Controlled drug release from polymeric delivery devices. III: In vitro-in vivo correlation for intravaginal release of ethynodiol diacetate from silicone devices in rabbits.

Forty female rabbits were implanted with silicone vaginal devices containing ethynodiol diacetate for up to 8 weeks. As predicted from in vitro studies, a Q - t1/2 (matrix-controlled) release profile was observed in vivo. The in vivo drug release profile was compared with in vitro data measured at three hydrodynamic conditions, and the diffusional resistance across the vaginal wall was estimated. Drug released from silicone devices yielded a prolonged plasma level when compared with data following intravaginal or intravenous administration of a solution dose. The rate constant for elimination was unchanged. The plasma concentration of the drug was related to the intravaginal drug release profile both theoretically and experimentally and was above the concentration required to inhibit fertilization.


Kinetics and mechanisms of monolayer interactions. III: models to explain time-dependent effects of injected cetrimonium bromide.

Two kinetic models are derived to explain the time-dependent effects of cetrimonium ions injected beneath an air-aqueous solution interface without any previously adsorbed or spread monolayer at different ionic strengths. The data show excellent fit and consistency with a nulticompartmental kinetic model which postulates a barrier or intermediate compartment between the ionic surfactant in the subphase and the sites on the surface. Such a barrier inhibits free diffusion of the surfactant from the bulk of the solution to these sites. The experimental data are not inconsistent with a model that postulates a time-dependent binding process and the absence of a diffusion-limiting subinterface since, within the limits of the error, the derived rate constants conform to the model prediction that they should be proportional to the surfactant-ion concentration.


Characterization of hydrogen bonding between selected barbiturates and polyethylene glycol 4000 by IR spectral analysis.

Several barbiturates and primidone were equilibrated with polyethylene glycol 4000 in pyridine. IR spectral properties of these samples indicate that seven disubstituted barbiturates complex with polyethylene glycol 4000 while five disubstituted barbiturates and two trisubstituted barbiturates as well as primidone do not. Forces responsible for complexation of barbiturates with polyethylene glycol 4000, as inferred from spectral data, consist of hydrogen bonds formed between N1 and N3 hydrogens of the barbiturate ring and two oxygen atoms of the --O--CH2CH2--O--moiety. Also, there appear to be three configurations of intermolecular hydrogen bonding sites between disubstituted barbiturates. Several factors affect the barbiturate-polyethylene glycol 4000 interaction, including the nature of the solvent, C5 substituents, the number of hydrogen bonds formed between reactants, and the 2-carbonyl group of the barbiturate ring. Complexes of polyethylene glycol 4000 with phenobarbital, butabarbital, and cyclobarbital are stable in water at 26 degrees or below, but complexes of polyethylene glycol 4000 with butethal, cyclopentenyl allylbarbituric acid, pentobarbital, and probarbital are not.


Binding of metronidazole and its derivatives to plasma proteins: an assessment of drug binding phenomenon.

Metronidazole and four derivatives were studied in vitro to investigate the differences in the extent of their binding to plasma proteins. Modification at the terminal portion of the alkyl side chain resulted in wide differences in the extent of binding. Molecular orbital calculations were performed by the CNDO and MINDO/2 methods to estimate the frontier electron density on the hetero atom at the 3'-position of the alkyl side chain. A linear correlation between the protein binding parameter (loge P) and the frontier electron density (qr) was observed for the binding of this group of trichomonicidal drugs. NMR spectroscopy was used to demonstrate that the alkyl side chain participated in the binding of these compounds to plasma proteins.


Utilization of model compounds to evaluate effects of slight chemical modifications on their distribution. Pharmacokinetic parameters in rats and mechanisms inferred for their transmembrane transport.

The pharmacokinetics of each of the model compounds benzoylformic acid (I), p-methylbenzoylformic acid (II), p-ethylbenzoylformic acid (III), D-(-)-mandelic acid (IV), D-(-)-p-methylmandelic acid (V), D-(-)-p-ethylmandelic acid (VI), and D-(-)-p-isopropylmandelic acid (VII) were studied in rats to determine the influence of slight chemical modifications of the compounds on their distribution pharmacokinetic parameters in rats. The effects of the specific chemical modifications considered were those of the less than CHOH group of IV against the less than C=0 group of I, the para-alkylation of I and IV, and the branched alkyl group (isopropyl) against the straight chain alkyl groups of the homologs of IV. While the disappearance of I from the blood was describable by the three-compartment open model, that of IV was describable by the two-compartment open model. The apparent volume of distribution of the central compartment (V1) for IV was smaller than that for I, but the volume of the peripheral compartment (V2) for IV was greater than that (V2 + V3) for I. The disappearance of V, VI, and VII from the blood was also describable by the two-compartment open model, but the apparent V1 and V2 for these compounds were lower than those for the parent compound, IV. However, the disappearance of II and II from the blood was describable by a one-compartment open model. Evaluation of the appropriate distribution pharmacokinetic parameters suggested that the peripheral compartment for the anions of these compounds consisted of moderately perfused tissues and that the transmembrane transport of these organic anions between the central and peripheral compartments occurs by diffusion mainly through the aqueous membrane pores, which are lined with polar portions of membrane proteins and/or phospholipids. The possible increased hydrophobic bonding between the alkyl groups of these compounds and the hydrophobic groups of the proteins and/or phospholipids of the membrane pores is implicated to decrease the distribution of the para-alkylated homologs into the peripheral compartments and, consequently, diminish the volumes of their peripheral compartments. The heteroporosity of the membranes of the tissues of the central compartment is proposed as the reason for the diminished volume of the central compartment for V and VI as compared to that of IV or VII.


Mechanistic evaluation of modifications of distribution. Pharmacokinetic parameters of model organic anions in presence of a model renal tubular secretion inhibitor in rats.

The effects of DL-tropic acid (VIII) on the distribution pharmacokinetic parameters of the model compounds benzoylformic acid (I), p-methylbenzoylformic acid (II), p-ethylbenzoylformic acid (III), D-(-)-mandelic acid (IV), D-(-)-p-methyl-mandelic acid (V), D-(-)-p-ethylmandelic acid (VI), and D-(-)-p-isopropylmandelic acid (VII) were studied in rats. Since VIII is a competitive inhibitor of renal tubular secretion of I-VII and since all of these compounds (I-VIII) are negligibly bound to plasma proteins and are neither metabolized nor reabsorbed from the renal tubules, they were considered as model compounds. Therefore, changes observed in the values of the distribution pharmacokinetic parameters of I-VII were attributed to the influence of VIII on the transmembrane transport of the compounds between body compartments in rats. The decrease in the apparent volumes of the central compartments for I, IV, and VII, the increase in the apparent volumes of the peripheral compartments for IV-VII, the absence of change in the volumes of the central or peripheral compartments for the other compounds, and the increase in the ratios of the rate constants of the transfer of compounds from one compartment into another for I and IV-VII were explained in terms of the "aqueous pore" mechanism for the transmembrane transport of the anions of the compounds as well as the heteroporosity of the tissue membranes.


Behavior of erythrocytes in ternary solvent systems.

The effect of ternary solvent systems on erythrocytes was investigated. Hemolysis experiments were run at 37degree in solutions containing various amounts of water, two nonaqueous solvents, and 0.9% sodium chloride. The nonaqueous solvents were propylene glycol, polyethylene glycol 400, dimethyl sulfoxide, dimethylformamide, and tetramethylurea. Ternary diagrams based on the critical hemolytic compositions of the various ternary systems are presented.


Micelle formation and its relationship to solubility behavior of 2-butyl-3-benzofuranyl-4-(2-(diethylamino)ethoxy)-3,5-diiodophenyl ketone hydrochloride.

Micelle formation by 2-butyl-3-benzofuranyl-4-[2-(diethylamino)ethoxy]-3,5-diiodophenyl ketone hydrochloride was studied by conductance measurements. The CMC was approximately 0.05% and was independent of temperature between 20 and 50degree. The heat of formation for the micelle was calculated to be 6.9 kcal/mole. The unusual solubility behavior of the compound was attributed to its ability to form micelles. Ultracentrifuge studies indicate the molecular weight of the micelle to be approximately 100,000. Anions such as chloride, sulfate, acetate, tartrate, and citrate significantly affect the equilibrium solubility of the compound. NMR spectroscopic data indicate that the solubility behavior, in part, is related to an effect on the CMC of the compound by the anionic environment.


Isolation and identification of three new flavones from Achillea millefolium L.

Column chromatography on silica gel of a petroleum ether extract of the flowering heads of Achillea millefolium L. allowed three flavones to be separated and identified. Spectral studies (PMR, mass spectrometry, and UV) and a comparison with data for compounds reported in the literature established the flavones as 5-hydroxy-3,6,7,4'-tetramethoxyflavone, artemetin, and casticin. These compounds have not been reported previously as constituents of A. millefolium.


Quantitative GLC determination of pentylenetetrazol in biological fluids.

A quantitative, sensitive, and specific GLC method was developed for the determination of pentylenetetrazol in water, plasma, and urine. The assay involves a single extraction of the sample into chloroform followed by centrifugation, evaporation, and chromatography. The method for pentylenetetrazol is reproducible, and the sensitivity limit of the assay is 0.5 mug of pentylenetetrazol/ml of biological fluid using a 2-ml sample. This method has a sensitivty sufficient to detect human plasma levels after therapeutic clinical doses and was successfully applied to monitor complete plasma level profiles of this drug in dogs. The data indicate that this drug is very rapidly absorbed following an oral dose, and the half-life of the drug in plasma is approximately 1 hr.


Enterohepatic circulation of tetracycline in rats.

The absorption of tetracycline hydrochloride excreted in the bile of rats was evaluated using the insitu intestinal preparation. For comparative purposes, the absorption of the drug from an aqueous solution having the same pH as that of the bile was also determined. After 4 hr, the amounts of tetracycline absorbed from the bile and aqueous solutions were 72.92 and 77.34%, respectively. There was no significant difference in the amount of drug accumulated in the gut tissue. The disappearance of the drug from the intestinal lumen was biexponential, and the kinetic parameters appeared to be similar. It was concluded that tetracycline excreted in the bile is readily absorbed from the rat intestine. Accordingly, biliary excretion does not seem to account for a significant elimination of this antibiotic from the body.


