tbuckley/cabot-search huggingface dataset:
Chronic obstructive pulmonary disease * 11: Fitness to fly with COPD
Authors: A O C Johnson
Journal: Thorax (2003)

<h3>Objective</h3> Screening colonoscopy9s effectiveness in reducing colorectal cancer mortality risk in community populations is unclear, particularly for right-colon cancers, leading to recommendations against its use for screening in some countries. This study aimed to determine whether, among average-risk people, receipt of screening colonoscopy reduces the risk of dying from both right-colon and left-colon/rectal cancers. <h3>Design</h3> We conducted a nested case–control study with incidence-density matching in screening-eligible Kaiser Permanente members. Patients who were 55–90 years old on their colorectal cancer death date during 2006–2012 were matched on diagnosis (reference) date to controls on age, sex, health plan enrolment duration and geographical region. We excluded patients at increased colorectal cancer risk, or with prior colorectal cancer diagnosis or colectomy. The association between screening colonoscopy receipt in the 10-year period before the reference date and colorectal cancer death risk was evaluated while accounting for other screening exposures. <h3>Results</h3> We analysed 1747 patients who died from colorectal cancer and 3460 colorectal cancer-free controls. Compared with no endoscopic screening, receipt of a screening colonoscopy was associated with a 67% reduction in the risk of death from any colorectal cancer (adjusted OR (aOR)=0.33, 95% CI 0.21 to 0.52). By cancer location, screening colonoscopy was associated with a 65% reduction in risk of death for right-colon cancers (aOR=0.35, CI 0.18 to 0.65) and a 75% reduction for left-colon/rectal cancers (aOR=0.25, CI 0.12 to 0.53). <h3>Conclusions</h3> Screening colonoscopy was associated with a substantial and comparably decreased mortality risk for both right-sided and left-sided cancers within a large community-based population.
Moving the genetics of inflammatory bowel diseases from bench to bedside: first steps towards personalised medicine
Authors: Stephan Brand
Journal: Gut (2013)

In the past decade, we have witnessed enormous progress in the understanding of the genetics of inflammatory bowel diseases (IBD), resulting in the discovery and confirmation of 163 IBD susceptibility regions by the end of 20121–3 which is the highest number of susceptibility genes discovered for any complex disease so far. However, clinically highly relevant gene associations are still very limited, thereby also limiting the use of genetic information in the current treatment of IBD patients. The European IBDchip project4 represents a large detailed genotype-phenotype analysis of IBD patients and starts to fill the gap between IBD genetics and clinically relevant information.

This European multicentre study analysed more than 1500 patients with Crohn's disease (CD) for CD susceptibility variants, identified in the meta-analysis of genome-wide association studies (GWAS) by Barrett et al ,5 regarding predictors for CD outcomes such as disease localisation and disease behaviour.4 The main result of this study was the identification of NOD2 as the most important genetic predictor for ileal disease, ileal stenoses, fistula and CD-related surgery. This confirms previous reports showing particularly strong associations with ileal involvement, ileal stenosis and need for surgery in patients homozygous for the p.Leu1007fsX1008 NOD2 variant.6 ,7 An inadequate immune response to bacterial antigens in patients with mutated NOD2 gene resulting in chronic ileal inflammation seems to be the starting point for a sequel of events leading to ileal stenoses and thereby increasing the risk for fistula formation,8 finally requiring surgery.6

Janus kinase 2 ( JAK2 ) was the other gene significantly associated with ileocolonic disease involvement and stenosing disease behaviour, although the disease associations with JAK2 were weaker than that with NOD2 .4 JAK2 is a key component of the signal transduction pathway of several cytokines including interleukin (IL)-12 and IL-23 which …
Noninvasive Evaluation of a Novel Swine Model of Renal Artery Stenosis
Authors: LILACH O. LERMAN, ROBERT S. SCHWARTZ, JOSEPH P. GRANDE, PATRICK F. SHEEDY, J. CARLOS ROMERO
Journal: Journal of the American Society of Nephrology (1999)

