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The effect of pesticides on human health is still controversial, particularly as regards long-term health effects like cancer. The literature does suggest, however, that they could be involved in the occurrence of brain tumors, although the results concerning residential exposure are scarce. Our objective was to investigate the association between residential proximity to agricultural pesticides and brain tumors among adults in France by using a geographical information system. CERENAT is a population-based case-control study carried out in France in 2004-2006. We used two geographical data sources on agricultural land use to create exposure scores based on crop surface areas near the residence, for open field crops, vineyards and orchards. Conditional logistic regression for matched sets was used to estimate Odds Ratios (ORs) and 95% confidence intervals (95%CI). We found a significant association between meningioma and proximity to open field crops above the 75th percentile (OR 2.30 95%CI 1.04-5.10). Non-significant associations were also found with proximity of vineyards above the 95th percentile (OR 1.90 95%CI 0.41-8.69) and orchards above the 95th percentile (OR 5.50, 95%CI 0.49-61.94). No significant association was found between glioma and proximity to agricultural land. Further investigations are needed, particularly to improve the quality and availability of geographical data on agricultural land use., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Little is known about the relationship between diet and central nervous system (CNS) tumors, especially in terms of their histological subtypes. This study investigated the overall associations between food groups, alcohol intake and CNS tumors, and in particular about the associations between neuroepithelial tumors and meningiomas., Methods: Data were collected through the CERENAT (CEREbral tumors: a NATional study) case-control study conducted in France during the period 2004-2010. Data were available for 1,479 subjects (494 cases, including 201 neuroepithelial tumors, 193 meningiomas, 100 other CNS tumors, and their 985 matched controls). Conditional logistic regressions for matched sets were adjusted based on the participants' educational level, occupation, smoking status and frequency of food group consumption., Results: A heavy consumption of grilled meat and poultry was associated with neuroepithelial tumors in a dose-related relationship (ORQ4vsQ1 = 3.72, 95% CI 1.62-8.52, p = 0.005). Higher fruit and vegetable intake was inversely associated with meningiomas (for fruits: ORQ4vsQ1 = 0.38, 95% CI 0.17-0.87, p = 0.06, for vegetables ORQ4vsQ1 = 0.26, 95% CI 0.11-0.62, p = 0.007). Consumption of alcohol on a daily basis was inversely associated with CNS tumors especially for meningiomas (ORQ4vsQ1 = 0.33, 95% CI 0.18-0.61, p = 0.001)., Conclusions: Results obtained in terms of grilled meat, fruits and vegetables consumption were in line with those published in epidemiological literature. Contradictions in results between neuroepithelial tumors and meningiomas confirmed the need to analyze the effects of dietary factors on the basis of the histological subtypes of CNS tumors., (© 2016 S. Karger AG, Basel.)

Unlabelled: The carcinogenic effect of radiofrequency electromagnetic fields in humans remains controversial. However, it has been suggested that they could be involved in the aetiology of some types of brain tumours., Objectives: The objective was to analyse the association between mobile phone exposure and primary central nervous system tumours (gliomas and meningiomas) in adults., Methods: CERENAT is a multicenter case-control study carried out in four areas in France in 2004-2006. Data about mobile phone use were collected through a detailed questionnaire delivered in a face-to-face manner. Conditional logistic regression for matched sets was used to estimate adjusted ORs and 95% CIs., Results: A total of 253 gliomas, 194 meningiomas and 892 matched controls selected from the local electoral rolls were analysed. No association with brain tumours was observed when comparing regular mobile phone users with non-users (OR=1.24; 95% CI 0.86 to 1.77 for gliomas, OR=0.90; 95% CI 0.61 to 1.34 for meningiomas). However, the positive association was statistically significant in the heaviest users when considering life-long cumulative duration (≥896 h, OR=2.89; 95% CI 1.41 to 5.93 for gliomas; OR=2.57; 95% CI 1.02 to 6.44 for meningiomas) and number of calls for gliomas (≥18,360 calls, OR=2.10, 95% CI 1.03 to 4.31). Risks were higher for gliomas, temporal tumours, occupational and urban mobile phone use., Conclusions: These additional data support previous findings concerning a possible association between heavy mobile phone use and brain tumours., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Plasmatic proteasome (p-proteasome) has recently been described as a new marker for metastatic melanoma. The objective of this study was to compare the diagnostic and prognostic values of p-proteasome with three other melanoma serological markers: S100B protein, melanoma inhibitory activity protein (MIA) and lactate dehydrogenase (LDH) in the plasma of 121 stage I-IV melanoma patients. Laboratory analyses were performed by standardized ELISA (p-proteasome, MIA), immunoluminometric assay (S100B) and colorimetry (LDH). We found that all markers were relevant for discriminating metastatic from nonmetastatic patients but p-proteasome displayed the highest diagnostic accuracy. P-proteasome and S100B were the most sensitive (58.1%) and p-proteasome and MIA the most specific (98.7 and 100%) in detecting metastatic disease. P-proteasome and S100B had the highest area under receiver operating characteristics curve, 0.811 (95% CI: 0.725-0.897) and 0.822 (95% CI: 0.738-0.906), respectively. These two markers were the best in detecting patients with lymph node metastases. S100B, MIA and LDH diagnostic accuracy was increased when these markers were combined with p-proteasome. As shown with univariate analysis, shorter progression-free and overall survival rates were significantly associated with elevated plasma levels of each markers. The multivariate Cox regression analysis identified p-proteasome as the only independent predictor of a poorer progression-free survival (p = 0.030). In conclusion, this comparative study established that p-proteasome quantification in combination with other melanoma biomarkers is an attractive approach for the biological follow-up of melanoma patients., (Copyright © 2012 UICC.)

