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Malnutrition is one of the greatest single threats to the world’s public health among children in developing countries according to the World Health Organization. It affects the child at the most crucial period, that is, stage of development, which can lead to permanent impairment in later life which includes reduced work capacity, growth retardation, and poor social and mental development. Half of all child deaths in India could be prevented if this one issue is tackled. Almost 11 million children die before they reach the age of five, four million of them in the 1st month of life. It is a significant public health problem described as a silent killer, silent emergency and invisible enemy affecting those who cannot express their voice and have to depend on others for their advocacy. The main objective of this study is to determine the effect of supplementation with the selected product on the nutritional status of the selected malnourished children. A baseline survey was conducted in four villages of Allahabad District, U.P. A total number of 382 respondents were selected (187 girls and 195 boys) for the present study. They belong to age group of 3–5 years. Four products were prepared with the help of incorporation composite flour. For each product, the basic recipes (control T0) have three variations T1, T2, and T3, respectively, were incorporated at different levels. The products such as Laddo, Biscuit; Mathri, and Chakli were developed. After supplementation, it is evident to note that there was a statistically significant improvement at 1% level and it was observed in the experimental and there was no increment in the weight of the selected subjects in the control group.

Introduction The increasing incidence of cesarean sections in India has caused a rise in the incidence of postpartum hemorrhage (PPH). There has been expanding interest in the role of misoprostol and tranexamic acid (TXA) in preventing and managing PPH during lower (uterine) segment cesarean section (LSCS). However, the lack of a published study comparing the efficacies of these drugs prompted us to conduct this study. Aims and objectives To compare the efficacies of sublingual misoprostol (600 μg) and intravenous TXA injection (500 mg) in reducing blood loss during LSCS by assessing intraoperative blood loss, perioperative hemoglobin (Hb) fall, and need for additional uterotonic agents. Materials and methods A total of 163 pregnant patients undergoing emergency/elective LSCS during the study period from 2013 to 2014 were randomly assigned to two groups — group I (82) received sublingual misoprostol 600 μg and group II (81) intravenous TXA 500 mg at cord clamping. Visual estimation of blood loss was done and 48 hours postoperative Hb and packed cell volume were measured to compare with preoperative values. Need for added uterotonics, blood transfusion, and adverse effects of drugs was assessed. The two groups were again subgrouped based on presence or absence of risk factors for PPH. Results The TXA significantly reduced blood loss compared with misoprostol (416 vs 505 mL) in patients without high-risk factors for PPH. Misoprostol caused significantly higher minor side effects while TXA reduced operation time. Conclusion The TXA can be routinely used after cord clamping along with oxytocin in patients undergoing elective/emergency LSCS to reduce perioperative blood loss, especially in those without risk factors for PPH. How to cite this article Bose D, Beegum R. Sublingual Misoprostol vs Intravenous Tranexamic Acid in reducing Blood Loss during Cesarean Section: A Prospective Randomized Study. J South Asian Feder Obst Gynae 2017;9(1):9-13.

In laparoscopy, tissue extraction might require morcellation for larger intra-abdominal specimens, especially in gynecological patients. specimen, the specimen needs to be reduced. The Food and Drug Administration (FDA) issued a press release in April 2014 that discouraged the use of devices used for morcellation - power morcellators. This article has the objective to review the literature related to complications by power morcellation of uterine fibroids in laparoscopy and offer recommendations to laparoscopic surgeons in gynaecology. Respecting women who have leiomyosarcoma, it can be concluded that the FDA directive was based on a mis­leading analysis due to inherent flaws in the trials analysed by it. Hence, the need of the hour are more accurate esti­mates regarding the prevalence of leiomyosarcoma among women having surgery for presumed leiomyomas. Modification of the FDA’s current restriction regarding power morcellation would empower each woman to allow surgeons and hospitals to make the most appropriate, informed choices regarding utilization of tissue extraction in individual patients undergoing uterine surgery without undermining the freedom of the woman to choose the best-suited procedure.

The Mars Science Laboratory entry vehicle successfully landed the Curiosity rover on the Martian surface on 5 August 2012. A phenolic impregnated carbon ablator heatshield was used to protect the spacecraft against the severe aeroheating environments of atmospheric entry. This heatshield was instrumented with a comprehensive set of pressure and temperature sensors. The objective of this paper is to perform an inverse estimation of the entry vehicle’s surface heating and heatshield material properties. The surface heating is estimated using the flight temperature data from the shallowest thermocouple. The sensitivity of the estimated surface heating profile to estimation tuning parameters, measurement errors, recession uncertainty, and material property uncertainty is investigated. A Monte Carlo analysis is conducted to quantify the uncertainty bounds associated with the nominal estimated surface heating. Additionally, a thermocouple driver approach is employed to estimate heatshield material properties using the flight data from the deeper thermocouples while applying the shallowest thermocouple temperature as the surface boundary condition.

