Synthesis of lysophosphatidylethanolamine analogs that inhibit renin activity. A series of lysophosphatidylethanolamine analogs containing saturated and methylene-interrupted cis-olefinic fatty chains was synthesized by phosphorylation and phosphonylation of respective fatty alcohols. Arachidonyl- and linolenylphosphorylethanolamines (12, 13), arachidonyl (2-phthalimidoethyl)phosphonate (17), and arachidonyl (2-aminoethyl)phosphonate (18) were found to be effective inhibitors of the renin-renin substrate reaction in vitro; lysophosphatidylethanolamine analogs 14-16 of lesser unsaturation were either weakly active or inactive. In a preliminary study, intramuscular administration of 25 mg/kg/day of arachidonyl (2-aminoethyl)phosphonate (18) to the hypertensive rat caused pronounced reduction (50 mm) in blood pressure within 3 days; upon continued dosage (15 mg/kg/day) of 18 for an additional 4 days, plasma renin activity was found to be 16 ng/0.1 ml/15 hr as compared with 69 ng/0.1 ml/15 hr before initial drug administration. Arachidonic acid (3), arachidonyl alcohol (8), and several corresponding tetraenoid ester, amide, mesylate, and glyceryl ether derivatives (4-7, 10, 11), that are not phosphate or phosphonate esters, were found to exhibit negligible or modest inhibition of renin activity in vitro.


Psychotomimetic phenylisopropylamines. 5. 4-Alkyl-2,5-dimethoxyphenylisopropylamines. A homologous series of 4-alkyl-2,5-dimethoxyphenylisopropylamines (alkyl = H through n-C5H11 and t-C4H9) was synthesized and compared with mescaline as serotonin agonists in a sheep umbilical preparation. The three-carbon homolog 6d was found to be the most potent of the straight-chain series in accordance with its observed psychotomimetic effectiveness in man.


Structure-activity relationships of antiarrhythmic 6-substituted decahydroisoquinolines. A series of diastereoisomeric 6-benzoyloxy- and 6-benzamido-2-methyldecahydroisoquinolines has been prepared and screened for antiarrhythmic effectiveness. In a continuation of our interest in identifying significant physicochemical properties of antiarrhythmic decahydroisoquinolines, octanol-water partition coefficients and pKa values have been determined for each member of the series. In general, antiarrhythmic activities superior to that of quinidine were observed. From a general structure-activity viewpoint, substitutions possessing greater lipophilicities produced compounds with superior antiarrhythmic properties. However, there appears to be optimal lipophilic character beyond which increased lipophilicity results in a decrease in antiarrhythmic potency. No discernible correlations with pKa values were evident. As noted in our earlier studies the esters were more potent and more lipophilic than the corresponding amides. No obvious correlations with stereochemistry were found; however, in three pairs of diastereoisomers, the more lipophilic cis compounds were found to be the superior isomers. A surprisingly high potency was noted with a tetrahydroisoquinoline benzamide--a finding unexpected from our earlier work. The 3,4-dichlorobenzamido grouping appeared to be the substituting moiety for optimal antiarrhythmic effectiveness.


Studies on 1-substituted 4-(1,2-diphenylethyl)piperazine derivatives and their analgesic activities. 1. The preparation and analgesic activities of a series of the entitled compounds (5-22) and the optical isomers of the 1-cyclohexyl derivative 5 are described. Reactions of N,N-bis(2-chloroethyl)-1,2-diphenylethylamine (3) with ammonia and primary amines gave N-(1,2-diphenylethyl)piperazine (4) and N1-substituted derivatives (5-20, 22), respectively. The alkylation of 4 afforded 12-21. Compounds 5-18 and 22 were also obtained by the reactions of 1,2-diphenylethylamine (23) and N-substituted 2,2'-dichlorodiethylamine. Racemate 5 was resolved with (+)- or (-)-2'-nitrotartranilic acid into its optical isomers [(+)-5 and (-)-5], and the absolute configuration of (+)-5 was determined to be S configuration by the synthesis and optical rotatory dispersion measurements. The most active members in this series of compounds were 5-7, which were approximately as potent as (-)-morphine. In the case of 5, the more potent enantiomer (S)-(+)-5 has the opposite configuration to that of (-)-N,N-dimethyl-1,2-diphenylethylamine (Spa) or (-)-morphine with respect to the (C-9) asymmetric center and belongs to a new series of compounds having potent analgesic activity.


Synthesis and antitumor activity of cyclophosphamide analogs. 1. Benzo annulated cyclophosphamide and related systems. Synthesis of 2-[bis(2-chloroethyl)amino]-3,4-dihydro-2H-1,3,2-benzoxazaphosphorin 2-oxide (2), which is a benzo annulated analog of cyclophosphamide [2-bis(2-chloroethyl)aminotetrahydro-2H-1,3,2-oxazaphosphorin 2-oxide (1)], was carried out in order to test for possible increased antitumor activity relative to 1 due to the presence of an oxidatively reactive C-4 benzylic site in 2. A structural isomer of 2, 2-[bis(2-chloroethyl)amino]-1,4-dihydro-2H-3,1,2-benzoxazaphosphorin 2-oxide (3), and cognate systems 2-[bis(2-chloroethyl)amino]-1,2,3,4-tetrahydro-1,3,2-benzodiazaphosphorin 2-oxide (4) and 2-[bis(2-chloroethyl)amino]-4H-1,3,2-benzodioxaphosphorin 2-oxide (5) were also prepared for comparative purposes. In vivo antitumor evaluation in mice against L1210 lymphoid leukemia indicated no significant activity for compound 2. Compounds 3 and 4 were likewise found to be inactive and only marginal activity was exhibited by 5.


Synthesis of some glycoside analogs and related compounds from 9-amino-6-(methylthio)-9H-purine. Additional information on the anticancer activity of 9-amino-9H-purine-6(1H)-thione and its derivatives was sought by the synthesis of some 9-(substituted amino)-6-(methylthio)-9H-purines in which the 9-substituent contained functional groups capable of either reversible or irreversible binding with an enzymatic site. Condensation of 9-amino-6-(methylthio)-9H-purine (1) with some carbonyl compounds followed by hydride reduction of the azomethine linkage in the intermediates leads to the 2-pyrrolylmethyl (8), 2,3,4-trihydroxybutyl (10), and the 1,5-dihydroxy-2- and 3-pentyl (11 and 12) compounds. A 4-hydroxybutyl derivative (13) was obtained by alkylation of 18, the 9-acetyl derivative of 1, with 4-chlorobutyl acetate followed by saponification. The cyclization of 13 and 11 with a sulfonyl chloride gave the 9-pyrrolidin-1-yl (27) and the 9-[2-(tosyloxymethyl)pyrrolidin-1-yl] (28), respectively. Acylation of 1 with ethyl L-2-pyrrolidine-5-carboxylate and ethyl 1-methyl-5-pyrrolidone-3-carboxylate, respectively, in Me2SO containing NaH gave the corresponding amides 15 and 17. Alkylation of 18 with 1-bromo-2-chloroethane and epichlorohydrin gave the N-(2-chloroethyl) and N-(1,2-epoxy-3-propyl) derivatives 19 and 20. The chloro group of the chlorobutyl derivative of 18 was displaced with KSCN and NaN3, respectively, to give the thiocyanate and azido derivatives 23 and 24. Hydrogenation of the latter gave the amine (25), which was acylated with ethyl chloroformate to give the (ethoxycarbonyl)amino compound 26. None of these compounds showed activity against L1210 leukemia cells implanted ip in mice on a single-dose schedule, suggesting that the activity observed in the simpler 9-aminopurines resulted from cleavage of the hydrazino linkage to give pH-purine-6(1H)-thione.


Synthesis of 6alpha-methyldigitoxigenin 3-acetate. In order to determine the influence of a 6alpha-methyl group activity, the 6alpha-methyl derivative of digitoxigenin 3-acetate 14 was prepared and pharmacologically tested in comparison with digitoxigenen 3-acetate. The synthesis of 6alpha-methyldigitoxigenin 3-acetate (14) was performed starting from 21-hydroxy-4-pregnene-3,20-dione (1). According to the cardiac activity determined on guinea-pig isolated heart and by slow infusion in the cat, the 6alpha-methyldigitoxigenin 3-acetate (14) is not more active than digitoxigenin 3-acetate.


Synthesis and some pharmacological properties of [1-beta-mercapto-beta,beta-diethylpropionic acid,2-(3,5-dibromo-L-tyrosine)]oxytocin. The synthesis of the protected polypeptide precursor of [1-beta-mercapto-beta,beta-diethylpropionic acid,2-(3,5-dibromo-L-tyrosine)]oxytocin was performed in a stepwise manner by solution techniques. This analog of oxytocin has two modifications, each of which taken alone gives analogs which inhibit some of the pharmacological responses to oxytocin. The S-ethylcarbamoyl protecting groups of beta-Mpa(beta-Et2)(Ec)-Dbt-Ile-Gln-Asn-Cys(Ec)-Pro-Leu-Gly-NH2 were removed in refluxing liquid NH3, and the resulting disulfhydryl compound was oxidatively cyclized in H2O-MeOH with ICH2CH2I. Purification was effected by partition chromatography and gel filtration. The analog possesses antioxytocic (pA2 = 7.08) and antiavian vasodepressor (pA2 = 7.38) activities but has neither agonist nor antagonist activity in the rat pressor assay. These potencies are close to those exhibited by [1-beta-mercaptopropionic acid,2-(3,5-dibromo-L-tyrosine)]oxytocin but different from those of [1-beta-mercapto-beta,beta-diethylpropionic acid]oxytocin.


2,3,4,5,6,7-hexahydro-1,6-methano-1H-3-benzazonine derivatives as analgesics. 10-Methoxy- (10) and 10-hydroxy-3-methyl-2,3,4,5,6,7-hexahydro-1H-3-benzazonine (11) have been synthesized from 7-methoxy-alpha-tetralone (1) via the 1-aminomethyl compound 4, which was converted to the amino acid derivative 7. Hydrogenation and cyclization of 7 afforded the lactam 9, which was reduced with LiAlH4, followed by N-methylation to give 10, from which 11 was obtained. Compounds 10 and 11 have analgetic activity, and the former was found to be comparable to codeine.


