tbuckley/cabot-search huggingface dataset:
Does Paclitaxel Improve the Chemoradiotherapy of Locoregionally Advanced Esophageal Cancer? A Nonrandomized Comparison With Fluorouracil-Based Therapy
Authors: David J. Adelstein, Thomas W. Rice, Lisa A. Rybicki, Marjorie A. Larto, Jay Ciezki, Jerrold Saxton, Malcolm DeCamp, John J. Vargo, John A. Dumot, Gregory Zuccaro
Journal: Journal of Clinical Oncology (2000)

PURPOSE: A phase II trial of accelerated fractionation radiation with concurrent cisplatin and paclitaxel chemotherapy was performed to investigate the role of the paclitaxel, when substituted for fluorouracil (5-FU), in the chemoradiotherapy of esophageal cancer. PATIENTS AND METHODS: Patients with an esophageal ultrasound stage of T 3 or N 1 or M 1 (nodal) esophageal cancer were treated with two courses of a cisplatin infusion (20 mg/m 2 /d for 4 days) and paclitaxel (175 mg/m 2 over 24 hours) concurrent with a split course of accelerated fractionation radiation (1.5 Gy bid to a total dose of 45 Gy). Surgical resection was performed 4 to 6 weeks later followed by a single identical postoperative course of chemoradiotherapy (24 Gy) in patients with significant residual tumor at surgery. Toxicity and results of this treatment were retrospectively compared with our previous 5-FU and cisplatin chemoradiotherapy experience. RESULTS: Between September 1995 and July 1997, 40 patients were entered onto this study. Although dysphagia proved worse in our 5-FU–treated patients, profound leukopenia and a need for unplanned hospitalization were significantly more common in the paclitaxel group. Thirty-seven patients (93%) proved resectable for cure. The 3-year projected overall survival is 30%, locoregional control is 81%, and distant metastatic disease control is 44%. When compared with a similarly staged cohort of 5-FU–treated patients, there was no advantage for any survival function studied. CONCLUSION: This paclitaxel-based treatment regimen for locoregionally advanced esophageal cancer produced increased toxicity with no improvement in results when compared with our previous 5-FU experience. Paclitaxel-based treatments must be carefully and prospectively studied before their incorporation into the standard management of esophageal cancer.
EXPERIMENTAL SYPHILIS IN THE RABBIT
Authors: Wade H. Brown, Louise Pearce
Journal: The Journal of Experimental Medicine (1920)

