tbuckley/cabot-search huggingface dataset:
Circulating Immune Complexes after Renal Transplantation
Authors: Yuet M. Ooi, Boon S. Ooi, Enrique H. Vallota, Martin R. First, Victor E. Pollak
Journal: Journal of Clinical Investigation (1977)

To assess the role of circulating immune complexes in the pathogenesis of acute rejection, sera were measured for such complexes by the (125)I-C1(q) binding assay in 45 normal subjects, 24 allografted patients undergoing acute rejection, and in 11 allografted patients in a quiescent phase. Increased C1(q)-binding activity (C1(q)-BA) was detected in 14 patients with acute rejection, 9 of whom had renal biopsies showing fibrin deposition in the vasculature together with cellular infiltrates in the tubulo-interstitial structures; renal histology was not available in the other 5 patients. The other 10 patients with acute rejection, whose biopsies showed only cellular infiltrates, and the 11 patients in a quiescent phase posttransplantation did not have increased levels of serum C1(q)-BA. Of the group with increased serum C1(q)-BA, serial studies in eight patients showed a correlation between increased serum C1(q)-BA and the occurrence of rejection; with reversal by therapy, serum C1(q)-BA returned to within normal levels. Complexes from six patients were analyzed by sucrose density gradient ultracentrifugation to have sedimentation coefficients ranging from 15S to 18.4S. After acid dissociation and analysis by double-diffusion techniques, C1(q)-reactive complexes were shown to contain IgG. Immunofluorescent studies done in five renal biopsies from this group revealed granular deposits of immunoglobulin, and (or) less frequently, of complement in the glomeruli or the tubular basement membranes. The findings suggest that circulating immune complexes may mediate the type of acute rejection characterized by fibrin deposition in the kidney. The role of circulating immune complexes arising from the recipient's original kidney disease could be excluded in 10 patients with humoral rejection, inasmuch as the underlying renal pathology was of a "nonimmunologic" nature; this was corroborated by sequential studies in six patients in whom circulating immune complexes could not be demonstrated before rejection. The participation of administered antilymphocyte globulin (ALG) as an antigen also appears to be excluded in four patients, two who were not given ALG, and in two of whom episodes of rejection occurred unrelated temporally to ALG administration.
Treatment of advanced breast cancer with sterically stabilized liposomal doxorubicin: results of a multicenter phase II trial.
Authors: M R Ranson, J Carmichael, K O'Byrne, S Stewart, D Smith, A Howell
Journal: Journal of Clinical Oncology (1997)

PURPOSE A multicenter phase II study to determine the activity and toxicity of Caelyx (Doxil; Sequus Pharmaceuticals Inc, Menlo Park, CA) in patients with metastatic breast cancer. PATIENTS AND METHODS Seventy-one patients with stage IV breast cancer were treated with Caelyx at doses of 45 to 60 mg/m2 every 3 to 4 weeks for a maximum of six cycles. Twenty-eight patients had received prior chemotherapy with a nonanthracycline regimen. Fifty-two patients had disease at multiple sites. Hepatic and pulmonary disease were the predominant metastatic site in 50 patients. Response was assessable in 64 cases. RESULTS Sixteen patients achieved a partial response and a complete response (overall response rate, 31%; (95% confidence interval, 20% to 43%). Twenty patients (31%) had stable disease on treatment. Neutropenia &gt; or = grade 3 occurred in 10% of cycles (27% of patients) and mucositis &gt; or = grade 3 in 10% of cycles (32% of patients). Significant alopecia was rare and routine prophylactic antiemetics were not required. At doses of 60 mg/m2 every 3 weeks, seven of 13 patients had &gt; or = grade 3 skin toxicity; overall, this toxicity complicated 25% of treatment cycles. The incidence of &gt; or = grade 3 skin toxicity was greatly reduced at doses of 45 mg/m2 every 4 weeks, occurring in five of 32 patients and affecting only 5% of 126 treatment cycles. CONCLUSION Caelyx is an active agent in advanced breast cancer with a safety profile that differs markedly from nonliposomal doxorubicin. A regimen of 45 mg/m2 every 4 weeks was well tolerated in this cohort of women with advanced poor-prognosis breast cancer. The mild myelosuppression seen with this regimen would favor its use in combination chemotherapy.
Interventions to optimize the use of colony-stimulating factors.
Authors: Heena Rathod, Sol Yoder
Journal: Journal of Clinical Oncology (2014)

