Quantum yield and image contrast of bacteriochlorophyll monolayers in photoelectron microscopy. The photoelectron quantum yield spectrum of bacteriochlorophyll aGg (Bchl a ) from Rhodospirillum rubrum was determined in order to evaluate the possibility of mapping photoreceptor distribution and organization in bacterial chromatophores. The quantum yield is on the order of 1 X 10(-3) electrons/incident photon at 180 nm and decreases to 2.5 X 10(-5) electrons/incident photon at 230 nm. Photoelectron micrographs confirm the high contrast predicted between monolayers of Bchl a against a lipid background (calcium arachidate). A significant contrast difference is found between the two monolayer orientations, demonstrating that photoelectron microscopy is a sensitive detector of asymmetry in Bch1 a monolayers.


Swimming speed distributions of bull spermatozoa as determined by quasi-elastic light scattering. 88 semen samples from 39 bulls have been investigated by the quasi-elastic light scattering technique. Normal, defective, and dead cells each yielded characteristic autocorrelation functions. The form of these functions indicates that the swimming speed distribution of normal cells is a gamma distribution with two degrees of freedom while that for defective or circular swimmers is a gamma distribution with one degree of freedom. The resulting analysis of the experimental autocorrelation functions yields the fraction of the sample that is normal, the fraction that is defective, and the average speed of each group. The average helical swimming speed of normal cells was found to be 384 micron/s, while the average trajectory speed of the circular swimmers was found to be 103 micron/s. The overall quality of the semen samples as determined by light scattering is compared to quality determination on the same samples by technicians from the artificial insemination industry.


The effects of calcium++ on bursting neurons. A modeling study. Many observed effects of ionized calcium on bursting pacemaker neurons may be accounted for by assuming that calcium has multiple effects on the membrane conductance mechanisms. Two models are proposed that represent extreme cases of a set of possible models for these multiple effects. Both models are a priori designed to account for directly observed phenomena, and both are found to be able to simulate a posteriori certain observed phenomena, including persistent inactivation, increasing spike width, and decreasing after-polarization. Experimental tests are proposed for the decision of validity between the set of models discussed and the null hypothesis, and for the decision of validity between the two models themselves. Extensions of the models are discussed. One of these extensions leads to a simulation of the behavior of the cell when placed in a calcium-free bathing medium.


Fluorescence changes in isolated broken chloroplasts and the involvement of the electrical double layer. We studied the effects of a variety of cations on chlorophyll fluorescence yield of broken chloroplasts prepared under carefully controlled ionic conditions. In the absence of light-induced electron transport and associated proton pumping, two types of cation-induced chlorophyll fluorescence changes could be distinguished in broken chloroplasts. These are termed "reversible" and "irreversible" fluorescence yield changes. Reversible fluorescence yield changes are characterized by antagonistic effects of monovalent and divalent cations and are prevented by the presence of 5 mM Mg2+ in the suspending media. Reversible-type fluorescence yield changes show little or no dependence on the structure, lipid solubility, or coordination number of the cation, but depend strictly on the net positive charge carried by the ion. It is proposed that these fluorescence changes are brought about through the interaction of monovalent or divalent cations with an electrical double layer at the interface of the outer surface of the thylakoid membrane and the surrounding aqueous solution. The results are interpreted in terms of the Gouy-Chapman theory of the diffuse double layer, indicating that the thylakoid outer surface bears an excess fixed negative charge density of about 2.5 muC/cm2, or approximately 1 negative charge per 640 A2 of membrane surface. Chlorophyll fluorescence quenching in isolated broken chloroplasts suspended in media containing 5 mM MgCl2 is also observed on addition of certain polyvalent cations to the medium. This type of cation-induced fluorescence change appears to be largely irreversible and may occur through specific binding of the cation to the thylakoid as a result of the high electrostatic attraction exerted by the negatively charged membrane surface.


On the relation between filament overlap and the number of calcium-binding sites on glycerinated muscle fibers. The formation of rigor complexes between the thick and thin filaments of glycerinated rabbit psoas muscle fibers causes the fibers to bind more calcium at any given level of free calcium. I studied the maximum amount of calcium bound as a function of filament overlap under rigor conditions. Fibers stretched to zero filament overlap (sarcomere length greater than 3.8 micron) bound exactly 75% as much calcium as fibers with maximum overlap. Between these extremes a linear relationship was found between maximum bound calcium and the length of the overlap zone. The results support the hypothesis that in the intact filament lattice one of the four calcium-binding sites of troponin depends for its existence on attachment between myosin and actin. In addition, the linear relation between maximum bound calcium and filament overlap is consistent with the assumption that the cooperative effect of rigor complex formation on calcium binding is limited to the binding site in the immediate vicinity of the rigor complex.


Differentiation between equilibrium and nonequilibrium kinetic systems by noise analysis. Methods for the differentiation between equilibrium and nonequilibrium steady-state kinetic mechanisms based on fluctuation and noise analysis are discussed. Specifically, the "sharpening" in the auto noise power spectrum is shown to be a useful indicator in identifying a nonequilibrium steady state.


The determination of amino acid pool sizes and turnover rates by gas chromatographic mass spectrometric analysis of stable isotope enrichment. Gas chromatography mass spectrometry has been used to determine the 15N enrichment of plasma glycine of rabbits at various times following the intravenous administration of 15N-glycine. These data were used to prepare isotope enrichment time decay curves for eleven individual animals. The slopes and intercepts of least squares lines that describe the decay curves were considerably more accurately than those reported in similar studies employing radioactive tracers. Individual glycine pool sizes (13.8-37.4 micronmoles per 100 g body wt), turnovers rates (2.66-3.36 pools h-1) and flux (50.4-99.7 micronmoles h-1 per 100 g body wt) were estimated from these parameters in a group of animals and compared with the literature values. These results demonstrate that low risk non-radioactive stable isotopes can be substituted for radioactive tracers in studies of human amino acid metabolism, with considerable saving in time and without loss in accuracy, when gas chromatography mass spectrometry is used to determine plasma amino acid and stable isotope enrichment.


Mass spectrometry of N-methylsulfonylureas. A re-examination. Some confusion has arisen in the literature regarding the electron impact mass spectrum of N-methyltolbutamide. The situation is complicated by the thermal lability of this compound which causes the formation of the corresponding N-methylsulfonamide. We present here spectral data at relatively low probe temperatures (and without an intervening gas chromatographic system) which we believe define the mass spectrum of N-methyltolbutamide more accurately than before. Similar data are presented for the analogous N-methylacetohexamide and show a rearrangement process for both substances not reported previously for this class of compounds.


Mass and infrared spectra of diaryl and aryl alkyl sulfate diesters. The synthesis and the infrared and mass spectra of diaryl and aryl alkyl sulfate diesters are described. The mass spectra of these two classes of compounds consistently showed an intense molecular ion and two or three additional intense, diagnostic ions. Their infrared spectra also gave information useful for characterizing and differentiating these two classes of compounds.


Determination of vincamine in plasma by selected ion monitoring. A sensitive and specific method for the determination of vincamine in plasma is described. The molecular ion (m/e 426) and the parent peak (m/e 367) of the TMS derivative are assayed simultaneously by selected ion monitoring. Sensitivity is 30 pg ml plasma. The suitability of the method for pharmacokinetic studies is assessed by measuring plasma level profiles in six volunteers receiving 20 mg of vincamine orally.


Mass spectrometry of uronic acid derivatives. XI--Structure elucidation by mass spectrometry of aldobiouronic and pseudoaldobiouronic acids and their beta-elimination products as per-o-methyl derivatives. Electron impact mass spectra of a series of aldobiouronic and pseudoaldobiouronic acid per-O-methyl derivatives and of the corresponding 4,5-unsaturated analogues, found normally among the products of methylation of uronic acid containing disaccharides as a result of methylation accompanying beta-elimination, have been studied. Using labelling experiments, metastable transition measurements and high resolution mass spectrometry, the fragmentation mechanisms of substances of this class have been deduced. Application of the information to the structure elucidation of this type of compound is discussed. It is concluded that from the mass spectra alone it is possible to determine the molecular weight, the cycle masses as well as the mode of linkage between the monomeric units. The appearance potentials of ions formed by cleavage of the glycosidic linkages have also been determined and the energetic differences encountered in the fission of the glycosidic linkages of various types of uronic acid containing oligosaccharides are discussed.


Structural biochemistry 15--mass spectrometry of permethylated nucleotides. Techniques have been summarized for the permethylation and mass spectral characterization of selected nucleotide monophosphates. The electron impact induced mass spectra are reproduced, and the fragmentation pathways observed are discussed in detail.


Identification of methotrexate and folic acid analogs by mass spectrometry. Methotrexate and folic acid analogs are polar molecules and attempts to obtain electron impact and chemical ionization mass spectra of these compounds by several laboratories have failed. We have found that methylation of this important class of compounds with diazomethane produces derivatives which are sufficiently volatile to allow their mass spectra to be recorded. The mass spectra of the methyl derivatives of five compounds, 4-amino-4-deoxy-N10-methylpteroylglutamic acid, 4-amimo-4-deoxypteroylglutamic acid, pteroylglutamic acid, 4-amino-4-deoxypteroic acid and N10-methylpteroylglutamic acid are presented, and the fragmentation pathways of these compounds discussed.


Chemical ionization mass spectrometry of the tumor promoter related 4aalpha-phorbol esters. The isobutane chemical ionization mass spectra of a series of 4aalpha-phorbol esters have been determined. Phorbol myristate acetate, a diester of phorbol, is the most potent known tumor promoter in mouse skin carcinogenesis. Several esters of the stereoisomer of phorbol have been synthesized to study the effect of structure and stereochemistry on tumor promotion. Conventional electron impact mass spectra of these esters gave little or no molecular weight information due to their low volatility, tendency to dehydrate and complex fragmentation to peaks in the low mass end of the spectrum. Isobutane chemical ionization mass spectrometry greatly enhanced the molecular ion region and through functional group selectivity established the identity of the various substituted esters.


