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1.
Int J Obes (Lond) ; 39(2): 279-87, 2015 Feb.
Article in English | MEDLINE | ID: mdl-24675715

ABSTRACT

BACKGROUND: Obesity severely affects human health, and the accompanying non-alcoholic fatty liver disease (NAFLD) is associated with high morbidity and mortality. Rapid and non-invasive methods to detect this condition may substantially improve clinical care. METHODS: We used liquid and gas chromatography-quadruple time-of-flight-mass spectrometry (LC/GC-QTOF-MS) analysis in a non-targeted metabolomics approach on the plasma from morbidly obese patients undergoing bariatric surgery to gain a comprehensive measure of metabolite levels. On the basis of these findings, we developed a method (GC-QTOF-MS) for the accurate quantification of plasma α-ketoglutarate to explore its potential as a novel biomarker for the detection of NAFLD. RESULTS: Plasma biochemical differences were observed between patients with and without NAFLD indicating that the accumulation of lipids in hepatocytes decreased ß-oxidation energy production, reduced liver function and altered glucose metabolism. The results obtained from the plasma analysis suggest pathophysiological insights that link lipid and glucose disturbances with α-ketoglutarate. Plasma α-ketoglutarate levels are significantly increased in obese patients compared with lean controls. Among obese patients, the measurement of this metabolite differentiates between those with or without NAFLD. Data from the liver were consistent with data from plasma. Clinical utility was assessed, and the results revealed that plasma α-ketoglutarate is a fair-to-good biomarker in patients (n=230). Other common laboratory liver tests used in routine application did not favourably compare. CONCLUSION: Plasma α-ketoglutarate is superior to common liver function tests in obese patients as a surrogate biomarker of NAFLD. The measurement of this biomarker may potentiate the search for a therapeutic approach, may decrease the need for liver biopsy and may be useful in the assessment of disease progression.


Subject(s)
Ketoglutaric Acids/blood , Metabolome , Non-alcoholic Fatty Liver Disease/blood , Obesity, Morbid/blood , Biomarkers/blood , Chromatography, Liquid , Disease Progression , Humans , Lipid Metabolism , Mass Spectrometry , Metabolomics/methods , Non-alcoholic Fatty Liver Disease/etiology , Non-alcoholic Fatty Liver Disease/metabolism , Non-alcoholic Fatty Liver Disease/physiopathology , Obesity, Morbid/complications , Obesity, Morbid/metabolism , Obesity, Morbid/physiopathology , Predictive Value of Tests
2.
HIV Med ; 14(4): 233-40, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23171036

ABSTRACT

OBJECTIVES: Insulin resistance in viral infections is common. We have explored the effectiveness of metformin for alleviating insulin resistance in HIV-infected patients and assessed the relevance of the ataxia-telangiectasia mutated (ATM) rs11212617 variant in the clinical response with the rationale that metformin modulates cellular bioenergetics in an ATM-dependent process. METHODS: HIV-infected patients (n = 385) were compared with controls recruited from the general population (n = 300) with respect to the genotype distribution of the ATM rs11212617 variant and its influence on selected metabolic and inflammatory variables. We also followed up a subset of male patients with HIV and hepatitis C virus (HCV) coinfection (n = 47) who were not receiving antiviral treatment and for whom metformin was prescribed for insulin resistance, which tends to have a higher incidence and severity in coinfected patients. RESULTS: Among the HIV-infected patients, human cytomegalovirus (91.9%) and HCV (62.3%) coinfections were frequent. Selected metabolic and/or inflammatory variables were significantly altered in infected patients. Treatment with metformin in HIV and HCV coinfected patients was well tolerated and significantly increased the sensitivity of peripheral tissues to insulin. The minor allele (C) of the rs11212617 variant was associated with treatment success and may affect the course of insulin resistance in response to metformin (odds ratio 1.21; 95% confidence interval 1.07-1.39; P = 0.005). There were no differences between treated and untreated patients in viral loads or variables measuring immune defence, indicating that toxicity is unlikely. CONCLUSIONS: We provide novel data suggesting that identification of the ATM rs11212617 variant may be important in assessing the glycaemic response to metformin treatment for insulin resistance in HIV-infected patients.