From a study of the phenomena of the primary infection on the one hand, and the phenomena of local spread, or dissemination, on the other, it is seen that a multiplicity of lesions develops in the testicle and scrotum of the rabbit which have much the same characteristics irrespective of their origin. Some of these lesions are clearly recognizable as primary lesions or parts of a primary reaction to infection, while others are just as clearly the results of dissemination of the virus from a primary focus of infection or correspond with lesions which are commonly spoken of as secondary lesions. The effort to draw a sharp line of distinction between these two groups of lesions or between a primary and a secondary stage of infection in the rabbit, however, would be largely an arbitrary procedure. The fact is that the tissues of the scrotum and testicle of the rabbit constitute favorable surroundings for the localization and development of pallidum infections. Under ordinary circumstances, a large part of the reaction to infection which expresses itself in the formation of lesions recognizable by ordinary methods of examination takes place in these tissues. These lesions present certain broad and general characteristics without regard to whether they are primary or secondary in origin; the reaction is merely a reaction to a syphilitic infection which in either case may assume the most diverse character. Further, it would appear that in rabbits infected with such strains of Treponema pallidum as we have used, the virus is never confined to the area occupied by the so called primary lesion, or chancre, but always spreads and always gives rise to a regional adenopathy. There may be no lesions to indicate the progress of this dissemination, but an examination of the inguinal nodes shows that dissemination occurs very soon after inoculation, and a pallidum reaction may be detected in these glands even before infection can be recognized in the scrotum. Subsequently lesions develop in all parts of the scrotum and testicle, sometimes involving the entire testicle or scrotum, and at others, forming focalized lesions with an especial predilection for certain locations such as the epididymis, the mediastinum testis, the tunics, and the dorsal folds of the scrotum. In some instances, more or less continuous lesions form along the course of the perivascular lymphatics, suggesting that this is one path taken in the dissemination of the organism. It is probable, however, that lesions of a gross character develop more as a result of accumulation of spirochetes than of mere invasion of the lymphatics since they are not a constant accompaniment of the local infection, while invasion of the lymphatics and extension of the infection to the regional lymph nodes occur in all cases.
A3.4 Expansion Of IGA-plasma cells as a sign for ear-nose-throat-involvment in granulomatosis with polyangiitis?
Authors: Hoyer Bimba, Taddeo Adriano, Cheng Qingyu, Khodadadi Laleh, Mei Henrik, Biesen Robert, Alexander Tobias, Radbruch Andreas, Burmester Gerd, Hiepe Falk
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> B cells are playing a major role in granulomatosis with polyangiitis (GPA, formerly known as Wegener's disease). This is reflected by autoantibodies directed against neutrophil granular encymes (ANCA) as well as in the success of B cell depleting therapies. Whether mucosal plasma cells play a role in ENT-involvement is yet unknown. IgA-ANCA are found in about 30% of GPA patients and more often in patients with ENT-GPA (Kelley et al). For a better understanding of the possible role of plasma cells in GPA we analysed B cells subsets in the peripheral blood of patients and found major changes correlating with disease activity (BVAS). <h3>Methods</h3> 18 patients with GPA (11 with active disease, 7 in remission) were analysed by flow cytometry and compared to 17 healthy donors and 6 patients with systemic sclerosis. Stainings for CD19, 20, 27, IgD, IgA and MHCII were performed and analysed by FlowJo-software. The study was approved by the Charité ethics committee and all patients signed informed consent. Statistical analysis was performed using GraphPadPrism. <h3>Results</h3> : Marked differences (p = 0.0018) were found regarding the number and frequency of plasmablasts/plasma cells in patients with active disease (6.4 ± 5.06/µl) as compared to patients in remission (2.5 ± 1.6/µl) or healthy donors (2.3 ± 1.2/µl). In patients with GPA a significant higher number of the plasma cells produced IgA as compared to healthy controls (p = 0.0028). The same was true in patients with systemic sclerosis. So far, no difference regarding the IgA plasma cells in the blood was observed between patients with ENT-GPA and patients with systemic GPA (sGPA), while sGPA patients tend to have more plasma cells in the blood. The number of plasma cells and IgA plasma cells correlate with disease activity (r = 0.9135, p&lt;0.0001). <h3>Conclusion</h3> The number of plasma cells in active GPA is increased. This implies a central role of plasma cells in the pathogenesis of GPA. A high frequency of these plasma cells is producing IgA, which could play a role in ENT-involvement. So far now diffenerce could be observed between ENT-GPA and sGPA but further studies and more detailed studies including the analysis of ENT biopsies are needed to further understand their role in disease pathogenesis.
Lung function decline in COPD trials: bias from regression to the mean
Authors: S. Suissa
Journal: European Respiratory Journal (2008)

The decline in lung function over time is a fundamental measure of disease progression among patients with chronic obstructive pulmonary disease (COPD). As a result, forced expiratory volume in one second (FEV1) decline has been used as a central outcome measure for many randomised controlled trials evaluating whether pharmacological treatments could modify the natural history of COPD. These trials, mostly focussed on assessing the benefit of inhaled corticosteroids, and their meta-analyses highlighted the complexities of analysing data from repeated FEV1 measurements over time, particularly in the context of studying COPD patients who discontinue follow-up early and in large numbers. This has lead to contradictory results and divergent conclusions 1–3. At present, the recent paper from the Towards a Revolution in COPD Health (TORCH) trial reports that the yearly decline in FEV1 was significantly slower with fluticasone, salmeterol or both compared with placebo 4.

A common misconception in the interpretation of these studies is that the effect of the study drug on FEV1 decline is likely to be greater than the data suggest. The rationale is that more patients receiving placebo were discontinuing the study drugs and the patients who dropped out early had a steeper decline in lung function than those who remained. Consequently, it has generally been believed that the resulting analysis “actually minimises the differences observed in the rate of FEV1 decline” 4.

To clarify this misconception, a fundamental aspect of the design and statistical analysis of these trials is addressed, namely bias from regression to the mean resulting from the absence of an authentic intent-to-treat approach. It is described based on the TORCH trial and illustrated using data from the Canadian Optimal randomised trial.

