tbuckley/cabot-search huggingface dataset:
Effects of anti-reflux surgery on weakly acidic reflux and belching
Authors: J. A. J. L. Broeders, A. J. Bredenoord, E. J. Hazebroek, I. A. M. J. Broeders, H. G. Gooszen, A. J. P. M. Smout
Journal: Gut (2010)

<h3>Background</h3> Laparoscopic Nissen fundoplication (LNF) is the most frequently performed operation for gastro-oesophageal reflux disease (GORD). However, 12% of the patients have persistent reflux symptoms and 19% develop gas-related symptoms after LNF. Weakly acidic reflux and inability to belch have been alleged to cause these symptoms, respectively. The effect of LNF on weakly acidic reflux and (supra) gastric belching was evaluated. <h3>Methods</h3> In 31 patients upper gastrointestinal endoscopy, stationary oesophageal manometry and 24-h impedance–pH monitoring off acid secretion inhibiting drugs was performed before and 6 months after primary LNF for GORD that was refractory to proton pump inhibitors. Patients filled out validated questionnaires on GERD-HRQoL before and 3, 6 and 12 months after surgery. <h3>Results</h3> LNF reduced reflux symptoms (18.6→1.6; p=0.015). The procedure drastically reduced the incidence (number per 24 h) of acid (76.0→1.6; p&lt;0.001) and weakly acidic (13.6→5.7; p=0.001) as well as liquid (53.4→5.4; p&lt;0.001) and mixed reflux episodes (36.3→1.9; p&lt;0.001). In contrast, gas reflux was reduced to lesser extent (35.6→25.7; p=0.022). Proximal, mid-oesophageal and distal reflux were reduced to a similar extent. Persistent GORD symptoms were neither preceded by acid nor by weakly acidic reflux. The number of air swallows did not change, but the number of gastric belches (GBs) was greatly reduced (68.5→23.9; p&lt;0.001). Twenty-three patients had supragastric belches (SGBs), both before and after surgery, whereas eight patients had no SGBs at all. The majority of SGBs were not reflux associated and the frequency was greatly increased after LNF (20.8→46.0; p=0.036). Reflux-associated SGBs were abolished after surgery (14.0→0.4; p&lt;0.001). <h3>Conclusions</h3> LNF similarly controls acid and weakly acidic reflux, but gas reflux is reduced to lesser extent. Persistent reflux symptoms are neither caused by acid nor by weakly acidic reflux. LNF alters the belching pattern by reducing GBs (air venting from stomach) and increasing SGBs (no air venting from stomach). This explains the increase in belching experienced by some patients after LNF, despite the reduction in gastric belching. It can be hypothesised that the reduction in GBs after LNF incites patients to increase SGBs in a futile attempt to vent air from the stomach.
Effect of sildenafil on oesophageal motor function in healthy subjects and patients with oesophageal motor disorders
Authors: A J Eherer
Journal: Gut (2002)