This paper will introduce Mars Entry Descent and Landing Instrumentation (MEDLI2) on NASA's Mars2020 mission. Mars2020 is a flagship NASA mission with science and technology objectives to help answer questions about possibility of life on Mars as well as to demonstrate technologies for future human expedition. Mars2020 is scheduled for launch in 2020. MEDLI2 is a suite of instruments embedded in the heatshield and backshell thermal protection systems of Mars2020 entry vehicle. The objectives of MEDLI2 are to gather critical aerodynamics, aerothermodynamics and TPS performance data during EDL phase of the mission. MEDLI2 builds up the success of MEDLI flight instrumentation on Mars Science Laboratory mission in 2012. MEDLI instrumentation suite measured surface pressure and TPS temperature on the heatshield during MSL entry into Mars. MEDLI data has since been used for unprecedented reconstruction of aerodynamic drag, vehicle attitude, in-situ atmospheric density, aerothermal heating, transition to turbulence, in-depth TPS performance and TPS ablation. [1,2] In addition to validating predictive models, MEDLI data has highlighted extra margin available in the MSL forebody TPS, which can potentially be used to reduce vehicle parasitic mass. MEDLI2 expands the scope of instrumentation by focusing on quantities of interest not addressed in MEDLI suite. The type the sensors are expanded and their layout on the TPS modified to meet these new objectives. The paper will provide key motivation and governing requirements that drive the choice and the implementation of the new sensor suite. The implementation considerations of sensor selection, qualification, and demonstration of minimal risk to the host mission will be described. The additional challenges associated with mechanical accommodation, electrical impact, data storage and retrieval for MEDLI2 system, which extends sensors to backshell will also be described.

The hypersonic regime of planetary entry combines the most severe environments that an entry vehicle will encounter with the greatest amount of uncertainty as to the events unfolding during that time period. This combination generally leads to conservatism in the design of an entry vehicle, specifically that of the thermal protection system (TPS). Each planetary entry provides a valuable aerodynamic and aerothermal testing opportunity; the utilization of this opportunity is paramount in better understanding how a specific entry vehicle responds to the demands of the hypersonic entry environment. Previous efforts have been made to instrument entry vehicles in order to collect data during the entry period and reconstruct the corresponding vehicle response. The purpose of this paper is to cumulatively document past TPS instrumentation designs for applicable planetary missions, as well as to list pertinent results and any explainable shortcomings.

A Monte-Carlo-based methodology is presented for physics-based probabilistic uncertainty analysis of aerothermodynamics and thermal protection system (TPS) material response modeling for aerocapture or direct entry missions. The objective of the methodology is to identify and quantify the most important sources of uncertainty in aeroheating and the resulting thermal protection material selection, design, and sizing based on inaccuracies in current knowledge of the parametric input modeling parameters. The resulting parametric modeling uncertainty would be combined with other uncertainty sources to determine the final aeroheating and TPS response modeling uncertainty for a given application, which can then be used to define appropriate margins and factors of safety that should be applied to the TPS. These techniques facilitate a risk-based probabilistic design approach, whereby the thermal protection system can be designed to a desired risk tolerance, and any remaining risk can be effectively compared to that of other subsystems via a system-level risk mitigation analysis. Modeling sensitivities, which are a byproduct of the uncertainty analysis, can be used to rank input uncertainty drivers. Key input uncertainties can then be prioritized and targeted for further analysis or testing. The strengths and limitations of this technique are discussed. Sample results are presented for two cases: Titan aerocapture and Mars Pathfinder. These cases demonstrate the utility of the methodology to quantify the uncertainty levels, rank sources of input uncertainty, and assist in the identification of structural uncertainties in the models employed.

NASA's Low Density Supersonic Decelerator Program is developing new technologies that will enable the landing of heavier payloads in low density environments, such as Mars. A recent flight experiment conducted high above the Hawaiian Islands has demonstrated the performance of several decelerator technologies. In particular, the deployment of the Robotic class Supersonic Inflatable Aerodynamic Decelerator (SIAD-R) was highly successful, and valuable data were collected during the test flight. This paper outlines the Computational Fluid Dynamics (CFD) analysis used to estimate the aerodynamic and aerothermal characteristics of the SIAD-R. Pre-flight and post-flight predictions are compared with the flight data, and a very good agreement in aerodynamic force and moment coefficients is observed between the CFD solutions and the reconstructed flight data.

Ar eview of the best-available data for calculating a complete set of binary collision integral data for the computation of the mixture transport properties (viscosity, thermal conductivity, and ordinary and thermal diffusion) of 13-species weakly ionized air is presented. Although the fidelity of the data varies, all collision integrals presented herein, except for electron-neutral interactions, are estimated to be accurate to within 25% over the temperature range of interest (300‐15,000 K) for reentry and laboratory plasmas. In addition, most of the dominant atom‐atom and atom‐ion interactions for dissociated weakly ionized air were derived from ab initio methods that are estimated to be accurate to within 10%. The accuracy and valid temperature range for electron-neutral interactions vary because of scarcity of the required cross-sectional data.

A Monte Carlo sensitivity analysis is used to build a plasma chemistry model for octacyclofluorobutane (c‐C4F8) which is commonly used in dielectric etch. Experimental data are used both quantitatively and qualitatively to analyze the gas phase and gas surface reactions for neutral radical chemistry. The sensitivity data of the resulting model identifies a few critical gas phase and surface aided reactions that account for most of the uncertainty in the CF2 and CF radical densities. Electron impact dissociation of small radicals (CF2 and CF) and their surface recombination reactions are found to be the rate-limiting steps in the neutral radical chemistry. The relative rates for these electron impact dissociation and surface recombination reactions are also suggested. The resulting mechanism is able to explain the measurements of CF2 and CF densities available in the literature and also their hollow spatial density profiles.

