[Nutritive antibiotic additives in animal feeding stuffs--a further form of environmental pollution (author's transl)]. Feeding domestic animals with mycelia, a by-product of vitamine production, gave rise to the side effect of markedly improved utilization of the fodder. This effect is not due to the vitamine and protein content but to the antibiotic content of this waste product. The nutritive effect was brought about by a larger number of different antibiotics in concentrations which were considerably lower than the therapeutically required doses. Therefore we speak, in this connection, of a nutritive addition of antibiotics to animal fodder. Since at the time of introducing this feeding method only the mutational resistance to antibiotics of pathogens was known and since the nutritive dosaging cannot select such therapeutically relevant degrees of resistance of the germs, no importance was attached to the development of the resistance and its effect on human medicine. However, during the last decade it has been found that the feeding of antibiotics is indeed capable of selecting the plasmidic resistance to antibiotics of the gram-negative intestinal bacteria in the faeces of the animals. For pigs, calves and hens--to quote only the most important animals--now contain a coliflora almost completely studded with R-factors. Owing to the transmissibility of the plasmids and the epidemiologically short path from animal to man, dangers emerge for the human medicine from this nutritive selection. Therefore the use of all antibiotics which select resistance plasmids, should be avoided in animal feed stuffs. It would be best, if antibiotics used in human medicine were not used in veterinary practice.


[Microbial emission, immission and changes in the germ count in the cooling water during operation of wet cooling towers. IV. Communication: microbial immission in the vicinity of wet cooling towers (author's transl)]. From the emission rates of the bacterial cooling tower emission determined in field measurements (see Comm. II) the mortality rate of enterbacteria on soil, grass and solid surfaces and the mortality rate in the atmosphere taken from literature the immission rates and the long-term effect on microbial surface flora were calculated and compared with our own measurements. The values used in the calculations include large margins for error. The atmospheric germ counts determined by experiment were no higher than the calculated values; they fluctuated in terms of concentration between 20 KBE m-3 and 200 KBE m-3 in ranges which were measured in areas with little or no anthropogenic influences. The maximum long-term surface load which occurs under these assumptions is 2.3.10(5) KBE M-2. This relatively small additional load (approx. 10(-3%) would hardly be noticeable in a number of colonies of approximately 10(10) KBE m-2 normally occurring in soil and grass samples.


[Reptile brain cerebrosides and cerebroside sulfates]. Studies have been made on the content of cerebrosides and cerebroside sulfates, as well as on their fatty acid composition in the brain of reptiles, subclass Anapsida (tortoises Emys orbicularis and Testudo horsfieldi) and subclass Lepidosauria (lizards Agama caucasica, A. sanguinolenta, Phrynocephalus mystaceus and snake Natrix tesselata). Total content of cerebrosides and cerebroside sulfates is higher in the brain of Lepidosaurians than in that of Anapsids. In the brain of tortoises, the content of cerebroside fraction with hydroxy fatty acids is significantly higher than of the fraction with normal fatty acids, which is also typical of the brain of homoiothermic mammals and birds. In the brain of Lepidosaurians, concentration of hydroxycerebrosides is considerably lower than of cerebrosides with normal fatty acids, which is similar to lower vertebrates -- amphibians and fishes. Low content of hydroxycerebrosides was found in all the Lepidosaurians investigated, irrespectively of their ecological conditions, being therefore dependent on their phylogenetic position. The composition of fatty acids, both normal and hydroxyderivates, as well as that of glycolipids from the brain of Anapsids and Lepidosaurians is essentially similar. However, some interspecific differences were noted in the pattern of fatty acids of cerebrosides and cerebroside sulfates of the brain, which concern the content of saturated and long chain fatty acids.


[Comparative study of binding of Scorpaena porcus scorpion fish insulin and pig insulin by specific muscle plasma membrane receptors]. Insulin from the scorpion-fish and porcine insulin have been compared with respect to their capacity to interact with the specific receptors in plasma membrane of skeletal muscle fibers of rats. Both insulins inhibited membrane binding of insulin-125J; the dose of porcine insulin which inhibited binding by 50% was equal to 3.7 nM, that of fish insulin -- to 100 nM. These figures indicated lower affinity of fish insulin to mammalian receptors (4% of the porcine affinity), being in accordance with lower biological activity of fish insulin in diaphragmal test. Other peculiarity of fish insulin was revealed in studies on dissociation of insulin-125J, which was previously bound to isolated diaphragm muscle of the rat. In contrast to mammalian insulin, it was not capable of increasing the dissociation when being added to a solution in doses from 7.10(-11) to 7.10(-9) M. This fact is analysed in term of the "site--site" interactions concept.


[Sex differences in the gonadotropins of the Black Sea plaice Scophthalmus maeoticus]. No quantitative differences in the effect of acetone-dried pituitaries from male and female plaice upon loach-recipients (Misgurnus fossilis) have been found in testing the activity of the glands on plaice-recipients. This fact suggests the existence of qualitative differences between gonadotropins from plaice males and females. This conclusion was supported in the experiments on the effect of purified gonadotropic fractions, isolated separately from male and female hypophyses, on maturation of the loach. Three gonadotropic fractions obtained by preparative disc-electrophoresis in polyacrylamide gel, differ in their biological activity and electrophoretic mobility. The activity of gonadotropic fractions in males is higher, than in females; electrophoretic mobility of two fractions is also higher in males, whereas the third fraction does not exhibit sexual differences.


[Comparative analysis of thermoregulation in the nests of certain species of social insects]. Studies have been made on thermal regulation in the nests of families of the honey bee Apis mellifera, wasp Dolihovespula silvestris and bumblebees Bombus terrestris, B. agrorum and B. lapidaris during their maximum development. It was shown that thermoregulation significantly stimulated the brood in the nest. Among the species investigated, the highest thermoregulatory capacities are exhibited by honey bees, this fact being associated with the large number of individuals in their colonies. During cooling, bees group around the brood and their bodies make a cover of thermal insulation. Sheltering of the nests plays the main role in heat preservation of wasps and bumblebees. The latter, using contact method of heating of cells with the brood, provide rather constant temperature for its development. Honey bees, wasps and bumblebees react to overheating in the nests essentially in a similar way, i. e. by active aeration of their nests by vigorous wing beatings. The frequency of beatings increases with the increase in temperature.


[Changes in the sensitivity of the heart of marine mollusks to acetylcholine during the spawning period]. In experiments on 5 species of marine bivalve molluscs (Spisula sachalinensis, Callista brevisiphonata, Mactra sulcatoria, Peronidia venulosa, Mya japonica) it has been shown that the level of sensitivity of cardiac muscle to ACh corresponds to functional condition of the reproductive system. During the discharge of mature sexual products, significant increase in the sensitivity to the mediator is observed -- from threshold ACh concentrations about 10(-9) M to 10(-15)--10(-17) M during spawning. If the spawning time is shifted, the onset of the increase in cardiac sensitivity is shifted as well. This parallelism is absent in species with portional mode of reproduction -- Crenomytilus grayanus and Modiolus difficilis.


[Type II neurons in the trunk of the cockroach Periplaneta americana]. Staining the nervous system by methylene blue, studies have been made on the topography and structure of type II neurones in the trunk of the cockroach. Small quantity of cells innervating various tissues was found together with 3 varieties of neurones, located near the nervous trunks, as well as 4 pairs of the abdominal stretch receptors (one pair of unicellular and one pair of bicellular receptors in tergites and sternites).


[Demonstration of different type cholinoreceptors on the membrane of an isolated Planorbarius corneus mollusk membrane]. In experiments on isolated and identified neurones of the pedal ganglion of the gastropod mollusc P. corneus, it was demonstrated that biphasic response to ACh may be obtained both to superfusion and electrophoretic application. Fast (depolarizing) phase may be imitated by a nicotinomimetic drug, suberyldicholine, and blocked by d-tubocurarine. These data indicate that this phase results from activation of nicotinic cholinoreceptors. Slow (hyperpolarizing) phase may be evoked by a muscarinomimetic, dioxolane F-2268, which is taken as an indication of the muscarinic nature of cholinoreceptors responsible for this phase. Experiments on completely isolated neurones directly show that both kinds of cholinoreceptors belong to the same neurone. Biphasic pattern of the response depends on the level of the membrane potential and on the conditions of ACh application. The fast phase is more evident at membrane hyperpolarization, the slow one--at depolarization. The fast phase is more readily obtained by superfusion by high concentrations of ACh or at close position of electrophoretic micropipette to neuronal surface, whereas the slow phase may be easily obtained by superfusion with low concentrations of ACh or when the micropipette is not attached so closely to the cell.


[Embryogenetic features of the serum protein composition of chicken blood]. Protein composition of the blood serum in chick embryos of two breeds and in their hybrids has been investigated by polyacrylamide gel electrophoresis. Significant changes in the proportion of protein components of pre-albumin, albumin and post-albumin zones during prenatal development of chicks were observed. These changes are alleviated in hybrid embryos. The decrease in protein content of post-albumin zone, which contains foetoproteins, takes place to the end of incubation. This decrease is less significant in hybrid chicks as compared to that in the original hen breeds.


[Quantitative determination of immunoglobulins in the hemagglutination inhibition reaction. I. A method of expressing the results based on a comparison with a standard and using a logarithmic scale]. The sources of errors in the quantitative determination of immunoglobulins in the passive hemagglutination inhibition test are considered. The influence of some factors (the quality of erythrocyte diagnostic reagents, the non-standard working dose of the antiserum) can be reduced if in each test the material under study is compared with a known preparation having known serological activity (standard preparation). A suggestion is made on the advisability of expressing the results of the test in the logarithmic (log2) scale of serological activity units (SAU), where the activity of 100 IU/ml is considered to be 10 units. The serological activity of the standard preparation used in this research was determined against a set of Hyland reference sera. The average level and varibility of immunoglobulin content in the sera of healthy adults were determined with the use of 104 serum samples. The average level was 10.2 +/- 0.1 SAU for IgG, 10,4 +/- 0.1 SAU for IgA and 9.6 +/- 0.1 SAU for IgM, with sigma for all immunoglobulins being about 1.0. The reproducibility of the passive hemagglutination inhibition test was satisfactory; the variability of the results after repeated tests seldom exceeded 1 SAU.