Absolute configuration of the major metabolite of 5,5-diphenylhydantoin, 5-(4'-hydroxyphenyl)-5-phenylhydantoin. Chemical conversions, optical comparisons, and chiroptical measurements (CD) were employed to determine the absolute configuration of the enantiomers of 5-(4'-hydroxyphenyl)-5-phenylhydantoin (HPPH) (1b and 1c). Studies on a key intermediate, (-)-2-cyclohexyl-2-phenylglycine (5b), led to the reexamination of the well-known rule of Clough-Lutz-Jirgensons. Optical comparisons by means of derivatization into hydantoins and 3-phenyl-2-thiohydantoins (application of Freudenberg's rule of shift) gave conclusions which were consistent with chiroptical measurements on the above compounds. Thus, (-)-HPPH (1c), the major metabolite of 5,5-diphenylhydantoin in man, has the S configuration. This assignment was confirmed by X-ray single-crystal structure analysis of (+)-HPPH 10-(+)-camphorsulfonate (18b).


Teaching students the relationship between quality and cost of medical care. The usefulness of hospital charges as a means of teaching medical students the relationship between the quality of the cost of medical care provided by primary care physicians (internists and family physicians) is presented. The comparative role of these two types of primary care physicians as "generators of costs" is described. The cost of hospital care provided by primary care physicians is also compared with the cost of care provided by the cardiologist, a prototype of the highest quality of secondary and tertiary care for cardiovascular diseases. Data indicate that internists generated hospital costs that were consistently higher than family physicians. Moreover, a comparison of costs generated by internists, family physicians, and cardiologists in managing patients with cardiovascular diseases revealed that cardiologists generated lower costs than the other two types of specialists. It is believed that case studies such as this will provide evidence that will enable undergraduate medical students to reflect upon their own attitudes toward their developing role as "generators of cost".


The characteristics of medical students and their views of the first year. The results of a national longitudinal study of the educational choices of a large sample of students are summarized with emphasis on the results for medical students. Surveyed as college seniors, students were followed up a year later. The senior results indicated that the future medical students were usually bright, academically successful, male, and frequently from relatively affluent families. Their self-conceptions and work values were consistent with the career of medicine. As medical students, they reported that they worked hard. They did not describe their professors as particularly good teachers, but they felt they had good relations with them. Similarly, although they felt the first year offered limited opportunities for individualization, they were generally quite satisfied with their schools.


Issues and methods in curriculum evaluation. Studies of medical school curricula need not meet the criteria of systematic experimental designs. Instead of compromising aspects of the curriculum to meet such requirements as random sampling, the authors suggest the development of representative curricular research. Such designs require the development of population validity, ecological validity, and referent generality. Examples of these aspects of representative design are derived from the development of a health-maintenance-organization-based primary care curriculum.


A systems approach to patient care, curriculum, and research in family practice. The system of data recording and retrieval which defines a family practice population of patients is described. It is organized at two levels, as a series of manual instruments or as a single instrument used as data input to a computer. Depending on resources available, it is possible to record demographic and morbidity data from the patient populations of both teaching and nonteaching practices. Data have been collected from a patient population of 88,000 in 26 practicing sites in Virginia, totaling 380,000 diagnostic and follow-up visits. Presentations are made of some of this data. The costs of this recording process in nonteaching practices, the use of such data as an educational resource for the training of primary care physicians, and the evaluations of health care delivered are discussed.


A clinical clerkship in psychiatry.

A clinical clerkship in psychiatry. A clinical clerkship was organized around the goal of teaching information and skills that would be needed by the nonpsychiatrist physician. In most clinical clerkships the students work on an inpatient service. In the clerkship described here the setting is an outpatient clinic, which provides a more relevant experience. Videotaped psychiatric interviews are used extensively and have been found to provide a valuable teaching format. They are effective in holding student interest, in avoiding the practical difficulties of live interviews, and in teaching active listening and interviewing technique, as well as in demonstrating a variety of psychopathology. Field trips to state psychiatric hospitals, institutions for mental defectives, clinics for treating alcoholics or addicts, and other mental health facilities have been used but have not been found to be a very valuable part of the program.


Interactions of liver encoplasmic reticulum membranes and polysomes in vitro. The interactions of various preparations of endoplasmic reticulum membranes and polysomes have been studied by means of a sandwich sucrose gradient that clearly isolates free ribosomes, smooth endoplasmic reticulum (S.E.R.) and rough endoplasmic reticulum (R.E.R.) from the microsomal fraction of rat liver homogenates. Reconstructed rough membranes separate well from the native R.E.R. but occupy the same position along the gradient as the S.E.R. and the rough membranes, stripped of their ribosomes by means of LiCl. Native R.E.R. and S.E.R. do not bind any added labeled polysomes at 0 degree C; previous treatment with LiCl does not modify the behavior of S.E.R. The presence of cell sap during the binding reaction does not increase polysome fixation by stripped-rough membranes but protects in some way the polysomes and preserves all their original functional capacity of amino acid incorporation into protein.


Calcium-binding of Synaptosomes isolated from rat brain cortex. II. Inhibitory effects of magnesium ions and some other cations. As in our previous report (Kamino, Uyesaka & Inouye, J. Membrane Biol. 17:13 1974), the absorbance changes of murexide caused by Ca2+ and followed up by a dual wavelength spectrophotometer were applied to measure synaptosomal Ca2+-binding in the presence of cations such as Rb+, Mn2+ or La3+. All the cations tested showed a significant inhibition of synaptosomal Ca2+-binding except Li+. The inhibitory effects could be divided into the following three categories: (1) noncompetive, co-operative K+-type, which includes alkali metal ions. The potency of inhibition is K+ greater than Rb+ greater than Cs+ greater than Li+, Na+ =0; (2) competitive Mn2+ -type which includes many divalent cations. The inhibitory potency was found to be in the following order: Mn2+ greater than Sr2+ greater than Cd2+, Ba2+ greater than Mg2+; (3) nonspecific, noncompetitive La3+ -type; among the cations tested, La3+ and Ce3+ were found to markedly reduce the Ca-binding capacity of synaptosomal particles, resulting in a noncompetitive inhibition, at least in the range of Ca2+ concentration used.


Fluorescence polarization in a planar array of pigment molecules: theoretical treatment and application to flavins incorporated into artificial membranes. A quantitative fluorescence polarization theory of molecules bound to two-dimensional plane layers has been developed when the electronic transition moments of absorption and emission are parallel within the fluorescent molecules. The transition moments are assumed to be in preferred orientation with respect to the normal to the plane and to be randomly oriented within the plane (rotational symmetry with the normal as axis of symmetry). Three basic model distributions of transition moments are investigated quantitatively. These model distributions represent a simplification but in most cases may be expected to describe reality with sufficient accuracy. For all distributions, two cases of different mobility of molecules are treated: (a) the lifetime of fluorescence is small compared with the characteristic relaxation time of the distribution, and (b) the lifetime of fluorescence is long, so that a complete reorientation of transition moments during the excited state can take place. From the quantitative calculations four characteristic quantities are derived, which are appropriate for the analysis of experimental data. Experiments are carried out with phosphatidylcholine bilayer membranes which contain three differently substituted amphiphilic flavins. All three flavins yield similar data. Their analyses predict free and fast mobility of the flavin chromophore.


Measurement of membrane potential and estimation of effective fixed-charge density in membranes. Electrical potentials Em arising across cross-linked phenolsulfonate membrane separating NaCl solutions of molality M1 and M2 have been measured at 25 degrees C. These values of Em have been used in the Nernst equation to calculate values for the apparent transport number ti(app) for the counterion or the co-ion in the membrane. Values of ti(app) together with the limiting value for the cation transport number in the aqueous phase have been used in the equation developed by Kobatake and co-workers to evaluate the membrane permselectivity Ps as a function of external electrolyte concentration. With the help of the equation relating Ps to phiX, the effective fixed-charge density in the membrane (where phi is a constant, 0 less than phi less than 1, and X is the membrane stochiometric charge density and can be evaluated by chemical analysis of the membrane phase), values for phiX and phi have been determined. Values of phi were low in dilute solutions and increased with increase in the concentration of the external solution. Similar behavior was noted in the case of another membrane system, cross-linked polymethacrylic acid in contact with KOH solutions. On the other hand, the membrane system, "untreated" collodion in contact with KCl solutions, exhibited a behavior in which the values of phi, low in dilute solutions, increased and then decreased following a gradual increase in the external concentration. This slight divergence in its behavior was attributed to the heterogeneity of the collodion membrane structure. The reliability of this potentiometric method to estimate effective fixed-charge density in membranes has been discussed in relation to a similar but old method due to Teorell, Meyer and Sievers. Also the significance of the values derived for phi has been pointed out.


Determination of the resistance in series with the membranes of giant axons. Measurements of the resistance in series with the excitable membrane for giant axons of two different phylla (the squid Loligo pealii and the marine worm Myxicola infundibulum) were obtained. Efforts were made to take into account the errors introduced by the finite rise-time of the measuring apparatus. The series resistance value, obtained very quickly by the method described, may be used in setting the compensation potentiometer to offset this resistance in voltage-clamp measurements. Estimates of the resistance of the periaxonal tissue layer were made. Analyses were done on some of the problems involved in attempting to make an unambiguous determination of the series resistance.


Studies on the brush border membrane of the mouse duodenum. I. Membrane isolation and analysis of protein components. Brush border membranes have been isolated from villus epithelial cells of the adult Swiss mouse duodenum. Preparations of these membranes are not contaminated by other organelles as judged from electron-micrographs of sectioned pellets of brush borders. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of proteins from brush borders solubilized in Tris-sodium dodecyl sulfate buffer reveals a reproducible Coomassie Brilliant Blue pattern of 17 bands. By comparing the brush border protein band positions with those of standard proteins run concurrently on sodium dodecyl sulfate-polyacrylamide gel slabs it is estimated that the 17 brush border proteins and subunits have molecular weights ranging from over 250,000 to around 16,000. Periodate-fuchsin sulfite staining shows that the five more slowly migrating, high molecular weight proteins are glycoproteins. The two proteins of smallest molecular size react positively with Oil Red O but have very small amounts of lipophilic amino acid residues, which indicates that the lipid extractable from the gels in these areas is a contaminant and is not bound to the proteins.


