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9,178,362
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Utilization of algal polysaccharides by human colonic bacteria, in axenic culture or in association with hydrogenotrophic microorganisms.
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The ability of different hydrolytic bacteria from the human colon to grow on various algal polymers (carrageenans, Palmaria palmata xylan, ulvan, desulphated ulvan and laminaran) was investigated and the interactions between Bacteroides thetaiotaomicron and H2-utilizing microorganisms (one methanogenic archaea and an acetogenic bacterium) were studied during laminaran degradation. None of the algal polysaccharides supported the growth of any of the hydrolytic species tested, except for laminaran, which allowed substantial growth of B thetaiotaomicron. This suggested that bacterial consortia were involved in algal polymer breakdown rather than one specific bacterial species. The presence of H2-utilizing microorganisms did not increase the extent of laminaran degradation by B thetaiotaomicron. Whereas the decrease in formate and H2 concentrations attested to their utilization by both hydrogenotrophic microorganisms, the large increase in acetate production observed in the coculture with acetogenic bacteria was mainly due to acetogenic fermentation of sugars released during laminaran hydrolysis.
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9,178,364
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Human placental ecto-enzymes: studies on the plasma membrane anchorage and effect of inhibitors of ATP-metabolizing enzymes.
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The human placental microvillar membrane contains several ectoenzymes, including 5'-nucleotidase, alkaline phosphatase and ATP-diphosphohydrolase (ATP-DPH), which might be involved in the extracellular metabolism of nucleotides. The type of anchorage to the plasma membrane of the two first enzymes has been shown to be via a glycosyl-phosphatidylinositol. In the present study, using an enzymatic approach, we show that the ATP-DPH should be attached to the plasma membrane through a different type of anchorage. We were also interested in the search of compounds which could interact differentially with this enzyme to be used as a tool for studying the other two hydrolytic enzymes in the presence of ATP-DPH. Here we report several inhibitors of ecto-ATPases which seem to be a useful tool for studying these three enzymes.
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9,178,363
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GAP-43 phosphorylation by PKC in rat cerebrocortical synaptosomes: effect of antidepressants.
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Recent evidence, including our previous work, indicates that changes in both c-AMP and phospholipid-dependent protein kinases (PKA and PKC) may be involved in neuroadaptive mechanisms occurring in brain after repeated administration of antidepressants. The purpose of this study was to examine the phosphorylation of a major PKC substrate involved in modulation of neurotransmitter release, GAP-43, in a synaptosomal preparation from rat cerebral cortex after repeated administration of fluxetine (FL) and desipramine (DMI). Groups of male rats were treated for 21 days with either FL (5 mg/kg/day, i.p.), DMI (10 mg/kg/day, i.p.) or vehicle (controls) and cortical synaptosomes were prepared 48 h or 24 h after the last injection. Synaptosomal membrane proteins were resolved by SDS-PAGE. Western immunoblotting and immunoprecipitation with anti-GAP-43 antibody have identified the GAP-43 protein as a single distinct band of apparent molecular weight of 56 kDa. The extent of phosphorylation of GAP-43 protein by native PKC in synaptosomes of rats treated with either FL or DMI was not significantly different from that observed in control animals. The previously observed suppression of basal PKC activity in rat cortical synaptosomes by FL and DMI treatment was thus not reflected in altered GAP-43 phosphorylation. It is thus unlikely that changes in GAP-43 phosphorylation are involved in antidepressant-induced modulation of 5-HT release.
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9,178,365
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Clinical value of cytokine antagonists in infectious complications.
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Plasma levels of antiinflammatory compounds (which counteract inflammation, cortisol, IL-1 receptor antagonist, IL-1ra; soluble IL-2 receptor, sIL-2r, soluble intercellular adhesion molecule-1, sICAM-1; interleukin-10, IL-10) were synchronously determined in a consecutive series of 25 patients with severe bacterial infections. Serum levels of cortisol, IL-1ra, sIL-2r, sICAM-1 and IL-10 were significantly higher in patients with infection compared with healthy volunteers. Bacterial infection results in the production of inflammatory and proinflammatory cytokines from macrophage/monocyte, which are thought to be involved in the pathogenesis of systemic inflammatory response syndrome (SIRS). We found that counter-inflammatory compounds can also be released during infectious insults. These results suggested that the biological activity of inflammatory mediators is inhibited by natural antiinflammatory compounds, and the body itself might down-regulate excessive inflammatory cascades through counteracting the inflammatory responses and restore homeostasis.
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9,178,366
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Potentiation of acetaminophen hepatotoxicity by acute physical exercise in rats.
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Effects of acute physical exercise on the acetaminophen-induced hepatotoxicity were examined in adult female rats. Rats were forced to move at a speed of 10 m/min for 2 hr in a rotating cage. Immediately following the exercise bout rats were treated with acetaminophen (APAP; 700 mg/kg, i.p.). The physical exercise enhanced the hepatotoxicity of APAP as shown by increases in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities measured 24 hr following the treatment. A significant decrease in hepatic glutathione (GSH) was observed in the rats forced to exercise suggesting that the enhancement of APAP hepatotoxicity was associated with the depression of this endogenous tripeptide. The role of adrenergic stimulation in the exercise-induced hepatic GSH depression was examined by pretreating the animals with a receptor specific adrenergic antagonist, such as prazosin HCl (15 mg/kg, i.p.), propranolol HCl (15 mg/kg, i.p.), and yohimbine HCl (15 mg/kg, i.p.) 15 min prior to the exercise bout, but neither of the antagonists prevented the GSH depression. Administration of alpha-tocopherol acetate (450 mg/kg/day for 3 days and 150 mg/kg on day 4, i.p.) did not affect the exercise-induced GSH depression or lipid peroxidation in liver homogenates as determined by increases in malondialdehyde formation. These results suggest that neither adrenergic stimulation nor oxidative stress plays a significant role in the enhancement of APAP hepatotoxicity and hepatic GSH depression induced by acute physical exercise.
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9,178,367
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Bilobalide, a constituent of Ginkgo biloba L., potentiates drug-metabolizing enzyme activities in mice: possible mechanism for anticonvulsant activity against 4-O-methylpyridoxine-induced convulsions.
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Anticonvulsant effects of bilobalide, one of the constituents of Ginkgo biloba L., on the convulsions induced by 4-O-methylpyridoxine (MPN) were investigated in mice. Bilobalide reduced the duration and incidence of MPN-induced convulsions depending on its dose and the period of treatment. In addition, the anticonvulsant effect was manifested more than 24 hours after treatment and the effect lasted for 7 days after its withdrawal. In mice treated with bilobalide (30 mg/kg, p.o., once a day for 4 days), hepatic 7-methoxycoumarin O-demethylase activity was potentiated, and the disappearance of MPN in blood after MPN injection was faster than in controls. From these results, it is assumed that the anticonvulsant effect of bilobalide against convulsions induced by MPN partly involves modulation of hepatic drug-metabolizing enzyme activity, which leads to accelerated elimination of MPN.
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9,178,369
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Proinflammatory cytokines downregulate gene expression and activity of constitutive nitric oxide synthase in porcine pulmonary artery endothelial cells.
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We evaluated the effects of cytokines on the catalytic activity and expression of porcine pulmonary artery endothelial cell (PAEC) constitutive (eNOS) and inducible (iNOS) isoforms of nitric oxide synthase (NOS). Exposure of PAEC to the combination of IFN-gamma, TNF-alpha, and IL-1 beta did not alter iNOS activity in cytosolic and membrane fractions but significantly (p < 0.01) reduced eNOS activity in the membrane fraction, but not in the cytosolic fraction, after a 24-h exposure. The cytokine-induced loss of membrane fraction eNOS activity was associated with significant reductions of eNOS mRNA and protein content (p < 0.01 for both). Treatment with the protein synthesis inhibitor, cycloheximide, but not the transcriptional inhibitor actinomycin D prevented cytokine-induced reduction of eNOS mRNA expression. These results suggest that cytokine-induced loss of catalytic activity of eNOS is associated with a reduction in eNOS mRNA and protein mass and that cytokines alter eNOS mRNA stability. Inhibition of protein synthesis prevented reduction of eNOS mRNA by cytokines, suggesting that the mechanism by which cytokines alter eNOS mRNA stability involves protein synthesis.
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9,178,368
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Endothelial dysfunction in the perfused kidney from the streptozotocin-induced diabetic rat.
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The vasodilator effects of acetylcholine were examined in methoxamine-preconstricted perfused kidneys taken from rats with streptozotocin (STZ)-induced diabetes. Acetylcholine-dependent vasodilatation was significantly weaker in STZ-induced diabetic rats than in age-matched controls, and it was completely abolished by treatment with 60 mM K+ plus NG-nitro-L-arginine (L-NNA) plus methylene blue in the control rats and was significantly but not completely inhibited by these treatment in the diabetic rats. Although acetylcholine-induced vasodilation was not affected by indomethacin in control rats, it was attenuated by indomethacin in the diabetic rats. Arachidonic acid-induced vasoconstriction was slightly but significantly increased in the diabetic rats. Acetylcholine increased significantly the level of 6-keto-prostaglandin F1 alpha in the effluent from perfused kidneys from diabetic rats. These results suggest that the endothelium-dependent vasodilatation induced by acetylcholine in the renal vascular bed of age-matched control rats is due to the release of nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF), whereas the vasodilatation induced by acetylcholine in the STZ-diabetic kidney also involves prostaglandin I2 as well as NO and EDHF.
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9,178,371
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Metabolism of tacrolimus (FK 506) in rat liver microsomes. Effect of rifampin and dexamethasone.
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The in vitro metabolism of tacrolimus (TAC, FK 506) was investigated in the liver microsomes prepared from normal rats as well as rats treated with dexamethasone (DEX) and rifampin (RIF). The rate of tacrolimus metabolism was similar in control and RIF treated rat liver microsomes, whereas it significantly increased in microsomes obtained from dexamethasone treated rats. Seven different possible metabolites were identified in the microsomal preparations from rats treated with rifampin or dexamethasone whereas the microsomes from the control rats failed to produce the mono-demethylated and monohydroxylated metabolite of TAC (TAC+2, m/z = 805.5). There was an apparent difference in the amount of individual metabolites formed in different groups. This indicates quantitative differences in the induction of cytochrome P450 3A, an enzyme sub family known to be primarily responsible for tacrolimus metabolism. Lack of induction of tacrolimus metabolism by rifampin can be attributed to the lack of effect of rifampin in inducing cytochrome P450 3A in rats.
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9,178,370
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The Na+/K+ATPase mediates the alpha 1-adrenoceptor stimulated increase in 86Rb(+)-uptake in isolated ventricular cardiomyocytes from adult rat heart.
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The aim of the present study was to identify the mechanism(s) responsible for the alpha 1-adrenoceptor stimulated increase in potassium uptake in ventricular cardiomyocytes isolated from adult rat heart. The Na+/K+ATPase blocker ouabain the Na+/K+/2Cl(-)-cotransporter blocker bumetanide, the Na+/H(+)-exchanger blocker HOE 694 and the potassium channel blocker 4-aminopyridine were used as experimental tools. 86Rb+ was used as potassium analogue. The basal 86Rb(+)-uptake rate was 0.25 +/- 0.01 ml/g protein x min. Maximal alpha 1-adrenoceptor stimulation increased the 86Rb(+)-uptake 38 +/- 2%. Ouabain dose dependently eliminated the alpha 1-adrenoceptor stimulated response with a -logIC50-value of 3.64 +/- 0.23. Bumetanide did not affect the stimulated response, and there was no effect of bumetanide on the ouabain sensitive component. HOE 694 and 4-aminopyridine had no effect on the stimulated 86Rb(+)-uptake. Ouabain and HOE 694 also dose dependently inhibited a portion of the basal 86Rb(+)-uptake (about 60% and 20%, respectively), but there was no effect of bumetanide or 4-aminopyridine on the basal 86Rb(+)-uptake. The results show that the Na+/K+ATPase alone mediates the alpah 1-adrenoceptor stimulated increase in potassium uptake in this preparation of ventricular cardiomyocytes isolated from adult rat heart.
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9,178,372
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Lack of long-term facilitation of ventilation after exposure to hypoxia in goats.
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Episodic hypoxia has been shown to induce augmented normoxic ventilatory drive or long-term facilitation (LTF, continued hyperventilation after termination of hypoxic stimulation) in awake dogs and awake goats. The main objective of these experiments was to examine whether continuous isocapnic hypoxia in awake goats elicits LTF and additionally, to determine if goats exhibit hypoxic ventilatory decline (roll-off) during the hypoxic exposure. Goats were exposed to either 4 h of isocapnic hypoxia (n = 10) or 30 min of isocapnic hypoxia (n = 7). Ventilation (VE), tidal volume and frequency were measured before, during and following the end of the isocapnic hypoxia (PaO2 40 Torr) exposure. During the 4 h period of hypoxia, VE increased in a time-dependent manner in a typical pattern of acclimatization, reaching a mean of 40.8 +/- 3.6 L/min at the end of 4 h. Five minutes after return to normoxia, VE was 13.0 +/- 0.8 L/min, not different than control VE (13.1 +/- 0.9 L/min) measured prior to the hypoxic exposure and remained unchanged from this value for another 30 min. During the 30 min hypoxic exposure, VE increased upon exposure to hypoxia, remained significantly elevated throughout the hypoxic exposure, but promptly returned to control levels upon return to normoxia. These results indicate that continuous isocapnic hypoxia elicits neither long term facilitation of ventilation nor hypoxic ventilatory decline in awake goats.
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9,178,373
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Passive constriction of the upper airway during central apneas: fiberoptic and EMG investigations.
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We studied five adult male patients with central sleep apnea syndrome (> 75% of the monitored events being central) during sleep using a fiberoptic scope and EMG monitoring of the superior and middle constrictors of the pharynx and the genioglossus and geniohyoid muscles. The fiberoptic investigation revealed a spontaneous decrease in the size of the airway during central apneas, without negative intrathoracic pressure or activation of the superior and middle pharyngeal constrictor muscles. We found a mean maximum decrease of 71 +/- 7% in the cross-sectional area of the airway and an absence of superior-middle pharyngeal constrictor EMG discharge. We did not observe any complete collapses of the airway.
