtained by the reaction of N,N-dialkylethoxycarbonylacetamides with alpha-naphthol and with substituted alpha-naphthols. The products on treatment with formaldehyde and morpholine or piperidine or N-methylpiperazine are transformed into the 2-dialkylamino-3-dialkylaminomethyl-4-oxo-4H-naphtho [1,2-b]pyrans. Pharmacological investigation has shown that 2-dimethylamino (K 12164), 2-(N-ethyl, N-methyl)amino- (K 12087) and 2-diethylamino-4-oxox-4H-naphtho [1,2-b]pyran (K 12165) show clear neurotropic activity of the neuroleptic type whereas compounds of the isomeric series, 1H-naphtho-[2,1-b]pyrans, studied previously (1), show anticonvulsive and sedative activity. This difference in pharmacological activity has prompted a more complete comparative examination of the activity of the two series of compounds. Study of antagonism to the effects of reserpine by both 4H-naphtho [1,2-b]pyrans and 1H-naphtho [2,1-b]pyrans has shown that in the latter series the 1-oxo-3-dimethylamino- (K 8291), the 1-oxo-3-(N-ethyl, N-methyl)amino- (K 8409) and the 1-oxo-3-diethylamino-1H-naphtho [2,1-b]-pyran (K 8292) have marked neurotropic activity of the antidepressive type.


Prostaglandins X. An improved route for synthesis of PGF2beta analogues. Esterification with inversion is a highly stereospecific reaction by which one-step conversion of PGF2alpha to PGF2beta is obtained with very satisfactory yield.


[Synthesis of quinazolinic and benzoxazinonic acids and study of their anti-inflammatory activity]. The preparation of some phenylalkonic acids where the phenylalkanoic moiety is introduced into the position 3 of derivatives of 4(3H)quinazolinone, 2,3-dihydro-4(1H)quinazolinone or of 2,3-dihydro-4H-1,3-benzoxain-4-one is described. The products were tested for antinflammatory activity but proved to be devoid of significant activity.


Charge-transfer complexes of p-hydroxyphenylbutazone. C.T.-complexes of p-hydroxyphenylbutazone with various complexing agents of the amine-type are described. Some correlations between molecular structure and equilibrium constants as well as spectroscopic parameters are reported.


Synthesis and pharmacological properties of some new 1,1-diarylacetic acid derivatives. A series of 13 new 1,1-diphenylacetic acid derivatives was synthesized via common transformations of 2-phenyl-2-(p-nitrophenyl) propio- and butyronitriles. The compounds were submitted to pharmacological screening. 2-Phenyl-2-(p-aminophenyl)propionamide (VIII) showed high anticonvulsant activity.


[Research on nitrogen heterocyclic compounds. X. New method of synthesis of pyrrolo/1,2-a/quinoline and its derivatives]. The synthesis of pyrrolo[1,2-a]quinoline derivatives from 1-arylpyrroles bearing an acetic acid or acetonitrile moiety on the benzene or pyrrole nucleus is described. Pyrrolo [1,2-a]quinoline derivatives have some pharmaceutical interest as cyclic analogues of 9H-pyrrolo[1,2-a]indole and 5H-pyrrolo[2,1-c] [1,4]-benzodiazepine, the basic structures of the antitumor antibiotics mitomycin C, anthramycin and tomaymycin.


[Synthesis of 2-aminoisoindolin-1-ones with or without 6-substituents]. The synthesis of 5- and 6-chloro, 5- and 6-methoxy, 5,6-dimethoxy, 6-amino and 6-nitro-2-aminoisoindolin-1-ones (III b...h), starting from the substituted phthalides (Vb...g), are reported. Chloro and methoxy-derivatives (III b...f) have been prepared by reduction of phthalazin-1-(2H)-ones (Ib...f) with zinc and acids under controlled conditions to afford the 3,4-dihydrocompounds (II), that have been rearranged to (III b...f) with hydrazine hydrate or hydrochloric acid (Scheme 3). The synthesis of 6-nitro and 6-amino-derivatives (III g,h) have been respectively accomplished by hydrolysis and hydrogenolysis of 6-nitro-2-benzylidenaminoisoindolin-1-one (IV g), prepared by chlorination and ring closure with sodium carbonate of benzylidenhydrazide of 5-nitro-2-hydroxymethyl-benzoic acid (Scheme 2).


[Strychnine-neuronographic study of orbital cortex projections to structures of the pons varolii]. In adult cats, it was shown that the orbital cortex had direct contra - and ipsilateral projections to oral and caudal reticular nuclei of the pons, to caudal part of the Guden neuclei, to pons covering nucleus, to sulure nucleus, to trigeminal nuclei, and to such conducting formations, as the trapezoid body and pyramidal tract. The orbital gyri connections were mostly ipsilateral and to the caudal part of caudal reticular nucleus of the pons, to oral part of the reticular giganto-cellular nucleus, and to the own pons nuclei. The highest firing rate and amplitude were recorded in the inhibition zone of the reticular formation (the site of overlapping of the oral and caudal reticular nuclei of the pons).


[Properties and organization of pyramidal neurons of the rat motor cortex]. Antidromic potential sin cortical neurons elicited by stimulation of pyramids and different segments of the spinal cord were studied with the aid of extracellular recording in rats. Axons of about 2/3 of the cells under study formed the cortico-spinal tract passing through the ventral portion of the dorsal column up to the lumbar segments of the spinal cord. Conduction velocity along the cortico-spinal axons varied from 2.3 to 17.0 m/sec.


[Relations between hypothalamic autostimulation and current strength]. In order to examine effects of current intensity of the self-stimulation rate and to study evoked behavioural, somatic, and visceral responses, 105 electrodes were implanted in 35 cats in the lateral hypothalamus. Electrical stimulation produced all kinds of behavioural patterns depending upon both the electrode location and the current intensity. Three types of self-stimulation curves were differentiated on the basis of curve shapes and the maximum rate of self-stimulation.


[Receptor responses to amino acids recorded from the surface of the olfactory bulb]. Spontaneous activity and evoked responses were studied in different parts of the carp olfactory bulb. Application of 10(-3) GABA to the bulb surface elicited some or no changes in the patterns of activity, according to the site of application. This finding suggests the receptor's axons to be the source of activity recorded on the surface of rostral or middle bulb portions. During stimulation with 10(-2)--10(-9) M amino acids, a rapid increase in the spike activity occurred. The concentration-response relations were revealed for a number of amino acids. Some groups of receptor axons possessed a selective sensitivity to histamine and to water from aquarium with fishes.


[Influence of the ventro-medial nuclei of the hypothalamus on adrenocortical function under conditions of muscular stress]. After repeated stimulation of hypothalamic ventro-medial nuclei with square electrical stimuli, swimming during 20 min with a load equal to 10% of body weight increases the weight of adrenal glands, the width of the cortical layer, and the width of glomerular fascicular, and reticular zones, decreasing at the same time the ascrobinic acid and cholesterin contents in the gland as well as the eosinophil content in the peripheral blood. After lesion of the ventro-medial nuclei, the same effects of the swimming are less obvious than in normal, with no stimulation whatever.


[Responses of lumbar flexor motoneurons to stimulation of limb afferents]. Interaction of PSPs elicited by stimulation of hindlimb and forelimb afferent nerves was studied in lumbar flexor motoneurons of anesthetized cats. Activation of forelimb afferents evoked EPSPs of considerable duration; no IPSPs were observed. Stimulation of hindlimb flexor afferents evoked EPSPs in the same motoneurons, their early component being of segmental origin and their late component--of spino-bulbo-spinal one. Interaction of afferent systems of fore--and hindlimbs caused a long-lasting depression of EPSPs. The depression of EPSPs was not followed by generation of IPSPs in motoneurons, Possible integrative levels of interlimb inhibitory coordination are discussed.