Determination of mercury-containing pharmaceuticals by vapor phase atomic absorption spectroscopy.

A procedure was developed for the determination of mercurials of pharmaceutical interest. Protic acid cleavage of the compound was followed by reduction of the resulting mercuric ion and vapor phase atomic absorption spectroscopy. This procedure was applied to 11 different mercurial compounds in various pharmaceutical preparations and offers excellent sensitivity with respect to presently used compendial assays. Comparative analytical data between this procedure and compendial methodology are presented.


GLC determination of hexadiphane in pharmaceutical preparations.

A specific, rapid, and sensitive GLC method for purity control of hexadiphane and its determination in pharmaceutical perparations is described. The method utilizes an extraction of the free base, followed by GLC on a 0.5% OV-17 column at isothermal temperature for 6 min and then the temperature was programmed. Results from this method and from a titrimetric method were compared, and no significant differences were found.


Diffusion model for fluidized-bed drying.

A sucrose-lactose-starch granulation was used to study particulate motion and attrition in a fluid bed dryer. There is some classification of material in the dryer as drying proceeds; fine particles are dried faster and become less dense, and the less dry but denser large particles show some (although not great) accumulation tendencies in the lower central area. Unlike countercurrent rotary drying, fluid bed drying cannot be accounted for by water diffusion inside the granule as the rate-limiting step. In its place, a model of external water vapor diffusion is proposed and is supported by vapor-concentration curves and by the linear dependence of the rate constants on the linear air velocities. The dried granulation exhibits the same trend as does countercurrent dried material in that larger particles have higher moisture contents than do smaller particles. Quantitative relationships between content of moisture and size were developed and are supported by experimental data. The granulation, upon storage, does not equilibrate, indicating that this type of water distribution is a problem in batch process granulations as well as in the earlier reported case of granulations for continuous production.


Spectrofluorometric determination of the antibiotic lasalocid in blood.

A spectrofluorometric assay was developed for the determination of the antibiotic lasalocid in dog blood, based on the intrinsic fluorescence of the compound in ethyl acetate. The assay can measure "total" levels of drug and any metabolites present. The specificity of the assay was verified by TLC separation of the dog blood extract, which indicated the presence of only intact drug. The overall recovery (+/- SD) of lasalocid was 62.0 +/- 3.6% in the concentration range of 1.0-10 mug of compound/ml of dog blood. The sensitivity of the assay is 0.5 mug/ml. The assay was applied to the determination of blood levels of lasalocid in the dog following the intravenous administration of a 5-mg/kg dose.


Electron-capture GLC determination of timolol in human plasma and urine.

A GLC procedure was developed for measuring nanogram quantities of timolol in plasma and urine. The unchanged drug was extracted into heptane-4% isoamyl alcohol from alkalinized plasma or urine, together with a homolog of timolol which served as the internal standard. The compounds were subsequently back-extracted into 0.1 N HC1 and then into chloroform following adjustment of the acid phase to an alkaline pH. The compounds in the chloroform extract were derivatized with heptafluorobutyrylimidazole to form the diheptafluorobutyryl derivatives; these were quantitated by electron-capture GLC. Recovery of timolol added to normal plasma and urine was quantitative and reproducible, and no interfering substances were observed in normal biological samples. The method is capable of measuring concentrations as low as 2 ng/ml in plasma or 20 ng/ml in urine. After a 10-mg oral dose of 14C-timolol, peak plasma levels of approximately 30 ng/ml were ovserved in 1-2 hr.


Synthesis of dl-4xi-(2-carboxyethyl)-cis-hexahydropyrrolo-[3,4-d]imidazol-2-one (bisnorazabiotin).

Bisnorazabiotin was synthesized in a six-step sequence from 1,5-dioxo-2-carbethoxypyrrolizidine. It is anticipated that the molecule will serve as a cofactor for biotin-requiring enzymes.


Sodium chloride equivalents, cryoscopic properties, and hemolytic effects of certain medicinals in aqueous solution. III: Supplemental values.

A supplemental table of sodium chloride equivalents and freezing-point depressions at various concentrations for 44 different substances in aqueous solution is presented. Also given in the table is the isosmotic concentration of each material that can form such a solution. The degree of hemolysis of human erythrocytes was determined in 24 different isosmotic solutions, and the data are presented in a table to supplement the previously pub lished values. Eleven isosmotic solutions prevented hemolysis, and 13 others failed to prevent hemolysis.


Tumor-inhibitory agent from Montezuma speciosissima (Malvaceae).

The petroleum ether extract of Montezuma speciosissima Sesse and Moc. demonstrated tumor-inhibiting properties in the P-338 lympocytic leukemia test system (3PS). The constituent responsible for this activity was shown to be a symmetrically substituted 2,2'-dinaphthol, identified as gossypol (C30H30O8).


Bioavailability analysis of chlorpromazine in humans from pupilometric data.

Results of studying the time variation of the miotic response intensity for periods of 6 to 8 hours after dosing in up to 16 normal human subjects who received various oral liquid and intravenous doses of chlorpromazine are reported. Relative to oral liquid doses of chlorpromazine syrup, intravenous doses of the drug slowly infused over a consistent time interval of 30 minutes are approximately 11 times as potent in eliciting miotic response activity. Miotic activity was found to be quite dose sensitive as seen from the response vs. time profiles and the dose-effect curves constructed as plots of areas under the response curves and peak response intensities. The dose-effect curves are approximately linear for both intravenous and oral dosing over the majority of the dose ranges studied. Pupilometry is demonstrated as providing a highly sensitive, reliable, rapid and convenient method for detecting differences in both rates and extents of systemic chlorpromazine bioavailability after parenteral or oral dosing with chlorpromazine. Pupilometry allows comparative bioavailability studies to be readily completed for low oral doses, e.g., 10 mg/70 kg, which are not possible to perform even under the most ideal conditions, using the best direct assay techniques presently available. It is precisely at such low oral doses that bioavailability between oral dosage forms are most pronounced and the use of pupilometry has its greatest utility.


Effect of portacaval shunt on the disposition of drugs with and without first-pass effect.

The pharmacokinetic parameters of lidocaine, antipyrine and salicylamide were studied in dogs before and after construction of a portacaval shunt. The systemic availability of antipyrine was not altered significantly by the surgical procedure whereas the availability of lidocaine and salicylamide, drugs with a marked first-pass effect, was increased from 14.8 +/- 2.8 to 81.3 +/- 5.2% and from 21.8 +/- 7.8 to 57.5 +/- 2.5%, respectively. Of the 78% first-pass extraction of salicylamide, 36% is due to hepatic extraction whereas the remaining 42% is accounted for by intestinal wall extraction. The presence of a portacaval shunt also reduced the plasma clearance of lidocaine and antipyrine, but not salicylamide. The apparent volume of distribution was decreased only with salicylamide. Surgical construction of a portacaval shunt in dogs in a good model to evaluate first-pass effect. Physicians should adjust downward the dose of drugs with a first-pass effect. Physicians should adjust downward the dose of drugs with a first-pass effect in patients with a surgical portacaval shunt or endogenous portal systemic shunts such as seen in cirrhosis of the liver.


Effects of route of administration and blood flow on hepatic drug elimination.

The effects of route of administration and blood flow on the elimination of lidocaine, diphenylhydantoin and propranolol have been investigated in the isolated perfused rat liver. After administration directly into the portal vein, drug concentrations in the reservoir were the same at a given flow rate as concentrations in the hepatic vein after drug was placed directly into the reservoir. The apparent clearance of the drug calculated from these concentrations gave an estimate of intrinsic drug clearance, which is an estimate of the activity of the drug-metabolizing enzymes. Intrinsic clearance is defined as drug clearance when flow is not rate limiting and therefore should be independent of flow. This was confirmed by showing that, at steady state, neither hepatic venous drug concentrations nor concentrations in the reservoir after portal venous administration of lidocaine were affected by altering hepatic blood flow from 10 to 20 ml/min. Propranolol was given as a single dose into the reservoir at flows of 10 and 20 ml/min. The area under the concentration-time curve (AUC) in the reservoir was decreased by increased flow, but AUC for hepatic venous blood was unchanged. Although AUC in hepatic venous blood was unchanged. Although AUC in hepatic venous blood was unchanged, higher peak concentrations and a more rapid half-life was seen in keeping with the clearance of drug from the reservoir. These data suggest that after oral drug administration, steady-state concentrations or AUC in systemic blood is dependent only on the activity of the enzymes involved (i.e., intrinsic clearance) and unaffected by flow, provided drug is completely absorbed and eliminated only by the liver. Furthermore, this will apply even to drugs whose systemic clearance and drug half-life after i.v. administration is profoundly affected by altered hepatic blood flow.


Metabolism, tissue distribution and covalent binding of tripelennamine and its N-nitroso derivative in the rat.

Benzyl-14C-labeled tripelennamine and its N-nitroso derivative (NDT) were administered (20 mg/kg; 50 muc/kg i.p.) separately to control and phenobarbital-pretreated rats. Tissue distribution and covalent binding of the two compounds in liver, lung, kidney, fat and muscle tissues, as well as in the plasma, were determined at 4 and 24 hours after the administration. No specific localization of the test compounds to any tissue or to the plasma was observed. The in vivo covalent binding of both the compounds to the proteins of the tissues and plasma was low; the highest binding occurred in the liver (approximately 25 pmol/mg of protein). Within 24 hours about 78% of the injected tripelennamine and its metabolites was excreted into the urine whereas only about 35% of the radioactivity of NDT was eliminated. Pretreatment with phenobarbital accelerated the elimination of both substances. The metabolites of the drug and NDT were isolated from urine, hydrolyzed by glucuronidase-sulfatase and identified as their trimethylsilyl derivatives by gas chromatography-mass spectrometry. Tripelennamine was found to be extensively metabolized by N-demethylation and aromatic hydroxylation pathways. By contrast most of the NDT was eliminated as NDT and hydroxylated metabolites; very little was excreted as N-demethylated metabolites. The hydroxylated metabolites identified were p-hydroxybenzyl, p-hydroxybenzyl-5-hydroxypyridyl and m,p-dihydroxybenzyl derivatives of the drug, its N-demethylated analog and NDT. The catechol formation with NDT was found to be 4 times that observed with tripelennamine.


