Plasma brain natriuretic peptide as a surrogate marker for cardioembolic stroke

<p>Abstract</p> <p>Background</p> <p>Cardioembolic stroke generally results in more severe disability, since it typically has a larger ischemic area than the other types of ischemic stroke. However, it is difficult to differentiate cardioembolic stroke from non-cardioembolic stroke (atherothrombotic stroke and lacunar stroke). In this study, we evaluated the levels of plasma brain natriuretic peptide in acute ischemic stroke patients with cardioembolic stroke or non-cardioembolic stroke, and assessed the prediction factors of plasma brain natriuretic peptide and whether we could differentiate between stroke subtypes on the basis of plasma brain natriuretic peptide concentrations in addition to patient's clinical variables.</p> <p>Methods</p> <p>Our patient cohort consisted of 131 consecutive patients with acute cerebral infarction who were admitted to Kagawa University School of Medicine Hospital from January 1, 2005 to December 31, 2007. The mean age of patients (43 females, 88 males) was 69.6 ± 10.1 years. Sixty-two patients had cardioembolic stroke; the remaining 69 patients had non-cardioembolic stroke (including atherothrombotic stroke, lacunar stroke, or the other). Clinical variables and the plasma brain natriuretic peptide were evaluated in all patients.</p> <p>Results</p> <p>Plasma brain natriuretic peptide was linearly associated with atrial fibrillation, heart failure, chronic renal failure, and left atrial diameter, independently (F_4,126= 27.6, p < 0.0001; adjusted R²= 0.45). Furthermore, atrial fibrillation, mitral regurgitation, plasma brain natriuretic peptide (> 77 pg/ml), and left atrial diameter (> 36 mm) were statistically significant independent predictors of cardioembolic stroke in the multivariable setting (Χ²= 127.5, p < 0.001).</p> <p>Conclusion</p> <p>It was suggested that cardioembolic stroke was strongly predicted with atrial fibrillation and plasma brain natriuretic peptide. Plasma brain natriuretic peptide can be a surrogate marker for cardioembolic stroke.</p

Loss of Cannabinoid Receptor CB1 Induces Preterm Birth

Preterm birth accounting approximate 10% of pregnancies in women is a tremendous social, clinical and economic burden. However, its underlying causes remain largely unknown. Emerging evidence suggests that endocannabinoid signaling via cannabinoid receptor CB1 play critical roles in multiple early pregnancy events in both animals and humans. Since our previous studies demonstrated that loss of CB1 defers the normal implantation window in mice, we surmised that CB1 deficiency would influence parturition events.Exploiting mouse models with targeted deletion of Cnr1, Cnr2 and Ptgs1 encoding CB1, CB2 and cyclooxygenase-1, respectively, we examined consequences of CB1 or CB2 silencing on the onset of parturition. We observed that genetic or pharmacological inactivation of CB1, but not CB2, induced preterm labor in mice. Radioimmunoassay analysis of circulating levels of ovarian steroid hormones revealed that premature birth resulting from CB1 inactivation is correlated with altered progesterone/estrogen ratios prior to parturition. More strikingly, the phenotypic defects of prolonged pregnancy length and parturition failure in mice missing Ptgs1 were corrected by introducing CB1 deficiency into Ptgs1 null mice. In addition, loss of CB1 resulted in aberrant secretions of corticotrophin-releasing hormone and corticosterone during late gestation. The pathophysiological significance of this altered corticotrophin-releasing hormone-driven endocrine activity in the absence of CB1 was evident from our subsequent findings that a selective corticotrophin-releasing hormone antagonist was able to restore the normal parturition timing in Cnr1 deficient mice. In contrast, wild-type females receiving excessive levels of corticosterone induced preterm birth.CB1 deficiency altering normal progesterone and estrogen levels induces preterm birth in mice. This defect is independent of prostaglandins produced by cyclooxygenase-1. Moreover, CB1 inactivation resulted in aberrant corticotrophin-releasing hormone and corticosterone activities prior to parturition, suggesting that CB1 regulates labor by interacting with the corticotrophin-releasing hormone-driven endocrine axis

p53 status of newly established acute myeloid leukaemia cell lines

We analysed the status of the p53 gene and protein in eight newly established acute myeloid leukaemia (AML) cell lines representing blast cells of either de novo leukaemia patients in first remission or patients with relapsed and chemotherapy-resistant disease causing their death. There were no mutations in the p53 gene in any of the cell lines as analysed by single-strand conformation polymorphism of amplified exons 5–8. However, the p53 protein was clearly and consistently expressed in all of these cell lines, as shown by immunohistochemistry, Western blotting and flow cytometry. The consistently expressed p53 protein was located in both the nucleus and the cytoplasm of all the cell lines and, as shown by flow cytometry, it was mostly in a conformation typical of the mutated protein. These AML cell lines offer a tool for studying the production and function of the p53 protein and its possible role in cell cycle regulation and chemoresistance as well as in the regulation of apoptosis in AML. © 1999 Cancer Research Campaig

