Antiallergic action of 6-ethyl-3-(1h-tetrazol-5-YL) chromone (AA-344) on immediate hypersensitivity reaction in rats. A newly synthesized compound, 6-ethyl-3-(1H-tetrazol-5-yl)chromone (AA-344) given intravenously or orally inhibited considerably the 72-hr passive cutaneous anaphylaxis (72-hr PCA) induced by IgE in rats. The antiallergic action of AA-344 was neither due to the antihistamine or antiserotonin effect nor was it mediated via adrenergic mechanisms. The results obtained in a double sensitization with two IgE antibodies suggest that AA-344 may not impair antigen-antibody combination but probably prevents the release of chemical mediators including histamine. This assumption was supported by observation that AA-344 inhibited a reduction in the skin histamine content caused by the 72-hr PCA, without effect on the compound 48/80-induced histamine reduction. AA-344 also partially inhibited the IgGa-mediated 3-hr PCA in rats. These results indicate that the inhibitory action of AA-344 on the immediate hypersensitivity reactions is due to prevention of the release of chemical mediators from the mast cells, by acting on some process in sequential events leading to the mediator release following antigen-antibody combination.


Differential antagonism of antiavoidance, cataleptic and ptotic effects of neuroleptics by biperiden. The interaction between neuroleptics and an anticholinergic, biperiden, in the antiavoidance, catalepsy and ptosis tests was investigated in mice for the purpose of predicting the extrapyramidal side-effects of neuroleptics. The cataleptic effect of most neuroleptics used was antagonized to some extent by biperiden, while the ptotic effect was hardly influenced. The antiavoidance effect of haloperidol, trifluperidol and perphenazine was markedly antagonized and that of chlorpromazine moderately. However, the effect of thioridazine, chlorprothixene, levomepromazine and clozapine was little antagonized. In neuropharmacological tests, haloperidol, trifluperidol and perphenazine exhibited a selective antidopaminergic activity, while chlorprothixene, levomepromazine and clozapine showed antidopaminergic, antiadrenergic and also anticholinergic activities when similar doses were given. These results indicate that biperiden antagonism may be marked in the tests related to the extrapyramidal symptoms and in drugs liable to induce extrapyramidal side effects, however, there would be little or no antagonism in drugs possessing the anticholinergic property and eliciting few extrapyramidal side-effects.


Effects of dimorpholamine on frog sciatic nerve-sartorius preparation. The present study describes the potentiating effect of dimorpholamine on twitch contraction of skeletal muscle and its mechanism on a cellular basis. Low concentrations (about 2 x 10(-5) g/ml) of dimorpholamine potentiate the twitch contraction of frog sartorius muscle. In relatively high concentrations of 10(-4)--10(-3) g/ml, however, the potentiation was followed by depression. Endplate potential was not affected by the drug. Dimorpholamine depolarized slightly the muscle membrane. The contracture tension vs. membrane potential relationship was hardly affected by the drug in the presence of 2 x 10(-7) M tetrodotoxin. Action potentials recorded from muscle fibers treated with ethylene glycol showed marked and progressive increases in duration during exposure to the drug, and were finally blocked. It was concluded that twitch potentiation caused by dimorpholamine is due to the prolongation of the action potential. A likely molecular mechanism of this drug is discussed in terms of the kinetic model proposed by Adrian et al. (J. Physiol. 208, 607--644, 1970) for the excitable membrane of frog sartorius muscle.


Effects of palytoxin on mechanical and electrical activities of guinea pig papillary muscle. Effects of palytoxin (PTX) on isolated papillary muscles of guinea pigs were studied in an attempt to elucidate the mechanical and electrical activities. Inotropic effects of PTX above 3 x 10(-9) g/ml; an early positive inotropic effect, slowly developing contracture accompanied by decline in phasic tension, appearance of aftercontractions and arrhythmias at high doses. The positive inotropic effect of PTX was enhanced in high Ca2+ medium but was not modified by propranolol. PTX induced a sustained depolarization and decrease in the amplitude, upstroke velocity and duration of action potential. During development of depolarization, arrhythmias occurred, which lasted for 5--10 min and reappeared 30--60 min after. Oscillatory afterpotential often appeared. Neither reserpine nor practolol prevented the PTX-induced arrhythmia while propranolol prevented it. Tetrodotoxin slowed the development of depolarization due to PTX and inhibited PTX-arrhythmias. In low Na+ medium, PTX exerted fewer effects on resting and action potentials and produced no arrhythmia. The results suggest that PTX-induced depolarization is responsible for the generation of contracture and arrhythmia and that the depolarization is due to the change in membrane Na permeability.


The apparent loss of cytochrome P-450 associated with metabolic activation of carbon tetrachloride. Carbon monoxide inhibited the carbon tetrachloride-induced NADPH oxidation rate. The addition of methylviologen to the incubation mixture under the atmosphere of nitrogen resulted in the enhancement of the reductase activity of microsomes for carbon tetrachloride, as determined by chloroform formation. The addition of methylviologen also enhanced the carbon tetrachloride-induced loss of cytochrome P-450, while the apparent content of cytochrome b5 and the activity of NADPH-cytochrome c reductase remained unchanged. Under a strong inhibition of lipid peroxidation by addition of EDTA, carbon tetrachloride induced a clear loss of cytochrome P-450 to the extent similar to that seen in the absence of EDTA. These results indicate that cytochrome P-450 is directly degraded in association with the reductive metabolism of carbon tetrachloride by cytochrome P-450.


In vivo direct effects of cholinergic agents on the inferior mesenteric and cardiac ganglia with relation to their receptors in the dog. The relative contribution  of nicotinic and muscarinic receptors to the cholinergic transmission of the inferior mesenteric ganglion was studied in spinal dogs by recording changes in perfusion pressure of the inferior mesenteric artery as an indicator of ganglionic function. Preganglionic stimulation elicited a frequency (2.5--320 Hz)-dependent rise in the perfusion pressure, which was inhibited by i.v. hexamethonium (C6) (10 mg/kg) or atropine (0.1 mg/kg) administered after C6. Acetylcholine (ACh) (0.1--1000 microgram) administered into the inferior mesenteric artery to reach the mesenteric ganglion induced a dose-dependent rise in perfusion pressure and this dose-response curve was shifted to the right by C6 or atropine. Bethanechol (1--1000 microgram) i.a. produced a dose-dependent rise in the pressure, which was abolished after i.v. atropine. Tetramethylammonium (1--300 microgram) i.a. elicited an increase in the pressure thought the effects were decreased at larger doses, and these effects were strongly inhibited by i.v. C6. ACh (5--100 microgram) administered into the right subclavian artery to reach the cardiac sympathetic ganglia caused a dose-dependent positive chronotropic effect, which was inhibited by i.a. C6 or atropine. The results suggest that the inferior mesenteric ganglion seems to differ from the cardiac ganglia in relative contribution of nicotinic and muscarinic receptors to the cholinergic transmission.


Cyclic adenosine 3',5'-monophosphate levels in response to norepinephrine in rectum of postnatal rats. Age-related changes in cyclic adenosine 3',5'-monophosphate levels in response to norepinephrine (NE) in the rectum of postnatal rats and the localization of cyclic AMP in the rectum were studied. During the first 2 weeks after birth, the basal levels of cyclic AMP were high, NE responses to cyclic AMP contents were minimal and thereafter, the basal cyclic AMP levels rapidly declined, while NE response significantly increased compared to those seen in tissues from adult rats. Furthermore, cyclic AMP immunofluorescence was visualized in smooth muscle and postganglionic neurons of the myenteric plexus. NE application produced an increase of cyclic AMP immunofluorescence in smooth muscle. These results indicate that NE response to cyclic AMP levels in rat rectum is age-dependent and suggest that the majority of beta-adrenoceptors associated with cyclic AMP generating system are localized in the smooth muscle of rat rectum.


Intestinal microflora and bile acids. In vitro cholic acid transformation by mixed fecal culture of rats. In vitro cholic acid (CA) transformation by mixed fecal culture was investigated. Concentrations of glucose, peptone, and yeast extract in the medium and the initial pH of the medium markedly affected the CA transformation. Yeast extract enhanced the transformation, whereas high concentrations of glucose and peptone inhibited it. When the initial pH of the medium was below 6.5, CA was converted to 7-keto-deoxycholic acid (7KD), and formation of deoxycholic acid (DC) was not observed. In contrast, with an initial pH of 7.0, about 60% of the CA was converted to 7KD after 3 days of incubation, and then DC gradually formed after 4 days of incubation, following the disappearance of 7KD. The formation of DC in the cultured samples was paralleled in each case by disappearance of 7KD. In pure culture systems, Escherichia coli and some strains of Bacteroides formed 7KD from CA. No DC formation was observed in pure cultures of any of the strains examined.


[The effect of betadrenol on examination anxiety (author's transl)]. The effect of betadrenol on examination anxiety was tested in a double-blind study simulating "examination situations". The sample consisted of 60 normal students. After a test examination without prior treatment, each subject was given a single dose of either 40 or 100 mg betadrenol, or a benzodiazepine derivative at the recommended dosage, or a placebo. The test was repeated one hour later. Heart rate, blood pressure and skin resistance were measured continually throughout the progressively complicated psychological test. The increase in the heart rate was significantly lower in the betadrenol-treated subjects than in those given benzodiazepine or a placebo. The behaviour of the blood pressure was similar. Significant improvements in subjective condition and skin resistance in response to betadrenol were contrasted with deterioration after benzodiazepine, and no change after placebos. Improvement in mental alertness in the betadrenol group differed significantly from that in the benzodiazepine group, and there was also an improving trend in reactions. This shows that betadrenol can subdue examination anxiety. Betadrenol was far more effective than a benzodiazepine derivative in all the parameters tested, including psychophysical performance relating to control of a motor vehicle.


The gastric microenvironment in populations at high risk to stomach cancer. The gastric juice of patients with atrophic gastritis from the high-risk gastric cancer region of Nariño, Colombia, was analyzed for nitrate, nitrite, and thiocyanate content. Patients whose gastric juice pH is greater than 5 have significant elevation of nitrite values. The possible role of nitrite in gastric carcinogenesis is discussed.


