Optimising the response to acute clinical deterioration: the role of observation and response charts

We sought the role of the hospital inpatient observation and response chart (ORC) in reducing adverse outcomes. We sourced articles written in English and published in PubMed. Track, trigger and response systems can be tiered and use single parameter or aggregate scoring systems, the latter being more prone to error. The documentation and detection of abnormal vital signs can be affected by choice of trigger and response and by ORC design. There is considerable variation in the design of ORC and of rapid response systems (RRS) in general, and this impairs assessment of their efficacy. A high rate of modification of pre‐determined triggers and poor sensitivity of measured outcomes further compromise systematic review. The best‐designed ORC and RRS should optimise the frequency of response team activation to minimise adverse patient outcomes without excess resource utilisation. The role and the risks of electronic data recording are under‐explored. Detecting and responding to deteriorating patients relies on accurate and clear documentation of vital signs. ORC design and staff education on ORC implementation and usage are integral to minimising ALF and optimising patient outcomes. Standardisation of the design of both the ORC and the hospital RRS are overdue.     

Role of endogenous biological response modifiers in pathogenesis of infectious diseases

Biologic response modifiers (BRMs) interact with the host immune system and modify the immune response. BRMs can be therapeutically used to restore, augment, or dampen the host immune response. Although they have been used for decades, their clinical applications have been expanded in the past decade for diagnosis and treatment of many diseases including cancers, immunologic disorders, and infections. This article discusses endogenous biological response modifiers (ie, naturally occurring immunomodulators as a part of the host immune system), which play vital roles as regulators of both innate and adaptive immune responses.     

心肺运动试验中窦房结变时效应频率应答特性的初步探讨

采用最大症状限制性心肺运动试验的方法，依据运动过程中心率与机体作功和体内代谢强度的变化关系研究４０名正常人运动中窦房结变时效应的频率应答特性，探讨心率储备和影响最大心率的主要因素。结果显示：心率与作功呈直线相关（Ｙ＝７５＋０．４１Ｘ，ｒ＝０．９８６３，Ｐ＜０．００１）。运动中心率与代谢当量亦呈直线相关（Ｙ＝５２．３＋１１．０１Ｘ，ｒ＝０．９１５２，Ｐ＜０．００１）。影响最大心率的主要因素是氧耗量、二氧化碳量和每分通气量。运动过程中心率与运动负荷和代谢的线性关系反映了窦房结频率应答的特性，即代谢性频率应答。窦房结的这种特性可能是单传感器频率应答性起搏器不能完全符合生理需要的基本原因。     

恩替卡韦治疗慢性HBV感染者KIR基因多态性与疗效的相关性研究

目的探讨慢性HBV感染者杀伤细胞免疫球蛋白样受体(killer immunoglobulin-like receptor,KIR)基因多态性及其与应用恩替卡韦疗效差异相关性。方法采用序列特异性引物聚合酶链反应(PCR-SSP)法,对60例应用恩替卡韦治疗的慢性HBV感染者(试验组)和60例健康对照者(对照组)的KIR基因进行基因分析,比较试验组和对照组的差异。60例患者中18例为治疗完全应答者(完全应答组),42例为非完全应答者(非完全应答组),比较2组之间差异。结果通过试验组和对照组的16种KIR基因分析,框架基因KIR2DL4、3DL2、3DL3和3DP1存在于所有个体中,其基因频率均为1.0。试验组KIR 2DS2和KIR2DS3基因型频率高于对照组(P值依次为0.038和0.035);完全应答组KIR2DS1、KIR3DS1和KIR2DL5基因型频率高于非完全应答组(P值依次为0.010、0.029和0.018)。结论 KIR2DS2、KIR2DS3可能是HBV的易感基因型,KIR2DS1、KIR3DS1、KIR2DL5可能与恩替卡韦抗HBV治疗有效应答有关。     

Expression of immune genes in skin of channel catfish immunized with live theronts of Ichthyophthirius multifiliis