The separation and identification of dopamine 3-O-sulfate and dopamine 4-O-sulfate in urine of Parkinsonian patients.

A method is described for the isolation and measurement of dopamine 3-O-sulfate and dopamine 4-O-sulfate. The sulfate isomers of dopamine were synthesized chemically by the reaction of dopamine with sulfuric acid. The isomers were isolated by anion-exchange column chromatography and the identities of the two isomers were confirmed by gas chromatography coupled with mass spectrometry. A method is described for the assay of the two isomers by high-pressure liquid chromatography. When Parkinsonian patients were treated with 4.0 g/day of L-dopa, the amount of dopamine 3-O-sulfate excreted in the urine was 19.6 times that of dopamine 4-O-sulfate. When untreated Parkinsonian patients received tracer quantities of 3H-L-dopa either intravenously or orally, 3H-dopamine 3-O-sulfate was the predominant isomer but the amounts were only 3 times those of the 4-isomer. Greater quantities of both isomers were excreted when 3H-L-dopa was given orally as compared to intravenous administration. Since dopamine 3-O-sulfate is the predominant sulfate isomer, it is concluded that sulfate conjugation of dopamine could possibly compete with 3-O-methylation in determining the resultant conjugated product.


Effects of divalent cations, cation chelators and an ionophore on morphine analgesia and tolerance.

The analgesic effect of morphine was antagonized in mice by intracerebroventricular injection of Ca++, Mg++ and Mn++ and was potentiated by ethylene glycol tetraacetic acid but was not altered by Sr++, Ba++, Ni++, Hg++, Cd++ or ethylenediamine tetraacetic acid. The antagonistic effect of Ca++ was not altered by pretreatment with pargyline or 6-hydroxydopamine indicating that altered release of catecholamines or serotonin was not involved in this action of Ca++. Induction of morphine tolerance by pellet implantation also did not alter the antagonistic effect of Ca++. The antagonistic effects of Ca++ and naloxone were additive in both nontolerant and tolerant animals and the apparent affinity of naloxone for its receptors, as estimated by in vivo pA2 determinations, was not altered by Ca++. However, the ionophore X537A was found to increase greatly the narcotic antagonist effect of a low dose of Ca++ although the ionophore alone did not alter the effects of morphine. This indicates that Ca"++ must penetrate cell membranes in order to reduce the analgesic effects of morphine. These findings indicate the importance of Ca++ localization in the actions of narcotic agonists and antagonists.


Disposition of naloxone: use of a new radioimmunoassay.

Understanding of the pharmacology of the narcotic antagonist naloxone has been limited by the lack of a convenient and sensitive method of assay. A radioimmunoassay for naloxone has been developed and is described. It is applicable for drug analysis in either serum or brain. The limit of sensitivity of the assay was 0.1 ng. Naloxone glucuronide, noroxymorphone (nor-naloxone) and morphine were not recognized by the antibody whereas naltrexone and 6-hydroxynaloxone were able to displace naloxone-3H from the antibody. The assay was of sufficient sensitivity to follow the serum levels of naloxone in man for up to 2 hours after an i.v. injection of 0.4 mg. In animal studies, the biologic half-lives of naloxone or morphine (5 mg/kg) were compared after s.c. injection in rats. The peak serum levels A (1 mu/mo), time to peak serum levels (less than 1/2 hour), and serum half-life (40 minutes) were comparable. However, the brain entry and egress of the two compounds differed markedly. Peak brain levels of naloxone occurred within 15 minutes and had declined by 50% within 1 hour, whereas the peak brain levels of morphine were sustained for up to 2 hours. At peak serum levels, the brain/serum ratio for morphine was 0.1 whereas for naloxone it was 15 times greater. We suggest the high brain/serum ratio of naloxone contributes to its potency whereas the rapid egress from the brain is important in the short duration of action of naloxone.


The depressant effect of halothane and sodium thiopental on the spontaneous and evoked activity of dorsal horn cells: lamina specificity, time course and dose dependence.

The effects of halothane and sodium thiopental on dorsal horn cell unit activity were studied in the lumbar spinal cord of decerebrate, low thoracic spinal cats. Both halothane (0.5, 1 and 1.5%) and sodium thiopental (2.5, 5 and 10 mg/kg) depressed, in a dose-dependent manner, the spontaneous firing frequency of cells in Rexed laminae I, V and VI and the evoked firing frequency of cells in laminae I and V. They, however, had no effect on cells in lamina IV. The maximum depression of cell activity occurred 5 to 8 minutes after inhalation of halothane and 2 to 3 minutes after the intravenous administration of sodium thiopental. The recovery of cell activity occurred within 15 to 30 minutes after discontinuation of halothane and within 10 to 30 minutes after intravenous administration of sodium thiopental. The depressive effect of halothane and sodium thiopental, both primarily hypnotic anesthetics, on lamina VI cells is in contrast to our previous finding that morphine sulfate, nitrous oxide and ketamine hydrochloride, primarily analgesic agents, had no significant effect on this lamina.


Local anesthetics and barbiturates: effects on evoked potentials in isolated mammalian cortex.

Slices of olfactory cortex from guinea pig, incorporating the lateral olfactory tract (LOT), were maintained in a glucose-bicarbonate solution in vitro. Stimulation of the LOT produced: 1) A summed LOT action potential; 2) A monosynaptic surface-negative wave (N-wave); and 3) A polysynaptic surface-positive wave (P-wave) as recorded from the pial surface of the slice at 24 degrees C. During a period of single stimulus pulses to the LOT, local anesthetics and barbiturates, applied to the incubating solution, depressed the amplitude of the action potential (while increasing its latency and threshold) with the following potencies: tetracaine greater than cocaine greater than lidocaine greater than procaine greater than pentobarbital greater than phenobarbital. The order of potencies was similar for the synaptic potentials. Each local anesthetic or bartiturate first depressed the P-wave, the N-wave and then the LOT potential, with all three potentials being affected within a narrow range of drug concentrations. There was a good linear relationship between drug potency on all potentials and the distribution coefficients of the drugs in octanol-water. During a period of double stimulus pulses to the LOT, up to 10 seconds apart, low concentrations of barbiturates depressed the N-wave to the second pulse with little effect on the first, conditioning pulse, an effect not seen with local anesthetics. The bath concentrations required for this effect of both barbiturates were similar to previous reports of blood concentrations required for general anesthesia. It appears that local anesthetics have actions on brain similar to those reported for other tissues and that barbiturates share some of the actions of local anesthetics, but exert a selective depression on repetitively elicited synaptic potentials.


Inhibitory effects of adenine nucleotide analogs on the isolated guinea-pig taenia coli.

The inhibitory actions of adenosine diphosphate (ADP), adenosine monophosphate (AMP), adenosine and 16 adenine nucleotide and nucleoside analogs on the isolated guinea-pig taenia coli preparation were compared with those of adenosine triphosphate (ATP). Responses were quantitated as magnitude of maximal relaxation, time taken to reach maximal relaxation and activity relative to that of ATP. Inhibitory responses induced by the 5'-di- and triphosphates of 2-chloroadenosine and 2-methylthioadenosine resembled those elicited by ADP and ATP, but the 2-substituted analogs were markedly more potent. AMP and adenosine were less active than ATP; their activities were enhanced by 2-chloro substitution but not by 2-methylthio substitution. 2-Methylthio-AMP and 2-methylthioadenosine were the only analogs which did not elicit maximal relaxation of the taenia coli. 6'-Deoxyhomoadenosine 6'-phosphonic acid was inactive. Adenine nucleotide analogs in which the polyphosphate moiety was modified had steeper log dose-response curves than ATP and induced greater maximal responses than ATP. Analogs in which the polyphosphate alpha, beta-anhydride oxygen was replaced by methylene took up to 5 times longer than ATP to cause maximal relaxation. Other analogs with modified or unmodified polyphosphate side chains caused rapid relaxation of the taenia coli. There was no apparent correlation between relative activity and time to reach maximal response. The findings obtained indicate that di- or triphosphate groupings are of prime importance in binding adenine nucleotides to the putative smooth muscle receptor which mediates their inhibitory responses, and that hydrolysis of the terminal phosphates of adenosine 5'-polyphosphates is not a requirement for inhibitory activity. Reasons for the distinctive inhibitory actions of the phosphate-modified adenine nucleotide analogs are considered.


Interactions between several rare earth ions and calcium ion in vascular smooth muscle.

The effects of lutetium (Lu+++), europium (Eu+++) and neodymium (Nd+++) on 45Ca distribution, 45Ca movements and contractions were examined in rabbit aortic smooth muscle. Tension responses to norepinephrine were markedly inhibited by all three rare earth ions; K+-induced responses and those to histamine were partially blocked. Addition of 1.5 mM Lu+++, Eu+++ or Nd+++ to the bathing solution reduced 45Ca uptake (Nd+++ greater than Eu+++ greater than greater than Lu+++), produced a maintained increase in 45Ca efflux from strips of media-intimal layer washed out in a 0-Ca++ solution (Nd+++ greater than Eu+++ greater than Lu+++), and, when present during 45Ca incubation (before 45Ca washout), altered the release of 45Ca elicited by addition of 1.5 mM Ca++ during the 45Ca washout (inhibition by Nd+++ greater than Eu+++ greater than Lu+++). The 3-fold greater uptake of 45Ca in a 0-Ca++ and 1.5 mM Lu+++ solution than in an equivalent Sr++ solution results from a decreased effect of Lu+++ upon the slower 45Ca washout component. The actions of Lu+++ were quantitatively similar to those of low La+++ concentrations (0.05-0.10 mM), whereas those of Nd+++ and Eu+++ resembled effects obtained with equimolar concentrations of La+++. Thus, the three rare earth ions produce qualitatively similar alterations in 45Ca uptake and superficial binding. The difference observed can be attributed to variations in their affinity for superficial Ca++ binding sites and in their ability to block Ca++ uptake.


Interaction of prostaglandin A2 and prostaglandin B2 on vascular smooth muscle tone, vascular reactivity and electrolyte transport.