Unimportance of perivascular H+ AND K+ activities for the adjustment of pial arterial diameter during changes of arterial blood pressure in cats. The role of perivascular H+ and K+ in the adjustment of pial arterial diameter during changes in arterial blood pressure was investigated in chloralose anesthetized cats. Blood pressure was reduced by i.v. mecamylamine or pentolinium and was increased by i.v. hypertensin. Pial arterioles and arteries with a control diameter ranging from 37--218 microns at a spontaneous mean arterial blood pressure of 128 +/- 16 (SD) mm Hg were studied. Vascular diameter as measured by TV image splitting showed the typical reactions, i.e. constriction during increase (up to 200 mm Hg) and dilation during decrease in blood pressure (down to 60 mm Hg). Perivascular H+ and K+ activities were measured using pH microelectrodes (Hinke type) and K+ ion exchanger microelectrodes, respectively. Under control conditions perivascular pH was 7.25 +/- 0.11 (SD) and K+ activity was 2.46 +/- 0.65 (SD) mM, respectively. During changes in blood pressure the vascular reactions of pial arteries were not accompanied by significant alterations in perivascular H+ or K+ activity. From these data it can be concluded that mechanisms other than those which are mediated by H+ or K+ are involved in the adjustment of pial arterial diameter during changes in arterial blood pressure.


Thermal perturbation differential spectra of ribonucleic acids. I. Hydration effects. A relatively important change in UV absorption is observed upon thermal perturbation of nucleotide solutions. Comparison of these thermal perturbation spectra of nucleic acid residues with solvent perturbation spectra of the same compounds suggests that this spectral change can most probably be attributed to temperature induced hydration change of the bases. This conclusion is confirmed by the results obtained from acid-base perturbation spectra of these nucleotides as well as thermal perturbation spectra of nucleotides containing modified bases. It is shown that this temperature dependent change in UV absorption is also present in dinucleoside monophosphates. In that case, this effect is superimposed upon the well known change in absorbance due to the unstacking of the bases during heating.


[Study of minimal cardiac transit times in normal persons during beta-sympathicolysis (author's transl)]. The effects of single equipotent doses of Propranolol and Carazolol on cardiac haemodynamics of normal persons were investigated in a placebo-controlled double-blind study by radiocardiographic measurements of minimal cardiac transit times (MTTs). 90 min after oral application of 40 mg Propranolol a significant (p less than 0.005) prolongation of MTTs between the right auricle and the aortic root by 25% could be observed. A corresponding effect after treatment with 5 mg Carazolol was not recognizable (p greater than 0.05). Both substances strongly reduced the heart rate. The negative chronotropic effects of both beta-blockers were indistinguishable (p greater than 0.05).


An influence of diet on transplantation immunity. It was discovered by chance that mice raised under otherwise entirely conventional conditions of husbandry but fed upon autoclaved diet (diet A) had stronger cell-mediated immune reactions than those of mice raised under the same conditions but with an unmodified diet (diet B) : skin allografts were rejected more quickly, transplantation tolerance was more difficult to procure and fibrosarcomas induced by the injection of methylcholanthrene (MCA) arose more slowly and less often. Analysis showed that these findings could be explained at least in part by the discovery of Mertin & Hunt (1976, p. 928) that a partial deprivation of polyinsaturated fatty acids led to an intensification of cell-mediated immunity; on the other hand, experiments with dietary mixtures made it seem unlikely that this was the whole explanation and pointed towards some positive immunopotentiation by an ingredient of autoclaved diet. This, it was proposed, might be a compound of unknown composition resulting from the interaction of vitamin A with other dietary constituents. This interpretation was not supported by direct evidence but by confirming that retinol derivatives, especially retinyl acetate, could exercise an immunopotentiation of the kind and degree under investigation: retinyl acetate could counteract the immunosuppressive action of linoleic acid, though retinyl methyl ether was ineffective. Although retinyl derivatives may protect against MCA tumours by impeding its metabolic conversion to an oncogenic form, the effects of an autoclaved diet upon skin allograft survival, the induction of tolerance and the formation of tumours is probably mediated through an immunological mechanism.


The effects of sleep on neurons in isolated cerebral cortex. Slabs of cat parietal cortex with some 2 mm of underlying white matter were surgically isolated from the rest of the nervous system, without interference with the superficial blood supply. Wire micro-recording electrodes were inserted into the isolated cortex; bone, muscle and skin wounds were repaired and the animal allowed to recover from anaesthesia. The adequacy of surgical isolation was examined histologically 8--12 weeks after operation. Only one of the six preparations reported here showed surviving neural connections with the rest of the brain. Soon after operation, spontaneous bursts of neural activity appeared within the isolated area. These became more frequent until neural discharge was continuous but irregular. Our records were made from this time onwards. The interval distributions obtained from neurons within the isolated area did not differ significantly from log-normal curves. When the unrestrained animal fell asleep, there was no significant alteration in the model interval or geometric standard deviation of interval distributions recorded from cells in isolated cortex. The interval distributions of neurons in isolated cerebral cortex resembled those of neurons in the intact cortex of an alarmed animal. It is concluded that the reduction of modal interval that is shown by neurons in intact cortex when an animal falls asleep is probably due to the neural influence of infracortical structures.


The effect of repetitive stimulation on the passive electrical properties of the presynaptic terminal of the squid giant synapse. The resting electrical properties of the presynaptic terminal of the squid giant synapse have been determined by using constant current pulses. After short periods of repetitive stimulation, the terminal resistance, time constant and capacitance are found to be increased. These changes are absent in terminals bathed in artificial sea water containing no calcium, and sea water containing 5 mM cobalt. It seems likely that these changes are associated with transmitter release.


Leishmania in phlebotomid sandflies. VII. On the taxonomic status of Leishmania peruviana, causative agent of Peruvian 'uta', as indicated by its development in the sandfly, Lutzomyia longipalpis. The name Leishmania peruviana was given by Velez (1913) to the parasite responsible for a form of cutaneous leishmaniasis known as 'uta'; this disease occurs in the Peruvian Andes. Clinical similarities between uta and 'oriental sore', which is caused by Leishmania tropica of the Eastern Hemisphere, have, however, led to the suggestion that uta is simply due to L. tropica, which was introduced into Latin America by African slaves or European immigrants. Leishmania species are divisible into three distinct sections, according to their pattern of development in their natural (phlebotomine) vectors. One of these sections, the PERIPYLARIA, contains the subspecies of Leishmania braziliensis, and is characterized by parasites that undergo a phase of development attached to the wall of the hindgut (pylorus and ileum), in addition to multiplication in the midgut and subsequent invasion of the foregut. Such development is unknown in any other group of leishmaniae, including those groups of the section SUPRAPYLARIA, which includes parasites of the L. tropica complex. Three isolates of L. peruviana were studied in laboratory-bred sandflies, Lutzomyia longipalpis (Lutz & Neiva), and all showed consistent and prolific development of rounded or stumpy flagellates attached to the wall of the hindgut and, in some instances, growth of free, elongate promastigotes throughout the midgut. Development of both L. tropica and L. major, in the same insect, was restricted to massive development of free flagellates in the midgut, up to the cardial valve. From the behaviour of L. peruviana in the sandfly, its slow growth in hamster skin and the small size of its amastigotes, it is concluded that this parasite is (a) distinctly different from both L. tropica and L. major, and (b) closely related to subspecies of L. braziliensis within the section PERIPYLARIA. On this evidence it is also concluded that L. peruviana is indigenous to the American continent. The specific name is best retained for the time being (rather than L. braziliensis peruviana).


Phenobarbitone modulation of postsynaptic GABA receptor function on cultured mammalian neurons. The anticonvulsant barbiturate phenobarbitone increases membrane current and conductance responses to gamma-aminobutyric acid (GABA) in cultured mouse spinal neurons. Analyses of GABA current fluctuations under control conditions and in the presence of phenobarbitone show that the principle action is to increase the average time during which GABA-activated channels remain open. The duration of minature synaptic currents with a time constant of decay similar to the mean open-time of GABA-activated channels is prolonged by the drug. The results suggest that (1) the synaptic events are GABA-mediated and (2) the enhancement of these events by barbiturate is due to the postsynaptic action of the drug.


MIF-I's differential actions as an opiate antagonist. The effects of MIF-I (Pro-Leu-Gly-NH2) were examined in three experimental conditions in which the opiate antagonist naloxone is active. MIF-I was found to block the analgesic effects of enkephalins and also morphine in the tail-flick test but not in the vas deferens assay. Unlike naloxone, MIF-I did not seem to reduce food intake in VMH-lesioned rats. The results suggest the possibility that MIF-I may represent a class of naturally occurring opiate antagonists with varying activities in independent situations.


Stroke due to vasculitis.

Stroke due to vasculitis. Vasculitis should be suspected as a cause of stroke in younger patients or older patients with an elevated erythrocyte sedimentation rate, especially in the presence of systemic disease and mononeuritis multiplex. Corticosteroids and cyclophosphamide show promise of producing remission.


[Mosquito: the most frequent cause of prurigo in children. Correlation with the intradermal tests in the diagnosis of allergy]. The clinical dermal manifestations induced by hypersensitivity toward mosquito bites were studied in 50 patients of both sexes whose ages ranged between 0 and 15 years. Among 13 forms of lesions found papules and vesicles were the most frequent. A predominance of females when compared to other statistical data was evidenced. The correlation of these lesions with atopy is assessed, and pruritus, scratching and secondary infection are pointed out as factors worsening this state. Among sensitive subjects, skin tests using a 100 UNP concentration of the whole mosquito body extract were the most reliable.


[Chronic inflammatory neuromyopathies in adults treated for gluten-sensitive enteropathy. A report on three cases with microvascular nerve and muscle lesions (author's transl)]. Neuromyopathies developed in three patients with gluten-sensitive enteropathy, a long time after they had been cured of their digestive disease by following a gluten-free diet. These cases differed radically from typical deficiency neuropathies by the presence of microvascular inflammatory lesions in nerves and muscles. The semiological findings were similar in all 3 cases, and were distinguished by the association of signs eveking lesions of the largest myelinated nerves fibers to the posterior rami with lesions in the muscles. Corticotherapy improved the condition but did not affect its chronic course. Nerve and muscle biopsies revealed the presence of segmentary microrascularitis, mainly lymphohistiocytic. The probable mechanism of these histological changes is alterations in the circulating immune-complexes, usually found in gluten-sensitive enteropathy, producing various types of associated disorders. Some of these immune-complexes would not be related straight to digestive intolerance to gluten, but would persist during the gluten-free diet period, and could be responsible for the micro-angiitis.


