Ab initio quantum mechanics/molecular mechanics method with periodic boundaries employing Ewald summation technique to electron-charge interaction: Treatment of the surface-dipole term.

We have developed a combined quantum mechanics/molecular mechanics (QM/MM) method with periodic boundary condition (PBC) treatment of explicit electron-charge interactions in a theoretically rigorous manner, for an accurate description of electronic structures for molecules in the condensed phase. The Ewald summation technique is employed for the calculation of the one-electron Hamiltonian in an ab initio framework. We decompose the Coulomb interactions into two components: those within the same cell and those between different cells. The former is calculated in the same way as the conventional QM/MM calculation for isolated systems; this article focuses on our novel method for calculating the latter type of Coulomb interactions. The detailed formulation of the Hamiltonian of this new QM/MM-PBC method, as well as the necessary one-electron integrals and their gradients, is given. The novel method is assessed by applying it to the dilute water system and a system with a coumarin molecule in water solvent; it successfully reproduces the electronic energies, frontier orbital energies, and Mulliken population charge of the real-space limit calculated by QM/MM using large isolated systems. We investigated the contribution from each term of the Hamiltonian and found that the surface-dipole term in the Ewald summation technique is indispensable for QM/MM-PBC calculations. The newly developed QM/MM-PBC method is promising for tackling chemical reactions and excited states of molecules in the condensed phase.

Rapid susceptibility testing for slowly growing nontuberculous mycobacteria using a colorimetric microbial viability assay based on the reduction of water-soluble tetrazolium WST-1.

Rapid susceptibility testing for slowly growing nontuberculous mycobacteria (NTM) using a colorimetric microbial viability assay based on the reduction of the water-soluble tetrazolium salt {2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, monosodium salt (WST-1)} using 2,3,5,6-tetramethyl-1,4-benzoquinone as an electron mediator was developed. Using the Clinical and Laboratory Standards Institute (CLSI) method, a long-term incubation time (7-14 days) was required to determine the minimum inhibitory concentrations (MICs) of the slowly growing NTM. The MICs for a variety of different antibiotics against the slowly growing NTM were determined by the WST-1 colorimetric method and compared with those obtained using the broth microdilution methods approved by the CLSI. Good agreement was found between the MICs determined after 3-4 days using the WST-1 colorimetric method and those obtained after 10-14 days using the broth microdilution method. The results suggest that the WST-1 colorimetric assay is a useful method for the rapid determination of the MICs for the slowly growing NTM.

Clinical efficacy of protein-bound polysaccharide K in patients with gastric cancer undergoing chemotherapy with an oral fluoropyrimidine (S-1).

BACKGROUND: The aim of the present study was to evaluate the clinical significance of protein-bound polysaccharide K (PSK) in patients with primary gastric cancer who were being treated with an oral fluoropyrimidine (S-1). METHODS: Clinical reports of 190 gastric cancer patients treated with S-1 chemotherapy, with or without PSK, at Kochi Medical School between 2007 and 2012 were investigated retrospectively to analyze survival. The neutrophil:lymphocyte ratio (NLR) was also evaluated as indicator of the immunoenhancing effect of PSK. RESULTS: Overall survival was significantly longer in patients treated with S-1 + PSK than in those given S-1 alone (hazard ratio for death, 0.608; 95% confidence interval 0.375-0.985; P = 0.041). Furthermore, there was a tendency for changes in the NLR during chemotherapy to be lower in the S-1 + PSK group than in the S-1 group, but the difference did not reach statistical significance (P = 0.054). When patients were divided into groups based on preoperative NLR (i.e. <2.5 and ≥2.5), the mean (±SEM) NLR 1 month after the beginning of chemotherapy in the NLR ≥2.5 subgroup was significantly lower in patients treated with S-1 + PSK rather than S-1 alone (1.7 ± 0.7 vs. 3.3 ± 4.1, respectively; P = 0.043). CONCLUSIONS: Immunochemotherapy using PSK improves the survival of patients with advanced gastric cancer. The NLR may be a useful biomarker for evaluating prognosis in these patients.

A rapid microplate method for the proliferation assay of fungi and the antifungal susceptibility testing using the colorimetric microbial viability assay.