Subject(s)
Coinfection/metabolism , Cytomegalovirus Infections/metabolism , HIV Infections/metabolism , Hypoglycemic Agents/therapeutic use , Insulin Resistance , Metformin/therapeutic use , Adult , Ataxia Telangiectasia Mutated Proteins , Cell Cycle Proteins/genetics , Cytomegalovirus/isolation & purification , DNA-Binding Proteins/genetics , Female , Genotype , HIV Infections/virology , Humans , Insulin Resistance/genetics , Male , Middle Aged , Protein Serine-Threonine Kinases/genetics , Tumor Suppressor Proteins/genetics
3.
QJM ; 108(10): 795-801, 2015 Oct.
Article in English | MEDLINE | ID: mdl-25660598

ABSTRACT

BACKGROUND: The factors related to ascending aorta dilation (AAD) in patients with bicuspid aortic valve (BAV) are not completely understood. In addition, the role of cholesterol metabolism in AAD has not been studied. METHODS: We analyzed the relationship between different lipid parameters and the ascending aorta diameter/presence of aortic dilatation in 91 consecutive patients with BAV. RESULTS: We observed a positive linear correlation between the total cholesterol, low-density lipoprotein (LDL) cholesterol and apolipoprotein B (ApoB) levels and the ascending aorta diameter. The patients with AAD had higher LDL cholesterol and ApoB levels. Whereas LDL cholesterol and ApoB were identified as independent factors predictors of the aortic root diameter, only ApoB predicted the diameter of the ascending aorta. On the other hand, the levels of ApoB were an independent factor related to the dilatation of the aortic root. CONCLUSIONS: We have observed that cholesterol is associated with ascending aorta diameter and dilation in BAV patients. Further experimental and clinical studies are needed to explain the pathobiology of this association.


Subject(s)
Aorta/physiopathology , Aortic Valve/abnormalities , Apolipoproteins B/blood , Cholesterol, LDL/blood , Heart Valve Diseases/blood , Adult , Aged , Bicuspid Aortic Valve Disease , Dilatation, Pathologic , Female , Humans , Linear Models , Male , Middle Aged , Multivariate Analysis , Prospective Studies
4.
Clin Microbiol Infect ; 21(7): 711.e1-8, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25882366

ABSTRACT

Very little information is available on the involvement of newly characterized adipokines in human immunodeficiency virus (HIV)/antiretroviral therapy (ART)-associated lipodystrophy syndrome (HALS). Our aim was to determine whether apelin, apelin receptor, omentin, RBP4, vaspin and visfatin genetic variants and plasma levels are associated with HALS. We performed a cross-sectional multicentre study that involved 558 HIV type 1-infected patients treated with a stable highly active ART regimen, 240 of which had overt HALS and 318 who did not have HALS. Epidemiologic and clinical variables were determined. Polymorphisms in the apelin, omentin, RBP4, vaspin and visfatin genes were assessed by genotyping. Plasma apelin, apelin receptor, omentin, RBP4, vaspin and visfatin levels were determined by enzyme-linked immunosorbent assay in 163 patients (81 with HALS and 82 without HALS) from whom stored plasma samples were available. Student's t test, one-way ANOVA, chi-square test, Pearson and Spearman correlations and linear regression analysis were used for statistical analyses. There were no associations between the different polymorphisms assessed and the HALS phenotype. Circulating RBP4 was significantly higher (p < 0.001) and plasma omentin was significantly lower (p 0.001) in patients with HALS compared to those without HALS; differences in plasma levels of the remaining adipokines were nonsignificant between groups. Circulating RBP4 concentration was predicted independently by the presence of HALS. Apelin and apelin receptor levels were independently predicted by body mass index. Visfatin concentration was predicted independently by the presence of acquired immunodeficiency syndrome. HALS is associated with higher RBP4 and lower omentin in plasma. These two adipokines, particularly RBP4, may be a link between HIV/ART and fat redistribution syndromes.


Subject(s)
Anti-Retroviral Agents/administration & dosage , Anti-Retroviral Agents/adverse effects , Cytokines/blood , HIV Infections/complications , HIV Infections/drug therapy , HIV-Associated Lipodystrophy Syndrome/pathology , Lectins/blood , Retinol-Binding Proteins, Plasma/analysis , Adult , Aged , Case-Control Studies , Cross-Sectional Studies , Cytokines/genetics , Enzyme-Linked Immunosorbent Assay , Female , GPI-Linked Proteins/blood , GPI-Linked Proteins/genetics , Genotype , Humans , Lectins/genetics , Male , Middle Aged , Plasma/chemistry , Polymorphism, Genetic , Retinol-Binding Proteins, Plasma/genetics , Young Adult
5.
FEBS Lett ; 460(1): 81-5, 1999 Oct 22.
Article in English | MEDLINE | ID: mdl-10571065