Phosphate buffer stimulates somatostatin release into the antral lumen of anaesthetized cats. The effect of variations of intra-antral pH on the intraluminal release of somatostatin was studied. Acute pouches were created in anaesthetized cats, and the pouches were perfused with solutions differing in pH. Somatostatin levels were then measured in the perfusates. In this model phosphate buffer was a potent stimulator of intra-antral somatostatin release, whereas perfusion with 0.1 M HCl failed to release somatostatin by itself. Since phosphate buffer also releases gastrin, the releasing effect ought to be exerted beyond the mechanism that can be blocked by somatostatin. (Thus the stimulatory effect of phosphate buffer might be exerted on the membranes of the endocrine cells.)


Effect of two types of beta-adrenergic blockade on gastric acid secretion during pentagastrin stimulation in non-vagotomized and in vagotomized gastric fistula dogs. The effect of beta-adrenoceptor blockade by propranolol and practolol on submaximally pentagastrin-stimulated gastric acid secretion was studied in conscious non-vagotomized and in vagotomized gastric fistula dogs. Propranolol (0.5 mg/kg) intravenously augmented gastric acid output in vagotomized dogs, more after truncal and selective vagotomy than after parietal cell vagotomy. Vagally innervated dogs also showed an increase, but to a lesser degree and not statistically significant. The increase restored the acid output to preoperative levels in the vagotomized dogs. Practolol (1.0 mg/kg) intravenously resulted in a slight and insignificant increase in acid output in dogs with truncal vagotomy and had only a negligible effect in vagally innervated dogs and after selective and parietal cell vagotomy. It is concluded that propranolol augments pentagastrin-stimulated acid output in vagotomized dogs, and this augmentation was most pronounced in the totally vagotomized stomach. Practolol had minor influence on gastric acid secretion. This effect of the two beta-blocking agents indicates that beta 2-blockade is most important for the secretory augmentation. The restoration of postvagotomy acid secretion to preoperative levels suggests that adrenergic influence is important for the decrease in pentagastrin-stimulated acid secretion after vagotomy.


Sulphasalazine treatment during breast feeding. The steady-state concentrations of sulphasalazine and sulphapyridine in serum and mother's milk have been measured in 12 nursing patients who were being treated with sulphasalazine. The results show that sulphasalazine passes only in negligible amounts or not at all into milk. The concentration of sulphapyridine in milk was about 40% of the serum concentration in the mother. We therefore conclude that sulphasalazine may safely be given during nursing.


Secretion at the parietal cell level--a look at rabbit gastric glands. By various means, morphological, response to secretagogues, ion requirements and active membranes, the rabbit gastric gland preparation has been shown to be an adequate substrate for a study of the complete spectrum of the reactions leading to acid secretion. In fact, it is rapidly becoming the model of choice.


A simple analytical technique for the determination of hexavalent chromium in welding fumes and other complex matrices. A systematic study of analytical methods for the determination of hexavalent chromium showed that currently existing techniques are unsatisfactory when used with welding fumes, the s-diphenylcarbazide method proposed by the U.S. National Institute for Occupational Safety and Health permitting less than 1% recovery of hexavalent chromium from synthetic welding fumes of known composition. A new (carbonate leaching) technique is proposed which permits better than 80% recovery of both soluble and insoluble chromium (VI). This technique is then used as part of a general method for the determination of total chemical composition as distributed among sample fractions of different solubility. The method is specifically designed for use in the analysis of small samples and is especially suitable for the routine evaluation of health risks as found in the work environment.


[Controlled therapeutic study of spontaneous bucco-linguo-facial dyskinesias (author's transl)]. A triple blind study has been conducted according to an original methodology to compare the effects of thioproperazine and tiapride on the spontaneous bucco-linguo-facial dyskinesias in the elderly. Side effects have been balanced to obtain a quantitative evaluation. Thioproperazine (3 x 3 mg/day) and tiapride (3 x 100 mg/day) reduce both significantly the number of dyskinesias, the former being more active than the latter. On the other hand, side effects of thioproprerazine are significantly higher than those of tiapride which are themselves not different from those induced by the placebo. Taking into account these results and the fact that dyskinesias represent a benign condition, the tiapride appears to be the first choice drug.


Metabolism of benzo[a]pyrene in isolated human scalp hair follicles. Human scalp hair follicles contain an enzyme system that metabolizes the carcinogen benzo[a]pyrene. The major ethyl acetate soluble metabolites are 7,8-dihydro-7,8-dihydroxybenzo[a]pyrene,9,10-dihydro-9,10-dihydroxybenzo[a]pyrene and 3-hydroxybenzo[a]pyrene. Addition of 1,1,1-trichloropropene-2,3-oxide (TCPO), an inhibitor of epoxide hydratase, prevents the formation of the dihydrodiols. The overall metabolism can be inhibited by the addition of alpha-naphthoflavone. The metabolism of benzo[a]pyrene in a cell culture of human scalp hair follicles has also been investigated. The results show that the activity of arylhydrocarbon hydroxylase (AHH) and epoxide hydratase (EH) is maintained in culture.


Lethal synergism between morphine or other narcotic analgesics and propranolol. Interactions of (+/-)-propranolol HCl with various narcotics were determined in albino rats. The 24-h intraperitoneal (i.p.) LD50 of morphine sulfate + saline was 15--16 times greater than for morphine + propranolol in both sexes although morphine was nearly twice as toxic to males as to females. The potency ratios for LD50's with saline vs. with propranolol were: codeine, 1.9, (+/-)-methadone, 6.0; (-)-alpha-acetylmethadol, 2.8 (72 h). The toxicity of levorphanol also was greatly increased with propranolol, but the dose-effect relationship showed non-parallelism vs. levorphanol + saline. Albino mice and mongrel dogs also showed synergism between morphine and propranolol. Mortality after morphine and propranolol was antagonized by naloxone or naltrexone in rats and mice. The potency ratio in rats for morphine + saline vs. morphine + practolol was 3.5. However, the synergism between propranolol and the narcotics probably was unrelated to beta-adrenergic blocking effects of propranolol because of the apparent equivalence of (+)-, (-)- and (+/-)-propranolol in rats for synergism with morphine.


The Rift Valley fever epizootic in Egypt 1977-78. 2. Ecological and entomological studies. Epidemiological factors related to the introduction, spread and maintenance of Rift Valley fever (RVF) virus were studied during the 1977-78 epizootic in Egypt, Culex pipiens is the most ubiquitous and prevalent mosquito species in the Nile Valley and Delta. Isolation of RVF virus from unengorged C. pipiens, and demonstration of laboratory transmission of the virus by this species, strongly implicate it as the chief vector in Egypt. Virus transmission to man also occurs by contamination when handling infected meat and by inhaling natural virus aerosols. Wild rodents apparently do not serve as RVF virus reservoirs. Domestic sheep, cattle, buffaloes, camels, goats, donkeys and dogs act as amplifying hosts. Over 30% of the camels sampled at the southern border of Egypt were serologically positive for antibodies to RVF virus and it appears likely that the virus was introduced into Egypt, either by these animals or by other vehicles from the south.


[Scanning microscopical observations on the foregut structures o mosquitoes and their role for the ingestion of microfilariae (author's transl)]. Experiments on the transmission of Brugia malayi by various mosquitoes had shown that microfilariae ingested by some species were badly damaged when they reached the stomach, but were much less hurt in others. The structures of the foregut likely to cause these injuries, were investigated and documented by scanning microscope techniques. In Anopheles albimanus, A. arabiensis, A. stephensi and A. pharoensis which have well developed armatures the microfilariae showed a high rate of destruction. In A. stroparvus as well as in Aedes aegypti, Ae. togoi and Culex fatigans in which these structures are missing or poorly developed the larvae were much less affected. From the size, shape and position of the different papillae, spines, rods and cones observed it can be concluded and confirmed that the pharyngeal armature (buccopharyngeal bar) will be by far the most important structure responsible for the injuries of the microfilariae. However, it appears that the characteristics of different filaria species can play an important role in preventing such damages.


[Course and modification of Hypomyces ochraceus m 359 autolysis]. Growth and natural autolysis of the ascomycete Hypomyces ochraceus were investigated in shake cultures by measuring dry weight, pH value, and uptake of carbohydrate. The alkaline autolysis resulted in maximum loss of 53% of dry weight during an incubation period of 35 days. Early autolysis was induced by limitation of oxygen, increasing temperature, addition of peracetic acid, and sodiumacide. Autolysis is discussed to be derived from deficiency of energy.


[Histone-heparin complexes].

[Histone-heparin complexes]. Histones form insoluble complexes with heparin and neutralize its anticoagulant action. The plasmin degradation products of histones do not possess these properties. Plasmin also digests histones in complexes with heparin. Breakdown of the histones in these complexes causes release of heparin from them.


Practical experiences with flunitrazepam in anesthesia. Flunitrazepam was used in general and local anesthesia. Little effect was noted on the respiratory and cardiovascular systems. In our patients there was an impressive period of amnesia and often we observed a central anticholinergic syndrome, which could be reversed by the use of physostigmine salicylate (0.04/kg body weight).


Congenital persistent proximal type renal tubular acidosis in two brothers. Two brothers showed severe and persistent hyperchloraemic metabolic acidosis (capillary blood pH 7.07--7.15) due to a low renal bicarbonate threshold at 11 mmol/l. The maximal tubular capacity for bicarbonate reabsorption was reduced to about half the normal. A high dose of acetazolamide (25 mg/kg) lowered the tubular bicarbonate reabsorption substantially, indicating the presence of carbonic anhydrase. Both the glomerular filtration rate, the renal blood flow and the renal concentrating capacity were slightly reduced. The clinical characteristics were: growth retardation, mental retardation, nystagmus, corneal opacities, cataract, glaucoma and enamel defects of the permanent teeth. Serum thyroxine was pathological low without clinical signs of hypothyreosis. The erythrocytes showed an increased osmotic resistance. Autopsy of the younger brother, who died 4 1/2 years old, revealed thyroid and thymus weights of 25% of the normal. The kidney tubular cells were swollen with vacuoles. The glomeruli had a normal appearance.


On the antiarrhythmic activity of one N-substituted piperazine derivative of trans-2-amino-3-hydroxy-1, 2, 3, 4-tetrahydroanaphthalene. The antiarrhythmic activity of the compound N-(trans-3-hydroxy-1,2,3,4-tetrahydro-2-naphthyl)-N-(3-oxo-3-phenyl-2-methylpropyl)-piperazine hydrochloride, referred to as P11, is studied on anaesthesized cats and Wistar albino rats, as well as on non-anaesthesized rabbits. Four types of experimental arrhythmia are used--with BaCl2, with chloroform-adrenaline, with strophantine G and with aconitine. The compound P11 is introduced in doses of 0.25 and 0.50 mg/kg intravenously and 10 mg/kg orally. The compound manifests antiarrhythmic activity in all models of experimental arrhythmia used, causing greatest inhibition on the arrhythmia induced by chloroform-adrenaline (in 90 per cent) and with BaCl2 (in 84 per cent). The results obtained are associated with the beta-adrenoblocking and with the membrane-stabilizing action of the compound.


