[Detection of endonuclease activity and several features of chromatin autolysis in brain cell nuclei]. The presence of Ca2+, Mg2+-dependent endonuclease activity in isolated brain cell nuclei was demonstrated and a comparison of some peculiarities of chromatin autolysis in rat brain and liver cell nuclei was carried out. Endogenous brain nuclease hydrolyzes chromatin into its structural subunits; its specific activity is 10,5 times as low as compared to the endogenous nuclease activity in rat liver nuclei. The dependency of the chromatin autolysis rate on pH and ionic composition of the incubation medium in isolated rate brain and liver nuclei appeared to be the same. The presence of Mn2+ changed the autolysis nature both in brain and in liver cell nuclei, the relative (as compared to Mg2+-dependent) Mn2+-dependent activity being higher in the brain cell nuclei. Possible differences of brain and liver chromatin structure (e. g. the presence of regions free of nucleosomic organization in brain chromatin) are assumed.


[Cytochrome P-450 catalyzed oxidation of 1-piperidinoanthraquinone]. Oxidation of 1-piperidinoantraquinone (1-PA) in microsomal fractions of rat liver was studied. The only product of complete oxidation of 1-PA--(N-antraquinone-1)-delta-aminovaleric acid-was identified using paper and thin-layer chromatography. The participation of cytochrome P-450 in oxidation of 1-PA was demonstrated by sharp inhibition, involving blowing of the microsomes with CO and treatment with sodium deoxycholate. Studies of differential spectra of cytochrome P-450 in the presence of 1-PA are indicative of the first type of binding between 1-PA and cytochrome P-450. The binding constants (Ks) and the kinetic parameters (Km and V) for the above substrate in control microsomes and in those induced by phenobarbital and 3-methyl cholanthrene were determined. The results obtained suggest that cytochrome P-450 is involved in oxidation of a number of heterocyclic compounds resulting in the opening of the ring.


[Ribonuclease of Bacillus intermedius 7 P. Purification by chromatography on phosphocellulose and several characteristics of the homogeneous enzyme]. A new procedure for isolation of homogenous ribonuclease of Bac. intermedius from a commercial source is described. The yields of 140 mg of RNAse from 200 g of the enzymic powder were attained. The amino acid composition of the enzyme was determined. The RNAse contains neither the sulfhydryl groups nor the disulfide bonds and has only one histidine residue. At the same time the amount of aromatic amino acid residues is relatively high. The enzyme is highly resistant to heat and acid treatment but is less stable in an alkaline solution. The pH optimum of the RNAse for the RNA digestion is 8,5; the temperature optimum for this reaction is 37 degrees. A spectrophotometric method for the RNAse activity assay using polyA as a specific substrate was developed. The purified product provides a suitable starting material for structural studies.


[Effect of intersubunit interaction in horse liver alcohol dehydrogenase on the kinetics of ethanol oxidation]. The kinetics of enzymatic oxidation of ethanol in the presence of alcohol dehydrogenase within a wide range of ethanol and NAD concentrations (pH 6.0--11.5) were studied. It was shown that high concentrations of ethanol (greater than 0.7--5 mM, depending on pH) and NAD (greater than 0.4--0.8 mM) activate alcohol dehydrogenase from horse liver within the pH range of 6.0--7.9. A mechanism of activation based on negative cooperativity of ADH subunits for binding of ethanol and NAD was proposed. The catalytic and Michaelis constants for alcohol dehydrogenase were calculated from ethanol and NAD at all pH values studied. The changes resulting from the subunit cooperativity were revealed. The nature of ionogenic groups of alcohol dehydrogenase, which affect the formation of complexes between the enzyme and NAD and ethanol, and the rate constants for catalytic oxidation of ethanol was assumed. The biological significance of the enzyme capacity for activation by high concentrations of ethanol within the physiological range of pH in the blood under excessive use of alcohol is discussed.


[Isolation and properties of N-acetyl-beta-D-hexosaminidase from the fungus Hohenbuechelia serotina]. N-Acetyl-beta-D-hexosaminidase (EC 3.2.1.52) isolated from the fruit bodies of Hohenbuechelia serotina (Fr.) splits N-acyl-p-nitrophenyl-beta-D-glucosaminides acylated at the amino group of the aminosugar by fatty acids, substituted benzoic acids and some amino acids and peptides. The enzyme was purified about 210-fold by chromatography on CM-Sephadex C-50 and DEAE--Sephadex A-50 and by gel filtration of Sephadex G-200 with a yield of 4%. The enzyme had pI 6,6. Some properties of the enzyme, pH-optimum, thermal stability and substrate specificity were studied. The Michaelis constants for some p-nitrophenyl-beta-D-glucosaminides were were calculated. p-Nitrophenyl N-acetyl-beta-D-glucosaminides were calculated. p-Nitrophenyl N-acetyl-beta-D-glucosaminide and D-galactosaminide at concentrations more than 0,3 mM inhibited the enzyme.


Imaginal response events in systematic desensitization: a pilot study. The primary focus of systematic desensitization (SD) is physiological responsivity in the presence of a conditioned aversive stimulus. However, SD also effects changes in motorapproach behavior and self-report. This study explores the possibility that SD directly affects the motor response system by way of conditioning covert approach responses in the presence of the imaginal aversive stimulus. Two independent variables were investigated: the content of instructions and actual covert motor responses during SD. Twenty-four subjects were classified as high- or low-responders on the basis of electromyographic responsiveness to instructions to imagine movement. Half the high- and half the low-responders were given a series of instructions to imagine-motor-approach behavior toward snakes. The remaining subjects received instructions to imagine only the snakes themselves with no reference to motor response. Imaginal scenes of 30-sec duration were alternated with relaxation periods of the same length. A significant difference was found between the posttreatment scores of high- and low-responders on performance measures, the high-responders performing better. The difference between the two instruction groups was not statistically significant. Self-report data suggested some subjects given instructions to imagine only snakes actually imagined themselves approaching snakes. Therefore, data were re-analyzed after instruction groups were reconstructed accordingly. A statistically significant difference was found on both factors. Continued investigation may further support imagery as covert behavior, open to empirical study.


Continuous production of NADP by immobilized Brevibacterium ammoniagenes cells. Whole cells of Brevibacterium ammoniagenes IAM 1645 having the polyphosphate NAD-kinase were successfully immobilized in a polyacrylamide gel lattice. The immobilized cells were activated by treatment with organic solvents or detergents. The pH optimum of the immobilized cells for the production of NADP was 7.0, and divalent metal ions were required to maintain the elevated activity of polyphosphate NAD-kinase. Highly pure NADP was continuously produced in high yield by the immobilized cell column. The half-life of this column was about eight days.


Immobilization of microbial cells containing NAD-kinase. Microbial cells having NAD-kinase activity, Brevibacterium ammoniagenes, were immobilized by the radiation-copolymerization method under low temperature with the activity recovery of more than 80%. Compared to the native microbial cells the immobilized cells were more stable against heat and pH change. The immobilized cells were subjected to the 5 hr reaction repeatedly 20 times without any activity loss.


Immobilization and characterization of D-amino acid oxidase. Optimal conditions with respect to pH, concentration of glutaraldehyde and enzyme, and order of addition of enzyme and crosslinking reagent were established for the immobilization of hog kidney D-amino acid oxidase to an attapulgite support. Yields of 40 to 70% were generally attained although when low concentrations of enzyme were used yields were consistently greater than 100%. It is suggested that this is due to a dimer leads to monomer shift at low protein concentrations. The stability of soluble D-amino acid oxidase was dependent on the buffer in which it was stored (pyrophosphate-phosphate greater than borate greater than Tris). Stability of immobilized enzyme was less than soluble in pyrophosphate-phosphate buffer, but storage in the presence of FAD improved stability. In addition, treatment of stored, immobilized enzyme with FAD before assay restored some of its activity. The immobilized D-amino acid oxidase was less stable to heat (50 degrees C) than the soluble enzyme from pH 6 to 8 but was more stable above and below these values. Apparent Km values for D-alanine, D-valine, and D-tryptophan decreased for the immobilized enzyme compared to the soluble.


[Changes in postsynaptic excitation processes in the presence of phenazepam]. The new psychotropic drug phenazepam inhibits the impulse activity of the neurons which compose visceral ganglia of the garden snail (Helix aspersa) and suppresses stimulating postsynaptic potentials arising in application of acetylcholine to the membrane of isolated neurons. The electrostimulating membrane parameters are not generally changed. Postsynaptic depression of the stimulation of the cholinoreceptive membrane is suggested to be one of the possible mechanisms of the pharmacological action of the drug.


Salicylate blockade of granulocyte adherence and the inflammatory response to experimental peritonitis. Aspirin profoundly inhibited the in vitro augmentation of human and mouse granulocyte adherence to nylon fiber induced by the bacterial products Escherichia coli endotoxin and Staphylococcus aureus culture filtrate. Granulocytes obtained from normal volunteers during the 48 hr following ingestion of aspirin did not respond normally to endotoxin stimulation. Furthermore, pretreatment of mice with sodium salicylate prior to intraperitoneal infection with Streptococcus pneumoniae impaired granulocyte exudation and resulted in uncontrolled bacteremia and greater lethality of infection.


Sensitivity of mouse vas deferens to neurotransmitters: changes after morphine treatment. 1. The pharmacological responses of the isolated vas deferens of the mouse were investigated after acute and chronic treatment with morphine. 2. The addition of morphine to the bath did not alter the responses of the vas deferens to exogenous noradrenaline, adrenaline or dopamine. 3. Low doses of morphine depressed the responses to acetylcholine. Very high concentrations of the opioid (8.5 x 10(-4) M) completely abolished, in about 50% of the preparations, the responses to exogenous acetylcholine, while in the other 50% a potentiation of the responses to low concentrations of acetylcholine was observed. 4. The vas deferens of mice chronically treated with morphine showed increased sensitivity to exogenous noradrenaline, but decreased sensitivity to acetylcholine. 5. A fresh amount of morphine added to the bath enhanced the responses of morphine-tolerant preparations to noradrenaline but not to dopamine or acetylcholine. The specificity of this phenomenon was demonstrated by the use of pentobarbitone instead of the opioid. 6. These results are in agreement with the theory that tolerance could result from a form of disuse supersensitivity.


Minor tranquillisers and road accidents. In a prospective study of 43,117 people, prescriptions issued by general practitioners over two years were linked with records of hospital admissions and deaths. For 57 people injured or killed while driving cars, motorcycles, or bicycles the medicines that had been dispensed in the three months before were compared with those dispensed for 1,425 matched controls. There was a highly significant association between use of minor tranquillisers and the risk of a serious road accident (relative risk estimate 4.9). the increased risk of accidents to drivers given tranquillisers could be due to the known psychomotor effects of these drugs or to effects of the conditions being treated. Whatever the reason, patients taking drugs such as diazepam should be warned that they are at special risk.