[Reactions of nervous elements to K+ accumulation in the medium and functional potassium feedback at the synapse]. Increase in (K+)n leads to biphasic cahnges of MP and AP in the frog nerve. The first (ascending) phase at minor K+ accumulation is associated with activation of the membrane electrogenic ionic pump, the second (descending) phase at major K+ accumulation--with deploraization of the membrane. The rhythmic postsynaptic activity (50 Epp/sec.) produces the positive shift of ErevEpp. The latter indicates a potassium accumulation in synaptic cleft. The increase of (K+) in the medium leads also to biphasic change of the quantum contant of the synaptic transmission. The data obtained point out to participation of the synaptic potassium functional feedback (FF) in the phenomena of postactivational potentiation and presynaptic pessimum in the neuromuscular synapse. Hypotheses of participation of the potassium FF of neuro-neuronal synapses in the phenomena of conditioning and domineering, are advanced.


[Summation of arterial pressure responses to simultaneous stimulation of the central ends of the two vagus nerves]. In anesthetized vagotomized cats, electrical stimulation of the n. vagus was followed by an increase or decrease of blood pressure (BP) and heart rate, and of responses of these parameters to simulation of the other n. vagus. On increase of the strength of stimulation the testing response had multiphase variations. Mean depressor response of BP changed in the same way as the conditioning stimulus, while the pressor response changed in the opposite way. The vasomotor center is concluded to have an autoregulation mechanism which maintains activity of the center by increasing or decreasing the sensitivity to vagal afferents.


[Effect of fat on renal water excretion under conditions of disorders in the secretion of antidiuretic hormone]. The fat antidiuretic effect was studied in rats with inhereted diabetes insipidus (DI rats). In these animals the decrease of urine flow after fat ingestion was less stable and less profound as compared with non--DI: sunflower oil produced no effect in 12 DI rats out of 19, the per cent of inhibition in the other 7 being not more than 50%. No changes in urine osmalality were observed during the period of fat inhibition, while a significant decrease in creatinine excretion was revealed. Fat antidiuresis in DI rats was not affected by ethanol administration. These findings corroborate the assumption that fat ingestion in healthy animals is accompanied by the ADH release. It seems that changes in glomerular filtration rate are involved in the mechanism of this kind of antidiuretic response, at least in rats with impaired ADH secretion


[Principles of convergence and dominance]. The development of views on the convergence and dominant principles in cerebral cortex activity is described in this paper. The modern conceptions of the stable and dynamic synaptic inflows converging on somatodendritic membrane of the same neuron are presented. Also the significance of excitation level for neuronal constellation simultaneous activity and the possibility of the activity traces fixation in the multisensory neuron chains are considered.


[Interrelationships between the tissue link of the hemostatic system and the sympatho-adrenal system following transfusion of heterogenous blood]. In an experiment using 86 white rats it was found that during incompatible hemotransfusion shifts take place not only in the humoral but also in the tissue link of the hemostatic system. It was also seen that the rise of the functional condition of sympatho-adrenal system precedes those changes of hemostatic figures of the tissues. The interrelationships between a tissue link of the hemostatic system and sympatho-adrenal system under the incompatible hemotransfusion were demonstrated.


[Role of mechanical properties of the external ocular membrane in the dynamics of intraocular pressure]. Changes of the intraocular pressure in alterations of the central arterial pressure are an accepted fact. Disbalance of the above changes occurring at that is considered to be a display of active regulatory mechanisms. In this study, comparison of the pulse waves and short--term changes of arterial pressure with oscillations of the intraocular pressure occurring at that, has been made. Analysis of all the changes was made with the aid of a mathematical model. Amplitude--phasic characteristics of the eye membrane were studied for ascertaining of effect of different factors on the amplitude and form of the intraocular pressure pulse waves. In experimental conditions, the differences in dynamics of the level and in form of the pulse oscillations between the central arterial and the intraocular pressures were shown to be due not to functioning of active regulatory mechanisms but to the elastic--viscous features of the eye membrane.


[Electrophysiologic characteristics of rapid auditory adaptation]. In 32 rabbits, dependence of character of fast auditory adaptation on frequency of the sound stimulation was shown. Specific features of the adaption in conditions of switching off of the inner ear receptors with streptomycine were revealed. The fast adaptation was concluded to have a peripheral mechanism. Methods of the adaptation studying with the acid of action potentials of the 8th nerve and microphone potentials of the cochlear were compared under conditions of sound overload, and differences in results of measuring the fast adaptation were explained from the standpoint of dependence upon intensity of sound simulation.


[Functional specialization of stretch receptors in the triceps surae muscle of cats]. The behavior of 300 receptors in response to stepwise changes in muscle length was studied in passive m. triceps surae of cats anesthetized with nembutal. Distinct differences in receptor behavior were demonstrated, and receptors were divided into three functional groups according to their sensitivity to slow stretch (0.6 mm/sec in the limit range of 10 mm). The 1st group (elementary dynamic receptors) showed obvious sensitivity (over 70/sec) to dynamic components of stimulus and did not respond to static stretch in the physiological range. It was impossible to study the silent period during muscle contraction and stretch. The units of the 2nd group (elementary static receptors) reached maximal discharge frequency of 20--25/sec in the same range of muscle stationary stretch. The dynamic response of these receptors slightly exceeds the static response. The 3rd group, comprising 80% of units, served as universal detector of both dynamic and static phases of a stimulus. Some units showed significant dynamic response (over 70/sec) and moderate static response (about 30--40/sec), others exhibited moderate dynamic and static responses. The behavior of the receptors of universal type is similar to that of the well--known primary and secondary endings of the muscle spindles. Asto the endings of two elementary types they should be further indentified.


[Properties of the mechanoreceptors of the nipple of the guinea pig mammary gland. (Rapidly adapting mechanoreceptor units)]. Two types of rapidly adapting mechanosensitive units have been found in skin of the teat of guinea--pig mammary gland (RA1 and RA2). They wee not both spontaneously active. RA1 and RA2 have no position response. The relation between average frequency of discharge and displacement velocity at a constant displacement amplitude was linear for RA1. With constant velocity displacements, frequency versus displacement curves assume a horizontal orientation of relatively low discharge frequencies and are then displaced upward as velocity increases for RA1. The number and frequency of afferent impulses of RA1 decreased during repeated ramp mechanical stimulation. Vibratory tuning points were in the range of 10--25 Hz for RA1. 20% of mechanosensitive units were RA2, which have a high velocity threshold and rarely produce more than 2--3 impulses to high velocity. The fatigue of RA2 is not prominent. RA1 were classed as the velocity detectors and RA2 as "transient" detectors.


[Transcallosal modulation of a focus of maximal activity in the motor cortex]. In cats, EPs from 170 symmetrical points of the motor cortex were recorded  during bilateral and unilateral stimulation of nerves of hind--and forelimbs. Charts of localization of the maximal activity foce (MAF) were drawn. Transection of the corpus callosum was shown to be followed by narrowing of MAFs during bilateral stimulation and by their enlargement during unilateral stimulation. The effect of MAF enlargement was found to be due to summation of thalamocortical and transcallosal projections in animals with intact callosal system, while the MAF narrowing effect--to be determined by reciprocal transcallosal influences. Existence of the spatial transcallosal modulation of thalamocortical projection in the motor cortex is supposed.


[Transcallosal modulation of functional interhemispheric asymmetry]. The course and mechanisms of individual functional interhemispheric asymmetry (FIA) were studied with the aid of evoked potentials (EP) in the visual, auditory, and motor cortex of cats. The FIA was revealed in majority of the animals. It was peculiar by its bilateral origin and mosaic character. A combined summation--reciprocal (dominant) type of interhemisphere interrelationships was shown to underlie the FIA. A spatial-strength transcallosal modulation of the FIA is supposed to exist.


[Strength of synaptic stimulation and morpho-functional reorganization of the neuron]. In the Retzius cell of the leech, synaptic threshold and three-fold threshold stimulation 1/sec was followed by readjustment of the cell spike activity according to the stimulation rhythm. After cessation of the stimulation the initial bioelectrical activity restores. The membrane potential remains unaltered during the three-fold threshold stimulation. Electron-microscopically, the Retzius cells develop different ultrastructural changes. In case of the threshold stimulationthe changes indicate an intensification of the synthetic processes and, on the contrary, the three-fold threshold stimulation is followed by a decrease in the proteinmetabolism. In the first case, the amount of granular endoplasmatic reticulum increases and in the second case -- decreases. The same is true for the total amount of ribosomes. During synaptic stimulation, the Retzius cell mitochondria remain unlatered while during the three-fold threshold stimulation the mitochondria swell, their matrix clears up, and their krysts become reduced.