[The etiology of the refracture of the forearm in childhood (author's transl)]. The etiology of the refracture after forearm fractures in childhood has been studied in a follow-up examination of 199 patients with dislocated forearm fractures. The incidence of the refracture was 13%. In all cases the primary fracture was a greenstick fracture of at least one of the two forearm bones. The incompletely broken through greenstick fracture was found to be significantly responsible for the refracture. Duration of immobilisation or residual axis deviation at consolidation showed no relationship. The pathophysiology is briefly discussed. In every greenstick-fracture of the forearm the necessity of completing the fracture by total reposition is emphasized to prevent a refracture.


[First experiences with the external mini-fixator of Jaquet (author's transl)]. The external mini-fixator of Jaquet is a new way for external stabilization in hand surgery. The technique of applying the external mini-fixator is described and the results in the treatment of 23 cases of infected non-unions, non-unions with defect and arthrodeses are reported.


[Mechanical force exercised on the elbow joint in olecranon fractures (author's transl)]. Opinion is fairly unanimous on the need for surgical treatment of disclocated olecranon fractures. However, opinions differ regarding the mechanical backgrounds and practical application of the presently widely used tension wiring. The article attempts to clarify the picture of the forces involved in the humero-ulnar joint. Basing on the points of attack of these forces and on the influence of the ligamentum collaterale ulnare, the fractures are subdivided into three groups with individual demands on the respective fixation method and the permissible post-operative exercise therapy. Post-operative plaster immobilisation is not indicated in these cases.


[Fractures of the calcaneus. Orthopaedicotechnical management and long-term results following surgical or conservative first treatment (author's transl)]. 75 fractures of the calcaneus were followed up in a long-term study in 64 patients. 27 of these patients were older than 10 years. 22 were operated (or reoperated) later. 16 of these received a double arthrodesis. The early and late results were compared. There was no difference between the results obtained with the surgically treated and the conservatively treated patients (functional or closed repositioning and plaster cast). The late operations are discussed. Emphasis is given to the orthopaedicotechnical possibilities which, in the authors' opinion, should be utilised more often.


[Ossifications of soft parts after operative treatment of luxation fractures of the ankle joint (author's transl)]. Operative treatment of luxation fractures of the ankle joint has caused a drop in poor late results, to one-quarter of the total number of patients compared with about one-half with the conservative procedure. Part of the unsatisfactory results is caused by ossifications in region of the interosseous membrane and tibiofibular syndesmoses. The incidence of such ossifications within a closed series of 200 own operatively treated cases was examined and pathogenetic factors were discussed. Further improvement of the treatment results of ankle joint fractures appears possible via subtle operation technique and omission of routine application of fixation screws for safeguarding lesions of the syndesmoses.


[Tessellated epithelium cancers in a traumatic chronic ulcer (author's transl)]. The major part of chronic skin ulcers resulting from a trauma show no tela peculiarities during the whole of their development apart from the formation of chronic granulation tissue. In a few cases there is a malign degeneration, which is often detected too late. Based on the experience of two cases, the necessity of exercising a precise control of their development is pointed out. This can be achieved by taking biopsies and by histological treatment.


[Treatment of the relapsing dislocation of the patella (author's transl)]. From 1970-1977, twenty-five patients were given surgical treatment for relapsing dislocation of the patella. The mean age of the patients was 22 years. The case material consisted of 18 female and 7 male patients. The average frequency rate of dislocation was three to fifteen times. (Reported from the BB-Accident Hospital Tübingen). The combined surgical method with gracilis muscle restraint described by Krogius, was used in this clinic in view of its traditionally successful application. Additional antepositioning of the patella according to Bandi was effected in intraoperatively discovered retropatellar arthrosis. Relapses of dislocation were reported in two cases. Good postoperative results were obtained in 14 patients, satisfactory results in 5 patients, and an unsatisfactory outcome in three patients. Redislocation was reported twice. Since this disease occurs preferably in juveniles, surgical treatment to prevent further dislocations should be effected well in time to avoid early retropatellar arthrosis. Since dislocations of the patella are frequently adjusted spontaneously without any treatment, critical and detailed anamnesis is imperative in every patient with a distorted knee joint.


[Late surgical treatment of traumatic rupture of the oesophagus (author's transl)]. The article reports on a 21-year old patient admitted on an in-patient basis after compressed air injury with a severe open craniocerebral lesion, and in whom the diagnosis of rupture of the oesophagus was made two weeks later only. Late surgical management by means of oesophagus suture and sealing of the diaphragm, was successful. The article discusses the symptoms and possibilities of treatment of traumatic rupture of the oesophagus, basing on the present case, and surgical treatment is advocated even if the 48-hour limit has been exceeded.


Immunization against Nippostrongylus brasiliensis in the rat. A study on the use of antigen extracted from adult parasites and the parameters which influence the level of protection. It was found that protective immunity in excess of 90% reduction in worm burden could be stimulated against Nippostrongylus brasiliensis in rats by using an extract of adult Nippostrongylus worms. The level of protection achieved was influenced by several factors. Thus, the use of Bordetella pertussis as adjuvant significantly increased the level of protection which, in addition, was shown to be influenced by the amount of worm antigen used. Furthermore, antigen administered in multiple doses was more effective than a single inoculum and, when using such a regime, the interval between doses was also found to be critical. The route of antigen administration was important and, while protection was achieved by subcutaneous and oral administration, the intraperitoneal route was the most effective. Using the optimal immunization regime of 3 doses of 5 mg worm protein and 4 x 10(10( B. pertussis organisms, as adjuvant, levels of protective immunity in excess of 90% reduction in worm burden were shown to exist for at least 60 days after the last dose. It was found that adult worm extracts did not stimulate any obvious immunity against larval forms of N. brasiliensis.


The ultrastructure of cultured Plasmodium gallinaceum ookinetes: a comparison of intact stages with forms damaged by extracts from blood fed, susceptible Aedes aegypti. The ultrastructure of intact, mature and immature ookinetes of Plasmodium gallinaceum is compared with corresponding stages which have been damaged by Aedes aegypti extracts prepared during blood digestion. The study reveals some new details of ookinete ultrastructure. In particular the composition, development and mode of formation of the pellicle of plasmodial ookinetes is shown to be similar to that of other sporozoans. The pellicle is composed of three membranes, develops in the growing protrusion of the retort-shaped early ookinete and its inner layer is probably formed by fusion of peripheral vesicles. Staining with ruthenium red indicates the presence of a surface coat. Furthermore Golgi-like structures and lysosomes can be observed. After exposure to A. aegypti extracts the parasites exhibit signs of severe cell damage and degeneration, such as disintegration and vacuolization of the cytoplasm. Damage of the plasma membrane is demonstrated by its permeability for ruthenium red. Cell damage is particularly prominent in those cell parts which are not covered by the pellicle and therefore suggests a protective function for this structure.


Acid hydrolases of trypanosomatid flagellates. Homogenates from 5 species of Trypanosomatids were screened for the presence of a series of acid hydrolases. The insect flagellae, Crithidia sp., contains 5 enzymes reminiscent of plant parasitism, which were absent from or of very low specific activity in parasites of the genera, Trypanosoma and Leishmania. The latter mammalian parasites, on the other hand, exhibited higher acid proteinase and alpha-D-mannosidase activity levels.


Identification by the blood incubation infectivity test of Trypanosoma brucei subspecies isolated from game animals in the Luangwa Valley, Zambia. A total of 7 stocks of Trypanosoma brucei subspecies, isolated from naturally infected game animals in the Luangwa Valley, Eastern Province, Zambia were examined using a modified version of the Blood Incubation Infectivity Test (BIIT). One stock giving consistent BIIT responses typical of T.b. rhodesiense, was obtained from warthog (Phacochoerus aethiopicus). Four other stocks, 2 from hyaena (Crocuta crocuta), 1 from a waterbuck (Kobus ellipsiprymnus) and 1 from a lion (Panthera leo) responded like T.b. brucei. One stock from a waterbuck and 1 from a giraffe (Giraffa camelopardalis) failed to infect mice after incubation in human serum for 30 min at 37 degrees C when first tested, but after 5 or 6 further serial passages in mice and even with serum incubation time increased to 5 h, they retained infectivity.


A trypanosomiasis survey of wild animals in the Luangwa Valley, Zambia. Between 1971 and 1974 546 wild animals of 34 species were examined for trypanosomes; 79 infections (9 mixed) were diagnosed and 29 stocks were cryopreserved. Of 14 stocks of the subgenus Trypanozoon tested by the blood incubation infectivity test three (two from Kobus ellipsiprymnus and one from Phacochoerus aethiopicus) retained their infectivity to rodents. There are indications that the number of animals harbouring trypanosomes is far in excess of those showing detectable parasitaemias even when using a combination of diagnostic methods. The standard microhaematocrit method involving microscopic examination of the buffy layer from a microhaematocrit tube between a slide and coverslip, and the inoculation of experimental animals produced the most satisfactory results.


Ixodes ricinus: vector of a hitherto undescribed spotted fever group agent in Switzerland. A tick/rickettsial survey in various parts of Switzerland revealed the presence of a new, hitherto undescribed spotted fever group rickettsia ("Swiss agent") in up to 11.7% of I. ricinus collected off vegetation. Infection in ticks was found to be generalized with rickettsiae developing intracellularly and occasionally also intranuclearly. As a result of massive growth in ovarial tissues, including the germinative cells, the rate of transovarial and filial infection was 100%. The "Swiss agent" appears to be nonpathogenic for guinea pigs, domestic rabbits, and Swiss mice, but in male meadow voles (Microtus pennsylvanicus) it produces a microscopically detectable infection in the tunica vaginalis. The rickettsia grows well in tissue culture systems including chick embryo fibroblast, Vero, and vole tissue cells, when inoculated via yolk sac into 5-day-old hens' eggs, it kills 100% of the embryos after 5 to 7 days. Antigenic relatedness of the "Swiss agent" to rickettsiae of the spotted fever group was indicated by indirect and direct fluorescent antibody staining. Preliminary serologic typing by microimmunofluorescence and by microagglutination indicated that the "Swiss agent" differs from all prototype strains of spotted fever group rickettsiae studied so far.


