Additional direct medical costs of nosocomial infections: an estimation from a cohort of patients in a French university hospital.

We estimated the direct additional medical costs of nosocomial infections (NI) using a cohort study in acute and longer-term care at Nîmes University Hospital in France. Patients hospitalised between May 2001 and January 2003 with NI were considered as exposed; all others were eligible as non-exposed. Thirty patients were randomly chosen for each site of infection: respiratory tract, bloodstream, surgical site, urinary tract and other sites for a total of 150 exposed patients. Each exposed patient was matched with a non-exposed patient according to gender, age, severity of the underlying disease, diagnosis according to hospital discharge records, ward type and length of hospitalisation before inclusion. Additional direct medical costs for the exposed patients compared to the non-exposed and the difference between actual costs and the diagnosis-related group rate were measured. Costs resulting from laboratory tests, radiology, surgery and exploratory examinations, and antimicrobial agents were estimated to be Euro2421 for a respiratory tract infection, Euro1814 for a surgical site infection, Euro953 for a bloodstream infection and Euro574 for a urinary tract infection. Total additional costs of NI (direct medical costs and costs of extra length of stay) in acute care were estimated to be up to Euro3.2 million per year (95% confidence interval: 2,275,063-4,132,157). In conclusion, both prevention of avoidable NI and better estimation of the actual costs of NI should be priorities for all healthcare facilities.

Access to electronic hepatitis C medical files by general practitioners.

OBJECTIVES: Hepatitis C virus (HCV) infection is a recognized public health issue in France. Institutional networks were created to improve healthcare practices and facilitate multi-disciplinary care for chronic diseases. The electronic medical file is one of the tools used by the networks to optimize patient care. METHODS: The main objective of this study was to determine what proportion of general practitioners in the Languedoc-Roussillon region of southern France would be interested in using the electronic medical files for patients with HCV infection. A random sample of 20% of the general practitioners in the region was selected and stratified by administrative district of practice. Among them, a telephone survey identified those interested in the hepatitis electronic medical files and following patients with hepatitis C. A more detailed questionnaire was sent to these interested physicians in order to obtain further information. RESULTS: Thirty-seven percent of the general practitioners concerned by the question followed patients with HCV infection. The advantages and disadvantages the physicians associated with use of these files were mostly related to the physician's age, attendance of continuing education courses and internet access. CONCLUSION: This study highlighted the fact that a significant number of general practitioners would be interested in accessing electronic medical files for patients with HCV infection. Considering these findings it might be useful to propose a working group including general practitioners and specialists in order to develop a concrete project for implementing electronic medical files for patients with HCV infection.

Descriptive epidemiology of 13,038 newly diagnosed and histologically confirmed meningiomas in France: 2006-2010.

PURPOSE: This work describes the clinical epidemiology and pathology for patients undergoing surgery for newly diagnosed meningiomas in France between 2006 and 2010. METHODS: The methodology is based on a multidisciplinary national network previously established by the French Brain Tumor DataBase (FBTDB) (in French: Recensement national histologique des tumeurs primitives du système nerveux central [RnhTPSNC]), and the active participation of the scientific societies involved in neuro-oncology in France. RESULTS: From 2006 to 2010, 13,038 incident cases of meningioma with histological validation were identified and analyzed (9769 women, 3269 men, resection 98.2%, cryopreservation 20.5%). For each histological subtype of meningioma (meningothelial, fibrous, transitional, psammomatous, angiomatous, rare variety, microcystic, secretory, lymphoplasmacyte-rich, clear-cell, chordoid, rhabdoid, metaplastic, atypical, papillary, anaplastic and not otherwise specified), number of cases, sex, median age, cryopreservation and surgery were reported. Among the various histological subtypes, atypical meningioma (grade II) slightly, but significantly, increased after 2007. Headache, sensory-motor impairments and seizures were the most frequent clinical symptoms. Time between the first clinical symptom and surgery ranged from 0 to 314 months, and was <3 months in 37% of cases. At the time of surgery, 9% of patients were asymptomatic. DISCUSSION/CONCLUSION: Given the number of meningiomas not histologically-validated, we can estimate that the gross incidence rate for meningiomas operated in France is about 4.2 per 100,000 person/year. To our knowledge, this work is the most important study evaluating the different subtypes of meningiomas and it validates the relevance of histological databases for central nervous system tumors.

