tbuckley/cabot-search huggingface dataset:
Immune Reactivity to a Glb1 Homologue in a Highly Wheat-Sensitive Patient With Type 1 Diabetes and Celiac Disease
Authors: Majid Mojibian, Habiba Chakir, Amanda J. MacFarlane, David E. Lefebvre, John R. Webb, Claire Touchie, Jacob Karsh, Jennifer A. Crookshank, Fraser W. Scott
Journal: Diabetes Care (2006)

In type 1 diabetes, the environmental factors that induce the patient’s immune system to attack and destroy the insulin-secreting β-cells are not known. There is evidence that some cases of type 1 diabetes could be wheat related (1,2). Exposure to wheat protein was a risk factor for development of type 1 diabetes autoantibodies in high-risk infants (1,2), and as many as 2–8% of type 1 diabetic patients have celiac disease (3), also known as gluten-sensitive enteropathy. Some studies in animals also suggest that wheat could be involved (4–7). Recently, a wheat protein, WP5212, with 80% amino acid homology to wheat storage globulin-1 (Glb1), was identified as the first candidate diabetes-related wheat protein in diabetes-prone rats (5). We report the case of a highly wheat-sensitive patient with type 1 diabetes/celiac disease who displayed strong antibody and T-cell responses to this protein.

A 28-year-old Caucasian female, with a 10-year history of type 1 diabetes, presented early in 1999 with diarrhea followed by oral ulcerations and severe lip swelling (Fig. 1 A ). At diagnosis, anti-gliadin IgG, anti-tissue transglutaminase IgA, and endomysial antibodies were present. The diarrhea and lip swelling improved initially with a gluten-free diet, but the symptoms recurred within a few months with worsening of the oral ulcerations, lip swelling, and continued diarrhea. Despite 6 months of a standard gluten-free diet, a duodenal biopsy showed mild villous atrophy. Colonoscopy and small bowel follow-through were normal. Biopsy of the oral lesion showed noncaseating granulomas, which were negative for IgG, IgA, IgM, C3, fibrinogen, and albumin with no histological evidence of eosinophilia. The patient was evaluated by a clinical allergist. Skin prick tests for several foods, including wheat, were all negative, and there was no evidence of IgE-mediated food allergy. In December 2001, the mucosa of her lower lip …
Association of Transmission Intensity and Age With Clinical Manifestations and Case Fatality of Severe &lt;EMPH TYPE="ITAL"&gt;Plasmodium falciparum&lt;/EMPH&gt; Malaria
Authors: Hugh Reyburn
Journal: JAMA (2005)

There are concerns that malaria control measures such as use of insecticide-treated bed nets, by delaying acquisition of immunity, might result in an increase in the more severe manifestations of malaria. An understanding of the relationships among the level of exposure to Plasmodium falciparum, age, and severity of malaria can provide evidence of whether this is likely.To describe the clinical manifestations and case fatality of severe P falciparum malaria at varying altitudes resulting in varying levels of transmission.A total of 1984 patients admitted for severe malaria to 10 hospitals serving populations living at levels of transmission varying from very low (altitude >1200 m) to very high (altitude <600 m) in a defined area of northeastern Tanzania, studied prospectively from February 2002 to February 2003. Data were analyzed in a logistic regression model and adjusted for potential clustering within hospitals.Specific syndromes of severe malaria; mortality.The median age of patients was 1 year in high transmission, 3 years in moderate transmission, and 5 years in low transmission areas. The odds of severe malarial anemia (hemoglobin <5 g/dL) peaked at 1 year of age at high transmission and at 2 years at moderate and low transmission intensities and then decreased with increasing age (P = .002). Odds were highest in infants (0-1 year: referent; 2-4 years: odds ratio [OR], 0.83; 95% confidence interval [CI], 0.72-0.96), 5 to <15 years: OR, 0.44; 95% CI, 0.27-0.72; > or =15 years: OR, 0.44; 95% CI, 0.27-0.73; P<.001) and high transmission intensity areas (altitude <600 m: referent; 600 m to 1200 m: OR, 0.55; 95% CI, 0.35-0.84; >1200 m: OR, 0.55; 95% CI, 0.26-1.15; P for trend = .03). The odds of cerebral malaria were significantly higher in low transmission intensity areas (altitude of residence <600 m: referent; 600 m to 1200 m: OR, 3.17; 95% CI, 1.32-7.60; >1200 m: OR, 3.76; 95% CI, 1.96-7.18; P for trend = .003) and with age 5 years and older (0-1 year: referent; 2-4 years: OR, 1.57; 95% CI, 0.82-2.99; 5 to <15 years: OR, 6.07; 95% CI, 2.98-12.38; > or =15 years: OR, 6.24; 95% CI, 3.47-11.21; P<.001). The overall case-fatality rate of 7% (139 deaths) was similar at high and moderate levels of transmission but increased to 13% in low transmission areas (P = .03), an increase explained by the increase in the proportion of cases with cerebral malaria.Age and level of exposure independently influence the clinical presentation of severe malaria. Our study suggests that an increase in the proportion of cases with more fatal manifestations of severe malaria is likely to occur only after transmission has been reduced to low levels where the overall incidence is likely to be low.
Variability Among US Intensive Care Units in Managing the Care of Patients Admitted With Preexisting Limits on Life-Sustaining Therapies
Authors: Joanna L. Hart, Michael O. Harhay, Nicole B. Gabler, Sarah J. Ratcliffe, Caroline M. Quill, Scott D. Halpern
Journal: JAMA Internal Medicine (2015)