ABSTRACT

We undertook the characterization of an actin gene and its proximal promoter in the oyster Crassostrea gigas. A complete actin cDNA was identified, sequenced and its amino acid sequence deduced. Comparative analysis showed a high homology with actin of other species and that this gene is closer to the cytoplasmic form of actins than to the muscle type. A probe derived from the 5'-untranslated region of the cDNA was then used to isolate the actin gene from a genomic library. The gene was sequenced and shown to contain a single 643 bp intron. A 1670 bp fragment upstream from the open reading frame was isolated and sequenced. This upstream region displays typical features of actins such as a serum response element (CarG box). This fragment was cloned into the promoterless vector pGL3-basic and the resulting construct was transfected into cells of dissociated oyster heart primary cultures. Its capacity to express the luciferase in this in vitro homologous system was monitored and showed high expression levels. This is the first complete actin sequence reported so far for the oyster C. gigas and its promoter is the first available among bivalves.


Subject(s)
Actins/genetics , Ostreidae/genetics , Promoter Regions, Genetic , Actins/chemistry , Amino Acid Sequence , Animals , Base Sequence , Cells, Cultured , Cloning, Molecular , DNA-Binding Proteins/genetics , Gene Expression Regulation , Genes, Reporter , Molecular Sequence Data , Mutation , Nuclear Proteins/genetics , Serum Response Factor , Transfection
6.
DNA Cell Biol ; 16(9): 1111-22, 1997 Sep.
Article in English | MEDLINE | ID: mdl-9324313

ABSTRACT

Endonuclease G (Endo G) is a nuclease of prokaryotic lineage found in the mitochondria of vertebrates that has been suggested to play a role in mitochondrial DNA (mtDNA) replication. We have isolated and sequenced the entire mouse endo G gene, determined the limits of the mRNA, and mapped the promoter region. The coding sequence of the single copy gene is interrupted by two introns and analysis of the transcripts does not support a model by which more than one Endo G isoform could be produced by alternative splicing. We have also characterized a full-length human Endo G cDNA and comparison at the protein level of the human, bovine, and murine nucleases indicates a high degree of conservation except in the respective mitochondrial targeting signals. Endo G is ubiquitously expressed and the steady-state levels of its mRNA vary by a factor greater than seven between different tissues. The relationship between the mtDNA copy number and Endo G mRNA levels is not strictly proportional but tissues richer in mtDNA have higher amounts of the mRNA and vice versa.


Subject(s)
Endodeoxyribonucleases/genetics , Gene Expression Regulation, Enzymologic/genetics , Alternative Splicing , Amino Acid Sequence , Animals , Base Sequence , Cattle , Cloning, Molecular , DNA, Complementary/genetics , DNA, Mitochondrial/genetics , Gene Dosage , Genes/genetics , Humans , Mice , Molecular Sequence Data , Organ Specificity , Promoter Regions, Genetic/genetics , RNA, Messenger/genetics , Restriction Mapping , Sequence Analysis, DNA
7.
IEEE Trans Biomed Eng ; 46(10): 1171-5, 1999 Oct.
Article in English | MEDLINE | ID: mdl-10513119

ABSTRACT

Nowadays, information fusion constitutes a challenging research topic. Our study proposes to achieve the fusion of several knowledge sources. This, in order to detect the esophagus inner wall from ultrasound medical images. After a brief description of information fusion concepts, we propose a system architecture including both model and data fusion. The data fusion is accomplished using fuzzy modeling, which can be seen as a monosensor/multiple sources data fusion system. The model fusion is performed using a full-adapted snake theory, which projects the fuzzy decision into the binary decision space.


Subject(s)
Endosonography/methods , Esophagus/diagnostic imaging , Fuzzy Logic , Image Enhancement/methods , Computer Simulation , Endoscopes , Endosonography/instrumentation , Equipment Design , Esophageal Neoplasms/diagnostic imaging , Humans , Transducers
8.
J Chemother ; 14(2): 175-80, 2002 Apr.
Article in English | MEDLINE | ID: mdl-12017373