A sensitive analytical method for pyrrolizidine alkaloids. The mass spectra of retronecine derivatives. The pyrrolizidine alkaloids in Senecio jacobaea can be hydrolyzed to the common base, retronecine, and derivatized to form the bistrifluoroacetate, bisheptafluorobutyrate, diacetate and bistrimethylsilyl ether. The analysis of the fluorinated compounds by electron capture provides sensitivity for detection of these alkaloids. The bond weakening effect in the ion formed on electron impact, between the allylic carbon and alkyl ester oxygen due to the electron withdrawing fluorinated groups of the ester, changes the driving force for fragmentation from the nitrogen alpha-cleavage reaction to a charge site migration. This yields alkyl-oxygen bond cleavage and formation of a stabilized allylic cation which is the base peak.


Use of a time averaging computer for high resolution field desorption mass spectrometry. Field desorption mass spectra often contain few peaks, the largest of which are [M]+. and [M+H]+ ions. Because of this lack of fragmentation accurate mass measurement is of primary concern in field desorption mass spectrometry. Although total ion yield per quantity of sample may rival electron impact or chemical ionization methods, ion yield per unit time is low. For this reason and because of varying [M]+./[M+H]+ ratios, elemental compositions as determined from stable isotope peaks are difficult to obtain. Low ion yield per unit time demands an integrating method for best high resolution results. The use of photoplates to obtain high resolution field desorption data is the only method reported thus far which takes advantage of integrating capability. This paper describes the use of a time averaging computer as an integrator for peak matching high resolution field desorption mass spectrometry using electrical detection. Accuracies better than 20 ppm are consistently obtained. Due to the sensitivity of the technique a wider range of reference compounds can be employed. This method incorporates the advantages of integrating capability with electrical detection, overcoming detection sensitivity problems associated with photoplates.


Urinary excretion of 5beta-pregnane-3alpha,20alpha,21-triol in human gestation. The steroids in urine from normal pregnant women have been studied. After extraction of conjugate steroids, solvolysis and enzymatic hydrolysis, the liberated steroids were separated by chromatography on Sephadex LH-20, and were analysed by gas-liquid chromatography and gas chromatography mass spectrometry. The following steroids were isolated and completely identified in the LH-20 fraction 7: 5beta-pregnane-3alpha,20alpha-diol, 5beta-pregnane-3alpha,17,20alpha-triol, 5beta-pregnane-3alpha,20alpha,21-triol and 5alpha-pregnane-3beta,16alpha,20alpha-triol. In addition, two metabolites tentatively identified as 5xi-pregnane-2xi,3xi,20xi-triol and 2xi,3xi,16xi-trihydroxy-5xi-pregnan-20-one, have not been reported as occcurring in urine from pregnant women. The 5beta-pregnane-3alpha,20alpha,21-triol was detected only in the third trimester of pregnancy and the urinary excretion values are between 320 and 650 microgram per 24 h. With the present data, it is not possible to establish the precursor(s) of this steroid. However, these results tentatively suggest that 5beta-pregnane-3alpha,20alpha,21-triol arises from foeto-placental unit.


Quantitative determination of tiamenidine hydrochloride in human serum using gas chromatography mass spectrometry. A method has been developed for the blood level determination of the antihypertensive agent tiamenidine hydrochloride. The serum samples are mixed with deuterium labelled tiamenidine hydrochloride as an internal standard and extracted with methylene chloride. The extracts are derivatized with heptafluorobutyric acid anhydride and analysed by means of gas chromatography mass spectrometry using the selected ion monitoring technique to measure the molecular ion intensities of the bis-heptafluorobutyryl derivatives of tiamenidine hydrochloride and of the internal standard. Using 5 ml serum, the limit of detection is 0.2 ng ml-1 with an accuracy of +/- 0.17 ng (Syx of the calibration curve).


Abnormal metabolites of isoleucine in a patient with propionyl-CoA carboxylase deficiency. A number of previously unrecognized abnormal metabolites have been identified and quantitated in the urine of a patient with an inherited deficiency of propionyl-CoA carboxylase. These included the isoleucine metabolites 2-methyl-3-hydroxybutyric acid and 2-methylacetoacetic acid. These isomers 3-hydroxyvaleric acid and 3-oxovaleric acid were found, which may be products of the condensation of propionyl-CoA with acetyl-CoA catalyzed by 3-oxoacyl-CoA thiolases. Following a load of isoleucine, 2-methylbutyrylglycine was identified. This metabolite has not previously been observed in man.


Quantitative field desorption mass spectrometry. V. Discussion of methodology and examples of applications. The possibilities for the application of field desorption mass spectrometry in quantitative analyses are described and evaluated. The advantages of and the sources of errors in the use of different standards as well as in the application of different methods such as photographic detection, single ion monitoring, repetitive scanning, selected ion monitoring, and double ion detection are illustrated by representative examples. Sensitivity and precision of the different techniques are evaluated. Most importantly, the use of stable isotope labelled compounds as internal standards has enabled quantitative determination with good precision, accuracy, and sensitivity. In order to demonstrate the capabilities of the methods, examples of applications are presented and the scope of quantitative analysis with field desorption mass spectrometry is discussed.


A highly specific and sensitive determination of gamma-aminobutyric acid by gas chromatography mass spectrometry. A procedure for the identification and quantification of picomole quantities of gamma-aminobutyric acid in tissue samples is given. This procedure combines the chemical specificity of dinitrophenylation with that of gas chromatography mass spectrometry to eliminate the interferences encountered with other direct derivatization procedures. Only a limited number of dinitrophenyl amino acid ethyl esters and some fatty ethyl esters are detected in the solution used for analysis. Identification is based on retention time and on the relative abundances of the three major ion fragments of the gamma-aminobutyric acid derivative. Quantitation is accomplished using isotope dilution techniques with [2H2]gamma-aminobutyric acid as an internal standard. The procedure has been successfully applied to samples of human cerebrospinal fluid and to extracts of ganglia from the mollusc, Aplysia californica.


Quantitative determination of nifedipine in human plasma by selected ion monitoring. A highly sensitive and specific method for the determination of nifedipine in plasma is described. Nifedipine was oxidized to its pyridine analogue with nitrous acid and determined by selected ion monitoring. Deuterium labeled nifedipine was used as an internal standard. Plasma levels as low as 5 ng ml-1 were measured. The usefulness of the method was demonstrated by obtaining plasma concentration curves for humans after an oral dose of 10 mg.


Identification of hydroxylated chlorodibenzo-p-dioxins, chlorodibenzofurans, chlorodiphenyl ethers and chloronaphthalenes as their methyl ethers by gas chromatography mass spectrometry. The methyl ethers of a number of hydroxylated (poly)chlorodibenzo-p-dioxins, chlorodibenzofurans, chlorodiphenyl ethers and chloronaphthalenes, representing all different hydroxy substitutions, were synthesized and their mass spectra investigated. With the exception of the methoxy derivatives of the chlorodibenzofurans, it appeared that the mass fragmentation patterns of the structural isomers of each class of compounds were very specific and allowed unambiguous assignment of the position of the methoxy group in the molecule. The different fragmentation patterns can be explained in terms of plausible mechanisms resulting in stable charge delocalized (oxonium) ions. Because of its diagnostic value, this method is useful in the structure elucidation of hydroxylated metabolites of pure isomers of chlorodibenzo-p-dioxins, chlorodiphenyl ethers and chloronaphthalenes.


Identification of ejaculate derived propylamine found in collagen sponge contraceptives. Propylamine is identified as one of the compounds present in odoriferous intravaginal contraceptive sponges from sexually active women. This compound also appears in samples of human ejaculate incubated at 37 degrees C for seven days. We have identified propylamine by gas liquid chromatography, mass spectroscopy and as N-propylbenzoylamide. Evidently the compound forms enzymatically from spermine and spermidine. We believe that this is the first time that propylamine has been identified as forming from human tissue.


Some considerations on quantitative methodology and detection limits in organic mass spectrometry. Mass spectrometric sensitivity data for the compounds cholesterol, cholestane, DDT, decafluorotriphenylphosphine, morphine, LSD and methyl stearate have been developed over a period of time and under a variety of conditions. This information is presented on both a relative and an absolute basis. With the exception of morphine, relative sensitivies were reproducible to within a factor of three over a six month period. This reproducibility facilitates quantitation and a single standard can be used for calibration of organic compounds from various classes. Detection limits of 50 femtograms for LSD are realized for samples introduced via the direct inlet probe.


Determination of imipramine in plasma by high pressure liquid chromatography and field ionization mass spectrometry: increased sensitivity in comparison with gas chromatography mass spectrometry. A quantitative method is reported for the determination of imipramine in plasma samples in the low nanogram and subnanogram range. The sensitivity and precision of the technique, which involves high pressure liquid chromatography and direct probe field ionization mass spectrometry, are approximately an order of magnitude greater than are offered by gas chromatography mass spectrometry with selected ion monitoring using deuterated or other types of internal standards. [2H6]Imipramine, labeled in the ethylene bridge and in the aromatic rings, serves as the isotopic diluent. The method has been used for the determination of the comparative bioavailabilities of two different commercial preparations of imipramine. In these tests, subjects ingested a 25 mg tablet of one or the other drug preparation together with a solution containing an equivalent amount of imipramine deuterated in the ethylene bridge ([2H2]imipramine). The latter served as an internal check for intrasubject variability in absorption of the imipramine tablets. Typical results from one of the subjects are presented.


Analysis of double-substrate limited growth. Mathematical models which relate the growth rate of a microorganism to a single limiting substrate concentration have long been established. In recent years, it has become apparent that, under certain conditions, the growth rate of an organism may be simultaneously limited by two or more substrates. Mathematical models of double-substrate limitation fall into two categories: interactive and noninteractive models. A discussion of both types of models is presented in both conceptual and mathematical terms. An analogous case of an enzyme which requires two different substrates to produce a single product is presented. This enzyme analog indicates that both types of double-substrate limitation models appear to be feasible under certain conditions. Based upon stoichiometry and specific growth rate-substrate concentration contour plots, a method for determining the operational conditions which will lead to double-substrate limitation is presented.


Pectinolytic activity of Saccharomyces fragilis cultured in controlled environments. Seven of 30 yeast stock cultures, covering nine genera, and 13 of 39 yeasts isolated from grapes gave positive reactions when screened for pectinolytic activity on pectin gel plates. The seven stock cultures covered six species and four genera. Only one of the yeasts, Saccharomyces fragilis Y49, excreted discernible pectinolytic activity into the fluid of shake flask cultures; the activity was partially constitutive and was repressed by high oxygen tensions.