Sildenafil blocks phosphodiesterase type 5 which degrades nitric oxide (NO) stimulated 3'5'-cyclic monophosphate (cGMP), thereby relaxing smooth muscle cells in various organs. We used sildenafil as a tool to investigate the role of the NO-cGMP pathway in the oesophagus of healthy volunteers and patients with hypercontractile oesophageal motility disorders.Six healthy male volunteers participated in a randomised double blind study on two separate days before and one hour after oral intake of either sildenafil 50 mg or placebo. Oesophageal manometry was performed to determine vector volume of the lower oesophageal sphincter (LOS) and pressure amplitudes of the oesophageal body. Four of the volunteers underwent 12 hour ambulatory oesophageal manometry on two separate days, once with sildenafil 50 mg and once with placebo. An activity index for spontaneous swallowing was calculated for every hour of the study. Eleven patients with hypercontractile oesophageal motility disorders took part in an open study of the effect of 50 mg sildenafil on manometric features of their disorder and on the clinical response to sildenafil taken as required.In healthy subjects, sildenafil significantly reduced LOS pressure vector volume and pressure amplitudes in the distal half of the oesophageal body. In three of four subjects the inhibitory effect of sildenafil lasted at least eight hours. In nine of 11 patients, manometric improvement after sildenafil was observed but only four had an improvement in oesophageal symptoms with sildenafil taken as required. Two of these four patients however experienced side effects and did not want to continue treatment.Sildenafil lowers LOS pressure and propulsive forces in the body of the oesophagus of healthy subjects as well as in patients with nutcracker oesophagus, hypertensive LOS, and achalasia. The effect of sildenafil on the oesophageal body may last for up to eight hours in healthy volunteers. A subset of patients with hypertensive LOS or nutcracker oesophagus may benefit from sildenafil but side effects are a limiting factor.
A CT-BASED SCORE TO PREDICT THE SUCCESS OF INTERVENTIONAL REVASCULARIZATION OF CHRONIC TOTAL CORONARY OCCLUSIONS
Authors: Annika Schuhbaeck, Stephanie Lehnhardt, Tobias Pflederer, Dieter Ropers, Johannes Rixe, Christian Schneider, Andreas Rolf, Christian Hamm, Stephan Achenbach
Journal: Journal of the American College of Cardiology (2012)
Risk of recurrent subarachnoid haemorrhage, death, or dependence and standardised mortality ratios after clipping or coiling of an intracranial aneurysm in the International Subarachnoid Aneurysm Trial (ISAT): long-term follow-up
Authors: Andrew J Molyneux, Richard SC Kerr, Jacqueline Birks, Najib Ramzi, Julia Yarnold, Mary Sneade, Joan Rischmiller
Journal: The Lancet Neurology (2009)

BackgroundOur aim was to assess the long-term risks of death, disability, and rebleeding in patients randomly assigned to clipping or endovascular coiling after rupture of an intracranial aneurysm in the follow-up of the International Subarachnoid Aneurysm Trial (ISAT).Methods2143 patients with ruptured intracranial aneurysms were enrolled between 1994 and 2002 at 43 neurosurgical centres and randomly assigned to clipping or coiling. Clinical outcomes at 1 year have been previously reported. All UK and some non-UK centres continued long-term follow-up of 2004 patients enrolled in the original cohort. Annual follow-up has been done for a minimum of 6 years and a maximum of 14 years (mean follow-up 9 years). All deaths and rebleeding events were recorded. Analysis of rebleeding was by allocation and by treatment received. ISAT is registered, number ISRCTN49866681.Findings24 rebleeds had occurred more than 1 year after treatment. Of these, 13 were from the treated aneurysm (ten in the coiling group and three in the clipping group; log rank p=0·06 by intention-to-treat analysis). There were 8447 person-years of follow-up in the coiling group and 8177 person-years of follow-up in the clipping group. Four rebleeds occurred from a pre-existing aneurysm and six from new aneurysms. At 5 years, 11% (112 of 1046) of the patients in the endovascular group and 14% (144 of 1041) of the patients in the neurosurgical group had died (log-rank p=0·03). The risk of death at 5 years was significantly lower in the coiling group than in the clipping group (relative risk 0·77, 95% CI 0·61–0·98; p=0·03), but the proportion of survivors at 5 years who were independent did not differ between the two groups: endovascular 83% (626 of 755) and neurosurgical 82% (584 of 713). The standardised mortality rate, conditional on survival at 1 year, was increased for patients treated for ruptured aneurysms compared with the general population (1·57, 95% CI 1·32–1·82; p<0·0001).InterpretationThere was an increased risk of recurrent bleeding from a coiled aneurysm compared with a clipped aneurysm, but the risks were small. The risk of death at 5 years was significantly lower in the coiled group than it was in the clipped group. The standardised mortality rate for patients treated for ruptured aneurysms was increased compared with the general population.FundingUK Medical Research Council.
Detrended fluctuation analysis of peak expiratory flow and exacerbation frequency in COPD
Authors: Gavin C. Donaldson, Terence A.R. Seemungal, John R. Hurst, Jadwiga A. Wedzicha
Journal: European Respiratory Journal (2012)