[In vitro fertilization and smoking: use of urinary cotinine and expired air carbon monoxide measurements]. / Fécondation in vitro et tabac: intérêt de la cotininurie et de l'analyseur de monoxyde de carbone expiré.

OBJECTIVE: To study the correlation between expired air carbon (EACO) and urinary cotinine, and to determine the impact of tobacco smoking on in vitro fertilization (IVF) results. PATIENTS AND METHODS: We studied prospectively 221 patients in our ART center from October 2002 to October 2004: 51 active smokers, 85 passive smokers, and 85 non-smokers. Patients were classified into active, passive smokers, or non-smokers, based on a questionnaire. We measured urinary cotinine and EACO on the embryo transfer day and we recorded the IVF parameters. RESULTS: Two hundred and twenty-one patients were included. We observed a 17.2% reduction of estradiolemy (P=0.05), a 1.5% reduction of pregnancies (NS), a 7.8% reduction of infants born alive (NS), a 28.5% reduction of twin pregnancies (P=0.06), as well as a 10% increase of miscarriages (NS) in the active smokers in comparison with non-smokers (the same trends were observed between active and passive smokers). EACO and urinary cotinine were well correlated. There was a negative correlation between estradiolemy and urinary cotinine (R=-0.15, P=0.02). DISCUSSION AND CONCLUSION: Tobacco smoking intensity may be dilatory on IVF results. There is a high correlation between EACO and urinary cotinine. Other larger studies would probably obtain results more statistically significant.

[General practitioners' and intensivists' relationships: intensivists' point of view from eight French southern regional areas]. / Relations entre médecin traitant et médecin réanimateur: l'opinion des réanimateurs de huit départements du sud de la France.

OBJECTIVES: Assessment of relationship between general practitioners and intensivists. STUDY DESIGN: Intensivists were questioned by phone from June 14th to September 28th 2004. METHODS: 245 out of 264 intensivists from 8 French Southern regional areas were questioned concerning their relationship with critically ill patients' general practitioner. RESULTS: Patients were mainly admitted into Intensive care Unit (ICU) from the Emergency Department (55%). An information letter from the general practitioner was reported for 20% of admitted patients but 50% of these letters was assumed as not informative. The informations concerning the patient's medical history, therapies, and disease leading to admission and the patient's status were assessed with 6.5, 7.0, 6.0 and 2.0, respectively (maximal note=10). The intensivists contacted the general practitioner for 30% of admitted patients. During the stay in ICU, 33% general practitioners were reported to request informations by phone or visit in ICU. When the stay in ICU was>10 days, the general practitioner was nearly never regularly informed about patient's status. When the patient was discharged from the ICU, 80% of intensivists used an exhaustive typed report to inform the general practitioner. The overall relationship between the general practitioner and the intensivist was assessed as 5.5/10. Insufficient information in the general practitioner's letter at admission, the lack of request for information during the stay in ICU, the lack of contact with the general practitioner by the intensivist and an intensivist's age between 46 and 55 were associated with a relationship assessment<4/10).

Factor V Leiden and prothrombin G20210A polymorphisms as risk factors for miscarriage during a first intended pregnancy: the matched case-control 'NOHA first' study.

Factor V Leiden (FVL) and prothrombin G20210A (FIIG20210A) mutations are associated with a higher risk of miscarriage: we sought to understand whether this association differs by clinical time of unexplained miscarriage, and by ethnic origin, among women with no previous thrombotic episode, during the first intended pregnancy. We performed a case-control study nested in a cohort of 32 683 women. We analyzed 3496 pairs of women matched for classical confounding factors. The FVL and FIIG20210A mutations were associated with an increased risk of miscarriage in Caucasian women [odds ratio (OR) 3.19, 95% confidence interval (CI) 2.37-4.30, P < 0.001 and OR 2.36, 95% CI, 1.72-3.24, P < 0.001, respectively]. Among non-Caucasian women, the mutations were rare and the associations with risk of miscarriage less clear. FVL and FIIG20210A mutations were independent risk factors for miscarriages only for women with related clinical signs occurring from the 10th week of gestation on (OR 3.46, 95% CI 2.53-4.72, P < 0.001 and OR 2.60, 95% CI 1.86-3.64, P < 0.001, respectively). These results indicate that FVL and FIIG20210A mutations are associated with a significant risk of spontaneous abortion which clinical signs occur from the 10th week on of the first intended pregnancy.

Evolution of fluoroquinolone resistance among Escherichia coli urinary tract isolates from a French university hospital: application of the dynamic regression model.