[Structural-functional organization of hemostatic clots]. The studies were carried out to verify the hypothesis on the structural-functional organization of the hemostatic clot. For this purpose the influence of the platelets and their aggregate condition on the mechanical properties of the clot was investigated. Redistribution of platelets into aggregated, caused by addition of ADP and mixing, led to the inhibition of the clot retraction. This was reflected in the form of reduction of am on the thromboelastogram. Simultaneous recording of thrombloelastogram, coagulbbogram, and platelet degranulation demonstrated that processes of viscid metamorphosis of platelets and fibrin filaments sedimentation were followed by active clot contraction. The clot is a fibrin-platelet structure whose nodes contain blood platelets, and cells--the rest blood elements. The clot retraction takes place due to contractile properties of platelets.


[Effect of oxytocin on the electrical potential and ion permeability of the apical membrane of frog gall bladder epithelial cells]. The influence of oxytocin on the intracellular Na+ and K+ concentrations, the level of transmembrane potential differences, and on the relative ionic permeability (PNa/PK) of the apical zones of the superficial epithelium membrane was studied in experiments on the isolated frog gallbladder (GB). Oxytocine introduced into the outer incubation solution in a dose of 20 mulliunits/ml caused a reduction of transmembrane potential difference, and an increase of PNa/pk coefficient and an insignificant shift of the Na+ and K+ concentrations in the intracellular medium. Thirty minutes after the oxytocine action of the organ the membrane potential (MP) of the cells decreased from 52.7 mV to 38.7 mV (the cell is negatively charged inside), and PNa/PK increased from 0,083 (control) to 0,175 (test) with a simultaneous increase in the intracellular Na+ concentration by 18.3 milliequiv./kg of (H2O)i. Such a shift in the intracellular Na+ and K+ concentrations may cause  a decrease of the MP by only--0.7 mV, but actually the membrane potential decreased by--14.0 mV. Thus, the reduction of the transmembrane potential difference results from increase of PNa/PK under the influence of oxytocine. No electrogenic ionic transport through the apical membrane of frog gallbladder epithelial cells was revealed.


[Role of the pituitary-adrenal system in mechanism regulating vascular permeability during stress]. Disturbances of the microvascular permeability were studied by the "vascular labelling" technique during the immobilization stress of hypophysectomized and adrenalectomized rats. Animals with sham operations served as controls. As revealed, hypophysectomy and adrenalectomy caused disturbances of vascular permeability in the mesentery. Vascular permeability disturbances in the hypophysectomized and adrenalectomized rats under conditions of immobilization were more expressed than in the sham-operated animals. Removal of the pituitary and adrenal glands produced mast cell degranulation at the earlier immobilization period.


[Comparative assessment of contra- and ipsiversive reactions induced by electrical stimulation of the caudate nucleus in cats]. High-frequency stimulation of the caudate nucleus provoked 2 types of rotatory movements of the head and body in the contra- and ipsilateral direction in unrestricted cats. The contralateral rotations (CR) were provoked from a more extensive area chiefly occupying the dorso-mediocentral portions of the head of the nucleus. In difference from them, the ipsilateral rotations (IR) originated from the ventro-lateral area, possessed tonic component more frequently, were more pronounced and less sensitive to L-DOPA and chlorpromazine. Unilateral damage of the area of CR led to the ipsilateral pose asymmetry. When this asymmetry disappeared administration of L-DOPA or apomorphine readily provoked rotation in the same direction. Destruction of the areas in which the ipsilateral reactions originated gave an opposite result.


[Analgesia induced by creation of a generator of excitation in the midbrain]. Experiments were conducted on albino rats. An excitation generator in the dorsal nucleus of the midbrain raphe was created by means of tetanus toxin. Formation of the excitation generator in this nucleus led to the development of general analgesia, expressed against physiological pain (nociceptive stimulation) and the central pathological pain (pain syndrome of spinal origin). A conclusion was drawn that prolonged analgesia occurring in activation of certain structures of the brain was caused by the origination in them of excitation generators causing prolonged activation of these structures.


[Determination of local muscular blood flow in the hindlimbs of dogs following electrolysis of conducting vascular prostheses previously implanted in the abdominal portion of the aorta]. Peripheral blood flow in the posterior limbs in electrolysis of electroconductive vascular prosthesis preliminarily implanted into the abdominal aorta was experimentally determined on 25 mongrel dogs. Following reestablishment of the main blood flow a positive electrical potential (3--4 V) was fed on the prosthesis by means of a current conductor. Tissue blood flow was radiographically studied with xenon-133. Results of this investigation showed that during feeding the positive potential to the electroconductive prosthesis an increase of tissue blood flow occurred in the canine posterior limbs. After the cessation of the current feeding to the prosthesis the tissue blood flow occurred in the canine posterior limbs. After the cessation of the current feeding to the prosthesis the tissue blood flow decreased to the initial values. A conclusion was drawn that a positive potential from the source of direct current should be fed constantly to the electroconductive prosthesis or prolonged stable tissue blood flow increase.


[Blood cholesterol and hepatic bile secreting function in rats of different ages under normal conditions and after maintenance of an atherogenic diet]. The quantity of bile secreted during 24 hours and the concentration of total bile acids in adult 11--12-months-old and aged 27--29-month-old rats were determined by cannulation of common bile duct. As revealed, the difference in bile acid production and in the concentrations of cholesterol fractions in the liver and plasma between the adult and aged rats on a standard diet was insignificant. But the excretion of bile acids was markedly elevated both in adult and aged rats on atherogenous diet. The level of total and ester cholesterol in the plasma was higher in aged rats than in adult animals.


[Concentration of acid and alkaline phosphatases in the lymphoid elements of peripheral blood and the hematopoietic organs of intact rats and mice]. The content of acid and alkaline phosphatases in the intact mongrel rats in the lymphoid elements of the peripheral blood, bone marrow and lymphoid organs (the thymus, spleen, lymph node) was studied. The mean values of the percentage of cells containing the enzymes were obtained; their organ and specific characteristics is presented.


[Effect of O,N'=dichlorodiphenyldichloroethane and pertan in vitro on glutathione reductase activity in the adrenals of dogs and guinea pigs]. Glutathione reductase is activated by o,p'-dichlorodiphenyldichlorethane (o,p'-DDD) and pertan added in a concentration of 312 micrometer to the homogenate and cytoplasmic fraction of the dog adrenals. At a concentration of 156 micrometer o,p'-DDD and pertan failed to influence the glutathione reductase activity of the dog adrenal glands. Added in vitro, o,p'-DDD and pertan activate glutatione reductase of the quinea pig adrenal glands. O,p'-DDD does not affect the glutathione reductase activity of the liver and kidney cytoplasmic fraction in dogs. This observation confirms the high specificity of o,p'-DDD action on the adrenal glands.


[Resynthesis of rhodopsin in rats with hereditary retinal dystrophy]. Resynthesis of rhodopsin both in the retina and the eye cup was studied in albino rats (Campbell line) and in rats with pigmented eyes (Hunter line) with hereditary retinal dystrophy. Wistar rats and those of MSU line were used as controls, respectively. The rate of resynthesis of rhodopsin after its bleaching in the retina of dystrophic animals appeared to be much less than that  in the normal ones, and decreased during the disease. When clear morphological changes were seen, only 50% of the previously bleached pigment was capable of regeneration during 2 hours of dark adaptation, the time being quite adequate for complete regeneration of rhodopsin in normal animals. It was found that in Campbell and Hunter rats breakdown and resynthesis of rhodopsin takes place not only in the retina but also in the layer of outer segment debris of photoreceptors located between the pigment epithelium cells and the retina.


[Recovery responses in the bodies of rats following irradiation with microwaves (2400 MHz)]. During microwave irradiation (SHF-field, 2400 Mc/s) of rats in the range of capacity density of from 100 mW/cm2 to 800 mW/cm2 the function of regenerative effect and the time interval between the irradiation cycles (power densityconst) approximates the logistic one, whereas that of the power density and the time interval between the irradiation cycles (regeneration level = const) approximates the linear one.


[Tryptophan uptake by glia and synaptosomes of rabbit cerebral cortex]. The authors studied the engulfment of L-tryptophane-14C by gliacytes and synaptosomes of the rabbit cerebral cortex. The system of engulfment of the gliacytes was characterized by a high affinity to tryptophane (Km = 0.8 micrometer). Engulfment of tryptophane by synaptosomes had a lower affinity (Km = 50 micrometer). Psychotropic substances--chlorpromazine and imipramine produced an inhibitory influence on glial engulfment. The leading role of gliacytes in the trophic provision of the neurons and the normal course of neurodynamic processes is confirmed.


[Effect of gamma-aminobutyric acid derivatives on sleep disorders in neuroses]. Electropolygraphic studies showed that under gamma-amino-butyric acid (GABA) derivatives various neurotic patients with sleep disorders had a tendency towards an increase in total sleep duration due to an accretion of basic sleep stages (the 2nd stage, delta-sleep, and rapid sleep), a statistically significant reduction in the number of spontaneous wake-ups, time of awakedness during night and the movements activation index. A detailed analysis of some electrographic data within the sleep stages revealed a tendency towards an increase in number of the 2nd stage sleep spindles, of delta-index in the 3rd and 4th sleep stages, as well as an increase in the average readings of rapid eye movements in the absence of any marked changes in  their specific occurrence per time unit. GABA derivatives in the used dosage caused similar changes in the sleep patterns in case of its disturbances, with a relatively more pronounced action of sodium oxybutyrate.


[Effect of papaverine on the tonus and contraction of depolarized taenia coli musculature in guinea pigs]. Experiments were performed on the isolated strips of guinea pig taenia coli. The smooth muscle was depolarized in a solution with high potassium concentration (120 mM KCl). The effect of papaverine (in concentration of from 10(-5) to 3.10(-5) g/ml) on the tonus and the contractile off-response originating after the ending of longlasting strong polarizing current was investigated. It was found that: 1) papaverine abolished the concentrations induced by drugs (histamine, acetylcholine, bradykinin); 2) papaverine reduced the tonus of depolarized muscle and eliminated its increase under the effect of a rise of the external calcium concentration; 3) papaverine had no effect on the amplitude and the ascending phase of the contractile off-response; 4) papaverine accelerated the discending phase of the contractile off-response. The data obtained suggest: 1) there are chemoexcitable calcium channels in the cellular membrane which are blocked by papaverin; 2) there are calcium "leakage" channels in the cellular membrane responsible for the tone maintenance which are blocked by papaverine; 3) papaverine has a negligible effect on the electroexcitable calcium channels.


[Effect of dopamine on gastric smooth muscle in rats and characteristics of the alpha-adrenoreceptors of gastrointestinal tract muscle cells]. Dopamine and phenylephrine decreased the tone of the smooth muscles of the isolated rat stomach strips in concentractions of 10(-6) M and higher. The curves of the concentration-effect have the same slope. Dopamine effects are unchanged in the presence of propranolole (5.10(-6) g/ml). Phentholamine (as well as dihydroergotamine and tropaphen) shows an equal degree of antagonism towards both phenylephrine and dopamine. It is suggested that dopamine and phenylephrine relax the stomach muscles by influencing the alpha-adrenoreceptors. The latter differe from alpha-adrenoreceptors of the ejaculatory duct of rats by a high sensitivity to the blocking influence of some neuroleptics--haloperidol, trifluoperazine, chlorpromazine, pA2 for which (8.11--8.64) is of the same range as pA2 for alpha-adrenolytic drugs (7.76--8.46). The features of resemblance and difference between alpha-adrenoreceptors of the gastrointestinal tract muscles and the inhibitory dopamine receptors of the nerve cells are being discussed.


[Antibody-forming cells in rat spleen following midbrain injury]. The number of plaque-forming cells (PFC) in the spleen of rats immunized with sheep red blood cells after the injury of the anterior or the posterior portions of the medial hypothalamus, and also of the thalamus displayed no significant difference from the number of PFC in the spleen of intact animals. The titres of hemolysing and hemagglutinating antibodies in the animals with injuries of the mid-brain were somewhat lower than in the intact animals. A reduction of the circularing antibodies level was not associated with localization of the foci of injury and apparently served as the sequence of the craniocerebral trauma.


[Effect of enzymes involved in the contact phase of blood clotting on the functional activity of neutrophils related to phagocytosis]. The influence of the product of blood coagulation contact phase of factor XII and of its activated form on the reduction reaction of nitrobule terazolium by human neutrophils was investigated. In all the cases the product of blood coagulation contact phase induced substantial stimulation of neutrophils. The neutrophil reactions with factor XII were irregular. They were more regular and intensive after the activation of this factor. An assumption was made on the mediated influence of the product of blood coagulation contact phase on neutrophils through the activation of intercommunicated blood plasma enzyme systems.


[Relationship between the effectiveness of the antitumor action of sarcolysine and the latency period between transplantation and tumor appearance]. Sarcoma induced with 3-methylcholantrene in mice was transplanted to syngeneic recipients. The latent period of the tumour growth varied from 7 to 26 days. Sarcolysine was injected once when the tumour became palpable. When the tumours were revealed 7 to 8 and 10 to 15 days after the inoculation, the tumour growth inhibition was accompanied by increased survival of mice, particularly marked at the latter period. When the tumours were revealed 17 to 20 or 22 to 26 days after the transplantation, inhibition of the tumour growth was not accompanied by any increase of survival.


[Liver tumors induced in mice by prenatal and postnatal administration of ortho-aminoazotoluene]. The authors studied the prenatal and postnatal blastomogenic action of orthoaminoazotoluol (OAAT) on the liver of CBA mice. OAAT was administered to mice intragastrically in oil solution, thrice, 4 mg each time (a total of 12 mg). Twelve months after the OAAT administration tumours of the liver during the postnatal period were revealed in 89.3% of female mice (11.5% in control), and in 78.7% of male mice (68.5% in control). In the experimental progeny subjected to OAA action during last 4--5 days of the prenatal period the liver tumours appeared in females at the age of 12 months in 54.8% of cases (5.3% in control), and in males--in 81.1% (35.2% in control). In this progeny, particularly in the male animals malignant neoplasms occurred more frequently than in the intact animals and those subjected to the action of OAAT during the postnatal period.


[Relationship between androgenization and differentiation of hypothalamic centers]. Dependence of the sterilizing action of androgen on differentiation of the hypothalamic centers was studied during the postnatal development of female rats. Asynhronous differentiation in the development of the arcuate nucleus (tonic centre) and suprachiasmatic nucleus (cyclic centre) was observed. Neurocytes of the arcuate nucleus started to produce secretory granules in 20-day embryos, while in the suprachiasmatic nucleus the neurocytes with secretory granules appeared in 5--7-day rats. Injection of testosterone propionate induced an anovulatory cycle in females the first 7 days after birth; this is associated with the inhibition of development of the hypothalamic cyclic centre.


[Microphotometric study of the activity of oxidative enzymes in the endometrial epithelium of rats following ovariectomy and administration of testosterone propionate]. A method of comparative microphotometry was applied to the study of the oxidative enzymes in the epithelial lining of the uterine cavity and the glandular epithelium of the ovariectomized rats during the climacteric disturbances. There was an increase in the activity of lactic dehydrogenase (LDH) and glucose-6-phosphoric dehydrogenase (G-6-PDH) and a fall of the succinic dehydrogenase (SDH) and NAD- and NADP-diaphorases activity in the cells of the epithelial lining the uterine cavity. The glandular epithelium displayed an elevation of the LDH activity and a sharp fall of the SDH, NAD- and NADP-disphorases activity. Administration of testosterone-propionate caused an marked elevation of the activity of the oxidative enzymes in the epithelium of the rat endometrium in comparison with level of their activity in control animals and rats given no hormone.


[Kinetics of hematopoietic stem cells in the bone marrow of hepatectomized mice]. Two-thirds of the liver was removed from (CBA X C57BL/6j) F1 female mice. A significant increase of the number of endogenous colonies count in the spleen of partially hepatectomized mice was observed on the 5-th day after the operation. This increase was not associated with the changes in the number of stem cells in the bone marrow as partial hepatectomy at different times after the operation exerted no effect on the number of colony-forming units (CF1) in the bone marrow.


[Effect of regeneration of hematopoietic organs on the number and type of splenic colonies]. Two thirds of the spleen or the bone marrow of the tibia were removed in CBA mice. Hemopoietic splenic colonies were obtained and examined microscopically on the 8th day after the lethal irradiation of mice and injection of the spleen cell suspension. An increase of the number of colonies and a significant rise of the number of granulocytopoietic colonices in comparison with their number in control was seen in the experimental animals. The number of other hemopoietic colonies remained unchanged. The authors suggest that these changes could be caused by the local influence of the proliferating spleen stroma, or by a factor secreted from the regenerating stroma of the hemopoietic organs.


[Development of the seminiferious tubules and rete testis during the prenatal period of human ontogenesis]. The sources of origin and the peculiarities of formation of the seminal ducts and rete testis during the prenatal period of ontogenesis in man were studied. It has been established that the seminal duct sand the ducts of the rete testis form from the cellular cords of the coelomic epithelium and the primordial germ cells which appear simultaneously in the septum of the testis and the primordial germ cells which appear simultaneously in the septum of the testis and central part of its parenchyma in the embryos, 13.0--17.0 mm long. By plastic and graphic reconstruction, as well as by methods of subtle preparation under binocular microscope MBC-I control it was revealed that the seminal ducts anastomosed between themselves both within the limits of one and the adjacent lobules. The ducts of the rete testis do not form anastomoses, but superimpose over one another, creating an impression of a rete. Approaching the tunica albuginea they merge, continuing into the cuctuli efferentes testis.


[Renal pathomorphology of rats fed irradiated food products over a long period]. Morphological changes were studied in the kidneys of albino rats and their progeny fed only with irradiated food for 20 months. Morphological signs of the autoimmune process in the form of the membraneous-proliferative glomerulonephritis in combination with characteristic disturbances of the blood vessels and extensive lymphoid-histiocyticeosinophilis infiltration of the stroma were revealed.


[Postnatal histogenesis and cell proliferation in the parietal region of mouse neocortex under normal conditions and following brain injury]. Postnatal histogenesis of the parietal area of the neocortex and proliferative capacity in it of the main cell types were studied in mice under normal conditions and in stab wound of the brain by analysing 3H-thymidine-labeled cells on semithin sections. As revealed, microneurons failed to form in the parietal cortex of mice during the postnatal period either by migration of undifferentiated cells or by proliferation. Injury of the right hemisphere did not cause any change in the way of histogenetic transformations of cells migrating into the cortex of the parietal area in the direction of their differentiation into microneurons.


[Ultrastructure of unstabilized fibrin]. The structure of non-stabilized fibrin was studied by electron microscopy. Non-stabilized fibrin was shown to consist of a network of fibers (fibrils, from 2 to 10 mu in length, and up to 200 A in width). Negative contrasting with uranyl-acetate demonstrated non-stabilized fibrils to be made up of 5 to 10 longitudinally striated protofibrils and to be characterized by transverse striations with the main period of about 200 A. Comparison of the ultrastructure of stabilized and non-stabilized with factor XIIIa fibrin fibers demonstrated their morphological affinity.


[Determination of sperm activity by the light scattering method]. A possibility of determination of sperm activity on light scattering spectra was studied. The laser homodyne light beating spectrometer was used for the measurements. Bovine sperm solutions were investigated. As shown, the sperm activity defined by spermatozoa motility could be determined through light scattering spectrum half-width. The advantages of the new method as compared with routine method of sperm activity determination are discussed.


[Method of light microscopy of pulmonary tissue in small laboratory animals]. The authors suggest a method of biomicroscopy of the lungs with the use of a modified experimental lung fixator offering a possibility of carrying out vital examination of microcirculation of the lung tissue not only in artificial, but also in spontaneous respiration of the animals.


[Detachable plethysmoreceptor for determining the volumetric blood flow rate in the calf and forearm by venous occlusion plethysmography]. The dismountable air plethysmoreceptor suggested by the author, in difference from the fixed ones, permits to put it on and take it off the limb under study rapidly and frequently. Due to flexibility of the internal wall of this plethysmoreceptor, it is possible to record the circulation without any preliminary supply of air into the cavity of the plethysmoreceptor.


