[Behaviour of aflatoxin during production of processed cheese (author's transl)]. The problem of aflatoxin determination in processed cheese can be solved by the destruction of the emulsion with 6 m urea solution; the detection limit is 0.1-0.05 ppb B1 respectively G1. Examination of 115 trade samples resulted in 2 positive processed cheese samples only. This result cannot be reffered to the destruction of aflatoxins by the melting process, because neither at melting temperatures of 80-138 degrees C nor by melting salts and pH adjustments considerable losses could be observed, mostly below 5%.


The nitrosation products of creatine and creatinine in model systems. The formation of N-nitrososarcosine from creatine, creatinine-5-oxime and l-methylhydantoin-5-oxime from creatinine was investigated in model solutions under various conditions (temperature, pH, concentration of sodium nitrite). N-nitrososarcosine was formed from creatine only in strongly acidic medium and its concentration increased with temperature and concentration of sodium nitrite. No N-nitrososarcosine was detected at 0 degrees C and in the presence of an equimolar amount of sodium nitrite. Creatinine-5-oxime and l-methylhydantoin-5-oxime was formed from creatinine in a broad region of pH, the highest concentration of these compounds was found in pH 3.6. The main reaction product was l-methylhydantoin-5-oxime. At a given pH, the concentrations of these two oximes increased generally with increased temperature and/or concentration of sodium nitrite. No oxime were detected at O degrees C and in the presence of equimolar amounts of sodium nitrite. Likewise was studied the influence of temperature on the decomposition of the above mentioned compounds. The activation energies of the studied reactions in acidic medium were 4.12 (n-nitrososarcosine), 19.3 (creatinine-5-oxime), and 20.2 kcal/mol (l-methylhydantoin-5-oxime), respectively.


[Examinations to phenomenon of shock-lung (author's transl)]. The pathogenesis of shock lung as well as the success of therapy in this condition was studied in 79 cases of extrathoracic trauma. The water-, hemoglobin-, and DNA contents of the lungs were measured in order to determine the extent of edema, the rate of perfusion, and proliferation. The cases were divided into two groups according to whether they had or had not received medical therapy before death. The data from these two groups were compared using statistical methods in which time of survival was especially taken into account. The fluid balance, pO2, pCO2, central venous pressure, pH of the serum, total serum protein and serum creatinine were also studied in these cases. Results of the study are as follows. Three phases of the posttraumatic syndrome of shock-lung could be distinguished: phase I (initial phase): blood perfusion is increased, edema is beginning to form, and medical treatment has not yet begun. Phase II (early phase = sydrome of early respiratory failure): pulmonary edema is developing rapidly while perfusion is decreasing. Phase III (late phase = syndrome of late respiratory failure): proliferative changes predominante and the edema is still increasing. The mean weight of the lungs was 397 g (s = 170) in phase I, 774 G (S = 361) In phase II, and 1124 g (s = 310) in phase III. The survival times correlated significantly and positively with the amount of water and DNS in the lungs and significantly and negatively to the amount of hemoglobin in the lungs. Thus, increasing pulmonary edema and increasing proliferative changes occurred with decreasing pulmonary perfusion. This correlation was even noted in groups of patients who had not received medical treatment and whose survival times were short. In treated cases, the fluid balance was significantly and negatively correlated to the total serum protein.


[Bacteriological findings in materials from patients with nonspecific odontogenic infections]. The results of bacteriological studies made between 1964 and 1971 by workers at the Varia Laboratory, Institute of Medical Microbiology on 767 patients treated at the Clinic of Gnathofacial Surgery, Department of Medicine, Friedrich Schiller University at Jena, are evaluated. The testees (x=275) were included in groups with specific diagnoses, and a breakdown was made according to the detection of aerobic pus-forming germs. Gram-positive cocci were detected in 92% of the cases and their pathogenetic representatives, 76,5% of the cases. Rodshaped germs (Enterobacteriaceae, Pseudomonas) were observed only in 37,9% of the cases. Staphylococcus aureus, which accounted for 62,5%, was the most frequently observed species. It was followed, in order of frequency of detection, by greening streptococci and Staphylococcus epidermidis. Monoinfection was far more frequently observed than multi-infection. Also, the problems associated with the differentiation of streptococci are pointed out since other investigators found streptococci to be the most frequent agents producing odontogenic infections.


Alkaline phosphatase of Thiobacillus thioparus. Partial purification and properties of the enzyme. Soluble alkaline phosphatase from Thiobacillus thioparus cells was purified about 230-fold. The enzyme had a mol. wt. of 50 000 daltons, optimum pH at 10.5, and was heat-resistant in the presence of diethanolamine. Polyacrylamide-gel electrophoresis demonstrated contamination of the preparation with inactive proteins and the presence of two active bands. The enzyme activity was distinctly stimulated by increasing concentrations of Tris or diethanolamine. In the presence of glycine, 1 mM-Zn2+ enhanced the enzyme activity; in Tris or diethanolamine buffers the activity was stimulated by 1 mM-Mg2+ whereas Zn2+ had a strong inhibitory effect. Glycine at concentrations exceeding 25 mM also inhibited the enzyme. Specificity of the enzyme is fairly broad.


Purification and properties of L-asparaginase from Mycobacterium phlei. 1. L-asparaginase from M. phlei was purified about 170-fold with an 11% yield. The purification procedure consisted of: fractionation with ammonium sulphate; adsorption of contaminating proteins on calcium phosphate gel; chromatography on Sephadex G-150 and DEAE-cellulose. The specific activity of the final preparation was 32.6 i.u./mg protein. 2. Molecular weight of the enzyme as determined by Sephadex G-100 filtration amounted to 126 000. Optimum pH was 8.8-9.2. The enzyme did not hydrolyse L-glutamine over the pH range 4-9, and was inhibited by D-asparagine. The apparent Michaelis constant for L-asparagine was 0.7 mM; energy of activation, 9800 cal/mole. 3. On polyacrylamide-gel electrophoresis the final preparation revealed two protein bands, one of which was coincident with the enzyme activity.


The synthesis and properties of N6-substituted 2-amino-purine derivatives. 1. The synthesis, ultraviolet absorption spectra, and behaviour in alkali of N6-methoxy-, N6-methyl, hydroxy-, and N6-hydroxy-2-aminopurines have been described 2. N6-Methoxy-2-aminopurine riboside 5'-pyrophosphate has been prepared and used for polymerization with polynucleotide phosphorylase. 3. The copolymer containing N6-methoxy-2-aminopurine riboside and adenosine residues has been obtained; attempts to synthesize the homopolymer have not been successful. 4. All the purine analogues synthesized have been tested and shown to act mutagenically on Salmonella typhimurium TA1530.


Amnesic action of and skills related to driving after intravenous flunitrazepam. Amnesic action, skills related to driving and the ability to discriminate the fusion of flickering light were measured double-blind in 29 healthy volunteers before and after three doses of intravenous flunitrazepam. Every subject experienced amnesia for the pinching of the abdomen after being injected with flunitrazepam. Even the smallest dose of flunitrazepam (0.01 mg/kg) caused the amnesia without affecting the level of consciousness. The late effects of flunitrazepam were the most harmful to coordination. With 0.01 mg/kg eye-hand coordination was slightly impaired for as long as 6 h after the injection, and after 0.02 and 0.03 mg/kg the impairment was still significant (P less than 0.05) at the last observation period 10 h after the injection. It was concluded that, because the amnesic action of flunitrazepam is more effective than that of clinically comparable doses of diazepam, further clinical experiments with flunitrazepam are warranted. Its longer and more harmful effects on psychomotor performance than those of equipotent doses of diazepam suggest that doses of 0.02 mg/kg or more of flunitrazepam should be avoided in outpatient anaesthesia or sedation.


A comparison of the effects of the inhalation of 4% and 8% fluroxene in the pregnant primate. A comparison was made of the effects of inhalation of 4% fluroxene (n = 5) and 8% fluroxene (n = 5) in pregnant monkeys. Measurements of maternal arterial blood pressure, heart rate, cardiac output, total peripheral resistance, uterine blood flow, fetal heart rate and arterial blood pressure, and maternal and fetal blood gas levels were made. Inhalation of 4% fluroxene for 20 minutes produced little change in maternal hemodynamics and was well tolerated by the fetus. Fluroxene 8% inhaled for a similar 20-minute-period produced a significant decrease in maternal blood pressure (--27%), total peripheral resistance (--32%), and uterine blood flow (--27%) and lowered the level of maternal fetal exchange.


Reduction of psychotomimetic side effects of Ketalar (ketamine) by Rohypnol (flunitrazepam). A randomized, double-blind trial. A double-blind controlled trial based on 140 women undergoing abortus provocatus was employed to study whether the frequency of side effects after administration of the anaesthetic Ketalar (ketamine) could be reduced by a con-current dose of Rohypnol (flunitrazepam). The control group was given ketamine alone. The dosage of ketamine was 2 mg/kg body weight, supplemented if necessary by 1 mg/kg, in combination with either 2 mg flunitrazepam or placebo. No other anaesthetics were used. On several counts, the combination of ketamine and flunitrazepam was proved to reduce the adverse reactions seen with ketamine alone. Motor restlessness and confusion in the awakening state occurred with significantly less severity and frequency. Amnesia for dreams was significantly more frequent. Memory of dreams was often unpleasant after ketamine alone. The influence on pulse rate was significantly smaller and no significant changes in systolic blood pressure were seen, whereas a significant increase occurred with ketamine alone. Less pronounced fluctuations in diastolic blood pressure occurred with the combination ketamine-flunitrazepam. Respiratory rate increased significantly with both treatments, but respiratory minute volume was lower with the ketamine-flunitrazepam combination.


The experiment on the protein exposed to acoustic wave in model of hair cells. Why do animals have intense troubles mainly in the basal turns of their cochleae by exposure to sound and the ototoxity? I thought that the protein in cells had an important relation to this subject. So I performed this experiment. I made model of hair cells of silicon and poured three kinds of solutions of protein into them. And I checked the ionization of the protein and its denaturation by giving strong energy of oscillation to them like the same idea of photoelectric effect. As the result, as for the protein liquid, I noticed the increase of volts just after it was exposed to sound and about 3 hours later, I observed the figure decreased gradually. From this phenomenon, I presumed that the protein in sensory cells became a factor of the stimulation by receiving strong energy conversely. Low-percent protein liquid had less effect caused by sound.