The effects of prostaglandin A2 (PGA2) and prostaglandin B2 (PGB2) on vascular smooth muscle tone, electrolyte movements and responses to vasoactive stimuli were evaluated with superfused canine tibial arteries. PGA2 and PGB2 constricted superfused tibial arteries. PGB2 was 10.7 (8.3-14.1) times more potent as a constrictor than PGA2. PGA2 and PGB2-induced vasoconstriction was associated with a decrease in 22Na efflux and a tendency toward an increase in cellular sodium (expressed as micromoles per gram of wet weight). These prostaglandins also decreased the total potassium content of tibial arteries. 45Ca exchange was enhanced by PGA2 and PGB2. The time course of PG-induced increases in 45Ca efflux was similar to the temporal increase in force produced by PGA2 and PGB2. The duration of the contractile response to barium chloride was greatly prolonged during superfusion with both PGA2 and PGB2. These effects were probably not mediated by PG-induced alterations in the resting membrane potential of tibial arteries since presumed depolarization by both high potassium and zero-potassium physiologic saline solutions did not mimic the effects of these prostaglandins on vascular smooth muscle tone or responses to barium chloride. These data suggest that PGA2 and PGB2 may increase tone of vascular smooth muscle by inhibition of those processes involved in sequestration of calcium ion, i.e., the relaxation process, rather than acting on the contractile process.


Effect of ouabain and its interaction with diphenylhydantoin on cardiac arrhythmias induced by hypothalamic stimulation.

Cardiac arrhythmias induced by central nervous system stimulation in the cat were used to evaluate the possible central nervous system effects of ouabain and diphenylhydantoin. Electrical stimulation of the posterior portion of the hypothalamus resulted in alterations of cardiac rhythm, and recordings from cardiac-bound sympathetic nerves revealed continuous activity during the time of arrhythmia. Intravenous administration of small doses of ouabain (i.e., 10-30 mug/kg) prevented both the arrhythmias and the associated hyperactivity on the sympathetic nerves. The antiarrhythmic effect was not present in animals with denervated baroreceptors indicating that the ouabain effects were due to sensitization of baroreceptor reflexes. Intravenous administration of large but subarrhythmic doses of ouabain (i.e., 60-80 mug/kg) converted a subarrhythmogenic hypothalamic electrical stimulus to a threshold stimulus for arrhythmias. The increased response of the heart to brain stimulation in the presence of these doses of ouabain was associated with an increased discharge of cardiac sympathetic nerves, indicating that ouabain was exerting its arrhythmogenic enhancing effect on the central nervous system rather than on the heart. Pretreatment with diphenylhydantoin prevented the arrhythmias produced by the combination of ouabain and hypothalamic stimulation. Prevention of the arrhythmia was associated with prevention of the associated sympathetic hyperactivity responsible for the arrhythmia, thus indicating a central nervous system site of action of diphenylhydantoin. These data suggest that central nervous effects of ouabain and diphenylhydantoin are important in the ability of these drugs to alter cardiac rhythm.


Evidence for a transient potassium membrane current dependent on calcium influx in crab muscle fibre.

1. Voltage-clamp experiments were achieved on crab muscle fibre with the double sucrose-gap technique. 2. The accuracy of the imposed voltage has been controlled with an impaled micro-electrode connected to an external circuit. 3. Step depolarizations elicit two kinds of records. In type I fibres, the initial current exhibits only an inward calcium component. In type II fibres, the initial current exhibits a hump, transient outward current, mixed with the calcium current; these fibres exhibit always action potentials with fast repolarization. 4. A potassium origin is suggested for this outward current, due to its dependence on [K]o and its inhibition by TEA. 5. In fibres with a composite initial current, the voltage dependence of the availability of the measured inward current appears complex. It can be shown to be the sum of a simple calcium inactivation (which is observed alone in TEA solution) and a fast potassium inactivation. This potassium conductance is nearly half-available at the resting membrane potential. 6. The origin of the transient outward current is tentatively described. Consecutive to a transient internal increase of calcium ions (due to the calcium current) its activation curve is shifted in an hyperpolarizing direction resulting in an increased activation for an apparent identical depolarization. 7. This fast outward current which overlaps the calcium inward current can account for the low amplitude and the variability of the electrical activity of crab muscle fibres.


Effects of deindividuation, removal of responsibility, and coaction on impulsive and cyclical aggression.

The influence of two deindividuating variables, altered responsibility and coaction in groups, on one's tendency to deliver noxious or helpful stimulation impulsively and in a cyclical pattern to a target person was investigated in a laboratory experiment with use of 96 male and female junior college students. Analysis of variance revealed that, as hypothesized, Ss who coacted in groups of three and who had the responsibility for their behavior removed delivered noxious (but not helpful) stimuli more impulsively than Ss who worked alone and were made to feel responsible (p less than .01). Ss responded in a more cyclical pattern which delivering aversive tones than when delivering facilitating tones (p less than .005). A marginally significant finding was that Ss in groups responded in a more cyclical pattern than Ss alone only when the response was seen as aversive. It was concluded that the probability of impulsive and cyclical aggression may be increased by altered responsibility and coaction.


Sex differences in preadolescent self-esteem.

It was predicted from the theories of Bardwick that 1) made self-esteem would be greater than female self-esteem only among the older children of the preadolescent sample, 2) reading achievement would correlate with self-esteem for boys in all age groups but only for the younger girls, and 3) individual self-esteem items that showed sex differences would be sex-role related. Data on self-esteem and reading score were collected on 307 urban children in second through sixth grades. Analysis of results confirmed predictions 1 and 3, but not prediction 2. Reading score did not show a significant correlation with self-esteem for girls at any age level tested. Results were discussed in terms of differing sources of male and female self-esteem.


Melanin as a predictor in the acquisition of developmental skills.

Seventy-two subjects were randomly drawn across grades K-12 and administered an instrument designed to measure developmental skills within seven skill area categories. A three-way ANOVA, fixed effects model, was used for data analysis. Subjects were blocked by eye color, sex, and grade level for the purpose of investigating the relationship between eye color and sex to self-paced and reactive behaviors. Significant differences were obtained on the main effect of eye color in five of the seven categories examined. There were three significant first order interactions (sex X eye color) and one three-way interaction. The findings support the hypothesis of Worthy that eye color is a dependable predictor of subjects' general behavioral competency area (self-paced or reactive) and adds considerable support for his thesis that self-paced and reactive behaviors are to some degree inherited.


Cognitive tempo and the mode of representation in emotionally disturbed and normal children.

The relationship between cognitive tempo, MA, and mode of representation as inferred from equivalence groupings was investigated in 60 emotionally disturbed and normal boys and girls. No differences on any of the measures were obtained between the two groups of children or between males and females, so the data were combined for further analysis. A significant negative correlation between MA and both the number of errors on the Matching Familiar Figures Test (MFF) and the proportion of analytic concepts on the equivalence task was found. MFF latency was related to MFF errors only. On the other hand, MFF errors were related inversely to the proportion of both superordinate and functional concepts. Results were discussed in terms of supporting the previous findings of Olver and Hornsby in regard to equivalence and MA. Contrasts between the present findings and those of Kagan, Rosman, Day, Albert, and Phillips were discussed, and the differences in the nature if the array emphasized.


Ethanol induced slowing of human reaction time and speed of voluntary movement.

This study tested the hypothesis that a CNS depressant (ethanol) would affect self-initiated psychomotor movement speed as much as the speed of an homologous movement made in response to an external stimulus. Four normal Ss (three male, one female, aged between 33-45 years) provided well-practiced measures of reaction time and a simple homologous traverse movement (a) in response to a signal from the E and (b) initiated at the S's own discretion. Performance by each S under ethanol conditions (B. A. L. .22%) was compared with his own baseline (pre- and postdrug) scores. Traverse originated by the S was consistently faster in the nondrug condition. Under peak-ethanol, both forms of traverse were slowed significantly in all Ss. Speed reductions were similar but consistently greater for self-initiated movement. A single S who repeated the experimental sequence under a minimally effective dosage (B. A. L. .08%) showed no important reduction in reactive movement speed, but was slowed significantly in self-initiated traverse measured concomitantly. The selective sensitivity of self-initiated movement to ethanol provides added evidence that a higher level of neural organization underlies control of human voluntary action.


Linguistic nonimmediacy and self-presentation.

It has been previously shown that Ss accurately infer communicators' levels of negative effect on the basis of communicators' levels of linguistic nonimmediacy (the degree of verbal indirectness with which a communicator refers to himself or to that about which he communicates). It was hypothesized that Ss would also rely on communicators' levels of linguistic nonimmediacy for impression formation, specifically that Ss would perceive communicators using lower levels of linguistic nonimmediacy as more authoritative and as having a more positive character than communicators using higher levels of linguistic nonimmediacy. The hypothesis was partially confirmed in a study of 12 college students who rated samples of student speeches by means of McCroskey's impression formation instrument for public speakers. The results were discussed in terms of the role of language in self-presentation and the role of interpretative procedures in social interaction.


Social decentering and locus of control in children.

Relationships beteen social decentering, personality variables, and social competence were investigated for children attending a seven-week therapeutic summer camp. Ss were 23 males and females ranging in age from 10 to 13 years old had been referred to the camp because they lacked age-appropriate social skills. Feffer's Role Taking Task was used to measure social decentering, and counselor ratings of camper adjustment were measures of social competence. Predicted positive relationships between decentering and competence were found. Striking sex differences were found, however, when comparisons were made between social decentering and two personality variables--the Nowicki-Strickland Locus of Control Scale and the Kiddie Mach. Predicted negative correlations were found between Role Taking Task scores and externality and machiavellianism for females, but not for males. Implications concerning age by sex interactions in the study of personality correlates of social decentering were discussed.


Authoritarianism and All in the Family.

A questionnaire survey of a random sample of the adult population of Portland, Maine (N = 233) was used to determine (a) any relationship between authoritarianism and viewing the television program All in the Family, and (b) viewers' perceptions of the major character, Archie Bunker. No relationship was found to exist between authoritarianism and viewing. Archer Bunker was found to be a likable loser. Viewers generally disagreed with him and found him dissimilar to themselves. High authoritarians judged him slightly more positively on all dimensions than did low authoritarians. Recent speculation as to the popularity and effects of the show were discussed in terms of the data.