Objective: Clinical guidelines should provide a framework for managing patients hospitalized in intensive care units. Little is known about guideline compliance in real-life practice. To evaluate compliance rates for a large bundle of intensive care unit practice guidelines and determine factors associated with noncompliance to these guidelines., Design, Setting, and Patients: A bundle of 13 clinical guidelines was elaborated by a group of senior physicians. Four external consultants validated the process. Then, a 1-day audit was performed at 66 participating adult intensive care units in 39 institutions by a group of 64 junior investigators supervised by senior intensivists. At the bedside, investigators collected data from 625 patients hospitalized in those units., Interventions and Measurements: The eligibility and compliance rates were determined for each clinical recommendation. The rate of full compliance to each eligible clinical guideline was calculated. Mortality data were requested 28 days after the completion of the audit., Main Results: The eligibility rate ranged from 11% (sepsis bundle) to 80% (identified closest relative). The median compliance rate was 75% (60-100), ranging from 24% (sedation monitoring) to 96% (identified closest relative and bacteriological sampling before initiating antibiotics). Our results showed that only 24% (20-27) of patients in our cohort received fully compliant care. The 28-day survival probability was .77 (.73-.80)., Conclusions: At the bedside, clinical guidelines are fully applied in 24% of patients. Our study underlines the need to both improve the process of implementation and become cognizant of excessive proliferation of clinical guidelines.

Background: The most-used prognostic scheme for malignant gliomas included only patients aged 18 to 70 years. The purpose of this study was to develop a prognostic model for patients ≥70 years of age with newly diagnosed glioblastoma., Methods: A total of 437 patients ≥70 years of age with newly diagnosed glioblastoma, pooled from 2 tertiary academic institutions, was identified for recursive partitioning analysis (RPA). The resulting prognostic model, based on the final pruned RPA tree, was validated using 265 glioblastoma patients ≥70 years of age from a data set independently compiled by a French consortium., Results: RPA produced 9 terminal nodes, which were pruned to 4 prognostic subgroups with markedly different median survivals: subgroup I = patients <75.5 years of age who underwent surgical resection (9.3 months); subgroup II = patients ≥75.5 years of age who underwent surgical resection (6.4 months); subgroup III = patients with Karnofsky performance status of 70 to 100 who underwent biopsy only (4.6 months); and subgroup IV = patients with Karnofsky performance status <70 who underwent biopsy only (2.3 months). Application of this prognostic model to the French cohort also resulted in significantly different (P < .0001) median survivals for subgroups I (8.5 months), II (7.7 months), III (4.3 months), and IV (3.1 months)., Conclusions: This model divides elderly glioblastoma patients into prognostic subgroups that can be easily implemented in both the patient care and the clinical trial settings. This purely clinical prognostic model serves as a backbone for the future incorporation of the increasing number of potential molecular prognostic markers., (Copyright © 2012 American Cancer Society.)

Introduction: Fluid therapy is one of the major elements of severe sepsis and septic shock management. A systematic initial fluid bolus is recommended before evaluation of left ventricular filling pressure by the use of indicators of fluid responsiveness, preferentially dynamic ones. A massive fluid therapy could be damaging for the patient. Dynamic indicators of fluid responsiveness are not often relevant in the emergency department. This study was aimed to evaluate the use of indicators of fluid responsiveness by emergency practitioners during septic shock management., Study Design: Cross sectional survey using anonymous self-questionnaire., Methods: We included all practitioners working in public emergency department of Languedoc-Roussillon (France). Primary-end point was the use of one indicator of fluid responsiveness at least. Uni- and multivariate analysis was conducted to find associated factors., Results: Of 232 practitioners included, we collected 149 questionnaires (response rate=64%). Hundred and eight practitioners (72% [64-79%]) used at least one indicator of fluid responsiveness. Fifty-six practitioners (38% [30-46%]) used echocardiography, 54 practitioners (36% [29-44%]) used blood lactate concentration, 45 practitioners (30% [23-38%]) used passive leg raising. The use of indicators of fluid responsiveness is associated with easy access to echography device (odd ratio=2.94 [1.16-7.62], P=0.03)., Conclusion: Emergency practitioners use preferentially less invasive and less time-consuming indicators of fluid responsiveness., (Copyright © 2012 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier SAS. All rights reserved.)

Background and Purpose: This work aimed at prospectively record all primary central nervous system tumor (PCNST) cases in France, for which histological diagnosis was available. The objectives were to (i) create a national database and network to perform epidemiological studies, (ii) implement clinical and basic research protocols, and (iii) harmonize the health care of patients affected by PCNST., Methods: The methodology is based on a multidisciplinary national network already established by the French Brain Tumor DataBase (FBTDB) (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 2004 to 2009, 43,929 cases of newly diagnosed and histologically confirmed PCNST have been recorded. Histological diagnoses included gliomas (42,4%), all other neuroepithelial tumors (4,4%), tumors of the meninges (32,3%), nerve sheath tumors (9,2%), lymphomas (3,4%) and others (8,3%). Cryopreservation was reported for 9603 PCNST specimens. Tumor resections were performed in 78% cases, while biopsies accounted for 22%. Median age at diagnosis, sex, percentage of resections and number of cryopreserved tumors were detailed for each histology, according to the WHO classification., Discussion/conclusion: Many current applications and perspectives for the FBTDB are illustrated in the discussion. To our knowledge, this work is the first database in Europe, dedicated to PCNST, including clinical, surgical and histological data (with also cryopreservation of the specimens), and which may have major epidemiological, clinical and research implications., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