We investigated whether exacerbation frequency in chronic obstructive pulmonary disease (COPD) was related to an exponent α which quantifies self-similarity in daily peak expiratory flow (PEF) and is calculated using detrended fluctuation analysis (DFA). We examined data from COPD patients who recorded an increase in respiratory symptoms and post-bronchodilator PEF on daily diary cards. We also investigated PEF data from a double-blind, placebo-controlled trial of the anti-cholinergic agent, tiotropium. In the observational study there were 308 patients with COPD (195 males; mean± sd age 68.3±8.4 yrs, forced expiratory volume in 1 s (FEV 1 ) 1.12±0.46 L, FEV 1 % predicted 44.5±16.4%). The mean± sd α over the first year was 0.944±0.19 and it was positively related to the frequency of exacerbations per year (p=0.009). In the clinical trial, α was lower in COPD patients randomised to tiotropium, mean± sd 0.87±0.21 (n=48) than on placebo, mean± sd 0.95±0.19 (n=52; p=0.035). Power analysis showed that fewer patients would be required for clinical studies with α as the outcome measure than exacerbation frequency. DFA shows that daily PEF in COPD has long-term correlations which are related to exacerbation frequency. Monitoring of PEF and use of α may result in smaller COPD patient sample sizes in trials.
Cellular Constituents of Immune Escape within the Tumor Microenvironment
Authors: Sid P. Kerkar, Nicholas P. Restifo
Journal: Cancer Research (2012)

Abstract Established tumors are complex masses that contain not only neoplastic cells but also nontransformed cellular elements such as stromal cells, the neovasculature, and the full gamut of immune cells. However, evidence suggests that, unlike cells found in lymphoid organs that productively respond to acute infections, immune cells in tumors are dysregulated and functionally impaired. Tumor masses can contain regulatory lymphocytes, myeloid-derived suppressor cells, alternatively activated macrophages, and dendritic cells. Ablation or reprogramming of this aberrant microenvironment might dramatically augment cancer therapies, and this strategy is currently being deployed in a variety of clinical trials. A better understanding of the cellular constituents of tumors and the mechanisms involved in immune evasion may help guide the next generation of innovative cancer immunotherapies. Cancer Res; 72(13); 3125–30. ©2012 AACR.
Surgery for lung metastases from colorectal cancer: analysis of prognostic factors.
Authors: P Girard, M Ducreux, P Baldeyrou, P Rougier, T Le Chevalier, J Bougaran, P Lasser, B Gayet, P Ruffié, D Grunenwald
Journal: Journal of Clinical Oncology (1996)

To identify prognostic factors of improved survival after resection of isolated pulmonary metastases (PM) from colorectal cancer.A retrospective analysis of the records of all patients with PM from colorectal cancer who underwent thoracic surgery with curative intent before December 1992 at a single surgical center was performed. Univariate (log-rank) and multivariate (Cox's model) analyses of survival were used to identify significant prognostic factors.Eighty-six patients with PM from colon (n = 49) or rectal (n = 37) cancer underwent 102 thoracic operations, which included 21 bilateral and 10 incomplete resections. The 5- and 10-year probabilities of survival (Kaplan-Meier) after the first thoracic operation were 24% (95% confidence interval [CI], 15% to 35%) and 20% (95% CI, 13% to 31%), respectively. Sex, age, site of the primary tumor (colon or rectum), disease-free interval (DFI), and previous resection of hepatic metastases were found not to be statistically significant prognostic factors. Complete resection, a limited number ( < two) of PM, and a normal prethoracotomy serum carcinoembryonic antigen (CEA) level were predictors of a longer survival duration by univariate analysis, but only complete resection (P = .024) and preoperative CEA level (P = .001) were identified as independent prognostic factors by multivariate analysis. The estimated 5-year survival rate of patients with a normal prethoracotomy CEA level was 60%, as compared with 4% in cases with elevated ( > 5 ng/mL) CEA level.Besides resectability, the prethoracotomy serum CEA level appears the most reliable predictor of survival in patients with isolated PM from colorectal cancer.
Role of Tumor Necrosis Factor-α and TRAIL in High-Dose Radiation–Induced Bystander Signaling in Lung Adenocarcinoma
Authors: Mohammed M. Shareef, Nuan Cui, Ravshan Burikhanov, Seema Gupta, Sabapathi Satishkumar, Shahin Shajahan, Mohammed Mohiuddin, Vivek M. Rangnekar, Mansoor M. Ahmed
Journal: Cancer Research (2007)

