Autoantibodies against bactericidal/permeability-increasing protein in patients with cystic fibrosis

Cystic fibrosis (CF), a genetic disorder, is characterized by chronic pulmonary infection/inflammation which leads to respiratory failure. The presence of anti-neutrophil cytoplasmic autoantibodies (ANCA) has previously been observed in the sera of patients with CF. In view of the known relationship of ANCA with primary vasculitis and of their putative pathogenetic role in these disorders, we studied the presence, specificity and isotype of ANCA and their clinical associations in 66 adult CF patients. None of the 66 CF samples had autoantibodies to the major ANCA antigens, proteinase 3 or myeloperoxidase. However, 60/66 (91%) CF samples contained IgG and 55/66 (83%) IgA, autoantibodies to bactericidal/permeability increasing protein (BPI), a recently characterized ANCA specificity. All the IgA anti-BPI-positive samples were also IgG anti-BPI-positive. The autoantibody specificity was confirmed by inhibition assay and immunoblotting of CF sera against a neutrophil granule preparation. Furthermore, in this cross-sectional study, anti-BPI levels were inversely correlated with the observed reductions in FEV1 and FVC (IgA anti-BPI and FEV1: r = 0.508, <it>p</it> &lt; 0.0001), and both IgG and IgA anti-BPI levels were higher in CF patients with secondary vasculitis (<it>n</it> = 6) than in those without (<it>p</it> &lt; 0.05). ANCA with specificity for BPI were present in the majority of CF sera in this study and autoimmune processes may be associated with the development of pulmonary injury in CF.      

The effect of cuff pressure deflation rate on accuracy in indirect measurement of blood pressure with the auscultatory method

The importance of cuff deflation rate in the auscultatory method of measuring blood pressure was investigated using a computer-based model. To determine the relationship between the cuff deflation rate and the measurement error, two cuff deflation protocols were used, one based on heart rate (mm Hg per heartbeat), the other on a constant rate (mm Hg per second). The different deflation protocols and rates were tested using a constant blood pressure of 120/80 mm Hg and heart rates ranging from 40 to 120 beats/min. It was confirmed that a cuff deflation rate that is time based will introduce larger errors at low heart rates. Using heart rate as a basis for cuff deflation rate yields a constant error that is independent of heart rate. The currently used standard of 3 mm Hg/s could result in a maximum error of 2.5 mm Hg in both systolic and diastolic pressures at a heart rate of 72 beats/min. The maximum systolic and diastolic errors increase to more than 4 mm Hg at 40 beats/min. A deflation rate of 2 mm Hg/beat, however, yields a maximum error of 2 mm Hg for both systolic and diastolic pressures, independent of heart rate. A cuff deflation rate based on heart rate is recommended to help minimize changes in measurement error when measuring blood pressure if a wide range of heart rates will be encountered.Supported by grants from IVAC, San Diego, CA, and Physio Control, Redmond, WA.     

Factors influencing capnography in the bain circuit

The Bain circuit provides continuous fresh gas flow near the airway. The potential mixing of this fresh gas with expired gas may prevent reliable analysis of expired gas. We therefore investigated the interaction of sampling site, fresh gas flow rate, expiratory flow rate, and sampling flow rate on expiratory capnography. Sampling near the fresh gas outlet yielded inaccurate results under several of these conditions. The magnitude of the error was related to the fresh gas and expiratory flow rates. A reliable sampling region near the endotracheal tube was identified.     

Genetic control of specific immune suppression. IV. Responsiveness to the random copolymer L-glutamic acid(50)-L-tyrosine(50) induced in BALB/c mice by cyclophosphamide