UNLABELLED: A rapid microplate method for the proliferation assay of fungi and the antifungal susceptibility testing using the colorimetric microbial viability assay based on the reduction in a tetrazolium salt 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, monosodium salt (WST-8) with 2-methyl-1,4-napthoquinone as the electron mediator was developed. The proposed method was useful to measure the proliferation of 18 kinds of moulds and seven kinds of yeasts, including representative pathogens such as Aspergillus spp., Candida spp. and Cryptococcus spp. Linear relationships between the absorbance and viable fungal cell density were obtained for all fungi, suggesting that the absorbance change reflected the fungal proliferation. In addition, the minimum inhibitory concentrations (MICs) against a variety of different pathogenic moulds and yeasts for amphotericin B, itraconazole and 5-flucytosine were determined by susceptibility testing using the proposed method and compared with those obtained using the conventional broth microdilution method. There was an excellent agreement between the results obtained using the WST-8 colorimetric method and those obtained using the conventional Clinical and Laboratory Standard Institute method. The WST-8 colorimetric assay is a useful method for rapid determination of accurate MICs for a variety of different fungi. SIGNIFICANCE AND IMPACT OF THE STUDY: A rapid microplate method for the proliferation assay of fungi and the antifungal susceptibility testing using the colorimetric microbial viability assay based on reduction in a tetrazolium salt (WST-8) was developed. The WST-8 colorimetric method was useful to measure the proliferation of a variety of different fungi. In the antifungal susceptibility testing, there was a good agreement between the MICs determined after 24 h using the WST-8 colorimetric method and those obtained after 48-96 h using the broth microdilution method. The proposed method was superior to conventional methods in terms of its rapidity towards a variety of different fungi.

Evaluation of energy recovery and CO2 reduction potential in Japan through integrated waste and utility management.

This paper examines the potential of integrated waste and utility power management over the mid-term planning horizon in Japan. Energy recovery and CO(2) emission reduction were estimated under two situations: (1) energy recovery efforts within the current waste management/power generation framework and (2) integrated waste management with sewage treatment systems and electric power industries. Scenario simulation results showed that under the current policy framework it is not feasible to achieve large energy recovery and CO(2) emission reduction, while the integrated waste management scenarios show the potential of large energy recovery which is equivalent to about an 18 million t-CO(2) emission reduction. The utilization of dry wastes for power generation at existing fossil power stations is significant in achieving the result. We also consider the effects of the 'CO(2) emission per GW generated' for electric power generation on the total CO(2) emission reduction because it varies by country and assumptions selected. Although this research did not include an economic analysis, based on estimated CO(2) emissions and energy recovery, the integrated scenarios indicate a large potential in countries that have high dependence of fossil power generation and relatively low power generation efficiency.

Usefulness of sparfloxacin against Chlamydia pneumoniae infection in patients with bronchial asthma.

The efficacy of sparfloxacin (SPFX) for the control of bronchial asthma was evaluated in 26 patients with suspected Chlamydia pneumoniae infection. Patients were randomly allocated to receive SPFX 200 mg/day (n = 14) or control treatment (n = 12) for 21 days. Significant improvements in serum C-reactive protein levels, and significant decreases in peripheral eosinophil counts, serum eosinophil cationic protein (ECP) and sputum ECP were observed in the SPFX-treated group at day 21. SPFX-treated patients also had a significantly reduced frequency of asthma symptoms, reduced inhalant beta2-stimulant use, and significant increases in morning peak expiratory flow. At the end of the study, C. pneumoniae was undetectable in two SPFX-treated patients who underwent polymerase chain reaction testing, but one control patient who was tested still had detectable levels of C. pneumoniae. These results suggest that SPFX could be used to control bronchial asthma in patients with suspected persistent C. pneumoniae infection.

Antibacterial activity and clinical efficacy of sparfloxacin in Mycobacterium avium-intracellulare complex infection.

In Japan the incidence of atypical mycobacteriosis has steadily increased, with Mycobacterium avium-intracellulare complex (MAC) the most common infecting organism. A standard chemotherapy regimen for MAC infection has not been established because of significant resistance to anti-mycobacterial drugs. Sparfloxacin has good antimicrobial activity against several acid-fast bacteria and is expected to be an effective drug for treating mycobacteriosis. We examined the effects of adding sparfloxacin to anti-tuberculotic combination therapy in six patients with MAC pulmonary disease. Drug susceptibility was also assessed using the agar dilution method. The minimum inhibitory concentrations (MICs) for sparfloxacin, levofloxacin, isoniazid, rifampicin, streptomycin, ethambutol and clarithromycin was measured in clinical isolates from all patients; sparfloxacin showed the lowest MIC. Bacteriological and clinical improvements were observed in the four patients who completed the study. Dosing was discontinued in two patients because of pruritic skin eruptions. Sparfloxacin shows promise as an anti-mycobacterial agent for treating MAC pulmonary disease.

