tbuckley/cabot-search huggingface dataset:
What is the most effective treatment for severe gastro-oesophageal reflux disease?
Authors: J. Maret-Ouda, N. Brusselaers, J. Lagergren
Journal: BMJ (2015)

Gastro-oesophageal reflux disease (GORD) is defined as “a condition which develops when reflux of stomach contents causes troublesome symptoms and/or complications.”1 GORD can be categorised as mild or severe; it is considered severe when the patient experiences severe symptoms due to reflux of gastric contents, develops complications, or both.2 Complications are commonly diagnosed endoscopically as oesophagitis with confluent mucosal erosions.3 Other presentations of severe GORD include peptic strictures and Barrett’s oesophagus, a metaplasia in which parts of the native oesophageal squamous epithelium are replaced by specialised columnar epithelium. The main alternatives for treatment of severe GORD are continuous treatment with a proton pump inhibitor and surgery with fundoplication; which is the more effective is not clear. The treatment decision largely depends on the recommendations of the clinician.

We did a systematic literature search of Medline, Cochrane, and Web of Science to identify relevant randomised clinical trials, meta-analyses, and systematic reviews, using the search terms gastro-oesophageal reflux disease, proton pump inhibitors, and fundoplication. Although severity of GORD was not always specified, patients eligible for long term proton pump inhibitor or fundoplication typically have severe GORD. From the identified studies, we did backward and forward citation tracking to identify other relevant articles.

### Reflux control

A Cochrane systematic review of a large patient sample (n=1232) from four randomised clinical trials comparing proton pump inhibitors and fundoplication found that reflux symptoms were less frequent after fundoplication compared with proton pump inhibitor treatment, but surgical patients more often had dysphagia.2 Two of the trials included in the Cochrane review measured recurrence of GORD, defined as the need for and an inadequate response to increased drug treatment or the need for added proton pump inhibitor after surgical treatment. One (n=554) found treatment failure in 10% and 7% three years after fundoplication and proton pump …
Subendothelial Lipoprotein Retention as the Initiating Process in Atherosclerosis
Authors: Ira Tabas, Kevin Jon Williams, Jan Borén
Journal: Circulation (2007)

The key initiating process in atherogenesis is the subendothelial retention of apolipoprotein B–containing lipoproteins. Local biological responses to these retained lipoproteins, including a chronic and maladaptive macrophage- and T-cell–dominated inflammatory response, promote subsequent lesion development. The most effective therapy against atherothrombotic cardiovascular disease to date—low density lipoprotein–lowering drugs—is based on the principle that decreasing circulating apolipoprotein B lipoproteins decreases the probability that they will enter and be retained in the subendothelium. Ongoing improvements in this area include more aggressive lowering of low-density lipoprotein and other atherogenic lipoproteins in the plasma and initiation of low-density lipoprotein–lowering therapy at an earlier age in at-risk individuals. Potential future therapeutic approaches include attempts to block the interaction of apolipoprotein B lipoproteins with the specific subendothelial matrix molecules that mediate retention and to interfere with accessory molecules within the arterial wall that promote retention such as lipoprotein lipase, secretory sphingomyelinase, and secretory phospholipase A 2 . Although not the primary focus of this review, therapeutic strategies that target the proatherogenic responses to retained lipoproteins and that promote the removal of atherogenic components of retained lipoproteins also hold promise. The finding that certain human populations of individuals who maintain lifelong low plasma levels of apolipoprotein B lipoproteins have an ≈90% decreased risk of coronary artery disease gives hope that our further understanding of the pathogenesis of this leading killer could lead to its eradication.
Lorazepam for the Prevention of Recurrent Seizures Related to Alcohol
Authors: Gail D'Onofrio, Niels K. Rathlev, Andrew S. Ulrich, Susan S. Fish, Eric S. Freedland
Journal: New England Journal of Medicine (1999)