Effects of metoprolol in angina pectoris. A subacute study with exercise tests and a long-term tolerability study. Eighteen patients with angina pectoris, who had previously participated in a cross-over study with 20 mg metoprolol t.i.d. and placebo, have been included in this study. During an introductory six-month open tolerability study, all patients were treated with 50 mg metoprolol t.i.d. and during a subsequent cross-over study, the efficacy of this dose was compared with that of placebo under double-blind conditions. An exercise was performed at the end of each cross-over period. Metoprolol, in a dose of 50 mg t.i.d., gave a significant improvement compared with placebo in respect of the number of anginal attacks, nitroglycerin consumption and daily subjective assessment of the patients' anginal symptoms. Metoprolol also gave a significant increase in exercise capacity, both until the appearance of 1 mm ST segment depression and until the end of exercise. Heart rate and blood pressure were reduced both at rest and during exercise. No severe unwanted effects were observed during this study ranging over eight months, and none of the patients had any signs or symptoms of cardiac failure or pulmonary dysfunction on any occasion. Unwanted effects reported were mild to moderate, and the frequency was the same as during placebo treatment. No abnormal laboratory findings were observed and the relative heart volume was not significantly changed. Administration of 50 mg metoprolol t.i.d. seems to be of greater benefit than 20 mg metoprolol t.i.d., previously investigated in these patients.


Effect of sugars, hydrogen ion concentration and ammonium nitrate on the formation of citric acid by Aspergillus niger. Aspergillus niger Mulder strain when grown on a synthetic medium containing urea as the sole source of nitrogen at pH 5.2, formed a mixture of citric and gluconic acids. On growing the organism at pH 2.0 the gluconic acid content was reduced but citric acid yield remained low. Addition of NH4NO3 to the medium lowered the gluconic acid yields to undetectable levels with a simultaneous increase in the citric acid content. Of the sugars used for the production of citric acid, sucrose in an unautoclaved medium was found to be the best carbon source. Sucrose medium if autoclaved at pH 2.0, or a mixture of glucose and fructose instead of sucrose gave lower yields of citric acid. Under optimum conditions only citric acid was produced and the yield was 66-68 per litre after a growth period of about 10 days.


Arylsulfatases A and B in metachromatic leukodystrophy and Maroteaux-Lamy syndrome: studies with 4-methylumelliferyl sulfate. Metachromatic leukodystrophy and Maroteaux-Lamy syndrome can be diagnosed by assay of leukocyte or fibroblast arylsulfatase A and B activity with the fluorogenic substrate 4-methylumbelliferyl sulfate. The arylsulfatases are extracted into a 27000 x g supernatant by sonication in 0.9% sodium chloride and then separated with CM-32 on columns or in test tubes. In 0.05 M sodium acetate pH 6.0, arylsulfatase A is not absorbed while arylsulfatase B is retained by the resin. The arylsulfatase B is then eluted from the resin with 0.3 M sodium chloride. The arylsulfatase A activity obtained from normal leukocytes and fibroblasts is linear for the initial 10 minutes of the reaction, is stimulated 3-fold by 6 mM lead acetate and inhibited 80% by 0.24 mM silver nitrate. After separation with CM-32, the arylsulfatase B activity is stimulated 3-fold by Triton X-100 (0.1%). Arylsulfatase A but not arylsulfatase B is destroyed by heat (60 degrees). Both leukocyte and fibroblast arylsulfatase A activity was reduced to 11% of control values in metachromatic leukodystrophy. Essentially no arylsulfatase B activity was detected in cells from patients with Maroteaux-Lamy syndrome. Metachromatic leukodystrophy heterozygotes but not Maroteaux-Lamy syndrome heterozygotes can also be distinguished by this method. A heat inactivation technique utilizing the differential thermal stabilities of the two enzymes for diagnosis of patients with Marotezux-Lamy syndrome is also described. The advantages of these 4-methylumbelliferyl sulfate assay procedures over the p-nitrocatechol sulfate method of assay are greater sensitivity, selectivity for the desired enzyme and potential for use in large scale testing.


Identification of Tay-Sachs by hexosaminidase analysis of urine and tear samples. 1. Two readily obtainable biological fluids, i.e., urine and tears, were investigated as possible substitutes for serum and leukocytes for the detection of Tay-Sachs disease (TSD) heterozygotes based on Quantitative hexosaminidase A (Hex A) determinations. 2. Hexosaminidase isoenzyme patterns were determined, by means of an automated DEAE-cellulose microcolumn procedure, for serum, urine and tear samples from normals, TSD carriers, normal pregnancies, carrier-pregnancies and TSD children. 3. Normal pregnancy and TSD carrier sera gave almost identical hexosaminidase patterns with multiple intermediate peaks. Whereas, urine and tear samples from normal pregnant women showed hexosaminidase isoenzyme patterns resembling those of normal controls. These results suggested that use of these fluids might eliminate the effect of pregnancy of the Hex A ratio which occurs when serum is used as the test fluid. In addition these fluids are most economical and simpler to obtain than a blood sample. 4. About 200 urine samples, from the various categories listed above, were analyzed for Hex A with both the heat denaturation and pH inactivation methods and the results compared with serum and leukocyte levels from many of the same individuals. With either method, the wide overlap between the urinary Hex A normal and heterozygote ranges would require retesting with leukocytes of about 30% of the subjects. These results would preclude the use of urines as a suitable fluid for the mass screening of the Ashkenazic Jewish population for TSD heterozygotes.


[Contribution to the knowledge of Swiss piroplasmas]. The authors identify 3 species of Babesia, which parasitize cattle in Switzerland (Babesia major, B. divergens and B. hovis). They also confirm the presence of B. canis in a dog in the proximity of Geneva. Finally, for the first time in Switzerland, they point out the presence of non-identified Babesia in various rodents (Apodemus sylvaticus, A. flavicollis and Clethrionomys glareolus).


[Apropos of the asexual multiplication of the tetrathyridia larva of Mesocestoides corti Hoeppli, 1925 (Cestoda: cyclophyllidea). (Prelimary note )]. In Tetrathyridia of Mesocestoides corti exist large basophilic cells which are often seen in various stages of mitosis. From their distribution in larvae and from their capacity to form the regeneration blastema after experimental amputation of 2 suckers, it is supposed that these cells are very important for regeneration.


[The biological cycle of Caryophyllaeus brachycollis Janiszweska, 1953 (Cestoda carophyllaeidae) a parasite of Barbus meridionalis Risso, 1826 in the south of France]. Caryophyllaeus brachycollis Janiszweska, 1953 has been found for the first time in France in Barbus meridionalis Risso, 1926. Experimentally, the procercoid develops in Tubifex sp. and never in Limnodrilus sp. The different possibilities of life cycle of C. brachycollis in Europe have been compared.


[Rats and bilharziasis in Guadeloupe].

[Rats and bilharziasis in Guadeloupe]. The rats in Guadeloupe (Rattus rattus and Rattus norvegicus) may play a  part in schistosomiasis in three ways: - by harbouring fertile S. mansoni, a fact which serves to increase the total population of the parasite and may eventually take part in the infestation of man; - by harbouring a great number of Ribeiroia marini, a trematode whose larval stages sterilize Biomphalaria glabrata, the vector of schistosomiasis; - simply by eating B. glabrata. The quantitative influence of these contradictory roles played by the rats upon schistosomiasis in Guadeloupe has yet to be studied.


[The chronobiology of the cercaria of Ribeiroia marini (Faust and Hoffman, 1934) parasite of Biomphalaria glabrata: effect of the photoperiod on the rhythm of emergence]. Ribeiroir marini cercariage emerge from the snail-host during the night, according to a circadian rhythm. The photoperiod is the synchronizer of this rhythm. Inversion of the photoperiod is immediately followed by inversion of the periodicity of emergence. No cercaria emerge in continuous light conditions. This inhibitory effect of light exerts its influence on the emergence but not on the production of cercariae. The rhythmic emergence is almost maintained in continous dark, but darkness cannot induce emergence at any time. It is possible that an innate production rhythm interferes with the emergence rhythm.


[Contribution to the study of Microphallidae Travassos 1920 (trematoda). XXXII. Microphallus breviatus n. sp., a species with an abbreviated evolutive cycle from a Mediterranean pond in the Languedoc]. Contribution to the study of Microphallidae Travassos, 1920 (Trematoda). XXXII. - Microphallus breviatus n. sp., a short life-cycle species of a mediterranean pond of Languedoc. The whole larval life-cycle of M. breviatus takes place in one host, Hydrobia ventrosa (Montagu), Mollusc Hydrobiidae. Hepato-pancreatic sporocysts produce morphologically altered xiphidio-cercariae which become encysted metacercariae in the sporocyts themselves. This species is defined in the genus by the anatomic characteristics of its cercariae and metacercariae, allied with its uncommon biology including two hosts only.


[Evolutive cycle of Paratimonia gobii, Prevot and Bartoli 1967 (trematoda-monorchiidea)]. The cycle of Paratimonia gobii PREVOT & BARTOLLI, 1967 (Trematoda-Monorchiidae), a parasite of Pomatoschistus microps (Teleostei gobiidae), has been discovered and carried out experimentally. The mollusc, first intermediary host,  is Abra ovata (Lamellibranchiata, Scrobiculariidae). The gymnocephalous cercaria leaves the mollusc, then sucked in by the respiratory stream, becomes encysted in the inhaling siphon of another Abra. The accumulation of metacercaria results in the autonomy of this siphon and it is this cut-off organ which is becoming part of the alimentary chain of the final host allows the continuation of the cycle.


[A new nematode (allantonematidae) parasite of Heliophilus (T diptera, syrphidae)]. For the second time, the authors have found a new entomophagous nematode parasitic in Syrphidae. The first species, which was described as Syrphonematidae nov. fam., is living in the duct of various aphidophagous species of Syrphidae. This one has been found in the hemocoel of adults of Helophilus trivittatus Fabricius and H. pendulus Linneaus (Eristalinae with aquatic rat tailed larvae). It seems to belong to the genus Iotonchium (Allantonematidae), which was known as yet only by the free-living stages. This work could bring the proof that the genus Iotonchium is really parasite of insect as it was supposed by T. GOODEY and J. B. GOODEY. The three distinct forms which are living in the body cavity of the host are briefly described. The life cycle, which differs from those of all other Allantonematidae, is discussed. This species requires further studies, especially on the free-living stages which have to be obtained for the comparative study of the morphology of the various forms and for life history.


[Vegetation analysis used for the detection of exophile tick populations in the south-east of France: the example Ixodes ricinus (Linne 1758) (acarina, ixodoidea)]. The cross-linking relation between the evidence of outside living tick populations and specific vegetation units allows for efficiently using the vegetation maps, and more especially the medium scale maps. Ixodes ricinus is referred to here as an example. The limitations of this data derived from such maps are evaluated by the authors. They suggest some means aiding in improving their efficiency through the knowledge of the ecological variables playing a role in the species settlement.


[An abnormally formed Ctenophthalmus assimilis assimilis (siphonapteres hystrichosyllidae)]. A female flea is described the body of which is abnormally formed and compressed. It is characterized by a split along its back, raised up abdominal segments and by a shortening of its head. These anomalies might be explained by longitudinal compression of the body during pupation. The possibility of a mutation is not excluded.


Advantages of x-ray microanalysis in the field of medical mycology. A new apparatus, which combines an electron microprobe and a scanning electron microscope, has been used. This apparatus enabled to conduct a systematic elemental analysis of two species among Aspergillaceae. All elements in the periodic table whose atomic numbers lie between boron and uranium can be detected.


[Hepatic amebiasis in the Kilimanjaro region. Serodiagnosis on micro-specimens of dried blood and attempts at treatment with tinidazole (fasigyn)]. Amoebic dysentery appears to be rare in the northeast of Tanzania. Hepatic amoebiasis, on the other hand, is apparently widespread since at least 200 cases are seen every year at the Kilimanjaro Christian Medical Centre. This incidence of cases enabled us to carry out trials on the spot with a new imidazole derivative, Tinidazole. Formerly the difficult diagnosis based on clinical symptoms had to be buttressed by radiological evidence and possibly by the result of puncture. Indirect fluorescent antibody tests for the diagnosis of amoebiasis were performed elsewhere on all the patients, using for this purpose microspecimens of dried blood. In 12 cases out of 34 an agglutination test with sensitized latex particles was performed on the spot. This latter test has the practical advantage of being easy to employ. It cannot, however, be considered as a screening test since it is subject to downward and upward errors. The indirect fluorescent antibody test has been found to be constantly and highly positive, certain antibody titres attaining 1/6400. This fully confirms the value of the method even under special working conditions. Seventeen of our 34 patients (2 women and 15 men ranging in age from 20 to 75 years) were treated with 2 g of Tinidazole per day in a single dose for 2 to 3 consecutive days. Puncture to evacuate pus was also performed where abscesses had collected. Tolerance on the whole was good without a single sign of cardiovascular or urinary toxicity. However, paraesthesia of the hands was observed in one case, transitory thrombocytopenia in one other patient, and increased alkaline phosphatases. Minor disorders were also observed in our series of patients: mild vertigo (7 cases), headache (6 cases), and dry mouth (2 cases). After 8 months the therapeutic results were as follows: 12 complete cures out of 17, 2 improvements with final cure probable, 3 partial failures necessitating supplementary treatment with Metronidazole (2.4 g per day for 2 days). These preliminary trials appear to the encouraging and the study is being continued with series compared with cases treated with Emetine or Metronidazole.


[Epidemic of autochthonous hepatic and intestinal amebiasis in a place near Grenoble]. We had the opportunity of studying an epidemic of autochthonous amoebiasis occurring in the autumn of 1974 in a small town of 4000 inhabitants 30 km from Grenoble. Attention was originally attracted by the occurrence in this town of two cases of hepatic amoebiasis and one of intestinal amoebiasis identified by rectoscopy. Systematic investigations (coproctic examinations and serological tests for amoebiasis by indirect antibody fluorescence) were then carried out on everyone in the locality with digestive disorders which were possibly referable to amoebiasis, and on the other members of their families. A total number of 148 coproctic examinations were made and in two cases revealed the presence of vegetative forms of Entamoeba histolytica. In both cases the infestation provoked few symptoms (asthenia, vague abdominal discomfort, intermittent and apparently banal diarrhoea). On the other hand 20 out of 94 serological tests revealed positive results, 14 of which were equal to or greater than a titre of 1/100, a level at which all risks of non-specificity are virtually ruled out under our experimental conditions. Material reasons made it impossible to subject these cases to repeated faecal checks, but in two of them at least the rectoscopic appearances were very suggestive of subacute intestinal amoebiasis. Moreover, amoebic disease appears to be well confirmed by the results obtained among the patients as a whole by treatment with Metroinidazole. A variety of hypotheses on the origin of this epidemic have been put forward and then abandoned (market garden produce, receipt by certain families of exotic frut from overseas). In actual fact water seems to be the point of departure, for, although specimens of water taken at 7 different levels in the water supply system failed to reveal the presence of a single amoeba, bacteriological analyses during autumn 1974 showed signs of faecal contamination. The locality, which is situated at the foot of the Chartreuse massif, receives its water solely from springs but there is a holiday camp for the staff of an international airline situated above the main water catchment.


[Leishmaniasis in south-eastern France- -ecology, epidemiology, prophylaxis]. A study of the ecology, epidemiology and prophylaxis of Leishmaniasis in the southeast of France is reported; different methods of the survey are recorded. Between 1965 and 1975, 972 cases of canine Leishmaniasis and from 1968 to 1975 89 cases of visceral human Leishmaniasis and only 3 cases of oriental sore were observed in the "Bouches du Rhône", "Var" and "Vaucluse" Departments. The strains isolated from canine and human visceral Leishmaniasis had a malate dehydrogenase XI whereas Leishmania tropica had a MDH I; no wild animals have been found with Leishmaniasis.  The suburbs of the towns, the hills in the center of Marseilles or surrounding Toulon as well as the villages are the principal foci of Phlebotomus perniciousus (96%) as the vector. The biotopes are isolated houses with little gardens surrounded by dry-stone walls exhibiting holes named "barbacanes", with chalky soil and xerophytes. The killing of infected dogs is the best protection of men whereas keeping dogs in sandfly-proof kennels from twilight until one hour after sunrise is best in order to protect this animal. This is quite different from the observations made by RIOUX in the Cevennes.


[Presence of Angiostrongylus cantonensis at la Réunion]. The eosinophilic meningitis due to Angiostrongylus cantonensis is well known on Madagascar and on Mauritius Island, but was never described on Reunion Island. Two cases have been lately oberved in Doctor Jay's department at Gabriel Martin's hospital. Local achatines were dissected and contained larvae which, when absorbed by rats, were found in there brains ten days later. These larvae belong certainly to Angiostrongylus genus, but the species has not yet been found with certitude. Lately infested rats are passing through the normal laps of time for adult maturation until they will be sacrified for further examinations.


Mucocutaneous lymph node syndrome with coronary artery aneurysm. A white North American girl with clinical features of the mucocutaneous lymph node syndrome had a myocardial infarct and angiographic evidence of a coronary artery aneurysm and mitral regurgitation. The mucocutaneous lymph node syndrome has been extensively diagnosed in Japan in recent years. It appears to be a distinct entity, although not precisely separated from polyarteritis nodosa in childhood. The condition may be more common than previously realized.


Mucocutaneous lymph node syndrome in the United States. Sixteen patients with an unusual and distinct symptom complex were encountered during a four-year period. Principal features of this syndrome are (1) fever lasting more than seven days; (2) conjunctival injection; (3) changes in the mouth consisting of erythema of the oropharynx, "strawberry tongue", and erythema of the lips; (4) indurative edema of hands and feet with palm and sole erythema followed by desquamation of the fingertips; and (5) an erythematous rash. Associated features were lymphadenopathy, pyuria, aseptic meningitis, diarrhea, arthritis, and arthralgia. Although usually a self-limited illness, one patient died with massive coronary artery thrombosis on the 19th day of illness. This syndrome appears to be clinically and pathologically similar to mucocutaneous lymph node syndrome, an illness prevalent in Japan but previously unrecognized by American clinicians. Pathologic features suggest a relationship to infantile periarteritis nodosa.


Inhibition of nocturnal acid secretion in duodenal ulcer patients by an H-2 histamine antagonist-cimetidine. A controlled double-blind investigation. A new H-2-receptor antagonist, cimetidine, was tested as to its ability to suppress overnight gastric acid secretion in 8 male duodenal ulcer patients. In a double-blind controlled investigation, each volunteer was studied during four consecutive nights. In randomized order they received either 100, 200, or 300 mg of cimetidine or a placebo. No untoward clinical orlaboratory effects of the drug were found. Single-dose oral administration of 300 mg cimetidine caused a significant (P less than 0.05) inhibition of overnight gastric acid secretion for an 8-hr period, with the intragastric pH staying between 3.5-6.0. Cimetidine, because of its potent gastric acid inhibitory effect, may become an important therapeutic agent in the management of peptic ulcer disease.


Treatment of chronic radiation enteritis and colitis with salicylazosulfapyridine and systemic corticosteroids. A pilot study. Four patients with severe chronic radiation enteritis and/or colitis were treated with anti-inflammatory drugs that are used conventionally in the treatment of idiopathic inflammatory bowel disease. Salicylazosulfapyridine (SASP) was used in the treatment of all four patients, while one patient received oral prednisone together with SASP. All four patients were treated and observed for over one year, with follow-up observations now extending to over three years. The four patients showed striking clinical improvement, accompanied by improvement in the radiographic appearance of affected bowel, complete or almost complete in three and incomplete in the fourth patient. The results of this pilot investigation are encouraging and call for wider clinical trials of the same  and related drugs in larger groups of patients with chronic radiation enterocolitis, a serious condition that has until now not been successfully treated with drugs.


Elevated serum gamma-glutamyl-transferase (transpeptidase) and histological liver damage in alcoholism. In 66 alcoholic patients, serum gamma-glutamyl-transferase (transpeptidase) (GGTP) activity was studied in relationship to other biochemical liver function tests and histological liver damage. Elevated serum GGTP activity was the single most common biochemical abnormality (74%) and, when present was accompanied by histological abnormalities in all but one case. In seven patients, including two with alcoholic cirrhosis, this was the only biochemical abnormality. The mean serum GGTP was highest in the cirrhotic group. There was some correlation between serum GGTP activity and the degree of histological hepato-cellular necrosis. The values showed a wide scatter, however, and 12 patients had normal serum GGTP activity when histological damage was present. While elevated serum GGTP levels in alcoholism may be partly related to structural liver damage, other mechanisms, such as hepatic microsomal enzyme induction or alcoholic pancreatic damage, may also play a role.


