Hepatitis C virus (HCV) infection usually recurs after orthotopic liver transplantation (OLT), and most patients develop graft damage. This study compared the efficacy of interferon alfa (IFN‐α) and ...ribavirin monotherapies in liver transplant recipients with chronic hepatitis C in the graft. Thirty OLT recipients with chronic hepatitis C were randomized to receive either IFN‐α (3 MU three times a week) or ribavirin (up to 1.2 g daily) for 24 weeks. Virological, biochemical, and histological responses to treatment were assessed. Twenty‐eight patients completed the treatment regimen, two ribavirin‐treated patients being withdrawn because of severe hemolysis. Normalization of serum aspartate aminotransferase was achieved in 13 of 14 patients receiving ribavirin (93%) and 6 of 14 patients receiving IFN‐α (43%; P = .01). Lobular inflammation was reduced in 9/14 ribavirin‐treated (64%) and 3 of 14 IFN‐α–treated patients (21%; P = .05), each of whom had a biochemical response. However, the total histological activity index did not improve in either the interferon (P = .43) or the ribavirin (P
= .96) group. Posttreatment viremia levels were significantly reduced in IFN‐α–treated (P = .05) but not in ribavirin‐treated (P = .88) patients. Hemolysis occurred in all ribavirin‐treated patients, with serum hemoglobin decreasing to <10 g/dL in 50%. Total leukocyte and lymphocyte counts decreased significantly during ribavirin treatment (P = .02 and P = .004, respectively). We concluded that in patients with chronic hepatitis C after OLT, IFN‐α retains an antiviral effect whereas ribavirin is superior in achieving normalization of serum aspartate aminotransferase levels and reducing lobular inflammation, but not the total histological activity index. These findings provide a rationale for combination therapy in the post‐OLT setting, although patients must be carefully monitored for hemolysis.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Purpose
To conduct a systematic literature review and meta-analysis of studies of lympho-hematopoietic cancers (LHC) and breast cancer risk among persons occupationally exposed to ethylene oxide ...(EO).
Methods
We performed a literature search for articles available in PubMed and Web of Science databases to identify literature and subsequently systematically searched the reference lists of identified studies, published review papers and meta-analyses, as well as relevant government or regulatory documents. We qualitatively reviewed 30 studies and conducted meta-analyses on 13 studies. Pooled risk estimates were calculated using random effects models, stratifying by occupational group, cancer type and decade of publication.
Results
The overall meta-relative risks (meta-RRs) for LHC and breast cancer, respectively, were 1.48 (95% CI 1.07–2.05) and 0.97 (95% CI 0.80–1.18). The meta-RR’s for LHC among EO production and EO sterilization workers were 1.46 (95% CI 0.85–2.50) and 1.07 (95% CI 0.87–1.30), respectively. We observed higher risks of LHC in the earlier published studies, compared to the later studies, and the meta-RR’s for the 1980s, 1990s, 2000s, and the 2010s, respectively, were 3.87 (95% CI 1.87–8.01), 1.38 (95% CI 0.85–2.25), 1.05 (95% CI 0.84–1.31), and 1.19 (95% CI 0.80–1.77).
Conclusions
The most informative epidemiology studies, which were published in the 2000s and 2010s, do not support the conclusion that exposure to EO is associated with an increased risk of LHC or breast cancer.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
While Quebec Public Health reported a total of 10 cases who resided in the region at time of diagnosis, the report cited an unpublished 2001 study by Siemiatycki et al, titled Comparaison du risque ...de mésothéliome de la plèvre entre les régions minières et les autres régions de la province, that identified seven additional women who were domestically exposed, however not residing in the region at diagnosis. ...the only documentation of the 17 cases in the Quebec report, which was cited as Finkelstein’s primary reference, was a sum of 10 cases identified by Quebec Public Health5 and 7 cases identified by Siemiatycki. ...Finkelstein did not cite or acknowledge the Siemiatycki report, nor did he indicate how he derived the 95% CI associated with the relative risk (RR) that was necessary for his analysis. ...Finkelstein’s findings are not reproducible based on the available information.