Tanzania filariasis project. Survey methodology and clinical manifestations of bancroftian filariasis. In a Bancroftian filariasis survey on the coast of Tanzania microfilaria rates rose with age reaching 53% in the 60-69 year group followed by a slight fall above this age. The most important clinical manifestations were hydrocoele, funiculitis and elephantiasis, with hydrocoele presenting the most serious public health problem. Hydrocoele rates increased with age reaching 90% above the age of 70. The highest proportion of large hydrocoeles were also in the older age groups. A satisfactory methodology was established for the planning of future surveys leading to control.


Gastrointestinal graft-versus-host disease in man. A clinicopathologic study of the rectal biopsy. Evaluation of the diagnostic utility of the rectal biopsy in graft-versus-host disease (GVHD), using the crypt abscess as a major diagnostic criterion, was based on 52 patients who had received marrow allografts for leukemia or aplastic anemia. Thirty-six of these patients had acute GVHD by skin biopsy criteria. These 36 patients demonstrated a strong association of the rectal crypt abscess with severity of clinical GVHD. High stool volume also correlated strongly with the crypt abscess. Patients without clear evidence of GVHD usually had normal rectal histology. Serial studies showed a good correlation of rectal biopsy results with the clinical course of acute GVHD. Patients with chronic GVHD had rectal mucosal damage only during the acute phase. Rectal ileal and cecal disease accurately. The rectal biopsy is a useful adjunct to serial skin biopsies in the diagnosis of GVHD in man.


[Emphysema and "emphysembronchitis" in the age and their treatment (author's transl)]. Short review about pathogenesis, morphology and pathophysiology of emphysema and chronic bronchitis. Critical remarks to the terminology. Following reference to the peculiarity oft both diseases, their mutual influence and the necessity of differential diagnosis. Both diseases are incurable but treatable. At last review about therapeutic possibilities.


[Bronchial obstruction in the aged--symptom or diagnosis? (author's transl)]. Airflow obstruction is not a clinical entity. The presence of obstruction has to be documented, at least by a timed forced vital capacity. Consequently, information must be sought about the quality and severness of the functional disturbance (pathogenesis, reversibility by medication, follow-ups). Because of the great number of possible irritants and responses, the differentiation of bronchial and extrabronchial obstruction is of great importance for the elderly patient (bronchitis plus emphysema?). The impact of other disorders on the bronchi is being discussed (e.g. pulmonary embolism, left heart failure). These considerations should be part of the routine before therapy is being initiated.


[Pulmonary embolism in the elderly patient (author's transl)]. Pulmonary embolism has a high incidence in old patients and is often not recognized. In most cases the embolism is of unknown origin, although the deep venous system of the lower extremities is involved in almost 95%. The diagnostic procedure consists of evaluation of clinical symptoms and findings. ECG and chest X-ray are often not conclusive. Confirmation of the diagnosis is possible by ventilation-perfusion scanning of the lung. Pulmonary angiography is of no value in the elderly patient, because of the lack of consequences. Besides local therapy of a thrombosis, therapy consists of administration of heparin, while oral anticoagulation should be used only with precaution. The efficacy of platelet aggregation inhibiting substances remains to be determined. The main point are prophylactic measures in patients with risk factors or in high risk situation.


Estimation of cardio-pulmonary function by means of the age equivalent. Many of the cardio-pulmonary function variables depend on age showing a deterioration with increasing age. Reversing this relationship age can be estimated by cardio-pulmonary variables. In the present study, age was estimated using a multiple regression equation including variables measured at rest and at exercise. The difference between estimated and chronological age is called the age equivalent. (delta A). Formulas for estimating delta A have been established in 59 strictly defined normal subjects and applied on groups of athletes, smokers and foundry workers. Using the delta A, factors such as physical fitness, smoking habits, heaviness of work and dust exposure can be discriminated. It is concluded that the age equivalent is more useful in epidemiological surveys than in individual analysis of functional capacity. The age equivalent may be an approach to data reduction in cardio-pulmonary function analysis.


[Examinations of the pulmonary function of untrained and physically trained old men (author's transl)]. In tests there were determined the vital capacity and absolute and relative seconds capacity of 180 physical-trained sportsmen aged 55 to 89 and of 175 untrained, but clinically healthy test persons. The results of the different age-intervals are compared statistically. It was noticed, that vital capacity and absolute seconds-capacity of both groups decrease statistically significant with the age. Vital capacity and seconds capacity are in all age-intervals on a higher level with the trained sportsmen than the control group. The relative seconds-capacity showed no significant difference between the two groups. There is a clear statistic connexion between the vital capacity and the time obtained in a 5 000 meters run. One can suppose that in contrast to juvenile sportsmen a good pulmonary function is a contributory determinant of the performance of old sportsmen.


[Influenza immunization, clinical results and serological tests (author's transl)]. 207 patients of a geriatric department were immunized against influenza with either tween-ether-split-vaccine or subunit-vaccine in a double blind study. For 6 months the following data were daily registered: rest in bed, fever over 38,5 degrees C, rhinitis, laryngopharingitis, bronchitis, pneumonia, enteritis, medication with antibiotics or chemotherapeutics. In cases with fever over 38,5 degrees C blood tests were taken for serological examination. The immune response against influenza A was excellent in both groups, the titer was higher in the subunit group, only one patient showed influenza infection. The immune response against the type B Hongkong was not satisfactory in both groups. The clinical data showed a significant lower incidence of rhinitis, laryngopharingitis and bronchitis in the group immunized with the tween-ether-split-vaccine. This effect was more distinct within the first 3 months after the immunization than within the second 3 months.


[Calcification of the ligament. ant. of the spina (disease of Forestier) (author's transl)]. On the basis of the examination on a rich old-age patient material it may be established that. 1. Radiomorphologically the Forestier's disease essentially differs from the banal spondylosis. 2. Age is of particular importance in its genesis -- it is primarily a disease of old age men. 3. It is localized for the most part on the dorsal vertebral part. 4. As compared to the multiple radiomorphological signs clinical symptoms are, in general, neglectable. 5. Additional search for the relationship with diabetic metabolic disturbances in gerontological patients seems advisable.


[The aging skin (author's transl)].

[The aging skin (author's transl)]. Aging of the skin appears in circumscribed as well as in generalized forms. The localized alterations may be subdivided in such of inflammatory origin and in hyperplastic ones. The latter include benign and also precancerous tumors. The generalized and usually premature manifestations of cutaneous senescence are almost always part of some hereditary disease which frequently also affects the viscera, sense organs, skeleton, and the nervous system.


A study on liquid diet in geriatric patients. The intake of energy and nutrients was studied during 16 days in nine geriatrics immobilized patients who had received a conventional liquid diet for an extended period of time. The intake of energy averaged only 870 kcal/24 h. Fat intake was very low, averaging 16 g/24 h, which corresponds to 17 per cent of the total energy intake. The mean protein intake was 33 g/24 h. To improve the energy and nutrient content a food supplementation was added to the liquid diet. During the following 16 days the intake of energy increased to a daily mean of 1380 kcal. Fat and protein intake increased to 38 and 73 g/24 h, respectively. No essential change in the volume consumed after addition of the food supplementation was observed. Urinary nitrogen excretion was analyzed during the study. A positive nitrogen balance occurred after the patients had received the food supplementation.


Alzheimer's disease or "Alzheimerism"?

Alzheimer's disease or "Alzheimerism"? Recognition that chronologic age is not per se a cause of dementia opens the way for a more active approach to Alzheimer-type dementias as a specific disease syndrome. "Alzheimerism" in many respects is to the cholinergic brain system what Parkinsonism is to the dopamineragic. Whether cell loss or choline acetyltransferase deficiency comes first is still unclear, as is the role of vasopressin. There is a real possibility that research might produce a palliative for ACh-based defects similar to the action of L-dopa in dopaminergic defects.


[Pharmacotoxic psychoses in patients with neurological disorders during old age (author's transl)]. 23.3 per cent out of 180 old patients (age above 60 years, 71 y in the mean) suffering from chronic cerebral disorders (3 large groups of disease) developed pharmacotoxic psychoses. This relative high percentage can be explained by psychotoxic side effects of the modern antiparkinson-therapy. The incidence to psychotoxicity of combined L-Dopa seems to be less marked in patients without Parkinson's disease when compared to patients with progredient nigrostriatal degeneration. Toxic delirium as a result of treatment with antidepressants, diuretics and digitalis was observable only in a few percentage. This occurance was even less pronounced in comparison to acute developing exogene psychoses in the same group of patients when drugs were not administered.


[The hypnotic effect of the new benzodiazepine derivative lormetazepam when given intravenously (author's transl)]. 1. 7 groups of 3 healthy male volunteers each, at the age of 21--27 years received various doses of Lormetazepam (0.0635 to 4.0 mg/70 kg). -- 2. The drug was injected intravenously during 60 s. Before, during and up to 4 hours after the injections the EEG, eye-movements, ECG and respiration was recorded and blood pressures measured at given time intervals. -- 3. The vigilo-somnograms showed after the injections a change in the EEG-stages, indicating a reduction of alertness, transitions into reduced wakefulness or beginning stages of sleep. Corresponding to clinical signs one can speak with i.v. applied doses of 0.0635 to 0.5 mg/70 kg of tranquilizing, with 1 mg/70 kg of sedative and with 2--4 kg of hypnotic effects. There has been a good dosage-efficiency relation. -- 4. Side-effects or unwarranted symptoms have not been seen during the clinical observations.


[Physiopathology of coronary stenosis].

[Physiopathology of coronary stenosis]. The blood and oxygen needs of the heart are considerable. At rest, the left ventricle uses twenty times as much oxygen as skeletal muscle and on effort its consumption is five times greater again. The level of extraction of oxygen from coronary blood by the myocardium is very high at rest and thus can only increase by limited amounts on effort. Coronary venous blood is the most desaturated in the body. Furthermore, the anaerobic capacity of the heart is limited. As a result, the increased oxygen needs of the heart on effort can be dealt with only an increase in coronary flow. There is in fact a balance between myocardial oxygen supply and needs.


