Dietary supplementation of vitamin D3 and calcium partially recover the compromised time budget and circadian rhythm of lying behavior in lactating cows under heat stress.

Heat stress (HS) impedes cattle behavior and performance and is an animal comfort and welfare issue. The objective of this study was to characterize the time budget and circadian rhythm of lying behavior in dairy cows during HS and to assess the effect of dietary supplementation of vitamin D3 and Ca. Twelve multiparous Holstein cows (42.2 ± 5.6 kg milk/d; 83 ± 27 d in milk) housed in tiestalls were used in a split-plot design with the concentration of dietary vitamin E and Se as main plots (LESe: 11.1 IU/kg and 0.55 mg/kg, and HESe: 223 IU/kg and 1.8 mg/kg, respectively). Within each plot cows were randomly assigned to (1) HS with low concentrations of vitamin D3 and Ca (HS, 1,012 IU/kg and 0.73%, respectively), (2) HS with high concentrations of vitamin D3 and Ca (HS+D3/Ca; 3,764 IU/kg and 0.97%, respectively), or (3) thermoneutral pair-fed (TNPF) with low concentrations of vitamin D3 and Ca (1,012 IU/kg and 0.73%, respectively) in a Latin square design with 14-d periods and 7-d washouts. Lying behavior was measured with HOBO Loggers in 15-min intervals. Overall, cows in HS spent less time lying per day relative to TNPF from d 7 to 14. Daily lying time was positively correlated with milk yield, energy-corrected milk yield, and feed efficiency, and was negatively correlated with rectal temperature, respiratory rate, fecal calprotectin, tumor necrosis factor-α, and C-reactive protein. A treatment by time interaction was observed for lying behavior: the time spent lying was lesser for cows in HS than in TNPF in the early morning (0000-0600 h) and in the night (1800-2400 h). The circadian rhythm of lying behavior was characterized by fitting a cosine function of time into linear mixed model. Daily rhythmicity of lying was detected for cows in TNPF and HS+D3/Ca, whereas only a tendency in HS cows was observed. Cows in TNPF had the highest mesor (the average level of diurnal fluctuations; 34.2 min/h) and amplitude (the distance between the peak and mesor; 17.9 min/h). Both the mesor and amplitude were higher in HS+D3/Ca relative to HS (26.6 vs. 25.2 min/h and 3.91 min/h vs. 2.18 min/h, respectively). The acrophase (time of the peak) of lying time in TNPF, HS, and HS+D3/Ca were 0028, 0152, and 0054 h, respectively. Lastly, a continuous increase in daily lying time in TNPF was observed during the first 4 d of the experimental period in which DMI was gradually restricted, suggesting that intake restrictions may shift feeding behavior and introduce biases in the behavior of animals. In conclusion, lying behavior was compromised in dairy cows under HS, characterizing reduced daily lying time and disrupted circadian rhythms, and the compromised lying behavior can be partially restored by supplementation of vitamin D3 and Ca. Further research may be required for a more suitable model to study behavior of cows under HS.

A Multicenter Case-control Study of the Effect of Acute Rejection and Cytomegalovirus Infection on Pneumocystis Pneumonia in Solid Organ Transplant Recipients.

