tbuckley/cabot-search huggingface dataset:
Effect of acute stress on oesophageal motility in patients with gastro-oesophageal reflux disease.
Authors: B T Johnston, R J McFarland, J S Collins, A H Love
Journal: Gut (1996)

Sixty four per cent of people with heartburn believe that it is exacerbated by stress. An alteration in oesophageal motility is one possible mechanism for this apparent change with stress. This study aimed to assess the effect of acute stressors on oesophageal motility in patients with gastro-oesophageal reflux disease (GORD).Sixty patients were studied. Twenty had oesophagitis, 20 had increased oesophageal acid exposure on pH monitoring but no endoscopic oesophagitis, and 20 had neither oesophagitis nor abnormal oesophageal acid exposure. Oesophageal motility was studied in these patients during psychological stress (Stroop test) and physical stress (cold pressor test).Blood pressure (BP) and heart rate increased in response to both stressors (mean systolic BP increased by > 10 mm Hg, diastolic BP by > 4 mm Hg and heart rate by > 3 beats per minute (p < 0.00001). The amplitude, duration, and velocity of propagation of oesophageal peristaltic contractions were not altered by the stressors. The percentage of simultaneous waves increased in patients with oesophagitis during the cold pressor test (median increase in these patients was 6% (p < 0.05)). This effect was not noted in the patients without oesophagitis.Acute stressors did not induce significant changes in oesophageal motility in patients with GORD but no oesophagitis. For these patients, dysmotility is not likely to be a cause of oesophageal symptoms which are exacerbated by stress. There was, however, a significant increase in simultaneous waves during cold pressor stress in patients with oesophagitis.
951-74 Mechanisms of Balloon Angioplasty of In-Stent Restenosis: An Intravascular Ultrasound Study
Authors: Gary S. Mintz, Jeffrey J. Popma, Augusto D. Pichard, Kenneth M. Kent, Lowell F. Satler, S. Chiu Wong, Benjamin Kleiber, Jack A. Painter, Mary K. Kehoe, Martin B. Leon
Journal: Journal of the American College of Cardiology (1995)
Risk factors in schoolchildren associated with a family history of unheralded myocardial infarction or uncomplicated stable angina in male relatives
Authors: Filippo Crea, Achille Gaspardone, Fabrizio Tomai, Carol Shoulders, Anna De Fazio, Francesco Versaci, Maria Iamele, Carla Roncaglioni, Maria Gioffré, Attilio Maseri, Pier A. Gioffré
Journal: Journal of the American College of Cardiology (1994)
Foetal Defects Following Insulin Coma Therapy in Early Pregnancy
Authors: I. G. Wickes
Journal: BMJ (1954)

<h3>Background</h3> The relative frequency of compressive and non-compressive myelopathies and their aetiologies have not been evaluated extensively in most sub-Saharan African countries. The case of Cameroon is studied. <h3>Methods</h3> Admission registers and case records of patients in the neurology and neurosurgery departments of the study hospital were reviewed from January 1999 to December 2006. <h3>Results</h3> 224 (9.7% of all admissions) cases were non-traumatic paraplegia/paraparesis or tetraplegia/tetraparesis and 147 were due to myelopathies, representing 6.3% of all cases admitted during the study period and 65.6% of cases of paraplegia or tetraplegia; 88% were compressive myelopathies. Aetiologies were dominated by primary and secondary spinal tumours (mainly prostate carcinoma, lymphoma and liver carcinoma) that each accounted for 24.5% of cases. Other causes included spinal tuberculosis (12.9%), tropical spastic paraparesis (five positive for human T cell lymphotrophic virus (HTLV)-I and one for HTLV-II) (4.8%), spinal degenerative disease (4.1%), acute transverse myelitis (4.1%), HIV myelopathy (1.4%), vitamin B12 deficiency myelopathy and multiple sclerosis (0.7%). No aetiology was found in 21.1% of participants. <h3>Conclusions</h3> Myelopathies in our setting are dominated by spinal compressions. Metastasis is a leading cause of spinal cord compression with liver carcinoma being more frequent than reported elsewhere. Infections nevertheless remain a major cause of spinal cord disease and both cancers and infections constitute public health targets for reducing the incidence of myelopathies.
Excess granulation tissue development during treatment with cyclosporin
Authors: S.H. Wakelin, R.W. Emmerson
Journal: British Journal of Dermatology (1994)