[Effects of hypoxia on the coronary circulation and myocardial metabolism]. The effects of hypoxia on coronary flow (Qcor) and myocardial metabolism differ according to whether the situation is acute, and transient, or chronic and prolonged (chronic hypoxia at high altitudes). Acute hypoxia induces a marked increase in Qcor which is associated, in the case of severe hypoxia, with the production of lactate and pyruvate in the coronary venous blood, indicating abnormal aerobic metabolism of the myocardium, blocked by the lack of oxygen. A study of the effects of chronic hypoxia at high altitudes (HA) carried out at 3700 metres in 17 normal subjects revealed a significant decrease (of 24 to 28 per cent) in Qcor in comparison with a group of 12 normal subjects studied at sea level, using the same method (method of KETY-SCHMIDT with N2O and tritiated water method). The finding at HA of a decrease in myocardial oxygen consumption for a given external cardiac work load in comparison with the sea level group would suggest an increase in left ventricular work yield. Associated with other favourable changes in the myocardium (increase in terminal and capillary circulation, quantitative and qualitative improvement in the respiratory enzyme chain) the apparently beneficial effects of chronic hypoxia at HA may be suggested as a means for the prevention of coronary disease.


[Hemodynamic effects of beta blockers].

[Hemodynamic effects of beta blockers]. Beta-blockers have been used in cardiology for the past 15 years in three directions: angina pectoris, cardiac arrhythmias, and hypertension. The haemodynamic effects are real: --imposed bradycardia, whether the basal rhythm be sinus or atrial fibrillation; --confirmed myocardial depression which reduces the energy needs of the myocardium; --fall in systolic pressure, the mechanism of which remains open to discussion. The theories explaining these haemodynamic effects are reviewed. The harmful effects of these substances are defined, together with the drug combinations which may avoid or counteract them.


[Principles of analysis and the value of coronaro-ventriculography in coronary surgery]. The examination which precedes any operation for revascularisation of the myocardium, coronaro-ventriculography, which has become a routine examination in specialised centres, should gain even further in reliability by anatomical examination of the vessels which it is used to study in vitro. A perfect knowledge of the distribution of the vessels (the numerous and sometimes unrecognised variations are a source of diagnostic error) and of the characteristics of the lesions (atheromatous in most cases) is essential for the accurate interpretation of a coronary arteriogram. Difficulties in analysis of the latter are numerous and the physician interpreting the examination should be fully aware of them before any decision regarding surgery is taken. Ventriculography routinely analyses, zone by zone, the contours of the left ventricle. In certain cases this segment study is associated with overall analysis of ventricular volumes and stroke fraction.


[The anesthesiologist and the hemodynamic effect of anti-arrhythmic agents (excluding beta blockers)]. On the basis of a haemodynamic study involving the intravenous administration of disopyramide, a review is undertaken of the haemodynamic action of various anti-arrhythmics likely to be used pre- or peroperatively by the anaesthetist. All anti-arrhythmic agents have possible haemodynamic properties which may prove troublesome for the anaesthetist: --all (with the possible exception of bretylium tosylate) have negative inotropic properties; --all (with the exception of disopyramide) decrease peripheral resistance. These effects are as a rule slight in the healthy subject but may give rise to difficulties during anaesthesia of a patient with a damaged myocardium.


[Anesthesia for aorto-coronary bypass].

[Anesthesia for aorto-coronary bypass]. The authors have analysed a series of 357 patients undergoing aortocoronary bypass. The onset of complications was studied in relation to the past history, the anaesthetic protocol, the period of extra-corporeal circulation and the type of myocardial protection. Complications consisted of acute hypertensive episodes, arrhythmias, peroperative myocardial ischemia and myocardial infarction. The degree of beta-blocker therapy and above all its continuation up to the time of operation would seem to be an important factor in effective myocardial protection.


[Anesthesia-recovery from aorto-coronary bypass surgery (100 recent cases)]. The authors report their experience of anaesthesia and postoperative recovery in cases of myocardial revascularisation surgery. On the basis of their last 100 bypass operations, they define the problems encountered according to the operative indications, previous treatment and the surgical technique, and attempt to provide answers to these problems. The difficulties (arrhythmias, myocardial ischaemia, hypertensive crises) occurred during the first 48 hours. They then consider the most current problem, that of the preoperative treatment of these patients (nitroglycerine, beta-blockers, amiodarone). They conclude that, paradoxically, in this type of surgery the operative risk is low as long as the indication for surgery is valid and myocardial protection effective.


[Accidents and complications seen during anesthesia and postoperative recovery in coronary surgery]. One hundred and six cases of myocardial revascularisation ECC performed during 1976 and 1977 were reviewed in order to assess the accidents and complications seen in surgery of this type. The course of the operation, and above all during the pre-ECC phase, was felt to be marked above all by hypertensive crises. During the immediate postoperative phase the picture was dominated by haemodynamic problems. Moderate left ventricular failure was common and responded rapidly to restoration of water and electrolyte and blood volume balance. Sympathomimetic amines were also used as necessary. Severe low output states were seen in only 8.5 per cent of cases. Analysis of factors interfering with the operation showed that the prior myocardial state had the most influence on the postoperative course.


[Problems encountered by the anesthetist-intensive care specialist during aorto-coronary bypass surgery]. The authors analysed a series of 400 aorto-coronary bypasses performed between 1970 and April 1978. A notable improvement in the statistics was seen during the second period between 1976 and April 1978. During this period, 248 patients were operated upon with a mortality of 4 per cent. The progress made was in large part attributed to improved preoperative assessment, in particular a complete ventricular assessment, improved peroperative myocardial protection and the use of the intra-aortic counter-pressure balloon and of sodium nitroprussiate.


[Problems encountered by the anesthetist-intensive care specialist during aorto-coronary bypass surgery]. The authors studied a series of 288 patients undergoing surgery for aorto-coronary bypass. The anaesthetic protocol and operative protocol are described and particular emphasis is placed upon the aortic clamp time. Mortality and peri-operative complications are then analysed. The treatment of such complications is based essentially upon vasodilators and where necessary intra-aortic counter-pressure balloon device to provide circulatory assistance.


[Accidents and complications during aorto-coronary bypass surgery. 100 cases]. Using a series of 100 patients undergoing aorto-coronary bypass surgery in the department of Professor MATHEY at Laennec Hospital, the authors analyse the incidence of accidents and complications during the per- and postoperative phases. Acute hypertensive crises accounted for the most common complication, occurring in 49 per cent of cases. The authors attribute these hypertensive crises to inadequate neuroplegia in the anaesthetic protocol. Other complications are analysed in relation to the type of myocardial protection.


[Risk factors in coronary artery bypass surgery. 55 observations]. The incidence of complications after aorto-coronary bypass surgery were studied in a series of 55 patients in relation to the duration of extra-corporeal circulation and the value of myocardial protection. The length of the period of extra-corporeal circulation played a significant role in the onset of complications whilst there was no significant difference between the group of patients operated upon under hypothermia and those in normothermia.


[Complications and anesthetic protocol during coronary arteriography at the Henri Mondor Hospital - report of 1977-1978]. Four hundred and sixty cases of selective coronary arteriography were collected at the Henri Mondor Hospital over a period of one year. All were carried out under conscious neuroleptanalgesia. This technique would appear to offer: comfort for the operator and patient and the prevention of complications.


[Anesthesia and intensive care during aorto-coronary bypass surgery. Prospective study of 162 consecutive cases]. The authors studied a series of 162 patients undergoing surgery for aorto-coronary bypass by saphenous graft. In each case, the anesthetic technique was classical neuroleptanalgesia. Per and postoperative care included standard water and electrolyte balance, hpeparinisation from the 12th hour and routine prophylactic antibiotics. In addition, special treatment was given whenever necessary: vasodilators, essentially IV nitroglycerine; catecholamines; anti-arrhytmic agents; intra-aortic counter pulse balloon. The autors evaluate the effects of the use of these different types of treatment, in particular on electrocardiographic abnormalities and haemodynamic complications and analyse peri-operative mortality and morbidity.


[Prevention of complications following aorto-coronary bypass surgery. Proposed solutions]. In the light of per- and post-operative complications seen in the past, the most suitable anaesthetic protocol for aorto-coronary bypass surgery would appear to be neuroleptanalgesia. This anaesthetic technique appears to decrease the incidence of per- and postoperative hypertensive crises. In addition, the use of cardioplegia also made it possible to decrease the incidence of postoperative complications in a recent group of 39 patients.


[Effect of drugs used in anesthesia on endocardial viability ratio (EVR) in cardiac surgery]. Endocardial viability ratio, arterial blood pressure, heart rate, central venous pressure and left ventricular diastolic pressure were examined in 50 patients undergoing one or more aorto-coronary grafts. General anaesthesia was obtained by morphine, diazepam, pancuronium and a mixture of oxygen and nitrous oxide. Morphine anesthesia did not effect EVR. Only mean arterial pressure showed a significant increase at the time of surgical stimulation. During sternotomy, EVR fell progressively in patients with hypertension. Tachycardia alone did not modify it. This hypertension was better treated by sodium nitroprussiate than by halothane or enflurane with regard to protection of the sub-endocardial layer against ischaemia. Under the influence of sodium nitroprussiate EVR rapidly reached values greater than those obtained under halothane or enflurane. In the hour following extra-corporeal circulation, endocardial viability ratio improved without any significant variation in classical haemodynamic parameters.


[Role of premedication in the prevention of accidents during aorto-coronary bypass]. Study of the type of premedication used in aorto-coronary bypass surgery involved 60 clinical cases of patients operated upon in the department of Professor GALEY (Henri Mondor Hospital, Creteil). The choice of drugs used showed the important role of tranquilisers and anxiolytics: diazepam, dipotassium chlorazepate, to which, in the majority of cases, were added an antihistamine: promethazine and a parasympatholytic: atropine. No accidents or complications were seen during the pre-anaesthetic period, and above all during the induction of anaesthesia in these patients, more than half of whom were in major cardiovascular decompensation. This would appear to confirm the efficacy of the drugs chosen for the premedication of these patients.


[Retrospective study of recent variations in patient recruitment for aorto-coronary bypass surgery and the prognostic significance of new therapeutic propositions]. Seventy four records of aorto-coronary bypass surgery have been examined. Three groups were made up, succeeding each other in time, characterised by changes in factors of gravity, therapeutic solutions and early clinical results. Five patients underwent peroperative haemodynamic assessment in order to attemps to define the role of nitroglycerine used during this period. The results obtained were such that it is reasonable to suspect the existence of potentialisation of therapeutic benefits under the influence of nitroglycerine for injection, in patients previously treated with beta-inhibitors.