A two-dimensional axisymmetric helicon plasma source with three-dimensional wave components is modeled. Plasma fluid equations are solved self-consistently with helicon wave equations. Electron inertia is taken into account to simulate the propagation of electrostatic wave components. The purpose of this paper is to describe the model in detail and present the results to verify wave propagation characteristics, power deposition mechanisms, especially bulk versus peripheral power absorption. We also study the effect of wave absorption characteristics on discharge plasma density and temperature profiles.

The heat shield of the Mars Science Laboratory (MSL) was equipped with thermocouplestacks to measure in-depth heating of the thermal protection system during atmosphericentry. The heat load derived from the thermocouples in the stagnation region was found tobe 33 lower than corresponding post-flight predictions of convective heating alone. It washypothesized that this difference could be attributed to radiation from the shock-heated gas,a mechanism not considered in post-flight analyses of flow fields. In order to test thehypothesis and quantify the contribution of shock-layer radiation to total surface heating,ground tests and simulations (both flow and radiation) were performed at several pointsalong the best-estimated entry trajectory of MSL. The present paper provides anassessment of the quality of the radiation model and its impact to stagnation point heating.Although the impact of radiative heating is shown to be significant, it only accounts for 43of the discrepancy. Additional factors behind the remaining discrepancy are discussed.

Objective: Histamine H3 receptors and α2-adrenoceptors are presynaptic receptors that modulate norepinephrine (NE) release from sympathetic nerves innervating the cardiovascular system. We previously showed that cardiac H3 receptors are activated in sepsis, and that this activation leads to a decrease in the adrenergic response (AR) [J. Appl. Physiol. 85 (1998) 1693-1701] H3-receptors and α2-receptors appear to be coupled to GTP binding regulatory proteins (G) that modulate transmitter release by reducing calcium current into the nerve terminals through neuronal calcium channels. There may also be interaction between H3-receptors and α2-receptors on AR that may occur either at the receptor or a more downstream level. Methods: In the present study, we examined the effect of septic plasma on AR in a canine ventricular preparation in which field stimulation was used to produce AR. We determined whether there was interaction between H3-receptors and α2-adrenoceptors and tested whether H3 activation would attenuate the α2-agonist and α2-antagonist effects of clonidine and yohimbine, respectively. We also determined whether the mechanism by which septic plasma decreases the adrenergic response involves inactivation of an inhibitory G protein and used pertussis toxin (PTX) to assess this effect. Results: We found that septic plasma attenuated AR produced by field stimulation, and that this decrease was mediated by a PTX sensitive inhibitory G protein. H3 activation also attenuated the α2-agonist and α2-antagonist effects on adrenergic activation as compared with nonseptic plasma. Conclusion: We conclude that presynaptic sympathetic dysfunction may contribute to cardiovascular collapse in sepsis.

We present a coupled plasma and collisionless sheath model for the simulation of high-density plasma processing reactors. Due to inefficiencies in numerical schemes and the resulting computational burden, a coupled multidimensional plasma and sheath simulation has not been possible for gas mixtures and high-density reactors of practical interest. In this work, we demonstrate that with a fully implicit algorithm and a refined computational mesh, a self-consistent simulation of a reactor including both the plasma and sheath is feasible. We discuss the details of the model equations, the importance of ion inertia, and the resulting sheath profiles for argon and chlorine plasmas. We find that at low operating pressures (10-30 mtorr), the charge separation occurs only within a 0.5-mm layer near the surface in a 300 mm inductively coupled plasma etch reactor. A unified simulation eliminates the use of offline or loosely coupled and oversimplified sheath models which generally leads to uncertainties in ion flux and sheath electrical properties.

Recently it has been recognized that the neutral gas in inductively coupled plasma reactors heats up significantly during processing. The resulting gas density variations across the reactor affect reaction rates, radical densities, plasma characteristics, and uniformity within the reactor. A self-consistent model that couples the plasma generation and transport to the gas flow and heating has been developed and used to study CF4 discharges. A Langmuir probe has been used to measure radial profiles of electron density and temperature. The model predictions agree well with the experimental results. As a result of these comparisons along with the poorer performance of the model without the gas-plasma coupling, the importance of gas heating in plasma processing has been verified.

We propose a semianalytical ion dynamics model for a collisionless radio frequency biased sheath. The model uses bulk plasma conditions and electrode boundary condition to predict ion impact energy distribution and electrical properties of the sheath. The proposed model accounts for ion inertia and ion current modulation at bias frequencies that are of the same order of magnitude as the ion plasma frequency. A relaxation equation for ion current oscillations is derived which is coupled with a damped potential equation in order to model ion inertia effects. We find that inclusion of ion current modulation in the sheath model shows marked improvements in the predictions of sheath electrical properties and ion energy distribution function.

In the heart, histamine (H3) receptors may function as inhibitory presynaptic receptors that decrease adrenergic norepinephrine release in conditions of enhanced sympathetic neural activity. We hypothesized that H3-receptor blockade might improve cardiovascular function in sepsis. In a canine model of Escherichia coli sepsis, we found that H3-receptor blockade increased cardiac output (3.6 to 5.3 l/min, P< 0.05), systemic blood pressure (mean 76 to 96 mmHg, P < 0.05), and left ventricular contractility compared with pretreatment values. Plasma histamine concentrations increased modestly in the H3-blocker–sepsis group compared with values obtained in a nonsepsis–time-control group. In an in vitro preparation, histamine H3 activation could be identified under conditions of septic plasma. We conclude that activation of H3 receptors may contribute to cardiovascular collapse in sepsis.