The objective of this study was to evaluate differential expression of innate and adaptive immune genes, including immunoglobulin, immune cell receptor, cytokine, inflammatory protein , toll‐like receptors (TLR) and recombination‐activating gene (RAG) in skin from channel catfish, Ictalurus punctatus after immunization with live theronts of Ichthyophthirius multifiliis (Ich) by intraperitoneal injection. The immunized catfish showed significantly higher survival rate (95%) than those of mock‐immunized control fish (0% survival) after the theront challenge. The gene expression of innate immune system, such as cytokines (IL‐1β type a, IL‐1β type b, IFN‐γ, TGF1‐β and TNF‐α) and inflammatory proteins (NF‐kB and iNOS 2), showed significant upregulation at day 1 (D1) post‐immunization. Expression of TLR genes exhibited a rapid increase from hour 4 (h4) to D10 post‐immunization. Genes of the adaptive response, such as the cell receptor MHC I, CD8⁺, CD4⁺ and TCR‐α, showed upregulation at D1, D6 and D10. The TCR‐β expression increased rapidly at h4 and remained upregulated until D10. Immunoglobulin IgM upregulation was detected from h4 until D2 while IgD expression was increased from D1 until D10. Rapid upregulation of innate and adaptive immune genes in skin of catfish following live theront vaccination was demonstrated in this study ultimately resulting in significant protection against Ich infection.     

Predictive value of rapid virological response and early virological response on sustained virological response in HCV patients treated with pegylated interferon alpha-2a and ribavirin

BACKGROUND AND AIM: The therapeutic effect of pegylated interferon (peg-IFN)-alpha-2a combination with ribavirin on patients with chronic hepatitis C virus (HCV) infection is dependent on the rapidity of the virological response. The aim of this study was to investigate the predictive value of rapid virological response (RVR) and early virological response (EVR) on sustained virological response (SVR) in HCV patients treated with peg-IFN-alpha-2a and ribavirin. METHODS: The HCV genotypes of 105 patients with chronic hepatitis C were detected by enzyme-immunoassay. Patients received subcutaneous 180 microg peg-IFN-alpha-2a once weekly plus daily ribavirin. Patients with genotype 1 were treated for 48 weeks and patients with genotype 2 or 3 were treated for 24 weeks. HCV RNA was assessed by qualitative PCR at pretreatment, at weeks 4 and 12 during treatment, and at week 24 of follow-up. Virological response rates at different weeks were investigated, with RVR defined as serum HCV RNA undetectable after 4 weeks and EVR defined as HCV RNA either undetectable or decrease by >or=2 log(10) after 12 weeks. The effects of virological response rates at different weeks on SVR were analyzed. RESULTS: Of the 105 patients, 44 (41.9%) were genotype 1, 46 (43.8%) were genotype 2, and 15 (14.3%) were genotype 3. RVR rates (19.5%) of patients with genotype 1 were significantly lower than those (60.7%) of genotype 2 or 3 (chi(2) = 16.836, P = 0.000); and EVR rates (73.2%) of patients with genotype 1 were significantly lower than those (96.7%) of genotype 2 or 3 (chi(2) = 12.220, P = 0.000). The SVR rates (86.7%) of patients who had achieved RVR were significantly higher than those (43.9%) of patients who had not achieved RVR (chi(2) = 19.713, P = 0.000). The positive predictive value of RVR in all patients was higher than that of EVR, but there was no significant difference between RVR and EVR. The negative predictive value of RVR in all patients or with genotype 1 was significantly lower than that of EVR. In univariate analysis, HCV RNA level (P = 0.014), genotype (P = 0.001), RVR (P = 0.000) and EVR (P = 0.000) were associated with effect of treatment. However, in stepwise regression analysis, the independent factors associated with effect of antiviral therapy were RVR (OR = 6.501, P = 0.001), EVR (OR = 2.776, P = 0.003) and genotype (OR = 3.061, P = 0.024). CONCLUSIONS: The RVR and EVR rates of patients with genotype 1 were significantly lower than those of patients with genotype 2 or 3. RVR had a similar predictive value as EVR on SVR. Genotype, HCV RNA level, RVR and EVR were associated with SVR. Genotype, RVR and EVR were independent factors for predicting the effect of antiviral therapy.     