<h3>Importance</h3> Although the end-of-life care patients receive is known to vary across nations, regions, and centers, these differences are best explored within a group of patients with presumably similar care preferences. <h3>Objective</h3> To examine the proportions of patients admitted to the intensive care unit (ICU) with limitations on life-sustaining treatments and the proportions of such patients who receive aggressive care across individual ICUs. <h3>Design, Settings, and Participants</h3> Retrospective cohort study using the Project IMPACT database (from April 1, 2001, to December 31, 2008) including 141 ICUs in 105 hospitals in the United States and 277 693 ICU patient visits. We used logistic regression analysis models adjusted for available patient characteristics and clustered visits by individual ICU. The full analysis was last performed in October 2014. <h3>Main Outcomes and Measures</h3> Outcomes included the provision of (1) cardiopulmonary resuscitation, (2) new forms of life support, and the (3) addition or (4) reversal of treatment limitations. <h3>Results</h3> Of the ICU admissions evaluated, 4.8% (95% CI, 4.7%-4.9%) had previously established treatment limitations. Patients admitted with treatment limitations were more likely to be older with more functional limitations and comorbidities. Among patients who survived to hospital discharge, more experienced reversals of existing treatment limitations during the ICU stay (17.8% [95% CI, 17.0%-18.7%]) than additions of new limits (11.7% [95% CI, 11.1%-12.4%]) (<i>P</i> &lt; .01). Among patients who died, 15.7% (95% CI, 14.7-16.8%) had received cardiopulmonary resuscitation. After risk adjustment, ICUs varied widely in the proportions of patients admitted with treatment limitations (median, 4.0%; range, &lt;1.0%-20.9%), the proportions of those who received cardiopulmonary resuscitation (37.7% [95% CI, 3.8%-92.4%]), the proportions of new forms of life support (30.0% [95% CI, 6.0%-84.2%]), and, among survivors, the proportion who had new treatment limitations established (11.2% [95% CI, 1.9%-57.3%]) and reversal of treatment limitations during or following ICU admission (20.2% [95% CI, 1.8%-76.2%]). The observed variability could not be consistently explained using measurable center-level characteristics. <h3>Conclusions and Relevance</h3> Intensive care units vary dramatically in how they manage care for patients admitted with treatment limitations. Among patients who survive, escalations in the aggressiveness of care are more common during the ICU stay than are de-escalations in aggressiveness. This study cannot directly measure whether care received was consistent with patients' preferences but suggests that ICU culture and physicians' practice styles contribute to the aggressiveness of care.
Sorafenib-Induced Bilateral Osteonecrosis of Femoral Heads
Authors: Marielle Guillet, Thomas Walter, Jean-Yves Scoazec, Thierry Vial, Catherine Lombard-Bohas, Jérôme Dumortier
Journal: Journal of Clinical Oncology (2009)

