tbuckley/cabot-search huggingface dataset:
CD4 Counts as Predictors of Opportunistic Pneumonias in Human Immunodeficiency Virus (HIV) Infection
Authors: Henry Masur
Journal: Annals of Internal Medicine (1989)

Study Objective: To determine if circulating CD4+ lymphocyte counts are predictive of specific infectious or neoplastic processes causing pulmonary dysfunction. Design: Retrospective, consecutive sample study. Setting: Referral-based clinic and wards. Patients: We studied 100 patients infected with human immunodeficiency virus (HIV) who had had 119 episodes of pulmonary dysfunction within 60 days after CD4 lymphocyte determinations. Measurements and Main Results: Circulating CD4 counts were less than 0.200 X 109 cells/L (200 cells/mm3) before 46 of 49 episodes of Pneumocystis pneumonia, 8 of 8 episodes of cytomegalovirus pneumonia, and 7 of 7 episodes and 19 of 21 episodes of infection with Cryptococcus neoformans and Mycobacterium avium-intracellulare, respectively. In contrast, circulating CD4 counts before episodes of non-specific interstitial pneumonia were quite variable: Of 41 episodes, 11 occurred when CD4 counts were greater than 0.200 X 109 cells/L. The percent of circulating lymphocytes that were CD4+ had a predictive value equal to that of CD4 counts. Serum p24 antigen levels had no predictive value. Conclusions: Pneumocystis pneumonia, cytomegalovirus pneumonia, and pulmonary infection caused by C. neoformans or M. avium-intracellulare are unlikely to occur in HIV-infected patients who have had a CD4 count above 0.200 to 0.250 X 109 cells/L (200 to 250 cells/mm3) or a CD4 percent above 20% to 25% in the 60 days before pulmonary evaluation. Patients infected with HIV who have a CD4 count below 0.200 X 109 cells/L (or less than 20% CD4 cells) are especially likely to benefit from antipneumocystis prophylaxis.
A receptor for type I antiarrhythmic drugs associated with rat cardiac sodium channels.
Authors: R S Sheldon, N J Cannon, H J Duff
Journal: Circulation Research (1987)

We assessed the effects of type I antiarrhythmic drugs on the binding of ligands to receptors on voltage-sensitive sodium channels of rat cardiac myocytes. The radioligand was [3H]batrachotoxinin A 20 alpha-benzoate ([3H]BTXB), a toxin that binds to the sodium channel. The 8 drugs tested inhibited [3H]BTXB binding in a dose-dependent fashion with IC50 values from 1.34 microM for O-demethylencainide to 811 microM for procainamide. A log-log plot of IC50 versus mean therapeutic serum concentration yielded a regression line with slope of 1.17 and r of 0.95. Scatchard analysis of [3H]BTXB binding showed that lidocaine reduced the maximal binding without altering the KD for [3H]BTXB binding, indicating allosteric inhibition. The inhibition by lidocaine of [3H]BTXB binding was reversible within 30 minutes when the samples were diluted from 390 to 39 microM lidocaine. In other studies, the stereoisomers of tocainide were shown to have a threefold to fourfold difference in IC50 for inhibition of [3H]BTXB binding. The binding of antiarrhythmic drugs to this site is saturable, reversible, and stereospecific and occurs at pharmacologically relevant concentrations with similar rank order of potency in vivo and in vitro. This suggests that binding at this site relates to pharmacologic activity.
Cost-Effectiveness of Surgically Induced Weight Loss for the Management of Type 2 Diabetes: Modeled Lifetime Analysis
Authors: Catherine L. Keating, John B. Dixon, Marjory L. Moodie, Anna Peeters, Liliana Bulfone, Dianna J. Maglianno, Paul E. O'Brien
Journal: Diabetes Care (2009)

