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Biomedical subjects

M Tanguy

Publications and source records attributed to M Tanguy.

At least 19 recordsLinked to original sources
PubMed2006

AGS3, an alpha(1-3)glucan synthase gene family member of Aspergillus fumigatus, modulates mycelium growth in the lung of experimentally infected mice.

The cell wall of human fungal pathogen Aspergillus fumigatus protects the fungus against threats from environment and interacts with the host immune system. Alpha(1-3)glucan is the major polysaccharide of Aspergillus fumigatus cell wall, and it has been shown to contribute to the virulence of diverse fungal pathogens. In A. fumigatus, three putative alpha(1-3)glucan synthase genes AGS1, AGS2 and AGS3 have been identified. AGS1 is responsible for cell wall alpha(1-3)glucan biosynthesis, but strains with deletions of either AGS1 or AGS2 are not defective in virulence [Beauvais, A., Maubon, D., Park, S., Morelle, W., Tanguy, M., Huerre, M., Perlin, D.S., Latgé, J. P., 2005. Two alpha(1-3) glucan synthases with different functions in Aspergillus fumigatus. Appl. Environ. Microbiol. 71, 1531-1538]. In contrast, we present evidence that AGS3 is also responsible for cell wall alpha(1-3)glucan biosynthesis and can modulate the virulence of A. fumigatus. An AGS3 deletion strain was found to produce faster and more robust disease than the parental strain in an experimental mouse model of aspergillosis. The apparent hyper-virulence in the AGS3-deleted mutant was correlated with an increased melanin content of the conidial cell wall, a better resistance to reactive oxygen species and a quicker germination rate. These results suggest an indirect role for AGS3 in virulence through an adaptive mechanism.

Animals↗
PubMed2005

Two alpha(1-3) glucan synthases with different functions in Aspergillus fumigatus.

Alpha(1-3) glucan is a main component of the Aspergillus fumigatus cell wall. In spite of its importance, synthesis of this amorphous polymer has not been investigated to date. Two genes in A. fumigatus, AGS1 and AGS2, are highly homologous to the AGS genes of Schizosaccharomyces pombe, which encode putative alpha(1-3) glucan synthases. The predicted Ags proteins of A. fumigatus have an estimated molecular mass of 270 kDa. AGS1 and AGS2 were disrupted in A. fumigatus. Both Deltaags mutants have similar altered hyphal morphologies and reduced conidiation levels. Only Deltaags1 presented a reduction in the alpha(1-3) glucan content of the cell wall. These results showed that Ags1p and Ags2p were functionally different. The cellular localization of the two proteins was in agreement with their different functions: Ags1p was localized at the periphery of the cell in connection with the cell wall, whereas Ags2p was intracellularly located. An original experimental model of invasive aspergillosis based on mixed infection and quantitative PCR was developed to analyze the virulence of A. fumigatus mutant and wild-type strains. Using this model, it was shown that the cell wall and morphogenesis defects of Deltaags1 and Deltaags2 were not associated with a reduction in virulence in either mutant. This result showed that a 50% reduction in the content of the cell wall alpha(1-3) glucan does not play a significant role in A. fumigatus pathogenicity.

Amino Acid Sequence↗
PubMed2002

[An atypical Demons-Meigs syndrome].

Meigs'syndrome is defined as a hydrothorax with ascites and benign ovarian tumor, both of which resolve on removal of the tumor. Pseudo-Meigs'syndrome or atypical Meigs'syndrome occurs when a pelvic mass other than an ovarian fibroma is present with hydrothorax and ascites. Both these syndromes should be nevertheless considered in women who present hydrothorax and ascites. This case concerns a 50-year-old woman who presented a pseudo-Meigs'syndrome (Hydrothorax and uterine leiomyoma). The distinction between these two syndrome is useless, because tumour removal is the only treatment.

Ascites↗
PubMed2000

Evidence for the need of bedside accuracy of pulse oximetry in an intensive care unit.