Abstract In the present study, ionizing radiation (IR)–induced bystander effects were investigated in two lung cancer cell lines. A549 cells were found to be more resistant to radiation-conditioned medium (RCM) obtained from A549 cells when compared with the H460 exposed to RCM procured from H460 cells. Significant release of tumor necrosis factor-α (TNF-α) was observed in A549 cells after IR/RCM exposure, and the survival was reversed with neutralizing antibody against TNF-α. In H460 cells, significant release of TNF-related apoptosis-inducing ligand (TRAIL), but not TNF-α, was observed in response to IR, RCM exposure, or RCM + 2Gy, and neutralizing antibody against TRAIL diminished clonogenic inhibition. Mechanistically, TNF-α present in RCM of A549 was found to mediate nuclear factor-κB (NF-κB) translocation to nucleus, whereas the soluble TRAIL present in RCM of H460 cells mobilized the nuclear translocation of PAR-4 (a proapoptotic protein). Analysis of IR-inducible early growth response-1 (EGR-1) function showed that EGR-1 was functional in A549 cells but not in H460 cells. A significant decrease in RCM-mediated apoptosis was observed in both A549 cells stably expressing small interfering RNA EGR-1 and EGR-1−/− mouse embryonic fibroblast cells. Thus, the high-dose IR-induced bystander responses in A549 may be dependent on the EGR-1 function and its target gene TNF-α. These findings show that the reduced bystander response in A549 cells is due to activation of NF-κB signaling by TNF-α, whereas enhanced response to IR-induced bystander signaling in H460 cells was due to release of TRAIL associated with nuclear translocation of PAR-4. [Cancer Res 2007;67(24):11811–20]
Granulomatous slack skin: report of a case associated with Hodgkin's disease and a review of the literature
Authors: G. NOTO, G. PRAVATÀ, S. MICELI, M. ARICÒ
Journal: British Journal of Dermatology (2006)

We report a case of granulomatous slack skin (GSS) associated with Hodgkin's disease, and review the literature on this entity. GSS, a variant of cutaneous T‐cell lymphoma, clinically presents with erythematous patches in the flexures, which gradually transform into bulky, pendulous areas of skin. Histology shows an elastolytic granulomatous infiltrate, with atypical lymphoid cells, and occasional epidermotropism. As far as we are aware, 10 cases of GSS, including our patient, have been reported in detail. The male: female ratio of these cases is 9:1, and the age range 15–51 years. Five cases were associated with Hodgkin's disease, one with small lymphocytic lymphoma, and one developed cutaneous T‐cell lymphoma. The axillae, abdomen and groins were the most frequently affected areas. No definitive management for GSS has been established. Surgery has been performed in localized forms, and systemic treatments have included corticosteroids, dapsone, chlorambucil, nitrogen mustard, and radiotherapy. Our patient was treated with chemotherapy for his Hodgkin's disease, and this resulted in complete remission of the lymphoma. Subsequent maintenance therapy with interferon‐alpha produced good control of the cutaneous lesions.
Civilisation and the colon: constipation as the "disease of diseases"
Authors: J. Whorton
Journal: BMJ (2000)

The publication in April 2000 of the results of a clinical trial that found high fibre cereals had no protective effect against colorectal adenomas stirred up considerable media attention and shook a cherished tenet of popular health culture.1 After all, boxes of All-Bran have been assuring us for nearly two decades that they contain “at last, some news about cancer you can live with,”2 and the manufacturers of high fibre cereals have enjoyed unprecedented profits thanks to the assumption that their products provide insurance against colon cancer. What will happen to “the high fibre feeding frenzy”3 that has possessed Americans for the past 20 years now that that assumption has been challenged?