Escherichia coli urinary tract isolates were collected in 1997-2003 from Nimes University Hospital in order to investigate long-term trends in antibiotic resistance and to explore the relationship between antibiotic use and the emergence of resistance. Time-series analysis (ARIMA models) and dynamic regression models were used to investigate relationships between antibiotic use and resistance to ofloxacin and ciprofloxacin. Significant increases were seen in the frequency of ofloxacin (8.9 to 16.7%) and ciprofloxacin resistance (6.2 to 10.1%) (p < 0.001). Using multivariate dynamic regression analysis, it was found that an increased use of one defined daily dose (DDD)/1000 patient-days for ofloxacin, ciprofloxacin and norfloxacin induced average increases of 0.81%, 0.65% and 0.53% in E. coli ofloxacin resistance (p < 0.01), with average delays of 4, 4 and 6 months, respectively. An increase of 1 DDD/1000 patient-days of ciprofloxacin, ofloxacin and norfloxacin use induced increases of 0.73%, 0.82% and 0.63% in E. coli ciprofloxacin resistance (p < 0.01), with average delays of 4, 4 and 5 months, respectively. The use of nalidixic acid was not associated significantly with an increase in resistance to fluoroquinolones by multivariate analysis.

Recombinant human FVIIa for reducing the need for invasive second-line therapies in severe refractory postpartum hemorrhage: a multicenter, randomized, open controlled trial.

BACKGROUND: Case reports on recombinant human factor VIIa (rhuFVIIa) use in women with severe postpartum hemorrhage (PPH) showed encouraging results, but no randomized controlled trial (RCT) is available. PATIENTS AND METHODS: Eighty-four women with severe PPH unresponsive to uterotonics were randomized to receive one early single rhuFVIIa infusion (n = 42) or standard care (no rhuFVIIa; n = 42). The primary efficacy outcome measure was the reduction of the need for specific second-line therapies, such as interventional hemostatic procedures, for blood loss and transfusions. The primary safety outcome measure was the number of deaths and thrombotic events during the 5 days following rhuFVIIa infusion. RESULTS: rhuFVIIa was associated with a reduction in the number of patients who needed second-line therapies compared with controls (standard care). Specifically, 39/42 (93%) patients in the standard care arm received second-line therapies and 22/42 (52%) patients in the rhuFVIIa arm (absolute difference, 41%; range, 18-63%; relative risk RR, 0.56 [0.42-0.76]). The delivery mode (vaginal or Cesarean section) did not affect the primary outcome. No death occurred. Two venous thrombotic events were recorded in the rhuFVIIa arm: one ovarian vein thrombosis and one deep vein thrombosis with a non-severe pulmonary embolism. CONCLUSION: This open RCT in women with severe PPH refractory to uterotonics shows that rhuFVIIa reduces the need for specific second-line therapies in about one in three patients, with the occurrence of non-fatal venous thrombotic events in one in 20 patients.

Factors associated with clinical and virological failure in patients receiving a triple therapy including a protease inhibitor.

OBJECTIVE: To determine the predictors of virological and clinical failure in patients receiving a protease inhibitor as part of triple therapy. METHODS: From the French Hospital Database on HIV, 1402 protease inhibitor-naive patients starting a highly active antiretroviral therapy regimen with ritonavir, saquinavir-hard gel capsule (hgc) or indinavir between July 1996 and March 1997, and with measured HIV RNA at baseline and at 12 months, were studied for progression to a new AIDS-defining event (ADE) or death. Virological failure was defined as plasma HIV RNA > 1000 copies/ml at 12 months. Multivariate analyses were performed using Cox models for clinical outcomes and logistic regression for virological outcomes. RESULTS: During a median follow-up of 14.1 months, 94 (6.7%) patients experienced an ADE or died. At 12 months, 700 patients (49.9%) had virological failure. In the multivariate analysis, baseline CD4 cell count and viral load were found to be independent predictors of both virological and clinical failure. Neither the type of the first protease inhibitor taken nor previous antiretroviral therapy experience was associated with risk of clinical progression. For virological failure, the use of saquinavir-hgc was associated with a significant 1.96-fold increase in risk compared with indinavir; pre-treated patients were at higher risk than antiretroviral therapy-naive patients. CONCLUSION: In this study with large samples of patients, the use of saquinavir-hgc was associated with higher risk of virological failure at 12 months than were ritonavir and indinavir; no differences between protease inhibitors were found for clinical progression. As biases cannot be excluded, a longer duration of follow-up will be necessary to answer the question of whether the results are really discrepant or simply reflect the delay between virological failure and clinical manifestations.