Abstract. Intrarenal hemodynamics and excretory function distal to renal artery stenosis are difficult to quantify noninvasively. In this study, a swine model of chronic unilateral renal artery stenosis, achieved by implantation of an intravascular device that leads to a gradual and progressive luminal area narrowing, was developed and evaluated. Bilateral cortical and medullary volumes, blood flows, and segmental tubular dynamics were assessed in the intact kidneys of seven pigs using electron-beam computerized tomography before and 1 mo after implantation of the device. Within 1 mo, a 66% angiographic stenosis was significantly correlated with a 25% increase in BP. The volume and blood flow were markedly lower in the stenotic compared with the contralateral kidney and cortex, while the medulla exhibited minimal changes. In the stenotic kidney, intratubular contrast content has decreased in all nephron segments, especially in the distal tubule, where it correlated with an increase in serum creatinine and stenosis severity. In the contralateral kidney, dilution of proximal tubular fluid correlated with the increase in BP, likely due to pressure-natriuresis. In conclusion, the swine model closely resembles human renovascular hypertension. In the stenotic kidney, the hemodynamic impairment of the cortex is dissociated from the relatively preserved renal medulla, and the earliest effect on excretory function is observed in the distal nephron, where the fall in the amount of fluid reaching that segment is directly proportional to the renal arterial compromise. Electron-beam computerized tomography shows promise to noninvasively quantify, follow-up, and study changes in concurrent, in vivo intrarenal hemodynamics and segmental tubular function in renovascular hypertension.
Murine Salmonellosis Studied by Confocal Microscopy: <i>Salmonella typhimurium</i> Resides Intracellularly Inside Macrophages and Exerts a Cytotoxic Effect on Phagocytes In Vivo
Authors: Agneta Richter-Dahlfors, Alison M.J. Buchan, B. Brett Finlay
Journal: The Journal of Experimental Medicine (1997)

Salmonella typhimurium is considered a facultative intracellular pathogen, but its intracellular location in vivo has not been demonstrated conclusively. Here we describe the development of a new method to study the course of the histopathological processes associated with murine salmonellosis using confocal laser scanning microscopy of immunostained sections of mouse liver. Confocal microscopy of 30-μm-thick sections was used to detect bacteria after injection of ∼100 CFU of S. typhimurium SL1344 intravenously into BALB/c mice, allowing salmonellosis to be studied in the murine model using more realistic small infectious doses. The appearance of bacteria in the mouse liver coincided in time and location with the infiltration of neutrophils in inflammatory foci. At later stages of disease the bacteria colocalized with macrophages and resided intracellularly inside these macrophages. Bacteria were cytotoxic for phagocytic cells, and apoptotic nuclei were detected immunofluorescently, whether phagocytes harbored intracellular bacteria or not. These data argue that Salmonella resides intracellularly inside macrophages in the liver and triggers cell death of phagocytes, processes which are involved in disease. This method is also applicable to other virulence models to examine infections at a cellular and subcellular level in vivo.
From an ACE polymorphism to genome-wide searches for eQTL
Authors: Florent Soubrier
Journal: Journal of Clinical Investigation (2013)

Angiotensin I–converting enzyme (ACE, or DCP1) is a zinc metallopeptidase that converts angiotensin I into the vasoactive and aldosterone-stimulating peptide angiotensin II and cleaves bradykinin into inactive peptides. Plasma ACE measurement is widely used for the diagnosis of sarcoidosis. While enzyme concentrations are highly stable in an individual, there is a high level of interindividual variability. In 1990, we identified an insertion/deletion polymorphism in ACE that functions as a quantitative trait locus (QTL), accounting for half of the interindividual variability. Since then, technological advances have allowed for the elucidation of expression QTLs (eQTL). Such studies are allowing researchers to determine how underlying genetic predisposition contributes to human disease.
Atypical Antipsychotic Agents, Retinopathy, Nephropathy, and Cardiovascular Disease
Authors: Zachary T. Bloomgarden
Journal: Diabetes Care (2006)

This is the seventh and final in a series of articles on presentations at the American Diabetes Association Annual Meeting, San Diego, California, 10–14 June 2005.

