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Biomedical subjects

M Carles

Publications and source records attributed to M Carles.

At least 19 recordsLinked to original sources
PubMed2002

[Motives for the prescription of antibiotics in the emergency department of the University Hospital Center in Nice. A prospective study].

OBJECTIVES: Since April 1999, we have set-up an infectious disease consultation in the emergency unit of the University Hospital in Nice. Unjustified antiobiotherapy is often initiated. We therefore conducted a survey to study the motives and validity of antibiotic prescriptions. METHOD: This prospective study was conducted in two phases. The first consisted in asking the emergency physicians prescribing antibiotics to fill-in a questionnaire giving information on the diagnosis established and the antiobiotherapy proposed. In the second phase, the diagnoses and corresponding treatments were submitted to 4 experts who assessed the acceptability of the diagnoses and the antibiotics prescribed. The experts only had access to the clinical and para-clinical data available. Moreover, their therapeutic judgement was based on previously published consensuses. RESULTS: The 6-month survey collected 117 questionnaires that could be analysed. The rate of error in diagnosis was of 33% (39/117). Thoracic x-rays could not be interpreted in 11% of cases. In single variant analysis, factors of erroneous diagnosis were due to its interpretation by an internist, the diagnostic category of "broncho-pulmonary infections" and the lack of documentation. In multi variant analysis, only the lack of documentation was related to erroneous diagnosis (OR = 5.5; IC 95% (2.03; 15.30), p < 0.0002). The rate of antibiotherapy not adapted to the diagnosis made by the physician was of 32% (37/117). In 24 cases the modalities of the prescription were incorrect and in 13 cases the prescription was unjustified. Only the status of the prescriber (internist) was statistically associated with an antibiotherapy not adapted to the diagnosis (OR = 2.2; IC 95% (0.93; 5.26), p < 0.05). CONCLUSION: Unjustified antibiotherapy in an emergency unit is generally due to erroneous diagnosis of infection. The lack of documentation and inexperience of the prescribers appear to be the two elements contributing to unjustified antibiotherapy.

Anti-Bacterial Agents↗
PubMed2001

Chips and Qi: microcomponent-based analysis in traditional Chinese medicine.

Over the last 50 years or so Traditional Chinese medicine (TCM) has been subject to intensive basic and clinical research. Although the effectiveness and remarkable safety of TCM have been documented after controlled clinical studies, there are several herbal and animal parts that are toxic or difficult to identify. DNA polymorphism-based assays have recently been developed for the identification of herbal medicines. In this approach, small amounts of DNA are amplified by the polymerase chain reaction and the reactions products are analyzed by gel electrophoresis, sequencing, or hybridization with species-specific probes. With the DNA based identification of TCM materials as an example, chip-based analytical micro devices were developed with the goal of fabricating an integrated device that will enable sample preparation, amplification, and analysis on a single microchip-based device ("lab-on-a-chip"). The application of a silicon-based polymerase chain reaction microreactor and a DNA microarray for the DNA sequence-based identification of toxic medicinal plants is reported here.

DNA, Plant↗
PubMed2001

An evaluation of the brachial plexus block at the humeral canal using a neurostimulator (1417 patients): the efficacy, safety, and predictive criteria of failure.

UNLABELLED: To evaluate the efficacy and safety of the multiple peripheral nerve block technique at the humeral canal (humeral block) with the use of a neurostimulator, we prospectively studied 1417 patients undergoing upper limb surgery with a brachial plexus block at the humeral canal (1468 blocks). The success rate (defined as sensory block [in all nerve distributions] and/or the absence of another anesthetic technique required to allow surgery) was 95%. The threshold of minimal stimulation used to locate each nerve before injecting the anesthetic solution was the unique predictive factor for identified failure. For the median nerve, the threshold was 0.8 mA with a relative risk of failure (RRf: relative risk evaluated by series of Taylor with a 95% confidence interval) = 1.49 (P = 0.04), for the radial nerve the threshold was 0.6 mA (RRf 1.3, P = 0.02), and 0.7 mA for the ulnar nerve (RRf 1.36, P = 0.04). For any equal or higher stimulation level, the risk of failure of the humeral block increased. For the musculocutaneous nerve, we did not observe a significant stimulation threshold for the risk of failure; although beyond 0.7 mA, the RRf was always more than 1.3. Adverse events occurred in 7% of all cases and were usually minor (nausea/vomiting, anxiety, local pain). Our study provides supplementary information on the efficacy and safety of this technique. Stimulation thresholds are clinically identified for the first time as the main factor linked to the failure of a technique using a neurostimulator. We conclude that the humeral block is a reliable peripheral block allowing good success rates results with minor complications, which can be used as an alternative to the axillary block. IMPLICATIONS: We prospectively evaluated the feasibility and the factors causing failure of a peripheral nerve block technique (humeral block) using neurostimulation in a large number of patients. The importance of the level of stimulation for the success of the block was evaluated for the first time.

