tbuckley/cabot-search huggingface dataset:
Mouse-Human Experimental Epigenetic Analysis Unmasks Dietary Targets and Genetic Liability for Diabetic Phenotypes
Authors: Michael L. Multhaup, Marcus M. Seldin, Andrew E. Jaffe, Xia Lei, Henriette Kirchner, Prosenjit Mondal, Yuanyuan Li, Varenka Rodriguez, Alexander Drong, Mehboob Hussain, Cecilia Lindgren, Mark McCarthy, Erik Näslund, Juleen R. Zierath, G. William Wong, Andrew P. Feinberg
Journal: Cell Metabolism (2015)
LEFT VENTRICULAR DIASTOLIC DYSFUNCTION IS AN INDEPENDENT PREDICTOR OF LONG-TERM MORTALITY IN PATIENTS WHO UNDERWENT LIVER TRANSPLANT FOR END STAGE LIVER DISEASE
Authors: Nandan Thirunahari, Adam Raskin, Ifad Ur Rahman, Rudzinski Wojciech, Christine Gerula, Baburao Koneru, Nikolaos Pyrsopoulos, Marc Klapholz
Journal: Journal of the American College of Cardiology (2014)
Diagnosis of Clostridium difficile Colitis
Authors: Anil Minocha
Journal: Annals of Internal Medicine (1996)

Letters15 September 1996Diagnosis of Clostridium difficile ColitisAnil Minocha, MD and Robert J. Richards, MDAnil Minocha, MDUniversity of Oklahoma Health Sciences Center, Oklahoma City, OK 73126Search for more papers by this author and Robert J. Richards, MDUniversity of Oklahoma Health Sciences Center, Oklahoma City, OK 73126Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-125-6-199609150-00020 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Manabe and colleagues [1] have provided valuable guidelines for diagnosing C. difficile colitis in hospitalized patients. The study group was defined as patients who had C. difficile toxin as shown by enzyme-linked immunoassay or cytotoxin tissue culture assay. Although this definition of C. difficile colitis is adequate for clinical purposes, we should remember that the presence of C. difficile toxin is not always associated with C. difficile colitis. On the basis of a positive cytotoxin tissue culture assay, C. difficile was present in 34 of 268 patients (12.7%) in Manabe and colleagues' study. This prevalence is similar ...References1. Manabe YC, Vinetz JM, Moore RD, Merz C, Charache P, Bartlett JG. Clostridium difficile colitis: an efficient clinical approach to diagnosis. Ann Intern Med. 1995; 123:835-40. Google Scholar2. Bartlett JG. Pseudomembranous enterocolitis and antibiotic-associated colitis. In: Sleisenger MH, Fordtran JS, eds. Gastrointestinal Disease: Pathophysiology, Diagnosis, Management. Philadelphia: WB Saunders; 1993:1174-89. Google Scholar Author, Article, and Disclosure InformationAffiliations: University of Oklahoma Health Sciences Center, Oklahoma City, OK 73126 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 September 1996Volume 125, Issue 6Page: 515KeywordsAntibioticsAntimicrobialsC difficile colitisCytotoxinsDiarrheaEnzyme linked immunosorbent assayTissue culturesToxins Issue Published: 15 September 1996 CopyrightCopyright © 1996 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
A Randomized, Placebo-Controlled Dose-Comparison Trial of Haloperidol for Psychosis and Disruptive Behaviors in Alzheimer’s Disease
Authors: D.P. Devanand, Karen Marder, Kristin S. Michaels, Harold A. Sackeim, Karen Bell, Maria A. Sullivan, Thomas B. Cooper, Gregory H. Pelton, Richard Mayeux
Journal: American Journal of Psychiatry (1998)

Objective:The goal of this study was to compare the efficacy and side effects of two doses of haloperidol and placebo in the treatment of psychosis and disruptive behaviors in patients with Alzheimer’s disease.Method:In a 6-week random-assignment, double-blind, placebo-controlled trial (phase A), haloperidol, 2–3 mg/day (standard dose), and haloperidol, 0.50–0.75 mg/day (low dose), were compared in 71 outpatients with Alzheimer’s disease. For the subsequent 6-week double-blind crossover phase (phase B), patients taking standard- or low-dose haloperidol were switched to placebo, and patients taking placebo were randomly assigned to standard- or low-dose haloperidol.Results:For the 60 patients who completed phase A, standard-dose haloperidol was efficacious and superior to both low-dose haloperidol and placebo for scores on the Brief Psychiatric Rating Scale psychosis factor and on psychomotor agitation. Response rates according to three sets of criteria were greater with the standard dose (55%–60%) than the low dose (25%–35%) and placebo (25%–30%). The advantage of standard dose over low dose was replicated in phase B. In phase A, extrapyramidal signs tended to be greater with the standard dose than in the other two conditions, primarily because of a subgroup (20%) who developed moderate to severe signs. Low-dose haloperidol did not differ from placebo on any measure of efficacy or side effects. Conclusions:The results indicated a favorable therapeutic profile for haloperidol in doses of 2–3 mg/day, although a subgroup developed moderate to severe extrapyramidal signs. A starting dose of 1 mg/day with gradual, upward dose titration is recommended. The narrow therapeutic window observed with haloperidol may also apply to other neuroleptics used in Alzheimer’s disease patients with psychosis and disruptive behaviors. Am J Psychiatry 1998; 155: 1512-1520
Second Wanless report welcomed by public health experts
Authors: Colleen Shannon
Journal: BMJ (2004)