Some observations on the calcium ion binding to the eggshell matrix. The calcified matrix of the hen eggshell has been demineralized with the EDTA. Aliquots of this material are soluble in water and have been characterized by column chromatography and by chemical analyses. Of particular interest is the high hexosamine and uronic acid content, which confirms the protein-polysaccharide nature of this water-soluble material. The calcium ion binding to the eggshell matrix has been studied by the equilibrium dialysis technique at different pH values, with both free and blocked carboxylic groups. The material with the free carboxylic side chain groups binds more calcium ions with increasing pH value. When the carboxylic groups have been previously blocked with a water-soluble carbodiimide, the calcium ion binding rapidly decreases. The residual capacity to bind calcium ions in the material with the carboxylic functions modified is probably due to the sulfate ions. In agreement with previous observations on other calcified substrates, the calcium ion binding seems to depend on the presence of ionized carboxylic functions of the matrix.


Growth temperature-dependent stearoyl coenzyme A desaturase activity of Fusarium oxysporum microsomes. The characteristics of the microsomal stearoyl CoA desaturase (EC 1.14.99.5) of vegetative Fusarium oxysporum cells grown at different temperatures were studied. The enzyme had an unusual preference for NADPH (Km = 38 micrometers) over NADH (Km = 89 micrometers) as electron donor, and a relatively high optimum pH of 8.3. Enzyme activity was highest in microsomes from cells grown at 37 degrees C and lowest in cells grown at 15 degrees C. This result correlated well with the observed changes in oleic acid content of the microsomal lipids. Both NADPH-linked reductase activities and hemoprotein content were lowest in cells grown at 37 degrees C. Spectrophotometric analysis of the microsomal hemoproteins indicated the absence of cytochrome b5 and the presence of a b-type heme with a pyridine hemochrome alpha band absorption maximum at 565 nm. Labile sulfide analysis and inhibitor studies with thenoyltrifluoroacetone suggested a role for an iron-sulfur protein in the electron transfer system associated with the desaturase.


Horseradish peroxidase. XXXII. pH dependence of the oxidation of L-(-)-tyrosine by compound I. The rate of oxidation of L-(-)-tyrosine by horseradish peroxidase compound 1 has been studied as a function of pH at 25 degrees C and ionic strength 0.11. Over the pH range of 3.20--11.23 major effects of three ionizations were observed. The pKa values of the phenolic (pKa = 10.10) and amino (pKa = 9.21) dissociations of tyrosine and a single enzyme ionization (pKa = 5.42) were determined from nonlinear least squares analysis of the log rate versus pH profile. It was noted that the less acidic form of the enzyme was most reactive; hence, the reaction is described as base catalyzed. The rate of tyrosine oxidation falls rapidly with the deprotonation of the phenolic group.


Nitrogen-metabolizing enzymes of Diplodia maydis, a Zea mays L. stalk rot causing fungus. The nitrogen source available to Diplodia maydis in vivo is reported to affect the severity of stalk rot in maize. Nitrate and (or) ammonium salts were tested for their effect on the type of nitrogen metabolism found in Diplodia maydis in vitro. The level of glutamate dehydrogenase remained essentially constant on either nitrogen salt but nitrate reductase was induced by growth on nitrate salts and was not extractable on ammonium salts. Properties of nitrate reductase reported here are similar to those reported for the higher plant and Neurospora crassa enzymes. Thr relationship of nitrogen metabolism in Diplodia maydis to Zea mays L. stalk rot is discussed.


Properties of malate dehydrogenase isolated from Methanospirillum hungatii. A NADH-linked oxygen-tolerant malate dehydrogenase was purified 270-fold from cell extracts of Methanospirillum hungatii. Inhibitors of the enzyme included ADP, alpha-ketoglutarate, and excess NADH. Inhibition patterns for ADP were competitive with respect to NADH and non-competitive with respect to oxalacetate. Inhibition by alpha-ketoglutarate was non-competitive with oxalacetate as variable substrate and uncompetitive with respect to NADH. alpha-Ketoglutarate is surmised to function as an end-product inhibitor of the enzyme in reactions converting oxalacetate to alpha-ketoglutarate. No enzyme activity was detected in the direction of malate conversion to oxalacetate, in keeping with a strictly biosynthetic function of the enzyme. An analysis of variance of intial rate data fit to sequential and ping-pong equations showed that a sequential mechanism was perferred. The malate dehydrogenase of M. hungatii resembles those of many other bacteria and eucaryotic cells respect to molecular weight (61,700) and reaction mechanism, but may be regulated differently.


Characterization of an enzyme from Rhizoctonia praticola which polymerizes phenolic compounds. An extracellular phenol oxidase from the fungus Rhizoctonia praticola which polymerizes various xenobiotic phenols was isolated and characterized. The enzyme was purified by DEAE-cellulose and Sephadex G-200 chromatography followed by preparative polyacrylamide gel electrophoresis. Atomic absorption and EPR spectroscopy indicated the presence of copper, and SDS gel electrophoresis revealed a molecular weight of 78,000. With 2,6-dimethoxyphenol as substrate, the enzyme showed a pH optimum of 6.7--6.9, and a temperature optimum of 40 degrees C. According to these and additional characteristics it appears that the enzyme belongs to the class of laccases.


Agenesis or atrophy of the testis and vas deferens. In this study the author examines the relationship between agenesis or atrophy of the testis and of the vas deferens. From a prospective study of 237 cases of unilateral and bilateral undescended testis, 12 cases of agenesis of a testis were seen; 9 of the 12 cases were associated with agenesis of the vas deferens and in 3 of these unilateral renal agenesis was also present, not necessarily ipsilaterally. Three other cases of testicular agenesis and four cases of extreme testicular atrophy were seen. In all seven, the vas deferens was present in part or in its entirety and roentgenography disclosed a normal upper urinary tract. Agenesis of the vas deferens was seen only in patients with monorchism. No patient was anorchid. It is concluded that an important link exists between agenesis of the vas deferens and agenesis of the testis.


Approach to drug therapy for hypertension. Prevention of complications of hypertension requires the lowering of blood pressure. The therapeutic goal is to achieve and maintain a diastolic pressure of less than 90 mm Hg with minimal adverse effects. The treatment of patients with established diastolic blood pressures between 90 and 104 mm Hg (determined from three separate readings) should be individualized; general measures such as weight loss and salt restriction should be tried first as an alternative to drug therapy. Patients with diastolic pressure in excess of 104 mm Hg should be treated with antihypertensive drugs; the first step should be the use of a thiazide diuretic in addition to general measures. Patients with diastolic pressures of 90 to 115 mm Hg may require the addition of a beta-adrenergic-receptor antagonist, methyldopa or clonidine if the therapeutic goal is not achieved; rarely they require the further addition of hydralazine or prazosin. Patients with diastolic pressures of 116 to 129 mm Hg usually require initially both a thiazide diuretic and a beta-blocker, methyldopa or clonidine; if the therapeutic goal is not achieved, hydralazine or prazosin is added, and if a further hypotensive effect is required guanethidine can be added. Patients with severe hypertension (diastolic pressures greater than 130 mm Hg) may require urgent treatment with combinations of drugs of all three levels. Emphasis should be placed on individualized therapy and patient compliance in the assessment of therapeutic failures. These "step-care" guidlines represent a framework for antihypertensive therapy devised from information available in 1977. It is not a rigid scheme and should be adjusted to the individual patient to ensure as normal a life as possible.


Mutagenicity of the non-carcinogenic dibenzylnitrosamine and an alpha-acetoxy derivative. The mutagenicity of a non-carcinogenic nitrosamine, N,N-dibenzylnitrosamine (I), and a chemically synthesized alpha-acetoxy derivative, N-(alpha-acetoxy-benzyl)-N-benzylnitrosamine (II), has been examined in Salmonella typhimurium TA100 and TA1535. Compound (I) was non-mutagenic when tested directly or in the presence of a metabolic activation system while (II) was highly mutagenic when tested directly. This is the first report on the conversion of a non-mutagenic N-nitrosamine to a mutagen by the formation of an alpha-acetoxy derivative.


DNA damage induced in vivo evaluated with a non-radioactive alkaline elution technique. A modification of the alkaline filter elution test was used to study damage to liver DNA of NMRI mice following in vivo treatment with various hepatocarcinogens and drugs causing liver enlargement. Liver cell nuclei were prepared and lysed on top of polyvinyl filters. DNA was eluted, and the amounts both remaining on the filter and in the eluate were measured colorimetrically. Dimethylnitrosamine (DMN), diethylnitrosamine (DEN), N-nitrosomorpholine and methyl methanesulfonate (MMS) caused significant enhancement of DNA passage through the filters, whereas N-acetylaminofluorene (AAF), 4-dimethylaminoazobenzene (DAB), phenobarbital, halothane and CCl4 did not. The applicability of this short term test is discussed.


The effect of beta-adrenoceptor and Ca2+ antagonist drugs on the hypoxia-induced increased in resting tension. Using isolated, Langendorff-perfused, electrically-paced guinea-pig hearts, we have investigated the rise in resting tension that occurs when mammalian heart muscle becomes hypoxic. Substrate-depletion, tachycardia, hyperthyroidism, and inotropic interventions (ouabain, isoprenaline, and beta-receptor antagonists at concentrations which increase inotropic state) enhanced the rate of development of this increase in resting tension. 3.86 mumol.litre-1 propranolol, 0.22 to 2.20 mumol.litre-1 verapamil or removing Ca2+ from the extracellular phase at the start of the hypoxic episode prevented (or delayed) the rise in resting tension. Adding these same agents or removing Ca2+ from the extracellular phase after the hypoxia-induced rise in resting tension had started to develop failed to prevent its progression. These results provide some support for an hypothesis that the hypoxia-induced increase in resting tension is independent of an enhanced Ca2+ influx.


[Immunological aspects of nucleolar activation. III. Changes in nucleolar activation after application of S III pneumococcal polysaccharide in vivo]. Intraperitoneal application of 0.7 microgram S III pneumococcal polysaccharide led to a significant increase in the values of nucleolar activation in small, medium, and large lymphocytes, plasmoblasts, and plasmatic cells in a white mouse. Macrophages did not respond to the application of S III by an increase in nucleolar activation. The study tested the possibility of using the observation of the functional morphology of the nucleous for observing the changes in the activation of B-cells after administration of nonspecific mitogen and a thymus-independent antigen.