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9,178,374
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Cardiorespiratory effects of L-glutamate microinjected into the rat ventral medulla.
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We investigated the cardiorespiratory effects elicited by microinjections of L-glutamate (L-glu, 25 nmol, 200 nl) at various sites in the ventral medulla (VMS) of urethane-anesthetized rats. The results demonstrated that regions responsive to the drug are located along a column in the VMS extending from the VI cranial nerve to the first cervical nerve in the caudal medulla. Within this column three breathing patterns were elicited from four distinct areas. In the most rostral and caudal portion of this hypothetical column, the breathing patterns observed in response to L-glu were similar and characterized by increases in minute ventilation, tidal volume, inspiratory drive, respiratory frequency, mean arterial blood pressure (MAP) and heart rate (HR). In the regions located between the areas described above two different breathing patterns were obtained without significant changes in MAP or HR. These patterns were characterized by decreases and increases in the respiratory indices analyzed, with the exception of respiratory frequency, which decreased in both regions. These results suggest that within the VMS discrete areas may act as functional units modulating cardiorespiratory responses while in others these functions are spatially segregated.
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9,178,375
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gamma-Aminobutyric acid contributes to modulation of cardiorespiratory control after chronic ventilatory loading.
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Diseases imposing chronic ventilatory loads may depress ventilation and cause chronic hypercapnia. This may be a result of mechanical loading imposed on pre-existing decreased respiratory drive or functional alteration of neural circuits involved in ventilatory control. To evaluate these possibilities, chronic resistive airway loading was imposed in rats via a circumferential tracheal band which tripled tracheal resistance (obstructed group). Sham surgery was performed in controls. After 8 weeks, animals were anesthetized (urethane) and tracheostomy performed relieving increased tracheal resistance. The ventral medullary surface (VMS) was exposed and the intermediate area (IA) identified. The integrated diaphragm EMG (EMGDI) was recorded. The obstructed group was hypercapnic while controls were eucapnic (PCO2, 45.1 +/- 7.9 vs. 37.6 +/- 3.4 Torr; P < 0.001). Respiratory rate (RR) remained lower in obstructed than in control animals despite relief of the resistive load by tracheostomy (58.5 +/- 5.1 vs. 75.4 +/- 5.4 bpm; P < 0.05). Application of 1 mM bicuculline soaked pledgets (BIC) to the IA of the VMS significantly increased EMGDI in obstructed but not in control animals (27.5 +/- 5.5 vs. 5.2 +/- 4.4%; P < 0.006). RR was unaffected. Mean arterial pressure increased with BIC in obstructed but not control animals (23.0 +/- 6.5 vs. 4.5 +/- 3.5%; P < 0.02). These data suggest that alteration of cardiorespiratory control occurs during chronic resistive hypercapnic loading and that GABAergic neurons in the VMS participate in this adaptive response.
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9,178,376
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Contribution of vagal afferents to breathing pattern in rats with lung fibrosis.
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In anesthestized male Wistar rats with bleomycin-induced lung fibrosis we examined the influence of lung vagal non-myelinated and myelinated afferents in setting breathing pattern. Fourteen days after intratracheal instillation of bleomycin, lung compliance, total lung capacity (TLC) and inspiratory capacity were reduced while functional residual capacity and residual volume were increased. Baseline tidal volume (VT) was decreased and frequency (fR) increased in the bleomycin treated rats compared with controls. Selective vagal C-fiber blockade did not affect fR or VT in any group. Vagotomy resulted in an increase in VT and decrease in fR in both groups with the percent increase in VT/TLC and decrease in fR being significantly greater in the bleomycin rats compared with controls. Vagotomy also attenuated the significantly elevated PCO2 in the bleomycin treated rats suggesting that bleomycin-induced alterations in breathing pattern contribute to blood gas abnormalities. We conclude that vagal myelinated afferents contribute to the rapid shallow breathing in bleomycin treated rats.
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9,178,377
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Morphological determinants of peripheral lung mechanical changes induced by capsaicin.
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We studied the morphological elements associated with airway and pulmonary tissue responses to capsaicin in mechanically ventilated guinea pigs. Lungs were excised and frozen in liquid nitrogen 3 and 20 min after capsaicin infusion (1 or 100 micrograms/kg i.v.). Using image analysis, we obtained contraction index (CI) and peribronchial edema area (CUFF) for both central (C) and peripheral airways (P). We also assessed alveolar size (mean linear intercepts, Lm) and tissue distortion (standard deviation of the number of intercepts, SDI). Multiple regression analysis showed significant associations between pulmonary tissue resistance (Rti) and CUFFP (p < 0.001); pulmonary dynamic elastance and SDI (p = 0.002); and airway resistance and CUFFC (p < 0.0001). Our results suggest that increases in Rti observed in guinea pigs after capsaicin infusion are primarily dependent on changes in the small airways, mainly peribronchiolar edema; the increase in lung elastance is related to distortion of parenchymal tissues; and large airway edema contributes significantly to airway resistance.
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9,178,378
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Respiratory mechanics after chronic diethylcarbamazine.
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This study was performed to evaluate the role of diethylcarbamazine (DEC), the drug of choice for treating Lymphatic Filariasis and Tropical Pulmonary Eosinophilia, on respiratory mechanics of higid rats. Thus, during 30 days two groups of six rats each received intraperitoneally either isotonic saline solution, or 12 mg/kg per day of DEC. Thereafter, they were sedated, anesthetized, paralysed and mechanical ventilation followed. After airway occlusion at end inspiration, respiratory system, pulmonary and chest wall resistive pressures (delta P1,rs, delta P1,L, and delta P1,w, respectively) and viscoelastic/inhomogeneous pressures (delta P2,rs, delta P2,L and delta P2,w, respectively) were determined in each group. Total delta pressures (delta Ptot) were calculated as the sum of delta P1 and delta P2, yielding the values of delta Ptot,rs, delta Ptot,L, and delta Ptot,w, respectively. Respiratory system, lung and chest wall static (Est,rs, Est,L, and Est,w, respectively) and dynamic elastances (Edyn,rs, Edyn,L, and Edyn,w, respectively), and the corresponding delta elastances (calculated as Edyn-Est) were also obtained. DEC therapy significantly decreased delta Ptot,rs, delta P tot,L, delta P2,rs, delta P2,L, Est,ts, Est,L, delta Ers and delta EL, in relation to the respective control values. It can be concluded that DEC decreases respiratory system impedance, being potentially useful for allowing airway dilation at the lung periphery.
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9,178,379
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Oxygen transport with oscillations of inspired oxygen concentration.
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A theoretical model predicts that forced inspiratory oxygen concentration oscillations can be used to recover cardiorespiratory data and elicit information about the oxygen transport system (Hahn, 1996). The effects of hypoxia on the penetration of these generated oxygen oscillations into arterial and venous blood were explored in dogs exposed to a graded severity of hypoxia. Continuously recorded sinusoidal oxygen oscillations in the respired partial pressure, blood tension and mixed-venous saturation show that the transmission of forced oxygen oscillations from the lungs to the arterial blood depends on the mean arterial saturation. When mean inspired oxygen is high enough to fully saturate arterial haemoglobin, an inspired oscillation can only be transmitted in the blood as an oscillation in oxygen tension. However, in the presence of arterial hypoxaemia, oscillations in both the oxygen saturation and partial pressure of arterial blood are observed. Under these conditions, the oxygen saturation and partial pressure oscillations are also transmitted to mixed-venous blood. Our data illustrates that the link between the arterial and mixed-venous oscillations is non-linear and dependent on the sigmoidal binding relationship between oxygen and haemoglobin.
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9,178,380
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A reconciliation of continuous and tidal ventilation gas exchange models.
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Continuous-ventilation mathematical gas exchange models are widely used since their analytical equations are amenable to physiological interpretation. They describe qualitatively the respiratory system's response to changing physiological conditions, but do not calculate accurate values for respiratory parameters when experimental tidal ventilation expired gas data are inserted into their analytical expressions. A simple mathematical expression is presented to reconcile continuous and tidal ventilation gas exchange models. Tidal ventilation experimental data can then be inserted into conventional continuous ventilation equations to produce more accurate measures of lung volume. This hypothesis is tested with controlled experimental tidal ventilation tracer gas data obtained from both wash-out and forced inspired sinusoid experiments, using a mechanical lung model with known volume; tidal volume, VT; and series 'airway' dead space VD. We show that the subtraction of 1/2 (VT + VD) from the lung volume calculated from the continuous ventilation theory can produce lung volume measurements which agree with the true lung volume to within +/-5%, for physiological lung volume values, for both wash-out and forced sinusoid techniques.
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9,178,381
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CPR training without an instructor: development and evaluation of a video self-instructional system for effective performance of cardiopulmonary resuscitation.
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Traditional classroom-based instruction of cardiopulmonary resuscitation (CPR) has failed to achieve desired rates of bystander CPR. Video self-instruction (VSI) is a more accessible alternative to traditional classroom instruction (TRAD), and it achieves better CPR skill performance. VSI employs a 34-min training tape and an inexpensive manikin. VSI combines simplified and reordered content focusing on the delivery of one-rescuer CPR with the 'practice-as-you-watch' approach of an exercise video. Performance of CPR skills immediately following VSI was compared to performance immediately following TRAD using an instrumented manikin, a valid and reliable skill checklist, and an overall competency rating. Compared with TRAD subjects, VSI subjects performed more compressions correctly (P < 0.001), more ventilations correctly (P < 0.001), and more assessment and sequence skills correctly (P < 0.001). TRAD subjects delivered twice as many compressions that were too shallow, and underinflated the lungs twice as often. VSI subjects were rated 'competent' or better 80.0% of the time, compared with TRAD subjects, who achieved this rating only 45.1% of the time (P < 0.001). TRAD subjects were rated to be 'not competent' in performing CPR nearly 10 times more often than VSI subjects (P < 0.001). Subjects 40 years of age and older performed better after VSI than after TRAD. Superior skill performance among subjects exposed to VSI persisted 60 days following training. VSI has the potential to reach individuals unlikely to participate in TRAD classes because of its greater convenience, lower cost, and training in about 0.50 h compared with 3-4 h for TRAD classes.
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9,178,382
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Improving cardiopulmonary resuscitation skills retention: effect of two checklists designed to prompt correct performance.
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Previous research has shown that regardless of an individual's experience, life support skills such as cardiopulmonary resuscitation (CPR) are poorly performed as soon as 1 month following training. The purpose of this study was to compare the effects of two checklists designed to prompt correct CPR performance. We compared the performance of 169 undergraduate students, at the time of course assessment, with retention testing that occurred 2 months following the course assessment. Students were randomly assigned to a control group, a short version of a CPR checklist and a longer more detailed version. Two groups of variables were created: procedural and compression-ventilation variables. In addition, an overall-performance variable was created, summarizing performance on the procedural variables. Binary variables were assessed with chi 2-tests of independence. One-way ANOVAs, using 'group' as the between-subjects factor, were used to assess each continuous variable. Comparisons between groups yielded significant differences of P < 0.05. The long checklist generally led to superior performance on the procedural variables. The results support the hypothesis that remembering the steps of CPR is too complex for some. Though preliminary, the findings of this study indicate that the detailed checklist was an effective strategy to improve the post-course performance of CPR.
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9,178,383
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Outcome of out-of-hospital cardiorespiratory arrest in south Glamorgan.
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During 138 weeks an emergency medical service (EMS) of mixed skill-level attempted to resuscitate 954 patients from prehospital cardiac arrest (883 attempts per million population per year); 75% of the arrests were of cardiac cause. This paper is one of the first analyses from europe to use the 'Utstein template' to report outcomes of such arrests. In cases where an arrest rhythm could be recorded, 38.4% were ventricular fibrillation (VF), 45.5% were asystolic, and the remainder were either electromechanical dissociation or respiratory arrests. Using univariate analysis factors associated with a greater likelihood of survival include the presence of a witness, bystander-initiated cardiopulmonary resuscitation (CPR), early CPR and VF as the arrest rhythm. Twenty of 155 cases (13%) survived where VF arrest was witnessed by non-EMS personnel.
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9,178,384
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Quality of mechanical, manual standard and active compression-decompression CPR on the arrest site and during transport in a manikin model.
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The quality of mechanical CPR (M-CPR) was compared with manual standard CPR (S-CPR) and active compression-decompression CPR (ACD-CPR) performed by paramedics on the site of a cardiac arrest and during manual and ambulance transport. Each technique was performed 12 times on manikins using teams from a group of 12 paramedic students with good clinical CPR experience using a random cross-over design. Except for some lost ventilations the CPR effort using the mechanical device adhered to the European Resuscitation Council guidelines, with an added time requirement of median 40 s for attaching the device compared with manual standard CPR. Throughout the study, in comparison with mechanical CPR the quality of CPR with either manual method was significantly worse. In particular, there were considerable individual variations during stretcher transport. With S-CPR and ACD-CPR the median compression times were 38 and 31%, significantly lower than the recommended 50%, and 46-98% of the decompression efforts with ACD-CPR were too weak, particularly during transport on the stairs. With both manual methods, there were no significant differences in the CPR effort between the site of the arrest and the ambulance transport. However, compression rates were reduced and became more erratic during stretcher transport to the ambulance. When walking horizontally, a median of 19% of S-CPR compressions and 84% of ACD-CPR compressions were to weak. On the stairs, 68% of S-CPR compressions and 100% of ACD-CPR compressions were too weak. In conclusion, when evaluated on a manikin, in comparison with manual standard and ACD-CPR, mechanical CPR adhered more closely to ERC guidelines. This was particularly true when performing CPR during transport on a stretcher.
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9,178,385
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Combined epicardial-transthoracic electrode paddle placement: a method for defibrillation during open-chest cardiac resuscitation.