OBJECTIVE: To compare pulse oximetry saturation (Spo2 with arterial blood gas saturation (SaO2) obtained during clinical routine to determine the optimal lowest reliable value of SpO2 in ventilator-dependent patients before setting up a nurse-directed protocol of FIO2 titration. DESIGN: Prospective clinical study. SETTING: Surgical intensive care unit in a university hospital. PATIENTS: Thirty-three patients with a pulse oximeter probe in whom arterial blood gas was measured with a radial artery line. INTERVENTIONS: SPO2 was recorded by the nurses and compared with SaO2 obtained by blood gas analysis with a co-oximeter. Two sensors currently used in our surgical intensive care unit and connected to a monitor (HP OmniCare M1165/66A; Hewett Packard, Andover, MA) were tested. In group I, the Durensor DS 100A (Nellcor Puritan Bennett, Pleasanton, CA), a reusable sensor, was used. In group II, the Oxisensor D25L (Nellcor Puritan Bennett), a nonreusable sensor, was used. MEASUREMENTS AND MAIN RESULTS: In group 1, 64 data pairs were obtained. In this group, SaO2 ranged from 87 to 98% and SpO2 ranged from 92 to 100%. The bias was -1.90% and the limits of agreement ranged from -5.56 to 1.76%. In group 11, 47 data pairs were obtained. In this group, SaO2 ranged from 87 to 99% and SpO2 ranged from 92 to 100%. The bias was -2.49% and the limits of agreement ranged from -6.62 to 1.64%. CONCLUSIONS: In the range of SaO2 tested, regardless of the sensor used, SpO2 overestimated SaO2. Large limits of agreement were found. Based on this result, the authors concluded that before defining a nurse-directed protocol of FIO2 titration with SpO2, the material used daily must be evaluated. A minimum threshold SpO2 value of 96% in both groups I and II is more reliable to ensure SaO2 > or = 90%.

Blood Gas Analysis↗
PubMed1998

Evaluation of a new semi-continuous cardiac output system in the intensive care unit.

PURPOSE: A new semi-continuous thermodilution cardiac output (CCO) system has been developed recently (Opti-Q and Q-vue Abbott critical care system). The aim of this study was to compare the accuracy and reproducibility of this new device with conventional ice-bolus thermodilution cardiac output (BCO). METHODS: Fifteen critically ill patients who needed pulmonary artery catheterization were prospectively investigated. Eighty seven paired data using BCO and CCO methods were compared. Reproducibility was assessed from 90 BCO and 87 CCO determinations by calculation of the mean standard error (SEM) and according to Bland and Altman methodology. RESULTS: The BCO and CCO ranged from 2.46 to 11.20 L.min-1 and from 1.75 to 10.05 L.min-1 respectively. Bias (mean difference between BCO and CCO) was null (0.002 L.min-1, P = 0.98), precision (SD of the bias) was 0.74 L.min-1 and the limits of agreement (mean difference +/- 1.96 SD) ranged from -1.45 to 1.45 L.min-1. The threshold to consider two cardiac outputs as different (3 x SEM) was equivalent for BCO and CCO (0.54 and 0.465 L.min-1 respectively). According to the Bland and Altman method, reproducibility of CCO was greater than that of BCO; bias of repeated measurements of BCO and CCO were 0.15 L.min-1 (P < 0.05) and 0.047 L.min-1 (NS), respectively. CONCLUSION: Compared with BCO, this new device was accurate but cannot be considered as interchangeable regarding the limits of agreement. Reproducibility of CCO was superior to BCO.

APACHE↗
PubMed1998

Theiler's virus infection of perforin-deficient mice.