OBJECTIVE To estimate the cost-effectiveness of surgically induced weight loss relative to conventional therapy for the management of recently diagnosed type 2 diabetes in class I/II obese patients. RESEARCH DESIGN AND METHODS This study builds on a within-trial cost-efficacy analysis. The analysis compares the lifetime costs and quality-adjusted life-years (QALYs) between the two intervention groups. Intervention costs were extrapolated based on observed resource utilization during the trial. The proportion of patients in each intervention group with remission of diabetes at 2 years was the same as that observed in the trial. Health care costs for patients with type 2 diabetes and outcome variables required to derive estimates of QALYs were sourced from published literature. A health care system perspective was adopted. Costs and outcomes were discounted annually at 3%. Costs are presented in 2006 Australian dollars (AUD) (currency exchange: 1 AUD = 0.74 USD). RESULTS The mean number of years in diabetes remission over a lifetime was 11.4 for surgical therapy patients and 2.1 for conventional therapy patients. Over the remainder of their lifetime, surgical and conventional therapy patients lived 15.7 and 14.5 discounted QALYs, respectively. The mean discounted lifetime costs were 98,900 AUD per surgical therapy patient and 101,400 AUD per conventional therapy patient. Relative to conventional therapy, surgically induced weight loss was associated with a mean health care saving of 2,400 AUD and 1.2 additional QALYs per patient. CONCLUSIONS Surgically induced weight loss is a dominant intervention (it both saves health care costs and generates health benefits) for managing recently diagnosed type 2 diabetes in class I/II obese patients in Australia.
Noninvasive Magnetic Resonance Spectroscopic Imaging Biomarkers to Predict the Clinical Grade of Pediatric Brain Tumors
Authors: Loukas G. Astrakas, David Zurakowski, A. Aria Tzika, Maria K. Zarifi, Douglas C. Anthony, Umberto De Girolami, Nancy J. Tarbell, Peter McLaren Black
Journal: Clinical Cancer Research (2004)

Abstract The diagnosis and therapy of childhood brain tumors, most of which are low grade, can be complicated because of their frequent adjacent location to crucial structures, which limits diagnostic biopsy. Also, although new prognostic biomarkers identified by molecular analysis or DNA microarray gene profiling are promising, they too depend on invasive biopsy. Here, we test the hypothesis that combining information from biologically important intracellular molecules (biomarkers), noninvasively obtained by proton magnetic resonance spectroscopic imaging, will increase the diagnostic accuracy in determining the clinical grade of pediatric brain tumors. We evaluate the proton magnetic resonance spectroscopic imaging exams for 66 children with brain tumors. The intracellular biomarkers for choline-containing compounds (Cho), N-acetylaspartate, total creatine, and lipids and/or lactate were measured at the highest Cho region and normalized to the surrounding healthy tissue total creatine. Neuropathological grading was done with WHO criteria. Normalized Cho and lipids and/or lactate were elevated in high-grade (n = 23) versus low-grade (n = 43) tumors, which multiple logistic regression confirmed are independent predictors of tumor grade (for Cho, odds ratio 24.8, P &amp;lt; 0.001; and for lipids and/or lactate, odds ratio 4.4, P &amp;lt; 0.001). A linear combination of normalized Cho and lipids and/or lactate that maximizes diagnostic accuracy was calculated by maximizing the area under the receiver operating characteristic curve. Proton magnetic resonance spectroscopic imaging, although not a proxy for histology, provides noninvasive, in vivo biomarkers for predicting clinical grades of pediatric brain tumors.
Adhesions of pacing catheter to tricuspid valve: adhesive endocarditis
Authors: H. D. Friedberg, G. F. D'Cunha
Journal: Thorax (1969)

A case is reported in which the presence of endocardial pacemaker catheter electrodes provoked an unusual reaction—an adhesive endocarditis. Two pacemaker catheters were in the right ventricle during the last nine months of life. The normal reaction to these foreign bodies of fibrin deposition and endothelialization was intensified so that the first catheter could not be removed after 17 days. Because one catheter was introduced from the left side of the neck, it lay in a commissure of the tricuspid valve to which it was firmly adherent. This constitutes a potential hazard if the removal of the catheter is forcibly attempted, although it does not interfere with the function of the tricuspid valve. Despite this, thrombosis was absent and generally is not a problem with modern materials.
Wegener's granulomatosis simulated by a T cell lymphoma of the lung
Authors: J H Small, A. Round, R H W Simpson, A D Ferguson
Journal: Thorax (1991)

A case of primary T cell lymphoma of the lung associated with antineutrophil cytoplasmic antibody simulated Wegener9s granulomatosis, the patient having features compatible with but not diagnostic of Wegener9s granulomatosis.
Prevalence of C-terminal gag cleavage site mutations in HIV from therapy-naïve patients
Authors: Jens Verheyen, Elena Knops, Bernd Kupfer, Osamah Hamouda, Sybille Somogyi, Ulrike Schuldenzucker, Daniel Hoffmann, Rolf Kaiser, Herbert Pfister, Claudia Kücherer
Journal: Journal of Infection (2008)
The genetics of Richter syndrome reveals disease heterogeneity and predicts survival after transformation
Authors: Davide Rossi, Valeria Spina, Clara Deambrogi, Silvia Rasi, Luca Laurenti, Kostas Stamatopoulos, Luca Arcaini, Marco Lucioni, Gabrielle B. Rocque, Zijun Y. Xu-Monette, Carlo Visco, Julie Chang, Ekaterina Chigrinova, Francesco Forconi, Roberto Marasca, Caroline Besson, Theodora Papadaki, Marco Paulli, Luigi M. Larocca, Stefano A. Pileri, Valter Gattei, Francesco Bertoni, Robin Foà, Ken H. Young, Gianluca Gaidano
Journal: Blood (2011)
Deep Brain Stimulation for Intractable Psychiatric Disorders
Authors: Wayne K. Goodman, Ron L. Alterman
Journal: Annual Review of Medicine (2010)

Deep brain stimulation (DBS) has virtually replaced ablative neurosurgery for use in medication-refractory movement disorders. DBS is now being studied in severe psychiatric conditions, such as treatment-resistant depression (TRD) and intractable obsessive-compulsive disorder (OCD). Effects of DBS have been reported in ∼100 cases of OCD and ∼50 cases of TRD for seven (five common) anatomic targets. Although these published reports differ with respect to study design and methodology, the overall response rate appears to exceed 50% in OCD for some DBS targets. In TRD, &gt;50% of patients responded during acute and long-term bilateral electrical stimulation in a different target. DBS was generally well tolerated in both OCD and TRD, but some unique, target- and stimulation-specific adverse effects were observed (e.g., hypomania). Further research is needed to test the efficacy and safety of DBS in psychiatric disorders, compare targets, and identify predictors of response.
Prolonged fluid shear stress induces a distinct set of endothelial cell genes, most specifically lung Krüppel-like factor (KLF2)
Authors: Rob J. Dekker, Simone van Soest, Ruud D. Fontijn, Sonia Salamanca, Philip G. de Groot, Ed VanBavel, Hans Pannekoek, Anton J. G. Horrevoets
Journal: Blood (2002)
Butyrate inhibits inflammatory responses through NFkappa B inhibition: implications for Crohn's disease
Authors: J-P Segain
Journal: Gut (2000)

Proinflammatory cytokines are key factors in the pathogenesis of Crohn's disease (CD). Activation of nuclear factor kappa B (NFkappaB), which is involved in their gene transcription, is increased in the intestinal mucosa of CD patients. As butyrate enemas may be beneficial in treating colonic inflammation, we investigated if butyrate promotes this effect by acting on proinflammatory cytokine expression.Intestinal biopsy specimens, isolated lamina propria cells (LPMC), and peripheral blood mononuclear cells (PBMC) were cultured with or without butyrate for assessment of secretion of tumour necrosis factor (TNF) and mRNA levels. NFkappaB p65 activation was determined by immunofluorescence and gene reporter experiments. Levels of NFkappaB inhibitory protein (IkappaBalpha) were analysed by western blotting. The in vivo efficacy of butyrate was assessed in rats with trinitrobenzene sulphonic acid (TNBS) induced colitis.Butyrate decreased TNF production and proinflammatory cytokine mRNA expression by intestinal biopsies and LPMC from CD patients. Butyrate abolished lipopolysaccharide (LPS) induced expression of cytokines by PBMC and transmigration of NFkappaB from the cytoplasm to the nucleus. LPS induced NFkappaB transcriptional activity was decreased by butyrate while IkappaBalpha levels were stable. Butyrate treatment also improved TNBS induced colitis.Butyrate decreases proinflammatory cytokine expression via inhibition of NFkappaB activation and IkappaBalpha degradation. These anti-inflammatory properties provide a rationale for assessing butyrate in the treatment of CD.
Serial computed tomographic evaluation in desquamative interstitial pneumonia
Authors: M. Akira, S. Yamamoto, H. Hara, M. Sakatani, E. Ueda
Journal: Thorax (1997)

Desquamative interstitial pneumonia (DIP) may represent the early stage and usual interstitial pneumonia (UIP) the late stage of the same disease. The purpose of this study was to evaluate the computed tomographic (CT) features of DIP, to evaluate the changes in pattern and extent of disease over time, and to determine whether the appearances of DIP on the CT scan change to those of UIP during follow up.Sequential CT evaluation was conducted on eight patients with DIP over a mean (SD) follow up period of 3.2 (1.3) years (range 1.6-6.5). The relative extents of ground glass and honeycombing were determined from serial CT scans. Changes in the extent and appearance of the disease were examined in paired anatomically comparable CT sections.Common features on the CT scans of patients with DIP were a homogeneous increase in lung attenuation (n = 5), linear areas of attenuation (n = 5), relatively well preserved lung architecture (n = 5), and the presence of small cysts (n = 6). Uncommon features were architectural distortion (n = 3), and traction bronchiectasis (n = 1). In six patients with DIP with cystic spaces these did not change with time in three cases, in two they regreased, and in one patient they increased. Open lung biopsy samples from patients with DIP with many cystic lesions showed dilated alveolar ducts and bronchioles and/or pulmonary cysts, as well as numerous macrophage-filled air spaces and mild fibrosis, but no typical honeycomb cysts were seen.Some of the microcysts in DIP are different from the honeycomb cysts seen in UIP, and some of the cysts seen in patients with DIP resolve with time. DIP does not progress to UIP in the short term.
Changes in diastolic cardiac function in developing and stable perinephritic hypertension in conscious dogs.
Authors: R J Gelpi, A Pasipoularides, A S Lader, T A Patrick, N Chase, L Hittinger, R P Shannon, S P Bishop, S F Vatner
Journal: Circulation Research (1991)

The effects of developing perinephritic hypertension (2-3 weeks) and a more stable period of perinephritic hypertension (approximately 14 weeks) were examined on indexes of left ventricular (LV) diastolic function in conscious, chronically instrumented dogs. The complete period of diastole was studied using indexes of isovolumic relaxation (tau), early filling (LV +dD/dt), and stiffness (myocardial stiffness and chamber stress/diameter ratio). During developing hypertension, increased LV end-diastolic pressure, LV end-diastolic stress, peak filling rate, myocardial stiffness, and the stress/diameter ratio increased (p less than 0.05); the time constant tau was not changed. These changes were associated with preserved baseline levels of coronary blood flow (radioactive microspheres) but an impaired coronary vasodilator response to adenosine. Acute administration of phenylephrine in the normotensive dogs caused increases in systolic and diastolic stress and resulted in increases in myocardial stiffness and in the stress/diameter ratio similar to values observed in developing hypertension. During stable hypertension, LV end-diastolic stress, peak filling rate, and both parameters of late-diastolic function (myocardial stiffness and stress/diameter ratio) returned toward control values, but the isovolumic relaxation time constant was increased. Quantitative histological evaluation revealed no increase in stainable connective tissue in dogs with stable hypertension compared with control dogs, and hydroxyproline concentration was not increased in the subendomyocardium, midmyocardium, or subepimyocardium of the dogs with chronic perinephritic hypertension. Thus, in developing hypertension, major alterations in diastolic function were observed that were not structurally related, since these changes 1) could be induced in normal dogs by increasing preload and afterload acutely with phenylephrine and 2) were improved during the ensuing stable period of hypertension.
Comorbidity of Anxiety Disorders With Anorexia and Bulimia Nervosa
Authors: Walter H. Kaye, Cynthia M. Bulik, Laura Thornton, Nicole Barbarich, Kim Masters
Journal: American Journal of Psychiatry (2004)

A large and well-characterized sample of individuals with anorexia nervosa and bulimia nervosa from the Price Foundation collaborative genetics study was used to determine the frequency of anxiety disorders and to understand how anxiety disorders are related to state of eating disorder illness and age at onset.Ninety-seven individuals with anorexia nervosa, 282 with bulimia nervosa, and 293 with anorexia nervosa and bulimia were given the Structured Clinical Interview for DSM-IV Axis I Disorders and standardized measures of anxiety, perfectionism, and obsessionality. Their ratings on these measures were compared with those of a nonclinical group of women in the community.The rates of most anxiety disorders were similar in all three subtypes of eating disorders. About two-thirds of the individuals with eating disorders had one or more lifetime anxiety disorder; the most common were obsessive-compulsive disorder (OCD) (N=277 [41%]) and social phobia (N=134 [20%]). A majority of the participants reported the onset of OCD, social phobia, specific phobia, and generalized anxiety disorder in childhood, before they developed an eating disorder. People with a history of an eating disorder who were not currently ill and never had a lifetime anxiety disorder diagnosis still tended to be anxious, perfectionistic, and harm avoidant. The presence of either an anxiety disorder or an eating disorder tended to exacerbate these symptoms.The prevalence of anxiety disorders in general and OCD in particular was much higher in people with anorexia nervosa and bulimia nervosa than in a nonclinical group of women in the community. Anxiety disorders commonly had their onset in childhood before the onset of an eating disorder, supporting the possibility they are a vulnerability factor for developing anorexia nervosa or bulimia nervosa.
Low density lipoprotein enhances the cellular action of arginine vasopressin in rat glomerular mesangial cells in culture.
Authors: S Ishikawa, M Kawasumi, K Okada, T Saito
Journal: Journal of Clinical Investigation (1994)

The present study was undertaken to determine whether low density lipoprotein (LDL) modulates the cellular action of arginine vasopressin (AVP) in rat glomerular mesangial cells in culture. AVP increased cellular free calcium ([Ca2+]i) in a dose-dependent manner. When cells were preincubated for 24 h with 10 microgram/ml LDL, the 1 x 10(-7) M AVP-mobilized [Ca2+]i was 874 nM, a value significantly greater than that of 375 nM in the intact cells. AVP caused a biphasic change in cellular pH (pHi), namely, an early acidification followed by a sustained alkalinization, and the change in pHi produced by AVP was also enhanced by LDL. AVP stimulated a 2.2-fold increase in [3H]thymidine incorporation, an effect significantly greater in the presence of 10 micrograms/ml LDL. Furthermore, 1 x 10(-7) M AVP significantly activated mitogen-activated protein kinase from 14.0 to 24.5 pmol/mg protein. Such an activation was significantly enhanced by the LDL pretreatment. Both [3H]thymide incorporation and mitogen-activated protein kinase were not altered by 10 micrograms/ml LDL. [3H]AVP receptor binding was not affected by the LDL pretreatment. 1 x 10(-7) M AVP increased inositol trisphosphate production by 1.9-fold, an effect significantly greater in the presence of LDL. These results indicate that LDL enhances the cellular action of AVP and the AVP-stimulated cellular proliferation in glomerular mesangial cells. A site of action of LDL is the hydrolysis of phosphatidylinositol.
The Intrarenal Vascular Lesions Associated with Primary Antiphospholipid Syndrome
Authors: DOMINIQUE NOCHY, ERIC DAUGAS, DOMINIQUE DROZ, HELENE BEAUFILS, JEAN-PIERRE GRÜNFELD, JEAN-CHARLES PIETTE, JEAN BARIETY, GARY HILL
Journal: Journal of the American Society of Nephrology (1999)

Abstract. Even 10 yr after the identification of the antiphospholipid syndrome (APS), renal involvement in the course of APS is still relatively unrecognized, and is probably underestimated. The association of anticardiolipin antibodies and/or lupus anticoagulant with the development of a vaso-occlusive process involving numerous organs is now confirmed. In a multicenter study, 16 cases of “primary” APS (PAPS) were found and followed for 5 yr or more, all with renal biopsy. In all 16 cases of PAPS, there was a vascular nephropathy characterized by small vessel vaso-occlusive lesions associated with fibrous intimal hyperplasia of interlobular arteries (12 patients), recanalizing thrombi in arteries and arterioles (six patients), and focal cortical atrophy (10 patients). In combination, these led to progressive destruction of the kidney, accelerated by acute glomerular and arteriolar microangiopathy in five patients. Focal cortical atrophy is a distinctive lesion, present in 10 biopsies, and likely represents the histologic and functional renal analogue to the multiple cerebral infarcts detected on imaging studies. The clinical hallmark of this vascular nephropathy in PAPS is systemic hypertension, only variably associated with renal insufficiency, proteinuria, or hematuria. The ensemble of histologic renal lesions defined in this study should aid in the separation of the lesions found in cases of secondary APS, especially systemic lupus erythematosus, into those lesions related to APS and those related to the underlying disease.
<i>TFAP2E–DKK4</i>and Chemoresistance in Colorectal Cancer
Authors: Matthias P.A. Ebert, Marc Tänzer, Benjamin Balluff, Elke Burgermeister, Antje Karen Kretzschmar, David J. Hughes, Reimo Tetzner, Catherine Lofton-Day, Robert Rosenberg, Anke C. Reinacher-Schick, Karsten Schulmann, Andrea Tannapfel, Ralf Hofheinz, Christoph Röcken, Gisela Keller, Rupert Langer, Katja Specht, Rainer Porschen, Jan Stöhlmacher-Williams, Tibor Schuster, Philipp Ströbel, Roland M. Schmid
Journal: New England Journal of Medicine (2012)

Chemotherapy for advanced colorectal cancer leads to improved survival; however, predictors of response to systemic treatment are not available. Genomic and epigenetic alterations of the gene encoding transcription factor AP-2 epsilon (TFAP2E) are common in human cancers. The gene encoding dickkopf homolog 4 protein (DKK4) is a potential downstream target of TFAP2E and has been implicated in chemotherapy resistance. We aimed to further evaluate the role of TFAP2E and DKK4 as predictors of the response of colorectal cancer to chemotherapy.