The influence of males and females on the psychophysical judgments of females.

A transfer paradigm was employed to test the hypothesis that females influenced by males on one task would show more carryover of the influence effect to other tasks than would females influenced by other females. Thirty female college students made judgments on three cross-modal matching tasks. Experimental subjects gave their judgments on one task along with two male or two female confederates, who appeared to give discrepant judgments. They then made another series of private judgments on the other two tasks. Comparison to a control group and to an original series of provate judgments revealed a significant direct influence effect, but minimal transfer to the other two tasks. There was a nonsignificant tendency for the subjects to be more directly influenced by other females than by males, but this influence by the other females was accompanied by a decline in task confidence. Influence by males on females did not result in lowered confidence. This finding may be restricted to quantitative tasks and to American college students.


A comparison of two measures of ego identity in high school adolescents.

A sample of 279 male and female high school seniors participated in a study on ego identity and personality structure. The adolescents completed the Constantinople Inventory of Psychosocial Development (IPD) and, on the basis of the principal components method of factor analysis, were found to group on three factors: Adolescent Identified, Industry Crisis, and Unresolved Crisis. A further subsample of 86 adolescents also completed the Rasmussen Ego Identity Scale (EIS). Comparisons of the two instruments yielded significant positive relationships on subscales, but indicated differential sources of identity scores and resultant possible misclassification of subjects through the use of a single identity score measure.


Studies in the neurophysiology of learning: IX. Conditioning of evoked potentials due to cerebral stimulation.

The hypothesis to be tested was that if characteristic undulatory evoked potentials could be produced by electrical stimulation of the lateral hypothalamus, sensory stimuli originally neutral should evoke such potentials, if only of smaller amplitude. The results of experiments on four albino rats are reported. Stimulation of the lateral hypothalamus by electrical current at 200 biphasic rectangular pulses per second results in 7-12 cycles-per-second undulations persisting for about .5 second and derivable from several regions of the cerbrum. By means of the Pavlovian paradigm, it was possible to condition these to an auditory and to a visual stimulus. The conditioned undulations had smaller amplitudes, did not persist as long to CS as to US, and were characterized by considerable lability. From 100 to 300 CS-US pairings were required.


Behavior therapy versus "will power" in the management of obesity.

In a study of the management of obesity 43 patients were randomly assigned to behavior therapy, will power, and no-treatment control groups. The behavioral treatment involved contingency contracting, stimulus control, self-monitoring, energy expenditure, and group reinforcement procedures over an 18-week period. The will power patients were told to do the same thing as the behavior therapy patients; however, instead of having formal contingencies and meeting regularly, they were told to apply "will power" on their own, as this was the most important aspect of losing weight. The third group was a standard no-treatment control group. Analyses of covariance indicated that (a) the behavior therapy group lost significantly more weight than the will power (p less than .05) and no-treatment control (p less than .01) groups, and (b) the will power and no-treatment control groups did not differ significantly from each other. An 18-week maintenance follow-up of the behavior therapy group indicated that there was no significant weight gain from the end of treatment to follow-up. Also, an analysis of time spent per patient suggested that the behavioral treatment employed in this study was more efficient than previous treatments.


Two new species of Eimeria from colubrid snakes in Iowa.

Oocysts of Eimeria natricis sp. n. and Eimeria sipedon sp. n. were isolated from 2 Northern Water Snakes, Natrix sipedon sipedon (Linnaeus), in Iowa. Oocysts of E. natricis were elongate, slightly ovoid, averaging in size 32.3 X 17.5 mum; sporocysts averaged 15.7 X 8.2 mum. Oocysts of E. sipedon were broadly ovoid averaging in size 18.0 X 15.9 mum; sporocysts averaged 12.0 X 7.4 mum. In both species, sporocyst residua were present, but micropyles, polar granules and oocyst residua were lacking.


Eimeria cicaki sp. n. and Isospora thavari sp. n. from the house lizard Gehyra mutilata Boulenger in Malaysia.

Oocysts and endogenous stages  of new species of Eimeria and Isospora from the house lizard, Gehyra mutilata, are described. The ellipsoid to subspherical 2-layered oocysts of E. cicaki averaged 24.0 X 21.0 mum. Polar granules are present. Micropyle and oocyst residuum are absent. Ellipsoid sporocysts average 12.2 X 9.0 mum. A sporocyst residuum is present, but the Stieda body is absent. Endogenous stages are in epithelial cells of the small intestine. The subspherical single-layered oocysts of I. thavari average 23.8 X 22.8 mum. The polar granule is present; micropyle and oocyst residuum are absent. Ellipsoid sporocysts average 12.8 X 9.4 mum. Stieda body and sporocyst residuum are present. There are endogenous stages in epithelial cells of the small intestine.


Quantitative ultrastructural investigations of the life cycle of Trypanosoma brucei: a morphometric analysis.

The quantitative ultrastructure of the developmental stages of Trypanosoma brucei brucei in its vector Glossina morsitans was studied by morphometric analysis. Values from ectoperitrophic midgut forms, proventricular forms, epimastigote and metacyclic forms in the salivary gland are compared with results from bloodstream forms, published previously. Significant differences in the volume densities of the trypanosome's single mitochondrion, of microbody-like organelles and in the surface densities of inner and outer mitochondrial membranes were found throughout the whole life cycle. A great increase in volume density of the mitochondrion was observed after transfer to the insect host; reduction took place during metacyclic development. Parallel to the biogenesis of the mitochondrion a reduction of microbodies was found in proventricular forms and there was a great increase in metacyclic forms concomitant with the regression of the mitochondrion. Metacyclic forms had a close quantitative morphologic similarity to bloodstream forms. The results are discussed in connection with changes in structure and in oxidative metabolism.


Fine structure of the oocyst walls of Isospora serini and Isospora canaria and excystation of Isospora serini from the canary, Serinus canarius L.

Oocysts of Isospora serini and Isospora canaria, from the canary Serinus canarius, were broken, added to a cell suspension, fixed in Karnovsky's fluid, and studied in the electron microscope. The oocyst wall of each species had an electron-lucent inner layer, a more osmiophilic middle layer and an outer layer of electron-lucent (I. serini) or electron-dense material interspersed with some electron-lucent material (I. canaria). A few, relatively large lipid-like bodies were present in the outer or middle layer of the oocyst wall of I. canaria. As many as 9 membranes were present in the oocyst wall of I. canaria and 3 in that of I. serini. When exposed to a trypsin-sodium taurocholate fluid, sporozoites of I. serini excysted from 5-month-old sporocysts in vitro, but not from sporocysts stored for more than 6 months. No excystation occurred in 15-month-old I. canaria sporocysts. Similarities and differences in excystation between I. serini and other Isospora, Eimeria, and Sarcocystis species are discussed.


Growth in vitro and metabolism of Plasmodium vinckei chabaudi.

An in vitro system, based on the rocker dilution technic, has been developed that supports intraerythrocytic growth of a rat-adapted strain of Plasmodium vinckei chabaudi from ring to schizont stages; some reinvasion was obtained, although invariably, this was associated with a decrease in parasite numbers. Pertinent features were the very high buffer content of the medium and the low oxygen tension of the gaseous phase. Lactate production, glucose utilization, and 3H-leucine and 3H-adenosine incorporations were investigated for their suitability to monitor parasite growth. Throughout an 18-hr incubation there was a continuous and increasing production of lactate and utilization of glucose, which correlated well with the development of the parasites from ring to schizont stages. During the same period, there was a low but continuous and increasing incorporation of 3H-leucine into parasite protein. However, 3H-adenosine was incorporated only for the 1st hr of incubation, after which time no net incorporation occurred. Parasites grew normally from ring to schizont stages even in the absence of adenosine from the dilution medium.


Isolation of amylopectin granules and identification of amylopectin phosphorylase in the oocysts of Eimeria tenella.

Amylopectin granules were purified from Eimeria tenella oocysts following digestion with sodium dodecyl sulfate and pronase. The oval granules had a uniform size of 0.5 X 0.7 mum, and consisted of only glucose polymers. alpha-Amylase treatment yielded 235 nmoles of maltose from the granules from 10(6) unsporulated oocysts and 93 nmoles maltose from those from 10(6) sporulated oocysts. Amylopectin phosphorylase activity was detected in the cytoplasm of unsporulated oocysts of E. tenella. It had a specific activity of 13 U/mg protein in crude extracts, and a pH optimum of 6.0. The Km values determined were 9.1 mM for glucose-1-phosphate and 5.6 mM for glucose end groups in potato amylopectin. Enzyme activity declined at a linear rate during sporulation, sporulated oocysts containing less than 8% of the activity of unsporulated oocysts. No amylase-type activity was found in the parasite.


[Comparison between gastric radiology and fiber endoscopy (author's transl)].

This paper summarizes the experience from 1969 to 1972 of a mixed team of radiologists and endoscopists at the Northern Marseilles University Hospital Centre. The patients were unselected and the team were not given all the information. After recalling the clinical and radiological conditions, together with the endoscopic conditions of the examination, the authors define the criteria which they chose to orient patients towards fiber endoscopy, i.e. either frankly abnormal radiology, or a radiological examination classed as normal in 563 cases, but which the team considered doubtful. They then report their results. Under these conditions, the results seem to be less unfavourable for radiology than would have been thought, for only 7% of the results were made by endoscopy alone (96 cases out of 1,500). In both benign and malignant ulcer, fiber endoscopy simply confirmed the radiological diagnosis and, in 54% of all the examinations, fiber endoscopy confirmed the normal character of radiology. However, in deciding whether carcinoma or benign ulcer, i.e. 11% of the cases of carcinoma and 14% of the cases of benign ulcer, radiology completely omitted the diagnosis of the lesion which might seem unacceptable. They conclude by asking radiologists to improve their technique of lesion detection and concentrate their examination on the smallest visible lesion in areas considered diffcult to explore radiologically. They are more and more circumspect about giving a full etiological diagnosis of lesions by radiology, especially in gastric ulceration where fiber endoscopy and direct biopsy seems more and more advisable.