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We present a case of open-chest cardiac massage where ventricular fibrillation developed and a direct current shock was required. In the absence of 'surgical' electrode paddles, standard paddle electrodes were used; one small electrode was placed directly on the exposed epicardial surface and the second electrode was placed on the lateral chest wall. Defibrillation was achieved with a 100 J shock. This combined epicardial-transthoracic electrode paddle placement technique allows defibrillation to be accomplished when open chest cardiac massage is being performed and no 'surgical' electrode paddles are available.
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9,178,386
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Open-chest cardiac massage without major thoracotomy: metabolic indicators of coronary and cerebral perfusion.
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To compare the coronary and cerebral perfusion achieved using a novel method of minimally-invasive, direct cardiac massage to that obtained using bimanual, open-chest cardiac massage.
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9,178,387
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High dose naloxone does not improve cerebral or myocardial blood flow during cardiopulmonary resuscitation in pigs.
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In a prospective, randomized, placebo-controlled, double-blind trial we tested the hypothesis that naloxone given during cardiopulmonary resuscitation (CPR) enhances cerebral and myocardial blood flow. Twenty-one anesthetized, normoventilated pigs were instrumented for measurements of right atrial and aortic pressures, and regional organ blood flow (radiolabeled microspheres). After 5 min of untreated fibrillatory arrest, CPR was commenced using a pneumatic chest compressor/ventilator. With onset of CPR, an i.v. bolus of 40 micrograms/kg b.w. of epinephrine was given, followed by an infusion of 0.4 micrograms/kg per min. After 5 min of CPR, either naloxone, 10 mg/kg b.w. (group N, n = 11) or normal saline (group S, n = 10) was given i.v. Prior to, and after 1, 15, and 30 min of CPR, hemodynamic and blood flow measurements were obtained. After 30 min of CPR, mean arterial pressure was significantly higher in group N (26 +/- 5 vs. 13 +/- 3 mmHg, P < 0.05). Groups did not differ with respect to myocardial perfusion pressure or arterial blood gases at any time during the observation period. Regional brain and heart blood flows were not different between N and S at any point of measurement. We conclude that high-dose naloxone does not augment cerebral or myocardial blood flow during prolonged closed-chest CPR.
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9,178,388
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The relationship between airway carbon dioxide excretion and cardiac output during cardiopulmonary resuscitation.
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There is currently no practical method for determining cardiopulmonary resuscitation (CPR) efficacy in the field. We investigated the relationship between the volume of carbon dioxide (CO2) excreted in the airway (CO2EX) when tidal volume and respiratory rate are controlled, and cardiac output (CO), an indicator of CPR efficacy, to determine the potential of CO2EX as a practical noninvasive field monitor of CPR efficacy. Thirteen mongrel dogs were anesthetized, instrumented and ventilated 13 times/min at a fixed tidal volume with an infrared airway CO2 sensor. CO2EX = (PCO2/bar. press) x (tidal vol) x (breaths/min), and expressed in ml/min per kg. Sequences of control, CPR with 3-4 different compression forces, and recovery measurements were recorded 10-15 times/animal. CO2EX and CO fell simultaneously with ventricular fibrillation. CPR immediately increased CO2EX and CO. Both changed consistently and in the same direction as compression force. Return of spontaneous circulation immediately increased CO2EX and CO above controls, with a gradual return to control levels. CO2EX was always below 8 ml-CO2/min/kg during CPR and above this during spontaneous circulation. With alveolar ventilation controlled, CO2 movement is regulated by CO, CO distribution and CO2 stores shifts. Normally, CO accounts for 15% of CO2EX variability. In this study CO accounted for > or = 65% of CO2EX variability during CPR, indicating CO2EX changes were primarily due to CO changes. When ventilation is controlled, CO2EX during CPR reliably tracks changes in CO. Therefore, CO2EX may provide a practical noninvasive method of determining CPR efficacy as the CPR is being performed.
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9,178,390
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Future directions for resuscitation research. V. Ultra-advanced life support.
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Standard external cardiopulmonary resuscitation (SECPR) frequently produces very low perfusion pressures, which are inadequate to achieve restoration of spontaneous circulation (ROSC) and intact survival, particularly when the heart is diseased. Ultra-advanced life support (UALS) techniques may allow support of vital organ systems until either the heart recovers or cardiac repair or replacement is performed. Closed-chest emergency cardiopulmonary bypass (CPB) provides control of blood flow, pressure, composition and temperature, but has so far been applied relatively late. This additional low-flow time may preclude conscious survival. An easy, quick method for vessel access and a small preprimed system that could be taken into the field are needed. Open-chest CPR (OCCPR) is physiologically superior to SECPR, but has also been initiated too late in prior studies. Its application in the field has recently proven feasible. Variations of OCCPR, which deserve clinical trials inside and outside hospitals, include 'minimally invasive direct cardiac massage' (MIDCM), using a pocket-size plunger-like device inserted via a small incision and 'direct mechanical ventricular actuation' (DMVA), using a machine that pneumatically drives a cup placed around the heart. Other novel UALS approaches for further research include the use of an aortic balloon catheter to improve coronary and cerebral blood flow during SECPR, aortic flush techniques and a double-balloon aortic catheter that could allow separate perfusion (and cooling) of the heart, brain and viscera for optimal resuscitation of each. Decision-making, initiation of UALS methods and diagnostic evaluations must be rapid to maximize the potential for ROSC and facilitate decision-making regarding long-term circulatory support versus withdrawal of life support for hopeless cases. Research and development of UALS techniques needs to be coordinated with cerebral resuscitation research.
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9,178,389
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Effects of manual high-impulse CPR on myocardial perfusion during cardiac arrest in pigs.
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The aim of the study was to compare the effect of a 30 and 50% duty cycle on coronary perfusion pressure (CPP) and end tidal carbon dioxide (ETCO2) and to determine whether a duty cycle of 30% can be achieved manually. After 3 min of ventricular fibrillation cardiac arrest, pigs were resuscitated in two groups with changing duty cycles every 3 min: group A starting with 50 and then 30%; and group B starting with 30 and then 50%. After administration of epinephrine, duty cycles in group A were 50 and then 30%, in group B initially 30% and then 50% Before administration of epinephrine, no significant differences in CPP between the 30 and 50% duty cycles were found; after epinephrine CPP increased with both duty cycles. ETCO2 did not vary before epinephrine; after epinephrine, there were statistically significant differences but there is doubt regarding the clinical relevance of these differences. Survival was 4/6 in group A and 3/5 in group B (NS). It is possible to perform a manual duty cycle of 30%. However, our data do not support the use of a 30% duty cycle during cardiopulmonary resuscitation (CPR).
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9,178,393
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Arthroscopy-assisted synovectomy in the treatment of chronic synovitis of the knee.
|
The place of arthroscopy-assisted synovectomy in the treatment of inflammatory synovitis of the knee was evaluated by studying 26 patients who underwent this procedure between November 1992 and September 1995. Half the patients had rheumatoid arthritis. Twenty-three patients (28 knees) were reevaluated after a mean follow-up of 32 months (range, 4-50 months). The arthroscopic synovectomy was done either as the first-line synovectomy procedure, after failure of triamcinolone hexacetonide injection into the joint, or as the second-line synovectomy procedure, after failure of osmic acid or yttrium-90 synovectomy. Except in one patient with severe arthritis, arthroscopic synovectomy produced statistically significant improvements regarding pain (visual scale), function (Lequesne's index), range of flexion, amount of joint fluid and knee circumference. The range of extension of the knee was normal at baseline and remained so after the procedure. Overall efficacy was similar for first-line and second-line procedures. Results were rated good to very good by 71% of the patients and 61% of the physicians overall and the overall improvement in knee arthritis as perceived by the patients was 60%. The procedure was well tolerated in 93% of cases. The mean time needed to achieve a stable improvement was 3.2 weeks for pain, 4.7 weeks for swelling and 3.6 weeks for range of motion. One case each of hemarthrosis and stiffness of the knee were recorded, with a full recovery in both cases. Arthroscopic synovectomy is effective and safe but more burdensome and expensive than osmic acid or radiation synovectomy, and consequently deserves a place of choice in patients who have failed to respond to either of the last two methods.
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9,178,394
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Inflammatory joint disease after immunizations. A report of two cases.
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Serious adverse effects of immunizations are uncommon. The hepatitis B vaccine has been implicated in a few dozen cases of extraarticular, systemic, or inflammatory joint disorders. We report two cases in which hepatitis A vaccination (Havrix, Smith Kline Beecham) was followed by a connective tissue disorder or a spondylarthropathy in two healthy males aged 50 and 24 years, respectively. Both patients were HLA B27-negative but carried the HLA DR1 and/or DR4 antigen. The outcome was favorable after treatment with a corticosteroid or a nonsteroidal antiinflammatory agent. The pathophysiology of immunization-related rheumatic disorders may involve circulating immune complexes and/or a mechanism similar to that seen in reactive arthritis, i.e., a genetically-determined susceptibility to the bacterial or viral antigens contained in vaccines.
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9,178,395
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Polyostotic Paget's disease. A search for lesions of different durations and for new lesions.
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We conducted a medical record-based study of 169 patients with polyostotic involvement identified among 200 Paget's disease patients. Follow-up was 15 to 41 years in 31 cases. The pelvis was the only bone that was more likely than not to be involved bilaterally. All the other paired bones were more likely to be involved unilaterally and when both sides were involved the two lesions were very often frankly asymmetric. In a given patient, the duration of the various pagetic lesions, estimated from their size and from data provided by an earlier study on the rate of progression of pagetic lesions, was similar in some cases and showed marked differences in others. Aggregation of the lesions into two or three disease duration groups was seen in some patients, suggesting that Paget's disease may occur in two or three waves. When we reviewed the radiographs from 30 patients with a mean follow-up of 23 years, we found new lesions in ten patients. However, a review of bone scans from 18 patients with a mean follow-up of 11 years failed to uncover any firm evidence of new lesion development, perhaps because all these patients received bisphosphonate therapy (etidronate, tiludronate, pamidronate). We also found data suggesting that the disease process spread across a joint in some patients, even in the absence of degenerative joint disease. In particular, in several cases an extensive pagetic lesion was seen on one side of a joint and a considerably smaller lesion on the other side.
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9,178,396
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Hip axis length measurement using dual-energy X-ray absorptiometry.
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Hip axis length (HAL) has been reported, in the United States, to influence the risk of hip fractures independently from age and proximal femoral bone mineral density. Last-generation dual-energy X-ray absorptiometry units can perform automatic hip axis length measurements. The present study was designed to evaluate the feasibility of this measurement in clinical practice and to establish the range of normal values obtained in French women using single- and fan-beam absorptiometry. Short-term reproducibility determined by performing two measurements with repositioning in 50 women was 1.67%. Long-term reproducibility calculated based on five measurements taken at six-month intervals in 60 women was 1.5%. No statistically significant differences were found between hip axis length on the right and left sides in 50 women. Mean values calculated based on measurements in 190 women aged 54 +/- 12 years (single-beam absorptiometry) and in 50 women aged 80 +/- 5 years (fan-beam absorptiometry) were 10.4 +/- 0.6 cm and 11.5 +/- 0.7 cm, respectively. Hip axis length was correlated with height but not with age or femoral neck bone mineral density. Our data are consistent with studies conducted in the United States. The interpretation of hip axis length measurements requires knowledge of the type of X-ray beam used (single or fan-shaped). Whether hip axis length predicts the hip fracture risk in Europeans remains to be demonstrated.
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9,178,397
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Bone mineral density in patients given oral vitamin K antagonists.
|
Divergent results have been obtained in studies of bone mineral density in patients under oral vitamin K antagonists.
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9,178,399
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Efficacy of misoprostol in the prophylaxis of gastroduodenal lesions induced by short-term nonsteroidal antiinflammatory drug therapy in elderly patients. A multicenter double-blind, placebo-controlled trial.
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Advanced age is an established risk factor for gastrointestinal toxicity of nonsteroidal antiinflammatory drugs, and the duration of use of these agents in elderly patients should be kept as short as possible. A multicenter, double-blind, placebo-controlled trial was conducted to evaluate the efficacy of misoprostol in preventing gastrointestinal toxicity in elderly patients (> or = 65 years) given nonsteroidal antiinflammatory agents for no more than ten days. Patients who were to receive a nonsteroidal antiinflammatory agent for ten days to treat an acute rheumatic condition were randomly allocated to treatment with either a placebo or misoprostol in a dose of 200 micrograms bid. The primary efficacy criterion was the result of a gastroduodenal endoscopic evaluation done on day 10. The outcome of the rheumatic condition, changes in serum creatinine levels, and clinical safety were also evaluated. The study population included 208 subjects with a mean age of 81.4 +/- 6.4 years, of whom 81.3% were women. The misoprostol group (n = 104) and the placebo group (n = 104) were comparable at baseline. The incidence of endoscopically visible gastric lesions after ten days of nonsteroidal antiinflammatory drug therapy was significantly lower in the misoprostol group (25%) than in the placebo group (43%) (P = 0.001). In contrast, no statistically significant difference was found for the incidence of duodenal lesions between the two groups. The incidence of gastroduodenal ulcers was significantly lower (P < 0.021) in the misoprostol group (4.1%) than in the placebo group (13.5%). Changes in serum creatinine levels on day 10 versus baseline were similar in the two groups. The nonsteroidal antiinflammatory drug was well tolerated clinically when given alone or in combination with misoprostol.
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9,178,400
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Osteoporotic vertebral fractures in a man under high-dose inhaled glucocorticoid therapy. A case-report with a review of the literature.