[Immunological properties of malignant and nonmalignant L-cell sublines. I. Obtaining a malignant L-cell subline and its immunological cross reactivity with nonmalignant cells]. LS cells, the malignant subline of benign L cells, were obtained from L cells by selection carried out by means of their cultivation in the abdominal cavity of allogenic mice. When inoculated subcutaneously in a dose of 1 x 10(6) into the back, LS cells took and progressively grew in 70% of syngeneic animals. The preliminary immunization with L cells protected 30% of mice inoculated subsequently with L cells.


[Hemolytic properties of El Tor cholera vibrios]. The hemolytic factor of Vibrio cholerae, biotype eltor, is bound to the cellular structures and can be liberated into the environment. The inhibiting action of proteases on the hemolytic activity of vibrios suggests that the proteinaceous hemolysin component of these organisms plays an important role in the process of red blood cell lysis. The inhibition of the hemolytic activity of vibrios by Ca2+ ions seems to be connected with the activation of intracellular phospholipases.


[Isolation of nonagglutinating vibrios in acute gastrointestinal diseases in Kiev Province]. The results of the bacteriological examination of material obtained from 71 patients with acute gastrointestinal diseases for the presence of vibrioflora, as well as the results of surveying different groups of population for the detection of vibrio-carriers are presented. The clinical and epidemiological data obtained in the course of various diseases caused by nonagglutinating vibrios are analyzed. The biological properties of nonagglutionating vibrio cultures isolated from patients and vibrio-carriers are described. The data thus obtained substantiate the necessity of carefully evaluating nonagglutinating vibrio cultures isolated from humans with due regard for the existing epidemic situation.


[Nonpathogenic Neisseria on the mucosa of the respiratory tract in healthy persons and patients with infectious-allergic bronchial asthma]. The comparative study of Neisseria strains, isolated from the bronchi and the pharynx of healthy persons and infectious asthma patients, was made. Nonpathogenic Neisseria isolated from bronchial asthma patients were represented by the same species as those in the pharyngeal flora of healthy persons. Only N. perflava occurred in the pharynx and the bronchi of infectious asthma patients twice as often as in healthy persons. Neisseria colonies in the R-form were shown to prevail in the cultures obtained by the inoculation of the smears taken from asthma patients.


Preparation of subcellular fractions from granulation tissue by density gradient centrifugation. The 7000 g pellet of homogenized mature sponge-induced granulation tissue was fractionated by centrifugation in a stepwise sucrose gradient in order to study the synthesis and secretion of collagen and other components of this tissue on the subcellular level. As indicated by chemical and enzymatic assays, by electron microscopy and by incorporation experiments, the collagen-synthethesizing rough endoplasmic reticulum fraction was isolated free from the secretory vesicles (smooth endoplasmic membranes and Golgi elements) and fibrous extracellular matrix. Collagen differed from other proteins in the distribution among the subcellular fractions. In pulse-chase experiment the translocation of 14C-labelled collagen was demonstrated from the rough endoplasmic reticulum through the secretory vesicles to extracellular fibrillar collagen. This fractionation method will be used to study the modulation of collagen synthesis and secretion in the reparative tissue.


Chemical modification of rat liver arginase. Chemical modifications were used to search for catalytically important residues of rat liver arginase. The results of carbamoylation, nitration and diazotization suggest that lysyl and tyrosyl residues are not involved in the catalytic function of arginase. The modification of 5--6 tryptophanyl residues by N-bromosuccinimide or 2-hydroxy-5-nitrobenzyl bromide led to about 90% inhibition of the enzyme activity. Photooxidation of 21 histydyl residues also led to considerable inactivation of arginase. The modification of tryptophanyl and histidyl residues did not cause dissociation of the enzyme into subunits.


Adenine cycle in hepatopancreocytes of Helix pomatia (Gastropoda). Intact hepatopancreocytes were obtained from hibernating or active purinotelic snails, H. pomatia (Gastropoda). When incubated with [14C]glycine or [14C]formate, they synthesized de novo purine compounds, including also adenylates, adenosine and adenine. Hepatopancreocytes resynthesized also adenylates and other purine compounds from [3H]adenine or from [3H]adenosine split by the H. pomatia cell enzyme to adenine; the resynthesis of ADP+ATP was proportional to adenine concentration. Thus all reactions of the postulated adenine cycle: AMP leads to adenosine leads to adenine leads to AMP occur in the intact hepatopancreocytes; this cycle could probably be responsible for maintenance of the high level of adenylates during winter sleep.


Isolation of wheat ribosomes free of high molecular weight inhibitors of the natural messenger translation. The cell-free extract from wheat germ contains an inhibitor interfering with translation of a natural template (BMV RNA). The inhibitor affects neither the translation of poly(U) nor the aminoacylation of tRNA. It exhibits the activity of protein kinase (ATP:protein phosphotransferase, EC 2.7.1.37). The inhibitor is found in lipoprotein aggregates which can be separated from ribosomes on Sepharose 2B column. Ribosomes purified on the Sepharose are several times more active in translation of BMV RNA than those isolated by conventional methods.


Acyl esters of polyprenols: specificity of microsomal transacylase for polyprenols of different chain length and saturation. Transfer of fatty acids from phospholipids to polyprenols, catalysed by the transacylase from rat liver microsomes, was investigated. The specificity of the enzyme for polyprenols of different chain length and different degree of saturation was studied using individual isoprenologues, the preparation of which in highly tritiated form is described. It was found that short-chain polyprenols are better substrates for the enzyme than long-chain polyprenols, and alpha-saturated better than unsaturated or multiply saturated polyprenols. Short-chain, alpha-saturated single isoprenologues were several-fold more active as acyl acceptors than natural dolichol.


Methylation and tautomerism of 1-substituted 5-fluorocytosines. 1. Methylation and thiation of 5-fluorouracil led to 1,3-dimethyl-5-fluoro-4-thiouracil, the amination of which was examined under various conditions. At high dilution, and in the presence of a large excess of NH3, 1,3-dimethyl-5-fluoro-4-thiouracil was converted to 1,3-dimethyl-5-fluorocytosine in 60% yield. 2. Two procedures were employed for methylation of 5-fluoro-1-methylcytosine and 5-fluorocytidine. Treatment of each of these with diazomethane in alcohol-ether gave a complex mixture of products, the major one of which was the desired 3-methyl derivative. By contrast, treatment with methyl iodide in dimethylsulphoxide led exclusively to the 3-methyl derivatives in much better yeilds. 3. Ultraviolet absorption spectra and pKa values are presented for 1-substituted N-methyl-5-fluoro- and 5-bromo-cytosines. The basicity method was applied to determine the tautomeric equilibrium constants of the 1-substituted 5-halogenocytosines. The results show that the proportion of the imino forms of these compounds is of the same order of magnitude as for 1-substituted cytosines, and hence is unlikely to account for the observed mutagenic effects of 1-substituted 5-halogenocytosines.


Effect of anaerobiosis and glucose on the content of haem and its precursors in intact yeast cells. The content of haem and its precursors was determined in yeast cells grown under various conditions. The cells grown aerobically on 2% galactose contain about three times more haem (about 300 nmoles/g dry wt.) than the cells grown on 10% glucose. A trace amount of haem was found in anoxia irrespective of the carbon source used. The "efficiency" of the first enzyme of the haem biosynthetic pathway--delta-aminolevulinic acid (ALA) synthetase--expressed as the sum of all intermediates of the pathway in the cells grown on galactose, is similar in anaerobic and aerobic cells. The "efficiency" of the second enzyme--ALA dehydratase--is lower about three times both in anoxia and under conditions of glucose repression. In anoxia, not haem but delta-aminolevulinic acid is the main biosynthetic product. The role of glucose repression and of the feedback mechanisms in regulation of haem synthesis in yeast is discussed. A method for haem determination in the intact yeast cells, based on the formation of pyridine haemochrome, is described.


Conformation of the N(CH3)2 group in cytosine and in simple model pyrimidines and pyridines. Steric effects of ortho-methyl substitution on infrared spectra and molecular dipole moments. Infrared spectra of amino and dimethylamino derivatives with and without an ortho-methyl group of 4- and 5-substituted pyrimidines, 4-substituted pyridine, benzene and of the respective cytosines were recorded in the region of skeletal ring vibrations. Integrated intensities of ring vibration(s) v8 at about 1600 cm-1 sensitive to the presence of electron-donating substituents were used for elucidation of the steric effects of ortho-methyl on the mesomeric interaction between the -N(CH3)2 group and the ring. Molecular dipole moments were also determined experimentally in benzene for simple pyrimidine and pyridine derivatives and analysed vectorially with the use of component group moments in terms of the N(CH3)2 group conformation. The data point to a progressive twist of the dimethylamino group in hindered derivatives in the order: pyrimidine-5 greater than pyridine-4 greater than pyrimidine-4. They are also in agreement with the essential planarity of sterically crowded m41,4,4,5cytosine.


RNA synthesis in newly isolated and cultivated mesophyll protoplasts. Tobacco leaf mesophyll protoplasts exhibit low incorporation of [3H]uridine and 32P into RNA, up to 12 h of cultivation, irrespective of the presence of phytohormones. After 24 h of cultivation a dramatic increase in RNA synthesis is observed; it is the highest in the heterogeneous nucleoplasmic RNA fraction. The protoplasts cultivated in the absence of phytohormones show lower incorporation of precursors.


Structure and tautomerism of the neutral and monoanionic forms of 2-thiouracil, 2,4-dithiouracil, their nucleosides, and some related derivatives. Ultraviolet and infrared spectrophotometric techniques have been utilized to demonstrate that the monoanionic form of 2-thiouracil in aqueous medium consists of an equilibrium mixture of two tautomeric monoanions, one due to dissociation of the N1 proton, the other to dissociation of the N3 proton, in the approximate ratio 1:1. In contrast to 2,4-diketopyrimidines, and 4-thiouracil, where monoanion formation involves charge delocalization, the two tautomeric monoanions of 2-thiouracil appear to have the charge localized on the O4 position. The neutral forms of 2,4-dithiouracil and 2,4-dithiouridine are in the dithione form in both aqueous and non-aqueous media. The monoanionic form of 2,4-dithiouracil consists of a mixture of two tautomeric monoanions, the predominant one of which is that with the proton on the ring N3, and with charge delocalization on both isomeric monoanions. Such charge delocalization is also present in the monoanion of 2,4-dithiouridine. For the reference compound 2-methylthiopyrimidone-4, the dominant, virtually exclusive, form in chloroform is that with the hydrogen localized on the ring N3, whereas in aqueous medium there is a 1:1 equilibrium mixture of two neutral tautomeric forms, one with the hydrogen on N3, the other with the hydrogen on N1.


