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Sökning: WFRF:(Blomquist Carl)

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  • Al-Rashidi, Faleh, et al. (författare)
  • A new de-airing technique that reduces systemic microemboli during open surgery: a prospective controlled study.
  • 2009
  • Ingår i: The Journal of thoracic and cardiovascular surgery. - Mosby. - 1097-685X. ; 138:1, s. 157-162
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: We have evaluated a new technique of cardiac de-airing that is aimed at a) minimizing air from entering into the pulmonary veins by opening both pleurae and allowing lungs to collapse and b) flushing out residual air from the lungs by staged cardiac filling and lung ventilation. These air emboli are usually trapped in the pulmonary veins and may lead to ventricular dysfunction, life-threatening arrhythmias, and transient or permanent neurologic deficits. METHODS: Twenty patients undergoing elective true left open surgery were prospectively and alternately enrolled in the study to the conventional de-airing technique (pleural cavities unopened, dead space ventilation during cardiopulmonary bypass [control group]) and the new de-airing technique (pleural cavities open, ventilator disconnected during cardiopulmonary bypass, staged perfusion, and ventilation of lungs during de-airing [study group]). Transesophageal echocardiography and transcranial Doppler continually monitored the air emboli during the de-airing period and for 10 minutes after termination of the cardiopulmonary bypass. RESULTS: The amount of air embolism as observed on echocardiography and the number of microembolic signals as recorded by transcranial Doppler were significantly less in the study group during the de-airing time (P < .001) and the first 10 minutes after termination of cardiopulmonary bypass (P < .001). Further, the de-airing time was significantly shorter in the study group (10 vs 17 minutes, P < .001). CONCLUSION: The de-airing technique evaluated in this study is simple, reproducible, controlled, safe, and effective. Moreover, it is cost-effective because the de-airing time is short and no extra expenses are involved.
  • Fehringer, Gordon, et al. (författare)
  • Cross-Cancer Genome-Wide Analysis of Lung, Ovary, Breast, Prostate, and Colorectal Cancer Reveals Novel Pleiotropic Associations
  • 2016
  • Ingår i: Cancer research. - 1538-7445. ; 76:17, s. 5103-5114
  • Tidskriftsartikel (refereegranskat)abstract
    • Identifying genetic variants with pleiotropic associations can uncover common pathways influencing multiple cancers. We took a two-staged approach to conduct genome-wide association studies for lung, ovary, breast, prostate and colorectal cancer from the GAME-ON/GECCO Network (61,851 cases, 61,820 controls) to identify pleiotropic loci. Findings were replicated in independent association studies (55,789 cases, 330,490 controls). We identified a novel pleiotropic association at 1q22 involving breast and lung squamous cell carcinoma, with eQTL analysis showing an association with ADAM15/THBS3 gene expression in lung. We also identified a known breast cancer locus CASP8/ALS2CR12 associated with prostate cancer, a known cancer locus at CDKN2B-AS1 with different variants associated with lung adenocarcinoma and prostate cancer and confirmed the associations of a breast BRCA2 locus with lung and serous ovarian cancer. This is the largest study to date examining pleiotropy across multiple cancer-associated loci, identifying common mechanisms of cancer development and progression.
  • Flach, Carl-Fredrik, 1977-, et al. (författare)
  • A truncated form of HpaA is a promising antigen for use in a vaccine against Helicobacter pylori.
  • 2011
  • Ingår i: Vaccine. - 1873-2518. ; 29:6, s. 1235-1241
  • Tidskriftsartikel (refereegranskat)abstract
    • HpaA is a Helicobacter pylori-specific lipoprotein that has been shown to be an effective protective antigen for mucosal vaccination against H. pylori infection in mice. However, detergents are needed for the purification of full-length HpaA (HpaA(full)), which might confer toxicity, thus making HpaA(full) unsuitable for use in a human vaccine. We here describe a recombinantly produced truncated version of HpaA (HpaA(trunc)), which is easily purified without the use of detergents. Evaluation in the murine H. pylori infection model showed that sublingual immunization with HpaA(trunc) was equally immunogenic and protective as immunization with HpaA(full). Immunization with a combination of HpaA(trunc) and recombinant UreB protein induced strong immune responses to both antigens and importantly had a strong synergistic effect on protection, associated with synergistically increased expression of IL-17 in the stomach. Notably, sublingual immunization with HpaA(trunc) and UreB was superior to corresponding intragastric immunization with regard to the level of protection induced. In conclusion, HpaA(trunc) is a promising, readily produced, non-toxic recombinant antigen for inclusion in a mucosal vaccine against H. pylori infection, which may preferably be given sublingually together with UreB.