Alcohol abuse is one of the most common causes of seizures in adults. In a randomized, double-blind study, we compared lorazepam with placebo for the prevention of recurrent seizures related to alcohol. Over a 21-month period, we studied consecutive patients with chronic alcohol abuse who were at least 21 years of age and who presented to the emergency departments of two hospitals in Boston after a witnessed, generalized seizure. The patients were randomly assigned to receive either 2 mg of lorazepam in 2 ml of normal saline or 4 ml of normal saline intravenously and then observed for six hours. The primary end point was the occurrence of a second seizure during the observation period.Of the 229 patients who were initially evaluated, 186 met the entry criteria. In the lorazepam group, 3 of 100 patients (3 percent) had a second seizure, as compared with 21 of 86 patients (24 percent) in the placebo group (odds ratio for seizure with the use of placebo, 10.4; 95 percent confidence interval, 3.6 to 30.2; P<0.001). Forty-two percent of the placebo group were admitted to the hospital, as compared with 29 percent of the lorazepam group (odds ratio for admission, 2.1; 95 percent confidence interval, 1.1 to 4.0; P=0.02). Seven patients in the placebo group and one in the lorazepam group were transported to an emergency department in Boston with a second seizure within 48 hours after hospital discharge.Treatment with intravenous lorazepam is associated with a significant reduction in the risk of recurrent seizures related to alcohol.
LOCAL SPECIFIC THERAPY OF EXPERIMENTAL PNEUMOCOCCAL MENINGITIS
Authors: Fred W. Stewart
Journal: The Journal of Experimental Medicine (1927)

1. Extensive acute, fibrinopurulent meningitis may be produced in dogs by the intracisternal injection of virulent Type I pneumococci. 2. Given an equal number of virulent infecting organisms, the rate of establishment of infection depends upon the phase of growth and the quantitative growth per cc. of culture plus an uncontrollable individual factor in the animal. 3. The pathology of pneumococcal meningitis is discussed. It resembles very closely the similar disease in man. 4. Systematic lavage and treatment with optochin-serum mixtures by the method of quadruple puncture, as described above, have resulted in cures of Type I pneumococcal meningitis in dogs. 5. The important factor in obtaining cures is to bring all regions of the meninges into frequent contact with the therapeutic agent. 6. In the absence of such contact, incomplete sterilization results and "reinfection" is almost inevitable. 7. Protocols show the necessity of repeated negative cisternal fluids, both on smear and on culture, before sterilization can be assured. 8. Recovered dogs subjected to meningeal reinfection show some degree of resistance.
Efficacy of Gemcitabine in Patients with Non–Small Cell Lung Cancer According to Promoter Polymorphisms of the Ribonucleotide Reductase M1 Gene
Authors: Soo-Ok Kim, Ju-Yeon Jeong, Mi-Ran Kim, Hyun-Ju Cho, Jin-Yung Ju, Yong-Soo Kwon, In-Jae Oh, Kyu-Sik Kim, Yu-Il Kim, Sung-Chul Lim, Young-Chul Kim
Journal: Clinical Cancer Research (2008)

Abstract Purpose: High ribonucleotide reductase M1 (RRM1) expression in resected lung cancers has been associated with better clinical outcomes. However, gemcitabine-treated patients with high tumoral RRM1 expression generally evidence poor prognoses due to the decreased efficacy of gemcitabine therapy. This study was designed in accordance with the hypothesis that polymorphisms (−37 and −524) of the RRM1 promoter gene sequence, which regulate RRM1 expression, could influence the efficacy and prognosis of lung cancer patients treated with gemcitabine-based chemotherapy. Experimental Design: A retrospective dataset of 97 patients with advanced non–small cell lung cancer treated with gemcitabine regimens as a first-line treatment was studied in this work. The allelotyping of RRM1 promoter polymorphisms was conducted via real-time PCR using genomic DNA obtained from peripheral WBC. Results: The RRM1 promoter allelotype was RR37CC-R524TT in 58 patients, RR37AC-RR524CT in 29 patients, and other allelotypes in 10 patients. The response rate for gemcitabine-containing chemotherapy was 49.5%. The response rate was significantly higher in the RR37AC-RR524CT group (65.5%) compared with the group containing other allelotypes (42.6%; P = 0.039). Overall survival and progression-free survival did not differ significantly by allelotype. Conclusions: We detected significant differences in response rates to gemcitabine-based chemotherapy according to the allelotypes of the RRM1 promoter sequence, which could be determined using the germline DNA. Further functional and clinical studies will be required before this can be used as a predictive marker.
Genetic variants in Protocadherin-1, bronchial hyperresponsiveness and asthma subphenotypes in German children
Authors: Antoaneta Toncheva, Kathrin Suttner, Sven Michel, Norman Klopp, Thomas Illig, Christian Vogelberg, Andrea von Berg, Albrecht Bufe, Andrea Heinzmann, Otto Laub, Ernst Rietschel, Burkhard Simma, Thomas Frischer, Jon Genuneit, Erika von Mutius, Michael Kabesch
Journal: European Respiratory Journal (2012)

