[Isolation of the enzyme lipase from Pseudomonas fluorescens 533-5b and its characterization]. From the culture liquid of Pseudomonas fluorescens 533-5b, lipase (partially purified by sulphate ammonium precipitation and dialysis) was isolated. The following properties of the enzyme were examined: effect of pH and temperature, effect of bile salts, substrate specificity, and stability during storage. The optimal action of the preparation was at 55 degrees C and pH 7.5-8.0. Sodium salts of cholic, taurocholic, deoxycholic, and glycocholic acids at concentrations over 0.5%, as a rule, activated lipolysis. The enzyme preparation was stable during storage: activity losses were no more than 15% during a 2 month storage at 4 degrees C. Lipase of Ps. fluorescens 533-5b was capable to utilize as substrates many vegetable oils (olive, corn, castor, mustard) as well as synthetic triglycerides containing carboxylic acids with short and long carbon chains.


[Effect of pH on the conformation properties and enzyme activity of alpha-amylase from Aspergillus terricola]. The effect of pH values on the conformation state of the protein globule and enzyme activity of alpha-amylase isolated from the culture liquid of the fungus Aspergillus terricola was studied. By the method of dispersion of optical rotation, it was demonstrated that together with the disordered structure the alpha-amylase macromolecule in its native form contained alpha-helix and beta-structures. With a pH change the enzyme macromolecule showed two conformational transformations: with a pH decrease from 4.0 to 2.0 alpha-helix uncoiled, and with a pH increase from 8.0 to 12.0 beta-form degraded. Hydrolytic activity of alpha-amylase was found to vary symbatically with the specific optic rotation in the above pH range.


Concurrent daily infection of calves with Fasciola hepatica and Ostertagia ostertagi. Three groups of calves were infected daily with either 1500 Ostertagia ostertagi larvae, 20 Fasciola hepatica metacercariae, or 1500 O ostertagi plus 20 F hepatica metacercariae. Weekly measurements were taken of calf weight, faecal egg output, plasma concentrations of albumin, plasma activities of sorbitol dehydrogenase, gamma glutamyl transpeptidase and pepsinogen and standard haematological indices. Calves were killed either 10 or 21 weeks after daily infections began. F hepatica infection had little influence on the size and structure of the O ostertagi worm population or vice versa. Mean worm burdens found at 20 weeks in those animals infected with both F hepatica and O ostertagi were 293 flukes and 20,641 nematodes. While this level of infection is similar to that seen in the disease complex in the field, there was no evidence of clinical disease or any difference in weight gain between the groups in this experiment. Factors other than additive worm burdens are obviously important for the expression of disease under field conditions.


Vasomotor rhinitis--pathophysiological aspects. Vasomotor rhinitis is commonly defined as an unspecific hyperractivity of the nasal mucosa. The symptoms might be due to increased parasympathetic activity to the nose with the release of vaso-secretory active substances. Experimental data from the cat suggest that the postganglionic parasympathetic mediator of nasal secretion is cholinergic, whereas the vascular responses appears to be due to a different mechanism. Apart from a rich sympathetic and parasympathetic innervation of the nasal mucosa there are other nerve fibres containing substance-P (SP) and vasoactive intestinal polypeptide (VIP). The secreto-vasomotor responses can be influenced by activation of these fibres and the atropine resistant vasodilatation seen following Vidian nerve stimulation thus may partly be due to activation and release of SP and VIP. Furthermore, other vasoactive substances released such as e.g. SRS or Kallikrein may participate in these reactions.


[Ionized fluorine in the plasma and urine of subjects treated with organofluorine drugs prescribed in rheumatology]. The elimination of ionized urinary fluorine was studied in groups of eight subjects treated during several days with niflumic acid, flufenamic acid, sulindac, antrafenine and floctafenine. Sulindac and floctafenine do not changes this elimination. After administration of niflumic acid, flufenamic and antrafenine, the urinary elimination of ionized fluorine increase in all the subjects. This increase is manifested from the start of treatment and persists for several days after it has been stopped. The administration of three drugs also results in an elevated level of ionized plasmic fluorine the duration of treatment. The results prove the existence in the human organism of a metabolic process capable of effecting the ionization of the organic fluor contained in the drugs studied. This biotransformation causes a fluorine impregnation of endogenous origin that is permanent and relatively stable, and whose consequences are examined (risk of fluorine osteosis and possibility of therapeutic application).


Allergic granulomatous angiitis.

Allergic granulomatous angiitis. A 15-year-old boy died after a 3 years' illness; asthmatic bronchitis, recurrent heart failure and eosinophilia were the essential manifestations. The autopsy elicited a diagnosis of allergic granulomatous angiitis, because of angiitis with fibrinoid necrosis and granulomatous lesions in vascular and extravascular regions. The most important differential diagnostic aspects of this disease are discussed, especially the resemblances to Wegener's granulomatosis, hypersensitivity angiitis and polyarteritis nodosa.


Blood eosinophil leucocyte and eosinophil cationic protein. In vivo study of the influence of beta-2-adrenergic drugs and steroid medication. The in vivo effect of beta-2-adrenergic stimulating and blocking drugs and of corticosteroid medication on blood eosinophils and serum eosinophil cationic protein (S-ECP) has been studied. The beta-2-adrenergic drugs, salbutamol and terbutaline, had an eosinopenic effect. They were able to decrease S-ECP concentration, which administration of steroid was not, indicating that only the adrenergic stimulators affect leucocyte secretion. Care must be taken in interpretation of blood eosinophil count and S-ECP concentration, and the actual medical treatment must be known.


[Effect of a chronic alpha adrenergic receptor blockade on basal secretion of renin in essential hypertension]. To investigate the effect of chronic alpha-adrenergic receptor blockade on renin release, plasma renin activity (PRA) was determined overnight at short intervals in 9 patients with essential hypertension before and after 7 days medication with phenoxybenzamine (20 mg orally/day). Inhibition of basal (supine) renin secretion in response to alpha-adrenergic receptor blockade was more apparent in patients with elevated PRA (n = 3) than in those with normal PRA. On the other hand, patients with low PRA (n = 2) even showed an increase in renin release. In addition, night-day variations with secretory episodes in PRA were blunted during drug administration. It is suggested that alpha-adrenergic receptor blockade inhibits renin secretion distal to its blockade of specific adrenergic receptors. However, the increase in renin release during phenoxybenzamine observed in patients with low PRA indicates that the responsiveness of renin secretion to stimulatory effects (most probably induced by the lowered blood pressure in our patients) remained intact during alpha-adrenergic receptor blockade.


Both photons and fluoride ions excite limulus ventral photoreceptors. Illuminating Limulus ventral photoreceptors with dim light results in a response composed of discrete waves. In the dark, adding 10 mM sodium fluoride to the artificial seawater that bathes the photoreceptor includes discrete waves. The fluoride-induced waves are similar to those evoked by light. These findings suggest that fluoride induces a process similar or identical to visual excitation of the photoreceptor.


Synaptic potentials effect the release of transmitter from locust nonspiking interneurons. An excitatory synaptic potential in a local nonspiking interneuron of a locust is able to effect the release of chemical transmitter. The consequence is that a discrete inhibitory synaptic potential is evoked in an identified postsynaptic motoneuron. These local interactions between interneurons and motoneurons are of behavioral significance in that they ensure the correct operation of a resistance reflex.


beta-Adrenergic regulation of adenosine 3',5'-monophosphate concentration in brain microvessels. Norepinephrine increases the concentration of adenosine 3',5'-monophosphate (cyclic AMP) in an incubated suspension of brain microvessels. This response can be matched by other drugs that stimulate the beta receptors, but the alpha-adrenergic agonist phenylephrine is without effect; beta-adrenergic blockade abolishes the response while alpha-adrenergic blockade produces no change. The data support the contention that cerebral capillary function is subject to adrenergic neural control.


[Orthostatic hypotension and obstructive hypertrophic cardiomyopathy (author's transl)]. The authors relate two cases of idiopathic hypertrophic subaortic stenosis detected after orthostatic hypotension with syncope. This type of detection has not been described till now. Relations between idiopathic hypertrophic subaortic stenosis and orthostatic hypotension are debated as well as relation between IHSS and systemic hypertension which has existed previously in the two cases. It seems suitable to call up IHSS systematically before every orthostatic hypotension at least in elderly. Beta-blockers can in such cases considerably improve orthostatic symptoms.


[Hyperacute periarteritis nodosa complicating Basedow's disease]. The symptoms and the evolution of necrotizing vasculitis vary greatly. The authors illustrate the case of an 18 year old patient with a history of frequent allergic manifestations (urticaria and others) who was found to have, in septembre 1975, a typical case of Grave's disease. During the following 2 months she was treated with an iodide derivative. One year later the clinical signs increased to the point where a treatment associating lugol, carbamizole and propanolol was deemed necessary. Less than 2 months later there developed a polyvisceral disease with oscillating fever, polyarthralgia and necrotizing vasculitis. The plurivisceral nature of the illness was further illustrated by the presence of a hyperreflexia, a glomerulopathy and retinal exsudats. A muscle biopsy revealed the necrotizing vasculitis with granulomas typical of periarteritis nodosa. Cardiac, neurologic and renal complications were responsable for a rapid down-hill course and despite corticoïdes and immunosuppresive drugs, the patient died after a few weeks of treatment. That periarteritis nodosa should complicate the evolution of Grave's disease suggests a connection between the two, very probably immunologic in nature. The role of drugs capable of inducing vasculitis must be explored, especially the iodide derivatives, the antithyroïd medications or their association. Such cases, even though they may be rare, should incite special care in the prescription of antithyroïd drugs in the allergic patient.


[Dyskinetic syndromes in psychiatric patients (author's transl)]. The clinical effects of tiapridal on dyskinesias of all types were evaluated in adult psychiatric patients. Results demonstrated that the product was effective against alcoholic tremors and the motor disturbances provoked by neuroleptics. It was also noted that tiapridal possesses other useful properties including quite marked anxiolytic and antidepressant activities.


[The atypical forms of psychic excitation or hidden excitations (author's transl)]. If the different forms of depression of humour are nowdays well known and easily surrounded and treated, it's for from being the case for the forms of excitation of humour, though they are as numerous. In these forms, indeed, whether they are atypical maniac attacks of hypomania, it may happen that the pathological nature of psychic excitation posses unnoticed, as well for the patient as for his familiars, or it may also happen that the excitation of humour desguises with "masks" suggesting other troubles, mental or not, which bad to delays in the setting of adapted treatments. These "masks" are essentially: -- hysteria and perturbations of character, in the neurosis register; -- delirious aspects, schizophrenical or confusional, in the psychosis register. In these states of hidden excitation, the most difficult thing, nevertheless, is to obtain from the patient a sincere claim for cares, contrarily to what can be noticed in the states of hidden deppression in which the somatical or psychological "complaints" of the patients are very easily exposed to the physician, a generalist as well as a specialist, and the treatments can be searched for.