This work aimed to prospectively record all primary central nervous system tumor (PCNST) cases in France, for which histological diagnosis is available. The objectives were to (i) create a national registry and a network to perform epidemiological studies; (ii) implement clinical and basic research protocols; and (iii) harmonize the health care of patients affected by PCNST. For 5 years, 25 756 cases of newly diagnosed and histologically confirmed PCNST have been recorded. Histological diagnoses included glioma (48.9%), all other neuroepithelial tumors (5%), meningioma (28.8%), nerve sheath tumors (8.4%), lymphoma (3.2%) and others (5.7%). Cryopreservation was reported for 6018 PCNST specimens. Tumor resections (R) were performed in 78% cases, while biopsies accounted for 22%. Median age (MA), sex, percentage R and number of cryopreserved tumors were detailed for each histology; for example, out of 6053 glioblastomas (MA 63 years, male 59.4%, R 62%, 1611 were cryopreserved), and out of 37 atypical teratoid/rhabdoid tumors (MA 2 years, male 56.8%, R 94%, 17 were cryopreserved). This database or databank dedicated to PCNST cases contains detailed data on clinical, histological and other characteristics, such as the inclusion of data on cryopreserved specimens that are not available in other European registries. Therefore, this is a valuable resource that can be used for planning future epidemiological and clinical research., (© 2011 The Authors; Brain Pathology © 2011 International Society of Neuropathology.)

Arteriovenous fistula (AVF) is still in 2010 the gold standard of vascular(2) access in haemodialysis (HD) patients. Nevertheless it may be difficult to obtain and/or to use AVF in elderly. With this prospective randomised pilot study, we compare two strategies of vascular access in 70 years old or more new HD patients. AVF were compared to tunnelled jugular vein catheters (TIJC) with taurolidine as bacterial lock solution. Results were as follow: [table: see text] The responses with the visual analogic scale of comfort was 8/10 for TIJC and 5/10 with AVF * P<0.05. In five TIJC patients, heparin was added with success to taurolidine because of partial clotting of catheters. Albuminemia was significantly lower in AVF failure patients compared to AVF success patients (24.8g/L vs 31.1g/L). This pilot study allows to conclude that TIJC is an acceptable challenge to AVF in haemodialysed patients of 70 years or more in a two years long use., (Copyright © 2011 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.)

Plasmatic proteasome (p-proteasome) also called circulating proteasome has recently been described as a tumor marker. We investigated the diagnostic and prognostic accuracies of p-proteasome levels in a melanoma population classified according to the American Joint Committee on Cancer staging system. Using an ELISA test, we measured p-proteasome levels in 90 patients and 40 controls between March 2003 and March 2008. The subunit composition of p-proteasomes was determined in metastatic melanoma by proteomic analysis. The mean p-proteasome levels were correlated with stages (P < 0.0001; r(S) = 0.664). They were significantly higher in patients with stage IV and stage III with lymph node metastasis (9187 ± 1294 and 5091 ± 454 ng/ml, respectively) compared to controls (2535 ± 187 ng/ml; P < 0.001), to stage I/II (2864 ± 166 ng/ml; P < 0.001) and to stage III after curative lymphadenectomy (2859 ± 271 ng/ml; P < 0.001). The diagnostic accuracy of p-proteasome was evaluated by receiver operating characteristic analysis. With a cut-off of 4300 ng/ml, diagnostic specificity and sensitivity of p-proteasome for regional or visceral metastases were respectively 96.3% and 72.2%. In univariate analysis, high p-proteasome levels (>4300 ng/ml) were significantly correlated with an increased risk of progression [hazard ratio (HR) = 7.34; 95% CI 3.54-15.21, P < 0.0001] and a risk of death (HR = 5.92; 95% CI 2.84-12.33, P < 0.0001). In multivariate analysis, high p-proteasome levels were correlated with a poorer clinical outcome in the subgroup analysis limited to patients with disease stages I, II and III. Proteomic analysis confirmed the presence of all proteasome and immunoproteasome subunits. Taken together, these results indicate that p-proteasomes are a new marker for metastatic dissemination in patients with melanoma., (© 2010 John Wiley & Sons A/S.)

Meningococcal disease is a major public health concern in Sahelian Africa, where over half of the cases reported worldwide occur. In an effort to find annual spatial clusters of meningococcal disease and in order to study their evolution in Niger from January 2002 to June 2008, a prospective study of routine national surveillance data was conducted pertaining to patients with suspected bacterial meningitis. The diagnoses were obtained by analysing patients' cerebrospinal fluid, using polymerase chain reaction or bacteriology. SatScan using Poisson's model was used to calculate the relative risk (RR) of occurrence of spatial clusters. In the 2002-2003 period, 15 spatial clusters of meningococcal meningitis were detected in a total of 3,979 cases with a maximum number of 558 cases per cluster in the south-eastern part of the country (70.5% of all cases that year; RR = 7.85; P <0.001). Other clusters were found in the following years in approximately the same area as those detected in 2002-2003. These clusters were identified in the southeast, which allowed us to identify high-risk groups in this part of the country. Statistically significant spatio- temporal patterns were found, which should be useful in establishing hypotheses for prospective studies on epidemic tendencies and empirical risk factors in the African meningitis belt.

This report, an audit requested by the French government, describes oncological patterns of care, prognostic factors, and survival for patients with newly diagnosed and histologically confirmed glioblastoma multiforme (GBM) in France. The French Brain Tumor DataBase, which is a national multidisciplinary (neurosurgeons, neuropathologists, radiotherapists, neurooncologists, epidemiologists, and biostatisticians) network, prospectively collected initial data for the cases of GBM in 2004, and a specific data card was used to retrospectively collect data on the management and follow-up care of these patients between January 1, 2004, and December 1, 2006. We recorded 952 cases of GBM (male/female ratio 1.6, median age 63.9 years, mean preoperative Karnofsky performance status [KPS] 79). Surgery consisted of resection (RS; n = 541) and biopsy (n = 411); 180 patients did not have subsequent oncological treatment. After surgery, first-line treatment (n = 772) consisted of radiotherapy (RT) and temozolomide (TMZ) concomitant +/- adjuvant in 314 patients, RT alone in 236 patients, chemotherapy (CT) alone in 157 patients, and other treatment modalities in 65 patients. Median overall survival was 286 days (95% CI, 266-314) and was significantly affected by age, KPS, and tumor location. Median survival (days, 95% CI) associated with these main strategies, when analyzed by a surgical group, were as follows: RS + RT-TMZ((n=224)): 476 (441-506), biopsy + RT-TMZ((n=90)): 329 (301-413), RS + RT((n=147)): 363 (331-431), biopsy + RT((n=89)): 178 (153-237), RS + CT((n=61)): 245 (190-361), biopsy + CT((n=96)): 244 (198-280), and biopsy only((n=118)): 55 (46-71). This study illustrates the usefulness of a national brain tumor database. To our knowledge, this work is the largest report of recent GBM management in Europe.

