tbuckley/cabot-search huggingface dataset:
Double blind multicentre comparison of omeprazole 20 mg once daily versus ranitidine 150 mg twice daily in the treatment of cimetidine or ranitidine resistant duodenal ulcers.
Authors: J C Delchier, J P Isal, S Eriksson, J C Soule
Journal: Gut (1989)

The purpose of the present study was to compare omeprazole 20 mg once daily and ranitidine 150 mg twice daily in healing duodenal ulcers unhealed by previous treatment with cimetidine greater than or equal to 0.8 g or ranitidine greater than or equal to 0.3 g daily for at least six weeks. In a double blind multicentre trial, 151 patients were randomly assigned to either omeprazole or ranitidine. Clinical assessments and endoscopies were carried out at two and four weeks. Patients characteristics were similar in both groups. Statistical analysis (chi 2 test) did not show any significant difference in healing rate (p greater than 0.20) irrespective of the method of calculation. On an 'intent-to-treat' analysis (n = 151), healing was: omeprazole 46.6%, ranitidine 43.3% at day 15 and omeprazole 70.7%, ranitidine 68.4% at day 29; and among the patients who completed treatment, healing was: omeprazole 48.3%, ranitidine 46.3% at day 15 (n = 125; 95% confidence interval of the difference--17 to 21) and omeprazole 79.6%, ranitidine 75.4% at day 29 (n = 115; 95% confidence interval of the difference--13 to 21). After a further four weeks treatment with omeprazole, healing occurred in 16/20 (80%) who still had active disease at day 29. Patients on omeprazole and on ranitidine experienced similar decrease in day time and night time epigastric pain and in heartburn. Multivariate analysis (logistic regression) did not indicate any influence on age, sex, smoking and alcohol habits, previous drug administered, duodenitis and duodenal erosions on the healing rate. In this model, healing rate was not significantly influenced by previous treatment duration (p = 0.09 at day 15 and p greater than 0.2 at day 29) but was significantly influenced by ulcer size (p = 0.04 at day 15 and p = 0.02 at day 29). Forty one patients complained of adverse events: 19 on omeprazole (four trial withdrawals), 22 on ranitidine (three trial withdrawals).
Double-Blinded Randomized Study of High-Dose Calcitriol Plus Docetaxel Compared With Placebo Plus Docetaxel in Androgen-Independent Prostate Cancer: A Report From the ASCENT Investigators
Authors: Tomasz M. Beer, Christopher W. Ryan, Peter M. Venner, Daniel P. Petrylak, Gurkamal S. Chatta, J. Dean Ruether, Charles H. Redfern, Louis Fehrenbacher, Mansoor N. Saleh, David M. Waterhouse, Michael A. Carducci, Daniel Vicario, Robert Dreicer, Celestia S. Higano, Frederick R. Ahmann, Kim N. Chi, W. David Henner, Alan Arroyo, Fong W. Clow
Journal: Journal of Clinical Oncology (2007)

Purpose To compare the safety and activity of DN-101, a new high-dose oral formulation of calcitriol designed for cancer therapy, and docetaxel with placebo and docetaxel. Patients and Methods Patients with progressive metastatic androgen-independent prostate cancer and adequate organ function received weekly docetaxel 36 mg/m 2 intravenously for 3 weeks of a 4-week cycle combined with either 45 μg DN-101 or placebo taken orally 1 day before docetaxel. The primary end point was prostate-specific antigen (PSA) response within 6 months of enrollment, defined as a 50% reduction confirmed at least 4 weeks later. Results Two hundred fifty patients were randomly assigned. Baseline characteristics were similar in both arms. Within 6 months, PSA responses were seen in 58% in DN-101 patients and 49% in placebo patients (P = .16). Overall, PSA response rates were 63% (DN-101) and 52% (placebo), P = .07. Patients in the DN-101 group had a hazard ratio for death of 0.67 (P = .04) in a multivariate analysis that included baseline hemoglobin and performance status. Median survival has not been reached for the DN-101 arm and is estimated to be 24.5 months using the hazard ratio, compared with 16.4 months for placebo. Grade 3/4 adverse events occurred in 58% of DN-101 patients and in 70% of placebo-treated patients (P = .07). Most common grade 3/4 toxicities for DN-101 versus placebo were neutropenia (10% v 8%), fatigue (8% v 16%), infection (8% v 13%), and hyperglycemia (6% v 12%). Conclusion This study suggests that DN-101 treatment was associated with improved survival, but this will require confirmation because survival was not a primary end point. The addition of weekly DN-101 did not increase the toxicity of weekly docetaxel.
Morphologic response of the mucosa of human small intestine to x-ray exposure.
Authors: J S Trier, T H Browning
Journal: Journal of Clinical Investigation (1966)