[Action of N-butylnorsympathone on the effects of cardioaccelerator nerve stimulation in the dog]. In Dogs anaesthetized with pentobarbital (30 mg . kg-1), N-butylnorsympathone (20 mg . kg-1 i.v.) reduced the bradycardia induced by stimulating the cardiac nerve (1, 2, 5, 10 Hz). Phentolamine (1 mg . kg-1 i.v.) or yohimbine (0.3 mg . kg-1 i.v.), two potent alpha-adrenoceptor blocking agents known to block presynaptic alpha-adrenoceptor induced a recovery of the effect of cardiac nerve stimulation. Prazosine (0.050 mg . kg-1 i.v.) an alpha-adrenoceptor blocking agent known to be ineffective on presynaptic alpha-adrenoceptors did not induce a recovery. However neither phentolamine or yohimbine were able to prevent the effects of N-butylnorsympathone. Neither haloperidol (0.050 to 2 mg . kg-1 i.v.) or pimozide (0.20 to 1 mg . kg-1 i.v.) induced a recovery or prevented the effects of N-butylnorsympathone. These results suggest that N-butylnorsympathone may stimulate presynaptic receptors which do not resemble classical presynaptic alpha-adrenoceptors or dopamine receptors.


Evaluation of the cytotoxicity of dihydroxytryptamines and 5-hydroxytryptamine antagonists as cytotoxic agents in dimethylhydrazine-induced adenocarcinomata. The cytotoxicity of 5,6-dihydroxytryptamine (5,6-DHT), 5,7-dihydroxytryptamine (5,7-DHT), bromolysergic acid diethylamide (BOL), methysergide, and cyproheptadine, and also of 5,6-DHT together with either BOL, methysergide, or cyproheptadine in dimethylhydrazine-induced (DMH) carcinomata of rat colon was evaluated by estimating the percentage of necrotic cells in histological sections of tissues taken 15 h after injection of each of the drugs. In addition, the influence of methysergide and cyproheptadine on the tumour cell mitotic rate was estimated by means of a stathmokinetic technique. Both 5,6-DHT and 5,7-DHT were cytotoxic at each dose tested and for each of these agents the percentage of necrotic cells was directly correlated with the dose of drug used. BOL was not found to be cytotoxic to the colonic carcinomata, whereas both methysergide and cyproheptadine did cause detectable tumour cell necrosis. Methysergide was also found to accelerate tumour cell proliferation, whereas cyproheptadine did not. BOL competitively inhibited the cytotoxicity of 5,6-DHT and neither methysergide nor cyproheptadine potentiated the effect of 5,6 DHT.


A comparison of reaction conditions for the automated determination of gamma-glutamyltransferase activity in serum. The methods of Rosalki and Tarlow and the Scandinavian Committee on Enzymes for the determination of gamma-glutamyltransferase activity in serum have been compared, with an automatic reaction-rate analyzer in which the reaction is initiated by the addition of a concentrated solution of gamma-glutamyl-p-nitroanilide. Results are approximately 4% lower by the Scandinavian method, because of its lower substrate concentration. However, both methods are of comparable reproducibility. The greater stability of the more dilute substrate solution specified in the Scandinavian method has been confirmed, but attempts to stabilize solutions of gamma-glutamyl-p-nitroanilide at the higher concentrations recommended by Rosalki and Tarlow by the addition of organic solvents were accompanied by some enzyme inhibition. The comparative instability of the substrate solutionof Rosalki and Tarlow is unlikely to lead to erroneous results; however, the Scandinavian formulation offers the advantage of a more economical use of reagents, at the expense of a small and probably unimportant reduction in sensitivity.


The biochemical consequences of cardiopulmonary bypass surgery in children. The changes in serum enzyme activities after successful and uncomplicated cardiopulmonary bypass (CPB) surgery in children are described. After maximum serum enzyme activities were attained, they thereafter declined steadily without any secondary peaks of activity, to be at or near normal activities by the seventh day after surgery. The possible sources and mechanisms of enzyme leakage from tissues after CPB are discussed. The concentration of some physiologically important constituents were determined in pump prime fluids and in the common circulation on bypass. The consequences of haemodilution on small children were undesirably reduced concentrations of magnesium, calcium and albumin, and this state persisted for some days after the end of bypass. Some possible implications of such unphysiological pump primes are discussed. We suggest that ASp AT, Ala AT, CK-MB, magnesium, calcium and urea should be routinely monitored for the first four days after surgery.


N-Acetyl-beta-D-glucosaminidase activity in normal and chronic lymphocytic leukaemic lymphocytes. N-Acetyl-beta-D-glucosaminidase (EC 3.2.1.30) activity was measured fluorimetrically in: (a) lymphocytes from 20 normal donors, (b) enriched B and T lymphocyte populations prepared by E rosette sedimentation from 8 normal subjects, (c) lymphocytes from 15 untreated B cell chronic lymphocytic leukaemic patients. The pH profiles and optima (4.7) were similar in all preparations. Normal B lymphocytes had higher activity than normal T lymphocytes and both these preparations and normal unfractionated lymphocytes had significantly higher activity than chronic lymphocytic leukaemic lymphocytes. The apparent Michaelis constants were similar in normal unfractionated, B enriched and T enriched lymphocytes, whereas a reduced affinity for the enzyme was observed in the leukaemic lymphocytes. The difference in enzyme content between normal and chronic lymphocytic leukaemic lymphocytes cannot therefore be explained on the basis of a high B cell percentage in patients with chronic lymphocytic leukaemia.


Isolation of kidney brush border gamma-glutamyl transpeptidase from urine by specific antibody gel chromatography. The IgG fraction of antiserum directed against gamma-glutamyl transpeptidase (gammaGTP, EC 2.3.2.2) isolated from human kidney brush border membranes after limited proteolysis, was covalently bound to cyanogen bromide-activated Sepharose. With this antibody-gel, gammaGTP present in the urine of patients as a result of tubular damage was immunospecifically prepared by affinity chromatography. The enzyme isolated from the urine samples gave a complete cross-reaction wiht gammaGTP artificially cleaved off from brush border fragments. Since labelled anti-gammaGTP sera gave a specific immunofluorescence only of the luminal portion of cortical tubule, the use of immunosorption chromatography appears to be an important approach for the isolation of urinary kidney tissue antigens of a defined origin.


Arylsulphatases A and B in human diploid fibroblasts: differential assay with 4-methylumbelliferylsulphate and AgNO3. A new technique is introduced for the differential assay of arylsulphatases A and B in centrifuged homogenates of cultured human skin fibroblasts, using 4-methylumbelliferyl-sulphate as a substrate and AgNO3 as a selective inhibitor of arylsulphatase A. The method can be applied in the diagnosis of metachromatic leucodystrophy, mucopolysaccharidosis type VI and mucosulphatidosis. Normal arylsulphatase activities were found in fibroblasts derived from patients with mucopolysaccharidoses types II, III-A and IV, known to be caused by deficiencies of various other sulphatases.


Selectivity of beta adrenoreceptor antagonist drugs assessed by histamine bronchial provocation. In a double-blind, within-patient, randomized study, 12 mild asthmatics were given single oral doses of propranolol (80 mg), metoprolol (100 mg), timolol (10 mg), or placebo. Resting heart rate and forced expiratory volume in one sec (FEV1) were measured before and 90 min after treatment. Nonspecific bronchial reactivity was measured by inhaled histamine at 90 min. Following each active drug, resting heart rate changed to a similar extent and to a greater degree than after placebo (p less than 0.01). Changes in FEV1 were small and not different from those after placebo. In contrast, after each active drug, bronchial reactivity increased more than after placebo. The degree of reactivity with each active drug was similar but the differences from corresponding placebo values were significant (p less than 0.05). We conclude that, in mild asthmatics, nonspecific bronchial reactivity is a more sensitive index of airway effects than resting FEV1. Moreover, in the context of this study, since the beta-blockers were given in doses likely to induce equivalent cardiac beta-blockade, there is no evidence to suggest that any one of them is more "cardioselective" than the others.


Effect of pH and urine flow on urinary nicotine excretion after smoking cigarettes. Effects of pH and urine flow on urinary excretion of nicotine were examined in 11 smokers after they had smoked 3 cigarettes during water diuresis. Plasma nicotine showed a slight but nonsignificant rise after smoking. Urinary excretion of nicotine increased significantly from the pre-smoking levels of 258 +/- 76 and 252 +/- 147 (mean +/- SEM) ng/15 min to the peaks of 2,587 +/- 1,224 and 2.561 +/- 584 ng/15 min 30 and 45 min after the start of smoking. Thereafter, urinary nicotine tended to decrease and rise with changes in urinary flow. There was a correlation between urinary nicotine and urinary flow after smoking (r = 0.26, p less than 0.05). Eleven subjects were grouped based on the mean urinary pH throughout the experiment. No significant amount of nicotine was excreted in the group with pH above 7.5 while groups with pH below 7.4 excreted substantial nicotine after smoking. There was a negative correlation between urinary pH and nicotine excretion (r = -0.58, p less than 0.001). Urinary excretion of nicotine cannot be used as an index of smoking unless pH and urine flow are controlled.


Evaluation of a community-based poison education program. This study suggests that: (1) a program directed at a specific town and coordinated by a local community group is more effective in transmitting poison control knowledge than is a statewide poison prevention week effort; (2) that transmission of educational material is optimized through programs directed at a specific age group (in this study ages 6 through 14); and, (3) that information about where to get the poison center number and actual acquisition of Ipecac syrup in homes was well transmitted.


Treatment plan for acute and chronic adrenergic poisoning crisis utilizing sympatholytic effects of the B1-B2 receptor site blocker propranolol (Inderal) in concert with diazepam and urine acidification. In a large series of patients who have abused a variety of commercially available "amphetamine-like" agents as well as "street drugs" with CNS stimulant activity, the specific lytic effects of propranolol (Inderal) were utilized to reverse the dangerous hyperkinetic cardiovascular and frightening CNS phenomena noted in these non-comatose individuals. Presented here is a logical and clinically proven mode of therapy by which the authors have consistently, successfully, and safely managed such patients in "adrenergic crisis" by judicious titration of electrolytes, propranolol, and diazepam.


The pharmacology of isolation-induced aggressive behavior in mice. This review attempts to summarize the literature on the effects of drugs on isolation-induced aggression in mice. In spite of the fact that each investigator that was surveyed utilized different methodologies (e.g., induction techniques, testing conditions, scoring systems), the results from the various laboratories are generally in agreement in many respects. Fighting in isolated mice has been shown to be selectively antagnoized (i.e., antifighting activity at doses significantly below doses producing neurological impairment in isolated mice) by antidepressants, neuroleptics, anticholinergics, antiserotonergics, and antihistamines; however, aggression was nonselectively antagonized by anxiolytics, muscle relaxants, anticonvulsants, sedatives, and hypnotics. Emphasis is placed on the necessity to determine pharmacological selectivity whenever antagonistic effects are observed; this can only be accomplished by measuring neurological impairment (ataxia) in the isolated mice by utilizing a test such as an inclined-screen, preferably immediately following aggression testing. Since isolated mice have been shown to exhibit marked differences in drug sensitivities and in metabolic dispositions of many classes of drugs as compared to group-housed controls, statements concerning drug selectivity or specificity are meaningless without some evidence for a lack of neurological impairment in isolated, aggressive mice.