Effects of ropivacaine on human neutrophil function: comparison with bupivacaine and lidocaine.

BACKGROUND AND OBJECTIVE: Neutrophils are important both for the immunological defence system and for the inflammatory tissue autoinjury mechanism. However, many local anaesthetics impair certain neutrophil functions. The aim was to assess the effects of ropivacaine, bupivacaine and lidocaine on human neutrophils from adult volunteers. METHODS: Chemotaxis, phagocytosis, reactive oxygen species production, intracellular calcium ion ([Ca2+]i) concentrations and protein kinase C activity were measured in the absence and presence of ropivacaine, bupivacaine or lidocaine. The lowest concentrations of the local anaesthetics were similar to those clinically observed in the plasma. RESULTS: Bupivacaine did not affect any neutrophil function (P > 0.05). Ropivacaine failed to change chemotaxis or phagocytosis, while lidocaine suppressed both these neutrophil functions. Ropivacaine (15, 150 microg mL(-1)) and lidocaine (20, 200 microg mL(-1)) impaired neutrophil production of O2-, H2O2 and OH- (P < 0.05) at similar rates (by 7-10%). These same concentrations of ropivacaine and lidocaine suppressed [Ca2+1i elevation. Finally, neither ropivacaine nor bupivacaine inhibited protein kinase C activity, while lidocaine did. CONCLUSIONS: Suppression of the [Ca2+]i response in neutrophils by ropivacaine may represent one of the mechanisms responsible for the impairment of neutrophil functions. It should be emphasized that the inhibitory effects of ropivacaine are minor and are attained only at high concentrations, which may minimize the clinical implication of ropivacaine-associated impairment of reactive oxygen species production. Further studies using in vivo systems are required to identify the inhibitory effects of ropivacaine on reactive oxygen species production in clinical settings.

Evaluation of atomic integrals for hybrid Gaussian type and plane-wave basis functions via the McMurchie-Davidson recursion formula.

A convenient formalism is developed for the evaluation of atomic integrals composed of a hybrid Gaussian type function and plane-wave (GTF-PW) basis set, based upon the recursion scheme proposed by McMurchie and Davidson [L. E. McMurchie and E. R. Davidson, J. Comput. Phys. 26, 218 (1978)] which was originally for Gaussian type basis functions. We show that revisions of recursion relations in the original article are necessary in order to allow systematic production of overlap, kinetic energy, nuclear attraction, and electron repulsion integrals in compact forms. Involving easy calculation of complex incomplete gamma functions, the recursion relations enable the use of hybrid GTF-PW basis functions with arbitrarily large angular momentum. This basis function can be applied to the first-principle calculation for solids involving localized electron orbitals.

Epidemiological studies of tobacco smoking and dependence in Japan.

In this study, we attempted to determine the prevalence of tobacco or nicotine dependence in current smokers in Japan and to assess the relationship between alcoholism and tobacco or nicotine dependence. The subjects consisted of 246 alcohol-dependent and 1,111 non-alcohol-dependent individuals. We used a questionnaire, consisting of items obtained from the World Health Organization's The ICD-10 Classification of Mental and Behavioural Disorders: Clinical Descriptions and Diagnostic Guidelines (ICD-10) and the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) criteria for tobacco or nicotine dependence. The prevalence of tobacco dependence diagnosed according to the ICD-10 criteria was 23.9% among all subjects. The prevalence of tobacco dependence diagnosed according to the ICD-10 criteria was higher in alcohol-dependent individuals (58.1%) than in nondrinkers or social drinkers (12.8%). Alcohol-dependent subjects consumed significantly more nicotine per day than did nondrinkers or social drinkers. The prevalence of nicotine physical dependence diagnosed by using DSM-IV criteria for nicotine withdrawal was 2.4% in alcohol-dependent individuals, whereas only 0.3% of nondrinkers or social drinkers exhibited nicotine physical dependence. These results indicate to us that the potential for nicotine physical dependence is not much stronger than that reported among current smokers.