Introduction: The French Express study compared two alveolar recruitment managements (maximal versus standard) in Acute Respiratory Distress Syndrome (ARDS) patients ventilated with 6 ml/kg of ideal body weight (IBW). The objective of the present study was to assess in a single intensive care unit, the impact of Express study on the mechanical ventilation settings in non-included ARDS patients., Patients and Methods: From 16 October 2002 to 14 January 2005 all consecutive eligible but non-included patients in Express study were studied. The maximal and minimal tidal volumes, and the minimal and maximal respiratory rates were retrospectively recorded. These parameters were compared according to the date of patient's admission and then the patients were separated in four quartiles (14, 15, 15, 15 patients)., Results: From the first to the last study period separated by 26 months, the mean maximal tidal volume decreased from 9.0+/-1.3 to 7.4+/-1.0 ml/kg of IBW (p=0.03), the proportion of patients ventilated with a maximal tidal volume greater than 8 ml/kg decreased from 93% to 20% (p<0.01), the median minimal respiratory rate increased from 14 to 18 b/min (p=0.03) and the proportion of patients with a respiratory rate less than 20 b/min decreased from 100% to 73% (p<0.01). There were correlations between the time of patient's admission and the maximal tidal volume (r=-0.43, p<0.01), the minimal tidal volume (r=-0.28, p<0.04) and the minimal respiratory rate (r=0.33, p<0.02)., Conclusion: The participation in Express study led physicians to modify their mechanical ventilation settings. The maximal tidal volume decreased and the minimal respiratory rate increased in the ARDS eligible but non-included patients., (Copyright 2010 Elsevier Masson SAS. All rights reserved.)

Background and Purpose: Glioblastoma, the most common malignant primary brain tumor in adults, is usually rapidly fatal. The current care standards for newly diagnosed glioblastoma consist, when feasible, in surgical resection, radiotherapy, and chemotherapy, as described in the Stupp protocol. Despite optimal treatment, nearly all malignant gliomas recur. If the tumor is symptomatic for mass effect, repeated surgery may be proposed., Methods: We retrospectively analyzed the survival of patients with histologically confirmed primary glioblastoma (WHO grade 4) who were operated in two centers between January 2004 and December 2007. All patients who underwent a second resection for recurrent glioblastoma were included., Results: During this period, 320 patients were operated in the two centers, with 240 surgical resections and 80 surgical biopsies. In the surgical resection group, 8.3% (20 patients) underwent a second surgical resection for glioblastoma. The mean age was 52 years. At the end of the study, seven patients were alive. The median survival was 24 months and progression-free survival was 7.5 months., Conclusions: The effect of resection of recurrent glioblastoma on survival has not been extensively studied. No randomized trials have been conducted. Our data were globally identical to other retrospective studies. Selected patients with recurrent glioblastoma may be candidates for repeated surgery when the situation appears favorable based on assessment of the individual patient's factors. Factors such medical history, neurological status, location of the tumor, and progression-free survival have been proven in retrospective studies to give better results., (Copyright 2009 Elsevier Masson SAS. All rights reserved.)

Background: The intrathoracic blood volume index (ITBVI) and central venous pressure (CVP) are routinely used to predict fluid responsiveness in critically ill patients with acute circulatory failure (systolic blood pressure < 90 mm Hg or vasopressor requirement). However, they have never been compared., Methods: In this prospective interventional study, we included 35 (21 men) mechanically ventilated and sedated patients with acute cardiovascular failure requiring cardiac output measurement (transpulmonary thermodilution technique). Fluid responsiveness was defined as an increase in stroke index (cardiac output/heart rate/body surface area) > or =15%. Receiver operating characteristic curves were generated for ITBVI and CVP., Results: Fluid challenge induced a stroke index increase > or =15% in 18 (51%) patients (responders). At baseline, no studied hemodynamic variables were different between responders and nonresponders. The areas under the receiver operating characteristic curves were 0.64 [95% CI: 0.46-0.80] for ITBVI and 0.68 [95% CI: 0.50-0.83] for CVP, without any statistical difference (P = 0.73). The best cut-off values for CVP and ITBVI were 9 mm Hg (sensitivity = 61%; specificity = 82%) and 928 mL . m(-2) (sensitivity = 78%; specificity = 53%)., Conclusion: ITBVI is similar to CVP in its ability to predict fluid responsiveness in critically ill patients with acute circulatory failure.

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.

Objective: 1) To assess the prevalence of stress urinary incontinence (SUI) and urge urinary incontinence (UTI) in elite women athletes versus the general female population, and 2) to analyze the conditions of occurrence of urine loss in search of etiological clues in elite athletes. DECISION: An anonymous self-questionnaire was collected transversally from women aged 18 to 35 years. The exposed group was composed of elite female athletes; the non-exposed group was made up of women in the same age range accepting to answer the questionnaire., Results: A total of 157 answers from elite athletes and 426 from control subjects were available for analysis. Urinary incontinence prevalence was 28% for athletes and 9.8% for control subjects (p = .001). There was no significant difference in the relative prevalence of SUI between the athletes and control subjects. Athletes reported urine loss more frequently during the second part of the training session (p < 0.0003), and the second part of competition (p < 0.05). Urinary incontinence prevalence was 9.87% in physically-active control subjects versus 9.84% in sedentary control subjects (NS). Even a small quantity of urine loss was felt to be embarrassing. Most incontinent women did not dare to speak of their condition to anybody., Conclusions: There is a very high prevalence of urinary incontinence in women athletes. Detailed studies of the patho-physiology of this problem are necessary to formulate preventive recommendations.