92 Background: The Food and Drug Administration approved granulocyte colony-stimulating factors filgrastim (fil) and pegfilgrastim (peg) for use in the prevention of chemotherapy-induced neutropenia. The objective of this study was to characterize and optimize the current utilization of these costly colony-stimulating factors within a tertiary care health system. Methods: Data parameters and improvement measures were defined based on the current literature, national guidelines and institutional standards. Data was collected retrospectively by chart review and analyzed to develop interventions that would optimize fil/peg utilization. Existing policies and procedures were updated, and feedback and approval was obtained through collaborative groups. Improvement measurements will be reassessed post implementation of the proposed interventions. Results: Chart review yielded 156 fil/peg orders. The following observations and interventions were applied. All indications were determined appropriate per established oncology guidelines; however, 3 patients received an unwarranted fil/peg dose within a week of peg administration. An electronic alert was created to prevent administration of an additional fil dose if a recent peg dose had been administered. Of inpatient fil orders (n=38), 24% of weight-based dose rounding and 32% of predetermined discontinuation parameters were not compliant with the institutional standards. Fill electronic order entries were modified to automatically round doses based on patient weight. If an additional one-time absolute neutrophil count (ANC) discontinuation parameter was applied, it is anticipated that fil treatment duration could decrease in 30% of patients. The one-time ANC discontinuation parameter for fil was added. Conclusions: Although our system’s utilization of colony-stimulating factors was in compliance with national guidelines and institutional standards, opportunities for optimization were identified and targeted for improvement.
Can forced oscillation technique parameters predict airway hyperresponsiveness to histamine
Authors: Hiroaki Hayashi, Takahiro Tsuburai, Kentaro Watai, Chihiro Mitsui, Masanori Fukuhara, Takafumi Minami, Hidenori Tanimoto, Yuma Fukutomi, Chiyako Oshikata, Jun Ito, Kiyoshi Sekiya, Naomi Tsurikisawa, Yuji Maeda, Akio Mori, Masami Taniguchi, Maki Hasegawa, Kazuo Akiyama
Journal: European Respiratory Journal (2014)

Background   Measurement of airway hyperresponsiveness (AHR) is more sensitive than spirometry for diagnosing and monitoring asthma. However, because the measurement of AHR is invasive, safer and less invasive methods are needed. Forced oscillation technique (FOT) is a rapid, noninvasive method of measuring the resistance and reactance of the respiratory system at rest.    Objective   To assess whether FOT parameters predict the level of AHR to histamine in stable adult Japanese asthmatics.    Methods   We recruited 62 stable asthmatics that were being treated with inhaled corticosteroids and investigated the correlations between AHR to histamine and FOT parameters. For each patient, we determined fraction of exhaled nitric oxide (FeNO), forced expiratory volume in 1 s (FEV 1 ), and percentage predicted FEV 1  (%FEV 1 ) with standard techniques, and resistance at 5 Hz (R5) and 20 Hz (R20), the difference between R5 and R20 (R5 – R20), reactance at 5 Hz (X5), frequency of resonance (Fres), and low-frequency reactance area (ALX) with a MostGraph FOT machine (Chest Co., Ltd., Tokyo, Japan). We then determined the logarithm of the provocative concentration of histamine producing a 20% fall in FEV 1  (Log PC 20 ).    Results   R5, R20, X5, Fres, and ALX were significantly correlated with FEV 1  and %FEV 1 . Log PC 20  was significantly correlated with R5 ( r  = –0.446,  P   r  = –0.401,  P  = 0.001), and R5 – R20 ( r  = –0.401,  P  = 0.001). There were no significant correlations between the FOT parameters and FeNO.    Conclusion   FOT parameters measured with a MostGraph FOT machine may predict the level of AHR to histamine in stable adult asthmatics.
Independent validation of prognostic value of 22 microRNAs (miRs) in stage I-II lung adenocarcinoma (AC)
Authors: Marcin Skrzypski, Krzysztof Goryca, Amelia Szymanowska-Narloch, Ewa Jassem, Piotr Czapiewski, Wojciech Biernat, Ryszard Pawlowski, Witold Rzyman, Jacek Jassem
Journal: European Respiratory Journal (2012)

