Venous thromboembolism associated with long-term use of central venous catheters in cancer patients.

Long-term central venous catheters (CVCs) have considerably improved the management of cancer patients because they facilitate chemotherapy, transfusions, parenteral nutrition, and blood sampling. However, the use of long-term CVCs, especially for chemotherapy, has been associated with the occurrence of upper-limb deep venous thrombosis (UL-DVT). The incidence of clinically overt UL-DVT related to CVCs has been reported to vary between 0.3% and 28.3%. The incidence of CVC-related UL-DVT screened by venography reportedly varies between 27% and 66%. The incidence of clinically overt pulmonary embolism (PE) in patients with CVC-related UL-DVT ranges from 15% to 25%, but an autopsy-proven PE rate of up to 50% has been reported. Vessel injury caused by the procedure of CVC insertion, venous stasis caused by the indwelling CVC, and cancer-related hypercoagulability are the main pathogenetic factors for CVC-related venous thromboembolism (VTE). Several studies have assessed the benefit of the prophylaxis of UL-DVT after CVC insertion in cancer patients. According to the results of these studies, prophylaxis with low molecular weight heparin or a low fixed dose of warfarin has been recently proposed. However, the limitations of the experimental design of the prophylactic studies do not allow definitive recommendations. The recommended therapy for UL-DVT associated with CVC is based on anticoagulant therapy with or without catheter removal. This review focuses on the epidemiology, pathogenesis, diagnosis, prevention, and treatment of VTE in cancer patients with long-term CVC.     

Inhibition of ischemia/reperfusion injury and chronic graft deterioration by a single-donor treatment with cobalt-protoporphyrin for the induction of heme oxygenase-1

Today, the major problem in organ transplantation is not acute graft rejection but chronic graft deterioration. In addition to alloantigen-specific events, alloantigen independent factors like donor age, previous diseases, consequences of brain death, and perioperative events of ischemia/reperfusion injury have a major impact on long-term graft function. The induction of the stress protein heme oxygenase-1 (HO-1) protects cells from injury and apoptosis. Here, we tested the protective effects of HO-1 induction in a clinically relevant kidney transplant model. Induction of HO-1 expression following cobalt-protoporphyrin (CoPP) treatment in organ donors prolonged graft survival and long-term function remarkably following extended periods of ischemia. Positive effects were observed with both optimal and marginal grafts from old donor animals. Structural changes characteristic for chronic rejection, as well as graft infiltration by monocytes/macrophages and CD8+ T cells, were substantially reduced following HO-1 induction. Up-regulation of HO-1 expression before organ transplantation was also associated with reduced levels for tumor necrosis factor (TNF)-alpha mRNA, increased levels for interferon (IFN)-gamma, and bcl-x, and insignificant differences for CD25, interleukin (IL)-2, IL-4, IL-6, and IL-10 mRNA levels. The significant improvement of long-term graft function following induction of HO-1 expression in donor organs suggests that this strategy may be a novel clinical treatment option with particular relevance for transplantation of marginal organs.     

When the treatment goal is not cure: are cancer patients equipped to make informed decisions?

PURPOSE: Informed decision making now is considered the underpinning of ethical medical practice. We aimed to determine the extent to which patients with incurable cancer are adequately informed of their prognosis and treatment options and encouraged to participate in treatment decisions. PATIENTS AND METHODS: One hundred eighteen cancer patients with incurable disease presenting for an initial consultation with one of nine oncologists at two Sydney tertiary referral hospitals participated in the study. Consultations were recorded on audiotape to permit a content analysis of doctor-patient interactions. We devised a coding system to assess disclosure of information and to evaluate doctor encouragement of patient participation in treatment decision making. Patient recall, satisfaction, anxiety, and perceptions of the decision-making process were assessed to determine the effects of informed decision making on patient outcomes. RESULTS: Most patients were informed about the aim of anticancer treatment (84.7%), that their disease was incurable (74.6%), and about life expectancy (57.6%). An alternative to anticancer treatments was presented to 44.1%, 36.4% were informed about how anticancer treatment would affect quality of life, and 29.7% were offered a management choice. Oncologists checked patient understanding in only 10.2% of consultations. Although greater information disclosure did not seem to elevate anxiety levels, greater patient participation in the decision-making process was associated with increased anxiety levels (P =.0005), which persisted over a 2-week time span. CONCLUSION: Most patients were well informed, but important gaps remain, especially concerning information about prognosis and alternatives to anticancer treatment. These gaps invite the question concerning whether patients are led toward anticancer treatment.     