Azulfidine therapy for ulcerative colitis in infancy. The reported patient represents an example of extensive colonic disease at an uncommon age of involvement. The significant response to salicylazosulfapyridine therapy with this degree of involvement at this age is uncommon. This case suggests the value of an initial trial of medical therapy with salicylazosulfapyridine before the use of steroids or colectomy is contemplated in infants with ulcerative colitis.


[Treatment of immediate post-operative agitation (author's transl)]. Though organic causes and operative factors can produce post-operative agitation, a background of anxiety, alcoholism, or neurosis plays a major role in its development. Excellent results were obtained with tiapride in 58 patients with post-operative agitated states. Local and general tolerance were both excellent. Furthermore, an association of tiapride-corticoids was effective in treating post-anaesthetic spasm of the glottis.


Alphaviruses in Peninusular Malaysia: I. Virus isolations and animal serology. A survey of the activity of three alphaviruses (Sindbis, getah and chikungunya) in Peninsular Malaysia was conducted between 1962 and 1970. Serum samples were examined from 3,917 vertebrates representing a wide variety of wild and domestic animals throughout the peninsula for hemagglutination-inhibiting and neutralizing antibodies. A total of 548,939 mosquitoes were collected from different habitats, including jungle, rural, suburban and urban areas, and the majority of the females taken were examined for the presence of virus. Two strains of Sindbis virus and one strain of getah virus were isolated from pools of Culex mosquitoes collected in and around domestic animal shelters. Analysis of the serological results indicated that, 1) getah virus is associated principally with large domestic animals, particularly swine, 2) Sindbis virus is associated with large domestic animals and birds, especially domestic ducks, and 3) chikungunya virus, which has not yet been isolated in Malaysia, appeared to be present at a very low level of activity, probably with wild monkeys as the vertebrate hosts.


[Headaches of dental origin (author's transl)]. Headaches are frequent symptoms. Their etiology is due to multiple disturbances of various origins : vascular, digestive, arthrosic, ophthalmologic, ORL. The origin of a headaches is not always quickly revealable to the physician, and the usual analgesics do not soothe the pain. The studied cases prove that most of the headaches are accompanied by dental functional signs, and a panoramic radiography of the jaw can guide the diagnosis. For each studied case, the stomatologic treatment leads to the complete withdrawal of the aching symptom; therefore the presence of the dental etiology in headaches is proved.


Distribution and density of mosquitoes in two endemic areas for bancroftian filariasis in Sorsogon, Philippines. Mosquito density in Rangas where abaca is in abundance is much higher, almost twice, than that of Putiao where abaca is absent. The adult density of Aedes poecilus over Aedes ananae in the two areas combined is 3 to 4 times whereas the larval density of the former is much lower than Aedes ananae. The banana axils is a favorite breeding place for Aedes poecilus but may also utilize the abaca axils. This finding is very favorable in the transmission of bancroftian filariasis because this species of banana is planted around houses even closer to human dwelling than the abaca plants. Aedes poecilus being more anthropophylic than zoophylic can be domesticated as Culex quinquefasciatus and Aedes aegypti which again is a factor in favor of ideal transmission of the disease. The fact that bananas are planted around houses both in villages and towns, transmission of the disease could easily occur in both places, which should be borne in mind when planning a control program. The number of dissected mosquitoes is too small to be of significance in vector determination.


[Phlegmon of the fore arm succeeding to a dog-bite : respective role of the miscellaneous bacteria involved in this mixed infection (author's transl)]. The authors report a case of a severe mixed infection (phlegmon of the fore arm) succeeding to a dog bite. A complex flora has been isolated from this phlegmom : Pasteurella multocida, Pasteurella pneumotropica, Streptococcus mitis, Actinomyces sp., Bacteroides melaninogenicus, and a Gram- bacteria related to group II j. The pathogeny of such diseases is discussed, dwelling in one hand on the part of synergistic development of these various germs and in the other hand on the part played by saliva in the severity of animal or human bites. This kind of wound requires careful disinfection and radical debridment without omitting a preventive broad-spectrum antibiotherapy.


Djenkol bean as a cause of urolithiasis. An 8-year-old boy was admitted into the hospital with symptoms of anuria after consumption of 12 djenkol beans. Laparotomy showed a urethral calculus, size 2.0 x 0.4 cm, which was found to contain djenkolic acid 65 gm/100 gm stone with a small amount of protein, sodium, potassium and uric acid. This calculus contained no calcium, magnesium, phosphorus, ammonium salt, oxalate, carbonate, cystine and fibrin. The solubility of L-djenkolic acid in urine at 37 degrees C was found to be pH dependent, i.e., the higher the pH, the increase in solubility of djenkolic acid. D-pencillamine also showed similar effect, increasing the solubility of L-djenkolic acid in the urine at pH 5.7 in vitro. The cause and mechanism of formation of djenkolic acid crystals and calculi were discussed.


Some biochemical parameters for qualification of bull semen. Since the macroscopical and microscopical examination of bull semen does not in all cases appear to give conclusive indications concerning the fertilizing capacity, an investigation of some biochemical parameters was undertaken. It was shown that the following biochemical examination could furnish some more information about the quality of the semen: (1) Determination of the phenylalanine- alpha-ketoglutarate transminase activity both in the seminal plasma and in the whole semen. A high transminase activity in the plasma points to leakage out of the spermatozoa, thus indicating an affection of the spermatozoa. In that case larger amounts of basic amino acids and of leucine were often found in the seminal plasma than would normally be observed. (2) Gas chromatographic examination of the steroids occurring both in the seminal plasma and in the spermatozoa. In a number of infertile bulls small peaks of progesterone were found together with those of other, unidentified compounds. (3) Investigation of the carbohydrate metabolism in the semen. In a number of fertile bulls the following deviations were found: a. the presence of quite a lot of fructose in the spermatozoa; b. the presence of glucuronic acid and/of other foreign compounds in the spermatozoa or in the plasma; c. an elevated pH in the seminal plasma some 2 to 3 hours after ejaculation; d. a low phenylalanine- alpha-ketoglutarate transaminase activity in the whole semen (the spermatozoa had been disrupted by freezing). (4) Investigation of the presence of reducing aldehydes (glycoladehyde and glyceraldehyde) inside the spermatozoa. The determinations mentioned under 1, 3c and 3d can easily be carried out in the laboratories of each District Animal Health Service and of the A.I. stations; the same is true of the occurrence of amino acids in the seminal plasma and of fructose and aldehydes inside the spermatozoa if facilities are available for electrophoresis and chromatography.


[Mechanisms of the structural changes in erythrocyte membranes under the action of a shift in pH]. The effect of pH shifts (5--10) on erythrocyte "ghosts" has been studied using the IR spectroscopy. The process of regulation has been shown to take place within pH 7.15--8 range involving both protein (transition testified by absorption band changes 1520, 1540, 1635, 1645, 1585, 1696, 3305 CM-1) and lipid membrane components testified by absorption band splits 1745, 1470, 1380, 720 AND 1242 cm-1. The transition from a lesser to a higher regulating state of membrane structure happens unevenly, since the above changes take place within the narrow pH 7.15--8 interval, near the homeostase limit, being never observed at pH 5--7.15 or 8--10. It is supposed that the increase in regulation of both protein, phospholipid and lipid membrane fields is of phasic nature which presumably constitutes the basis for pH action mechanism as a regulation factor.


[NADPH-dependent oxidation in endoplasmic reticulum of rat liver after valexon administration]. Changes of different type are detected in components of NADPH-dependent oxidation. The changes begin in different periods (1, 5, 15 days) after administration of valexon to the animals. In the first day the hydroxylase activity is inhibited against a background of the uridine diphosphate glucuronyl transferase activity increase and intensification of ascorbic acid excretion with urine. Five days after the uridine diphosphate glucuronyl transferase activity becomes normal, the ascorbic acid excretion remains intensified and the demethylase and hydroxylase activities increase. Fifteen days later the hydroxylase activity becomes normal, but the demthylase activity and intensity of ascorbic acid excretion are still increased.


[Isoelectric spectra of liver tissue and blood serum albumin for rabbits of different age]. The isoelectric spectrum of albumin isolated from the liver and blood serum of 30-, 45- and 90-day rabbits was studied. By the method of isoelectric focusing in the boron-borate buffer--mannitol system. It is shown that the liver albumin displays heterogeneity ans is separated into four-five fractions, with pJ 4.8-6.0. Age peculiarities are found for the isoelectric spectrum of this protein. The serum albumin spectrum for rabbits of the studied age groups is characterized by the presence of a homogeneous peak with pJ 5.59, 5.57 and 5.47 corresponding to 30, 45 and 90-day age, respectively. Identity of serum albumin and protein of some liver albumin spectrum components is established by analyzing the pattern of the isoelectric spectrum for a mixture of preparations of 90-day rabbit proteins under comparison.


[Isoelectric fractions of healthy human serum albumin and their ability to bind bilirubin]. The article deals with the isoelectric spectrum of human serum albumin isolated by electrophoresis in polyacrylamide gel, on agar-agar, by salting out with ammonium sulphate and also by the Cohn method. It is shown that the way of albumin isolation, except the Cohn method, does not affect the quantitative and qualitative characteristics of its isoelectric spectrum obtained on ampholines by focusing. Fractions isolated from healthy people have always pI 4.7, 5.1, 5.5, their ratio being different. Albumin and its fractions are identical immunochemically. Dispersion of the fraction content optic rotation, except the fraction with pI 5,1, is the same as in initial albumin. Bilirubin is bound mainly (80%) by the fraction with pI 4.7 and it is absent in the fraction with pI 5.5.


[Ribonuclease of cultured young pig kidney cells]. Two alkaline RNases and three forms of the enzyme are detected in the cell cytoplasm of the pigling kidney culture transplanted line (IB-RS-2) by gel filtration through Sephadex G-100, G-150 and by chromatography on molselect SE-50. The former two RNases are in complex with the enzyme inhibitor and the latter three forms manifest their action in the pH acid region.


