tbuckley/cabot-search huggingface dataset:
Low adherence to colonoscopy in the screening of first-degree relatives of patients with colorectal cancer
Authors: L. Bujanda, C. Sarasqueta, L. Zubiaurre, A. Cosme, C. Munoz, A. Sanchez, C. Martin, L. Tito, V. Pinol, A. Castells, X. Llor, R. M Xicola, E. Pons, J. Clofent, M. L de Castro, J. Cuquerella, E. Medina, A. Gutierrez, J. I Arenas, R. Jover
Journal: Gut (2007)

Colonoscopy is one of the methods of choice for screening relatives of patients with colorectal cancer.To evaluate the rate of adherence to colonoscopy in first-degree relatives of patients with colorectal cancer and describe the lesions found.A prospective, cross-sectional, multicentre, nationwide study was conducted. The study population was composed of first-degree relatives of patients with colorectal cancer selected randomly from the EPICOLON study. Seventy-four index patients were included. These had 342 living first-degree relatives (parents, siblings and children), of whom 281 were interviewed.The adherence rate was 38% (107/281). Adherence was greater in families with a higher degree of familial aggregation for colorectal cancer (88.9% for Amsterdam vs 33.3% for Bethesda and sporadic cancer; p<0.05), an index patient aged under 65 years (60% for patients <65 years vs 32.9% for patients >or=65 years; p<0.05) and an index patient who was female (46.2% for women vs 31% for men; p = 0.28). Adherence was also greater in relatives under 65 years (54% in patients <65 years vs 18% in patients >or=65 years; p = 0.05), in female relatives (49% in female relatives vs 27.3% in male relatives; p<0.05) and in siblings and children (40% in siblings and children vs 13% in parents; p<0.05). Lesions were found in 26% (28/107) of the study population. Nine (8.4%) individuals had a total of 18 advanced lesions.These results indicate that adherence to colonoscopy in our population of first-degree relatives was low. The adherence was more frequently associated with a higher degree of familial aggregation, a relative age of under 65 years, a sibling or offspring relationship, and female sex.
Evaluating noninvasive ventilation using a monitoring system coupled to a ventilator: a bench-to-bedside study
Authors: C. Rabec, M. Georges, N. K. Kabeya, N. Baudouin, F. Massin, O. Reybet-Degat, P. Camus
Journal: European Respiratory Journal (2009)

Empirically determined noninvasive ventilation (NIV) settings may not achieve optimal ventilatory support. Some ventilators include monitoring modules to assess ventilatory quality. We conducted a bench-to-bedside study to assess the ventilatory quality of the VPAP TM III-ResLink TM (ResMed, North Ryde, Australia). We tested the accuracy of minute ventilation (MV) and leak calculations given by VPAP TM III-ResLink TM compared to those measured by a bench model at varied leak levels and ventilator settings. We systematically assessed NIV efficacy using this system from 2003 to 2006. Ventilation was considered inadequate if leak (&gt;24 L·min −1 ), continuous desaturation (&gt;30% of the trace) or desaturation dips (&gt;3%) were present. On the bench test, both methods were highly correlated (r = 0.947, p&gt;0.0001 and r = 0.959, p&lt;0.0001 for leak and MV, respectively). We performed 222 assessments in 169 patients (aged 66.42±16 yrs, 100 males). Abnormalities were detected on 147 (66%) out of 222 occasions. Leak was the most common abnormality (34.2%) followed by desaturation dips (23.8%). The most effective therapeutic solutions were a chin strap if leak was detected (61.2%) and expiratory positive airway pressure increase for desaturation dips (59.5%). In 15.7% of cases, when abnormalities persisted, a polygraphy was performed. The systematic use of this device enables NIV to be optimised, limiting the indication of sleep studies to complex cases.
Tumor Regression in Patients With Metastatic Synovial Cell Sarcoma and Melanoma Using Genetically Engineered Lymphocytes Reactive With NY-ESO-1
Authors: Paul F. Robbins, Richard A. Morgan, Steven A. Feldman, James C. Yang, Richard M. Sherry, Mark E. Dudley, John R. Wunderlich, Azam V. Nahvi, Lee J. Helman, Crystal L. Mackall, Udai S. Kammula, Marybeth S. Hughes, Nicholas P. Restifo, Mark Raffeld, Chyi-Chia Richard Lee, Catherine L. Levy, Yong F. Li, Mona El-Gamil, Susan L. Schwarz, Carolyn Laurencot, Steven A. Rosenberg
Journal: Journal of Clinical Oncology (2011)

Adoptive immunotherapy using tumor-infiltrating lymphocytes represents an effective cancer treatment for patients with metastatic melanoma. The NY-ESO-1 cancer/testis antigen, which is expressed in 80% of patients with synovial cell sarcoma and approximately 25% of patients with melanoma and common epithelial tumors, represents an attractive target for immune-based therapies. The current trial was carried out to evaluate the ability of adoptively transferred autologous T cells transduced with a T-cell receptor (TCR) directed against NY-ESO-1 to mediate tumor regression in patients with metastatic melanoma and synovial cell sarcoma.A clinical trial was performed in patients with metastatic melanoma or metastatic synovial cell sarcoma refractory to all standard treatments. Patients with NY-ESO-1-positive tumors were treated with autologous TCR-transduced T cells plus 720,000 iU/kg of interleukin-2 to tolerance after preparative chemotherapy. Objective clinical responses were evaluated using Response Evaluation Criteria in Solid Tumors (RECIST).Objective clinical responses were observed in four of six patients with synovial cell sarcoma and five of 11 patients with melanoma bearing tumors expressing NY-ESO-1. Two of 11 patients with melanoma demonstrated complete regressions that persisted after 1 year. A partial response lasting 18 months was observed in one patient with synovial cell sarcoma.These observations indicate that TCR-based gene therapies directed against NY-ESO-1 represent a new and effective therapeutic approach for patients with melanoma and synovial cell sarcoma. To our knowledge, this represents the first demonstration of the successful treatment of a nonmelanoma tumor using TCR-transduced T cells.
Carotid Atherosclerosis and Coronary Heart Disease in the Metabolic Syndrome
Authors: Enzo Bonora, Stefan Kiechl, Johann Willeit, Friedrich Oberhollenzer, Georg Egger, Riccardo C. Bonadonna, Michele Muggeo
Journal: Diabetes Care (2003)

The present study aimed at prospectively evaluating carotid atherosclerosis and coronary heart disease (CHD) in subjects with the metabolic syndrome.Within a prospective population-based survey examining 888 subjects aged 40-79 years, 303 subjects were identified as fulfilling World Health Organization (WHO) criteria and 158 as fulfilling the National Cholesterol Education Program (NCEP)-Adult Treatment Panel (ATP)-III criteria for diagnosing the metabolic syndrome. The 5-year change in carotid status, as assessed by echo-duplex scanning, and incident fatal and nonfatal CHD, as assessed by medical history and death certificates, were compared in subjects with the metabolic syndrome and in the rest of the sample (control subjects).Compared with the control subjects, subjects with the metabolic syndrome by WHO criteria had an increased 5-year incidence and progression of carotid atherosclerosis: 51 vs. 35% developed new plaques (P = 0.021) and 34 vs. 19% developed carotid stenosis >40% (P = 0.002) after adjusting for several confounders. Subjects with the metabolic syndrome by these criteria also had an increased incidence of CHD during follow-up: 8 vs. 3% in control subjects (P = 0.012). Similar results were found when the NCEP-ATPIII criteria were used.Subjects with the metabolic syndrome are at increased risk for both progressive carotid atherosclerosis and CHD.
Gestational Glucose Intolerance in Multiple Pregnancy
Authors: Francesco Corrado, Francesco Caputo, Graziella Facciolà, Alfredo Mancuso
Journal: Diabetes Care (2003)