Oligo(A) and double-stranded segments in polyadenylated and non-polyadenylated RNA from cytoplasm and nuclei of chick embryo. Chick embryonic RNA was fractionated by affinity chromatography on oligo(dT)-cellulose and poly(U)-Sepharose into three classes: poly(A)+RNA containing poly(A) segments of 100 and more residues, poly(A)-oligo(A)+RNA containing oligo(A) segments of about 25 residues, and poly(A)-oligo(A)-RNA which bound to neither of the beds used and which contained double-stranded segments of 300 and more base pairs. These three classes of RNA were found in cytoplasmic as well as in heterogeneous nuclear RNA. Double-stranded segments in hnRNA, unlike those in cytoplasmic RNA, were intermolecular in nature; this may explain the occurrence of "giant" molecules in hnRNA.


[Hepatic function in vivo and in the isolated liver of rats poisoned with parathion]. Enzyme determinations and hepatic histological studies were carried out in normal rats and in rats intoxicated with the organophosphorus pesticide parathion. No significative evidence of hepatocellular damage was seen in parathion -- intoxicated rats as responsible of the impaired bile flow and sulfobromophthalein biliary excretion that were previously reported. On the contrary, the isolated perfused rat liver from normal and intoxicated rats showed a similar behavior when the perfusate flow through the liver was maintained at a similar rate. We conclude that altered hepatic blood flow may be a factor determinant of an impairment of bile flow and of biliary excretion of several organic anions like sulphobromopthalein that were observed in parathion -- intoxicated rats.


[Hodgkin's disease developing in the course of a chronic liver disease with ulcerative colitis immunosuppressed with azathioprine]. A case of a 49 year old patient suffering from ulcerative colitis and chronic hepatitis with cirrothic transformation is presented who under prolonged immunosuppressive treatment with azathioprine 50 mg daily and 10 mg daily of prednisone developed Hodgkins disease whose diagnosis was at the autopsy. The association between hepatic cirrhosis and lymphoproliferative disorders such as lymphosarcoma and lymphatic leukemia were already described (19,20). Recently, an article was published on a similar case to ours (23) in which the patient, suffering from chronic hepatopathy submitted to azathioprine and corticoids, developed Hodgkin's disease. The link between ulcerative colitis, the chronic hepatopathy and the development of Hodgkin's disease that could have arisen as a consequence of the prolonged immunosuppressive treatment are discussed. The apparition of malignancies in patients submitted to immunosuppression owing to renal transplantation are compared with the apparition of malignancies in patients submitted to immunosuppression because of a number of other diseases.


[Biliary lipids and the cholesterol saturation rate in relation to lecithin administration by oral route]. Lecithin is, at present, a contradictory drug to increase the solubility degree of bile cholesterol. Our main purpose in this work was to study the lipidic bile composition of gallstone patients under lecithin treatment, in order to value its action on biliary lipids and cholesterol saturation rate. Men and women with gallstones and radiologically functioning gallbladder were included. They were divided into 2 groups: "A", including 12 patients and "B", 13. In both groups, percentage values of cholesterol, phospholipids, total bile acids and cholesterol saturation rate were determined, before and after the administration of lecithin, everyday during a period of 30 years, 8 grams on group "A" and 2 grams placebo, on group "B". No significant differences were found in the studied samples. Before and after the administration of 8 grams of lecithin orally. Total bile acids: 67--78 +/- 4,42, 72,07 +/- 4,61 p greater than 0,05; cholesterol; 15,88 +/- 2,29, 1689 +/- 2,87 p greater than 0,05; phospholipids 16,25 +/- 3,10, 12,04 +/- 2,29 p greater than 0,05; cholesterol saturation rate; 1,70 +/- 0,24, 2,10 +/- 0,36 p greater than 0,05. It is concluded that lecithin orally administered on patients with the established characteristics and diet and the used methodology results in a useless treatment to increase the solubility of bile cholesterol.


[Caustic esophagogastric lesions].

[Caustic esophagogastric lesions]. The authors treated is an emergency, severe esofagogastric lesions, in adults, by caustics ingestions. They present seven cases and discuss six deaths. Critical analysis of these observations compared with the findings of pathology and in the literature, permit one to consider the therapeutic indications. The early surgical treatment is suggested as the best way to obtain a more acceptable survival.


[Intestinal resorption with 3H labeled enzyme mixture (wobenzyme)]. 0.2 g of an enzyme mixture (Wobenzym) labelled with 3H-acetic anhydride, were given orally to guinea pigs, which were arranged in 4 groups of 5 animals. The animals of each group were sacrificed at intervals of 30 minutes, 2, 4 and 24 hours after application. Radioactivity of the small and large intestine, plasma, urine, liver, heart, kidney, and skeletal muscle were determined. It could be shown that the labelled mixture of enzymes was absorbed from the intestine and was demonstrable in significant amounts in plasma, urine, heart, kidney, liver and skeletal muscle.


[Radiosynoviorthesis with yttrium-90-silicate. Results compared to aurum-198-colloid and whole body radiation load]. The results of the radiosynoviorthesis with yttrium-90 silicate in 36 joints, are reported. In comparison to the radiogold therapy in 64 joint, yttrium-90 was a little more effective. Additionally, the body distribution of radioactive yttrium after radiosynoviorthesis of knee joints, was measured in 6 patients. It could be shown that the uptake of the regional lymphnodes was between 4 and 5% of the yttrium administered. The radiation dose of the regional lymphnodes certainly exceeds 1000 rad. The results point to the importance of a careful selection of patients for radiosynoviorthesis.


[The effect of aldosterone antagonists in juvenile heart surgery]. In children with congenital heart disease duration and extent of hyperaldosteronism and the influence of spironolactone after surgery with a heart-lung-machine, were evaluated by direct measurement of plasma aldosterone levels. Secondary hyperaldosteronism as seen in 11 patients without spironolactone-therapy after surgery did not persist very long. 14 children receiving spironolactone immediately after surgery showed an onset of drug efficacy at a period when plasma aldosterone in the group without spironolactone had begun to fall. As a practical consequence, spironolactone treatment should be initiated a few days prior to surgery in order to achieve full efficacy on the day of surgery.


[Studies of the thrombocytopoietic factor. III. Modification of the method of determination of serum thrombocytopoietic activity]. A medification of the previously described method of thrombocytopoietic activity (ATS) determination is reported using mouse instead of rats as laboratory animals. This makes possible to reduce significantly the volume of blood necessary for ATS determination. The error of the method was 8.6--11.6% when the results were calculated in impulses per 1 mg of platelet protein (imp/mg BP) and 5.5--9.2% when presented as a percentage of total activity adsorbed to the platelets.


[Phytohemagglutinin-stimulated lymphocyte proliferation in a diffusion chamber in vivo]. Lymphocyte proliferation stimulated with phytohaemagglutinin (PHA) was studied in vivo. For control aims experiments were done also lymphocytes without PHA. In the investigations the technique of diffusion chamber was used. Chambers with lymphocytes (1 X 10(6) cells in a chamber) were implanted into the peritoneal cavity of mice. On the 1st, 3rd, 6th, 10th, 13th, 17th and 29th days of culture the number of cells and the proportions of blast cells and small lymphocytes were determined. It was demonstrated that peripheral blood lymphocytes exposed to PHA proliferated in vivo. This was expressed initially as a rise in the blood cell count and this rise decreased more slowly than the number of cells in non-stimulated cultures.


[Value of low ionic-strength salt solution in indirect antiglobulin tests with erhythrocytes]. A series of comparative investigations were carried out for estimation of the value of the indirect antiglobulin test (IAT) in the modification of Löw and Messeter in which a suspension of erythrocytes in low ionic-strength salt solution called by the authors LISS, is used for incubation of erythrocytes with tested serum, that is in phase I of this test. The results of these experiments demonstrated a significant superiority of this modification over the conventional techniques, particularly over the tile technique used generally in this country. The IAT-LISE method allows not only phase I to be reduced from 60 to 20 minutes, but increasing the intensity of the reaction it facilitates also detection of blood group antibodies and extends the range of their discovery, which is of particular importance in the compatibility tests before blood transfusion. These results were a basis for routine application of this method nad it was concluded that the IAT-LISS modification should be introduced widely in the Polish serological laboratories. Attention is called to a number of technical details important to obtain reproducible and une quivocal results.


Möbius syndrome. Neuropathologic observations. Neuropathologic findings in an infant with congenital right facial and bilateral lateral rectus palsy (Möbius syndrome) are presented. Multiple microscopic foci of necrosis were found in the lower pontine tegmentum, involving the region of the intramedullary course of 6th and 7th cranial nerves. The significance of pathologic findings in this infant and 14 additional published cases of Möbius syndrome is discussed.


Demyelination produced by experimental allergic neuritis serum and anti-galactocerebroside antiserum in CNS cultures. An ultrastructural study. Cultures of mouse cerebellum were exposed to sera from rabbits with experimental allergic neuritis induced by whole peripheral nerve immunization (WN-EAN) and to rabbit anti-galactocerebroside (GC) antisera, and were studied by electron microscopy. Both antisera produced almost identical demyelinative patterns. These consisted of large intramyelinic splittings, "smudged" changes of myelin, degeneration of oligodendrocytes, and phagocytosis of myelin by astrocytes, changes similar to those described after application of whole spinal cord-induced experimental allergic encephalomyelitis (WM-EAE) sera. In addition, patterns which have been considered more characteristic of in vivo demyelinative lesions have been found, susch as vesicular disruption of myelin lamellae and peeling off and phagocytosis of myelin by phagocytic mononuclear cells with electron dense cytoplasm. The morphologic similarities between demyelinative patterns in central nervous system (CNS) cultures induced by anti-GC antiserum and WN-EAN serum and WM-EAE serum, and the fact that elevated antibody titers to GC are found in sera from rabbits with WN-EAN and WM-EAE (Saida, et al., 1977), support the concept that anti-GC antibody is the major factor in the production of CNS demyelination in vitro by sera from rabbits with WN-EAN and WN-EAE.


Ultrastructure of neurofibrillary tangles in progressive supranuclear palsy. The fine structure of neurofibrillary tangles in the hippocampal gyrus, substantia nigra, pontine nuclei and locus coeruleus of the brain was postmortem studied in a case of progressive supranuclear palsy. Straight tubules and twisted tubules were observed in both the cortical and subcortical neurofibrillary tangles. Most tubules appeared separately in each neuron but a few straight tubules were mixed with the twisted tubules in the cortical tangles. The implication and possible significance of this findings are discussed.