ABSTRACT

The authors determined the pharmacokinetic parameters of a new immediate-release ciprofloxacin suspension in tube-fed intensive care patients with bacterial pneumonia, to compare two dosage regimens: 500 mg b.i.d and 750 mg b.i.d. in this prospective clinical trial. The 20 patients were critically ill and on mechanical ventilation and enteral feeding with bacterial pneumonia. They were randomized to receive two different ciprofloxacin dosages: 500 mg b.i.d (group 1) versus 750 mg b.i.d. (group 2). Blood samples were collected from these patients after reaching steady-state and the pharmacokinetic parameters were determined. The mean (range) serum steady-state concentration at 2 h after enteral administration was: C(max 500) = 2.6 (1.2-4.3) mg/L in group 1 and C(max 750) = 3.5 (1.5-5.9) mg/L in group 2. The mean (range) calculated 12-h area under the serum concentration was high in both groups: AUC(0-12 (500)) = 24.7 (12.9-36.2) mg.h/L in group 1 and AUC(0-12 (750)) = 28.9 (18.3-47.5) mg.h/L in group 2. In conclusion, ciprofloxacin oral suspension was well absorbed via nasogastric route in intensive care patients with severe pneumonia, achieving reliable pharmacokinetic parameters for most of the pathogens and important cost reduction compared to intravenous delivery. However, with less susceptible pathogens such as Staphylococcus aureus or Pseudomonas aeruginosa, higher dosages than 750 mg b.i.d. should be given.


Subject(s)
Anti-Infective Agents/pharmacokinetics , Ciprofloxacin/pharmacokinetics , Pneumonia, Bacterial/metabolism , Administration, Oral , Adult , Aged , Aged, 80 and over , Anti-Infective Agents/administration & dosage , Biological Availability , Ciprofloxacin/administration & dosage , Critical Illness , Dose-Response Relationship, Drug , Drug Monitoring , Female , Humans , Male , Middle Aged , Prospective Studies
9.
J Chemother ; 14(4): 361-5, 2002 Aug.
Article in English | MEDLINE | ID: mdl-12420853

ABSTRACT

The degree of penetration of an antibiotic into the infection site is an important factor in its therapeutic efficacy, particularly in bone and joint infections. In the present study, we examined the bone tissue penetration of isepamicin at a dose of 15 mg/Kg, and the results were correlated to microbiologic data to estimate the clinical efficacy of isepamicin in bone infections. In this open-label, single-arm, noncomparative study, subjects of similar age, body weight, height and creatinine clearance who were undergoing elective total hip replacement received a single, parenteral 15 mg/Kg dose of isepamicin. Plasma and bone tissue samples were collected a mean 1.3 hours later and analyzed by a high-pressure liquid chromatography method. Twelve patients (3 men and 9 women; mean age, 73.5 years; mean body weight, 53.5 Kg, mean creatinine clearance, 58.5 mL/min) were enrolled. The mean +/- SD plasma concentration of isepamicin at the time of bone removal was 43.0 +/- 10.4 microg/mL. The mean +/- SD isepamicin concentrations were 11.6 +/- 7.1 microg/mL in cancellous bone tissue and 12.0 +/- 7.3 microg/mL in cortical bone tissue. The mean +/- SD ratios of isepamicin concentration in bone and plasma (bone/plasma) were 0.28 +/- 0.14 for cancellous bone tissue and 0.31 +/- 0.20 for cortical bone tissue. The concentrations achieved in both cancellous and cortical bone tissue were greater than the minimum concentrations required to inhibit the growth of 90% of strains (MIC90) of most of the susceptible pathogens commonly involved in bone infections.


Subject(s)
Anti-Bacterial Agents/pharmacokinetics , Bone and Bones/metabolism , Gentamicins/pharmacokinetics , Adult , Aged , Aged, 80 and over , Biological Availability , Female , Hip/surgery , Humans , Infusions, Intravenous , Male , Microbial Sensitivity Tests , Middle Aged
10.
J Chemother ; 14(1): 54-8, 2002 Feb.
Article in English | MEDLINE | ID: mdl-11892900