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.

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.

Background: The prognostic value of cardiac troponin T (cTn-T) in a mixture of patients with both acute and chronic congestive heart failure (CHF), simultaneously assessed and compared with neurohormonal factors, has not yet been thoroughly evaluated. Thus, we focused on the prognostic value of cTn-T in comparison with atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and plasma norepinephrine (PNE) in this population., Methods: Prognostic correlates of elevation of cTn-T, ANP, BNP, PNE were analyzed in 63 acute and chronic CHF patients followed up to record worsening CHF and cardiac death., Results: cTn-T (> or =0.03 microg/L) was found in 17.4% (11 of 63) of patients. cTn-T correlated with ANP, BNP, PNE. Acute CHF patients were more positive for cTn-T and BNP. In our cohort, neither cTn-T (> or =0.03 microg/L) nor PNE were associated with increased mortality and worsening HF in CHF patients. After adjustment, BNP was the only independent predictor of cardiac events (RR, 3.23; p=0.01)., Conclusions: BNP emerged as the only independent predictor of cardiac events in a mixture of patients with both acute and chronic CHF, suggesting that it is the analyte that best reflects long-term prognosis in a diverse population enrolled to mirror the "real world" situation.

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.

Objectives: To evaluate plasma levels of dehydroepiandrosterone sulphate (DHEAS) in a cohort of HIV-infected patients and to analyse factors associated with DHEAS levels., Methods: We conducted a cross-sectional survey in the Nîmes University Hospital cohort of HIV-infected patients in south-eastern France. All HIV-infected patients with at least one outpatient visit between 1 January and 1 September 2002 were included in the study. Sociodemographic, clinical, therapeutic, immuno-virological and plasma DHEAS level data were collected during this period. Hepatitis C virus (HCV) coinfection was defined as the presence of HCV antibody with positive RNA. To identify factors associated with plasma DHEAS levels, Spearman's rank correlation and univariate and multivariate linear regression analyses were used., Results: The DHEAS plasma level was measured in 137 patients (104 men and 33 women), 37 (27.0%) of whom were HCV coinfected. The median age of the patients was 39.1 years [interquartile range (IQR): 34.9-48.7] for women and 41.8 years (36.5-47.7) for men. The median DHEAS level was 5.5 micromol/L (IQR: 2.3-8.8) for the whole sample of 137 patients, and was lower in women (2.4 micromol/L; 1.5-6.6) than in men (6.1 micromol/L; 2.5-9.0) (P<0.01), and lower in patients coinfected with HCV (2.1 micromol/L; 0.6-6.7) than in those not coinfected (6.6 micromol/L; 3.0-9.1) (P<0.01). Of all prognostic factors studied in the variance covariance analysis, three factors were associated with DHEAS: age, gender and HCV coinfection. Subgroup analysis revealed that the age-adjusted mean of the DHEAS level was lower in HCV coinfected patients for both women (1.3+/-1.1 micromol/L) and men (4.0+/-0.7 micromol/L), compared with patients not HCV coinfected (women, 5.3+/-0.7 micromol/L; men, 7.2+/-0.4 micromol/L) (P<0.01)., Conclusions: This is the first report of the determination of DHEAS plasma levels in HIV/HCV coinfected patients. When age and sex were taken into account, the DHEAS plasma level was found to be significantly lower in HCV coinfected patients. To date, the pathophysiology of such findings is unknown.

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.

Purpose: This study was designed to define the different types of strictures, the factors favoring their occurrence, and their treatment after ileal pouch-anal anastomosis., Methods: Between January 1981 and June 1996, 1,884 ileal pouch-anal anastomoses were constructed at the Mayo Clinic in Rochester, Minnesota. Data were collected prospectively and included age, gender, type of underlying diseases (chronic ulcerative colitis familial adenomatous polyposis), proctologic antecedents, technique of anastomosis, intraoperative difficulties, and postsurgical complications. Strictures were categorized as nonfibrotic and fibrotic on the basis of the presence or absence of a fibrotic segment at the anal canal anastomosis that was responsible for pouch-outlet obstruction requiring at least one dilation., Results: Strictures occurred in 213 patients (11.2 percent; 11 percent for chronic ulcerative colitis and 12 percent for familial adenomatous polyposis; P = not significant). Strictures were nonfibrotic in 86.4 percent of patients and fibrotic in 13.6 percent. A greater number of strictures were observed after a handsewn anastomosis (12 percent) than after a stapled anastomosis (4 percent; P = 0.03). Intraoperative technical difficulties were associated with 13 percent of all strictures regardless of the type of stricture (fibrotic, 7.5 percent; nonfibrotic, 14 percent; P = 0.4). Postoperative complications such as abscess, fistula, and pouch retraction were found in 13 percent of cases and were primarily associated with fibrotic strictures. Treatment included dilation, which was successful in 95 percent of nonfibrotic strictures but in only 45 percent of fibrotic strictures (P = 0.0001). Surgical treatment was required in 25 strictures (12 percent), including excision of the strictured segment with mucosal advancement flap (5 patients), excision of the pouch with permanent ileostomy (9 patients), or redo pouch (3 patients). With one exception, all excised pouches were associated with other perianastomotic complications, such as abscess, fistula, and pouch retraction. The remaining eight patients had other surgical procedures because of abscess (n = 3), division of an obstructive bridge (n = 2), and débridement and curettage of a fistula (n = 3) with dilation for associated strictures., Conclusions: Strictures were observed in 11.2 percent of the patients in this study. Nonfibrotic strictures responded well to anal dilation, whereas fibrotic strictures were more commonly associated with intraoperative or postoperative complications, often necessitated surgical therapy to salvage pouch function, and were eventually responsible for pouch failure in nine patients.