A comparison of atenolol, labetalol, esmolol, and landiolol for altering human neutrophil functions.

IMPLICATIONS: Neutrophils play a pivotal role in the antibacterial host defense system. Atenolol, labetalol, esmolol, and landiolol at clinically relevant concentrations failed to change neutrophil functions. Our findings indicate that we may be able to use these beta-antagonists without great caution in clinical settings.

Therapeutic time-window of a group IIA phospholipase A2 inhibitor in rabbit acute lung injury: correlation with lung surfactant protection.

OBJECTIVE: We attempted to determine whether group IIA secretory phospholipase A2 (sPLA2-IIA) blockade after the onset of lung injury exerted therapeutic efficacy in the treatment of oleic acid (OA)-induced acute lung injury by using S-5920/LY315920Na, a novel specific inhibitor of sPLA2-IIA, with special interest in the changes of lung surfactant. DESIGN: Prospective animal study. SETTING: University laboratory. SUBJECTS: Forty Japanese white rabbits. INTERVENTIONS: The rabbits, under anesthesia, were endotracheally intubated and mechanically ventilated and then were divided into the following groups: OA + vehicle groups, intravenous infusion of OA for the first 2 hrs (0.1 mL x kg(-1) x hr(-1)) with the addition of vehicle (1 or 2 hrs after OA administration, each n = 9, total 18 rabbits); OA + S-5920/LY315920Na groups, treated identically to the OA control with the addition of S-5920/LY315920Na (1 mg/kg bolus followed by infusion at 0.5 mg x kg(-1) x hr(-1)) after OA (1 or 2 hrs after OA administration, each n = 9, total 18 rabbits); saline control groups, treated with saline instead of OA with the addition of vehicle (1 hr after OA administration, 4 rabbits). Arterial blood gas, lung mechanics, lung inflammation, lung surfactant phospholipids, and production of inflammatory mediators in the lung were measured. MEASUREMENTS AND MAIN RESULTS: Treatment with S-5920/LY315920Na 1 hr after OA infusion, but not 2 hrs after infusion, significantly attenuated the lung injury, as estimated by hypoxemia, decreased lung compliance, pulmonary edema, and vascular permeability. The therapeutic efficacy was similar to that found in our previous pretreatment study. The treatment after 1 hr dramatically inhibited OA-induced surfactant degradation in the bronchoalveolar lavage fluid (BALF), without affecting the concentrations of thromboxane A2, leukotriene B4, and interleukin-8 in BALF. The degree of surfactant degradation in BALF paralleled well with the severity of the lung injury. Furthermore, recombinant human sPLA2-IIA reproduced the similar hydrolysis pattern of isolated surfactant in vitro, which was inhibited by S-5920/LY315920Na. CONCLUSIONS: Our results indicate that therapeutic blockade of sPLA2-IIA ameliorated lung dysfunction via protection of surfactant degradation in an animal model of acute lung injury, and they suggest a new strategy in treating clinical acute lung injury.

The effects of lidocaine on nitric oxide production from an activated murine macrophage cell line.

UNLABELLED: Nitric oxide (NO), overproduced by activated macrophages, is important in the pathogenesis of various diseases, including septic shock and inflammatory tissue injury, as well as antibacterial host defense mechanisms. We examined the effects of lidocaine on NO production and the expression of inducible NO synthase (iNOS) protein and messenger RNA (mRNA) in activated macrophages. Murine macrophage-like cell line RAW 264 was stimulated for 8 h with lipopolysaccharide (10 mg/mL) and interferon-gamma (50 U/mL) in the presence of various concentrations of lidocaine (0-500 mg/mL). NO production was assessed by measuring levels of the stable metabolites, nitrite and nitrate (NOx), in the culture medium with an automatic analyzer using the Griess reaction. Expression of iNOS mRNA in harvested RAW 264 was quantified by Northern blot analysis using mouse iNOS complementary DNA probe. Expression of iNOS protein in the cells was assessed by Western blot analysis using anti-iNOS antibody. Lidocaine dose-dependently attenuated the increase in NOx levels in response to the stimulants. The drug at any concentration failed to decrease iNOS mRNA expression in RAW 264. Lidocaine at 500 mg/mL decreased iNOS protein levels. These data suggest that lidocaine reduced NO production in activated macrophages at multiple levels after transcription. The inhibitory site appeared to vary with the dose of lidocaine. IMPLICATIONS: Lidocaine dose-dependently inhibited nitric oxide production by activated macrophages, presumably at levels after transcription. The attenuating effect of lidocaine on organ injuries previously reported may be explained by the ability of the drug to suppress this inflammatory mediator.