Background:  Recently,  Protocadherin-1 (PCDH1),  located on chromosome 5q31-33, in the vicinity of the cytokine gene cluster containing several known candidate genes for asthma and allergy ( interleukin-4, interleukin-5,  interleukin-13  and  RAD50) , was reported as a novel susceptibility gene for bronchial hyperresponsiveness (BHR) and asthma.   Objectives:  We aimed to define linkage disequilibrium (LD) between the region comprising  PCDH1  and the cytokine gene cluster. Next, for a comprehensive analysis of the  PCDH1  locus we conducted detailed fine mapping of the  PCDH1  region and investigated effects of single nucleotide polymorphisms (SNPs) in BHR, asthma and related phenotypes.   Methods:  Genotype information was acquired from Illumina HumanHap300Chip genotyping, MALDI-TOF MS genotyping and imputation. Associations were investigated in a population of at least 1,303 (651 asthmatics) from two German study populations (MAGICS and ISAAC II).   Results:  No relevant LD between 14  PCDH1  tagging SNPs and 98 SNPs within the cytokine cluster was detected. There were no significant associations with BHR, atopy, allergic rhinitis and atopic eczema. However, rs7719391 was associated with asthma (OR=0.85, p=0.039) and non-atopic asthma (OR=0.69, p=0.009). The exonic SNP rs3797054 previously reported to be associated with BHR and asthma, was significantly associated with non-atopic asthma (OR=0.70, p=0.019) in our study. Significant associations with non-atopic asthma were observed also for rs11167761 (OR=1.54, p=0.021), rs3935792 (OR=1.32, p=0.039), rs2974704 (OR=0.43, p=0.009).   Conclusions:   PCDH1  polymorphisms may specifically affect the development of non-atopic asthma in children.  These authors contributed equally: Mrs. Antoaneta Toncheva, Dr. Kathrin Suttner, and Mr. Sven Michel.
Sleep-Disordered Breathing and Mortality: A Prospective Cohort Study
Authors: Naresh M. Punjabi, Brian S. Caffo, James L. Goodwin, Daniel J. Gottlieb, Anne B. Newman, George T. O'Connor, David M. Rapoport, Susan Redline, Helaine E. Resnick, John A. Robbins, Eyal Shahar, Mark L. Unruh, Jonathan M. Samet
Journal: PLoS Medicine (2009)

Sleep-disordered breathing is a common condition associated with adverse health outcomes including hypertension and cardiovascular disease. The overall objective of this study was to determine whether sleep-disordered breathing and its sequelae of intermittent hypoxemia and recurrent arousals are associated with mortality in a community sample of adults aged 40 years or older.We prospectively examined whether sleep-disordered breathing was associated with an increased risk of death from any cause in 6,441 men and women participating in the Sleep Heart Health Study. Sleep-disordered breathing was assessed with the apnea-hypopnea index (AHI) based on an in-home polysomnogram. Survival analysis and proportional hazards regression models were used to calculate hazard ratios for mortality after adjusting for age, sex, race, smoking status, body mass index, and prevalent medical conditions. The average follow-up period for the cohort was 8.2 y during which 1,047 participants (587 men and 460 women) died. Compared to those without sleep-disordered breathing (AHI: <5 events/h), the fully adjusted hazard ratios for all-cause mortality in those with mild (AHI: 5.0-14.9 events/h), moderate (AHI: 15.0-29.9 events/h), and severe (AHI: >or=30.0 events/h) sleep-disordered breathing were 0.93 (95% CI: 0.80-1.08), 1.17 (95% CI: 0.97-1.42), and 1.46 (95% CI: 1.14-1.86), respectively. Stratified analyses by sex and age showed that the increased risk of death associated with severe sleep-disordered breathing was statistically significant in men aged 40-70 y (hazard ratio: 2.09; 95% CI: 1.31-3.33). Measures of sleep-related intermittent hypoxemia, but not sleep fragmentation, were independently associated with all-cause mortality. Coronary artery disease-related mortality associated with sleep-disordered breathing showed a pattern of association similar to all-cause mortality.Sleep-disordered breathing is associated with all-cause mortality and specifically that due to coronary artery disease, particularly in men aged 40-70 y with severe sleep-disordered breathing. Please see later in the article for the Editors' Summary.
Transfer of MHC-class-I molecules among liver sinusoidal cells facilitates hepatic immune surveillance
Authors: Katrin Schölzel, Frank A. Schildberg, Meike Welz, Carolin Börner, Sergej Geiger, Christian Kurts, Mathias Heikenwälder, Percy A. Knolle, Dirk Wohlleber
Journal: Journal of Hepatology (2014)
PinX1 suppresses bladder urothelial carcinoma cell proliferation via the inhibition of telomerase activity and p16/cyclin D1 pathway
Authors: Jian-Ye Liu, Dong Qian, Li-Ru He, Yong-Hong Li, Yi-Ji Liao, Shi-Juan Mai, Xiao-Peng Tian, Yan-Hui Liu, Jia-Xing Zhang, Hsiang-Fu Kung, Yi-Xin Zeng, Fang-Jian Zhou, Dan Xie
Journal: Molecular Cancer (2013)