[Effect of the cholinesterase inhibitor armin on meuromuscular synapse function of the frog sartorius muscle]. The organophosphurus inhibitor of cholinesterases armin(2-10-9--2-10-4 M) prolonged postjunction potentials and in concentration 2-10-9--2-10-7 M increased the amplitude of miniature end-plate potentials (m. e. p. p. s and quantum content of e.p.p.s. These parameters were increased again after washing. Thus, armin (2-10-9--2-10-7 M) exerts anticholinesterase effect only. In concentrations 2-10-6--2-10-4M, in addition to the anticholinesterase effect, it affects presynaptic membrane and inhibits postsynaptic membrane cholinoreceptors.


[Changes in nystagmus following otolith stimulation]. In rabbits, stimulation of the otolith organs was shown to exert a double effect on nystagmus evokedby adequate stimulation of semicircular canals' receptors: The immediate and the delayed. On simultaneous stimulation of the two portions of vestibular apparatus, inhibition of systagmus occurs. In the course of aftereffect of the otolith stimulation, both the activated and the inhibited responses as well as the responses similar to control can be revealed, depending on the time interval between presentationsof otolith and cupulous stimuli.


[Mechanism of inhibition of erythropoiesis during post-transfusion polycythemia]. In mouse with posttransfusion polycytemia, depression of erythropoiesis suggests that, in response to erythrocytes transfusion, not only the differentiation of erythropoietin-sensitive cells is interrupted (cessation of inflow of the labelled erythrocytes into the circulation on the 8th day), but the proligeration of differentiated erythroid precursors is also inhibited (fall of amount of labelled erythrocytes during first days). This was corroborated by analysis of the experimental data with the aid of mathematical model of erythropoiesis. The model revealed that, in posttransfusion polycytemia, division of 40 percent of all divisionable erythroid precursors was halted.


[Effect of multiple hydrocortisone administrations on the kinetics of 22Na in slices of rat cerebral cortex]. The dynamics of 22-Na efflux from slices of rat brain cortex incubated in McIlwains medium was studied with the aid of improved compartmental analysis. Hydrocortisone (HC) was injected during 8 days. The isotope efflux followed 3-exponential kinetics. The kinetic analysis was made on the basis of 3-compartmental models of Na exchange. Administration of HC decreased the content of Na in fast-exchanged (extracellular) fraction and increased its content in the slow-exchanged (intracellular) fractions. HC elevated the speed constants of intercompartmental Na flows for intracellular fractions, especially the influx constants. The values of stationary Na flows between extra- and intracellular compartments were significantly increased. The data obtained are discussed with regard to direct action of HC on ionic exchange in tissue.


Pituitary and adrenal control of pancreatic endocrine function in the duck. II. Plasma free fatty acids, aminoacids, and insulin variations following hypophysectomy and replacement therapy with growth hormone and corticosterone. The levels of plasma free fatty acids, aminoacids and insulin were studied in normal, hypophysectomized and beef growth hormone and/or corticosterone treated hypophysectomized ducks. Hypophysectomy decreased plasma free fatty acids, aminoacids and insulin levels; growth hormone and growth hormone + corticosterone treatments in hypophysectomized animals induced opposite changes, while corticosterone alone only increased the concentrations of plasma aminoacids and insulin. However, corticosterone enhanced the growth hormone effects on the three parameters. It is suggested that four feed-back mechanisms may be involved in the control of glucagon secretion by the anterior pituitary and the adrenal cortex : glucose-glucagon, free fatty acids-glucagon, aminoacids-glucagon and insulin-glucagon. In addition, in these experiments, insulin and glucagon always varied in opposite directions.


[Diabetes of idiopathic haemochromatosis and common diabetes mellitus. Results of a prospective study of 97 families with idiopathic haemochromatosis (author's transl)]. The purpose of this study was to investigate through an epidemiological approach two controversial aspects of the pathogenesis of the diabetes mellitus of idiopathic haemochromatosis (I.H.) : the possible inheritance of the gene(s) for common diabetes mellitus (C.D.), and the diabetogenic role of iron overload. More than 80% of the living first degree relatives of 97 patients with I.H. were examined, while data were collected by inquiry concerning first degree relatives who had refused investigations or had died. Data on the more distant family members were also collected by inquiry. Physical examination and estimation of serum iron level and unsaturated-iron-binding capacity were systematically performed. When an anomaly had been thus detected further investigation for iron overload was carried out by mean of a deferoxamine test and eventually by liver biopsy. Evaluation of carbohydrate metabolism included testing for post-prandial glycosuria, estimation of post-prandial blood sugar, and eventually an oral glucose tolerance test. The results were compared to those of an inquiry for family history of diabetes in 100 patients with C.D. successively admitted to our department. Among the first degree relatives of patients with C.D. the prevalence of overt diabetes was 33 of 612 (5.4 %); whereas in the I.H. group it was 8 of 735 (1.1 %). The differences between the C.D. and I.H. groups were significant, whether the total I.H. group (p less than 10(-5)) or only I.H. proposite having overt diabetes (p less than 2 X 10(-2)) were considered. With respect to the more distant relatives the number of affected families was significantly higher in the C.D. group (31 of 100) than in the total I.H. group (5 of 97 ; p less than 10(-5)) or in the I.H. sub-group diabetic proposite (3 of 36 ; p less than 10(-2)). The frequency of carbohydrate intolerance in relatives bore no relation to the carbohydrate pattern of propositi. Carbohydrate intolerance was frequently found in relatives with iron overload (17 of 72). However, no correlation was observed between blood sugar and serum iron level or unsaturated-iron-binding-capacity, relatively gross parameters. Thus, the pathogenesis of diabetes mellitus associated with I.H. remains uncertain, but the inheritance of gene(s) for common diabetes is unlikely to play a determinant role.


Relationship between plasma insulin, the size and number of adpocytes and habitual calory intake in a group of 186 obese women. In a group of 186 obese women, no correlation was found between post-glucose load insulinemia, measured at 13:00 hrs, and the degree of overweight, nor between post-glucose insulinemia and mean adipocyte diameter. Significant correlations were found between post-glucose insulinemia and daily caloric intake, and between post-protein insulinemia and mean adipocyte diameter. Post-glucose and post-protein load insulinemia were interrelated.


[Dynamic epidemiology of diabetes mellitus (author's transl)]. Epidemiology as practiced to day has become outmoded. The authors propose a dynamic epidemiology, that is one applied throughout the country and which is in a stak of continuous development. This implies ascertainment of the major causes of diabetes : heredity and environment. Thus conceived, dynamic epidemiology can hope to tackle prevention in the prediabetic stage of a widespread chronic disease. A description is given of the method of application and a test of effectiveness.


Foetal rat pancreas in organ culture: effects of media supplementation with various steroid hormones on the acinar and islet components. Foetal rat pancreas (20-day postcoitum) was grown in organ culture using a natural media (serum and chick embryo extract). The media was supplemented with several adrenal and gonadal steroids; precursors, glucocorticoids, mineralocorticoids, estrogens, androgens and progesterone. The effects of the steroids on the pancreatic explants were quantitated biochemically by analysis of amylase and insulin in the incubated culture media and in the explanted pancreatic tissue, and morphologically by quantitative morphometric analysis. corticosterone, hydrocortisone, aldosterone and dexamethasone fully preserved the acinar cell component. The effect was concentration-dependent. Deoxycorticosterone and cortexolone had intermediate effects even at the highest concentration. Gonadal steroids had no effect on the acinar or islet component in this culture system. Some of the steroids inhibited the selective islet growth seen in the control explants as well as inhibiting insulin secretion. The relationship between these data and other work in this area is summarised. In addition, the possible implications of these data relating to normal in vivo pancreatic development are discussed.


Morphogenesis of lines and nets.

