Determination of the Optimal Single Dose Treatment for Acoziborole, a Novel Drug for the Treatment of Human African Trypanosomiasis: First-in-Human Study.

Background And Objectives: Acoziborole is a novel boron-containing candidate developed as an oral drug for the treatment of human African trypanosomiasis (HAT). Results from preclinical studies allowed progression to Phase 1 trials. We aimed to determine the best dose regimen for all stages of HAT.

Absence of QTc prolongation in a thorough QT study with imeglimin, a first in class oral agent for type 2 diabetes mellitus.

Purpose: Imeglimin is the first in a new class of oral antidiabetic agents, the glimins, currently in development to improve glycemic control in patients with type 2 diabetes mellitus. A thorough QT study was conducted to establish electrophysiological effects of therapeutic and supratherapeutic doses of imeglimin on cardiac repolarization.

Methods: In this randomized, double-blind, four-period, placebo and active controlled crossover study, healthy subjects were administered a single dose of imeglimin 2250 mg, imeglimin 6000 mg, moxifloxacin 400 mg, and placebo.

Randomized study of the effect of gadopiclenol, a new gadolinium-based contrast agent, on the QTc interval in healthy subjects.

Aims: We investigated the effect of gadopiclenol, a new gadolinium-based contrast agent, on the QTc interval at clinical and supraclinical dose, considering the relative hyperosmolarity of this product.

Methods: This was a single centre, randomized, double-blind, placebo- and positive-controlled, 4-way crossover study. Forty-eight healthy male and female subjects were included to receive single intravenous (i.

Evaluation of the effects on the QT-interval of 4 artemisinin-based combination therapies with a correction-free and heart rate-free method.

Several antimalarial drugs are known to prolong ventricular repolarization as evidenced by QT/QTc interval prolongation. This can lead to Torsades de Pointes, a potentially lethal ventricular arrhythmia. Whether this is the case with artemisinin-based combination therapies (ACTs) remains uncertain.

Effects of Dihydroartemisinin-Piperaquine Phosphate and Artemether-Lumefantrine on QTc Interval Prolongation.

QT/QTc interval prolongation reflects delayed cardiac repolarization which can lead to Torsade de Pointes and sudden death. Many antimalarial drugs prolong QT/QTc interval. However, due to confounding factors in patients with malaria, the precise extent of this effect has been found to be highly variable among studies.

Association of Oral Contraceptives With Drug-Induced QT Interval Prolongation in Healthy Nonmenopausal Women.

Importance: Women are at higher risk of drug-induced torsade de pointes (TdP) than men. Androgens are protective. Influence of oral contraception on drug-induced TdP and QT prolongation is controversial.

GENomE wide analysis of sotalol-induced IKr inhibition during ventricular REPOLarization, "GENEREPOL study": Lack of common variants with large effect sizes.

Unlabelled: Many drugs used for non-cardiovascular and cardiovascular purposes, such as sotalol, have the side effect of prolonging cardiac repolarization, which can trigger life-threatening cardiac arrhythmias by inhibiting the potassium-channel IKr (KCNH2). On the electrocardiogram (ECG), IKr inhibition induces an increase in QTc and Tpeak-Tend (TpTe) interval and a decrease of T wave maximal amplitude (TAmp). These changes vary markedly between subjects, suggesting the existence of predisposing genetic factors.

Effects of HIV protease inhibitors on cardiac conduction velocity in unselected HIV-infected patients.

We examined the prevalence and the extent of prolongation of the PR and QRS intervals and their relation to anti-HIV treatments and other clinical characteristics in 970 HIV-infected patients, 749 treated with antiretroviral therapy and 221 untreated. Age, body mass index, heart rate, and treatment with β-blockers and HIV protease inhibitors (PIs) were independent predictors of increase in the duration of the PR interval. Male gender, Caucasian ethnicity, heart rate, duration of antiretroviral therapy, and use of PIs were independent predictors of an increase in the duration of the QRS interval.

Comparison of long term outcome in patients with or without aortic ring abscess treated surgically for aortic valve infective endocarditis.

Objective: To assess the long term prognostic significance of aortic valve ring abscess in patients with aortic endocarditis.

Patients: A consecutive series of 75 patients who had surgery for aortic infective endocarditis between 1981 and 1989; 35 had aortic ring abscesses (group 1) and 40 did not (group 2). Mean age did not differ between the two groups.

[Endocarditis caused by heart valve prosthesis. Apropos of 35 cases].

35 cases of prosthetic valve endocarditis are reported. The diagnostic is based on clinical, echocardiographic, bacteriological and anatomical aspects. Heart failure, neurologic complications, positive culture of prosthesis, Staphylococcus aureus infection and perivalvular abscess are factors of a bad prognosis.

[Screening for a frequent cardiac disorder: mitral valve prolapse].

Mitral valve prolapse (MVP) screening using bidimensional echocardiography was performed on 171 healthy subjects from Lorraine of both sexes, aged 20 to 60 years. Six men and seven women presented this valvular disease. In the Lorraine population, the estimated prevalence of MVP was 7.

[Palmaz's vascular intraluminal stent. Preliminary results].

Palmaz's stent is a fenestrated, expansible metallic stent with an apparently small tendency to thrombogenesis, so that anticoagulants are necessary only during the preintimalization period. This stent has recently been introduced in human pathology and has been used in this study for percutaneous or surgical correction of residual or recurrent post-angioplasty lesions. The development, theoretical indications and preliminary results obtained with the insertion of 25 Palmaz's stents into peripheral arteries are presented.