Split T Cell Tolerance against a Self/Tumor Antigen: Spontaneous CD4+ but Not CD8+ T Cell Responses against p53 in Cancer Patients and Healthy Donors

Analyses of NY-ESO-1-specific spontaneous immune responses in cancer patients revealed that antibody and both CD4+ and CD8+ T cell responses were induced together in cancer patients. To explore whether such integrated immune responses are also spontaneously induced for other tumor antigens, we have evaluated antibody and T cell responses against self/tumor antigen p53 in ovarian cancer patients and healthy individuals. We found that 21% (64/298) of ovarian cancer patients but no healthy donors showed specific IgG responses against wild-type p53 protein. While none of 12 patients with high titer p53 antibody showed spontaneous p53-specific CD8+ T cell responses following a single in vitro sensitization, significant p53-specific IFN-γ producing CD4+ T cells were detected in 6 patients. Surprisingly, similar levels of p53-specific CD4+ T cells but not CD8+ T cells were also detected in 5/10 seronegative cancer patients and 9/12 healthy donors. Importantly, p53-specific CD4+ T cells in healthy donors originated from a CD45RA− antigen-experienced T cell population and recognized naturally processed wild-type p53 protein. These results raise the possibility that p53-specific CD4+ T cells reflect abnormalities in p53 occurring in normal individuals and that they may play a role in processes of immunosurveillance or immunoregulation of p53-related neoplastic events

ONYX-015: mechanisms of action and clinical potential of a replication-selective adenovirus

Accumulated knowledge in the molecular processes of tumour development combined with the availability of genetically modified viruses resemble the basis for new promising cancer therapeutics. The main advantages of employing replication-competent viruses are achievement of tumour selective killing and amplification of their oncolytic potential within the tumour mass. In this review, we describe the development of ONYX-015, one of the first and most advanced replication-competent viruses for cancer therapy. We discuss the molecular biology of this therapeutic approach and the interesting results obtained with this virus in clinical trials

Instruments to assess the perception of physicians in the decision-making process of specific clinical encounters: a systematic review

<p>Abstract</p> <p>Background</p> <p>The measurement of processes and outcomes that reflect the complexity of the decision-making process within specific clinical encounters is an important area of research to pursue. A systematic review was conducted to identify instruments that assess the perception physicians have of the decision-making process within specific clinical encounters.</p> <p>Methods</p> <p>For every year available up until April 2007, PubMed, PsycINFO, Current Contents, Dissertation Abstracts and Sociological Abstracts were searched for original studies in English or French. Reference lists from retrieved studies were also consulted. Studies were included if they reported a self-administered instrument evaluating physicians' perceptions of the decision-making process within specific clinical encounters, contained sufficient description to permit critical appraisal and presented quantitative results based on administering the instrument. Two individuals independently assessed the eligibility of the instruments and abstracted information on their conceptual underpinnings, main evaluation domain, development, format, reliability, validity and responsiveness. They also assessed the quality of the studies that reported on the development of the instruments with a modified version of STARD.</p> <p>Results</p> <p>Out of 3431 records identified and screened for evaluation, 26 potentially relevant instruments were assessed; 11 met the inclusion criteria. Five instruments were published before 1995. Among those published after 1995, five offered a corresponding patient version. Overall, the main evaluation domains were: satisfaction with the clinical encounter (n = 2), mutual understanding between health professional and patient (n = 2), mental workload (n = 1), frustration with the clinical encounter (n = 1), nurse-physician collaboration (n = 1), perceptions of communication competence (n = 2), degree of comfort with a decision (n = 1) and information on medication (n = 1). For most instruments (n = 10), some reliability and validity criteria were reported in French or English. Overall, the mean number of items on the modified version of STARD was 12.4 (range: 2 to 18).</p> <p>Conclusion</p> <p>This systematic review provides a critical appraisal and repository of instruments that assess the perception physicians have of the decision-making process within specific clinical encounters. More research is needed to pursue the validation of the existing instruments and the development of patient versions. This will help researchers capture the complexity of the decision-making process within specific clinical encounters.</p