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41.
42.
Jeremy D. Robertson Pauline Higgins Jamie Price Scott Dunkley Giulio Barrese Julie Curtin 《Thrombosis research》2014
Introduction
It has been postulated that factor VIII (FVIII) products containing von Willebrand factor (VWF) may improve immune tolerance induction (ITI) success rate in patients with haemophilia A and poor prognostic factors.Materials and methods
We conducted a retrospective cohort analysis of a FVIII/VWF concentrate (BIOSTATE®) for ITI in paediatric patients with severe haemophilia A (SHA) and inhibitors, from January 2003 to December 2011 at 3 paediatric-only Haemophilia Treatment Centres in Australia. Response to ITI was assessed at or before 33 months and at completion of ITI. Fifteen male patients with SHA were included in the analysis.Results
BIOSTATE was used for primary ITI in 8 patients (2 years, range 1.1–11.5 years) and for salvage ITI in 7 patients (9.9 years, range 1.1–15.4). At the end of the observation period there were 11 patients who achieved a complete response with BIOSTATE after a median duration of 21 months (range 5–85 months); a partial response was achieved in 2 patients in whom ITI is ongoing. Therefore, the overall response rate was 86.6%. Two patients were deemed treatment failures: one due to non-compliance after 18 months of ITI and another in whom a partial response had not been achieved after 22 months of ITI.Conclusion
BIOSTATE was well-tolerated and effective when used for primary or salvage ITI in this cohort of paediatric patients with SHA and a high-level inhibitor. 相似文献43.
The hinge region in androgen receptor control 总被引:2,自引:0,他引:2
Clinckemalie L Vanderschueren D Boonen S Claessens F 《Molecular and cellular endocrinology》2012,358(1):1-8
The region between the DNA-binding domain and the ligand-binding domain of nuclear receptors is termed the hinge region. Although this flexible linker is poorly conserved, diverse functions have been ascribed to it. For the androgen receptor (AR), the hinge region and in particular the (629)RKLKKL(634) motif, plays a central role in controlling AR activity, not only because it acts as the main part of the nuclear translocation signal, but also because it regulates the transactivation potential and intranuclear mobility of the receptor. It is also a target site for acetylation, ubiquitylation and methylation. The interplay between these different modifications as well as the phosphorylation at serine 650 will be discussed here. The hinge also has an important function in AR binding to classical versus selective androgen response elements. In addition, the number of coactivators/corepressors that might act via interaction with the hinge region is still growing. The importance of the hinge region is further illustrated by the different somatic mutations described in patients with androgen insensitivity syndrome and prostate cancer. In conclusion, the hinge region serves as an integrator for signals coming from different pathways that provide feedback to the control of AR activity. 相似文献
44.
Although less extensively studied compared to pulmonary obstructive diseases, restrictive lung disease (RLD) is highly prevalent and frequently disabling in the adult and, more, the elderly population. The underlying conditions may be either primarily pulmonary diseases, such as idiopathic pulmonary fibrosis, or non respiratory conditions secondarily affecting the lung, e. g. congestive heart failure, or else conditions affecting the lung expansion, e. g. obesity or rib cage deformity. The diagnosis is frequently based on the measurement of surrogate indexes such as the forced vital capacity (FVC) used as a proxy for total lung capacity (TLC). As a consequence, diagnosis of RLD is often characterized by poor specificity. In the elderly, worsening in the quality of life and poor prognosis are variably, but significantly, associated to RLD, being the underlying condition an important source of variability. Several causes of RLD are preventable and treatable conditions. A prompt identification of these conditions may allow to slow the decline of respiratory reserve and, thus, to preserve both personal independence and resistance to acute respiratory infections. This review gives an update on the latest evidence available on the prevalence and the prognosis of RLD in the elderly. Studies were identified through systematic searches of the electronic database MEDLINE. Reference list of eligible papers were also manually searched. 相似文献
45.
46.
Helen Ingoldsby Mark Webber Deirdre Wall Carl Scarrott John Newell Grace Callagy 《Breast (Edinburgh, Scotland)》2013,22(5):879-886
Oncotype DX is an RT-PCR assay used to predict which patients with ER-positive node-negative (NN) disease will benefit from chemotherapy. Each patient is stratified into a risk category based on a recurrence score (RS) and the TAILORx trial is determining the benefit of chemotherapy for patients with mid-range RSs.We tested if Oncotype DX and TAILORx risk categories could be predicted by standard pathological features and protein markers corresponding to 10 genes in the assay (ER, PR, Ki67, HER2, BCL2, CD68, Aurora A kinase, survivin, cyclin B1 and BAG1) on 52 patients who enrolled on TAILORx. Immunohistochemistry for the protein markers was performed on whole tissue sections.Classification and regression tree (CART) analysis correctly classified 69% of cases into Oncotype DX risk categories based on the expression of PR, survivin and nuclear pleomorphism. All tumours with PR staining (Allred score ≥2) and marked nuclear pleomorphism were in the high-risk category. No case with PR <2, low survivin (≤15.5%) and nuclear pleomorphism <3 was high-risk. Similarly, 77% of cases were correctly classified into TAILORx categories based on nuclear pleomorphism, survivin, BAG1 and cyclin B1. Ki67 was the only variable that predicted the absolute RS with a cut-off for positivity of 15% (p = 0.003).In conclusion, CART revealed key predictors including proliferation markers, PR and nuclear pleomorphism that correctly classified over two thirds of ER-positive NN cancers into Oncotype DX and TAILORx risk categories. These variables could be used as an alternative to the RT-PCR assay to reduce the number of patients requiring Oncotype DX testing. 相似文献
47.