Most of the trials to date are not designed for a full intent-to-treat …
Validation of an instrument for injury data collection in rugby union
Authors: Alexandra McManus
Journal: British Journal of Sports Medicine (2000)

Objective —To provide the basis for collecting rugby union injury data using a rigorously validated injury report form. Methods —Seven stages were used to assess face, content, and criterion validity of the rugby union injury report form. A 22 member panel plus four sporting bodies assessed the form for face validity, and an expert panel assessed it for content and criterion validity. Panel members were consulted until consensus was reached. A yardstick developed by an expert panel using the Delphi technique was used to assess the reliability of the form. An independent panel of 10 viewed a series of five videotaped injuries, three times over a five week period to assess inter-rater and intrarater reliability. The form was then trialed by 40 people in situ during four games. Results —The rugby union injury report form for games and training was developed, and the face, content, and criterion validity successfully assessed. A seven step protocol to create a yardstick was also developed to assist in the validation process. Both inter-rater and intrarater reliability results indicated a 98% agreement. The 40 trialists who completed forms in situ during four games were found to have an inter-rater reliability agreement of 98% for nine injuries. Conclusions —A measurement instrument for injury data collection in rugby union was successfully developed and validated, providing researchers with a basis for future studies in this area. A procedure to develop future injury data collection instruments in other sports was also developed.
Crossed Radioimmunoelectrophoretic Studies of Bee Venom Allergens
Authors: L. Aukrust, R. Einarsson, S. ÖHman, S. G. O. Johansson
Journal: Allergy (1982)

Crossed immutioelectrophoresis (CIE) glass slides of boney bee venom showing 18 immunoprecipitates were used in crossed radioimmunoelectrophoresis (CRIE) experiments with sera from 25 patients allergic to honey bee venoms. Phospholipase A, acid phosphatase, hyaluronidase and melittin were demonstrated in the immunoprecipitates during zymograpbic techniques and direct hemolysis of sheep erythrocytes. The CRIE experiments verified the allergenicity of these proteins. In addition, another antigen (Ag‐1) with allergenic activity was identified. This allergen is probably identical to the previously described allergen C in honey bee venom. The presence and complexity of multiple forms of the known allergenic proteins in honey bee venom, was well illustrated in the CIE/CRIF system employed.
Haptoglobin 1-1 Genotype Is Associated With Poorer Cognitive Functioning in the Elderly With Type 2 Diabetes
Authors: Ramit Ravona-Springer, Anthony Heymann, James Schmeidler, Elizabeth Guerrero-Berroa, Mary Sano, Rachel Preiss, Keren Koifman, Hadas Hoffman, Andrew Levy, Jeremy M. Silverman, Michal Schnaider-Beeri
Journal: Diabetes Care (2013)

Haptoglobin (Hp) genotype (Hp 1-1, 1-2, or 2-2) is associated with risk for type 2 diabetes complications, but its relationship with cognitive compromise, a growing concern in type 2 diabetes, has rarely been studied. This study investigated whether Hp genotype is associated with cognitive function in cognitively normal elderly diabetic subjects.Relationships of Hp genotype with episodic memory, semantic categorization, attention/working memory and executive function, and an overall cognitive score were examined in subjects from the Israel Diabetes and Cognitive Decline (IDCD) study.In the present analysis, 812 subjects participated (84 with Hp 1-1, 335 with Hp 1-2, and 393 with Hp 2-2 genotypes). Average was 72.9 years of age (SD 4.7), and Mini-Mental State Exam (MMSE) was 28.0 (SD 1.8). Compared with subjects with Hp 1-2 genotype, Hp 1-1 subjects performed significantly worse in semantic categorization (F=7.03; P=0.008) and the overall cognitive score (F=5.57; P=0.02). A separate stepwise multiple regression analysis demonstrated that compared with subjects with Hp 2-2 genotype, Hp 1-1 subjects performed significantly worse in semantic categorization (F=4.18; P=0.04) and the overall cognitive score (F=4.70; P=0.03). The contribution of cardiovascular risk factors to cognition was significantly higher in subjects with Hp 1-1 genotype compared with Hp 2 carriers (Hp 1-2 and Hp 2-2) in the semantic categorization (P=0.009) and attention/working memory (P=0.002) cognitive domains.Compared with Hp 2 carriers, those with Hp 1-1 genotype present lower cognitive performance. Stronger relationships between cardiovascular risk factors and cognition in the latter group may suggest an underlying vascular mechanism.
Assessment of Clinical Skills of Residents Utilizing Standardized Patients
Authors: Paula Stillman, David Swanson, Mary Beth Regan, Mary M. Philbin, Virginia Nelson, Thomas Ebert, Bryson Ley, Thomas Parrino, Jeannette Shorey, Alfred Stillman, Elaine Alpert, Joel Caslowitz, David Clive, James Florek, Milton Hamolsky, Charles Hatem, Janice Kizirian, Richard Kopelman, David Levenson, Gilbert Levinson, Jack McCue, Henry Pohl, Fred Schiffman, Joel Schwartz, Michael Thane, Marshall Wolf
Journal: Annals of Internal Medicine (1991)