Studies on the structure of milk fat globule membrane. Milk fat globule membrane was solubilized with sodium dodecyl sulfate and mercaptoethanol and the membrane proteins were separated by SDS-polyacrylamide gel electrophoresis. The membrane preparations contained three major size classes of polypeptide of 155,000, 62,500 and 43,500 daltons. At least five glycopeptides were separated of which two stained intensely with periodic acid-Schiff reagent, but poorly with coomassie blue. Trypsin hydrolysis of whole cream and isolated milk fat globule membrane revealed major differences in the rates of protein hydrolysis. Many of the membrane proteins of whole cream resisted proteolysis compared with the same proteins in the isolated membrane. Two glycopeptides were resistant to trypsin digestion in either preparation. Treatment of whole cream with neuraminidase led to the release of at least 70% of the protein-bound sialic acid. Whole cream and isolated membrane samples were iodinated with 125I in the presence of lactoperoxidase and hydrogen peroxide. The membrane proteins were significantly more accessible to lactoperoxidase-125I i in isolated membrane compared with the proteins of whole cream. Polypeptides of molecular weight 43,500 and approximately 48,000 daltons were predominantly labelled in whole cream and could be eluted from the fat globules with magnesium chloride (1.5m). The results strongly suggest that the proteins of milk fat globule membrane are asymmetrically arranged in the membrane and that most of the protein-bound sialic acid is present on the external surface of milk fat globules.


Sodium fluxes through the active transport pathway in toad bladder. To assess the active components of sodium flux across toad bladder as a function of transepithelial potential, unidirectional sodium fluxes between identical media were measured before and after adding sufficient ouabain (1.89 X 10(-3)M) to eliminate active transport, while clamping transepithelial potential to 0, 100 or 150 mV. Evidence was adduced that ouabain does not alter passive fluxes, and that fluxes remain constant if ouabain is not added. Hence, the ouabain-inhibitable fluxes represent fluxes through the active path. Results were analyzed by a set of equations, previously shown to describe adequately passive fluxes under electrical gradients in this tissue, here modified by the insertion of E, the potential at which bidirectional sodium fluxes (beta E, and theta E) through the active pathway are equal. According to these equations, beta E and theta E are the logarithmic mean of bidirectional fluxes through the active path at any potential, and the flux ratio in this path is modified by a constant factor Qia, which represents the ratio of the bulk diffusion coefficient to the tracer diffusion coefficient in this pathway. The data are shown to conform closely to these equations. Qia averages 2.54. Hence, serosal-to-mucosal flux vanishes rapidly as potential falls below E. Mean E in these experiments was 158 +/- 1 mV. Thus, linear dependence of net flux in both active and passive pathways on potential is present, even though the sodium fluxes in both paths fail to conform to the Ussing flux ratio equation. Qip less than 1 in the passive path (qualitatively similar to exchange diffusion) and Qia greater than 1 in the active path (as in single file pore diffusion). Both of these features tend to reduce the change in serosal-to-mucosal sodium flux induced by depolarization from spontaneous potential to zero potential ("short-circuiting").


The effect of anti-L on ouabain binding to sheep erythrocytes. Binding of 3H-ouabain was studied in high potassium (HK) and low potassium (LK) sheep red cells. In particular, we investigated the effect of anti-L, an antibody raised in HK sheep against L-positive LK sheep red cells, on 3H-oubain binding and its relation to K+ -pump flux inhibition in LK cells. HK cells were found to have about twice as many 3H-ouabain binding sites and a higher association rate for 3H-ouabain than homozygous LL-type LK cells. The number of 3H-ouabain molecules bound to heterozygous LM-type LK cells is lower than that on LL cells, but the rate of ouabain binding is between that of HK and LL red cells. A close correlation was observed between the rates of 3H-oubain binding and fraction K+-pump inhibition. Exposure of LM and LL cells to anti-L did not affect the number of 3H-ouabain molecules bound at saturation, but increased the rates of glycoside binding and K+ -pump inhibition proportionately, so that for LK cells in the presence of anti-L, the rates of the two processes approximate those of HK cells. These data exclude the possibility that anti-L generates entirely new pump sites in LK sheep cells, but suggest that the antibody increases the affinity of the existing -a+ -K+ pumps for the glycoside.


Hypotonic hemolysis of human red blood cells: a two-phase process. Previous use of hemolysis time measurement to determine permeability coefficients for the red blood cell membrane rested on the assumption that cells swelling in a hypotonic medium hemolyzed immediately on reaching critical volume. By preswelling red cells to various volumes prior to immersion in hemolytic solutions we extrapolate to the hemolysis time of red cells immersed at critical volume and thereby find a significant period of time during which the cells apparently remain in a spherical form prior to release of hemoglobin. Revised estimates of permeability coefficients follow from including this spherical (nonswelling) phase. In addition, the appreciation of a characteristic time period during which the membrane is under tension provides new opportunity to study physical and chemical properties of the membrane.


Voltage jump/capacitance relaxation studies of bilayer structure and dynamics. Studies on oxidized cholesterol membranes. A voltage-jump technique for the study of the time course of small, voltage-induced changes in the structure of single bilayers is presented, and a method is introduced whereby electromechanical (electrostrictive) phenomena can be separated from dielectric relaxations. As no foreign molecules need be introduced into the bilayers, the question about probe artifacts is eliminated. The time constants and amplitudes of dielectric relaxations in oxidized cholesterol bilayers at 21 degrees C, along with their tentative identification are: (a) tau = 3.3 msec, deltaC/Co = 0.8% and tau = 0.7 msec, deltaC/Co = 0.6%: reorientation in the plane of the membrane of domains or clusters of dipoles. (b) tau = 155 musec, deltaC/Co = 1.5-3%: rotational reorientation of individual molecules. (c) tau = 18 musec, deltaC/Co - 1.4%: small amplitude reorientations individual dipoles about an axis lying in the plane of the membrane. Electrostictive effects with time constants between about 2 and 50 msec were also detected. A temperature study of both the dielectric and electrostrictive phenomena is reported. The application of the technique to other membrane compositions and to a variety of BLM problems is discussed.


Estimation of surface charges in some biological membranes. The resting membrane potential data existing in the literature for the giant axon of the squid, frog muscle and barnacle muscle have been analyzed from the standpoint of the theory of membrane potential due to Kobatake and co-workers. The average values derived for the effective charge density phi chi (where phi is a constant, 0 less than phi less than 1, and represents the fraction of counterions that are free, and chi is the stoichiometric charge density in the membrane) present on the different biomembranes existing in their normal ionic environment are 0.3, 0.325 and 0.17 M for the squid axon, frog and barnacle muscles, respectively. On the assumption that the values of phi are 0.4 and 0.2 for nerve and muscle membranes, respectively, values of 0.75, 1.62 and 0.85 M have been derived for the stoichiometric charge density (chi) present in the respective biological membranes. These correspond to 1 negative charge per 222, 103 and 195 A2 of the membrane area of the squid axon, frog and barnacle muscles, respectively.


A model of NaCl and water flow through paracellular pathways of renal proximal tubules. To explain how hydrostatic pressure differences between tubule lumen and interstitium modulate isotonic reabsorption rates, we developed a model of NaCl and water flow through paracellular pathways of the proximal tubule. Structural elements of the model are a tight junction membrane, an intercellular channel whose walls transport NaCl actively at a constant rate, and a basement membrane. Equations of change were derived for the channel, boundary conditions were formulated from irreversible thermodynamics, and a pressure-area relationship typical of thin-walled tubing was assumed. The boundary value problem was solved numerically. The principal conclusions are: 1) channel NaCl concentration must remain within a few mOsm of isotonic values for reabsorption rates to be modulated by transtubular pressure differences known to affect this system: 2) basement membrane and channel wall parameters determine reabsorbate tonicity; tight junction parameters affect the sensitivity of reabsorption to transmural pressure; 3) channel NaCl concentration varies inversely with transmural pressure difference; this concentration variation controls NaCl diffusion through the tight junction; 4) modulation of NaCl diffusion through the tight junction controls the rate of isotonic reabsorption; modulation of water flow can increase sensitivity to transmural pressure; 5) no pressure-induced change in permeability of the tight junction or basement membrane is needed for pressure to modulate reabsorption; and 6) system performance is indifferent to the distribution of active transport sites, to the numerical value of the compliance function, and to the relationship between lumen and cell pressures.


Permeability characteristics of the adipocyte cell membrane and partitioning characteristics of the adipocyte triglyceride core. The unidirectional rates of passive permeation of a homologous series of saturated fatty acids and bile acids into rat epididymal adipocytes were measured to determine the permeability characteristics of this mammalian cell membrane. For fatty acids containing 5 to 12 carbon atoms the logarithm of the permeability coefficient was a linear function of the number of carbons in the fatty acid chain: fatty acids with less than five carbon atoms showed anomalously high permeabilities. Using the data for the fatty acids with 5 to 12 carbon atoms, the incremental free energy of transfer (delta delta F w leads to l) of the -CH2 moiety from the aqueous environment into the fat cell was calculated to equal -547 cal mole-1. The delta delta F w leads to l of the -OH moiety calculated from data using bile acids as the probe molecules was +1,225 cal mole-1. After rupturing the fat cells by freeze-thawing, partition ratios also were measured between bubber and the lipid phase of the adipocyte core using both the fatty acid series and a series of terminal diols as probe molecules. Using these partition ratios delta delta F w leads to l for the -CH2 and -OH substituent groups was calculated to equal -830 and +2,070 cal mole-1, respectively. On the basis of these studies, two conclusions were drawn. First, like many epithelial surfaces and the erythrocyte membrane, the fat cell membrane exhibits anomalously high permeabilities to small molecular weight, polar compounds. Since this behavior in the adipocyte, as in the erythrocyte, cannot be attributed to structures such as tight junctions, it must be explained on the basis of some physico-chemical feature of the cell membrane itself. Secondly, the values of the delta delta F w leads to l indicate that the adipocyte membrane is less polar than the intestinal and gallbladder membranes but more polar than the membranes of Nitella and the erythrocyte.


Fusion in phospholipid spherical membranes. I. Effect of temperature and lysolecithin. A study concerning membrane contact and fusion phenomena was made for phospholipid spherical bilayer systems with respect to temperature. Specific temperatures were obtained for the spherical bilayer membranes of phosphatidyl choline (PC) and phosphatidyl serine (PS) which indicated a greater degree of membrane fusion and were designated Tf (the fusion temperature -- PC: 43 degrees C, PS: 38 degrees C). These temperatures were reduced by about 10 degrees C for the membranes incorporated with 20% lysophosphatidyl choline. The results of the contact and fusion observed in the spherical membranes are compared and discussed with the conductance characteristics of the PC and PS planar bilayer membranes as well as dissolution study on the phospholipid monolayers formed at the air/water interface with respect to temperature. Also, a possible molecular mechanism of membrane fusion is discussed in terms of the fluidity and instability of the membrane.