[Anastomoses of the hepatic arteries angiographic appearances (author's transl)].

On the basis of 3,000 selective arteriograms of the coeliac trunk, the authors described the radiological appearance of anastomoses existing between the hepatic arteries. The anatomical study of COUINAUD had shown their existence. The increasingly frequent use of hepatic arteriography makes the demonstration easier. Such anastomoses exist under normal conditions but are more obvious, since they are increased in size, in various pathological states, in particular when there is obstruction of a hepatic artery. The anastomoses are of two types: of small calibre and usually situated in the porta hepatis or in the upper part of the hepatic pedicle; of wide calibre, a true embryonic rest, providing a communication between branches of the hepatic arteries. Such anastomoses may function in both directions. They are of great value under pathological conditions, avoiding hepatic necrosis. They are particularly common in complications following surgery on the common or other bile ducts.


[Ultrasonic diagnosis of pancreatic conditions: a new tentative at a rational approach based on the analysis of 300 cases which were checked (with real time and degraded intensity scale). (author's transl)].

For a long time, echotomography of the pancreas was limited to the identification of pseudocysts. Little by little, those using ultrasound learnt how to construct images of the pancreatic gland itself, and faced with the changes in size and shape of the latter to recognize lesional processes. Analysis of the pancreatic echostructure represents an important step in the progress of the diagnosis of lesions. Echotomography, the results of which must be compared with those of roentgenological methods of exploration, as well as the clinical and laboratory data, enables the attainment of very fiable diagnoses of chronic pancreatitis with or without pseudo-cysts, of acute pancreatitis or of rare cystic tumors. The precision of the results however depends fundamentally on technical data: it is necessary to combine with the classical apparatus, with manual displacement of the wave, a tomo-echoscopic apparatus, with real time; above all, it is necessary to use the degraded intensity scale. This scale is innate in real time apparatuses. At present it takes the form of a complementary module, on the classical apparatuses. Without these technical conditions, real time and degraded intensity scale, it seems impossible to attack the problem of ultrasonic diagnosis of pancreatic conditions, except by exposing oneself to disappointments which would unmeritedly cast discredit on the method. Six years of experience, several thousands of pancreatic examinations, three hundred pancreatic lesions which were anatomically checked has however convinced us of the importance of echotomography in this field.


[Selective tomography in the study of the temporo-mandibular joint. (author's transl)].

The majority of temporo-mandibular pains and dysfunction can be related directly or indirectly to the occlusal relationship of the teeth. The first manifestation is a slight reduction of the interarticular space, that must be early diagnosed, to prevent organic changes. Tomography is the one technique able to give a exact information of temporo-mandibular joint. But if we ask to that examination to detect very slight change of the interarticular space, the technique must be accurate and established in function of morphology of the patient; we have observed great variations in direction of the axis of condyles from one person to the other, and even from one side to the other for the same subject. So that, the first stage of the roentgen examination will be a radiograph taken in submentovertical (Hirtz) position. We measure the angle formed by the axis of each condyle and the sagittal median plane. The maim beam wil be directed in the axis of the condyle for sagittal tomography and perpendicularly for frontal tomography. It is important to state precisely that for tomography "closed mouth", the patient must be in terminal occlusion during the whole examination. For tomography "open mouth" we place a wedge between dental arches.


[Radiological atteration of sacro-iliac junctions in secondary hyperparathyroidism (author's transl)].

The systematic exploration of the skeleton on patients in periodic hemodialysis, has shown a high incidence in alteration of sacro-iliac junctions. In respect of osteodystrophic alteration of the phalanges, the appearance is late and with continued hemodialytic treatment there is a turn for the worse. The exact definition has been obtained only with tomography. The radiological picture show a pseudoenlargement of the articular cleft, with shaded aspect of outlines and phenomena of periarticular bone thickening.


[Abnormalities of the aortic arches discovered at bronchography in children with bronchial disorders (author's transl)].

In four children, aged respectively 2, 6, 8 and 11 years, an abnormality of the aortic arches was discovered fortuitously during bronchoscopy. The latter was carried out in an attempt to assess bronchial lesions in children suffering from chronic or recurrent bronchopneumonia. The authors stress the importance of careful examination of the mediastinum in such cases, the diagnosis of the causal vascular abnormality (double aortic arch in all four cases) being possible by simple radiological examinations with no element of aggression.


[Post-traumatic pseudo-aneurysm of the anterior cerebral artery (author's transl)].

The authors report a case of post-traumatic pseudo-aneurysm of the pericallosal artery in an 11 year old child. The lesion was secondary to a perforating wound of the roof of the right orbit, the eye itself being undamaged.


[Gaseous encephalography under ketamine hydrochloride general anesthesia in the child (author's transl)].

The aim of this technical note is to show that ketamine hydrochloride anesthesia, owing to the preservation of muscle tone, enables one to safely and comfortably carry out gaseous encephalography on a simple radiological table in the toddler or child. However the authors very strictly select the indications for this investigation. Whenever the child's clinical condition leads one to suspect intracranial hypertension and/or a cerebral tumor, they think it more prudent, owing to the vasopressor effect of ketamine hydrochloride and a possible elevation in the cerebrospinal fluid pressure, to transfer the child to a specialized neuroradiological center, where the investigations would be carried out under the best technical conditions, and close to a neurosurgical unit which is capable of intervening rapidly in case of complications. The authors voluntarily limit their indications to children suffering from psychomotor retardation, epilepsy or neurological disorders which make one suspect a congenital malformation.


[Pelvimetry (author's transl)].

A simple and precise technique for pelvimetry, delivering only a low dose of irradiation, is described. It includes the usual lateral view, but for the AP uses that of Fernstroëm. The technique and results are described.


[The uterine contents (author's transl)].

The technique used for radiological examination of the uterine contents must be adapted to the reason for which it is being carried out. In particular, a study of bony maturation of the foetal knee may be carried out using a localised film, with compression and in lateral view, of the maternal abdomen. The technique of the large scoit film in ventral decubitus is reviewed; the study of the uterine contents, on lateral projection, which localisation and compression is described.


[Measurement of the anteversion angle of the femoral neck (author's transl)].

The recommended technique is based on the principles of descriptive geometric. The views of the femoral neck in two perpendicular positions suffice to measure two projected angles, the degrees of which are used to make up a very simple drawing which gives the exact value of the anteversion angle.


[Trial of a new flexible cassette in general radiology (author's transl)].

The flexible cassette is a detector of undisputable value, particularly in the radiology of patients who have been subjected to trauma, patients who cannot be transported and above all in "locked" joints. Thus the authors think that it is indispensable for all radiologists to have a set of flexible cassettes at their disposal.


Deafness in middle age--how big is the problem?

Screening for hearing defect by questionnaire and audiogram was undertaken in two group practices in the South-east of England in a total of 2,278 people aged 40-64 years.The prevalence of deafness in the combined populations of these two practices as measured by audiogram was found to be 5.8 per cent (+/- 0.5 per cent; one standard error). This figure is much more than estimates derived from American data for use in Britain. The prevalence of deafness was shown to increase with lower social class and age. The questionnaire was found to be unreliable for prevalence studies, but was thought to have some use as a screening instrument.There was an incidental finding of increased hearing defects in the left ears of men. The firing of rifles was felt to be a possible explanation of this.


Long-surviving hypertensives--a 15-year follow-up.

In a London suburban general practice 87 hypertensives have been followed up for more than 15 years. These represented one third of all those (270) aged 30-59 diagnosed as being hypertensive. Females outnumbered males by 2.5: 1. Most (85 per cent), had mild or moderate high blood pressure at first diagnosis with a diastolic blood pressure less than 120mm Hg.At assessment 15-25 years from first diagnosis, 58 (78 per cent) were still alive and of these 51 (58 per cent) were well and had no obvious ill effects; 17 (20 per cent) had complications from their high blood pressures. Deaths occurred in 19 (22 per cent) after more than 15 years of observation.I suggest that within the condition which we label as hypertension there are many in whom the condition is relatively benign and may be left untreated with hypotensives. These tend to be women rather than men, the older rather than the younger, and those with lower diastolic blood pressures.Once diagnosed, high blood pressure is not necessarily a progressive condition. In one third (30 per cent) of this group the diastolic blood pressures fell during the period of observation, in 18 per cent it remained unchanged and in 52 per cent it rose.


Deaths and complications from hypertension.

In a long term follow-up over 25 years in a general practice the observed courses of complications and deaths in a group of 704 hypertensives were recorded and compared with those that occurred in the practice as a whole over the same period. The risks to the hypertensives were calculated as ratios of the observed: expected (O/E) complications and mortalities.Of the total number of complications and deaths (418), one half were cardiovascular and one-third were strokes.The O/E rates for coronary artery diseases as a whole showed no extra risks for the hypertensives, but the risks for young female hypertensives were appreciably higher. The O/E rates were nearly three times higher for females. The risks of hypertensives suffering from coronary artery diseases fell with age in both sexes.The observed rates for strokes were nearly four times greater than those expected. The O/E rates were similar in males and females. There was a decline with age.An unexpected finding was the higher O/E rate for dementia in elderly female hypertensives.The findings confirm the higher risks of complications and deaths for hypertensives, but within the whole spectrum of hypertension are some groups who are more vulnerable than others. These are males and those under 60 years of age. These vulnerables probably account for less than one half of all hypertensives diagnosed. It is suggested that a much more discriminating policy for the management of hypertension is accepted in order to make diagnosis and treatment of those hypertensives who really need intensive care practical, feasible, and possible.


The choice of practice location.

A ten per cent sample survey of all general practitioners in England and Wales in 1969-70 included two questions about the choice of practice location. The most common reasons given were the absence of any real alternatives (in the immediate post-war period), the influence of family or friends, the existence of medical contacts in the area, and favourable points about the practice itself.In considering possible future moves, general practitioners would pay closest attention to the educational facilities of an area, its rural or coastal location, its social and cultural amenities, and the practice conditions. The conclusion is drawn that financial incentives are unlikely to contribute much towards a more equal distribution of general-practitioner manpower. More thought should be given to recruitment to the medical profession in under-doctored areas through the development of the highest professional standards and facilities in such places.