Objective: To determine the reliability and validity of "standardized patients" to assess clinical performance of internal medicine residents. Design: Each resident spent 2 half-days interacting with 19 standardized patients (nonphysicians taught to portray patients in a reproducible fashion). Each resident was asked to obtain focused histories, perform relevant physical examinations, and provide patient education or counseling. At the end of each 10- to 15 minute encounter, the resident was asked to identify positive findings on physical examination and to prioritize a differential diagnosis. Other, more traditional indicators of clinical skills were also obtained. Participants: Three hundred ten residents from nineteen internal medicine training programs in the New England region of the United States. Results: Reproducible estimates of data gathering and interviewing skills were achieved with 1 day of testing. Validity analyses were difficult to interpret because of the lack of an external "gold standard." However, faculty judgments of performance from reviewing videotapes corresponded with standardized-patient-based scores. Differences in group performance were also demonstrated across years of training and between U.S. or Canadian and foreign medical graduates. Conclusions: Systematic and effective procedures for developing standardized-patient-based test materials and for training standardized patients have been developed. This technique is best used for measuring data gathering and interviewing skills. Correlations with commonly used evaluation methods were generally low; this may be because standardized patients measure different skills. Local use of this technique by residency programs and the development of regional consortia sharing resources, costs, and expertise are advocated.
Relationship of Mammographic Density and Gene Expression: Analysis of Normal Breast Tissue Surrounding Breast Cancer
Authors: Xuezheng Sun, Gretchen L. Gierach, Rupninder Sandhu, Tyisha Williams, Bentley R. Midkiff, Jolanta Lissowska, Ewa Wesolowska, Norman F. Boyd, Nicole B. Johnson, Jonine D. Figueroa, Mark E. Sherman, Melissa A. Troester
Journal: Clinical Cancer Research (2013)

Abstract Purpose: Previous studies of breast tissue gene expression have shown that the extratumoral microenvironment has substantial variability across individuals, some of which can be attributed to epidemiologic factors. To evaluate how mammographic density and breast tissue composition relate to extratumoral microenvironment gene expression, we used data on 121 patients with breast cancer from the population-based Polish Women's Breast Cancer Study. Experimental Design: Breast cancer cases were classified on the basis of a previously reported, biologically defined extratumoral gene expression signature with two subtypes: an Active subtype, which is associated with high expression of genes related to fibrosis and wound response, and an Inactive subtype, which has high expression of cellular adhesion genes. Mammographic density of the contralateral breast was assessed using pretreatment mammograms and a quantitative, reliable computer-assisted thresholding method. Breast tissue composition was evaluated on the basis of digital image analysis of tissue sections. Results: The Inactive extratumoral subtype was associated with significantly higher percentage mammographic density (PD) and dense area (DA) in univariate analysis (PD: P = 0.001; DA: P = 0.049) and in multivariable analyses adjusted for age and body mass index (PD: P = 0.004; DA: P = 0.049). Inactive/higher mammographic density tissue was characterized by a significantly higher percentage of stroma and a significantly lower percentage of adipose tissue, with no significant change in epithelial content. Analysis of published gene expression signatures suggested that Inactive/higher mammographic density tissue expressed increased estrogen response and decreased TGF-β signaling. Conclusions: By linking novel molecular phenotypes with mammographic density, our results indicate that mammographic density reflects broad transcriptional changes, including changes in both epithelia- and stroma-derived signaling. Clin Cancer Res; 19(18); 4972–82. ©2013 AACR.
Chemotherapy with Preoperative Radiotherapy in Rectal Cancer
Authors: Jean-François Bosset, Laurence Collette, Gilles Calais, Laurent Mineur, Philippe Maingon, Ljiljana Radosevic-Jelic, Alain Daban, Etienne Bardet, Alexander Beny, Jean-Claude Ollier
Journal: New England Journal of Medicine (2006)