Clinical disorders of calcium, phosphate, magnesium, and hydrogen ion metabolism: diagnostic approach. Information concerning normal concentrations of serum calcium, phosphate, magnesium, and hydrogen ion, as well as clinically useful data concerning absorption and excretion of these physiologically important ions, are reviewed. Clinical approaches to diagnosis of these electrolyte disturbances are summarized with special emphasis on interpretations of these disorders in children.


Gonadal venography for preoperative localization of nonpalpable testes in adults. Gonadal venography was attempted in an effort to locate preoperatively ten nonpalpable testes in adults. In five attempts, neither selective catheterization nor complete visualization of the gonadal vein could be accomplished and no definitive information was obtained regarding the presence or location of a gonad. However, in 4 cases we were able either to visualize the position of the nonpalpable testis or predict correctly the absence of testicular tissue by the appearance of an abrupt termination or absence of the gonadal vein. One false negative study was obtained.


Uropharmacology: X. Central nervous system stimulants and depressants. Several drugs that are utilized primarily for their effects on the central nervous system also affect lower urinary tract function. Most of these effects are produced by the action of these drugs on adrenergic and cholinergic receptors or by direct action of lower urinary tract musculature. Central nervous system stimulants and depressants which are known to affect the storage or evacuation role of the lower urinary tract are discussed.


Bruising and muscle pH with mixing groups of cattle pre-transport. The effects on bruising and muscle pH of mixing cows and steers at loading, and 96 hours before loading, for transport to slaughter were examined. A second experiment investigated the effect on bruising of mixing two strange groups of steers at loading, 24 and 96 hours before loading. All cattle were hornless Bos indicus crossbreds from the same property in north Queensland. The bruise score, bruise trim weight and muscle pH of mixed cows and steers did not differ significantly from that of those transported separately. Mixing of two strange groups of steers did not significantly affect bruising. Time of mixing had no noteworthy effect on bruising. Cows bruised significantly (P less than 0.01) more than steers. These results have important implications for low cost beef management.


[Acid-base equilibrium in mother and fetus during labor and the resistance of newborn calves]. Investigated were a total of 59 cows presenting normal processes, of giving birth as well as dystocia, the time of delivery lasting 2, 10, 24, and 36 hours. Seventeen cows with dystocia were treated intravenously with 500 cm3 of a 4 per cent solution of sodium bicarbonate and 40 g glucose. It was found that the changes in the pH values, alkali reserves, glycogen, and the peroxydase activity of the neutrophiles in the mothers and fetuses were dependent on the duration of parturition. Cases of difficult labour with a prolonged calving period led to lowering the pH values the alkali reserves, and the enzyme activity of leukocytes both in the cows and the newborn calves. Newborns delivered 24 and 36 hours from the beginning of the parturition act showed low resistance and had weakly expressed phagocytic and bactericidal blood activity. The intravenous application of 50 ml of a 4% solution of sodium bicarbonate and 40 g glucose to cows with dystocia up to the 10th day led to a compensatory response on behalf of the acid-base balance in the calves.


[Serum 5-nucleotidase activity in chronic hepatobiliary diseases]. Serum activity of 5-H studied in 178 patients with chronic liver bile diseases: chronic hepatitis, liver cirrhosis, neoplasms of the liver and bile ducts, benign biliary diseases, chronic alcoholism, liver enzymopathies. Enzyme activity is elevated in all diseases but reaches its highest in the presence of biliary stasis. In comparison with APh, gamma-GTP, LAP and cholesterol the deviations of 5-H in biliary stasis are quantitatively better manifested. The diagnostic value (reliability) of six indices for the differential diagnosis of biliary stasis was studied. APh, 5-H, gamma-GTP have a high diagnostic sensitivity, whereas Lp-H, cholesterol and 5-H revealed a high specificity and the highest "predicting" value. The method used for the assessment of 5-H activity is distinguished for its reliable analytical qualities and is appropriate for routine labour diagnostics.


[Comparative analysis of the morphogenesis of the Getah virus in cell cultures of vertebrates and mosquitoes]. Reproduction of Getah virus (the genus Alphavirus) in piglet kidney (PK) and A. aegypti mosquito cell cultures was studied morphologically. Inoculation of PK cells resulted in the development of a lytic infection. Virus morphogenesis in these cells showed the features known for other alphaviruses. In mosquito cell cultures persistent infection developed which was not accompanied by any marked changes in morphology or proliferative activity of the culture. All the morphological and cytochemical data indicate that a certain role in the establishment and maintenance of virus persistence in A.  aegypti cell culture may be played by exo- and endophagocytic processes owing to which a peculiar "self-purification" of the cells from the virus and its components occurs. Incubation of the persistently infected culture of mosquito cells at a suboptimal temperature resulted in a marked reduction in the number of newly formed virions which sharply increased with the shift up to the optimal temperature. The experimental results give some insights into certain aspects of alphavirus ecology.


[Pathomorphological studies of the testes in various forms of hypogonadism in young men]. The authors studied 32 biopsies of testes of patients, aged 18 to 26 with various forms of male hypogonadism: Klinefelter's syndrome--16, primary hypotrophy pogonadism with other known and unknown etiology--6, cryptorchism--1, secondary hypogonadism--4, later puberty--3. The materials were studied by the standard histological techniques. The authors report about definite structural changes with the various forms of hypogonadism, manifested in the elements of seminal tubules, Sertoli's cells, basal membrane of the ducts and Leydig's cells, situated in the interstitial spaces.


[Comparative study of interferon production in mice with the graft versus host reaction]. Mice with graft versus host reaction (GVHR) show a decreased production of serum interferon and that produced by the bone marrow and spleen cells and blood leukocytes in vitro upon inoculation with Newcastle disease virus. Interferon induction with lipopolysaccharide of Flexner bacteria resulted in activation of production of serum interferon and that induced in spleen cell and blood leukocyte suspensions. Serum interferon production after administration of poly(I) . poly(C) was similar in mice with GVHR and controls.


[Comparative study of the antiviral properties of histones of animal and plant origin]. The antiviral properties of histones of animal (thymus) and plant (French beans) origin were studied in plants and with a plant virus, tobacco mosaic virus (TMV). Histones of the thymus and French beans were shown to be able to inhibit TMV reproduction. The antiviral properties of histones were found to depend on their concentration, pH, and to be determined by the modes of their introduction into leaves. The manifestation of the antiviral properties of histones seems to require not only their direct contact with virus but also a certain exposure on the leaf. The similarities of antiviral protective mechanisms of plants and animals determined by substances of the protein nature are discussed.


[Bromazepam in the treatment of somatized psychogenic disorders (author's transl)]. The clinical effects are reported of the benzodiazepine derivative, bromazepam (Lexotanil) in the treatment of psychosomatic disorders in the course of neurotic, psychovegetative, and masked depressive syndromes. The drug was administered orally in 301 patients (178 males, and 123 females). Target symptoms were anxiety, tension, and varied organic dysfunction of psychogenic origin. The optimum daily dosage was three times 3 mg; the duration of treatment ranged from 1 week to 34 months. The effect of treatment was considered excellent in 51.5%, good in 42.5%, moderate in 2%, and absent in 4%. The most responsive target symptoms were psychogenic disorders of the cardiovascular system and of the gastrointestinal tract, as well as anxiety, while no true antidepressive effect was observed. Drug tolerance is excellent. Slight fatigue, vertigo or a mild reduction in psychomotor activity were complained of by about 10% of the patients and usually occurred with daily doses of 18 mg or more, whereas no other side effects were observed. There was no obvious tendency to drug dependence even after after long-term treatment of up to 34 months. Bromazepam appears to be a superior compound to other anxiolytic and psychovegetatively active minor tranquillisers on account of its mild hypnotic action. Its anxiolytic effect causes additional indirect sleep induction in the above-mentioned conditions.


[Acute pharmacotoxic psychoses in patients with chronic cerebral disorders]. 269 patients suffering from progredient, chronic either primary or secundary cerebral diseases (Parkinson's disease, cerebral vascular diseases, cerebral atrophic dystrophy, Huntington's chorea, muliple sclerosis have been studied in the last two years. 44 of these patients developed pharmaco-toxic psychoses during drug treatment (low and medium dosis). The psycho-pathological rating resulted in an acute organic brain syndrome with predominance of confusion, sometimes progressing to delirium. EEG was changed during the psychotic stage. These changes cannot be decided from organic psychoses, which are not related to drugs. Patients with Parkinson's disease showed a relatively high incidence to psychoses during drug treatment (51.47%). In patients without Parkinson's disease, but on treatment with antidepressants, neuroleptics, diuretics and digitalis, pharmacotoxic psychoses only could be observed in 4.4% of the patients. However, the same group of patients showed an acute organic brain syndrome in 12.43%, when not on treatment. Combined treatment with L-DOPA plus peripherally acting decarboxylase inhibitors resulted in a high incidence to psychoses in idiopathic Parkinsonism but the same dosis produced this side effect only in a few patients with cerebral atrophic dystrophy. The ratio was 5:1 between the former group and the later one. That means, that L-DOPA is a much more psychotoxic substance in Parkinsonism when compared to other cerebral diseases. These pharmacotoxic psychoses could be correlated with the progredience of the disease. These pharmacotoxic psychoses are not only dependent from age and duration of treatment. Evidence exist, that there might be a correlation between the incidence for pharmacotoxic psychoses and the lack of surviving dopaminergic neurons in the nigro-striatal areas. Treatment with very low doses of neuroleptics suppresses pharmacotoxic psychoses but allow a further anti-Parkinson therapy which is of vital necessity.


[New aspects of long-term asthma therapy]. Asthma is a chronic disease requiring long-term treatment, principally on an ambulant basis. A regimen is described involving all the measures which are practicable in ambulant use--elimination of allergens, hyposensitization and multiple drug treatment with corticosteroids, ACTH, beta-adrenergic agents, anticholinergics, theophylline, sodium cromoglicate and the new compound, ketotifen--taking into account both the aetiology and pathogenesis of the disease and synergistic effects of the available medicines. The immediate aim is to give the patient sustained freedom from symptoms. Once this has been achieved, multiple drug treatment can gradually give way to a protective/prophylactic regimen. Two-and-a-half years of experience with the oral antianaphylactic histamine-release inhibitor, ketotifen, have convinced us that this new drug is very suitable both as part of a multiple-drug regimen designed to bring the condition under control, and as a prophylactic for subsequent protection against further attacks. An additional advantage of ketotifen is the very low incidence of adverse  reactions. Brief reference is also made to the treatment of infections and to the role of psychotherapy, breathing exercises and sport in asthma therapy.


[Inhibition of blood platelet function]. Blood platelets play a decisive role in haemostasis and thrombosis. Besides the known approaches for preventing thrombosis by inhibition of the plasmatic coagulation, it seems promising to prevent thrombus formation, particularly in the arterial vasculature, by pharmacological control of platelet functions. Drugs with antiaggregating effects are described from the clinico-pharmacological point of view. Non-steroidal antiphlogistics - especially acetylsalicylic acid - several vasodilators, alpha- and beta-adrenergic receptor blockers, as well as some others have been used therapeutically. To test these drugs for the prophylaxis of thrombosis, long-term prospective clinical trials are necessary.


[The exocrine pancreatic function in chronic renal insufficiency (author's transl)]. 46 patients, who suffered from chronic renal insufficiency (serum creatinine: 1,4-14,9 mg%) and had not yet been dialysed, were given a secretin-pancreozymin-test. Statistical evaluation of the results and comparison with a healthy reference group showed amylase secretion, total secretory volume and bicarbonate secretion to be significantly reduced in patients with serum creatinine levels above 4,0 mg%. No signs of secondary hyperparathyroidism (laboratory data, osseous changes) were observed. Blood base excess and increased serum creatinine levels were significantly related. Together with influences of low protein diet metabolic acidosis going along with chronic renal insufficiency is consequently considered to be the pathogenic factor responsible for alterations in the exocrine function of the pancreas and for the occurrence of chronic pancreatitis.


Serum opsonic deficiency produced by Streptococcus pneumoniae and by capsular polysaccharide antigens. The opsonic requirements for phagocytosis of S. pneumoniae types 6, 7, 18, and 23 were determined in normal and C2 deficient serum, and in normal serum chelated with magnesium ethyleneglycoltetraacetic acid. All four strains were effectively opsonized via the alternative complement pathway, a finding suggesting that the capsular polysaccharides of these strains activated complement via the alternative pathway. Since bacteremic pneumococcal disease is often associated with circulating capsular polysaccharide, it was considered that this cellular component may activate complement in vivo and impair host defenses by producing an opsonic defect for pneumococci. To examine this hypothesis, serum was incubated with suspensions of whole S. pneumoniae types 6, 7, 18, or 23 or with purified capsular polysaccharide from each of these types, and residual complement activity and opsonic capacity were measured. Hemolytic C 3--9 complement activity and opsonic capacity for 3H-thymidine labeled Salmonella typhimurium, a species effectively opsonized via the alternative pathway, were reduced in serum following incubation. Polysaccharide concentrations as low as 1 microgram/ml inhibited serum opsonic capacity for salmonella. Whole pneumococci and pneumococcal capsular polysaccharide also inhibited the opsonic activity of human C2 deficient serum for salmonella, further evidence for activation of complement via the alternative pathway. Pneumococcal capsular polysaccharide markedly inhibited the opsonic capacity of normal serum for the homologous pneumoccal type. Thus, amounts of pneumococcal capsular polysaccharide, similar to those found in the serum of patients with pneumococcal disease, bring about decomplementation of serum via activation of the alternative pathway and inhibit pneumococcal opsonization.


Production of protein by fungi from agricultural wastes. I. Standardization of certain factors for maximum protein production. Several fungi were screened for protein production in a simple medium using either sugarcane bagasse, wheat straw or cowdung as substrate. Out of them Rhizoctonia melongina, Pleurotus ostreatus, and Coprinus aratus proved promising and were taken up for further studies. Optimum conditions of temperature, incubation, and pH for maximum growth and protein production by the three fungi were then ascertained and standardized.


[The influence of hypnotics on the development of morphological and biochemical wound reaction (author's transl)]. The influence of hypnotics (barbital and carbromal) on the development of the early wound reactions in mechanically injured skin of guinea pigs was investigated: 1) The cellular reactions in incised wounds were retarded after moderate intoxication by hypnotics (300 mg/kg barbital; 3 g/kg carbromal). The histomorphological changes in wounds were inhibited by carbromal twice as much as by barbital. The hitherto published investigations had not shown any retardation of the early cellular inflammation by weakening influences such as loss of blood or alcohol without symptoms of shock (Berg et al., 1977) or local disturbances by acids and bases (Kampmann et al., 1978). 2). A moderate delay of the activity of structure bound enzymes was found in barbital intoxication, a stronger restriction under the influence of carbromal. 3) After barbital intoxication significant elevation of histamine or serotonin in wounds was not seen. Under the influence of carbromal there was also no increase of histamine but an increase of serotonin. Thus, although the cellular reactions seem to be the most reliable indicator among the methods for the determinations of wound age under devitalizing influences, their value is reduced in cases of intoxications by hypnotics needing treatment. Possible pathophysiological connections of the alterations of morphological and biochemical wound reaction with shock are discussed.


A comparative study of different factors involved in mass cultivation of rhizobia, using shakers and fermentors. Growth was proportionally linear to increasing load of inoculum although an inoculum load of 6 to 8% was optimum to obtain uniform number of viable cells, beyond which the number of viable cells did not increase. From the point of view of contamination with other microorganisms and the nodulating ability of cultures, fermentor cultures were better than shake cultures. When growth of Rhizobium was studied in relation to unit of mannitol consumed, it was observed that fermentors are more economical for culturing rhizobia than shakers.


Cellulose-decomposing fungi.

Cellulose-decomposing fungi. The present article gives a survey of the cellulose-decomposing fungi. It is concerned with the micro-organisms having the capability of degradating cellulose sources. It includes the factors influencing cellulose-decomposing fungi, cellulose-decomposing enzymes, mechanisms of degradation, and factors influencing the cellulolytic enzymes (cellulases).


Lipase productivity of a lipolytic strain of Thermoactinomyces vulgaris. An attempt was made to evaluate the lipase productivity by Thermoactinomyces vulgaris with various nutritional and environmental factors. Results suggest optimum conditions for production, viz. age of inoculum 18 hours, 55 degrees C, pH 6.8, 0.2% yeast extract, specific substrates, and shaken cultures incubated for 24--36 hours. Lipases are induced by corn oil in presence of yeast extract or of certain substitutes; starch could replace these at 55 degrees C. A suggestion is given of a regulatory system of lipase synthesis, involving the supply of starch to initiate growth, allowing induction of lipase by the inductive substrate.


Identity and lipase activity of an isolate of Thermoactinomyces vulgaris. An actinomycete with thermophilic nature and strong lipolytic activity was isolated by enrichment from an Egyptian soil. It proved to be Thermoactinomyces vulgaris. Variabilities justifying Adansonian systematics were reported and discussed. The potential relation of an occasional drop in successfully resumed activity to an auto-inhibition phenomenon has been notified. Optimum conditions for the activity of the extracellular lipase(s), including stability, suggest the practical importance of the enzyme(s) in the growth filtrates.


[Visualization by electronmicroscopy of 28 nm virusparticles (astroviruses) in faeces of newborns with acute nonbacterial gastroenteritis (author's transl)]. On occasion of an epidemic of acute nonbacterial gastroenteritis virus particles were visualized by electronmicroscopy in the faeces of 76 newborns; these particles had the following properties: mean diameter 28 nm; ether-resistent, stable at pH 3.0; buoyant density 1.33--1.34 g/ml in CsCl. About 10% of these particles had a definite star-like structure on their surface. Due to these properties the virusparticles were considered to be astroviruses. The virus was not cytopathogenic for cell cultures susceptible for enteroviruses, and not pathogenic for newborn mice.


Enterotoxicity of Aeromonas hydrophila: skin responses and in vivo neutralisation. Culture filtrates and partially purified enterotoxins of 6 strains of Aeromonas hydrophila isolated from faeces of diarrhoeic and healthy persons, drinking water, sewage and faeces of domestic animals caused induration and increased capillary permeability in skin of adult albino rabbits. The activities were less in crude enterotoxins indicating partial loss during purification. Heat treatment for 30 min at 60 degrees C and 56 degrees C inactivated the induration and permeability effects of culture filtrates and crude enterotoxins respectively. The activities were most pronounced at pH 8.0 showing gradual loss of activities at lower pH values disappearing completely in culture filtrates at 3.0 and in crude toxins at 4.0. The induration and permeability factor activities of crude enterotoxin were neutralised proportionally in vivo with antitoxin raised against the same in rabbits. Suppression effect was more when antitoxin was injected prior to inoculation of toxin. This study demonstrates that the assay of the activity of skin permeability factor being an easier process than loop test, may be used for assay of enterotoxin of A. hydrophila.


[The effect of organic phosphoric esters on the experimental peptic ulcer (author's transl)]. The authors have investigated some organic phosphoric esters such as dimethoate, malatione, and trichlorphone in order to see whether they influence the genesis of the reserpine ulcer induced in rats or whether they act on the existing ulcer. Another objective of the investigation was to determine whether the aggravating effect of these compounds on the experimental gastric ulcer can be mitigated or prevented with isopropamide and gastrixon, two compounds known to be used in the therapy of ulcers. It was found that 1. dimethoate and trichlorphone considerably aggravate the genesis of the experimental peptic ulcer in rats, and that also malathione exercises this exacerbating effect still to some extent, 2. that the already existing experimental ulcer is aggravated by all three organic phosphoric esters and that 3. the severe experimental damage to the stomach can be reduced or prevented with Isopropamide and even more effectively with Gastrixon. As to the interpretation of the phenomena observed the authors take the view that--provided the effects mentioned apply also to man--with this a new risk was detected in the field of the chemical plant protection which may well gain importance for the health of a population.


[Proliferative reaction in the lymph node of recipients after the transplantation of the splenic cells of burned syngeneic donors]. Thermal burn was shown to induce in the splenocyte population in mice the appearance of cells capable of producing proliferative reaction in the regional lymph node. Spleen cells taken on days 1--2 after a burn were found to be most active. A direct relation between the number of transplanted cells and marked proliferation process in the lymph node was established. The proliferative process was mainly the consequence of the proliferation of donor cells. The process resulted, probably, either from the stimulation of cell division under the influence of proliferation factors, or from the activization of autoreactive lymphocyte clones.