巨噬细胞与结核分枝杆菌的免疫反应的研究进展

巨噬细胞是结核分枝杆菌在机体内的主要宿主细胞.细胞介导的免疫反应是机体抗结核分枝杆菌的主要免疫保护机制,巨噬细胞可通过吞噬、溶酶体融合,提呈结核分枝杆菌抗原,产生多种细胞因子、反应氧中间产物和反应氮中间产物,以及细胞凋亡等多种途径来杀灭结核分枝杆菌;同时,结核分枝杆菌也可采取各种方式来逃逸巨噬细胞的免疫作用.本文就巨噬细胞与结核分枝杆菌的免疫反应的研究进展作一综述.     

巨噬细胞与结核分枝杆菌的免疫反应的研究进展

巨噬细胞是结核分枝杆菌在机体内的主要宿主细胞.细胞介导的免疫反应是机体抗结核分枝杆菌的主要免疫保护机制,巨噬细胞可通过吞噬、溶酶体融合,提呈结核分枝杆菌抗原,产生多种细胞因子、反应氧中间产物和反应氮中间产物,以及细胞凋亡等多种途径来杀灭结核分枝杆菌;同时,结核分枝杆菌也可采取各种方式来逃逸巨噬细胞的免疫作用.本文就巨噬细胞与结核分枝杆菌的免疫反应的研究进展作一综述.     

Evaluation of initial virological response to adefovir and development of adefovir-resistant mutations in patients with chronic hepatitis B

Summary.  The aims of the present study were to assess initial virological response (IVR) to adefovir (ADV) treatment for chronic hepatitis B, to identify patients with suboptimal response and to determine the incidence of ADV-resistant mutants. All patients treated with ADV for at least 12 months were evaluated for virological response and ADV resistance. IVR was defined as a reduction ≥4 log₁₀ IU/mL in hepatitis B virus (HBV)-DNA at month 6. Forty-two patients were analysed. Mean treatment duration was 23 ± 7 months; 50% had prior lamivudine (LAM) therapy (LAM resistance 62%); 88% were hepatitis B e antigen (HBeAg)-negative; and 76% carried genotype D. IVR was seen in 40.5% of patients. Higher baseline ALT level was the only factor associated with IVR ( P  = 0.043). Patients with IVR achieved undetectable HBV-DNA at month 12 in 77% of cases compared with only 5% of those without IVR ( P  < 0.001). Five (12%) patients developed ADV-resistant mutations: rtN236T in four cases and one case with an rtV207L change, which has not been previously reported. This mutation was accompanied by viral rebound and alanine aminotransferase (ALT) flare. The cumulative probability of ADV-resistant mutations at 12 and 24 months was 5% and 17% respectively. IVR defined as a reduction ≥4 log₁₀ IU/mL in HBV-DNA at month 6 is a useful tool to predict virological response at month 12 and to identify patients with suboptimal response to ADV. Cumulative probability of ADV resistance is higher than previously reported for nucleos(t)ide-naïve patients.     

Differential Effects of Facial Nerve Transection on Heat Shock Protein 70 Expression in the Developing and Adult Hamster Facial Nucleus

In this study, the effects of axotomy on heat shock protein 70 (hsp70) protein levels were analyzed by immunoblotting with a hsp70 antibody that recognized constitutive and inducible forms of the protein. The right facial nerve of postnatal day 4 (neonate) or 100 (adult) hamsters was transected at its exit from the stylomastoid foramen, with the left nerve serving as internal control. Postoperative survival times were 2, 6, 12, and 24 h, with 3 animals per time point. Tissue punches containing individual facial nuclear groups were collected and homogenized. Approximately 10 g of total protein was loaded onto paired gels and electrophoretically separated. Immunoblots of one gel from each pair were prepared, with the other gel stained in 0.2% Coomassie blue and used for verification of equality of lane loading. The results indicate that hsp70 protein levels increase in the adult, but decrease in the neonate, after axotomy. It is concluded that a stress response to cellular damage is an initial component of the classically described axon reaction and that hsp70 plays a role in mediating motoneuron survival after peripheral nerve transection.     