Effects of unstirred layers on the steady-state zero-current conductance of bilayer membranes mediated by neutral carriers of ions. Some effects of diffusion polarization and chemical reactions on the steady-state zero-current conductance of lipid bilayers mediated by neutral carriers of ions have been studied theoretically and experimentally. Assuming that ion permeation across the interfaces occurs via a heterogeneous reaction between ions in the solution and carriers in the membrane, the relationship between the conductance and the aqueous concentration of carriers is shown to be linear only in a limited range of sufficiently low concentrations. At higher carrier concentrations, which for the most strongly bound cations are within the range of the experimentally accessible values, the conductance is expected to become limited by diffusion of the carried ion in the unstirred layers and therefore reach an upper limiting value independent of the membrane properties. This expectation has been successfully verified for glyceryl-monooleate membranes in the presence of the ions K+, Rb+ and NH+4 and carriers such as valinomycin and trinactin. The experimental results support, at least for the present system, the generally accepted view that complexation between ions and the macrocyclic antibiotics occurs at the membrane surface; it is shown, in fact, that for a different mechanism, such as that by which the complexes would form in the aqueous solutions and cross the interfaces as lipid-soluble ions, the same type of saturation would be expected to be observable only for unrealistically high values of the rate constants of the ion-carrier association. A previously proposed criterion to distinguish between these two mechanisms, based on the dependence of the conductance on the ion concentration, is discussed from the viewpoint of this more comprehensive model.


Properties of the conductance induced in lecithin bilayer membranes by alamethicin. Current-voltage relations have been measured across lecithin bilayers doped with alamethicin molecules. The results show that there are two aspects of the induced conductances, a voltage-dependent and a voltage-independent conductance. Both have been characterized as a function of alamethicin and KCl concentration. The two aspects of the conductances do not show the same changes with those two variables. The voltage-independent conductance is affected very little by changes in KCl concentration, and its dependance on alamethicin concentration reveals that it is produced by two or three alamethicin molecules. The voltage-dependent conductance is shifted by the changes in KCl concentration only when the concentrations are greater than or equal to 100 mM; below 100 mM KCl the slope of the log conductance-voltage curve is also reduced. The effect of changing alamethicin concentration reveals that nine or ten molecules are involved for KCl concentrations larger than 100 mM; if the KCl concentration is less than 100 mM, the effect of changing the alamethicin concentration is reduced. Time-dependent measurements have also been performed; only one time constant was found and it is strongly voltage-dependent. Also a very slow voltage-dependent absorption process is found. These results can be explained if it is assumed that pores are formed of a mixture of charged and uncharged alamethicin molecules when a voltage is applied and that uncharged alamethicin can also form pores without applying a voltage, once the absorption process has been started by previously applied voltages. The voltage dependence of the time constant seems to indicate that the voltage-dependent pore formation is produced by aggregates of charged alamethicin rather than independent molecules.


Osmotic regulation in the marine alga, Codium decorticatum. I. Regulation of turgor pressure by control of ionic composition. Codium decorticatum regulates its internal ionic composition and osmotic pressure in response to changes in external salinity. Over a salinity range of 23 to 37% (675 to 1120 mosmol/kg) Codium maintains a constant turgor pressure of 95 mosmol/kg (2.3 atm), observed as a constant difference between internal and external osmotic pressures. The changes in internal osmotic pressure are due to changes in intracellular inorganic ions. At 30 0/00 salinity the major intracellular ions are present in the following concentrations (mmol/kg cell H20): K+, 295; Na+, 255; Cl-, 450. At different salinities intracellular ion concentrations remain in constant proportion to the external ion concentrations, and thus the equilibrium potentials are approximately constant. The potential difference between the vacuole and seawater (-76 mV), whici is predominantly a K+ diffusion potential, is also constant with changing salinity. Comparison of the equilibrium potentials with the vacuole potential suggests that Cl- is actively absorbed and Na+ actively extruded, whereas K+ may be passively distributed between the vacuole and seawater. Turgor pressure does not change with environmental hydrostatic pressure, and increasing the external osmotic pressure with raffinose elicits a response similar to that obtained by increasing the salinity. These two results suggest that the stimulus for turgor regulation is a change in turgor pressure rather than a change in internal hydrostatic pressure or ion concentrations.


Intra-subject controlled time-out (social isolation) in the modification of self-injurious behaviour. This study deals with the controlling of self-injurious behaviour in a profoundly retarded girl. The main therapeutic tool, social isolation, was carried out under normal ward conditions and was statistically evaluated in an intra-subject design without reversal conditions. The procedure reduced the self-injurious behaviour to a near-zero level.


Some aspects of carbohydrate metabolism in Prader-Willi syndrome. Three patients with Prader-Willi syndrome are reported. The subjects presented chemical diabetes mellitus. All patients were hypersentsiive to exogenous insulin and they showed poor adrenal medullary response to hypoglycaemics. It was postulated that the poor adrenal medullary response to the insulin injection may be a contributing factor in the excessive hypoglycaemic response, and that the diabetes mellitus observed in the patients could be due to inactivation of endogenous insulin.


Long arm deletion of chromosome no. 6 in a mentally retarded boy with multiple physical malformations. In a severe mentally retarded boy with multiple physical malformations cytogenetic analysis by the method of heat Giemsa staining confirmed the long arm deletion of chromosome No. 6--46, XY, del(6) (q2). Cytogenetic finding in parents were normal.


Microcirculation of traumatized spinal cord. A correlation of microangiography and blood flow patterns in transitory and permanent paraplegia. A relationship of microangiography and blood flow patterns in the contused feline spinal cord is reported. In transitory traumatic paraplegia, an injury from which there is a return of function in several weeks, impaired vascular perfusion occurs in the white matter through 1 hour after contusion, then stabilizes and returns to normal by 24 hours. In permanent traumatic paraplegia, an injury from which no sensory or motor function returns, the vascular perfusion of the white matter continues to decrease after 1 hour and returns to normal by 24 hours at which time irreversible damage has occurred to the major sensory and motor tracts. Within the first 30 minutes post-trauma, intramedullary vasospasm is noted. In both the transitory and permanent lesions the gray matter becomes hemorrhagic and has no evidence of perfusion by fluorescent techniques by 1 hour after injury.


Pulmonary aerobic bacterial flora after aspiration pneumonitis. Preventive antibiotic therapy in patients with aspiration pneumonitis remains controversial. Observations from culture of bronchial secretions indicate that patients who aspire of gastric contents whould receive antibiotics prophylactically only if there is another infective focus present or strongly suspected. Otherwise antibiotics should be withheld until clinically or radiologically indicated.


Isolated posterior cruciate ligament injury: literature review and case reports. A review of the recent literature on posterior cruciate ligament injury reveals few descriptions of isolated injury. The major findings in this injury include abrasions over the anterior tibial surface, presence of a posterior drawer sign, recurvatum of the knee, bloody effusion, and X-ray evidence of avulsion of the posterior tibial margin. The mechanism of injury appears to be a direct blow to the anterior tibial surface with the knee acutely flexed and the posterior capsule lax. The force of the blow drives the tibia posterior, thereby causing a tension injury to the posterior cruciate ligament while actually increasing the laxity in the posterior capsule. All injuries were treated surgically through a posterior approach using internal fixation of the avulsion fracture. Satisfactory wound and fracture healing occurred in all cases and function at 3 months was good with ligamentous stability present.


Diagnosis of osteochondral fractures in acute traumatic patellar dislocations using air arthrography. A case of osteochondral fracture following acute patellar injury has been presented, demonstrating the usefulness of air arthrography in diagnosis of selected cases.


Homicidal death by air rifle.

Homicidal death by air rifle. A fatal injury of the brain from a penetrating air rifle is described. Deaths due to air rifles are extremely rare; only four other cases were found in the recent English-language literature. All deaths resulted from pellet wounds of the brain. The portal of entry for the pellet was the eye in two instances and the frontal bone of a child in the other two.


Synovitis secondary to non-metallic foreign bodies. Eight cases of non-metallic foreign body synovitis are presented. In all cases, an apparently innocuous penetrating injury led to synovitis, and early articular cartilage destruction. Delay in appropriate diagnosis frequently occurred because of confusion regarding the management of these injuries. Pitfalls identified were: 1) failure to appreciate the seriousness of the initial injury and to debride the wound appropriately; 2) failure to obtain satisfactory initial radiographs; 3) failure to explore the wounds surgically; 4) failure to appreciate that a symptom-free interval may follow foreign body penetration. Synovectomy was necessary in six cases to ensure removal of either microscopic or hidden gross particulate matter. Pathologically, these specimens showed chronic synovitis and foreign body granuloma. The implications of such foreign bodies to longterm joint degeneration are discussed.


Two false aneurysms of the common carotide artery--a delayed complication of penetrating cervical trauma. An unusual case of false aneurysms of the common carotid artery is presented, and the topic of penetrating cervical trauma and its management is briefly reviewed.


Penetrating intracranial foreign bodies in children. Four cases illustrating low-velocity penetrating injuries from foreign bodies are presented. The importance of formal intracranial exposure is emphasized. When used in these four cases, all patients had good recoveries. In children, penetration of the brain is likely because of the fragility of the orbital roof. The English-language literature on penetrating intracranial foreign bodies is also reviewed.


Injuries in children sustained in free falls: an analysis of 66 cases. Sixty-six children who fell distances up to 96 feet were studied to determine the frequency and patterns of injuries sustained. Upper extremity, skull, and femoral fractures were most common; there was only one pelvic fracture and one os calcis fracture. Two of the children died, and 64 children returned to normal activities.


Correction by hyaluronidase of the interstitial tissue transport defect during shock: a new approach to therapy. We have demonstrated a defect in tissue perfusion during hemorrhagic shock in dogs that is due in part to poor capillary flow, and in part to a defect in interstitial tissue diffusion. Treatment with whole blood alone improves capillary flow but diffusion remains defective. The use of hyaluronidase appears to correct the interstitial diffusion defect observed during shock.


A technique for measuring blood pressure in a medical evacuation helicopter. In view of the increasing use of helicopters in the evacuation of patients in both military and civilian settings and the longer missions being flown, more efficient methods of monitoring patients' vital signs are needed. One such method has been evaluated utilizing the ultrasonic flowmeter to measure blood pressure. This study indicates that a reliable technique is now available for measuring systolic blood pressure even in low flow states in the noisy environment of a medical evacuation helicopter.