Results from a population-based survey Our objective was to evaluate the diagnostic proficiency of the World Health Organization (WHO) and the National Cholesterol Education Program (NCEP)-III definitions (1,2) for the metabolic syndrome in a Mexican nationwide, population-based survey.Details of the sampling procedures have been previously described (3).The population was composed of 2,158 men and women aged 20 -69 years sampled after a 9-to 12-h fasting period.For the WHO criteria, insulin resistance was diagnosed if a nondiabetic case had fasting insulin concentrations Ն126 pmol/l (21 U/ml) (Ͼ75th percentile in Mexican adults).The ageadjusted prevalence was 13.61% for the WHO criteria (n ϭ 268) and 26.6% for the NCEP-III definition (n ϭ 574).After excluding patients with diabetes, the prevalence was 9.2 and 21.4%, respectively.The agreement between the definitions was assessed in 1,969 subjects; 189 cases were eliminated due to the lack of a urine sample.The number of abnormal cases was lower using the WHO criteria.Only 237 of the 545 subjects (43.4%) who fulfilled the NCEP criteria were diagnosed as affected using the WHO definition.Just 16 of 253 cases (6.3%) detected by the WHO definition did not fulfill the NCEP definition.The agreement between the criteria was moderate ( ϭ 0.507).On the other hand, the subjects diagnosed using the WHO recommendations had a worse profile than the cases detected by the NCEP-III definition only-they had a higher BMI and higher non-HDL cholesterol, triglyceride, and glucose concentrations.The demonstration of insulin resistance among the nondiabetic population caused the lack of agreement in 202 of the 242 cases that fulfilled the NCEP definition but failed the WHO criteria.Other reasons for disparity were the higher thresholds used by the WHO criteria; these differences explained the lack of agreement in 66 of the 152 cases with diabetes.In conclusion, the prevalence of the metabolic syndrome is influenced by the selection of the diagnostic criteria.The WHO criteria identified a lower number of cases than the NCEP-III definition.These differences were explained mainly by the inclusion of abnormally high insulin concentrations as a diagnostic criterion.However, the presence of insulin resistance may help to identify patients more severely affected (4).
Recurrent Deletion of the Short Arm of Chromosome 3 in Human Renal Cell Carcinoma: Shift of the &lt;italic&gt;c-raf 1&lt;/italic&gt; Locus&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: J R Teyssier, I Henry, C Dozier, D Ferre, J J Adnet, M Pluot
Journal: JNCI Journal of the National Cancer Institute (1986)

A cytogenetic study performed on 6 human renal cell carcinomas after short-term culture on extracellular matrix with serum-free medium showed aneuploidy without structural changes in 2 tumors and a rearrangement of the short arm of chromosome 3 in 4 tumors, including deletions and a translocation involving the 3p14 and 3p21 bands. Chromosomal in situ hybridization with a c-raf 1 probe demonstrated that in 2 renal cancers with del3(p14 or 21) the cellular oncogene had shifted from 3p25 to 3p14 as a result of an interstitial deletion.
Loss of <i>Rad51c</i> Leads to Embryonic Lethality and Modulation of <i>Trp53</i>-Dependent Tumorigenesis in Mice
Authors: Sergey G. Kuznetsov, Diana C. Haines, Betty K. Martin, Shyam K. Sharan
Journal: Cancer Research (2009)

RecA/Rad51 protein family members (Rad51, Rad51b, Rad51c, Rad51d, Xrcc2, and Xrcc3) are essential for DNA repair by homologous recombination, and their role in cancers has been anticipated. Here we provide the first direct evidence for a tumor suppressor function for a member of the Rad51 family. We show that Rad51c deficiency leads to early embryonic lethality, which can be delayed on a Trp53-null background. To uncover the role of Rad51c in tumorigenesis, we have exploited the fact that Rad51c and Trp53 are both closely located on the mouse chromosome 11. We have generated double heterozygous (DH) mice carrying mutant alleles of both genes either on different (DH-trans) or on the same chromosome (DH-cis), the latter allowing for a deletion of wild-type alleles of both genes by loss of heterozygosity. DH-trans mice, in contrast to DH-cis, developed tumors with latency and spectrum similar to Trp53 heterozygous mice. Strikingly, Rad51c mutation in DH-cis mice promoted the development of tumors of specialized sebaceous glands and suppressed tumors characteristic of Trp53 mutation. In addition, DH-cis females developed tumors significantly earlier than any other group.
Cigar Smoking and Cancers of the Upper Digestive Tract
Authors: C. La Vecchia, C. Bosetti, E. Negri, F. Levi, S. Franceschi
Journal: JNCI Journal of the National Cancer Institute (1998)