Effects of changes in arterial carbon dioxide tension on oxygen consumption during cardiopulmonary bypass. The effects of changes in arterial carbon dioxide tension (PaCO2) on the oxygenation of tissues in 34 patients undergoing surgery for aortocoronary bypass were studied while temperature, systemic blood flow, and the delivery of oxygen to the peripheral tissues remained constant. Mixed venous and superior vena caval oxygen tensions (PvO2 and PsvcO2, respectively) and oxyhemoglobin saturations and the in vivo partial pressure of oxygen at which 50 percent of the hemoglobin is saturated (P50) increased with PaCO2, while peripheral vascular resistance, in vitro P50, the level of 2,3-diphosphoglyceric acid in the red blood cells, and the level of lactate in the blood remained constant. There was a close correlation between increases in PaCO2 and increases in PvO2 (r = 0.912; P less than 0.001) but not increases in PsvcO2 (r = 0.364; not significant). This indicated that the total-body consumption of oxygen diminished with increases in PaCO2 but that some regional redistribution of oxygen consumption occurred between the superior and inferior vena caval vascular beds. Since the level of lactate in the blood remained constant and since signs of metabolism acidosis did not develop, the reduced oxygen consumption due to increases in PaCO2 did not result in detectable increases in anaerobic metabolism.


The metabolic disposition of norgestrel in female rhesus monkeys. Following single intragastric doses of d- and dl-[24C]norgestrel (Ng), rhesus monkeys excreted 29.5 +/- 2.0 (SE) and 52.6 +/- 5.4% of the administered radioactivity in urine. Fecal excretion accounted for 57.1 +/- 4.0 and 37.2 +/- 4.4%, respectively. Urinary radioactivity was separated into neutral, acidic, and conjugated fractions. The neutral and conjugated fractions contained Ng; 2 alpha, 16 alpha- and 16 beta-hydroxy-Ng; 3 alpha,5 beta-tetrahydro-Ng and 16 beta-hydroxy-3 alpha,5 beta-tetrahydro-Ng and their glucuronides. However, the bulk of the radioactivity in these fractions was associated with more polar metabolites. The acidic fraction contained unstable metabolies which lose 14CO2 at pH values below 5. The most abundant of these metabolites was isolated as its stable methyl ester. The structure of a 13-ethyl-D-homogon-4-ene-3,17 alpha-dione-17 carboxylic acid is proposed for the metabolite which decomposes to 13-ethyl-D-homogon-4-ene-3,17 alpha-dione [D-homo-G]. The probable mechanism of the metabolite's formation is postulated. Quantitative differences in urinary metabolite patterns were observed following the administration of d- and dl-Ng. Ng is the major identified drug-related entity in plasma. The d-Ng concentrations in plasma measured by radioimmunoassay were in good agreement with those determined by fractionation and radiometry. The latter method indicated the presence of D-homo-G and a glucuronide of 3 alpha,5 beta-tetrahydro-Ng following the administration of d- and dl-Ng.


Pharmokinetics of 2'-deoxycoformycin in normal and L1210 leukemic mice. Following intravenous administration, 2'-deoxycoformycin (0.25 mg/kg) was rapidly distributed to tissues of both normal mice and mice bearing L1210 leukemia cells and readily eliminated, primarily by urinary excretion. Elimination of 2'-deoxycoformycin from plasma was biphasic, and half-lives for the alpha- and beta-phases of 10 and 33 min for normal mice and 7 and 40 min for L1210-bearing animals. The volume of distribution at steady state was approximately 20 ml, suggesting that the drug was distributed in the total body water for both groups of mice. The kidney, liver, small intestine, spleen, thymus, and L1210 tumor had tissue/plasma ratios greater than or equal to 1 at 15 min after dosing. In both groups, greater than 90% of the dose of 2'-deoxycoformycin was recovered in the urine within 3 hr. As determined by bioautography of urine samples, no detectable metabolism occurred. The presence of the L1210 tumor caused changes in the tissue distribution of 2'-deoxycoformycin. At later time periods, tissues from tumor-bearing mice contained significantly higher levels of this drug when compared to normal mice. However, the tumor was without significant effect on blood levels or urinary excretion of 2'-deoxycoformycin.


Studies on disposition and metabolism of tolmetin, a new anti-inflammatory agent, in rats and mice. I. Absorption, distribution, and excrection of [14C]tolmetin radioactivity. [14C]Tolmetin was rapidly and almost completely absorbed in both rats and mice. The major portion of the drug was shown to be absorbed from the upper part of the duodenum, and a small portion from the stomach. Tissue levels of radioactivity comparable to blood levels were found only in liver and kidney, and other tissue levels were lower than those in blood, possibly because of the considerable plasma protein binding of the drug. Radioactivity disappeared from most tissues at rates similar to that from blood, and no appreciable radioactivity was found in rat and mouse tissues 24 hr after dosing. Correspondingly, radioactivity was excreted mostly in urine within this time period. Mouse fetuses contained significantly less radioactivity than did maternal tissues in autoradiography. No significant differences were found in absorption, distribution, and excretion of radioactivity when single or five consecutive daily doses of [14C]tolmetin were administered to rats.


Studies on disposition and metabolism of tolmetin, a new anti-inflammatory agent, in rats and mice. II. Urinary metabolites. A new urinary metabolite of tolmetin was found in rat urine and identified as the hydroxymethyl metabolite (tolmetin-OH), an intermediate in the formation of the known carboxy metabolite (tolmetin-COOH). In rats of two strains, the following percentages of the urinary reactivity of [14Ia1tolmetin were found in 24 hr: unchanged tolmetin-COOH (58--60%), tolmetin-OH (18--24 %), and its conjugate 6--14%. Mouse urine contained the unchanged drug (about 20%), its conjugate and tolmetin-COOH (60%). Similarly to mouse urine, human urine contained negligible amounts of tolmetin-OH.


The absorption, distribution and excretion of photomirex in the rat. The absorption, distribution, and excretion of photomirex were investigated in the rat. Photomirex was absorbed slowly after oral administration, appeared in the blood at 1.5 hr, and reached the peak concentration 4 hr after dosing. Elimination from the blood was studied in rats receiving single intravenous doses; the semilog-arithmic decay curve was found to be triphasic. The highest concentrations were present in the rat, liver, and skin. Approximately 38--42% of the orally dosed photomirex was excreted in the feces in the first 3 days and 51--55% was eliminated in 28 days. Only trace amounts of photomirex were found in the urine (less than 0.09% of the total dose in 24 hr). Photomirex constituted about 95% of the total radioactivity found in the tissues and feces. No metabolite was detected in the radioactive material extracted from tissues or feces.


Possible molecular mechanism of mirex-induced hepatobiliary dysfunction. Male Sprague-Dawley rats were treated with mirex, po, at 0, 5, 10, and 50 mg/kg/day in 0.4 ml of corn oil for 3 days. Forty-eight hours after the last treatment, the biliary excretion of exogenously provided polar metabolites of 14C-imipramine was suppressed at all levels of mirex in a dose-dependent manner. Biliary excretion of phenolphthalein glucuronide was suppressed at high doses of mirex. These effects of impaired biliary excretion were accompanied by increased bile flow. Persistence of the mirex-induced biliary excretory dysfunction toward otherwise readily excretable, preformed metabolites suggests aberration of transport of these substances from the liver to bile. Whereas mitochondrial Mg++-ATPase and microsomal Na+-K+-ATPase activities were both inhibited by exposure to mirex in a dose-dependent manner, the latter activity was consistently inhibited to a higher degree. These results are suggestive of mirex-induced interference with energy production and utilization in the manifestation of hepatobiliary dysfunction.


Diastereoisomeric glucuronides of oxazepam. Isolation and stereoselective enzymic hydrolysis. Oxazepam glucuronide isolated from swine urine by previously published methods was separated into its diastereoisomers by ion-exchange chromatography on a preparative scale. Quantitative high-performance liquid chromatography was used to monitor the separation. The two isomers were obtained in analytically pure form and then characterized by elemental analysis, oxazepam content, mass spectrometry, ultraviolet spectroscopy, optical rotation and optical rotatory dispersion-circular dichroism. The latter permitted the assignment of the dextrorotatory and the levorotatory isomers to the (S)- and (R)- configurations, respectively. Rates of enzymic hydrolysis depend on the configuration of the substrate as well as on the enzyme preparation used. Rate of cleavage was highest with the (S)-(+)-glucuronide and beta-glucuronidase from Escherichia coli. This enzyme possesses the highest degree of stereoselectivity; it hydrolyzes the (S)-(+)-isomer more than 400 times faster than the (R)-(-)-form. Bovine liver glucuronidase is less stereoselective, whereas glucuronidase preparations of molluscan origin exhibit little stereoselectivity. The ready hydrolysis of one of the glucuronides by an enzyme from an intestinal microorganism may play a role in the enterohepatic circulation of oxazepam.


Uptake and excretion of benzo[a]pyrene and its metabolites by the rat pancreas. Following intravenous administration of [3H]benzo[a]pyrene ([3H]BP) to rats, uptake of radioactivity by the pancreas, per g of tissue, was approximately 16% of that of the liver. At 5 min following administration, unmetabolized BP in the pancreas, liver, and blood constituted 79, 50, and 49% of total BP uptake, respectively. The total uptake and unmetabolized BP in these tissues declined in a biphasic manner over the 2-hr observation period, during which only 0.03% of the total administered dose was excreted in pancreatic juice, as compared to 39% in bile; all radioactivity in pancreatic juice and bile was due to polar BP metabolites, including 3-hydroxy-BP. Pretreatment of rats with methylcholanthrene induced a significant increase in biliary, but not pancreatic, excretion of radioactivity. Administration of secretagogues caused a 2-fold increase in pancreatic, but not biliary, radioactivity.


Benzo[a]pyrene metabolism by hepatic and extrahepatic tissues in streptozotocin-diabetic rats. The metabolism of benzo[a]pyrene (BP) by microsomes from hepatic and extrahepatic tissues of female diabetic rats was investigated. Diabetes was produced by the administration of streptozotocin, 60 mg/kg iv, and BP metabolism was studied 7 or 10 days later. BP metabolism was increased in hepatic microsomes by 75% in diabetic animals. Cytochrome P-450 levels were similarly increased. BP mono-oxygenase activity was tripled in intestinal microsomes of diabetic rats, and returned to control values on insulin treatment. The BP mono-oxygenase activity in lung microsomes from diabetic rats decreased by 40%, and was increased to control levels after insulin treatment. No significant changes in BP metabolism were observed in the kidney and adrenal tissues of diabetic animals.