Background: About 50% of NSCLC patients (pts) will develop distant metastases following pulmonary resection. Currently, apart from clinical stage at diagnosis, there are no reliable factors to select the high risk pts for adjuvant chemotherapy. We previously demonstrated prognostic value of 22 miRs in frozen tissue samples of early stage SqCLC, and the feasibility of their expression assessment in formalin fixed paraffin embedded (FFPE) samples (Skrzypski et. al. J Clin Oncol 2010; 28;15s). In this study, we validated the prognostic value of these miRs in an independent cohort of early AC pts.  Methods: FFPE tumor samples were obtained from 82 stage I-II AC pts who underwent radical pulmonary resection, 44% of whom developed distant metastases. Median follow-up of pts who did not develop metastases was 5.53 years (range, 3,01-8.9 years). miRs were isolated from tumor tissue with RecoverAll kit (Ambion). Expression of 22 miRs previously found to be related to the risk of metastases was analyzed by RT-PCR assay (Appliedbiosystems). Raw data were normalized vs. the expression of U6. Individual miRs were correlated with distant metastases-free survival (MFS).  Results: MiR-222* (p=0,0003) and miR-222 (p=0,002) were significantly related to MFS. Using the median of the miR-222* expression as a cut-off value, the median MFS was 2.12 years in the high risk group, and not reached in the low risk group (HR=1.95). Using the median of the miR-222 expression as a cut-off value, the median MFS was 2.56 years in the high risk group, and not reached in the low risk group (HR=1.78).  Conclusions: MiR-222* and miR-222 are strong predictors of distant relapse in operable early AC.
Contrasting exercise cerebral oxigenation in COPD patients with and without chronic heart failure
Authors: Mayron F. Oliveira, Flávio Ferlin Arbex, Maria Clara N. Alencar, Aline S. Souza, Rita C. Lima, Luiz A. Medina, Wladimir M. Medeiros, Luiz Eduardo Nery, Dirceu R. Almeida, J. Alberto Neder
Journal: European Respiratory Journal (2013)

Background:  Cerebral oxygenation (COx) increases during progressive exercise, a key adjustment to performance that is impaired in patients with chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF). Association of COPD and CHF could potentiate these deleterious phenomena.  Objective:  To evaluate COx as assessed by continuous-wave near-infrared spectroscopy in response to incremental cycle ergometry exercise test in COPD-CHF versus COPD alone.  Methods : 24 males (13 with COPD-CHF (FEV 1 = 59.6 ± 17.5% pred; left ventricle ejection fraction (LVEF)= 34 ± 6% )) and 10 with COPD (FEV 1 = 48.6 ± 16.0% pred; LVEF= 64 ± 4%) were submitted to cardiopulmonary exercise test. ΔCOx (fold-changes in HbO 2 ), oxyhemoglobin saturation (SpO 2 ), and cardiac output (QT) by impedance cardiography were assessed. Variables were analyzed at peak exercise and up to an iso-work rate of 40 W (area under the curve, AUC).  Results:  COPD-CHF had lower peak oxygen uptake (VO 2 ) ( p  p  vs.  37 ± 3 ( p  2  AUC, however, was higher in the former group (p p  Conclusion : Increases in cerebral oxigenation were lessened in COPD-CHF overlap compared to COPD on isolation. These findings are more likely to be related to hemodynamic deficits as blood oxygenation was better in patients with coexisting COPD-CHF.
Getting more for their dollar: Kaiser v the NHS
Authors: D. U Himmelstein
Journal: BMJ (2002)

EDITOR—The NHS is little cheaper than health care in the United States, according to Feachem et al.1 What's next on their agenda? War is peace? Freedom is slavery? The authors purport to show Kaiser's efficiency relative to the NHS. This task is hard, given two undisputed facts: firstly, the United Kingdom's per capita health expenditure is $1569, the United States's $4358; and secondly, Kaiser's casemix adjusted costs are about average for the United States. Undeterred, Feacham et al use an outrageous price adjustment, exclude many of Kaiser's costs, and ignore Kaiser's avoidance of the sickest and most expensive patients.

Feachem et al's price adjustment inflates NHS costs by 52%, assuming that the NHS plays no part in constraining drug prices, administrators' or specialists' incomes, etc. Conversely, the adjustment excuses the US system from responsibility for the world's highest drug costs and the billions wasted on healthcare executives and other hangers on. Feachem et al adjust away the price controls that are an important advantage of non-market systems.