Background and Objectives: The aim of this study was to establish a correlation between a thermal measurement and a magnetic resonance imaging (MRI) signal during laser-induced interstitial thermotherapy (LITT) in liver., Study Design/materials and Methods: Pig liver was irradiated for 15 minutes with a diode laser at two different powers, 0.5 W (450 J) and 1.5 W (1,350 J). Tissue temperature was monitored every 20 seconds using thermocouples. Thermosensitive MRI sequences (T(1)-weighted Turbo-Flash) were acquired with the same irradiation parameters. Correlation between MRI signals (SI) and temperature measures was defined at two different distances from the fiber (5 and 10 mm)., Results: At 0.5 W, temperatures rose progressively up to a maximum increase of 9.5 degrees C at 5 mm and 4 degrees C at 10 mm after 15 minutes. The corresponding MRI signal decreased progressively to -27.6 SI at 5 mm and -18.5 SI at 10 mm. At 1.5 W, temperatures rose dramatically at 5 mm, reaching a plateau. The temperature elevation measured at the end of the irradiation was of 30 degrees C whereas at 10 mm it was only 14.5 degrees C. The MRI signal varied accordingly, remaining inversely proportional to temperature (-76 SI at 5 mm and -35.5 SI at 10 mm)., Conclusions: An inversely proportional relationship was observed between MRI signal in sequential Turbo-Flash and temperature. MRI should allow to analyze heat diffusion in the liver, and thus to monitor real-time LITT treatments., (Copyright 2003 Wiley-Liss, Inc.)

Purpose: Spontaneous blood echogenicity in vein ultrasound images may be a marker for an increased erythrocyte aggregability, but a reliable quantitative evaluation method is a prerequisite for its use in clinical studies. We compared a simple scoring system of blood echogenicity intensity and pattern, with automatic image analysis., Material and Methods: 157 femoral and popliteal vein digitized ultrasound sequences were reviewed by two independent observers who chose an image, delimited an area of interest (ROI), and graded blood echogenicity intensity and pattern, using a four class score. Each observer reviewed the images selected by the other, without and with ROI. The computer calculated first and second order parameters describing echo intensity and spatial organization., Results: Inter-observer reproducibility of subjective assessment was poor (Kappa<0.5), whereas the automatically calculated ROI average gray level intensity relatively to the whole image (tau(1)) effectively separated all grades of intensity. No parameter effectively separated patterns., Conclusion: Tau(1) is a simple parameter for the in vivo evaluation of blood echogenicity intensity. It should be evaluated in standardized conditions for clinical hemorheology studies in correlation with in vitro erythrocyte aggregation measurements.

A prospective, hospital-based, multicenter study was undertaken to identify the reasons for hospital admission, to describe antibiotic treatment before and during hospitalization, and to determine the outcome of community-acquired pneumonia (CAP). Data collected included prehospital management of CAP, Pneumonia Outcome Research Team (PORT) classification on admission, in-hospital antibiotic treatment, and predictors of death within 30 days. Among the 215 patients (mean age, 66.7 years; M:F ratio, 1.1) recruited, 24 (11.2%) were living in nursing homes. CAP had been diagnosed prior to admission in 55 (25.6%) patients. At admission, 75 (34.9%) patients had a low risk of death (PORT classification I-II). A pathogen was isolated for 55 (25.6%) patients, primarily Streptococcus pneumoniae (n=18), atypical agents (n=16), influenza virus (n=10), and respiratory syncytial virus (n=4). Amoxicillin (with or without clavulanate), cefotaxime, or ceftriaxone monotherapy was prescribed to 121 (56.3%) patients. Dual combination therapy was prescribed to patients at higher risk of death (PORT classification III-V; OR, 3.09). Mortality was 7%. Logistic-regression analysis identified nursing-home residency (OR, 8.36), serum creatinine > or =88 micromol/l (OR, 7.88), and Pneumonia Outcome Research Team classification (OR, 1.02) as independent predictors of death. CAP remains a serious disease for elderly persons living in nursing homes. This population should benefit from immunization with pneumococcal and influenza vaccines.

Objective: To investigate the occupational and environmental risk factors related to non-Hodgkin's lymphoma (NHL)., Methods: A case-control study was performed during the 1992-1996 period in Languedoc-Roussillon, southern France. Four hundred and forty-five cases of histologically diagnosed NHL were declared. One thousand and twenty-five randomly selected population controls were interviewed about their medical histories; occupational exposures, such as chemicals, pesticides, and electromagnetic radiation; and toxic habits., Results: The following factors were independently and significantly related to NHL as a result of the multivariate analysis: a previous hematopoietic malignancy (ORa = 11.5, 95% CI 2.4-55.4), a history of hives (ORa = 1.7, 95% CI 1.2-2.2), benzene exposure > 810 days (ORa = 4.6, 95% CI 1.1-19.2), daily welding (ORa = 2.5, 95% CI 1.2-5.0), and activity of radio operator (ORa = 3.1, 95% CI 1.4-6.6). To be an agricultural professional seemed slightly related to NHL in reference to non-professionals (ORa = 1.5, 95% CI 1.0-2.1). All of these results have also been adjusted for age, gender, education level, and urban setting., Conclusions: As some of the reported associations were based on a very small proportion of exposed subjects, further investigations are necessary to confirm our results. However, the findings suggest that factors related to altered immune functions such as a history of hematopoietic malignancy, history of hives, occupational exposure to benzene, or being an agricultural professional might increase the risk of NHL. Currently, underlying mechanisms for these associations are still unclear, and further investigations focused on interactions between immunity alterations and different chemicals would be of great interest.