ABSTRACT

The degree of penetration of an antibiotic into the infected site is an important criterion for therapeutic success. This is particularly true for bone and joint infections. The association of piperacillin and tazobactam has been widely used in the treatment of serious infections including bone infections, but no study has been devoted to the subject of its diffusion into synovial tissue. Our objective was to quantify piperacillin/tazobactam synovial tissue penetration and to estimate the efficacy of the association against the microorganisms usually encountered in joint infections. In an open-label study, 6 subjects with similar age, weight, height and creatinine clearance, who were undergoing elective total hip replacement, received a single, parenteral, 4 g/500 mg dose of piperacillin/tazobactam. Plasma and synovial tissue samples were collected and analyzed by a validated HPLC method. The mean concentrations of piperacillin and tazobactam 1.5 h after the initiation of infusion were 69.9 +/- 4.9 microg/mL and 7.7 +/- 0.3 microg/mL, respectively, in plasma and 37.1 +/- 2.1 microg/g and 2.8 +/- 0.4 microg/g, respectively, in synovial tissue. The synovial tissue/plasma ratios were 0.5 +/- 0.0 for piperacillin and 0.4 +/- 0.0 for tazobactam. The piperacillin/tazobactam ratios were 9.1:1 in plasma and 13.5:1 in synovial tissue. The concentrations achieved in synovial tissue are above the MICs of most of the susceptible pathogens usually involved in joint infections, which suggests that the piperacillin/tazobactam combination should be effective in the treatment of most joint infections caused by susceptible microorganisms.


Subject(s)
Drug Therapy, Combination/pharmacokinetics , Penicillanic Acid/pharmacokinetics , Piperacillin/pharmacokinetics , Synovial Membrane/metabolism , Aged , Aged, 80 and over , Arthroplasty, Replacement, Hip , Humans , Middle Aged , Penicillanic Acid/analogs & derivatives , Piperacillin, Tazobactam Drug Combination
11.
Phytomedicine ; 18(5): 414-24, 2011 Mar 15.
Article in English | MEDLINE | ID: mdl-21211952

ABSTRACT

The incidence of obesity and related metabolic diseases is increasing globally. Current medical treatments often fail to halt the progress of such disturbances, and plant-derived polyphenols are increasingly being investigated as a possible way to provide safe and effective complementary therapy. Rooibos (Aspalathus linearis) is a rich source of polyphenols without caloric and/or stimulant components. We have tentatively characterized 25 phenolic compounds in rooibos extract and studied the effects of continuous aqueous rooibos extract consumption in mice. The effects of this extract, which contained 25% w/w of total polyphenol content, were negligible in animals with no metabolic disturbance but were significant in hyperlipemic mice, especially in those in which energy intake was increased via a Western-type diet that increased the risk of developing metabolic complications. In these mice, we found hypolipemiant activity when given rooibos extract, with significant reductions in serum cholesterol, triglyceride and free fatty acid concentrations. Additionally, we found changes in adipocyte size and number as well as complete prevention of dietary-induced hepatic steatosis. These effects were not related to changes in insulin resistance. Among other possible mechanisms, we present data indicating that the activation of AMP-activated protein kinase (AMPK) and the resulting regulation of cellular energy homeostasis may play a significant role in these effects of rooibos extract. Our findings suggest that adding polyphenols to the daily diet is likely to help in the overall management of metabolic diseases.


Subject(s)
AMP-Activated Protein Kinases/metabolism , Aspalathus/chemistry , Energy Intake/drug effects , Liver/metabolism , Plant Extracts/pharmacology , Polyphenols/pharmacology , 3T3-L1 Cells , AMP-Activated Protein Kinases/drug effects , Adipose Tissue, White/drug effects , Adipose Tissue, White/enzymology , Animals , Cholesterol/blood , Cholesterol, Dietary/administration & dosage , Diet, High-Fat/adverse effects , Disease Models, Animal , Eating/drug effects , Enzyme Activation/drug effects , Fatty Liver/etiology , Fatty Liver/prevention & control , Liver/drug effects , Liver/enzymology , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , Plant Extracts/administration & dosage , Plant Extracts/chemistry , Polyphenols/administration & dosage , Polyphenols/chemistry , Triglycerides/blood , Weight Gain/drug effects
12.
Curr Mol Med ; 11(6): 453-64, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21663591

ABSTRACT

Atherosclerosis in symptomatic peripheral arterial disease affects wide portions of numerous arteries in lower extremities. The resulting active inflammation in a considerable amount of arterial tissue facilitates systemic detection via measurement of inflammation-related variables. We reasoned that the combined assessment of defense against oxidative stress, in the form of paraoxonase-1 (PON1), and monocyte migration measured as circulating (C-C motif) ligand 2 (CCL2), may play a role in the evaluation of these patients. Plasma CCL2 and serum PON1-related variables, assessed by their interaction with functional genetic variants, were measured in a cross-sectional study in patients with symptomatic PAD. We found that PON1 activity and concentration were significantly lower and CCL2 concentration higher in PAD patients compared to controls, that the combination of plasma CCL2 and PON1- related values, especially PON1 concentration differentiated, almost perfectly, controls from patients and that the expression of CCL2 and PON1 generally co-localized in the atherosclerotic lesion. Since no association with genetic variants was found, such a relationship is probably the result of the disease. Our data suggest a coordinated role between CCL2 and PON1 that may be detected in blood with simple measurements and may represent an indicator of the extent of atherosclerosis.