Abstract Background PIN2/TRF1-interacting telomerase inhibitor1 (PinX1) was recently suggested as a putative tumor suppressor in several types of human cancer, based on its binding to and inhibition of telomerase. Moreover, loss of PinX1 has been detected in many human malignancies. However, the possible involvement of PinX1 and its clinical/prognostic significance in urothelial carcinoma of the bladder (UCB) are unclear. Methods The PinX1 expression profile was examined by quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, and immunohistochemistry (IHC) in UCB tissues and adjacent normal urothelial bladder epithelial tissues. PinX1 was overexpressed and silenced in UCB cell lines to determine its role in tumorigenesis, development of UCB, and the possible mechanism. Results PinX1 expression in UCB was significantly down-regulated at both mRNA and protein level as compared with that in normal urothelial bladder epithelial tissues. PinX1 levels were inversely correlated with tumor multiplicity, advanced N classification, high proliferation index (Ki-67), and poor survival ( P &lt; 0.05). Moreover, overexpression of PinX1 in UCB cells significantly inhibited cell proliferation in vitro and in vivo, whereas silencing PinX1 dramatically enhanced cell proliferation. Overexpression of PinX1 resulted in G1/S phase arrest and cell growth/proliferation inhibition, while silencing PinX1 led to acceleration of G1/S transition, and cell growth/proliferation promotion by inhibiting/enhancing telomerase activity and via the p16/cyclin D1 pathway. Conclusions These findings suggest that down-regulation of PinX1 play an important role in the tumorigenesis and development of UCB and that the expression of PinX1 as detected by IHC is an independent molecular marker in patients with UCB.
Catheter Ablation for Paroxysmal Atrial Fibrillation
Authors: Hakan Oral, Christoph Scharf, Aman Chugh, Burr Hall, Peter Cheung, Eric Good, Srikar Veerareddy, Frank Pelosi, Fred Morady
Journal: Circulation (2003)

Segmental ostial catheter ablation (SOCA) to isolate the pulmonary veins (PVs) and left atrial catheter ablation (LACA) to encircle the PVs both may eliminate paroxysmal atrial fibrillation (PAF). The relative efficacy of these 2 techniques has not been directly compared.Of 80 consecutive patients with symptomatic PAF (age, 52+/-10 years), 40 patients underwent PV isolation by SOCA and 40 patients underwent LACA to encircle the PVs. During SOCA, ostial PV potentials recorded with a ring catheter were targeted. LACA was performed by encircling the left- and right-sided PVs 1 to 2 cm from the ostia and was guided by an electroanatomic mapping system; ablation lines also were created in the mitral isthmus and posterior left atrium. The mean procedure and fluoroscopy times were 156+/-45 and 50+/-17 minutes for SOCA and 149+/-33 and 39+/-12 minutes for LACA, respectively. At 6 months, 67% of patients who underwent SOCA and 88% of patients who underwent LACA were free of symptomatic PAF when not taking antiarrhythmic drug therapy (P=0.02). Among the variables of age, sex, duration and frequency of PAF, ejection fraction, left atrial size, structural heart disease, and the ablation technique, only an increased left atrial size and the SOCA technique were independent predictors of recurrent PAF. The only complication was left atrial flutter in a patient who underwent LACA.In patients undergoing catheter ablation for PAF, LACA to encircle the PVs is more effective than SOCA.
Trying to find a cure for cystic fibrosis: CFTR biomarkers as outcomes
Authors: Kris De Boeck
Journal: European Respiratory Journal (2013)