Pharmacokinetis of alpha- and beta-isomers of racemic endosulfan following intravenous administration in rabbits. The pharmacokinetics of the alpha- and beta-isomers of endosulfan in rabbits was investigated following intravenous injection. Endosulfan (2 mg/kg) was given as a mixture of the two isomers in the ratio 70:30. The plasma concentration-time data for alpha-endosulfan was best fitted to the three-compartment model with a terminal slope half-life of 235 +/- 168 (SD; N = 6) hr. The data for beta-endosulfan was adequately described by the two-compartment model, the corresponding half-life was 5.97 +/- 2.41 hr. The total distribution volumes during the terminal slopes were, however, similar for alpha- and beta-endosulfan (675 +/- 246 and 565 +/- 126 ml/kg, respectively). Consequently, the plasma clearance was considerably lower for alpha-endosulfan (2.70 +/- 1.3 ml/hr/kg) than for beta-endosulfan (70.1 +/- 18.6 ml/hr/kg). The alpha-isomer had a higher fraction unchanged in the urine (37% of dose) than did the beta-isomer (11%) and a slightly higher fraction unchanged in feces (2.7% and 0.4%, respectively) at 5 days. Thus, the two isomers of endosulfan showed pronounced differences in their pharmacokinetic profile. These dissimilarities may partly explain reported differences in toxicity between the alpha- and beta-isomer.


Maturational changes in adrenal xenobiotic metabolism in male and female guinea pigs. In young (25-day-old) guinea pigs, adrenal and hepatic benzo[a]pyrene (BP) hydroxylase activities were similar but the rates of ethylmorphine (EM) demethylation were greater in adrenals than liver. Between 25 and 50 days of age no sex differences in adrenal or hepatic enzyme activities were demonstrable. The rates of adrenal BP and EM metabolism increased with age in guinea pigs of both sexes; activities reached significantly higher levels in males than females. In contrast, hepatic metabolism of BP and EM declined with maturation and activities were similar in males and females at all ages. Neither microsomal cytochrome P-450 concentrations no NADPH-cytochrome c reductase activities correlated with the maturational changes or sex differences in xenobiotic metabolism. Adrenal microsomal steroid 21-hydroxylase activity did not change significantly with aging and was not sex-dependent. The results indicate that opposite changes occur in adrenal and hepatic xenobiotic metabolism as a function of aging, resulting in substantially greater adrenal than hepatic activity in sexually mature animals. The data also suggest that adrenal microsomal drug and steroid metabolism are independently regulated.


Neuropsychological correlates of anticonvulsants and epileptiform discharges in adult epileptics. Neuropsychological correlates of anticonvulsants and of EEG epileptiform discharges were examined through the administration of neuropsychological measures to groups of adult epileptics. Among the anticonvulsants, performances with high and low serum phenytoin levels were compared and performances with sulthiame vs. phenytoin and carbamazepine vs. phenytoin were evaluated. Various drug effects from these studies were noted and there was some suggestion that the neuropsychological impacts of specific anticonvulsants may be selective rather than general. The neuropsychological correlates of the topographic distribution and average rate of occurrence of discharges were considered. Striking neuropsychological correlates were found with the poorest performances in connection with discharges which were generalized and those which were at a rate greater than 1/min. The importance of using a broad range of neuropsychological measures was stressed.


Effect of neurotransmitters on the in vitro release of immunoreactive thyrotropin-releasing hormone from rat mediobasal hypothalamus. The in vitro release of TRH from hypothalamic fragments or purified nerve endings (synaptosomes) has been evaluated after incubation for 10 min in the presence of various concentrations of K+ or neurotransmitters. Release of the hormone from fragments but not from synaptosomes was enhanced in the presence of 56 mM K+ in a Ca++ -dependent manner. Neurotransmitter effects were thus tested on the fragments. Addition of histamine (10 (-7)-10(-5) M) induced a significant increase over the basal release of TRH. A comparable effect was obtained with dimaprit (10(-5) M), a highly specific agonist of histamine H2 receptors; conversely, the response to histamine was blocked by the addition of a H2 (metiamide; 10(-6) M) but not of a H1 (mepyramine; 10(-6) M) antagonist to the incubation medium. Dopamine (10(-7) M) slightly inhibited the release of TRH, but antagonists of dopamine receptors (10(-7)-10(-6) M fluphenazine or 10(-6) M alpha-flupentixol) exhibited an inhibitory effect by themselves, so that specific receptors involved in mediating dopamine actions could not be further characterized. In contrast, noradrenalin, serotonin gamma-aminobutyric acid and acetylcholine (tested at concentration of 10(-7) M) did not alter the basal release of the tripeptide.


Nutrition and somatomedin. V. Action and measurement of somatomedin inhibitor(s) in serum from diabetic rats. Serum from normal rats stimulates growth cartilage in vitro; this stimulation is attributed to somatomedin activity. In contrast, serum from diabetic rats may produce dose-response lines with negative slopes and, in combination studies, suppress the stimulatory activity of serum from normal rats; this is attributed to somatomedin inhibitory factor(s). Somatomedin inhibitory activity in serum from diabetic rats cannot be attributed to recognized catabolic factors, such as glucocorticoids or free fatty acids. The inhibitory activity is resistant to 100 C heat at neutral pH but is partially removed by 100 C heat at pH 5.5. Somatomedin inhibitory activity can be estimated as the ability to decrease the stimulation of rat cartilage incubated for 2 days with serum from normal rats. With this method, serum from diabetic rats provides linear inhibition of both sulfate and thymidine uptake. This procedure is simple, reproducible, and allows detection of inhibitory activity in as little as 5 microliter whole serum. It allows identification of individual samples enriched in inhibitory activity and should be useful in further studies of somatomedin inhibitory factor(s).


ACTH release in pituitary cell cultures. Effect of neurogenic peptides and neurotransmitter substances on ACTH release induced by hypothalamic corticotropin releasing factor (CRF). The effects of various neurogenic peptides and neurotransmitter substances on the release of ACTH induced by hypothalamic corticotropin releasing factor (HY-CRF) were investigated using monolayer cultured anterior pituitary cells. Test substances were given in combination with 0.05-0.1 hypothalamic extract (HE)/ml, because HE evoked a significant ACTH release and a linear dose response relationship was demonstrated sequentially between 0.0165 HE/ml and 0.5 HE/ml. Relative high doses of lysine-vasopressin showed a slight additive effect on the release of ACTH induced by 0.1 HE/ml. Leu-enkephalin, dopamine, prostaglandin E1 and E2 slightly reduced the release of ACTH induced by HY-CRF, but the inhibitory effect of these substances were not dose-related. Other tested substances including luteinizing hormone releasing hormone, thyrotropin releasing hormone, somatostatin, melanocyte stimulating hormone release inhibiting factor, beta-endorphin, neurotensin, substance P, vasoactive intestinal polypeptide, angiotensin II, norepinephrine, serotonin, acetylcholine, histamine and gamma-amino butyric acid showed neither agonistic nor antagonistic effect on the release of ACTH induced by HY-CRF. These results indicate that the release of ACTH is controlled specifically by HY-CRF and corticosterone, and modified slightly by some other substances such as vasopressin and prostaglandins, and that the effect of most other neurogenic peptides and neurotransmitter substances is negligible or non-physiological at the pituitary level.


Immunoreactive somatostatin in the hypothalamus and other regions of the rat brain: effects of insulin, glucose, alpha- or beta-blocker and L-dopa. Effects of various hormonal and pharmacological manipulations on somatostatin distribution were investigated to elucidate the physiological significance of somatostatin in the hypothalamus and the other regions of the rat brain. Immunoreactive somatostatin (IRS) was measured by radioimmunoassay newly developed. Insulin induced an increase of hypothalamic IRS and a decrease of plasma RGH, while glucose administration resulted in the opposite responses, which were not significant. Insulin also increased IRS in the thalamus and the brain stem. The insulin-induced increase of hypothalamic IRS was reduced by hyperglycemia. Glucagon reduced IRS initially and then increased it with an elevation plasma RGH. L-dopa did not affect hypothalamic IRS, although it decreased plasma RPRL. Phentolamine slightly increased plasma RGH and decreased IRS in most regions of the rat brain, while propranolol increased IRS in these regions. Pretreatment with propranolol significantly increased plasma RGH 120 min after insulin administration, and hypothalamic IRS decreased initially by pretreatment with propranolol, and then it increased significantly. When pretreated with propranolol, glucagon markedly increased plasma RGH and decreased IRS significantly. From these findings it is concluded that hypothalamic IRS may participate in the hormonal regulatory system in correlation to plasma RGH, as observed in studies on plasma GH and hypothalamic IRS following insulin, glucose, propranolol or phentolamine administration, but IRS in other regions of the brain may have some other actions as a neurotransmitter or a modulator, because of no significant correlation between plasma GH or PRL and IRS in these regions following various stimuli. In addition, glucose homeostasis and adrenergic mechanism may be important factors in regulating IRS in the rat brain.


Perinatal evolution and hormonal control of adrenal tyrosine hydroxylase activity in the rat. The evolution of adrenal tyrosine hydroxylase activity has been measured in the rat fetus from 18 1/2 days of gestation until 24 h after birth. This activity increases gradually in the fetal adrenals with a sudden and transient increase between 0 and 6 h postpartum. It is suggested that a nervous mechanism related to the stress of birth is responsible for this increase. Fetal decapitation reduces adrenal tyrosine hydroxylase activity at term. This reduction can be partially prevented by administering adrenocorticotropic hormone (ACTH) to the decapitated fetus; cortisol administration has no effect. The results indicate that ACTH has a direct action on adrenal tyrosine hydroxylase in the fetus as it does in the adult.


Aminomalonic acid and its congeners as potential in vivo inhibitors of L-asparagine synthetase. Aminomalonic acid is a strong in vitro inhibitor of L-asparagine synthetase from Leukemia 5178Y/AR and from mouse pancreas; the agent is formally competitive with L-aspartic acid (Ki = 0.0023 M and 0.0015 M for the tumoral and pancreatic enzymes, respectively). Since aminomalonic acid is unstable and inert in vivo as an inhibitor of L-asparagine synthetase, attempts were made to deliver it to the site of its intended action via precursors: the diamide (2-aminomalonamide), the diester (diethylaminomalonate), and the keto acid (ketomalonic acid). Each of these putative 'pro drugs' was shown to be susceptible to metabolism to aminomalonate by mammalian and bacterial enzymes, in vitro. In vivo, aminomalonamide failed to inhibit tumoral L-asparagine synthetase at any time period up to 24 h after its oral or intraperitoneal administration. The diester and keto acid were similarly inactive. However, with specialized techniques it was possible to demonstrate that the diamide significantly inhibited the amidation and/or incorporation of L-aspartic acid into the L-asparaginyl residues of protein. Chemical manipulations of aminomalonic acid aimed at introducing irreversibly reacting functions are warranted.