Effect of methylprednisolone on phospholipase A(2) activity and lung surfactant degradation in acute lung injury in rabbits.

Glucocorticoids are the most potent and widely used anti-inflammatory agents, but they are not particularly effective against early phase of acute respiratory distress syndrome. We investigated whether methylprednisolone, a synthetic glucocorticoid, could inhibit increase of phospholipase A(2) activity in the lung and lead to protection against a model of acute respiratory distress syndrome in rabbits. Infusion of oleic acid (0.1 ml/kg/h, i.v. for 2 h) provoked pulmonary hemorrhage and edema, protein leakage and massive neutrophil infiltration, resulted in severe hypoxemia and impaired lung compliance, accompanying the increase of phospholipase A(2) activity and interleukin-8, and degradation of surfactant in the bronchoalveolar lavage fluid. Infusion of methylprednisolone (60 mg/kg/h, i.v. for 30 min before the oleic acid and then 0.5 mg/kg/h, i.v. for 6 h) did not improve the above described lung injury induced by oleic acid, nor did it suppress phospholipase A(2) activity and degradation of surfactant in bronchoalveolar lavage fluid, while it strongly reduced interleukin-8 levels in both plasma and bronchoalveolar lavage fluid. We conclude that methylprednisolone did not attenuate oleic acid-induced acute lung injury and this can be explained partly by its failure to reduce the increase of phospholipase A(2) activity and the surfactant degradation in the lung, which might also account for its clinical ineffectiveness against early acute respiratory distress syndrome.

Coordinate induction of collagenase-1, stromelysin-1 and urokinase plasminogen activator (uPA) by the 120-kDa cell-binding fibronectin fragment in fibrocartilaginous cells: uPA contributes to activation of procollagenase-1.

Specific fibronectin (Fn) fragments found in synovial fluid of arthritic joints potentially contribute to the loss of cartilage proteoglycans by inducing matrix metalloproteinase (MMP) expression. However, whether or not the Fn fragment-modulated changes in expression of MMPs result in a net increase in matrix-degradative activity through alterations in the balance between MMP activation and inhibition has not been established. To understand the mechanisms by which proteolytic Fn fragments may contribute to joint degeneration, conditioned medium from fibrocartilaginous cells exposed to Fn, its 30-kDa fragment containing the collagen/gelatin-binding domain, its 120-kDa fragment containing the central cell-binding domain, and the RGD peptide were assayed for MMPs, and MMP activators and inhibitors. We found that the 120-kDa fragment of Fn (but not intact Fn), the 30-kDa fragment, and the RGD peptide, dose-dependently induced procollagenase-1 and prostromelysin-1 and decreased levels of the tissue inhibitor of metalloproteinases (TIMPs) -1 and -2. The alpha5beta1 integrin was implicated in the induction of collagenase by the 120-kDa Fn fragment, since collagenase induction was abrogated in the presence of blocking antibody to this integrin. Conditioned medium from cells exposed to the 120-kDa Fn fragment also demonstrated increased levels of the activated collagenase-1, which resulted in significantly elevated collagen degradative activity. That the urokinase plasminogen activator (uPA) was involved in the activation of procollagenase-1 was suggested by findings that the 120-kDa Fn fragment induced uPA coordinately with procollagenase-1, and the activation of procollagenase-1 was dose-dependently inhibited in the presence of plasminogen activator inhibitor-1. These data demonstrate that the 120-kDa cell-binding fragment of Fn induces a net increase in matrix-degradative activity in fibrocartilaginous cells by concomitantly inducing MMPs and their activator, uPA, while decreasing TIMPs.

Diclofenac and flurbiprofen with or without clonidine for postoperative analgesia in children undergoing elective ophthalmological surgery.