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A 65-year-old man had surgery in June 1995 for femoral neuralgia. The plain films of the spine were normal at the time. In September of the same year, when he was beginning to walk gradually longer distances, he started experiencing back pain. Crush fractures of T8 and L2 were seen on plain films. His pain worsened, and he was admitted in December 1995. A third set of plain films disclosed fractures of all the vertebral bodies from T8 through L5, with increased density of the endplates of the same vertebras. Serum and urinary levels of calcium and phosphate were normal. Dual-energy X-ray absorptiometry demonstrated osteoporosis predominating in the trabecular bone. Evidence of increased bone resorption was seen on the histomorphometric study. Large amounts of dihydroxypyridinoline were found in the urine. Investigations for the classical causes of osteoporosis in males were unrewarding. Careful questioning revealed that the patient had been taking inhaled beclomethasone for seven years to treat chronic obstructive lung disease. Serum levels of cortisol and ACTH were low, consistent with a diagnosis of treatment-induced hypercorticism. To our knowledge, this is the first reported case of osteoporotic vertebral fractures in a male due to inhaled glucocorticoid therapy. Inhaled glucocorticoids are generally believed to induce only minimal systemic effects. However, decreased serum osteocalcin levels and increased urinary excretion of bone resorption markers have been reported in patients under inhaled beclomethasone therapy. Low spinal bone mineral density values correlated with the degree of pituitary-adrenal gland suppression as evaluated using the ACTH test have also been found in several groups of patients treated with inhaled glucocorticoids.
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9,178,401
|
A new case of insufficiency fracture in a patient with tabes dorsalis.
|
A new case of insufficiency fracture in a patient with tabes dorsalis is reported. Whereas the osteoarthropathies and bone lesions due to tabes dorsalis are well known, only one other case responsible for bone loss has been reported in the medical literature.
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9,178,402
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Multifocal malignant fibrous histiocytoma of the spine.
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A 40-year-old patient was seen because of a three-month history of low back pain unresponsive to standard therapy. Crush fractures of T12 and L2 were seen on plain radiographs. A magnetic resonance imaging study disclosed lesions of all the vertebral bodies from T12 to the sacrum sparing the disks and epidural space. Histologic features of a vertebral biopsy specimen was consistent with malignant fibrous histiocytoma of the bone. The multifocal distribution caused some reluctance to accept this diagnosis, which was, however, confirmed by detailed immunohistochemical studies and reevaluation of the histologic slides by independent observers who were unaware of the initial diagnosis. Chemotherapy with doxorubicin and cisplatin was started but the patient died 15 months after the diagnosis. Malignant fibrous histiocytoma mainly affects the metaphyses of the long tubular bones. The spine is a very uncommon site of localization of this tumor. The multifocal spinal lesions in our patient may have been produced by metastases from an unidentified primary or by direct spread via the perivertebral soft tissues of a primary located in a vertebral body. The management of malignant fibrous histiocytoma relies on a combination of surgery and chemotherapy. Although complete excision of the tumor can be followed by prolonged survival, the prognosis is bleak in unresectable forms.
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9,178,406
|
Patients' acceptance of waiting for cataract surgery: what makes a wait too long?
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The patient's perspective about waiting for elective surgery is an important consideration in the management of waiting lists, yet it has received little attention to date. This study was undertaken to assess the acceptability of personal waiting times from the perspective of patients, and to examine waiting time and patient characteristics associated with the perception that a wait for cataract surgery is too long. The international prospective study was conducted in three sites with explicit waiting systems: Manitoba, Canada; Denmark; and Barcelona, Spain. Patients over the age of 50 years were recruited consecutively from ophthalmologists' practices at the time of their enlistment for first-eye cataract surgery. Anticipated waiting time, opinions about personal waiting time, and patients' visual and health characteristics were identified by means of telephone interviews. The 550 patients interviewed at the time of enlistment for surgery anticipated waits varying from < 1 to 24 months. Clinical visual acuity measures were obtained from patients' ophthalmologists/cataract surgeons. Results indicated that anticipated waiting time was the strongest predictor of patients' tolerance of waiting for cataract surgery. Patient dissatisfaction increased with the duration of the anticipated wait. Patients in all three sites were accepting of waits of three months or less, and considered waits exceeding six months to be excessive. Response to waits between three and six months varied across study sites. Patients with low tolerance for waiting had greater self-reported difficulty with vision, as assessed by a Cataract Symptom Score and expressed trouble with vision. Patients' acceptance of waiting was not associated with clinical visual acuity measures or socio-demographic characteristics. The patient perspective on acceptability of waiting times for cataract surgery suggests that restricting waiting times to less than six months and preferably less than three months and utilizing self-reported measures of visual difficulty in prioritizing patients may contribute to improved management of waiting systems. Patients are more tolerant of their personal waiting times than responses to questions about waiting for elective surgery in general would indicate, and appear to accept waiting times that are longer than those identified as reasonable by specialists.
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9,178,407
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Meanings in policy: a textual analysis of Canada's "Achieving Health For All" document.
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This paper presents a textual analysis of a key Canadian health policy document--Achieving Health for All (AHFA). It begins by establishing the importance of policy language and an interpretive approach to reveal dominant meanings and assumptions. This approach points out the significance of language and its contexts (text and intertext) and of developing a formal analytic strategy, based on semiotics. The paper concludes with a detailed, illustrated analysis of AHFA, suggesting that the document's discourse, through appealing to all, with emphases on the nation, community and all Canadians, establishes a frame of individual responsibility and rights, health promotion and broad health determinants--a frame that resonates with the cost-constrained nature of health care delivery-as found in provincial reform documents in the 1980s and 1990s.
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9,178,408
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Health status and risk factors of seminomadic pastoralists in Mongolia: a geographical approach.
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The particular lifestyle of nomadic or seminomadic people has much to do with their health status. This discussion of the conceptual basis and some preliminary results of the 1992-94 health status and risk factor survey in Mongolia serves to highlight some of the relationships existing between the general health status and potential risk factors observed among pastoral nomads. In addition to graphic description of the data, a statistical analysis suggests significant associations between certain health status indicators and gender, location, lifestyle factors (e.g. smoking) socio-economic status, preventive health care and the physical environment. With regard to locational factors, there are strong regional differences in a wide-ranging number of health status indicators. The results of this study, obtained as they were at the threshold of Mongolia's economic and political transformation, will serve as a baseline against which to evaluate future changes in the health of Mongolians.
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9,178,410
|
Community and self: concepts for rural physician integration and retention.
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Low physician availability in rural areas of the United States is a long-standing issue. While most research has focused upon the locational decisions of physicians to understand the causes of the problem, a relatively new and neglected research focus is the retention of rural physicians. This paper takes the perspective that integration of physicians within rural communities is the basis for retention. It introduces concepts of self and community as a basis for understanding "domains" of rural physician integration. From data collected during in-depth qualitative research in rural Kentucky, a framework of integration domains is developed. The three domains of physician self, medical community, and community-at-large are elaborated with examples from the data. To further explain the relationships among the integration domains and their value, the findings are combined with three concepts from social theory. Social capital, core participation, and community reconstruction add dynamic and meaningful aspects to the context in which integration and retention occur, and they provide a conceptual basis to use when investigating or devising actions to facilitate integration.
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9,178,409
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Urban ecological structure and perceived child and adolescent psychological disorder.
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This research examined the distribution and ecological correlates of referrals of children and adolescents to the Regional Children's Centre, a psychological assessment and treatment centre located in Windsor, Ontario, Canada. Referral data were collected by the Regional Children's Centre for the study period April 1992 through March 1994. The ecological structure of the study area was derived using principal components analysis of a set of socio-economic indicator variables from the 1991 Census of Canada and a cluster analysis of component scores. Referral rates were calculated for each ecological area for two referral subgroups; modi/conduct/stress-related concerns and neurophysiologically based concerns. The distribution of referrals was tested using the Poisson probability test. This test revealed that, for both subgroups analysed, the distribution of referrals in the study area was non-random. Stepwise multiple regression revealed a significant ecological relationship between the mood/conduct/stress-related concerns referral rate and the ecological structure of the study area. No such relationship was found, however, when examining referrals for neurophysiologically based concerns.
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9,178,411
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Intra-household allocation of food and health care: current findings and understandings--introduction.
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This work offers an anthropological analysis of intra-household processes underlying gender- and age-specific differences in individual nutritional and health care allocations and outcomes in particular cultures. Based on recent ethnographic studies in India, Nepal, Madagascar, Mexico, and Peru, correspondences are analyzed between local cultural ("emic") and scientist-policy maker practitioner ("etic") understandings of nutrition, health, and human development, and the relative "values" of females, males, and children of different ages. The data and analyses clarify specific epidemiological and demographic findings on age and gender bias in nutrition and health and highlight the multiple cultural, economic, and biological factors that contribute to gender- or age-based discrimination or neglect. Recent advances in nutrition policy have argued for a broader concept of nutritional security, one that incorporates both food quantity and quality, and of nutrition as "food, health and care" (International Conference on Nutrition, World Declaration and Plan of Action for Nutrition, FAO/WHO, Rome, 1992). These ethnographic findings; lend strong support for such broader nutrition concepts and associated nutrition policies. The studies also suggest ways in which anthropological questions, methods, and data and community-based research can help predict or identify the nutritionally vulnerable within households and help other social and medical scientists design more effective interventions.
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9,178,412
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Social class, gender and intrahousehold food allocations to children in South Asia.
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In the 1980s research on gender-biased food distribution to children within the household in South Asia yielded important findings. Many studies report evidence of substantial discrimination against daughters, but others do not. This paper reviews research of the 1980s with attention to social differentiation in gender bias. My hypothesis is that different results concerning gender bias in intrahousehold allocations are expectable, given variations in gender hierarchy throughout South Asia. Results of the review indicate that seemingly "contradictory" results are often accurate reflections of social status differences within South Asia that create varying female health and nutritional outcomes.
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9,178,413
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Food allocation in rural Peruvian households: concepts and behavior regarding children.
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Intrahousehold food allocation is an important determinant of child health and survival. In this paper I explore the ways in which food is distributed to young children in Ura Ayllu, a farming community located in the southern Peruvian highlands (Province of Sandia, Department of Puno, Peru). Quantitative data on energy intake and growth status are analyzed for two groups of children: toddlers (one through three years) and preschoolers (four through six years). The analyses indicate no gender differences in energy intake or growth among toddlers (one through three years) and preschoolers (four through six years) and that young children do not appear to be deprived of food relative to older household members, especially adults. Relative to standards specific to Andean populations, the mean caloric content of the toddler diet falls slightly below the estimated requirement for the age group while the preschooler diet is found to be calorically adequate. This paper also examines the ideological bases that shape food allocation within households. Regarding the local concepts and cultural rules that guide food allocation to children, Ura Ayllinos view young children as developmentally immature and believe their dietary and health needs are different from those of older children and adults. Infants and young children are considered weak (debil) and vulnerable to illness. Parents state that young children should not feel hunger which is thought to weaken a person and make him more susceptible to the natural and supernatural agents that cause illness. Certain dietary practices, such as on-demand breastfeeding and snacking between meals, suggest that parents try to avoid the experience of hunger and the potential for illness by making food available to their children. This study suggests that young Ura Ayllu children are viewed as having a right to food based on local concepts of child development, personhood, and general health maintenance.
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9,178,414
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Health care allocation and selective neglect in rural Peru.
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This study of health care allocation to children in northern Puno, Peru, utilizes quantitative and qualitative data to explore differential resource allocation to children in rural Andean households. As part of a broader ethnographic study of health in two communities, quantitative data on reported health status, symptoms, and treatments (both lay and specialist) were collected for 23 children under the age of 7 over a one year period. Additional data were collected from local health post records. Data were analyzed by gender, and by three age groups (birth to 1 year, 1-3 years, 4-6 years) to determine if differences existed in the allocation of health care. The data suggest a pattern of discrimination against females and younger children, especially infants under age one, despite the fact that these groups were reported to be sicker. Differences were especially significant in the allocation of biomedical treatments, the most costly in terms of parental time, effort, and money. Ethnographic data on child illness, gender, and developmental concepts help to explain why children of different genders and ages may be treated differently in the rural andes. They provide a context in which to interpret health care allocation data, and, in the absence of a population-based study, reinforce findings based on the limited study sample. Female children are valued less because of their future social and economic potential. Females are also regarded to be less vulnerable to illness than male children, meaning that less elaborate measures are necessary to protect their health. Young children are thought to have a loose body-soul connection, making them more vulnerable to illness, and are though to be less human than older individuals. The folk illnesses uraña (fright) and larpa explain child deaths in culturally acceptable ways, and the types of funerals given to children of different ages indicate that the death of young children is not considered unusual. Health care allocation and ethnographic data suggest that selective neglect (passive infanticide) may be occurring in rural Peru, possibly as a means of regulating family size and sex ratio. It is important to go beyond placing blame on individual parents or on culture, however, to address the underlying causes of differential health care allocation, such as poor socioeconomic conditions, lack of access to contraceptives, and female subordination.
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9,178,416
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Cultural factors, caloric intake and micronutrient sufficiency in rural Nepali households.
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This study examined the allocation of food within 105 Nepali households using a combination of recall and observation methods. While a relationship exists between caloric intake and sufficiency of intake of several key micronutrients (i.e., beta carotene, vitamin C and iron) for the study population as a whole this relationship is weaker for certain subgroups. In particular, micronutrient intakes of adolescent girls and adult women are much less likely to be tried to total caloric consumption when compared with the intakes of other household members. This gender differential appears linked in part to specific food beliefs and practices that tend to reduce women's consumption of micronutrient-rich foods, such as dietary restrictions during menstruation, pregnancy and lactation. Overlapping with these beliefs and practices, an overall pattern of disfavoritism of females in the intrahousehold allocation of food is evident in the study communities. While staple food items (i.e. rice, lentil soup, bread, etc.) are distributed fairly equally, side dishes usually containing a higher proportion of micronutrients (i.e. vegetables, meat, yogurt, ghee, etc.) are often preferentially allocated to valued household members, including adult males and small children (of both sexes).
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9,178,415
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Why are boys so small? Child growth, diet and gender near Ranomafana, Madagascar.