[Characterization of a protease from Thermoactinomyces vulgaris (thermitase). 3. Substrate specificity and properties of partially purified thermitase]. During the process of cultivation of Th. vulgaris several proteases are formed. In the present investigation the extensively purified major component was used. The substrate specificity was determined by means of 7 proteins, 7 amino acid esters, 5 fatty acid esters and 15 amino acid 4-nitroanilides. Among the protein substrates tested, urea denaturated hemoglobin was split best, followed by gelatin, casein, field bean protein, serum albumin and gluten. The weakest rate of hydrolysis was observed with elastin. In contrast to this acetyl-(L-ala)3-methylester, that is a substrate for elastase, was split best from all the esters tested. Only 8% of this activity could be found with the chymotrypsin substrates acetyl-L-tyr-ethylester and acetyl-L-phe-ethylester and 1% of the above activity with the trypsin substrates tosyl-L-arg-methylester and benzoyl-L-arg-methylester. The fatty acid esters and the p-nitroanilides were hydrolyzed much more slowly. The pH-optimum of thermitase was found in the weakly alkaline region of pH 7 to 9. There were only small differences between the individual high and low molecular substrates. The temperature optimum was between 60 and 75 degrees C for esters and p-nitroanilides as substrates and at 90 degrees C for casein. It should be mentioned that the enzyme was quickly inactivated at temperatures above 70 degrees C.


Some central nervous actions of centrophenoxine (Meclofenoxat) in animals. In experiments with rats and mice it was been found that centrophenoxine in acute experiments in large doses has inhibitory effects on the central nervous system. Centrophenoxine has no analgesic action. When administered subchronically, centrophenoxine aggravates both the pentetrazol and the maximal electroshock seizures.


Studies on column fractionation of immune cells. VII. Electrophoretic mobility and functional behavior of mouse spleen cells after fractionation on a weakly basic ion exchanger. After passing normal mouse spleen cells through columns of a weakly basic ion-exchanger, the percentage of cells with B cell-typical electrophoretic mobility (EPM) is 90% after fractionation at pH 8.0 and 10--20% at pH 5.0. However, the characterization of fractionated cells with regard to theta-antigen as well as graft-versus-host reaction shows that separation of T- and B-lymphocytes had not occurred. After incubation of the separated cells for 2 h at 37 degrees C the EPM returned to that of unseparated cells. It appears that the net charge of T- and B-lymphocytes is changeable depending on pH, temperature and separation material.


Gastro-oesophageal reflux after surgical treatment of hiatal hernia with and without severe reflux complications. A follow-up study. One hundred and sixteen patients operated upon for hiatal hernia with gastro-oesophageal reflux and with or without reflux complications were postoperatively examined by personal interview, X-ray study, pH measurements and study of the oesophageal motility 1 to 10 years postoperatively. The patients without severe reflux complications were operated upon mainly with a modified Husfeldt hernia repair and the patients with complications, such as oesophageal stricture and shortening, underwent various surgical procedures. The main reason for unsatisfactory clinical results, with persistent reflux symptoms, was gastro-oesophageal reflux uncorrected by the surgical procedure. However, gastro-oesophageal reflux was detected even in completely asymptomatic patients. It was found that the reflux symptoms were influenced by the oesophageal motility. The clinical results were better and recurrence of hernia and the occurrence of pathological reflux were lower in patients operated upon for hernia without severe reflux complications. Creation of a competent antireflux barrier between the oesophagus and stomach for control of gastro-oesophageal reflux is much more difficult in patients with severe reflux complications.


The effect of different extraction procedures on two different molecular weight species of serum NSILA and on the carrier protein of small molecular weight NSILA (NSILA-S). The influence of Dowex-50 adsorption chromatography on the recovery of two different forms of serum NSILA, large and small mol. wt. NSILA, and on the recovery of the binding protein of the small mol. wt. form was studied and compared with another extraction procedure, gel filtration on Sephadex G-50 in 1 M acetic acid. Partially purified NSILA-S is adsorbed to Dowex-50 at pH 6.8. It can be eluted with 20 mM NH4OH and appears unchanged with regard to its biological activity and molecular weight. Adsorption of 125I-labelled NSILA-S to Dowex-50 does not change its binding characteristics to serum. When serum is chromatographed on Sephedex G-50 in 1 M acetic acid, NSILA is obtained in a large and in a small molecular weight form (NSILA-S). After recombination of the small molecular weight NSILA fraction with the "stripped" serum fraction, which contains large mol. wt. NSILA and a specific carrier protein for NSILA-S, re-chromatography of this mixutre on Sephadex G-50 at neutral pH yields NSILA mostly in the void volume. It adsorbs to Dowex-50. After elution from Dowex, acidic gel filtration on Sephadex G-50 results in an elution pattern which is completely different from that of NSILA-S. Adsorption of serum to Dowex-50 results in a dramatic decrease of the NSILA-S binding activity. It is concluded that Dowex-50 adsorption chromatography of serum 1) inactivates most of the serum NSILA-S binding protein 2) leads to the loss of acid dissociable small mol. wt. NSILA (NSILA-S). Therefore, Dowex-50 adsorption chromatography is not suitable for the subsequent determination or further purification of NSILA-S from whole serum.


Differential properties of human chorionic gonadotrophin and human luteinizing hormone binding to plasma membranes of bovine corpora lutea. Plasma membranes of bovine corpora lutea contain common receptor sites for [125I]human chorionic gonadotrophin (hCG) and [125I]human luteinizing hormone (hLH) to which hLH binds with 4-fold lower affinity than hCG. The presence of additional sites for hLH was indicated by the lack of saturation of [125I]hLH binding as compared to [125]hCG and lower degree of inhibition of binding by 830 pM of unlabelled hCG, when [125I]hLH instead of [125I]hCG was used. Differences in [125I]hCG and [125I]hLH binding were observed by exposing receptors to increasing temperatures and pHs and by pre-treating membranes with dimethyl sulphoxide, Triton X-100, various enzymes and protein reagents. The above differences can only be reconciled by differential responses of common hCGhLH sites and additional sites for hLH.


DOPA peroxidase activity in the chloragogen cells of the earthworm, Lumbricus terrestris L. DOPA peroxidase activity of the cytosol of chloragocytes in the earthworm was proved by biochemical and histochemical methods, respectively. Chloragocyte DOPA peroxidase do not hydroxylate tyrosine, but it may oxidize besides DOPA other phenolie compounds in the presence of hydrogen peroxide. Probable participation of this enzyme in the detoxication of phenolie compounds and in the formation of chloragosomes was discussed.


[Arylsulfatase A and B activity in acute lymphoblastic leukemia in children]. The activity of arylsulphatase A and B was determined in peripheral blood lymphoblasts in 23 children with acute lymphoblastic leukaemia before starting treatment. A low level of activity was found in the group of leukaemic children with poor prognosis, while in children with better prognostic indices this reactivity was high. The course of changes in this activity was traced also during induction of remission of leukaemia and during 3-year maintenance treatment.


[Tachylalia: clinical and acoustic study of 149 subjects (author's transl)]. Speech was studied subjectively (listening to recordings) and objectively (measurement of durations) in 67 Parkinsonians, 10 subjects with neurological disorders and 72 psychiatric patients. Acceleration of speech was greatest in the Parkinsonians (8.5 syllables per second). The total duration of a sentence read by several of tachylalic Parkinsonians was the same as that of normal control subjects reading as fast as they could. The duration of the pauses between words varied greatly in all categories of subjects. Almost half of the tachylalic Parkinsonians (10 out of 23) had a speaking time (excluding pauses) shorter than the shortest duration recorded among same-age normal controls. The authors attach particular significance to the cases in which tachylalia is observed in the absence of lesions in the central gray nuclei. These cases suggest that speech automatisms are regulated at several levels.


Pharmacokinetics of femoxetine in man.

Pharmacokinetics of femoxetine in man. The pharmacokinetics of a structurally new 5HT-uptake inhibitor, femoxetine (FG 4963), with antidepressant properties have been investigated in man using a radioactive as well as a non-labelled substance. A two compartment open model gives a good description of the data, both after oral and intravenous administration. The substance was almost completely absorbed after an oral dose, but only 5-10% reached the systemic circulation due to extensive first pass metabolism. The metabolites had distribution and excretion rates similar to the parent compound. Only a small part (less than 2%) was excreted as femoxetine in the urine. The urinary excretion of the parent compound varied more than a 100-fold depending on the pH of the urine. The urine pH, however, did not influence the plasma concentration of femoxetine. Most of the substance (up to 80%) was eliminated by urinary excretion of metabolites, and only a small part of the radioactive dose was excreted in the faeces (up to 11%). The pharmacokinetic parameters were not found to be dose dependent in the range investigated, but it was not possible to decide whether the bioavailability was dependent on the dose. The variation between subjects was rather large, giving only a limited possibility for prediction of the plasma concentration from one subject to another.


Effects of beta-adrenoceptor agonists on airway smooth muscle and on slow-contracting skeletal muscle: in vitro and in vivo results compared. Ten beta-adrenoceptor agonists were examined with respect to a) relaxation of pilocarpine-contracted trachea and depression of contractions of the soleus muscle of the guinea-pig in vitro and b) counteraction of histamine-induced bronchospasm and depression of contractions of the soleus muscle of the cat in vivo. There was a close correlation between the results obtained in vitro and results obtained on the corresponding tissues in vivo in spite of the different species used. A close correlation was also observed between effects on airway smooth muscle and on the soleus muscle contractions in vitro as well as in vivo for all compounds examined.


Delirium tremens and related clinical states. Aetiology, pathophysiology and treatment. Definitions of Delirium Tremens (DT) and related clinical states are discussed together with the concepts of aetiology and pathogenesis in relation to psychiatric disease. The withdrawal theory which considers reduction or cessation of alcohol intake as an important precipitating factor in DT is discussed; this theory is supported by experimental studies of ethanol withdrawal in man and by studies indicating cross dependence between ethanol and several other CNS depressors; the arguments in the literature for and against the withdrawal theory are discussed. Other possible aetiological factors such as type of liquor, hypovitaminosis, liver disease, dysfunction of the adrenals and fat emboli are reviewed, and it is concluded that these factors are unimportant as precipitating or specific aetiological factors in DT. Possible pathophysiological mechanisms are discussed, especially concerning electrolyte metabolism and cerebral blood flow and oxygen consumption. It is concluded that the pathophysiology of the disease is poorly understood, and some possibilities for future research are indicated. The discussion about treatment of DT is concentrated on drug treatment, and the literature concerning antipsychotics and sedatives is reviewed. It is concluded that barbital, a long-acting barbiturate, is the most effective treatment; diazepam can be recommended as an acceptable alternative. Finally, practical recommendations concerning treatment are given.