We conducted a prospective, randomized study to compare the efficacy of preoperative diclofenac, flurbiprofen, and clonidine, given alone, as well as the combination of diclofenac and clonidine, and flurbiprofen and clonidine in controlling postoperative pain in 125 children. The patients (ASA I, 2-12 years) undergoing elective ophthalmological surgery were allocated to one of five groups: rectal diclofenac 2 mg.kg(-1) following oral placebo premedication, i. v. flurbiprofen 1 mg.kg(-1) following placebo premedication, oral clonidine premedication, rectal diclofenac 2 mg.kg(-1) following clonidine, and i.v. flurbiprofen 1 mg.kg(-1) following clonidine. The children received clonidine (4 microg.kg(-1)) or placebo 105 min before anaesthesia. Diclofenac or flurbiprofen was given immediately after induction of anaesthesia. Anaesthesia was induced and maintained with sevoflurane and nitrous oxide in oxygen. Postoperative pain was assessed by a blinded observer using a modified objective pain scale (OPS). No opioids were administered throughout the study. Rectal diclofenac 2 mg.kg(-1) i.v. flurbiprofen 1 mg.kg(-1), oral clonidine 4 microg.kg(-1) provided similar OPS scores and requirement for supplementary analgesics during 12 h after surgery. Combination of oral clonidine and one of these nonsteroidal analgesics minimized postoperative pain. Our findings suggest that this combined regimen may be a promising prophylactic approach to postoperative pain control in children undergoing ophthalmological surgery.

Oral clonidine premedication does not change efficacy of simulated epidural test dose in sevoflurane-anesthetized children.

BACKGROUND: Caudal epidural anesthesia is often used as an adjunct to general anesthesia and for postoperative pain relief in children. In anesthetized children, epinephrine and isoproterenol are reliable indicators to detect accidental intravascular injection of a test dose. Oral clonidine, a useful premedicant in pediatric anesthesia, modifies hemodynamic responses to sympathomimetics, including catecholamines. The aim of the current study was to determine whether oral clonidine premedication alters the efficacy of a simulated intravascular test dose containing epinephrine or isoproterenol in sevoflurane-anesthetized children. METHODS: One hundred twenty children (aged 1-7 yr) were randomly divided into six groups; control-saline, control-epinephrine, control-isoproterenol, clonidine-saline, clonidine-epinephrine, and clonidine-isoproterenol. The three clonidine groups received oral clonidine 4 microg/kg [DOSAGE ERROR CORRECTED] as premedication, whereas the three control groups did not receive any premedication. Anesthesia was maintained with sevoflurane at a level of 1.2 minimum alveolar concentration. After hemodynamics were stable, 0.1 ml/kg of 1% lidocaine containing epinephrine 0.5 mg/kg or isoproterenol 75 ng/kg was intravenously given to the two epinephrine or isoproterenol groups, respectively, to simulate intravascular injection of a test dose. The saline groups received saline alone instead of the test dose. Heart rate, blood pressure, and T-wave amplitude of electrocardiogram were recorded before and after administration of study drugs for subsequent analysis. RESULTS: Test solution containing epinephrine increased heart rate, systolic blood pressure, and T-wave amplitude. Oral clonidine had no effect on elevation of these variables in response to epinephrine. The isoproterenol-containing test dose produced a prominent increase in heart rate and a less pronounced increase in systolic blood pressure and T-wave amplitude. Oral clonidine also failed to modify isoproterenol-induced hemodynamic and T-wave changes. Calculated sensitivity and specificity of epinephrine or isoproterenol were all 100% based on a new heart rate criterion (positive if >/= 10 beats/min) and were unaltered by oral clonidine premedication. CONCLUSIONS: Epinephrine or isoproterenol is a reliable marker to detect accidental intravascular injection of a test dose with 100% sensitivity and specificity based on a new heart rate criterion in sevoflurane-anesthetized children. These data suggest that oral clonidine premedication does not alter the efficacy of a simulated epidural test dose containing epinephrine or isoproterenol.

Attenuation of hyperoxia-induced diaphragmatic dysfunction with lidocaine in hamsters.