The Gauss‐Seidel line relaxation method is modie ed for the simulation of viscous e ows on massively parallel computers. The resulting data-parallel line relaxation method is shown to have good convergence properties for a seriesoftestcases.Thenewmethodrequiressignie cantlymorememorythanthepreviouslydevelopeddata-parallel relaxation methods, but it reaches a steady-state solution in much less time for all cases tested to date. In addition, the data-parallel line relaxation method shows good convergence properties even on the high-cell-aspect-ratio grids required to simulate high-Reynolds-number e ows. The new method is implemented using message passing on the Cray T3E, and the parallel performance of the method on this machine is discussed. The data-parallel line relaxation method combines the fast convergence of the Gauss ‐Seidel line relaxation method with a high parallel efe ciency and thus shows promise for large-scale simulation of viscous e ows.

In sepsis, myocardial depression may be caused by mediators released as part of the inflammatory reaction, lumour necrosis factor alpha (TNF alpha) is one mediator that may contribute to this depression. In the present study, we contrasted the effects of TNF alpha and septic plasma fraction (SP) obtained from an E. coli model on contractile tension in intact and skinned canine ventricular trabecular (VT) preparations. The objectives were to determine whether SP or TNF alpha could impair contractile tension at the level of the myofilaments, and to determine the extent to which TNF alpha may account for myocardial depression found in E. coli sepsis.Measurements of isometric tensions were made after TNF alpha and SP (10,000 to 30,000 MW fraction) were added to respective intact or skinned canine VT preparations. In the skinned preparation, trabeculae were chemically skinned with Triton X-100.Septic plasma caused a decrease in contraction in the intact preparation compared with preseptic plasma (50 +/- 7 vs 33 +/- 7%, P0.05), but had no effect in the skinned preparation. On the other hand, TNF alpha (30 ng.ml-1) caused an approximately 50% reduction in tension (29 +/- 2 mg vs 16 +/- 5 mg) in the skinned preparation (P0.05), but had no effect in the intact preparation.These results suggest that TNF alpha and SP act through different mechanisms. While SP requires an intact membrane, TNF alpha impairs function by a direct effect on the myofilaments.

This paper presents measurements of equilibrium radiation obtained in the NASA Ames Research Center's EAST facility and the University of Queensland's X2 facility. These experiments were aimed at measuring the level of radiation encountered during conditions relevant to Orion lunar return into Earth's atmosphere. The facilities have targeted the same nominal test conditions of 10 km/s and 26.6 Pa (0.2 Torr). In addition, variations on the nominal shock speed have also been the focus of recent testing in the EAST facility. A comprehensive comparison between the EAST data and NEQAIR is presented in this paper with preliminary X2 comparisons where appropriate. Since the two facilities have different dimensions, and the tests have different shock speeds, NEQAIR simulations are used as a point of reference for the EAST and X2 comparison. Results obtained by independently reducing the data from both facilities are compared. The present analysis endeavors to provide a better understanding of the uncertainty in the measurements, as well as provide an initial comparison between EAST and X2. Furthermore, the present analysis explores various radiative mechanisms to determine if they are due to physical processes relevant to flight, or are just facility dependent phenomena. These phenomena include effects such as the magnitude of the background continuum.

The aim of this work was to determine the relationship between peak twitch amplitude and sarcoplasmic reticulum (SR) Ca2+ content during changes of stimulation frequency in isolated canine ventricle, and to estimate the extent to which these changes were dependent upon sarcolemmal Na(+)-Ca2+ exchange. In physiological [Na+]o, increased stimulation frequency in the 0.2-2-Hz range resulted in a positive inotropic effect characterized by an increase in peak twitch amplitude and a decrease in the duration of contraction, measured as changes in isometric force development or unloaded cell shortening in intact muscle and isolated single cells, respectively. Action potentials recorded from single cells indicated that the inotropic effect was associated with a progressive decrease of action potential duration and a marked reduction in average time spent by the cell near the resting potential during the stimulus train. The frequency-dependent increase of peak twitch force was correlated with an increase of Ca2+ uptake into and release from the SR. This was estimated indirectly using the phasic contractile response to rapid (less than 1 s) lowering of perfusate temperature from 37 degrees C to 0-2 degrees C and changes of twitch amplitude resulting from perturbations in the pattern of electrical stimulation. Lowering [Na+]o from 140 to 70 mM resulted in an increase of contractile strength, which was accompanied by a similar increase of apparent SR Ca2+ content, both of which could be abolished by exposure to ryanodine (1 x 10(-8) M), caffeine (3 x 10(-3) M), or nifedipine (2 x 10(-6) M). Increased stimulation frequency in 70 mM [Na+]o resulted in a negative contractile staircase, characterized by a graded decrease of peak isometric force development or unloaded cell shortening. SR Ca2+ content estimated under identical conditions remained unaltered. Rate constants derived from mechanical restitution studies implied that the depressant effect of increased stimulation frequency in 70 mM [Na+]o was not a consequence of a decreased rate of refilling of a releasable pool of Ca2+ within the cell. These results demonstrate that frequency-dependent changes of contractile strength and intracellular Ca2+ loading in 140 mM [Na+]o require the presence of a functional sarcolemmal Na(+)-Ca2+ exchange process. The possibility that the negative staircase in 70 mM [Na+]o is related to inhibition of Ca(2+)-induced release of Ca2+ from the SR by various cellular mechanisms is discussed.