### Diabetes and atypical antipsychotic agents

John Newcomer (St. Louis, MO) discussed changes in adiposity and insulin sensitivity with the atypical antipsychotic agents ziprasidone, risperidone, aripiprazole, quetiapine, clozapine, and olanzapine, addressing the diabetes risk seen during treatment. Among persons with schizophrenia, approximately half are obese, half to three-quarters smoke, 10–14% have diabetes, particularly with coexisting depression, and there are also increased prevalences of hypertension and dyslipidemia. Metabolic syndrome, Newcomer stated, is present in ∼40% of persons with schizophrenia. Persons with schizophrenia have increased rates of cardiovascular disease (CVD). The mortality due to myocardial infarction is 19% greater among persons with any mental illness and is 34% greater among persons with schizophrenia (1) than in a control population. CVD, then, is of similar importance to suicide as a cause of death in these patients, whose overall mortality is increased by half, leading to a 20% shorter lifespan than in persons without schizophrenia (2).

A major issue is weight gain with the atypical antipsychotic agents. Although weight gain occurs with conventional antipsychotic agents such as haloperidol, greater weight gain definitely occurs with chlorpromazine, olanzapine, and clozapine and may occur with risperidone and quetiapine. A meta-analysis of weight change during randomized, controlled, 10-week trials showed that olanzapine and clozapine were associated with a 4-kg weight gain, while haloperidol and risperidone were associated with a 2-kg weight gain (3). Quetiapine leads to ∼4-fold and olanzapine ∼10-fold weight gain, while other antipsychotic agents give 2-fold greater rates of weight gain than those seen in nontreated schizophrenic persons. In 1-year studies, ziprasidone, risperidone, quetiapine, and olanzapine are associated with weight gains of ∼1, 2, 4, and 6 kg. The degree of weight gain appears to …
OFD1, the Gene Mutated in Oral-Facial-Digital Syndrome Type 1, Is Expressed in the Metanephros and in Human Embryonic Renal Mesenchymal Cells
Authors: Leila Romio, Victoria Wright, Karen Price, Paul J.D. Winyard, Dian Donnai, Mary E. Porteous, Brunella Franco, Giovanna Giorgio, Sue Malcolm, Adrian S. Woolf, Sally A. Feather
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Oral-facial-digital syndrome type 1 (OFD1) causes polycystic kidney disease (PKD) and malformations of the mouth, face and digits. Recently, a gene on Xp22, OFD1, was reported to be mutated in a limited set of OFD1 patients. This study describes mutation analysis in six further OFD1 families. Additionally, gene expression was sought in human development. In two OFD1 kindreds affected by PKD, a frameshift mutation and a splice-site mutation were detected. In four apparently sporadic cases, three frameshift and a missense mutation were found. Using RT-PCR of RNA from first-trimester normal human embryos, both alternative splice forms of mRNA (OFD1a and OFD1b) were found to be widely expressed in organogenesis. Northern blot detected OFD1 mRNA in metanephros, brain, tongue, and limb, all organs affected in the syndrome. A polyclonal antibody directed to a C-terminal OFD1a epitope detected a 120-kD protein in the metanephros and in human renal mesenchymal cell lines. In normal human embryos, OFD1a immunolocalized to the metanephric mesenchyme, oral mucosa, nasal and cranial cartilage, and brain. Moreover, using normal human renal mesenchymal cell lines, the immunoreactive protein colocalized with γ-tubulin, suggesting that OFD1 is associated with the centrosome. First, it is concluded that OFD1 mutations would generally be predicted to result in unstable transcripts or nonfunctional proteins. Second, OFD1 is expressed in human organogenesis; on the basis of the metanephric expression pattern, the results suggest that OFD1 plays a role in differentiation of metanephric precursor cells. E-mail: [email protected]
Hyperbilirubinemia in Breast-Fed Infants
Authors: A J NEWMAN, S GROSS
Journal: JAMA (1963)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Regulation of solute and water balance and cell volume in the central nervous system.
Authors: K Strange
Journal: Journal of the American Society of Nephrology (1992)