A 53-year-old man diagnosed with hepatocellular carcinoma(HCC) occurring in post–hepatitic C cirrhosis was ﬁrst treated withright hepatectomy in May 2004. Because of cytologically proven re-currence as mediastinal and vertebral metastases, he was treated withchemotherapycombininggemcitabineandoxaliplatinefromDecem-ber 2004 to January 2005. The bone lesions extended and becamepainful, so the patient received analgesic lombar radiotherapy in Sep-tember 2005 and cimentoplasty in September 2007. In addition, sor-afenib (Nexavar; Bayer Pharmaceuticals Group, Montville, NJ) at adosage of 800 mg per day was started in February 2008. Initial serumlevel of alpha fetoprotein (AFP) was 180 ng/mL. Ten months afterstarting the treatment, the patient suffered from hip pain when walk-ing. Physical examination was normal except for pain on active andpassive leg mobilization. Blood tests were unremarkable, except forhepaticcytolysisrelatedtoongoinghepatitisC.TheserumlevelofAFPwas 600 ng/mL. Magnetic resonance imaging of the femoral headsshowedbilateralosteonecrosis(Fig1);asubchondrallineofdemarca-tion bounded a low signal intensity on T1- and T2-weighted images,corresponding to the necrotic area. There were bone marrow edemaand subchondral ﬁssures. The patient did not receive (at that time orpreviously)corticosteroidorbiphosphonatetreatment.Sorafenibwasstopped and we declared this adverse event to the pharmacovigilancecenter of Lyon, France, in February 2009 (number LY20090440).SorafenibisanoralmultikinaseinhibitorthatinhibitsRafserine/threonine kinases and tyrosine kinase receptors involved in tumorgrowth and angiogenesis. It has demonstrated preclinical and clin-ical activity in several tumor types, including advanced HCC.
A randomized trial of polytetrafluoroethylene-membrane-covered stents compared with conventional stents in aortocoronary saphenous vein grafts
Authors: Volker Schächinger, Christian W Hamm, Thomas Münzel, Michael Haude, Stephan Baldus, Eberhard Grube, Tassilo Bonzel, Thomas Konorza, Ralf Köster, Roman Arnold, Jürgen Haase, Peter Probst, Jürgen vom Dahl, Franz-Josef Neumann, Harald Mudra, Benno Hennen, Ludger Thiele, Andreas M Zeiher
Journal: Journal of the American College of Cardiology (2003)
Tobacco cessation clinics in Europe: Data from eSCCAN project
Authors: Agnès Delrieu, Joseph Osman, Bertrand Dautzenberg
Journal: European Respiratory Journal (2012)

The eSCCAN project aims to federate smoking cessation clinics in Europe to share and improve practices.  Method: Identification of eSCCAN experts in 26 of the 27 European countries has allowed to organize meetings and internet communication to reach a consensus among the smoking cessation clinics in Europe and to specify their number.  Results: The current estimate is that there is about 2500 tobacco cessation clinics in Europe. A minority of them are centers of councelling to stop smoking without the possibility of prescription; a higher number is made of doctors9 offices or paramedics. The vast majority consists of tobacco cessation clinics with several health professionals and all facilities for smoking cessation.  Examples of good and bad practices have been described on many topics such as rendez-vous delays, that must be less than 3 weeks for a first appointment.  Some definitions have met consensus as the definition of healing, and in particular the period which defines a successful cessation. While waiting to close the debate, the recommendation is to record the cessation at 3, 6 and 12 months, with a particular focus at 6 months.  A code and a self-audit in many languages are available on the website for a first evaluation of the activity of the consultations that will enable future improvement.  Conclusions: The project provides real rapprochement eSCCAN knowledge to practices for smoking cessation in Europe that support in each country in Europe less than 10% of smokers, but disseminate knowledge and contribute to the assessment for teaching and research.
Contrasting Behavior of the p18INK4c and p16INK4a Tumor Suppressors in Both Replicative and Oncogene-Induced Senescence
Authors: Sladjana Gagrica, Sharon Brookes, Emma Anderton, Janice Rowe, Gordon Peters
Journal: Cancer Research (2011)

The cyclin-dependent kinase (CDK) inhibitors, p18(INK4c) and p16(INK4a), both have the credentials of tumor suppressors in human cancers and mouse models. For p16(INK4a), the underlying rationale is its role in senescence, but the selective force for inactivation of p18(INK4c) in incipient cancer cells is less clear. Here, we show that in human fibroblasts undergoing replicative or oncogene-induced senescence, there is a marked decline in the levels of p18(INK4c) protein and RNA, which mirrors the accumulation of p16(INK4a). Downregulation of INK4c is not dependent on p16(INK4a), and RAS can promote the loss of INK4c without cell-cycle arrest. Downregulation of p18(INK4c) correlates with reduced expression of menin and E2F1 but is unaffected by acute cell-cycle arrest or inactivation of the retinoblastoma protein (pRb). Collectively, our data question the idea that p18(INK4c) acts as a backup for loss of p16(INK4a) and suggest that the apparent activation of p18(INK4c) in some settings represents delayed senescence rather than increased expression. We propose that the contrasting behavior of the two very similar INK4 proteins could reflect their respective roles in senescence versus differentiation.
Clinical presentation and outcome of venous thromboembolism in COPD
Authors: L. Bertoletti, S. Quenet, P. Mismetti, L. Hernández, J.J. Martín-Villasclaras, C. Tolosa, M. Valdés, M. Barrón, J.A. Todolí, M. Monreal
Journal: European Respiratory Journal (2011)