The diagnosis of pregnancy in general practice.

In 1,631 pregnancies presenting to general practitioners, the reliability of three proprietary slide tests for the diagnosis of pregnancy was assessed both against the outcome and against the results of hospital tests done at the same time. When all patients were considered the reliability of such tests done in the surgery was 85 per cent against a 90 per cent for hospital tests and when only patients who were more than 42 days pregnant were included, the accuracy figure rose to 87 per cent in general practice and 91 per cent in hospital.The time delay before the results of the hospital test was assessed showed a mean of three days which is considered unacceptable if there are urgent clinical reasons for the test being done. The doctors participating listed their reasons for doing tests and in 54 per cent of cases urgent confirmation or otherwise of the pregnancy was considered essential by either doctor or patient. In the remaining 46 per cent this confirmation was considered simply helpful rather than essential. The study showed that the accuracy of the test, when delegated to a nurse, was acceptable and that in a proportion of three to one the participating doctors considered that the test was of value and worthwhile in patient care.


Family portraits--a method of recording family history.

Family doctors are particularly concerned with family relationships. Family relationships are generally poorly recorded in general practice in the traditional records. Conversion to A4 folders in the practice provided an opportunity to develop a diagramatic representation of family structure and thus create for each patient a family ;portrait.'


Moving to a health centre--the effect on workload and patients.

A detailed study of the workload of an urban practice was made during a six-month period before and after moving into a health centre to see if the pattern changed after the move. It was found that the services provided enabled a much greater proportion of routine work to be done by the practice nurse so that the doctor could spend more time with the patients seen by him.A survey of the opinion of patients showed that the great majority was pleased with the services offered in the new premises and did not feel that they had lost contact with their own doctor.


Referral letters from general practitioners.

If continuity of care is to be preserved, then the process by which a patient is referred to hospital is important. We have analysed a series of letters of referral from general practitioners with special reference to the diagnoses made and the inclusion of a relevant history.


Patients' satisfaction and reported acceptance of advice in general practice.

Patients' views were sought by questionnaires and home visits on how satisfied they were with the care they received from their general practitioners and how much of the advice received they were prepared to accept. The results showed a high degree of satisfaction and a higher level than has been found in hospital. Studies like this may identify difficulties which some patients may have and help doctors to make difficult advice easier to follow.


Postherpetic neuralgia.

Postherpetic neuralgia was studied in a general-practice population (3,600-3,800) for 26 years, 1947-1972. Postherpetic neuralgia followed 46 (14.3 per cent) of the 321 cases of zoster. No neuralgia occurred after zoster in those under 30 years old. The incidence was strongly associated with age, the highest, 34.4 per cent of the zosters, being in people over 80 years old.Women, especially between 50 and 69 years old, suffered more zoster than men, and women with zoster suffered more postherpetic neuralgia.The incidence of neuralgia was not affected by the anatomical location of the zoster. The duration of neuralgia was unrelated to the age of the patient. Cranial neuralgias lasted much longer on average than neuralgia in other sites. Lumbar and sacral neuralgia were short-lived.


Organising a physiotherapy service in general practice.

This paper describes three years' experience of running a domiciliary physiotherapy service based on general practice and financed by limited voluntary funds.The need arose from the remoteness of, and lack of, open access to, hospital physiotherapy. This was particularly so for elderly patients who were often frail and mentally confused. In addition there were obvious advantages in properly instructing relatives in management and treatment, especially since many of the patients and their relatives expressed a desire for home treatment.There was also a desire on the part of the general practitioners, nurses, and ancillary workers to develop further the teamwork in the health services of the four villages involved. Details of the constitution of the voluntary service and its financial arrangements are given.The results of the service and the nature of its work are described. There were no difficulties experienced in selecting the correct patients for treatment and the type of equipment required was almost all normally available through the health authority nursing service. There was no great need for expensive or heavy equipment and no transport problems arose.It was found that one hour of physiotherapist's time per 1,000 patients per week was adequate to cover all patients requiring short-term intensive therapy and to allow a small amount of palliative therapy in addition, although this had not been the original intention of the service.The physiotherapist averaged about 40 hours work per month and under these conditions the travelling and costs averaged 1.54 miles and 83 pence per visit. With self-determined hours of work and flexible timing, these conditions proved ideal for a married physiotherapist with the responsibility of a young family. Expansion of the hours of work in this particular area would have led to wasteful visits devoted to palliative and placebo therapy; and extension of the service beyond the area defined, would have increased travelling time at the expense of working time. Thus there appear to be considerable advantages in keeping general-practice based domiciliary physiotherapy work on a part-time basis and looking for staff living close to the practice.


Physiotherapy in general practice.

Approximately nine per cent of all episodes and of all consultations in this practice during a two-year period were for musculo-skeletal disorders. Absence of ready access to hospital physiotherapy departments stimulated us to explore the possibilities of organising a private physiotherapy service.A scheme has now been in operation for over two years in which a physiotherapist treats patients on the practice premises. In this way it has been possible to provide prompt effective treatment at about one third of normal private physiotherapy charges. The scheme has succeeded from the points of view of therapeutic efficacy, of convenience to patients, to doctors and to physiotherapist, and of economy. The range of conditions treated and the results of treatment are described.


Evidence of the Royal College of General Practitioners to the Select Committee of Parliament on the Abortion (Amendment) Bill.

The Royal College of General Practitioners is, of course, fully aware that the regulation of the conditions for abortion is inevitably difficult and complex and that opinions are often difficult to reconcile.Nevertheless, the College has been able to establish the grave concern of many of its members at the proposals outlined in this Bill. The College has not received one single letter in support of the Abortion (Amendment) Bill.The College notes that the Lane Committee (1974) carried out a very full and detailed review of the working of the Abortion Act and published its view only last year. The College notes that the Lane Committee took evidence from those with every shade of opinion, examined in detail virtually every published scientific report on abortion in this country, and, furthermore, commissioned and published specific evidence about the working of the 1967 Abortion Act.The College notes that the Lane Committee contained members, in addition to general practitioners, who were lawyers, administrative medical officers, psychiatrists, gynaecologists, social workers, and women representing the public, and that its work took about three years to carry out.The Royal College of General Practitioners endorses the work of the Lane Committee and therefore recommends that the recommendations of that Committee should be implemented instead of the proposals in the Abortion (Amendment) Bill.


Doctors and drug dependency. Beyond the fringe.

Three widely different fringe organisations outside the National Health Service working on the treatment of drug dependence are described.The immense problems facing one organisation dealing with barbiturate addiction are emphasised, with hope for more widespread recognition of this addiction by general practitioners combined with more strenuous efforts by medical politicians to reduce the sources of supply.


Experiments on egg transfer in the cow and ewe: dependence of conception rate on the transfer procedure and stage of the oestrous cycle.

The effects on embryo survival of procedures used in transferring eggs non-surgically were investigated in three experiments in ewes and heifers. In Exp. 1, two techniques for introducing eggs into the uterus through the cervix in heifers were compared; namely (i) deposition of the eggs high into the uterine horn or (ii) into the body of the uterus. Both methods were followed by inflation of the uterus with carbon dioxide. Out of a total of 34 heifers, only one became pregnant by the use of Method (i). Non-surgical egg tansfers early (Days 3 to 5) or later (Days 6 to 9) in the oestrous cycles of heifers  were carried out in Exp. 2. Three transfer procedures were compared: (i) pipette transfer of an egg into the body of the uterus through the cervix (control), (ii) the control procedure performed under Fluothane anaesthesia, or (iii) followed by inflation of the uterus with carbon dioxide. Wide transfers carried out early in the cycle, pregnancies resulted in 1/10, 0/10 and 1/10 of the heifers in the control, carbon dioxide and Fluothane groups, respectively. With late transfers, 7/20, 1/10 and 8/20 heifers became pregnant in the respective treatment groups. This trend for pregnancy rate to be improved when late transfers were done in the control and Fluothane groups was significant only at the 10% level of probability when both groups were pooled. It was tentatively concluded, however, that non-surgical transfers of fertilized eggs to heifers may be best done during mid-cycle, after Day 6. Fluothane anaesthesia did not improve conception rate. Inflation of the uterus with carbon dioxide appeared to be deleterious when used at the mid-cycle stage in heifers. In Exp. 3, it was found that inflation of the ewe's uterus with carbon dioxide or nitrogen following the surgical thansfer of an egg did not affect the incidence of pregnancy. The introduction of 50 mul liquid Fluothane into the lumen of the uterus was embryotoxic.


The effects of alpha-chlorohydrin on the composition of rat and rabbit epididymal plasma: a possible explanation of species difference.

The relationship between the antifertility effect of alpha-chlorohydrin and changes in composition of luminal plasma from the cauda epididymidis of rats and rabbits has been investigated. At each dose regimen studied, the fertilizing capacity of rats treated with alpha-chlorohydrin was reduced to zero. The levels of sodium, potassium, glycerylphosphorylcholine (GPC), acid phosphatase and alkaline phosphatase in epididymal plasma were not markedly affected by drug treatment. The most noticeable change was a considerable increase in the concentration of lactic dehydrogenase (LDH) at all dose levels and of glutamic-oxaloacetic transaminase (GOT) after 7 days of treatment with 8 and 16 mg/kg. The effect of cold shock on the composition of epididymal plasma showed that LDH and GOT are, at least in part, derived from spermatozoa. In contrast, alpha-chlorohydrin did not have an antifertility action in the rabbit, and the only notable change in the compositon of epididymal plasma was an increase in the level of GPC.  These results provide evidence that, in the rat, alpha-chlorohydrin or a metabolite primarily exerts its antifertility effect by a direct action on the spermatozoa, whilst in the rabbit a barrier may exist to the entrance of the drug into the lumen of the epididymal duct.


Nucleic acid metabolism of cells of the luminal epithelium and stroma of the rat uterus during early pregnancy.

The uptake of [5-3H]uridine into RNA and DNA of the cells of the uterine luminal epithelium, stroma and myometrium of the rat has been studied in early pregnancy using a technique for separation of the cell fractions before quantitative analysis. Comparisons of the metabolism between the pregnant and pseudopregnant horn of the unilaterally ovariectomized rat has shown that RNA and DNA synthesis are markedly increased by 04.00 hours on the morning of Day 5 in the pregnant horn. This increased metabolism occurs in all cell fractions and before the zona pellucida is shed. The results are discussed in relation to the onset of the decidual response.