T-tubule endocytosis in dystrophic chicken muscle and its relation to muscle fiber degeneration. Pectoralis muscles from normal and dystrophic chickens were investigated 2 h after an i.v. injection of horseradish peroxidase, by cytochemical and biochemical techniques to demonstrate peroxidase activity. Light microscopic examination of dystrophic muscles showed that peroxidase activity could be detected inside a population of fibers, in deliminated bodies often restricted to segments of the muscle fiber. Such bodies containing peroxidase were not observed in normal muscle fibers. Electron microscopy of dystrophic muscle fibers revealed that numerous vesicles containing peroxidase were frequently present in fiber regions with signs of cytoplasmic degradation. These vesicles, which occasionally were found to be coated, were 50--100 nm in size and appeared to be derived from t-tubules. Larger (up to 1.7 micrometers) inclusions containing peroxidase and delimited by a single membrane were also present at degenerating areas of dystrophic muscle fibers. These bodies seemed to be formed by fusion between several primary t-tubule vesicles and probably also lysosomes. Vacuoles containing the peroxidase were frequently encountered. Biochemical determination of horseradish peroxidase activity, performed after extensive washing of the muscle tissue, showed that dystrophic muscles contained about twice as much peroxidase as normal control muscles. It is suggested that endocytosis from t-tubules is an early and essential pathological phenomenon in dystrophic muscle fibers, which may be related to lysosomal function and muscle fiber degeneration


An ultrastructural study of the cerebrospinal fluid in visna. An electron microscopic examination was done on 8 samples of cerebrospinal fluid (CSF) from Icelandic sheep infected by the intracerebral route with visna virus. The specimens were collected 1 month, 2 months, and 4 years after infection. A differentail cell count done on low-power electron micrographs showed that the cellular exudate was composed of mononuclear cells mainly macrophages and lymphocytes with a few plasma cells. Macrophages were with one exception more numerous than lymphocytes and an increased proportion of macrophages showed evidence of phagocytosis with time after infection. Reactive lymphocytes were in general more numerous than small lymphocytes. Various stages in the maturation of plasma cells were observed. The cellular composition in the CSF is compatible with the view that visna is an immunopathological process. Myelin figures and fragments of myelinated axons were observed in two specimens indicating an active myelin-breakdown. The possibility that escape of myelin into the CSF may lead to sensitization to myelin antigens and perpetuation of this chronic neurologic affection is discussed. Visna virions could not be demonstrated.


Blood-brain barrier opening to horseradish peroxidase in acute arterial hypertension. Acute arterial hypertension was induced in male Wistar rats using two experimental techniques: (1) i.v. injection of Aramine and (2) infusion of physiological saline as a bolus via internal carotid artery. Horseradish peroxidase (HRP) was injected i.v. prior to both experimental procedures and subsequently localized in the brain by light and electron microscopy. In the saline infusion (pressure pulse) model, colloidal lanthanum was also applied as a diffusion tracer following fixation of the cerebral endothelium. In the Aramine model, extravsation of HRP correlated with abrupt elevation of blood pressure. In the pressure pulse model HRP extravasation was consistently visualized in the affected hemisphere. Electron microscopy showed consistent labeling of plasmalemmal vesicles by HRP in segments of cerebral endothelium. However, HRP was also clearly visualized in junctional pools suggesting focal opening of endothelial tight junctions as a pathway for extravasation of this tracer in both hypertensive models. Colloidal lanthanum not transported by plasmalemmal vesicles across endothelium after fixation of the brain also bypassed consecutive membrane appositions of endothelial tight junctions indicating existance of interendothelial pathways to macromolecules in acute arterial hypertension.


Apert's syndrome with central nervous system anomalies. The pathologic anatomy of the central nervous system is described in a patient with Apert's syndrome. Multiple developmental anomalies of the brain were noted including disturbances of rhinencephalic organization. The association between maldevelopment of the rhinencephalon and the face is well known. Cranial vault malformations may also be associated with maldevelopment of the rhinencephalon.


Pseudoviral hollow-cored vesicles in multiple sclerosis brain. Novel, superficially 'virus-like' hollow-cored particles 50--60 nm in diameter were found in the perivascular extracellular space of the brain from a patient who died with acute multiple sclerosis (MS). It is concluded that they are not virions but are derived from myelin undergoing vesicular demyelination. This case demonstrates the need for caution in the interpretation of unusual electron microscopic appearances.


Pituitary adenomas secreting more than two hormones. A case of pituitary adenoma secreting more than two hormones is presented. Morphological findings of this tumor have been correlated with biological behavior and with hormonal activity.


Encephalopathy in infantile hepatic cirrhosis. The cases are described of two sibs who developed hepatic cirrhosis in early infancy, accompanied by profound mental retardation. Post mortem in one sib there were multiple foci of demyelination with abundant cellular infiltration, scattered throughout the brain. These unusual pathological changes are briefly commented.


Optic neuropathy in a horse.

Optic neuropathy in a horse. A 10-month-old thoroughbred colt developed sudden complete blindness; no other neurological abnormality was detected. At necropsy 3.5 months later lesions were confined to both optic pathways in which there was extensive degeneration of axons and myelin and gliosis. The cause of the optic lesion was not determined but the lesion may be a toxic neuropathy.


Skeletal muscular atrophy in malignant tumour diseases: neurogenic or unspecific? Muscles from patients who had died from malignant tumours were examined with regard to changes in the intramuscular nerve twigs and the axon terminals or the motor end-plates, respectively. Three muscles from each of 120 cases were obtained at autopsy and stained with conventional methods. Nineteen cases with pronounced small-group and sometimes large-group atrophy were selected. Myelin and axon preparations displayed various changes of the small nerve branches and the axon terminals. Their significance for the atrophy frequently observed in the muscles of cancer patients is discussed.


Observations of amyloid angiopathy and senile plaques by the scanning electron microscope. Blood vessels with amyloid angiopathy and senile plaques in the cortices of the brains with Alzheimer's disease and senile dementia were observed by means of a scanning electron microscope. the results obtained were as follows: The blood vessels with amyloid angiopathy were surrounded by solid substances. The senile plaques consisted of rough solid substances, contained degenerated cell processes, and almost all plaques existed around the degenerated capillaries with amyloid angiopathy. From the above described findings, we suggest that the senile plaque has an extremely cose relationship to the capillary which had undergone amyloid angiopathy.


Neurofibrillary changes in the cerebral cortex of a patient with subacute sclerosing panencephalitis (SSPE). Biopsy fragments from the frontal cortex of one patient with SSPE were studied with ultrastructural methods. Special attention was given to the presence of neurofibrillary tangles observed in all cortical layers. These tangles were composed either of filaments with a diameter of 10 -- 12 nm or of paired helical filaments 22 -- 24 nm at their widest and periodically reduced to 10 nm about every 80 nm. These tangles were observed in all cortical layers, while those formed by single filaments were only visualized in layer 3. The simultaneous appearance of both types of tangles in the same patient suggests that they may be chemically related, which is in keeping with recent chemical data concerning the nature of the neurofilament protein subunit.


The role of Schmidt-Lanterman incisures in Wallerian degeneration. I. A quantitative teased fibre study. It is conventionally accepted that during the early stages of Wallerian degeneration of myelinated peripheral nerve fibres Schmidt-Lanterman incisures represent the sites at which the myelin sheath, together with enclosed axoplasm, is segmented into myelin ovoids. This mechanism is considered by some authors to be facilitated by the progressive intercalation of additional incisures in order to allow the later division of primary ovoids. We have demonstrated that this reported increase in the number of incisures is a misinterpretation of the changes occurring. By 36 h after crush of the rat sural nerve most myelinated fibres showed segmentation at incisures to form myelin ovoids. At 12 h and 24 h after crush, however, no ovoids were apparent and the number of incisures present was determined from teased fibres by light microscopy using oil immersion. There was no increase in the number of incisures either internodally or paranodally at 12 h and 24 h compared with a normal control population of fibres. However at 12 h, and to a greater extent at 24 h, incisures were more readily apparent than in normal fibres. It is likely, therefore, that previous reports have confused an increase in the number of incisures with an increase in their perceptibility resulting from their progressive dilatation.


The role of Schmidt-Lanterman incisures in Wallerian degeneration. II. An electron microscopic study. The electron microscopy of changes at Schmidt-Lanterman incisures in Wallerian degeneration has been described only briefly previously. We have demonstrated that the changes up to 36 h after nerve crush are chiefly peri-incisural. At 12 h and 24 h 'incisural dilatation' consisted of an intraperiod line separation of peri-incisural myelin lamellae, which began among inner (adaxonal) lamellae extending later to outer (abaxonal) lamellae. The incisure itself showed little or no change. At 36 h, ovoid formation was apparent in most fibres. The sites of fibre cleavage to form ovoids occurred adjacent to incisures at the focal regions of myelin lamellae separation. Even within ovoids the incisures themselves remained intact at 36 h. The fine structural changes at incisures following nerve crush provide an understanding of the increased perceptibility of incisures by light microscopy during early Wallerian degeneration.


Prekallikrein activator and kallikrein in acetone- and kaolin-activated rat plasma. Activation of plasminogen-free rat citrated plasma (RCPL-P) with acetone/kaolin yielded BAEe-esterase activities of 0.6--0.8 U/ml. Gel filtration demonstrated one single peak of BAEe-esterase activity (mol. wt. approximately 135000) with a kininogenase-esterase ratio (3.3) close to that known for human plasma kallikrein (2.7). Similarly activated rat citrated plasma (RCPL) revealed on gel filtration an additional esterase peak (mol. wt, approximately 47,000) with a low kininogenase-esterase ratio (0.3), and should accordingly not be used for a BAEe-esterase assay of rat plasma kallikrein. Acetone activation of RCPL-P and of RCPL yielded prekallikrein activator (PKA) activities which were about doubled by treatment with kaolin to 1.9--2.1 and 3.5--4.2 PKA-U/ml respectively. Gel filtration of acetone-activated RCPL-P or RCPL revealed two peaks of PKA activity, mol. wt. approximately 110,000 corresponding to activated factor XII (XIIa), and mol. wt. approximately 33,000 corresponding to XII fragments (XIIf). Kaolin-treatment of acetone-activated RCPL-P, but not of RCPL, caused an extensive fragmentation of XIIa to the 4--6 times more active XIIf. The lower yield of PKA-activity in acetone/kaolin-activated RCPL-P, as compared with activated RCPL, seems to be due to the absence of a factor of significance for the activation of factor XII, which is not plasmin, plasma kallikrein, or high molecular weight kininogen.