Brazilian plants with possible action on the central nervous system: a study of historical sources from the 16th to 19th century

Brazil is a country rich in biodiversity, endemism, and cultural diversity, inhabited by different types of population. European expeditions and the migratory processes that began in the 16th century greatly contributed both to cultural diversity and to Brazilian popular therapeutics, and produced the first records on medicinal plants in Brazil. This study comprises a bibliographical survey of historic books found in Sao Paulo libraries (16th through 19th centuries) on medicinal plants exerting effects on the central nervous system (CNS). Thirty-four plants native to Brazil were selected from the reading of the books. Of these 34 plants, 13 were also recorded in ethnopharmacological studies among modern Brazilian communities and 16 have been studied phytochemically. Only eight have been the object of pharmacological studies, six of these, recently, with a request for a patent. Results showed that most of the species recorded in this study have been reported as medicinal for centuries, but have never been the object of pharmacological investigation down to the present time. Such results provide ideas for a selection of these species as potentially bioactive to be included in future pharmacological studies.     

Mammalian reovirus, a nonfusogenic nonenveloped virus, forms size-selective pores in a model membrane

During cell entry, reovirus particles with a diameter of 70-80 nm must penetrate the cellular membrane to access the cytoplasm. The mechanism of penetration, without benefit of membrane fusion, is not well characterized for any such nonenveloped animal virus. Lysis of RBCs is an in vitro assay for the membrane perforation activity of reovirus; however, the mechanism of lysis has been unknown. In this report, osmotic-protection experiments using PEGs of different sizes revealed that reovirus-induced lysis of RBCs occurs osmotically, after formation of small size-selective lesions or "pores." Consistent results were obtained by monitoring leakage of fluorophore-tagged dextrans from the interior of resealed RBC ghosts. Gradient fractionations showed that whole virus particles, as well as the myristoylated fragment mu1N that is released from particles, are recruited to RBC membranes in association with pore formation. We propose that formation of small pores is a discrete, intermediate step in the reovirus membrane-penetration pathway, which may be shared by other nonenveloped animal viruses.     

MOZ-TIF2-induced acute myeloid leukemia requires the MOZ nucleosome binding motif and TIF2-mediated recruitment of CBP

The MOZ-TIF2 fusion is associated with acute myeloid leukemia (AML) with inv(8)(p11q13). MOZ is a MYST family histone acetyltransferase (HAT), whereas TIF2 is a nuclear receptor coactivator that associates with CREB binding protein (CBP). Here we demonstrate that MOZ-TIF2 has transforming properties in vitro and causes AML in a murine bone marrow transplant assay. The C2HC nucleosome recognition motif of MOZ is essential for transformation, whereas MOZ HAT activity is dispensable. However, MOZ-TIF2 interaction with CBP through the TIF2 CBP interaction domain (CID) is essential for transformation. These results indicate that nucleosomal targeting by MOZ and recruitment of CBP by TIF2 are critical requirements for MOZ-TIF2 transformation and indicate that MOZ gain of function contributes to leukemogenesis.     

A new food guide for North American vegetarians

In summary, this vegetarian food guide has a number of advantages over previous guides designed for this population:

• It is based on current nutritional science. This guide aims to provide sufficient nutrient intake based on the most recent dietary reference intakes and addresses concerns such as balance of fats in diets.

• It provides information about how to meet calcium needs that is appropriate to a wide range of individuals, including those who follow lacto-ovo-vegetarian diets and vegan diets.

• It promotes the concepts of variety and moderation. Many other guides for both vegetarians and nonvegetarians direct consumers only to dairy foods to meet calcium needs, whereas this guide emphasizes the wide variety of foods that can meet calcium requirements.

