中药注射剂在肾功能不全患者及老年人中的合理应用

目的了解本院中药注射剂在肾功能不全及老年患者中的使用规范情况,为调整用药剂量、保证疗效和减少不良反应提供依据。方法抽取本院2011年2月—3月应用中药注射剂的病历100份,监测患者血清肌酐值,计算肌酐清除率,并分析中药注射剂使用情况。结果 100例患者中有14例肌酐清除率超过标准,其中有5例属于中度损害,9例属于轻度损害。有9例血肌酐含量在正常范围内,但因为年龄偏大,导致肌酐清除率异常。结论许多因素可影响肌酐的产生及代谢,可能出现血肌酐水平正常而肌酐清除率下降的分离现象,因此常会造成对已有肾功能损害程度的低估,故临床工作中应依据肌酐清除率而不是血肌酐水平调整患者用药剂量。     

Betaine homocysteine methyl transferase 1, a novel auto-antigen associated with anti-Golgi immune reactivity

Anti-Golgi antibodies are rare autoantibodies that have been described in systemic autoimmune diseases. Not all Golgi auto-antigens are known. The objective of this study was to identify a novel auto-antigen associated with anti-Golgi immune reactivity. Sera from a patient with Golgi immune reactivity and from a control individual were used for Western blotting after 2-dimensional gel separation of a rat Golgi-enriched extract. Betaine homocysteine S-methyltransferase 1 (BHMT1) was identified as an auto-antigen by MALDI-TOF/TOF mass spectrometry. Using human recombinant BHMT1, a strong positive blotting signal was obtained with serum from the patient but not from a control. Pre-absorption of the serum sample with reactivity to BHMT1 with recombinant human BHMT1 resulted in decreased reactivity on Western blotting and in disappearance of the Golgi-like pattern on indirect immunofluorescence. Using immunocytochemistry, we confirmed the subcellular localization of BHMT1 to the Golgi apparatus. Antibodies to BHMT1 were found in four of 80 samples with a Golgi-pattern on indirect immunofluorescence. The antibodies were not associated with a specific clinical condition. We identified BHMT1 as a novel auto-antigen associated with anti-Golgi immune reactivity.     

Implication of transfected cell lines for the detection of alloantibodies against human neutrophil antigen-3

BACKGROUND: Alloantibodies against human neutrophil antigen‐3 (HNA‐3) are responsible for the fatalities reported in transfusion‐related acute lung injury. Consequently, reliable detection of these alloantibodies is mandatory to improve blood transfusion safety. In this study, we developed stable cell lines for the detection of HNA‐3 antibodies. STUDY DESIGN AND METHODS: HEK293T were transfected with HNA‐3a or HNA‐3b constructs and sorted by flow cytometry according to high surface expression. Transfected cells were tested with sera containing HNA‐3 antibodies in flow cytometry and antibody capture assay (ACA). The results were compared with granulocyte agglutination test and granulocyte immunofluorescence test. RESULTS: In flow cytometry, 12 of 14 HNA‐3a sera reacted specifically with HNA‐3aa cells. One serum sample showed positive reaction with HNA‐3bb cells. All HNA‐3b sera recognized HNA‐3bb cells. No reaction was observed with broad reactive antibodies against HLA Class I. In ACA, all HNA‐3a sera (12/12) showed positive reactivity with HNA‐3aa cells with no cross‐reactivity with HNA‐3bb cells. Again, all HNA‐3b sera reacted with HNA‐3bb cells only. Furthermore, genotyping of 249 individuals detected a new HNA‐3 allele caused by a nucleotide substitution C>T at Position 457 leading to L₁₅₃F mutation in choline transporter‐like protein‐2. This mutation impairs polymerase chain reaction with sequence‐specific primers based HNA‐3a typing. However, analysis with cells expressing F₁₅₃ isoform showed that this mutation did not alter the binding of HNA‐3 antibodies. CONCLUSIONS: This study demonstrated that HEK293T cells expressing stable recombinant HNA‐3 are suitable for the detection of HNA‐3 alloantibodies allowing reliable screening of blood products.     

Nurses' patient-education work: conditional factors - an integrative review

friberg f., bergh a.-l. & granum v. (2012) Journal of Nursing Management 20, 170–186
Nurses’ patient-education work: conditional factors – an integrative review Aim The aim of this review was to identify conditional factors for nurses’ patient-education work and to identify foundational aspects of significance when designing studies on this patient-education work. Background A few reviews of nurses patient education work exist, published up to 30 years ago, spawning interest in performing a review of more recent studies. Evaluation A search of CINAHL, MEDLINE and ERIC was made for articles dating from 1998 to 2011. Thirty-two articles were selected and an integrative review was performed. Key issues Conditional factors were identified and beliefs and knowledge, environment, organization, interdisciplinary cooperation, collegial teamwork and patient education activities. A model was developed to describe foundational aspects of significance when designing studies. Conclusions The conditional factors are to be seen as either enabling or hindering the accomplishment of evidence-based patient education and the level of person centredness, patient safe care and ethics – something that has to be considered when designing studies. Implications for nursing management More detailed studies are required to clarify the nature of patient education work and to create realistic conditions that enable the role to be fulfilled in everyday work. Such knowledge is of significance for nursing management in developing supportive activities for nurses.     