Morphogenesis of lines and nets. Complex linear appearing structures and networks (e.g. blood vessels, leaf veins, nerves) are formed reproducibly during the development of nearly every organism, but the molecular mechanism leading to such patterns is still unknown. A model is proposed in which a few simple coupled biochemical reactions are able to generate such structures. Among undifferentiated cells, a local peak of differentiation-inducing substance (activator) is formed by autocatalysis and lateral inhibition. The activator peak triggers the differentiation of the cell at that location. Due to changes in metabolism, the differentiated cell repels the activator peak and drives it to a neighbouring cell which then also differentiates. The repulsion between the activator peak and the already differentiated cells forces the activator peak to move ahead of the tip of the extending filament. Long filaments of differentiated cells may be formed, which can split, branch laterally, reconnect with each other and grow towards specific target cells. Partial differential equations describing the mutual interaction of the substances involved were presented and solved with a computer. The resulting patterns show self-regulating properties and other features found in the leaf vascular system, the pattern of tracheae in insect epidermis, and other biological networks.


Time-lapse filming of cellular interactions within living tissues. III. The role of cell shape. By a further development of the technique for time-lapse filming of organ cultures, it has become possible to observe the internal structure of the living tissues and to study the dynamics of intercellular contacts within the tissue. This method has been applied to a study of the interaction between the tissues of the chick chorioallantoic membrane and non-malignant fibroblasts, polyoma virus-transformed fibroblasts, and Harding-Passey melanoma cells. The behaviour of these cells in the absence and in the presence of colcemid has been investigated. From these studies it is concluded that disturbances in cell shape brought about by colcemid do not affect the invasive properties whereas the surface polypodial activity shown by the malignant cells is a major factor in tumour invasion.


An established cell line from the newt Notophthalmus viridescens. An established cell line, derived from the dorsal iris of the eastern North American newt, Notophthalmus viridescens, is described. The cells display an epithelial-like behaviour in culture, grow relatively slowly, possess considerably larger chromosomes than mammals and are heteroploid, although some near-diploid cells are present in the culture. The line is characterized by a strong tendency to overlapping and aggregation in spite of its origin from adult tissue.


Effects of mitogenic and antigenic stimulaton on the thymidine kinases of mouse spleen cells in vivo and in vitro. The DNA-synthesizing ability of mouse spleen cells in vitro and in vivo is paralleled by their levels of cytoplasmic thymidine kinase. However, a very high level of nuclear-associated enzyme activity developed in cultures of both non-stimulated and mitogen-transformed lymphocytes. This activity did not appear in the spleens of mice during the primary immune response to sheep erythrocytes (SRC) or following administration of Convanavalin A (Con A). Feedback inhibition studies with TTP demonstrated that the nuclear enzymes were more sensitive than the cytoplasmic activities. The thermal stabilities of the nuclear enzymes were also found to be greater than the corresponding cytoplasmic ones. Furthermore, analysis of the rate of thermal inactivation indicated that both the cytoplasmic and nuclear enzymes present in transformed lymphocytes in vitro were far more heat-stable than those activities normally found in the mouse spleen, even after antigenic challenge with SRC in vivo or incubation in vitro in the absence of mitogenic stimulation.


An in vitro analogue of early chick limb bud outgrowth. Our culture system appears to represent an in vitro analogue of early chick limb morphogenesis. Organized mesodermal cell accumulations resembling limb buds were derived from a monolayer of limb mesoderm cells when covered by limb ectoderm which included the apical ectodermal ridge (AER). The ridge retained its normal configuration when grown over a limb mesoderm monolayer and the mesoderm cells accumulated under the ridge to form a multilayered structure (10-25 cells in thickness) with the characteristic shape of a limb bud. Ectoderm which did not include the ridge failed to promote the formation of limb-like mesodermal accumulations thus the action of the ridge appears to be specific. The AER-elicited expression of mesodermal cell behaviour leading to early limb outgrowth is discussed in terms of possible morphogenetic mechanisms involved i.e. differential mitosis, cell migration, changes in cell shape and especially the adhesive properties of the cells.


Protein labelling patterns in oocytes of Xenopus laevis. Soluble and microsomal proteins synthesized at various stages of oogenesis in Xenopus laevis were compared by 3H and 14C dual-isotope labelling with subsequent mixing and analysis on sodium dodecyl sulfate (SDS)-polyacrylamide gels. The results indicated that the proteins labelled in all the stages of oogenesis studied are remarkably similar. However, the patterns in the small and medium-sized oocytes are more similar to one another than to the patterns characteristic of large oocytes. The greatest differences were found when comparing the microsomal proteins. The labelling patterns of oocyte proteins in vitro were not significantly different from the in vivo patterns for the stages of oogenesis studied. These results indicate that (1) there is little quantitative contribution of proteins to either the soluble or microsomal fractions from extra-oocytic sources in vivo and (2) the in vitro system itself has little effect on the labelling patterns over the incubation period.


Induction of haemoglobin synthesis in Friend leukaemia cells without the necessity of mitosis. Friend leukaemia cells (745A) were cultured in a soft agar containing 2% dimethylsulfoxide. In situ observation of the marked individual cells verified that the majority of haemoglobin-synthesized cells had not divided during cultivation. This is a direct proof that mitosis is unnecessary for the induction of erythroid differentiation of Friend leukaemia cells.


On the diversity of sperm histones in the vertebrates. I. Changes in basic proteins during spermiogenesis in the newt Notophthalmus viridescens. Sperm histones display great variability in contrast to the conservation of most classes of somatic histones. To study this paradox, this series of papers examines the variation of histone patterns in the testis and sperm of vertebrates, particularly amphibians and reptiles, and attempts to relate such variation to genetically based sex determination as hypothesized by Bloch [Genetics Supplement 61, 93 (1969)]. In the present study we have investigated spermiogenesis in the newt Notophthalmus viridescens viridescens. Cytochemical experiments indicate that the basic nuclear proteins undergo progressive shifts from somatic type histone leads to very arginine-rich "stable protamine" in the later spermatids leads to protamine in the mature sperm. Electrophoresis of Notophthalmus histones extracted from chromatin reveals that the pattern of testes specific basic proteins in the urodele is distinct from the pattern of testicular proteins in the anurans Bufo americanus and Xenopus laevis. Species within the class Amphibia therefore exhibit considerable diversification in their type of basic sperm proteins.


The surface charge of mesodermal and neural cells of Triturus embryos. The electrical surface charge of disaggregated mesodermal and neural cells of the neurula stage of Triturus vulgaris embryos is estimated by using the apparatus described in Figure 1. The results showed a significant difference between the net charges of these two cell types: the neural cells had a clearly negative charge, whereas the mesodermal cells seemed to be more or less neutral. The difference of the surface charges may partly explain the "sorting-out" phenomenon in the mixed reaggregates of the disaggregated cells.


[Natural history of unstable angina. Observations on 157 cases (author's transl)]. 157 cases affected with "unstable angina" and hospitalized were observed over a period of from 8 to 24 months (average observation time: 16 1/2 months). The patients were treated with: nitroderivates, beta blocking drugs (when not contra-indicated); treatment of side affects (hypertension; arrhythmias, decompensation, associated pathology, correction of risk factors of coronary heart disease). 9 cases were lost and 148 were studied for the course of the illness. 10.6% died from cardiopathy (2.8% through sudden death; 7.4% from myocardial infarction); there was a 12.1% total incidence of myocardial infarction; 50% of the cases were alive but with sumptoms of stabilized angina, whilst 32.4% were completely asymptomatic. Coronographic alterations and myocardial contractility negatively affect the course of the illness. Negative effects (disease or infarction) were not checked in the cases of stenosis of only one coronary branch. In the casuistry, there were no negative effects in patients with stenosis of one coronary branch, and in cases of two or more branches, negative effects were 28%. 41% of patients with alterations of ventrical contractility gave negative results. An asymptomatic course of the illness was checked more frequently in the intermediate stages than in angina cases.