The mammalian brain is composed of four distinct fluid compartments: blood, cerebral spinal fluid, interstitial fluid surrounding glial cells and neurons, and intracellular fluid. Maintenance of the ionic and osmotic composition and volume of these fluids is crucial for the normal functioning of the brain. Small changes in intracellular or extracellular solute composition can dramatically alter neuronal signaling and information processing. Because of the rigid confines of the skull and complex brain architecture, changes in total brain volume can cause devastating neurological damage. As a result, it is not surprising to find that the composition and volume of brain intracellular and extracellular fluids are controlled tightly under both normal conditions and in various disease states. Osmotic and ionic balance in the central nervous system is regulated by solute and water transport across the blood-brain barrier, the choroid plexus, and the plasma membrane of glial cells and neurons. Despite its clinical and physiological significance, however, little is known about the underlying cellular and molecular mechanisms by which the central nervous system's osmotic and ionic balance is maintained. In this review, the current understanding of osmoregulation in the mammalian brain and its role in various disease processes such as hyponatremia, renal failure, and hypernatremia will be summarized. A detailed understanding of brain osmoregulatory processes represents a fundamental physiological problem and is required for the treatment of numerous disease states, particularly those encountered in the practice of nephrology.
Granulomatous Bronchiolitis Associated with Crohn's Disease
Authors: OLIVIER VANDENPLAS, SIMONE CASEL, MONIQUE DELOS, JEAN-PAUL TRIGAUX, MICHEL MELANGE, ERIC MARCHAND
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Symptomatic bronchopulmonary disorders have been only occasionally reported in Crohn's disease, although several studies have documented the possibility of latent involvement of the respiratory tract. We report the case of a patient with long-standing Crohn's disease who presented with acute transient chest pain and a recent history of mild dyspnea and nonproductive cough. Chest radiographs were normal, while high-resolution computed tomography demonstrated a mosaic pattern of attenuation that was consistent with a bronchiolar disorder. Pulmonary function tests showed mild airway obstruction and normal diffusion indices. Thoracoscopic lung biopsy demonstrated focal infiltration of the bronchiolar walls by mononuclear cells and non-necrotizing granulomas. To our knowledge, this is the first account of isolated granulomatous bronchiolitis in Crohn's disease. These findings suggest that a granulomatous inflammatory process of the bronchioles could be involved in the development of airway obstruction in patients with Crohn's disease.
High-Dose Atorvastatin Reduces Total Plasma Levels of Oxidized Phospholipids and Immune Complexes Present on Apolipoprotein B-100 in Patients With Acute Coronary Syndromes in the MIRACL Trial
Authors: Sotirios Tsimikas, Joseph L. Witztum, Elizabeth R. Miller, William J. Sasiela, Michael Szarek, Anders G. Olsson, Gregory G. Schwartz
Journal: Circulation (2004)