OBJECTIVE: Toxic free radicals cause dysfunction of respiratory muscles, probably leading to respiratory distress. Exposure to high concentrations of oxygen generates plenty of free radicals. Lidocaine scavenges the reactive molecules. The purposes of the current study were first to examine whether hyperoxia impairs diaphragmatic function, and second, to assess the effects of lidocaine on hyperoxia-induced diaphragmatic dysfunction, if developed. DESIGN: Prospective, randomized animal study. SETTING: University research laboratory. SUBJECTS: Forty and 48 adult male Golden-Syrian hamsters (110-150 g) in parts I and II studies, respectively. INTERVENTION: In the part I study, hyperoxia for 5 and 6 days reduced diaphragmatic contractility and enhanced fatigue. In the part II study, hamsters were randomly allocated to one of six groups (n = 8 each): exposure to air for 6 days with saline (group A-S) or lidocaine infusion (group A-L), exposure to 100% oxygen for 5 days with saline (group 05-S) or lidocaine (group 05-L), and exposure to 100% oxygen for 6 days with saline (group 06-S) or lidocaine (group 06-L). Saline or lidocaine (2 mg/kg/hr) was subcutaneously given immediately before exposure to air or oxygen. Diaphragmatic contractility and fatigability were assessed in vitro using muscle strips excised from the costal diaphragms. Diaphragmatic levels of malondialdehyde (MDA), an index of free radical-mediated lipid peroxidation, were measured. These variables were compared between groups. MEASUREMENTS AND MAIN RESULTS: Twitch and tetanic tensions in groups 05-S and 06-S were reduced compared with group A-S. Tensions generated during fatigue trials were also decreased in groups 05-S and 06-S. MDA levels were elevated in diaphragms from these groups. In groups 05-L and 06-L, contractile dysfunction, deterioration of fatigability, and MDA formation in the diaphragm were attenuated. CONCLUSIONS: Lidocaine attenuated hyperoxia-induced diaphragmatic dysfunction assessed by contractile profiles and fatigability in hamsters. This beneficial effect may be attributable, in part, to inhibition of lipid peroxidation.

[Anesthetic management in pediatric interventional cardiology].

Interventional cardiology (n = 108) and cardiac angiography (n = 481) procedures in pediatrics performed between January 1996 and December 1998 were reviewed. Means (SD) of duration of anesthesia for interventional cardiology and cardiac angiography were 245 (130) and 152 (48) minutes, respectively (P < 0.001). Incidences of long operations requiring over 6 hours of anesthesia were 12 and 0%, respectively (P < 0.001). Incidences of hemodynamic derangements were 17 and 2.9%, and catheter-related complications were 7.4 and 0.83%, respectively (P < 0.001). Incidences of ICU admission were 7.4 and 0.62% those of emergency surgery were 4.6 and 0%, and those of blood transfusion were 4.6 and 0%, respectively (P < 0.001). Incidences of cardiopulmonary resuscitation, and cardioversion were also higher in interventional cardiology (P < 0.05), and all these emergency cases were rescued successfully. The risk of cardiac angiography is higher compared with general surgery, and the risk of interventional cardiology is higher than cardiac angiography in pediatrics. This study reconfirms that anesthesiologists should play an active role in care of pediatric patients undergoing high-risk procedures outside the operating room.

The effect of phosphodiesterase III inhibitors on human neutrophil function.

OBJECTIVES: Neutrophils play an important role in ridding the body of bacteria and cellular debris. Several neutrophil functions are thought to be regulated by inotropes that increase cellular levels of cyclic adenosine monophosphate, including phosphodiesterase (PDE) inhibitors. We have investigated the effect of amrinone, milrinone, and olprinone, type III PDE (PDE-III) inhibitors, on several human neutrophil functions. DESIGN: Prospective in vitro study. SETTING: Academic research laboratory. SUBJECTS: Neutrophils isolated from 12 healthy adult volunteers. INTERVENTIONS: We measured chemotaxis, phagocytosis, reactive oxygen species production, intracellular calcium ion concentration, and cyclic adenosine monophosphate levels in neutrophils in the absence and the presence (at clinically relevant concentrations, 10 times, and 100 times those concentrations) of amrinone, milrinone, or olprinone. We also measured reactive oxygen species production under the same condition in a xanthine-xanthine oxidase system MEASUREMENTS AND MAIN RESULTS: None of the PDE-III inhibitors impaired neutrophil chemotaxis or phagocytosis. Amrinone at clinically relevant or higher concentrations and milrinone at high concentrations reduced superoxide, hydrogen peroxide, and hydroxyl radical levels in neutrophils and in the xanthine-xanthine oxidase system. Olprinone did not have those effects, and none of the PDE-III inhibitors had an effect on intracellular calcium ion concentration or cyclic adenosine monophosphate production in neutrophils stimulated by a chemotactic factor. CONCLUSIONS: The ability of amrinone to scavenge reactive oxygen species at clinically relevant concentrations while not affecting neutrophil function suggests that the PDE inhibitor can be used without detriment in severely ill patients.