Search for epizootic-like Venezuelan encephalitis virus at enzootic habitats in Guatemala during 1969-1971. Seventy-four strains of Venezuelan encephalitis (VE) virus recovered from sentinel hamsters or mosquitoes at enzootic habitats in Guatemala in the two years following the 1969 epidemic-equine epizootic were examined for ability to produce small plaques in Vero African green monkey kidney cell cultures, like isolates obtained during the epizootic. (a) One strain recovered from a sentinel hamster in late October 1969 at an enzootic habitat near the epicenter of the hemagglutination-inhibition (HI) and equine-virulence properties like epizootic virus; this strain retained its small plaque characteristic after inoculation and recovery from bloods of three horses. (b) None of the other 73 strains produced uniformly small plaques, but 31 formed a few small plaques among large ones. Virions from small plaques of five strains were cloned twice in Vero cell cultures. Four clones produced uniformly small plaques after one more passage in Vero cells; three had hemagglutination-pH properties compatible with epizootic virus or intermediate between epizootic and enzootic virus, but HI tests with these three hemagglutinins or with antibody to the fourth cloned strain showed them to be like Central American enzootic virus. One of three cloned strains tested in horses produced encephalitis and death in one of four horses; another strain produced encephalitis with recovery in one of two horses. (c) Thus these small Vero plaque clones resembled Central American enzootic strains of VE virus in HI and equine-virulence tests, and the small Vero plaque characteristic was not a satisfactory marker for consistently isolating equine-virulent, epizootic VE virions. Nevertheless, this technic led to recognition of one epizootic strain isolated at an enzootic habitat in Guatemala at the end of 1969 outbreak. Whether this strain was there before the outbreak or subsequently penetrated the habitat is uncertain. During the next two years, this strain did not become dominant in that enzootic focus.


Search for persistent epizootic Venezuelan encephalitis virus in Guatemala, El Salvador and Nicaragua during 1970-1975. Evidence was sought during 1970-1975 of persistence of equine-virulent Venezuelan encephalitis (VE) virus in regions of Central America that were heavily involved in the epidemic-equine epizootic of 1969. (a) Four sentinel horses were exposed in an arid, upland region of the Atlantic drainage of Guatemala during August-October 1970, but no horse became infected. (b) The epicenter region of the 1969 outbreak, in southwestern Guatemala and southwestern El Salvador, was studied during July 1970-February 1974; no antibody developed in sentinel horses, sentinel hamsters did not die, mosquitoes yielded no virus, wild rats had no detectable VE virus HI antibody. Unexplained decreases in populations of wild terrestrial mammals possibly limited maintenance of VE virus. However, mosquitoes were plentiful and present in the same species composition found at a focus of enzootic VE virus about 35 km northwest of the epicenter region. (c) In studies at two Guatemalan ranches near the epicenter, where horses died in 1969, VE viruse infected sentinel horses along one of three lakes on one ranch during the wet season of 1972 but not during the dry or wet seasons of 1973; the titers of neutralizing antibodies in these four horses were higher against an enzootic strain of VE virus than against an epizootic strain. During 1970 and 1971, VE virus was isolated from sentinel hamsters exposed at a marsh on the other ranch, but Vero plaque characteristics were those of enzootic VE virus. (d) The only epizootic activity of VE virus discovered in Central America in 1970-1975 occurred in Nicaragua between April and June 1972. Several hundred horses died, and N antibody, like that engendered by epizootic virus, was found in two young, unvaccinated horses. Whether this represented persistence of epizootic VE virus or reintroduction of virus is unknown.


A decrease in cell-mediated immunity in uremia associated with an increase in activity of suppressor cells. The graft-versus-host (GVH) reactivity of uremic and control spleen cells was studied by popliteal lymph node assay in the rat. The reaction evoked by cells from animals with severe uremia was conspicuously weaker than that evoked by control cells. The magnitude of the GVH reaction induced by control cells was directly proportional to dose, while with the uremic cells the same increases in dose led only to insignificant increases in the strength of the GVH reaction. When mixtures of syngeneic control and uremic cells were used, the GVH reactivity of the control cells was suppressed. The activity of uremic spleen cells can be enhanced (restored) by removal of the sub-population of cells adherent to glass wool. The GVH reaction induced by uremic cells so treated became directly proportional to dose. The removal of the adherent cell population from the uremic spleen cell suspension also led to the disappearance of the suppressor effect in mixtures of control and uremic cells. These results indicate that a decrease in GVH activity of rat uremic spleen cells is due to an increase in suppressor cell activity in the uremic spleen cell population.


Coronary vascular sympathetic beta-receptor innervation. Recent studies indicate that coronary vessels have alpha- and beta-2-adrenergic receptors and that the alpha receptors are functionally innervated. We studied whether the beta-2-vasodilator receptors are functionally innervated, using a dog in situ modified Langendorff preparation with constant coronary perfusion pressure. The beating, nonworking heart and systemic circulation were supported with a pump oxygenator. Stimulation of the left stellate ganglion increased coronary blood flow and decreased coronary sinus oxygen tension from prestimulation control values. After beta-1-receptor blockade (practolol, 10 mg/kg), stellate stimulation decreased coronary blood flow and decreased coronary sinus oxygen tension from prestimulation control values, revealing alpha-receptor vasoconstriction. After the addition of alpha-receptor blockade (Dibozane, 5 mg/kg), stellate stimulation increased coronary blood flow and coronary sinus oxygen tension a small amount from prestimulation values. Finally, after the addition of beta-2-receptor blockade (propranolol, 2 mg/kg), stellate stimulation increased flow and coronary sinus oxygen tension slightly from prestimulation control values. Direct intracoronary injections of isoproterenol, norepinephrine, and epinephrine gave results consistent with the presence of beta-1 myocardial receptors and alpha and beta-2 coronary receptors. We conclude that there is little functional innervation of coronary vascular beta-2 receptors. Intracoronary injections of isoproterenol and epinephrine activated beta-2-receptor coronary vasodilation after beta-1-receptor blockade, but norepinephrine did not.


Uric acid excretion by the pig kidney.

Uric acid excretion by the pig kidney. The handling of uric acid by the pig kidney has been investigated during continuous urate infusion in unrestrained, unanesthetized animals. Urate-to-inulin clearance rates in excess of 1 were found under all experimental conditions, demonstrating only net secretion by the pig kidney. The demonstration of a secretory maximum was precluded owing to a progressive reduction in the GFR associated with high rates of urate infusion. Urate clearance was independent of urine flow rate up to 10 ml/min. The administration of probenecid inhibited urate secretion, but urate-to-inulin clearance ratios below unity were not observed. Pyrazinamide or pyrazinoic acid, at doses which either inhibited secretion or promoted uricosuria in other species, did not alter urate excretion in the pig. Probenecid together with pyrazinamide exerted the same inhibitory effect on urate secretion as probenecid alone. Pyrazinoic acid was reabsorbed at all infusion rates. It is concluded that the pig kidney eliminates uric acid by filtration and secretion only.


Heart rate and rhythm and intracranial pressure. Cardiac slowing during elevated intracranial pressure (ICP) could be due to direct activation of central nervous system (CNS) centers or it may be secondary to baroreceptor reflexes activated by the associated pressor response. In five pentobarbital-anesthetized dogs when ICP was raised to 50 mmHg the heart rate decreased 34.4 beats/min (+/-4.8 SE). This cardiac slowing occurred when ICP was elevated after sinoaortic denervation (-24 +/- 4.43 beats/min) and also during elevated ICP when changes in arterial pressure were prevented (-32.3 +/- 4.25 beats/min). These results indicate that the cardiac slowing is largely of CNS origin. In dogs given morphine with pentobarbital to achieve slower heart rates, raising ICP to 50 mmHg by left-sided intracranial balloon inflation led to cardiac dysrhythmias in 9 of 12 dogs. By contrast, raising ICP to 50 mmHg by right-sided intracranial balloon inflation only produced progressive sinus bradycardia. These responses were related to a combined enhancement of vagal and sympathetic activity. Differences observed between right- and left-sides balloon inflation may be partly related to asymmetrical engagement of the cardiac autonomic nerves. The results suggest that left-sided intracranial lesions are more likely to produce cardiac dysrhythmias.


Effects of hypoxia and Freon 12 on mechanics of cardiac contraction. Data are presented which indicate that the mechanism of tension depression and subsequent recovery from dichlorodifluoromethane (Freon 12), an aerosol gas recently described as a potent cardiac depressant agent, differs from that of hypoxia. To analyze these differences, 22 rat papillary muscles, contracting isometrically in a myograph, were studied during and subsequent to 15-min interventions of of hypoxia. Freon 12 with adequate oxygenation, or Freon 12 combined with hypoxia. During each of the three interventions the developed force (F) was markedly depressed, while peak shortening velocity (Vpm) was selectively more depressed by Freon and Freon combined with hypoxia than by hypoxia alone. While hypoxia shortened the time to peak force (TTP) and one-half relaxation time (RT1/2) markedly, Freon 12 with adequate oxygenation slightly shortened RT1/2 (P is less than 0.001) but failed to shorten TTP significantly. In contrast, Freon 12 administered during hypoxia shortened TTP and RT1/2 significantly (P is less than 0.001), more than did hypoxia or Freon 12 alone. Posthypoxic prolongation of TTP and RT1/2 was not seen during recovery from Freon 12. This prolongation was depressed during recovery from Freon 12 given either during hypoxia or during recovery from hypoxia. The results indicate that Freon 12 and hypoxia act synergically, although the mechanisms through which they mediate their actions on myocardial tissue are not identical.


Management of interpersonal issues in systematic desensitization. The authors use the management of typical clinical problems that arise during systematic desensitization as a model for the analysis and solution of problems associated with behavior therapy techniques. Three main problem areas are considered: initiation of the technique, therapist and patient difficulties, and therapeutic decision making. The discussion is designed primarily to help therapists with varied backgrounds to deal with clinical issues that arise in the application of behavior therapy techniques such as systematic desensitization.


Reduced high-energy phosphate levels in rat hearts. I. Effects of alloxan diabetes. Significant alterations in heart carbohydrate and lipid metabolism are present 48 h after intravenous injection of alloxan (60 mg/kg) in rats. It has been suggested that uncoupling of oxidative phosphorylation occurs in the alloxanized rat heart in vivo, whereas normal oxidative metabolism has been demonstrated in alloxan-diabetic rat hearts perfused in vitro under conditions of adequate oxygen delivery. We examined the hypothesis that high-energy phosphate metabolism might be adversely affected in the alloxan-diabetic rat heart in vivo. Phosphocreatine and ATP were reduced by 58 and 45%, respectively (P is less than 0.001). Also, oxygen-dissociation curves were shifted to the left by 4 mmHg, and the rate of oxygen release from blood was reduced by 21% (P is less than 0.01). Insulin administration normalized heart high-energy phosphate compounds. ATP production was accelerated in diabetic hearts perfused in vitro with a well-oxygenated buffer. These studies support the hypothesis that oxidative ATP production in the alloxan-diabetic rat heart is reduced and suggest that decreased oxygen delivery may have a regulatory role in the oxidative metabolism of the diabetic rat heart.