Adolescent↗
PubMed2000

Comparison of the renal effects of low to high doses of dopamine and dobutamine in critically ill patients: a single-blind randomized study.

OBJECTIVE: The renal effects of dopamine in critically ill patients remain controversial. Low-dose dobutamine has been reported to improve renal function. We compared the effects of various doses of dopamine and dobutamine on renal function in critically ill patients. DESIGN: Prospective, single-blind, randomized study. SETTING: University hospital, 19-bed multidisciplinary intensive care unit. PATIENTS: Twelve hemodynamically stable patients with mild nonoliguric renal impairment. INTERVENTIONS: Each patient randomly received four different doses of dopamine and dobutamine (placebo, 3, 7, and 12 microg/kg/min). Each infusion lasted for 4 hrs. Cardiac output and systemic hemodynamic variables were measured using a pulmonary arterial catheter at the beginning (HO) and the end (H4) of each infusion. The bladder was emptied at HO and H4 to determine urine volume and to collect samples. MEASUREMENTS AND MAIN RESULTS: The cardiac index increased significantly with both dopamine and dobutamine (p < .001). Mean arterial pressure (MAP) increased, with the maximum effect of 20% seen with 12-microg/kg/min dopamine infusion (p < .01). No change in MAP was seen with dobutamine. Dobutamine infusions did not change any renal variables. Conversely, all dopamine infusions significantly increased diuresis, creatinine clearance, and the fractional excretion of sodium (p < .01). Creatinine clearance increased from 61+/-16.9 (SD) mL/min to a maximum of 85.7+/-30 mL/min at the 7-microg/kg/min dose; fractional excretion of sodium increased from 0.26%+/-0.28% to a maximum of 0.62%+/-0.51% at the 12-microg/kg/min dose (p < .01). During dopamine infusions, there was a significant relationship between MAP and creatinine clearance (p = .018). CONCLUSIONS: At all doses studied, 4-hr infusions of dopamine significantly increased creatinine clearance, diuresis, and the fractional excretion of sodium in stable critically ill patients. Conversely, dobutamine did not modify these variables. Although the level of MAP might partially contribute to the improvement in renal variables, it is more likely that the activation of renal dopamine receptors played a prominent role.

Adrenergic beta-Agonists↗
PubMed2000

Prolonged low-dose dopamine infusion induces a transient improvement in renal function in hemodynamically stable, critically ill patients: a single-blind, prospective, controlled study.

OBJECTIVE: To evaluate the length of the effects of long-term (48 hrs), low-dose dopamine infusion on both renal function and systemic hemodynamic variables in stable nonoliguric critically ill patients. DESIGN: Prospective, single-blind, controlled clinical study. SETTING: University hospital, 19-bed multidisciplinary intensive care unit. PATIENTS: Eight hemodynamically stable, critically ill patients with a mild nonoliguric renal impairment (creatinine clearance between 30 and 80 mL/min). INTERVENTIONS: Each patient consecutively received 4 hrs of placebo, followed by a 3 microg/kg/min dopamine infusion during 48 hrs, then a new 4-hr placebo period. We measured cardiac output and other hemodynamic variables by using a pulmonary artery catheter. The bladder was emptied to determine urine volume and to collect urine samples. Measurements were performed at six times: after the initial control of 4 hrs of placebo (C1); after 4 hrs (H4), 8 hrs (H8), 24 hrs (H24), and 48 hrs (H48) of dopamine infusion; and after the second control of 4 hrs of placebo (C2). MEASUREMENTS AND MAIN RESULTS: We saw no significant change in systemic hemodynamic variables with dopamine at all times of infusion. Diuresis, creatinine clearance, and the fractional excretion of sodium (FENa) at C1 and C2 were not different. Urine flow, creatinine clearance, and FENa increased significantly 4 hrs after starting dopamine (for all these changes, p < .01 vs. C1 and C2). The maximum changes were obtained at H8, with an increase of 50% for diuresis, 37% for creatinine clearance, and 85% for FENa (for all these changes, p < .01 vs. C1 and C2). But these effects waned progressively from H24, and both creatinine clearance and FENa at H48 did not differ from control values. CONCLUSIONS: In stable critically ill patients, preventive low-dose dopamine increased creatinine clearance, diuresis, and the fractional excretion of sodium without concomitant hemodynamic change. These effects reached a maximum during 8 hrs of dopamine infusion. But despite a slight persistent increase in diuresis, improvement in creatinine clearance and FENa disappeared after 48 hrs. According to these data, it is likely that tolerance develops to dopamine-receptor agonists in critically ill patients at risk of developing acute renal failure.

APACHE↗
PubMed1999

Efficacy and safety of an intravenous induction therapy for treatment of disseminated Mycobacterium avium complex infection in AIDS patients: a pilot study.

Monotherapy with macrolides for the treatment of disseminated Mycobacterium avium complex (MAC) bacteraemia leads to drug resistance and relapse of bacteraemia. Gastrointestinal intolerance is a common reason for treatment withdrawal of multidrug regimens. We have assessed the efficacy and safety of initial parenteral therapy together with a macrolide, for disseminated MAC infection, defined as two positive blood cultures, in AIDS patients. Patients received a daily infusion of amikacin 15 mg/kg + ethambutol 20 mg/kg + ciprofloxacin 400 mg/day, for 1 month, together with a macrolide by oral route. Fifteen patients were included and 13 (86%) achieved negative culture before the end of parenteral therapy.

AIDS-Related Opportunistic Infections↗
PubMed1998

Synergistic activation of the N-methyl-D-aspartate receptor subunit 1 promoter by myocyte enhancer factor 2C and Sp1.

The N-methyl-D-aspartate (NMDA) subtype of glutamate receptor plays important roles in neuronal development, plasticity, and cell death. NMDA receptor subunit 1 (NR1) is an essential subunit of the NMDA receptor and is developmentally expressed in postnatal neurons of the central nervous system. Here we identify on the NR1 promoter a binding site for myocyte enhancer factor 2C (MEF2C), a developmentally expressed neuron/muscle transcription factor found in cerebrocortical neurons, and study its regulation of the NR1 gene. Co-expression of MEF2C and Sp1 cDNAs in primary neurons or cell lines synergistically activates the NR1 promoter. Disruption of the MEF2 site or the MEF2C DNA binding domain moderately reduces this synergism. Mutation of the Sp1 sites or the activation domains of Sp1 protein strongly reduces the synergism. Results of yeast two-hybrid and co-immunoprecipitation experiments reveal a physical interaction between MEF2C and Sp1 proteins. The MEF2C DNA binding domain is sufficient for this interaction. Dominant-negative MEF2C interferes with expression of NR1 mRNA in neuronally differentiated P19 cells. Growth factors, including epidermal growth factor and basic fibroblast growth factor, can up-regulate NR1 promoter activity in stably transfected PC12 cells, even in the absence of the MEF2 site, but the Sp1 sites are necessary for this growth factor regulation, suggesting that Sp1 sites may mediate these effects.

Binding Sites↗
PubMed1998

Mild hyperlactatemia in stable septic patients is due to impaired lactate clearance rather than overproduction.

A prospective study was conducted on 34 stable septic patients to determine whether mild hyperlactatemia is a marker of lactate overproduction or an indicator of lactate underutilization during sepsis. Plasma lactate clearance and lactate production were evaluated by modeling the lactate kinetic induced by an infusion of 1 mmol/kg L-lactate over 15 min. The patients were divided in two groups depending on their blood lactate: < or = 1.5 mmol/L (n = 20, lactate = 1.2+/-0.2 mmol/L) or > or = 2 mmol/L (n = 10, lactate = 2.6+/-0.6 mmol/L). The hyperlactatemic patients had a lower lactate clearance (473+/-102 ml/kg/h) than those with normal blood lactate (1,002+/-284 ml/kg/h, p < 0.001), whereas lactate production in the two groups was similar (1,194+/-230 and 1,181+/-325 micromol/kg/h, p = 0.90). A second analysis including all the patients confirmed that the blood lactate concentration was closely linked to the reciprocal of lactate clearance (r2 = 0.73, p < 0.001) but not to lactate production (r2 = 0.03, p = 0.29). We conclude that a mild hyperlactatemia occurring in a stable septic patient is mainly due to a defect in lactate utilization.