[Role of intra-aortic balloon pumping in coronary surgery for stenosis of the left common coronary trunk]. Surgical treatment for stenosis of the left main coronary artery is associated with a high risk related to particular vulnerability to acute myocardial ischaemia during the period of induction of anaesthesia. Eight cases of stenosis of the left main coronary artery undergoing surgery with preoperative insertion of an intra-aortic counter-pressure balloon are reported here. The results - eight successes - as opposed to four failures seen prior to the use of this technique and in similar cases, leads the authors to suggest stenoses of the left main coronary artery as a further criterion indicating the need for routine preoperative intra-aortic counter-pressure


[Pathology of endocrine polyneoplasms (polyadenomatoses) (author's transl)]. The term "endocrine polyadenomatoses" includes two types of pathological entities in which there are an association of at least two endocrine tumors having no physiological relationships, and hereditary familial characteristics: Wermer's syndrome (Type I): pancreatic endocrine tumor, pituitary adenoma, and hyperplasia or adenoma of the parathyroids. Sipple' syndrome (Type II): medullary thyroid cancer, one of two pheochromocytomas, and parathyroid hyperplasia. The multifocal character of the pancreatic D-cell lesions in the first type, and the bilateral nature of the thyroid and adrenal lesions in the second type are particular features of each of them. Apart from some parathyroid lesions, for which the origin is still debatable, these endocrine tumors enter into the framework of the apudomes and are derived therefore from the neural crest. The association of other tumoral varieties of the APUD (carcinoid) type with nervous tissue tumors, and with dysmorphic anomalies suggests that these syndromes are the expression of a dysgenesis affecting more or less completely, structures derived from the neural crest.


[Physiology, physiopathology, and classification of polyendocrine adenomatosis (author's transl)]. The various elements derived from the neural crest are reviewed and their relationship with the APUD system discussed. The resulting physiopathological consequences imply that there is a common embryonic origin for cells which appear to be unrelated. A classification of the various pathological affections involving these cells, is proposed.


[Hormone assays in polyadenomatosis (author's transl)]. Radioimmunological assays of peptidic hormone levels is now an essential procedure for the diagnosis of polyadenomatosis. The diversity of pathological associations found in polyadenomatosis cannot be completely explained by the unitary theories that have been proposed. Neither the APUD system, nor the common embryonic origin, nor the reduction in calcitonin excretion can fully explain the clinical picture: a logical explanation has still to be discovered. In practice, ectopic secretions are frequent in type 2 polyadenomatosis (medullary cancer, pheochromocytoma, neurofibroma, Marfan's syndrome, hyperparathyroidism) contrary to what is observed in type 1 cases (pituitary, parathyroid, pancreas).


[Wermer's syndrome (author's transl)].

[Wermer's syndrome (author's transl)]. The authors present a brief report on a familial case of Wermer's syndrome, and review the principal characteristics of this "multiple endocrine neoplasm" which usually affects the parathyroids, pancreas, and anterior pituitary.


[Sipple's syndrome: type II endocrine polyneoplasia (author's transl)]. Sipple's syndrome is a generally familial polyneoplastic affection associating a medullary thyroid cancer and a pheochromocytoma. The overall picture of the syndrome has, in fact, become larger now that it is known that there is previous hyperplasia of thyroid C cells and chromaffin cells in relation to neoplasms. Increase in plasma thyrocalcitonin levels is the best indicator of medullary cancer, and the discovery of this hormone in pheochromocytomas has shown the secretory origin of the two tumors, the cells of which have a common embryological origin in the neural crest. Sipple's syndrome is often associated with hyperparathyroidism, hyperplasia without adenoma (endocrine polyneoplasia type II a), or phacomatosis and a dystrophic condition (type II b or III). The authors discuss the nosology of the syndrome and its relation to the diffuse endocrine and APUD systems.


[Endocrine polyadenomatosis: progressive neurocristopathy (author's transl)]. Endocrine polyadenomatosis forms but a part of the larger group of neurocristopathy disorders. This term includes those affections due to lesions of cells, tissues, or organs derived from the neural crest. The common origin of the various neuro-endocrine cells within the neural crest suggests that there is a denominator of embryologic pathogenicity for the different polyendocrine affections. Knowledge of these is essential for early diagnosis of the different neuro-endocrine lesions, together with a systematic search for any familial associations.


[Prolactin adenoma and Wermer's syndrome. A 10-year follow-up of a case with two parathyroid tumors, as adrenal adenoma, and a malignant pancreatic tumor (author's transl)]. A man of 38 years of age was found to have a type I endocrine polyadenomatosis in 1969. He was operated upon for removal of tumor of the islets of Langerhans with lymph gland metastases, and the head of the pancreas was removed. This was followed at a later date by ablation of two parathyroid adenomas. A clinically silent adenoma of the left adrenal was not removed and a silent and enclosed pituitary tumore was discovered. There were no clinical or hormonal signs of progression of the pancreatic tumor ten years later, but hypertension and behavioural disorders had developed. Catecholamine levels were normal. Selective blood aldosterone levels were just within significant values. A massive increase in prolactin secretion (more than 100 times the normal) was noted. This could be reduced by bromocriptine, and the possible role of prolactin in the behavioural disorders present is discussed.


[Double paraneoplastic syndrome and anaplastic carcinoma of the lung. ADH and ACTH levels in the tumoral tissue (author's transl)]. A double paraneoplasic syndrome with hypersecretion of ADH and ACTH revealed the presence of a small cell bronchial cancer in a man aged 62 years. Water and electrolyte anomalies due to the hypersecretions were of such a degree that an occlusive syndrome occurred. Very high levels of ADH and ACTH were found in the tumoral tissue. The measurement of these levels is rarely conducted at the present time but was able to define the mechanism of abnormal secretion of these two hormones in this case.


[Periarteritis nodosa in an addict with a hepatitis B injection (author's transl)]. The authors describe a case of a drug addict with a hepatitis B who was found to have periarteritis nodosa and a nephrotic syndrome. The course was rapidly fatal and autopsy confirmed the diagnosis. This new case questions the hypothesis suggested of possible toxicity of hard drugs (especially the amphetamines) as being an etiological factor for periarteritis nodosa observed in addicts. Hepatitis B virus, which is involved in the etiology of periarteritis nodosa and some nephrotic syndromes (also reported in addicts) is, in fact, very prevalent in users of hard drugs by the parenteral route.


[Lupos erythematosus discovered during the course of a toxicodermia (author's transl)]. The authors describes four cases of lupus erythematosus (LE) diagnosed during the course of a medication toxicodermia, which was always acute and variable in its severity (in one case it concerned a Lyell's syndrome). The lupus affection was made evident by the toxicodermia and lupic manifestations may regress spontaneously after recovery from the skin disorder. This emphasizes the value of clinical and biological testing for the presence of LE in severe cases of toxicodermia in women, more particularly immunofluorescent studies of the basal structures in the cutaneous lesions.


[Betablockers and skin (author's transl)]. Up to now betablockers, with the exception of erythermalgia, have been rarely used as therapeutic agents in dermatology. However, cutaneous drug reactions are numerous. A review of the literature about practolol cutaneous effects and their possible mechanisms has shown that a great variety of clinical states can be encountered. All betablockers have been known to produce harmful side effects, although less frequently. In conclusion, the description of each new case of cutaneous drug reaction probably due to betablocker must be assessed.


Lethal irradiation: treatment with immune cell populations. Lethally irradiated mice have been successfully treated by the inoculation of allogeneic spleen cell populations, without the development of a secondary graft-versus-host (GVH) reaction. This has been accomplished by eliminating those cells responsible for GVH reaction, using a density gradient ultracentrifugation technique. The therapeutic potential for this technique is great. It may well provide a modus operandi to treat patients exposed to otherwise lethal doses of radiation, as well as facilitate therapy of patients with cancer and immune deficiency diseases.


Orotic acid and non-protein nitrogen overload in sheep. Experiments were conducted in sheep to investigate the protective effect of orotic acid versus acetic acid (0.2 g/kg body weight) against the effects of the administration of urea (0.5 g/kg) into the rumen. Blood ammonia levels, motility of the reticulo rumen and food intake were measured. The quantity of ammonia nitrogen produced in the rumen was only 162 +/- 21 mg NH3-N/100 ml 2 hours after the urea and orotic acid addition instead of 229 +/- 31 mg NH3-N for urea and acetic acid. The blood ammonia level was reduced by 47% when orotic acid was used instead of acetic acid. The long-lasting inhibition of the contractions of the reticulo-rumen by urea was restricted to 120 and 80 min by acetic and orotic acid respectively. The amount of food intake which was halved by urea was only reduced by 40.7% when both acetic acid and urea were administered. Reduction in the amount of food intake due to urea was suppressed by the administration of orotic acid.


Modulatory actions of neurotransmitters. A relatively shorttime ago the individual neuron was viewed as functioning by means of the simple summation of brief inhibitory or excitatory events. The complexity of the nervous system was the outcome largely of the connections between neurons. Recent studies have uncovered a new set of phenomena that indicate that relatively complex information processing may occur  at the level of the individual neuron. For example, rather than producing additive effects, synaptic inputs can produce multiplicative effects that serve to alter the gain of the system. In addition, synaptic inputs may be able to alter specific classes of other inputs selectively. One could envision that each class of synaptic input to a cell could be selectively depressed or enhanced by a corresponding modulatory input. Since the modulatory actions can be transmitted intracellularly via second messengers, an extensive array of presynaptic connections may be unnecessary. It remains to be determined which of the modulatory phenomena currently reviewed are functionally important and which are only pharmacological or experimental curiosities. Are there any common attributes of the various synaptic phenomena that have been termed modulatory? The most common features of modulatory synaptic effects are long-duration of action and contingent action. Contingent action refers to the property that modulatory transmitters often have little or no effects in themselves, but instead they alter the effects of other events. Long-duration and contingent action endow modulatory effects with properties ideally suited to the control of behavioral modulations such as learning, motivational state, arousal, and sensitization. While there is no necessary connection between behavioral modulation and neural modulation, the available evidence from invertebrates suggests that there often is a connection. It is likely that examples of neuromodulation in vertebrates also will be tied to behavioral modulation.