Yeast argininosuccinate synthetase. Purification; structural and kinetic properties. Yeast argininosuccinate synthetase has been purified to homogeneity. The enzyme was found to have a molecular weight of 228,000 as determined by gel sieving. It is composed of identical subunits of Mr 49,000 as shown by gel electrophoresis. The quaternary structure as determined by cross-linking of the subunits with glutaraldehyde, followed by gel electrophoresis with dodecylsulfate, is tetrameric. The saturation functions by citrulline and aspartate are hyperbolic; with MgATP as the variable substrate a sigmoid character, dependent on the concentration of citrulline, aspartate, argininosuccinate and arginine, was observed. The positive cooperativity is reduced by increasing  concentrations of citrulline and aspartate; it is increased by argininosuccinate and arginine. Kinetic analysis provided evidence for a random addition of substrates. Initial velocity studies as well as product and dead-end inhibition studies comply with a rapid-equilibrium random model, except for the interconversion of the central quaternary complexes; the different kinetic constants  have been established on the basis. Yeast argininosuccinate synthetase has a double metabolic function: anabolic in the biosynthesis of arginine, catabolic as the first enzyme of citrulline utilization as nitrogen source. The kinetic properties of the enzyme point to a physiologically well-adjusted activity for both roles and to an economic and efficient utilization of ATP.


The binding of 1-anilino-8-naphthalene sulfonate to the hemocyanin of Octopus vulgaris. The binding of 1-anilino-8-naphthalene sulfonate (ansyl) to native and copper-free hemocyanin of Octopus vulgaris has been studied in different conditions by measuring the fluorescence properties of the probe in the presence of hemocyanin. Native hemocyanin, either in the oxygenated or in the deoxygenated state, does not bind ansyl. The binding of ansyl with apohemocyanin induces a strong increase (from 0.004 to 0.6 -- 0.7) of the quantum yield and a blue shift from 520 nm to 460 nm of the emission maximum indicating the presence of ansyl binding sites in the protein. Experimental evidence is reported that the binding occurs at the copper-binding site of the protein. The dissociation constants of the ansyl-hemocyanin complexes are equal to about 10(-4) M, i.e. they are of the same order of those obtained with other proteins. The number of binding sites (n) of apohemocyanin for ansyl depends on the conformational state of the protein and ranges from 0.15 -- 0.80 mol/mol protein (Mr 50,000), depending on pH, ionic strength, and urea concentration. A negative interaction between the ansyl binding sites has been suggested.


Kinetic analysis of the interaction of the phosphatidylcholine exchange protein with unilamellar vesicels and multilamellar liposomes. The mode of action of the phosphatidylcholine exchange protein from bovine liver has been studied by using unilamellar vesicles and multilamellar liposomes both of which membranes contain phosphatidylcholine and phosphatidic acid. The protein-mediated exchange of phosphatidylcholine between vesicles and liposomes fit the kinetic model presented in a previous study [V.D. Besselaar et al. (1975) Biochemistry, 1j, 1852]. Kinetic analysis of the rates of exchange indicate that the apparent dissociation constant of the exchange protein-vesicle complex decreases with an increasing phosphatidic acid content of the vesicles. Both vesicles and liposomes of 10 mol% phosphatidic acid show the same dissociation constant; on the other hand, both the formation and the disruption of the protein-membrane complex was 50--100-times higher for the vesicles than for the liposomes. This implies that the exchange protein can discriminate between vesicles and liposomes. Equilibrium gel chromatography of a column of Bio Gel A-5m confirmed that the exchange protein binds more strongly to vesicles of an increased phosphatidic acid content. The protein-mediated exchange of phosphatidylcholine in the vesicle-liposome system demonstrates a pH optimum at 4.0 to 5.5. The kinetic analysis at pH 5.0 as compared to pH 7.4 indicates that the enhanced exchange at pH 5.0 can solely be accounted for by altered interaction of the exchange protein with the liposomes.


Quaternary structure of higher plant glyceraldehyde-3-phosphate dehydrogenases. 1. NAD(P)+-induced changes in the aggregational state of prepurified NADP-linked glyceraldehyde-3-phosphate dehydrogenase (EC 1.2.1.13) were used to isolate the enzyme from Spinacia oleracea, Pisum sativaum and Hordeum vulgare. Each of the three plant species contains two separate isoenzymes. Isoenzyme 1 (fast moving during conventional electrophoresis) precipitates with the ammonium sulfate fraction 55--70% saturation. It shows two separate subunits in dodecylsulfate gels, which are probably arranged as A2B2 in the native enzyme molecule. Isoenzyme 2 (slow moving during conventional electrophoresis) precipitates with the ammonium sulfate fraction 70--95%. It contains a sigle subunit of the same Mr as subunit A in isoenzyme 1 and is apparently a tetramer (A4). The molecular weights of subunits A/B for spinach, peas and barley were determined as 38,000/40,000, 38,000/42,000 and 36,000/39,000 respectively. 2. The NAD-specific glyceraldehyde-3-phosphate dehydrogenase (EC 1.2.1.12) was purified from Spinacia oleracea and Pisum sativum by affinity chromatography on blue Sepharose CL-6B. The enzyme from both plant species is shown to be a tetramer of subunits with Mr 39,000. 3. The present findings contrast with heterogeneous results obtained previously by other authors. These results suggested that there are considerable interspecific differences in the quaternary structure of glyceraldehyde-3-phosphate dehydrogenases from higher plants.


Clonal dominance of low-affinity antibodies in rabbit hyperimmune anti-streptococcal group A-variant polysaccharide antisera. Intraveneous hyperimmunization of selectively bred rabbits with streptococcal group A-variant vaccines elicits antibody responses of restricted heterogeneity at high antibody levels. In these antisera, IgG with dissociation constants Kd = 10(-6) M constitutes 90% and IgG with Kp = 10(-9) M accounts for only 10% of the group A-variant polysaccharide-specific antibodies. The low affinity antibody fraction represents the dominant clonotypes. Preparative isoelectric focusing in granulated (Ultrodex G-75) gels was used to successfully purify single-band material belonging to dominant spectrotypes. Affinity studies with these antibody fractions with the highest reported degree of purity yielded Kd = 10(-6) M values, thus confirming that clonal dominance is exclusively associated with low-affinity antibodies. Since it is known from previous work (M. Cramer and D. G. Braun, Scand. J. Immunol. 1975. 4:63) and from the rabbit antisera used here that clonal dominance of this sort is long-lived, this work fails to support the argument of immune maturation. The data more logically relate to antibodies that emerge with different subspecificities -- recognized in the antigen as a function of time in immunization procedures -- rather than to an inherent property of the immune system.


Differential enhancement of locomotor activity by dopamine agonists following chronic neuroleptic treatment: an animal model of tardive dyskinesia. Animals were administered clozapine or haloperidol for 22 days. Following treatment they were challenged with an apomorphine ester or lergotrile. Only haloperidol-treated animals exhibited significantly enhanced responses to apomorphine ester whereas administration of lergotrile potentiated locomotor activity in both treated groups. The results suggest that the use of different dopaminergic agonists may help to dissociate receptor supersensitivity arising from the antipsychotic actions of neuroleptics from that leading to the development of undesirable side effects.


Cardiac arrhythmias produced by bretylium in cats anesthetized with halothane. Bretylium given by rapid intravenous injection into cats anesthetized solely with halothane precipitates severe and unusually long-lasting ventricular arrhythmias. They are observed 20-70 sec following doses of bretylium ranging from 0.8 mg/kg to 15 mg/kg and last for 60 sec to just over half an hour. Bretylium also manifests signs of sympathetic involvement since it raises blood pressure and heart rate just prior to the onset of arrhythmias. Propranolol pretreatment prevents bretylium arrhythmias. From these results and from those of other investigations, it is concluded that bretylium arrhythmias are mediated through the release of endogenous noradrenaline stored in adrenergic neurons of the heart. These results call attention to the arrhythmogenic potential of bretylium in the presence of halothane anesthesia.


[Effect of tranquilizers on impulse conduction in the afferent pathways of visceral nerves]. Experiments on pyrolaxon-immobilized cats evidence that diazepam produces depression of evoked potentials in the specific, nonspecific and associative brain structures upon an electric stimulation of the visceral and somatic nerves, and also with accoustic and photostimulation; Meprotan (meprobamate) in doses of 40-100 mg/kg neither changes nor increases, and in doses of 100-150 mg/kg, reduces the amplitude of evoked potentials and at the sme time forces down the arterial pressure. Amizyl (benactyzine) inhibits the potentials evoked by stimulation of the vagus. The amplitude of responses arising on stimulation of the inferior cardiac, celiac and sciatic nerves, and also with acoustic and photostimulation neither changes nor increases.


[Effect of the adrenomimetics noradrenaline and mezaton on gastric secretion clinically and experimentally]. Chronic tests on dogs with fistulas in the fundal portion of the stomach and polychlorvinyl catheters implanted in the jugular vein brought evidence that infusion of norepinephrine or mesaton in a dose of 0.003-0.004 mg/kg for 1 1/2 and more hours inhibited the gastric secretion stimulated with carbocholine and histamine. In patients with duodenal and gastric localization of the ulcer an intramuscular injection of mesaton (10 mg) had no essential effect on the main characteristics of the basal gastric secretion.


Loss of adaptive mechanisms during aging. Factors contributing to modifications in the capability for enzyme adaptation as an expression of aging are reviewed. Specific examples of altered enzyme adaptations during aging include the responses of hepatic glucokinase activity to glucose and hepatic tyrosine aminotransferase activity to starvation in Sprague-Dawley rats. These impaired enzyme adaptations apparently are not the consequence of alterations in hepatic function during aging. Instead, they reflect disturbances in extrahepatic hormonal regulatory mechanisms. Specific examples include modifications in the control of circulating levels of insulin glucagon, corticosteroids, and thyroid hormones. Age-dependent changes in the regulation of circulating levels of insulin probably originate within the impaired ability of pancreatic islets of Langerhans to secrete the hormone in response to glucose. The rationale for exploiting this experimental approach as a means to understand biological aging is discussed.


Diet as a modulator of aging and longevity. The interrelationships between diet and life span are reviewed, with emphasis on results obtained in studies with experimental animals. Ad libitum feeding throughout life does not promote maximal survival and food restriction increases mean life span. The possible importance of total energy, carbohydrate, and protein intake are considered, as well as the influence of mode of feeding. A number of mechanisms that might explain how nutrition affects life span are discussed, including disease pattern, free radicals, neuroendocrine system, and protein turnover. The significance of these findings in relation to the health and life span of human subjects is not known and deserves further exploration. However, they emphasize the importance of diet as a tool to help explore the biochemical and physiological basis for aging in animal models.