Behavioral techniques in the treatment of a writing phobia. This paper presents the theoretical bases of the counterconditioning techniques of systematic desensitization and the extinction techniques of implosion therapy and flooding. A case history is presented in which progressive muscle relaxation, diaphragmatic breathing, and flooding were used to extinguish and countercondition a writing phobia in a junior-year occupational therapy student. Two target behaviors were selected for modification: to increase the number of words written within a specified time period, and, at the same time, to decrease the number of self-doubting thoughts. Twenty treatment sessions were conducted in which the subject practiced these techniques and wrote an essay during a specified time period. The results support the effectiveness of these techniques in modifying maladaptive anxiety or fear arising from a situation that is not objectively dangerous.


Combined effects of graded hyperkalemia on activation and recovery. We have demonstrated the progressive transmission delay in the A-V conduction system in graded hyperkalemia against a background of otherwise normal cations, and known blood gas relationships. This extends and further quantitates the work of others. We were unable to demonstrate sinoventricular conduction, as atrial activity was consistently recordable when surface P-waves disappeared. The His bundle appears to be the least susceptible conduction system structure to hyperkalemia. Finally, we have postulated the possible mechanism for the genesis of the sine wave, including loss of electrical gradient with resulting phase difference of QRS and T, associated with maintenance of His bundle activity with progressive, distal, Purkinje blockade.


The intestinal absorption of folates.

The intestinal absorption of folates. Dietary folates, existing primarily in the form of pteorylpolyglutamates, are absorbed in the jejunum by a process involving hydrolysis and subsequent intestinal transport of pterolymonoglutamyl folate. Current evidence indicates that one (or more) intestinal mucsoal enzyme(s), termed folate conjugase, is required for the hydrolysis of pteroylpolyglutamate to pteroylmonoglutamyl folate. Unresolved controversies include the mucosal location of hydrolysis (surface versus intracellular), whether the transport of pteroylmonoglutamate is active or passive, and the relation of intestinal mucosal metabolism of pteroylmonoglutamate to its intestinal transport.


Cytotoxicity of oxidation derivatives of cholesterol on cultured aortic smooth muscle cells and their effect on cholesterol biosynthesis. Aortic smooth muscle cell death is an important initial lesion of atherosclerosis. A number of autooxidation products of cholesterol which has been recognized recently has the capability of inducing rabbits' aortic smooth cell death in vitro. Twelve oxidation derivatives of cholesterol, available commercially, were dissolved in small amounts of ethanol, then added to the culture medium at levels not exceeding 0.8%. The medium contained 10% fetal calf's serum which served as an in situ vehicle for the sterols. The degrees of cytotoxicity were graded and measured as percentage of dying and dead cells in the cultures within 24 hr. 25-Hydroxycholesterol and cholesthan-3 beta, 5 alpha, 6 beta-triol, were the most toxic compounds among the sterols tested. When these oxidation derivatives of cholesterol were added to these cultured cells, they significantly depressed activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase, a regulatory enzyme of cholesterol biosynthesis (up to 83% inhibition by 25 hydroxycholesterol at a 3 microgram/ml concentration in culture medium) but the sequence of degree of inhibition was not exactly correlated with that of cytotoxicity. Various mechanisms are speculated. Purified cholesterol showed no cytotoxic effect and minimal inhibition of cholesterol biosynthesis.


Clinical significance of hyperparathyroidism in familial multiple endocrine adenomatosis type I (MEA I). In order to investigate the suggestion that hyperparathyroidism in patients with familial MEA I has a mild and nonprogressive clinical course, we have compared clinical, biochemical, roentgenologic and histologic features of 29 patients with hyperparathyrodism originating from six families with the MEA I syndrome with those of 28 unselected patients with isolated nonfamilial hyperparathyroidism. The patients from the families with MEA I were significantly younger, had lower serum calcium and inorganic phosphate concentrations and a lower incidence of elevated alkaline phosphatase levels. Furthermore, they had multiple enlarged parathyroid glands and recurrence of the disease significantly more often. There was, however, no significant difference in the incidence of renal impairment, urolithiasis, subperiosteal resorption or large bone cysts on roentgenograms, histologic changes in bone biopsy specimens or mortality due to hyperparathyroidism. Therefore, the suggestion that this type of hyperparathyroidism has a milder clinical course is not confirmed in the present study.


Chronic graft versus host disease: a syndrome of disordered immunity. A chronic, debilitating syndrome related to graft-versus-host disease (GVHD) has been recognized in long-term survivors following allogeneic bone marrow transplantation. In six of 20 marrow graft recipients who survived for more than one year after receiving a transplant, this complication developed; they were studied to better define the syndrome. There was no association between the sex of either donor or recipient, HLA type, blood group, conditioning regimen or marrow cell dose and subsequent development of chronic GVHD. All six patients had mild to moderate manifestations of acute GVHD following prompt engraftment. Chronic GVHD was characterized in each patient by progression to scleroderma-like skin involvement with hyperkeratosis, reticular hyperpigmentation, atrophy with ulceration and fibrosis with limitation of joint movement. A sicca syndrome was prominent in five patients. Four patients had idiopathic interstitial pneumonitis. Infectious complications were frequent, and DNA viral infections were prominent. Autoimmune hemolytic anemia was present in three patients, and one patient had antinuclear antibody (ANA). A spectrum of immune abnormalities was observed including hypergammaglobulinemia, immunoglobulin M (IgM) paraprotein, elevated circulating immune complexes, plasma cell hyperplasia, lymphocytotoxic antibodies and autoantibodies to autologous or donor lymphocytes. Despite clinical similarity to collagen vascular diseases, none of these patients had anti-DNA antibodies or antibodies to smooth muscle, thyroid or extractable nuclear antigens. In one patient, a skin graft from the marrow donor remained healthy despite progressive involvement in recipient skin, whereas unrelated skin grafts were rejected. Immunosuppressive therapy and plasmapheresis have not been effective. Four patients have died (median survival 458 days from transplantation). Chronic GVHD appears to be a syndrome of disordered immune regulation features of immunodeficiency and autoimmunity.


A scoring system for nonstressed antepartum fetal heart rate monitoring. A scoring system developed to assess nonstressed antepartum fetal heart rate records has been evaluated. The system scores from 0 to 2 for each of five factors, i.e., baseline rate, amplitude and frequency of fluctuation, decelerations, and accelerations. A total of 1,367 nonstress tests in 284 patients were retrospectively reviewed. Three groups of patients were delineated with respect to the fetal heart rate scores. When the group with the highest score of 8 to 10 and a perinatal mortality rate (PNM) rate of 4.7/1,000 was compared with the groups having intermediate (5 to 7) and low (less than or equal to 4) scores, there was a highly significant increase in PNM to 69.8/1,000 (p less than 0.01) and 433/1,000 (p less than 0.001), respectively. A significant increase in low Apgar scores at 1 and 5 minutes, in fetal acidosis (low umbilical arterial pH), and in duration of intensive care nursery stay was also seen as the fetal heart rate score progressively deteriorated from the 8 to 10 group to the less than or equal to 4 group. We conclude that this scoring system clearly delineates normal from prepathologic and pathologic changes in fetal heart rate and can be used as warning of impending fetal death.


II. Multifactorial analysis of intrapartum fetal heart rate tracings. The first 30 minutes and the last 30 minutes of 1,996 intrapartum FHR tracings were analyzed for baseline FHR, variability (amplitude and frequency of oscillations), accelerations, and decelerations. A modified FHR scoring system incorporating these FHR features was employed. According to the association between various FHR scores and the incidence of low Apgar scores, FHR patterns were grouped into three basic categories with distinct prognostic significance: (1) normal FHR patterns, (2) compensated distress patterns, and (3) decompensated distress patterns. It is concluded that the prognostic significance of FHR tracings is increased by incorporating several FHR monitoring criteria in the analysis.


Effects of some autonomic drugs on duodenal smooth muscle. Longitudinal muscle strips (LMS) and circular muscle strips (CMS), 2 mm wide and 1.5--2 cm long, from opossum duodenum were exposed to some autonomic agonists. The cholinergic agonists, acetylcholine, carbachol, methacholine, and bethanechol stimulated only tonic contractions in LMS and tonic followed by phasic contractions in CMS. These effects were abolished by atropine 10(-6) M. The ED50S of all cholinergic agonists for LMS were significantly lower than for CMS. Norepinephrine caused initial contraction (abolished by phenoxybenzamine, 10(-4) M), followed by relaxation (abolished by propranolol, 10(-5) M), and isopropylnorepinephrine caused relaxation (abolished by propranolol, 10(-5) M) in both layers. There were no differences in relative potencies for adrenergic agonists between the layers. Tetrodotoxin did not affect the response to adrenergic agonists. Thus, the potency of cholinergic agonists is greater in longitudinal than in circular muscle, and the layers respond differently to cholinergic agonists. The alpha-adrenergic receptors mediate contraction and beta-adrenergic receptors mediate relaxation on the duodenal smooth muscle.


Drug uptake into everted intestinal sacs. II. Inhibition of secretion by hypertonicity. Mucosal hypertonicity, metabolic inhibitors, or absence of glucose and oxygen enhance mucosal-to-serosal influx of the cationic drug, pralidoxime (PAM), into sacs of everted rat jejunum in vitro. Conversely, efflux of PAM, which is twice the influx rate, is inhibited by mucosal hypertonicity or cyanide and iodoacetate. When sacs containing PAM, 0.87 mM, and glucose, 10 mM, were placed in identical drug- and sugar-containing mediums, the inside (serosal) concentration of PAM fell by over half in 120 min, whereas that of glucose more than doubled. Mucosal hypertonicity depressed PAM efflux and glucose influx regardless of serosal osmolarity. Although azide and mucosal hypertonicity each depressed glucose uptake and oxygen consumption while accelerating net PAM influx, azide more effectively depressed glucose and oxygen uptake, whereas hypertonicity caused greater acceleration of PAM uptake. Hypertonicity did not affect PAM binding to intestinal tissue. Varying mucosal pH did not change PAM or glucose uptake. Thus, mucosal hypertonicity apparently enhances net mucosal-to-serosal transfer of PAM by blocking its active secretion from serosa to mucosa.