[The combination of penicillin G and ofloxacin: a response to the empirical treatment of community acquired pneumonia].

The aim of this study was to assess the clinical efficacy of a combination of penicillin G and ofloxacin in the treatment of community acquired pneumonia. Thirty eight patients (23 males, 15 females, mean age 62.8 years +/- 19.

Penetration of ciprofloxacin into heart valves, myocardium, mediastinal fat, and sternal bone marrow in humans.

The penetration of ciprofloxacin into heart tissue (valve and myocardium), mediastinal fat, and sternal bone marrow was the object of a prospective nonrandomized study involving 36 patients undergoing mitral and/or aortic valve replacement. Patients were divided into two groups of 18. Group 1 patients were administered a single 400-mg intravenous dose of ciprofloxacin over a 1-h period.

[Role of laser angioplasty in the management of peripheral arteriopathies. Report of 79 cases].

From May 1988 to November 1989, 79 of the 341 patients admitted to our center requiring angioplasty for peripheral artery disease were treated by laser angioplasty (LA) associated with secondary dilatation. Laser angioplasty was performed with and Nd-YAG laser coupled by an optical fiber to 1.8, 2.

[In vivo bactericidal effect of ciprofloxacin, ofloxacin and pefloxacin against Staphylococcus aureus].

The bactericidal activity of ciprofloxacin, ofloxacin, pefloxacin, against methicillin sensitive S. aureus (2 different strains) was studied on a model of infected fibrin clots inserted subcutaneously in rabbit. The quinolones were delivered intravenously, as a single daily dose of 100 mg/kg/day.

Mitral valve prolapse as a risk factor for infective endocarditis.

The frequency of mitral valve prolapse was assessed in 48 patients with mitral valve endocarditis and in 96 controls matched for age and sex, attending a routine family screening clinic or having surgery of the limbs. The frequency of mitral valve prolapse in cases with endocarditis (9 of 48 patients) was more than three times that in controls (6 of 96) (odds ratio 3.5; 95% confidence interval [CI] 1.

Significance of spontaneous obstruction of high degree coronary artery stenoses between diagnostic angiography and later percutaneous transluminal coronary angioplasty.

Among 265 patients with severe coronary artery stenoses amenable to percutaneous transluminal coronary angioplasty, 13 (5%) developed new total coronary occlusion of the vessel to be dilated during the period between diagnostic coronary angiography and repeat coronary angiography at the time of the operation. Time from diagnostic to "therapeutic" angiography (76 +/- 74 vs 31 +/- 31 days, p less than 0.0001), degree of coronary stenosis on diagnostic angiography (85 +/- 7 vs 80 +/- 8%, p less than 0.

[In vivo bactericidal activity of an oxacillin-netilmicin combination against Staphylococcus aureus. Influence of the rhythm of netilmicin administration].

The bactericidal activity of two regimens of netilmicin (8 mg/kg/day) given intravenously once a day (od) or thrice daily (tid) both alone and in combination with oxacillin (200 mg/kg/day) was compared using a model of fibrin clots infected with a strain of Staphylococcus aureus (10(7) CFU/g) sensitive to methicillin and netilmicin (clinical isolate) and implanted subcutaneously in rabbit. This study shows that: 1) Netilmicin given alone as both single and divided doses results in early bacterial killing but does not exert a bactericidal effect after 24 hours because of a significant late increase of the number of bacterial. 2) The netilmicin-oxacillin combinations are more bactericidal at 1 h, 2 h and 24 h than oxacillin alone (P less than 0.

[Bases of antibiotherapy in neuromeningeal infections].

An early treatment and an adequate antimicrobial chemotherapy are major prognostic factors for bacterial meningitis, brain abscesses and related infections. The necessity of an early therapy requires to begin an empiric antibiotic treatment prior to obtain microbiological results. The principles that apply to empiric therapy of other types of infections are equally applicable to the treatment of central nervous system (CNS) infections and include: the capacity of achieving adequate levels of antibiotic in the CNS and for the brain (pharmacokinetic criteria), the knowledge of the most likely etiologic agents for central nervous system infections and their antibiotic susceptibility (bacteriological criteria).

[Pyoderma gangrenosum: treatment with plasma exchange (4 cases)].

Four patients with pyoderma gangrenosum were treated by plasma exchange. The series included one woman (cervical localization) and three men (sural localization in 1 case, multiple trunk and facial localizations in the second case and multiple, recurrent localizations on trunk and limbs in the third case). In 2 cases another disease was associated (ulcerative colitis in 1 case and Crohn's disease in the other).

Staphylococcus aureus mediastinitis: prognostic usefulness of an early medicosurgical therapy.

Six cases of acute Staphylococcus aureus mediastinitis after median sternotomy were reported. Five resulted from an asymptomatic disseminator of S aureus present in the operating room. Each case was characterized by an acute bacteremic phase, occurring after a mean interval of 8.

[Treatment of post-traumatic and post-neurosurgical bacterial meningitis with ceftriaxone alone or in combination with fosfomycin].

From 1984 to 1986, 13 patients (10 adults, 3 children) with bacterial meningitis following neurosurgery or traumatism were given ceftriaxone alone 6 times at a dose of 40 mg/kg one IV injection per day, or in association 7 times with fosfomycin at a dose of 200 mg/kg/day, 3 IV perfusions every 4 h. The bacteriological diagnosis was confirmed in 9 cases (3 Staphylococcus aureus, 4 Streptococcus pneumoniae, 1 Klebsiella, 1 Peptococcus). In vitro neither synergy nor antagonism were observed between the two antimicrobial agents.