Prolonged and repeated exposure to sublethal doses of total body irradiation induce significant morphologic changes in the mucosa of the small intestine of laboratory animals.These changes include decreased mitosis in the intestinal crypts, necrosis of crypt epithelial cells, and decreased height of crypts and villi (2-5).In man, submucosal fibrosis (6, 7) and mucosal and submucosal lymphangiectasia (8) have been noted together with gastrointestinal malabsorption
Tumor Necrosis Factor α Is a Critical Component of Interleukin 13–Mediated Protective T Helper Cell Type 2 Responses during Helminth Infection
Authors: David Artis, Neil E. Humphreys, Allison J. Bancroft, Nancy J. Rothwell, Christopher S. Potten, Richard K. Grencis
Journal: The Journal of Experimental Medicine (1999)

In vivo manipulation of cytokine and/or cytokine receptor expression has previously shown that resistance to infection with the caecum-dwelling helminth Trichuris muris is dependent on interleukin (IL)-4 and IL-13 while susceptibility is associated with a T helper cell type 1 (Th1) cytokine response. Using gene-targeted mice deficient in tumor necrosis factor (TNF) receptor signaling and anti–TNF-α monoclonal antibody treatment, we have extended these studies to reveal a critical role for TNF-α in regulation of Th2 cytokine–mediated host protection. In vivo blockade of TNF-α in normally resistant mice, although not altering IL-4, IL-5, or IL-13 production in the draining lymph node, significantly delayed worm expulsion for the duration of treatment. IL-13–mediated worm expulsion in IL-4 knockout (KO) mice was also shown to be TNF-α dependent, and could be enhanced by administration of recombinant TNF-α. Furthermore, TNF receptor KO mice failed to expel T. muris, producing high levels of parasite-specific immunoglobulin G2a and the generation of a predominantly Th1 response, suggesting that the absence of TNF function from the onset of infection dramatically alters the phenotype of the response. These results provide the first demonstration of the role of TNF-α in regulating Th2 cytokine–mediated responses at mucosal sites, and have implications for the design of rational therapies against helminth infection and allergy.
Inosine Reduces Systemic Inflammation and Improves Survival in Septic Shock Induced by Cecal Ligation and Puncture
Authors: LUCAS LIAUDET, JON G. MABLEY, FRANCISCO GARCIA SORIANO, PÁL PACHER, ANITA MARTON, GYÖRGY HASKÓ, CSABA SZABÓ
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Inosine is a naturally occurring purine formed from the breakdown of adenosine. Here we have evaluated the effects of inosine in a murine model of polymicrobial sepsis induced by cecal ligation and puncture (CLP). Mice subjected to CLP were treated with either inosine (100 mg / kg, intraperitoneally) or vehicle 1 h before and 6 h after CLP. After 12 h tumor necrosis factor α , interleukin 6 (IL-6), and IL-10 were measured in plasma. Biochemical markers of organ damage, liver NAD+/ NADH (indicator of the mitochondrial redox state), plasma nitrate, tissue myeloperoxidase (MPO, indicator of neutrophil accumulation) and malondialdehyde (MDA, indicator of lipid peroxidation), liver and lung chemokines (macrophage inflammatory protein 1 α [MIP-1 α ] and MIP-2), and ex vivo vascular reactivity in aortic rings were also measured. Mice treated with inosine had significantly lower levels of circulating cytokines. Organ damage was significantly reduced by inosine treatment, which was associated at the tissue level with an increased hepatic NAD+/ NADH ratio, decreased MPO activity in the lung, reduced MDA formation in the gut and liver, and decreased MIP-1 α and MIP-2 in the lung and liver. Furthermore, inosine significantly improved endothelium-dependent relaxant responses of aortic rings. These effects were associated with significant improvement of the survival of CLP mice treated with inosine, an effect that was still observed when inosine treatment was delayed 1 h after CLP, especially when it was associated with appropriate antibiotic treatment. Thus, inosine reduced systemic inflammation, organ damage, tissue dysoxia, and vascular dysfunction, resulting in improved survival in septic shock.
Pten constrains centroacinar cell expansion and malignant transformation in the pancreas
Authors: Ben Z. Stanger, Bangyan Stiles, Gregory Y. Lauwers, Nabeel Bardeesy, Michael Mendoza, Ying Wang, Amy Greenwood, Kuang-hung Cheng, Margaret McLaughlin, Dennis Brown, Ronald A. DePinho, Hong Wu, Douglas A. Melton, Yuval Dor
Journal: Cancer Cell (2005)
Zone Electrophoretic Studies of Plasma Proteins in Rheumatoid Arthritis and Ankylosing Spondylitis
Authors: T. E. Hunt, J. A. Trew
Journal: Annals of the Rheumatic Diseases (1954)

