[Secondary pulmonary alveolar proteinosis in a transplant patient]. / Protéinose pulmonaire secondaire chez un patient greffé.

INTRODUCTION: Pulmonary alveolar proteinosis (PAP) is a rare disease characterized by alveolar accumulation of lipoproteinaceous material, caused by a macrophagic clearance disorder. We present a case of PAP in a patient taking the immunosuppressant drug mycophenolate mofetil (MMF) in the context of invasive pulmonary aspergillosis, of which we discuss the pathophysiology and treatment as reported in the literature. CASE REPORT: A 43-year-old man with cardiomyopathy received a heart transplant and was treated by MMF, tacrolimus and corticosteroids. Three months after the transplant, he presented with acute oxygen-dependent respiratory failure. The diagnosis of PAP seemed likely on the CT scan and was confirmed by bronchoalveolar lavage, as was the diagnostic of invasive pulmonary aspergillosis (IPA). However, GM-CSF autoantibodies were not found. As there existed a suspicion of MMF imputability, the treatment was discontinued and an antifungal treatment was started. The patient was reassessed one month after discontinuation of MMF and found to have clinically and radiologically improved. Four other cases of MMF-induced PAP have been reported in the literature. CONCLUSIONS: MMF and IPA could be predisposing cofactors for the occurrence of secondary PAP.

Factors associated with pregnancy after in vitro fertilization in infertile patients with posterior deep pelvic endometriosis: A retrospective study.

INTRODUCTION: The management of posterior deep endometriosis is not consensual. This is due to a great heterogeneity of data from the literature. Many series were small and overall, predictors of pregnancy were not all included and analyzed by multivariate analysis. We conducted this study to evaluate the factors associated with pregnancy during the first two in vitro fertilization (IVF) attempts in infertile women with posterior deep endometriosis. MATERIAL AND METHODS: 230 women were included in this retrospective observational study, between January 1st, 2007 and September 30th, 2013, at the University Hospital of Lille. A large set of variables were recorded and their association with the chance of pregnancy was analyzed by multivariate analysis (MVA), including patients' features, endometriosis items, surgery procedures and IVF data. RESULTS: After 2 IVF attempts, 48.7% of the 230 women achieved a pregnancy, including 39.1% of ongoing pregnancies. Logistic regression analysis retained five variables significantly associated to the chance of pregnancy: oocyte retrieval number (OR=0.468 (0.296-0.739) p=0.001), age (OR=0.888 (0.811-0.974) p=0.011), single embryo transfer number (OR=1.494 (1.036-2.153) p=0.031), presence of a recto-uterine nodule (OR=0.454 (0.235-0.877) p=0.019) and IVF technique (OR=0.509 (0.272-0.951) p=0.034). CONCLUSION: The presence of a recto uterine nodule is associated with a lower chance of pregnancy after IVF. It has to be checked by prospective studies whether the finding of a recto-uterine nodule whose pejorative effect has not been reported so far should encourage to perform surgery before IVF in patients with deep endometriosis.

[Hepatitis B and pregnancy. Part 2. Nine practical issues about delivery and neonatal care]. / Hépatite B et grossesse. Partie 2. Neuf questions pratiques concernant l'accouchement et la prise en charge néonatale.

In France, the hepatitis B maternal-fetal transmission prevention strategy is based on serovaccination at birth. Serum therapy is to inject 30IU/kg of anti-HBs specific immunoglobulins of human origin in the first hours of life, which in practice corresponds to 1ml or 100IU. Vaccination should also be performed during the first hours of life, and a new injection should be performed at 1month and 6months. In infants less than 32weeks and/or less than 2kg, lower vaccine response leads to prescribe an additional injection at 2months. This serovaccination reduces the risk of mother to child transmission from 57 to 4 %. The failure risk factors of serovaccination are high maternal viral load (greater than or equal to 7 log) and/or the presence of HBeAg. The delivery route does not change the risk of maternal-fetal transmission of hepatitis B when serovaccination at birth was well conducted. Likewise, breastfeeding does not change the risk of maternal-fetal transmission of hepatitis B after serovaccination. It is recommended by WHO. During labor, the pH in utero should be done only when strictly necessary, the published data do not allow to conclude on the risk of transmission.

[Hepatitis B and pregnancy. Part 1. Thirteen practical issues in antenatal period]. / Hépatite B et grossesse. Partie 1. Treize questions pratiques en période anténatale.

In France, the prevalence of chronic hepatitis B is about 1% in pregnant women (usually asymptomatic carriers of HBsAg). The risk of maternal-fetal transmission of hepatitis B is particularly high when viral load measured by PCR is higher in mothers (above 7 log) or HBeAg is present. In case of maternal-fetal transmission of hepatitis B, the risk to the newborn of developing subsequent chronic hepatitis B is very high (90%), with long-term complications such as cirrhosis and hepatocellular carcinoma. The prevention of maternal-fetal transmission is based on systematic testing for hepatitis B during pregnancy, followed by serovaccination of the newborn at birth. If necessary, amniocentesis can be realised but will avoid the realization of a transplacental gesture. In case of high viral load, the establishment of a maternal antiviral treatment with lamivudine or tenofovir from 28SA can further reduce the risk of transmission. Given the low resistance it induces, tenofovir should be used preferentially.

Management of glioblastoma: comparison of clinical practices and cost-effectiveness in two cohorts of patients (2008 versus 2004) diagnosed in a French university hospital.

WHAT IS KNOWN AND OBJECTIVE: Therapeutic options for the management of glioblastoma (GBM) have greatly evolved over the last decade with the emergence of new regimens combining radiotherapy plus temozolomide and the use of bevacizumab at recurrence. Our aim was to assess the clinical and economic impacts of those novel strategies in our center. METHODS: A single-center retrospective chart review was conducted on patients newly diagnosed with a GBM over two periods (year 2004, group 1 or year 2008, group 2) with limitations to those eligible to radiotherapy after initial diagnosis. The type of medical management was described and compared, as well as overall survival and total costs from diagnosis to death or the last follow-up date. Cost analysis was performed under the French Sickness Fund perspective using tariffs from 2012. RESULTS: One hundred twenty-two patients were selected (49 in group 1 and 73 in group 2) with similar baseline characteristics within the two groups. Patients from group 2 received more frequently temozolomide radiochemotherapy (71% vs. 39%, P < 0·05) as first-line treatment as well as bevacizumab regimen at recurrence (48% vs. 6%, P < 0·05); the median overall survival was increased between the two periods (respectively 17 vs. 10 months, P < 0·05). The mean total cost per patient was 54,388 € in group 1 and 71,148 € in group 2 (P < 0·05). Hospital care represented the largest expenditure (76% and 58% in groups 1 and 2 respectively) followed by chemotherapy drugs costs (11% and 30% respectively). The total cost difference between the two groups was explained by the increasing use of temozolomide and bevacizumab. The incremental cost-effectiveness ratio was estimated at 54,355 € per life-year gained. WHAT IS NEW AND CONCLUSION: As far as we know, this is the first study reporting the total cost of GBM management based on the French perspective, as well as the cost-effectiveness of clinical practices in term of cost per life-year gained. Those novel strategies have contributed to improve overall survival while inducing a substantial, but acceptable, increase of total costs.

Short communication: Feed iodine concentrations on farms with contrasting levels of iodine in milk.

In a previous study, milk iodine concentration from 501 farms across Canada was found to vary considerably and appeared to be influenced by feeding practices. Farms with contrasting levels of milk iodine from a subset of 200 participating farms were used to determine the relationship between milk iodine concentration and the concentration of this mineral in different feeds and complete diets given to lactating dairy cows. The 30 farms with the lowest levels of iodine in milk (low group) and the 30 farms with the highest levels (high group) were selected. Samples of bulk tank milk, all feed ingredients, and water were collected. Additionally, each farmer completed a questionnaire providing information on feeding management. The iodine offered on each of the farms was estimated from the amount of the feed in the diet recommended by the Ration'L software (Valacta, Ste-Anne-de-Bellevue, QC, Canada) and the iodine concentration in the feed sampled and analyzed using inductively coupled plasma mass spectrometry. The dietary concentration of iodine offered daily was 33% lower for the low group compared with the high group; that is, 1.20±0.099 versus 1.81±0.195 mg/kg of dry matter (DM), respectively. Milk iodine concentrations averaged 146±13.9 µg/kg for the low group and 487±44.6 µg/kg for the high group. A linear relationship was found between dietary iodine concentration and milk iodine level, as follows: milk iodine (µg/kg)=145 (±66.9)+113 (±39.4) dietary iodine concentration (mg/kg DM). However, the low R(2) value (0.15) indicates that other factors, such as milking management and the presence of goitrogens, may have affected the concentrations of iodine in milk. Forages supplied approximately 17% of iodine requirements in the average lactating cow diet. Therefore, variations in the iodine content of forages are unlikely to cause iodine overfeeding. In contrast, 27% of the mineral mix samples presented iodine concentrations >100,000 µg/kg of DM (and up to 322,000 µg/kg of DM). More than 85% of the farms tested were feeding iodine levels higher than the dietary iodine recommendations (0.5 mg of iodine/kg of DM). Iodine supplements should be used with caution in lactating cow diets.

Iodine concentration in milk sampled from Canadian farms.

A study was conducted to determine the iodine concentration in milk and the relationship between that concentration and milking and feeding management practices. Milk samples were collected from the bulk tanks of 501 farms in all provinces of Canada. With a view to obtaining further information about farm management, a questionnaire was completed at each of the selected farms. Total iodine concentration (organic and inorganic) in the milk was determined using inductively coupled plasma mass spectrometry. The farms were grouped for each of the variables and, based on significant differences in iodine concentrations, 15 variables were selected for further analysis. A general linear model was fitted, with milk iodine as the response variable to main and two-way interaction effects. The mean iodine concentration in Canadian milk was 304 ± 8.4 µg/kg, with concentrations ranging from 54 to 1,902 µg/kg. Analysis of the questionnaire data suggested that component feeding was associated with lower iodine levels in milk than the levels obtained with total mixed rations. Neither the use of mineral supplementation nor the form of supplementation affected iodine levels in milk. Washing and dipping the teats before milking affected iodine in milk. The method of application of the teat sanitizers appears to be important, given that spray applications (inline or hand spraying) were associated with higher levels than those observed with the dip-cup procedure. In conclusion, Canadian milk iodine concentration varies considerably and appears to be influenced by feeding and milking practices.

[Cyclosporin-induced toxic neuromyopathy]. / Neuromyopathie toxique induite par la ciclosporine.

INTRODUCTION: Cyclosporine is an immunosuppressive treatment whose side effects limit its usefulness. Among neurological side effects, neuropathies or myopathies have been reported, specially inpatients given combinations of cyclosporine with co-enzyme A reductase inhibitors. CASE REPORT: We report here the case of a 67-year-old woman who developed few months after a kidney graft sensorimotor disorders which progressed rapidly. Since all etiologies of such a disorder were ruled out, the hypothesis of toxicity exclusively induced by cyclosporine was suggested and confirmed by the improvement observed after its withdrawal. CONCLUSION: This observation highlights the fact that cyclosporine may induce neuromyopathies even when given alone at the therapeutic dosage.

[Role of high-dose chemotherapy with hemopoietic stem-cell support in the treatment of adult patients with high-grade glioma]. / Place de la chimiothérapie intensive avec autogreffe de cellules souches hématopoïétiques dans le traitement des tumeurs gliales de haut grade chez l'adulte.

Despite surgery, post-operative irradiation and adjuvant conventional chemotherapy, prognosis of high-grade gliomas remains poor. Carmustine (BCNU) has been shown to have limited activity at conventional dosage but is still the standard chemotherapy. Activity of chemotherapy is limited by the blood-brain barrier impermeability and high levels of expression of multidrug resistance proteins on tumor and/or endothelial cells. Despite high response rates, development of intra-arterial chemotherapy remains limited because of frequent acute brain toxicity related to drug administration. High-dose intravenous chemotherapy rescued by autologous hemopoietic stem cell transplantation is an alternative that might increase drug delivery through the blood-brain barrier and tumor control. Several phase I-II trials using high-dose BCNU were published. The maximum tolerated dose seems to be 800 mg/m2 and interstitial pneumonitis and hepatitis are dose-limiting toxicities. Few phase I-II trials of high-dose therapy were published using drug combinations. High response rates in patients with progressive tumor were observed and in adjuvant setting, encouraging results in terms of median survival time and long survivors were published. No phase III trial was reported to date. Future investigations should include randomized trials comparing high-dose and conventional-dose chemotherapy and development of new high-dose regimens that incorporate new drugs such as temozolomide.

Evaluation of an SOS-Chromotest-based approach for the isolation and detection of sediment-associated genotoxins.

