tbuckley/cabot-search huggingface dataset:
Long-term proton pump induced hypergastrinaemia does induce lineage-specific restitution but not clonal expansion in benign Barrett's oesophagus in vivo
Authors: Jolanta A Obszynska, Paul A Atherfold, Manoj Nanji, Deborah Glancy, Sonia Santander, Trevor A Graham, William R Otto, Kevin West, Rebecca F Harrison, Janusz AZ Jankowski
Journal: Gut (2009)

Barrett's oesophagus is a common premalignant lesion caused partly by acid reflux. Although the requisite therapy, proton pump inhibitors (PPIs), have been implicated in the progression of Barrett's oesophagus in animal models, harmful effects of prolonged PPI therapy in Barrett's oesophagus is both inconclusive and controversial. We therefore aimed to test the role of PPI-induced hypergastrinaemia in vitro and see whether any biological parameters were useful surrogates of long-term therapy in man.We undertook detailed serological and tissue assessment of gastrin and CCK(2) receptors in 90 patients randomised to different doses of PPI therapy during a detailed 2-year follow-up. We also undertook a comprehensive study of cell models to study the consequential biological effects of gastrin on the mucosa.Gastrin and its cognate receptor CCK(2)R were expressed highest in the stomach, then less in Barrett's oesophagus and least in squamous oesophagus (SqE) (n=20 paired t-test, p<0.01). Analysis of the change in Barrett's oesophagus segment length change in 70 patients who were randomised to high or low PPI dose showed no difference over 2 years (n=70 t-test, p=0.8). Prolonged PPI use did, however, increase the serum gastrin, (36 pg/ml+/-57 pg/ml to 103 pg/ml+/-94 pg/ml (paired t test, p<0.05)). In vitro gastrin also induced changes in OE33(E)(cckr) Barrett's oesophagus cells, but not OE21(E)(cckr) squamous cells, transfected with CCK(2)R; migration was induced by 1 ng/ml of gastrin but proliferation only increased with 100 ng/ml (paired t-test, p<0.01) and both were abolished by antagonists.While the short-term effects of gastrin enhance epithelial restitution in Barrett's oesophagus (but not squamous mucosa) there is no clinical evidence that Barrett's oesophagus length expands over time. This study, which is the largest and longest term randomised controlled trial of gastrin biology in Barrett's oesophagus, is further proof of the clinical safety of PPI therapy.
Statins and<i>Clostridum difficile</i>: a clinically relevant interaction?
Authors: Sandra Dial
Journal: Gut (2012)

Statins are a class of lipid-lowering drugs which decrease cholesterol synthesis and have beneficial effects on cardiovascular disease. Observational studies have ascribed many other beneficial effects of statins, including reduced risk of infections, cancer and Alzheimer's.1 The authors argue that these myriad beneficial observations are plausible as ‘pleiotropic’ or multiple effects of statins including anti-inflammatory, antioxidant, immunomodulatory, antiapoptotic, antiproliferative, antithrombotic, antimicrobial and endothelium-protecting properties2 have been demonstrated in the laboratory. However, are these beneficial effects too good to be true?

It has been suggested that many of the apparent observed beneficial effects of statins can be explained by a ‘healthy user effect’. Statin users, especially compliant users, have been shown to be more likely to be insured, live at home, to have stopped smoking and to be more likely to engage in other positive health behaviours such as undergoing cancer screening and being vaccinated.3 4 Studies using administrative databases often are unable to adjust for these variables, and three studies on patients with pneumonia4–6 which adjusted for some of these variables found no decreased risk of pneumonia associated with current use of statins, and even reported a tendency towards increased risk.

Motzkus-Feagans and colleagues7 …
Long-Term Effects of Low-Calorie Diet on the Metabolic Syndrome in Obese Nondiabetic Patients
Authors: Fulvio Muzio, Luca Mondazzi, Domenico Sommariva, Adriana Branchi
Journal: Diabetes Care (2005)

The prevalence of obesity is increasing among western populations, bringing about a parallel rise in the prevalence of the metabolic syndrome (1), which is strictly related to overweight (2). There is full agreement that lifestyle changes primarily focused on weight reduction are the first-line approach to patients with the metabolic syndrome (3). In short-term trials, even a modest weight reduction has been shown to favorably affect the components of the metabolic syndrome such as hypertension, lipid abnormalities, and glycemic control (4–8). The long-term effects of weight loss on the cluster of factors that comprise the metabolic syndrome have been studied in both overweight (9) and mildly obese (10) patients. We report here the extent to which a 2-year treatment program with a low-calorie, low-fat diet altered components of the metabolic syndrome in obese, nondiabetic patients presenting with the syndrome.