This paper is a report of our investigations into the estimation of plasma proteins by zone electro- phoresis; and the relationship between the level of the plasma fibrinogen and the erythrocyte sedi- mentation rate in patients with rheumatoid disease.The effects of various forms of treatment is also described. MaterialThe material in this study consists of 172 zone electro- phoretic analyses of plasma proteins; 23 from eighteen normal subjects and 149 from 25 patients suffering from rheumatoid arthritis or ankylosing spondylitis.Sixteen replicate analyses were carried out on serum obtained from one of the normal subjects.In addition, plasma fibrinogen levels were determined, by precipitation, on 173 occasions, in the patients and in fourteen of the healthy persons.Sedimentation rates were performed concurrently in all instances.Twenty of the patients were diagnosed as having typical peripheral rheumatoid arthritis, four of these being children under the age of 12; one patient had pure ankylosing spondylitis, and four were suffering from spondylitis with peripheral joint involvement.All patients were hospitalized in the Arthritis Research and Treatment Centre, Regina General Hospital, under the auspices of the Saskatchewan Division of the Canadian Arthritis and Rheumatism Society.The ages of the normal subjects varied from 19 to 45 years, and those of patients extended from 7 to 79 years.The sex incidence of the healthy persons was evenly divided and among the patients there were thirteen men and twelve women.None of the normal group was thought to have any concurrent illness.Amongst the patients, rheumatoid disease had been present for only 6 months in two cases, but five persons had been afflicted for more than 15 years.The average duration of arthritis was 44 years.Most of the patients were in the more advanced stages of the disease.
Low-dose aspirin use and recurrent gout attacks
Authors: Yuqing Zhang, Tuhina Neogi, Clara Chen, Christine Chaisson, David J Hunter, Hyon Choi
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objective</h3> To examine the association between cardioprotective use of low-dose aspirin and the risk of recurrent gout attacks among gout patients. <h3>Methods</h3> We conducted an online case-crossover study of individuals with gout over 1 year. The following information was obtained during gout attacks: the onset dates, symptoms and signs, medications, and exposure to potential risk factors, including daily aspirin use and dosage, during the 2-day hazard period prior to the gout attacks. The same exposure information was also obtained over 2-day control periods. <h3>Results</h3> Of the 724 participants analysed, 40.5% took aspirin ≤325 mg/day during either a hazard or a control period. Compared with no aspirin use, the adjusted OR of gout attacks increased by 81% (OR=1.81, 95% CI 1.30 to 2.51) for ≤325 mg/day of aspirin use on two consecutive days. The corresponding ORs were stronger with lower doses (eg, OR=1.91 for ≤100 mg, 95% CI 1.32 to 2.85). These associations persisted across subgroups by sex, age, body mass index categories and renal insufficiency status. Concomitant use of allopurinol nullified the detrimental effect of aspirin. <h3>Conclusions</h3> Our findings suggest that the use of low-dose aspirin on two consecutive days is associated with an increased risk of recurrent gout attacks. Recommended serum urate monitoring with concomitant use and dose adjustment of a urate-lowering therapy among patients with gout may be especially important to help avoid the risk of gout attacks associated with low-dose aspirin.
Alterations in microRNA-124 and AMPA receptors contribute to social behavioral deficits in frontotemporal dementia
Authors: Eduardo Gascon, Kelleen Lynch, Hongyu Ruan, Sandra Almeida, Jamie M Verheyden, William W Seeley, Dennis W Dickson, Leonard Petrucelli, Danqiong Sun, Jian Jiao, Hongru Zhou, Mira Jakovcevski, Schahram Akbarian, Wei-Dong Yao, Fen-Biao Gao
Journal: Nature Medicine (2014)
Enteropathy precedes type 1 diabetes in the BB rat
Authors: S Graham
Journal: Gut (2004)