Objectives: Recording the time at which the insertion of a pulmonary artery catheter was decided., Study Design: Prospective and descriptive study., Patients: Critically ill patients in an university hospital., Methods: The times at which the insertion of a PAC was decided were recorded. For each pulmonary artery catheterization, immediate complications were recorded (arterial puncture, pneumothorax, ventricular arrhythmia, hard and failed pulmonary artery catheterization)., Results: One hundred and forty-nine patients were included (99 males, age = 63 +/- 15 year, body mass index = 25 +/- 6 kg.m-2, median Apache II score = 16). One hundred and sixty-five PAC insertions were decided (16 patients requiring two PACs). Nine arterial punctures, two pneumothoraces, 42 ventricular arrhythmias, 32 hard and eight failed pulmonary artery catheterizations occurred. Thirty-four PAC insertions were decided between 9 and 10 am whereas = 3 PAC insertions per hour were decided between 1 and 9 am., Conclusion: The rate of decision of PAC insertion are decreased during the second half of the night (1 to 9 AM).

From November 1998 to February 1999 we prospectively evaluated the prevalence of resistance to penicillins, cephalosporins, carbapenem, quinolones, aminoglycosides, and trimethoprim-sulfamethoxazole (SXT) in 320 Escherichia coli isolates isolated from hospitalized patients with acute urinary tract infections (UTIs). We also studied for these strains risk factors for resistance to amoxicillin-clavulanic acid (AMC), fluoroquinolones (FQs), and SXT. Resistance rates were consistent with those from major recent studies reported in the literature. Multivariate analyses selected the following factors as being significantly associated with E. coli resistance: (i) for resistance to AMC, prior (1 year) UTI (odds ratio [OR] = 2.71, P = 0.006), prior (1 year) urinary catheter (OR = 2.98, P = 0.0025), and prior (6 months) antibiotic exposure (OR = 2.68, P = 0.005); (ii) for resistance to FQs male sex (OR = 3.87, P = 0.03), with a trend toward significance for age >65 years (OR = 7.67, P = 0.06) and prior (1 year) UTI (OR = 2.98, P = 0.07); and (iii) for resistance to SXT, male sex (OR = 1.91, P = 0.046), hospitalization in an intermediate-term-care unit (OR = 2.18, P = 0.008), and prior (1 year) UTI (OR = 2.03, P = 0.03). Ours results suggest that prior UTI is a common risk factor for resistance to the different antibiotics tested. Although few studies on risk factors for E. coli resistance to antibiotics have been published, careful interpretation of their findings, taking into consideration the population, infection site, and period studied, should contribute to the formulation of a better strategy that can be used to overcome antibiotic resistance.

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.

Unlabelled: We compared the quality of anesthesia provided by mepivacaine 2% or a mixture of lidocaine 2%-bupivacaine 0.5%, both with hyaluronidase, in caruncle single-injection episcleral (sub-Tenon) anesthesia. Sixty patients undergoing cataract surgery were included in this randomized, double-blinded study. The time to the onset of blockade, maximal akinesia, need for supplemental injection, and time to recovery were recorded. With mepivacaine, the time to onset was slightly shorter, and the akinesia score higher, than with the mixture. Although statistically significant, these differences are small. With mepivacaine, the time to recovery was shorter. We conclude that the reproducible short duration of the block may be an advantage in outpatient surgery., Implications: We compared the classic mixture of lidocaine 2% plus bupivacaine 0.5% to mepivacaine 2% for caruncle episcleral (sub-Tenon) anesthesia for cataract surgery. Mepivacaine provided a more efficient block with a quicker onset and a quicker recovery. However, these differences were very small and were of little clinical interest.

Background: Regional anesthesia and especially peribulbar anesthesia commonly is used for cataract surgery. Failure rates and need for reinjection remains high, however, with peribulbar anesthesia. Single-injection high-volume medial canthus episcleral (sub-Tenon's) anesthesia has proven to be an efficient and safe alternative to peribulbar anesthesia., Methods: The authors, in a blind study, compared the effectiveness of both techniques in 66 patients randomly assigned to episcleral anesthesia or single-injection peribulbar anesthesia. Motor blockade (akinesia) was used as the main index of anesthesia effectiveness. It was assessed using an 18-point scale (0-3 for each of the four directions of the gaze, lid opening, and lid closing, the total being from 0 = normal mobility to 18 = no movement at all). This score was compared between the groups 1, 5, 10, and 15 min after injection and at the end of the surgical procedures. Time to onset of the blockade also was compared between the two groups, as was the incidence of incomplete blockade with a need for supplemental injection and the satisfaction of the surgeon, patient, and anesthesiologist., Results: Episcleral anesthesia provided a quicker onset of anesthesia, a better akinesia score, and a lower rate of incomplete blockade necessitating reinjection (0 vs. 39%; P < 0.0001) than peribulbar anesthesia. Even after supplemental injection, peribulbar anesthesia had a lower akinesia score than did episcleral anesthesia. Peribulbar anesthesia began to wear off during surgery, whereas episcleral anesthesia did not., Conclusion: Medial canthus single-injection episcleral anesthesia is a suitable alternative to peribulbar anesthesia. It provides better akinesia, with a quicker onset and more constancy in effectiveness.

Background: Liver iron deposits are frequent in viral C cirrhotic patients but their role is not well defined., Aims: To investigate the effect of liver iron excess on the prevalence of hepatocellular carcinoma (HCC) in patients with viral C cirrhosis., Methods: Hepatic iron was evaluated retrospectively using a semiquantitative method in liver biopsies of 104 viral C cirrhotic patients, 48 with HCC and 56 controls (HCC free). Corrected total iron score (0-60) was defined by the sum of three scores: hepatocytic iron score (0-36), sinusoidal iron score (0-12), and portal iron score (0-12), multiplied by 3/3, 2/3, or 1/3 according to the heterogeneous iron localisation in the nodules., Results: After adjustment for known risk factors for HCC, regression analysis showed that iron deposits (corrected total iron score >0) were more frequent in HCC patients than in controls (odds ratio 4.94; 95% confidence interval 1.59-15. 32; p=0.0056). The median of corrected total iron score was significantly higher in HCC patients than in controls (odds ratio 1. 092; 95% confidence interval 1.01-1.13; p=0.021). This liver iron overload was sinusoidal (odds ratio 5.2; 95% confidence interval 1. 82-15.11; p=0.0022)., Conclusions: Liver iron deposition was more frequent and more important in viral C cirrhotic patients with HCC than in HCC free controls. Liver iron overload seems to contribute to the development of HCC in patients with viral C cirrhosis.