BACKGROUND: Pneumocystis pneumonia (PCP) is associated with morbidity and mortality in solid organ transplant (SOT) recipients. In this case-control study, we determined the association between posttransplant PCP and 3 variables: cytomegalovirus (CMV) infection, allograft rejection, and prophylaxis. METHODS: Eight transplant centers participated. For each case (SOT recipient with PCP), 3-5 controls (SOT recipients without PCP) were included. Controls were matched to the cases based on transplant center, type of allograft, and date of transplantation (±6 months). RESULTS: We enrolled 53 cases and 209 controls. Transplant types included kidney (n = 198), heart (n = 30), liver (n = 15), kidney-pancreas (n = 14), and lung (n = 5). PCP occurred beyond 12 months after transplantation in 43 (81.1%) cases. Thirty-four cases (64.1%) required admission to the intensive care unit, and 28 (52.8%) had mechanical ventilation. Allograft failure occurred in 20 (37.7%) cases, and 14 (26.9%) died. No patient developed PCP prophylaxis breakthrough. The proportion of female sex (P = .009), kidney dysfunction (P = .001), cardiac diseases (P = .005), diabetes mellitus (P = .03), allograft rejection (P = .001), CMV infection (P = .001), and severe lymphopenia (P = .001) were significantly higher in cases. In the logistic regression model, CMV infection (adjusted odds ratio [aOR], 4.6 [95% confidence interval {CI}, 2.0-10.5]) and allograft rejection (aOR, 3.0 [95% CI, 1.5-6.1]) significantly increased the likelihood of PCP. CONCLUSIONS: PCP was mostly a late-onset disease occurring after complete course of prophylaxis, particularly among patients with CMV infection or allograft rejection. PCP is associated with significant allograft loss. Extended prophylaxis targeting recipients with allograft rejection or CMV infection may reduce the risk of PCP.

Suppressive antibiotic therapy with oral tetracyclines for prosthetic joint infections: a retrospective study of 78 patients.

PURPOSE: This study aimed at describing the use of oral cyclines (i.e., doxycycline and minocycline) as suppressive antibiotic therapy (SAT) in patients with periprosthetic joint infections (PJIs). METHODS: Medical charts of all patients with surgical revisions for PJIs who were given cycline-based SAT because of a high failure of various origins were reviewed. Data regarding tolerability and effectiveness of cycline-based SAT were analysed. RESULTS: Seventy-eight patients of mean age 64 ± 17 years received cycline-base SAT in the period from January 2006 to January 2014. PJIs involved the knee in 37 patients (47%), the hip in 35 (45%), the elbow in 4 (5%), and the shoulder in 2 (3%) and were qualified as early in 31 patients (39.7%). Staphylococcus spp. were the most common pathogens accounting for 72.1% of the total number of bacterial strains identified. All included patients had surgery which consisted in debridement and implant retention in 59 of them (75.6%). Doxycycline and minocycline were prescribed as SAT in 72 (92%) and 6 (8%) patients, respectively. Adverse events were reported in 14 patients (18%), leading to SAT discontinuation in 6 of them (8%). After a mean follow-up of 1020 ± 597 days, a total of 22 (28.2%) patients had failed including 3 cases (3.8%) with documented acquisition of tetracycline resistance in initial pathogen(s). CONCLUSIONS: Our results suggest that oral cyclines used as SAT in patients treated for PJI have an acceptable tolerability and effectiveness and appear to be a reasonable option in this setting.

But other than mesothelioma? An estimate of the proportion of work-related cancers in Quebec.

BACKGROUND: More than 30 exposures in the workplace are proven carcinogens. In the present study, we aimed to estimate the burden of occupational cancer in Quebec so as to increase awareness among stakeholders and to prioritize research activities. METHODS: Work-attributable fractions-that is, the proportions of cancers attributable to work-as published in Finland and the United Kingdom were applied to Quebec 2002-2006 cancer incidence and mortality data to estimate the number of work-related cases for 28 cancer sites. RESULTS: Overall, 6.0% of incident cancers (men: 9.1%; women: 2.7%) and 7.6% of cancer deaths (men: 11.8%; women: 2.8%) could be attributable to work, resulting annually in an average of 2160 new cancer diagnoses and 1190 cancer deaths in Quebec. Incident cancers of the lung, prostate, skin, bladder, and (female) breast were the most numerous; cancer sites resulting in more deaths were lung, (female) breast, and pleura. During the same period, compensation statistics reported annual averages of 94.3 incident cancers and 61.9 cancer deaths, mostly involving mesothelioma (64% of compensated incident cancers) and lung cancer (30% of compensated incident cancers). CONCLUSIONS: Increased recognition of workplace cancers by all stakeholders, from workers and employers to treating physicians, will foster appropriate preventive measures for safer workplaces.