Theiler's virus, a murine picornavirus, infects the central nervous systems of C57BL/6 mice and is cleared after approximately 10 days by a process which requires CD8+ cytotoxic T cells. We used perforin-deficient C57BL/6 mice to test the role of this protein in viral clearance. Perforin-deficient mice died from viral encephalomyelitis between days 12 and 18 postinoculation. They had high levels of viral RNA in their central nervous systems until the time of death. In contrast, viral RNA had disappeared by day 11 postinoculation in wild-type C57BL/6 mice. Cytotoxic T cells can kill infected cells by two main mechanisms: the secretion of the pore-forming protein perforin or the interaction of the Fas ligand with the apoptosis-inducing Fas molecule on the target cell. Our results demonstrate that clearance of Theiler's virus from the central nervous system in C57BL/6 mice is perforin dependent.

Animals↗
PubMed1994

Human hepatocytes express trifluoroacetylated neoantigens after in vitro exposure to halothane.

Biotransformation of anaesthetic halothane by cytochrome P450-dependent monooxygenases resulted in the production of reactive intermediate trifluoroacetyl (TFA) halide, capable of covalently binding to hepatocyte proteins. TFA-modified liver proteins can act as antigens and are implicated in the pathogenesis of halothane hepatitis in humans. The aim of this study was to investigate the formation of TFA-neoantigens in halothane-treated primary cultures of adult human hepatocytes and to evaluate the usefulness of this in vitro model for studying immune-mediated halothane hepatotoxicity. Cultured human hepatocytes were incubated with halothane under constant temperature, atmosphere and anaesthetic concentration conditions. The results obtained show that halothane-treated hepatocytes isolated from seven different donors produced TFA-antigens as detected by immunocytochemical and western immunoblot analysis using rabbit anti-TFA antiserum. TFA-adducts were localized mainly in the endoplasmic reticulum and in small amounts on the plasma membrane of parenchymal cells. By immunoblotting, several neoantigens, with molecular masses from 42 to 100 kDa, were detected in halothane-exposed hepatocytes. These observations are consistent with the formation of TFA-adducts through metabolism of the anaesthetic and suggest that primary cultures of human hepatocytes represent a suitable in vitro model to study the pathogenesis of immune-mediated halothane hepatotoxicity.

Antibody Specificity↗
PubMed1994

[Preoxygenation before induction for cesarean section].

In pregnant women at term, the oxygen reserve is decreased while the oxygen consumption is increased, carrying the risk of hypoxaemia during periods of apnea. Moreover, intubation of the trachea can be difficult. Therefore preoxygenation is of particular importance. The conventional method of preoxygenation consists in a 3-5 min breathing of 100% O2. However, in some obstetric emergencies, there may not be an adequate delay of time available for this technique. Recently, 4 maximally deep inspirations were demonstrated to be as effective as a 5-min inhalation of 100% O2 for preoxygenation. To determine whether these two techniques were equivalent before induction of a general anaesthesia for Caesarean section, 27 pregnant women at term (ASA 1 or 2) were studied. Following premedication with atropin sulfate (0.5 mg), the patients were randomly allocated into two groups. Group A (n = 12) was denitrogenated with 100% O2 for 4 min and group B (n = 15) with 4 maximally deep inspirations of 100% O2 within 30 s. Oxygen was administered at a flow rate of 10 L.min-1 via a non rebreathing anaesthesia system and a tight fitting face mask. Arterial saturation was assessed by pulse oximetry. General anaesthesia was induced with thiopentone (7 mg.kg-1) and succinylcholine (1.5 mg.kg-1). The trachea was intubated without previous ventilation and the delay required for the SpO2 to decrease to 93% was measured. This time was 137.9 +/- 79.2 s (extremes 85-320) in group A and 144.5 +/- 57.3 s (extremes 60-285) in group B respectively. These times were not significantly different.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

[Severe acute pancreatitis: diagnostic approaches and therapeutic implications].

