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Biomedical subjects

G Potel

Publications and source records attributed to G Potel.

At least 37 records · Page 2Linked to original sources
PubMed1999

Prognostic factors in acute cardiogenic pulmonary edema.

The purpose of this study was to determine the clinical and biological findings at admission in the Department of Emergency Medicine associated with a poor prognosis, and to evaluate early response to treatment as a prognostic factor. It was a prospective cohort study with a 5-month follow-up. One hundred eighty-six patients admitted for acute cardiogenic pulmonary edema were included. Features were analyzed at the admission and on response to initial treatment. The main outcome measure was survival at 2 end-points: hospital discharge, and 5 months of follow-up. Multivariate analysis showed that in-hospital mortality was associated with marbleization (mottling) odd-ratio (OR) = 9.0), low diuresis (OR = 4.0), high breath rate 6 hours after admission (OR = 4.0), and chronic digoxin use (OR = 3.39). Five-month mortality was associated with a bedridden state (OR = 9.0), marbleization (mottling) (OR = 5.5), myocardial infarction (OR = 3), and poor early response to initial treatment (OR = 3.2). In addition to well-known factors, the response to initial treatment evaluated 6 hours after admission was a major determinant of outcome.

Acute Disease↗
PubMed1999

[Treatment of venous thromboembolic disease in the elderly].

The incidence of deep vein thrombosis and pulmonary embolism is higher in the elderly due to the greater frequency of risk factors among this age group. Classic treatment with heparin and subsequently oral anticoagulant is still the most commonly used. Older patients may be at increased risk for anticoagulant-related bleeding for several reasons: increased anticoagulant effect of warfarin, increased prevalence of comorbidity and incidence of adverse drug reactions. As well as the usual contra-indications to such treatment, the psychological and physical well being of the patient must be assumed before an oral anticoagulant can be given. Careful prescribing is required: a low starting dose, a strict monitoring regime, for a limited duration. The indications for use of an inferior vena cava filter are wider in the older age group, not only for those in whom heparin is contraindicated, or has failed, but also for those who require treatment indefinitely with contra-indications to oral anticoagulant. Careful consideration of risk factors and the use of an individually designed prophylactic treatment are the best way to tackle this difficult problem in the elderly person.

Aged↗
PubMed1999

[IgA deficiency and multiple Staphylococcus aureus perirenal abscesses. A case report].

The authors report the case of a patient with IgA deficiency who presented with a low-grade renal abscess. Due to the atypical nature of the clinical features and imaging, the diagnosis was not established prior to surgery. Despite radical surgery, the abscess recurred several weeks later. In the light of this case, the authors discuss the various possible diagnoses that must be considered in the presence of these types of images and the therapeutic approach during initial management. They discuss the various immune deficiencies to be investigated in a particular infectious context.

Abscess↗
PubMed1998

In vivo simulation of human pharmacokinetics in the rabbit.

The evaluation of drugs in vivo is often based on experimental models using small animals such as mice, rats and rabbits. However, these models could be improved to correspond more closely to the human situation if the pharmacokinetics of the drugs tested in animals were similar to that observed in humans. The use of a computer-controlled pump allowing an adequate flow of tobramycin and amikacin to be infused into rabbits enabled us to simulate the human pharmacokinetics of these antibiotics in vivo in this study. The function defining the rate of infusion required to perform the simulation of an intravenous bolus was first determined generally and symbolically for linear pharmacokinetic models independently from the number of compartments involved. The practical simulation of a decreasing monoexponential serum profile with a half-life of 2 h (one-compartment model for the human pharmacokinetics of aminoglycosides) was then studied for tobramycin and amikacin on the basis of a two-compartment model in the animal. The kinetics obtained had an apparent elimination half-life of 1.97 and 1.86 h, respectively. Linearity of the semilogarithmic regressions of the profiles obtained was quite sound. Finally, an a posteriori analysis of the pharmacokinetic model and its parameters is proposed on the basis of the results obtained after simulation.

Amikacin↗
PubMed1998

Comparative study of methods of measuring acute pain intensity in an ED.

The best one-dimensional method for routine self-assessment of acute pain intensity in a hospital emergency department is unknown. In this study, an 11-point numerical rating scale (NRS), a simple verbal rating scale describing five pain states (VRS), and a visual analogue scale (VAS) were presented successively on admission to 290 patients with acute pain (200 with and 90 without trauma). VAS and NRS were closely correlated for both traumatic (r = .795) and nontraumatic pain (r = .911). The VAS could not be used with 19.5% of patients with trauma and the VRS with 11% of patients without trauma, whereas the NRS could be used with 96% of all patients. The NRS proved more reliable for patients with trauma, giving equivalent results to those with the VAS for patients without trauma. These two scales showed better discriminant power for all patients. Thus, the NRS would appear to be the means for self-evaluation of acute pain intensity in an emergency department.

Acute Disease↗
PubMed1997

Bactericidal effect of pefloxacin and fosfomycin against Pseudomonas aeruginosa in a rabbit endocarditis model with pharmacokinetics of pefloxacin in humans simulated in vivo.

The bactericidal activity of pefloxacin and fosfomycin alone and in combination against Pseudomonas aeruginosa was evaluated in an experimental rabbit endocarditis model after 24 h of treatment. Two strains with intermediate susceptibility to pefloxacin and good susceptibility to fosfomycin were tested. The serum kinetics obtained during administration of 400 mg every 12 h in humans were simulated in the animals using computer-controlled variable-flow infusion. Fosfomycin was administered as a continuous infusion at a constant flow, allowing a steady-state concentration of 47.4 +/- 11.9 mg/ml to be reached in serum. In valvular vegetations, pefloxacin was less bactericidal than fosfomycin, and in combination treatment, it reduced (but did not abolish) the bactericidal effect of fosfomycin. The duration of the pretreatment interval (12-48 h) had a negative effect on the bactericidal activity of both drugs, especially that of fosfomycin.

Animals↗
PubMed1997

Adaptive resistance of Pseudomonas aeruginosa induced by aminoglycosides and killing kinetics in a rabbit endocarditis model.

Adaptive resistance following the first exposure to aminoglycosides is a recently described in vitro phenomenon in Pseudomonas aeruginosa and other aerobic gram-negative bacilli. We investigated the in vivo relevance of adaptive resistance in P. aeruginosa following a single dose of amikacin in the experimental rabbit endocarditis model. Rabbits with P. aeruginosa endocarditis received either no therapy (control) or a single intravenous (i.v.) dose of amikacin (80 mg/kg of body weight) at 24 h postinfection, after which they were sacrificed at 5, 8, 12, 16, or 24 h postdose. Excised aortic vegetations were subsequently exposed ex vivo to amikacin at 2.5, 5, 10 or 20 times the MIC for 90 min. In vivo adaptive resistance was identified when amikacin-induced pseudomonal killing within excised aortic vegetations was less in animals receiving single-dose amikacin in vivo than in vegetations from control animals not receiving amikacin in vivo. Maximal adaptive resistance occurred between 8 and 16 h after the in vivo amikacin dose, with complete refractoriness to ex vivo killing by amikacin seen at 12 h postdose. By 24 h postdose, bacteria within excised vegetations had partially recovered their initial amikacin susceptibility. In a parallel treatment study, we demonstrated that amikacin given once daily (but not twice daily) at a total dose of 80 mg/kg i.v. for 1-day treatment significantly reduced pseudomonal densities within aortic vegetations versus those in untreated controls. When therapy was continued for 3 days with the same total daily dose (80 mg/kg/day), amikacin given once or twice daily significantly reduced intravegetation pseudomonal densities versus those in controls. However, amikacin given once daily was still more effective than the twice-daily regimen. These data confirm the induction of aminoglycoside adaptive resistance in vivo and further support the advantages of once-daily aminoglycoside dosing regimens in the treatment of serious pseudomonal infections.

Amikacin↗
PubMed1997

[Mesenteric venous thrombosis and antithrombin III deficiency: diagnosis before an acute digestive hemorrhage].

Mesenteric venous thromboses are often associated with antithrombin III deficiency. We can suspect this clinical diagnosis in patients with nonspecific abdominal pain syndrome and personal or familial history of mesenteric venous thrombosis. We report the case of a 63-old-male caucasian with antithrombin III deficiency and rectal bleeding who was diagnosed with mesenteric venous thrombosis at exploratory laparotomy. This case emphasizes the necessity of a careful history in all patients without an obvious diagnosis. In this way, we can invoke the diagnosis of mesenteric venous thrombosis quickly and begin the heparin therapy while waiting for the results of further confirmatory tests.

Antithrombin III Deficiency↗
PubMed1996

The effect of rifampicin on adaptive resistance of Pseudomonas aeruginosa to aminoglycosides.

Using the dynamic chequerboard technique, we confirmed that rifampicin produces a synergistic bactericidal effect when combined with amikacin or netilmicin. Adaptive resistance was suppressed when rifampicin was added to aminoglycoside after, but not during, first exposure to amikacin or netilmicin. The effect of rifampicin on adaptive resistance could account for the synergy between rifampicin and aminoglycosides.

Adaptation, Physiological↗
PubMed1996

Influence of pH on adaptive resistance of Pseudomonas aeruginosa to aminoglycosides and their postantibiotic effects.

Adaptive resistance to aminoglycosides in Pseudomonas aeruginosa and other gram-negative bacilli is usually induced by the initial exposure to the drug. We investigated the influence of pH on the adaptive resistance of a clinical P. aeruginosa strain to aminoglycosides in vitro and on their postantibiotic effects. For adaptive resistance, the first-exposure concentrations of both amikacin and netilmicin were one, two, four, and eight times the MIC of each drug and the second-exposure concentrations were two times the MIC of each drug. Adaptive resistance was greater and more prolonged with higher initial aminoglycoside concentrations, and the bactericidal effects of the aminoglycosides were concentration dependent at pH 7.4. At pH 6.5, the killing rates of amikacin and netilmicin were far lower than those observed at pH 7.4. At pH 5.5, amikacin and netilmicin exerted practically no bactericidal effect on the P. aeruginosa strain used. However, with media at pH 5.5 and 6.5, adaptive resistance of P. aeruginosa preexposed to amikacin and netilmicin was also clearly exhibited, with the degree of adaptive resistance depending on the bactericidal effects of both drugs on nonpreexposed controls. Maximal adaptive resistance occurred between 0 and 4 h after preexposure. The postantibiotic effects of amikacin and netilmicin against the P. aeruginosa strain were shown to be concentration dependent and were reduced at acidic pHs. No changes in outer and inner membrane proteins occurred during the adaptive-resistance interval.

Adaptation, Physiological↗
PubMed1996

In vivo antibacterial effects of simulated human serum profiles of once-daily versus thrice-daily dosing of amikacin in a Serratia marcescens endocarditis experimental model.

Once-daily dosage of aminoglycosides is currently under consideration. The lower toxicity of this regimen has been clearly established, but there are conflicting experimental and clinical data concerning its efficacy. It is inadvisable to optimize human therapy by extrapolation from experimental studies since animal and human pharmacokinetics differ. The simulation of human pharmacokinetics in experimental infectious models would seem to offer a more rational approach. We used computer-controlled infusion of amikacin at a variable flow rate to simulate human pharmacokinetics in a Serratia marcescens rabbit endocarditis model and to compare two therapeutic regimens (once-daily versus thrice-daily doses). The doses corresponded to simulations of 15 and 30 mg/kg of body weight per day in humans, and antibacterial activity was measured in vegetations (Veg) after 24 h of treatment. The results show that the dose corresponding to 15 mg/kg/day failed to produce a significant reduction of CFU (6.8 +/- 0.9 and 6.4 +/- 0.8 log10 CFU/g of Veg, respectively, for once-daily and thrice-daily doses versus 7.6 +/- 1.0 for controls). A significant reduction was observed only for the dose corresponding to 30 mg/kg/day in humans (5.2 +/- 1.5 and 5.4 +/- 1.1 log10 CFU/g of Veg, respectively, for the two regimens). With this model, the efficacy of amikacin was similar for both regimens after 24 h of treatment simulating human pharmacokinetics.

Amikacin↗
PubMed1995

[Critical serum concentration of antibiotics. A therapeutic tool and means of comparative evaluation].

It is difficult to predict the clinical activity of antibiotics solely on the basis of in vitro data. Experimental models measuring the relationship between serum concentration and in vivo activity are essential for comparing the activity of different compounds currently available. The critical serum concentration can be used to compare the intrinsic activity of antibiotics on a given bacterial strain. When compared with the minimal inhibiting concentration measured in vitro, "activity loss" can be determined for each antibiotic placed in contact with bacteria in an infected tissue. The relevance of this therapeutic tool in comparison with other methods is discussed.

Animals↗
PubMed1995

Comparative efficacies of ciprofloxacin and pefloxacin alone or in combination with fosfomycin in experimental endocarditis induced by multidrug-susceptible and -resistant Pseudomonas aeruginosa.

The in vivo efficacy of ciprofloxacin or pefloxacin alone or in combination with fosfomycin was evaluated in experimental aortic valve endocarditis induced in 133 rabbits by a multidrug-susceptible or multidrug-resistant strain of Pseudomonas aeruginosa. Therapy was initiated early (12 h after infection), when bacterial counts in aortic valve vegetations were relatively low, or late (48 h after infection), when vegetations contained a larger inoculum. Antibodies were administered as a continuous 24-h intravenous infusion. Mean steady-state levels of ciprofloxacin (64 mg/kg), pefloxacin (64 mg/kg), and fosfomycin (300 mg/kg) in serum were 2.5, 4.2, and 63.9 mg/liter, respectively. For the multidrug-susceptible strain, all regimens except pefloxacin alone significantly reduced the number of CFU per gram of vegetation versus controls, whether treatment was performed early or late. For the multidrug-resistant strain, none of the regimens showed differences from untreated controls, except ciprofloxacin-fosfomycin, which significantly reduced bacterial counts in vegetations compared with controls when therapy was begun early (4.1 +/- 1.1 log10 CFU/g of vegetation; P < 0.001 versus the control). These data suggest that combination of fosfomycin with ciprofloxacin or pefloxacin is more effective than ciprofloxacin or pefloxacin alone for the therapy of severe infections caused by multidrug-susceptible P. aeruginosa.