#### Summary points

Throughout human history, bowel irregularity has been considered to be dangerous to health

In the 19th century medical scientists formulated a theory of “intestinal autointoxication”—self poisoning from one's own retained wastes

The public became prey to marketers of anticonstipation foods, drugs, and devices; All-Bran was introduced in the early 1900s to combat autointoxication

Recent clinical evidence suggests that cereal rich in fibre does not have a protective effect against bowel cancer, but because constipation has a historic hold over the public mind, people may continue to believe that bran is protective

Not much, most likely. It isn't just that the epidemiologists continue to remind us that there are many observational studies of population groups that show a correlation between consumption of a bulky diet and low incidence of colorectal cancer,4 or that the gastroenterology authorities continue to recommend daily ingestion of a minimum of 30 grams of fibre.5 More important than anything the experts have to say, I would wager, is human intuition, which has seen bowel irregularity to be dangerous from as far back as health literature can be traced. The oldest …
Long-Term Efficacy Results of EORTC Genito-Urinary Group Randomized Phase 3 Study 30911 Comparing Intravesical Instillations of Epirubicin, Bacillus Calmette-Guérin, and Bacillus Calmette-Guérin plus Isoniazid in Patients with Intermediate- and High-Risk Stage Ta T1 Urothelial Carcinoma of the Bladder
Authors: Richard J. Sylvester, Maurizio A. Brausi, Wim J. Kirkels, Wolfgang Hoeltl, Fernando Calais Da Silva, Philip H. Powell, Stephen Prescott, Ziya Kirkali, Cees van de Beek, Thierry Gorlia, Theo M. de Reijke
Journal: European Urology (2009)
RETRACTED: Tracheobronchial transplantation with a stem-cell-seeded bioartificial nanocomposite: a proof-of-concept study
Authors: Philipp Jungebluth, Evren Alici, Silvia Baiguera, Pontus Blomberg, Béla Bozóky, Claire Crowley, Oskar Einarsson, Tomas Gudbjartsson, Sylvie Le Guyader, Gert Henriksson, Ola Hermanson, Jan Erik Juto, Bertil Leidner, Tobias Lilja, Jan Liska, Tom Luedde, Vanessa Lundin, Guido Moll, Christoph Roderburg, Staffan Strömblad, Tolga Sutlu, Emma Watz, Alexander Seifalian, Paolo Macchiarini
Journal: The Lancet (2011)
Increase in ventilation caused by aminophylline in the absence of changes in ventral medullary extracellular fluid pH and carbon dioxide tension.
Authors: S Javaheri, J A Evers, L J Teppema
Journal: Thorax (1989)