Feachem et al trim Kaiser's costs by subtracting profits and high administrative expenses. Yet both are integral to the competitive market they extol. They falsely equate Kaiser's coverage with the NHS's, although Kaiser covers only miniscule amounts of nursing home care. Finally, many Kaiser patients—more than 12% according to a Kaiser memo—receive care outside Kaiser, costs which the authors exclude. Thus, Feachem et al understate Kaiser's actual costs.

Contrary to Feachem et al's assertions, Kaiser cares for a relatively inexpensive slice of the population. Their claim that Kaiser cannot avoid the expensively ill by booting them out is technically correct; when Kaiser members lose their jobs (for example, because of illness) and hence employer paid coverage, Kaiser must offer them individual policies. But Kaiser may charge whatever it likes—often thousands per month. …
A nested case-control study of serum 25-hydroxyvitamin D levels and risk of adult-onset asthma – The HUNT study
Authors: Xiao-Mei Mai, Arnulf Langhammer, Carlos A. Camargo, Yue Chen
Journal: European Respiratory Journal (2011)

Background: The impact of low vitamin D status on the development of asthma is not clear. We conducted a nested case-control study to investigate the relation of baseline serum 25-hydroxyvitamin D [25(OH)D] levels and adult-onset asthma.

Methods: A total of 25,616 adults aged 19-55 years who participated in the second Norwegian Nord-Trondelag Health Study (HUNT), were followed-up for 11 years. A nested case-control study consisted of all the new onset asthma cases during the follow-up (n=600) and a random sample of non-asthma controls (n=2013). Baseline blood samples were available in 584 asthma cases and 1958 non-asthma controls. Baseline serum 25(OH)D levels were measured by automated antibody-based chemiluminescence assay.

Results: The mean level of baseline serum 25(OH)D was slightly lower in asthma cases compared with controls in both men (geometric mean: 51 vs. 54 nmol/L, p=0.04) and women (geometric mean: 52 vs. 55 nmol/L, p=0.02). Men with a serum 25(OH)D levels <50 nmol/l at baseline had a significantly higher risk of asthma (crude OR 1.75, 95%CI 1.14-2.68) compared with those with a serum 25(OH)D level of 75 nmol/l or higher. After adjustment for age, smoking, family history of asthma, education, physical activity, social benefit, and economic difficulties, the OR was 1.60 (95% CI 1.02-2.50). Further adjustment for body mass index (BMI) yielded an OR of 1.47 (95%CI 0.93-2.32). In women, baseline serum 25(OH)D level was not associated with the risk of asthma in either unadjusted or adjusted models.

Conclusions: After adjustment for BMI and other covariates, baseline levels of serum 25(OH)D were not independently associated with adult-onset asthma.
Antibodies to Early Epstein-Barr Virus-Induced Antigens in Burkitt&amp;amp;s Lymphoma&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Gertrude Henle, Werner Henle, George Klein, Peter Gunven, Peter Clifford, Richard H. Morrow, John L. Ziegler
Journal: JNCI Journal of the National Cancer Institute (1971)

The relation between antibodies to early Epstein-Barr virus (EBV)-induced antigens (EA) and antibodies to other EBV-related antigens was investigated as well as the significance of anti-EA in Burkitt's lymphoma (BL). Anti-EA was clearly distinct from antibodies to EB viral capsid antigens (VCA), EBV-dependent cell membrane antigens, and precipitating antibodies. Whereas anti-EA was found only in sera which showed also anti-VCA at titers of ≧:40, sera with high anti-VCA titers did not necessarily contain anti-EA. This type of discordance was frequent among the relatively few sera from African control children with high anti-VCA titers, but was relatively rare among the many sera with high anti-VCA titers from BL patients. Presence or absence of anti-EA reflects to a considerable extent the prognosis of patients with BL after chemotherapy. Most sera obtained shortly before death had high titers of anti-EA. Among patients who died without anti-EA were several who were moribund when admitted and several in whom death was due to complications while the presenting tumors were in remission. In contrast, over half the patients who survived for at least 2 years, some as long as 9 years to date, lacked this antibody or had only low titers. Recurrences, as late as 5 years after initial successful treatment, were more frequent among long-term survivors who had continuously high anti-EA titers than among patients who were admitted without anti-EA. Possible explanations for the apparent prognostic significance of anti-EA in BL were discussed.
Clinical trials in primary care
Authors: S. Wilson, B Delaney, A. Roalfe, R Hobbs, J. N Rao
Journal: BMJ (1999)

