Plasma coagulation markers in patients with solid tumors and venous thromboembolic disease receiving oral anticoagulation therapy.

PURPOSE: To correlate the concentration of plasma coagulation markers at baseline and during follow-up in patients with solid tumors and venous thromboembolic disease with the risk of recurrence and death. EXPERIMENTAL DESIGN: Patients (N = 223) with first episode of venous thromboembolic disease received oral anticoagulation with warfarin for a target international normalized ratio of 2 to 3. Plasma coagulation markers were measured before instituting warfarin and at 3 monthly intervals, thereafter. RESULTS: The median duration of oral anticoagulation was 6.7 months (range 2 weeks to 11 months). Major bleeding episodes occurred in 18 patients (8%), and minor hemorrhagic events occurred in 15 (6.7%) patients. Patients with advanced malignancy (P = 0.032), history of surgery (P = 0.057), and those with poor performance status (P = 0.001) were more likely to encounter major bleeding episodes. Recurrence of venous thromboembolic disease was diagnosed in 31 patients (14%). At univariate analysis, advanced stage of cancer (P = 0.03), performance status > 1 (P = 0.001), treatment with chemotherapy (P = 0.01), the presence of metastatic liver disease (P = 0.03), higher d-dimer (P = 0.001), and thrombin antithrombin complex levels (P = 0.01) were features predictive of recurrent venous thromboembolic disease. At multivariate analysis, poor performance status (P = 0.01) and d-dimer levels (P = 0.001) were predictors of recurrent venous thromboembolic disease. Persistent activation of coagulation as indicated by an upward trend in d-dimer (P = 0.001) and antithrombin (P = 0.001) was observed in patients who developed recurrent thrombosis. Similar upward trends in d-dimer (P = 0.001), antithrombin (P = 0.001), and prothrombin fragment F1 + 2 (P = 0.001) was observed in the 76 patients who died during the study period and in the patients who received chemotherapy. CONCLUSIONS: Successful oral anticoagulation with warfarin in patients with cancer and venous thromboembolic disease is more likely to be achieved in patients with early stage tumors and good performance status. The persistence of activation of hemostasis as shown by plasma coagulation markers is a strong predictor of recurrence and poor outcome.     

Radioprotective potential of primitive hematopoietic precursors forming colonies in diffusion chambers in mice

Abstract: The purpose of this study was to determine the radioprotective ability of primitive hematopoietic precursors which form colonies in diffusion chambers in mice (CFU-D). Thirty-two lethally irradiated female ICR mice were injected with 5 to 7 male ICR mouse bone marrow-derived CFU-D colonies each. Fourteen of these mice survived over 30 days and were sacrificed at intervals up to a year. As a control, 20 lethally irradiated female ICR mice received cells from intercolony areas. All of these mice died before day 20. DNA samples obtained from hematopoietic organs and liver from 8 sacrificed mice were analyzed for the presence of CFU-D colony-derived cells. Only in 1 ICR mouse was CFU-D colony origin DNA detected by Southern analysis in all hematopoietic organs: bone marrow, spleen, thymus and lymph nodes. In 6 mice, only selected hematopoietic organs were repopulated by CFU-D colony-derived cells as judged by Southern analysis. In some of these mice, the remaining hematopoietic organs contained small CDU-D-derived cell populations which could be detected by more sensitive polymerase chain reaction (PCR). In 1 mouse, the presence of CFU-D-derived cells in all hematopoietic organs was only demonstrated by PCR. These findings suggest that lethally irradiated mice can be rescued by CFU-D-derived daughter cells. They appear to have the potential to give rise to clones containing lymphoid and myeloid cells in all hematopoietic organs, at least temporarily. Thus, it can be concluded that CFU-D represents a very primitive hematopoietic precursor cell with radioprotective capability.     

The Notch pathway in colorectal cancer

Colorectal cancer (CRC) is the third leading cause of cancer death worldwide. It is also the third most common cancer diagnosis among men, and the second most common cancer diagnosis among women. Globally, CRC can account for nearly 694,000 annual deaths. It is widely appreciated that CRC is the result of dysregulated cellular pathways that promote an inappropriate stem‐cell‐like phenotype, apoptotic resistance, unchecked proliferation and metastatic spread. While no single pathway is responsible for all of these attributes, an array of recent studies suggests a pivotal role for abnormal Notch‐1 signaling in CRC, in part due to interconnectivity of Notch with other pathways. This review will summarize recent evidence for a role of Notch signaling in CRC, will consider interconnectivity between Notch and other pathways involved in CRC and will discuss the possible utility of targeting Notch as a CRC therapeutic.     

Association of Helicobacter pylori infection with cardiovascular disease--is it just a myth?

Objective

To test the hypothesis that Helicobacter pylori infection is associated with a higher rate of documented cardiovascular disease (CVD) in subjects undergoing elective upper gastrointestinal endoscopy.

Methods

202 consecutive patients (median age 60 years, 101 men) were studied. H. pylori infection was established by a rapid urease test in a gastric tissue sample (CLO test) and by histological examination of gastric mucosa from the stomach antrum and body. CVD was documented by completion of the Rose questionnaire. The association of H. pylori infection with CVD was determined by multivariate logistic regression modelling after adjusting for potential confounding factors.

Results

A total of 104 (51.5%) subjects were found H. pylori positive. Forty patients had a confirmed history of CVD. Multiple logistic regression analysis verified the strong associations of CVD with established risk factors of atherosclerotic disease but not with H. pylori infection.

Conclusion

Our findings suggest that there is no association of H. pylori infection with CVD. Eradication of H. pylori to prevent CVD is not warranted.     

Fixed Dose IV rt-PA and Clinical Outcome in Ischemic Stroke Patients With Body Weight >100 kg: Pooled Data From 3 Randomized Clinical Trials

Background and Purpose

The ASA/AHA guidelines recommend a fixed dose of 90 mg of intravenous (IV) recombinant tissue plasminogen activator (rt-PA) for acute stroke patients weighing more than 100 kg. We aimed to determine if body weight >100 kg (and receiving <0.9 mg/kg dose) independently influence patient clinical outcomes following IV rt-PA treatment.

Erythroid stem cell culture in serum-depleted medium

Summary Techniques are described for the culture of multipotential, primitive, and mature mammalian erythroid colony-forming stem cells obtained from bone marrow, spleen, blood, or fetal tissues in semisolid cultures under defined, serum-deprived growth conditions. Inasmuch as colony formation is critically dependent on the presence of tissue-specific growth factors, the addition of purified recombinant interleukin-3 and erythropoietin affords the opportunity to examine the specific growth requirements of undifferentiated hematopoietic cells in a critical and quantitative manner through terminal differentiation for extended periods of time.     

Spinal Dural Arteriovenous Fistulas: A Review

Obstructive sleep apnea (OSA) has been found to be an independent risk factor for stroke in large epidemiological studies. The mechanisms underlying this relationship have been investigated over the past 2–3 decades, with a particular focus on identifying pathophysiological pathways and risk modification strategies. Despite the advancements made, the specific understanding of the implicated mechanisms is still limited. This brief review focuses on presenting some of the epidemiological evidence of the linkage between OSA and stroke, discussing mechanistic pathways and the potential effect of OSA treatment in modulating the risk for stroke in these patients. Future directions for research in this field are also discussed.