[Fistulated diffusion chamber and its use in studying microbial associations in vivo]. The fistulated diffusion chamber intended for the cultivation of microbial associations in vivo was elaborated. The interralation between the yeast-like Candida albicans fungi, staphylococci, shigella Sonnei, the influence of each one upon the macroorganism, and its response to their combined action were studied.


[Obtaining and rearing germ-free miniature piglets for biomedical research]. The method of obtaining and rearing germfree miniature piglets for medical-biological research is described. The gnotobiotes were reared in rigid organic glass isolation cells up to 3 months. Milk diets supplemented with minerals and vitamins were used for nutrition. The gnotobiotes gained weight well during the whole observation period.


Erythrokinetics and ferrokinetics of a viral-induced murine erythroblastosis. A variant of Rauscher leukemia virus, designated RLV-A, induced a slow progressive impairment of erythropoiesis in BALB/c mice. Identified in this study were a shortened red cell 51-cr half-time, anemia with indices showing minimal but significant hypochromia, ineffective erythropoiesis, and infiltration of the liver, spleen, and peripheral blood with erythroid pecursors. Ferrokinetic studies indicated a normal plasma iron turnover in infected mice but a decreased red cell iron turnover. Large amounts of 59Fe were taken up by the enlarged liver and spleen. Peak splenic heme 59Fe synthesis was delayed 12 hr in the infected mice. The substantial increase in the splenic intraerythrocytic nonheme iron pool and the hypochromic indices indicate a process analogous to that seen in the sideroblastic anemias. The disease produced by this RLV-A variant may prove useful for studying various aspects of the preleukemic sideroblastic anemias and DiGuglielmo syndrome.


Three-dimensional model of bone marrow.

Three-dimensional model of bone marrow. Three-dimensional scale models of bone marrow from a hypertransfused and a normal rat were constructed. The model of marrow from the hypertransfused rat demonstrated the existence of distinct erythroblastic islands in situ in which the erythroblasts underwent sychronous maturation. Macrophages were found in close association with the developing erythroblasts. The immature erythroblasts were tightly grouped, but as they matured they began to move apart. Erythroblasts in individual clusters were found to be at the same stage of morphologic maturation. In contrast, the model of marrow from the normal rat showed a majority of clusters containing erythroblasts at various stages of maturation. Erythropoiesis was not spatially restricted to the area proximal to the sinuses but was found to occur over the entire marrow space. Thrombopoiesis, however, was found to take place exclusively in the immediate vicinity of the marrow sinuses.


Osmotic fragility of peripheral blood lymphocytes in chronic lymphatic leukemia and malignant lymphoma. The osmotic fragility (OF) of peripheral blood lymphocytes from patients with chronic lymphatic leukemia (CLL) and non-Hodgkin malignant lymphoma (ML) was investigated employing an automatic recording method and compared with that of lymphocytes from healthy subjects and from patients suffering from various non-neoplastic diseases. The curves from CLL and ML showed a pattern of increased lymphocyte OF compared with those of the two control groups, and the difference was statistically significant ( less than 0.001). In CLL the increase in OF was more pronounced than in ML, and the shape of the curve was different from that in the other groups. The employment of peripheral blood lymphocyte OF as an additional diagnostic parameter in the diagnosis of CLL and ML is suggested.


Asynchronous globin chain synthesis in rabbit reticulocyte lystates induced by hemin-controlled repressor. To define further the role of hemin-controlled repressor (HCR) in globin synthesis, we studied its effect on the synthesis of individual globin chains in a rabbit reticulocyte lysate cell-free system. In the presence of HCR there was a marked globin chain imbalance, resulting in a lowered alpha/beta ratio. These findings in vitro may have relevance to certain clinical heme deficiency states in which a similar globin chain imbalance has been observed.


Consistent activation of fetal hemoglobin synthesis in cultured adult bone marrow cells. The production of fetal hemoglobin was investigated in plasma clot cultures of adult bone marrow cells from normal donors and from individuals with homozygous HbS or HbC disease. Synthesis of gamma and beta chains was assessed either by 35S-methionine labeling of cultures and measurement of the radioactivity incorporated into the methionine-containing tryptic peptides of the gamma and beta subunits or by 3H-leucine labeling and measurement of the radioactivity incorporated into the globin chains of Hbs F0 and A0 isolated by ion-exchange chromatography. The cultures from all individuals responded with increased production of HbF. Cultured cells from subjects without a hemoglobinopathy produced an average of 8.2% gamma chains (range 3.1%-20.3%), while cultured cells from subjects homozygous for HbS or HbC produced an average of 16.6% gamma chains (range 12.2%-20.4%). These findings indicate that fetal Hb production was regularly enhanced in adult bone marrow cells triggered in vitro to clonal growth in the plasma clot culture system.


Water distribution in blood during sickling of erythrocytes. Plasma urea and protein determinations proved suitable for measuring changes in total diffusible water and plasma volume in whole blood. Deoxygenation by saturation with carbon dioxide at 25 degrees C caused no change in plasma urea, but a significant increase in plasma protein concentration was induced with both normal and sickle-cell (HbSS) blood. Thus in HbSS blood there was no binding or trapping of water as a result of sickling and there was a normal influx of water into the cells (Bohr effect) despite the polymerization of the hemoglobin molecules with sickling. Consistent with this observation was the finding that the deoxygenation induced a similar increase in concentration of the plasma cations, sodium plus potassium. HbSS erythrocytes neither lost nor gained water under the more physiologic conditions of deoxygenation with a 95% nitrogen, 5% carbon dioxide gas mixture.


Aplastic anemia with fetallike erythropoiesis following androgen therapy. A 43/4-yr-old black girl with acquired aplastic anemia had an increase in total hemoglobin (Hb) from 4.5 to 16.8 g/dl and fetal hemoglobin (HbF) from 0.8 g/dl (18.8%) to 9.6 g/dl (60.2%) following combined androgen-adrenal steroid therapy. Discontinuation of the drugs was followed by a decline in both HbF and total Hb. Reinstitution of the combined steroids prompted a second rise in total and fetal hemoglobin. During these responses the subject's erythrocytes exhibited an increased i antigen score and a low level of red cell carbonic anhydrase. The glycine:alanine ratio at position 136 of the gamma chains of HbF was of the fetal type (proportion of chains with glycine residues, 0.74). Hemoglobin A2 was low (0.4%). The synthesis of alpha and non-alpha chains was balanced. These results indicate that the stimulation of red cell proliferation in this subject, in response to androgen therapy, resulted in the production of cells with several characteristics of "fetal" erythrocytes.


Partial purification of renal lysosomal substances producing angionecrosis and increased vascular permeability. The lysosomal contents of hog kidney cortex, which induce angionecrosis and/or an increase of vascular permeability, were obtained by differential centrifugation and osmotic shock treatment, and were purified by various chromatographic techniques and electrophoresis. The material producing an increase in vascular permeability of the rabbit skin was purified 600-fold over the homogenate; however, it showed practically no angionecrotic activity. Another substance producing angionecrosis without pressor activity was partially purified.


Pharmacological in vitro analysis of amine-mediated vasomotor functions in the intracranial and extracranial vascular beds. The cerebrovascular system (the extra- as well as intracerebral vessels) receives a well-developed innervation by the adrenergic (originating in the superior cervical sympathetic ganglia) and cholinergic nerves. In addition, recent immunohistochemical studies have shown the presence of vasodilatory peptidergic nerve fibres. There may be an association of cerebral blood vessels also with various aminergic nerve systems of intracerebral origin. Besides the nerves, amine-containing mast cells are often located in close relation to the brain vessels. The specific receptors mediating the contractile and dilatory response of the various vasoactive amines--noradrenaline, dopamine, 5-hydroxytryptamine, histamine, acetylcholine--have been characterized in detail in pharmacological experiments. There is a number of major differences in the reactivity of cerebral vessels as compared to vasomotor functions in the peripheral circulation. The observations and results provide a basis for a better understanding of physiological neurogenic control mechanisms in the cerebral circulation, and they may also have implications for the interpretation of pathophysiological phenomena related to, for example, migraine and the vasospasm following subarachnoid hemorrhage.


Smooth muscle cells in the development of plasmatic arterionecrosis, arteriosclerosis, and arterial contraction. Plasmatic arterionecrosis, the causative lesion of hypertensive cerebral hemorrhage, follows upon medial muscle cell necrosis. The development of medial muscle cell necrosis, the earliest cerebral arterial change seen in hypertensive rats, was inhibited when these animals were fed a cholesterol and lard-supplemented diet. Insudation of fibrin was noted in the arterial intima of hypertensive rats with bilaterally constricted renal arteries. Removal of the constriction induced a fall in the elevated blood pressure and an increase of intimal muscle cells. These were responsible for the dissolution of the deposited fibrin, leading to arteriosclerosis. These myointimal cells may originate from the endothelium. Arterial contraction caused by methoxamine hydrochloride often induced the intrusion of one medial muscle cell into another and increased endothelial permeability. 12-24 h after contraction, the arterial segments showed medial muscle cell necrosis, endothelial desquamation with platelet adhesion, and blood plasma infiltration.


Differences in the response of three embryologically distinct segments of the isolated canine posterior vena cava to vasoactive substances. The canine posterior vena cava was excised and divided into three embryologically distinct segments: segment A (supradiaphragm), segment B-C (intrahepatic and that between liver and renal veins), and segment D (infrarenal). Circular and longitudinal strips were cut from each segment, suspended in Krebs bicarbonate solution and isometric tensions were recorded. The responses to six vasoactive agents, as well as transmural neural stimulation were studied. Maximum tension and ED50 were obtained for norepinephrine, epinephrine, acetylcholine, bradykinin, histamine and 5-hydroxytryptamine (5-HT). The responses were not only quantitatively, but qualitatively different among the three segments. Bradykinin constricted the strips in A and B-C but not in D. 5-HT (less than 10(-5) M) caused a dose-dependent contraction in A and D through its direct stimulating action, while in C, a contractile response appeared only after administration of a higher dose of 5-HT. This was due to an indirect sympathomimetic action of the agent. Segment B-C, which histologically contained massive longitudinal muscle bundles in the outer layer of the wall, exhibited spontaneous, rhythmic contractions. The existence of a cholinergic excitatory innervation, in addition to adrenergic, was demonstrated in C by transmural neural stimulation.


Atherogenic mechanisms: enhancement of regression of atheromatous lesions by phthalazinol. Atherosclerosis was produced in rabbits by feeding 1% cholesterol pellets for 15 weeks to 35 male rabbits divided into two equal groups--the placebo control and phthalazinol group--with a comparable serum cholesterol level. The phthalazinol group was given 20 mg/kg of the compound daily. 13 rabbits of both groups were on 15 weeks of the treatment and the remaining 22 rabbits were treated for 30 weeks. The treated group exhibited a statistically significant increased removal of cholesterol from atherosclerotic aortas and improvement in pathological changes. This enhancing effect was more marked in the animals treated for 30 weeks. Such evidence indicates that there are substances capable of enhancing the removal of cholesterol from atheromatous lesions. In light of the pharmacological properties of phthalazinol, the possible role of thromboxane A2 released from platelets adhered and aggregated on atheromatous plaques, in the progression of atherosclerosis is worthy of continued investigation.


Increased vascular collagen biosynthesis by hypertension and reversal by antihypertensive drugs. Collagen synthesis was increased in aortas, mesenteric arteries, cerebral microvessels, pial artery, basilar artery and decreased in the heart of rats made hypertensive with deoxycorticosterone acetate-salt or the spontaneously hypertensive animal. The markers of collagen biosynthesis that were elevated were prolyl hydroxylase, prolyl hydroxylase-related antigen, total collagen content and the incorporation of labelled proline into total protein and into collagen. The antihypertensive drugs reserpine and chlorthiazide could both prevent the increase or reduce the increase in collagen synthesis.


High-energy phosphate metabolism of isolated coronary arteries in the dog. The correlation between phosphate metabolism and isometric contraction was investigated in helical strips from dog coronary artery. Adenosine triphosphate (ATP) and creatine phosphate (CP) contents of resting strips did not significantly change during anoxia. ATP content remained unchanged during potassium-contracture under aerobic conditions but was significantly reduced by anoxia. Pretreatment with iodoacetate resulted in a striking reduction in ATP content with a less marked decrease in CP content. ATP-depleting effect of iodoacetate was reduced slightly by the addition of pyruvate, but contractile response was not restored. It is considered that high-energy phosphates provided by anaerobic glycolysis can meet the energy requirements of resting coronary vessels but are insufficient for maintaining active tension. In resting strips equilibrated for 2 h in oxygenated bath solution, the reactivity to KCl and anoxia appears to be dependent on the availability of ATP.


Estimate of cellular force generation in an arterial smooth muscle with a high actin: myosin ratio. An in vitro preparation from the media of the pig carotid artery develops somewhat higher force/cell cross-sectional area with one-fifth the myosin content of skeletal muscle cells. The following results suggest that this performance reflects cellular properties rather than the arrangement of cells within the tissue: (1) force development at the peak of the length-force curve is independent of the length of the tissue segment in a strip of constant cross-section, and (2) average cell length is directly proportional to tissue length. We conclude that the contractile system of arterial smooth muscle cells is specialized for force generation and that the mechanical properties of the pig carotid media preparation provide valid estimates of cellular function.


Responses of smooth muscle to quick load change studied at high time resolution. Quick-release and quick-stretch experiments have been performed on preparations of smooth muscle from rat portal vein and rabbit urinary bladder. The low equivalent mass of the isotonic lever (8 mg) implied that inertial oscillations were limited to the first 5-10 msec after the load step. The high time resolution achieved in this way enabled us to separate three components in the length response to a step change in force: (1) an immediate passive elastic recoil, (2) an isotonic velocity transient lasting 50-75 msec and (3) shortening of the contractile element after its full adjustment to the new load. The maximal series elastic recoil was about 10% of the total muscle length in portal vein but only some 3% in urinary bladder. Stiffness of series elasticity increased in proportion to force and was about 3 times higher in bladder than in portal vein at any force level. Force-velocity relations for loads less than Po could be fitted to Hill's equation; Vmax in 4 AC-stimulated portal veins was 0.53 +/- 0.03 muscle lengths/sec and in 8 K+-activated bladder preparations 0.18 +/- 0.01 muscle lengths/sec. Application of loads greater than Po produced rates of lengthening greater than expected from an extrapolation of Hill's hyperbola. The nature of the transient component is discussed in the light of recent studies of force and velocity transients in skeletal muscle.


Ion transport in tonic and phasic vascular smooth muscle and changes during deoxycorticosterone hypertension. The washout of radioisotopes was studied in aorta, femoral artery and portal mesenteric vein from controls and rats made hypertensive with injection of deoxycorticosterone (DOC) acetate. Experiments were also conducted on tonic (pulmonary artery) and phasic (portal mesenteric vein) smooth muscle from rabbits. The rate constants for the washout of 42K, 36Cl and 24Na from aorta were significantly elevated in the DOC hypertensives. Acute removal of extracellular K slowed the washout of 24Na by 50%, however, the rate constant for the DOC group remained higher than the controls. Increased turnover of 42K was also observed in the femoral artery and in a vessel (portal mesenteric vein) not exposed to the effects of high blood pressure in the rat. The rate constants for the washout of 42K, 36Cl and 24Na from phasic smooth muscle in rabbit were greater than the tonic type. Ouabain significantly slowed 24Na washout, however, the rate constant for the portal mesenteric vein remained higher than the pulmonary artery. DOC hypertension was associated with increased ion transport at several vascular sites. A similar change was observed for the phasic vascular smooth muscle from normal rabbits. A question is raised whether increased spontaneous activity of arteries reported to accompany DOC hypertension is the consequence of a membrane in transition from tonic to phasic behavior.


Mechanisms by which smooth muscle sensitivity may be altered by calcium. 6-Hydroxydopamine (6-OHDA) increased the sensitivity of rat, rabbit and guinea pig portal veins to norepinephrine (NE), methoxamine (ME), barium (Ba++) and calcium (Ca++) but not to potassium (K+). Reserpine potentiated the responses of NE, ME and Ca++ but not Ba++ or K+ in rabbit and guinea pig veins and did not alter the sensitivity of rat veins to all agonists tested. Cocaine only potentiated the NE responses of the veins and decreased the sensitivity of rabbit and guinea pig veins to K+. 6-OHDA increased 48Ca-influx in all veins whereas reserpine increased 45Ca-influx only in rabbit and guinea pig veins. Cocaine failed to increase 45Ca-influx in all veins tested. NE, ME and K+ increased 45Ca-influx in the veins from the different animals. The agonist-induced 45Ca-influx was greater in most of the supersensitive veins than in the control veins. In veins that failed to develop supersensitivity, agonist-induced 45Ca-influx did not differ from that of the control veins. It is concluded that the development of super- and subsensitivity exhibits species variation and that the alteration in Ca++ influx would be consistent with the changes in sensitivity of the venous smooth muscle.


The acute and chronic effects of cadmium on the estuarine mysid, Mysidopsis bahia. Mysids, small shrimp-like crustacea, proved to be a practical bioassay animal for investigating the effects of cadmium in seawater and may serve this purpose for other pollutants. In the laboratory under flow-through test conditions, the mysid, Mysidopsis bahia, was more sensitive to cadmium than other crustaceans tested. LC50 values were 15.5 microgram/l within 96 hrs and 11.3 microgram/l during a 17-day life cycle, whereas LC50's for other selected crustaceans were between 120 and 720 microgram/l. Results of life-cycle bioassays can aid in the establishment of water quality criteria for marine and estuarine organisms.


Metal toxicity to embryos and larvae of seven freshwater fish species--I. Cadmium. The embryos and larvae of seven freshwater fish were exposed to low concentrations of cadmium in soft water. All species were killed or their growth retarded by concentrations ranging from about 4 to 12 microgram Cd/liter. The larvae were consistently more sensitive than the embryos. The agreement between these results and those from life-cycle chronic toxicity studies indicates that embryo and larval exposures will give reliable estimates of the chronic toxicity of cadmium to additional fish species. A 60-day exposure period appears to be appropriate for determining larval sensitivity to cadmium.


A simple inexpensive method for estimating underwater weight. A description is given of a simple, inexpensive and versatile method for estimating underwater weight. The use of a portable stock tank allows the determination of % Fat by underwater weighing without requiring a swimming pool, built-in tank, or special facility. Twenty-eight college students were weighed on two separate testing sessions 24-48 hours apart. Ten trials were performed at each session. The mean of the last five trials was used in determining underwater weight. The test-retest reliability coefficient was high, r = 0.98, and most of the successive trial correlations were above 0.99. The mean % Fat for the women (N = 9) was 22.2 +/- 5.9 and for the men (N = 19) was 13.7 +/- 5.1.


Classification and radiographic features of uterine malformations: hysterosalpingographic study. A series of 13470 hysterosalpingographic investigations demonstrated congenital uterine malformations in 1160 cases (8.6%). Uterus arcuatus and uterine hypoplasia, the latter ranking as a malformation on embryological grounds, together accounted for two-thirds of the cases, uterus unicornis unicollis and uterus bicornis unicollis together for over a quarter and the others, uterine didelphys, uterus bicornis bicollis and uterus septus/subseptus, for much smaller percentages. Each malformation is described and illustrated by typical hysterosalpingograms. In addition to its decisive importance in diagnosis, hysterosalpingography it also valuable in planning surgical correction in many cases.


Ioglycamide (Biligram) studies in man. Radiological opacification of the bile duct. A comparison of a number of different methods. Intravenous cholangiography was carried out in 80 anicteric patients using ioglycamide (Biligram). Twenty patients were given a 30 ml ampoule of 35% ioglycamide as a slow hand injection over ten minutes; the remainder were given ioglycamide by one hour slow drip infusion at a rate of 2, 3, or 4 mg per kg body weight per minute. The radiological opacification of the bile duct was then assessed independently by two radiologists. There was a statistically significant difference between the bile duct opacification found in patients given either 3 or 4 mg/kg/min of ioglycamide for one hour compared with those given ioglycamide either by ten minute injection or by 2 mg/kg/min drip infusion.