Changes of pituitary sensitivity to LH-RH during the rat estrous cycle

The plasma LH (luteinizing hormone) response to 200 ng of LH-RH (LH-releasing hormone) injected subcutaneously at different stages of the estrous cycle in normal rats under Surital anesthesia was maximal during the afternoon of proestrus and lowest on diestrus I. The area under the plasma LH curve measured at 13:00 on proestrus was approximately 7-fold higher than that obtained at 15:30 h on diestrus I. Intermediate responses were found on diestrus II, estrus and morning of proestrus. An approximately 2.5-fold higher LH response was observed on proestrus than on diestrus I after injection of [D-Ala²], des Gly-NH₂¹⁰] LH-RH ethylamide at 15:00 h. That these marked changes of LH response are not secondary to interference by endogenous LH-RH, changes of the metabolism or transport of exogenous LH-RH or modification of plasma LH clearance is ascertained by the finding of similar changes of pituitary sensitivity to LH-RH under in vitro conditions using pituitaries collected at the same stages of the estrous cycle. As measured both in vivo and in vitro, not only the amplitude but also the speed of LH response are maximal during the afternoon of proestrus and minimal on diestrus I.     

The reality of cancer treatment in a developing country: the effects of delayed TKI treatment on survival,cytogenetic and molecular responses in chronic myeloid leukaemia patients

Cancer patients in developing and low‐income countries have limited access to target therapies. For example, tyrosine kinase inhibitor (TKI) therapy for chronic myeloid leukaemia patients (CML) is often delayed. In Bosnia, 16% of patients received immediate TKI treatment (<3 months of diagnosis), while 66% of patients received therapy after a median 14‐month wait period. To assess the effect of delayed treatment on outcome, three patient groups were studied according to the time they received TKI treatment (0–5 months, 6–12 months and >13 months delay). The primary endpoints were complete cytogenetic (CCyR) and major molecular response (MMR) at 12 months. At 12 months of therapy, CCyR and MMR rates on imatinib decreased significantly: CCyR was achieved in 67% of patients in the immediate imatinib treatment group, 18% of patients in 6–12 months group and 15% of patients in >13 months wait group. MMR rates at 12 months occurred in 10% of patients with immediate treatment, 6% of those in 6–12 months group and 0% of patients in >13 months wait group. However, CCyR and MMR rates in patients on nilotinib were not associated with duration of treatment delay. Our data suggests that the deleterious effect of a prolonged TKI therapy delay may be ameliorated by the more active TKI nilotinib.     

白色念珠菌sap2基因真核表达质粒的构建及免疫原性研究

目的构建以白色念珠菌SAP2蛋白编码基因sap2为目的基因的真核重组表达质粒,并对其免疫原性进行分析。方法RT-PCR法自白色念珠菌标准菌株ATCC64550中获取sap2基因,插入真核表达载体pcDNA3.1中,将真核表达经质粒大抽提并定量后免疫BALB/c小鼠,ELISA法检测抗体产生水平,流式细胞仪检测细胞免疫。结果RT-PCR法克隆出全长为1 197 bp的sap2基因;用构建的pcDNA3.1-SAP2免疫小鼠,能诱导产生效价为1∶1 600的IgG抗体,同时CD4^＋T和CD8^＋T细胞百分比增高。结论成功获取了白色念珠菌sap2蛋白基因,真核表达质粒能够诱导动物的体液免疫和细胞免疫。     

Modulation of anti-idiotypic immune response by immunization with the autologous M-component protein in multiple myeloma patients

Multiple myeloma is characterized by a proliferation of clonal B lymphocytes and plasma cells. The idiotypic structure of clonal immunoglobulin (Ig) expressed on the tumour B-cell surface can be regarded as a tumour-specific antigen and, as such, a potential target for anti-idiotypic T and B cells in an immune regulation of the tumour-cell clone. Active immunization using the autologous monoclonal Ig as a 'vaccine' was shown to induce tumour-specific immunity in murine B-cell tumours and in human B-cell lymphoma. With the aim to induce or amplify an anti-idiotypic response in multiple myeloma, five stage I–III patients were repeatedly immunized with the autologous monoclonal IgG. Induction of idiotype-specific cellular immunity was analysed in vitro by an enzyme-linked immunospot assay (interferon-γ and interleukin-4 secreting cells). B cells secreting anti-idiotypic IgM antibodies were also analysed. An anti-idiotypic T-cell response was amplified 1.9–5-fold in three of the five patients during immunization. The number of B cells secreting anti-idiotypic antibodies also increased in these three patients. In two of the patients induction of idiotype-specific immunity was associated with a gradual decrease of blood CD19⁺ B cells. The induced T-cell response was eliminated during repeated immunization. Further studies are warranted to optimize the immunization schedule in order to achieve a long-lasting T-cell immunity against idiotypic determinants on the tumour clone. A role for immunity in controlling the tumour clone remains to be established.     