[Prinzmental's angina and disturbances of the stimulus conduction (author's transl)]. Our series (30 cases) of variant angina as well as the reports from literature, were reviewed, to investigate the consequences of an acute regional ischemia on seno-atrial, atrio-ventricular and intraventricular conduction. Sinoatrial conduction was never affected independently from the anterior or posterior localization of the ischemia. A junctional impairment of atrio-ventricular conduction was rather frequent in cases of variant angina affecting the inferior wall, ranging in different series from 8% to 25%. Only one case of bundle branch block was observed. Hemiblocks were found to be extremely rare, while a deviation of the main axis of the QRS on the frontal plane, especially to the left in cases with anterior localization of the ischemia, was observed quite frequently. This axis deviation, in the absence of  changes of the initial vector of the QRS compatible with the diagnosis of hemiblocks, were considered to be depending on a parietal block.


[Comparative evaluation of the isometric test and of dynamic exercise in the diagnosis of coronary insufficiency (author's transl)]. Fifty patients with exertional coronary insufficiency performed an exercise test on a bicycle-ergometer and an isometric exercise with an instrument set up by the authors with the collaboration of the technical laboratory of the hospital. All cases had EKG positivity during dynamic exercise and only 2 patients had a positive EKG answer during isometric exercise. Angina occured in 70% of cases during dynamic exercise and in 12% of cases during isometric exercise. The difference in the increasing heart rate of the two types of exercise was statistically significant, as was the difference between absolute values of heart rate reached at the end of the exercise. The difference in the values of arterial pressure reached in the two types of exercise was also statistically significant. Moreover the comparison of product heart rate, time arterial pressure, time 10(-2) bordered on statistical significance. 31 of the 50 patients who underwent coronary angiography, demonstrated severe impairment. During isometric exercise a higher percentage of disturbances was observed. The authors came to the conclusion that isometric exercise is not advisable for the diagnosis of coronary insufficiency, either for the low specificity or the potential risk.


[On 23 cases of postinfartual interventricular septal rupture surgically treate. Immediate e long term results (author's transl)]. An experimental study on myocardial viability after acute occlusion of the left anterior descending coronary artery (LAD) for period of six hours is described. For this study 24 adult dogs were used in which an acute myocardial infarction for an area of 20-30% of left ventricul were obtained with ligatures completely occluding the LAD and his collaterals. Following ligature release, on the LAD only, ECG, BP, VCP and histology were studied with the general clinical conditions. The Authors affirm that clinical and ECGraphic data became worse after reperfusion; instead histological data show the possibility of recovery of many muscolar cells of ischemic and neighbouring areas.


[On 23 cases of postinfartual interventricular septal rupture s]. Twenty-three patients with ventricular spetal rupture complicating acute myocardial infarction underwent surgical repair. In 15 patients the interval between occurrence of myocardial infarction and operation varied from 2 to 18 days and in 8, from 2 to 9 months. In the group of the patients operated on early after the myocardial infraction (less than three weeks) the hospital mortality was 60%; in the group of patients operated on later, the ospital mortality was 12%. Tir six patients had a cardiac catheterization which showed a decrease of the end diastolic left ventricular pressure and a decrease of the pulmonary pressure. In two patients a residual small left-to-right shunt was present. The Aentricular septum is surgical; B) the surgical closure of the rupture should be delayed when possible from three to six w-eks after the infarction; C) in the patients operated on early after the myocardial infarction the operative risk is high, but the long-term results are good, as they are in the patients operated on later after infarction.


[Importance of coronarographic evaluation in valvular diseases for correct surgical indication (author's transl)]. Among 100 patients who underwent cardiac catheterization for acquired valvular disease, selective coronaryangiography showed in 25 cases obstructive changes of coronary arteries, in many instances of such severity to modify the therapeutic program (myocardial revascularization associated with valvular repair, counter-indication to surgical therapy). Coronary artery alterations were discovered in patients without clinical and electrocardiographic signs of coronary insufficiency, and, on the contrary, normal coronary tree was found in patients with positive clinical and electrocardiographic findings. The importance of coronarography in the haemodynamic study of valvular patients is stressed, even in absence of evident clinical signs of coronary insufficiency. The preoperative evaluation of the coronary arteries is fundamental for a correct surgical indication and for the results of surgical therapy.


[Problems of fascicular asyncronism in advanced left bundle branch blocks with marked axial deviation towards the left (author's transl)]. Twelve patients, showing advanced left bundle branch blocks with axial deviation toward the left (beyond -45 degrees) were studied by clinical, radiological and vectocardiographic examinations. All of them showed a marked cardiomegaly and half of them had also severe congestive heart failure. The left axial deviation may be connected to an asyncronism of the left ventricular activation, due to a delayed excitation of the antero-superior wall because of a lesion of the anterior fascicle. The authors think that this asynchronism of the activation should be evident in ECG test by a more delayed intrinsecoid deflection in aVL than in V6, as has been previously pointed out in the isolated anterior fascicular block. This ecgraphic datum was found in two patients only. The other possible causes of a left axial deviation in advanced left bundle branch block are discussed.


[The right bundle branch blocks with posterior loop (author's transl)]. The AA. have analysed 39 VCG which show terminal slowed down forces definitely directed towards the right and the back. It is presumed that such electrical patterns have to be classified amongst defects which deal with right intraventricular conduction. Both the ECG and UCG test have been classified in groups: some of them simulating BFA, others BFP. An analysis of the different developing ways of the vectorial loops has been made. The AA. think that in some cases the particular direction of the terminal forces could be compatible with an isolated and zonal right conduction defect in the posterior region of the right ventricle. In other cases the coexisting electrical pathology of the left ventricle is likely to be responsible for it. At the end the distinguishing diagnostic criteria of the ECG are discussed.


[Syncope during potassium depletion (author's transl)]. The onset of serious arrhythmias during potassium depletion occurs rather frequently in female subjects who have undergone hypotensive-diuretic treatment, independently from the duration and doses of drugs. These arrhythmias which produce a cardiac arrest, can also occur in subjects not affected with heart disease. They are not necessarily preceeded by clinical prodrumus or other types of minor arrhythmias not accompanied by other important electrocardiographic or serum-logical alterations of hypokaliemia. The most commonly observed type is the "torsades de pointe", though cases of ventricular tachycardia or ventricular fibrillation are also documented. The ethiopathogenesis is discussed with regard to the alterations of the basic electrocardiogram as well as to the kind of major arrhythmia. In most cases , lidocaine has given the most satisfactory thmias, results in the treatment of these arrhythmias, probably because of the modality of the action which is substantially different from the other antiarrhythmic drugs.


[The hypotensive effect of propranolol: pathophysiological and clinical approach (author's transl)]. The hypotensive effect of propranolol and its correlation with the fall in heart rate, plasma volume and plasma renin activity produced by this drug, were studied in 20 hypertensive hospitalised patients. Heart rate and plasma volume fell to approximately the same level (20%) in all cases, while the hypotensive response varied according to the pretreatment levels of plasma renin activity. Patients with low renin did not respond, while those with normal renin and especially those with high renin responded with a significant fall in blood pressure which was directly correlated to the fall of plasma renin activity. It is concluded that propranolol might be the specific treatment for hypertension in those cases which are accompanied or caused by high plasma renin.


[Horseshoe lung, cardiac malposition and pulmonary vascular anomalies: a characteristic syndrome (author's transl)]. The clinical, radiological, haemodynamic and angiocardiographic features of a very rare anatomo-clinical entity (i.e. the horseshoe lung), associated with heart malposition and anomalies of the venous and arterial pulmonary vasculature are reported. The horseshoe lung is a pulmonary malformation which essentially consists of partial fusion of the lungs behind the pericardial sack. Of this entity only two cases have been previously reported in the literature, in which the diagnosis was made at necropsy. The reported case is the first in which the diagnosis was made in a living patient. The essential characteristic considered pathognomonic of the syndrome are described.


[Primary pericardial mesothelioma: report of a case (author's transl)]. A case of primary pericardial mesothelioma in a 36-year-old man is reported. The disease, with an atypical clinical onset and rapidly fatal course, was diagnosed before death, by means of clinical examination, chest X-rays, cineangiography and microscope examination of pericardial and pleural exudate, revealing the presence of malignant mesothelial cells. Postmortem examination confirmed the diagnosis and revealed thoracic and extrathoracic metastasis. The clinical, anatomic, pathologic aspects, as well as treatment of primary pericardial mesothelioma are discussed.