Public health leaders believe that a report from a former banker has created a “once in a lifetime” opportunity to put the prevention of disease at the top of the agenda for the NHS and across government.

Derek Wanless, a former chief executive of the NatWest bank, was asked by the government to review the state of public health in England and to make recommendations for improving it. Significantly, he took his brief not from the Department of Health but from the Treasury.

Last week Mr Wanless called for an end to “30 years of talking” and the introduction of a coherent policy framework for public health. Mr Wanless also wants tough targets on smoking and obesity, for local government as well as the NHS. The government is to publish a white paper on public health this summer.

Securing Good Health for the Whole Population is …
The Familial Mediterranean Fever Gene — Cloned at Last
Authors: B M Babior, Y Matzner
Journal: New England Journal of Medicine (1997)

Familial Mediterranean fever is an inherited condition prevalent among people of the Near East — Arabs, Turks, Armenians, and Sephardic Jews.1 Transmitted as an autosomal recessive trait, familial Mediterranean fever is characterized by sporadic episodes of acute inflammation of the pleural, peritoneal, and joint spaces and, occasionally, the pericardial space and the tunica vaginalis of the testis. These episodes usually last only a few days, but chronic arthritis develops in a few patients. There may be a painful, localized erysipelas-like rash that fades in a few days. Peritonitis due to familial Mediterranean fever resembles an acute abdomen, but laparotomy shows . . .
Complete complementary DNA-derived amino acid sequence of canine cardiac phospholamban.
Authors: J Fujii, A Ueno, K Kitano, S Tanaka, M Kadoma, M Tada
Journal: Journal of Clinical Investigation (1987)

Complementary DNA (cDNA) clones specific for phospholamban of sarcoplasmic reticulum membranes have been isolated from a canine cardiac cDNA library. The amino acid sequence deduced from the cDNA sequence indicates that phospholamban consists of 52 amino acid residues and lacks an amino-terminal signal sequence. The protein has an inferred mol wt 6,080 that is in agreement with its apparent monomeric mol wt 6,000, estimated previously by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Phospholamban contains two distinct domains, a hydrophilic region at the amino terminus (domain I) and a hydrophobic region at the carboxy terminus (domain II). We propose that domain I is localized at the cytoplasmic surface and offers phosphorylatable sites whereas domain II is anchored into the sarcoplasmic reticulum membrane.
Alendronate coated poly-lactic-co-glycolic acid (PLGA) nanoparticles for active targeting of metastatic breast cancer
Authors: Sanjay I. Thamake, Sangram L. Raut, Zygmunt Gryczynski, Amalendu P. Ranjan, Jamboor K. Vishwanatha
Journal: Biomaterials (2012)
Drug resistance in the mouse cancer clinic
Authors: Sven Rottenberg, Piet Borst
Journal: Drug Resistance Updates (2012)

Drug resistance is one of the most pressing problems in treating cancer patients today. Local and regional disease can usually be adequately treated, but patients eventually die from distant metastases that have become resistant to all available chemotherapy. Although work on cultured tumor cell lines has yielded a lot of information on potential drug resistance mechanisms, it has proven difficult to translate these results to clinical drug resistance in patients. The controversy regarding the contribution of ABC transporters to drug resistance in patients is one example. The study of genetically engineered mouse models (GEMMs), which closely resemble cancer in human patients, can help to bridge this gap. In models for BRCA1- or BRCA2-associated breast cancer, we observed a substantial synergy between the defect in homology-directed DNA repair and sensitivity to DNA-targeting drugs. Nevertheless, tumors are not easily eradicated and eventually drug resistance develops. In this review we will discuss the use of the new generation mouse models to address major clinical problems, such as mechanisms of drug resistance, predicting chemotherapy response or characterizing the nature of residual tumor cells that escape eradication. Moreover, we will address the contribution of ABC transporters to drug resistance in our model.
Something's New in PKU
Authors: W. Eugene Knox
Journal: New England Journal of Medicine (1978)