Arbovirus surveillance in six states during 1972. A virus surveillance project was established and maintained during 1972 along 10 major river drainages in six states. Mosquitoes, biting flies, and blood specimens from sentinel equines were collected during 83 field trip visits to 141 arthropod collecting sites and 22 sentinel locations from April into December 1972. There were 173,074 mosquitoes tested and 303 arboviruses isolated from 11 of 41 species. From 13,388 biting flies tested, 8 arbovirus isolations were obtained in 1 of 5 species. There was no isolation of Venezuelan equine encephalitis (VEE) virus. Western equine encephalitis (WEE) virus isolates were the most numerous and were followed by Turlock, St. Louis encephalitis, Hart Park, California encephalitis, and Bunyamwera (BUN) group viruses. The first isolation of WEE from the mosquito Cullex (Mel). erraticus is reported, as is the extension of the ranges for Buttonwillow virus from California to New Mexico and Texas. Also a single isolation of the BUN group from Culicoides variipennis extends the range of this virus-vector relationship from California to Texas. New distribution records for mosquito species previously unreported for Arizona, Louisana, New Mexico, and Oklahoma are reported. The sentinel burros detected WEE serologic conversions at two sites in New Mexico and at one in Texas. The surveillance project provided state and federal officials with current information on the status of arbovirus activity, including the absence of VEE activity during 1972, and it demonstrated the existence of the potential for WEE epizootics and epidemics throughout a wide geographic area of the Western United States.


A note on the use of trypsinized human group O erythrocytes in arbovirus titrations. Twenty-two different arbovirus antigens derived from five antigenic groups were examined for their ability to agglutinate normal and trypsinized human group O erythrocytes. Trypsinization rendered the cells susceptible to agglutination by 18 viruses,chiefly in the pH 5.85 to 6.2 range, yielding hemagglutinin titers comparable with those obtained with gander cells at their optimal pH.


Respiratory effects of 'lissive" anaesthesia using gallamine. 'Lissive anaesthesia', the administration of a small dose of a non-depolarising muscle relaxant to a patient breathing nitrous oxide, oxygen and an anaesthetic vapour, is a technique popularly employed for minor procedures. In this study, the effects of intravenous gallamine triethiodide (40 mg) on the blood-gas status of 20 patients under general anaesthesia with oxygen, nitrous oxide and halothane after pethidine and atropine premedication, were assessed. The results are compared with those obtained from a control group of 10 patients anaesthetised in an identical manner, but omitting the muscle relaxant drug. All patients in both the relaxant and control groups in this study developed respiratory acidaemia. The rise in mean arterial carbon dioxide tension was, however, greater after injection of gallamine. Significant hypoxia or metabolic acidaemia was not encountered, except in one grossly obese patient in the gallamine group. The implications of these findings are discussed.


Anaesthetic induction for Caesarean section with propanidid. Propanidid was used for the induction of anaesthesia at Caesarean section in 50 healthy mothers. All parturients were considered to have normal placental function. Anaesthesia was maintained with nitrous oxide, oxygen, muscle relaxant and controlled ventilation. The patients were tilted laterally with a 15 degrees rubber wedge during the procedure in order to obviate the effects of aorta-caval occlusion. At the time of delivery, arterial blood was drawn from the mother and from the vessels of a double clamped section of umbilical cord, for blood-gas analysis. The results obtained are compared with those previously reported in a similar series anaesthetised with thiopentone, gas, oxygen and relaxant. Maternal blood-gas and acid-base levels were similar in the two groups at delivery. The clinical status of the infants in the present series, as judged by the modified Apgar score at 2 minutes after birth, was satisfactory. Umbilical venous and arterial pH values after propanidid were both 0-054 units (P less than 0-001) less than those following thiopentone; and average base deficits were 3-1 (Uv) and 3-9 (Ua) mEq/litre greater after propanidid (P less than 0-001). Mean oxygen levels in the umbilical cord bloods were 8-0 (Uv) and 3-5 (Ua) mmHg lower (P less than 0-001 & P less than 0-025 respectively) in the propanidid group. Derived oxygen contents was also significantly less than in the previous thiopentone series. (Ma-Uv) and (Ma-Ua) gradients were 0-053 and 0-051 pH units higher after propanidid than that following thiopentone (P less than 0-001). Mean (Ma-Uv) and (Ma-Ua) base deficits were 3-5 and 3-9 mEq/litre greater (P less than 0-001). Five patients offered definite evidence of factual recall, of whom three experienced pain. Propanidid, therefore, appeared to be associated with a greater degree of foetal acidaemia than did thiopentone. In addition, painful factual recall during surgery was encountered in 6 percent of cases. It is concluded that propanidid, although theoretically offering advantages over thiopentone to the obstetric anaesthetist, in practice, did not fulfil this promise.


The use of AH8165 for Caesarian section. The use of AH8165, a new non-depolarising relaxant, for Caesarian section is reported. The rapidity of action and the absence of significant placental transfer of the drug were confirmed. AH8165 has a definite place in obstetric anaesthesia.


Cerebral arterio-venous oxygen difference: a bedside test for cerebral death. A bedside test is described which compares the patients cerebral arterio-venous oxygen difference with a predicted norm at various levels of arterial CO2 tension. In patients in coma depasse this difference is reduced and is unresponsive to variations in arterial carbon dioxide tension. The test also confirms lack of respiratory efforts in the presence of adequate carbon dioxide tension.


Flunitrazepam, a new benzodiazepine compound in general anaesthesia. Clinical and statistical considerations on the first thousand cases. Flunitrazepam, a derivative of benzodiazepine was used for induction and maintenance of anaesthesia in 933 patients. The induction dose was from 1,786 to 2,053 mg. The total dose of 2-2.66 mg was sufficient for maintenance of hypnosis for about 2 hours. The undesirable side effects were very rare. The average time of hypnosis after a single dose of flunitrazepam was 50.1 sec. The sedative action of the drug lasted for some time after regaining of consciousness. In most patients there was no need for administration of analgetics during first 24 hours after the operation. The authors believe that surgical anaesthesia will greatly benefit from this drug.


[Constant outflow anesthesia with the combination of alfatesine and fentanyl]. In a previous work, the authors showed the value of administering Alfatesine, in interventions of long duration, at a constant rate by using an automatic syringe, and by combining it with destromoramide. In this new work the authors present an analagous study carried out in 47 subjects, in which dextromoramide was replaced by fentanyl. The automatic syringe used was the Braun Perfusor IV equipped with a 50 ml syringe containing 0.3 ml. of CT 13.41 and 0.006 mg. of fentanyl per ml. Induction was achieved at graduation 10, 14 ml of the mixture having been injected in approximately 60 seconds. Maintenance of anesthesia was ensured at graduation 6 corresponding to an hourly administration of 27 to 30 ml of the mixture (9 ml of CT 13.41 and 0.18 mg of fentanyl). The patients were adults of average weight 64 kg., who had undergone sometimes major orthopedic surgery, of an average duration of 161 mn. The results are looked at from the angle of quality of the anesthesia and of the awakening and of the side effects. They confirm the non-accumulation under these conditions of use and these doses of CT 13.41 used and reveals an analagous behaviour of fentanyl. Reserves are however made owing to the mode of elimination of fentanyl, on the use of such a technique in anuric patients or in renal insufficiency.


[Combination of R3365 (piritramide) and dehydrobenzperidol in animals. Respiratory effects and analgesia]. 1 -- Respiratory depression has been studied in the no anaesthetized rabbit by analysis of the blood gases after an injection of Piritramide (R 3365) and dehydrobenzperidol. 2 -- The respiratory depression induced by Piritramide alone is less important after an injection of dehydrobenzperidol; the most interessant cases are: -- mixture dehydrobenzperidol 400 mug/kg. Pirittramide 1000 mug/kg; --dehydrobenzperidol (400 mug/kg) injected 15 minutes before Piritramide (1000 mug/kg). 3 -- The addition of Dehydrobenzperidol does not take the analgesic activity of Piritramide decrease by it increases it.


[Variations in the activity of various curarizing substances as a function of the time of administration]. This experiment was carried out upon the male-adulte-AF SPF-Wister Rat, anesthetized by the use of pentobarbital-Na at the only dosage of 40 mg/kg/IP and put under artificial ventilation. The animals were divided into two groups: Group I, "diurnal animals" curarized between 10 a.m and 4 p.m; Group 2, "nocturnal animals" curarized between 9 and 12 p.m. Four drugs of the curarimimetic (pachycurare, non-depolarizing) type: gallamine, D-tubocurarine, pancuronium and AH-8165 were studied at doses presenting the same activity. The total curarizing effect measured by the surface defined by the curve of curarization within ten mns was constantly and significantly lowered in "nocturnal animals": a 25 p. 100 diminution with gallamine, 20 p. 100 diminution with D-tubocurarine, 27 p. 100 diminution with pancuronium, 19 p. 100 diminution with AH-8165. The hypothesis is that this diminution in the action of curarizing substances may be, to a great extent, in keeping with the rise of their metabolism -- the hepatic enzymatic activity being, in the rat, a nocturnal animal, definitely increased during the night.


[2 cases of respiratory assistance with a membrane oxygenator]. The authors report two cases of artificial ventilation with the assistance of a membrane oxygenator that was used, on the one hand, in the case of a 'malignant pneumopathy' and, on the other hand, in the case of a cardio-respiratory failure after a complete mending of a tetralogy of Fallot. Recovery was obtained in the second case. They specify the method and the watching of anti-coagulation. They insist upon the merit of a re-injection of oxygenated blood into the ascending aorta. They recall the necessity to lay down instructions according to very strict criteria, by taking into account the degree and the visceral repercussions of hypoxia and the reversibility of lung lesions in so far as it is a matter of a very heavy palliative therapy upon whose efficiency it is difficult to pass a judgment.


[The setting up of a computer system for records of first entries at the emergency medical assistance service in Montpellier]. The setting up of a computing device to exploit the files of first transports at the MONTPELLIER SAMU was started essentially in order to constitute a document both accurate and of easy access, able to memorize the physical and mental behaviour of a patient in a transient state. The results thus obtained include: 1 -- An analytical study with a part devoted to general data such as the number of injured people or of patients, the number of calls from various sources, the means of intervention etc. and a more specific part dealing with type of accident the determination of the traumatic impacts, the first therapy etc.; 2 -- A synthetical study that constitutes the second phase of the dealing with information thanks to the drawing up of graphs indicating the number of calls per accident according to the time, the age, the number of serious cases etc.