[Radioactive immunoassay of digoxin during digitalis therapy (author's transl)]. Measurements of plasma-digoxin concentrations (radioactive immunoassay) after single oral administration of different doses of beta-methyldigoxin, given by tablets or drops, were made. Their behaviour after more prolonged treatment with the same cardiac glycoside was also evaluated. The utility of radioimmunoassay of serum digoxin levels during digitalis therapy is confirmed.


[Correlation between results of bicycle stress test and coronaric arteriography. Study of 153 patients (author's transl)]. In 153 patients the results of bicycle stress test were compared with data obtained from coronaric arteriography. There were corresponding results from both tests in most cases. There are other discrepancies which cannot be explained by defining the stress test as "unspecific" or "not very sensitive". In fact, each time, time differences can be referred, besides method limits, to particular physio-pathological stages of the coronaric disease (collateral circulation, Prinzmetal angina) or they can be considered completely independent of the coronaric disease (myocardial disease without coronaric disease, enzymatic defects; haemoglobinic alterations, etc.). The two tests have different indications, but they can also complementary information.


[Aortic sinus aneurysm. The angiographic diagnosis (author's transl)]. Three cases of aortic sinus aneurysm and three cases of prolapse and regurgitation of the aortic valve associated with ventricular septal defect are discussed from an angiographic point of view. It is pointed out that aortic regurgitation into the left ventricle might be helpful for a correct diagnosis. Aortic regurgitation, in fact, is the result of an anatomically unsupported aortic valve that becomes gradually distorted by haemodynamic influences. This pathogenetic mechanism is often found in subpulmonar and infracrestal ventricular septal defect.


The results of "exercise therapy in coronary prone individuals and coronary patients". The authors followed for at least two years 483 patients (430 coronary prone patients and 53 with proved coronary heart disease), to determine whether physical training could decrease coronary risk factors and improve exercise tolerance in the trained group as compared with the conventionally treated group (way of life, diet, drugs). There was no significant difference among the two groups for blood lipid profile, blood pressure (at rest and during exercise), functional capacity and mortality. In the authors' opinion this could be explained by the inadequate training program (45 minutes twice a week) and by a possible overlapping of the groups.


[Effects of lidocaine on supraventricular arrhythmias (author's transl)]. Using Lidocaine intravenously in 99 patients with atrial arrhythmias, it was observed that the drug has a regularising effect in 41 from 45 atrial arrhythmia, atrial tachycardia with block and accelerated ectopic supraventricular tachycardia, where the enhanced focal activity should be taken into account. No effect was observed in functional supraventricular tachycardia, paroxysmal atrial flutter and fibrillation and tachyarrhythmia in WPW syndrome, where the re-entry mechanism plays the major role. The effect of the drug is short lived, but may be prolonged by using the drug in perfusion or repeatedly with an intramuscular method. Lidocaine acts by depressing the enhanced atrial focal activity, and therefore may be of value in the treatment of these kinds of arrhythmias.


[Effects of Bunaphtine on right atrial and ventricular monophasic action potentials in man. Preliminary note (author's transl)]. Effects of Bunaphtine on right atrial and ventricular monophasic action potentials were investigated in 6 patients using the technique of endocavitary recording with a suction electrode. The authors found that the drug, given intravenously in the usual therapeutic dosages, increases the total duration of MAP both atrial and ventricular, together with quite a proportional ERP prolongation. At ventricular level MAP's increase in correlated to a prevailing and strong increase of phase 3. However, the variations of the MAP's amplitude, its O dv/dt phase and the cardiac specific conduction's alterations (noted only at higher dosages) have been inconstant and poor on the whole. On the basis of these results, the mechanism of the action of the drug is discussed.


Congenital extracardial malformations accompanying congenital heart disease. A statistical review of 1,354 autopsies performed in cases of congenital heart disease in three major Italian hospitals was carried out. In 446 cases one or more extracardial malformations were found; those most commonly encountered were malformations of the urinary tract, anomalies of the respiratory tract, malformations of the intestine and spleen and trisomy 21. Ventricular septal defects and persistent common atrioventricular canals occurred in a higher percentage of cases with extracardial malformations than in those where congenital heart defects were the only malformations. The reverse was true of endocardial fibroelastosis and transposition of the great vessels. Ventricular septal defects are particularly common in the Klippel-Feil syndrome, in trisomy 18 and, together with a persistent common atrioventricular canal and atrial septal defects, in trisomy 21. The typical picture of so-called "congenital heart disease associated with asplenia" was found in cases with splenic agenesis, either with or without situs inversus viscerum, but also in cases with situs inversus viscerum without asplenia.


[Corrected transposition of the great vessels. A clinical review of 21 cases (author's transl)]. Clinical and instrumental features of 21 cases of congenitally corrected transposition of the great vessels are reviewed. We confirm the rarity of the isolated form of the disease and its frequent association with ventricular septal defect and pulmonary stenosis. Electrocardiographically, the inversion of the first vectors is represented more frequently by the absence of the q wave on the left precordial leads than by the presence of the q wave on the right precordial leads; a very frequent electrocardiographic feature is a positive T wave on the right precordial leads. The angiographic image of the two ventricles in the lateral projection where they appear as crossing each other in their upper part were described. We confirm the poor results of the surgical treatment of the disease and the non-benign prognosis, because of the other associated cardiac anomalies.


[Experimental revascularization of acute myocardial infarction. II: Activity of various oxidoreductive tissutal and serum enzymes (author's transl)]. The behaviour of some enzymatic activities, such as monoamino oxidase (MAO), diamino oxidase (DAO), catalase, peroxidase and creatin chinase (CPK) have been studied both in blood serum and myocardial tissue of acute infarcted dogs (obtained by coronary occlusion). The most significant results are the changes of the DAO activity (--50% from the control) and peroxidase activity (+60%), 6 hours after acute ischemia. The effect of reperfusion was studied 2 hours later. A recovery of DAO activities was shown, while the peroxidase activities stayed elevated. All the enzymatic activities studied were evaluated in the serum, under the same experimental conditions. An increase of all these activities was observed until 6th hour of coronary occlusion. The reperfusion of acute ischemia, after six hours, causes a further increase of CPK and MAO activities and a decrease of catalase peroxidase and particulary evident DAO activities. The results of this experiment show that reoxygenation, under our experimental conditions, increases a further enzymatic release and in part causes a metabolic recovery of heart muscle.


[The participation of the cholinergic system in the genesis of the reflex vasodilatation in the gracilis muscle of the dog (author's transl)]. These experiments were undertaken to demonstrate the participation of the cholinergic system in the reflex vasodilatation in the gracilis muscle of the dog evoked by rapid i.v. injection of norepinephrine. The analysis of the integrated areas of vasodilatation curves after pretreatment with atropine showed a significant decrease of the reflex vasodilatation suggesting the participation of the cholinergic system to the mechanism underlying the phenomenon. The residue vasodilatation was completely abolished by the subsequent i.a. administration of phentolamine. On the other hand, guanethidine too could, also without pretreatment with atropine, nullify the reflex vasodilatation. This effect, therefore, does not permit the ruling out of the existence of a cholinergic component in the reflex vasodilatation since the actions of these drugs are not yet completely known.


[The kinetocardiogram in complete left bundle branch block. Correlations between the kinetocardiogram and systolic time intervals (author's transl)]. The authors studied the possible correlations between the behaviour of the systolic time intervals, as measured by the electrophonosphygmographic patterns, and the behaviour of the kinetocardiogram recorded on left precordium, in 23 cases of complete LBBB. The results tend to confirm the possibility of distinguishing the distal from the proximal level of the conduction defect in a non invasive way, as already indicated in literature. Evidence for the former is the observation of a lengthening of the isovolumetric contraction time, of an increase of the PEP/LVET and ICT/LVET ratios, of a pansystolic bulge in KCG with a pathological amplitude of the atrial waves, all showing a left ventricular dysfunction. Evidence for a proximal level of conduction defect is: the normal length of the ICT, the normal PEP/LVET and ICT/LVET ratios, the absence of pathological atrial waves in KCG. The presence of paradoxical outward movement (POM) in KCG also in the latter case, even though only rarely observable as a pansystolic bulge, could be related to the existence of a form of ventricular dyssynergy, due to the deranged conduction of the impulse (ventricular dyskinesis from inter- or intra-ventricular asynchrony).