<b>Background and aims:</b> There is increasing evidence implicating intestinal immune responses to dietary proteins in the pathogenesis of type 1 autoimmune diabetes (T1D). Here we investigated the association between intestinal pathology and dietary factors in T1D by examining the mucosal architecture in the BB rat model. <b>Methods:</b> BB control (BBc) and diabetes prone (BBdp) rats were fed either a diabetes retardant hydrolysed casein based diet or one of two cereal based diets that promote the development of diabetes. Intestinal architecture was assessed in the jejunum by microdissection, histology, and immunohistology, and by measuring peroxidase activity and brush border invertase levels. <b>Results:</b> Enteropathy was present in BBdp rats soon after weaning, as assessed by increases in crypt length and in the proliferative activity of crypt epithelial cells in the jejunum, and this remained constant until 120 days of age. There was also a decrease in invertase activity, as well as increased numbers of intraepithelial lymphocytes, increased levels of mucosal peroxidase activity, and infiltration of the mucosa by CD4<sup>+</sup> T lymphocytes. Equivalent enteropathy was present at all times in BBdp rats and was not influenced by the nature of the diet or by thymectomy at three weeks at age, procedures which prevent the development of diabetes. <b>Conclusion:</b> Enteropathy is a consistent feature in the diabetes prone BB rat but it precedes the onset of insulitis and appears to be due to mechanisms distinct from those which cause diabetes. The beneficial effects of the diabetes retardant hydrolysed casein diet on diabetes are not due to an effect on intestinal architecture per se but mucosal damage may be necessary for the development of autoreactivity in the pancreas.
<i>Tuberous Sclerosis Complex 2</i> Loss of Heterozygosity in Patients with Lung Disease and Cancer
Authors: Li Zhang, Gustavo Pacheco-Rodriguez, Wendy K. Steagall, Jiro Kato, Mary Haughey, Joseph R. Fontana, Vincent C. Manganiello, Joel Moss
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Lymphangioleiomyomatosis (LAM) is a rare multisystem disease affecting primarily women.It is characterized by cystic lung destruction, lymphatic infiltration, and renal angiomyolipomas, Definition of abbreviation: CNS = central nervous system.*Data are collected from catalog of somatic mutations in cancer database (14).
An Apolipoprotein A-I Mimetic Works Best in the Presence of Apolipoprotein A-I
Authors: Mohamad Navab, G.M. Anantharamaiah, Alan M. Fogelman
Journal: Circulation Research (2005)

al 1 report that an apolipoprotein A-I (apoA-I) mimetic peptide, D-4F, reduced wall thickness and improved vasoreactivity in the fascialis artery (internal diameter 180 to 240 m) in low-density lipoprotein (LDL) receptor-null mice on a Western diet.If the mice also lacked apoA-I, D-4F improved vasoreactivity but it did not reduce wall thickness.The authors concluded that apoA-I or some critical threshold of high-density lipoprotein (HDL)-cholesterol was required for maximum effectiveness of D-4F. 1 In previous studies these authors reported that LDL caused endothelial nitric oxide synthase to produce more superoxide anion relative to nitric oxide and the balance between nitric oxide and superoxide anion was restored by the apoA-I mimetic peptide 4F. 2 In vivo 4F improved vasoreactivity in LDL receptor null mice fed a Western diet and in a mouse model of sickle cell disease. 3Both of these mouse models were wild-type for apoA-I. 3F is an 18-aa peptide that has no sequence homology with apoA-I but forms a class A amphipathic helix and mimics the lipid binding properties of apoA-I. 4Oral administration of 4F synthesized from all D-amino acids (D-4F) has been shown to dramatically reduce atherosclerosis in mouse models with wildtype apoA-I. 5Oral D-4F synergized with pravastatin to increase intestinal apoA-I synthesis and increase plasma apoA-I levels and caused lesion regression in old apoE-null mice. 6ral administration of D-4F to apoE-null or C57BL/6 mice caused the formation of small cholesterol-containing particles with pre-␤ mobility that were enriched in apoA-I and paraoxonase activity, rendered HDL antiinflammatory, and promoted reverse cholesterol transport from intraperitoneally injected cholesterol-loaded macrophages. 7Oral D-4F also significantly reduced lipoprotein lipid hydroperoxides (LOOH) except for pre-␤ HDL fractions in which apoA-I, paraoxonase activity, and LOOH all increased. 7ral administration of D-4F to monkeys with wild-type apoA-I decreased lipoprotein-LOOH, 8 increased paraoxonase activity, 4 caused the formation of pre-␤ HDL, 4 and rendered HDL antiinflammatory. 8Addition of D-4F to human plasma in
Drug overdose has become leading cause of death from injury in US
Authors: M. McCarthy
Journal: BMJ (2015)

