Prediction of results of antiarrhythmic drug therapy in patients with malignant ventricular tachyarrhythmias, based on the prognostic value of left ventricular contractility parameters

In 44 patients (3 women and 41 men, mean age 54 +/- 11 years) with malignant ventricular tachyarrhythmias (MVT) we assessed dependence of results of testing of antiarrhythmic drugs and efficacy of their long term use for prevention of recurrences of MVT on topography of derangement of local left ventricular (LV) contractility. Regional LV contractility was assessed with transthoracic echocardiography and radionuclide ventriculography (RNV). Testing of antiarrhythmic drugs was performed under control of repetitive intracardiac electrophysiological studies. Duration of follow-up was 28 (13 - 61) months. According to ROC-analysis most precise markers of positive results of drug testing were values of local ejection fraction (EF) in apical LV segment (10th segment on RNV) above 55%. Signs predisposing to absence of MVT recurrences during long term use of antiarrhythmic drugs were lack of mitral regurgitation (above I degree) according to echocardiography data, values of local EF in segment of lateral LV wall (4th segment on RNV) exceeding 42%, or value of LV end diastolic volume less than 365 ml according to RNV data. Parameters of local LV contractility are most precise markers of results of the use of antiarrhythmic drugs in patients with MVT, their diagnostic value is hair than that of global LVEF. Efficacy of antiarrhythmic drugs at electrophysiologic testing and long term follow-up are associated with different parameters of local LV contractility.     

EGLN1 involvement in high-altitude adaptation revealed through genetic analysis of extreme constitution types defined in Ayurveda

It is being realized that identification of subgroups within normal controls corresponding to contrasting disease susceptibility is likely to lead to more effective predictive marker discovery. We have previously used the Ayurvedic concept of Prakriti, which relates to phenotypic differences in normal individuals, including response to external environment as well as susceptibility to diseases, to explore molecular differences between three contrasting Prakriti types: Vata, Pitta, and Kapha. EGLN1 was one among 251 differentially expressed genes between the Prakriti types. In the present study, we report a link between high-altitude adaptation and common variations rs479200 (C/T) and rs480902 (T/C) in the EGLN1 gene. Furthermore, the TT genotype of rs479200, which was more frequent in Kapha types and correlated with higher expression of EGLN1, was associated with patients suffering from high-altitude pulmonary edema, whereas it was present at a significantly lower frequency in Pitta and nearly absent in natives of high altitude. Analysis of Human Genome Diversity Panel-Centre d'Etude du Polymorphisme Humain (HGDP-CEPH) and Indian Genome Variation Consortium panels showed that disparate genetic lineages at high altitudes share the same ancestral allele (T) of rs480902 that is overrepresented in Pitta and positively correlated with altitude globally (P < 0.001), including in India. Thus, EGLN1 polymorphisms are associated with high-altitude adaptation, and a genotype rare in highlanders but overrepresented in a subgroup of normal lowlanders discernable by Ayurveda may confer increased risk for high-altitude pulmonary edema.     

COX2 and p53 risk-alleles coexist in COPD

BACKGROUND: Cigarette smoke stimulates airway epithelial cells to release pro-inflammatory cytokines which influence various inflammation-related genes, including COX2, whereas p53 expression is known to alter in such a condition. Since both the genes share several common physiological functions including inflammation and oxidative stress, we investigated within gene and gene-gene interactions towards susceptibility to the disease. METHOD: In a prospective gene-association study we conducted PCR-RFLP for genotyping the COX2 -765G/C and 8473T/C and p53 72Pro/Arg polymorphisms in 229 COPD patients and 147 healthy controls. RESULTS: The -765GC+CC genotypes of COX2 and Pro/Pro+Pro/Arg genotypes of p53 were prevalent in patients with significant odds ratio, 2.05 and 2.30, respectively (p=0.001; p=0.009, respectively), as a consequence, the -765C and 72Pro alleles were prevalent (p相似文献   

Assessment of perioperative transfusion therapy and complications in sickle cell disease patients undergoing surgery