Subject(s)
Aryldialkylphosphatase/blood , Atherosclerosis/metabolism , Chemokine CCL2/blood , Peripheral Arterial Disease/blood , Aged , Aged, 80 and over , Aryldialkylphosphatase/genetics , Atherosclerosis/pathology , Chemokine CCL2/genetics , Cross-Sectional Studies , Humans , Male , Middle Aged , Oxidative Stress , Peripheral Arterial Disease/drug therapy , Peripheral Arterial Disease/genetics , Peripheral Arterial Disease/metabolism
13.
Phytomedicine ; 17(3-4): 186-91, 2010 Mar.
Article in English | MEDLINE | ID: mdl-19765963

ABSTRACT

Diet supplementation and/or modulation is an important strategy to significantly improve human health. The search of plants as additional sources of bioactive phenolic compounds is relevant in this context. The aqueous extract of Hibiscus sabdariffa is rich in anthocyanins and other phenolic compounds including hydroxycitric and chlorogenic acids. Using this extract we have shown an effective protection of cultured peripheral blood mononuclear cells from the cellular death induced by H(2)O(2) and a significant role in the production of inflammatory cytokines. In vitro, the extract promotes the production of IL-6 and IL-8 and decreases the concentration of MCP-1 in supernatants in a dose-dependent manner. In humans, the ingestion of an acute dose of the extract (10g) was well tolerated and decreased plasma MCP-1 concentrations significantly without further effects on other cytokines. This effect was not due to a concomitant increase in the antioxidant capacity of plasma. Instead, its mechanisms probably involve a direct inhibition of inflammatory and/or metabolic pathways responsible for MCP-1 production, and may be relevant in inflammatory and chronic conditions in which the role of MCP-1 is well established. If beneficial effects are confirmed in patients, Hibiscus sabdariffa could be considered a valuable traditional herbal medicine for the treatment of chronic inflammatory diseases with the advantage of being devoid of caloric value or potential alcohol toxicity.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Cell Survival/drug effects , Chemokine CCL2/blood , Hibiscus/chemistry , Inflammation Mediators/metabolism , Leukocytes, Mononuclear/drug effects , Plant Extracts/pharmacology , Adult , Antioxidants/pharmacology , Cell Culture Techniques , Chemokine CCL2/biosynthesis , Female , Flowers , Humans , Hydrogen Peroxide , Interleukin-6/biosynthesis , Interleukin-8/biosynthesis , Leukocytes, Mononuclear/metabolism , Male , Middle Aged , Phenols/pharmacology , Plant Extracts/chemistry , Reference Values , Young Adult
16.
Anesth Analg ; 92(2): 442-7, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11159248

ABSTRACT

We investigated the usefulness and reliability of the Gram stain value versus quantitative cultures in the early diagnosis of ventilator-associated pneumonia (VAP) using the protected bronchoalveolar lavage (PBAL). One hundred four mechanically ventilated patients (age = 52 +/- 19; SAPS II = 38 +/- 15) with a strong suspicion of VAP were consecutively included. One hundred sixteen PBAL were performed and mini-bronchoalveolar lavage were analyzed using the Gram stain standard method and the conventional quantitative culture technique. VAP diagnosis was based on a positive quantitative culture of mini-bronchoalveolar lavage fluid (cutoff > or = 10(3) CFU/mL). A final diagnosis of VAP was established in 67 patients and there was no infection in 49 cases. Regarding detection of bacteria using the Gram stain, we found a sensitivity of 76.2%, a specificity of 100%, a positive predictive value of 100% and a negative predictive value of 75.4%. There was a good agreement with the final diagnosis (kappa statistic 0.73; concordance 86.2%). The degree of qualitative agreement between Gram stain and quantitative cultures was analyzed in the VAP group: the correlation was complete in 39% (26 of 67 VAP), partial in 28% (19 of 67 VAP) and there was no correlation in 33% (22 of 67 VAP). We conclude that despite its overall "good agreement," the Gram stain is of limited use for the rapid diagnosis of VAP and unreliable for the early adaptation of empirical antimicrobial therapy when using the noninvasive PBAL procedure.


