Impact of catheter ablation versus medical therapy on cognitive function in atrial fibrillation: a systematic review

Journal of Interventional Cardiac Electrophysiology - Atrial fibrillation is associated with an increased risk of cognitive impairment. It is unclear whether the restoration of sinus rhythm with...     

Prognostic value of blood pressure in ambulatory heart failure: a meta-analysis and systematic review. Ambulatory blood pressure predicts heart failure prognosis

Heart Failure Reviews - Previous primary studies have explored the association between blood pressure (BP) and mortality in ambulatory heart failure (HF) patients reporting varying and contrasting...     

Ontario familial colon cancer registry: methods and first-year response rates

The Ontario Familial Colon Cancer Registry (OFCCR) is a novel registry that collects family history information, epidemiologic data, blood samples and tumour specimens from a population-based sample of colorectal cancer patients and their families. Families are classified as either high familial risk, intermediate familial/other risk or low (sporadic) risk for colorectal cancer. Obtaining high response rates in genetic family studies is especially challenging because of both the time commitment required and issues of confidentiality. The first-year response rate was 61%, resulting in 1,395 participating probands. In an attempt to assess potential response bias, we compared participants with non-participants. The age and sex of participants did not differ from non-participating probands; however, cases in rural areas were somewhat more likely to participate. To date, 57% of 1,587 relatives participated; females were more likely to participate, and relatives of low familial risk were least likely to participate. The OFCCR is an excellent resource that will facilitate the study of genetic and environmental factors associated with colorectal cancer.     

In vitro control of Mycobacterium bovis by macrophages.

Mycobacterium bovis is frequently seen inside macrophages in vivo. The outcome of M. bovis infection depends on T cell interactions with macrophages, however mycobacteria are thought to be relatively resistant to macrophage killing. Little is known about the immunological mechanisms which control intracellular growth of M. bovis, and in the absence of T cell help the organism is capable of intracellular survival and replication. We have investigated the role of macrophages in controlling growth of virulent M. bovis or M. bovis BCG in vitro. At a multiplicity of infection of 5:1, macrophages from a range of animal species including cattle, deer, possums, ferrets and mice restricted growth of BCG while M. bovis grew progressively. Inter-species variation in controlling growth of M. bovis by alveolar macrophages was observed. Pre-treatment of macrophages with interferon-gamma and lipopolysaccharide inhibited intracellular growth of M. bovis. Addition of freshly recruited macrophages further inhibited M. bovis, and intracellular growth was arrested by activated fresh macrophages. Our observations suggest that na?ve macrophages can prevent BCG growth, while T cell activation in conjunction with freshly recruited macrophages is required for preventing growth of M. bovis.     

Visceral hyperalgesia and intestinal dysmotility in a mouse model of postinfective gut dysfunction

BACKGROUND & AIMS: We established the concept that transient enteric infection may lead to persistent gut dysfunction, evident in vitro, in nematode-infected mice. The present study determined whether gut dysfunction in this model involves motor and sensory changes reminiscent of changes found in patients with postinfective irritable bowel syndrome (PI-IBS) and investigated underlying mechanisms. METHODS: Mice infected up to 70 days previously with Trichinella spiralis (Tsp) underwent videofluoroscopy with image analysis to assess upper gastrointestinal motility. Pseudoaffective responses to colorectal distention (CRD) were assessed using a barostat and validated by single fiber recordings from spinal nerves during CRD. Tissues were examined at different time points for histology, immunohistochemistry, and cytokine analysis. Some mice received dexamethasone intraperitoneally on days 23-25 PI or Tsp antigen orally on days 29, 43, and 57 PI. RESULTS: From day 28 PI, no discernible inflammation was present in the gut. Frequency and propagation velocity of intestinal contractions decreased, and retroperistalsis increased at days 28 to 42 PI. CRD induced an allodynic and hyperalgesic response in PI mice, which was accompanied by increased single unit discharge. Gavage of Tsp antigen induced T-cell responses and sustained gut dysfunction for 70 days PI. Administration of dexamethasone postinfection normalized dysmotility and visceral hyperalgesia. CONCLUSIONS: Long-lasting gut dysmotility and hyperalgesia develop in mice after transient intestinal inflammation. These changes are maintained by luminal exposure to antigen and reversed by corticosteroid treatment. The findings prompt consideration of this as a model of PI-IBS.     