[Structuro-metabolic mechanisms for integrating several endocrine organs]. Mechanisms of integration in the neuroendocrine system in the regimens of physiological rhythm (oestral cycle) and of isolated effect upon one link of the system (metapyrone administration) were studied with the aid of qualitative histoenzymological analysis of adenohypohysis and adrenal cortex, estimating the comoplex reorganization of various structural components of adenohypophysis and adrenal cortex in response to specific depression of glycocorticoid synthesis. The role of the so called unspecific reorganization in the maintenance of functional response to isolated effects upon certain endocrine functions is discussed along with the necessity of further studies on the principles of interaction in the endocrine system using morphofunctional analysis.


Assessment of uteroplacental hemodynamics in complicated pregnancy. Examination of the uteroplacental hemodynamics was performed on 109 occasions in women admitted to the hospital in the third trimester because of various complications of pregnancy. The radioactive tracer 113m In was injected intravenously and the build-up and equilibrium times were measured over the placenta, myometrium and heart. The placental build-up times were most informative, with prolonged values being recorded in about one quarter of these cases. When those extending beyond three minutes were further studied, they were usually found to be associated with severe complications of pregnancy. This did not obtain in cases with shorter placental build-up times.


Vaginal adenocarcinoma in a gravida with prenatal DES exposure. The article presents a case of a young pregnant woman with vaginal carcinoma who had been exposed to diethylstilbestrol (DES) in utero. Surgical excision of the lesion was attempted but failed. Interstitial irradiation was then applied and proved successful. The patient's infant, as well as two subsequent children, were delivered by cesarean section after normal pregnancies. There was no evidence of metastatic disease or recurrence in 11 1/2 years following the initial diagnosis. Since 1965, a rising incidence of vaginal adenocarcinoma in women who were exposed to (DES) in utero has been reported. These women should be examined regularly after menarche for prompt evaluation and treatment of precancerous lesions such as adenosis, cervical erosion or transverse ridges. Since most of these patients are young, a conservative treatment is recommended. Extensive surgery and pelvic irradiation is indicated, however, in the cases of widespread disease.


Improved surveillance of maternal deaths. This study explains and verifies an apparent increase in the New Jersey resident maternal mortality rate from 1.7 per 10,000 live births by the state's traditional method to 3.1 per 10,000 live births by a new method of surveillance instituted in late 1974. In 1975, the maternal mortality rate by the traditional method was 1.5 per 10,000 and by the expanded method, 3.0 per 10,000. The traditional method compiled data from death certificates submitted to the State Vital Statistics Office. The expanded method found additional deaths by review of Annual Maternity Services Reports from hospitals and by close follow-up of individual reports of maternal deaths from medical examiners, physicians and hospitals.


Jaundice during pregnancy in Ibadan, Nigeria. The clinical features of hepatitis during pregnancy and the effect of this complication on the mother and the fetus were evaluated in 45 patients with jaundice who were treated at the University College Hospital, Ibadan, Nigeria, from July 1976 to January 1978. Viral hepatitis was the cause of jaundice in 23 of the 45 patients in this prospective study. Three of these patients had the fulminant type of jaundice which resulted in maternal deaths. The peak incidence of the disease occurred in the last trimester. Hepatitis had a deleterious effect on the outcome of pregnancy; the effect was directly related to the severity of the disease, especially when associated with pyrexia. It is postulated that, by lowering resistance to infection, malnutrition may play a significant role in the pathogenesis of hepatitis during pregnancy.


Postponement of preterm birth with salbutamol. Salbutamol was administered intravenously and orally to 58 patients who were admitted to the hospital because of premature labor. Pregnancy was postponed until at least 36 weeks' gestation in 34 of these patients. The success of this therapy was measured by a parameter of the prolongation index which was inversely related to the Bishop's score. This measurement was highest among patients in whom pregnancy was successfully prolonged.


Heat loss in Nigerian newborn infants in the delivery room. Fifty-three vigorous infants were randomly assigned to six different groups (A-F). The babies in groups A and F were not dried and were either exposed wet to room air or warmed under the radiant heater. The other groups of infants were quickly dried and exposed to room air (group B), wrapped with one sterile sheet (group C), wrapped with two towels (group D) or placed under the radiant heater (group E). The infants exposed to room air lost twice the amount of heat when compared with those insulated with two towels. The amount of heat loss by evaporation could not be demonstrated. The role of high relative humidity as an important determinant of the degree of heat loss by evaporation is stressed.


Progestogen treatment of uterotubal (cornual) block. High dose progestogen was used to treat 112 cases of primary sterility due to uterotubal block, after tuberculosis and cornual myomata were excluded as causes of the condition. The duration of sterility ranged from three to 18 years. Patients were treated for six or 12 months, depending on their responses to the drug. The results of treatment were very favorable; bilateral and unilateral patency was achieved in 74.0% and 11.6% of the patients, respectively. Pregnancy occurred in 42.8% of all cases studied.


The value of simple tests in the detection of human ovulation. Cervical mucus viscosity (CMV) and fern test (FT), leukocyte alkaline phosphatase (LAP) activity, basal body temperature (BBT) and serum luteinizing hormone (LH) levels were determined during 31 normal menstrual cycles of 29 volunteers. The day of the serum LH surge was taken as a reference point in evaluating the reliability and sensitivity in predicting ovulation of the other tests studied. Serum LH surge was accompanied by a sudden decrease in CMV, an increase in LAP activity, a gradual increase in FT and biphasic changes of BBT. In about 95% of cycles studied, the lowest values of CMV and peak values of LAP activity appeared on the day of the serum LH surge or one day before or one day after. The lowest point of the BBT coincided with the LH surge in only 26% of cycles. In 53% of cycles, the span was greater than one day before or after the LH peak. The FT corresponded to the LH surge in only 33% of the cycles, while in an additional 33% the preovulatory FT response occurred more than one day before or after the LH surge. The results indicate that CMV and LAP tests are rapid, simple and reliable for monitoring follicular maturation and the timing of ovulation when carried out daily, and may be of value in monitoring treatment during the induction of ovulation.


The place of sling operations in treating genital prolapse in young women. A review of 260 cases of genital prolapse in women less than 35 years of age is presented. Thirty-six percent of the women were less than 25 years old, and 73.5% were less than 30 years. Until 1965, a total of 85 patients had undergone either Manchester operations or simple colporrhaphies after a conventional method of treatment. Since then, a different surgical approach was elected, and patients were divided into four groups according to the severity of their conditions and the types of operation required. The abdominal sling operation was performed on 110 patients, and the vaginal sling operation was performed on 18 women. Other patients had Manchester operations or simple colporrhaphies,


A program of IUD insertions by paraprofessionals and physicians in the Philippines. A program of IUD insertions by paramedics and physicians was undertaken at the José Fabella Memorial Hospital. Both Lippes C and D were inserted in the postpartum and interval periods. Results show that paramedics can safely and effectively perform IUD insertions, although there are indications of a need to periodically monitor, and perhaps retrain, personnel, be they paramedic or physician, in the techniques of IUD insertion.


Continuation of abdominal pregnancy complicated by preeclampsia three weeks after birth of an intrauterine twin. A case of heterotopic pregnancy in a 22-year-old multigravida is presented. The extrauterine baby was delivered alive three weeks after the intrauterine pregnancy had ended at term in spite of an associated preeclampsia. The inhibition of lactation resulting from the continuation of the extrauterine pregnancy resulted in marasmus for the first baby. The implications and especially the etiology of preeclampsia occurring in extrauterine pregnancy are discussed.


A new instrument for the management of shoulder dystocia. Shoulder dystocia is a serious obstetric complication and remains an enigma to most obstetricians. Because of its rarity (1:10 000), improvements in management can hardly be gained through the experience of a single individual. However, a new obstetric instrument (shoulder born) has been developed by the author that may prove to be of value in the management of shoulder dystocia by forming a channel which facilitates delivery of the anterior shoulder with minimal trauma.


Sarcoma botryoides in a Nigerian female infant. A case of sarcoma botryoides has been reported in a 10-month-old Nigerian female infant. The tumor has behaved true to form by its location and histologic appearance. The prognosis in this child is still guarded, as chemotherapy has been the only form of treatment. Although she has been under observation for one year now, there has been no local recurrence of the tumor.


Menarchal age in Nigerian schoolgirls: its relationship to their height, weight and menstrual profile. Interviews with 119 students in a girls' residential secondary school in Ondo, Nigeria, revealed that 105 of them had menstruated, their mean age at menarche being 13.85 years, their mean height 156.8 cm and their mean weight 51.13 kg. The duration of menstrual bleeding was 4.43 days, the heaviest occurring at 1.82 days. Dysmenorrhea was reported by 32%. There was no correlation between the weight/height ratio and the mean age of the study group who were menstruating and the 14 students who were not. However, the difference in mean weight and height of those who had and had not attained menarche was significant. It is suggested that certain levels of weight and height are critical to achievement of spontaneous menstruation.


The significance of sinusoidal fetal heart rate pattern during labor and its relation to fetal status and neonatal outcome. Twenty-seven cases of sinusoidal fetal heart rate were studied. This group had a mean scalp pH of 7.288, significantly lower (p less than 0.005) than that of the control group. The mean one-minute Apgar score was 7.148, significantly lower (p less than 0.001) than the control group's mean score. Almost half (48,15%) of the fetuses had a one-minute Apgar score of 7 or less. Every fetus was viable. Amplitude of the pattern was found to correlate with neonatal depression, the larger the amplitude, the more profound the depression. Over 96% of the fetuses had cord-related deceleration patterns, and nearly 63% had obvious cord complications. It is postulated that sinusoidal patterns are an umbilical cord-related phenomenon, resulting from an alternating hypovolemia and hypervolemia. Clinicians are urged to scrutinize carefully any cases of this pattern, and perform an immediate fetal scalp blood pH determination. If the pH determination obtained is less than 7.25, the authors suggest intervention and operative delivery.


Autologous transfusion in obstetrics and gynecology. Two cases are presented which illustrate the use of autologous blood transfusion for elective surgery in obstetrics and gynecology. The advantages and disadvantages are described and review of the pertinent literature over the past century is summarized.