This retrospective study was undertaken to examine the management and outcome of children who developed isolated masseter muscle spasm (MMS) after the administration of intravenous succinylcholine during anesthetic induction. The inhalation anesthetics used for induction were continued in all of these cases. The medical records of 68 patients (male/female ratio, 1.7:1), identified from approximately 42,000 anesthetics given during the period 1980-1989, were reviewed. Fifty-seven children (2.3-12 yr old) were diagnosed as having isolated MMS, i.e., MMS without spasm of other muscles; 11 experienced generalized rigidity in combination with MMS. Anesthetic and postoperative management of these two groups differed. The overall incidence of MMS was 0.3% of inhalation anesthetics during which succinylcholine was given. Intraoperative arrhythmias occurred in 33% of the patients who developed isolated MMS and more frequently in older children. Most children experienced some degree of hypercarbia and/or metabolic acidosis, but the significance of these abnormalities in the spontaneously ventilating, fasting child is unknown. Serum creatine kinase levels when measured 18-24 h postoperatively were elevated in all but one child (n = 45). There was no long-term morbidity and no mortality. We conclude that failure of the masseter muscles to relax after succinylcholine is not uncommon in children. Based on our experience, and accepting that MMS may be part of the clinical spectrum of malignant hyperthermia, we believe that anesthesia can be continued safely in cases of isolated MMS when careful monitoring accompanies diagnostic evaluation. This differs from the current practice of discontinuing the anesthetic or switching to a nontriggering anesthetic technique.

An investigation of the aerothermodynamic environment of the Huygens entry probe has been conducted. A Monte Carlo simulation of the trajectory of the probe during entry into Titan's atmosphere was performed to identify a worst-case heating rate trajectory. Flowfield and radiation transport computations were performed at points along this trajectory to obtain convective and radiative heat-transfer distributions on the probe's heat shield. This investigation identified important physical and numerical factors, including atmospheric CH4 concentration, transition to turbulence, numerical diffusion modeling, and radiation modeling, which strongly influenced the aerothermodynamic environment.

We report some of the unique pharmacological properties of a semipurified endogenous inotropic factor (EIF) present in the extract of the porcine left ventricle. EIF produced the following effects: (a) increase in isometric contractile force developed by electrically driven canine right ventricular trabecula, reaching a maximum with 60-100 microliters/ml concentration; (b) inhibition of Na-pump activity in canine portal vein; (c) no digitalis-like cardiac toxicity, e.g., increased diastolic tension or spontaneous diastolic mechanical oscillatory activity, despite inhibition of the sodium pump; (d) a small increase in sarcoplasmic reticular Ca release from the heart but a large increase in transsarcolemmal Ca influx as seen in biphasic contractions, an action similar to that produced by digitalis-like substances; and (e) prolongation of the action potential duration and refractory period of the canine isolated trabeculae. This latter action may confer a unique antiarrhythmic property to EIF.

In septic shock, the extent to which lactic acidosis (LA) is a consequence of splanchnic lactate overproduction (SLP) or impaired hepatic lactate extraction (HLE) is not clear. We examined SLP and HLE in E. coli sepsis in dogs. We further determined the effects of vasopressor treatments, which included phenylephrine, dopamine, norepinephrine, and a combination of dobutamine and norepinephrine treatment, on SLP and HLE in respective groups. The animals were studied while anesthetized and ventilated. During sepsis, SLP increased as compared with presepsis (-0.017 versus 0.07 mmol/min, p < 0.05), but this increase could not be explained by reduced splanchnic oxygen delivery (SOD). During sepsis, HLE increased as compared with baseline (0.8 versus 8%, p < 0.05), but was significantly lower than that found during lactic acid loading in nonseptic dogs. None of the vasopressor treatments had a detrimental effect on SLP. These results indicate that LA in sepsis occurs secondary to an increase in splanchnic lactate production that is not related to reduced splanchnic oxygen delivery, as well as to a decrease in hepatic lactate extraction. Effects of different vasoactive agents did not alter either splanchnic lactate production or hepatic lactate extraction in this sepsis model.