Adult↗
PubMed1997

Animal models of cardiovascular disease for pharmacologic drug development and testing: appropriateness of comparison to the human disease state and pharmacotherapeutics.

For proper drug development, targeting and testing the use of suitable animal models that are well controlled with regard to duration, degree, and stage of the disease are vitally needed. Furthermore reliable phenotyping and genotyping with regard to functional physiology as well as cellular biochemistry and molecular biology are vital to early decision making in drug discovery, development, and successful clinical development. The use of animal models allows the design of clinical trials without the complication of having to impose "accepted treatment modalities" on top of investigative agents. With the availability of human myocardium for study as a result of cardiac transplantation programs, experimental findings previously reported in several animal models of heart disease have been questioned with regard to suitability for comparison to the human condition. With the development and application of sophisticated techniques and biochemical assays to the study of heart tissue several adaptive changes have been identified and labeled "markers of heart failure." Several animal models share some of these adaptive changes in common with failing human myocardium, but not others. The goal of this report is to point out similarities and differences reported to date in failing and nonfailing human myocardium to that reported in animal models of human heart disease. This discussion indicates important dissimilarities found in several key animal models that have resulted in the development of cardioactive agents and therapeutic interventions for the treatment of human heart disease and the unexpected outcomes. Although focusing on heart failure, a vital goal of this report is to emphasize some key principles supporting the need for clear, comprehensive, and unbiased evaluation of animal models currently in use to study any disease condition, as well as the need for further model development and study in open collaborative efforts.

Animals↗
PubMed1996

[Comparative profitability of hepatic biopsy and microbiological tests in patients with HIV infection].

OBJECTIVES: Diagnostic liver biopsy is proposed in HIV-positive patients who present unexplained fever. This invasive procedure is truly useful if it allows establishing a difficult diagnosis or improves survival rate. We conducted a retrospective study to determine the diagnostic and prognostic power of liver biopsy in HIV-positive patients with fever. METHODS: One hundred thirty-eight liver biopsies were performed in 129 patients. Utility was defined as demonstration of the pathogen or identification of a tumoral process. RESULTS: The liver biopsy met the utility criteria in 27 cases showing mycobacterial infections (n = 22) and herpes hepatitis, type 1 herpes simplex virus, cytomegalovirus and cryptococcosis infections (n = 1 each). These last 4 diagnoses were also possible with other tests. Comparing non-contributive liver biopsies (n = 111) with those demonstrating hepatic mycobacterial infection (n = 22) showed that the two groups were not different in terms of demographic data. Splenomegalia was more frequent in the non-contributive group (68% vs 37%, p = 0.007) as was superficial lymph node enlargement (45% vs 12%, p < 10(-3)). Laboratory tests were not discriminating. Mycobacterial infection was diagnosed in 22 patients in the non-contributive group. Bacteriological samples were positive for mycobacterium in 20 of the 22 patients in the contributive group. The mean delay to the first positive test for mycobacterium was 15 +/- 8 days compared with 30 +/- 10 days for liver tissue cultures. Mean survival after liver biopsy was 10 months: patients with a positive Ziehl-Neelson stain on the liver biopsy did not have a longer survival (9.7 +/- 7.6 vs 10.2 +/- 10.4 months). CONCLUSION: In most cases, liver biopsy in HIV-positive patients with fever provides a diagnosis which can be obtained with non-invasive techniques without improving prognosis.

AIDS-Related Opportunistic Infections↗
PubMed1996

Liver biopsy is not useful in the diagnosis of mycobacterial infections in patients who are infected with human immunodeficiency virus.

Liver biopsy (LB) has been advocated for the detection of mycobacterial infections in patients infected with human immunodeficiency virus (HIV). To determine the effect of the use of this procedure on survival, we compared it terms of yield with histological findings and noninvasive microbiological procedures. We reviewed the cases of 98 patients who underwent 106 LBs as part of the diagnostic screening for fever of unknown origin. LB revealed 17 cases of mycobacterial infection. For all but one patient, the results of at least one noninvasive procedure were positive. In 85 cases where infections were not diagnosed by LB, 17 had infections documented by other procedures. When all culture results are considered, the mean (+/- SD) incubation time to the first positive culture was 15 +/- 5 days, whereas the mean (+/- SD) incubation time to the first positive culture of an LB specimen was 28 +/- 9 days. The survival time was not significantly increased for patients who underwent LB and had positive Ziehl-Neelsen-stained smears; these patients survived a mean (+/- SD) of 12 +/- 11 months, whereas patients with negative smears survived a mean (+/- SD) of 9 +/- 10 months. Noninvasive studies are preferable to LB for the diagnosis of mycobacterial infections in HIV-infected patients.