More than 44 000 people in the United States died as a result of a drug overdose in 2013 (figure⇓), making it the leading cause of death from injury in the country, says a report on the effect of injuries released on 17 June.1 Overall, injuries killed more than 193 000 people in 2013 in the US and were the leading cause of death among people aged 1 to 44 years, the report said.



The report details the health effects of injuries in the US and scores individual states on the basis of their injury prevention efforts. It was prepared by the Trust for America’s Health, a non-profit health advocacy organization, with support from the Robert Wood Johnson Foundation.

The state scores were based on whether the state had implemented such measures as requiring children to ride in car seats and restricting teenagers’ driving after 10 pm or whether they had reached certain …
A METHOD FOR THE STUDY OF INDUCED INTERFERENCE WITH TRANSPLANTABLE TISSUE GROWTH
Authors: Douglas A. MacFadyen, James B. Murphy
Journal: The Journal of Experimental Medicine (1939)

1. A design of experiments and technical procedure is described for the study of interference with transplantable tissue growth by test agents. The methods are guided by the principle of randomization and are based on the pairing of test and control in each host. 2. A system of analysis, employing well known statistical measures, is applied to results obtained with these methods and shows that they lead to consistently reproducible results. 3. A simple analytical method is proposed for correlating results obtained with different kinds of transplantable tissue in different strains of animals. This method is based on the condensation of an extended frequency distribution of events in control series of cases into a three category array of a normal frequency distribution. The three categories of test action are the inhibitory, the ineffectual, and the accelerative.
Exercise program improves therapy-related side-effects and quality of life in lymphoma patients undergoing therapy
Authors: F. Streckmann, S. Kneis, J.A. Leifert, F.T. Baumann, M. Kleber, G. Ihorst, L. Herich, V. Grüssinger, A. Gollhofer, H. Bertz
Journal: Annals of Oncology (2014)
Comment re: Detection of Cervical Precancer by HPV Genotype
Authors: Arnold-Jan Kruse, Brigitte F.M. Slangen
Journal: Cancer Research (2010)

We read with interest the article by Safaeian and colleagues (1). Using data from the Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesions Triage Study (ALTS), they show that diagnosis of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) due to human papillomavirus (HPV)-18 is delayed compared with HPV16 lesions. It has been suggested that the cytologic changes detected after HPV18 infection, unlike those detected after a HPV16 infection, underestimate the severity of the underlying histologic abnormality and thus may explain their findings (2). Collins and colleagues (3) suggested that early integration of HPV18 might be an explanation for this observation.  Another possible explanation for their findings may be that some acethowhite lesions could be located out of the reach of visual evaluation (endocervix). Moreover, conventional cytology often misses lesions that are located higher up in the endocervix. Therefore, the reduced accessibility of these lesions may also be an explanation of the findings of Safaeian and colleagues (4). The design of the ALTS has a unique opportunity to give more insight into this, as histologically confirmed high-grade lesions were treated by the loop electrosurgical excision procedure (LEEP; ref. 5). Furthermore, an endocervical curettage was done at the discretion of the clinician. Information about the extension of the precancerous lesion in the LEEP specimen and the status of the endocervical curettage for the HPV16 versus the HPV18/45 CIN3+ subgroups can be very informative for the readership of the journal. We appreciate the importance of the work, but for daily practice in a colposcopy unit, it may be of clinical value to know if a HPV18/45-positive cytology report should also alert the gynecologist for lesions with a substantial risk of a location higher up in the cervical canal, next to the awareness of the mild colposcopic impression that HPV18/45-positive CIN3+ may give during colposcopy. We hope that the authors would be able to share their data on the LEEP procedure and endocervical curettage to give more insight into this.  Disclosure of Potential Conflicts of Interest  No potential conflicts of interest were disclosed.