Relation of minor cardiac troponin I elevation to late cardiac events after uncomplicated elective successful percutaneous transluminal coronary angioplasty for angina pectoris.

There is little information about the relation between mild cardiac troponin I (cTn-I) increase after coronary interventions and late outcome. We therefore focused on the long-term outcome and the clinical, morphologic, and procedural correlates of elevation of cTn-I compared with cardiac troponin T, creatine kinase (CK), CK-MB activity and mass, and myoglobin in 105 patients with successful elective percutaneous transluminal coronary angioplasty (PTCA) for stable or unstable angina. Patients with myocardial infarction and those with unstable angina who had a detectable increase in serum markers before PTCA were excluded. Markers were measured before and after the procedure and for 2 days. Patients were followed up to record recurrent angina, myocardial infarction, cardiac death, repeat PTCA, or elective coronary artery bypass graft surgery. Procedure success was achieved in all cases. Elevation in cTn-I (> or =0.1 microg/L) was observed in 23 of 105 patients (22%) (median peak: 0.25 microg/L); 18% had cardiac troponin T (cTn-T) release (> or = 0.1 microg/L, median peak 0.21); 11.4% CK-MB mass (> or =5 microg/L), and 7.6% myoglobin (> or =90 microg/L) release. Five and 2 patients had elevated CK and CK-MB activity, respectively. Fourteen of 18 patients with cTn-T elevation had a corresponding elevation in cTn-I (kappa 0.68; p = 0.001). Patients positive for cTn-I had more unstable angina (p = 0.042) and heparin before PTCA (p = 0.046), and had longest total time (p = 0.004) and single inflation (p = 0.01). By multivariate logistic regression, predictors of postprocedure cTnI elevation were maximum time of each inflation (odds ratio 9.2; p = 0.0012), type B lesions (odds ratio 6.6; p = 0.013), unstable angina (p = 0.041), and age > or =60 years (p = 0.032). Clinical follow-up was available in 103 patients (98%) (mean 19+/-10 months). Kaplan-Meier survival analysis showed that cTn-I elevation was not an important correlate of cardiac events (p = 0.34, by log-rank analysis). The incidence of recurrent angina, myocardial infarction, cardiac death, and repeat revascularization after 12 months was not different in patients positive or negative for cTn-I. We conclude that cTn-I elevation after successful PTCA is not associated with significantly worse late clinical outcome. Levels of cTn-I allow a much higher diagnostic accuracy in detecting minor myocardial injury after PTCA compared with other markers, but there is no association with periprocedural myocardial cell injury and late outcome when cTn-I and other markers are considered.

Risk factors of failure and immediate complication of subclavian vein catheterization in critically ill patients.

OBJECTIVE: To identify the risk factors of failure and immediate complication of subclavian vein catheterization (SVC). DESIGN: Prospective observational study. SETTING: Surgical critical care unit of a tertiary university hospital. PATIENTS: Critically ill patients requiring a first SVC. INTERVENTION: Subclavian vein catheterization was attempted in 707 patients without histories of surgery or radiotherapy in the subclavian area. Failed catheterizations, arterial punctures, pneumothoraces and misplacements of the catheter tip were recorded. Risk factors of failure and immediate complication were isolated among patients' characteristics, procedure parameters (side and number of venipunctures) and the operator's experience using a univariate +/- multivariate analysis. MEASUREMENTS AND MAIN RESULTS: Five hundred sixty-two SVCs (79.5%) were achieved without adverse events. Among the remaining 145 catheterizations, 67 (9.5%) failures, 55 (7.8%) arterial punctures, 22 (3.1%) pneumothoraces and 30 (4.2%) misplacements of the catheter tip occurred. More than one venipuncture was the only risk factor of failed catheterization [2 venipunctures, odds ratio =7.4 (2.1-26); >2 venipunctures, odds ratio =49.1 (16.8-144.1)]. More than one venipuncture and age 77 years or more were predictive of the occurrence of immediate complications [2 venipunctures, odds ratio =3.6 (1.8-7.0); >2 venipunctures, odds ratio =14 (7.7-25.3); age >or=77, odds ratio =1.8 (1.0-3.1)]. The operator's training was not predictive of failed catheterization or immediate complication. CONCLUSION: For SVC, more than one venipuncture is predictive of failed catheterization and immediate complication. Age 77 years or more was predictive of immediate complications.