  • Nord, Helena, et al. (författare)
  • Characterization of novel and complex genomic aberrations in glioblastoma using a 32K BAC array
  • 2009
  • Ingår i: Neuro-Oncology. - 1522-8517 .- 1523-5866. ; 11:6, s. 803-818
  • Tidskriftsartikel (refereegranskat)abstract
    • Glioblastomas (GBs) are malignant CNS tumors often associated with devastating symptoms. Patients with GB have a very poor prognosis, and despite treatment, most of them die within 12 months from diagnosis. Several pathways, such as the RAS, tumor protein 53 (TP53), and phosphoinositide kinase 3 (PIK3) pathways, as well as the cell cycle control pathway, have been identified to be disrupted in this tumor. However, emerging data suggest that these aberrations represent only a fraction of the genetic changes involved in gliomagenesis. In this study, we have applied a 32K clone-based genomic array, covering 99% of the current assembly of the human genome, to the detailed genetic profiling of a set of 78 GBs. Complex patterns of aberrations, including high and narrow copy number amplicons, as well as a number of homozygously deleted loci, were identified. Amplicons that varied both in number (three on average) and in size (1.4 Mb on average) were frequently detected (81% of the samples). The loci encompassed not only previously reported oncogenes (EGFR, PDGFRA, MDM2, and CDK4) but also numerous novel oncogenes as GRB10, MKLN1, PPARGC1A, HGF, NAV3, CNTN1, SYT1, and ADAMTSL3. BNC2, PTPLAD2, and PTPRE, on the other hand, represent novel candidate tumor suppressor genes encompassed within homozygously deleted loci. Many of these genes are already linked to several forms of cancer; others represent new candidate genes that may serve as prognostic markers or even as therapeutic targets in the future. The large individual variation observed between the samples demonstrates the underlying complexity of the disease and strengthens the demand for an individualized therapy based on the genetic profile of the patient.
  • Raghavan, Sukanya, 1974-, et al. (författare)
  • Sublingual immunization protects against Helicobacter pylori infection and induces T and B cell responses in the stomach. Sublingual immunization against H. pylori infection
  • 2010
  • Ingår i: Infection and immunity. - 1098-5522. ; 78:10, s. 4251-60
  • Tidskriftsartikel (refereegranskat)abstract
    • Sublingual (SL) immunization has been described as an effective novel way to induce mucosal immune responses in the respiratory and genital tracts. We examined the potential of SL immunization against Helicobacter pylori to stimulate immune responses in the gastrointestinal mucosa and protect against H. pylori infection. Mice received two SL immunizations with H. pylori lysate antigens and cholera toxin as an adjuvant, and after challenge with live H. pylori bacteria, their immune responses and protection were evaluated, as were immune responses prior to challenge. SL immunization induced enhanced proliferative responses to H. pylori antigens in cervicomandibular lymph nodes and provided at least the same level of immune responses and protection as corresponding intragastric immunization. Protection in SL-immunized mice was associated with strong H. pylori-specific serum IgG and IgA antibody responses in the stomach and intestine, with strong proliferation and gamma interferon (IFN-γ) and interleukin-17 (IL-17) production by spleen and mesenteric lymph node T cells stimulated with H. pylori antigens in vitro, and with increased IFN-γ and IL-17 gene expression in the stomach compared to levels in infected unimmunized mice. Immunohistochemical studies showed enhanced infiltration of CD4(+) T cells and CD19(+) B cells into the H. pylori-infected stomach mucosa of SL-immunized but not unimmunized H. pylori-infected mice, which coincided with increased expression of the mucosal addressin cell adhesion molecule (MAdCAM-1) and T and B cell-attracting chemokines CXCL10 and CCL28. We conclude that, in mice, SL immunization can effectively induce protection against H. pylori infection in association with strong T and B cell infiltration into the stomach.
  • Rosendahl, Mikkel, et al. (författare)
  • The risk of amenorrhoea after adjuvant chemotherapy for early stage breast cancer is related to inter-individual variations in chemotherapy-induced leukocyte nadir in young patients : Data from the randomised SBG 2000-1 study
  • 2009
  • Ingår i: European Journal of Cancer. - 0959-8049 .- 1879-0852. ; 45:18, s. 3198-3204
  • Tidskriftsartikel (refereegranskat)abstract
    • Study aim: Amenorrhoea is a common side-effect to chemotherapy of premenopausal women. We examine the association between chemotherapy-induced leucopaenia and the development of amenorrhoea in premenopausal women with breast cancer. Materials and methods: in a multi-centre, randomised, controlled study, 1016 premenopausal women received seven series of FEC (F: fluorouracil, E: epirubicin and C: Cyclophosphamide) for early stage breast cancer. In the first series, all patients received standard dose (F: 600 mg/m(2), E: 60 mg/m(2) and C: 600 mg/m(2)). Patients with leukocyte nadir 1.0-1.9 x 10(9)/l continued with standard dose for the remaining six series (STANDARD(REGISTERED), n = 279). Patients with leukocyte nadir &gt;= 2 x 10(9)/l were randomised to standard (STANDARD(RANDOMISED), n = 373) or increased (TAILORED, n = 364) dose of E and C. After each series, leukocyte nadir was evaluated. Absent bleeding after the 5th-7th series of FEC was interpreted as amenorrhoea. Results: The risk of amenorrhoea increased with age. In age-stratified analysis of the STANDARD groups (equal dose, different initial leukocyte nadir) low leukocyte nadir was associated with amenorrhoea for patients in the age-group 25-39 years (P = 0.010). In age-stratified analysis in the randomised groups (different doses, same initial leukocyte nadir) a dose related increased risk of amenorrhoea was found for age-groups 25-39 (RR: 1.15, 95% confidence interval (CI): 1.06-1.24) and 40 44 years (RR:1.21, 95% CI: 1.001-1.47). Conclusion: Age is the most important risk factor of amenorrhoea after FEC chemotherapy. However, for younger patients, lower leukocyte nadir in response to STANDARD FEC treatment or increased doses of C and E were associated with increased risk of amenorrhoea. (C) 2009 Elsevier Ltd. All rights reserved.
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