We thank P. Lebecque for his interest in our paper [1].His comment as to whether measurement of cystic fibrosis transmembrane conductance regulator (CFTR) biomarkers are truly response measures relates to the recent paper by DURMOWICZ et al. [2] entitled ''Change in sweat chloride as a clinical end point in cystic fibrosis clinical trials: the ivacaftor experience''.These authors also point towards the uncertainty of using established measurements such as sweat chloride as a clinical end-point.We are indeed in the early days of clinical use of CFTR modulators and much is to be learned about how improving CFTR biomarkers relates to clinical efficacy.In our further discussion, we will, as DURMOWICZ et al.[2] do, discuss only ivacaftor and lumacaftor monotherapy [3][4][5], since data on ataluren and on ivacaftor/lumacaftor combination therapy are only available as abstracts.CFTR biomarkers as surrogate end-points: improving CFTR function must ameliorate cystic fibrosis lung disease http://ow.ly/nv6Uh
Long-term Outcomes of Patients Receiving a Magnetic Sphincter Augmentation Device for Gastroesophageal Reflux
Authors: Robert A. Ganz, Steven A. Edmundowicz, Paul A. Taiganides, John C. Lipham, C. Daniel Smith, Kenneth R. DeVault, Santiago Horgan, Garth Jacobsen, James D. Luketich, Christopher C. Smith, Steven C. Schlack-Haerer, Shanu N. Kothari, Christy M. Dunst, Thomas J. Watson, Jeffrey Peters, Brant K. Oelschlager, Kyle A. Perry, Scott Melvin, Willem A. Bemelman, André J.P.M. Smout, Dan Dunn
Journal: Clinical Gastroenterology and Hepatology (2015)
Sexual Well-Being Among Partnered Women With Breast Cancer Recurrence
Authors: Barbara L. Andersen, Kristen M. Carpenter, Hae-Chung Yang, Charles L. Shapiro
Journal: Journal of Clinical Oncology (2007)

Purpose A woman's risk for sexual disruption after breast cancer recurrence has received little clinical or research attention. Patients and Methods Breast cancer patients recently diagnosed with recurrence (n = 60) were initially assessed at baseline and completed follow-ups at 4, 8, and 12 months. They were compared by age, stage, and duration and frequency of follow-up with matched patients who remained disease free (n = 120). Using linear mixed modeling, the groups were compared in their trajectories of change on measures of sexuality, relationship satisfaction, cancer-specific stress, and physical functioning. Recurrence subgroups, those with locoregional versus distant disease and those younger versus older than 52 years, were also compared. Results At baseline, the recurrence group had significantly lower intercourse frequency and physical functioning compared with the disease-free group and these differences were maintained. There were no significant differences in the frequencies of kissing or sexual and relationship satisfactions. For the recurrence group patients, the heightened stress of the diagnostic/early recurrence treatment period declined to the lower disease-free levels by 12 months. This effect was largely due to improvement of the patients with distant disease. Finally, sexual changes were most notable for younger patients. Conclusion To our knowledge, this is the first longitudinal, controlled study of sexuality—sexuality in the context of other quality of life domains—for women coping with recurrence. Despite disruption, patients maintained their sexual lives. Younger and distant recurrence patients, however, may have greatest risk of sexual disruption. The factors contributing to sexual disruption remain unknown, and studies investigating strategies to help patients maintain this aspect of quality of life are needed.
Angiogenic Protein Cyr61 is Expressed by Podocytes in Anti-Thy-1 Glomerulonephritis
Authors: Kazutomo Sawai, Kiyoshi Mori, Masashi Mukoyama, Akira Sugawara, Takayoshi Suganami, Masao Koshikawa, Kensei Yahata, Hisashi Makino, Tetsuya Nagae, Yuriko Fujinaga, Hideki Yokoi, Tetsuro Yoshioka, Akihiro Yoshimoto, Issei Tanaka, Kazuwa Nakao
Journal: Journal of the American Society of Nephrology (2003)

Dynamic recovery of glomerular structure occurs after severe glomerular damage in anti-Thy-1 glomerulonephritis (Thy-1 GN), but its mechanism remains to be investigated. To identify candidate genes possibly involved in glomerular reconstruction, screening was performed for genes that are specifically expressed by podocytes and are upregulated in glomeruli of Thy-1 GN. Among them, cysteine-rich protein 61 (Cyr61 or CCN1), a soluble angiogenic protein belonging to the CCN family, was identified. By Northern blot analysis, Cyr61 mRNA was markedly upregulated in glomeruli of Thy-1 GN from day 3 through day 7, when mesangial cell migration was most prominent. By in situ hybridization and immunohistochemistry, Cyr61 mRNA and protein were expressed by proximal straight tubules and afferent and efferent arterioles in normal rat kidneys and were intensely upregulated at podocytes in Thy-1 GN. Platelet-derived growth factor-BB (PDGF-BB) and transforming growth factor-beta1 (TGF-beta1), of which the gene expression in the glomeruli of Thy-1 GN was upregulated in similar time course as Cyr61, induced Cyr61 mRNA expression in cultured podocytes. Furthermore, supernatant of Cyr61-overexpressing cells inhibited PDGF-induced mesangial cell migration. In conclusion, it is shown that Cyr61 is strongly upregulated at podocytes in Thy-1 GN possibly by PDGF and TGF-beta. Cyr61 may be involved in glomerular remodeling as a factor secreted from podocytes to inhibit mesangial cell migration.