Thecal deformity after lumbar myelography with iophendylate (Myodil) and meglumine iothalamate (Conray 280). A study of repeat myelograms carried out in 93 patients revealed that the incidence of thecal scarring following Conray lumbar radiculography is high (61% of all cases), and only slightly lower than that found after Myodil myelography (74%). Possible factors affecting the incidence of arachnoiditis and the radiological and clinical significance of this condition are considered.


Pneumatosis coli in non-Hodgkins lymphoma. Two patients with poorly differentiated lymphoma who developed pneumatosis coli are described. In one case, the intramural gas was associated with diffuse nodular submucosal deposits of tumour. An annular stricture due to lymphoma was the underlying aetiology of the pneumatosis coli in the second case. The pathogenesis of pneumatosis coli in the context of malignant lymphoma is discussed.


Gonad dose in cineurethrocystography.

Gonad dose in cineurethrocystography. The technical factors used for cineurethrocystography for the true lateral projection in females are given. The midline radiation dose has been measured with LiF TLD inserted into the vagina in 19 examinations. The average dose recorded was 148 mrad, the range being 50 to 306 mrad; the average number of cine frames exposed was 96. Data obtained using a Rando phantom indicated that the average ovary dose would be 30% greater than the mid-line dose since the near ovary receives a higher dose than the more distant one. The technique used for men is also given, the average gonad dose in six men being 123 mrad, range 56 to 243 mrad when simple lead foil gonad protection was used; the average number of cine frames was 107. The dose in one man without gonad protection was 1575 mrad for 112 cine frames. The results for both sexes compare favourably with those of others reported in the literature and with gonad doses recorded in typical IVP examinations.


An improved technique for interstitial radiotherapy of the tongue. An improvement of the plastic tube afterloading technique for interstitial radiotherapy of the tongue is described. This modification allows most of the work to be done outside the patient's mouth. The anchorage for the intra-oral ends of the polythene tubes is produced by transfixing then with a silk thread. This obvioates the need to form loops and simplifies afterloading. It provides a method for crossing the entire lingual end of the implant. All areas and volumes of lower jaw structures are accessible to this form of treatment. Removal of the implant, irrespective of position, is simple and rapid.


Solitary neurofibroma of the trachea.

Solitary neurofibroma of the trachea. The patient was a 60-year-old white male who, for 18 months, had complained of a substernal wheeze on exertion, exertional dyspnoea and cough, and attacks of acute respiratory distress. There was no haemoptysis or dyshpagia and he was treated for bronchial asthma until bronchoscopy revealed the tumour which had not been recognized in plain chest films. He showed no evidence of a neurofibromatosis and apart from reduction in pulmonary function tests on a PO2 of 74, his laboratory tests were negative. There was no family history of neurofibromatosis. He underwent thoracotomy and a smooth rounded pedunculated tumour, 2.5 cm in diameter, arising from the posterior wall of the trachea, 3 cm above the carina was excised. He has had no tumour recurrence.


Ultrastructure and pathogenesis of human urinary calculi. The ultrastructure of human urinary calculi was studied using scanning and transmission electron microscopy. The hydroxyapatite constituent of the stones was often present in the form of sperical aggregates of the minute apatite crystallites (1 to 10 mu in diameter). In most cases, the sperical apatite deposits consisted of concentric lamellae of crystallites. The spherical apatite deposits, described in detail for the first time in urolithiasis, were similar to those found in a variety of calcified tissues including nephrocalcinosis and malakoplakia.


Transient ureteric dilatation in neonates with imperforate anus: a report of 4 cases. In a series of 64 patients with imperforate anus, 4 were identified with ureteric dilatation without vesico-ureteric reflux. The appearance resembled that of the primary obstructive megaureter. However, since the dilation resolved spontaneously in each case, it is concluded that the condition represents a separate entity, the cause of which has not yet been elucidated.


Methyl cholanthrene and cadmium induced changes in rat prostate. Cadmium workers have been thought to be more likely to develop prostatic cancer. The present study compares the effects of cadmium on rat prostate as compared with a known carcinogen, 20 methyl cholanthrene. The various histological effects produced are discussed. Possibly the most important aspect is the stratification and primitive clear cells found in rat prostatic acini in cadmium injected rats.


Prednimustine therapy for advanced prostatic cancer. 23 patients with advanced, hormonal-resistant, prostatic cancer were treated with daily oral prednimustine--a combination of prednisolone and chlorambucil. 8 patients (35%) subjectively responded with disappearance of skeletal pain and improvement in appetite, weight and sense of well being. 3 patients had objective evidence of tumour regression. Clinical toxicity was moderate, and only occasional myelosuppression was encountered. The ease of administration and predictable toxicity of prenimustine make it a potentially useful agent, alone or in combination, for advanced prostatic cancer.


The testes after torsion.

The testes after torsion. In torsion of the testis a large proportion of testes saved by surgery develop secondary atrophy. External manual reduction may be used as a first treatment, but surgical fixation is mandatory before the patient leaves the hospital. Prophylactic fixation of the contralateral testis should always be performed as 30% of the patients will otherwise develop symptoms. The preventive operation causes no discomfort to the patient and no harm to the testis. The fertility of the torsion patients is reduced. Patients treated for unilateral testicular torsion seem to have bilateral testicular abnormality resulting in decreased spermatogenesis.


Control of bleeding after renal biopsy with epsilon-amino-caproic acid. EACA proved useful in controlling severe bleeding after renal biopsy. In 6 patients who required transfusion for prolonged or severe bleeding, haemorrhage ceased and no further transfusions were necessary after EACA therapy. No serious side-effects were encountered.


Comparison of combined and single-agent chemotherapy in non-Hodgkin's lymphoma of favourable histological type. Sixty-six untreated patients with advanced non-Hodgkin's lymphoma of favourable histological type were allocated alternately to initial treatment with cyclophosphamide, vincristine, and prednisolone or with chlorambucil. The complete remission rate was higher in the group receiving combination chemotherapy, but the overall response rate was the same for both groups. The mean duration of complete remission was the same as that of good partial remission, and was the same for both treatments. The duration of remission was influenced by histological type and extent of disease at presentation, but not age. Those who responded to the initial treatment (whether with complete or with good partial remission) survived significantly longer than did non-responders. It is concluded that neither treatment is satisfactory and that new treatment programmes are needed for patients with a favourable prognosis, especially young patients with extensive disease.


Coeliac disease and immunological disorders. Out of 314 patients with coeliac disease, 63 had associated disorders of known or suspected immunological cause (excluding aphthous stomatitis and dermatitis herpetiformis). Autoimmune diseases appeared to occur more often in patients with coeliac disease than in the normal population, 52 such diseases being found in 45 patients. Of individual disorders, diabetes mellitus, thyroid diseases, and ulcerative colitis seemed to be more common than expected. Atopy (asthma and eczema) occurred in 7% of the patients. Most of these immunological disorders developed when the patients were on normal diet. A gluten-free diet and virtually normal jejunum did not prevent their development, and the diet had little ameliorating effect on their course apart from an occasional dramatic improvement in atopic patients.


Diet and retarded growth.

Diet and retarded growth. The diets of 36 children below the third centile for height but with no organic disease were compared with the diets of a control group. In most cases retarded growth was associated with a long-continued deficiency in calorie intake. When the diets were reassessed about a year later the shortfall in calorie intake was significantly reduced. This improvement, which tended to be followed by an increase in the rate of growth in height, might have been due to alteration in the child's circumstances or improvement in the family attitudes and feeding habits or both. Advice given at the clinic is thought to have played a part in bringing these changes about.


Fluorouracil cardiotoxicity.

Fluorouracil cardiotoxicity. Our of 140 patients treated with intravenous 5-fluorouracil, four developed ischaemic chest pain within 18 hours of either the second or third dose. In three of these patients the pain recurred after subsequent doses. Predose electrocardiograms in two cases were normal. None of the four patients had a history of ischaemic heart disease, although all had received left ventricular irradiation. Although cardiotoxicity is a rare complication of fluorouracil treatment, it merits wider recognition.


Firm, patient, and process variables associated with length of stay in four diseases. Factors associated with length of stay in three London teaching hospitals during 1972 and 1975 were examined in patients treated for myocardial infarction, cerebrovascular disease, inguinal hernia without obstruction, and gall stones. Statistical analyses were carried out with multiple regressions on log lengths of stay.Increased length of stay was associated with infection in all four groups and with the seriousness of operative procedures in all but patients with cerebrovascular disease. Although age was a significant variable in patients with hernias and gall stones, it had relatively little practical effect on length of stay. Other significant variables in at least one disease were obesity, number of abnormalities in blood chemistry, administration of parenteral fluids or oxygen, or use of monitoring devices, and whether chest radiography was carried out, blood electrolytes and urea were measured, or anticoagulants were used. Patients with cerebrovascular disease who were not discharged to their own homes stayed on average more than two and a half times longer than other patients.Between a third and a half of the variance was explained by these variables and the variation among firms. The method described is reproducible in other hospital settings, and the study shows that much new information could be available routinely without mounting expensive field trials.


Psychosis in young doctors.

Psychosis in young doctors. Three young men who had serious psychotic illnesses as final-year medical students, with damaging recurrences later in two, have subsequently succeeded as clinical practitioners. One has so far completed five healthy years, the others two years each, since treatment with phenothiazines and support.


Nature, nurture, and childhood overweight. The relative importance of dietary and familial factors in determining weight in early infancy were studied in 203 5-year-old children. Their age at weaning, energy intake in infancy and at 5 years, and maternal percentage expected weight were studied in relation to their percentage expected weight. Neither the estimated energy intake in infancy nor the intake at 5 years correlated significantly with their percentage expected weight at 5 years. Overweight 5-year-olds had not been weaned earlier than normal-weight 5-year-olds. There was a significant correlation between the percentage expected weights of the mothers and those of their children at 5 years of age, although the children of overweight mothers did not have higher energy intakes than the children of underweight mothers. A familial, perhaps genetically determined, tendency to overweight seems to be more important in determining whether a child will be overweight at 5 years old than early weaning and overfeeding in infancy.