Journal Article Excess granulation tissue development during treatment with cyclosporin Get access S.H. Wakelin, S.H. Wakelin Department of Dermatology. Royal Berkshire Hospital, Reading, Berkshire RG1 5AN, U.K. Search for other works by this author on: Oxford Academic Google Scholar R.W. Emmerson R.W. Emmerson Department of Dermatology. Royal Berkshire Hospital, Reading, Berkshire RG1 5AN, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 131, Issue 1, 1 July 1994, Pages 147–148, https://doi.org/10.1111/j.1365-2133.1994.tb08482.x Published: 01 July 1994
Plasma asymmetric dimethylarginine and hyperemic myocardial blood flow in young subjects with borderline hypertension or familial hypercholesterolemia
Authors: Hannu Päivä, Juha Laakso, Hanna Laine, Reijo Laaksonen, Juhani Knuuti, Olli T Raitakari
Journal: Journal of the American College of Cardiology (2002)
Publicity for Hazards of Monoamineoxidase Inhibitors
Authors: M. N. Cox
Journal: BMJ (1965)

vasodilatation may occur, as in the well- known tache cerebrate.Although localized bullous lesions are sometimes seen in bar- biturate coma, evidence is presented to show that these are not necessarily specific for bar- biturate intoxication, and it is suggested that such lesions may occur in states of coma unconnected with barbiturates and indeed with any drug.-Weare, etc.,
Paper OK, title wrong
Authors: N. Moore
Journal: BMJ (2011)

The paper at the centre of the recent news article used disproportionality analysis to compare reports of pancreatitis and pancreatic or thyroid cancer to the US Food and Drug Administration associated with sitagliptine or exenatide versus four other drugs used in diabetes—rosiglitazone, nateglinide, repaglinide, and glipizide.1 2 They found …
Characterization of a novel subset of CD8(+) T cells that expands in patients receiving interleukin-12.
Authors: J A Gollob, C P Schnipper, E Orsini, E Murphy, J F Daley, S B Lazo, D A Frank, D Neuberg, J Ritz
Journal: Journal of Clinical Investigation (1998)

IL-12 has significant antitumor activity in mice that may be mediated by CD8(+) T cells. We show in this report that repeated subcutaneous injections of IL-12 in patients with cancer resulted in the selective expansion of a subset of peripheral blood CD8(+) T cells. This T cell subset expressed high levels of CD18 and upregulated IL-12 receptor expression after IL-12 treatment in vivo. In normal subjects, these CD3(+)CD8(+)CD18(bright) T cells expressed IL-12 and IL-2 receptors and adhesion/costimulatory molecules to a greater degree than other CD8(+) and CD4(+) T cells. They appeared morphologically as large granular lymphocytes, although they did not express NK cell markers such as CD56. In addition, CD8(+)CD18(bright) T cells were almost exclusively T cell receptor (TCR) alphabeta+, and exhibited a TCR Vbeta repertoire that was strikingly oligoclonal, whereas the Vbeta repertoire of CD18(dim) T cells was polyclonal. Although CD8+CD18(bright) T cells demonstrated little functional responsiveness to IL-12 or IL-2 alone in vitro, they responded to the combination of IL-12+IL-2 with strong IFN-gamma production and proliferation and enhanced non-MHC-restricted cytolytic activity. In contrast, CD18(dim) T cells were not activated by IL-12 or IL-2, alone or in combination. These findings demonstrate that CD8+CD18(bright) T cells are a unique population of peripheral blood lymphocytes with features of both memory and effector cells that are capable of TCR-independent activation through combined stimulation with IL-12+IL-2. As this activation results in IFN-gamma production and enhanced cytolytic activity, these T cells may play a role in innate as well as acquired immunity to tumors and infectious pathogens. Additional studies will be necessary to determine whether CD8+CD18(bright) T cells mediate the antitumor effect of IL-12 or IL-2 administered to cancer patients, and if so, whether maximal activation of these T cells with the combination of IL-12+IL-2 in vivo can augment the clinical effectiveness of these cytokines.
Abstract LB-306: A novel RNA oligonucleotide improves liver function and inhibits liver carcinogenesis in vivo.
Authors: Vikash Reebye
Journal: Cancer Research (2013)