AIDS-Related Opportunistic Infections↗
PubMed1996

Dilated cardiomyopathy in turkeys: an animal model for the study of human heart failure.

Many animal models of heart failure developed to date do not mimic pathophysiologic changes recently described in the failing human myocardium. In human endstage heart failure, abnormalities in morphology, electromechanical coupling, and myocardial energetics have been described. However, studies of human myocardium are limited by lack of appropriate controls, the fact that all patients have endstage heart failure, and exposure of patients to different therapeutic regimens. In contrast to many animal models, the myopathic turkey heart (i.e., idiopathic dilated cardiomyopathy or furazolidone-induced cardiomyopathy) is similar to the myopathic human heart in terms of gross morphology, myocardial energetics, muscle physiology myofilament properties, Ca2+ metabolism, and the beta-receptor-adenylyl cyclase signaling system.

Actin Cytoskeleton↗
PubMed1995

[Persistent diarrhea in HIV infected patients: role of Enterocytozoon bieneusi].

OBJECTIVES: To determine the epidemiologic, clinical and aetiologic features of chronic diarrhoea in patients with human immunodeficiency virus (HIV) infection. METHODS: Between January 1992 and April 1993, all HIV positive patients with chronic diarrhoea were enrolled in a prospective study. There were 46 patients in the study group including 33 (22 homosexuals) in stage C according to the 1993 Centers for Disease Control classification. RESULTS: Thirty-four pathogenic agents were isolated in 26 of the patients (57%). Enterocytozoon bieneusi was the most frequently found pathogen (11 patients, 24%) followed by Cryptosporidium sp (8 patients). Enterocytozoon bieneusi was found in association with other pathogens in 7 patients. All patients with microsporidiosis were in stage C (p = 0.04) and had a longer duration of diarrhoea (19.6 vs 9.8 weeks, p = 0.03), greater weight loss (9.6 vs 2.1 kg, p = 0.0003) and a lower Karnofsky index (48% vs 67%, p = 0.01). Prophylaxy with dapsone or pyrimethamine during the 3 months prior to inclusion had been more frequent (p = 0.04 and p = 0.05 respectively) in patients without microsporidiosis. CONCLUSION: Microsporidiosis should be suspected as a probable cause of chronic diarrhoea in HIV positive patients with a CD4 count < 100/mm3. Multiple infections may be a factor leading to treatment failure. Microsporidiosis seems to be linked to homosexual intercourse.

AIDS-Related Opportunistic Infections↗
PubMed1995

Prevention of Pneumocystis carinii pneumonia and of cerebral toxoplasmosis by roxithromycin in HIV-infected patients.

The prevention of cerebral toxoplasmosis and of Pneumocystis carinii pneumonia is an essential objective in the management of patients infected with HIV. Given that roxithromycin is active in vitro against Toxoplasma gondii and that in 1989 Dolermann reported the effective treatment of P. carinii respiratory infections with erythromycin, a randomized pilot study was undertaken in 52 patients infected with HIV. Patients were treated with either: a monthly dose of pentamidine aerosol (300 mg); roxithromycin once a week (300 mg t.i.d.); or a combination of pentamidine aerosol and roxithromycin. Intention to treat analysis was applied to these 52 patients, all of whom received at least one treatment dose. Five out of 18 patients treated with pentamidine aerosol, 1/17 patients treated with pentamidine aerosol + roxithromycin and none of the 17 patients treated with roxithromycin developed cerebral toxoplasmosis (p = 0.038). P. carinii pneumonia was diagnosed in one patient in the pentamidine aerosol-treated group, in one patient treated with roxithromycin and in none of the patients treated with pentamidine aerosol + roxithromycin (non-significant difference). Four cases of Mycobacterium tuberculosis and Mycobacterium avium-intracellulare infection were seen in the pentamidine aerosol-treated group (p = 0.028) and none in the roxithromycin groups. Adverse events leading to the discontinuation of treatment occurred in 5/34 (14.7%) patients treated with roxithromycin. Nausea, abdominal pain and raised transaminases occurred in four patients and a skin allergy in the final patient. Roxithromycin appears to be effective in the prevention of pulmonary pneumocystis infection and of cerebral toxoplasmosis in HIV-infected patients. However, these results require confirmation in a larger study.

AIDS-Related Opportunistic Infections↗