Elsewhere in this issue of the Journal is an instructive illustration of Murphy's Law applied to medicine: if anything can go wrong, it will. On the basis of biochemical principles, three possible defects would allow phenylalanine to escape metabolism and accumulate to injure the immature developing brain in that paradigm of avoidable mental deficiency, classic phenylketonuria. The potential defects are the familiar one of the hydroxylating enzyme protein itself, a defect of a second enzyme that regenerates the biopterin cofactor needed in the hydroxylation and a simple deficiency of biopterin itself. Jervis1 showed that the phenylalanine hydroxylating enzyme system . . .
The Thyroid and Its Diseases
Authors: Sheldon S. Stoffer
Journal: JAMA (1996)

The first edition of this text was a solo effort by J. H. Means published in 1937. The work was largely based on the clinical experience of the thyroid clinic of the Massachusetts General Hospital. This now classic first edition was beautifully written and steeped in clinical insights. The authors of the current sixth edition carry on the tradition of excellence extending back almost 60 years, presenting all of clinical thyroidology in a readable and cohesive manner. Each of the three authors is an outstanding authority in the field with an average of 35 years in the practice of thyroidology. More than a decade has passed since the last edition. Of course, substantial advances in clinical thyroidology have occurred in the interim. The sixth edition has been extensively rewritten and is really a new textbook. <i>The Thyroid and Its Diseases</i>has perhaps lost some of the historic flavor of previous
Unicef warns of polio risk in conflict regions
Authors: J. Wise
Journal: BMJ (1999)

Civil conflicts, such as those in Kosovo and Angola, are threatening the eradication of polio-myelitis, according to the children's charity Unicef.

The organisation's annual report, published last week, reported that the number of confirmed cases of polio worldwide last year was 5108, compared with 35251 10 years ago. However, Carol Bellamy, Unicef's executive director, …
LABOKATOEY AIDS IN CLINICAL DIAGNOSIS.
Authors: C. E. RUTH
Journal: JAMA (1904)

A diagnosis may be anatomic, clinical or etiologic. By anatomic diagnosis is meant a description of the tissue changes that have taken place in the body as a result of disease, based on a study of the dead body. By clinical diagnosis is meant an opinion as to the nature, cause, probable course and termination of a pathologic process, based on a study of the living body. By etiologic diagnosis is meant the identification of the specific cause of a given pathologic process in an individual case. To illustrate: By means of the physical signs and a study of symptoms, the physician establishes the clinical diagnosis of lobar pneumonia. The exudate from the lungs is examined and the pneumococeus and staphylococcus are found, which establishes the etiologic diagnosis. The patient dies, and at necropsy a study of the gross and microscopic changes in the lungs is made, which comprises the
Effects of High-Dose Oral Insulin on Immune Responses in Children at High Risk for Type 1 Diabetes
Authors: Ezio Bonifacio, Anette-G. Ziegler, Georgeanna Klingensmith, Edith Schober, Polly J. Bingley, Marietta Rottenkolber, Anke Theil, Anne Eugster, Ramona Puff, Claudia Peplow, Florian Buettner, Karin Lange, Jörg Hasford, Peter Achenbach
Journal: JAMA (2015)