LANDSCAPE CHANGES IN A LOWLAND IN BENIN: ECOLOGICAL IMPACT ON PESTS AND NATURAL ENEMIES.

Habitat management involving conservative biological control could be a good crop pest management option in poor African countries. A survey was conducted from August 2013 to July 2014 in a rainfed lowland region near Pélébina, northern Benin, in order to characterize spatiotemporal landscape changes and investigate their influence on the main crop pests and their associated natural enemies. The area was mapped mainly regarding crop fields and fallows. Visual observations were recorded and a database was compiled. Major landscape composition changes were noted between rainy and dry seasons, which affected the presence of both pests and natural enemies. Cereals (rice, maize and sorghum) and cotton were grown in the humid season, and then okra (Abelmoschus esculentus) was the dominant vegetable crop in dry season. These modifications impacted fallow abundance throughout the lowland. Different cotton (e.g. Helicoverpa armigera, Dysdercus sp., Zonocerus variegatus) or rice (e.g. Diopsis longicornis, D. apicalis) pests were observed during dry season in okra crops. Dry season surveys of Poaceae in two types of fallows ('humid', 'dry') revealed the presence of very few stem borers: only 0.04% of stems sampled were infested by stem borers, with a mean of 1.13 larvae per stem. Known cereal stem borer species such as Busseola fusco, Coniesta ignefusalis, Sesamia calamistis were not clearly identified among these larvae because of their diapausing stage and white color. Unexpected pollinators (Hymenoptera Apidae, genus Braunsapis, Ceratina and Xylocopa) and predators (Crabronidae, genus Dasyproctus) were found in the stems. Sweep-net collection of insects in humid fallows allowed us to describe for the first time in Benin seven Diopsidae species (23% of adults bearing Laboulbeniomycetes ectoparasitic fungi). Some of these species were captured in rice fields during rainy season. Parasitoids (adult Chalcidoidae and Ichneumonoidae) were observed during both seasons but their impact on stem borers was hard to determine, even during the rainy season, due to their low abundance and the difficulty of identification. Predators (Reduviidae, Odonata) were found mainly in humid fallows and rice fields. Regarding our observations, we suggest the presence of alternate host crops such as okra during the dry season for rainy season crop pests. Moreover, fallows also had a real ecological role as a habitat resource for many guilds of insects (pollinators, pests, predators). The management of these landscape components should be the focus of a long-term study with the aim of enhancing pest management of rainy season crop pests.

Telesonography: virtual 3D image processing of remotely acquired abdominal, vascular, and fetal sonograms.

PURPOSE: To design and test a new telesonography technique using remote volume acquisition by untrained operators in locations without access to trained sonographers, postprocessing, and interpretation done at expert centers. MATERIALS AND METHODS: The technique was tested with 84 sonograms of organs acquired in pregnant women (n = 8) and patients with various abdominal pathologic conditions (n = 11) located in French Guyana (France), Ceuta (Spain), and Murighiol (Romania). An operator inexperienced in sonography (US) placed the transducer over the predetermined acoustic window for each organ, then swept it from a -45° to a +45° position to scan the targeted organ. The acquired volume dataset was sent to an expert center via the Internet and reconstructed using a proprietary software, which allowed a trained sonographer to navigate through the appropriately reconstructed sonograms. RESULTS: After three-dimensional processing at the expert center, the organs scanned in the obstetrical cases were adequately visualized by the expert in seven of eight (88%) examinations of the fetal head, femur, and umbilical cord and eight of eight (100%) examinations of the fetal abdomen and placenta, whereas in the general abdominal cases, the liver, gallbladder, portal vein, and right kidney were correctly visualized in 10 of 11 (91%) examinations. CONCLUSIONS: Telesonography allowed untrained operators to scan and transfer the US volume datasets over the Internet to an expert center where an expert sonographer could navigate through the reconstructed US volume and visualize sonograms of diagnostic quality.

Early Transmural Response Assessed Using Magnetic Resonance Imaging Could Predict Sustained Clinical Remission and Prevent Bowel Damage in Patients with Crohn's Disease Treated with Anti-Tumour Necrosis Factor Therapy.

BACKGROUND: Magnetic resonance imaging [MRI] is a promising tool to evaluate therapeutic efficacy in ileocolonic Crohn's disease [CD]. AIMS: We aimed to assess the feasibility of early MRI evaluation (week 12 [W12]) to predict corticosteroid-free remission [CFREM] at W52 and prevent long-term bowel damage. METHODS: All patients with active CD needing anti-tumour necrosis factor [anti-TNF] therapy were consecutively enrolled in this multicentre prospective study. MRI was performed before starting therapy, at W12 and W52. CFREM was defined as Crohn's Disease Activity Index < 150, C-reactive protein < 5 mg/L and faecal calprotectin < 250 µg/g, with no switch of anti-TNF agents, no bowel resection and no therapeutic intensification between W12 and W52. RESULTS: Among 46 patients, 22 [47.8%] achieved CFREM at W52. Anti-TNF agents were able to heal almost all CD lesions as soon as W12 [p < 0.05]. Early transmural response defined as a 25% decrease of either Clermont score (odds ratio [OR] = 7.7 [1.7-34.0], p < 0.001) or Magnetic Resonance Index of Activity (OR = 4.2 [1.3-13.3], p = 0.015) was predictive of CFREM at W52. Achieving at least two items on W12-MRI among ulceration healing, disappearance of enlarged lymph nodes or sclerolipomatosis, ΔADC [apparent diffusion coefficient] > +10% or ΔRCE [relative contrast enhancement] > -30% was associated with a likelihood of CFREM at W52 of 84.6% vs 37.5% in patients without transmural response [p < 0.001]. Early transmural response could prevent bowel damage progression over time using Clermont score (hazard ratio = 0.21 [0.0-0.9]; p = 0.037). CONCLUSION: Evaluation of early transmural response by MRI is feasible and is a promising end point to monitor therapeutic efficacy in patients with CD.

Heterozygous neuregulin 1 mice display greater baseline and Delta(9)-tetrahydrocannabinol-induced c-Fos expression.

Cannabis use may increase the risk of developing schizophrenia by precipitating the disorder in genetically vulnerable individuals. Neuregulin 1 (NRG1) is a schizophrenia susceptibility gene and mutant mice heterozygous for the transmembrane domain of this gene (Nrg1 HET mice) exhibit a schizophrenia-related phenotype. We have recently shown that Nrg1 HET mice are more sensitive to the behavioral effects of the main psychoactive constituent of cannabis, Delta(9)-tetrahydrocannabinol (THC). In the present study, we examined the effects of THC (10 mg/kg i.p.) on neuronal activity in Nrg1 HET mice and wild type-like (WT) mice using c-Fos immunohistochemistry. In the lateral septum, THC selectively increased c-Fos expression in Nrg1 HET mice with no corresponding effect being observed in WT mice. In addition, THC promoted a greater increase in c-Fos expression in Nrg1 HET mice than WT mice in the central nucleus of the amygdala, the bed nucleus of the stria terminalis and the paraventricular nucleus of the hypothalamus. Consistent with Nrg1 HET mice exhibiting a schizophrenia-related phenotype, these mice expressed greater drug-free levels of c-Fos in two regions thought to be involved in schizophrenia, the shell of the nucleus accumbens and the lateral septum. Interestingly, the effects of genotype on c-Fos expression, drug-free or following THC exposure, were only observed when animals experienced behavioral testing prior to perfusion. This suggests an interaction with stress was necessary for the promotion of these effects. These data provide neurobiological correlates for the enhanced behavioral sensitivity of Nrg1 HET mice to THC and reinforce the existence of cannabinoid-neuregulin 1 interactions in the CNS. This research may enhance our understanding of how genetic factors increase individual vulnerability to schizophrenia and cannabis-induced psychosis.

Heterozygous neuregulin 1 mice are more sensitive to the behavioural effects of Delta9-tetrahydrocannabinol.

RATIONALE: Cannabis use may precipitate schizophrenia especially if the individual has a genetic vulnerability to this mental disorder. Human and animal research indicates that neuregulin 1 (Nrg1) is a susceptibility gene for schizophrenia. OBJECTIVES: The aim of this study was to investigate whether dysfunction in the Nrg1 gene modulates the behavioural effects of Delta(9)-tetrahydrocannabinol (THC), the major psychotropic component of cannabis. MATERIALS AND METHODS: Heterozygous Nrg1 transmembrane-domain knockout mice (Nrg1 HET) were treated with acute THC (0, 5 or 10 mg/kg i.p.) 30 min before being tested using open field (OF), hole board (HB), light-dark (LD), elevated plus maze (EPM), social interaction (SI) and prepulse inhibition (PPI) tests. RESULTS: Nrg1 HET mice showed differences in baseline behaviour with regard to locomotor activity, exploration and anxiety. More importantly, they were more sensitive to the locomotor suppressant actions of THC compared to wild type-like (WT) mice. In addition, Nrg1 HET mice expressed a greater THC-induced enhancement in % PPI than WT mice. The effects of THC on anxiety-related behaviour were task-dependent, with Nrg1 HET mice being more susceptible than WT mice to the anxiogenic effects of THC in LD, but not in the EPM, SI and OF tests. CONCLUSIONS: Nrg1 HET mice were more sensitive to the acute effects of THC in an array of different behaviours including those that model symptoms of schizophrenia. It appears that variation in the schizophrenia-related neuregulin 1 gene alters the sensitivity to the behavioural effects of cannabinoids.

Study of the antimicrobial and antifouling properties of different oxide surfaces.

Membrane separation processes find applications in an array of fields as they use far less energy and chemical agents than competing processes. However, a major drawback of membrane technology is that biofilm formation alters membrane performances. Preventing biofilm formation is thus a pivotal challenge for larger-scale development of membrane processes. Here, we studied the comparative antibacterial activities of different inorganic membranes (ceramic and zeolite-coated ceramic with or without copper exchange) using several bacterial strains (Escherichia coli, Staphylococcus aureus, and Bacillus subtilis). In static conditions, alumina plates coated with Cu-exchanged zeolite showed significant bactericidal activity. In dynamic mode (circulation of a contaminated nutrient medium), there was no observable bacterial adhesion at the surface of the Cu-exchanged material. These results confirm the antifouling properties of the Cu-mordenite layer due to both the increased hydrophilicity and antibacterial properties of the active layer.Tests performed with tubular filtration membranes (without copper exchange) showed a significant decline in membrane hydraulic properties during filtration of culture media containing bacteria, whereas copper-exchanged membranes showed no decline in hydraulic permeability. Filtration tests performed with concentrated culture media containing spores of B. subtilis led to a significant decrease in membrane hydraulic permeabilities (but less so with Cu-exchanged membranes). The surfaces showed less effective global antifouling properties during the filtration of a concentrated culture medium due to competition between bacterial growth and the bactericidal effect of copper. Analyses of copper leached in solution show that after a conditioning step, the amount of copper released is negligible.

Epidemiology of infectious encephalitis causes in 2016.

We performed a literature search in the Medline database, using the PubMed website. The incidence of presumably infectious encephalitis is estimated at 1.5-7 cases/100,000 inhabitants/year, excluding epidemics. Infectious encephalitis and immune-mediated encephalitis share similar clinical signs and symptoms. The latter accounts for a significant proportion of presumably infectious encephalitis cases without any established etiological diagnosis; as shown from a prospective cohort study where 21% of cases were due to an immune cause. Several infectious agents are frequently reported in all studies: Herpes simplex virus (HSV) is the most frequent pathogen in 65% of studies, followed by Varicella-zoster virus (VZV) in several studies. Enteroviruses are also reported; being the most frequent viruses in two studies, and the 2nd or 3rd viruses in five other studies. There are important regional differences, especially in case of vector-borne transmission: Asia and the Japanese encephalitis virus, Eastern and Northern Europe/Eastern Russia and the tick-borne encephalitis virus, Northern America and Flavivirus or Alphavirus. Bacteria can also be incriminated: Mycobacterium tuberculosis and Listeria monocytogenes are the most frequent, after HSV and VZV, in a French prospective study. The epidemiology of encephalitis is constantly evolving. Epidemiological data may indicate the emergence and/or dissemination of new causative agents. The dissemination and emergence of causative agents are fostered by environmental, social, and economical changes, but prevention programs (vaccination, vector controls) help reduce the incidence of other infectious diseases and associated encephalitis (e.g., measles).

Cytomegalovirus infection in kidney transplant recipients: Evolution of approach through three eras.

Cytomegalovirus (CMV) prophylaxis is recommended for high-risk patients, while preemptive therapy is considered acceptable for patients at moderate/low risk. After reviewing kidney transplant patients from 1992-1995 and 1996-1999, we decided to replace prophylaxis by preemptive therapy. Herein we have presented our data. From 1996-1999 we treated 129 patients with ganciclovir prophylaxis for 3 months if D+/R- or if they received depleting antibodies. The incidence of CMV was 13.2% versus 3.7% in the 1992-1995 cohort. The increase was associated with mycophenolate mofetil (MMF) use (P = .002). Forty-two percent of the D+/R- developed an infection with 89% of bouts occurring in the first month after cessation of prophylaxis. From 2002-2004, we never gave prophylaxis to 129 patients except when they received thymoglobulin. High-risk D+/R- patients were monitored by polymerase chain reaction (PCR) CMV for 3 months. The incidence of CMV was 17.1% with 54% of the D+/R- developing CMV. CMV infection occurred mostly during the first trimester posttransplantation. Creatinine at 1 year posttransplantation was worse in the presence of CMV infection (154.3 mumol/L-1.75 mg % versus 130.2 mumol/L-1.47 mg %, P = .03). Time to cure CMV infection was longer when MMF was discontinued: 36.7 days versus 69.9 days (P = .026). Our results indicated that CMV incidence is increasing: 3.7% (1992-1995) --> 13.2% (1996-1999) -->17.1% (2002-2004) and that it impairs 1 year graft function. Recovery was faster among patients still receiving MMF compared with those discontinuing MMF. Although MMF inhibits synthesis of anti-CMV IgM, it increases the anti-herpes virus effect of ganciclovir and may protect against chronic allograft nephropathy. Based on our experience, we plan to reintroduce prophylaxis in high-risk patients and to continue MMF when treating CMV infection.

Adequacy of estrogen suppression with aminoglutethimide and hydrocortisone as treatment of human breast cancer: correlation of hormonal data with clinical responses.

Human breast neoplasms can be divided into hormone-dependent and hormone-independent subtypes. Estrogen is the major hormonal stimulus for growth of the dependent tumors. Failure to respond to estrogen suppression therapy could reflect either an incomplete lowering of estrogens or the hormonal independence of the tumor. To address this issue, we compared the levels of several estrogens and other hormones in women experiencing objective responses (the responders) and disease progression (the progression group) during therapy with the aromatase-steroidogenesis inhibitor, aminoglutethimide, and replacement hydrocortisone. Pretreatment hormonal profiles of the estrogens, and androgens, ketosteroids, thyroxine, polypeptide hormones, and carcinoembryonic antigen did not differ significantly among response groups. During treatment, the levels of all estrogens were suppressed to a similar degree in the progression group and in the responders. Urinary estrone, for example, fell to 16.7 +/- 3.2% of basal in the responders versus 16.3 +/- 3.8% of basal in the progression group. These data suggested that lack of estrogen suppression did not explain the response to treatment in the patients receiving aminoglutethimide-hydrocortisone. This finding differs from our results in a similarly analyzed control group of patients treated with surgical adrenalectomy. Levels of the weak androgens, dehydroepiandrosterone sulfate and androstenedione, were found to be higher in the progression group compared to the responders. This observation could not be explained by differences in duration of treatment between groups. Analysis at 1 to 12 weeks, 13 to 24 weeks, and 25 to 36 weeks after initiating treatment indicated higher androgen levels at each time point in the progression group. In addition, the results were not attributable to differing serum levels of aminoglutethimide among responder groups. While the finding of higher androgen levels in the responder group remains unexplained, this study indicates that incomplete estrogen suppression is not responsible for lack of tumor response in patients with progressive disease during amino-glutethimide-hydrocortisone therapy.

Randomized trial of aminoglutethimide versus tamoxifen in metastatic breast cancer.

We compared antiestrogen therapy (tamoxifen) with an estrogen suppression regimen (aminoglutethimide-hydrocortisone) in postmenopausal women with metastatic breast carcinoma. Fifteen of 39 patients (38%) who received tamoxifen experienced an objective tumor regression (3 complete, 12 partial remissions), whereas 13 of 36 women (36%) receiving aminoglutethimide responded (one complete remission, 12 partial remissions). The median duration of response was similar. The site of tumor involvement appears to be important in choosing between these hormonal treatments. Aminoglutethimide appears to offer a greater chance of response in patients with bone involvement.

Cross-over comparison of tamoxifen and aminoglutethimide in advanced breast cancer.

Thirty-four postmenopausal patients with advanced breast cancer had an overall objective response rate of 47% when treated with aminoglutethimide and hydrocortisone initially and a response rate of 24% when crossed over to therapy with tamoxifen after progression on aminoglutethimide. A similar group of 32 patients experienced a response rate of 28% when treated with tamoxifen first and a 19% objective response rate on subsequent therapy with aminoglutethimide. Patients who failed to respond to the first therapy seldom responded on cross-over to the alternate therapy. Toxicities were acceptable with both forms of therapy. Tamoxifen and aminoglutethimide used sequentially are effective forms of palliative hormonal therapy in metastatic breast cancer.

Metabolomics: Perspectives on potential biomarkers in organ transplantation and immunosuppressant toxicity.

Organ transplantation is the treatment of choice for many end stage diseases. The development and appropriate use of new immunosupressants have considerably improved the outcome of patients in the last decades. However, noninvasive, sensitive and specific biomarkers for early detection of complications leading to graft dysfunction are still needed. Current transplantation monitoring mostly relies on non-specific biochemical tests whereas diagnosis of rejection is generally based on invasive procedures such as biopsies. New approaches based on large scale profiling of body fluids and tissues are needed to address the complexity and multifactorial aspect of organ transplantation complications. Metabolomics aim to characterize and quantify the metabolome, which is the collection of the low-molecular weight compounds rising from metabolic pathways. Extracted from tissues or detected in body fluids, the small molecules are measured using nuclear magnetic resonance spectroscopy or mass spectrometry. By profiling the downstream products of cellular activity, metabolomics is most likely to represent the immediate cellular response to stresses. Diagnostic applications have been proposed in cancer, cardiovascular diseases, kidney diseases, neurological diseases and many more. This review will focus on the potential applications of metabolomics in organ transplantation including follow up of graft function recovery, diagnostic of alloimmune rejection as well as monitoring of immunosuppressant toxicity.

Androgen priming and chemotherapy in advanced prostate cancer: evaluation of determinants of clinical outcome.

We conducted a randomized clinical trial in men with stage D2 prostate cancer to test whether androgen priming potentiates the efficacy of cytotoxic chemotherapy. Eighty-five men with progressive prostate cancer refractory to orchiectomy were treated continuously with aminoglutethimide and hydrocortisone to lower adrenal androgen secretion and were administered cyclic intravenous (IV) chemotherapy. The patients were randomized to receive either androgen priming or no additional treatment for three days before and on the day of chemotherapy. Median duration of follow-up was 43 months. Response rate (remission plus disease stabilization) was not significantly different between the stimulation and control arm when the analysis was restricted to evaluable patients (79% v 73%, respectively) or when it was extended to all patients (46% v 61%). Median duration of response was similar for the stimulation and control arm (9 and 10 months, respectively). Median survival was 10 months in the stimulation and 15 months in the control group (P = .0047). The androgen sensitivity of the tumors was supported by the greater toxicity in the stimulation arm associated with androgen administration. Factors found to be independently associated with improved clinical outcome included a high Karnofsky score and hematocrit, long duration of response to the initial castration, and normalization of an elevated serum acid phosphatase on treatment. We conclude that in this group of patients with advanced disease, androgen priming does not potentiate the efficacy of chemotherapy and is actually associated with a worse outcome. Furthermore, our data emphasize the heterogeneity of biologic behavior of prostate cancer.

Endoscopic Factors Influencing Fecal Calprotectin Value in Crohn's Disease.

BACKGROUND AND AIMS: Fecal calprotectin [fcal] is a biomarker of Crohn's disease [CD] endoscopic activity. Identifying the endoscopic situations in which fcal is less reliable remains unexplored. We aimed to determine the endoscopic factors influencing fcal level in CD. METHODS: Overall, 53 CD patients consecutively and prospectively underwent colonoscopy, with CD Endoscopic Index of Severity [CDEIS] calculation and stool collection. Fcal was measured using a quantitative immunochromatographic test. Correlation analysis was done with Pearson statistics. RESULTS: Fcal was correlated with CDEIS [0.66, p < 0.001]. In univariate analysis, fcal was correlated with the affected surface [0.65, p < 0.001] and the ulcerated surface [0.47, p < 0.001]. Fcal was significantly associated with ulceration depth, with median fcal of 867.5 µg/g, 1251.0 µg/g, and 1800.0 µg/g, in patients presenting with non-ulcerated lesions, superficial ulcerations [SU], and deep ulcerations [DU], respectively. Lesion locations did not influence fcal. In multivariate analysis, fcal was associated with affected surface [p = 0.04] and the presence of CD lesions. Moreover, fcal increased with the ulceration depth [p = 0.03]. However, ulcerated surface and CD location did not affect fcal. Using a receiver operating characteristic [ROC] curve, we showed that fcal of 400 µg/g was the best compromise between sensitivity [0.76] and specificity [0.77], whereas fcal ≥ 200 µg/g was highly sensitive [0.86] to detect SU or DU. CONCLUSIONS: Fcal is a very reliable biomarker to detect endoscopic ulcerations in CD. We suggest repeating measurement in case of intermediary results [200-400 µg/g] in daily practice. Fcal level is mostly influenced by the presence of CD lesions [even non-ulcerated], in a depth-related manner and by the affected surface.

[Renal extramedullary hematopoietic tumor revealing a hereditary spherocytosis in an adult patient]. / Révélation à l'âge adulte d'une sphérocytose héréditaire devant une tumeur rénale: forme frontière entre myélolipome et foyer d'hématopoïèse extra-médullaire.

INTRODUCTION: Myelolipomas and extramedullary hematopoietic tumors are uncommon benign tumors. They are variably composed of mature adipose tissue and hematopoietic tissue. Myelolipoma is usually observed in the adrenal gland and extramedullary hematopoietic tumors in the liver and spleen but may occasionally be found within solid tumors. CASE REPORT: A 62-year-old man without previous haematological history presented with a voluminous solitary bilateral renal tumor. Contrast-enhanced ultrasound CT-scan and scintigraphy with technetium-99m-nanocolloid and indium-111-chloride bone marrow were highly suggestive of extramedullary hematopoietic tumor. CT-guided biopsy suggested a diagnosis of myelolipoma. An atypical hereditary spherocytosis, undiagnosed until now, was demonstrated. CONCLUSION: We report, for the first time to our knowledge, a border form between extramedullary hematopoiesis tumor and myelolipoma of renal localisation revealing a hereditary spherocytosis in an adult patient.