Modulation of anti-idiotypic immune response by immunization with the autologous M-component protein in multiple myeloma patients

Multiple myeloma is characterized by a proliferation of clonal B lymphocytes and plasma cells. The idiotypic structure of clonal immunoglobulin (Ig) expressed on the tumour B-cell surface can be regarded as a tumour-specific antigen and, as such, a potential target for anti-idiotypic T and B cells in an immune regulation of the tumour-cell clone. Active immunization using the autologous monoclonal Ig as a ‘vaccine’ was shown to induce tumour-specific immunity in murine B-cell tumours and in human B-cell lymphoma. With the aim to induce or amplify an anti-idiotypic response in multiple myeloma, five stage I–III patients were repeatedly immunized with the autologous monoclonal IgG. Induction of idiotype-specific cellular immunity was analysed in vitro by an enzyme-linked immunospot assay (interferon-γ and interleukin-4 secreting cells). B cells secreting anti-idiotypic IgM antibodies were also analysed. An anti-idiotypic T-cell response was amplified 1.9–5-fold in three of the five patients during immunization. The number of B cells secreting anti-idiotypic antibodies also increased in these three patients. In two of the patients induction of idiotype-specific immunity was associated with a gradual decrease of blood CD19⁺ B cells. The induced T-cell response was eliminated during repeated immunization. Further studies are warranted to optimize the immunization schedule in order to achieve a long-lasting T-cell immunity against idiotypic determinants on the tumour clone. A role for immunity in controlling the tumour clone remains to be established.     

全身炎症反应综合征1 292例临床分析

目的 提高对危重病人发生全身炎症反应综合征（ＳＩＲＳ）的认识。方法 分析１２９２例ＳＩＲＳ的临床资料,病人至少符合２个ＳＩＲＳ标准,包括发热、体温过低、心动过速、呼吸急促或白细胞计数异常。结果 １２９２例患者中细菌学检查３４１例（２６．４％）,其中阳性者１３８例（４０．５％）,死亡３３例（２３．９％）。１２９２例患者中符合ＳＩＲＳ２项标准者４６７例（３６．１％）,３项者５２６例（４０．７％）,４项     

Guidelines for clinical protocols for chronic lymphocytic leukemia: recommendations of the National Cancer Institute-sponsored working group

The National Cancer Institute (NCI)-sponsored Chronic Lymphocytic Leukemia (CLL) Working Group was convened to develop a set of standardized eligibility, response, and toxicity criteria for clinical trials. We recognized the previous efforts in 1967 (published again in 1973 as the report of the Chronic Leukemia-Myeloma Task Force [1] and 1978 of Cancer and Leukemia Group B (CALGB) [2]). We have used these reports for guidance during the current effort. Several noteworthy developments in the past few years have made it necessary to modify the previous guidelines. First, the diagnostic criteria for CLL and its clinical staging have been developed and well defined. Second, although staging systems facilitated entry of comparable and relatively homogeneous groups of patients in clinical trials, the definitions of response (CR) and partial response (PR) were not uniformly adopted from the previous guidelines in the clinical trials (Tables IA, IB); therefore, comparisons of results obtained in different studies became difficult. Third, there has been an improvement in our understanding of the immunology and biology of CLL. Finally, we are witnessing the emergence of several chemotherapy agents that promise impressive activity in CLL (e.g., 2'-deoxycoformycin [3], fludarabine monophosphate [4, 5]), and thereby offer the potential for improving survival time in this disease. To best identify regimens worthy of continued pursuit in large comparative trials, standardized guidelines for evaluation are essential. A number of laboratory investigations are also presented for which scientific interest is high yet relevance remains to be determined; thus, they are presented as companion studies to the clinical trials. This mechanism allows for flexibility in the testing of these questions and for additional ideas in the future without requiring modification of an entire treatment protocol. The following guidelines were developed to be used as a form of standardization for clinical trials, incorporating current technologies, yet remaining relevant to the general hematology/oncology community. Based on the membership of the Working Group, it is expected that these guidelines will serve as the criteria for most clinical trials in the near future.