Evaluation of imipenem 1.5 g daily in febrile patients with short duration neutropenia after chemotherapy for non-leukemic hematologic malignancies and solid tumors: personal experience and review of the literature.

Numerous studies have demonstrated efficacy of imipenem-cilastatin, 50 mg/kg/day, as first line therapy in febrile patients with neutropenia of short duration consecutive to cytostatic chemotherapy. However, only two studies used low dosage of this antibiotic as 1.5 g/day, in prospective, double blind, randomized clinical trials, in this indication. Efficacy and tolerability of imipenem-cilastatin 0.5 g three times daily IV in 30-min infusions, as first-line empiric therapy, were retrospectively evaluated in our hematological unit. From January 1996 to September 2000, 30 neutropenic patients (12 females) with 45 febrile episodes were included. Median age was 57.5 years (31-75). Twenty-four of them had lymphomas, 4 solid tumors and 2 myelomas. There were 13 clinically documented infections, (CD, 28.8%), 16 microbiologically documented infections, (MD, 35.6%) and 16 febrile episodes corresponding to fever of unknown origin, (FUO, 35.6%). The median neutrophils count on nadir (n = 44), was 67/mm3 (8-369). The median duration of neutropenia was 5 days (3-15). Bacteremia was observed in 10 patients, urinary tract infection in 3 patients. The most frequently isolated microorganism was Escherichia coli. The overall success rate of the first line therapy was 66.7%. Adverse events were observed in 11.1% of the patients without necessity to stop treatment. The MD infections showed a lower rate of success compared with CD infections and FUO. These data were in accordance with the previous studies. The importance of number of microorganisms (p = 0.007) and of infected sites (p = 0.01) appeared as prognostic factors (univariate analysis). Although imipenem-cilastatin has been used in numerous studies as empiric broad-spectrum antibiotic therapy in the treatment of febrile neutropenic cancer patients, the exact dosage of this antibiotic is still not standardized. However, utilization of this antibiotic in monotherapy at low dosage seems to us to be safe and effective as usual dosage in the antimicrobial treatment ofthe febrile patients with post chemotherapy neutropenia of short duration.

Release kinetics of serum cardiac troponin I in ischemic myocardial injury.

OBJECTIVES: The study was undertaken to evaluate the release kinetics of cardiac troponin I (cTn-I) in ischemic myocardial injury. DESIGN AND METHODS: The reference range for cTn-I was established by determination of cTn-I in sera and plasma obtained from 622 healthy volunteers (Group 1). cTn-I was compared to: (a) Creatine kinase (CK) MB mass and myoglobin in 12 patients with severe skeletal muscle damage (Group 2); (b) CK-MB activity in 48 patients with myocardial infarction (MI) receiving intravenous thrombolysis (Group 3) (in this group, an additional 43 patients with MI were analyzed separately to characterize cTn-I patterns in thrombolyzed and nonthrombolyzed populations): and in 44 patients with unstable angina (Group 4). RESULTS: In Groups 1 and 2, no positive results (> or = 0.1 microgram/L) were obtained. In Group 3, the time-courses of cTn-I were mostly monophasic in form. A pathologic increase occurred earlier in cTn-I than in CK-MB activity (p = 0.0002); the period with increased cTn-I was longer (p = 0.001), the overall sensitivity of cTn-I (93.9%) was higher than that of CK-MB activity (p = 0.00001). cTn-I was more sensitive at admission (p = 0.0004). In additional patients, the cTn-I peak occurred and cTn-I disappeared significantly later in nonthrombolyzed than in the thrombolyzed group. In Group 4, positive tests results were detected in 45% of patients for cTn-I, 16% for CK-MB activity, and 32% for CK-MB mass. CONCLUSIONS: The cTn-I assay appears to be ideally suited for the detection of ischemic myocardial injury in complex clinical situations because of its high specificity; cTn-I indicates myocardial tissue damage in patients with unstable angina and is superior to CK-MB activity and mass in this respect.

Effects of selective reduction in triplet gestation: a comparative study of 80 cases managed with or without this procedure.