Chronic obstructive pulmonary disease (COPD) is a moderate risk factor for venous thromboembolism (VTE), but neither the clinical presentation nor the outcome of VTE in COPD patients is well known. The clinical presentation of VTE, namely pulmonary embolism (PE) or deep venous thrombosis (DVT), and the outcome at 3 months (death, recurrent VTE or bleeding) were compared between 2,984 COPD patients and 25,936 non-COPD patients included in the RIETE (Registro Informatizado de la Enfermedad TromboEmbólica) registry. This ongoing international, multi-centre registry includes patients with proven symptomatic PE or DVT. PE was the more frequent VTE presentation in COPD patients (n=1,761, 59%). PE presentation was more significantly associated with COPD patients than non-COPD patients (OR 1.64, 95% CI 1.49–1.80). During the 3-month follow-up, mortality (10.8% versus 7.6%), minor bleeding (4.5% versus 2.3%) or first VTE recurrences as PE (1.5% versus 1.1%) were significantly higher in COPD patients than in non-COPD patients. PE was the most common cause of death. COPD patients presented more frequently with PE than DVT. It may explain the worse prognosis of COPD patients, with a higher risk of death, bleeding or VTE recurrences as PE compared with non-COPD patients. Further therapeutic options are needed.
Effect of Growth Hormone upon Body Weight and Incidence of Bacterial Endocarditis in Rats Exposed to Hypoxia
Authors: FRANKLIN E. ROTH, C. WALTON LILLEHEI
Journal: Circulation Research (1954)

Somatotropic hormone (STH) administration accelerated the rate of gain of body weight in normal rats, and effectively neutralized the inhibitory effect of hypoxia on gain in body weight. STH administration caused a nonsignificant reduction in the incidence of bacterial endocarditis. STH had no detectable effect upon the usual hypertrophy of the adrenal glands and cardiac ventricles resulting from the stressful exposure. A sex difference was noted in the weight gain response of rats receiving STH.
A Human Immunoglobulin λ Locus Is Similarly Well Expressed in Mice and Humans
Authors: Andrei V. Popov, Xiangang Zou, Jian Xian, Ian C. Nicholson, Marianne Brüggemann
Journal: The Journal of Experimental Medicine (1999)

Transgenic mice carrying a 380-kb region of the human immunoglobulin (Ig) lambda light (L) chain locus in germline configuration were created. The introduced translocus on a yeast artificial chromosome (YAC) accommodates the most proximal Iglambda variable region (V) gene cluster, including 15 Vlambda genes that contribute to >60% of lambda L chains in humans, all Jlambda-Clambda segments, and the 3' enhancer. HuIglambdaYAC mice were bred with animals in which mouse Igkappa production was silenced by gene targeting. In the kappa-/- background, human Iglambda was expressed by approximately 84% of splenic B cells. A striking result was that human Iglambda was also produced at high levels in mice with normal kappa locus. Analysis of bone marrow cells showed that human Iglambda and mouse Igkappa were expressed at similar levels throughout B cell development, suggesting that the Iglambda translocus and the endogenous kappa locus rearrange independently and with equal efficiency at the same developmental stage. This is further supported by the finding that in hybridomas expressing human Iglambda the endogenous L chain loci were in germline configuration. The presence of somatic hypermutation in the human Vlambda genes indicated that the Iglambda-expressing cells function normally. The finding that human lambda genes can be utilized with similar efficiency in mice and humans implies that L chain expression is critically dependent on the configuration of the locus.
ADHD and Pregnancy
Authors: Marlene P. Freeman
Journal: American Journal of Psychiatry (2014)