The local ethics committee reviewed and approved the study, and each eligible participant gave written informed consent. We enrolled 41 patients (30 women and 11 men, age 58.7 ± 11.27 years [means ± SD]) with the metabolic syndrome as diagnosed according to the criteria of the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATPIII) (2). The inclusion criteria were age >18 years, BMI ≥30 kg/m2, and a willingness to adhere to the prescribed diet. The exclusion criteria …
A new double-tracer gas single-breath washout to assess early cystic fibrosis lung disease
Authors: Florian Singer, Georgette Stern, Cindy Thamrin, Chiara Abbas, Carmen Casaulta, Urs Frey, Philipp Latzin
Journal: European Respiratory Journal (2012)

In cystic fibrosis (CF), tests for ventilation inhomogeneity are sensitive but not established for clinical routine. We assessed feasibility of a new double-tracer gas single-breath washout (SBW) in school-aged children with CF and control subjects, and compared SBW between groups and with multiple-breath nitrogen washout (MBNW). Three SBW and MBNW were performed in 118 children (66 with CF) using a side-stream ultrasonic flowmeter setup. The double-tracer gas containing 5% sulfur hexafluoride and 26.3% helium was applied during one tidal breath. Outcomes were SBW phase III slope (SIII DTG ), MBNW-derived lung clearance index (LCI), and indices of acinar ( S acin ) and conductive ( S cond ) ventilation inhomogeneity. SBW took significantly less time to perform than MBNW. SBW and MBNW were feasible in 109 (92.4%) and 98 (83.0%) children, respectively. SIII DTG differed between children with CF and controls, mean± sd was -456.7±492.8 and -88.4±129.1 mg·mol·L −1 , respectively. Abnormal SIII DTG was present in 36 (59%) children with CF. SIII DTG was associated with LCI (r= -0.58) and S acin (r= -0.58), but not with S cond . In CF, steeply sloping SIII DTG potentially reflects ventilation inhomogeneity near the acinus entrance. This tidal SBW is a promising test to assess ventilation inhomogeneity in an easy and fast way.
STUDIES ON THE DISSOCIATION OF THE HOG CHOLERA BACILLUS
Authors: C. P. Li
Journal: The Journal of Experimental Medicine (1929)

When the "normal" MS form of hog cholera bacillus was grown for 3 weeks in broth and subsequently plated in semi-solid media, 2 variant forms appeared, a motile rough (MR) form and a nonmotile smooth (NS) form. The NS form subsequently gave rise to a third variant, namely, the nonmotile rough (NR) form. It is evident from the observations reported that in the case of the hog cholera bacillus the simple S and R conception of microbic dissociation is inadequate to account for the several variant forms. It appears necessary to combine the S and R with the H and O or the flagellar and somatic antigen conception to account for the phenomenon. The dissociation is represented by the following diagram: See PDF for Structure
Molecular Histopathology by Spectrally Reconstructed Nonlinear Interferometric Vibrational Imaging
Authors: Praveen D. Chowdary, Zhi Jiang, Eric J. Chaney, Wladimir A. Benalcazar, Daniel L. Marks, Martin Gruebele, Stephen A. Boppart
Journal: Cancer Research (2010)

Sensitive assays for rapid quantitative analysis of histologic sections, resected tissue specimens, or in situ tissue are highly desired for early disease diagnosis. Stained histopathology is the gold standard but remains a subjective practice on processed tissue taking from hours to days. We describe a microscopy technique that obtains a sensitive and accurate color-coded image from intrinsic molecular markers. Spectrally reconstructed nonlinear interferometric vibrational imaging can differentiate cancer versus normal tissue sections with greater than 99% confidence interval in a preclinical rat breast cancer model and define cancer boundaries to ± 100 μm with greater than 99% confidence interval, using fresh unstained tissue sections imaged in less than 5 minutes. By optimizing optical sources and beam delivery, this technique can potentially enable real-time point-of-care optical molecular imaging and diagnosis.
Fatal B-cell Lymphoma Following Chronic Lymphocytic Inflammation With Pontine Perivascular Enhancement Responsive to Steroids
Authors: Hjalmar J. De Graaff, Mike P. Wattjes, Annemieke J. Rozemuller-Kwakkel, Axel Petzold, Joep Killestein
Journal: JAMA Neurology (2013)

Recent reports on chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) suggest that patients who have a relapse respond very well and that disease progression can be avoided if timely corticosteroid therapy is started. We report on a well-documented patient who presented with clinical, radiological, and pathological characteristics of CLIPPERS and who had an unfavorable outcome.We present the clinical, imaging, laboratory, brain biopsy, and autopsy findings of a 57-year-old male patient with CLIPPERS who repeatedly responded well to high-dose corticosteroids. During follow-up, however, treatment failed, and he had a biopsy-confirmed diagnosis of lymphomatoid granulomatosis that evolved into fatal B-cell lymphoma of the central nervous system.The clinical and imaging features of CLIPPERS include an abundance of differential diagnoses, and the follow-up periods of the described cases classified as CLIPPERS have been limited. Therefore, the question remains whether CLIPPERS is an actual new disease entity or represents a syndrome that includes different overlapping diseases and their prestages. Our case report shows that a typical presentation of CLIPPERS does not uniformly imply a favorable outcome, even when timely treatment regimens have been given.
Hospital policy on advance directives. Do institutions ask patients about living wills?
Authors: S. V. McCrary
Journal: JAMA (1989)

Surveys have shown that a substantial proportion of the population has prepared an advance directive. The purpose of this exploratory study was to assess the existence and nature of hospital policy regarding these documents. A survey questionnaire was sent to 394 randomly selected hospitals in the United States. Of the 219 responding hospitals, 146 (67%) reported having a formal policy regarding advance directives. The large majority of those with a policy require the patient to notify the hospital of an advance directive, while only 4% of the respondents actively inquire about these documents. Hospitals in states with legislation that sanctions advance directives were significantly more likely to have a formal policy regarding these documents than hospitals in states without such legislation. Forty-six percent of the respondents reported having an ethics committee; however, the presence of an ethics committee was not significantly associated with the presence of a formal policy. Of the 69 hospitals that had both a formal policy and an ethics committee, only 30 (43%) reported that the policy had been reviewed by the ethics committee. Ethical and legal issues regarding hospital policy on advance directives are discussed. Hospitals should adopt formal policies to ask all adult patients at the time of admission whether they have prepared a living will, durable power of attorney, or similar document; and ethics committees should play a more active role in policy development. (<i>JAMA</i>. 1989;262:2411-2414)
Comparison of 99m technetium hexamethylpropylene-amine oxime labelled leucocyte with 111-indium tropolonate labelled granulocyte scanning and ultrasound in the diagnosis of intra-abdominal abscess.
Authors: M J Weldon, A E Joseph, A French, S H Saverymuttu, J D Maxwell
Journal: Gut (1995)

Fifty patients with suspected intra-abdominal abscess were investigated prospectively with ultrasound and with 99mTc-hexamethylpropylene-amine oxime (HMPAO) isotope labelled mixed leucocytes, using 111-In tropolonate granulocyte scanning as the reference standard. Twenty five patients had inflammatory bowel disease (three were postoperative): 21 of these had Crohn9s disease and four had ulcerative colitis. The remainder comprised nine with postoperative fever and 16 with fever and abdominal pain. An abscess was diagnosed when focal activity on serial 111-In tropolonate and 99m-Tc-HMPOA images at one, three, and 24 hours resulted in activity at least equal to liver activity at 24 hours. Thirteen abscesses were diagnosed using each type of white cell scanning, resulting in 100% sensitivity for 99m-Tc-HMPAO compared with 111-In tropolonate. Bowel inflammation was easily distinguished from abscess on serial images. Eight of these 13 abscesses were detected by ultrasound. Altogether 17 abscesses were found. Ultrasound detected 12, including four liver abscesses which were not purulent and had not been detected by white cell scanning. Ultrasound had a sensitivity of 71% (12 of 17) and a specificity of 87% (33 of 38) using all confirmed abscesses as the reference standard. White cell scanning showed a sensitivity of 76% (13 of 17: as a result of the four non-purulent liver abscesses) and a specificity of 100%. 99m-Tc-HMPAO scanning is as accurate as 111-In tropolonate scanning, and has several advantages including simplicity, availability, superior image quality, and reduced radiation dose. Both methods are more sensitive and specific than ultrasound for intra-abdominal abscess detection but ultrasound is advisable if a neutrophil infiltrate is not suspected.
Effect of Adjuvant Chemotherapy on Survival of Patients With Stage III Colon Cancer Diagnosed After Age 75 Years
Authors: Hanna K. Sanoff, William R. Carpenter, Til Stürmer, Richard M. Goldberg, Christopher F. Martin, Jason P. Fine, Nadine Jackson McCleary, Jeffrey A. Meyerhardt, Joyce Niland, Katherine L. Kahn, Maria J. Schymura, Deborah Schrag
Journal: Journal of Clinical Oncology (2012)

Few patients 75 years of age and older participate in clinical trials, thus whether adjuvant chemotherapy for stage III colon cancer (CC) benefits this group is unknown.
Activating<i>HRAS</i>Mutation in Agminated Spitz Nevi Arising in a Nevus Spilus
Authors: Kavita Y. Sarin, Bryan K. Sun, Charles D. Bangs, Athena Cherry, Susan M. Swetter, Jinah Kim, Paul A. Khavari
Journal: JAMA Dermatology (2013)

Spitz nevi are benign melanocytic proliferations that can sometimes be clinically and histopathologically difficult to distinguish from melanoma. Agminated Spitz nevi have been reported to arise spontaneously, in association with an underlying nevus spilus, or after radiation or chemotherapy. However, to our knowledge, the genetic mechanism for this eruption has not been described.We report a case of agminated Spitz nevi arising in a nevus spilus and use exome sequencing to identify a clonal activating point mutation in HRAS (GenBank 3265) (c.37G→C) in the Spitz nevi and underlying nevus spilus. We also identify a secondary copy number increase involving HRAS on chromosome 11p, which occurs during the development of the Spitz nevi.Our results reveal an activating HRAS mutation in a nevus spilus that predisposes to the formation of Spitz nevi. In addition, we demonstrate a copy number increase in HRAS as a "second hit" during the formation of agminated Spitz nevi, which suggests that both multiple Spitz nevi and solitary Spitz nevi may arise through similar molecular pathways. In addition, we describe a unique investigative approach for the discovery of genetic alterations in Spitz nevi.
Prevalence of chronic bronchitis in an industrial population in North India.
Authors: R C Joshi, R N Madan, A A Brash
Journal: Thorax (1975)

A survey for the prevalence of chronic bronchitis in an industrial population in North India is reported. The prevalence of chronic bronchitis is 12.5 percent in 473 subjects between the ages of 17 and 64 years. The prevalence rate of chronic bronchitis is comparable to that observed in areas of low community air pollution in Europe and North America. There is no age-related rise in the frequency of respiratory symptoms. The consumption of tobacco in these subjects is low and is comparable to tobacco consumption of light smokers. The prevalence of chronic bronchitis in smokers is five times the prevalence in non-smokers and is similar to the values reported for light smokers in other surveys. These observations suggest that cigarette smoking is associated with the development of chronic bronchitis, and the differences in the prevalence rate of chronic bronchitis between this survey and other surveys conducted in Europe and North America are mainly due to differences in smoking habits. Air pollution has a minor effect only and ethnic differences do not appear to play any part. Forced expired volume in one second shows a negative correlation with age. It is lower in asymptomatic smokers than in non-smokers and is lower in chronic bronchitis than in controls.
Pyloric stenosis in Turner's syndrome
Authors: H. van den Berghe
Journal: BMJ (1967)

Pyloric Stenosis in Turner's Syndrome SIR,-The prevalence of congenital hyper- trophic stenosis in the general population is estimated to be about 2 to 5 per 1,000 live births,'`and Carter was able to demonstrate that the sex ratio for this malformation amounted to 5:1, boys being more affected than girls.'Benson and King have drawn attention to a possibly high prevalence of this condition in patients with Turner's syn- drome.'We have investigated a series of 43 patients with Turner's syndrome and found two patients with congenital pyloric stenosis.'The diagnosis of Turner's syndrome in Case 1 was established at the age of 19 years on the following criteria:(1) Sexual infantilism with primary amenor- rhoea, infantile external and internal genitalia, and absence of breast development.
Identification of a Fibroblast Growth Factor Receptor 1 Splice Variant That Inhibits Pancreatic Cancer Cell Growth
Authors: Zhanbing Liu, Nicola Neiss, Shaoxia Zhou, Doris Henne-Bruns, Murray Korc, Max Bachem, Marko Kornmann
Journal: Cancer Research (2007)