Background Malignant hyperthermia (MH) is an important cause of anesthesia-induced death. Malignant hyperthermia susceptibility is diagnosed using the in vitro caffeine/halothane contracture test (CHCT) in fresh muscle biopsy specimens. The CHCT test is highly invasive, expensive, and lacks 100% specificity. Genetic and biochemical evidence provide strong support for the view that the substitution of cysteine for arginine 614 (Arg614Cys) in the human ryanodine receptor gene is one of several mutations that are likely to cause human MH. DNA testing was compared with CHCT as a means of predicting MH susceptibility in a large MH family in which the Arg614Cys mutation was detected. Methods A comparison of CHCT and DNA-based diagnosis was conducted in a large Manitoba Mennonite MH kindred identified by an index patient who died at age 45 yr of an MH crisis after general anesthesia. The presence of the Arg614Cys mutation was detected through a combination of polymerase chain reaction and restriction endonuclease digestion. Blood samples for DNA analysis were obtained from 68 family members, including 19 who had undergone muscle biopsies and 1 who had a documented crisis but did not undergo biopsy. Family members were classified as MH-susceptible or MH-normal on the basis of the CHCT. Results Twenty-two persons were found to be heterozygous for the Arg614Cys mutation. Five of these persons had prior positive CHCT results and one had an MH crisis but did not undergo biopsy. On DNA testing, 44 persons were found to be homozygous for the normal allele. Of these, ten had been classified as MH-normal and five as MH-susceptible on the basis of the CHCT. On reevaluation of the data obtained in our earlier CHCT diagnoses, we found that the condition of the muscle was poor, with no twitch, for three of five individuals homozygous for the normal allele but originally classified as MH-susceptible and for one who was homozygous for the normal allele and originally classified as MH-normal. Caffeine/halothane contracture test results for these four persons were considered invalid. The twitch response was good for the two remaining persons who were homozygous for the normal allele but classified as MH- susceptible, because contracture was observed with appropriately low levels of both caffeine and halothane. Conclusions An absolute correlation between DNA test results and CHCT assignment could not be made in this kindred. Possible explanations for discordance are that the Arg614Cys mutation is not linked to MH, that a second MH mutation is segregating in the family, or that there are errors in the CHCT. Because there is strong evidence supporting the causal nature of the Arg614Cys mutation, the discordant persons are not closely related within the pedigree as they would be if a second MH mutation were segregating, and the CHCT is not 100% accurate, we propose that the observed discordance between DNA test results and CHCT assignment in this kindred results from two false-positive diagnoses by the CHCT.

Background In a previous study, we showed that continuous arteriovenous hemofiltration (CAVH) reversed the depression in left ventricular (LV) contractility in canine Escherichia coli sepsis by the removal of a circulating substance the molecular weight of which is less than 30,000. Despite the normalization of LV contractility, however, we were unable to demonstrate an improvement in systemic arterial blood pressure (BP), presumably because the mechanisms underlying the depression in LV contractility and the decrease in BP are different in sepsis. In the current study, we examined the effect of combined treatment with CAVH and the alpha-adrenergic agonist phenylephrine on LV mechanics and tissue oxygen delivery in our canine E. coli model. Methods Measurements were obtained at baseline (condition B), after 4 h of sepsis (condition S), and after 2 h of CAVH and phenylephrine (condition P) (total of 6 h of sepsis). During P, phenylephrine was infused to restore BP to that found at baseline. The slope of the end-systolic pressure-dimension relation was used as the index of LV contractility; LV anterior-posterior dimensions were measured by sonomicrometry. Results During combined CAVH and phenylephrine treatment, the decrease in the slope of the end-systolic pressure-dimension relation otherwise observed at S was reversed. The slope (mean +/- SD) was 57.5 +/- 32 mmHg/mm at B versus 22.2 +/- 8 mmHg/mm at S (P < 0.05, B vs. S) versus 62 +/- 37 mmHg at P (P < 0.05 S vs. P) (analysis of variance). Mean BP was restored to that found at B (123 +/- 19 mmHg versus 82 +/- 14 mmHg (P < 0.05 B vs. S) versus 116 +/- 27 mmHg (P < 0.05 S vs. P). Combination treatment with CAVH and phenylephrine also improved stroke volume (39.3 +/- 13.5 versus 32 +/- 8 versus 44 +/- 12 ml) and tissue oxygen delivery during P compared with results obtained when phenylephrine was given alone. Conclusions Our study offers a rationale for the combined use of phenylephrine and CAVH in the reversal of cardiac depression and hypotension in sepsis.

We studied the changes in pial arteriolar diameter during hypoxia and 60 and 120 min after restoration of normoxia, using the closed cranial window technique in artificially ventilated and normocapnic rats. Pial arteriolar diameter increased 16 +/- 4% during hypoxia (PaO2 less than 25 mm Hg, lasting 10 min). Although blood pressure (BP), heart rate (HR), and blood gases returned to prehypoxic level when measured at 60 and 120 min after hypoxia, pial arterial diameter decreased significantly (13 +/- 5 and 16 +/- 6% below control levels, respectively). This posthypoxic vasoconstriction was reversed by treatment of the brain surface with L-660,711 (10(-5) M), a specific leukotriene D4 receptor antagonist. These data suggest that leukotrienes may be involved in delayed cerebral vasoconstriction that follows a brief period of hypoxia.

1. Hypoxia reversibly increased isometric tension in unstimulated canine isolated basilar artery rings. 2. Nordihydroguaiaretic acid (NDGA; 5 x 10(-6) M), an inhibitor of lipoxygenase and quinacrine (10(-5) M), which blocks the release of arachidonic acid from phospholipids by inhibiting the enzyme phospholipase A2, blocked hypoxia-induced contractions. 3. The preferential leukotriene D4 (LTD4) antagonist, L-660,711, also inhibited the hypoxia-induced contractions in concentrations ranging from 10(-8) M to 10(-5) M. The effects seen were statistically significant (P less than 0.05). Two components of inhibition were seen. 4. Arachidonic acid (5 micrograms ml-1) caused contraction of the isolated basilar artery rings. This response was inhibited by NDGA (5 x 10(-6) M) and L-660,711 (10(-5) M). 5. The LTD4 (10(-8) M-10(-7) M)-induced contraction was relaxed by L-660,711 in a dose-dependent manner. Both the contraction caused by LTD4 as well as that caused by hypoxia were relaxed by 5 x 10(-6) M adenosine. 6. Leukotriene(s) may be involved in hypoxia-induced contraction of canine isolated basilar artery. However, they may not be the sole mediator(s).

1. We previously isolated an extract from porcine left ventricle that possessed digitalis-like properties such as inhibition of cardiac and kidney Na+, K(+)-ATPase, displacement of [3H]-ouabain from its binding sites and cross reactivity with digoxin antibodies. The extract also had a positive inotropic effect on the guinea-pig heart. 2. In the present study the positive inotropic response of the extract was characterized in canine right ventricular trabeculae. Maximum inotropic response (501 +/- 20%) was produced by 300 microliters and the half maximal increase occurred with 125 microliters of the extract. 3. Ouabagenin produced aftercontractions in rapidly paced trabeculae. Equipotent and even greater amounts of the extract did not produce aftercontractions. 4. The extract increased the amplitude of the delayed component (P2) of biphasic contractions produced by replacing about 92-96% of the external Ca with Sr. A smaller increase in the size of the early component (P1) was also seen. 5. The extract decreased post-rest potentiation after rest for 30s and 2 min. After 8 min of rest, post-rest potentiation was converted to post-rest depression. 6. The extract (20 microliters) produced a decrease in the amplitude of the post-rest rapid cooling contracture (RCC) at all rest intervals. The steady state RCC, although greater than that in the control muscle, was increased to a lesser extent than the size of the steady state electrically driven contractions. 7. It is suggested that the extract from porcine left ventricle produces a positive inotropic response by increasing the trans-sarcolemmal influx of Ca. It also has additional effect(s) on the sarcoplasmic reticulum in that it may facilitate the loss of Ca from the sarcoplasmic reticulum and/or inhibit the uptake of Ca by the organelle.

1 Ouabain (10 mug/ml) caused an initial increase followed by a decrease in tension in guinea-pig taenia coli bathed in normal sodium and potassium containing medium. 2 The excitatory effect of ouabain was prevented by the elevation of extracellular potassium while the inhibitory effect was abolished in the absence of sodium in the bathing medium. 3 In the presence of sodium, the inhibitory effect of ouabain disappeared when the drug was washed out, but in the presence of lithium (which is not extruded by the Na-K pump) the inhibition was not abolished. 4 The inhibitory effect of ouabain was accompanied by an increase in tissue Na and a decrease in tissue K concentration. The increase in intracellular [45Ca] which occurred when extracellular [k] was varied, was also reduced by ouabain. 5 It is concluded that a high intracellular level of sodium inhibits contractions in visceral smooth muscle probably by a mechanism involving decreased Ca influx.

1. Reversible contraction of canine basilar artery, produced by hypoxia, persisted after mechanical and chemical removal of the endothelium. The removal of endothelium was confirmed by scanning electron microscopy as well as by the abolition or reversal of the relaxant response to acetylcholine or arginine8-vasopressin. 2. Hydroquinone, believed to block selectively endothelium-mediated relaxation, also preferentially attenuated hypoxic contractions even in the absence of endothelium but did not reduce responses to 5-hydroxytryptamine (5-HT) or high external potassium. 3. Contractions induced by red blood cell haemolysate, which occur independently of the endothelium, were also selectively attenuated by hydroquinone. 4. Contractions caused by hypoxia were inhibited by pretreatment with adenosine or by its application after contraction had developed. 5. Hypoxic contraction in canine basilar artery may result partly from a direct effect on smooth muscle as well as through the endothelium. 6. Hydroquinone may have an additional locus of action in smooth muscle cells besides its well known effect on the endothelium.

Previous studies have suggested that prazosin is a selective post-synaptic alpha-receptor blocker. It has also been suggested that it may have greater blocking actions on arterioles than on venous beds. These aspects have been investigated in cats anesthetized with pentobarbital. Prazosin had no effect on conductance in the acutely denervated hindlimb bed but caused a slowly developing vasoconstriction in the acutely denervated intestinal bed. The vasoconstrictor responses to sympathetic nerve stimulation were reduced to a similar extent in both vascular beds. Since maximal doses of prazosin produce only partial block of the alpha-receptor responses, there may be more than one type of postsynaptic alpha-receptor, and it is suggested that the postsynaptic receptors are of both alpha 1- and alpha 2-types. In the intestinal bed, prazosin produced similar reductions in both resistance and capacitance responses to sympathetic nerve stimulation. In isolated guinea pig aorta and portal vein, prazosin blocked the responses to noradrenaline competitively, and the pA3 values for the aorta and portal vein were similar. Thus, no selectivity for resistance vessels compared to capacitance vessels could be demonstrated in the intestine, and this result is compared to our previous observations in the liver. Although prazosin only reduced the vasoconstrictor responses to sympathetic nerve stimulation in the intestine, phenoxybenzamine reversed the response to a beta-receptor-mediated vasodilatation, as reported some years ago. These observations support our earlier hypothesis that nerve stimulation does not normally activate beta-receptors, but after phenoxybenzamine, the increased release of noradrenaline combined with alpha-receptor blockade results in a beta-receptor-mediated vasodilatation in the intestinal bed.