A series of experiments was conducted to evaluate an approach advanced by the St. Lawrence Centre (SLC) of Environment Canada for assessing the genotoxic potential of sediments. The SLC method entails the extraction, isolation and solvent exchange of the organic constituents in sediment, and the testing of these solubilized extracts with the SOS Chromotest (Escherichia coli PQ37). A total of five sediments, three variously contaminated by organic compounds and two reference materials certified for persistent organic chemicals, were Soxhlet-extracted. Each of the five extracts was then split, with a portion remaining in crude form and another portion fractionated into two molecular-weight classes of organic contaminants, thus yielding a total of 15 extract samples. The ability of the SOS Chromotest to detect genotoxins in the various organic extracts was evaluated and compared with that of the Ames Fluctuation Assay (Salmonella typhimurium, strain TA100). The intra-laboratory variance associated with the SOS Chromotest was also assessed. Procedural details are presented and results are discussed. The SOS Chromotest results were in good agreement with those of the Ames Fluctuation Assay, especially after metabolic activation. However, the E. coli PQ37 system was slightly more sensitive than the Salmonella assay for detecting genotoxins in the sediment extracts. The SOS Chromotest was also the most discriminating of the two assays, generating SOS-induction factors that were consistent with the organic contamination gradient reported in the sediment samples. The removal of macromolecules from the dichloromethane extracts by size-exclusion chromatography prior to testing enhanced the sensitivity of both test systems. The intra-laboratory variance of the SOS Chromotest ranged from 0.24% to 23.82%, depending on the extract sample. As applied in this study, the SOS Chromotest can serve as a sensitive test for screening the genotoxic potential of uncharacterized sediment extracts. A more sensitive assay would be appropriate, however, as a confirmation for definitive investigations, especially for the detection of direct-acting genotoxins.

[Amyotrophic lateral sclerosis manifesting as cognitive disorders. Value of brain perfusion scintigraphic tomography in intensive care]. / Sclérose latérale amyotrophique révélée par des troubles cognitifs. Intérêt de la tomoscintigraphie de perfusion cérébrale en réanimation.

BACKGROUND: Cognitive disorders have been described in amyotrophic lateral sclerosis, but usually after the diagnosis has ben established. CASE REPORT: A 57-year-old man was intubated for acute respiratory distress subsequent to pneumonia and diaphragm palsy. He had a 2-year history of drug-resistant depression and deterioration of cognitive functions. A pyramidal syndrome associated with biopsy-proven chronic neurogenic atrophy led to the diagnosis of amyotrophic lateral sclerosis. The electromyogram did not contribute to diagnosis. Brain MRI only evidenced moderate bilateral frontal-temporal atrophy. Brain SPECT demonstrated major perfusion defects in the frontal lobes. DISCUSSION: This patient had amyotrophic lateral sclerosis and frontal-temporal dementia with an unusually late onset clinical presentation: cognitive disorder was the inaugural sign. Brain SPECT and muscle biopsy enabled us to identify the cortical and peripheral motor neurone involvement in this uncooperative intensive care patient totally dependent on mechanical ventilation.

Toxicity evaluation of organic sediment extracts resolved by size exclusion chromatography using rainbow trout hepatocytes.

The (geno)toxicity of sediment dichloromethane extracts and fractions obtained by size exclusion chromatography were evaluated to investigate effects based on size fractionation. In this study, three sediments were selected according to their incremental contamination in PAHs and in PCBs: Hamilton harbour, Toronto bay and lake St. Clair sediments. Heavy metals, total sulfur and elemental sulfur (S8) were also determined in the (un)fractionated sediment extracts. The liver cells were exposed to concentrations of sediment extracts and fractionated samples for 24 h at 15 degrees C, afterwhich cell viability, cytochrome P4501A1 activity, available free Zn, DNA damage and oxidative stress were determined. The results showed that the sediment extracts contained high levels of sulfur most of which was found in the low molecular weight (LMW) region, i.e., the 2000-50 atomic mass unit (amu) fraction. Elemental sulfur (S8) accounted for 14-41% of extractable sulfur and were found to elute in the post-column volume (PCV) fraction despite its molecular weight of 256 amu. Heavy metals were found mainly in the HMW (i.e. the > 2000 amu) fraction and LMW fractions and very few or none were observed in the PCV fractions. In sediment extracts, sublethal effects were present principally by the HMW and LMW fractions suggesting that some chemicals were also associated with high molecular weight compounds of extractable organic matter. Less toxicity or effect was sometimes found in the extract indicating an antagonistic effect of the contaminants. We found that cell viability and genotoxicity evaluations could be performed on the unfractionated extracts while EROD, available Zn and oxidative stress measurements should be performed on the LMW fractions because of possible antagonist or shielding effects. Considering the cytotoxic responses, the best toxicity ranking in respect to contaminant levels in sediment extract was obtained with the LMW and PCV fractions which accounted for most of the toxic responses in the chromatographic fractions. Moreover, the shielding effect could be explained, in part, by the association of LMW contaminants to large macromolecules.