Abstract Fibroblast growth factor receptors (FGFR) play important roles in many biological processes. Nothing is presently known about possible roles of the human FGFR1-IIIb mRNA splice variant. In this study, we characterized for the first time the effects of FGFR1-IIIb expression on the transformed phenotype of human pancreatic cancer cells. The full-length FGFR1-IIIb cDNA was generated and stably expressed in PANC-1 and MIA PaCa-2 pancreatic cancer and TAKA-1 pancreatic ductal cells. FGFR1-IIIb–expressing cells synthesized a glycosylated 110-kDa protein enhancing tyrosine phosphorylation of FGFR substrate-2 on FGF-1 stimulation. The basal anchorage-dependent and anchorage-independent cell growth was significantly inhibited. These effects were associated with a marked reduction of p44/42 mitogen-activated protein kinase (MAPK) phosphorylation in combination with enhanced activity of p38 MAPK and c-Jun NH2-terminal kinase. FGFR1-IIIb expression inhibited single-cell movement and in vitro invasion as determined by time-lapse microscopy and Boyden chamber assay as well as in vivo tumor formation and growth in nude mice. Microscopic analysis of the xenograft tumors revealed a reduced Ki-67 labeling and a lower amount of tumor necrosis in FGFR1-IIIb–expressing tumors. Our results show that FGFR1-IIIb is a functional FGFR that inhibits the transformed phenotype of human pancreatic cancer cells. [Cancer Res 2007;67(6):2712–9]
Government defends NHS health checks for people aged 40-74 but promises evaluation
Authors: A. O'Dowd
Journal: BMJ (2015)

The government has defended the NHS Health Check programme despite calls from MPs for a full review of the scheme after concerns about its effectiveness and use of resources. However, two national research projects looking at its effect have been commissioned and are due to report early this year.

The government published its official response on 29 January to a report on national health screening from the House of Commons Science and Technology Committee, published in October last year.1 2 3

The NHS Health Check …
Use of Factor-Analyzed Symptom Dimensions to Predict Outcome With Serotonin Reuptake Inhibitors and Placebo in the Treatment of Obsessive-Compulsive Disorder
Authors: David Mataix-Cols, Scott L. Rauch, Peter A. Manzo, Michael A. Jenike, Lee Baer
Journal: American Journal of Psychiatry (1999)

No consistent predictors of outcome have been identified for the pharmaco-therapy of obsessive-compulsive disorder (OCD). Recent factor analytic studies have identified meaningful symptom dimensions that may be related to response to serotonin reuptake inhibitors and other treatments.A total of 354 outpatients with primary OCD were administered the Yale-Brown Obsessive Compulsive Scale Symptom Checklist, and its 13 main symptom categories were factor analyzed by using principal components analysis. The identified symptom dimensions were then entered into multiple regression models as outcome predictors of response to serotonin reuptake inhibitors and placebo response in a group of 150 nondepressed subjects who completed six double-blind, placebo-controlled trials with a serotonin reuptake inhibitor (clomipramine, fluvoxamine, fluoxetine, sertraline, and paroxetine). Eighty-four patients received a serotonin reuptake inhibitor and 66, placebo.The principal components analysis identified five factors that explained 65.5% of variance in outcome: symmetry/ordering, hoarding, contamination/cleaning, aggressive/checking, and sexual/religious obsessions. Serotonin reuptake inhibitors were significantly superior to placebo on all outcome measures. Initial severity of OCD was related to greater posttreatment severity of OCD. Higher scores on the hoarding dimension predicted poorer outcome following treatment with serotonin reuptake inhibitors, after control for baseline severity. No predictors of placebo response were identified. Exclusion of clomipramine did not modify the overall results, suggesting a cross-serotonin reuptake inhibitor effect.The identified symptom dimensions are largely congruent with those identified in earlier reports. Patients with OCD vary in their response to treatment with serotonin reuptake inhibitors. The presence of hoarding obsessions and compulsions is associated with poorer response to serotonin reuptake inhibitors.