OBJECTIVE: To evaluate the effect of selective termination in triplet pregnancies. DESIGN: Comparative, prospective, nonrandomized study. SETTING: All 80 pregnancies were managed in a single tertiary center by the same obstetrical team. PATIENTS: Eighty women with triplet pregnancies were divided into two groups: group I consisted of 48 women who wished to continue their pregnancies without reduction; in group II were 32 women who choose reduction generally to obtain twins. INTERVENTIONS: Selective terminations were performed after an average term of 9.6 weeks of gestation by transcervical or transabdominal approaches. MAIN OUTCOME MEASUREMENTS: The rate of miscarriage and prematurity, fetal growth, perinatal morbidity and mortality, and maternal complications in the two groups. RESULTS: Prematurity was lower in reduced pregnancies (95.5% in triplets versus 53.5%), especially between 24 to 32 weeks' gestation where prematurity was reduced by half. Birth weight was > 450 g higher in the reduced group. The perinatal mortality rate was lower for reduced pregnancies, but this difference was not statistically significant. Five life-threatening maternal complications occurred in triplets, with none in the reduced group. CONCLUSIONS: Selective terminations are effective in decreasing the rate of prematurity, improving fetal growth, and avoiding maternal complications. The procedure thus could be used in triplet gestations. The ultimate decision should be taken by the couple who must be well informed of the risks of the procedure before deciding.

Risk factors for multidrug-resistant Pseudomonas aeruginosa nosocomial infection.

A case-control study was conducted in a university hospital to determine the risk factors for nosocomial infection with multidrug-resistant Pseudomonas aeruginosa (MDR-PA) among all hospitalized patients and among those with a nosocomial infection due to P. aeruginosa. Eighty patients infected with MDR-PA, 75 infected with a non-MDR phenotype and 240 random controls were included in the 12-month study. Among all hospitalized patients, age, severity index, having a bedridden condition, transfer from other units, nasogastric feeding, urinary catheterization and exposure to beta-lactams (OR=2.5) or fluoroquinolones (OR=4.1) in the seven days before infection were linked to nosocomial infection due to MDR-PA. Among patients infected by P. aeruginosa, exposure to fluoroquinolones (OR=4.7) or surgery (OR=0.5) were linked to the isolation of MDR-PA. This study showed that, in addition to urinary catheterization, nasogastric feeding is an important risk factor in MDR-PA infection. Indeed, an imbalance in gut flora, modifications to the mucous membranes due to the use of nasogastric feeding and the selection pressures exerted by antibiotics were implicated in the occurrence of this infection.

Comparison of the diagnostic value of cardiac troponin I and T determinations for detecting early myocardial damage and the relationship with histological findings after isoprenaline-induced cardiac injury in rats.

Cardiac troponins I (cTnI) and T (cTnT) have been shown to be highly sensitive and specific markers of myocardial cell injury. The purpose of this study was to investigate the diagnostic value of cTnI and cTnT with regard to creatine kinase (CK) and lactate dehydrogenase (LD) and to determine whether they can be used for early diagnosis of myocardial damage in rats, and to examine the relationship between cTnl and cTnT release with histological examinations, using isoprenaline-induced cardiac muscle damage as an experimental model in the rat. Eighteen Wistar rats per group were treated with a single dose of either isoprenaline (iso) or with normal saline as a control group. The anti-cTnI and cTnT monoclonal antibodies (mAbs) employed in the cTnI (Access) and cTnT (Elecsys) assays cross-react with cTnI and cTnT of the rat. A highly significant rise of cTnl or cTnT was found already 2 h after iso. The time-courses of cTnI and cTnT were monophasic in form. The highest cTnI (mean+/-S.D., 1.1+/-2.3 ng/ml) and cTnT (mean+/-S.D. 3.6+/-30 ng/ml) were found 4 h after iso. cTnI and cTnT significantly increased in iso-treated rats in comparison with controls whether the differences between 2-, 4- and 6-h levels and basal levels were considered or not. The areas under cTnl and cTnT curves (AUC) (0-6 h) and the maximal cTnI and cTnT (0-6 h) after iso were significantly different from the controls. For CK and LD, no elevation in comparison with controls could be detected (except a trend for LD whether or not the difference between 6-h levels and basal levels were considered (P=0.08) and for LD AUC (0-6 h) (P=0. 059)). Correlations between maximal cTnI and cTnT and AUC were 0.69 (P=0.0001) and 0.60 (P=0.0066), respectively. Histological examinations of iso-treated rats revealed acute focal or multifocal myofibrillar degeneration of the myocardial tissue in ten out of 14 rats and showed the earliest alterations 4 h after iso in one treated rat. Only four of the controls exhibited evidence of mild changes and slight mononuclear cell infiltration. cTnl and cTnT peak values to at least 0.35 and 1.3 ng/ml, respectively, were necessary to detect histological myocardial cell injury after iso. cTnI and cTnT were found to be early markers for diagnosing iso-induced myocardial damage in comparison with CK and LD. Elevations of cTnI and cTnT appeared to relate to the severity of histologic changes after myocardial injury. Although there was a difference in the absolute concentration of results between cTnI and cTnT assays, due to a lack of standardization and heterogeneity in the cross-reactivities of mAbs to various troponin I and T forms, cTnI and cTnT can be used as easily measurable target parameters for detection of cardiotoxic and/or cardiodegenerative effects in rats.