The succulent euphorbias of Nigeria. III. Structure and potency of the aromatic ester diterpenes of Euphorbia poissonii Pax. The latex of Euphorbia poissonii was found to contain irritant aromatic diterpene esters based upon resiniferonol, 12-deoxy-16-hydroxy-phorbol and 12-deoxyphorbol. Four resiniferonol esters, 9,13,14-ortho-phenylacetyl-resiniferonol-20-0-[p-hydroxy-phenylacetate]; 9,13,14-orthophenylacetyl-resiniferonol-20-0-[m-methoxy-m'-hydroxy-phenylacetate]; 9,13,14-orthophenylacetyl-resiniferonol-20-0-acetate and resiniferonol-14-0-phenylacetate-20-0-[m-methoxy-m'-hydroxy-phenylacetate], were identified. Two further esters were identified as 12-deoxy-16-0-[2-methylbutyroyl]-phorbol-13-0-phenylacetate-20-0-acetate and 12-deoxy-16-0-[2-methylbutyroyl]-phorbol-13-0-phenylacetate. These compounds represent the first aromatic esters of this parent diterpene to be obtained from natural sources. The third group of compounds were identified as 12-deoxyphorbol-13-0-[p-hydroxy-phenylacetate]-20-0-acetate; 12-deoxyphorbol-13-0-[p-acetoxy-phenylacetate]-20-0-acetate; 12-deoxyphorbol-13-0-phenylacetate-20-0-acetate and 12-deoxyphorbol-13-0-phenylacetate. The irritant potency of the ten pure compounds was obtained using a mouse ear method for assessment of the irritant dose 50%.


Interaction studies between three antidepressant drugs (chlorimipramine, imipramine and zimelidine) and noradrenaline, tyramine and vagal stimulation on the heart rate and blood pressure in dogs. Anaesthetized Beagle dogs were given increasing intravenous doses of imipramine, chlorimipramine or zimelidine. At each dose interval the interference of the drug administered with the effects on blood pressure and heart rate of vagal stimulation, NA injection and tyramine injection was investigated. Also, the in vitro uptake of 5-HT into platelets after in vivo administration to unanaesthetized dogs of 5 mg chlorimipramine or 5 mg zimelidine was studied. Chlorimipramine and zimelidine were found to be about equipotent as regards 5 HT-uptake into platelets after in vivo administration. Imipramine and chlorimipramine potentiated the effects of NA after the 2 mg/kg dose. Imipramine but not chlorimipramine interfered with the effects of tyramine after the 4 mg/kg dose. Zimelidine did not interfere with either NA or tyramine at any dose level studied (maximal cumulative dose 62 mg/kg). The effect of vagal stimulation was significantly inhibited after 8 mg/kg (cumulative dose 14 mg/kg) of imipramine and 16 mg/kg (cumulative dose 30 mg/kg) of chlorimipramine and zimelidine, respectively. It is concluded that zimelidine in comparison with imipramine and chlorimipramine has no or at most a slight effect on peripheral adrenergic neurones. It has less pronounced anticholinergic properties than imipramine but is about equipotent to chlorimipramine in this respect.


The binding of phenprocoumon to human plasma proteins. By in vitro experiments with equilibrium dialysis and 5 micrograms PPC per ml an average of 99.7 +/- 0.2% was bound to serum proteins. The binding in a solution with the albumin concentration which was present in the serum samples did not differ from this binding or from the binding in plasma where coagulation was prevented with either heparin or citrate. The binding constant in albumin solutions at 37 degrees was 4.5 +/- 0.31/mol x 10(-5) and an average of 1.16 +/- 0.04 primary binding sites was found. The association constant for the PPC albumin interaction was temperature dependent and the results of thermodynamic calculations suggested a combined ionic and non-polar type of binding as the change in enthalpy contributed with 40% of change in free energy. A large positive entropy change was found (15.79 Kcal/mol/degree K). The addition of phytomenadione to albumin solutions and of menadione to plasma caused a considerable decrease in the protein bound fraction of PPC, indicating the relevance of a study concerning the possible clinical consequences of these interactions.


Haematological effects of nickel toxicity on a fresh water teleost, Colisa fasciatus. Colisa fasciatus, a freshwater teleost, were exposed for 90 hrs to 45 p.p.m. nickel sulphate under static test conditions. The treatment resulted in leucopenia due to reduction in the number of small lymphocytes and polycythemia with concomitant increases in the haematocrit and haemoglobin values, and in retardation of the erythrocyte sedimentation rate of the moribund fish. No differences in total thrombocyte count, clotting time, and hepatosomatic index were found between the control and the treated fish. Lymphopenia and erythrocytosis may be used in presumptive monitoring nickel toxicity in fish.


Displacement of nortriptyline and uptake of 14C-lidocaine in the lung after administration of 14C-lidocaine to nortriptyline intoxicated pigs. Six anaesthetized Swedish land-race pigs were intoxicated by an intravenous infusion of nortriptyline-HCl (NT) up to a concentration of 4.58 +/- 0.58 (mean +/- S.E.M.) microM in arterial whole blood. A rapid injection of 2 mg/kg b.wt. lidocaine-HCl in the right atrium was followed by a rise in arterial whole blood concentration of NT up to a maximum of 7.32 +/- 0.28 microM NT. Amount displaced NT from the cardio-pulmonary circulation after the 14C-lidocaine bolus, was calculated to be 0.66 +/- 0.03 mumol. Lung uptake of 14C-lidocaine during first-pass through the lung was not influenced to any statistically signficant degree compared to a control group. Thus, first pass uptake (FPU) was 30 +/- 8 (mean +/- S.E.M.)% and 39 +/- 5% respectively. The duration of the QRS-complex of the ECG was increased (P less than 0.01) during the infusion of NT from 0.07 +/- 0.01 (mean +/- S.E.M.) sec. to 0.14 +/- 0.02 sec. when 250 mg NT-HCl had been administered. The QRS-duration was decreased (P less than 0.01) after the injection of the 14C-lidocaine bolus to 0.09 +/- 0.01 sec. Mean arterial blood pressure and heartrate decreased slightly during the infusion of NT, but did not change immediately after the 14C-lidocaine bolus.


Interaction of salicylates and other non-steroidal anti-inflammatory agents in rats as shown by gastro-ulcerogenic and anti-inflammatory activities, and plasma concentrations. The interaction of salicylates and other non-steroidal anti-inflammatory drugs was studied in rats. Concurrent oral administration of sodium salicylate (SS) or salicylic acid (SA) and indomethacin (IND) significantly reduced the gastro-ulcerogenicity and the plasma concentrations of IND. Acetylsalicylic acid (ASA) failed to do so. IND had no significant influence on plasma concentrations of SA. Simultaneous administration of SS and IND intraperitoneally or subcutaneously showed the same pattern of interaction as for oral administration. Concurrent oral administration of SS and IND exerted similar anti-inflammatory activity as the single drugs. SS significantly antagonized the ulcerogenicity of ibuprofen and tended to antagonize the ulcerogenic activity of ASA, phenylbutazone, tolfenamic acid and naproxen. The results suggest that in rats SS and SA (but not ASA) interact with IND concerning both gastro-ulcerogenicity and plasma concentrations of IND (but not of SA) and that the interaction is systemic in nature. We propose that the ulcerogenic interaction might be explained partly by the reduced IND plasma concentrations and partly by a weaker inhibition by SS of the prostaglandin system in the rat stomach.


Intravenous glucose tolerance in lithium treated rats. A method for performing intravenous glucose tolerance tests in anaesthetized rats was developed, and factors influencing basal glucose tolerance was investigated. Glucose tolerance increased with increasing weight and body temperature, but decreased with fasting. Lithium administration increased glucose tolerance. The increase varied with the dose and the time interval between administration and glucose tolerance test. There was an immediate increase in glucose tolerance after lithium administration, which lasted under special conditions up to 24 hours. The duration was depending on the dose given and the fasting state of the animal.


Interactions between 1,2--propanediol (propylene glycol) and hexobarbital. The interaction between 1,2--propanediol and hexobarbital was studied with an anaesthesia threshold method, where hexobarbital is infused intravenously. The dose needed to obtain a burst suppression of one second or more is determined and given as per cent of a pre-experimental value obtained in the same rat. The effect of varying the interval between the intraperitoneal injection of 1,2--propanediol (2.06 g/kg) and the threshold determination was investigated. In the intervals, 10--50 min., the hexobarbital threshold doses were significantly decreased by 13--27% (n = 7--18). Four different doses between 0.25 and 2.06 g/kg of 1,2--propanediol were then tested after a fixed interval of 30 min. As in the time interval study the thresholds after 2.06 g/kg were significantly decreased. No certain depressant effect was seen with 1.03 and 0.52 g/kg. With the lowest tested dose of 1,2-propanediol (0.25 g/kg) there was instead a significant increase in the threshold dose (13%). This might be an excitatory effect, which could correspond to the well-known effect, seen with low doses of other depressants for instance ethanol.


The gliovascular interphase in irradiated brain tissue. Electron microscopic investigations. Horseradish peroxidase transport. The gliovascular interphase in irradiated brain tissue. Electron microscopic investigations. Horseradish peroxidase transport. Acta physiol. pol., 1979, 30 (4): 455--468. The gliovascular junction which is the morphological element of the blood-brain barrier was studied. For damaging the barrier 44 Wistar rats received single dose of 800 rads of gamma radiation from Co60. The observations were carried out in electron microscope and capillary permeability was tested by means of horseradish peroxidase. It was found that: astrocytes play a significant role in the normal function of the barrier maintaining efficient active transport, the capillary vessel is a barrier to transport of macromolecular substances which cannot pass into the brain tissue under normal conditions.


'Distensibility' of the papaverine-relaxed vascular bed in human subcutaneous tissue. The effect of an increase in vascular transmural pressure upon the blood flow in two subcutaneous vascular beds, maximally dilated by papaverine was studied in 6 healthy humans. Blood flow was measured on the dorsum of the hand and at the lateral malleolus by the local 133Xe washout technique. Increase in vascular transmural pressure was induced by lowering the labelled area various distances below heart level. Lowering the area caused an increase in blood flow. The increase was less pronounced in the legs than in the hand. As arterial perfusion pressure head remained constant during lowering, this indicates that the relative decrease in vascular resistance was smaller in the leg than in the hand. Experimental edema did not influence the relative decrease in vascular resistance. The results suggest that 'distensibility' of the resistance vessels is smaller in the leg than in the hand. This might be due to a structural adaptation of the vascular wall in vessels often subjected to increased hydrostatic pressure.