Osmotic flow of water in isolated frog gastric mucosa. A gravimetric procedure was used to measure net volume flow across bullfrog gastric mucosa mounted between chambers. A portion of the net volume flow towards the lumen was coupled to acid production. With an isotonic solution instilled on the luminal surface, the secreted acidity (ratio of increase in acid output to increase in volume flow) was hypertonic, in agreement with previous reports in mammalian stomach. Dilution of the secretory solution to 10% of normal nearly abolished the net volume flow coupled to acid production so that the mean secreted acidity rose to 1.87 M. Other experiments in which gastric juice was collected from this preparation showed that secretion into an initially empty lumen was only slightly hypertonic, as in mammalian stomach. The results indicate that instillation of secretory solution dilutes the endogenous osmotic gradient due to secreted HC1. This gradient is probably just outside the apical surface of the oxyntic cells of stomach.


Effect of natural variations in PaCO2 on plasma [HCO3-] in dogs: a redefinition of normal. Graded degrees of both chronic hyper- and hypocapnia are known to induce renal responses that significantly alter plasma bicarbonate concentration. These findings have raised the possibility that even normal variations in PaCO2 play an important role in determining the exact level of bicarbonate in plasma. To test this hypothesis, we examined the relationship between resting levels of PaCO2 and the plasma bicarbonate concentration in two groups of normal dogs, one ingesting a normal salt diet and the other a salt-restricted diet. The results indicate that values for bicarbonate within the normal range are highly dependent on the prevaling level of carbon dioxide tension ([HCO3-] = 0.35 PaCO2 + 9.0, r = 0.72). Accordingly, approximately 50% of the normal variance in bicarbonate concentration is explained simply by the variance in PaCO2. The joint confidence region for bicarbonate concentration and PaCO2, which can be derived from these data, provides a new and more rigorous definition of the normal range for acid-base values in the dog.


Pressor response buffering by beta-adrenergic and cholinergic vasodilation in tranquilized dogs. Buffering of alpha-receptor-mediated pressor responses by beta-adrenergic or cholinergic vasodilation in tranquilized, chronically instrumented gos was investigated. Increases in aortic pressure were produced in the same animal by intravenous injections of phenylephrine in the control state and in three successive experimental states by 1) pacing the heart to remove the reflex capability to lower heart rate, 2) pacing the heart and beta-blockade to remove beta-adrenergic vascular buffering, and 3) beta-blockade plus atropine to also remove cholinergic vascular buffering. The pressor response in each experimental state was greater than that in the state preceding it. With the combined beta-adrenergic and cholinergic blockade, the pressor response to an alpha-receptor stimulation was three times greater than that of the control state. From an analysis of the components of the pressor response, cardiac output, and peripheral resistance, it is suggested that normal buffering of an alpha-mediated pressor response may include beta-adrenergic and cholinergic vascular dilation in addition to a decrease in heart rate.


Acid-base equilibrium during acute long-lasting experiments in artificially ventilated cats. Experiments were carried out to study blood acid-base equilibrium in the cat during experiments with artificial ventilation. Blood acid-base equilibrium was examined in the arterial and venous blood by analyzing pH, carbon dioxide and oxygen partial pressure, and plasma bicarbonates. Artificial ventilation was regulated on the basis of this analysis; CO2 concentration in expired air was monitored throughout the experiment. An attempt was made to verify if artificial ventilation could be regulated indirectly only on the basis of CO2 concentration in expired air. The most appropriate acid-base equilibrium was maintained when CO2 concentration in expired air was kept within the range of 3.9-4.1%.


Metabolism of the acutely ischemic dog heart. I. Construction of a computer model. Construction of a computer model of glycolysis, the Krebs cycle, and related metabolism in acutely ischemic dog heart, involving 122 metabolites, 65 enzymes, and 406 chemical reactions, is described. A previous model of the same metabolism in normal-flow rat heart was modified to fit ischemic dog heart experimental data to within experimental error. The result resembles other models of ischemic heart preparations, implying common underlying mechanisms. The principal change made was reduction of enzyme amounts, consistent with the generally slower metabolism of large animals, suggesting that differing enzyme amounts are a major component of interspecies metabolic difference. Glycolytic intermediates oscillate, asynchronously and with large changes in level; pyridine nucleotides become highly reduced; pH falls, but mitochondria stay alkaline relative to cytoplasm even after oxidative phosphorylation stops.


Intestinal absorption of 25-hydroxyvitamin D3 in unanesthetized rat. We investigated the mechanism and characteristics of 25-hydroxyvitamin D3 (25-OH-D3) absorption in the unanesthetized rat by using a single-pass intestinal perfusion technique. The rate of 25-OH-D3 absorption remained linear for a wide range of concentrations (2-900 nM). Absorption rate of 25-OH-D3 increased as the pH, the bile acid concentration, and thickness of the unstirred water layer were decreased. Absorption did not change after the additions of fatty acids of varied chain lengths and degrees of saturation. In rats with lymph and bile fistulas, 18.5% and 16.3% of the infused radio-activity appeared in the lymph and bile drainage, respectively. These experiments indicate that 25-OH-D3 is absorbed by a passive diffusion mechanism that is influenced by the intestinal pH, bile acid concentration, and thickness of the unstirred water layer, but not by the presence of fatty acids. Approximately equal fractions of the infused hydroxylated vitamin are recovered from the lymphatic and biliary fluids.


Effects of acidosis on mechanical function and Ca2+ exchange in rabbit myocardium. The effects of acidosis on myocardial function and calcium exchange have been studied in the isolated but arterially perfused interventricular septum of the rabbit. Temperature was 28 degrees C and stimulation rate 48 beats/min. Acidosis was induced either by increase of the perfusate PCO2 (pH reduced from 7.35 to 6.68) or by decrease of the bicarbonate-chloride ratio (pH 7.35 to 6.72). The effect on calcium efflux was assessed by introduction of acidosis at different times during the washout of 45Ca2+ from the muscle. The uptake of 47Ca2+ was recorded directly with a NaI crystal and counter. An increase of perfusate PCO2 caused a rapid fall in developed tension. The efflux of slowly exchanging 45Ca2+ and the uptake of 47Ca2+ were inhibited. There was no rapid displacement of calcium from the muscle. Decrease of the bicarbonate-chloride ratio caused a slower fall of developed tension and neither the efflux nor uptake of calcium were altered. These results suggest that developed tension and calcium exchange in the myocardium are more responsive to acidosis within the cell or cell membrane than to extracellular acidosis.


[Patient survival with pacemaker (author's transl)]. The survival rate for age groups from 50--59, 60--69, 70--79, 80--89 was worked out from 1065 patients with implanted pacemakers form 1963 to the end of 1977. In all age groups the life expectancy was under the survival of the general population in the Federal Republic of Germany. Analysing the data it seems that two groups of different longevity superimpose in all age groups; the first group shows an unproportional high mortality rate in the first 12 months while the other has an almost identical survival to the tenth year. The initial high mortality rate respective to the increasing age probably results in accompaning diseases; in this aspect further studies are required.


[Frequency of bacteriuria in the aged (author's transl)]. 1125 inhabitants of 2 homes for aged people were tested for bacteriuria by dip slides. Increasing of age did not lead to higher frequency of bacteriuria, neither in women (n = 869), nor in men (n = 256). The persons were divided in the 4 decades of being 61--70, 71--80, 81--90, and 91--99 years old. The corresponding rates of bacteriuria (greater than or equal to 10(5) germs/ml) were 14.0, 15.0, 12.4, and 9.1%, respectively. The rate of reproducibility was 75.4%, indicating still smaller values in reality. The discrepancies to the much higher values reported in the literature may depend on the people tested: "normal persons" instead of hospital patients or patients' specimens having been sent to a microbiological laboratory.


[Influence of centrophenoxin administered for one year in high dose on maximal oxygen consumption in aged persons (author's transl)]. The influence of centrophenoxin (meclofenoxate) administration in a high daily dosage of 3 grams has been investigated in 10 persons with a mean age of 64 throughout 12 months. The mean age of the control group was 59. The function of bone marrow and a number of indicators of renal and hepatic function has shown no harmful changes after this long term treatment with an extremely high daily dosage. To investigate a possible influence on aging we chose the oral glucose tolerance test, a test battery for pulmonary function and the maximum oxygen consumption capacity. A highly significant (2P smaller than 0,335) influence of the drug for increasing the maximum oxygen input has been found. The hypothesis is presented, that this effect is due to an increase in cardiac functional capacity. Furthermore a significant decrease in fasting glucose levels has been found, while the glucose concentration one and two hours after administration of 100 grams of oral glucose have shown no significant changes. Body weight revealed a small but significant decrease. Side effects: we found a mild gastric pain in 4 patients that disappeared after 20 minutes. 5 Patients complained of a very small increase in jitteriness.


[The importance of age-homogenous member's in secondary groups--the example of choirs (author's transl)]. The investigation studies the influence of the age composition of secondary groups on their member's satisfaction by interviewing a representative sample of the members of Swiss Protestant choirs. The satisfaction with fellow members increases the lower the mean age of the choir is. Independently the older the respondents the more they want young members in their organization. Furthermore, there are indications for an optimal distance of age between the members. In total the influence of the age composition on the operationalizations of satisfaction is, low however. The hypothesis is deduced from the optimal distance of age that tendencies for age-homogeneous social relations will be more frequent in societies with large differences in behavior between their cohorts.


Comparison of the effects of nine beta-adrenergic blocking agents on intraocular pressure in rabbits. The intraocular pressure lowering effects of nine beta-adrenergic receptor blocking agents were compared using two different models of experimental ocular hypertension in rabbits. All the nine drugs possess, to different extents, a clear pressure-lowering action after topical administration into the conjunctival sac. For potency and duration of action, the best results were obtained with timolol and sotalol. Pindolol, oxprenolol, practolol, and propranolol are also fairly potent while less impressive effects were produced by atenolol, butidrine, and metoprolol. With the exception of propranolol, all the drugs were well tolerated by the ocular tissues.


Effects of volatile anesthetics on directly and indirectly stimulated skeletal muscle. Isolated guinea pig nerve-lumbrical muscle preparations were exposed to halothane, methoxyflurane, isoflurane, enflurane, fluroxene, and diethyl ether. The temporal courses of the effects on indirectly and directly elicited twitch responses were determined over a range of concentrations for each agent. When the anesthetics were compared at concentrations equivalent in terms of minimum alveolar concentration (MAC), a spectrum was observed in which halothane, methoxyflurane and isoflurane depressed the indirect twitch response at 3.5--5 MAC and the direct twitch response at 8--10 MAC. Diethyl ether and fluroxene depressed the indirect twitch response at 2--3.5 MAC and the direct twitch response at 3--6 MAC. Enflurane depressed the indirect response at 1.5--2.5 MAC and the direct response at 6--8 MAC. When the anesthetics were compared at concentrations equivalent in terms of their abilities to depress end-plate depolarization, however, all anesthetics were equipotent. Depression of the indirect twitch response occurred only when anesthetic concentrations were great enough to depress depolarization by 50 per cent.