Pipe smoking has been related to the risk of cancers of the upper digestive and respiratory tract, but quantification of the risk for exclusive pipe smokers is still limited. To analyse the association between exclusive pipe smoking and cancers of the upper digestive tract, we used data from a series of case–control studies conducted in Italy and Switzerland between 1984 and 1999. After excluding cigarette and cigar smokers, 41 male oral and pharyngeal cancer cases, 52 male oesophageal cancer cases and 1,032 male controls were included in the present analysis. Odds ratios (OR) of cancers were estimated by the mean of unconditional multivariate logistic regression, including terms for age, study centre, education, body mass index, and alcohol drinking. Compared to never smokers, exclusive pipe smokers had an OR of 8.7 [95% confidence intervals (CI): 4.0–18.9] of all upper digestive tract cancers. The OR was 12.6 for oral and pharyngeal and 7.2 for oesophageal cancer. Pipe smokers who were also heavy alcohol drinkers had an OR of 38.8 (95% CI: 13.6–110.9) as compared to never smokers and light drinkers. Thus, pipe smoking and heavy alcohol drinking appears to interact at least on a multiplicative model. ' 2007 Wiley-Liss, Inc.
The case for dedicated sickle cell centres
Authors: Graham Serjeant
Journal: BMJ (2007)

In Jamaica the word transition means death, but in the sickle cell vocabulary of the United States it refers to the transfer from paediatrician to adult physician. Most patients with sickle cell disease are now identified at birth and are followed by paediatricians with an interest in and knowledge of the disease. Then at an arbitrary age—12, 16, or 18 years, depending on the institution—patients must leave the doctor they have known from birth and are referred to a usually unknown doctor. The result is that many patients default from follow-up at a critical time of adolescence, when they face problems of delayed physical and sexual development, enuresis, leg ulcers, priapism, and an increasing incidence of bone pain crises.

Is this disruption in clinical care necessary? Yes, the administrators say; but then we should ask whether the patients are there for the system or the system is there to serve the patients. Is it possible to provide a seamless service for clinical care of sickle cell disease? Are the demands of managing these patients sufficiently different from those of other …
Hypoxia and Photofrin Uptake in the Intraperitoneal Carcinomatosis and Sarcomatosis of Photodynamic Therapy Patients
Authors: Theresa M. Busch, Stephen M. Hahn, E. Paul Wileyto, Cameron J. Koch, Douglas L. Fraker, Paul Zhang, Mary Putt, Kristen Gleason, Daniel B. Shin, Michael J. Emanuele, Kevin Jenkins, Eli Glatstein, Sydney M. Evans
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Response to photodynamic therapy depends on adequate tumor oxygenation as well as sufficient accumulation of photosensitizer in the tumor. The goal of this study was to investigate the presence of hypoxia and retention of the photosensitizer Photofrin in the tumors of patients with intra-abdominal carcinomatosis or sarcomatosis. Experimental Design: Tumor nodules from 10 patients were studied. In nine of these patients, hypoxia was identified in histological sections of biopsied tumor after administration of the hypoxia marker 2-(2-nitroimidazol-1[H]-yl)-N-(2,2,3,3,3-pentafluoropropyl)acetamide (EF5). In separate tumor nodules from 10 patients, Photofrin uptake was measured by fluorescence after tissue solubilization. Results: Hypoxia existed in the tumors of five patients, with three of these patients demonstrating at least one severely hypoxic nodule. Physiological levels of oxygen were present in the tumors of four patients. An association between tumor size and hypoxia was not evident because some tumor nodules as small as ∼2 mm in diameter were severely hypoxic. However, even these tumor nodules contained vascular networks. Three patients with severely hypoxic tumor nodules exhibited moderate levels of Photofrin uptake of 3.9 ± 0.4 to 3.9 ± 0.5 ng/mg (mean ± SE). The four patients with tumors of physiological oxygenation did not consistently exhibit high tumor concentrations of Photofrin: mean ± SE drug uptake among these patients ranged from 0.6 ± 0.8 to 5.8 ± 0.5 ng/mg. Conclusions: Carcinomatosis or sarcomatosis of the i.p. cavity may exhibit severe tumor hypoxia. Photofrin accumulation in tumors varied by a factor of ∼10× among all patients, and, on average, those with severe hypoxia in at least one nodule did not demonstrate poor Photofrin uptake in separate tumor samples. These data emphasize the need for reconsideration of the generally accepted paradigm of small tumor size, good oxygenation, and good drug delivery because this may vary on an individual tumor basis.
Dendritic cell–expanded, islet-specific CD4+ CD25+ CD62L+ regulatory T cells restore normoglycemia in diabetic NOD mice
Authors: Kristin V. Tarbell, Lucine Petit, Xiaopan Zuo, Priscilla Toy, Xunrong Luo, Amina Mqadmi, Hua Yang, Manikkam Suthanthiran, Svetlana Mojsov, Ralph M. Steinman
Journal: The Journal of Experimental Medicine (2007)