One year's experience with the Ypsilon-Y IUD. In 1975, a two-year study designed to test the new Ypsilon IUD was initiated by the Family Planning Center (Department of Obstetrics and Gynecology, Medical University), Debrecen, Hungary. From November 1975 through September 1976, Ypsilon-Y intrauterine devices (IUDs) were inserted in 300 women who had not previously used IUDs. The control group consisted of 300 Lippes Loop D users, all of whom were also first-time IUD users. The selection was made by randomization. After one year, the relevant rates (pregnancy, expulsion, medical removals) for the study group were: 3.9, 10.4 and 7.8, respectively. The corresponding values for the Lippes Loop D group were: 2.8, 5.7 and 7.8 per 100 women. Although the pregnancy rate for the control population was lower, the difference was not statistically significant. The frequency of expulsion in the Ypsilon-Y users was higher than that of the Lippes Loop D acceptors, but the difference was not statistically significant at the 0.05 level. The medical removal rates were almost the same in both groups. The total number of bleeding, pain and dysmenorrheic complaints in the two groups were also compared and showed that the Ypsilon-Y users did not report complaints as often as did the women wearing the Lippes Loop D. The difference was statistically significant. The relevant termination rates of the Ypsilon-Y were higher than those for the Lippes Loop D; however, the lower frequency of complaints in the study group suggests that the shape of the Y may be more suitable for the uterine cavity than the Loop D.


Serum estrone, estradiol and estriol concentrations during oral hormone therapy after oophorectomy. Serum estrone, estradiol and estriol concentrations during estradiolvalerate-norgestrel therapy for women who have undergone oophorectomy were studied. The patients in one group received 1 mg of estradiolvalerate in the morning and 2 mg of estriolsuccinate in the evening. The estrone and estradiol concentrations of the first and fifth day were at roughly the same level and the treatment caused no estrogen cumulation. The estriol concentrations on the fifth day were distinctly higher than on the first, owing to the conversion of estrone and estradiol into estriol. The other group of women were placed on a regimen of 2 mg of estradiolvalerate plus 0.5 mg of norgestrel in the morning and 2 mg of estriolsuccinate in the evening. Here again, the estrone and estradiol concentrations on the first and fifth days were similar.


Peptide contraception: antifertility properties of LH-RH analogues. A prototype LH-RH antagonist dampened the proestrous gonadotropin surge and blocked ovulation but had no effect on pregnant animals. In contrast, LH-RH and two highly potent LH-RH agonists terminated pregnancy when administrated prior to or following implantation. This contragestational effect, as well as other antireproductive properties of the agonists, coupled with the reversibility of their effects, strongly suggest that peptides may provide a new basis for contraception.


Cytohormonal assessment of ovarian function following tubal ligation. One hundred fifty postligation and 54 random cases matched for age and parity were studied. Vaginal cytologic samples and endometrial histologic samples were used for cytohormonal assessment of ovarian function. There was no indication of ovarian insufficiency following tubal ligation. The menstrual cycles were ovulatory. Menstrual disturbances were seen in 40.6% of the cases following tubal ligation. Cytohormonal comparison of these cases with that of dysfunctional uterine bleeding cases (who did not undergo tubal ligation) showed either similar or high maturation value. This may be due either to psychological stimulation or to low-grade infection following tubal ligation. There was complete cytomorphologic correlation.


The effect of oral thyrotropin-releasing hormone on thyroid function and the composition of breast milk in puerperal women. To determine the effect of oral administration of thyrotropin-releasing hormone (TRH) on the thyroid function and on the composition of breast milk in the early puerperium, six lactating women were treated with a single dose of 40 mg of synthetic TRH and six women were treated with placebo. Serial serum samples taken before and between one and 25 hours after TRH administration were assayed with specific radioimmunoassays for thyrotropin (TSH), triiodothyronine (T3) and total thyroxine (T4). Milk samples were collected three times a day and their major fatty acids were determined by gas-liquid chromatography and were compared with those obtained from normal lactating women. A statistically significant TSH elevation was observed between one and six hours after TRH administration, with a peak value of 23.7 +/- 10.6 mU/liter at three hours. The T3 concentration rose between three and nine hours after TRH administration, with a peak of 6.3 +/- 1.2 nmole/liter at six hours. The T4 elevation was statistically significant between six and 12 hours after TRH administration. The fatty acid content of milk samples from women treated with TRH did not differ from the normal series. A single daily dose of oral TRH thus caused a temporary thyroid stimulation. It is doubtful whether this could lead to hyperthyroidism since the levels of thyroid hormones became normal within ten hours after TRH administration.


Cesarean section with regional anesthesia using an extendable epidural block. Epidural analgesia was used for 86 deliveries by cesarean section. The placement of a catheter in the epidural space allowed adjustment of the extent of the block so that supplementary analgesia was required in only six patients. Continuous fetal heart rate monitoring was of practical clinical value, especially in treating maternal hypotension. Symptomatic hypotension was avoided or corrected by the intravenous infusion of Hartmann's solution and by the use of a lateral tilt of the operating table. Eleven patients had a blood pressure of less than 100 mm Hg, and in three of these, there was an adverse effect on the fetal heart trace.


Bilateral tubal pregnancy in the presence of an IUD: a case report. Bilateral tubal pregnancy was confirmed by histologic examination in a 32-year-old multipara with an intrauterine contraceptive device (IUD) in situ. The patient had developed intraperitoneal bleeding and hypovolemic shock. Bilateral salpingectomy was performed and was followed by a rapid recovery.


Fibrinolytic activity of menstrual blood in normal and menorrhagic women and in women wearing the Lippes Loop and the Cu-T (200). Assessment was made of the fibrinolytic activity in menstrual and peripheral blood of 30 normally menstruating and 30 menorrhagic patients and of 30 women wearing Lippes Loops and 15 wearing CU-T (200)s. Assessment was performed by measuring the area of lysis on heated and unheated fibrin plates. Also, histochemical identification of fibrin fibrils in the menstrual endometrium was performed by Mallory's phosphotungstic acid hematoxylin method. Results in the normally menstruating group were compared to those of the menorrhagic women, and together these were compared with results in the groups of women wearing intrauterine devices. The fibrinolytic activity in menstrual blood was significantly increased in menorrhagic patients compared to that in normally menstruating patients, but no significant difference was detected in the plasma of either group. The histochemical study of the normally menstruating endometrium revealed dense intravascular and extravascular deposits of fibrin. Less dense intravascular fibrin deposits, but no extravascular ones, were present in the menorrhagic patients. The increase in the fibrinolytic activity of menstrual blood and the decrease in the density of fibrin deposits in the menstrual endometrium of the menorrhagic women were thus associated and were probably involved in the excessive menstrual loss. The fibrinolytic activity of menstrual blood in women wearing Lippes Loops was higher than that in women with Cu-T (200)s and was associated with decreased density of fibrin fibrils in the menstruating endometrium. This may explain the increased blood loss associated with the use of the Lippes Loop.


Medical termination of pregnancy: public opinion in an urban population. The influence of religion, education and socioeconomic status on opinion regarding medical termination of pregnancy were examined. A random sample of 514 married, urban women was selected. The study revealed that religion, education and economic status influenced the formation of opinion regarding pregnancy termination. The women gave many reasons for considering it beneficial. The most common reasons were that pregnancy termination offered increased opportunities for better education and nutrition. The limitation of family size and elimination of unwanted pregnancies were also noted as needs of the community.


The fetal alcohol syndrome: some maternal characteristics. The characteristics of eight mothers of ten infants born with typical features of the fetal alcohol syndrome (FAS) are presented. These chronic alcoholic  mothers have poor obstetric histories, tend to have poor or no prenatal care and may repeat pregnancies which result in infants with FAS. Family planning counseling appears unhelpful.


Gonadal dysgenesis variants in sisters: a hitherto undescribed combination. The term "gonadal dysgenesis" covers a wide spectrum. This case report concerns two sisters with secondary amenorrhea who underwent systematic investigations, including karyotype analysis, tests for serum gonadotropins and laparoscopic gonadal biopsy. The diagnosis in each revealed a combination hitherto underscribed.


Intrauterine fetal arrhythmia: atrial premature beats. A case of antepartum fetal arrhythmia is reported. The diagnosis of atrial premature beats was confirmed during labor by simultaneous recording of fetal heart rate and fetal electrocardiogram. The possibility of fetal distress during labor was excluded by fetal heart rate and acid-base monitoring. The difficulty of reaching a definitive antepartum diagnosis of the arrhythmia and its significance in relation to fetal well-being are discussed.


Clonidine in the treatment of menopausal symptoms. Thirty-seven women complaining of hot flushes, sweating and other menopausal symptoms were treated with clonidine. A double-blind crossover trial with placebo controls was undertaken. The clonidine dose was 2 X 0.025 mg/24 hours-0.075 mg/24 hours, increased if necessary at intervals of two weeks. The effect of clonidine did not differ significantly from placebo effect in the treatment of the symptoms. Side effects during clonidine management were slight and no difference was seen in their incidence compared with that in the patients treated with the placebo. A definitive placebo response was perceivable in the decreasing of symptoms.


Pseudocyesis in infertile patients.

Pseudocyesis in infertile patients. In the African population, pseudocyesis is not an uncommon gynecologic disorder. The high premium on childbearing, as well as the deep-rooted cultural belief that children are a "security of old age" and continuation of the family, exposes the infertile woman to constant stress. The social and psychological satisfaction of parenthood is very important in this culture; while, for some patients, perception of the economic implication of children enhances the desire to have children.


Falope ring application via culdoscopy.

Falope ring application via culdoscopy. This report describes a series of 122 women who were sterilized with Falope ring application via culdoscopy and demonstrates the feasibility of the procedure.


History of Mendelson's syndrome.

History of Mendelson's syndrome. The history of Mendelson's Syndrome is briefly covered and the current problem of the condition in regard to prevention, amelioration and treatment is discussed.


A fresh look at magnesium trisilicate.

A fresh look at magnesium trisilicate. Confusion exists about the correct way to use magnesium trisilicate as an antacid prior to inducing general anaesthesia in the pregnant woman. The effectiveness of two-hourly doses of antacid is discussed with special reference to the rate at which the stomach empties. Consequently, it is important to know whether the patient is in labour and if so the type of analgesic used. Some of the chemical characteristics of Mist. Mag. Trisil. B.P.C. are discussed. It is shown that it is capable of raising the pH of the stomach contents above 3.0 within two minutes in comparatively small doses. Clinically it is shown to be almost completely effective in a large series of patients. Inadequate mixing of the alkali with the stomach contents when it is given as an immediate pre-induction dose leads to a hazard of acid regurgitation when anaesthesia is induced in these patients.


An antacid comparison trial.

An antacid comparison trial. A trial is described in which patients going into labour were randomly allocated to treatment with either Andursil or Magnesium Trisilicate Co. Following delivery of the baby the stomach is emptied and the volume and pH are measured. Table 5 summarizes the results of 1106 patients. Andursil was found to be more palatable by patients than was Magnesium Trisilicate Co, but the incidence of nausea and vomiting was similar in the two groups.


Therapeutics in childhood asthma.

Therapeutics in childhood asthma. The epidemiology and pathogenesis of childhood asthma is discussed, as is the pharmacology of drugs currently used in its control and prevention. Attention is drawn to the importance of adequate parent/child education if the prescribed therapeutic agents are to be used effectively.