[Tracheal stenosis after tracheotomy. Apropos of 12 cases in 227 observations]. Out of 543 tracheotomized patients, 227 survived and 12 of them developed a tracheal stenosis syndrome (5,28 p. 100) including: 3 supra-ostial stenosis, 1 ostial and supra-ostial stenosis, 1 ostial stenosis, 3 intermediate stenosis and 4 distal stenosis. In two cases, the stenosis was found out during the removal of the cannula and in the other cases from 3 days to 8 months after the decannulation. The deffered treatment consisted in an anti-inflammatory medical treatment treatment (one case), in a permanent dilation with an Albouker tube (two cases), and in a resection of the stenosed tracheal part plus an anastomosis. Good results were obtained in 9 cases including the recovery of a satisfactory tracheal diameter. Because of a recurrence of the stenosis after resection and anastomosis, it was necessary, in two cases, to resort to another resection and, upon another occasion, to place a permanent cannulation. Finally, in one case, 2 Rethi operations were necessary to get a sub-normal tracheal diameter. From these facts, it emerges that tracheal stenosis are less important if, during the tracheotomy, a partial resection of the tracheal wall is effected (rather than an inverted U flap folded back at the bottom) together with the putting in of a cannula equipped with an elongated cylindrical cuff requiring a less important filing-up pressure (although just as efficient as far as tightness is concerned).


Sympathoadrenal Neurochemistry and early weaning of swine. Three litters of pigs were weaned at 21 days of age, and 3 others were left with the sow. Pigs were killed at 21, 23, 28, or 39 days of age. Weaned pigs exhibited anxiety, gastrointestinal dysfunction, and decreased rate of body weight gain. Plasma glucose or liver glycogen concentrations were not decreased by weaning. Adrenal gland weights and tyrosine hydroxylase (EC 1.14.3a), dopamine beta-hydroxylase (EC 1.14.2.1), phenethanolamine-N-methyl transferase (EC 2.1.1), and monoamine oxidase (EC 1.4.3.4) activities were increased after weaning. Adrenal catecholamine and cortisol levels and dopa decarboxylase (EC 4.1.1.26) and catechol-o-methyl transferase (EC 2.1.1.6) activities were not significantly altered, although some increases were indicated. Cranial cervical ganglionic choline acetyltransferase (EC 2.3.1.6) and tyrosine hydroxylase activities were increased after weaning. Weaning of swine at 21 days of age is a stressful experience, and many effects persist for at least 18 days; however, growth was no longer impaired 18 days after weaning.


The source of a minor alpha 1-antitrypsin in variant serum. An antiserum produced against human alpha1-antitrypsin gave 2 precipitin lines by immunodiffusion when tested against sera displaying MZ or MS phenotypes. Only one line (major antigen) was seen with sera displaying M phenotype, but a second line (minor antigen) became evident when the serum was concentrated 5-fold. The minor antigen appeared to be a denatured form of alpha1-antitrypsin, because the major antigen was converted to the minor one when purified alpha1-antitrypsin was incubated between pH 2.95 and 4.0. Such incubation inactivated the protein irreversibly. The purified protein was also inactivated completely within 1 hour at pH 4.95, but the activity was recovered completely by incubation for 2 to 4 hours at pH 8.0. The immunologic properties of the reactivated a1-antitrypsin were the same as those of the original untreated protein.


Should fiberoptic bronchoscopy aspirates be cultured? The reliability of fiberoptic bronchoscopy as a method to study the bacteriology of the lower respiratory tract was tested. The procedure used was suction aspiration through the inner channel after topical anesthesia with lidocaine. To detect contamination by oropharyngeal bacteria, the aspirates were cultured in patients with no evidence of active infection, comparison was made with results of transtracheal aspiration cultures, and the aspirate was tested for the presence of an oral dye marker. Results with all 3 methods of analysis indicated contamination with oropharyngeal bacteria that were presumably introduced during instrumentation through the upper airways. An additional factor studied was the effect of topical anesthetics. Analysis of aspirates showed that as much as 96 per cent of the specimen was anesthetic solution. Lidocaine also proved toxic to lower respiratory tract pathogens, although there were significant differences between bacterial species. It was concluded that fiberoptic bronchoscopy as performed in this study does not reliably reflect the bacteriology of the lower respiratory tract.


Spirometric comparison of carbuterol and isoproterenol aerosol therapy in bronchial asthma. A double blind, matched-pair study of 28 adults and a double blind crossover study of 18 children. Two adrenergic aerosols were compared in a double blind, matched-pair study of 6 months' duration in 28 adult patients with chronic bronchial asthma, and in a double blind, crossover, short-term study in 18 children with severe asthma. In the adult study, one member of each pair was given either 150 mug of isoproterenol or 200 mug of carbuterol 4 times per day, by inhalation, for 6 months. In the childhood study, 18 children, 6 to 12 years of age, with moderate to severe asthma were studied in a double blind, crossover therapeutic trial in which high or low doses of aerosolized carbuterol or isoproterenol were given 4 times daily for 5 days each. Treatment results were evaluated by measuring forced vital capacity, 1-sec forced expiratory volume, and maximal mid-expiratory flow (FEF25-75%) at regulat intervals before and after administration of the respective test drugs. In the adult study, there was a significant difference between carbuterol and isoproterenol for forced vital capacity (P less than 0.02), for 1-sec forced expiratory volume (P less than 0.02), and for FEF25-75% (P less than 0.01) in favor of carbuterol. In the pediatric study, the difference between carbuterol and isoproterenol was significant (P less than 0.05) only for the FEF25-75% on the fifth day of treatment with the high dose administration of carbuterol. There was no associated toxicity of either drug with respect to electrocardiogram, blood chemistry, or subjective complaints. Tachyphylaxis (tolerance with time) to isoproterenol appeared to develop in one patient.


Psychomotor skills during subacute treatment with thioridazine and bromazepam, and their combined effects with alcohol. Twenty paid healthy students volunteered for a doubleblind cross-over trial on the effects of two weeks' treatment with placebo, thioridazine and bromazepam on psychomotor skills. The doses used were thioridazine 10 mg t.i.d. during the first week and 20 mg t.i.d. during the second week, or 6 mg of bromazepam t.i.d. during two weeks choice reaction test, two co-ordination tests, a divided attention test, flicker fusion, and proprioception tests were used. The psychomotor skills were measured in the afternoon of the 7th and 14th day of each treatment, 30, 90 and 150 minutes after the second daily administration of the drug in combination with either an alcoholic or a placebo drink. There were no significant differences between the test weeks. Thioridazine alone resembled placebo and had no major combined effect with alcohol. Bromazepam impaired reactive and co-ordinative skills and attention deteriorated. The combination of bromazepam and alcohol potentiated the deterious effects of the single agents, and this effect was most remarkable at 30 minutes. The subjects also gave exaggerated responses in the proprioceptive tests. No significant alterations were recorded in the flicker fusion frequency after any treatment.


A new method using p-benzoquinone for coupling antigens and antibodies to marker substances. A method using p-benzoquinone for coupling antigens and antibodies to enzymes and erythrocytes is described. The method involves the treatment of proteins (or polysaccharides) at pH 6 or 7 with an excess of p-benzoquinone. After removal of the unreacted reagent by gel filtration, the "activated" proteins were coupled at pH 8-9 with enzymes or erythrocytes. Biological activities of the proteins were not substantially modified by this treatment since 80-100% of the antigen binding capacity was found to be preserved in p-benzoquinone treated antibodies or Fab fragments. Anti-Ig antibodies (or Fab) were coupled by this procedure to peroxidase, alkaline phosphatase, lactoperoxidase, glucose oxidase and beta-galactosidase, and the conjugates obtained were found to be highly effective in detecting intracellular Ig by immunohistochemical techniques. Erythrocytes coated with sheep anti-mouse Ig antibody or Fab were used to titrate by passive hemagglutination serum Ig. The same erythrocytes were employed to detect by plaque assay mouse Ig secreting cells. Erythrocytes coated with peroxidase, alkaline phosphatase, bovine serum albumin, ribonuclease, Salmonella polysaccharide (B 27 +) and pneumoccocal polysaccharide SIII were employed to titrate serum antibody by passive hemagglutination and hemolysis and to detect mouse antibody secreting cells by plaque assay. All the antigens and antibodies coated erythrocytes prepared gave highly satisfactory and reproducible results.


[Ionization of the acid-base groups of polyene antibiotics in aqueous solutions]. The acid-base characteristics of polyenic antibiotics, such as nystatin, mycoheptin and levorin in aqueous solutions were studied. A special procedure provided the use of potentiometric titration for investigation of ionization of the groups of vater-insoluble substances. The ionization constants of the carboxylic and amine groups of the antibiotics at several temperatures were determined. It was found that ionization of the acid group did not practically depend on the temperature. At the same time the heat effect of the amine group ionization was significant and amounted to about 10 kcal/mole. Thermodynamic analysis of the ionization process of the polyenic antibiotics in aqueous solutions was performed. Integral components defining the process energetics were calculated.


Mechanism of action of miconazole: labilization of rat liver lysosomes in vitro by miconazole. Miconazole, a potent antifungal agent, labilizes rat liver lysosomes. Its labilizing effect is followed by measuring the release of lysosomal hydrolases, namely, acid phosphatase, beta-glucuronidase, and arylsulfatase A. The effect of miconazole is concentration dependent in the range of 10(-5) to 1.2 x 10(-4) M. However, at higher concentrations, miconazole inhibits enzyme release but does not inhibit enzyme activities per se. The effect of miconazole depends on the drug/lysosome ratio and is influenced by the pH of the incubation media, being minimal at alkaline pH. Membrane-active drugs such as nystatin, 2-phenethyl-alcohol, hexachlorophene, and digitonin have been compared with miconazole for their lysosome-labilizing action. The effect of miconazole on the lysosomal membrane is confirmed by a decrease in turbidity of the lysosomal suspension.


In vitro activity of josamycin against aerobic gram-positive cocci and anaerobes. Josamycin, a new macrolide antibiotic, was compared with ampicillin, erythromycin, and clindamycin in vitro against 25 isolates each of pneumococci, enterococci, Staphylococcus aureus, S. epidermidis, and nonenterococcal hemolytic streptococci and against 25 anaerobes including 10 Bacteroides fragilis. Minimal inhibitory concentration and minimal bactericidal concentration data were obtained for the aerobic organisms, using serial twofold tube dilutions in Mueller-Hinton broth. Minimal inhibitory concentrations were determined for the anaerobes by the agar dilution technique. Josamycin was comparable to erythromycin and clindamycin in activity against the pneumococci, streptococci, and staphylococci and was more active than clindamycin against enterococci. It was somewhat less active than ampicillin against enterococci and S. epidermidis and showed its greatest in vitro activity against anaerobes, being comparable to clindamycin.