Subject(s)
Bacteria/isolation & purification , Bronchoalveolar Lavage Fluid/microbiology , Pneumonia, Bacterial/diagnosis , Respiration, Artificial/adverse effects , Adult , Aged , Aged, 80 and over , Coloring Agents , Female , Humans , Male , Middle Aged
17.
Anesth Analg ; 92(1): 180-3, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11133623

ABSTRACT

UNLABELLED: The combination of opioids with local anesthetics is commonly used for epidural labor analgesia. We examined whether increasing sufentanil in doses of 5, 10, and 15 microg prolonged the duration of labor analgesia produced by ropivacaine. One hundred healthy parturients in the first stage of labor who requested epidural analgesia were enrolled. Parturients were randomized to receive 12 mL ropivacaine 0.2% alone or with sufentanil 5 microg, sufentanil 10 microg, or sufentanil 15 microg. The duration of analgesia, pain score, degree of motor blockade (using a four-point Bromage scale), heart rate, blood pressure, respiratory rate, oxygen saturation, and incidence of nausea and pruritus were recorded. The mean duration of epidural analgesia was 96 +/- 32 min for patients without sufentanil, 134 +/- 27 min for Group 5 (p < 0.01 versus control), 135 +/- 33 min for Group 10 (p < 0.01 versus control), 130 +/- 33 min for Group 15 (p < 0.01 versus control) without differences among sufentanil groups. Between 30 and 90 min, the sufentanil groups (5 microg, 10 microg, and 15 microg) had lower pain scores than the control group (p < 0.01 versus control) but there were no differences among the sufentanil groups. No patient in any group had a Bromage score more than 1. No significant difference was found for opioid-related side effects. We conclude that 5-10 or 15 microg sufentanil induced a similar prolongation of analgesia when combined with ropivacaine 0.2% for initiation of labor analgesia. IMPLICATIONS: We studied the effect of adding one of three possible sufentanil doses to epidural ropivacaine 0.2% for labor analgesia. Adding sufentanil increased the duration of analgesia but there was no advantage in adding more than 5 microg of sufentanil.


Subject(s)
Amides/administration & dosage , Analgesia, Epidural/methods , Analgesia, Obstetrical/methods , Analgesics, Opioid/administration & dosage , Anesthetics, Local/administration & dosage , Sufentanil/administration & dosage , Adult , Amides/adverse effects , Analgesia, Epidural/adverse effects , Analgesia, Obstetrical/adverse effects , Analgesics, Opioid/adverse effects , Anesthetics, Local/adverse effects , Blood Pressure/drug effects , Dose-Response Relationship, Drug , Double-Blind Method , Drug Therapy, Combination , Female , Heart Rate/drug effects , Humans , Nausea/chemically induced , Pregnancy , Prospective Studies , Pruritus/chemically induced , Ropivacaine , Sufentanil/adverse effects
18.
Br J Anaesth ; 87(2): 280-3, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11493502

ABSTRACT

The effect of sepsis on the minimum alveolar concentration of desflurane (MAC(DES)) in humans and other animals has not been reported previously. The aim of this study was to test the hypothesis that sepsis might alter MAC(DES) in a normotensive septic porcine model. Twenty-four young healthy pigs were premedicated with ketamine 10 mg kg(-1 )i.m and then anaesthesia was established with propofol 3 mg kg(-1) and the trachea was intubated. Baseline MAC(DES) in each pig was evaluated by pinching with a haemostat applied for 1 min to a rear dewclaw. MAC(DES) was determined by changing desflurane concentrations stepwise until purposeful movement appeared. Pigs were randomly assigned to two groups of 12 animals: the saline group received a 1 h i.v. infusion of saline solution while the sepsis group received a 1 h i.v. infusion of live Pseudomonas aeruginosa. Epinephrine and hydroxyethylstarch were used to maintain normotensive and normovolaemic haemodynamic status. In both groups, MAC(DES) was evaluated 5 h after infusion. Significant increases in heart rate, cardiac output, mean pulmonary artery pressure and pulmonary vascular resistance occurred in the sepsis group. MAC(DES) was 9.2% (95% confidence interval (CI) 6.8-10.6%) for the saline group and 6.7% (95% CI: 4.7-10.4) for the sepsis group (P<0.05). These data indicate that MAC(DES) is significantly decreased in this normotensive hyperkinetic septic porcine model.