Preoperative radiotherapy is recommended for selected patients with rectal cancer. We evaluated the addition of chemotherapy to preoperative radiotherapy and the use of postoperative chemotherapy in the treatment of rectal cancer.We randomly assigned patients with clinical stage T3 or T4 resectable rectal cancer to receive preoperative radiotherapy, preoperative chemoradiotherapy, preoperative radiotherapy and postoperative chemotherapy, or preoperative chemoradiotherapy and postoperative chemotherapy. Radiotherapy consisted of 45 Gy delivered over a period of 5 weeks. One course of chemotherapy consisted of 350 mg of fluorouracil per square meter of body-surface area per day and 20 mg of leucovorin per square meter per day, both given for 5 days. Two courses were combined with preoperative radiotherapy in the group receiving preoperative chemoradiotherapy and the group receiving preoperative chemoradiotherapy and postoperative chemotherapy; four courses were planned postoperatively in the group receiving preoperative radiotherapy and postoperative chemotherapy and the group receiving preoperative chemoradiotherapy and postoperative chemotherapy. The primary end point was overall survival.We enrolled 1011 patients in the trial. There was no significant difference in overall survival between the groups that received chemotherapy preoperatively (P=0.84) and those that received it postoperatively (P=0.12). The combined 5-year overall survival rate for all four groups was 65.2%. The 5-year cumulative incidence rates for local recurrences were 8.7%, 9.6%, and 7.6% in the groups that received chemotherapy preoperatively, postoperatively, or both, respectively, and 17.1% in the group that did not receive chemotherapy (P=0.002). The rate of adherence to preoperative chemotherapy was 82.0%, and to postoperative chemotherapy was 42.9%.In patients with rectal cancer who receive preoperative radiotherapy, adding fluorouracil-based chemotherapy preoperatively or postoperatively has no significant effect on survival. Chemotherapy, regardless of whether it is administered before or after surgery, confers a significant benefit with respect to local control. (ClinicalTrials.gov number, NCT00002523 [ClinicalTrials.gov].).
Low-Dose Aspirin Therapy in Patients With Type 2 Diabetes and Reduced Glomerular Filtration Rate
Authors: Yoshihiko Saito, Takeshi Morimoto, Hisao Ogawa, Masafumi Nakayama, Shiro Uemura, Naofumi Doi, Hideaki Jinnouchi, Masako Waki, Hirofumi Soejima, Seigo Sugiyama, Sadanori Okada, Yasuhiro Akai
Journal: Diabetes Care (2011)

OBJECTIVE Type 2 diabetes accompanied by renal damage is a strong risk factor for atherosclerotic events. The purpose of this study was to investigate the efficacy of low-dose aspirin therapy on primary prevention of atherosclerotic events in patients with type 2 diabetes and coexisting renal dysfunction. RESEARCH DESIGN AND METHODS The Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes (JPAD) trial was a prospective, randomized, open-label trial conducted throughout Japan that enrolled 2,539 type 2 diabetic patients without a history of atherosclerotic diseases. Patients were assigned to the aspirin group (81 mg/day or 100 mg/day) or the nonaspirin group and followed for a median of 4.37 years. The primary end points were atherosclerotic events of fatal and nonfatal ischemic heart disease, stroke, and peripheral arterial disease. RESULTS The analysis included 2,523 patients who had serum creatinine measured. In 1,373 patients with baseline estimated glomerular filtration rate (eGFR) 60–89 mL/min/1.73 m2, the incidence of primary end points was significantly lower in the aspirin group than in the nonaspirin group (aspirin, 30/661; nonaspirin, 55/712; hazard ratio 0.57 [95% CI 0.36–0.88]; P = 0.011). Low-dose aspirin therapy did not reduce primary end points in patients with eGFR ≥90 mL/min/1.73 m2 (aspirin, 9/248; nonaspirin, 11/270; 0.94 [0.38–2.3]) or those with eGFR &amp;lt;60 mL/min/1.73 m2 (aspirin, 29/342; nonaspirin, 19/290; 1.3 [0.76–2.4]). The Cox proportional hazard model demonstrated a significant interaction between mild renal dysfunction (eGFR 60–89 mL/min/1.73 m2) and aspirin (P = 0.02). CONCLUSIONS These results suggest a differential effect of low-dose aspirin therapy in diabetic patients with eGFR 60–89 mL/min/1.73 m2.