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Dietary and anthropometric data are analyzed by age, sex and household demographic structure for cultivators' children near Ranomafana National Park in the southeastern rain forest of Madagascar. The 1989 dry season cross-sectional survey of 613 0-9 year olds in seven communities identifies chronic dietary and growth deficits. In the 1989 sample, 62.2% of the children are below -2 s.d. height/age, while 9.4% are below -2 s.d. wright/height of the NCHS international standard. The 1990-1991 dry and wet season study of 40 and 39 6-9 year olds and their households in two adjacent hamlets provides further detail about intrahousehold dietary practices. Overall, weight/height status is worse during the wet season. Male anthropometric status is worse than that of females during the dry season, but shows less seasonal variation. The male dietary intake is similar to or sometimes less adequate than female dietary intake in the different age cohorts. Data are also analyzed by single- and multiple-parent households where children make different contributions to the socioeconomic needs. Older girls in single-parent households have increased workloads and dietary intake compared with their siblings or age-mates.
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9,178,418
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Physician location survey: self-reported and census-defined rural/urban locations.
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Using a survey of New York State Residence-Trained Family Physicians and the 1990 census data, this paper assesses the relative importance and consistency of factors associated with physician practice locations when different definitions of community size are used. By matching the zip code information with 434 physicians' practice locations, physician respondents' self-reported communities are linked to census-defined communities. It was found that the significant level of some variables could be affected when community classifications were based on survey responses rather than census data. It concludes that caution should be taken for interpreting rural-urban differences when data are solely based on self-reported practice locations.
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9,178,417
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Examining the gender gap in nutrition: an example from rural Mexico.
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Gender differences in nutrient and food intake were examined in Mexican Nutrition CRSP (Collaborative Research Support Program) infants (N = 75), preschoolers (N = 80), and school children (N = 91). No significant gender differences in dietary quality or quantity were seen for infants and preschoolers. For school children, the contribution of various foods to total energy intake (dietary quality) was also quite similar for girls and boys. Equity in dietary quality remained even under conditions of economic and demographic stress. Nevertheless, school girls consumed significantly less energy per day than boys (-300 kcal/d or 1.3 mJ/d), and less of all micronutrients examined. Gender differences in estimated basal metabolic rates of school children were slight (-20 kcal/d), and body composition and size were similar. When energy intakes were expressed as a percent of estimated requirement (calculated from age, sex and weight using WHO/FAO/UNU equations), intakes were adequate and not significantly different between girls (mean = 111%) and boys (mean = 113%). Playground observations showed girls to be less active than boys, which may reflect both cultural and biological influences. Apparently due to this lower activity, school girls consumed less energy, and may have been at much higher risk than boys of micronutrient deficiency. The lower food intakes of girls did not appear to be due to purposeful dietary discrimination, but rather to culturally patterned sex roles involving lower activity.
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9,178,419
|
Multiple-quantum magic-angle spinning and dynamic-angle spinning NMR spectroscopy of quadrupolar nuclei.
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Several aspects of the Multiple-Quantum Magic-Angle Spinning (MQMAS) technique (L. Frydman and J.S. Harwood, J. Am. Chem. Soc., 117 (1995) 5367) are compared with Dynamic-Angle Spinning (DAS). Examples of MQMAS spectra are shown for I = 3/2 nuclei with CQ up to 3.6 MHz, and for 27Al (I = 5/2) with CQ up to 10 MHz. The MQMAS linewidth is largely independent of the magnitude of the homonuclear dipolar interaction, while the spinning sideband manifold is similar to that observed in DAS experiments. MQMAS is technically simple and routinely useful for studying nuclei with short spin-lattice relaxation times, but care must be taken in its use for quantitative studies as the excitation of the triple-quantum coherence is not uniform. In this regard, MQMAS is most useful for samples with small quadrupolar coupling constants. In the specific case of 17O, DAS would give spectra with excellent resolution in comparison to MQMAS. The different advantages of DAS and MQMAS make them useful complementary techniques in many cases. Two additional methods are also presented for extracting the chemical shift anisotropy (CSA) directly for quadrupolar nuclei using the multiple-quantum scheme.
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9,178,420
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Multiple-pulse assisted line-narrowing by fast magic-angle spinning.
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Combined rotation and multiple-pulse experiments (CRAMPS) are reported that are performed under the conditions of fast magic-angle spinning. Quasi-static conditions, as are required for CRAMPS experiments, can be fulfilled approximately also for fast sample spinning conditions when windowless or semiwindowless sequences are applied. In order to allow direct detection for these cases also, appropriately timed detection windows are introduced without loss of resolution. In contrast to conventional CRAMPS experiments, high-speed MAS was found to play an important role also in the averaging of residual dipolar contributions. The resolution achieved in these first experiments is comparable to that of conventional CRAMPS experiments and the demands with respect to spectrometer hardware and tuning are much lower.
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9,178,421
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Two-dimensional spin-exchange solid-state NMR studies of 13 C-enriched wood.
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Two-dimensional high-resolution solid-state NMR has been used to study 13C-enriched wood. Wood is a complex material containing three major polymers: cellulose, hemicelluloses and lignin. The use of an enriched 13C-compound allows the observation of intra-molecular spin-diffusion driven by dipolar couplings. Correlations between spins at progressively longer distances have been obtained as the mixing time is increased, corresponding, for each of the separate polymer chains, to intra-unit and then to inter-unit interactions, and in the case of cellulose to inter-chain interactions. A straightforward qualitative analysis of the spin diffusion spectra is shown to yield the assignment of the carbon-13 spectrum. The cellulose resonances can all be sequentially assigned using the spin diffusion experiment. Using the experiments it is shown that, at least on a distance scale of several nanometres explored by the spin diffusion process, the three main components of wood occur in separate phases. Also, a question concerning the structure of the hemicellulose units is resolved by locating the O-acetyl group at the 2-position of the xylan chains.
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9,178,423
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Effects of finite pulse width on free induction decay.
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The shape of the free induction decay for the case in which the amplitude B1 (B1 = omega 1/gamma) of the RF pulse is comparable with local magnetic fields at sites of the nuclei is considered. It is shown that the shape of the FID G(t + tau) (where tau is the width of a RF pulse, t is the time after a RF pulse) depends on the shape of the FID G0(t) following a hard, delta function RF pulse and on the shape of the function F0(tau), which describes the evolution of the longitudinal nuclear magnetization Mz under the effect of the hamiltonian (H0-omega 1 I gamma), where H0 is the interaction hamiltonian of the nuclear spin system. Calculations of F0(tau) and G(t + tau) for different interaction hamiltonians H0 are presented.
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9,178,422
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51V magic-angle-spinning NMR and electric field gradient calculations in V2O5 and gamma-LiV2O5 crystals.
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51V Magic-angle-spinning (MAS) NMR has been applied to V2O5 at two different magnetic field strengths (4.7 and 7.1 T). Both the magnitude and relative orientation of the quadrupole and chemical shift (CS) tensors have been determined by iterative fitting of the 51V MAS NMR lineshapes at the two magnetic field strengths. The reliability of the results is discussed. Moreover, it is shown that previous low-field single-crystal data are fully consistent with the high-field powder-sample MAS NMR results provided that a slight noncoincidence between the CS tensor and the crystal frame axes is considered. The electric field gradient tensor at the vanadium and lithium sites is subsequently used to test several electronic structure calculation at an ab initio Hartree-Fock level in V2O5 and gamma-LiV2O5 crystals. It is shown that a wide distribution of oxygen charges must be considered to describe the particular environment of each type of oxygen atoms. Furthermore, this analysis supports the fact that the vanadyl bond is likely a short ionic bond. NMR is found to be a valuable experimental tool to get insight into the nature of chemical bonds in vanadium oxides.
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9,178,424
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Phospholipid headgroup dynamics in DOPG-d5-cytochrome c complexes as revealed by 2H and 31P NMR: the effects of a peripheral protein on collective lipid fluctuations.
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The dynamics of the glycerol headgroup of dioleoylphosphatidylglycerol (DOPG) in hydrated bilayers were studied by 2H and 31P NMR spectroscopy, and the effects of binding a peripheral protein, cytochrome c, were evaluated. The fast headgroup segmental motions (tau c, 10(-10)-(-13) s) of DOPG in fully hydrated bilayers were not affected upon binding of cytochrome c, as evaluated by the spin-lattice (T1) relaxation of deuterons in the DOPG glycerol headgroup. In contrast, the spin-spin (T2e) relaxation is strongly affected, indicating that slow cooperative bilayer motions (tau c, 10(-3)-10(-6) s) are enhanced upon the interaction with cytochrome c, 2H and 31P NMR spectral lineshape analysis reveal details of the nature of these motions. The importance of these effects are discussed in terms of a possible mechanism for modulating membrane-associated processes.
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9,178,428
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Synthesis of new delta 5-7-oxygenated and delta 5,7-unsaturated brassinosteroid analogs.
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We report on the synthesis of the brassinosteroid analogs (22R,23R)-3 beta, 7 beta, 22,23-tetrahydroxy-stigmast-5-ene (13), (22R,23R)-3 beta, 7 alpha, 22,23-tetrahydroxy-stigmast-5-ene (15), and (22R,23R)-3 beta, 22,23-trihydroxy-stigmast-5,7-diene (18) by means of the osmium-catalyzed asymmetric dihydroxylation of intermediate 1, available from stigmasterol. This reaction sequence produced the expected (22S,23S)- and (22R,23R)-triols 6 and 7 as well as the 22,23-diketo derivatives 2 and 3. The phytohormone activity of the new brassinosteroid analogs is discussed.
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9,178,426
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Synthesis and progestational activity of 16-methylene-17 alpha-hydroxy-19-norpregn-4-ene-3,20-dione and its derivatives.
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16-Methylene-17 alpha-hydroxy-19-norpregn-4-ene-3,20-dione 1 and its 17 alpha-acylated derivatives were synthesized. The length of the 17 alpha-side-chain ranges from C2-C6. As anticipated, compound 1 did not show any progestational activity or receptor binding activity; whereas, the acylated compounds, especially the butyrate, showed remarkable ability to bind to progesterone receptors. These compounds also showed progestational activity in an in vitro T47D cell culture assay in which progestins increase alkaline phosphatase activity and in an in vivo ovulation inhibition assay. All of the compounds synthesized were without estrogenic activities. The results showed that acylation of 16-methylene-17 alpha-hydroxy-19-norprogesterone can increase progestational activity. The progestational activities of these compounds varied with the 17 alpha-side chain.
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9,178,427
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7 beta-hydroxy bile alcohols: facile synthesis and 2D 1H NMR studies of 5 beta-cholestane-3 alpha, 7 beta, 12 alpha, 25-tetrol.
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A rapid and easily performed procedure for the synthesis of 5 beta-cholestane-3 alpha, 7 beta, 12 alpha, 25-tetrol by means of an efficient homologation sequence of the intermediate, 3 alpha, 7 beta, 12 alpha-triformyloxy-24-oxo-25-diazo-25-homo-5 beta-cholane is described. The reaction sequence involved treating the intermediate, alpha-diazoketone in methanol with 3% AgNO3 or Ag2O, anhydrous Na2CO3, Na2S2O/H2O resulting in the formation of homoursocholic acid in high yield. Esterification of the homoursocholic acid in methanol containing a catalytic amount of methanesulfonic acid under microwave irradiation conditions gave methyl homourscholate. The subsequent treatment of methyl homoursocholate with methyl magnesium iodide provided 5 beta-cholestane-3 alpha, 7 beta, 12 alpha, 25-tetrol in 88% yield. The products and synthetic intermediates prepared in these studies were fully characterized by the results of 1D and 2D NMR, and high-resolution mass spectral studies. These studies will help in further investigation of the defect of cholic acid biosynthesis in patients with cerebrotendinous xanthomatosis (CTX) as well as other inborn errors of bile acid metabolism.
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9,178,429
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The delta 5-3 beta-hydroxy steroid acyl transferase activities in tissues of the male rat and sheep.
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Pregnenolone and dehydroepiandrosterone and their sulphate and fatty acid ester derivatives are concentrated in the mammalian brain, as compared to the peripheral organs. Although biological functions have been postulated for the free steroid and sulphate conjugates, the role of steroid fatty acid esters in the central nervous system (CNS) has yet to be established. A comparison of the esterifying capacities of brain and peripheral organs of the male rat and sheep is made here. The male rat brain was found to possess a higher esterifying capacity than all other tissues examined, with 5.32 +/- 2.46 pmol dehydroepiandrosterone fatty acid esters synthesized/mg protein/h and 1.89 +/- 0.42 pmol pregnenolone fatty acid esters synthesized/mg protein/h. Sheep adrenal and sheep liver homogenates were found to have higher esterifying capacities than sheep brain. Within the brain of both species. delta 5-3 beta-hydroxy steroid acyl transferase enzyme(s) were concentrated in the microsomal fraction. The addition of a lecithin:cholesterol acyl transferase inhibitor to incubation assays resulted in a loss in enzyme activity. This effect was more significant in sheep brain microsomes than rat brain microsomes. It is likely that lecithin:cholesterol acyl transferase is more active in the sheep brain than the rat brain. Results from this study indicate that the steroid acyl transferase enzymes that are active in the mammalian brain are substrate specific.
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9,178,430
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Hydroxysteroid sulfotransferase activity in the rat brain and liver as a function of age and sex.
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The high concentrations of dehydroepiandrosterone sulfate and pregnenolone sulfate in the mammalian brain, despite the blood-brain barrier's impermeability to these compounds, and the apparent independence of these concentrations from those in plasma prompted us to investigate whether enzymatic sulfation of dehydroepiandrosterone was detectable in the rat brain. Low hydroxysteroid sulfotransferase activities were detectable in in vitro incubations of homogenates from all rat brain regions except the cerebellum, being highest in the hypothalamus and pons. This activity was not ascribable to enzyme in brain capillary blood. The activity was mainly cytosolic, although there was also significant activity in the partially purified nuclear fraction. The enzyme had different properties from those of hepatic isozymes, with a pH optimum of 6.5 and a high Km of approximately 2 mM for dehydroepiandrosterone. The enzyme was also active with pregnenolone as substrate. Activities in the brain were approximately 300-fold lower than in the liver but, as in the liver, these were higher in females than in males. The variations in brain activity as a function of age did not parallel those in the liver. Relatively high activities were found in the fetal brain and declined at birth, while activities were insignificant in the fetal liver and rose following birth. There was a major peak in activity in pubertal female brains, but this peak was less important, and later, in males. No evidence was found to indicate that the low brain enzyme activities and high Km were attributable either to the presence of an inhibitor or to the steroid sulfation actually being a secondary activity of another brain sulfotransferase. We discuss whether the sulfotransferase activities found are adequate to synthesize the dehydroepiandrosterone and pregnenolone sulfate found in brain.