A randomised feasibility/phase II study (SBG 2004-1) with dose-dense/tailored epirubicin, cyclophoshamide (EC) followed by docetaxel (T) or fixed dosed dose-dense EC/T versus T, doxorubicin and C (TAC) in node-positive breast cancer

The aim of the study was to evaluate the feasibility of tailored and dose-dense epirubicin and cyclophosphamide followed by docetaxel as adjuvant breast cancer therapy. Material and methods. Patients with node-positive breast cancer received either four cycles of biweekly and tailored EC (epirubicin 38-60-75-90-105-120 mg/m(2), cyclophosphamide 450-600-900-1200 mg/m(2)) followed by four cycles of docetaxel (60-75-85-100 mg/m(2)) (arm A) or the same regimen with fixed doses (E(90)C(600) + 4 → T(75) + 4) (arm B) or docetaxel, doxorubicin and cyclophosphamide (T(75)A(50)C(500)) every three weeks for six cycles (arm C). All patients received G-CSF support and prophylactic ciprofloxacin. Results. One-hundred and twenty-four patients were randomised in the study. In the A, B and C arm, 17% 19% and 3% of the patients had one or more cycles delayed due to side-effects whereas 24%, 5% and 15% experienced a grade 3 infection or febrile neutropenia. After the introduction of an extra week between the EC and T parts in the A and B arms, grade 3 hand-foot-skin reactions were reduced from 5 to 0.2%. Twenty-nine percent (A and B) and 20% (C) of the patients were hospitalised due to side-effects. Discussion. Dose-dense and tailored EC/T can be given with manageable toxicity and is after adjustment presently studied in the phase III Panther trial.     

Prognostic Significance of Stromal Platelet-Derived Growth Factor β-Receptor Expression in Human Breast Cancer

This study systematically analyzes platelet-derived growth factor (PDGF) receptor expression in six types of common tumors as well as examines associations between PDGF β-receptor status and clinicopathological characteristics in breast cancer. PDGF receptor expression was determined by immunohistochemistry on tumor tissue microarrays. Breast tumor data were combined with prognostic factors and related to outcome endpoints. PDGF α- and β-receptors were independently expressed, at variable frequencies, in the tumor stroma of all tested tumor types. There was a significant association between PDGF β-receptor expression on fibroblasts and perivascular cells in individual colon and prostate tumors. In breast cancer, high stromal PDGF β-receptor expression was significantly associated with high histopathological grade, estrogen receptor negativity, and high HER2 expression. High stromal PDGF β-receptor expression was correlated with significantly shorter recurrence-free and breast cancer-specific survival. The prognostic significance of stromal PDGF β-receptor expression was particularly prominent in tumors from premenopausal women. Stromal PDGF α- and β-receptor expression is a common, but variable and independent, property of solid tumors. In breast cancer, stromal PDGF β-receptor expression significantly correlates with less favorable clinicopathological parameters and shorter survival. These findings highlight the prognostic significance of stromal markers and should be considered in ongoing clinical development of PDGF receptor inhibitors.Platelet-derived growth factor (PDGF) α- and β-tyrosine kinase receptors exert important control functions in mesenchymal cells, such as pericytes, fibroblasts and vascular smooth muscle cells during development.¹ PDGF receptor activation has also been shown to be involved in multiple dimensions of cancer growth.² The clinical relevance of these findings is enhanced by the recent approval of tyrosine kinase inhibitors with PDGF receptor inhibitory activity, eg, imatinib, sunitinib, and sorafenib.PDGF receptor-dependent growth stimulation is well documented in malignant cells of some solid tumors, such as glioblastomas,^3,4,5,6,7 dermatofibrosarcoma protuberans^8,9 and a subset of gastrointestinal stromal tumors.^10,11 Also, in hematological malignancies such as chronic myelomonocytic leukemia and idiopathic eosinophilic syndrome, PDGF α- or β-receptor signaling has been shown to be activated through translocations or deletions of the PDGF receptor genes.^12,13,14 However, in most common solid tumors PDGF receptor signaling appears to be most important for the pericytes of the tumor vessels, and for the fibroblasts of the tumor stroma.Concerning the role of PDGF β-receptor signaling in pericytes, a series of experimental studies have demonstrated that stimulation of PDGF receptors on pericytes increases pericyte coverage of vessels in a manner that is associated with increased vessel function and, in some cases, also increased tumor growth.^15,16,17 Furthermore, vascular endothelial growth factor receptor-targeted antiangiogenic approaches in experimental tumor models appear to be most efficient on immature pericyte-poor vessels.¹⁸ Finally, combinations of vascular endothelial growth factor receptor- and PDGF-receptor inhibitors have been demonstrated to exert synergistic antiangiogenic effects.^19,20Studies in experimental tumor models have demonstrated that paracrine activation of PDGF receptors on fibroblasts acts as a potent signal for tumor stroma recruitment.^21,22 Other studies with PDGF antagonists have also demonstrated direct antitumoral effects of stromal PDGF receptor inhibition,^23,24 as well as beneficial effects on tumor drug uptake.^25,26,27,28The biological effects of PDGF receptors in tumor fibroblasts and pericytes, together with the advent of drugs with PDGF receptor-inhibitory activity thus motivates a systemic characterization of the expression pattern of PDGF α- and β-receptors in human tumors. In this study we have characterized the fibroblast and pericyte expression of PDGF α- and β-receptors in lymphomas and in colon, ovarian, prostate, lung and breast cancers. Furthermore the relationship between stromal PDGF β-receptor status and prognostic parameters and survival was analyzed in breast cancer.