Abstract Hepatocellular carcinoma (HCC) occurs predominantly in patients with liver cirrhosis. Therapies to simultaneously reduce tumour burden and improve liver function are limited. Here, we show an innovative RNA-based targeted approach to enhance endogenous albumin production whilst reducing liver tumour burden. We designed short activating RNA (saRNA) oligonucleotides to enhance expression of the transcriptional regulator and activator of albumin gene expression, CCAAT/enhancer-binding protein-α (C/EBPα). Increased levels of both C/EBPα and albumin mRNA in addition to a 3-fold increase in albumin secretion and a 50% decrease in cell proliferation were observed in saRNA transfected hepatocellular carcinoma cells (HepG2). Intravenous injection of C/EPBα-saRNA in a liver cirrhotic rat model with multifocal liver tumours caused a significant increase in circulating serum albumin levels, and reduction in circulating ALT and AST levels- suggesting an amelioration of liver function. Concomitantly a significant reduction in tumour burden and pre-neoplastic transformation placental glutathione S-transferase (GST-p) staining was observed. Using mRNA expression microarray, quantitative PCR, Western blot and methylation analysis of CpG islands in C/EPBα-saRNA transfected HepG2 cells, we found up-regulation of C/EBPα and albumin; and a negative regulation of IL6R, c-Myc and STAT3 phosphorylation. We demonstrate for the first time that a novel injectable saRNA oligonucleotide successfully reduces tumour burden and simultaneously improves liver function in a clinically relevant liver cirrhosis/HCC model. Citation Format: Vikash Reebye. A novel RNA oligonucleotide improves liver function and inhibits liver carcinogenesis in vivo. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-306. doi:10.1158/1538-7445.AM2013-LB-306 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Early Postoperative Endoscopy in the Operated Stomach
Authors: B.C. Manegold
Journal: Endoscopy (1981)

Early endoscopy in the upper alimentary tract after surgical operations on the stomach reveals multifarious diagnostic and therapeutic possibilities to give decisive help to patients when applied critically and rationally. The possibilities of endoscopy can differentiate between active and arrested bleeding episodes, can induce hemostasis, can diagnose and overcome sutureline insufficiencies, can differentiate the different kinds of stenosis in the lower esophageal junction. It can treat postoperative atony, diagnose perforation at an earlier stage, localize obstructive jaundice, remove intestinal foreign bodies and characterize unexpected postoperative histological findings.
Breaking good news
Authors: L. Farrell
Journal: BMJ (2012)

“How long does granny have, doctor?”

“Only a few days,” I said. I was young and beautiful and too green to know that the wise clinician always fudges the prognosis. Within minutes the message was winging its way across the globe.⇑

A few nights later and there were relatives tucked in every corner, swinging on the rafters, hanging from the roof, dangling from the curtains. Not that granny was an angel. To paraphrase Jonathan Swift: true …
Trends in candidemia and antifungal susceptibility in a university hospital in Northern Ireland 2001–2006
Authors: L. Metwally, M.J. Walker, P.V. Coyle, R.J. Hay, S. Hedderwick, B.V. McCloskey, H.J. O'Neill, C.H. Webb, R. McMullan
Journal: Journal of Infection (2007)
Multivariable Assessment of the 6-min Walking Test in Patients with Chronic Obstructive Pulmonary Disease
Authors: HENK F. van STEL, JAN M. BOGAARD, LOUS H. M. RIJSSENBEEK-NOUWENS, VIVIAN T. COLLAND
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Functional exercise tolerance in patients with chronic obstructive pulmonary disease (COPD) is often assessed by the 6-min walking test (6MWT). To assess if the use of multiple factors adds to walking distance in describing performance in the 6MWT, an exploratory factor analysis was performed on physiological measurements and dyspnea ratings recorded during testing. Eighty-three patients with mild to severe COPD performed repeated 6MWTs before inpatient pulmonary rehabilitation. Factor analysis on 15 variables yielded a stable four-factor structure explaining 78.4% of the total variance. Recorded heart rate variables contributed to factor 1 (heart rate pattern), walking distance, heart rate increase, and decrease contributed to factor 2 (endurance capacity), oxygen desaturation variables contributed to factor 3 (impairment of oxygen transport), and dyspnea and effort variables contributed to factor 4 (perceived symptoms). Walking distance decreased in half of the 53 patients measured posttreatment, but self-perceived change in exercise tolerance improved in 84% and was explained by change in walking distance, by less desaturation, and by less dyspnea (R(2) = 0.55, p = 0.005). Qualitative analysis showed that 29 of 53 patients improved in three or four factors. Performance in the 6MWT can be described with four statistically independent and clinically interpretable factors. Because clinically relevant changes consist of more than only walking distance, assessment of functional exercise tolerance in patients with COPD improves by reporting multiple variables.
Homosexuality and Medicine: A Reply
Authors: Edward G. Dreyfus
Journal: JAMA (1970)