• It focuses on foods that are commonly consumed by vegetarians.

GP and patient predictors of PSA screening in Australian general practice

OBJECTIVE: We determined GP and patient variables associated first with men's prior uptake of prostate-specific antigen (PSA) screening and, subsequently, its initiation during an 'index consultation' in Australian general practice. METHODS: From the practices of 60 GPs, we recruited a sample of 423 male patients aged 40-70 years. In a waiting room questionnaire completed before their 'index consultation' (retrospective component), men reported their previous PSA screening status. We obtained demographic and clinical data, including the presence of lower urinary tract symptoms (LUTS). Men also were mailed a questionnaire 2 days after their 'index consultation' to ascertain whether the GP had discussed PSA screening (prospective component) for prostate cancer and other behaviours. GPs themselves completed questionnaires eliciting demographic and practice characteristics as well as their propensity to screen and understanding of the evidence about PSA testing. GP and patient study variables were modelled simultaneously in analyses. RESULTS: Of those 348 men consulting with their regular GP, 80 (23.0%) reported previously having had a PSA screening test. Men were significantly and independently more likely ever to have had PSA screening if their regular GP reported a propensity to initiate screening [adjusted odds ratio (AOR) = 2.27, 95% confidence interval (CI) 1.23-4.20; P = 0.009]. GP age also was independently associated with men's PSA screening status [chi-squared (3) P < 0.0001] as was men's age and severity of LUTS (AOR = 2.38, 95% CI 1.58-3.57, P < 0.0001 and AOR = 1.79, 95% CI 1.00-3.19, P = 0.004, respectively). Current smokers were less likely ever to have had a PSA screening test (AOR = 0.34, 95% CI 0.16-0.69; P = 0.003). Discussion of PSA screening in their 'index consultation' was recalled independently more often by older men (AOR = 1.46, 95% CI 1.00-2.13; P = 0.04), those with moderate/severe LUTS (AOR = 1.94, 1.07-3.49; P = 0.04), those whose GP had performed or discussed a cholesterol test (AOR = 2.26, 95% CI 1.03-4.92; P = 0.04) and those whose GP had postgraduate training in family medicine (AOR = 3.13, 95% CI 1.23-8.00; P = 0.02). CONCLUSION: In the absence as yet of compelling evidence that PSA screening will prolong life or enhance its quality, our findings identify GP and patient factors that could be targeted to modify PSA screening.     

Regulation of tissue factor expression in smooth muscle cells with nitric oxide

OBJECTIVE: This study was undertaken to determine the effect of nitric oxide (NO) on tissue factor (TF) expression in vascular smooth muscle cells. STUDY DESIGN: Rat aortic smooth muscle cells (RASMCs) were exposed to NO delivered exogenously with the NO donor S-nitroso-N-acetylpenicillamine (SNAP) or produced endogenously after infection with an adenoviral vector carrying human inducible NO synthase (AdiNOS). Functional TF activity was assessed with chromogenic TF assay. TF antigen was determined with immunohistochemistry. Northern blot analysis was used to determine steady- state TF messenger RNA (mRNA). Electrophoretic mobility gel shift assay was performed to determine the nuclear binding activity of nuclear factor kappa-B (NFkappaB). NFkappaB activity was inhibited by either prior transduction of RASMCs with mutant IkappaB or treatment with pyrrolidine dithiocarbamate. RESULTS: RASMCs exposed to SNAP or infected with AdiNOS exhibited increased functional TF activity and antigen. Regardless of the source of NO, a time-dependent and concentration-dependent increase in TF activity was observed. Steady-state TF mRNA levels were also increased by NO delivered via either method. NFkappaB nuclear binding activity was also increased by NO. Inhibition of NFkappaB activity by either pyrrolidine dithiocarbamate treatment or mutant IkappaB transduction abrogated NO-induced enhancement of TF mRNA and functional activity. CONCLUSION: In RASMC, NO exposure results in upregulation of TF functional activity, antigen, and mRNA. This effect appears to be mediated by an NFkappaB-dependent pathway.