Subject(s)
Anesthetics, Inhalation/pharmacokinetics , Bacteremia/metabolism , Isoflurane/pharmacokinetics , Pulmonary Alveoli/metabolism , Animals , Bacteremia/physiopathology , Desflurane , Disease Models, Animal , Hemodynamics/drug effects , Isoflurane/analogs & derivatives , Swine
19.
Br J Anaesth ; 86(6): 832-6, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11573592

ABSTRACT

Sevoflurane is widely used in anaesthetic protocols for patients undergoing surgical procedures. However, there are no reports on the influence of sepsis on minimum alveolar concentration of sevoflurane (MAC(SEV)) in animals or in humans. The aim of this study was to test the hypothesis that sepsis could alter the MAC(SEV) in a normotensive septic pig model. Twenty young, healthy pigs were used. After they had received 10 mg kg(-1) of ketamine i.m. for premedication, anaesthesia was established with propofol 3 mg kg(-1) and the trachea was intubated. Sevoflurane was used as the sole anaesthetic agent. Baseline haemodynamic recording included electrocardiography, carotid artery blood pressure and a pulmonary thermodilution catheter. Baseline MAC(SEV) in each pig was evaluated by pinching with a haemostat applied for 1 min to a rear dewclaw. MAC(SEV) was determined using incremental changes in sevoflurane concentration until purposeful movement appeared. Pigs were assigned randomly to two groups: the saline group (n = 10) received a 1-h i.v. infusion of sterile saline solution while the sepsis group (n = 10) received a 1-h i.v. infusion of live Pseudomonas aeruginosa. Epinephrine and hydroxyethylstarch were used to maintain normotensive and normovolemic haemodynamic status. In both groups, MAC(SEV) was evaluated 5 h after infusion. Significant increases in mean artery pulmonary pressure, filling, epinephrine and vascular pulmonary resistances occurred in the sepsis group. MAC(SEV) for the saline group was 2.4% [95% confidence interval (CI) 2.1-2.55%] and the MAC(SEV) for the sepsis group was 1.35% (95% CI 1.2-1.45%, P<0.05). These data indicate that MAC(SEV) is significantly decreased in this normotensive septic pig model.


Subject(s)
Anesthetics, Inhalation/pharmacokinetics , Methyl Ethers/pharmacokinetics , Pulmonary Alveoli/metabolism , Sepsis/metabolism , Swine/metabolism , Analgesics , Anesthetics, Intravenous , Animals , Ketamine , Models, Animal , Premedication , Propofol , Sevoflurane
20.
Br J Anaesth ; 88(3): 369-73, 2002 Mar.
Article in English | MEDLINE | ID: mdl-11990268

ABSTRACT

BACKGROUND: Although the postanaesthesia care unit (PACU) can be noisy, the effect of noise on patients recovering from anaesthesia is unknown. We studied the sources and intensity of noise in the PACU and assessed its effect on patients' comfort. METHODS: We measured noise in a five-bed PACU with a sound level meter. Noise levels were obtained using an A-weighted setting (dBA) and peak sound using a linear scale (dBL). Leq (average noise level at 5-s intervals), maximum Leq (LeqMax), minimum Leq (LeqMin) and noise peaks (Lpc) were calculated. During recording, an independent observer noted the origin of sounds from alarms and noise above 65 dB intensity (P65dB). Two hours after leaving the PACU, patients were asked about their experience and to rank their complaints on a visual analogue scale (VAS) using unstructured and structured questionnaires. RESULTS: We made 20,187 measurements over 1678 min. The mean Leq, LeqMax and LeqMin were 67.1 (SD 5.0), 75.7 (4.8) and 48.6 (4.1) dBA respectively. The mean Lpc was 126.2 (4.3) dBL. Five per cent of the noise was at a level above 65 dBA. Staff conversation caused 56% of sounds greater than 65 dB and other noise sources (alarm, telephone, nursing care) were each less than 10% of these sounds. Five patients reported disturbance from noise. There was no significant difference in Leq measured for patients who found the PACU noisy and those who did not [59.5 (3.1) and 59.4 (2.4) dBA respectively]. Stepwise multiple logistic regression indicated that only pain was associated with discomfort. CONCLUSIONS: Even though sound in the PACU exceeded the internationally recommended intensity (40 dBA), it did not cause discomfort. Conversation was the most common cause of excess noise.


Subject(s)
Anesthesia Recovery Period , Health Facility Environment , Noise/adverse effects , Postoperative Care , Recovery Room , Adult , Aged , Anesthesia, General , Environmental Monitoring/methods , Female , France , Humans , Logistic Models , Male , Middle Aged , Patient Satisfaction , Prospective Studies , Speech
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