Attention deficit hyperactivity disorder (ADHD) has been increasingly recognized and treated in children and adults in recent years. As a result, a growing number of women enter their reproductive years treated with medication for ADHD or are diagnosed and start medication during their reproductive years. A common question in perinatal psychiatry regards the risk-benefit profile of pharmacotherapy for ADHD, particularly with stimulants. At this time, there are no guidelines to inform the treatment of ADHD across pregnancy and the postpartum period. Concerns about in utero exposure to stimulants are based primarily on the impact these medications might have on fetal growth. While stimulants do not appear to be associated with major congenital malformations, more human data regarding potential behavioral teratogenicity are needed in order to understand both the short- and long-term risks. Severity of illness, presence of comorbid disorders, and degree of impairment have an impact on treatment decisions. Crucial considerations include driving safety and ability to function in occupational roles. While most women can successfully avoid the use of stimulant medication during pregnancy, there are cases in which the benefits of stimulant treatment outweigh known and putative risks of in utero medication exposure.
Variation in germline mtDNA heteroplasmy is determined prenatally but modified during subsequent transmission
Authors: Christoph Freyer, Lynsey M Cree, Arnaud Mourier, James B Stewart, Camilla Koolmeister, Dusanka Milenkovic, Timothy Wai, Vasileios I Floros, Erik Hagström, Emmanouella E Chatzidaki, Rudolf J Wiesner, David C Samuels, Nils-Göran Larsson, Patrick F Chinnery
Journal: Nature Genetics (2012)
Incident Dysglycemia and Progression to Type 1 Diabetes Among Participants in the Diabetes Prevention Trial–Type 1
Authors: Jay M. Sosenko, Jerry P. Palmer, Lisa Rafkin-Mervis, Jeffrey P. Krischer, David Cuthbertson, Jeffery Mahon, Carla J. Greenbaum, Catherine C. Cowie, Jay S. Skyler
Journal: Diabetes Care (2009)

OBJECTIVE We studied the incidence of dysglycemia and its prediction of the development of type 1 diabetes in islet cell autoantibody (ICA)-positive individuals. In addition, we assessed whether dysglycemia was sustained. RESEARCH DESIGN AND METHODS Participants (n = 515) in the Diabetes Prevention Trial–Type 1 (DPT-1) with normal glucose tolerance who underwent periodic oral glucose tolerance tests (OGTTs) were followed for incident dysglycemia (impaired fasting glucose, impaired glucose tolerance, and/or high glucose levels at intermediate time points of OGTTs). Incident dysglycemia at the 6-month visit was assessed for type 1 diabetes prediction. RESULTS Of 515 participants with a normal baseline OGTT, 310 (60%) had at least one episode of dysglycemia over a maximum follow-up of 7 years. Dysglycemia at the 6-month visit was highly predictive of the development of type 1 diabetes, both in those aged &amp;lt;13 years (P &amp;lt; 0.001) and those aged ≥13 years (P &amp;lt; 0.01). Those aged &amp;lt;13 years with dysglycemia at the 6-month visit had a high cumulative incidence (94% estimate by 5 years). Among those who developed type 1 diabetes after a dysglycemic OGTT and who had at least two OGTTs after the dysglycemic OGTT, 33 of 64 (52%) reverted back to a normal OGTT. However, 26 (79%) of the 33 then had another dysglycemic OGTT before diagnosis. CONCLUSIONS ICA-positive individuals with normal glucose tolerance had a high incidence of dysglycemia. Incident dysglycemia in those who are ICA positive is strongly predictive of type 1 diabetes. Children with incident dysglycemia have an especially high risk. Fluctuations in and out of the dysglycemic state are not uncommon before the onset of type 1 diabetes.
Neutrophil migration into indomethacin induced rat small intestinal injury is CD11a/CD18 and CD11b/CD18 co-dependent
Authors: A W Stadnyk
Journal: Gut (2002)

Background: Neutrophils may exacerbate intestinal inflammatory diseases through secretion of proteolytic enzymes and reactive oxygen and nitrogen intermediates. Aims: To define the mechanisms involved in neutrophil infiltration into the non-steroidal anti-inflammatory disease inflamed intestine to develop strategies to regulate this process. Methods: The small intestinal epithelium of (15 mg/kg) indomethacin treated rats was examined for cytokine mRNA. The kinetics of neutrophil accumulation into the gastrointestinal tract (including lumen contents) of inflamed rats was determined using radiolabelled (111In) neutrophils injected intravenously followed by a three hour migration period. To determine which adhesion molecules were critical for migration, rats were also injected with function blocking monoclonal antibodies to the β2 (CD11/CD18) integrins. Results: Interleukin 1β, interleukin 1 receptor II, tumour necrosis factor α, and monocyte inflammatory peptide 2 but not monocyte chemoattractant protein 1 mRNA were detected in the epithelium within hours of indomethacin injection. Neutrophils were detectable in the small intestine and intestinal lumen by six hours and continued to accumulate until 48 hours post indomethacin injection. Neutrophil accumulation in the intestine was essentially blocked by anti-CD18, and partially blocked by either anti-CD11a or CD11b antibody treatment. Migration into the intestinal lumen was reduced by anti-CD11b. Conclusions: The small intestinal epithelium acts as one source of cytokines with properties important in the recruitment of neutrophils. In turn, neutrophil migration into the indomethacin inflamed small intestine is mediated by CD11a/CD18 and CD11b/CD18.