Observations on brilliant green agar with H2S indicator. Several formulations of brilliant green agar with an added H2S indicator were evaluated. Results were optimum with variations of a basic formula consisting of 40 g of tryptic soy agar (Difco), 8 g of lactose, 8 g of sucrose, 80 mg of phenol red, 1 g of sulfanilamide, 1.5 g of ferric ammonium citrate, 5 g of sodium thiosulfate pentahydrate, and 7 mg of brilliant green dye per liter. Brilliant green dye was added after sterilization of the other components This formulation supported good growth of all of 39 strains of Salmonella tested. Normal biochemical types formed pink colonies with black centers, and an H2S-negative S. choleraesuis formed pink colonies without black centers. Of other bacteria tested, only Enterobacter, Klebsiella, and a few Citrobacter strains showed significant growth in 24 h. When lactose was omitted from the formulation, a lactose-fermenting strain formed pink colonies with black centers, and differentiation of Salmonella from the Enterobacter-Klebsiella groups was equally good. Addition of xylose (4.0 g) and L-lysine hydrochloride (5.4 g) to the above formulation improved differentiation between Salmonella and the few Citrobacter strains that grew and produced more intense blackening in Salmonella colonies. Addition of an H2S indicator to brilliant green agar formulations aided in identification of Salmonella colonies, especially in mixtures with other bacteria. These media were judged to give better differentiation of salmonellae from other bacteria than Hektoen agar with added novobiocin (10 mg/liter).


Microbial formation and degradation of dimethylamine. Dimethylamine was formed from trimethylamine in soils of different pH values. The rate of disappearance of the secondary amine from soil was affected by pH and was markedly reduced under anaerobiosis. The accumulation of dimethylamine in cultures of Micrococcus sp. provided with trimethylamine depended on the nitrogen sources available to the bacterium but was not greatly influenced by the C-N ratio of the medium. Dimethylamine and nitrite accumulated in large amounts at pH 6.0 to 8.0 in cultures containing the tertiary amine and nitrate, but dimethylnitrosamine was apparently not produced.


Toxicity of ammonia to algae in sewage oxidation ponds. Ammonia, at concentrations over 2.0 mM and at pH values over 8.0, inhibits photosynthesis and growth of Scenedesmus obliquus, a dominant species in high-rate sewage oxidation ponds. Photosynthesis of Chlorella pyrenoidosa, Anacystis nidulans, and Plectonema boryanum is also susceptible to ammonia inhibition. Dark respiration and cell morphology were unaffected by any combination of pH and ammonia concentrations tested, thus limiting the apparent effect to inhibition of the normal function of the chloroplasts. Methylamine had the same effect as ammonia, and its penetration into the cells was found to be pH dependent. Therefore, the dependence of toxicity of amines to algae on pH apparently results from the inability to penetrate the cell membrane in the ionized form. When operated at 120-h detention time of raw wastewater, the high-rate oxidation pond maintained a steady state with respect to algal growth and oxygen concentration, and the concentration of ammonia did not exceed 1.0 mM. Shifting the pond to 48-h detention time caused an increase in ammonia concentration in the pond water to 2.5 mM, and the pond gradually turned anaerobic. Photosynthesis, which usually elevates the pH of the pond water to 9.0 to 10.0, could not proceed beyond pH 7.9 because of the high concentration of ammonia, and the algal population was washed out and reduced to a concentration that could maintain a doubling time of 48 h without photosynthesis bringing the pH to inhibitory levels. Under these conditions, the pH of the bond becomes a factor that limits the operational efficiency of the oxidation pond.


Production of extracellular alpha-glucosidase by a thermophilic Bacillus species. Production of extracellular alpha-glucosidase was studied with strain KP 1006 of a new species of thermophilic Bacillus, which was isolated from soil samples by enrichment at 65 C. alpha-Glucosidase production was maximum at 60 C and at an initial pH of 6.5. The final enzyme yield was increased by starch, maltose, glycerol, peptone, and yeast extract but reduced by acetate and gluconate, alpha-Glucosidase was formed in the cytoplasm and accumulated as a large pool during the logarithmic growth phase. At a midpoint of this period, the enzyme appeared in the culture broth, and its level increased until the end of the stationary phase.


Factors influencing the production of cellulases by Sporotrichum thermophile. Cellulase production and growth of a strain of Sporotrichum thermophile were studied by using a mineral salts medium supplemented with yeast extract and insoluble cellulose. The effects of cultural conditions, such as pH, nitrogen source, substrate concentration, and temperature, were examined. Maximum production of C1 and CX cellulases occurred at 45 C in 2 to 4 days, in the presence of 1% Solka/Floc as substrate, when NaNO3 or urea used as sources of nitrogen. Under these conditions, cellulolytic activity of culture filtrates appeared to be similar to that reported for Trichoderma viride grown in a favorable environment. However, comparable yields of cellulase were produced by S. thermophile in less than one-quarter the time required by mesophilic fungi.


Degradation of [8,9,-14C]endosulfan by soil microorganisms. Twenty-eight soil fungi, 49 soil bacteria, and 10 actinomycetes were tested as to their ability to degrade the insecticide endosulfan. Using 14C-labeled material, the qualitative as well as the quantitative formation of metabolities, as well as of 14CO2, could be followed. Sixteen fungi, 15 bacteria, and 3 actinomycetes were found capable of metabolizing more than 30% of the applied endosulfan. The major metabolities detected were endosulfate, formed by oxidation of the sulfite group, and endodiol, formed by hydrolysis of the ester bond. The majority of highly active fungi formed endosulfate as the major metabolite, whereas the majority of active bacteria formed endodiol. In addition to endosulfate and endodiol, individual cultures contained small quantities of endohydroxyether and two unidentified products. The very small quantities of 14CO2 evolved from cultures indicated that an extensive mineralization of the carbon skeleton of endosulfan did not occur.


Stabilization of a psychrotrophic Pseudomonas protease by calcium against thermal inactivation in milk at ultrahigh temperature. The heat-stable extracellular protease of Pseudomonas sp. (isolate MC60) was investigated. Heat resistance of the enzyme in milk at sterilization temperature was dependent on the presence of Ca2+. The half-life of the enzyme at ultrahigh temperature (149 C) in skim milk or milk-salts buffer with Ca2+ was approximately 7.0 s. Treatment of milk with chelators completely removed the heatstabilizing effect of milk. The enzyme was partially purified by ammonium sulfate precipitation and column chromatography on Sephadex G-100. At 21 C the enzyme retained greater than 85% activity after exposure to pH values between 5 and 10. Enzyme activity was reduced by metal chelating agents. Both Ca2+ and Zn2+ were required for optimal enzyme activity. Molecular weight was estimated at 48,000 by gel filtration.


N-Nitrosamine formation by cultures of several microorganisms. Of 38 pure cultures of microorganisms tested, only one, Pseudomonas stutzeri, was capable of forming dimethylnitrosamine from dimethylamine and nitrite during growth. Resting cells of P. stutzeri, Cryptococcus terreus, Escherichia coli, and Xanthomonas campestris formed dimethylnitrosamine, although no nitrosamine was found in growing cultures of the latter three organisms. No nitrosamine was produced by either growing cultures or resting-cell suspensions of Pseudomonas fragi or Proteus mirabilis. Boiled cells of P. stutzeri, but not those of C. terreus, E. coli, and X. campestris, formed dimethylnitrosamine, and this nitrosamine was also produced by extracts of E. coli cells at pH 5.0.


Influence of sewage discharge on nitrogen fixation and nitrogen flux from coral reefs in Kaneohe Bay, Hawaii. Nitrogen fixation was investigated in Kaneohe Bay, Oahu, Hawaii, a subtropical eutrophic estuary, by using the acetylene reduction technique on algal samples. No active, planktonic, N2-fixing blue-green algae or bacteria were observed. However, Calothrix and Nostoc capable of fixing N2 were cultured from navigational buoys and dead coral heads. Nitrogen fixation associated with these structures was greater in the middle sector than in the south and north sectors of the estuary. Experiments demonstrated that the fixation was photosynthetically dependent. Examination of the data showed that there was no significant correlation between rates of nitrogen fixation and concentration of combined nitrogen compounds in the Bay water. Fixation was significantly correlated to the inorganic N/P (atomic) ratio in the south and middle sectors but not in the north sector. The nutrient data indicate there was a flux of combined nitrogen, but not phosphate, from the reef flats.


Cultivation of mycoplasmas in a modified tissue culture medium. A new medium, which contained a chemically defined tissue culture base ("medium 199"), was developed for the cultivation of mycoplasmas. When supplemented with albumin, glucose, serum, and yeast extract, the new medium adequately supported the growth of Mycoplasma and Acholeplasma species.


Further evidence for the transmission of Mansonella ozzardi by Simulium amazonicum in Brazil. The transmission of Mansonella ozzardi was studied in two rubber collecting villages on the River Purus, state of Amazonas, Brazil. Haematophagous insects were collected from human and bovine baits during the day and night: 687 Mansonia amazonensis and 154 Culicoides sp. indet. were free from infection with M. ozzardi. The former species is probably not a vector, but the low numbers of culicoides dissected preclude any determination of its vector status. Thirty-five (0-99%) of 3530 Simulium amazonicum dissected were found naturally infected with larvae of M. ozzardi. Two hundred and ninety-nine M. amazonensis and 280 S. amazonicum were experimentally infected with M. ozzardi by feeding on volunteers. Microfilariae were detected in the blood meals of both species but no developing larvae were found in the thoracic muscles of M. amazonensis, confirming its non-vector status; 7-1% of the S. amazonicum dissected had filarial larvae in the thorax. There was a statistically significant difference between this rate and the natural rate of infection in this region, verifying that penetration of the thoraric muscles by M. ozzardi had occurred in the experimental infection. The data confirm the observation of Cerqueira (1959) that S. amazonicum transmits M. ozzardi in Brazil.


[Studies on the properties of acid erythrocyte phosphatase in sheep and the isoenzymes of sheep and goat acid erythrocyte phosphatase]. Ovine erythrocytic acid phosphatase showed two peaks of activity at pH 5.0 and 5.7 in acetate buffer with p-nitrophenylphosphate as substrate. The enzyme was only slightly inhibited by fluoride and L-phenylalanine, but high concentrations of urea strongly inhibited it. Activity of the enzyme was greater in goat erythrocytes than in sheep. By means of starch electrophoresis, three isoenzymes belonging to nine types were separated from the ovine enzymes, while three isoenzymes of five types were present in goats. Electrophoresis in polyacrylamide gel was suitable for detecting the rapidly migrating isoenzymes.