Diagnosis of acute pancreatitis (AP) can be obtained with a high level of accuracy by clinical assessment and determination of common laboratory parameters such as serum amylase and lipase concentrations. However, the key of an optimal management of patients with AP is based on an early discrimination between interstitial oedematous and necrotizing forms. The former resolves spontaneously whereas parenchymal necrosis acting as a focus for bacteria has a very high severity. In this respect, multifactor prognostic scoring systems and new biological assessments like C reactive protein are valuable methods for forecasting the prognosis of AP. However, these indicators of severity require a full 48 hour period of observation. In order to overcome these drawbacks, other prognostic criteria have been explored based mainly, on laboratory data. The most interesting ones are trypsinogen activation peptides and leucocyte elastase. Finally, the more useful tool is computed tomography (CT). Combined with high dose intravenous contrast agent, it allows an early identification of necrosis. Other goals of computed tomography are an accurate diagnosis of infection by guided needle aspirations and a preoperative recognition of devitalized and infected tissues, which require a careful surgical necrosectomy. A prolonged drainage is always recommended but relative merits of a conventional closed drainage and an open one are controversial. Another therapeutic challenge is gallstone associated to severe pancreatitis. An early stone removal is advocated by some authors but others prefer delayed surgery because of high mortality rates in case of emergency surgery. Delayed surgery until biological parameters of pancreatitis are normalized seems preferable. An early endoscopic sphincterotomy in an attractive alternative method.

Acute Disease↗
PubMed1993

Halothane-induced cytotoxicity to rat centrilobular hepatocytes in primary culture is not increased under low oxygen concentration.

BACKGROUND: Halothane can be metabolized by both oxidative and reductive pathways in the liver. This anesthetic can induce direct liver injury preferentially localized in centrilobular areas, probably in relation with lower oxygen tension. The reductive pathway has been related to liver damage; however, a correlation between lower oxygen concentration in centrilobular areas, the extent of reductive metabolism of halothane, and the degree of liver injury has not yet been demonstrated. This study was designed to better evaluate the toxicity of the reduced metabolites by using centrilobular and periportal rat hepatocyte subpopulations. METHODS: Adult rat hepatocytes, either as whole cell preparations or after separation in centrilobular and periportal cell subpopulations, were placed in primary culture and exposed to either 2% or 4% halothane under various oxygen concentrations. The enriched centrilobular hepatocyte subpopulations isolated by the digitonin-collagenase method were characterized by immunolocalization of glutamine synthetase. Three oxygen concentrations were tested: 5%, 20%, and 95%, and the main parameters measured were cell viability and fluoride ion formation. RESULTS: Viability of centrilobular hepatocytes was similar under 5% and 20% O2, but the unpurified hepatocyte population was more susceptible to 5% O2 (P < 0.01). Significantly higher cytochrome P-450 content was found in whole hepatocyte populations under 5% versus 20% oxygen, indicating that centrilobular hepatocytes that contained higher cytochrome P-450 monooxygenase activities were less sensitive to low oxygen concentrations. Halothane toxicity to centrilobular hepatocytes was enhanced under 95% versus 20% O2 (P < 0.05). By contrast, no significant difference was observed when the cells were maintained under 5% O2, although fluoride ions, indicative of reductive metabolism of halothane, were found in much higher amounts in the culture medium. Moreover, under 20% O2, halothane toxicity was significantly greater in centrilobular versus unpurified hepatocytes (P < 0.05). CONCLUSIONS: Isolated centrilobular hepatocytes appear to be more sensitive to halothane than their periportal counterparts in vitro. However, the authors' results support the conclusion that increased reductive metabolism of halothane induced by decreasing oxygen concentration is not a critical parameter for the occurrence of liver damage in these cells.

Animals↗
PubMed1993

Steady-state pharmacokinetics of dopamine in adult patients.

OBJECTIVE: To study the pharmacokinetics of dopamine in hemodynamically stable adult patients. DESIGN: Prospective clinical study. SETTING: University hospital intensive care unit. PATIENTS: Fourteen patients (aged 43 to 73 yrs) recovering from esophageal surgery. INTERVENTION: Dopamine was infused and blood samples were collected. MEASUREMENTS AND MAIN RESULTS: Plasma dopamine concentrations were measured at steady state and subsequently at the end of the dopamine infusion using high-performance liquid chromatography. Clearances, volume of distribution, mean residence times, half-lives, and elimination and distribution rate constants were derived. The clearances were independent of the infusion rate at 1, 3, and 6 micrograms/kg/min, and ranged between 0.050 and 0.056 L/min/kg. A two-compartment open model was fitted to the postinfusion plasma concentration data obtained at 3 and 6 micrograms/kg/min. On average, the steady-state volume of distribution and the apparent terminal elimination half-life increased with the dose: 0.78 to 1.58 L/kg, respectively, and 22.1 to 37.9 mins, respectively, for the rates of 3 and 6 micrograms/kg/min. The rate constant associated with the uptake of dopamine into the peripheral compartment (K12) was on average four to five times higher than the rate constant associated with the reverse process (K21). CONCLUSIONS: The redistribution of dopamine into the central compartment could be the main factor involved in the apparent terminal elimination of dopamine from plasma. Due to the relative rates of distribution and elimination, the attainment of a steady-state plasma concentration of dopamine should only depend on the terminal half-life. These results, which remain to be validated in a greater number of patients, indicate that the attainment of 90% of the plateau (i.e., in 3.3 half-lives) would require 70 to 125 mins, depending on the infusion rate.

Adult↗
PubMed1990

[Fatal maternal streptococcus A infection after cesarean section].

A case is reported of an infection with Streptococcus pyogenes, occurring 24 hours after an elective Caesarean section in a 30 year old woman. She worsened during the first 48 h, with shock (Pasys less than 70 mmHg, pH 7.28) as well as abdominal tenderness and guarding. Laparotomy revealed peritonitis, and subtotal hysterectomy was carried out. Gram positive cocci were found in the peritoneal exudate, with bacterial cultures yielding Streptococcus pyogenes. Histopathological examination of the specimen revealed necrosing endomyometritis with septic thrombophlebitis. During the immediate post-operative period, there were several prolonged episodes of circulatory arrest treated with dobutamine, adrenaline, and noradrenaline. Multiple organ failure occurred during the next five days, despite antibiotic therapy (vancomycin, tienamycin, amikacin) and intensive care. It included jaundice, thrombocytopaenia (10 G.l(-1] adult respiratory distress syndrome (ARDS). A further laparotomy was carried out because of abdominal and thigh cellulitis, with completion of the hysterectomy and bilateral salpingo-oophorectomy. Streptococcus pyogenes was still present in the peritoneal cavity. There followed an improvement, with a return to normal of the platelet count, haemodynamic stability such that vasoactive drugs were no longer needed, and a decrease in the degree of jaundice. However, the ARDS worsened, and the patient died 15 days after the Caesarean section. There have been recent reports of similar cases, suggesting an increase in the virulence of group A streptococci linked to a re-emergence of exotoxin A.

Adult↗
PubMed1990

Effects of halothane on human and rat hepatocyte cultures.

The aim of this study was to investigate direct cytotoxicity to human and rat hepatocytes in primary culture from halothane and compare it with that of isoflurane, which is known to be minimally metabolized and less toxic in vivo. Both human and rat parenchymal cells were isolated by the two-step collagenase perfusion method and after attachment to plastic were incubated with either volatile anesthetic for 24 h. All the cultures were maintained in 20% O2 condition and were not induced prior to anesthetic treatment. Temperature, atmosphere conditions, and anesthetic concentrations were kept constant during the study period. Evaluation of cytotoxicity was based on morphologic, biologic (determination of both extracellular and intracellular lactate dehydrogenase activity), and metabolic (protein synthesis and secretion) end points. Protein synthesis and secretion rates were found to be the most sensitive parameters in hepatocyte cultures from both species. Protein synthesis was inhibited by 18% and protein secretion by 50% in the presence of 1 and 1.25 mM halothane, respectively, in human cell cultures (P less than 0.05). With 1.25 mM halothane intracellular lactate dehydrogenase was also decreased; lactate dehydrogenase leakage and morphologic alterations were detected only beyond 5 mM halothane. By contrast, in rat hepatocyte cultures protein secretion was inhibited by 26% and protein synthesis by 20% in the presence of 0.1 and 0.75 mM halothane, respectively, whereas morphologic alterations and a 37% lactate dehydrogenase leakage increase were observed with the concentration of 1 mM (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

[Digestive stress hemorrhage. Physiopathology and prevention].