Intrabiliary pressure changes produced by narcotic drugs and inhalation anesthetics in guinea pigs. The effects of narcotic agents and two inhalation anesthetics on intrabiliary pressure (IBP) were measured before and after morphine (0.2 mg/kg), meperidine (2 mg/kg), fentanyl (0.002 mg/kg), or pentazocine (1 mg/kg) given intramuscularly to guinea pigs, and after halothane (0.5, 1.0, 1.5, or 2.0 MAC) or enflurane (same range of MAC) administered by inhalation. All narcotics except pentazocine significantly increase IBP, the increases ranging from 85.7% for meperidine to 143.4% for fentanyl. Pentazocine had no effect on IBP. Peak IBP increases occurred between 9 and 18 minutes after administration. The elevation of IBP produced by narcotics was reversed by atropine (0.05 mg/kg). No statistically significant alterations of IBP were noted during halothane or enflurane anesthesia.


Converting-enzyme activity and pressor responses to angiotensin I and II in the rat awake and during anesthesia. Plasma renin activity (rate of angiotensin I generation) does not increase during anesthesia with ketamine, fluroxene, halothane or enflurane in the sodium-repleted rat. However, blood pressure decreases when an angiotensin II antagonist, saralasin, is administered during halothane or enflurane anesthesia, but not  during ketamine or fluroxene anesthesia. Differences in the rates of conversion of angiotensin I to angiotensin II induced by various anesthetic agents could help explain these previous findings. To determine the effects of anesthetic agents on angiotensin I conversion, experiments were performed in vitro and in vivo. The activities of rabbit pulmonary converting enzyme in the presence and absence of halothane or fluroxene were measured as rates of appearance of the dipeptide, histidyl-leucine, a product of angiotensin I hydrolysis to angiotensin II. Halothane and fluroxene did not alter conversion. Infusions of angiotensin I and angiotensin II were given to Wistar rats to construct dose-blood pressure response curves. The animals were then anesthetized with ketamine or halothane and infusions were repeated. Angiotensin I and angiotensin II induced similar blood pressure responses in awake and anesthetized rats. However, ketamine accentuated the pressor responses to angiotensin I and angiotensin II, whereas halothane depressed the responses. With the anesthetic agents studied, there is no significant effect on conversion of angiotensin I to angiotensin II either in vitro or in vivo.


Gastric excretion of intravenously administered meperidine in surgical patients. We have demonstrated sequestration of unchanged meperidine in gastric juice of humans following intravenous administration. Concentrations attained were as great as 360 times plasma concentration. The drug was first detected between 5 and 15 minutes after administration. This phenomenon appears to be due to ionization and ion trapping of meperidine in gastric juice.


Effects of maternal position on epidural anesthesia for cesarean section, acid-base status, and bupivacaine concentrations at delivery. In 25 patients excellent clinical anesthesia for elective cesarean section was obtained with lumbar epidural block using an average dose of bupivacaine of 130 mg (18 ml of 0.75 per cent solution). Supplemental drugs were not needed. All infants had normal Apgar scores at delivery. Ten patients were kept in a 35--40 degree semi-sitting supine position during induction, while 15 patients were similarly semi-sitting but turned into the left lateral position. Maternal position did not affect the adequacy of the anesthesia or the clinical condition of the infants, but did alter acid-base state and bupivacaine concentrations in the infants. At delivery, the infants whose mothers had been supine had significantly lower pH values in umbilical cord blood than those whose mothers had been in the lateral position. Also, high concentrations of bupivacaine were found in the umbilical vein blood of infants whose mothers were supine.


[Hemodynamic and metabolic effects of barbiturates on the human central nervous system]. Anoxic cerebral ischemia results in an almost instantaneous stoppage of the EEG, and a depletion of the cerebral energy reserves with anaerobic orientation. The experimental work, especially of Safar and Michenfelder, have proven the significant cerebral protection under barbituric hypometabolism. The cerebral impacts of barbiturates in the animal, in vitro and in vivo, are multiple: decrease in glycolysis, energetic stabilisation, a blocking of the adenylcyclase activity, membrane stabilisation by trapping of the free radicals or by an increase of the cerebral osmolarity, ect... In man, the metabolic and the hemodynamic data, of which there is little, have only confirmed the reports of metabolic and circulatory depression made by Himwich as early as 1947. The use of barbiturates in postischemic protection poses a problem of their specificity. For an equivalent cerebral metabolic depression a protective effect could not be proven with the tilisation of halogens nor with the morphines... Other narcotics (Alfatésine, Gamma OE) also depress the CNS, but their protective effects are unknown. MICHENFELDER attributes the barbituric protection to the "functional neuron" block without interference at the metabolic level of cellular life. The specificity of barbiturates in this block has yet to be proven. In the  post-ischemic resuscitation, Safar insists, and rightly so, on the urgency to correct the cerebral hypoperfusion with a parallel barbituric induction. If there is no "specificity" in the narcotic hypometabolism, it would be logically imperative to use that which provides the best protection, in the shortest, delay, and with the least systemic depression.


[Metabolic effects of barbiturates on the anoxic brain:free radical trapping]. Different mechanisms have been proposed to explain the protector effect of barbiturates in cerebral ischemia. Among these is the particularly attractive hypothesis that the protection is obtained by an inhibition of the oxydo-reduction process in the respiratory chain in the mitochondria upstream of the Q coenzyme. Keeping this enzyme in the quinone state prevents the formation of the three radical at the level of lipoid complexes of the cellular and sub-cellular membranes, thus assuring the upkeep of the integrity of these structures. The absence of the free radicals equally protects the morphology of the endothelium, in limiting the aggregation of platelets in the arterial vessel lumens. The existence of the three radicals in the organism and their noxious effects are well established, however, that the protection brought about by the barbiturates be the results of free radical trapping remains still an hypothesis.


[Vasoreactivity of cerebral infarct to barbiturates and other intravenous anesthetics]. The effect of a barbiturate, Sodium thiopental (Nesdonal), on the cerebral circulation in 13 patients with a cerebral ischemic attack is studied. Its action is compared to the action of other intravenous anesthetics (Alfatésine - Etomidate - diazanalgésie) used in neuro-anesthésia. The study is on a total of thirty patients. The regional cerebral blood flow (RCBF) is measured by the intra-carotid injection of Xe133. The anesthetics studied acted like vasoconstrictive agents on the healthy brain. They diminish the RCBF. At the leel of ischemic lesions the response is abolished, even inversed : the flow remains unchanged, even increases. It is the inverse steal syndrome. This action, comparable to the action of hypocapnia, has both a diagnostic and a prognostic value.


[Experimental study of barbiturate application following anoxic encephalopathy]. The protective effect of thiopental on neurological lesions provoked by cerebral anoxie was studied in the monkey. Cerebral ischemia was induced by a cervical tourniquet applied for a period of 16 minutes. A control series of 10 animals received only the normal resuscitation. A series of 27 monkeys received either 90 mg/kg of thiopental at 5, 10, 15, 30 or 60 minutes following ischemia, or 120 mg/kg at the 30th or 60th minute. One third of the dose was administered within 5 minutes and the rest during the following 55 minutes. The results shows that the prevention, by thiopental, of the clinical and histological lesion secondary to cerebral anoxia is effective when this drug is administered before the 15th minute. With 90 mg/kg administered at the 30th or 60th minute the improvement was slight: with 120 mg/kg it was greater if the injection was given at the 60th rather than at the 30th minute. These results, along with the mechanisms which may explain the action of thiopental, are discussed.


[Clinical use of thiopental in post-ischemic encephalopathy; preliminary report]. Twenty patients suffering from post-ischaemic encephalopathy were treated with high doses of barbiturates during the period immediately following resuscitation. The duration of cerebral ischaemia was assessed retrospectively. The degree of ischaemic damage was evaluated on the one hand by the pupillary signs seen 10 minutes after the reestablishment of the circulation and secondly by enzyme levels in the CSF. This barbiturate load was not associated with major complications and the excretion of barbiturate continued for several days. The clinical signs seen 12 hours after ischaemia and continuous observation of the tracing of the cerebral function monitor made it possible to give an early favourable prognosis from a neurological standpoint. In all the patients (apart from one) in whom there was total cerebral ischaemia for less than 10 minutes, neurological recovery was complete.


[Effect of dobutamine on intra-pulmonary shunt]. A study of the development of intra-pulmonary shunts was carried out in ten subjects following an intra-venous administration of a 7.5 microgram/kg/min dose of dobutamine by electric syringe. All the subjects were on a respirator (FiO2=0,6 most often) and frequently with P.E.E.P. The shunts were determined at the FiO2 by which the subject was being treated. The cardiac flow was measured by thermodilution. In 9 cases out of 10 the intra-pulmonary shunt is sharply increased already in the first half hour by dobutamine. The shunt values are in the order of:  -- 17.94p. 100 +/- 7.19 before the drug -- 26.50 p. 100 +/- 12.85 half an hour after the infusion beginning. The shunt increase is thus 47p. 100 of the average original value after half an hour, which is significant (p less than 0.01). The shunt is then stable at the attained value (hourly average : 26.05 +/- 12.25). These observations are discussed in relation to the obtained effects on the cardiac outout, to the PaO2, and to the quantity of transported arterial oxygen. It appears in this series that, in spite of the shunt increase, there is no risk of cellular oxygen deficiency.


[Comparative study of the effects of dobutamine and dopamine in septic shock]. This work aims at the evaluation of the effects of dobutamine in the effects of dobutamine in the treatment of septic shock and to compare them to the effects of dopamine used in the same conditions. Eleven patients presenting with both a state of septic shock and confirmed cardiac insufficiency were submitted to the protocol. The dosage was determined by the clinical results : 6.22 microgram/kg/min for dopamine and 4.2 to 25 microgram/kg/min for dobutamine. The results show that although the effect on cardiac output is comparable with the two drugs, some differences in their effects delineates their respective distinct indications. Indeed, although dobutamine seems less arythmic, lovers more the ventricular filling pressure and increases less the intra-pulmonary shunt, dopamine causes less reduction in the systemic resistance which in the case of septic shock seems more logical. Nevertheless dobutamine is perhaps easier to handle.