Exposing the oral mucosa to antigen may stimulate immune tolerance. It is unknown whether treatment with oral insulin can induce a tolerogenic immune response in children genetically susceptible to type 1 diabetes.To assess the immune responses and adverse events associated with orally administered insulin in autoantibody-negative, genetically at-risk children.The Pre-POINT study, a double-blind, placebo-controlled, dose-escalation, phase 1/2 clinical pilot study performed between 2009 and 2013 in Germany, Austria, the United States, and the United Kingdom and enrolling 25 islet autoantibody-negative children aged 2 to 7 years with a family history of type 1 diabetes and susceptible human leukocyte antigen class II genotypes. Follow-up was completed in August 2013.Children were randomized to receive oral insulin (n = 15) or placebo (n = 10) once daily for 3 to 18 months. Nine children received insulin with dose escalations from 2.5 to 7.5 mg (n = 3), 2.5 to 22.5 mg (n = 3), or 7.5 to 67.5 mg (n = 3) after 6 months; 6 children only received doses of 22.5 mg (n = 3) or 67.5 mg (n = 3).An immune response to insulin, measured as serum IgG and saliva IgA binding to insulin, and CD4+ T-cell proliferative responses to insulin.Increases in IgG binding to insulin, saliva IgA binding to insulin, or CD4+ T-cell proliferative responses to insulin were observed in 2 of 10 (20% [95% CI, 0.1%-45%]) placebo-treated children and in 1 of 6 (16.7% [95% CI, 0.1%-46%]) children treated with 2.5 mg of insulin, 1 of 6 (16.7%[ 95% CI, 0.1%-46%]) treated with 7.5 mg, 2 of 6 (33.3% [95% CI, 0.1%-71%]) treated with 22.5 mg, and 5 of 6 (83.3% [ 95% CI, 53%-99.9%]) treated with 67.5 mg (P = .02). Insulin-responsive T cells displayed regulatory T-cell features after oral insulin treatment. No hypoglycemia, IgE responses to insulin, autoantibodies to glutamic acid decarboxylase or insulinoma-associated antigen 2, or diabetes were observed. Adverse events were reported in 12 insulin-treated children (67 events) and 10 placebo-treated children (35 events).In this pilot study of children at high risk for type 1 diabetes, daily oral administration of 67.5 mg of insulin, compared with placebo, resulted in an immune response without hypoglycemia. These findings support the need for a phase 3 trial to determine whether oral insulin can prevent islet autoimmunity and diabetes in such children.isrctn.org Identifier: ISRCTN76104595.
Milkman's Syndrome
Authors: Irving B. Brick, Rollin F. Bunch
Journal: New England Journal of Medicine (1947)

FROM time to time in routine radiologic bone studies lesions are encountered whose etiology is difficult to determine. Such a case is reported below because of its interest from a radiologic and medical point of view. Milkman1 , 2 presented a case of multiple spontaneous idiopathic symmetrical fractures in which forty-three fractures were noted and for which no etiology was established. Since Milkman's report 19 additional cases have been reported in the literature, with a review by Edeikin and Schneeberg.3 Of these cases, 16 were reported from Europe. All except 1 occurred in women.The main clinical characteristics of Milkman's syndrome are . . .
Deaths of children under 5 fall by 27% worldwide but maternal mortality remains same as in 1990
Authors: J. Zarocostas
Journal: BMJ (2009)

The number of children dying under the age of 5 worldwide fell 27% between 1990 and 2007, as a result, at least in part, of more interventions and strengthening of health systems, a World Health Organization report says.

The report puts progress down to several developments, including increased immunisation coverage, use of rehydration treatment, malaria interventions, and improved water and sanitation. But it says that progress has been “uneven.”

Many countries in sub-Saharan Africa, weighed down by civil strife, poverty, and high disease burdens, it says, are lagging behind in progress towards meeting the fourth millennium development goal, which specified that mortality in children under 5 should be reduced by two thirds between 1990 and 2015.

“There needs …
Binding of the Fap2 Protein of Fusobacterium nucleatum to Human Inhibitory Receptor TIGIT Protects Tumors from Immune Cell Attack
Authors: Chamutal Gur, Yara Ibrahim, Batya Isaacson, Rachel Yamin, Jawad Abed, Moriya Gamliel, Jonatan Enk, Yotam Bar-On, Noah Stanietsky-Kaynan, Shunit Coppenhagen-Glazer, Noam Shussman, Gideon Almogy, Angelica Cuapio, Erhard Hofer, Dror Mevorach, Adi Tabib, Rona Ortenberg, Gal Markel, Karmela Miklić, Stipan Jonjic, Caitlin A. Brennan, Wendy S. Garrett, Gilad Bachrach, Ofer Mandelboim
Journal: Immunity (2015)
DIDS-sensitive pHi regulation in single rat cardiac myocytes in nominally HCO3-free conditions.
Authors: M L Wu, M L Tsai, Y Z Tseng
Journal: Circulation Research (1994)