Background: Few experimental studies report effects of direct contusion on cardiac enzyme release. Cardiac troponins I (cTnI) and T (cTnT) have been shown to be highly sensitive and specific markers of myocardial cell injury. This investigation was designed to determine and compare the acute effects of quantified magnitudes of blunt cardiac trauma upon release of cTnI and cTnT in comparison with creatine kinase (CK) and lactate dehydrogenase (LD)., Methods: In 24 rabbit hearts prepared on a standard Langendorff apparatus, myocardial contusion (MC) was produced by a single blow with a ball falling from a predefined height, delivered directly to the surface of the heart. Hearts were divided into control (n = 6) and various quantified impacts: 75 mJoules (mJ) (n = 6), 100 mJ (n = 6), 200 mJ (n = 6). Coronary effluent samples for cTnI, cTnT, CK, and LD were collected at baseline, immediately after MC and 5, 15, 30, 45, and 60 minutes after MC. At the end of experiment, histologic condition was evaluated., Results: The anti-cTnI and cTnT MAbs used in the cTnI (Access) and cTnT (Elecsys) assays cross-react with cTnI and cTnT of the rabbit. The time-courses of cTnI, cTnT, CK, and LD were monophasic in form. After MC, all parameters rose significantly compared with baseline and with control group. The maximal release occurred immediately after MC. The area under the cTnI curve and the maximal cTnI concentration were linked to the contusion energy when increased at 200 mJ. Maximal concentrations and areas under cTnT, CK, LD time activity curve were not linked to the contusion energy level and showed no between-energy group differences. The correlation found between maximal cTnI and maximal cTnT concentrations was 0.70 (p = 0.0001). Histologic examination showed cellular disruption and after the more severe impact, the extent of pathologic changes was more extensive., Conclusion: After graded experimental MC, maximal cTnI concentration and area under cTnI curve increase with the power of impact kinetic energy. Levels of cTnI allow a much higher accuracy in detecting the extent of myocardial injury postMC in comparison with cTnT, CK, and LD in this experimental study. These results should be consistent with the more extensive cTnI release with more severe impact in patients with blunt chest trauma. Furthermore, because specificity and time-course of release, both cTnI and cTnT should have a role in the diagnosis and evaluation of such patients.

Increased plasma and CSF concentrations of substances which bind to brain benzodiazepine receptors have previously been reported in cirrhotic patients with hepatic encephalopathy (HE). However, their relationship to previous intake of pharmaceutical benzodiazepines has not been clearly established. In the present study, plasma levels of benzodiazepine receptor ligands (BZRLs) were measured using a sensitive radioreceptor assay in 12 control subjects with no evidence of hepatic, neurological or psychiatric illness, 11 cirrhotic patients without HE, 24 cirrhotic patients with moderate (grade I-II) HE and in 45 cirrhotic patients with severe (grade II-IV) HE. In addition, CSF concentrations of BZRLs were measured in 8 cirrhotic patients with HE and an equal number of age-matched controls. Recent intake (within 10 days) of pharmaceutical benzodiazepines was assessed by detailed review of medical files, and interviews with the patient, at least one family member as well as the pharmacist. Significantly increased plasma concentrations of BZRLs were observed in cirrhotic patients with severe encephalopathy (p < 0.02) compared to controls and to cirrhotic patients without (or with mild) neurological impairment. Increased plasma BZRLs could be accounted for by prior exposure to benzodiazepine medication in all cases. CSF concentrations of BZRLs in cirrhotic patients were not significantly different from control values. These findings do not support a role for "endogenous" benzodiazepines in the pathogenesis of HE in chronic liver disease but suggest that pharmaceutic benzodiazepines administered to cirrhotic patients as sedatives or as part of endoscopic work-up could have contributed to the neurological impairment in some patients.

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.

It is known that the endocrine system of experimental animals is susceptible to perturbation by radiofrequency (RF) radiation. Because of the recent interest in health and safety issues of cellular telephones, an experiment was designed to evaluate the effect of a 900 MHz RF radiation emitted by a Global System for Mobile radiotelephone (217 Hz impulses, one-eighth duty cycle, 2 W peak power) on human endocrine functions. Twenty healthy male volunteers aged from 19 to 40 were inducted in the present experiment. Each subject was exposed to RF radiation through the use of a cellular phone 2 h/day, 5 days/wk, for 1 month. Subjects were their own control. End points were serum adrenocorticotropin, thyrotropin, growth hormone, prolactin, luteinizing hormone, and follicle stimulating hormone concentrations. These end points were determined in nine weekly blood samples obtained starting 3 weeks before the commencement of the exposure and ending 2 weeks after exposures. All but one blood sample was drawn 48 h after each weekly session. The seventh drawing was performed the morning after the last weekly exposure. Within each individual, the preexposure hormone concentration was used as a control. Results indicated that all hormone concentrations remained within normal physiologic ranges. A difference was not noted among the nine weekly samples in five of six hormones studied. There was a significant change only in thyrotropin concentration, showing a 21% decrease on the seventh sampling. Because this change recovered fully during the postexposure period, it is concluded that 1 month of intermittent exposures to RF radiation from a cellular telephone does not induce a long-lasting or cumulative effect on the hormone secretion rate of the anterior pituitary gland in humans.