Effect of trimethoprim-sulfamethoxazole on the renal excretion of creatinine in man. Treatment with the chemotherapeutic combination of 160 mg. trimethoprim plus 800 mg. sulfamethoxazole twice daily increased the serum creatinine level by an average of 2 mg. per 1. in 21 patients. The effect was clearly reversible. The chemical analysis of creatinine was not affected by the addition of trimethoprim, sulfamethoxazole or their metabolites. In 2 subjects given the drug combination for 12 days renal excretion and 24-hour clearances of creatinine decreased but iothalamate 131I clearance was unchanged. Consequently, the rise in serum creatinine does not indicate any decrease in the glomerular filtration rate. The serum creatinine started to rise within 4 hours after oral administration of a single dose. The rise in serum creatinine could be produced with trimethoprim alone but not with sulfamethoxazole alone. When the plasma creatinine was raised to 100 mg. per l. in healthy subjects (by giving creatinine orally), trimethoprim increased the creatinine levels 10 times as much as at normal plasma levels. The effect was interpreted as a competitive inhibition of the mechanism for tubular secretion of creatinine through the base-secreting pathway.


The place of diagnostic ultrasound in the examination of kidneys not seen on excretory urography. An examination was done on 28 patients with renal failure, 20 with unilateral hydronephrosis, 8 with multicystic kidneys, 3 with hypoplastic or chronically infected kidneys, and single examples of renal vein thrombosis, renal artery occlusion, xanthogranulomatous pyonephrosis with perinephric abscess, trauma and tumor invading the whole kidney. The distinct ultrasonic appearances of the various conditions causing radiographic non-visualization of the kidney are described.


Long-term radiographic changes of the kidney following the ileal ureter operation. A long-term retrospective evaluation was done on the preoperative and postoperative radiographic studies from patients who had undergone the ileal ureter operation. The comparative studies demonstrated decreased or stable pelviocaliceal dilatation, no measurable parenchymal loss, frequent high pressure vesico-ileac reflux and decreased number of renal calculi. Radiographically there was no evidence of renal morphological deterioration.


Study on use of isolated segment of ileum in urological plastic operation. Studies were done on 33 cases of plastic reconstruction of the urinary tract with an isolated ileal segment. We found that electrolytes and other components in the urine can be absorbed or excreted by the isolated ileal mucosa. Although electrolyte balance was preserved in most cases the tendency for hyperchloremic acidosis and high blood urea nitrogen was observed in some patients with poor renal function. The degree and the incidence of these changes were influenced by the length of ileal segment used and the volume of urine excreted. These 2 factors were related to infection, which gave deleterious effects on renal function. Among the tests used for prognosis the excretory urogram was found to be the most simple and provided the best information.


Histologic appearance of the intestinal urinary conduit. The histology of intestinal urinary conduits (8 ileal and 2 sigmoid) in place for 10 months to 10 years was studied in 10 patients between 20 and 65 years old. It is concluded that the ileum and the large intestine do not undergo adaptive metaplastic transformation. The only changes observed are related to a condition of chronic irritation to which the response is a chronic inflammatory reaction. Structures proving to be the most resistant were the cells of Paneth. The latter were not damaged in appearance and number as compared to normal, even when the conduit was in place for 10 years.


Epidemiology and treatment of renal pelvic and ureteral tumors. Throughout the world the number of cases of renal pelvic and ureteral tumors has increased considerably during the last 2 decades. In Yugoslavia this increase has been exceptionally high since about 1953 or 1954. Many of our patients with these tumors come from regions where the population is affected by endemic nephropathy, the frequency of tumors in these regions being about 100 times higher than it is in other parts of Yugoslavia. In many cases these patients have renal failure and, therefore, conservative procedures are undertaken. Herein are reported the causes and results of therapy in 972 cases of renal pelvic and ureteral tumors collected in Yugoslavia. Particular attention has been paid to conservative operations (37 cases of renal pelvic and 64 cases of ureteral tumors), including their indications and possibilities. That many patients with renal pelvic and ureteral tumors have favorable conditions for a conservative procedure is confirmed by the comparatively good followup. However, in other cases a conservative operation is unreasonable and nephroureterectomy is mandatory.


Effects of formalin on bladder urothelium. Formalin instillation into canine bladders was followed by serial radiographic and histologic evaluation. A generalized slough of epithelial tissue was seen with the deposition of an amorphous substance. Telangiectasia resulted in moderate bleeding. No ureterovesical junction obstruction was seen and reflux occurring in 60 per cent of the animals reverted to normal. Correlation with clinical experience is made.


An evaluation of average flow rate in traumatic neurogenic bladder dysfunction. The average flow rate of 60 male patients with spinal cord injuries was studied in a simplified method with a urine cup and a stopwatch. Results were based on the level of the lesion, course of injury, sensation of micturition, cystometric type and cystographic change. The average flow rate of 60 patients with traumatic spinal cord injury was 10.62 plus or minus 5.37 ml. per second, while that of 10 normal adult male patients was 15.70 plus or minus 3.10 ml. per second. The average flow rate was better in patients who had normal or nearly normal proprioceptive sensation than in those without this sensation. Bladder deterioration was not noted on the cystograms of patients who had normal proprioceptive sensations. Therefore, patients with traumatic cord bladders with normal urinary sensation may have a good prognosis, while those with disturbed proprioceptive sensation may require some urological manipulation to reduce urethral resistance.


Antigenic deletion and prognosis of patients with stage A transitional cell bladder carcinoma. The mixed cell agglutination reaction was studied in 22 patients with stage A transitional cell bladder tumors. The absence of antigens on the original tumor was found to correlate with development of invasive cancer on followup. The presence of antigens on the original tumor correlated with failure to develop stage B or greater disease within 5 to 14 years of followup.


Evaluation of biological markers in bladder cancer. The value of biological markers of bladder cancer was studied in 66 patients. The markers included serum and urine carcinoembryonic antigens, serum and urine fibrinogen degradation products, total lymphocyte counts, urine lymphocytes and urine cytology. A high degree of accuracy (90 per cent) was found in correlating cytology and urinary fibrinogen degradation products with the activity of the disease. Serum and urine carcinoembryonic antigens, serum fibrinogen degradation products, total lymphocyte counts and urine lymphocytes were found to have no value in screening bladder cancer patients. Urinary fibrinogen degradation products and cytology in combination are recommended for screening and followup of patients at high risk.


The surgical correction of retrograde ejaculation. Two patients with retrograde ejaculation subsequent to Y-V plasty of the bladder neck underwent a surgical procedure to reconstruct the internal vesical sphincter and correct the phenomenon. The approach is transvesical and the internal vesical sphincter is reconstructed to the diameter of a No. 16 Foley catheter. The normal muscle of the bladder neck is approximated after the mucosa and scar tissue are excised. Both patients now have normal ejaculation and one has fathered a child.


Chemotherapy of bladder carcinoma with cyclophosphamide and adriamycin. We assigned 49 patients with transitional cell carcinoma of the bladder to 1 of 3 groups: 21 patients (group 1) received cyclophosphamide alone, 10 patients (group 2) received adriamycin alone and 18 patients (group 3) received cyclophosphamide and adriamycin. The objective responses were 52.3 per cent in group 1, 10 per cent in group 2 and 50 per cent in group 3. These results suggest a significant activity of the drugs (especially in groups 1 and 3) tested in bladder cancer.


Sphincter stretch: a new technique resulting in continence and complete voiding in paraplegics. A technique is described to facilitate voiding in the paraplegic, whereby external sphincter spasm is eliminated as a source of obstruction. Digital stretch on the anal sphincter combined with the Valsalva maneuver has resulted in satisfactory bladder emptying in 16 paraplegic patients. The technique has been found unsatisfactory in patients with contracted bladders or with incomplete lesions of the spinal cord.


Peyronie's disease: results with dermo-jet injection of dexamethasone. The results in 21 patients with Peyronie's disease who were managed with a course of dermo-jet percutaneous injections of dexamethasone into the plaques are described herein. These patients had 6 to 10 injections at intervals of 1 month for 6 months. In a high percentage of the cases there occurred a disappearance or decrease in the size of the plaques, pain on erection and discomfort during sexual relations. Also, there was a high rate of improvement in the chordee. Because of the natural history of resolution of the plaques and the small number of patients, statistical significance is not believed applicable, although 71 per cent of the patients had experienced prior failure with other modes of therapy. Eight patients experienced urinary or prostato-epididymal infections at some time in their medical history, correlating well with the inflammatory theory as the cause of the disorder.


Isolation and identification of the human malignant prostatic epithelial cell in pure monolayer culture. Isolation of the human malignant prostatic epithelial cell in pure monolayer culture was accomplished by clonal growth of single cells derived from metastatic deposits of prostatic carcinoma. Identification of these cells was established by the fact that the acid phosphatase of the prostatic epithelial cell is not inhibited by immersion in 10 per cent neutral formalin up to 24 hours, whereas all other acid phosphatases are destroyed by the formalin.


Sulfacytine: a new sulfonamide. Double-blind comparison with sulfisoxazole in acute uncomplicated urinary tract infections. A new sulfonamide, sulfacytine, was compared in a double-blind study with sulfisoxazole for the treatment of acute uncomplicated urinary tract infection in 98 outpatients. Patients received either 4 gm. sulfisoxazole or 1 gm. sulfacytine daily for 10 days. Evaluation was made of the bacteriologic and clinical success within the period of treatment and at some point after treatment. Bacteriologic success, or reduction of urine bacterial count from 100,000 or more micro-organisms per ml. to 1,000 or less, was observed in 95 to 100 per cent of the patients in each group during treatment as well as at the post-treatment evaluation. Clinical success, or the abolition of dysuria and frequency of urination and the reduction of pyuria to less than 10 white blood cells per high power field, was observed in 75 to 85 per cent of the patients. Adverse reactions were rare, involving 1 instance each of headache, nausea and hematuria in the sulfisoxazole group, and drug attributability was only possibly established. Mild laboratory abnormalities occurred in each group, 2 cases each of decreased white blood count and 1 instance of a lowered hemoglobin in a patient in the sulfacytine group. The results of our study seem to indicate that sulfacytine is an effective drug for the treatment of acute uncomplicated urinary tract infections.