Time-course of cardiac troponin I release from isolated perfused rat hearts during hypoxia/reoxygenation and ischemia/reperfusion.

The study was designed to determine the time-course of cardiac troponin I (cTn-I) release in isolated and Langendorff-perfused rat hearts during hypoxia and reoxygenation (H/Reox), and after various durations of total ischemia and subsequent reperfusion (I/R). For this purpose, in H/Reox, cTn-I was measured with the conventional Access immunoassay (ng/ml) and a new immunoassay which operates at pg/ml, and compared with creatine kinase (CK), lactate dehydrogenase (LD) and cardiac troponin T (cTn-T). In I/R, cTn-I was compared with CK and LD. The anti-Tn-I mAbs used in cTn-I assays cross-react with cTn-I of the rat. A clear difference between time-courses and concentration levels of cTn-I in I/R and H/Reox models was found. In I/R, maximum release of cTn-I, CK and LD similarly occurred within minutes following reperfusion; however cTn-I did not return to baseline values. cTn-I levels were not linked to the duration of ischemia. In I/R, we were only able to detect small cTn-I concentrations. In H/Reox experiments, cTn-I, CK and LD increased time-dependently. We found higher cTn-I maximal peak levels detected with the Access immunoassay than with the new assay (median, 0.346 ng/ml per min/g dry wt vs 132 pg/ml per min/g dry wt). cTn-T maximal concentrations were lower than maximal cTn-I levels (median, 0.117 ng/ml per min/g dry wt). Time-courses of cTn-I release were roughly similar with both assays in the H/Reox model (r = 0.90). These data indicate that the cTn-I time-course is related to experimental model (I/R or H/Reox), but also likely depends on the sensitivity of cTn-I assays in such experimental conditions.

Evaluation of cardiac troponin I and T levels as markers of myocardial damage in doxorubicin-induced cardiomyopathy rats, and their relationship with echocardiographic and histological findings.

BACKGROUND: Cardiac troponins I (cTnI) and T (cTnT) have been shown to be highly sensitive and specific markers of myocardial cell injury. We investigated the diagnostic value of cTnI and cTnT for the diagnosis of myocardial damage in a rat model of doxorubicin (DOX)-induced cardiomyopathy, and we examined the relationship between serial cTnI and cTnT with the development of cardiac disorders monitored by echocardiography and histological examinations in this model. METHODS: Thirty-five Wistar rats were given 1.5 mg/kg DOX, i.v., weekly for up to 8 weeks for a total cumulative dose of 12 mg/kg BW. Ten rats received saline as a control group. cTnI was measured with Access(R) (ng/ml) and a research immunoassay (pg/ml), and compared with cTnT, CK-MB mass and CK. By using transthoracic echocardiography, anterior and posterior wall thickness, LV diameters and LV fractional shortening (FS) were measured in all rats before DOX or saline, and at weeks 6 and 9 after treatment in all surviving rats. Histology was performed in DOX-rats at 6 and 9 weeks after the last DOX dose and in all controls. RESULTS: Eighteen of the DOX rats died prematurely of general toxicity during the 9-week period. End-diastolic (ED) and end-systolic (ES) LV diameters/BW significantly increased, whereas LV FS was decreased after 9 weeks in the DOX group (p<0.001). These parameters remained unchanged in controls. Histological evaluation of hearts from all rats given DOX revealed significant slight degrees of perivascular and interstitial fibrosis. In 7 of the 18 rats, degeneration and myocyte vacuolisation were found. Only five of the controls exhibited evidence of very slight perivascular fibrosis. A significant rise in cTnT was found in DOX rats after cumulative doses of 7.5 and 12 mg/kg in comparison with baseline (p<0.05). cTnT found in rats after 12 mg/kg were significantly greater than that found after 7.5 mg/kg DOX. Maximal cTnI (pg/ml) and cTnT levels were significantly increased in DOX rats compared with controls (p=0.006, 0.007). cTnI (ng/ml), CK-MB mass and CK remained unchanged in DOX rats compared with controls. All markers remained stable in controls. Analysis of data revealed a significant correlation between maximal cTnT and ED and ES LV diameters/BW (r=0.81 and 0.65; p<0.0001). A significant relationship was observed between maximal cTnT and the extent of myocardial morphological changes, and between LV diameters/BW and histological findings. CONCLUSIONS: Among markers of ischemic injury after DOX in rats, cTnT showed the greatest ability to detect myocardial damage assessed by echocardiographic detection and histological changes. Although there was a discrepancy between the amount of cTnI and cTnT after DOX, probably due to heterogeneity in cross-reactivities of mAbs to various cTnI and cTnT forms, it is likely that cTnT in rats after DOX indicates cell damage determined by the magnitude of injury induced and that cTnT should be a useful marker for the prediction of experimentally induced cardiotoxicity and possibly for cardioprotective experiments.