Hans-Ulrich Schildhaus Lars Schroeder Sabine Merkelbach-Bruse Elke Binot Reinhard Büttner Walther Kuhn Christian Rudlowski 《Breast (Edinburgh, Scotland)》2013,22(6):1066-1071
Male breast cancer (MBC) is a rare disease. To date, therapy is mainly based on studies and clinical experiences with breast cancer in women. Only little is known about molecular typing of MBC, particularly with regard to potential biological predictors for adjuvant therapy. In female breast cancer tumors with chromosome 17 centromere (CEP17) duplication, HER2 and/or Topoisomerase II alpha (Topo II-α) gene alterations have been suggested to be associated with poor prognosis and increased sensitivity to anthracycline-containing regimens.In a well characterized cohort of 96 primary invasive MBC, we studied CEP17, HER2 and Topo II-α alterations by fluorescence in-situ hybridization (FISH), and expression of hormone receptors (HR), HER2 and Ki67 by immunohistochemistry to define molecular subtypes. Tumor characteristics and follow-up data were available and correlated with molecular findings.HER2 amplification and Topo II-α amplification/deletion were exceptionally rare in MBC (6.3% and 3.1%, respectively). CEP17 polysomy were found in 9.4% of tumors. HER2, Topo II-α and CEP17 gene alterations were not correlated to patients outcome. 96.9% of our cases were HR positive. Triple negative tumors were found in only 3.1% of the cases. In nodal negative tumors luminal A subtypes were significantly associated with better overall survival.Our results provide evidence for a predominant male breast cancer phenotype, characterized by HR expression and a lack of HER2/Topo II-α alterations and CEP17 duplicates. Therefore, the impact of anthracycline sensitivity linked to HER2/Topo II-α alterations as found in female breast cancer has low clinical significance for this specific male breast cancer phenotype. 相似文献
48.
Seungtaek Lim Soohyeon Lee Jungwoo Han Byeong-Woo Park SeungIl Kim Seho Park Joo-Hang Kim Hye Jin Choi Joohyuk Sohn 《Breast (Edinburgh, Scotland)》2013,22(6):1205-1209
ObjectiveWe investigated the efficacy of maintenance hormone therapy (MHT), which was given to hormone positive metastatic breast cancer (MBC) patients in non-progression status to the previous chemotherapy.MethodsThis study retrospectively analyzed 76 MBC patients who had been treated with MHT from 2006 to 2010 at a single institute.ResultsFor the 76 patients reviewed, the median progression free survival (PFS) to MHT was 14.4 months (95% CI, 11.6–17.3). Prolonged PFS was associated with less previous palliative chemotherapy, fewer metastatic sites, and the absence of visceral metastasis in univariate analysis. Multivariate analysis showed that only the number of previous palliative chemotherapy (HR 1.73, 95% CI, 1.00–2.98; P = 0.04) remained as a significant variable. MHT was generally well tolerated.ConclusionsMHT showed considerable efficacy and tolerability in this study. Further randomized prospective study is warranted. 相似文献
49.
Willy Aasebø Jan Erikssen Jørgen Jonsbu Knut Stavem 《Scandinavian cardiovascular journal : SCJ》2013,47(2):79-84
Objectives. To assess how ethanol in potential lethal serum concentrations affects features of the ECG that may be associated with cardiac arrhythmias. Design. We included 84 patients, who were hospitalised with assumed acute ethanol intoxication. In the emergency room resting ECG was recorded and blood was collected for serum osmolality measurement used as a proxy for ethanol level. Thirty-two also had ECG recorded at discharge. Twenty-seven hospitalised patients without known alcohol ingestion served as controls. ECG segment durations were compared with controls and related to intoxication level. Results. In subjects with moderately elevated to high serum osmolality, the P wave and QTc intervals were prolonged compared with sober subjects. P wave, PR, QRS and QTc intervals were longer when the subjects had high blood ethanol levels (at admission) than at discharge (p-values: 0.0001, 0.0002, 0.010 and < 0.0001 for P wave, PR, QRS and QTc intervals. n = 32). Conclusions. Ethanol at high to very high blood concentration causes several changes in the ECG that might be associated with increased risk of arrhythmias. 相似文献
50.
Chun-Yen Chen Chii-Min Hwu Ming-Wei Lin Cheng-Ho Tsai 《Scandinavian cardiovascular journal : SCJ》2013,47(2):146-152
Background. The contribution of triglycerides (TG) to the extent of coronary artery disease (CAD) in hypertensive patients remained unclear. Methods. Consecutive 821 (aged 64.5±11.5 years, 482 males) hypertensive patients undergoing coronary angiography were included. The relationship of TG levels (<150 vs. ≥150 mg/dl) to the extent of CAD in all patients was examined by multiple logistic regression, adjusting for other CAD risk factors. In the lipid group, low levels of HDL were also adjusted. Results. Higher levels of TG were found in subjects with severe CAD compared to those with no or minimal CAD. The adjusted odds ratios for high levels of TG in the severe CAD subgroup versus the no or minimal CAD subgroup were 5.20 (95% CI, 3.13 to 8.63) in all patients and 7.51 (95% CI, 3.19 to 17.65) in the lipid group. Conclusions. High levels of TG are strong clinical markers of greater extent of CAD in hypertensive subjects undergoing coronary angiography. The results may have clinical relevance for physicians in therapeutic decision making. 相似文献