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9,178,431
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Preparation of 3-ketodesogestrel metabolites by microbial transformation and chemical synthesis.
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Specific microbial reactions were used for the preparation of metabolites of 3-ketodesogestrel (13-ethyl-17 beta-hydroxy-11-methylene-18,19-dinor-17 alpha-pregn-4-en-20-yn-3-one, the active from of the progestagen desogestrel. Clostridium paraputrificum transformed 3-ketodesogestrel (KDG) to the 5 beta-dihydro and tetrahydro metabolites 13-ethyl-17 beta-hydroxy-11-methylene-18,19-dinor-5 beta, 17 alpha-pregnan-20-yn-3-one and 13-ethyl-11-methylene-18,19-dinor-5 beta, 17 alpha-pregnan-20-yne-3 alpha, 17 beta-diol, respectively. The epimeric compound 13-ethyl-11-methylene-18,19-dinor-5 beta, 17 alpha-pregnan-20-yne-3 beta, 17 beta-diol was obtained by chemical reduction of the 3-oxo compound. Mycobacterium smegmatis converted KDG to metabolites of the 5 alpha H-series: 13-ethyl-17 beta-hydroxy-11-methylene-18,19-dinor-5 alpha, 17 alpha-pregnan-20-yn-3-one, 13-ethyl-11-methylene-18,19-dinor-5 alpha, 17 alpha-pregnan-20-yne-3 alpha, 17 beta-diol and 13-ethyl-11-methylene-18,19-dinor-5 alpha, 17 alpha-pregnan-20-yne-3 beta, 17 beta-diol. The ring A-aromatized analog of KDG 13-ethyl-11-methylene-18,19-dinor-17 alpha-pregna-1,3,5(10)-trien-20-yne-3,17 beta-diol was obtained by microbial 1-dehydrogenation with Rhodococcus rhodochrous. Additionally, chemical syntheses of the microbially obtained KDG metabolites listed above were carried out. These included Birch reduction, reduction of KDG with sodium borohydride in aqueous pyridine and in methanol, reduction of KDG with potassium selectride in tetrahydrofuran, and dehydrogenation of KDG with cupric-II bromide in acetonitrile. The problems encountered in chemical syntheses favor the microbial procedures. The compounds were characterized by mass spectra (MS), IR, and circular dichroism (CD). Complete assignments of 1H and 13C chemical shifts were made using homo- and heteronuclear 2-DN-NMR spectroscopy. Chromatographic [gas-liquid chromatography (GLC), high-performance liquid chromatography (HPLC), thin-layer chromatography (TLC)] data of all the prepared KDG metabolites are presented.
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9,178,432
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The sheep kidney contains a novel unidirectional, high affinity NADP(+)-dependent 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD-3).
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The 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) enzymes convert corticosterone and cortisol to 11-dehydrocorticosterone and cortisone, and are thought to convey extrinsic specificity to the mineralocorticoid receptor by limiting access of the relatively more abundant glucocorticoids to it. Two different 11 beta-hydroxysteroid dehydrogenases (11 beta-HSD) have been described and cloned. The liver-type, NADP(+)-dependent 11 beta-HSD-1, has an affinity in the micromolar range and bidirectional activity. The NAD(+)-dependent 11 beta-HSD-2 has a higher affinity, in the nanomolar range, and exhibits only oxidase activity. 11 beta-HSD-2, because of its affinity and co-localization with the mineralocorticoid receptor, is likely to serve as the "gatekeeper" for the mineralocorticoid receptor in the kidney. Although the rat kidney expresses both isoforms, only the high-affinity, NAD(+)-dependent 11 beta-HSD-2 has been reported in the sheep kidney. We found both 11 beta-HSD NAD(+)- and NADP(+)-dependent activities in sheep kidney to be present. The NAD(+)-dependent activity exhibited a Km similar to that reported in the literature, 3.85 +/- 1.28 nM for corticosterone and 21.3 +/- 5.8 for cortisol, was distributed in approximately equal amounts between microsomes and nuclei, and was unidirectional, converting corticosterone to 11-dehydrocorticosterone. The enzyme exhibited prominent substrate inhibition. The NADP(+)-dependent activity had a Km for corticosterone of 4 +/- 1.3 nM for a Km for cortisol of 35.2 +/- 2 nM, 100-fold lower than that described for the 11 beta-HSD-1 in the liver of sheep and other species, and was more prevalent in the microsomes than the nuclei. This enzyme was not inhibited by its substrate. The NAD(+)-dependent activity was approximately 3-10 times greater than the NADP(+)-dependent activity when incubated with 5 nM corticosterone substrate, but had similar activity when incubated with 100 nM substrate concentrations. CHOP cells (a modified Chinese hamster ovary cell line) transiently transfected with the sheep 11 beta-HSD-2 plasmid exhibited a marked preference for NAD+ as co-factor. Oxidation of corticosterone by transfected cells in the presence of NADP+ was present, but minimal; NADP+ did not support the metabolism of cortisol, the primary glucocorticoid of sheep. These data suggest the existence of another NADP(+)-dependent enzyme, 11 beta-HSD-3, which, because of its high affinity and unidirectional oxidase activity, may play a physiological role in the modulation of glucocorticoid binding to both the mineralocorticoid and glucocorticoid receptors.
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9,178,433
|
Rapid hydrogenation of unsaturated sterols and bile alcohols using microwaves.
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This paper describes an operationally simple, rapid hydrogenation of unsaturated sterols and bile alcohols in a domestic microwave oven. This has been achieved by the addition of catalytic amounts of Pd/C in methylene chloride/propylene glycol solvents in the presence of ammonium formate followed by microwave irradiation. It is suggested that this methodology will be helpful in the identification of saturated and unsaturated sterols with different side-chain structures in rare diseases: sitosterolemia, cerebrotendinous xanthomatosis (CTX), as well as atherosclerosis and diabetes mellitus. Sterols, such as cholesterol, campesterol, sitosterol, and bile alcohols with unsaturated side chains, were converted to their reduced congeners with high yield and purity.
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9,178,435
|
Drug treatment: explaining the gender paradox.
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There is something of a gender paradox in drug user treatment. Research consistently indicates that women possess "risk factors" associated with drug use relapse, yet women are no more likely, and possibly less likely, to relapse to drug use. Efforts to explain this paradox involve a longitudinal study of 330 women and men participating in outpatient drug-user treatment associated with the evaluation of the Los Angeles Target Cities Project funded by the Center for Substance Abuse Treatment. The findings offer no support for the drug severity and social support hypotheses, but some support for the treatment engagement hypothesis. Specifically, women participate more frequently in group counseling which, in turn, lowers their rate of relapse in spite of having more "risk factors." Further analyses indicate that the greater participation of women in group counseling does not stem from child-custody or other gender differences in the reasons for entering treatment, nor does it result from the enhanced services associated with the Target Cities Project. Rather, the differences in treatment engagement for women and men may result from gender norms concerning help-seeking, personal independence, strength, and control. The treatment and policy implications of these findings and recommendations for further research are discussed.
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9,178,436
|
A "parliamentary inquiry" into alcohol and drugs: a survey of psychoactive substance use and gambling among members of the Dutch parliament.
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In the fall of 1994 a survey was conducted on the use of alcohol and drugs and on gambling among members of the Dutch parliament. The survey indicated that almost two-thirds of the representatives sampled supported legalization of marijuana. A smaller majority (57%) was in favor of reducing the number of coffee shops selling marijuana. At least a quarter of the members of parliament had used marijuana themselves at one time or other. Alcohol consumption could be said to be "excessive" or "very excessive" for nearly 10% of the members of parliament. In general, the nature and extent of the parliamentarians' substance use was comparable to that in the Dutch general population.
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9,178,437
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Reducing parental risk factors for children's substance misuse: preliminary outcomes with opiate-addicted parents.
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Parents in methadone treatment were offered an experimental intervention, Focus on Families, designed to reduce their risk of relapse and their children's risk of substance use. Experimentally assigned volunteers participated in systematic group training in relapse prevention and parenting skills, and received home-based case management services. Immediate posttreatment outcome results reported here include analyses of covariance controlling for baseline measures. Analyses show experimental parents held more family meetings to discuss family fun, displayed stronger refusal/relapse coping skills, demonstrated stronger sense of self-efficacy in role-play situations, and had lower levels of opiate use than control subjects. No significant differences in family bonding, family conflict, or other measures of drug use were found. The utility of intervening with drug-addicted parents in methadone treatment is discussed in light of these findings.
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9,178,438
|
Rohypnol misuse in the United States.
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Rohypnol, a potent sedative-hypnotic drug prescribed extensively throughout the world, is illicit in the United States. Recently, this drug has gained popularity among United States youths as a cheap means of intoxication and subsequently has become the focus of numerous criminal investigations. College men are alleged to slip Rohypnol tablets into unsuspecting women's drinks and then sexually abuse their sedated victims. Although law enforcement agencies and drug policy groups consider Rohypnol to be an "imminent problem," little is actually known about patterns of misuse. Presented here is a brief overview of Rohypnol's contemporary appearance in the United States.
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9,178,439
|
Drug dependence scale in the Millon Clinical Multiaxial inventory.
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The Million Clinical Multiaxial Inventory (MCMI versions I, II, and III) includes a scale to assess drug use problems, Scale T-Drug Dependence. Detailed drug use data from a sample of 659 known drug users along with MCMI-II results were examined to determine the operating characteristics of the MCMI-II drug dependence scale. Operating characteristics, sensitivity, specificity, positive predictive power, negative predictive power, and overall diagnostic power were calculated for base rate cutoffs and for the number of prototypic items endorsed to determine the diagnostic efficiency of Scale T-Drug Dependence in identifying regular drug users. Prototypic item cutoffs provided higher levels of diagnostic and positive predictive power than did the standard base rate cutoffs.
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9,178,440
|
Drugs, crime, and HIV.
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The use of criminal justice authority is discussed as a possibility for keeping drug users in treatment to decrease drug use, decrease injection, and to reduce the spread of HIV. It is hypothesized that the perception of treatment and control is a central factor in the limited use of criminal justice authority by community drug treatment providers.
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9,178,441
|
The rules of drug taking: wine and poppy derivatives in the ancient world. VI. Poppies as a source of food and drug.
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Poppies were widely used during antiquity as a source of food, therapeutics, and poisons. It is likely that the alimentary value of poppy seeds was known in the Neolithic age, and there is some evidence that the neuropsychopharmacological effects of poppy juice were exploited during the Minoan civilization in the eastern Mediterranean basin. The Minoan civilization dates the attribution to poppies of symbolic meanings connected with rites of agricultural fertility. The persistence throughout antiquity of this symbolism is testified by literary and iconographic evidence of the attribution of poppies to goddesses of fertility, such as Demeter, Aphrodite, and Ceres.
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9,178,442
|
A prison-based alcohol use education program: evaluation of a pilot study.
|
Northern Territory prisoners were followed up after release to determine the effect of an alcohol education course on their alcohol consumption, drinking group, disruptive behavior, criminal activity, family relationships, how they use their time, general health, ability to cope and take responsibility. Measures were obtained both from prisoners and key informants, and two groups of prisoners were compared: those who completed the course and others who had not done the course. A high level of correspondence was found between measures from key informants and prisoners. The prisoners attending the course showed significant improvements on all dimensions when compared to the control subjects.
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9,178,443
|
Abstinence fear in methadone maintenance withdrawal: a possible obstacle for getting off methadone.
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The present study attempts to shed light on methadone maintenance patients expectations regarding withdrawal symptoms during voluntary methadone detoxification. The study includes two groups of subjects; one group who have tried on their own initiative to terminate their methadone maintenance treatment (Group 1) and one group that contains rehabilitated patients who have not tried to quit using methadone (Group 2). Two main results have emerged. Group 1 has negative expectations beforehand about the intensity of withdrawal which significantly exceed the later, actual experience. Group 2 has negative expectations about the intensity of withdrawal that significantly exceed the negative expectations of Group 1. The clinical implications of these results are discussed.
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9,178,444
|
Clinical evaluation of ceramic veneered titanium restorations according to the Procera technique.
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The aim of the present study was to present the design and one-year results of a study of crowns and fixed partial dentures (FPDs) made with the Procera system. All patients at one clinic needing fixed prosthodontic restorations during a two-year period were invited. All 260 patients accepted to participate and they received 333 ceramic veneered Procera restorations-242 single crowns and 91 FPDs. The loss of patients during the one-year follow-up was only 5%. The restorations were evaluated according to a modified version of the California Dental Association rating system. Practically all Procera restorations were judged as satisfactory both at base line and at the one-year follow-up examination. Two crowns and one FPD showed fractures of the ceramic veneering. Another FPD had a fracture of a welded joint. Three single crowns came loose but could be recemented. In conclusion, the ceramic veneered Procera titanium restorations were well accepted by the patients and the success rate was high during the one-year follow-up period.
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9,178,445
|
Remineralization of natural carious lesions with a glass ionomer cement.
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Remineralization of carious lesions at the histological level is of great benefit since this will arrest lesion progression. The ability of glass ionomer cement (GIC) to (1) release fluoride it originally contains and (2) release "loosely bound" fluoride acquired from its surroundings have been previously demonstrated. This in vitro study examined the potential for caries remineralization if the lesion was placed near a GIC. Sixteen mesiodistal sections were cut through extracted deciduous molars exhibiting approximal white spot lesions. Sections were "linked" to a plastic tooth restored with a GIC to simulate the abutting surfaces of adjacent teeth. Lesions were photographed in water under polarized light initially and after one- and two-week exposures to artificial saliva. The photographs were digitized, lesion body outlined, and the area corresponding to the body of the lesion was determined to provide a comparison over time. Sixty-two percent of the sections showed a quantitative reduction in lesion body size by an average of 43% after the first week and an additional 14% reduction after the second week. All but two sections demonstrated a qualitative change thereby illustrating that a reduction in pore volume size of the lesion body had also occurred. Therefore, fluoride released from a GIC has the potential to enhance remineralization of the early carious lesion in vitro. The greatest remineralization occurred during the first week of artificial saliva exposure.