To the Editor.—  In an article inThe Journal, Homosexuality and Medicine ( 212 :1199, 1970), the author develops the thesis that obligatory homosexuality, as distinct from episodic homosexual behavior, is of itself a serious form of illness, curable with conversion to heterosexuality in about one third of all cases. He further claims that because it is an illness, only physicians can understand and deal with it, and that no significant contribution can be made by jurists, clergymen, or social scientists.  I agree with the author that homosexuality is common and that something may need to be done about it, but I do not believe that he has made a good case for insisting that only physicians—specifically psychiatrists—can understand and deal with it.  The author has offered a number of reasons why he feels as he does, but these are not convincing. He has, on the basis of an as yet
722 INCIDENCE AND DETERMINANTS OF SPONTANEOUS HEPATITIS B SURFACE ANTIGEN SEROCLEARANCE: A COMMUNITY-BASED LONG-TERM FOLLOW-UP STUDY
Authors: J. Liu, H.-I. Yang, M.-H. Lee, S.-N. Lu, C.-L. Jen, L.-Y. Wang, S.-L. You, U.H. Iloeje, C.-J. Chen
Journal: Journal of Hepatology (2010)
Insulinotropin: glucagon-like peptide I (7-37) co-encoded in the glucagon gene is a potent stimulator of insulin release in the perfused rat pancreas.
Authors: S Mojsov, G C Weir, J F Habener
Journal: Journal of Clinical Investigation (1987)

Insulin secretion is controlled by a complex set of factors that include not only glucose but amino acids, catecholamines, and intestinal hormones. We report that a novel glucagon-like peptide, co-encoded with glucagon in the glucagon gene is a potent insulinotropic factor. The glucagon gene encodes a proglucagon that contains in its sequence glucagon and additional glucagon-like peptides (GLPs). These GLPs are liberated from proglucagon in both the pancreas and intestines. GLP-I exists in at least two forms: 37 amino acids GLP-I(1-37), and 31 amino acids, GLP-I(7-37). We studied the effects of synthetic GLP-Is on insulin secretion in the isolated perfused rat pancreas. In the presence of 6.6 mM glucose, GLP-I(7-37) is a potent stimulator of insulin secretion at concentrations as low as 5 X 10(-11) M (3- to 10-fold increases over basal). GLP-I(1-37) had no effect on insulin secretion even at concentrations as high as 5 X 10(-7) M. The earlier demonstration of specific liberation of GLP-I(7-37) in the intestine and pancreas, and the magnitude of the insulinotropic effect at such low concentrations, suggest that GLP-I(7-37) participates in the physiological regulation of insulin secretion.
WHO pulls three more AIDS drugs from list
Authors: Fiona Fleck
Journal: BMJ (2004)

In a major blow to efforts to get lifesaving AIDS treatment to millions of people in the world's poorest countries, the World Health Organization has withdrawn three more generic drugs from its original list of seven approved AIDS medicines.

The move came after laboratory tests failed to prove these three drugs have the same chemical make up (or bioequivalence), as their patented equivalents. Two other generic AIDS drugs were removed from the list in June for the same reason.

The lack of bioequivalence means that these generic copies may not be as effective as the original patented equivalents.

WHO requires proof of bioequivalence for products that …
Medical journal editors and publication bias
Authors: A. Brice, I. Chalmers
Journal: BMJ (2013)

Wager and Williams have exposed cavalier attitudes to biased under-reporting of research among medical journal editors.1 Only 55 (28%) of 200 websites they surveyed required clinical trial registration, and some senior editors felt that trial registration would do little to reduce publication bias.

When asked what other measures might address the problem, some editors suggested having clear journal …
Endoscopic MRI: Preliminary Results of a New Technique for Visualization and Staging of Gastrointestinal Tumors
Authors: K. Inui, S. Nakazawa, J. Yoshino, K. Yamao, H. Yamachika, T. Wakabayashi, N. Kanemaki, H. Hidano
Journal: Endoscopy (1995)