Background— Oxidized phospholipids (OxPL) are present within atherosclerotic plaques and bound by lipoprotein (a) [Lp(a)] in plasma. This study evaluated the impact of atorvastatin on oxidized LDL (OxLDL) in patients with acute coronary syndromes (ACS). Methods and Results— OxLDL-E06 (OxPL content on apolipoprotein B-100 [apoB] detected by antibody E06), apoB-100 immune complexes (apoB-IC), OxLDL autoantibodies, and Lp(a) levels were measured in 2341 patients at baseline and after 16 weeks of treatment with atorvastatin 80 mg/d or placebo. The OxLDL-E06 and apoB-IC data are reported per apoB-100 particle (OxPL/apoB, IC/apoB) and as total levels on all apoB-100 particles (total apoB-OxPL and total apoB-IC [eg, OxPL/apoB or IC/apoB×apoB-100 levels]). Compared with baseline values, atorvastatin reduced apoB-100 (−33%), total apoB-OxPL (−29.7%), total apoB-IC IgG (−29.5%), and IgM (−25.7%) ( P &lt;0.0001 for all), whereas no change or an increase was observed with placebo. When normalized per apoB-100, compared with placebo, atorvastatin increased OxPL/apoB (9.5% versus −3.9%, P &lt;0.0001) and Lp(a) (8.8% versus −0.7%, ( P &lt;0.0001). A strong correlation was noted between OxPL/apoB and Lp(a) ( R =0.85, P &lt;0.0001), consistent with previous data that Lp(a) binds OxPL. Conclusions— After atorvastatin treatment, total OxPL on all apoB-100 particles was decreased. However, there was enrichment of OxPL on a smaller pool of apoB-100 particles, in parallel with similar increases in Lp(a), suggesting binding by Lp(a). These data support the hypothesis that atorvastatin promotes mobilization and clearance of proinflammatory OxPL, which may contribute to a reduction in ischemic events after ACS.
Biliary secretion of S-nitrosoglutathione is involved in the hypercholeresis induced by ursodeoxycholic acid in the normal rat
Authors: Carlos M. Rodríguez‐Ortigosa, Jesús M. Banales, Israel Olivas, Iker Uriarte, José J.G. Marín, Fernando J. Corrales, Juan F. Medina, Jesús Prieto
Journal: Hepatology (2010)

Ursodeoxycholic acid (UDCA) induces bicarbonate-rich hypercholeresis by incompletely defined mechanisms that involve the stimulation of adenosine triphosphate (ATP) release from cholangiocytes. As nitric oxide (NO) at a low concentration can stimulate a variety of secretory processes, we investigated whether this mediator could be implicated in the choleretic response to UDCA. Our in vivo experiments with the in situ perfused rat liver model in anesthetized rats, showed that UDCA infusion increased the biliary secretion of NO derivatives, hepatic inducible NO synthase expression, and NO synthase activity in liver tissue. UDCA also stimulated NO release by isolated rat hepatocytes. In contrast to UDCA, cholic acid was a poor inducer of NO secretion, and tauroursodeoxycholic acid showed no effect on NO secretion. Upon UDCA administration, NO was found in bile as low-molecular-weight nitrosothiols, of which S-nitrosoglutathione (GSNO) was the predominant species. UDCA-stimulated biliary NO secretion was abolished by the inhibition of inducible NO synthase with Nω-nitro-L-arginine methyl ester in isolated perfused livers and also in rats whose livers were depleted of glutathione with buthionine sulfoximine. Moreover, the biliary secretion of NO species was significantly diminished in UDCA-infused transport mutant [ATP–binding cassette C2 (ABCC2)/multidrug resistance–associated protein 2 (Mrp2)–deficient] rats, and this finding was consistent with the involvement of the glutathione carrier ABCC2/Mrp2 in the canalicular transport of GSNO. It was particularly noteworthy that in cultured normal rat cholangiocytes, GSNO activated protein kinase B, protected against apoptosis, and enhanced UDCA-induced ATP release to the medium; this effect was blocked by phosphoinositide 3-kinase inhibition. Finally, retrograde GSNO infusion into the common bile duct increased bile flow and biliary bicarbonate secretion. Conclusion: UDCA induces biliary secretion of GSNO, which contributes to stimulating ductal secretion. (HEPATOLOGY 2010;)
Reducing Disability in Older Age
Authors: James F. Fries
Journal: JAMA (2002)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal