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Biomedical subjects

H Dupont

Publications and source records attributed to H Dupont.

At least 37 records · Page 2Linked to original sources

Monotherapy with a broad-spectrum beta-lactam is as effective as its combination with an aminoglycoside in treatment of severe generalized peritonitis: a multicenter randomized controlled trial. The Severe Generalized Peritonitis Study Group.

In a randomized trial conducted in 35 centers, we compared the clinical efficacy and safety of piperacillin plus tazobactam (TAZ) alone (monotherapy [MT]) versus those of TAZ combined with amikacin (AMK) (combined therapy [CT]) for the treatment of severe generalized peritonitis (SGP). Primary analysis consisted of blind assessment by an independent committee of the failure rate 30 days after the end of treatment in the modified intent-to-treat (ITT) analysis (mITT) population. Of the 241 patients with suspected SGP randomized into the study, 227 were eligible for ITT analysis, including 204 (99 in the MT group and 105 in the CT group) with confirmed SGP (mITT population). A total of 159 patients were eligible for per-protocol (PP) analysis. The clinical failure rates were equivalent in the mITT and PP populations (MT versus CT): 56 versus 52%, (odds ratio [OR] 0.87, 90% confidence interval [CI] = 0. 6 to 1.27) for mITT and 49 versus 49% (OR = 1.03, 90% CI = 0.67 to 1. 59) for PP analysis. Mortality rates (ITT population, 19%; PP population, 21%) and overall adverse event rates (ITT population, 55%; PP population, 54%) were also similar. Six patients (three in MT group and three in the CT group) developed acute renal failure. In conclusion, the addition of AMK to TAZ does not seem to be necessary for the treatment of SGP, even after adjustment for the simplified acute physiology score (SAPS II) and type of SGP.

Adolescent↗

In vitro activity and fecal concentration of rifaximin after oral administration.

Rifaximin showed moderately high MICs (the MIC at which 90% of the isolates tested were inhibited = 50 microg/ml) for 145 bacterial enteropathogens from patients with traveler's diarrhea acquired in Mexico during the summers of 1997 and 1998. Rifaximin concentrations in stool the day after oral administration (800 mg daily for 3 days) were high (average, 7,961 microg/g), proving the value of the drug.

Administration, Oral↗

[Evaluation of an activity score of prehospital medicine: activity scoring using Smur (CAS)].

OBJECTIVE: The activity of prehospital emergency medicine (PEM) teams is mainly assessed by the amount of medical interventions and their duration. However, these two parameters do not reflect workload correctly. The aim of this study was to compare a new activity scoring system for PEM teams (CAS) with the standard TISS score. STUDY DESIGN: Prospective comparative study. PATIENTS: This study included 4,650 patients, with a median age of 39 years [0-100], attended by PEM teams during 4,189 ambulance transports (83% primary transports and 17% interhospital transfers). METHODS: The CAS score derived from Omega scoring system is the sum of 51 items specifically suited for PEM, each one being rated 1, 3, 6 or 10. CAS and TISS, were prospectively determined for all medical ambulance transports over 1.5 year. Transport data and main diagnosis were collected. Results were analysed with non parametric statistical tests. RESULTS: Median duration of interventions (39 min [0-475]) and median CAS score (7 [0-72]) were comparable (R' = 0.38, P < 0.001). Median TISS was 3 [0-30]. CAS score was correlated with TISS (R' = 0.92, P < 0.001). CAS score was higher in men than in women (7 [0-72] vs 7 [0-45], P < 0.001). CAS scores in patients with cardiologic (11 [0-72]), respiratory (9 [0-31]) or neurological insults (9 [0-43]) were significantly higher than those of patients with other insults (P < 0.001). CONCLUSION: The CAS scoring system is a valuable indicator of medical team prehospital workload, probably more suited for prehospital emergency medicine than TISS.

Ambulances↗

Efficiency of inhaled nitric oxide as rescue therapy during severe ARDS: survival and factors associated with the first response.

PURPOSE: The purpose of this study was to determine if the response to inhaled nitric oxide (NO) as salvage therapy is an independent factor for survival in adult respiratory distress syndrome (ARDS) patients and to identify the factors that predict the response to inhaled NO during ARDS. MATERIALS AND METHODS: This was a multicenter, 2-year retrospective, clinical study in five university surgical or medical intensive care units, including all consecutive patients with ARDS in whom inhaled NO was tried. Clinical data (medical history, diagnoses), general severity scores (SAPS II, OSF), biological data, radiological and hemodynamic data at admission, at the beginning of the ARDS, and under treatment with inhaled NO were recorded. The NO response was defined as the variation of PaO2/Fio2 ratio before initiation and after 30 minutes of NO inhalation (VarPaO2/FiO2). RESULTS: Ninety-three patients aged 49 +/- 18 years were studied. Mean SAPS II was 45 +/- 16. Before the beginning of inhaled NO, PaO2/Fio2 ratio was 95 +/- 53 mm Hg and lung injury score 2.7 + 0.3. VarPao2/Fio2 when NO was started (11 +/- 4 ppm) was 26 +/- 44.5 mm Hg (median 17 mm Hg). Intensive care unit mortality was 74%. None of the parameters studied were predictors of response to inhaled NO, although there was a tendency for the youngest patients with the more severe hypoxemia to have a better response. Response to first inhaled NO test (VarPaO2/FiO2) was univariately associated with survival (Survivors: 45 +/- 44 mm Hg vs. Nonsurvivors: 20 +/- 43 mm Hg, P = .01), but this difference disappeared after adjusting for other prognostic factors (P = .16) selected by multivariate analysis. Finally, inhaled NO was continued for more than 1 day for 75 patients, and definitively stopped for 18 patients. Intensive care unit mortality (73% vs. 78%) was not different between these groups (P = .25, Log-rank test). CONCLUSIONS: We conclude that (1) efficacy of inhaled NO in improving oxygenation was moderate and difficult to predict, (2) response to first NO inhalation was not associated with prognosis, and (3) treatment of the most severe ARDS patients with inhaled NO did not influenced their intensive care unit survival.

Adult↗

Review article: travellers' diarrhoea.

In this review we will briefly consider the important aetiological agents and clinical expressions in travellers' diarrhoea, then we will review the prevention and therapy of the illness.

Diarrhea↗

Formation of complexes involving RasGAP and p190 RhoGAP during morphogenetic events of the gastrulation in xenopus.

In relation to the activation of the Src-family of tyrosine kinases during early morphogenetic events of gastrulation in Xenopus, we have identified two multiprotein complexes. The first complex, including RasGAP, p190 RhoGAP and p62, was previously characterized in murine fibroblasts overexpressing c-Src or transformed by v-Src and has been correlated with cytoskeleton remodelling. A second complex, not identified in other models includes tyrosine-phosphorylated p66SHC, Grb2, RasGAP and p190 RhoGAP. The association with p66SHC, considered as a negative regulator of ERK (extracellular signal-regulated kinase), p120RasGAP and p190RhoGAP, suggests a possible mechanism for coupling Ras and Rho signalling pathways. The interaction of RasGAP and p190 RhoGAP in two multiprotein complexes could constitute an additional level of Rho regulation during morphogenetic events of gastrulation.

Adaptor Proteins, Signal Transducing↗

Halothane and isoflurane increase spontaneous but reduce the N-methyl-D-aspartate-evoked dopamine release in rat striatal slices: evidence for direct presynaptic effects.

BACKGROUND: Experimental data suggest that volatile anesthetics induce significant changes in extracellular dopamine concentrations in the striatum, a restricted but functionally important brain area. In the present study, the authors used a superfused slice preparation to examine the effects of halothane and isoflurane on both spontaneous and N-methyl-D-aspartate (NMDA)-evoked dopamine release in the striatum, and whether these effects involved actions of these anesthetics mediated by gamma-aminobutyric acid receptors in this structure. METHODS: Radioactivity collected from 5-min fractions was compared in the absence (basal release) or presence (evoked release) of NMDA alone and combined with various pharmacologic or anesthetic agents in slices of the dorsolateral striatum and synaptosomes of the whole striatum preloaded with 3H-dopamine and superfused with artificial cerebrospinal fluid. RESULTS: In tetrodotoxin-treated striatal slices, halothane and isoflurane significantly increased dopamine basal release (EC50 = 0.33 mM and 0.41 mM for halothane and isoflurane, respectively). Both agents decreased the NMDA-evoked dopamine release in both the absence (IC50 = 0.15 mM and 0.14 mM for halothane and isoflurane, respectively) and presence (IC50 = 0.15 mM for both halothane and isoflurane) of tetrodotoxin in slices, and in synaptosomes (IC50 = 0.19 mM for both halothane and isoflurane). NMDA-induced dopamine release was significantly enhanced by bicuculline, a gamma-aminobutyric acid receptor antagonist. Halothane and isoflurane inhibitory effects on NMDA-evoked dopamine release were significantly reduced in the presence of bicuculline. CONCLUSION: These results indicate that halothane and isoflurane decrease the NMDA-evoked dopamine release by acting directly at dopamine terminals in striatal slices. They support the involvement of both depression of presynaptic NMDA receptor-mediated responses and enhancement of gamma-aminobutyric acid receptor-mediated responses in these effects.

Algorithms↗

[Early perioperative mortality in a multidisciplinary hospital].

OBJECTIVE: To evaluate the incidence and the causes of early intra- and postoperative deaths in a multidisciplinary hospital. STUDY DESIGN: Retrospective survey. PATIENTS: All patients receiving an anaesthetic between 1992 and 1995. METHODS: Analysis of all deaths occurring during anaesthesia and in the subsequent 24 hours. Demographic data (age, gender) and medical data (ASA physical class, type of surgery and degree of emergency) were recorded. The contribution of anaesthesia, surgery or patient disease to fatal outcome was analysed. RESULTS: The analysis included 52,654 patients who underwent either general anaesthesia or epidural analgesia. Perioperative mortality (n = 170) was 1/310 patients (0.32%). The risk factors for mortality (multivariate analysis) were: age > 64 years (odds-ratio [OR] 4.8), ASA class > or = 3 (OR 16.6), emergency surgery (OR 3.6), duration of surgery > 115 minutes (OR 37.4). Fifty percent of deaths (95% confidence interval [CI] = 42-58) were related to patient's underlying diseases and 29% to surgery (CI 95% = 22-36). The percentage of deaths linked to anaesthesia was 17.6% (CI 95% = 11.9-23.3, 1/1,755), consisting of 8.2% (CI 95% = 4.1-9.3, 1/3,761) totally due to anaesthesia and 9.4% (CI 95% = 5-13.8, 1/3,291) only partially. The main aetiologies of the deaths linked to anaesthesia were a mismanagement of severe haemorrhages (30%), respiratory complications (23%) or cardiac complications (23%). The mismanagement of an intraoperative critical situation (46%) and a mistake in the post-operative care (33%) were the main causes. DISCUSSION: In this survey, mortality due to anaesthesia was higher than the rates reported in other studies. Human error remained the main cause.

Adolescent↗

Disparate findings on the role of virulence factors of Enterococcus faecalis in mouse and rat models of peritonitis.

The role of Enterococcus faecalis in polymicrobial peritonitis is still debated. Virulence factors expressed in some enterococcal strains might be involved in the pathogenicity of these organisms. To clarify their role, three of these virulence factors (cytolysin, gelatinase, and aggregation substance) were studied in six isogenic strains of E. faecalis expressing various combinations of these factors. Since the pathogenic effects of enterococci are only moderate, the expression of their virulence might vary from one animal species to another and from one type of infection to another. Therefore, we evaluated these effects in two animal models, i.e., a systemic infection in mice in which we assessed the virulence of the strains in 50% lethal dose studies and a model of compartmentalized infection in rats in which the microbiologic and inflammatory effects of the strains were evaluated in monomicrobial or polymicrobial infection. In mice, significant differences were observed in the cumulative survival curves depending on the virulence factors (P < 0.0001 [log rank test]). In rats, monomicrobial infection induced only mild changes. In polymicrobial peritonitis, the virulence factors mainly increased the inflammatory response while the changes observed in the microbiologic response were minimal. The combination of two virulence factors did not significantly increase the severity of infection either in the mice model or the polymicrobial rat model. These data argue for species and model dependence of the role of the virulence factors studied here and suggest that other important factors may be involved in the pathogenicity of enterococci.

Animals↗

Leptospirosis: prognostic factors associated with mortality.

To determine the prognostic factors for leptospirosis, we conducted a retrospective study of data collected in the emergency department of our hospital between 1989 and 1993. Sixty-eight patients, for whom the diagnosis of leptospirosis was based on pertinent clinical and epidemiological data and positive serology, were included in this study. Fifty-six patients (82%) were discharged from the hospital, and 12 (18%) died. Multivariate logistic regression demonstrated that five factors were independently associated with mortality: dyspnea (odds ratio [OR], 11.7; 95% confidence interval [CI], 2.8-48.5; P < .05), oliguria (OR, 9; CI, 2.1-37.9; P < .05); white blood cell count, >12,900/mm3 (OR, 2.5; CI, 1.8-3.5; P < or = .01), repolarization abnormalities on electrocardiograms (OR, 5.9; CI, 1.4-24.8; P < or = .01), and alveolar infiltrates on chest radiographs (OR, 7.3; CI, 1.7-31.7; P < or = .01). Identification of these factors on admission might provide useful selection criteria for patients who need early transfer to the intensive care unit.

Adult↗

Screening of protein tyrosine kinases activated during neural induction in Xenopus.

We have screened Xenopus animal cap ectodermal cells during neural induction for protein kinases (PK) and protein tyrosine kinases (PTKs) after their renaturation in gels containing the polydispersed substrate poly(Glu, Tyr). Following guanidine hydrochloride denaturation, renaturation, and phosphorylation with [gamma-32P]ATP, kinase activity was detected by autoradiography. Incubation of gels in hot alkali after glutaraldehyde crosslinking completely eliminated the activity of non-PTK enzymes. This method is very sensitive and can be applied to development biology for the detection of PTKs in very small samples such as ectoderm explants dissected from animal caps in amphibian embryos. A large number of PTKs were visualized in uninduced and induced ectodermal cells. This procedure should be useful for investigating the role of PTKs in intracellular signaling during neural induction.

Animals↗

Fenofibrate: metabolism and species differences for peroxisome proliferation in cultured hepatocytes.

The hypolipidemic agent fenofibrate, which is a peroxisome proliferator in some rodents in vivo, was studied in cultured hepatocytes for its metabolism and effects on enzymatic induction related to peroxisome proliferation so as to lead to a better understanding of the mechanisms involved in peroxisome proliferation. [14C]-Fenofibrate was completely metabolized within 24 hr by primary cultures of rat hepatocytes and the metabolic pattern corresponded to that found in vivo. The main products were fenofibric acid and its glucuronidated form. Carbonyl reduction of fenofibric acid also occurred. The metabolic pattern of [14C]fenofibric acid was nearly the same as that of fenofibrate. Fenofibrate, fenofibric acid, and its reduced metabolite all induced peroxisomal (cyanide-insensitive) palmitoyl-CoA oxidation activity (PCOA) in rat hepatocytes, whereas derivatives lacking the carboxyl group were nearly inactive. The known species differences with respect to sensitivity to peroxisome proliferators in vivo was mirrored in cultured cells because fenofibric acid did not induce peroxisomal PCOA in primary culture of guinea pig hepatocytes nor in the human hepatoma cell line HepG2. The mechanistic association between the induction of CYP4A1-catalyzed lauric acid omega-hydroxylase (LAH) activity and peroxisomal PCOA induction was investigated. Fenofibric acid concomitantly induced LAH activity and peroxisomal PCOA in rat hepatocytes. Specific inhibition of LAH activity (-52%) by 10-undecynoic acid partially prevented induction of peroxisomal PCOA (-32%). The putative role of dicarboxylic acids, the oxidation product of omega-hydroxymonocarboxylic acids, in PCOA induction was further substantiated by the observed induction of peroxisomal PCOA by 1-12-dodecanedioic acid. We conclude that (1) fenofibric acid is the possible proximate peroxisome proliferator of fenofibrate in rat hepatocytes, (2) cultured hepatocytes reflect in vivo sensitivity to fenofibrate with respect to peroxisome proliferation, and (3) there is some evidence that the catalytic activity of the CYP4A1 enzyme mediates, at least in part, peroxisomal PCOA induction.

Animals↗

Pineal body metastasis.

We present a rare case of a pineal body metastasis developed from an oat cell carcinoma of the lung. Diagnosis by CT brain scan was easy but could have been difficult if the metastasis was solitary with the primary focus of tumor unknown. This lesion was temporarily radiosensitive but non-responsive to cytotoxic drugs and the patient died after other metastases developed.

Brain Neoplasms↗