[An unusual variant of urothelial carcinoma: the "nested variant of urothelial carcinoma." Report of two cases]. / Une variante particulière de carcinome urothélial: le "nested variant of urothelial carcinoma". A propos de deux cas.

We report two cases of a poorly known variant of transitional cell carcinoma, the "nested variant of urothelial carcinoma". This tumor is composed of small islands or nests of transitional cells, presenting little atypia and mimicking von Brünn's nests. This low grade tumoral variant seems to behave as a high grade tumor of the same stage. Deep biopsies are necessary to display tumoral invasion, which allows the diagnosis. Importance of the knowledge of this entity is highlighted in order to avoid misdiagnoses that could delay appropriate therapy.

Pathology of the central nervous system in Chester-Erdheim disease: report of three cases.

Chester-Erdheim disease is a rare form of non-Langerhans cell histiocytosis consisting of disseminated xanthogranulomatous infiltration and fibrosis that primarily involves the bones, visceral organs and systemic fatty spaces. Involvement of the central nervous system is variable, and neuropathological features have seldom been documented. We report the neuropathological findings in 3 autopsy cases. One patient had radiological and pathological bone changes characteristic of Chester-Erdheim disease. Neuropathology revealed multiple characteristic xanthogranulomas disseminated in the cerebral hemispheres, hypothalamus, cerebellum, and brainstem. The second patient presented first with cutaneous lesions characteristic of Langerhans cell histiocytosis. She subsequently developed bone abnormalities suggestive of Chester-Erdheim disease, which was confirmed by autopsy, raising the possibility of a common spectrum of histiocytosis including both diseases. Gross examination of the brain was normal, however, microscopy showed infiltration of the brain by characteristic non-Langerhans cell xanthogranulomas. The third patient presented with systemic features characteristic of Chester-Erdheim disease. Neurological signs included gait disturbance, seizures and confusion. Examination of the brain did not show any histiocytic infiltration, but did show changes suggestive of Hallervorden-Spatz syndrome. Association of Chester-Erdheim disease and Hallervorden-Spatz syndrome has not been previously reported. The relationship between both conditions is unclear.

Traumatismo abdominal en niños / Abdominal trauma in children

Se realizó una investigación sobre 171 casos de pacientes ingresados con el diagnóstico de Traumatismo Abdominal, entre el primero de enero de 1988 y el 31 de diciembre de 1994. Se encontró que ocurría una mayor incidencia en los varones escolares procedentes del medio urbano. Con una prevalencia anual casi invariable dentro del rango aproximado de los 24 casos. El promedio de estadía por hospitalización fue de 8,3 días. En 95 por ciento de los casos la evolución fue satisfactoria y solo 5 por ciento de Mortalidad. Los pacientes fueron diagnósticados al ingreso de acuerdo a su estado clínico y tratados médicamente casi todos hasta lograr su estabilización hemodinámica, en solo 70 casos (40 por ciento) estuvo indicada la laparotomía exploradora. Los casos que requirieron intervenciones quirúrgicas se les realizó la reparación de los órganos lesionados adoptando diferentes conductas de acuerdo al órgano y al tipo de lesión. En 19 casos surgieron complicaciones postoperatorias las cuales fueron resueltas satisfactoriamente

Cardiotonic agents. Synthesis and cardiovascular properties of novel 2-arylbenzimidazoles and azabenzimidazoles.

Novel 2-arylbenzimidazoles and azabenzimidazoles were synthesized, and their inotropic action was evaluated. Changes in left ventricular pressure, dP/dt max, were measured as an index of cardiac contractility. The structural features that impart optimal inotropic activity are presented. The most potent compounds were evaluated orally in conscious dogs with implanted Konigsberg pressure transducers. To investigate the mechanism of action, the most potent compounds were tested for their calcium-sensitizing properties and their potential for the inhibition of phosphodiesterase. Two compounds, 1 and 41, showed interesting in vitro and oral activity without side effects. They have a more potent calcium-sensitizing effect than MCI-154 and are under further investigation.