The principle of endoscopic ultrasonography--introducing the transducer of an external imaging method, such as ultrasonography, in combination with an endoscope into the gastrointestinal tract for higher-resolution imaging--has also been applied to magnetic resonance imaging (MRI). We report here on our preliminary experience with a new method of endoscopic MRI in the upper gastrointestinal tract.Endoscopic MRI was performed in 32 patients with esophageal (n = 8) or gastric diseases (n = 24), mostly tumors (n = 26). Most cancers were at an advanced stage (T3/T4). A prototype MRI endoscope connected to a 1.5 tesla MRI scanner was used. The accuracy of endoscopic MRI in visualizing and staging gastrointestinal lesions was assessed.The normal gastrointestinal wall consisted of three layers, and tumors were visualized as having a low signal intensity on both T1- and T2-weighted sequences. Destruction of the wall layers was found to be characteristic of malignancy. Sufficient images were obtained in seven of eight esophageal cases (88%), but in only 14 of 24 gastric cases (58%). In patients in whom adequate visualization was achieved, the endoscopic MRI results of local and regional staging were consistent with surgical, histopathological, CT and/or EUS results in all six esophageal cancer cases and in 89% (T stage) and 56% (N stage) of the nine patients with gastric cancer.These preliminary results of endoscopic MRI are the first to be reported in the English literature. They show the potential of the method for local and regional staging, three-dimensional visualization of lesions being a potential advantage. Further technical improvements are expected.
Abstract IA11: Using Molecular Profiling Strategies in Clinical Trials to Understand Resistance Mechanisms in the Era of Personalized Cancer Medicine
Authors: Lillian L. Siu
Journal: Clinical Cancer Research (2012)

Abstract Resistance to molecularly targeted agents remains a key challenge in cancer therapeutics. Even in the setting of oncogenically addicted tumor types matched with potent and specific kinase inhibitors, the duration of drug response is limited. For example, in the phase III trial of vemurafenib versus dacarbazine in patients with advanced malignant melanoma harboring BRAF V600E mutations, 48% of patients in the vermurafenib arm achieved an objective response with a progression-free survival of 5.3 months (Chapman et al. N Engl J Med 2011). A caveat to this clearly positive clinical trial is that there are patients whose tumors have the same mutations who did not respond to vemurafenib and amongst those who did, the duration of response remains limited. In tumors that harbor driver mutations or other genetic aberrations, mechanisms of resistance are of relevance, including both primary resistance that renders them insensitive to specific inhibitors, and evolved/acquired resistance that results in tumor growth despite initial sensitivity. Comprehensive molecular profiling of pre-treatment tumor samples and at progression would be informative to offer insight into such mechanisms of primary and evolved/acquired resistance and guide clinical trial designs to counteract them. Combinatorial strategies may be considered upfront for patients who have tumor characteristics suggestive of primary resistance. For patients with sensitive disease which evolve/acquire resistance during treatment, a repeat tumor biopsy may help detect newly emerged aberrations that are potentially druggable. Additional areas of interest in defining tumor resistance include the observations that same mutation may have different degrees of functionality in different tumor types (e.g. BRAF mutations in melanoma versus colorectal cancer) and different mutations of the same gene may confer different drug sensitivities (e.g. activating and inactivating BRAF mutations), These context-dependent phenomena further complicate the planning of histology-agnostic, mutation-specific clinical trials using targeted agents. Efforts to provide detailed tumor molecular profiling information in clinical trials are relevant to help distinguish signatures of sensitivity versus resistance.
Normoxic Stabilization of Hypoxia-Inducible Factor-1α by Modulation of the Labile Iron Pool in Differentiating U937 Macrophages: Effect of Natural Resistance–Associated Macrophage Protein 1
Authors: Helen J. Knowles, David R. Mole, Peter J. Ratcliffe, Adrian L. Harris
Journal: Cancer Research (2006)

Abstract Hypoxia-inducible factor (HIF) is a transcription factor with major roles in many cellular and systemic responses to hypoxia. Activation of HIF pathways under hypoxia is mediated by suppression of the Fe2+- and O2-dependent HIF hydroxylase enzymes that normally inactivate HIFα subunits. Mechanisms underlying induction of HIF in normoxic conditions are less clearly understood. In human cancers, infiltrating macrophages show up-regulation of HIF and it has recently been shown that normoxic expression of HIF-1α is essential for macrophage function. Here, we report studies of HIF-1α induction following phorbol-12-myristate 13-acetate (PMA)–induced differentiation of monocytic U937 and THP1 cells. HIF-1α was markedly up-regulated under normoxia in this setting and this involved failure of HIF-1α prolyl hydroxylation despite the presence of O2. Fluorescence measurements showed that differentiation was associated with marked reduction of the labile iron pool. Both the reduction in labile iron pool and the up-regulation of HIF-1α were suppressed by RNA interference–mediated down-regulation of the iron transporter natural resistance–associated macrophage protein 1. Up-regulation of HIF-1α following PMA-induced differentiation was also abolished by addition of Fe2+ or ascorbate. These results indicate that physiologic changes in macrophage iron metabolism have an important effect on HIF hydroxylase pathways and suggest means by which the system could be manipulated for therapeutic benefit. (Cancer Res 2006; 66(5): 2600-7)