Specific binding of 1,25 dihydroxyvitamin D3 in lymphocytes

We examined ten cellular or tissue sources of lymphocytes for specific binding of 1,25(OH)₂D₃, the hormonally active form of vitamin D₃. A specific-binding protein was found in three of these sources. Scatchard analysis of cytosol from a follicular lymphoma cell line revealed binding sites with a Kd of 7.0 × 10^?11 and a receptor concentration of 6.6 fmol/mg protein. Sucrose density centrifugation of ³H-1,25(OH)₂D₃ labeled cytosol showed a 3.75 peak which was absent in cytosols incubated with excess nonradioactive 1,25(OH)₂D₃. The relative amounts of vitamin D₃ metabolites required to displace 50% of the specifically bound ³H-1,25(OH)₂D₃ were 1,25(OH)₂D₃: 1,24,25(OH)₃D₃: 25(OH)D₃: 24,25(OH)₂D₃ = 1: 180: 1000: 2700. Excess vitamin D₃, cortisol, and estradiol failed to displace ³H-1,25(OH)₂D₃. Scatchard analysis of spleen cytosol from a patient with prolymphocytic transformation of chronic lymphocytic leukemia demonstrated a binding protein with a Kd of 1.2 × 10^?10 and a receptor concentration of 0.2 fmol/mg protein. DNA cellulose binding confirmed the presence of the specific-binding protein in this cytosol. Specific binding of ³H-1,25(OH)₂D₃ was also quantitated in a cell line from a patient with Burkitt's lymphoma with a Kd of 0.3 × 10^?10 and a receptor concentration of 29.6 fmol/mg protein. No specific binding of ³H-1,25(OH)₂D₃ was observed in lymphocytes from seven other malignant and nonmalignant sources. These results are the first to demonstrate a specific-binding protein for 1,25(OH₂D₃ in lymphocytes from tissue and from these specific cell lines. The presence of this protein in some lymphocytes but not others may reflect the state of activation of the lymphocytes.     

CERA (Continuous Erythropoietin Receptor Activator): a new erythropoiesis-stimulating agent for the treatment of anemia

Anemia is a common and debilitating condition in patients with chronic kidney disease and patients with cancer. Over the last 10 to 15 years, the introduction of erythropoietic therapy has transformed the management of anemia in both these conditions. The first therapeutic agent to be used for the stimulation of erythropoiesis was recombinant human erythropoietin (epoetin). At the turn of this century, darbepoetin alfa, a second-generation erythropoietic agent, became available. Darbepoetin alfa contains two additional N-linked carbohydrate chains, which confer greater metabolic stability in vivo. More recently, a third-generation molecule, Continuous Erythropoietin Receptor Activator (CERA), incorporating a large polymer chain, has been developed. CERA has an elimination half-life in humans that is considerably longer than the half-life of either epoetin or darbepoetin alfa. CERA may also have different receptor binding characteristics and pharmacology from other erythropoietic agents; these characteristics are the subject of ongoing investigation. CERA is currently in phase III clinical trials.     

High pre-treatment serum hepatitis B virus titre predicts failure of lamivudine prophylaxis and graft re-infection after liver transplantation

BACKGROUND/AIMS: Orthotopic liver transplantation has an established role for the treatment of patients with chronic liver failure secondary to hepatitis B virus (HBV) infection. Unfortunately, recurrent infection of the graft can be associated with aggressive disease, and with diminished graft and patient survival. Currently, the role of nucleoside analogues for prevention of graft re-infection is being evaluated. Preliminary results are encouraging, but treatment failure has been associated with emergence of drug-resistant virus. METHODS: We have studied ten consecutive patients who received lamivudine prophylaxis for prevention of HBV graft reinfection. Sequential sera, collected prelamivudine then during treatment before and after liver transplantation, were examined. Conventional serological markers were measured, as were serum viral DNA levels with a sensitive quantitative polymerase chain reaction assay. RESULTS: Lamivudine treatment effected a reduction in serum HBV levels, but six patients still had measurable viral DNA at the time of transplantation. Five patients developed graft re-infection with lamivudine-resistant virus. Resistant virus emerged 8 to 15 months post-transplant. The likelihood of emergence of resistant virus was related to the pre-treatment serum HBV titre. Persistent serum viral DNA positivity and evidence of graft re-infection during the early post-transplant period did not predict the subsequent emergence of resistant virus. CONCLUSIONS: Our observations suggest that the resistant species may be present in the viral quasispecies in the serum and liver of patients with high-level replication prior to lamivudine exposure. The resistant species can persist during lamivudine treatment prior to transplantation, and emerge following transplantation. These observations suggest strategies which might prevent the emergence of drug-resistant species, and imply that graft re-infection may be a preventable phenomenon.