Animals↗
PubMed1994

Teaching individualized antibiotic dosage regimens by means of two computer-assisted learning programs.

We developed two multidisciplinary tutorial programs (TOBRA-DIDACT and VANCO-DIDACT) for teaching the basic principles of antibiotic drug monitoring by simulation of repeated administrations to fictitious patients whose physio-pathologic characteristics were pre-defined in the programs. To illustrate the two types of bactericidal kinetics, we have chosen one time-dependent (vancomycin) and one concentration-dependent (tobramycin) antibiotic. These computer-assisted programs operate on an interactive mode. In each of them, three main steps are connected: (1) Various types of clinical cases are submitted to the student: for each of them, case report includes clinical characteristics, location of infection, bacterial strain and minimal bactericidal concentration. These data must be taken into account during the following steps. (2) The student has to establish the treatment schedule: route of administration, dose for each injection, intervals between injections and duration of infusion. (3) The result of the dosage scheme proposed by the student is represented by a simulation of plotting antibiotic plasma concentrations vs. time during the first 4 days of treatment. These curves are obtained by a monoexponential (TOBRA-DIDACT) or biexponential (VANCO-DIDACT) pharmacokinetic model. Peak and trough concentrations are calculated at steady-state. An expert system provides a commentary with each result to evaluate the efficacy of the treatment and to assist the student in improving his prescription. TOBRA-DIDACT and VANCO-DIDACT illustrate the influence of age, obesity, renal impairment, location of infection and bacterial strain on antibiotic therapy. They also show the role of route of administration, dosing and intervals between injections on therapeutic response.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Bacterial Agents↗
PubMed1994

Pharmacokinetics, toxicity, and efficacy of liposomal capreomycin in disseminated Mycobacterium avium beige mouse model.

Capreomycin was incorporated into multilamellar vesicles of pure dipalmitoylphosphatidylcholine. The pharmacokinetics and nephrotoxicity of capreomycin in the free and liposomal forms were studied in normal mice. The efficacies of the two forms were evaluated by using the Mycobacterium avium complex beige mouse model. Approximately 10(7) viable M. avium cells were injected intravenously. Seven days later, treatment with either liposomal or free capreomycin at 60 or 120 mg/kg of body weight was administered daily for 5 days. Mice were sacrificed 5 days after the end of treatment, and the viable bacteria in liver, spleen, lungs, and blood were counted. After 5 days of treatment with dosages of 60 or 120 mg/kg/day, the level of blood urea nitrogen increased in the group treated with free capreomycin but not in the group treated with liposomal capreomycin. After intravenous injection of 120 mg/kg, liposomes enhanced the diffusion of capreomycin in the spleen, lungs, and kidneys and increased the half-life in serum. The 120-mg/kg dose of liposomal capreomycin significantly reduced the number of viable mycobacteria in the liver, spleen, and blood compared with those in the controls. Although these results are promising, further studies are needed to assess the efficacy of liposomal capreomycin for the treatment of M. avium complex infections.

Animals↗
PubMed1994

In vivo bactericidal activities of ciprofloxacin and pefloxacin in an experimental model of Serratia marcescens endocarditis.

The critical concentrations of pefloxacin and ciprofloxacin in serum, corresponding to the lowest concentration in serum able to achieve a 2-log-unit reduction in the CFU in vegetations after a 24-h exposure at a steady-state concentration obtained by a continuous intravenous infusion, were determined in an experimental model of Serratia marcescens endocarditis in rabbits. In vitro data showed that the MICs of ciprofloxacin and pefloxacin were 0.06 and 0.25 mg/liter, respectively. The killing curves indicated a maximum killing rate at a concentration four times that of the MICs. In vivo, the critical concentrations of pefloxacin and ciprofloxacin in serum were 0.4 and 0.24 mg/liter, respectively, corresponding to a concentration of four times the MICs.

Animals↗
PubMed1993

[Acute ethyl alcohol intoxication].

Excessive intake of ethyl alcohol leads to acute intoxication and necessitates the same management as other forms of intoxication. Diagnosis is based on clinical examination, medical history and course. Determination of alcohol level in the expired air is of limited interest. If low or absent, it should direct clinical investigation toward a disorder having similar symptoms; if high, it does not necessarily explain the clinical picture. The severity of the intoxication must always be assessed carefully. Severity is linked either to a complication of acute alcohol intoxication (coma, inhalation, pneumopathy), or to an associated disorder, observed in 50% of the patients (cranial trauma, drug intoxication). Means of treatment and patient management are simple and well established.

Alcoholic Intoxication↗