Full text
Available for:
BFBNIB, CMK, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
The relative shortage of donor organs and lack of immediate availability mean that many patients with acute liver failure die before orthotopic liver transplantation can be performed. An effective ...temporary liver support system could improve the chance of survival with or without a transplant being ultimately carried out. Recent technological advances resulting in improved maintenance of hepatocyte viability and function in culture and bioreactor designs which facilitate adequate perfusion of the cellular component and removal of products of cellular metabolism have led to the development of a number of bioartificial devices for liver support. Three such devices have undergone preliminary clinical evaluation in the setting of acute liver failure, with a statistically significant reduction in raised intracerebral pressure along with improvements in consciousness level and some biochemical parameters associated with treatment with one of these. Several other devices with different characteristics have shown promise in vitro and/or in animal models but await clinical evaluation. Several new totally artificial systems have also been described, along with the emergence of isolated hepatocyte transplantation, with reports of successful ‘bridging’ to liver transplantation. Controlled trials on a multicentre basis in well‐defined patient groups and with standardized outcome measures will be required to properly evaluate the clinical value of each of these approaches to providing liver support in acute liver failure and cirrhosis. A better understanding of mechanisms underlying multiorgan failure and of factors inhibiting liver regeneration, thereby allowing a more targeted approach, will be essential to the further development of effective liver support strategies in these settings.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
IL28B polymorphisms strongly predict spontaneous and treatment-induced clearance of hepatitis C virus (HCV) infection. A recent study proposed a 32-base pair deletion in the CC-chemokine receptor 5 ...(CCR5) gene (CCR5-Δ32) interacting with the IL28B polymorphisms to influence spontaneous HCV clearance. The aim of this study was to clarify the role of CCR5-Δ32 in treatment-induced clearance of chronic hepatitis C (CHC). A cross-sectional cohort of 813 Caucasian patients with CHC genotype 1 (365 responders and 448 non-responders) who had received standard of care dual therapy with interferon (IFN)-α and ribavirin (RBV) was genotyped for the CCR5-Δ32 and IL28B polymorphisms to examine their interaction with respect to treatment response. CCR5-Δ32 did not influence treatment-induced recovery to IFN-α/RBV in CHC, and did not improve prediction of sustained virological response in the context of the IL28B polymorphisms in a multivariate model. CCR5-Δ32 homozygotes were significantly more frequent in those with CHC than healthy controls in the European cohorts (2.9% vs 0.4%, P<0.0001), but not in Australians of European ancestry. In conclusion, CCR5-Δ32 does not influence treatment response in the context of IL28B polymorphisms. Although CCR5-Δ32 may affect viral clearance within closely controlled geographical and genetic environments, we found no effect in larger cohorts treated with dual therapy.
Full text
Available for:
DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Hepatocyte growth factor (HGF) identical to scatter factor (SF) is a glycoprotein involved in the development of a number of cellular phenotypes, including proliferation, mitogenesis, formation of ...branching tubules and, in the case of tumour cells, invasion and metastasis. This fascinating cytokine transduces its activities via its receptor encoded by the c‐met oncogene, coupled to a number of transducers integrating the HGF/SF signal to the cytosol and the nucleus. The downstream transducers coupled to HGF/MET, most of which participate in overlapping pathways, determine the development of the cell's phenotype, which in most cell types is dual.
Full text
Available for:
BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
The purpose of this study was to evaluate the individual contributions of inhalation and dermal exposures to urinary glyphosate levels following the heavy residential consumer application of a ...glyphosate-containing herbicide.
A pilot study was conducted in which each participant mixed and continuously spray-applied 16.3 gallons of a 0.96% glyphosate-containing solution for 100 min using a backpack sprayer. Twelve participants were divided evenly into two exposure groups, one equipped to assess dermal exposure and the other, inhalation exposure. Personal air samples (n = 12) and dermal patch samples (n = 24) were collected on the inhalation group participants and analyzed for glyphosate using HPLC-UV. Serial urine samples collected 30-min prior to application and 3-, 6-, 12-, 24-hr (inhalation and dermal groups) and 36-hr (dermal group only) post-application were analyzed for glyphosate and glyphosate's primary metabolite (AMPA) using HPLC-MS/MS.
The mean airborne glyphosate concentration was 0.0047 mg/m
3
, and the mean concentrations of glyphosate for each applicator's four patch samples ranged from 0.04 µg/mm
2
to 0.25 µg/mm
2
. In general, urinary glyphosate, AMPA, and total effective glyphosate levels were higher in the dermal exposure group than the inhalation exposure group, peaked within 6-hr following application, and were statistically indistinguishable from background at 24-hr post-application.
This is the first study to characterize the absorption and biological fate of glyphosate in residential consumer applicators following heavy application. The results of this pilot study are consistent with previous studies that have shown that glyphosate is rapidly eliminated from the body, typically within 24 hr following application.
Full text
Available for:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Two 42-d experiments compared the nutritional value of YieldGard Rootworm corn (MON863; experiment 1) and YieldGard Plus corn (MON810 x MON863; experiment 2) to their respective nontransgenic ...controls and 6 commercial reference corn hybrids when fed to growing broilers. For each experiment, a randomized complete block design was used with 8 dietary treatments in each of 5 replicated blocks of pens. In experiment 1, no differences among diets were observed (P > 0.05) for final live weights and feed conversion. Broilers fed diets containing MON863 corn had adjusted feed conversion similar to the nontransgenic control and the population of control and commercial diets. On a weight basis, there were no differences among diets for chill, fat pad, and thigh, drum, and wing weights. Differences (P < 0.05) between MON863 and commercial corn diets were noted for breast meat, chill and thigh, drum, and wing weights on a percentage of weight basis. No differences were observed (P > 0.05) in the percentage of moisture, protein, and fat in breast meat or thigh meat across treatment diets. In experiment 2, there were no significant differences among diets for all broiler performance and carcass parameters evaluated. Broilers overall performed consistently and had similar carcass yields and meat compositions when fed diets containing MON863 corn or MON810 x MON863 corn as compared with their respective nontransgenic control and commercial diets, supporting a conclusion of similar feeding values among diets.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Talc has been used for over a century in a variety of cosmetic products. While pure cosmetic talc (free of asbestos) is not considered a risk factor for mesothelioma, it has been recently suggested ...that inhalation of cosmetic talc containing trace levels of asbestos is a risk factor for mesothelioma. Bulk analyses of cosmetic talcum products were performed in the 1960s and 1970s, however, the analytical methods used at that time were incapable of determining whether asbestos minerals were present in the asbestiform versus non-asbestiform habit. The distinction between these two mineral habits is critical, as non-asbestiform amphibole minerals do not present an asbestos-related cancer risk via inhalation. As such, we evaluated six historical talcum powders using modern-era analytical methods to determine if asbestos is present, and if so, to identify the mineral habit (asbestiform versus non-asbestiform) of the asbestos. Based on their labels, the products were produced by four manufacturers and sold between 1940 and 1977. The products were analyzed in duplicate by two laboratories using standard protocols. Laboratory A analyzed samples using X-ray diffraction (XRD) and polarized light microscopy (PLM), and Laboratory B analyzed samples using PLM and transmission electron microscopy (TEM) with energy dispersive X-ray analysis (EDX) and selected area electron diffraction (SAED). No asbestiform minerals were found in any of the products. Nonetheless, even if some historical cosmetic talcum products contained trace amounts (≤0.1%) of asbestiform minerals, any resulting asbestos exposure would be expected to be exceedingly low, and comparable to exposures from breathing ambient air.
Full text
Available for:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
PDF