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9,178,446
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Preauricular approach to the temporomandibular joint: a postoperative follow-up on nerve function, hemorrhage and esthetics.
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The aim of the present study was to report the incidence of facial and auriculotemporal nerve weakness, postoperative hemorrhage and disfiguring scars following TMJ surgery by the preauricular approach. One-hundred and fifty consecutive patients with a mean age of 37 years were studied. A total of 189 surgical procedures were performed by the same surgeon. Facial nerve function was estimated the day after surgery and after six weeks. After 16 months facial and auriculotemporal nerve function was assessed and the patient's estimation of the scar was registered. Postoperative hemorrhage occurred after 1% of the operations. Five percent of the patients had transient facial nerve weakness. Auriculotemporal nerve weakness was reported by 34% of the patients. None of the patients found the scars disfiguring. Although neurosensory disturbances were frequently found in the temporal region, the preauricular incision offers a safe and cosmetically acceptable access to the temporomandibular joint.
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9,178,447
|
Children's dental health in Europe.
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"Children's Dental Health in Europe" is a collaborative study of a total of 3200 children, comprising samples of 5- and 12-year-old children from eight EU-countries [Belgium, Germany, Greece, Ireland, Italy, Scotland (United Kingdom), Spain and Sweden] who have undergone clinical examination by well calibrated dentists. This study analyses the influence of a number of sociodemographic factors on the dental health of the actual children. Father's and/or mother's occupational status was used to determine the social class of the family, after construction of a family-social class variable, SocFam, and the accuracy of this variable was tested. In 15 of the 16 samples, both treatment provided and unmet treatment need were higher in children from low social class. The treatment need in children from low social class was significantly greater in the Belgium, German, Greek and Italian 5-year-old samples. The differences in both treatment need and treatment already received for children from high respectively low social class were significant in the Scottish and Spanish 12-year-old samples. Taking into account the total material of 1600 children in each age-group, risk indicators for caries, identified by logistic and multiple regression analyses, were social class of the family, the mother's smoking habits, and in the 5-year-olds the number of siblings.
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9,178,448
|
Caries risk assessment in adolescents.
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Detailed caries records and salivary microbiological tests were utilized to predict caries development in a group of 15-16-year-old Swedish adolescents. Both, caries experience and salivary microorganisms, correlated significantly with a subsequent 3-year increment of DFS. The strongest associations were recorded between the prevalence of baseline incipient lesions and the development of manifest caries (r = 0.51). Incipient lesions accounted for 27% of the 31% variability in the DFS increment explained by joined caries and salivary data. All predictors analysed showed insufficient sensitivity for identifying true caries active individuals. However, the combined sensitivity and specificity for incipient lesions and comprehensive caries record (incipient + manifest lesions) attained values allowing to predict caries development in the majority of individuals. Using precavity lesions as a sole predictor, 79-81% of the individuals were correctly classified with regard to their future caries levels. The addition of manifest caries increased the accuracy of classification to 86-89% depending on the stringency of screening and validation criteria.
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9,178,449
|
Tobacco preventive measures by dental care staff. An attempt to reduce the use of tobacco among adolescents.
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The purpose of the present study was to investigate the tobacco habits of children and adolescents within the catchment area of a public dental clinic before and after information about tobacco was given by dental care staff. The study was carried out over a three-year period on all 12- to 19-year-olds who came to the clinic for check-ups, 919, 933 and 859 individuals during each respective year. In the first year epidemiological data regarding use of tobacco were registered. Starting with the second year of the study coordinated information was given about the detrimental health effects of tobacco use. This consisted of individual information during the check-up, waiting-room information, and tobacco information in connection with dental health education in school. Use of tobacco was observed from the age of 14. Use was similar among boys and girls and increased with age. The proportion of tobacco users was 10.3%, 11.5%, and 7.3% for the respective years of the study. Statistical analysis shows that the reduction between the second and third year of the study is significant (p < 0.05). The result supports the hypothesis that tobacco information conveyed by dental care staff can influence the tobacco habits of children and adolescents.
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9,178,450
|
Traumatic oral vs non-oral injuries.
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This study comprised patients who sought consultation or treatment from a physician or dentist for injury caused by accident in a Swedish county (Västmanland 256510 inhabitants) during a period of one year. A total of 23690 (adjusted for non-responders) individuals were injured during the study period. Five per cent included oral injuries, 95% non-oral injuries, and 0.4% consisted of both oral and non-oral injuries. In total, oral injuries were the sixth most common part of the body that was injured. The incidence of oral injuries was 4.2/1000 inhabitants/year and of non-oral injuries 87.8/1000/year. Because practically all oral injuries were observed in individuals under the age of 30, the comparison between oral and non-oral injuries was made for the age interval 0-30 years. The highest risk of sustaining oral injuries was in the ages 0-12 years, where the annual incidence was 18/1000, making oral injuries the third most common form of injury. The study reveals substantial differences between oral and non-oral injuries with regard to age-groups, site of injury, and injury mechanism. Falls were the most common cause of oral injuries among those 0-6 years of age, whereas push and hit were the primary causes of oral injuries in the ages 16-30 years. Non-oral injuries were caused most frequently by falls in all age groups. Alcohol and violence were more likely related to oral than non-oral injuries for persons in the age interval 16-30 years. The number of oral injuries was higher during weekends and in the late evenings than at other times, whereas most non-oral injuries occurred during day-time hours, and were spread evenly throughout the week. The high incidence and special characteristics of oral injuries stress the importance of including oral injuries to achieve a high validity in body injury surveillance systems. Furthermore, the results indicate that epidemiological data are unique for oral injuries which should be taken into consideration when planning for prevention and organization of emergency resources.
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9,178,452
|
Male-mediated teratogenesis: spectrum of congenital malformations in the offspring of A/J male mice treated with ethylnitrosourea.
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Male mice of inbred strain A/J were intraperitoneally treated with ethylnitrosourea (ENU). On day 64-82 posttreatment, the males were mated with untreated virgin females of the same strain. Copulation involved sperm that were spermatogonial stem cells at the time of treatment. On day 18 of gestation, viable fetuses were inspected for external malformations. The most common malformation to occur spontaneously in the control group was cleft palate or cleft lip. Similarly, in the ENU-treated series, cleft palate or cleft lip was the predominant malformation, the frequency (15%) of which was significantly increased in the highest dose group (5 x 50 mg/kg) compared to control (8%). Based on these results and other data, we propose that a large fraction of external malformations in fetuses from mutagenized paternal germ cells are a result of increased yields of spontaneously occurring malformations.
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9,178,451
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Developmental and dysmorphogenic effects of glufosinate ammonium on mouse embryos in culture.
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The effects of glufosinate ammonium on embryonic development in mice were examined using whole embryo and micromass cultures of midbrain and limb bud cells. In day 8 embryos cultured for 48 hr, glufosinate caused significant overall embryonic growth retardation and increased embryolethality to 37.5% at 10 micrograms/ml (5.0 x 10(-5) M). All embryos in the treated groups exhibited specific morphological defects including hypoplasia of the prosencephalon (forebrain) (100%) and visceral arches (100%). In day 10 embryos cultured for 24 hr, glufosinate significantly reduced the crown-rump length and the number of somite pairs, and produced a high incidence of morphological defects (84.6%) at 10 micrograms/ml. These embryos were characterized by blister in the lateral head (100%), hypoplasia of prosencephalon (57.1%), and cleft lips (42.9%) at 20 micrograms/ml (10.0 x 10(-5) M). Histological examination of the treated embryos showed numerous cell death (pyknotic debris) present throughout the neuroepithelium in the brain vesicle and neural tube, but did not involve the underlying mesenchyme. In micromass culture, glufosinate inhibited the differentiation of midbrain cells in day 12 embryos with 50% inhibition occurring at 0.55 microgram/ml (2.8 x 10(-6) M). The ratios of 50% inhibition concentration for cell proliferation to cell differentiation in limb bud cells were 0.76 and 1.52 in day 11 and 12 embryos, respectively. These findings indicate that glufosinate ammonium is embryotoxic in vitro. In addition to causing growth retardation, glufosinate specifically affected the neuroepithelium of the brain vesicle and neural tube, leading to neuroepithelial cell death.
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9,178,453
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Evaluation of the developmental toxicity of 4-bromobenzene using frog embryo teratogenesis assay--Xenopus: possible mechanisms of action.
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Potential mechanisms of 4-bromobenzene-induced developmental toxicity were evaluated using frog embryo teratogenesis assay-Xenopus (FETAX). Early X, laevis embryos were exposed to 4-bromobenzene in two separate definitive concentration-response tests with and without an exogenous metabolic activation system (MAS) or selectively inhibited MAS. The MAS was treated with carbon monoxide (CO) to modulate P-450 activity, cyclohexene oxide (CHO) to modulate epoxide hydrolase activity, and diethyl maleate (DM) to modulate glutathione conjugation. Addition of the intact MAS, and particularly the CHO- and DM-inhibited MASs, dramatically increased the embryo lethal potential of 4-bromobenzene. Addition of the CO-inhibited MAS decreased the developmental toxicity of activated 4-bromobenzene to levels approximating that of the parent compound. Results from these studies suggested that a highly toxic arene oxide intermediate of 4-bromobenzene formed as the result of mixed function oxidase (MFO)-mediated metabolism may play an important role in the development toxicity of 4-bromobenzene in vitro. Furthermore, both epoxide hydrolase and glutathione conjugation appeared to be responsible for activated 4-bromobenzene detoxification.
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9,178,454
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Inhibitory effects of phenolic compounds on development of naturally occurring preneoplastic hepatocytic foci in long-term feeding studies using male F344 rats.
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Five phenolic compounds, namely caffeic acid, sesamol, hydroquinone, catechol, and 4-methoxyphenol, were fed to groups of 30 male F344 rats at dietary levels of 2, 2, 0.3, 0.8, and 2%, respectively, for 2 years. Retardation of body weight and elevated relative liver weights were noted for all groups. Formalin-fixed and paraffin-embedded liver tissues from rats killed terminally were cut and stained for glutathione S-transferase placental form (GST-P) and tumor growth factor alpha (TGF alpha) immunohistochemically. Numbers and areas of GST-P-positive (GST-P+) foci per unit area of liver section were measured, and the respective treated/control proportional values were calculated to be 58 and 57% for caffeic acid. 58 and 54% for sesamol, 71 and 71% for hydroquinone. 58 and 133% for catechol, and 49 and 39% for 4-methoxyphenol. These data were comparable with results obtained with medium-term liver bioassays (Ito test). However, no intergroup differences were detected with regard to quantitative findings for TGF alpha foci, which were relatively rare. Long-term inhibitory effects of phenolic compounds on liver carcinogenesis, predicted from the Ito test, were thus confirmed in the present feeding studies using quantitative analysis of immunohistochemically demonstrable GST-P+ foci as end point marker lesions.
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9,178,455
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Induction of feline immunodeficiency virus specific antibodies in cats with an attenuated Salmonella strain expressing the Gag protein.
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Salmonella typhimurium aroA strains (SL3261), expressing high levels of the Gag protein of feline immunodeficiency virus (FIV) fused with maltose binding protein (SL3261-MFG), were constructed using an invertible promoter system that allows the stable expression of heterologous antigens at levels toxic for bacteria. A SL3261 strain expressing the B subunit of cholera toxin by a similar system (SL3261-CtxB) served as a control in FIV-immunization experiments. Cats immunized once orally or intraperitoneally with SL3261-MFG or SL3261-CtxB all developed serum antibodies to SL3261 lipopolysaccharide and against maltose binding protein or the B subunit of cholera toxin, respectively. Two intraperitoneal immunizations with SL3261-MFG also resulted in the development of Gag specific serum antibodies. Two oral immunizations with SL3261-MFG primed for a Gag specific response, which was demonstrated upon FIV challenge. All challenged cats became infected and no significant differences in viral loads were found between SL3261-MFG and SL3261-CtxB immunized cats.
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9,178,457
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Immunogenic and protective properties of haemagglutinin protein (H) of rinderpest virus expressed by a recombinant baculovirus.
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The hemagglutinin (H) protein of Rinderpest virus expressed by a recombinant baculovirus used as a vaccine produced high titres of neutralizing antibody to Rinderpest virus in the vaccinated cattle, comparable to the levels produced by live attenuated vaccine. The immunized cattle were protected against a vaccine-virus challenge, as demonstrated by the failure of development of antibodies to N protein of the vaccine virus. The lack of replication of vaccine virus in the immunized cattle indicated that they are capable of showing a protective response if challenged with a virulent virus.
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9,178,458
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Potency testing of tissue culture rinderpest vaccine in rabbits.
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Rinderpest (RP) vaccine potency testing requires virulent bovine rinderpest virus (RPV). Use of virulent RPV is a biosafety hazard. In this study we had vaccinated rabbits with tissue culture RP vaccine at different doses and thereafter challenged with lapinized virus. No thermal reaction in vaccinated rabbits was observed. Serum neutralizing antibody response to vaccine was dose dependent until the second week post-vaccination but by the fourth week post-vaccination all the rabbits had similar neutralizing antibody titres. Vaccinated rabbits exhibited mild clinical signs as compared to unvaccinated controls after challenge. All the vaccinated rabbits survived challenge while only 40% unvaccinated rabbits survived challenge with virulent lapinized RPV. A strong anamnestic response in all the vaccinated rabbits was observed after challenge with lapinized virus. This study shows that rabbits could be used for potency testing of RP vaccine virus.
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9,178,456
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Determinants and kinetics of cytokine expression patterns in lungs of vaccinated mice challenged with respiratory syncytial virus.