Chronoendocrinological studies in athletes. Circadian rhythms of T3, TSH, cortisol and testosterone. Endocrine functions were studied in 83 healthy athletes, maintained under normal light-dark conditions, with normal activity-sleep patterns. In these subjects statistically significant circadian rhythms of T3, TSH, cortisol (CSL) and testosterone (T) were found; for each hormone two or three different types of circadian rhythm (with peaks of acrophase between: 6.30 a.m. and 1.30 a.m., 1.30 p.m. and 10.30 p.m., 10.30 p.m. and 6.30 p.m.) were observed. The following correlations have been demonstrated between the length of participation (in years) in performance sports and the mean circadian blood hormone concentration: a negative one for CSL (p less than 0.01) and a positive one for TSH (p less than 0.05). An increase of the mean circadian values of T concentration in venous blood was found in females fencers (n = 9).


Chronoendocrinological studies in athletes. Circadian rhythms of HGH and IRI. The serum concentrations of HGH and IRI studied over a 24-hour span in 83 healthy athletes under normal rest conditions in a normal living environment show statistically significant rhythms, validated and quantified by cosinor analysis; for each hormone three different types of the circadian rhythm (with a peak of acrophase between: 6.30 a.m. and 1.30 p.m., 1.30 p.m. and 10.30 p.m., 10.30 p.m. and 6.30 a.m.) were observed. The IRI response to a meal load underwent cyclic variations during the day.


Effect of 2,3-diphosphoglycerate (2,3-DPG) on haemoglobin affinity to oxygen in fetal and early postnatal period of life in pigs. The reported investigations demonstrated a low concentration of 2,3-DPG in fetal erythrocytes (4.52 mumol/g Hb) and a high affinity of haemoglobin in these erythrocytes to oxygen (P50 = 4.35 mm Hg) as compared with the values in adult pigs (30.91 mumol of 2,3-DPG/g Hb and P50 = 7.36 mm Hg). In the postnatal period the values of these parameters changed rapidly, with the most intense changes taking place within the first three days of life of suckling pigs, and the values typical of adult pigs were reached about the seventh day of life. No differences were observed in the structure of fetal and adult haemoglobin. The affinity to oxygen of haemoglobin solutions obtained from fetuses and adult pigs without 2,3-DPG was identical, and addition of exogenous 2,3-DPG caused indentical shifts of the dissociation curves of both haemoglobins. The factors responsible for the differnces in haemoglobin affinity to oxygen in the development of pigs are changes in the concentration of 2,3-DPG in the erythrocytes.


The effects of changes in the carotid sinus baroreceptor activity on splanchnic blood flow in anesthetized man. In 9 patients being subjected to abdominal surgery, electromagnetic blood flow measurements were obtained from the hepatic, mesenteric and iliac beds while the carotid sinus baroreceptors were stimulated by carotid sinus massage. Carotid sinus stimulation produced an average maximum decrease in mean arterial pressure of 21%. Hepatic and mesenteric blood flows decreased by 15% and calculated vascular resistances were not significantly changed in these vascular beds. Iliac blood flow, on the other hand, showed a slight increase and iliac vascular resistance was decreased by 29%. It is concluded that the splanchnic vascular bed is of less importance in the carotid sinus baroreflex control of systemic arterial pressure in anesthetized man.


Principal mechanisms controlling penile retraction and protrusion in rabbits. The effects on penile volume of nerve stimulations and drugs injected into the systemic circulation were studied plethysmographically. Dilator responses at selective perfusion of the penile artery were studied by measuring the perfusion pressure. The main results and conclusions are: The penis has an adrenergic vasoconstrictor supply coming from the sacrococcygeal parts of the sympathetic chains. A very low (0.2 Hz) vasomotor tone keeps the penis relaxed. If this tone is interrupted the penis will protrude but autoregulation will soon take over and eventually produce hyperinvolution of the penis. Two vasodilator paths, both with pelvic ganglionic relays, were found. 1) The pelvic parasympathetic nerves, probably having mainly non-cholinergic postganglionic neurons and operating quite effectively at low frequencies. 2) The sympathetic hypogastric nerves, presumably having at least partly cholinergic postganglionic neurons which, apart from muscarinic dilation of minute inflow resistance vessels to the erectile tissue, may also work by suppression of excitatory adrenergic neurotransmission. The pelvic and hypogastric vasodilator outflows work synergistically. The vasoconstrictor nerves are very strong and efficient antagonists of the vasodilator nerves.


Certain phosphate compounds in the erythrocytes of patients with primary hyperlipidaemia. The investigations were carried out in 30 patients with primary hyperlipidaemia (hypercholesterolaemia, hypertriglyceridaemia and mixed form). The serum total cholesterol and triglycerides, and in the erythrocytes the levels of AMP, ADP, ATP, ATP complex with Fe, MP, HDP and DGP were determined. Twenty blood donors served as a control group. The obtained results showed a statistically highly significant rise in ADP concentration in all investigated subgroups of hyperlipidaemic subjects, and a non-significant quantitative shift of other determined phosphate compounds.


Analysis of the length response to a force step in smooth muscle from rabbit urinary bladder. Responses to isotonic quick release of AC-stimulated smooth muscle strips from rabbit urinary bladder were analysed. Releases were performed at the peak of contraction and at a preset tension level in the contraction and relaxation phase. In other expts. responses at 37 degrees C and 27 degrees C were compared. The length response always consisted of 3 parts: (1) elastic recoil, (2) rapid length change (isotonic transient), (3) steady length change. Qualitatively, phases (1)-(3) could be distinguished also in responses to isotonic quick stretch. The immediate elastic recoils, phase (1), were described by exponential stress-strain relations. Stiffness was found to be somewhat lower during relaxation than during contraction. No effect of temperature on the elastic recoil was seen. The initial velocity in phase (2) was 2-3 times greater than the velocity 100 ms after release. By means of computer analysis of the length records during phases (2) and (3) two decaying exponential processes with widely different time constants could be separated. The time constant of the faster process was of the order of 15-30 ms at 37 degrees C. It decreased with increasing force steps and with increasing temperature. The amount of shortening associated with this process was correlated with the size of the force step, reaching a maximum of about 1.2% of the muscle length. The shortening velocities in phase (3), measured 100 ms after release, were described by Hill's equation. Vmax in the rising part and at the peak of contraction were 0.7 and 0.6 L/s respectively at 37 degrees C. Lower values were found during relaxation and at 27 degrees C. We suggest that part of the elastic recoil in phase (1) occurs in structures associated with the individual cross-bridges, that phase (2) is dominated by a change in the distribution of conformations of bridges in the attached position and that the shortening rate in phase (3) is determined by the entire cycle of events during turnover of bridges after the muscle has adapted to the new load. Observations on the force response to length steps and on shifts from isometric to afterloaded isotonic contraction and vice versa are consistent with this interpretation.


Glucagon effect on glycogen content of chicken liver and muscles. The experiments were carried out on broiler chickens divided randomly into two groups differing in the feeding level and, consequently, in the rate of weight gain. Half the chickens in each group were given a single dose of glucagon 150 micrograms/kg, and the other half received a control solution of glycine buffer. The chickens were investigated 1--1.5 hour after feeding and after 18--20 hours of starvation using the technique of biopsy of the liver and the external pectoral muscle. In the biopsy specimens the glycogen level was determined immediately before glucagon administration and 30--60--90 minutes after the injection. It was found that glucagon injection caused either a rise or a fall in the glycogen level in the liver and that the trend of these changes depended on the feeding level of the chickens and on the duration of starvation of the birds before treatment. The glycogen level in the pectoral muscle of the chickens kept on the higher feeding level was observed to fall one hour after glucagon administration.


Electromechanical delay in skeletal muscle under normal movement conditions. Electromechanical delays (EMD), the time from onset of EMG activity to change in acceleration or deceleration of the forearm, were studied in concentric and eccentric contractions of biceps and triceps brachii muscles. Horizontal flexion and extension movements were performed at varying speeds by 10 subjects. EMD time in concentric contractions for biceps was 41 +/- 13 ms and for triceps was 26 +/- 11 ms and was not influenced by the velocity of the movement. In eccentric contractions at the slow velocity the biceps EMD time was 38 +/- 13 ms and shortened to 28 +/- 10 ms at the faster velocity. The eccentric triceps EMD, however, was not significantly altered by movement velocity and averaged 30 +/- 7 ms. The data provided support for the hypothesis that stretching of the series elastic component, to a point where muscle force can be detected, is the primary determinant of the EMD phenomenon. However, there are complex interactions of the effects on EMD of muscle fiber type composition, whether the contraction is concentric or eccentric, and the velocity of the movement as well as possible gamma system influence. These complications require that consideration of electromechanical delay be made when phasic relationships between muscle force or joint torque generation from different muscles are inferred from EMGs.


Heparin effect on the activity of certain lysosomal hydrolases in dog pancreas (in vivo investigations). The effect of heparin doses of 1.5 and 6.0 mg/kg of body weight on pancreatic lysosomes was investigated in vivo in dogs. Latent activity of beta-glucuronidase, acid phosphatase and cathepsins in whole pancreatic homogenate, in the subfraction sedimenting at 15 000 x g, and in the supernatant was determined as an index of lysosomal stability. In the whole homogenate a rise in the total activity of beta-glucuronidase was observed, proportional to heparin dose while there was no effect of heparin on the latent activity of beta-glucuronidase and acid phosphatase. On the other hand, the proportion of the latent activity of cathepsins in their total activity increased in heparin-treated dogs, which points to a direct stabilizing effect of the drug on pancreatic lysosomes in the dog. Investigations of subfractions gave, in part only, results approaching those obtained in the whole homogenate.