1 Post-rest inotropy in canine ventricular myocardium has proved a useful indicator of sarcoplasmic reticular calcium release. This phenomenon is converted to rest depression by the calcium channel activator (agonist), Bay K 8644 as well as other chemically diverse agents such as caffeine and ryanodine. 2 Rapid cooling contractures and post-rest contraction amplitude were used as independent measures of sarcoplasmic reticular calcium content and release. Simultaneous recordings of transmembrane action potentials and their accompanying contractions were obtained to determine the association between electrophysiological and mechanical events. The present study was designed to elucidate the mechanism by which Bay K 8644, caffeine and ryanodine alter force production after variable periods of rest. 3 Bay K 8644 (1 μm) increased steady state contraction in response to a constant train of stimulation, caused rest-depression after 2 and 8 min rest, prolonged action potential duration and increased action potential plateau amplitude. Augmented steady state tension was not accompanied by any change in time to peak tension or rapid cooling contracture amplitude. However, the post-rest rapid cooling contracture was greatly diminished compared to that observed prior to Bay K 8644 treatment. 4 Caffeine (3 and 5 mm) caused rest-depression with an increase in steady state contraction amplitude. Along with this there was a slight decrease in action potential duration and plateau amplitude and an increase in time to peak tension. The rapid cooling contractures were virtually abolished at all conditioning intervals. The effect of caffeine on twitch tension and cooling contracture is consistent with the ability of this compound to inhibit calcium sequestration by the sarcoplasmic reticulum. 5 A combination of Bay K 8644 and caffeine caused significantly less rest-depression than that seen with Bay K 8644 alone. The augmented twitch tension was accompanied by a long time to peak tension and action potential duration. However, there was no increase in the amplitude of the rapid cooling contracture, either after a regular train of stimulation or after rest, compared to that seen after Bay K 8644. 6 Ryanodine (10 nm), produced rest-depression, reduced steady state twitch tension and augmented the rest-depression produced by Bay K 8644. The steady state rapid cooling contracture remained unchanged when both agents were present simultaneously, while the post-rest rapid cooling contracture was significantly depressed compared to that observed with Bay K 8644 alone. 7 Bay K 8644 and ryanodine appear to have similar actions with respect to promoting diastolic loss of calcium from the sarcoplasmic reticulum. Although caffeine also decreases post-rest potentiation, it antagonizes rest-depression caused by Bay K 8644. The data from these experiments suggest that this reversal is a result of depressed intracellular calcium buffering and enhanced myofilament sensitivity produced by caffeine in the presence of increased transmembrane calcium influx promoted by Bay K 8644.

1. Certain derivatives of progesterone are potent inhibitors of high affinity, specific binding of 3H-cardiac glycosides. The steroids interact at the cardiac glycoside site on Na,K-ATPase and inhibit the enzyme (the sodium pump) in cardiac and other tissues. However, the active congeners identified previously have been, unlike the cardiac glycosides, predominantly cardiodepressant. 2. Because a 14 beta-hydroxy substituent is an important determinant of activity of the cardiotonic cardiac glycosides, we synthesized 14 beta-hydroxyprogesterone. This derivative has about one-tenth the potency of the aglycone, ouabagenin, in a [3H]-ouabain binding assay. 3. Like ouabagenin, but in contrast to the cardiodepressant congeners of progesterone, 14 beta-hydroxyprogesterone consistently elicited positive inotropy in isolated cardiac muscle and enhanced both the magnitude and frequency of fluctuations in scattered light (an index of oscillatory intracellular release of calcium). 4. Thus, at least one hydroxylated derivative (and putative endogenous metabolite) of progesterone, mimics the cardiac effects of cardiac glycosides including enhanced contractility.

Positive inotropic concentration of the Ca-channel agonist, Bay K 8644, depressed contraction of canine right ventricular trabecula immediately after a rest period of 8 min, without decreasing action potential plateau amplitude. In contrast, high external Ca and ouabagenin caused only a slight decrease in post-rest contraction. Bay K 8644-induced post-rest depression was inversely related to the extracellular Ca concentration. Hence it could not be due to cellular Ca overload. Since post-rest potentiation is due to increased contribution of Ca from the sarcoplasmic reticulum, these results suggest that Bay K 8644 decrease the amount of releasable Ca from this structure during rest.

The perioperative period, and most particularly the anaesthetic itself, creates an interface between chronic and acute drug therapy. As the primary managers of this interface, anaesthetists must be aware of the actions and interactions of varied and complex medications. Antihypertensive agents present a significant potential for drug interactions during anaesthesia. With the exception of monoamine inhibitors, anti-hypertensives should be continued up to the time of surgery, Safe anaesthetic management requires anticipation of drug interactions, recognition of their effects, and knowledge of appropriate corrective therapy. This review has provided information and guidelines which help to accommodate these needs.

Isolated capsular muscle from cat spleen did not contract on exposure to a potassium-free bathing fluid. After exposure to conditions favouring downhill sodium and potassium movement (i.e. stimulation by noradrenaline in the absence of external potassium), subsequent reactivation of the sodium pump inhibited responses to noradrenaline. Under these special conditions, but not normally, the sodium pump may be behaving in an electrogenic manner.