Editor—Foy et al debate the role of financial incentives to improve the recruitment of patients to primary care based trials.1 The critical issue should more properly be whether the real costs of research should be borne by service practitioners. We suggest that they should not. This is especially true of general practice in the United Kingdom, since the NHS has an exclusively service agreement with the independent contractors in general practice. Indeed, the Culyer funding mechanism has set aside ad hoc funding specifically to meet the “excess service costs” of supporting research in primary care.

Ethical trials require participating clinicians and patients to be in equipoise and for informed consent to be obtained. Assessing eligibility, explaining a trial, addressing patients’ questions, obtaining consent, randomising patients, and collecting baseline data are time consuming. Grant proposals should include the true cost of research studies. Funding bodies cover the salaries of research staff and overheads; general practitioners should not be expected to give their time freely.

A randomised controlled trial, based in primary care, of the cost effectiveness of open access endoscopy and testing for Helicobacter pylori in the management of dyspepsia has recruited 920 dyspeptic patients from 44 general practices in the West Midlands region. Patients were recruited opportunistically within a consultation. We initially allowed 10 minutes for these activities and reimbursed excess costs at a rate of £10/patient recruited. After the first year a more realistic assessment of the time involved in recruiting patients was made. The practitioner’s time, exclusive of administrative costs, was estimated as 30 minutes per patient recruited. This additional workload led to some practices suspending recruitment at busy times. Our revised time estimates resulted in our increasing the payment to £50/patient recruited (BMA suggested rate of £108/hour).

We recently examined practice recruitment rates during the study (figure). Recruitment rates improved significantly between 1996 and 1997 after adjustment for practice list size and time in study (P<0.001 in logistic regression analysis). The observed improvement in recruitment rates could be ascribed to the introduction of a more acceptable payment, although this is unlikely to be the sole explanation. We attribute it to the combination of several measures introduced around this period—simplification of the study design, emphasis on the importance of the trial, regular newsletters, adequate financial reimbursement, and an adaptable approach to the work patterns in each practice. 

Research into the effectiveness of interventions in primary care needs to be undertaken in the general practice setting.2,3 Undertaking research has always had financial implications. Direct payments to general practitioners are no different from the more traditional forms of institutional support.
Metabolic changes and inflammation in obstructive sleep apnea
Authors: Emel Bulcun, Ersel Dag, Murat Tulmac, Dilay Ahad Cimen, Aydanur Ekici, Mehmet Ekici
Journal: European Respiratory Journal (2014)

Objective:There are different results on low grade inflammation and metabolic syndrome in patients with OSA. We investigated the relation between low grade inflammation and metabolic syndrome in patients with OSA.  Method:The study included 78treatment-naive OSA patients and 28 control group. Clinical information, BMI, SF-36, Epworth Sleepiness Scale, and serum CRP were collected. Overnight polysomnography and blood sampling was taken for glucose, insulin, cholesterol, triglycerides. Metabolic syndrome was defined according to NCEP criteria. Each patient was assigned a metabolic score according to the number of discrete components of metabolic syndrome.  Results: The components number and percentage of the metabolic syndrome and CRP levels were significantly higher in the patients with OSA than control group  . The component number of metabolic syndrome was correlated with theCRP, AHI and desaturation index. The component number of metabolic syndrome increased with an increase in AHI and desaturation index in multivariate analysis independently obesity.  Conclusion: OSA is associated with metabolic syndrome and low grade inflammation. The severity of the metabolic syndrome increased with an increase in OSA severity. Therapeutic approaches to OSA may decrease cardiovascular risk by decreasing frequency of metabolic syndrome in patients with OSA.
Responsibility for social care needs to be considered
Authors: C J Packham
Journal: BMJ (1996)

EDITOR,—The article by the Rationing Agenda Group was well thought out and comprehensive.1 I would like to comment on what should be health and what should be “other” forms of care responsibility—that is, social, etc. Although I agree that, ideally, social care should be the responsibility of agencies other than the NHS, …