Prognostic value of host immunocompetence in urologic cancer patients. To evaluate the prognostic significance of host immunocompetence in urologic cancer patients, the subsequent clinical course of 95 patients was determined a year after skin testing with dinitrochlorobenzene. A close correlation was demonstrated between dinitrochlorobenzene reactivity and prognosis among 38 transitional carcinoma patients. Of 19 patients with impaired reactivity 13 had tumor recurrences and 11 of these died of cancer within 1 year. Only 5 of 19 patients with normal dinitrochlorobenzene reactivity had recurrences and none died during the same interval. Although not statistically significant, similar results were observed among 10 renal cell carcinoma patients of whom 3 of 5 with impaired dinitrochlorobenzene reactivity had tumor recurrences, while 4 of 5 with normal reactivity remained free of tumor. One testis tumor patient with impaired dinitrochlorobenzene reactivity died of cancer, while 3 of 4 with normal reactivity remained free of tumor. Similarly, 1 patient with carcinoma of the penis with impaired dinitrochlorobenzene reactivity died of cancer, while 2 of 3 with normal reactivity remained free of tumor. In contrast, reactivity to dinitrochlorobenzene did not correlate with the clinical course of 38 prostatic carcinoma patients. Ten of 19 patients with normal dinitrochlorobenzene reactivity and 9 of 19 with impaired reactivity were dead or had symptomatic recurrences within 1 year, while 9 of 19 with normal reactivity and 10 of 19 with impaired reactivity were either free of tumor or asymptomatic. However, a trend toward a correlation between dinitrochlorobenzene reactivity and tumor progression was observed among patients not receiving endocrine therapy. The differences with respect to the prognostic significance of host immunocompetence between transitional carcinoma patients and those with prostatic carcinoma may be explained by fundamental differences in the biologic properties of these tumors, especially the endocrine sensitivity of prostatic carcinoma.


New Iglesias resectoscope with continuous irrigation, simultaneous suction and low intravesical pressure. The new Iglesias resectoscope that allows simultaneous suction, continuous irrigation and low intravesical pressure is described. Advantages of this instrument include no interruption, better endoscopic vision by a continuous clear inflow of more than 600 ml. per minute, a low intravesical pressure less than 10 mm. Hg during the transurethral resection, shorter operating time, less bleeding, easier teaching and no more wet floor and wet surgeon. Since the entire amount of irrigating fluid is collected blood loss can be calculated and the amount of absorption can be determined.


Blunt ureteral trauma with perineal urine fistulization: review of the literature. The first case of blunt ureteral disruption with external urine fistulization is presented. Reanastomosis with temporary urine diversion by a nephrostomy tube was successful. A review of the literature since 1950 revealed only 49 cases that proved this pathology should be considered in the differential diagnosis of post-traumatic hematuria or the development of mass in the flank. Nephrectomy is no longer used since a thorough attempt at reconstructive surgery will provide good functional results.


Chylous ascites following retroperitoneal lymphadenectomy. A case of postoperative chylous ascites accumulation after retroperitoneal lymph node dissection is reviewed. Although uncommon, this complication is distressing and because of the close proximity of the cisterna chyli to the renal pedicles it may be encountered with any retroperitoneal procedures involving this area. Avoidance of the complication by specific identification and ligation of these structures appears to be the best treatment. Several forms of operative and non-operative therapy have been noted and survival rates in the iatrogenic form of chylous ascites appear to be good based on a limited series of cases.


Necrotic stomatitis in a dolphin.

Necrotic stomatitis in a dolphin. Necrotic stomatitis of undetermined etiology was found in an Atlantic bottlenosed dolphin, Tursiops truncatus. The case history, treatment and hematologic findings are described. The animal remained anorectic throughout the course of the illness, and was force fed on a daily basis for approximately 5 weeks.


Detection and transmission of infectious hematopoietic necrosis virus in rainbow trout. Detection and transmission of Infectious Hematopoietic Necrosis Virus in rainbow trout (Salmo gairdneri) was studied at a commercial trout hatchery. Transmission of virus was demonstrated via water, feed and contaminated eggs. If eggs from carrier females were incubated several weeks in virus-free water, the resulting fry did not become infected. However, if fry subsequently became infected they were lifetime carriers. Infectious virus was readily detectable in most tissues of moribund fish; in carriers it was detected in sex products of spawning fish, and in samples from the intestine of post-spawning fish, but not in samples from blood, feces, kidney, or liver. The carrier rate was not significantly different between sexes. It was concluded that adult carriers are the reservoir of infection and that transmission occurs primarily when carriers shed virus and expose susceptable fish or eggs.


Effect of virulent Trichomonas gallinae on the band-tailed pigeon. Nine Trichomonas-free band-tailed pigeons (Columba fasciata fasciata) trapped in Colorado died from experimental infection with Jones' Barn Trichomonas gallinae 7.1 days (av.) post-inoculation. Three experimentally infected domestic pigeons (C. livia) used as controls died 5.7 days (av.) post-inoculation. Three band-tailed pigeons from Colorado naturally infected with avirulent T. gallinae. Trichomonads obtained from a fatal case of trichomoniasis in a band-tailed pigeon from California killed a band-tailed pigeon from Colorado; they did not kill five domestic pigeons but did induce severe oral caseation.


Experimentally transmitted marble spleen disease in pen-raised wild turkeys. Pen-raised North American wild turkeys (Meleagris gallopavo L.) were experimentally infected with marble spleen disease (MSD) to determine their susceptibility to this disease. Gross and microscopic lesions were consistent with experimental MSD in pheasants and domestic turkeys: an enlarged mottled spleen, intranuclear inclusion bodies, and absence of pulmonary edema and hemorrhage. Detectable levels of viral antigen were not demonstrable in sera of turkeys using the agar gell precipitin test.


Fish furunculosis caused by Aeromonas salmonicida var. achromogenes. An epizootic of sub-acute furunculosis caused by an acromogenic variety of Aeromonas salmonicida is described. Bacteriologic, serologic and virulence characteristics of the isolate are presented.


Congenital anomalies in a neonatal white-tailed deer in Alberta. In September, 1973, a live male 2-3 day old white-tailed deer (Odocoileur virginianus) with multiple anomalies of the head and forelimbs was found near Lethbridge, Alberta. Notable gross findings inculded brachygnathia inferior, atypical incisor tooth alignment, medially folded ears, humero-radial arthrogryposis and bowing of the radius and ulna. Hematologic determinations indicated increased erythrocyte, hemoglobin and hematocrit levels. Histopathologic examination revealed mineralized spherites in the cerebellum and midbrain.


Public health and the urban gray squirrel: mycology. From 180 gray squirrels (Sciurus c. carolinesis), 942 isolates of fungi representing 19 genera were recovered upon culture of hair-skin scrapings and toenails. Of the isolates, 170 represented known human pathogens and 142, squirrel pathogens. A human infection of Trichophyton mentagrophytes was derived from handling the squirrels. Skin lesions of seven squirrels were attributable to T. mentagrophytes and Mucor sp.


Whirling disease (Myxosoma cerebralis): control with ultraviolet irradiation and effect on fish. Water contaminated by Myxosoma cerebralis was disinfected with ultraviolet irradiation to control whirling disease. Irradiation at 18,000 microwatt seconds/cm2 (MWS/cm2) reduced infectivity of M. cerebralis by 31-86% and 27,650 MWS/cm2 reduced infectivity by 86-100%, even in the presence of a small amount of silt.


Experimental infection of white-tailed deer with rinderpest virus. White-tailed deer (Odocoileus virginianus) succumbed to experimental infection with virulent rinderpest (RP) virus that was also lethal to cattle and goats. The deer developed clinical signs typical of RP and died 5 and 6 days post-inoculation. Infection was confirmed by recovery of virus from blood before death, from lymph node tissue after necropsy, and demonstration of specific complement fixing antigen in those tissues. Electron micrographs of infected Vero cell cultures revealed extracellular virions and intracytoplasmic and intranuclear inclusions made of randomly distributed fibrillar strands.


Trypanosomes from mule deer, Odocoileus hemionus in Wyoming. Examination of mule deer, Odocoileus hemionus, from Wyoming in Spring, 1974 (8) and in Winter of 1974-75 (8) revealed trypanosomes in all 16 deer. Spring samples showed dividing epimastigotes as well as normal bloodstream forms. Winter samples showed only normal blood stream forms. These differences are considered to be seasonally related.


Control of house fly and stable fly breeding in rhinoceros dung with an insect growth regulator used as a feed additive. An insect grwoth regulator (IGR), Thompson-Hayward TH 6040 (N-(4-chlorophenyl)-N'-(2,6-difluorobenzoyl)urea), incorporated in the feed of rhinoceroses at rates of 1 and 0.1 mg/kg inhibited development of Musca domestica L. and Stomoxys calcitrans (L.) in the feces.


Mycotic granuloma in a tiger salamander. An unidentified brown-pigmented fungus was the cause of a granuloma in the left lumbar musculature of a captive female tiger salamander. Histologically, the fungus appeared in the granulomatous tissue both as round yeastlike budding cells and as long septate hyphae.


Toxoplasma gondii antibodies in free-living African mammals. Twelve species of free-living African mammals from Kenya, Tanzania, Uganda and Zambia were tested for antibodies to Toxoplasma gondii using the indirect hemagglutination test. Of 157 animals sampled, 20 (13%) were seropositive. T. gondii antibodies were detected in Burchell's zebra, (Equus burchelli), hippopotamus (Hippopotamus amphibius), African elephant (Loxodonta africana), defassa waterbuck (Kobus defassa), lion (Panthera leo), and rock hyrax (Procavia capensis), The highest titers were found in elephants, two having titers of 1:4096 and one of 1:8192. These results are discussed in relation to the maintenance of T. gondii among African wildlife.


Fluoroacetamide (1081) oisoning in wild birds. An outbreak of poisoning in four greylag geese (Anser anser) and 35-45 teal (Anas crecca) is described. Laboratory findings led to the conclusion that a wheat bait containing the rodenticide fluoracetamide (1081) caused the poisoning. Circumstantial evidence incriminated fluoracetamide as the cause of death in white-fronted geese (Anser albifrons), mallards (Anas platyrhynchos), and chukars (Alectoris chukar).


Ectopic fetuses in two cottontail rabbits. Mummified fetuses were discovered in the abdominal cavities of two cottontail rabbits (Sylvilagus floridanus) collected during separate years from the same geographical location in Virginia. One of these rabbits had a patent opening through the vaginal wall to the abdominal cavity. The uterus and vagina of the second rabbit appeared normal.