[Study of left ventricular function. Part II: systolic perimetric variations (author's transl)]. New parameters for the study of ventricular dynamic, which analyze the perimetric dimensional variations of the ventricular margin on the cineventriculographic projective plain, were introduced. Three usable methods for these determinations are described: 1) the systolic dimensional variation of the total perimeter; 2) the contribution to the total perimetric length and the systolic shortening of the anterior and posterior wall; 3) the contribution of the telediastolic and the telesystolic length to the anterior or posterior wall and the systolic shortening (in mm/m2 of the corporeal surface and in the percentage of the respective telediastolic length) of each marginal region.


[Aneurysm of the left ventricle in infants. Report of two cases successfully treated (author's transl)]. Aneurysm of the left ventricle in infants is quite a rare cardiac malformation. In this paper two cases are described, six and seven years old respectively, the first one with a subvalvular annular type of aneurysm, the second with an apical type, both surgically treated with success. Ths most known and most frequent aetiological factors are discussed as well as their possible complications. Surgical treatment (aneurysmectomy) is emphasized as the only effective therapy to date.


[Correlations between automaticity and conduction. Considerations in a case of left bundle branch block in phases 3 and 4 (author's transl)]. A case of phase-3 (tachycardia dependent) and phase-4 (bradycardia-dependent) left bundle branch block (LBBB) which illustrates some relationships between automaticity and conduction in the intraventricular conduction system is reported. The observations made were: a) a conspicuous spontaneous variability of the conductivity and block temporal zones in the left bundle branch (LBB), i.e. of the cycle duration determining either normal intraventricular conduction or block in the LBB; b) after isoproterenol, transient shortening of phase-3 block zone and disappearance of phase-4 block zone due to escape beats which rise from the LBB; c) transient change into not rate-dependent LBBB in consequence of catheter LBB injury and gradual successive reappearance of conductivity zone; d) short periods of 2:1 phase-4 LBBB. A coexisting phase-4 block in a LBB fascicle with electrocardiographic pattern not fulfilling the agreed diagnostic criteria for hemiblocks was also demonstrated. This intraventricular conduction defect was also characterized by conspicuous spontaneous variability of the block temporal zones. After isoproterenol, the duration of the cycle decreased where it occurred. After LBB traumatic injury, it lasted not rate-dependent longer than LBBB and no escape beats rising from the LBB injured fascicle appeared. During normal intraventricular conduction the ECG showed "ischemic" alterations in V1-V4 leads of variable degree related to LBB conductivity and block zone duration. Selective coronary angiograms were normal. These findings are discussed in an attempt to clarify the electrophysiological mechanism of rate-dependent intraventricular conduction defects.


[Hypolipidemic effects of DH581 during prolonged administration (author's transl)]. A new cholesterolol lowering agent, DH581, has been studied in eighteen patients with elevated cholesterol levels for more than one year. The data showed twelve patients studied as being cholesterol responders with an overall decrease of 21%. The Placebo period had an overall rise in cholester with a return of effect after re-administration of the drug. During the remainder of the study period, responders had a 17% decrease in cholesterol. Non-responders varied widely but did not demonstrate a significant cholesterol decrease. Triglyceride levels demonstrated wide fluctuation. Nine responders of eighteen patients studied had an overall decrease of 32% and the remainder demonstrated an increase in triglyceride values. Weight changes were not significant and did not account for the observed changes. There was no consistent relationship of sex to the observed response. DH581 appears to be effective antyhypercholesterolemic drug of low toxicity.


[On the method for determination of sinus node recovery time (author's transl)]. On the basis of personal experience of 22 patients, 11 with sick sinus node syndrome (SSNS) and 11 without, it was concluded that the seat and length of atrial stimulation has little importance for the determination of recovery time for corrected sinus node (RTCSN). The frequency of optimal stimulation seems to be 110 impulses per minute for 2 minutes, by which it generally reaches the maximum value of RTCSN. Using this method, the falsely normal RTCSN in SSNS subjects can be verified; in these cases the test should be repeated within a larger frequency scope.


["Variant" angina: clinical, electrocardiographic and coronarographic aspects in 40 cases. Considerations for treatment (author's transl)]. Forty patients with chest pain and the electrocardiographic aspects of Prinzmetal's variant angina were studied by means of selective coronary arteriography. In 36 cases (90%) severe coronary lesions could be demonstrated: in 75% of the cases a critical obstruction involved a single major coronary trunk; only in 15% two or more vessels were affected. The vessel most frequently involved by critical obstruction was the left anterior descending (57%); in 5 cases (12.5%) a severe stenosis of the common left coronary trunk was present. In 8 cases critical stenosis were reduced by coronary dilators and were completely resolved in 2 cases. Peripheral lesions with multiple secondary branches involvement were present in none of the cases. A common finding was the absence of evident collateral anastomotic circulation. The comparison of the electrocardiographic manifestations of the anginal crisis and the angiographic findings showed a strict correlation between the area of subepicardial lesion and the major coronary vessel distributing to the corresponding myocardial region. Of the 40 patients, 17 were treated medically and 23 underwent a surgical aortocoronary bypass: the results (surgical mortality 22%; complete success 52%) are compared with those in the literature. Prognosis appears to be severe: coronary arteriography must be performed under criteria of urgency, and the possibilities of treatment must be considered on the basis of the angiographic findings.


[Non-transmural myocardial infarctions. Evolutive ecgraphic and angiographic clinical aspects (author's transl)]. The authors report fifty-nine cases of non-transmural myocardial infarction. The diagnosis was made on the basis of clinical electrocardiographic data and enzyme changes. The clinical course was characterized by several chest pain attacks; a transmural myocardial infarction occurred in four patients a few days after admission. Out of fifty-five patients, followed for a nineteen - months period, six died, thirty-one were asymptomatic and fourteen complained of angina. In the last group, chest pain was generally present before the non-transumural myocardial infarction. The ECG were within normal limits in thirty-seven patients. The coronarographic patterns found in fifteen patients are also described and discussed.


[Effects of amiodarone on atrio-ventricular and ventriculo-atrial conduction in the Wolff-Parkinson-White syndrome (author's transl)]. In 10 patients with the Kent's bundle W.P.W. syndrome, the action of amiodarone (5 mg/kg i.v.) on conduction along the normal and anomalous pathways was studied. The drug actions were: 1) constant increase of the anomalous pathway E.R.P., in one case with antegrade functional block; 2) constant reduction of antegrade conduction velocity along the anomalous pathway, in one case with antegrade functional block; 3) reduction of retrograde conduction velocity along the anomalous pathway in 6 cases out of 8, including one with retrograde functional block; 4) constant increase of the A-V node E.R.P.; 5) reduction of sub Hisian A-V conduction velocity in 3 cases out of 7. Episodes of reciprocating tachycardia could be initiated by atrial electrostimulation in 5 patients before administration and in 3 following administration of the drug. In connection with the electrophysiological properties of the two atrio-ventricular pathways and on the mechanism of tachycardia, the use of this drug in prevention of the circus movement tachycardia in patients with the W.P.W. syndrome is discussed.


[Conduction disturbances associated with the sick sinus node syndrome. Study of fifteen cases with His bundle electrogram (author's transl)]. Disturbances in atrioventricular conduction were demonstrated in 17 out of 38 cases of sik sinus node syndrome (MNSA). 14 cases had BAV, in varying degrees, 9 had intraventricular conduction disturbances, 13 had pathological values of A-H, 6 pathological values of H-V, 4 contemporaneous lengthening of A-H and H-V. The ECG and hissian electrogram examinations enabled the identification of the seat and the extension of the conduction disturbance, which was schematized as nodal, nodal and truncular, intraventricular (mono-, bi-, and trifascicular) and diffused. It is possible that the damage to the conduction system associated with MNSA has the same etiology. The frequency of the association of MNSA with conduction disturbances suggests, in the case indicated, the use of a ventricular electrostimulation.