A prospective randomized study comparing high- and low-dose leucovorin combined with same-dose 5-fluorouracil in advanced colorectal cancer.

Although the efficacy of 5-fluorouracil (5-FU) modulated by leucovorin is well established for advanced colorectal cancer, the question of the most effective regimen and optimal dose of leucovorin remains unanswered. This prospective randomized trial compares low-dose (group 1) and high-dose (group 2) leucovorin, combined with the same dose of 5-FU to determine whether high-dose leucovorin was more beneficial than low-dose on overall survival. Inclusion criteria were: unresectable metastatic colorectal carcinoma, with or without evaluable tumor response; a performance status of less than grade 3 (World Health Organization classification); and no previous chemotherapy for metastases. Forty-two patients were randomized in group 1 (leucovorin, 20 mg/m2/day, days 1 through 5) and 41 patients in group 2 (leucovorin, 200 mg/m2/day, days 1-5). All the patients in the two groups received a 1-hour infusion of 400 mg/m2/day 5-FU every 4 weeks. The two groups were matched with no statistically significant differences in gender ratio, site of primary tumor, performance status, and tumor extent. Toxicity in the two regimens was low and not significantly different between the two groups. Overall median survival was 346 days in group 1 and 323 days in group 2 and was not significantly different between the two groups. At 1 year, the test of equivalence was significant (p < 0.01), demonstrating an absence of more than 20% benefit in 1-year survival for the high-dose regimen. The use of high-dose leucovorin combined with 5-FU in the 5-day regimen does not significantly improve overall survival for patients who have metastatic colorectal cancer.

Antibiotic prophylaxis against postpartum endometritis after vaginal delivery: a prospective randomized comparison between Amox-CA (Augmentin) and abstention.

The most common adverse outcome associated with vaginal delivery is endometritis. It plays a significant role in postpartum morbidity and mortality. There is considerable evidence to support the idea that a single dose of antibiotic after vaginal delivery might decrease the incidence of postpartum endometritis. In this study the evaluation of the efficacy of antibiotic prophylaxis was based upon comparison of a group of patients given a single dose of Amox-CA (Augmentin) with a group of patients without treatment. The study was performed in the Department of Obstetrics and Gynecology of the A. Béclère Public Hospital, Clamart, France (Paris-Sud University). The patients who were the subject of the study had delivered vaginally during the period of 1 year, and were free of any clinical diagnosis of chorioamnionitis or other extragenital infection, had a maternal temperature of less than 38 degrees C during labor and 1 h after delivery, and had no history of allergy to penicillins or cephalosporins. After application of exclusion criteria, 1373 patients were randomized and 1291 included 610 in Group I given Amox-CA and 681 in Group II without any antibiotic. A single dose of 1.2 g of Amox-CA was given by intravenous injection, 1 h after delivery, in Group I. Patients of Group II received no injection. Postpartum status was evaluated before the patient left hospital and 2 weeks later. The two groups were similar in terms of demographic and clinical parameters. Four patients developed endometritis in Group I (4/610, 0.66%). Sixteen patients in Group II developed endometritis (16/680, 2.38%) (P = 0.013; 95% confidence interval (CI), 0.36-3.08%).(ABSTRACT TRUNCATED AT 250 WORDS)