Previous reports from our laboratory have demonstrated the stimulation of specific suppressor T cells in genetic nonresponder mice after immunization with the terpolymer of L- glutamic acid, L-alanine, and L-tyrosine (GAT) (1,2) and with the copolymer of L-glutamic acid and L-tyrosine (GT) (3-5). These findings raise two important questions: (a) do the specific suppressor T cells inhibit an antibody response which would otherwise develop in nonresponder mice; and, (b) can specific helper T cells inhibit an antibody response which would otherwise develop in nonresponder mice; and, (b) can specific helper T-cell activity be detected in these animals. Responsiveness appears to be completely dominant over suppression in (responder x suppressor)F(1) hybrids, therefore, we have been unable to detect suppressor cells in these hybrids after conventional immunization with GAT (2). However , using special conditions of antigen administration, GAT helper activity could be demonstrated in nonresponder DBA/1 (“suppressor”) mice. Thus, GAT-specific helper activity was not detected in these nonresponder animals after immunization with GAT irrespective of the adjuvant used, but could be stimulated by macrophage-bound GAT or by GAT complexed with methylated bovine serum albumin GAT-MBSA (6). In the current report we have taken advantage of the fact that suppressor T-cell activity is more sensitive to cyclophosphamide treatment than T-cell helper activity (7) to demonstrate the presence of GT-specific helper activity in “nonresponder” BALB/c mice. We describe: (a) the dose of cyclophosphamide and conditions of treatment which inhibits the well-documented stimulation of specific suppressor T cells in BALB/c mice injected with GT previous to immunization with GT-MBSA, and (b) the ability of cyclophosphamide to permit the development of primary PFC responses to GT in these “nonresponder” mice. These cyclophosphamide-induced responses are not characterized by the high levels of antibody detected in genetic responder animals.     

Trends in treatment and overall survival among patients with proximal esophageal cancer

BACKGROUND The management of proximal esophageal cancer differs from that of tumors located in the mid and lower part of the esophagus due to the close vicinity of vital structures. Non-surgical treatment options like radiotherapy and definitive chemoradiation(CRT) have been implemented. The trends in(non-)surgical treatment and its impact on overall survival(OS) in patients with proximal esophageal cancer are unclear, related to its rare disease status. To optimize treatment strategies and counseling of patients with proximal esophageal cancer,it is therefore essential to gain more insight through real-life studies.AIM To establish trends in treatment and OS in patients with proximal esophageal cancer.METHODS In this population-based study, patients with proximal esophageal cancer diagnosed between 1989 and 2014 were identified in the Netherlands Cancer Registry. The proximal esophagus consists of the cervical esophagus and the upper thoracic section, extending to 24 cm from the incisors. Trends in radiotherapy, chemotherapy, and surgery, and OS were assessed. Analyses were stratified by presence of distant metastasis. Multivariable Cox proportional hazards regression analyses was performed to assess the effect of period of diagnosis on OS, adjusted for patient, tumor, and treatment characteristics.RESULTS In total, 2783 patients were included. Over the study period, the use of radiotherapy, resection, and CRT in non-metastatic disease changed from 53%,23%, and 1% in 1989-1994 to 21%, 9%, and 49% in 2010-2014, respectively. In metastatic disease, the use of chemotherapy and radiotherapy increased over time. Median OS of the total population increased from 7.3 mo [95% confidence interval(CI): 6.4-8.1] in 1989-1994 to 9.5 mo(95%CI: 8.1-10.8) in 2010-2014(logrank P 0.001). In non-metastatic disease, 5-year OS rates improved from 5%(95%CI: 3%-7%) in 1989-1994 to 13%(95%CI: 9%-17%) in 2010-2014(logrank P 0.001). Multivariable regression analysis demonstrated a significant treatment effect over time on survival. In metastatic disease, median OS was 3.8 mo(95%CI:2.5-5.1) in 1989-1994, and 5.1 mo(95%CI: 4.3-5.9) in 2010-2014(logrank P = 0.26).CONCLUSION OS significantly improved in non-metastatic proximal esophageal cancer, likely to be associated with an increased use of CRT. Patterns in metastatic disease did not change significantly over time.     

保定市社区老年人日常生活活动能力 及其影响因素分析

摘要:目的　探讨保定市社区老年人日常生活活动能力及其影响因素。方法　采用自制的一般情况、躯体状况问卷及日常生活活动能力评定量表（ADL）对符合要求的555例社区老年人进行一般情况、躯体状况及日常生活活动能力的调查。结果　保定市社区老年人日常生活活动能力整体得分均值为18.1045,多因素分析显示对社区老年人日常生活活动能力的主要影响因素是年龄、性别、文化程度、BMI、职业、听力障碍、视力障碍、慢性病、用药。结论　保定市社区老年人日常生活活动能力明显存在障碍,应根据影响因素进行有效干预,以提高该地区老年人的生存质量。