The efficacy of endoscopic therapy in bleeding peptic ulcer patients

Background. Endotherapy is the primary modality for the control ofbleeding from peptic ulceration.Objective. To assess the efficacy of endoscopic intervention for high-risk bleeding peptic ulcer disease and to benchmark our surgical and mortality rates.Methods. Two hundred and twenty-seven patients with pepticulcers stratified by Rockall and Forrest scores as being at high risk for rebleeding underwent therapeutic intervention (adrenalin injection) between January 2004 and December 2009. The median age of the patients was 57 years (range 19 - 87 years); 60% were males.Results. Primary endoscopic haemostasis failed in 51/227 patients (22.5%); 18 patients (7.9%) required surgery for bleeding not controlled at initial or second endoscopy; and 29 patients (12.8%) died, 12 by day 3 and 17 by day 30. Fifteen patients, all with significant medical co-morbidity, died after successful primary endotherapy, and 4 died after surgery. Surgical patients required more blood (odds ratio (OR) 1.45, p=0.0001) than those not undergoing surgery, but had similar mortality. Rebleeding was the only predictor of death in patients who died by day 3 (OR 18.77). A high Rockall score was the only predictor of death by day 30 (OR 1.98).Conclusion. The overall surgical and mortality rates were 7.9% and 12.8%, respectively. Over half the deaths resulted from medical co-morbidity, despite successful primary endotherapy. This finding is supported by the use of the Rockall score as a predictor of mortality at day 30. Improving the technical success of primary endoscopic haemostasis, currently 77.5%, has the potential to reduce rebleeding after primary endotherapy, a predictor of death at day 3 in this study

Subtidal macrozoobenthos communities from northern Chile during and post El Niño 1997–1998

Despite a large amount of climatic and oceanographic information dealing with the recurring climate phenomenon El Niño (EN) and its well known impact on diversity of marine benthic communities, most published data are rather descriptive and consequently our understanding of the underlying mechanisms and processes that drive community structure during EN are still very scarce. In this study, we address two questions on the effects of EN on macrozoobenthic communities: (1) how does EN affect species diversity of the communities in northern Chile? and (2) is EN a phenomenon that restarts community assembling processes by affecting species interactions in northern Chile? To answer these questions, we compared species diversity and co-occurrence patterns of soft-bottoms macrozoobenthos communities from the continental shelf off northern Chile during (March 1998) and after (September 1998) the strong EN event 1997–1998. The methods used varied from species diversity and species co-occurrence analyses to multivariate ordination methods. Our results indicate that EN positively affects diversity of macrozoobenthos communities in the study area, increasing the species richness and diversity and decreasing the species dominance. EN represents a strong disturbance that affects species interactions that rule the species assembling processes in shallow-water, sea-bottom environments

Peptides derived from the HIV-1 integrase promote HIV-1 infection and multi-integration of viral cDNA in LEDGF/p75-knockdown cells

<p>Abstract</p> <p>Background</p> <p>The presence of the cellular Lens Epithelium Derived Growth Factor p75 (LEDGF/p75) protein is essential for integration of the Human immunodeficiency virus type 1 (HIV-1) cDNA and for efficient virus production. In the absence of LEDGF/p75 very little integration and virus production can be detected, as was demonstrated using LEDGF/p75-knokdown cells.</p> <p>Results</p> <p>Here we show that the failure to infect LEDGF/p75-knockdown cells has another reason aside from the lack of LEDGF/p75. It is also due to inhibition of the viral integrase (IN) enzymatic activity by an early expressed viral Rev protein. The formation of an inhibitory Rev-IN complex in virus-infected cells can be disrupted by the addition of three IN-derived, cell-permeable peptides, designated INr (IN derived-Rev interacting peptides) and INS (IN derived-integrase stimulatory peptide). The results of the present work confirm previous results showing that HIV-1 fails to infect LEDGF/p75-knockdown cells. However, in the presence of INrs and INS peptides, relatively high levels of viral cDNA integration as well as productive virus infection were obtained following infection by a wild type (WT) HIV-1 of LEDGF/p75-knockdown cells.</p> <p>Conclusions</p> <p>It appears that the lack of integration observed in HIV-1 infected LEDGF/p75-knockdown cells is due mainly to the inhibitory effect of Rev following the formation of a Rev-IN complex. Disruption of this inhibitory complex leads to productive infection in those cells.</p

The effectiveness of pharmacological agents for the treatment of uveitic macular oedema (UMO): a systematic review protocol

PRISMA-P 2015 checklist: recommended items to include in a systematic review protocol. a (PDF 153 kb

Transnational corporations and the challenge of biosphere stewardship

This is the author accepted manuscript. The final version is available from Nature Research via the DOI in this recordSustainability within planetary boundaries requires concerted action by individuals, governments, civil society and private actors. For the private sector, there is concern that the power exercised by transnational corporations generates, and is even central to, global environmental change. Here, we ask under which conditions transnational corporations could either hinder or promote a global shift towards sustainability. We show that a handful of transnational corporations have become a major force shaping the global intertwined system of people and planet. Transnational corporations in agriculture, forestry, seafood, cement, minerals and fossil energy cause environmental impacts and possess the ability to influence critical functions of the biosphere. We review evidence of current practices and identify six observed features of change towards 'corporate biosphere stewardship', with significant potential for upscaling. Actions by transnational corporations, if combined with effective public policies and improved governmental regulations, could substantially accelerate sustainability efforts.Beijer FoundationErling-Persson Family FoundationMarianne and Marcus Wallenberg FoundationWalton Family FoundationDavid and Lucile Packard FoundationGordon and Betty Moore FoundationMistra: The Swedish Foundation for Strategic Environmental Researc

Phase I dose-escalation and pharmacokinetic study of temozolomide (SCH 52365) for refractory or relapsing malignancies

Temozolomide, an oral cytotoxic agent with approximately 100% bioavailability after one administration, has demonstrated schedule-dependent clinical activity against highly resistant cancers. Thirty patients with minimal prior chemotherapy were enrolled in this phase I trial to characterize the drug's safety, pharmacokinetics and anti-tumour activity, as well as to assess how food affects oral bioavailability. To determine dose-limiting toxicities (DLT) and the maximum tolerated dose (MTD), temozolomide 100–250 mg m−2 was administered once daily for 5 days every 28 days. The DLT was thrombocytopenia, and the MTD was 200 mg m−2 day−1. Subsequently, patients received the MTD to study how food affects the oral bioavailability of temozolomide. When given orally once daily for 5 days, temozolomide was well tolerated and produced a non-cumulative, transient myelosuppression. The most common non-haematological toxicities were mild to moderate nausea and vomiting. Clinical activity was observed against several advanced cancers, including malignant glioma and metastatic melanoma. Temozolomide demonstrated linear and reproducible pharmacokinetics and was rapidly absorbed (mean Tmax ~1 h) and eliminated (mean t1/2 = 1.8 h). Food produced a slight reduction (9%) in absorption of temozolomide. Temozolomide 200 mg m−2 day−1 for 5 days, every 28 days, is recommended for phase II studies. © 1999 Cancer Research Campaig