The fluorescent dye 2',7'-bis(carboxyethyl)-5,6-carboxyfluorescein (BCECF) was used to measure pHi in the spontaneously hypertensive rat (SHR) and in normal rat cardiac myocytes under nominally HCO3-free (20 mmol/L HEPES-buffered) conditions. When only the Na-H exchanger was blocked, the intrinsic buffering power (beta i) in SHR myocytes was significantly higher than when both the Na-H exchanger and 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS)-sensitive pHi regulators (the Na-HCO3 cotransporter and the Cl-HCO3 exchanger) were blocked. Similar low values for beta i were also found for normal rat myocytes in Na(+)-free conditions. In Cl(-)-free solution under nominally HCO3-free conditions, in both normal and SHR myocytes, the pHi slowly alkalinized (by 0.16 +/- 0.02 and 0.11 +/- 0.02 pH units, respectively); this alkalinization was also DIDS sensitive. The reacidification during NH4+ perfusion was inhibited 30.2 +/- 7.4% by DIDS. In addition, in the nominal absence of HCO3-, 100 mumol/L ATP acidified the pHi in both normal and SHR myocytes (by 0.21 +/- 0.03 and 0.33 +/- 0.03 pH units, respectively); this acidification was totally inhibited by 0.1 mmol/L DIDS. It has been shown, in rat cardiac myocytes, that ATP acidifies the pHi by 0.35 pH unit via stimulation of a DIDS-sensitive Cl-HCO3 exchanger in HCO3-containing solutions. Finally, we have shown, in normal cardiac myocytes, that two potent Na-H exchanger blockers, N-5-ethylisopropyl amiloride (EIPA) and N-5-methyl-N-isobutyl amiloride (MIA), only partially inhibited the pHi recovery from internal acidosis under nominally bicarbonate-free conditions. When DIDS was added at the same time as EIPA, pHi recovery from an internal acid loading was completely inhibited. Our results clearly demonstrate that in both normal and SHR cardiac myocytes, bicarbonate-dependent pHi regulators can be significantly activated under resting or acidified pHi in HEPES-buffered medium, probably because of the cellular production of CO2. The contribution of these bicarbonate-dependent pHi regulators, ie, the Na-HCO3 cotransporter and the Cl-HCO3 exchanger, cannot therefore be ignored even under nominally HCO3-free conditions.
A New Endoscopic Balloon for Sclerotherapy in Active Bleeding from Esophageal Varices
Authors: G. Sciaretta, A. Verri, P. Malaguti
Journal: Endoscopy (1985)

A new balloon for flexible endoscopes has been developed and used in 25 patients with esophageal varices: sclerotherapy was carried out as prophylaxis against rebleeding in 17 cases, and during active hemorrhage in 8 cases. The balloon was shown to be effective in controlling hemorrhage and enabling sclerosing injections to be carried out, both in emergency and in cases of bleeding response to injections.
Treatment of Orbital Metastases From a Primary Midgut Neuroendocrine Tumor With Peptide-Receptor Radiolabeled Therapy Using <sup>177</sup>Lutetium-DOTATATE
Authors: Rebecca Dobson, Sobhan Vinjamuri, James Hsuan, Melissa Banks, Monica Terlizzo, Hulya Wieshmann, Christina Daousi, Graeme P. Poston, Daniel J. Cuthbertson
Journal: Journal of Clinical Oncology (2013)
Steroid injections are helpful in rotator cuff tendinopathy
Authors: S. J Mellor, V. R Patel
Journal: BMJ (2002)

EDITOR—Speed discussed corticosteroid injections in tendon lesions.1 We agree that there is a lack of good randomised trials in this field, but we disagree with his conclusion that in rotator cuff tendinopathy, range of movement but not pain is improved by steroid injection.

Speed comments that …
The Common Cold: The Effect of Hot Humid Air on the Nasal Mucosa
Authors: Fred Rosner
Journal: JAMA (1994)

To the Editor.  —It is surprising that both articles 1,2 and the accompanying Editorial 3 on the use of heated humidified air for early treatment of the common cold fail to mention the efficacy of hot chicken soup in relieving the symptoms of this malady. 4 Chicken soup mobilizes nasal mucus better than other hot liquids 5 and inhibits the growth of pneumococci in vitro. 6 These findings give scientific respectability to what mothers have always known—chicken soup can alleviate the symptoms of an upper respiratory tract infection.
Neurologic Manifestations of von Hippel-Lindau Disease
Authors: John A. Butman
Journal: JAMA (2008)

von Hippel-Lindau disease (VHL) is an autosomal-dominant neoplasia syndrome that is the result of a germline mutation of the VHL tumor suppressor gene on the short arm of chromosome 3. Patients with VHL are predisposed to develop lesions of the central nervous system and viscera. Central nervous system lesions include hemangioblastomas (the most common tumor in VHL) and endolymphatic sac tumors (ELSTs). Visceral manifestations include renal carcinomas and cysts, pancreatic neuroendocrine tumors and cysts, pheochromocytomas, and cystadenomas of the reproductive adnexal organs. Despite their benign pathology, hemangioblastomas and ELSTs are a frequent cause of morbidity and mortality in patients with VHL. Recent molecular biologic investigations into these VHL-associated central nervous system lesions provide new insight into their origin and development. Emerging data from serial imaging and clinical surveillance protocols provide insight into the natural history of these lesions. Because of the dissimilar pathobiology and clinical course between hemangioblastomas and ELSTs, the optimal management strategies for these neurologic manifestations of VHL are very different.