[Study of several electrophysiological effects of procainamide in man (author's transl)]. Several electrophysiological aspects of the effects of procainamide were analyzed, using a method which allows direct study in man. The following electrophysiological parameters were determined under normal conditions in pace-maker carriers: myocardial stimulation threshold (M.S.T.), above-normal excitability phase (A.N.P.), effective refractory period (E.R.P.), pre-automatic pause (P.A.P.) and frequency of spontaneous rhythm (S.R.). After i.v. somministration of 10 mg/kg of procainamide in six subjects, and of 20 mg/kg in one, the modifications resulting from the examined parameters were analyzed. They showed that procainamide determines the constant elevation of the M.S.T., the shortening of duration of the A.N.P., lengthening of the E.R.P. and depression of the ventricular, but the superventricular automatism. Hypotheses on the electrophysiological mechanism of the observed effects are analyzed, and some clinico-electrophysiopathological correlations are traced, which help in the understanding of the anti-arrhythmic activity of procainamide.


[Plasma renin activity in renal veins in different types of arterial hypertension (author's transl)]. Peripheral plasma renin activity (PRA), vena cava and renal veins PRA were measured in 85 patients; arterial PRA was also measured in several cases. 25 patients had essential hypertension or primary aldosteronism; whereas in 60 patients renal or renovascular abnormalities were present. Peripheral PRA was elevated in 17/30 patients with parenchimal or excretory tract diseases. The following ratios came from the results of vena cava, and renal veins PRA were calculated: Ra/Rc and Rc/P according to Stockigt et al. and V-A/A according to Vaughan et al. The ratios were calculated only when v. cava PRA was greater than 4 ng/ml/3 hrs. A good correlation was found between v. cava can arterial PRA. Among the 60 cases with renal hypertension, 26 underwent either revascularization or nephrectomy surgery. Eleven of the 15 patients operated on for renovascular diseases showed a significant reduction of blood pressure (greater than 30 mmHg); all had high peripheral PRA and 6 had significant Ra/Rc and Rc/P (respectively greater than or equal to 1,5 and less than or equal to 1,3). The same patients also had V-A/A of the affected kidney greater than or equal to 0,48 and 5 also V-A/A of the controlateral kidney less than or equal to 0,23, both values being significant for a unilateral renin secretion and controlateral suppression. Among the 4 patients who were unsuccessfully operated on, only 2 had elevated peripheral PRA and 1 had Ra/Rc and Va-A/A greater than normal, but not significant values of Rc/P and Vc-A/A. 11 patients with small kidney or other forms underwent surgery; among the 6 cases with satisfactory results, 5 had high peripheral PRA, 2 showed significant ratios Ra/Rc and 3 a significant V-A/A for both kidneys. Only 1 of the patients not cured by surgery had supernormal peripheral PRA and none had any significant ratio. Therefore both methods for elaborating data obtained from the measurement of PRA in renal veins seem to offer similar prognostic indications. The finding of significant ratios is an almost sure criterium for predicting a surgical cure of renal hypertension, whereas the cases where we may expect a failure present ratios which are not significant. However, patients of the latter group may sometimes have successful results at surgery too, which demonstrates that other mechanisms may also be involved in the pathogenesis of this form of hypertension.


[Echocardiographic study of the Björk-Shiley disc prosthesis (author's transl)]. The echocardiography of 25 patients with Björk-Shiley disc prosthesis (16 aortic, 7 mitralic, 1 both mitralic and aortic and 1 both mitralic and tricuspidal) was studied. Mitralic prosthesis were placed with the shortest disc segment looking forward; aortic prosthesis faced the shortest disk segment looking towards the coronaric sinus. The echo's morphology is related to the multiple relationships among position and direction of the prosthesis and the probe. In the aortic echocardiogram, it is possible to recognize echoes from the ring dissociated by anterior and posterior aortic walls. Between them echoes corresponding to the open disc appear, making a quadrangular figure. The values of the internal diameter of the ring obtained were very similar to the real value (difference 0-1 mm). Mitralic echocardiogram is characterized by the valvular disc movement tracing the typical quadrangular pattern, which is due to its opening and closure. Echoes of the supporting apparatus can be recorded directing the probe toward the heart base. In aortic and mitralic prosthesis, disc movements can be estimated. Opening and closure speed rate and their correlation vary on a large scale, both within different patients and in the same patient. Maximum disc excursion appears to be a more homogeneous and constant data in long-term controls and can be used to estimate valvular functionality: in aortic prosthesis valve the obtained value (mean = 17.46 +/- 0.53 "ES") is similar to the real diameter of the disc, in mitral prosthesis valve the value obtained (mean = 17.50 +/- 0.74 "ES") is shorter than the real value.


[Tachycardia-bradycardia syndrome. An electrophysiological and pharmacological study (author's transl)]. In nine patients with the tachycardia-bradycardia syndrome, a dysfunction of sinusal automatism was observed, shown by a prolonged recovery time of sinus node for six of the patients, and by an insufficient response to atropine in all nine. In two of the five patients, where a study of seno-atrial conduction was possible a conduction defect at this level was noticed. In three patients (33%), asystole was observed: in one patient in the course of a tachycardial crisis; during the passage of an atrial fibrillation in sinusal rhythm in another, and following premature isolated atrial pulsations in the third. The observations of asystole pause in the third patient following premature isolated beats which were longer than those induced electrically, led to the conclusion that, more than a sinusal automatism or sino-atrial conduction defect, asystole can be due to repetitive re-entries that are not reproduced at the level of the sino-atrial junction. The atrial response obtained in another patient with atrial stimulation slightly superior to the threshold, seems to exclude an atrial inexcitability hypothesis. The paroxysmal tachycardia and the atrial fibrillation were the most frequently noted arrhythmias; atrial flutter was only rarely observed. A rotation of rhythm disturbances was recorded in four of the nine patients, both on diverse occasions and during one crisis. The atrial electrostimulation performed on a patient during asystole pauses occurred spontaneously during the course of a tachy cardial crisis, allowed conduction of the atria only for 1-2 stimuli, and did not impede the recovery of the tachycardial paroxysm. It is probable that the conduction disturbances and/or the atrial excitability, which have the same determining cause of sinusal dysfunction, can be responsible for atrial arrhythmias, with the characteristic symptom of the tachycardia-bradycardia syndrome.


[The influence of gastric acidity on digoxinemy (author's transl)]. The effect of gastric acidity on the absorption of a cardiac glucoside has been studied in vivo in three groups of patients with heart disease, measuring blood levels and urinary excretion of the digitalis compound by radioimmunologic assay. The median blood levels were lower in hyperacidic subjects and higher in hypoacidic patients; the urinary excretion of the digitalis compound showed no essential differences.


[Left ventricle-right atrial communication. Surgical, hemodynamic and clinical aspects (author's transl)]. Anatomical, clinical radiographic and electrocardiographic aspects in 12 cases of left ventricle-right atrial communication are described. The usual severity and precocity of symptoms are outlined. At cardiac catheterization the level of the shunt was not found to be exactly correlated with the anatomic type of the defect; the mean QP/QS was 2,7 (1,4-5,8); only one case of pulmonary hypertension was detected and the mean RP/RS was 0,19 (0,06-0,83). Contrastographic aspects are emphasized and the importance of having two orthogonal projections is outlined. 9 patients underwent surgical repair with good results, except for the patient with pulmonary hypertension, who died soon after the operation: this patient shouldn't have been operated on. In all cases only right atriotomy was made, and the defect was closed by a dacron patch; no patient had a tricuspid plastic; one perforation and one cleft of the septal leaflet of the tricuspid valve were sutured directly. In view of the simplicity of surgical correction, wide indications are possible, considering, too, that there have been no reports on the spontaneous closure of the defect.


[Coronary artery spasm induced by the somministration of ergonovine maleate in subjects with spontaneous angina (author's transl)]. In 6 patients affected by spontaneous angina with S-T elevation and coronariographic findings of obstruction, intravenous administration of ergonovine maleate determined the same clinical and ECG patterns of spontaneous episodes. The coronary arteriography during pain showed a marked spasm with occlusion of a large coronary vessel in four patients. In 2 patients with atypical chest pain and normal coronariogram, E.M. did not induce pain, ECG abnormality or coronariographic alterations. The role of spasm in spontaneous angina is discussed.