Most treatments that prevent autoimmune diabetes in nonobese diabetic (NOD) mice require intervention at early pathogenic stages, when insulitis is first developing. We tested whether dendritic cell (DC)–expanded, islet antigen–specific CD4+ CD25+ suppressor T cells could treat diabetes at later stages of disease, when most of the insulin-producing islet β cells had been destroyed by infiltrating lymphocytes. CD4+ CD25+ CD62L+ regulatory T cells (T reg cells) from BDC2.5 T cell receptor transgenic mice were expanded with antigen-pulsed DCs and IL-2, and were then injected into NOD mice. A single dose of as few as 5 × 104 of these islet-specific T reg cells blocked diabetes development in prediabetic 13-wk-old NOD mice. The T reg cells also induced long-lasting reversal of hyperglycemia in 50% of mice in which overt diabetes had developed. Successfully treated diabetic mice had similar responses to glucose challenge compared with nondiabetic NOD mice. The successfully treated mice retained diabetogenic T cells, but also had substantially increased Foxp3+ cells in draining pancreatic lymph nodes. However, these Foxp3+ cells were derived from the recipient mice and not the injected T reg cells, suggesting a role for endogenous T reg cells in maintaining tolerance after treatment. Therefore, inoculation of DC-expanded, antigen-specific suppressor T cells has considerable efficacy in ameliorating ongoing diabetes in NOD mice.
Physiology and pathophysiology of pleural fluid turnover
Authors: L. Zocchi
Journal: European Respiratory Journal (2002)

Tight control of the volume and composition of the pleural liquid is necessary to ensure an efficient mechanical coupling between lung and chest wall. Liquid enters the pleural space through the parietal pleura down a net filtering pressure gradient. Liquid removal is provided by an absorptive pressure gradient through the visceral pleura, by lymphatic drainage through the stomas of the parietal pleura, and by cellular mechanisms. Indeed, contrary to what was believed in the past, pleural mesothelial cells are metabolically active, and possess the cellular features for active transport of solutes, including vesicular transport of protein. Furthermore, the mesothelium was shown, on the basis of recent experimental evidence, both <i>in vivo</i> and <i>in vitro</i>, to be a less permeable barrier than previously believed, being provided with permeability characteristics similar to those of the microvascular endothelium. Direct assessment of the relative contribution of the different mechanisms of pleural fluid removal is difficult, due to the difficulty in measuring the relevant parameters in the appropriate areas, and to the fragility of the mesothelium. The role of the visceral pleura in pleural fluid removal under physiological conditions is supported by a number of findings and considerations. Further evidence indicates that direct lymphatic drainage through the stomas of the parietal pleura is crucial in removing particles and cells, and important in removing protein from the pleural space, but should not be the main effector of fluid removal. Its importance, however, increases markedly in the presence of increased intrapleural liquid loads. Removal of protein and liquid by transcytosis, although likely on the basis of morphological findings and suggested by recent indirect experimental evidence, still needs to be directly proven to occur in the pleura. When pleural liquid volume increases, an imbalance occurs in the forces involved in turnover, which favours fluid removal. In case of a primary abnormality of one ore more of the mechanisms of pleural liquid turnover, a pleural effusion ensues. The factors responsible for pleural effusion may be subdivided into three main categories: those changing transpleural pressure balance, those impairing lymphatic drainage, and those producing increases in mesothelial and capillary endothelial permeability. Except in the first case, pleural fluid protein concentration increases above normal: this feature underlies the classification of pleural effusions into transudative and exudative.