[Origination and importance of glycolysis for malignomas and utilization of this property in the chemotherapy of cancer (author's transl)]. Glycolysis is not of importance for the process of carcinogenesis. It is very likely, however, that certain molecular-biological and genetic changes are produced which enable the malignant cell to develop an intensive glycolysis, for instance, to form specialized glycolytic isoenzymes already during oncogenesis, and may possible become effective in the primary tumour. As soon as the capacity of the cancer cell to intensive aerobic and anaerobic glycolysis has become manifest, this process is an irreversible one. The extent of glycolysis of a malignoma is greatly dependent on the degree of its dedifferentiation and vascularization (glucose supply), although a direct correlation between growth and the amount of lactic acid formed does not seem to exist. However, a certain utilization of glucose is essential for cell proliferation (supply of basic substances). In many cases there is a correlation between the extent of glycolysis measurable under optimal conditions in vitro (glycolytic power) in a malignant tumour and its growth rate recognizable in vivo. The formation of a strong capacity for glucose degradation via the Embden-Meyerhof pathway that cannot be fully utilized by the whole tumour in vivo is first of all designed to ensure survival and proliferation of cells even at extremely low levels of glucose supply. This process can be regarded as an adaptation of cancer cells to a situation of unsufficient supply. This circumstance endows the cancer cell with an essential advantage over the normal cell which enables or even promotes its invasive and destructive growth and metastatic dissemination. In this respect they differ, for instance, from benignant neoplasms. The possibility is discussed to control neoplastic growth by adjusting an optimal pH difference between normal and tumour tissue by combined administration of detoxicated drugs which are converted to their toxic forms only in the tumour by means of strongly pH-dependent exogenous enzymes.


[The influence of role induction on the success of systematic desensitization of socially anxious students (author's transl)]. The so-called nonspecific factors involved in therapy have received little attention up to the present - namely, that of role induction (preparing the clients for treatment by informing them about the rationale of treatment, the treatment process, and their part in therapy). For this reason, we constructed an induction text for systematic desensitization according to the principles of instructional psychology (Ausubel), and proceeded to test it for understandability and therapeutic effectiveness. With control group design which assured the realization of the independent variable of role induction, the effective results of desensitization with role induction were compared both with those of simple desensitization and those of a waiting control group. The resultant differences in the group with role induction indicate the additional advantages of this technique for therapy. Essentially, role induction seems to manifest itself in terms of a contribution to more active, independent role formation on the part of the client.


Cell populations in a renal lesion produced by local injection of xenogeneic spleen cells in cyclophosphamide-treated rats. The frequency and distribution of donor and host lymphoid cells in different stages of a lesion produced by injecting mouse spleen cells beneath the renal capsules of rats treated 24 h previously with cyclophosphamide have been studied by immunofluorescent staining with species-specific anti-lymphocyte sera. Donor cells were predominant in the early stages of the reaction and penetrated the outer part of the renal cortex, but by day 7 when the lesion reached its maximum extent most of the infiltrating cells were of host origin. Donor cells never extended deeply into the kidney and they were not uniformly intermingled with the main mass of host cells but their presence seemed to be necessary for the maintenance of the reaction, since it began to decline when donor cells were no longer detectable in the injected kidney.


Facilitation of the growth of an allogeneic tumour by suppressor cells in newborn rats. The intravenous injection of as few as 15 Walker tumour cells into newborn rats consistently resulted in the development of pulmonary metastases and the death of the recipient within 2 weeks. Neither the outcome of tumour cell injection nor the interval until death could be modified by transferring 2 x 10(7) lymphocytes from tumour-immune adult rats to the neonataal hosts. In contrast with this failure to transfer adoptive anti-tumour immune responses to intact recipients, the administration of 350 rad irradiation before transfer of 10(6) immune lymphocytes constantly afforded protection against inoculated tumour cells. The simultaneous transfer of neonatal thymus cells with immune lymphocytes interfered with the establishment of an adoptive response in the irradiated newborn. Intiation of a graft-versus-host response in F1 hybrid neonates by injecting parental strain lymphocytes conferred resistance to tumour growth of the recpient, the magnitude of this effect increasing with the strength of the graft-versus-host reaction.


Suppressor cells in homograft tolerant rats. If sufficient normal syngeneic lymphocytes to effect skin graft rejection are transferred to homograft tolerant rats, a prolonged period elapses before lymphoid cells from the recipient acquire normal levels of GvH responsiveness against tissues of which the donor was previously tolerant (Silvers and Billingham, 1970; Elkins, 1972; Miyamoto and McCullagh, 1974). Although the ability of lymphoid populations of such animals to mount GvH reactions can be demonstrated to reside in donor type cells during the weeks immediately after transfer, reactive cells are ultimately derived from the host itself (Elkins, 1973; Miyamoto and McCullagh, 1974). Not only are lymphoid cells from tolerant rats which have been injected recently with normal lymphocytes poorly responsive in a GvH assay, but they have been observed in some experiments to suppress the GvH activity of normal syngeneic lymphoid cells (Elkins, 1972; Atkins and Ford, 1972). It is not clear whether the cells mediating suppression of the normal lymphocytes were derived from the tolerant host itself or, alternatively, from the normal lymphocytes injected into it to terminate the tolerant state. The present experiments sought to delineate the origin of any suppressor cells within populations of lymphocytes collected from rats in which tolerance had recently been terminated. The indicate that suppression of the normal donor cells within such populations may be exerted by cells derived from the tolerant host.


Efficacy of two minor tranquilizers in relieveing symptoms of functional gastrointestinal distress. Two minor  tranquilizers, diazepam and lorazepam were significantly better than a placebo preparation in relieving symptoms of functional gastrointestinal distress in 28 patients who took part in a double-blind cross-over trial. The beneficial therapeutic effect may be group- rather than preparation-specific. Both agents were also of significant benefit to the sub-group of patients with aerophagy as a major symptom.


Hydrallazine and beta-blockade in refractory hypertension with characterization of acetylator phenotype. In 30 refractory hypertensives a hydrallazine beta blocker combination was added to or substituted for previous antihypertensives. Over a mean period of 12 months a good or satisfactory blood pressure response resulted in 12 patients each, while six others had an unsatisfactory outcome. (Good = diastolic pressure (DP) less than 95 mmHg; Satisfactory = deltaDP greater than 15 mmHg or DP 95-105 mmHg; Unsatisfactory = DP greater than 105 mmHg or deltaDP less than 15mmHg.) Twelve of the patients had significant renal disease with serum creatinine greater than 2 mg/100 ml, but in these there was no evidence that renal hydrallazine retention potentiated an antihypertensive effect. Those with an unsatisfactory response were receiving slightly higher doses hydrallazine and propranol when compared with good responders. The average dose of hydrallazine was 258 mg/day and of propranolol 308 mg/day. Transient headache was not uncommon at the commencement of hydrallazine therapy. Angina and vertebro-basilar insufficiency were each aggravated in one patient, but resolved with dosage adjustment. A lupuslike rash developed in one patient, a slow acetylator on 300 mg hydrallazine/day who had received a total of 92 g over eleven months. The genetically determined acetylator phenotype was assessed in 75 subjects. A little over one third were found to be rapid acetylators. Those with slow acetylator phenotype did not show a more favourable phenotype did not show a more favourable blood-pressure response to equivalent doses of hydrallazine.


Neurotic and psychotic states attributed to Thai "Phii Pob" spirit possession. In Thailand, the term "Phii" refers to spirits and ghosts to which are generally attributed power over human beings. In the present, spirit possession is usually found in rural areas. However among several spirits, there is one particularly interesting spirit selected for this presentation, the phii pob. The "Phii Pob" is a common spirit in the Northeast, North and some provinces in the Central part of Thailand (Suwanlert, 1972). Thai believers consider that the phii pob differs from other spirits. It originates in a living person, then conceals itself in the body of that person, who is called th originating host; it is believed that the phii pob hiding within a person can leave the body of that person to possess another, who is called the possessed host. The victims almost always are females.


The effects of acidosis and alkalosis on coronary flow and cardiac nucleotide metabolism. The changes of the coronary flows and of the cardiac nucleotide metabolism during acidosis and during alkalosis were studied in 50 perfused guinea pig hearts with and without hypoxia. At pH 7.0 the coronary flows increased, and at pH 7.8 a significant reduction of the flows took place. At 20% O2, acidosis elicited a further flow increase, whereas alkalosis inhibited the flow increase produced by hyoxia. The increases after adenosine injections and after coronary occlusions were greater during acidosis and smaller during alkalosis than at pH 7.4. The cardiac nucleotide contents did not clearly differ from the controls whereas adenosine exhibits higher levels in acidotic hearts. Alkalosis always induced a decreased production of adenine nucleoside irrespective of the presence or the absence of hypoxia. At 20% O2 a decreased ATP level and increased ADP- and CrP-contents could be observed during alkalosis.


Biosynthesis of prostaglandins in rabbit kidney medulla. Properties of prostaglandin synthase. A simple radioactive-substrate assay for prostaglandin synthase (EC 1.14.99.1), which uses t.l.c. to measure simultaneously different prostaglandins synthesized from one precursor substrate, was developed. Rabbit kidney-medulla prostaglandin synthase catalyses the formation of prostaglandin E2, prostaglandin F2alpha and prostaglandin D2 from arachidonic acid. Fractionation of crude homogenates indicated that the microsomal fraction possessed the highest specific activity of prostaglandin synthase, whereas the soluble fraction exhibited little enzyme activity but rather contained a heat-labile inhibitory macromolecular factor(s), which might be attributed to the serum albumin present in this fraction. The microsomal fraction possessed low intrinsic enzyme activity, but the actvity could be fully stimulated by the presence of both GSH (reduced glutathione) and a phenolic cofactor. Only cysteine could partially replace GSH, whereas other thiols were inactive and some were even inhibitory. A variety of phenolic compounds, including catecholamines, dopamine (3,4-dihydroxyphenethylamine), 5-hydroxytryptamine and quinol, were active in stimulating prostaglandin synthase. In all cases, the stimulation was reflected in the synthesis of all three prostaglandins with ratios not significantly altered by different phenolic cofactors. The synthesis of each of the different prostaglandins appeared to have similar pH optima. The enzyme system was not inhibited by thiol-group inhibitors or a variety of metal chelators except for cyanide and 8-hydroxyquinoline. Characterization of the kidney-medulla prostaglandin synthase system indicated that it exhibited properties similar to those of the enzyme system present in seminal vesicles.


Interactions of some acceptors with superoxide anion radicals formed by the NADPH-specific flavoprotein in rat liver microsomal fractions. In rat liver microsomal fractions oxidation of adrenaline was effected by superoxide anion radicals (O2-), whereas cytochrome c, 2,6-dichlorophenol-indophenol and ferricyanide accepted electrons from NADPH-specific flavoprotein only directly. Nitro Blue Tetrazolium was reduced both by O2- and by the direct acceptance of electrons. Elevation of pH and addition of menadione shift the Nitro Blue Tetrazolium reduction towards the O2--dependent pathway. From the values of the kinetic constants for interaction of adrenaline and Nitro Blue Tetrazolium with NADPH-specific flavoprotein, the rates of generation of O2- in rat liver microsomal fraction were determined.