Toxin production by Clostridium botulinum type A under various fermentation conditions. The time of appearance and the quantity of toxin produced by the Hall strain of Clostridium botulinum type A were examined under various conditions. A 70-liter fermentor and a complex medium consisting of 2% casein hydrolysate and 1% yeast extract plus an appropriate concentration of glucose were employed. Optimal conditions for toxin production were as follows: a nitrogen overlay at a rate of 5 liters/min, an agitation rate of 50 rpm, a temperature of 35 degrees C, and an initial glucose concentration of 1.0% with the pH uncontrolled. Under these conditions, the maximum toxin concentration (6.3 x 10(5) mouse median lethal doses/ml) was attained within 24 h. Cell lysis was apparently not required to obtain maximum toxin concentrations under the fermentation conditions described.


Effect of environmental stress on Clostridium difficile toxin levels during continuous cultivation. A method for the continuous culture of Clostridium difficile has been described. It has been shown that subjecting continuous cultures of this microorganism to environmental stress results in increased levels of toxin in culture medium. Factors found to cause this release include alteration of the Eh from --360 to +100 mV or increasing the temperature from 37 to 45 degrees C. The increased toxin levels were not associated with a change in viable cell density or the numbers of spores present. Additional studies have shown that subinhibitory concentrations of vancomycin and penicillin, but not clindamycin, also cause an increase in toxin levels during continuous culture. The increase in supernatant toxin levels occurs concomitant with a decrease in sonicated cell extract toxin levels. The data suggest that a number of factors can cause a release of toxin from C. difficile into the surrounding medium.


Toxicity of parasporal crystals of Bacillus thuringiensis subsp. israelensis to mosquitoes. Toxicity of Bacillus thuringiensis subsp. israelensis (ONR-60A/WHO 1897) parasporal crystals to three medically important mosquito larvae is described. The numbers of larvae killed are in relation to crystal dry weight. The crystals are lethally toxic to Aedes aegypti Linnaeus (mean 50% lethal concentration [LC50] = 1.9 x 10(-4) micrograms/ml), Culex pipiens var. quinquefasciatus Say (LC50 = 3.7 x 10(-4) micrograms/ml), and Anopheles albimanus Wiedemann (LC50 = 8.0 x 10(-3) micrograms/ml). Purfied crystals of B. thuringiensis subsp. kurstaki, which are toxic to lepidopteran insects, are ineffective against the mosquito larvae. Likewise, B. thuringiensis subsp. israelensis parasporal crystals are not efficacious for larvae of the lepidopteran, Manduca sexta.


Enterovirus inactivation in soil.

Enterovirus inactivation in soil. The inactivation of radioactively labeled poliovirus type 1 and coxsackievirus B 1 in soils saturated with surface water, groundwater, and septic tank liquor was directly proportional to temperature. Virus persistence was also related to soil type and the liquid amendment in which viruses were suspended. At 37 degrees C, no infectivity was recovered from saturated soil after 12 days; at 4 degrees C, viruses persisted for at least 180 days. No infectivity was recovered from dried soil regardless of temperature, soil type, or liquid amendment. Additional experiments showed that evaporation of soil water was largely responsible for the decreased recovery of infectivity from drying soil. Increased rates of virus inactivation at low soil moisture levels were also demonstrated.


Phenotypic changes in the chemistry of Aspergillus nidulans: influence of culture conditions on mycelial composition. A quantitative study was made of macromolecular (nucleic acids, protein), carbohydrate and mineral (magnesium, potassium and phosphorus) components of Aspergillus nidulans in glucose limited chemostat cultures, under varying conditions of dilution rate, temperature, pH and NaCl concentration. The overall mineral content showed greatest variation in response to changes in culture salinity, which also affected the mycelial carbohydrate content. Concomitant and opposite changes in the content of cations and carbohydrates under conditions of increasing salinity may be interpreted in terms of mycelial osmoregulation. Slight variations in DNA content but gross fluctuations in the level of RNA were noted under the different cultural conditions examined. Co-ordinate changes in RNA and Mg2+ contents were evident only under certain conditions: dilution rate from 0.05--0.07 h-1 or temperature from 22--30 degrees C. The constant molar stoichiometry between RNA and Mg2+ characteristic of unicellular microorganisms was not a feature of fungal growth. The protein content was most affected by shifts of temperature and reached minimal values at 25 and 50 degrees C. The growth environment had a marked influence on the protein synthesising activity of RNA, which increased eightfold as the dilution rate was increased from 0.02--0.175 h-1, doubled within the temperature range 20--30 degrees C and fell by 50% between 40 and 50 degrees C. These observations are discussed in the context of the constant ribosomal efficiency in protein synthesis hypothesis.


[Peridural analgesia and by phenoperidine in normal labor. Therapeutic trial with a control series]. The perinatal effects of phenoperidine and of epidural anaesthesia were studied in a randomised trial in which only normal patients were studied. Foetal heart rate curves, pH, pCO2 and neonatal clinical behaviour demonstrated that both kinds of analgesia had no harmful effects.


Brain amines and peptides--their relevance to psychiatry. The amine theory of affective disorder and the dopamine and endorphin theories of schizophrenia are controversial but heuristically valuable concepts that have emerged from the psychobiological revolution of the last decade. That revolution stemmed largely from the development of techniques for localizing and assaying neuroregulators and their receptors in the brain under normal, pathological and experimental conditions. The data thus obtained are reviewed here, and the current status of the emergent psychobiological hypotheses assessed.


Polymorphism at the G6pd and 6Pgd loci in Drosophila melanogaster. III. Developmental and biochemical aspects. The electrophoretic variants of G6PD and 6PGD isolated from the Bogota Drosophila melanogaster population were characterized developmentally and biochemically. Changes in in vitro enzyme activity during development were comparable to those found for other dehydrogenases: an increase in the larval and adult stage and a decrease in the pupal stage. During the whole life cycle the "S" enzyme of both loci showed a higher activity than the "F" enzyme. MgCl2 had a stimulating effect on the activity of both enzymes whereas their heat stability was decreased. The allozymes of 6PGD had different Vmax's but were comparable with respect to Km values, pH optimum, and stability at 45 C. the allozymes of G6PD showed different Vmax's and differed in stability at 35 C, but had similar Km values and pH optima. As the difference in stability was probably due to differences in molecular structure of the allozymes, the differences in activity found at high pH and high MgCl2 concentration were most probably due to this difference in stability.


Comparison of the properties of the alcohol dehydrogenases from wild-type and mutant Chinese hamster somatic cells. Alcohol dehydrogenases (alcohol: NAD oxidoreductase, E.C. 1.1.1.1.) from allyl alcohol-resistant and wild-type Chinese hamster cells were purified using gel filtration, ion-exchange, and affinity-column chromatography. Both enzymes exhibited the same isozyme band patterns on electrophoresis and isoelectric focusing. Physicochemical properties of the two enzymes such as pH and temperature optima, Km values, and temperature stability were found to be the same within the experimental errors. The genetic significance of these findings is discussed.


Properties of the two common electrophoretic variants of phosphoglucomutase in Drosophila melanogaster. Phosphoglucomutase (PGM) of adult stage in Drosophilia melanogaster has been characterized by gel filtration, ion-exchange chromatography, and isoelectric focusing. The two common electrophoretic variants, PGMA and PGMB, differ with respect to their kinetic and stability parameters. PGMA is more thermostable than PGMB but shows the same pH optimum, equal dependence on Mg2+, and identical molecular weight. There is no significant kinetic difference between the two allozymes at the optimum pH values, but at pH 6.0 the Km value for glucose-1,6-diphosphate of PGMB is significantly higher than that of PGMA. This difference might explain the observed selective advantage of the PgmA allele in population studies.


Inosine 5'-monophosphate dehydrogenase of Escherichia coli. Purification by affinity chromatography, subunit structure and inhibition by guanosine 5'-monophosphate. Escherichia coli IMP dehydrogenase (EC 1.2.1.14) was purified by affinity chromatography on immobilized nucleotides. The enzyme binds to agarose-bound 8-(6-aminohexyl)-AMP, N6-(6-aminohexyl)-AMP and 8-(8-amino-octyl)-IMP but not to immobilized NAD+ or Cibacron Blue F3G-A. AMP proved to be an effective eluent. A large-scale purification scheme in which 8-(6-aminohexyl)-AMP-agarose was used resulted in a homogeneous preparation of IMP dehydrogenase. The enzyme was also purified by immunoprecipitation with monospecific antisera. Sodium dodecyl sulphate/polyacrylamide-gel electrophoresis, N-terminal amino acid analysis and tryptic 'finger-printing' demonstrated that IMP dehydrogenase comprises identical subunits of mol.wt. 58000. Trypsin and Pronase cleave the 58000-mol.wt. subunit into peptides of mol.wts. 42000 and 14000, with a concomitant decrease in enzyme activity. These observations rationalize much of the contradictory data on the subunit composition of the enzyme found in the literature. GMP appears to be a competitive inhibitor with respect to IMP, with no evidence for regulatory behaviour being found. The two purification procedures were also used to purify inactive mutant enzymes from guaB mutant strains of E. coli.


A re-evaluation of some basic structural and functional properties of Pseudomonas cytochrome oxidase. Determinations of iron content and dry-weight measurements on samples of Pseudomonas cytochrome oxidase were coupled with sodium dodecyl sulphate/polyacrylamide-gel-electrophoresis studies of both the native protein and covalently cross-linked oligomers in order to estimate the enzyme's molecular weight and spectral absorption coefficients. A value of epsilon(ox.) (410)=282x10(3) litre.mol(-1).cm(-1) was calculated for a dimeric protein molecule having a total molecular weight of 122000 (based on iron analysis). Steady-state kinetic observations of the enzyme-catalysed oxidation of reduced azurin by nitrite indicated a marked increase in enzyme inactivation as the pH was raised from 5.7 to 7.2. Since NO, a product of the nitrite reductase activity of Pseudomonas cytochrome oxidase, is known to bind to the enzyme, a study was undertaken to try to assess the potential of NO as a product inhibitor. Investigations showed that samples of the oxidized protein at pH values 4, 5 and 6 bound NO to both haem c and d(1) components, but oxidized enzyme samples at pH7 and above formed their reduced ligand-bound forms when placed under an atmosphere of the gas. Ascorbate-reduced enzyme samples at pH4, 5, 6 and 7 were also found to bind NO at both haem components, although at pH7 the rate of haem c binding was very slow. At pH8 and 9 only the ferrohaem d(1) bound NO. Titration experiments on the reduced protein over the pH range 5-7, with nitrite as a precursor of NO, showed that the haem d(1) had a much higher affinity than the haem c: experiments at pH5.2 and 5.9 with NO-equilibrated solutions revealed the same pattern of behaviour with the oxidized enzyme.