Toxoplasmosis in dasyurid marsupials.

Toxoplasmosis in dasyurid marsupials. During a histopathologic survey of 240 dasyurid marsupials a high prevalence of infection of Toxoplasma gondii was found in eight of thenine species examined. Amongst the infected species, endemic infection in field animals was proved in Dasyuroides byrnei, but there was also good evidence of laboratory infection probably derived from raw sheep tissues in their diet. Infection was never demonstrated in animals less than six months of age. The 21 Antechinus stuartii examined remained free from infection despited a lengthy stay in the laboratory and a similar diet. This freedom from infection may indicate a particular resistance to Toxoplasma infection by this species.


Presumptive paratuberculosis in a Virginia white-tailed deer. Paratuberculosis (Johne's disease) is described in a 5-month-old white-tailed deer (Odocoileus virginianus). Diagnosis was based on clinical signs and pathology.


Fascioloides magna (Bassi, 1875) in feral swine from southern Texas. Between 1971 and 1975, Fascioloides magna was found in 46 of 67 (69%) feral swine (Sus scrofa) in southern Texas. Flukes were recovered from swine in areas where F. magna commonly has been recovered from white-tailed deer and cattle. One to 12 flukes were recovered from each infected animal. Their presence was indicated by black hematin pigment on the liver and various other internal organs. Eggs were not detected in the gallbladder or feces of infected animals although mature flukes and eggs were recovered in the livers suggesting that, like cattle, feral swine can be infected but are aberrant hosts for the parasite and do not disseminate eggs.


Tularemia in Florida: Sylvilagus palustris as a source of human infection. The marsh rabbit, Sylvilagus palustris, was epidemiologically incriminated as the source of two human cases of tularemia. This represents the first published report of involvement for this species in the human disease.


Isolation and characterization of a herpesvirus from wild turkeys (Meleagris gallopavo osceola) in Florida. Viral agents producing both a syncytial-type cytopathic effect and type A intranuclear inclusion bodies in vitro were isolated from the kidneys of five of 10 wild turkeys. A plaque assay system for viral infectivity was developed and used to characterize one of the wild turkey viruses (WTV). WTV replication was inhibited by 5-bromodeoxyuridine, indicating the virus contained DNA as its genetic material. Virus infectivity could be transferred only as viable whole cell preparations; one cycle of rapid freezing and thawing completely inactivated the virus. Typical herpes-like virions were found within the nuclei when cells infected with WTV were examined by electron microscopy. WTV had characteristics typical of the herpes group of viruses.


Intussusception in a Florida manatee.

Intussusception in a Florida manatee. An intussusception resulting from an embedded fishhook and a mass of nylon cord, monofilament line, and wire was determined to be the cause of death in a Florida manatee (Trichechus manatus latirostris). Pathologic findings are given along with information on bacteria (Edwardsiella tarda), pesticide residues (DDE, PCB's and dieldrin), and parasites (Chiorchis fabaceus).


Serum dopamine-beta-hydroxylase activity in essential hypertension and in chronic renal failure with hypertension. Elevated serum DBH (dopamine-beta-hydroxylase) activity was found in essential hypertension. The elevated level was not reduced when blood pressure was brought to normotensive level by administration of thiazide or rauwolfia. In contrast, serum DBH activity was low in both normotensive and hypertensive patients treated on prolonged hemodialysis. However, there was no correlation between serum DBH activity and blood pressure level. It was suggested that the pathogenesis of high blood pressure might be different between essential hypertension and hypertension with chronic renal failure, and that measurement of serum DBH activity might help for clinical differentiation of essential hypertension from certain forms of secondary hypertension.


The effects of respiratory acidosis on plasma renin activity in the dog. The effects of arterial PCO2 on plasma activity was studied in chloralose anesthetized dogs undergoing carefully controlled respiratory acidosis. Plasma renin activity, measured by radioimmunoassay, was enhanced (P less than 0.001) during inhalation of CO2 despite insignificant changes in renal blood flow and arterial pressure. Although underlying mechanism remained to be investigated, activation of sympathetic nervous system and intrarenal effects of CO2 seemed to be involved in this enchancement.


Ultrastructure of the cardiac muscle of early human embryo. In order to compare the ultrastructural difference between cardiac myocytes of the 54 day gestational age and that of the 114 day gestational age, the human fetal hearts were studied by means of electron microscopy. In the 54 day heart, although the nexus was developed already, contractile elements were immature and there was no close association between myofibril and mitochondria, and also sarcoplasmic reticulum was not accomplished. On the contrary, in the 114 day heart, the contractile elements, mitochondria and sarcoplasmic reticulum were partially developed fairly well in myocytes.


Hypokalemia and metabolic alkalosis resulting from overuse of magnesium oxide. A 23 year old woman had taken large doses of magnesium oxide (up to 20 to 30g per day) initially for habitual constipation and later for idiopathic edema instead of diuretics, until the concealed abuse was discovered. During the abuse she showed hypokalemia and metabolic alkalosis. When the ingestion was stopped, the electrolyte imbalance recovered within two weeks.


Annular subvalvular left ventricular aneurysm -an autopsy case-. An case of annular submitral left ventricular aneurysm in a 67-year-old woman was presented. Complication of the severe tuberculosis might have played a part in the pathogenesis of the annular subvalvular left ventricular aneurysm.


[Effect of anoxia on the excitability of the canine ventricular muscle (author's transl)]. It has been believed that completion of refractory period does coincide with full repolarization in cardiac muscle. So, the duration of action potensial (APD) has not infrequently been derived from refractory period. But recently some authors pointed out that duration of total refractory period (TRP) was not identical with APD in anoxic state and prolonged severe anoxia might occasionally increase effective refractory period (ERP). Nevertheless, marked reduction has been consistently noted in APD by many workers during severe anoxic period. Then, it seems to deserve more detailed investigation whether the refractory period may represent APD under any condition. The purpose of this paper is to present the results of studies on the effects of anoxia on the relationship between refractoriness and transmembrane action potential.


[Laboratory studies on doxycycline intravenous (author's transl)]. The results of laboratory studies on doxycycline intravenous are summarized as follows: 1. The standard curves of doxycycline in five dilution systems were compared. Zones of growth inhibition were largest in the phosphate buffer solution at pH 7.2 and smallest in human serum. Lung system was close to the buffer system, liver system close to the serum system, and kidney system intermediate. 2. The doxycycline concentrations in blood of healthy male adults were compared by cross-over method. The concentration following intravenous injection of 200 mg, dissolved in 40 ml of 20% glucose and injected in 5 minutes, was high than that after oral administration of 200 mg immediately after the injection, but was same after 3 hours and thenafter. 3. No tendency of accumulation was observed in six volunteers injected intravenously with 100 approximately to 200 mg of doxycycline daily for three days. 4. In a patient with chronic broncho-bronchitis injected intravenously with 200 mg, the blood level reached a peak of 4.8 mcg/ml after 30 minutes, while the sputum level reached a peak of 1.8mcg/ml after 90 minutes. The sputum level was 30 to approximately 40% that of serum. 5. The urinary excretion of doxycycline was 94 mg/day (47.0%) after a single intravenous injection of 200 mg. and 53 mg/day (26.5%) after a single oral administration of 200 mg.


[Clinical studies on OE-7 chiefly in the treatment of acute respiratory infections (author's transl)]. The results of clinical studies on OE-7 (erythromycin stearate, enteric coated granule) were as follows. (1) Thirty-two cases with respiratory infections were treated OE-7 by the oral route of 300 mg every 6 hours in 5 cases and 400 mg every 8 hours in 27 cases. In 28 of 32 cases (87.5%) OE-7 was effective. Gram-positive cocci, namely pneumococcus, alpha- and beta-streptococcus, staphylococcus etc. are the most important pathogens in acute respiratory infections statistically and the most of them are susceptible to many chemotherapeutic agents, especially to erythromycin and penicillin. This is the case also with our studies. Acute exacerbation of asthmatic patients are frequently complicated with secondary respiratory infections caused by those pathogens and sometimes this condition in turn exacerbate asthmatic states. In our studies OE-7 displayed a good effect to such cases. (2) As the side effect gastrointestinal disturbances were slightly observed in 8 of 32 cases and allergic reactions in none. Hepatic and renal function test examined in 17 cases revealed no change after treatment. (3) The mean serum concentration of OE-7 by the oral route of 300 mg every 6 hours revealed about two times higher levels than by the same route of 400 mg every 8 hours, the peak was both reached after 3 hours after ingestion 1.96 mcg/ml and 0.97 mcg/ml respectively. This experiment was done for 5 healthy persons in the condition of free food ingestion and cross over in one week interval.


[Therapeutic effect of sulfobenzyl-penicillin (SB-PC) on the concentration of SB-PC in human bile (author's transl)]. Sulfobenzyl-penicillin (SB-PC) is currently being investigated for use in man. The purpose of this study was to evaluate effect of SB-PC on Salmonella typhosa and biliary excretion of SB-PC in disease of the biliary tract. 1) Clinically, typhoid carriers without cholelithiasis were initiated with 4.0 g/day of SB-PC. Stool and bile became negative for Salmonella typhosa 14 days after initial treatment. 2) In typhoid carriers with cholelithiasis, Salmonella typhosa were not isolated from bile, wall of the gallbladder and surface of gallstone, but were isolated from nuclei of gallstones. The treatment of typhoid carriers with cholelithiasis may belong to a most difficult problem. 3) Biliary excretion of SB-PC in the patient given a single dose of 2.0 g/day im. was markedly dependent on characteristics of the patient, situation of external drainage and volume of bile excretion. High concentration in bile in some patient was 298 mug/ml at 3 hours after administration. 4) In intravenous administration of single dose of 6.0 g. maximum concentration in bile was about 2,000 mug/ml at 2 hours after administration and bactericidal concentration was obtained for resistant bacteria (Pseudomonas, Proteus, etc.) in biliary infection. 5) As side effects, pain and redness were infrequent after im. administration. Toxicity was not experienced in the patients injected intravenously.