BACKGROUND: Perioperative blood transfusion is usually given to sickle cell disease patients to reduce or prevent perioperative morbidity. Assessment of such a practice was the subject of our study. METHODS: A retrospective one year survey of sickle cell disease patients undergoing surgery at Salmaniya Medical Complex, Bahrain was conducted. The medical records were reviewed to characterize the surgical procedure, transfusion management and perioperative complications. RESULTS: 85 sickle cell disease patients who underwent surgery were studied. Preoperatively, 21.2% had exchange transfusion (ETX), 24.7% had simple transfusions (STX) and 54.1% had no transfusion (NTX). 14.1% of all patients had postoperative complications, and 50% of those, had complications from the laparoscopic cholecystectomy group. The incidence of sickle cell crisis postoperatively was 22.2% in ETX group, 9.5% in STX group and 4.34% in the NTX group. The incidence of acute chest syndrome postoperatively was found to be 5.55% in the ETX group, 4.76% in the STX group and 4.34% in the NTX group. No intraoperative complications were recorded in all groups. All patients who had postoperative complications had a preoperative HBSS > 40%. CONCLUSION: Exchange transfusion does not prevent perioperative complications of sickle cell disease patients. HBSS > 40% carries a higher risk of postoperative complications.     

Targeting HER-2/neu in early breast cancer development using dendritic cells with staged interleukin-12 burst secretion

Overexpression of HER-2/neu (c-erbB2) is associated with increased risk of recurrent disease in ductal carcinoma in situ (DCIS) and a poorer prognosis in node-positive breast cancer. We therefore examined the early immunotherapeutic targeting of HER-2/neu in DCIS. Before surgical resection, HER-2/neu(pos) DCIS patients (n = 13) received 4 weekly vaccinations of dendritic cells pulsed with HER-2/neu HLA class I and II peptides. The vaccine dendritic cells were activated in vitro with IFN-gamma and bacterial lipopolysaccharide to become highly polarized DC1-type dendritic cells that secrete high levels of interleukin-12p70 (IL-12p70). Intranodal delivery of dendritic cells supplied both antigenic stimulation and a synchronized preconditioned burst of IL-12p70 production directly to the anatomic site of T-cell sensitization. Before vaccination, many subjects possessed HER-2/neu-HLA-A2 tetramer-staining CD8(pos) T cells that expressed low levels of CD28 and high levels of the inhibitory B7 ligand CTLA-4, but this ratio inverted after vaccination. The vaccinated subjects also showed high rates of peptide-specific sensitization for both IFN-gamma-secreting CD4(pos) (85%) and CD8(pos) (80%) T cells, with recognition of antigenically relevant breast cancer lines, accumulation of T and B lymphocytes in the breast, and induction of complement-dependent, tumor-lytic antibodies. Seven of 11 evaluable patients also showed markedly decreased HER-2/neu expression in surgical tumor specimens, often with measurable decreases in residual DCIS, suggesting an active process of "immunoediting" for HER-2/neu-expressing tumor cells following vaccination. DC1 vaccination strategies may therefore have potential for both the prevention and the treatment of early breast cancer.     

T lymphocyte subset profile and serum alpha-1-antitrypsin in pathogenesis of chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is an inflammatory disorder characterized by the presence of non-fully reversible airflow limitation. The study was undertaken to investigate the involvement of alpha-1-antitrypsin (alpha(1)AT) and T lymphocyte subsets in the pathogenesis of COPD. Blood samples of 50 subjects, including 25 healthy volunteers and 25 patients with COPD, were analysed. Serum trypsin inhibitory capacity (STIC) was determined by enzymatic assay. CD4(+) and CD8(+) T lymphocytes were enumerated in heparinized blood using a fluorescence activated cell sorter counter. The STIC in COPD patients was found to be decreased significantly than in controls (P < 0.01). In COPD patients with lower expression levels of alpha(1)AT, a highly significant decrease in the number of CD4(+) T lymphocytes (P < 0.0009) and CD4/CD8 ratio was observed compared with control subjects (P < 0.008). The mean +/- standard error of CD8(+) lymphocytes was found to be little different (only marginally decreased) in COPD patients compared to healthy controls; however, an alteration in the individual count of CD8(+) lymphocytes cells was observed in COPD patients. Using linear regression analysis, a negative correlation was observed between STIC and CD4(+) lymphocytes and CD8(+) lymphocytes (r = -0.40, P < 0.04; r = -0.42, P < 0.03, respectively) in COPD patients. An alteration in alpha(1)AT and T lymphocyte subsets in COPD patients suggested that interplay of these factors may be responsible for the progression of COPD.