A study was designed to investigate the possibility that changes in ventral medullary extracellular fluid carbon dioxide tension (PCO2) and hydrogen ion (H+) concentration mediate the ventilatory stimulation induced by systemic administration of aminophylline. Six cats with peripheral chemodenervation (bilateral carotid sinus nerve and vagal neurotomy) were studied while anaesthetised with chloralose urethane and breathing spontaneously at a regulated, constant, and somewhat raised end tidal PCO2. Variables were measured during steady state normoxaemia and 10 and 30 minutes after administration of 17 mg/kg aminophylline (mean (SD) blood concentration of theophylline 14.2 (1.5) mg/l). Aminophylline resulted in a significant and considerable increase in minute ventilation to 155% and 167% above baseline at 10 and 30 minutes. Mean (SD) values for arterial PCO2 were 5.6 (0.6), 5.6 (0.6), and 5.4 (0.6) kPa at 0, 10, and 30 minutes. Values for the ventral medullary extracellular fluid PCO2 were 7.6 (1.1), 7.5 (1.0), and 7.4 (1.0) kPa and for H+ concentration 62.7 (9.3), 62.6 (9.3), and 63.5 (8.0) nmol/l at 0, 10, and 30 minutes. After aminophylline infusion the PCO2 and H+ concentration of the extracellular fluid did not differ significantly from baseline values. It is concluded that in spontaneously breathing, peripherally chemodenervated cats the considerable increase in ventilation that follows an infusion of aminophylline is not mediated by change in the ventral medullary extracellular fluid PCO2 or hydrogen ion concentration.
Association of VEGF polymorphisms with childhood asthma, lung function and airway responsiveness
Authors: S. Sharma, A. J. Murphy, M. E. Soto-Quiros, L. Avila, B. J. Klanderman, J. S. Sylvia, J. C. Celedón, B. A. Raby, S. T. Weiss
Journal: European Respiratory Journal (2009)

Vascular endothelial growth factor (VEGF) is an angiogenic factor implicated in asthma severity. The objective of the present study was to determine whether VEGF single nucleotide polymorphisms (SNPs) are associated with asthma, lung function and airway responsiveness. The present authors analysed 10 SNPs in 458 white families in the Childhood Asthma Management Program (CAMP). Tests of association with asthma, lung function and airway responsiveness were performed using PBAT software (Golden Helix, Inc. Bozeman, MT, USA; available at www.goldenhelix.com ). Family and population-based, revpeated measures analysis of airflow obstruction were conducted. Replication studies were performed in 412 asthmatic children and their parents from Costa Rica. Associations with asthma, lung function and airway responsiveness were observed in both cohorts. SNP rs833058 was associated with asthma in both cohorts. This SNP was also associated with increased airway responsiveness in both populations. An association of rs4711750 and its haplotype with forced expiratory volume in 1 s (FEV 1 )/forced vital capacity (FVC) ratio in both cohorts was observed. Longitudinal analysis in CAMP confirmed an association of rs4711750 with FEV 1 /FVC decline over ∼4.5 yrs of observation. VEGF polymorphisms are associated with childhood asthma, lung function and airway responsiveness in two populations, suggesting that VEGF polymorphisms influence asthma susceptibility, airflow obstruction and airways responsiveness.
Low fat diets
Authors: Rhona MacDonald
Journal: BMJ (2001)

So, it's official: low fat diets don't do much to improve cardiovascular morbidity and mortality (p 757). This conclusion is both surprising and counterintuitive and no doubt will send health promoters into a spin.

In general we in the West are obsessed with fat and with low fat diets. But in true form we still want to have our cake and eat it—so …
β-Cell Mass and Turnover in Humans
Authors: Yoshifumi Saisho, Alexandra E. Butler, Erica Manesso, David Elashoff, Robert A. Rizza, Peter C. Butler
Journal: Diabetes Care (2012)

We sought to establish β-cell mass, β-cell apoptosis, and β-cell replication in humans in response to obesity and advanced age.We examined human autopsy pancreas from 167 nondiabetic individuals 20-102 years of age. The effect of obesity on β-cell mass was examined in 53 lean and 61 obese subjects, and the effect of aging was examined in 106 lean subjects.β-Cell mass is increased by ~50% with obesity (from 0.8 to 1.2 g). With advanced aging, the exocrine pancreas undergoes atrophy but β-cell mass is remarkably preserved. There is minimal β-cell replication or apoptosis in lean humans throughout life with no detectable changes with obesity or advanced age.β-Cell mass in human obesity increases by ~50% by an increase in β-cell number, the source of which is unknown. β-Cell mass is well preserved in humans with advanced aging.