Lesions of the gastroduodenal mucosa are seen very early on in virtually 100% of patients suffering from organ failure. Bleeding, even if it is only occult, defines acute stress-induced gastrointestinal tract bleeding (SGIB). The rates of SGIB vary according to the inclusion criteria: 13 to 100% microscopic SGIB, 2.3 to 9.5% haemorrhage with blood transfusion and/or shock. Gastrointestinal bleeding does not really influence the death rate of patients with SGIB (0 to 5% increase). Damage to the gastric mucosa may be due to an intraluminal aggression, and/or decreased mucosal and mural defence mechanisms. H+ ions and bile salts are mostly responsible for the former. Physiological quantities of H+ ions may be sufficient, as their abnormal diffusion into the gastric mucosa will reduce the mucosal pH (pHm), which is itself sensitive to microcirculatory modifications and systemic acidosis. There is a good correlation between bleeding and pHm. Bile salts are involved because of the usual increase in frequency and volume of gastric biliary reflux due to stress. Surfactant, mucosal alkaline layer and the microcirculation are all involved in gastric protection. The PGE2 synthetized by the gastric mucosa have a favourable influence on these 3 mechanisms. Changes in microcirculation and hypoxia are the predominant factors involved in stress-induced mucosal damage. The prevention of SGIB relies on the treatment of risk factors, a reduction of intraluminal aggression, and the support and/or stimulation of gastric defence mechanisms. Antacids and anti-H2 drugs aim to neutralize most of the H+ ions, being more efficient than placebo in increasing gastric pH greater than 4, although anti-H2 agents are responsible of a greater number of failures. The non-homogenous character of the patient groups studied and the diagnostic methods, as well as the increasing lack of placebo groups in the published studies make the interpretation of the results rather risky. Antacids and anti-H2 drugs are more efficient than placebo, and equally efficient, in preventing overt SGIB. Efficiency is increased by giving anti-H2 drugs continuously, and antacids hourly. Other agents are thought to protect mucosal cells, probably increasing mucosal defences. Amongst them are the prostaglandins, the most interesting of which are still being investigated, and sucralfate. The latter molecule is as efficient as antacids and anti-H2 drugs, and does not alter gastric pH, so reducing the number of nosocomial pneumonias. Its reduced cost and easy administration make it, at the present time, the treatment of choice of SGIB. The few rare contraindications of sucralfate will justify the infusion of anti-H2 drugs in those patients at risk.

Anti-Ulcer Agents↗
PubMed1987

[Prolonged intravenous infusion of morphine. Pharmacokinetic study].

Critically ill patients require optimal pain control without undesirable side-effects. Continuous intravenous morphine infusion is often chosen instead of the conventional intermittent administration. In the present study, the pharmacokinetic characteristics of morphine were studied in five subjects receiving a constant rate intravenous infusion with the attainment of a steady state. The plasma levels were compared with values derived from bolus intravenous administration in five other patients. The concentrations of unchanged morphine were determined in serum using high performance liquid chromatography with an electrochemical detector. The decay of plasma concentrations after a single dose fitted a triexponential function consistent with a three compartment pharmacokinetic model. Postinfusion plasma concentrations fitted a two compartment model. Derived values (mean +/- SEM) of total body clearance were significantly different between groups (p less than 0.05), while mean values of terminal elimination half-life (t 1/2 Kel) were similar. It was concluded that values of total distribution volume were significantly different. The extent of morphine distribution varied more than twofold between the two groups of patients. This was interpreted as a consequence of an important underestimation in the extent of distribution tissues after administration of a single dose.

Adult↗