Gastric acid secretion and drinking in the Atlantic cod (Gadus morhua) during acidic or hyperosmotic perfusion of the intestine. Cods were equipped with cannulae for drainage of the stomach and for separate perfusion of the stomach and intestine. Acidity, volume, and osmolality of the gastric outflow were measured. During perfusion of the intestine with a near-isosmotic saline (1 part sea-water, 2 parts distilled water, '33% SW') and the stomach with pure ('100%') SW, gastric acid output was high and volume output slightly above the infused volume. The osmolality of the gastric perfusate decreased during passage of the stomach. It was concluded that no drinking occurred, and that the decreased osmolality was due to dilution by gastric secretions and osmotically lost water. When substituting the isosmotic intestinal perfusion to a dehydrating perfusion (100% SW), gastric acid secretion was depressed but volume output was unaffected. Also perfusion of the intestine with acidified 33% SW depressed gastric acid secretion and in addition increased volume and osmolality of the gastric outflow. The results suggest that perfusion of the intestine depress the drinking reflex and that this depression is surmounted by intestinal acidification. Possible mediators of the intestinal feed-back mechanism for the inhibition of gastric acid secretion are discussed.


Effects of 1,3-diaminopropane on testosterone induced hypertrophy and polyamine synthesis in mouse kidney. The effects of prolonged treatment with 1,3-diaminopropane, a structural analogue of putrescine, on polyamine metabolism and growth in kidney tissue, were studied in mice in which renal hypertrophy was induced by testosterone treatment. Injections of 1,3-diaminopropane resulted in an almost total suppression of the testosterone induced stimulation of ornithine decarboxylase activity and prevented the accumulation of putrescine and spermidine in the kidneys. Renal spermine concentration was even lowered. Administration of 1,3-diaminopropane effectively prevented the testosterone induced increase in renal weight and RNA. In mice receiving 1,3-diaminopropane proteinuria was observed and histological examination revealed renal damage. Due to the nephrotoxic action of 1,3-diaminopropane caution is essential in relating the prevention of renal hypertrophy and the inhibition of polyamine synthesis.


Human forearm and kidney conversion of arachidonic acid to prostaglandins. The capacity of the human forearm and kidney to synthetize different prostaglandins (PGs) was studied, together with the quantitative relationship between the various PGs formed in these organs. 14C-labelled arachidonic acid (14C-AA) was infused in healthy male volunteers at a constant rate into the brachial or the renal artery, with simultaneous sampling of regional venous blood. The venous plasma content of 14C-PGs was extracted, separated with thin-layer chromatography (TLC) and quantified using fractionated liquid scintillation spectrometry. Most of the 14C-AA infused was metabolized and radiopeaks parallel to unlabelled standards of PGD2, PGE2, PGF2 alpha, 6-keto-PGF1 alpha and 13,14-dihydro-15-keto-PGE2 (Me) were obtained. The chromatograms of both the forearm and the kidney plasma contained all the peaks described, but the relative distribution of the 14C-PGs differed between the two tissues. In the cubital venous plasma, the main PG (apart from Me) was 6-keto-PGF1 alpha, indicating a considerable synthesis of PGI2 in the forearm. In the renal venous plasma, on the other hand, PGD2 accounted for the largest part of the authentic 14C-PGs found. Besides the tissue differences, large inter-individual variations were observed. The results demonstrate the existence of both a considerable tissue specificity and an appreciable inter-individual variation in the local conversion of AA to PGs in man.


Ribonuclease activities in developing experimental granulation tissue with reference to polysomes. The Mg2+-precipitable polysomes in experimental granulation tissue increase up to three weeks and decrease slowly thereafter. Polysomes from young granulation tissue are, on a weight basis, more active in cell-free protein synthesis than polysomes from old granulation tissue. RNase activity is highest in polysomes from 1-week tissue. The polysomes contain both acid and alkaline RNase, but the alkaline RNase is the latent form, manifested by the addition of p-chloromercuribenzoate (pCMB). The high RNase activity of granulation tissue renders the analysis of polysomal patterns and functions of the polysomes difficult. In the post-polysomal supernatant of granulation tissue the RNase activity is highest in 2-4 week old tissue; it is maximal at pH 7-8 and only slightly influenced by pCMB.


Changes in penile volume during some cardiovascular reflexes and reactions in rabbit. The effect of various cardiovascular reflexes and reactions on the plethysmographically recorded penile volume in rabbit was investigated. Stimulation of the aortic nerve or direct stimulation of the carotid sinus produced increase in penile volume, while carotid occlusion produced decrease. Brief volume load or protoveratrine given into the right atrium produced increase in penile volume. Asphyxia, hypercapnia, hypoxia, cyanide and lobeline produced decrease in penile volume, while hypocapnia increased it. Moderate blood taps decreased penile volume, while hypocapnia increased it. Moderate blood taps decreased penile volume. With the exception of the response to asphyxia all these reactions required intact vasomotor nerves. Clonidine increased penile volume if vasomotor nerves were intact but decreased it if the penis was decentralized. Penile volume decreased in shivering animals but increased on warming. Carotid occlusion impaired erectile responses to hypogastric and pelvic nerve stimulation. In certain experiments this effect was more pronounced in the latter case. It is concluded that the medullary neuron pool responsible for penile vasomotor tone participates in general reflex cardiovascular homeostasis and that this may have implications for normal erectile responses.


Intramural blood flows and flow distribution in the feline small intestine during arterial hypotension. The vascular reactions of the parallel-coupled vascular sections of the small intestine were studied during hypotension at two different levels of intestinal arterial inflow pressure, using a 85Kr elimination technique. The regional hypotension was accomplished by partially occluding the superior mesenteric artery with a clamp and maintained for 2 h. At the higher level (50-55 mmHg) total intestinal blood flow decreased but not to the same relative extent as blood pressure due to the autoregulatory capacity of the intestinal vascular bed. The flow autoregulation was also reflected in a decreased blood flow resistance. The distribution of blood to the muscularis and mucosa-submucosa layer, respectively, did not change significantly during or after hypotension as compared to the prehypotensive level, since the relative flow decrease was the same in the mucosa-submucosa and in themuscularis. At the lower arterial pressure level (30-35 mmHg) a more marked decrease of intestinal blood flow and flow resistance was observed as compared to the experiments performed at the 50-55 mmHg pressure level. Moreover, muscularis blood flow was relatively more decreased than blood flow in the mucosa-submucosa implying the fraction of total blood flow diverted to the muscularis was significantly decreased. Despite this redistribution of blood flow, a histological damage was apparent only in the mucosa, particularly at the villous tips.


Studies on ocular blood flow and retinal capillary permeability to sodium in pigs. A surgical technique was developed in pigs that permits access to the retinal venous plexus surrounding the optic nerve. The effect of surgery on ocular blood flow and capillary permeability was evaluated. Blood flow, determined by the labelled microsphere technique, did not differ significantly between operated and control eyes. Increased intraocular pressure in the operated eye reduced blood flow through the choroid and the anterior uvea in proportion to the reduction in perfusion pressure, while in the retina a smaller reduction in blood flow occurred indicating that autoregulatory mechanisms are involved in the control of retinal blood flow. The capillary permeability to sodium was studied by the single injection technique, using albumin as a reference substance. The fractional initial extractions from the choroidal and the retinal vessels were 0.77 and -0.001 respectively. The absence of a sodium extraction from the retinal vessel indicates that this part of the blood-retinal barrier was intact and that the blood drained by the retinal plexus is not mixed with blood from other sources.


Effect of vagus nerve stimulation on the secretory-granule volume of the principal cells of the mouse gallbladder epithelium. Experiments in mice were performed in order to investigate whether vagal activity could affect glycoprotein secretion from gallbladder principal cells. This cell type was studied with the electron microscope in control animals and after electric stimulation of the right or left nervus vagus. The volume density of glycoprotein containing granules was determined using morphometry. It was found that stimulation of the left vagus nerve significantly reduced the relative cellular volume of secretory granules in the principal cells of the gallbladder. Right vagus stimulation was accompanied by a weak but insignificant increase in secretory granule content. It is suggested that the left vagus nerve may exert a direct influence on glycoprotein secretion from gallbladder principal cells.


A study on the role of endogenous prostaglandins in the development of exercise-induced and post-occlusive hyperemia in human limbs. The contribution of endogenous PGs to the development of functional (exercise-induced) and reactive (post-occlusive) hyperemia was investigated in healthy volunteers. Leg blood flow during dynamic leg exercise was estimated by an indicator dilution technique. Forearm blood flow during supine leg exercise and forearm and calf blood flow following 5 min of arterial occlusion were measured plethysmographically. All subjects were examined before and after pretreatment with indomethacin, a PG synthesis inhibitor. During leg exercise, and in the absence of indomethacin, a 10-fold rise in leg blood flow was observed. Forearm blood flow increased moderately. Both these blood flow effects of exercise were unaffected by indomethacin. Following arterial occlusion a marked hyperemia developed in the forearm and the calf. Indomethacin significantly reduced the magnitude of the reactive hyperemia both in the forearm and in the calf, decreasing both the peak value and the duration of the vasodilation. These data reveal differences between the mechanisms behind functional and reactive hyperemia in man, suggesting an appreciable contribution of endogenous PGs to post-occlusive vasodilation only.


Effects of somatic treatments on mood in endogenous depression. The effects of ECT, amitriptyline, clomipramine, maprotiline and desipramine on the course of endogenous depression were compared in 105 patients using repeated self-administered mood questionnaires as the outcome measure. Remission was more rapid after ECT therapy than psychopharmacological treatment, but the absolute improvement did not differ significantly between ECT and other somatic therapies. Improvement in response to clomipramine was more rapid than to other psychopharmacological agents, and did not differ from that in response to ECT. The advantages and disadvantages of ECT for endogenous depression are discussed.


Interprofessional communicability and reliability of the Comprehensive Psychopathological Rating Scale (CPRS) as assessed by video-taped interviews. Five raters: two experienced psychiatrists, two psychologists (one acquainted with the use of the scale and one new to it) and an untrained social worker, participated in training sessions in the use of the CPRS. Videotaped interviews were used for assessing the level of inter-rater reliability and the communicability of the CPRS to unexperienced raters. As in previous studies, it was found that the CPRS is easily communicable and that a very satisfactory level of agreement among raters can be achieved.


Factors affecting the experience of the initial psychiatric consultation in outpatients with anxiety states. The experience of the first consultation was measured by a questionnaire in 42 outpatients with neurotic anxiety tension states. The correlation between this experience and the doctor's level of experience, the sex combinations of doctors and patients and the personality of the patient, as measured by an inventory 1-2 years after the end of the drug study (35 patients completed the inventory), was studied. Patients who had had a more favourable experience had more often been interviewed by doctors with longer psychiatric experience. Female patients tended to report a more favourable experience with male doctors than male patients did. Patients with a less favourable experience deviated more from the norms of the personality inventory with regard to, for instance, passive dependency than patients with a more favourable experience did, but the difference between the groups was not significant.