Role of Chlamydia trachomatis and HLA-B27 in sexually acquired reactive arthritis. Inflammatory arthritis, tendinitis, and fasciitis after non-specific urethritis ("sexually acquired reactive arthritis" (SARA)) was studied prospectively in 531 men with non-specific urethritis, with particular reference to the frequency of isolation of Chlamydia trachomatis and the presence of HLA-B27. Satisfactory cultures were obtained from the urethral swabs from 384 patients; and HLA typing was performed on 482, of whom 30 (6%) were HLA-B27-positive. Arthritis developed in 16 patients, and five of the 14 (36%) with satisfactory cultures were positive for C trachomatis; 135 of the patients without arthritis were also positive for C trachomatis, an identical proportion. Seven of the 15 patients (40%) with arthritis who were HLA-typed were HLA-B27-positive. Six of the 30 patients with HLA-B27 developed peripheral arthritis in contrast to only nine of the 452 patients lacking the antigen, suggesting a tenfold increase susceptibility. C trachomatis, however, was no more prevalent in cultures from HLA-B27-positive men than from the others. Thus carriage of C trachomatis is unlikely to be influenced by HLA-B27. C trachomatis may be an important pathogen in some cases of SARA but does not appear to be an exclusive trigger factor for this condition.


High incidence of vincristine-induced neuropathy in lymphomas. The incidence of vincristine-induced neuropathy was studied in 60 unselected patients, of whom 23 had lymphoma and 37 had other malignant disease. All were treated with vincristine combined with other cytotoxic agents. Fourteen of the patients with lymphoma (61%) developed neuropathy compared with five patients with leukaemia or non-lymphoid cancer (14%), even though all patients received comparable doses of vincristine. The difference between the two groups in the incidence of neuropathy was highly significant. Of the patients who developed neuropathy, 17 did so within the first three months of treatment and seven in the first month. Patients with lymphoma who are receiving vincristine should be observed carfully for symptoms and signs of neuropathy. Vincristine should be withdrawn if progressive neurotoxicity develops.


Methylmercury poisoning in Iraqi children: clinical observations over two years. The clinical features of 49 children who had eaten bread contaminated with methylmercury in rural Iraq were reviewed. Symptoms and signs relating to the nervous system--varying degrees of ataxia, weakness, and visual and sensory changes--dominated the clinical picture. The severity of poisoning was related to the blood mercury concentration, as was the degree of recovery. Follow-up over two years showed that children who had had mild or moderate poisoning slowly but steadily improved, some of them recovering normal function, though all had a residual generalized hyperreflexia. In some patients ataxia and motor weakness disappeared. Visual changes also improved, though less completely, and of 17 blind children, only five had recovered partial sight by the end of two years. Seven of the 18 children who suffered very severe poisoning were left physically and mentally incapacitated. The degree of clinical progress shown by these children was better than that shown by some other groups of patients, possibly because the poisoning was relatively acute and mercury consumption was stopped immediately after its effects had become obvious.


How obstetricians manage hypertension in pregnancy. One thousand and ninety-three obstetricians answered a questionnaire on the management of pregnant women with pre-existing hypertension and pre-eclampsia. They reported that they frequently used antihypertensive drugs (most often methyldopa and diuretics) in severe essential hypertension but tended to give sedatives in mild cases. Renal impairment was considered more important that raised blood pressure as an indication for terminating pregnancy; but even without a raised blood urea concentration over a quarter of respondents (especially the more senior obstetricians) would have considered it. The more junior obstetricians were more likely to admit the least severely affected patients to hospital. Pre-eclampsia was usually treated with bed rest and sedatives (most frequently diazepam); but the choice of drug varied with the seniority of the respondents, the more senior obstetricians tending to confine themselves to the more familial drugs. There was considerable unanimity in the replies, even though most of the treatments and practices have not been validated by controlled trials, and two-thirds of the obstetricians gave the same answers to most of the questions.


Diagnosis of pseudomembranous colitis.

Diagnosis of pseudomembranous colitis. Twenty-eight patients with histologically proved pseudomembranous colitis have been seen in one hospital since July 1975. All patients with the disease had received antibiotics, six for infections not requiring operations; the other 22 cases all occurred after major surgery. All the patients had diarrhoea; six patients also had fever with clinical signs of sepsis, and three had abdominal pain thought to be due to anastomotic dehiscence after colonic resection. Pseudomembranous colitis was associated with white blood counts over 15 000/mm3 in 17 patients and albumin concentrations of less than 30 g/1 in 18. Pseudomembranous colitis was an incidental finding at necropsy in two of six patients who had not had an operation. Of the 22 patients who had had major surgery, nine died from this complication; in all except two of these cases the diagnosis was made only at necropsy. If pseudomembranous colitis is suspected on clinical grounds or if there is an unexplained complication after colorectal surgery repeat sigmoidoscopy and testing for faecal toxins should be carried out to establish the diagnosis so that prompt supportive treatment can be given.


MVPP chemotherapy regimen for advanced Hodgkin's disease. During January 1968 to December 1972, 133 patients with advanced Hodgkin's disease (HD) were admitted to hospital for combination chemotherapy with mustine, vinblastine, procarbazine, and prednisolone (MVPP regimen). Remission rates were 76% among 49 untreated patients and 90% among 42 patients who had relapsed after radiotherapy. The corresponding five-year survival rates were 65% and 86% respectively. Provided the observed yearly mortality (6%) remains unchanged 75% of patients who had previously received no treatment or irradiation and achieved remission are expected to continue in first remission after five years. Forty-two patients had received prior chemotherapy. They had lower remission and five-year survival rates (40% and 33% respectively), and fewer than half of those achieving remission were still in first remission after five years. There were several reasons for the poor prognosis in this group, including advanced-stage disease (stage IVB), age over 40, and achievement of remission.Chemotherapy was administered on an outpatient basis. Haematological toxicity and immediate drug-related side effects were similar to those of other regimens but there was no appreciable neurotoxicity. Most deaths were due to either HD itself or complications of advanced disease. Five malignancies other than HD occurred in patients who had received both single-agent chemotherapy and radiotherapy before MVPP chemotherapy. Two patients developed osteonecrosis of the femoral heads.Combination chemotherapy has a profound effect on the prognosis of advanced HD. The MVPP regimen yields results comparable to those of other regimens but with perhaps less toxicity.


Incidence of salivary gland tumours in Scotland: accuracy of national records. Statistics on discharge diagnoses in Scotland during 1968-74 show the incidence of all tumours of major salivary glands to exceed 40/million population yearly. This is higher than in any other nationality except Canadian Eskimos. Studies in two hospitals showed that numerous errors occurred in reporting these tumours, but the figures were more likely to be too low than too high. Probably eastern Scotland at least has an unusually high incidence, although in other countries using different methods of analysis the reported figures are likely to be low. Statistics based on discharge diagnoses will continue to be neglected in research until the standard of completion of discharge diagnoses improves.


Intramuscular injections of iron compounds and oncogenesis in man. To evaluate the evidence for iron compounds as local carcinogens in man, histological material and clinical reports have been reviewed in seven of the eight published cases of tumours developing at the site of intramuscular injections. The microscopical appearances suggested benign lesions in two cases and a variety of tumours in the other five. In only two cases (a rhabdomyosarcoma and a fibrosarcoma) was the interval between injections and tumour development longer than six years. Of the remaining three tumours, one was considered to be a rather slowly growing haemangiopericytoma (with an interval of two years), one appeared to be a subcutaneous lymphoma with no evidence of having arisen in the gluteal muscles, and one was a pleomorphic sarcoma with a possible five-year interval. Sarcomas induced experimentally by iron compounds differ in being less variable in type and in containing abundant iron-containing macrophages, which were negligible in these human tumours.Although the total number of patients who have received intramuscular injections of iron compounds is not known, the present findings, in contrast to experimental work, do not support the view that such treatment carries a strong risk of tumour development.


Prevalence of hepatitis A and B infections in multiply transfused thalassaemic patients. Evidence of hepatitis B virus (HBV) and hepatitis A virus (HAV) infections was south in 148 multiply transfused patients with thalassaemia and in healthy controls (2040 for HBV and 217 for HAV). The prevalence of the HBV surface antigen or antibody to it was significantly higher in patients than in controls and increased with the number of blood transfusions. In contrast, the prevalence of antibody to HAV was significantly lower in patients than in controls and decreased with the number of blood transfusions. These results support the view that blood transfusion does not play any appreciable part in transmitting HAV. Indeed, regular blood transfusion, where donors almost all have HAV antibody, seems to give protection against infection.


Reduction of skin bacteria in theatre air with comfortable, non-woven disposable clothing for operating-theatre staff. Conventional loose-weave cotton operating garments were compared with clothing of a non-woven fabric to test their efficacy in reducing the dispersal of skin bacteria into theatre air. When men wore operating suits made of the non-woven fabric dispersal of skin bacteria was reduced by 72%. When all the operating-theatre staff wore suits and dresses of this fabric air bacterial counts during operating sessions were reduced by 55%; no reduction occurred when the fabric was worn by only the scrubbed team. The lowest levels of microbial contamination of the air in the operating theatre occurred when both the unscrubbed and scrubbed theatre staff wore clothes of non-woven fabric.


The psychological and social effects of myocardial infarction on wives. Eighty-two wives of men suffering a first myocardial infarction were interviewed while their husbands were in hospital, and again two months and a year after they went home. The wives had substantial and persistent psychological symptoms, and the husbands' illness had continuing effects on their work, leisure and social activities, and family life and marriage, their psychosocial disability being comparable to that of the patients. Measures of psychosocial adjustment before the illness and the quality of the marriage and of family life were good predictors of outcome for the wives. The women had a major role in the patients' readjustment during convalescence, and their attitudes and behaviour as well as the general quality of family life were important determinants of the rate and extent of the patients' recovery. The wives of patients with myocardial infarction should have more practical help and advice during the hospital period, and the whole family should be given advice and help throughout the convalescence.


Haemoglobin AIc concentrations after initial insulin treatment for newly discovered diabetes. Glycosylated haemoglobins AIa+Ib and AIc were measured serially in 10 consecutive cases of newly discovered non-acidotic diabetes before and after diet and insulin treatment. The average concentration of Hb AIc was 11.4% in untreated diabetics as compared with 4.3% in healthy controls. With prolonged optimal regulation of blood glucose Hb AIc slowly decreased to a mean concentration of 5.5%. The concentration of Hb AIc was significantly correlated with the fasting blood sugar value. The findings suggest that determining Hb AIc may give valuable information on the regulation of carbohydrate metabolism in the preceding one to two months and thus become an important aid to management.