Virologic and serologic studies on an outbreak of echovirus type 11 infection in a hospital maternity unit. An outbreak of echovirus type 11 (E-11) infection occurred among newborn babies in a hospital maternity unit in the summer of 1971. The results of studies are as follows: 1) Forty-one of 188 infants developed febrile illness with stomatitis during one and a half months from July to September. E-11 was isolated from stool specimens of 14 infants and two throat swabs. Antibody response to the virus was shown in all the 19 cases examined. Some of their mothers were suffering from subclinical infection. 2) The isolates were identified as a variant of E-11 which is not neutralized with antiserum against prototype E-11. Antiserum against the current virus neutralized both current and prototype viruses. 3) Sucrose gradient centrifugation of sera from infants revealed that the neutralizing antibody activity resided more predominantly in 19S than in 7S fractions. These antibodies reacted more specifically with the current strain than with the prototype Gregory strain.


[Functional state of the cardiovascular system in experimental acute occlusion of the terminal segment of the aorta]. In 30 experiments on dogs a study was conducted of the pathophysiological mechanisms of the disorders in central haemodynamics and myocardial contractility during an acute occlusion of the terminal aorta and after reestablishment of the circulation in the diseases extremities. In response to the occlusion an elevation was noted in the total peripheral resistance, in the force and rate of the cardiac contractions, and a compensatory hyperfunction of the heart developed. By 6 hours of the occlusion the total peripheral resistance increased, the force and rate of the cardiac contractions decreased, the myocardial tension increased, the external work of the heart decreased, and myocardial hypodynamy developed. In 45 min following the restoration of the circulation a reduction of the total peripheral resistance was observed, the myocardial contractility was inhibited, the phase structure of the cardiac cycle was disturbed. A further observation for 45 min failed to reveal any changes in the indices of cardio- and haemodynamics, the phase structure of the cardiac contractions and myocardial contractility, as compared to the data obtained in the preceeding study.


[State of hemodynamics, according to radiocardiographic data, in persons working in contact with ionizing radiation sources]. The presented results illustrate the study of the cardiovascular system by means of radiocardiography conducted in normal individuals working in contact with sources of ionizing radiation. The study includes 51 persons in the test group and 42 in the control group that was similar to the test one in terms of age, sex and type of work performed, with the only exception that these in the control group had no contact with ionizing radiation. Persons working under the effect of ionizing radiation displayed a moderate increase in the stroke and minute index and the circulating blood volume, with the blood flow rate somewhat decelerated. The changes were deeper in those with over 5 years of service, and in those with functional changes in the nervous system, like neurocirculatory dystonia. The moderate level of these reactions and their reversibility permit to interpret them as an adaptative reaction to the effect of low doses of ionizing radiation.


[Functional state of baroreceptors of the aortic arch in experimental hypertension]. The bioelectrical activity of the aortic nerve was studied in normal rabbits and in those with experimentally induced hypertension. Electroneurograms of the aortic nerve of rabbits with renal and coarctational (stenosis of the abdominal aorta) hypertension demonstrated the same burst-like activity synchronous with the systolic contractions of the heart that was noted in normotensive animals. The threshold of the transit of the burst-like activity of the aortic nerve into the uniform one in cases of acutely elevated arterial pressure (induced by injections of noradrenalin and angiotensin) and the threshold of the disappearance of the mentioned activity after an acute reduction of the arterial pressure (induced by injections of acetylcholine, tetra-ethylammonium or by acute bleeding) in rabbits with renal and coarctational hypertension are shifted upwards, as compared to those in normotensive rabbits. It is the more true of the former threshold. The depressor reaction to the administration of the ganglionic blocker -- tetra-ethyl-ammonium -- in renal hypertension during the initial 2 months of the disease remains unchanged, with the exception of the 4th and 8th weeks, when it is elevated. It is concluded that the baroreceptors of the aortic arch percept the chronically elevated arterial pressure as a normal one reacting adequately to its acute changes in either direction. Thanks to this the barorecptors of the aortic arch strive to maintain a high level of the arterial pressure and provide for a stabilization of hypertension.


[Distribution of sodium in the tissues in experimental salt hypertension]. The distribution of sodium in the aortal wall, myocardium and skin of rats was studied by a tracer technique. An increase of the bound fraction of extracellular sodium was found in the aortal wall and skin of rats with hypertension produced by a 90-day salt load. A positive correlation was found between the content of bound sodium in the aorta and the arterial pressure level.


[Relationship between corticosteroids, catecholamines and electrolytes in rats kept on sodium-rich diet]. The changes in the content of catecholamines, electrolytes and corticosteroids were studied dynamically and simultaneously in rats under salt stimulation. Long-term maintenance of the animals on sodium-rich diets results in its accumulation in blood plasma and heart muscle, the tissue depot of catecholamines diminishing at the same time. The changes in the functional state of the adrenal glands and of the catecholamines content in the myocardium are of a phased nature. The activation of the glucocorticoid function of the adrenal glands on the 18th day of the experiment is substituted by its reduction on the 56th day. The presence of a distinct relationship between the functional state of the adrenal glands and the level af adrenalin in the heart indicates the regulatory role of glucocorticoids in this experimental situation.


[Peculiarities of cardiac activity in renal form of experimental hypertension with different hemodynamic characteristics]. The main haemodynamic indices were studied in rabbits of two age groups (young -- 10--12 month, and old -- 3--4 years) under normal conditions and those with experimentally induced renal hypertension. Significant changes were observed in the proportion of the main parameters of haemodynamics -- cardiac output per 1 min and total peripheral resistance -- in the presence of persistent arterial hypertension, which permitted to single out three haemodynamic forms of experimentally induced renal hypertension. The first and second haemodynamic forms are characterized by a sharp enhancement of the total peripheral resistance and diverse changes in the values of cardiac output per 1 min.: the third haemodynamic form is predmoninatly characterized by an elevation of the cardiac output. The compensatory hyper-function of the myocardium in the first and second forms of renal hypertension develops usually isometrically, in the third form -- according to the mixed variant.


[Surgical treatment of patients with symptomatic hypertension]. Symptomatic hypertension is observed in numerous patients with elevated blood pressure. Special attention is paid in the paper to the diagnosis of coarctation of the aorta, nonspecific aortitis and renovascular hypertension. The possibility of diagnosing these lesions by means of the routine diagnostic techniques is indicated. The experimence of surgical treatment of 476 patients with coarctation of the aorta demonstrates the efficiency of the surgical procedures. No postoperative mortality cases have been observed in the recent 5 years. Non-specific aortitis that is the second-frequent process diseasing the aorta has a polymorphous clinical pattern. Hypertension is the leading symptom of aortitis. The results of various reconstructive procedures prove their high efficacy in decreasing the hypertension in patients with aortitis. According to the author's data, renovascular hypertension is found in 54% of the patients examined only on an out-patient basis. Among 354 operations, 204 included a reconstructive procedure on the renal artery. The importance of proper rehabilitation of the postoperative patients is emphasized.


[Psychovegetative interrelations in hypertensive disease and arterial hypotension]. Proceeding from an analysis of haemodynamic shifts in patients with hypertension and primary arterial hypotension, the paper demonstrates their specificity depending on the severity of the vascular syndrome, the form of functional exercise (physical, intellectual, emotional), and the nature of psychological conditioning (psychogeny, personality peculiarities). The obtained data are discussed with regard of the concepts of functional neurology.


[Sympathico-adrenal system in elderly patients with systolic hypertension]. A study of the catecholamines passage with urine in patients of advanced age with systolic hypertension has revealed features specific for the activity of their sympathico-adrenal-system by comparison with that in patients with hypertensive disease (with systolic-diastolic pressure rise) and in persons of the same age with normal pressure. In systolic hypertension an inhibition of the mediatory link finding its expression in a decreased noradrenaline excretion, was noted, while that of adrenalin remained normal which led to a fall in the ration noradrenaline/adrenalin. Inasmuch as adrenalin causes chiefly the rise of systolic pressure and noradrenaline -- that of diastolic it may be presumed that the established features of the sympathico-adrenalin activity appear to be a factor contributing to the systolic nature of the hypertension under review, which stems primarily from other major pathogenetic factors. At the same time in subjects of advanced age the reactivity of the mediatory link in systolic hypertension remains intact, this manifesting itself in a significantly increased noradrenaline passage, as compared to a low initial level following administration of insulin.


[Isolated and combined lesions of renal arteries in patients with vaso-renal hypertension]. In the course of a 10-year study of the problem of renovascular hypertension in the A.N. Bakuley Institute of Cardiovascular Surgery, concomitant pathology of other arterial systems was found in 144 patients among 218 cases of acquired lesions of the renal arteries. The combination of the lesions of the renal arteries with those of other arteries (branches of the aortic arch, descending thoracic and abdominal aorta, its visceral branches and the arteries of the lower extremities) is, according to the author, one of the main peculiarities of renovascular hypertension that predetermines its malignant course. A purposeful study of the state of the major vessels in a patient with arterial hypertension permits to reveal their lesion or intactness, and to conduct a detailed clinical investigation accordingly, as well as to choose the proper method of angiography and surgery.


[Primary aldosteronism and arterial hypertension]. The experience of surgical management of 16 patients with primary aldosteronism is summarized. The aspects of its diagnosis are analysed, and its possible atypical course indicated. The authors used pneumoretroperitoneography for determining the localization of the aldosteromas. The localization of an aldosteroma having been established, the best approach is the modified Smithweak's one, for the revision of both adrenal glands a median or transversal laparotomy is employed. All the 16 patients survived the operations favourably.


[Unusual localization of the excitation impulse block in acute myocardial infarct]. A case of an unusual localization of the conductivity block is described in a female patient with acute myocardial infarction, that was demonstrated by way of recording the electrical activity of the cardiac conductive pathways. The peculiarity of the case was also demonstrated to consist in the multiplicity of the levels of conductivity disorders. For the first time in the literature, the development of a block in the main stem of the bundle of his was traced in detail.


[Changes in the glucocorticoid function of the adrenal cortex in patients with myocardial infarct treated with trioxazine and aminazine]. A protracted observation over the glucocorticoid function of the adrenal gland in patients with myocardial infarction educed a biphasic nature of changes in the concentration of the plasma and urine corticosteroids in this affection. Most informative are shown to be the evidences of activation of the hypothalamo-hypophysial-adrenal system furnished by the biologically active 11-oxycorticosteroids in the peripheral blood plasma. Psychopharmacological drugs produced a less intensive activation of the glucocorticoid function of the adrenal cortex in the acute period of myocardial infarction and they smooth down a renewed rise in the level of steroid during the subacute period of the disease. Chlorpromazine displays a stronger antistress action than does trioxazine, but the available data justify recommending both these drugs for the treatment of patients with myocardial infarction.