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The development of a successful respiratory syncytial virus (RSV) vaccine will be advanced by an improved understanding of the pathogenesis of natural disease and vaccine-enhanced illness. Using a murine model, we have examined cytokine message expression and cytokine secretion in lungs of mice primed with killed or live antigens and challenged with RSV. Stable cytokine mRNA expression was achieved if the prime-challenge interval was 2 weeks. The pattern of expression of interleukin-4 (IL-4) and interferon-7 (IFN-gamma 1 mRNA was established by day 4 after challenge and was maintained at least through day 12, and was not affected by the concentration of priming immunogen or virus challenge. An enzyme-linked immunospot assay demonstrated that CD4+ T cells were responsible for the production of IL-4, while many cell types secreted IFN-gamma. These experiments begin to define the kinetics of cytokine expression and phenotypes of cytokine-producing cells following RSV infection, supporting previous findings that suggested aberrant infiltration of CD4+ T lymphocytes and excessive IL-4 secretion may play a role in the vaccine-enhanced disease associated with RSV.
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9,178,461
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Passive immunity against measles during the first 8 months of life of infants born to vaccinated mothers or to mothers who sustained measles.
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Neutralizing antibody titers of 47 infants whose mothers sustained measles (measles group) and 70 whose mothers were vaccinated (vaccine group) were compared at birth, 4 and 8 months of age. All children had antibodies at birth and 88% at 4 months. At 8 months, 49% had antibodies in the measles group and 15% in the vaccine group (P < 0.001). The geometric mean titers were significantly lower in the vaccine group than in the measles group and the difference corresponded to the antibody loss occurring in only 1.5 months of life. This small difference may reflect past exposure to wild virus of many vaccinated mothers.
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9,178,460
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Protection against tetanus toxin in mice nasally immunized with recombinant Lactococcus lactis expressing tetanus toxin fragment C.
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Mice inoculated intranasally (i.n.) with a recombinant strain of live Lactococcus lactis expressing tetanus toxin fragment C (TTFC), produced both serum and secretory antibodies to TTFC. Killed bacteria which had accumulated TTFC intracellularly in vitro also elicited protective serum antibody responses. There was no requirement for either colonization or invasion of the mucosa. In addition secretory antibody responses in the lung and nasal tissues were elicited after i.n. inoculation in the presence of an adjuvant.
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9,178,465
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Recognition of contiguous allele-specific peptide elements in the rubella virus E1 envelope protein.
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Peptides which bind to human HLA-DRB1 class II molecules in an allele-specific fashion were derived from the immunodominant E1 envelope protein of rubella virus. Two nonoverlapping E1 peptide epitopes were recognized by rubella virus-specific T cells in the context of independent HLA alleles when presented either separately or as a contiguous polypeptide containing both epitopes. Direct binding analysis of potential peptide epitopes to distinct HLA molecules provides a direct approach for selecting antigenic peptides useful for epitope-based vaccine targeted to multiple HLA types.
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9,178,462
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Total and isotype humoral responses in cattle vaccinated with foot and mouth disease virus (FMDV) immunogen produced either in bovine tongue tissue or in BHK-21 cell suspension cultures.
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The anti-foot and mouth disease virus (FMDV) serum antibody activity of protected and non protected animals immunized with inactivated FMDV originated in either bovine tongue tissue (BTTV vaccines) or BHK-21 cell suspension cultures (BHKV vaccines) was evaluated. The results show that 80-100% of the BTTV immunized and only 40-60% of the BHKV immunized animals with liquid-phase blocking sandwich ELISA (lp ELISA) serum titres of 1.5-1.7 U, were protected against the challenge with any of the four infectious FMDV argentine reference strains. This difference becomes almost marginal among BTTV and BHKV vaccinated animals with a strong anti-FMDV humoral response (i.e. lp ELISA titres > or = 1.95 U). Isotyping of the anti-FMDV response in immunized cattle with low lp ELISA titres revealed that BTTV vaccines were able to induce remarkably higher anti-FMDV IgG1 titres than their BHKV counterparts (i.e. mean titres of 1.95 and 1.35 U. respectively). This difference in specific IgG1 serum levels induced by BTTV and BHKV vaccines seems to be also limited to those animals with low anti-FMDV lp ELISA titres. These results together with the fact that the specific serum IgG1, but not the IgG2, isotype response of 219 vaccinated animals correlates almost linearly with their capacity to pass the challenge, suggests that the superior performance of BTTV vaccines is close related to their ability to raise a stronger anti-FMDV IgG1 response than BHKV vaccines.
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9,178,463
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Anthrax post-vaccinal cell-mediated immunity in humans: kinetics pattern.
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Seven groups (2596 subjects) were vaccinated with a human live anthrax vaccine (HLAV) by three different routes (scarification, subcutaneous and aerosol). The vaccinees were tested for anthrax cell-mediated immunity using the "Anthraxin" skin test at 7, 15, 30, 90, 180 and 365 days following vaccination. The kinetic pattern obtained from all groups, shows a significant, five-phased curve: phase I (2-6 days post-vaccination) shows a slow increase in positive Anthraxin skin reactions. Phase II (7-15 days post-vaccination) shows an exponential rise to a maximum at day 15. Phase III (16-30 days post-vaccination) shows a decrease to day 30. Phase IV (31-90 days post-vaccination) leads to a relative restoration of the positive skin reactions. During phase V (91-365 days post-vaccination) there is a continuous decrease in positive Anthraxin skin reactions. The loss of the skin test reaction on day 30 is a characteristic feature of post vaccination anthrax cell-mediated immunity. It may be due to a blockade of macrophages by lethal anthrax toxin released by the multiplying vaccine strain. Epidemiological observations of HLAV protective rates correlate with the phases of the skin reaction kinetics.
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9,178,459
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Inactivated hepatitis A vaccine: long-term antibody persistence.
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During the clinical development of safe, well tolerated and immunogenic vaccines against hepatitis A the persistence of protective antibodies was estimated, based on relatively short observation periods of 18 months to 3 years. We report here on longterm persistence of antibodies in volunteers who participated in one of the early clinical trials on inactivated hepatitis A candidate vaccines. In a randomized trial three groups of altogether 110 healthy adults, initially hepatitis A virus (HAV) seronegative persons were vaccinated with an inactivated hepatitis A vaccine according to the schedule 0-1-2-12 months. One group received 180 ELISA units, one group 360, and one 720 ELISA units per dose. Blood samples were taken prior to the first vaccination and at months 1, 2, 3, 4, 6, 12, 13, 18, 24, 36 and 84. The decrease of antibodies was characterized by two disappearance rates: a rapidly decreasing component and a slower decreasing one becoming predominant ca 12 months after booster vaccination. The disappearance of antibodies could be described by a two-component model which holds for t > or = 13 months. The estimated disappearance rates for the slow component (annual decrease) was found to be 11 and 13% for the 180 and 360 El. U groups, respectively (the 720 El. U group showed no decline, which was probably due to the small sample size). The estimated persistence of antibodies within protective range varied between 24 and 47 years depending on individual titres reached at month 13 and vaccination dose.
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9,178,470
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Yeast-secreted bovine herpesvirus type 1 glycoprotein D has authentic conformational structure and immunogenicity.
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Bovine herpesvirus-1 (BHV-1) glycoprotein D (gD), an envelope glycoprotein, engenders mucosal and systemic immunity protecting cattle from viral infection. Production of gD with authentic immunogenicity is required for a subunit vaccine. We placed the truncated BHV-1 gD gene, lacking its putative transmembrane and cytoplasmic domains, under the control of the methanol-inducible AOX1 promoter in the yeast Pichia pastoris. Truncated BHV-1 gD (tgD) was efficiently secreted into the culture medium as a 68 kDa protein using either the yeast alpha prepro or native BHV-1 gD signal sequences. The yeast-secreted tgD had N-linked glycosylation and appears to have authentic conformational structure and immunogenicity based on the following observations A panel of monoclonal antibodies recognizing five neutralizing epitopes reacted with yeast tgD. Sera from yeast tgD-immunized mice immunoprecipitated native BHV-1 gD and neutralized BHV-1 infection in vitro. Yeast tgD competitively blocked all reaction between native gD and monospecific gD polyclonal sera from cattle. Based on these data, yeast-derived BHV-1 tgD is an excellent candidate for a subunit vaccine.
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9,178,472
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A murine model of intranasal immunization to assess the immunogenicity of attenuated Salmonella typhi live vector vaccines in stimulating serum antibody responses to expressed foreign antigens.
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The lack of a practical small animal model to study the immunogenicity of Salmonella typhi-based live vector vaccines expressing foreign antigens has seriously impeded the vaccine development process. For some foreign antigens, stimulation of serum IgG antibody is the desired, protective immune response. We administered to mice, by orogastric or intranasal (i.n.) routes, attenuated delta aroC delta aroD S. typhi CVD 908 carrying a plasmid encoding fragment C (fragC) of tetanus toxin fused to the eukaryotic cell receptor binding domain of diphtheria toxin (fragC-bDt), and monitored serum antibody. While orogastric inoculation of three doses was not immunogenic, i.n. immunization elicited high titers of serum IgG tetanus antitoxin, generating peak ELISA geometric mean titers (GMT) of 27024 and 35658 with 10(8) and 10(9) c.f.u. dosages, respectively; 10(9) c.f.u. i.n. of an delta aroA S. typhimurium live vector stimulated a peak antitoxin GMT of 376 405. Mice immunized with the S. typhi live vector were 100% protected against challenge with 100 50% lethal doses of tetanus toxin that rapidly killed all control mice. Intranasal immunization with two doses of S. typhi expressing unfused fragment C under control of an anaerobically-activated promoter derived from nirB stimulated significantly higher titers of serum neutralizing antitoxin than fused fragC-bDt controlled by the same promoter (GMT 0.10 AU ml-1 vs 0.01 AU ml-1, P = 0.0095). Two i.n. doses of S typhi encoding fragC under control of powerful constitutive promoter 1pp led to significantly higher peak serum neutralizing antitoxin titers than the otherwise identical construct utilizing the nirB promoter (peak GMT 0.72 AU ml-1 vs 0.10 AU ml-1, P = 0.022). The i.n. route of inoculation of mice may constitute a practical breakthrough that could expedite the development of some S. typhi-based live vector vaccines by allowing, for the first time, quantitative measurement of serum antibody responses to candidate constructs following i.n. mucosal immunization.
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9,178,464
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Comparison between hepatitis B surface antigen (HBsAg) particles derived from mammalian cells (CHO) and yeast cells (Hansenula polymorpha): composition, structure and immunogenicity.
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The composition, structure and immunogenicity of hepatitis B surface antigen (HBsAg) particles derived from Chinese hamster ovary (CHO) cells and from cells of the yeast Hansenula polymorpha were compared. The particles were similar in size distribution (mean 20-33 nm), in shape (spherical), in gross composition (protein to lipid weight ratio of 60:40), and in types of lipids (phospholipids > > sterols = sterol esters = triacylglycerols). Differences related to genetic engineering and type of host cells were found in peptide and lipid compositions. CHO-HBsAg has three peptides: S, M and L, each in two forms of glycosylation, while the Hansenula-HBsAg has only the nonglycosylated S peptide. The electrical surface potential at the lipid/water interface of HBsAg derived from Hansenula is more negative than that of HBsAg derived from CHO, which was close to neutrality. Although the numbers of cysteine residues (all in the S peptides) are identical (14), 11 of them are free thiols in the CHO-HBsAg, compared with three to four in the Hansenula-HBsAg. The fact that 85% of the phospholipids are hydrolyzed by phospholipase C and that all the aminophospholipids react with trinitrobenzenesulfate suggests that the particles derived from both cell types are either leaky vesicles or have a lipoprotein-like structure. Subcutaneous injection into mice of fluorescein-isothiocyanate-labeled HBsAg particles from both sources resulted in their accumulation in the marginal sinus of lymph nodes. The humoral responses to subcutaneous injection into mice of CHO- and Hansenula-HBsAg were similar: however, the cytotoxic T lymphocyte response to CHO-HBsAg was lower.
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9,178,467
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Protection in a gerbil model of amebiasis by oral immunization with Salmonella expressing the galactose/N-acetyl D-galactosamine inhibitable lectin of Entamoeba histolytica.
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Infection with the enteric parasite Entamoeba histolytica can result in colitis and dysentery as well as abscesses at extra-intestinal sites. An effective vaccine must be able to protect against both mucosal and systemic disease. In this study an attenuated Salmonella strain that expressed a portion of the GalNAc lectin of E, histolytica was used to orally immunize gerbils. Animals were challenged by intrahepatic injection of amebic trophozoites. A significant decrease in size of amebic liver abscesses was observed in orally immunized animals. Oral immunization with a Salmonella-based vaccine was as effective as systemic immunization for protection against systemic challenge.
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9,178,466
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Protective responses in mice to vaccination with multiply administered cold-adapted influenza vaccine reassortants and wild-type viruses.
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Protective responses to influenza vaccine reassortants derived from the cold-adapted (ca) donor strains A/Leningrad/134/17/57 and B/USSR/60/69 and wild-type epidemic viruses were studied in two strains of mice. Preliminary experiments revealed that, when mixtures of three viruses were inoculated intranasally to mice with 50 microliters containing 10(6) EID50 per 200 microliters (10(5.4) EID50 per mouse), interference between strains did not occur. However, interference with the growth of the influenza reassortant B/60/32/R took place if its concentration in the mixture was reduced to 10(5) (10(4.4) per mouse) or if it was inoculated at 10(6) EID50 (10(5.4) per mouse) in the presence of the influenza reassortant R/34 and two other influenza A epidemic strains; interference was unrelated to serological responses to infection with B/60/32/R. Despite evidence of interference, mice inoculated with the same mixtures in two identical doses, three weeks apart, were able to clear a challenge from each of seven homotypic and heterotypic influenza A and B strains. Heterotypic clearance of influenza A challenge viruses was greater following mixed infection, indicating that common determinants within the surface antigen glycoproteins contributed to immune responses which were broader than could be expected to be induced by parenteral vaccination.
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