Electrooculographic (EOG) findings in manic-depressive illness. An electrooculographic (EOG) study was carried out in 20 depressed (12 with retarded and eight with agitated depression) and in 12 manic patients. Compared with controls, EOG ratios obtained from our patient's groups differed significantly and were low in depressive and high in manic patients. Appropriate treatment (tricyclics to depressives and haloperidol to manics) restored EOG ratio values to control levels. The observed EOG changes in manic-depressive illness are discussed in terms of their origin and the involvement of a neuroendocrine, dopamine-controlled, mechanism is postulated.


Factors related to drug compliance and attrition in neurotic outpatients treated with anxiolytics. Forty-six outpatients with anxiety-tension states took part in a study on the effects of anxiolytic drugs. At the first interview ratings were performed and the patients answered a questionnaire as to their experience of the consultation (n = 42). Based on follow-up examinations after 2, 4 and 8 weeks, three groups were formed: completers, who did not experience side-effects to be of such intensity that they changed the recommended dose (n = 15); deviators, who due to side-effects changed the recommended dose temporarily or permanently (n = 20); and attritors (n = 7). One to two years after the end of the drug study a personality inventory was sent out by post. It was returned by 35 patients. 1) Completers, deviators and attritors were similar with regard to age, education and social class. 2) They were also similar with regard to initial distress level. 3) Completers had the highest scores on scales measuring the personality traits defence of status and guilt-feelings and on the factor inex neurotic self-assertiveness, while attritors had the lowest scores. 4) Completers, deviators and attritors were similar with regard to experience of the first consultation. 5) Patients with a more favourable experience of the first consultation reported taking lower doses of the drugs.


Personality and depressive illness.

Personality and depressive illness. This paper reports an investigation into the relationship between personality (as measured by the Sixteen Personality Factor Questionnaire) and depressive illness type, as determined by responses to the Levine-Pilowsky Depression Questionnaire. When the effects of age and depressive severity are accounted for, a significant difference emerges between "endogenous" and "non-endogenous" depressive states in that the former are associated with a lower score on Factor E, indicating a more submissive, dependent personality. The possible implications of this finding are discussed.


Female alcoholics. V. Morbidity.

Female alcoholics. V. Morbidity. Data from the public health insurance societies regarding 66 female alcoholics, hospitalized for the first time for alcoholism at the Department of Alcohol Diseases, Karolinska Hospital, Stockholm, were studied, and the developmental pattern of morbidity was compared with that of 68 male alcoholics fulfilling the same criteria. The observation period was 15 years. The progress of the alcoholism was not reflected in data from the social insurance societies up to the time of the first clinical treatment. However, the morbidity increased in both sexes after the treatment period, with higher disability, severity, and frequency rates, a large number of persons with disability pensions and increasing social stigmatization. The proportion of women granted disability pensions increased to significantly higher values than that of men, and that of women in the general population. The women had significantly fewer registrations in social registers than the men during the whole period. Women and older patients had higher disability rates, more sick-days due to "mental diseases" and a higher severity rate before admission. All differences were equalized in the last part of the study.


Personality features of patients with primary affective disorder. Personality variables were assessed in outpatients with primary affective disorder by use of the Maudsley Personality Inventory (MPI) and the Marke Nyman Temperament Scale (MNTS). Significant differences between diagnostic groups were initially noted for the extraversion and neuroticism scales of the MPI. However, when mood was more rigorously controlled for, these differences largely disappeared, while interdiagnostic differences for the solidity scale of the MNTS emerged. The findings suggest that these measured aspects of personality may be quite state (mood) dependent even when patients are given test instructions previously reported to minimize mood effects. This was born out in a follow-up study for the N scale, but not the E scale, of the MPI. These data indicate that assessment of neuroticism in affectively ill patients will be contaminated by the presence of even mild depressive symptoms, a finding that has important implications for studies of personality in affective disorder.


Depression: factors related to 10-year prognosis. The 10 years' course of a series of 83 moderately severe depressions is presented, as well as factors governing the clinical and work prognosis. Depression was the fundamental disturbance in 75 cases during the index period. The depression was endogenous in 67 cases, reactive in eight, and neurotic in six cases. In the follow-up the drop-out from personal examination was 6.4%. Twenty per cent of the patients had been (almost) entirely free from symptoms of depression during the period of observation, 5% had been continuously depressive. There were no suicides. Twenty-seven patients felt some decrease in working capacity during the depressions, but only seven were unable to continue their previous work and three had changed work to prevent relapses. Fourteen of the patients had been sick-listed for more than 1 year of the observation period. Favourable factors for long-term course were: high intellectual capacity (for work prognosis, W), afraid of hurting others (W), white collar work (W), slight depression of mood during index period (for clinical course, C), favourable immediate outcome after index period (W). Unfavourable factors for long-term course were: low intellectual capacity (W), hysteroid personality (C), syntonic personality (W), asthenic personality, sensitivity to praise (C), tendency to feel under observation (W), and some symptoms during the index period: tendency to seclusion (C), ideas of reference (C), dryness of mouth (C), difficulty in falling asleep (C), dreamlike feeling (C), supplicating attitude (C). The implications of the results for nosology, care, and prevention of depressive states are discussed.


Effect of physical training on different categories of patients with intermittent claudication. The effect of supervised training was studied in 68 patients with intermittent claudication. Maximal walking distance was measured on a treadmill. Eight of the patients had resting pain in the leg when recumbent (group A), 25 had an initial walking distance of less than 500 m (group B), 11 had an initial walking distance of 500--1 000 m (group C), 24 had coronary insufficiency (group D). The study shows that training should be undertaken for at least three months. In some patients with resting pain, training led to relief of pain and surgical treatment was not necessary. Almost all patients without signs of coronary insufficiency increased their walking distance, compared to only 14 of the 24 patients with coronary insufficiency. Walking distance increased significantly in groups B and C and no significant difference was found between patients and proximal or distal arterial stenosis.


Prognostic significance of lymphopenia in sarcoidosis. During 1959--67, sarcoidosis were diagnosed in a series of 140 patients. All were followed up and 22 developed chronic sarcoidosis. In 134 patients (20 with chronic course) the initial granulocyte, monocyte and lymphocyte counts were known. No differences in granulocyte values were seen between different groups of sarcoidosis patients. Patients with erythema nodosum had significantly increased monocyte levels. Lymphopenia below 1 000/microliter was seen in only 7.5% of the patients. Lymphocyte counts below 1 500 microliter were a common finding, especially in patients developing chronic sarcoidosis. Significantly decreased lymphocyte values were also seen in patients older than 40 years at the time of diagnosis, in patients negative to 10 TU of PPD and in those with a disease requiring treatment with corticosteroids. A correlation was found between initial lymphopenia and less favourable prognosis, 85% of the patients having a very good prognosis. Patients with initial lymphopenia must be carefully followed up. The initial presence of erythema nodosum does not always guarantee a good prognosis.


Metabolic effects of glucocorticoid and ethanol administration in phenformin- and metformin-treated obese diabetics. Glucocorticoid administration for 24 hours to phenformin-treated obese diabetics increased blood lactate and lactate/pyruvate (L/P) ratio to higher levels than those found when only one drug was given. In one of 10 subjects, a metabolic acidosis with a blood lactate of 6.2 mmol developed during simultaneous administration of the two drugs. Diabetics treated with phenformin or metformin in equipotent dosages exhibited the highest blood lactate, L/P ratio, and beta-hydroxybutyrate levels during phenformin treatment, both before and during glucocorticoid administration. Ethanol administration to biguanide-treated diabetics resulted in identical increases in blood lactate and L/P ratio during phenformin and metformin treatment. These findings are consistent with the hypothesis that phenformin has a stronger inhibitory effect of gluconeogenesis than metformin. This may be one reason why lactic acidosis is seen much more often in phenformin- than metformin-treated patients.


Myocardial infarction in Malmö during the 10-year period 1963--1972. Myocardial infarctions in Malmö during the 10-year period 1963--1972 have been studied. The mortality from myocardial infarction decreased significantly among men during this period but not among women. The incidence of hospital-treated infarction increased significantly among men, mainly due to an increase in primary infarctions. The one-year survival in this hospital material did not improve during the period. The number of days of sick-leave during 12 months before primary infarction was significantly higher than expected. The duration of sick-leave during the year after primary infarction remained unchanged throughout the period. The mortality figures relate to all age groups, comprising 2 111 men and 1 409 women. The hospital incidence relates to men and women aged 65 years or below and comprises 1 323 men and 279 women during the period concerned. The reduced mortality and increased incidence of hospital-treated infarction are probaby explained by the fact that more men seek hospital treatment, leading to a better prognosis. The long duration of sick-leave after infarction is probably due to causes other than strictly medical factors.


Dobutamine in left heart failure after acute myocardial infarction. Dobutamine, a new positive inotropic drug, was given as i.v. infusion at a rate of 2.5--7.5 micrograms/kg/min to nine male patients with a moderately severe left heart failure. The patients were treated in our CCU for acute myocardial infarction (AMI) and had PEP/LVET above 0.40 on routine registrations of systolic time intervals, PEP (preejection phase), PEPI (PEP corrected for heart rate), LVET (left ventricular ejection time) and LVETI (LVET corrected for heart rate). Dobutamine increased contractility, measured as shortening of PEP and PEPI, and also increased ejection fraction, measured as PEP/LVET. Concomitantly, heart rate increased significantly but no changes were noted in systolic or diastolic BPs. The positive inotropic effect of dobutamine was thus accompanied by a positive chronotropic effect, which limits the usefulness of the drug in patients with recent AMI.


Atenolol administered once daily in primary hypertension. Effects on blood pressure in relation to pre-treatment plasma renin activity. The antihypertensive effect on the selective beta-1-adrenoceptor blocking agent, atenolol, given in doses of 100 and 200 mg once daily, was evaluated in 37 patients with primary hypertension. The drug induced an efficient reduction of BP, and in the whole patient series there was no difference in BP on either dosage. Exercise tests, performed in 10 patients, showed the same degree of partial beta-blockade 24 hours after intake of 100 and 200 mg atenolol. PRA decreased during treatment with atenolol but there was no correlation between the stimulated pretreatment renin level and the antihypertensive effect of atenolol. Side-effects were few and 35 out of 37 patients continued on atenolol treatment. Central nervous side-effects were not seen.