Histochemical observations on the lipid changes in the ovarian interstitial gland tissue of rats.

Lipid changes were studied histochemically in the ovarian interstitial tissue of untreated and hormone-treated rats during the oestrous cycle, pseudopregnancy, pregnancy and lactation. The hormones tested were LH, prolactin and oestradiol benzoate, alone or in combination. Conspicuous lipid changes occurred only in response to LH.


Effects on long-term cadmium exposure on the seminal vesicles of mice.

Male CBA-mice were exposed to cadmium by subcutaneous injection of 2-2 mumol CdCl2/kg body weight for 5 days/week for 6 months. A decrease in normal (testosterone-dependent) proteinuria was shown, and morphological examination of the seminal vesicles revealed a smaller weight and size as well as histological indication of lower secretory activity of the epithelium compared to controls. The findings are consistent with a theory implying a decreased testosterone activity in cadmium-treated animals.


Effect of epididymal isolation on the protein component of bull eididymal tissue.

Four fractions of protein from intact and 'isolated' bull epididymides were extracted. The total extractable protein was increased by isolation mainly due to increases in the lipoprotein and DNA-protein fractions. Changes of lipoprotein may be associated with the increase of lipid which also occurs in isolated tissue. This may reflect the increase of pentose cycle activity and lipogenesis due to the absence of spermatozoa in the epididymal tubules. Changes of DNA-protein may indicate a change of protein metabolism. Electrophoresis of protein fractions showed that individual proteins may be changed by the zonal origin of the epididymal tissue and the presence or absence of spermatozoa in the epididymal tubules.


Plasma progesterone, androstenedione and testosterone concentrations in freemartin heifers.

Plasma concentrations of testosterone, androstenedione and progesterone in freemartins, and normal cyclic and non-cyclic heifers were studied. The plasma testosterone concentrations were in general less than 10 pg/ml in all animals. The mean androstenedione concentration of 28 pg/ml in 10- to 12-month-old freemartins was significantly lower than the mean of 58 to 60 pg/ml for normal 10- to 12-month-old heifers. At 24 months of age the mean androstenedione concentration in the freemartins had risen significantly to 65 pg/ml.


Temporary sterility produced in male mice by 5-thio-D-glucose.

When 5-thio-D-glucose was fed to male mice at daily dose levels greater than 30 mg/kg sperm development was completely inhibited within 3 weeks and remained so without impairment of libido for the experimental period of 7 weeks. Removal of this substance from the diet resulted in a resumption of sperm development and fertility within 5 to 8 weeks. Normal litters were sired by males which had recovered after this treatment.


Relationship between the electrical activity of the oviduct and the uterus of the rabbit in vivo.

The electrical activity of the whole genital tract of the rabbit was recorded by means of chronically implanted electrodes after section of the uterotubal junction on one side. When the junction was intact, the activity of the isthmus and that of the proximal uterine horn occurred almost simultaneously, but uterine activity decreased after the junction was cut. During the preovulatory phase and also after administration of HCG, synchronos activity due to adrenergic drugs, smoke or oxytocin persisted on both sides of the uterotubal junction. Hypersensitivity of the isthmus and the proximal segment of the uterine horn was recorded on the cut side after ovariectomy. The concept of a local control mechanism in the region of the uterotubal junction with a positive control of the uterus by the oviduct is suggested.


Maturation iv vitro of ovarian oocytes of prepubertal and adult hamsters.

Oocytes of various sizes were isolated from ovaries of sexually mature and prepubertal hamsters and cultured ot determine whether all the oocytes were capable of maturing in vitro. It was found that only the oocytes that had attained maximum size (about 80 mum in the vitelline diameter) were capable of undergoing maturation in vitro. Smaller oocytes (less than 80 mum in diameter) failed either to initiate or to complete maturation. The oocytes which were capable of maturing in vitro (competent oocytes) were present in the ovaries of adult females 136 to 138 hr before ovulation. The competent oocytes first appeared in the ovaries of prepubertal females on the 23rd day after birth, about 10 days before puberty.


Evidence of prolactin cell deficiency in connection with low reproductive efficiency of female 'torpid' mice.

The pituitary of female 'torpid' mice at the age of sexual maturity was deficient in prolactin cells. This deficiency is thought to contribute to the infertility of the affected mice.


Correlation of colposcopically directed biopsy and conization with histologic diagnosis of cervical lesions.

This study describes 50 patients with abnormal cervical Papanicolaou smears who had colposcopically directed biopsies and then subsequent cervical conization. The objective was to test the accuracy of directed biopsies compared with that of standard method of diagnosis. A significant difference between the two methods occurred in 4% of patients. This figure is the same as that gained from a review of current literature (3.8%). There were no invasive carcinomas in this series.


Induction of midtrimester abortion with intraamniotic urea, intravenous oxytocin and laminaria.

Midtrimester abortion was accomplished in 75 patients by the intraamniotic instillation of 80 g of urea and the intravenous administration of oxytocin. In 33 of the patients, laminaria tents were inserted into the cervix. No severe complication occurred; all fetuses were stillborn. A single urea instillation was effective in 94.6% of the patients. The mean instillation-abortion interval was significantly (p less than 0.02) shorter in patients with laminaria tents than in those without. The tents probably prevent cervical rupture in s-me patients. Significant but transient changes occurred in platelet count and blood urea nitrogen one hour after urea instillation. Surgical removal of the placenta was required in 18.7% of the 75 patients; infection occurred in 2.6%. The combined use of urea, oxytocin, and laminaria appears to be an effective and relatively safe method of inducing abortion during the second trimester.


The effect of isoxsuprine treatment of estrogen levels in maternal and umbilical cord plasma.

Estrogen concentrations in maternal plasma were determined in ten apparently normal patients attending clinic in the last trimester of pregnancy before, during, and after a maximum of four weeks isoxsuprine treatment. Eleven control patients were also studied at similar times of pregnancy. Isoxsuprine treatment appeared to have no specific effect on the levels of either estradiol alone or on total estrogens with all patients studied showing some increase in the concentrations of these estrogens as the pregnancies approached term. In four other patients treated with isoxsuprine for pregnancy complications, changes in plasma total estrogen concentrations during treatment were variable and did not correlate with the amount administered. The levels of estradiol in umbilical cord plasma from 17 isoxsuprine-treated pregnancies were similar to those observed in 24 non-treated pregnancies.


The choleretic action of Genebile in a dog.

A procedure for cannulating the bile duct of the dog is described. An intramuscular injection of Genebile increased the bile flow rate. A possible mechanism for this increase is suggested.


A method for the in vitro study of drug transfer across ruminal epithelium.

A simple method for the in vitro study of drug diffusion across ruminal epithelium is described. The characteristics of the isolated membrane were defined by studies of ketone production from butyrate, histological studies, phenolsulphonthalein penetration and permeability to pentobarbital, antipyrine and tetraethylammonium. The preparation was found to be suitable for studies of less than 12 hours duration; after that time the integrity of the membrane as a barrier was lost due to degenerative changes. The method had a primary advantage in that experimental variables could be rigorously controlled.


Chronic fluoride poisoning in sheep.

Chronic fluoride poisoning in sheep and cattle was diagnosed on a farm in the Vredenburg district, Cape Province, and confirmed by laboratory analysis. The source of the poisoning was pastures contaminated with rock phosphate dust containing 2,1 to 3,3% of fluoride emitted from a fertilizer factory. Tabulated analyses of blood, liver, bone, pasture and water are given.


Chlamydiosis in a beef herd.

Chlamydial infection in a large beef herd is illustrated and discussed. The pre-natal and post-natal losses that occurred during 1972 are highlighted. Total pre-natal losses for the nine calving herds comprising 2,915 animals varied between 3,7% and 12,4%. Between 1,2% and 11,4% of the calves born alive in the nine herds died before weaning with 70% of the losses occurring within the first three weeks of life. Chlamydial organisms were demonstrated in pre-natal and post-natal losses from all nine herds. Clinical manifestations and lesions involving the intestinal, respiratory, nervous, skeletal, reticulo-endothelial and urinary systems were observed in chlamydia-infected calves. Invariably at autopsy in chlamydia positive cases there was some degree of a fibrinous inflammatory process present. Serological evidence showed that chlamydial organisms had been present on both farms prior to the 1972 investigations.


Haemoglobin types in African cattle.

The migration of domesticated animals in Africa is of particular interest to the anthropologist and ethnologist in that it may provide valuable information concerning the migration of human tribes that accompanied these animals. Haemoglobin C is only found to be present in indigenous breeds of African cattle and can therefore be used as one of the best genetic markers of these animals. Haemoglobin B has been established in many breeds in Africa and India. It seems that the further away the animals migrated from India, the lower is the frequency of HbB. Breed comparisons from numerous breeds in Africa are made, including the results of the present investigations on breeds of different countries in Southern Africa.


Standard serum chemical and haematological values in the chacma baboon (Papio ursinus).

Blood chemical and haematological determinations were carried out on 64 baboons. The blood chemical and haematological values determined were found to be in general agreement with the values for man and other primate species. Some blood constituents however, did show noteworthy differences. Marked sex differences were demonstrated in some blood chemical and haematological parameters.


Experimental Phomopsis leptostromiformis mycotoxicosis of pigs.

The susceptibility of the domestic pig to intoxication by the causative mycotoxin of lupinosis was established experimentally. The symptomatology and pathology of the disease produced by the administration of toxic cultures of the fungus, Phomopsis leptostromiformis (Kühn) Bubák ex Lind to pigs are described. The toxin induced severe loss of weight and, in many cases, posterior paresis or paralysis. The principal gross lesions were generalised icterus, orange-red discoloration of the liver, nephrosis and, in some, enterorrhagia. Microscopically there was severe necrosis of hepatocytes and kidney tubular epithelium as well as myocardial degeneration. In the more chronic cases hepatocytes became anaplastic and arranged in acini. The production of toxin by P. leptostromiformis on yellow maize is reported and a method for production of toxic material is described.