tbuckley/cabot-search huggingface dataset:
Genetic and Epigenetic Analysis of <i>CHEK2</i> in Sporadic Breast, Colon, and Ovarian Cancers
Authors: Louise H. Williams, David Choong, Sandra A. Johnson, Ian G. Campbell
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Germ-line variants in CHEK2 have been associated with increased breast, thyroid, prostate, kidney, and colorectal cancer risk; however, the prevalence of somatic inactivation of CHEK2 in common cancer types is less clear. The aim of this study was to determine if somatic mutation and/or epigenetic modification play a role in development of sporadic breast, colon, or ovarian cancers. Experimental Design: We undertook combined genetic and epigenetic analysis of CHEK2 in sporadic primary breast, ovarian, and colon tumors [all exhibiting chromosome 22q loss of heterozygosity (LOH)] and cancer cell lines. Expression of Chk2 was assessed by immunohistochemistry in 119 ovarian tumors. Results: Two novel germ-line variants were identified; however, none of the primary tumors harbored somatic mutations. Two CpG clusters previously implicated in CHEK2 silencing were investigated for evidence of hypermethylation. No methylation was detected at the distal CpG island. The proximal CpG cluster was methylated in all tumor and normal DNA, suggesting that this might not represent a true CpG island and is not relevant in the control of CHEK2 expression. Twenty-three percent of ovarian tumors were negative for Chk2 protein by immunohistochemistry, but there was no significant correlation between LOH across the CHEK2 locus and intensity of Chk2 staining (P = 0.12). Conclusions: LOH across the CHEK2 locus is common in sporadic breast, ovarian, and colorectal cancers, but point mutation or epigenetic inactivation of the retained allele is uncommon. Loss of Chk2 protein in ovarian cancer was not associated with allelic status, suggesting that inactivation does not occur as a consequence of haploinsufficiency.
Age at onset versus family history and clinical outcomes in 1,665 international bipolar‐I disorder patients
Authors: ROSS J. BALDESSARINI, LEONARDO TONDO, GUSTAVO H. VAZQUEZ, JUAN UNDURRAGA, LORENZA BOLZANI, AYSEGUL YILDIZ, HARI‐MANDIR K. KHALSA, MASSIMO LAI, BEATRICE LEPRI, MARIA LOLICH, PIER MARIO MAFFEI, PAOLA SALVATORE, GIANNI L. FAEDDA, EDUARD VIETA, TOHEN MAURICIO
Journal: World Psychiatry (2012)

Early onset in bipolar disorder (BPD) has been associated with greater familial risk and unfavorable clinical outcomes. We pooled data from seven international centers to analyze the relationships of family history and symptomatic as well as functional measures of adult morbidity to onset age, or onset in childhood (age <12), adolescence (12-18), or adulthood (19-55 years). In 1,665 adult, DSM-IV BPD-I patients, onset was 5% in childhood, 28% in adolescence, and 53% at peak ages 15-25. Adolescent and adult onset did not differ by symptomatic morbidity (episodes/year, percentage of months ill, co-morbidity, hospitalization, suicide attempts) or family history. Indications of favorable adult functional outcomes (employment, living independently, marriage and children, and a composite measure including education) ranked, by onset: adult > adolescent > child. Onset in childhood versus adolescence had more episodes/year and more psychiatric co-morbidity. Family history was most prevalent with childhood onset, similar over onset ages 12-40 years, and fell sharply thereafter. Multivariate modeling sustained the impression that family history and poor functional, but not symptomatic, outcomes were associated with younger, especially childhood onset. Early onset was more related to poor functional outcomes than greater symptomatic morbidity, with least favorable outcomes and greater family history with childhood onset.
Use of Thiazolidinediones and Risk of Heart Failure in People With Type 2 Diabetes: A Retrospective Cohort Study
Authors: Andrew J. Karter, Ameena T. Ahmed, Jennifer Liu, Howard H. Moffet, Melissa M. Parker, Assiamira Ferrara, Joe V. Selby
Journal: Diabetes Care (2004)

There is a growing concern that use of thiazolidinediones (TZDs) is associated with congestive heart failure (CHF) (1), though the causality of this relationship has not been established. Commentaries and case reports about this potential side effect have frequently appeared in the press, but peer-reviewed, large-scale epidemiologic studies have been absent. A few European nations have already limited the use of TZDs despite the absence of empirical evidence. A recently published, longitudinal observational study by Delea et al. (2) reported that initiation of TZDs was associated with an increased risk of incident CHF (hazard ratio 1.7; P < 0.001). While we welcome this first population-based study of TZD use and CHF, we have serious concerns regarding the methodology employed.

Our primary concern with the study by Delea et al. (2) is the potential for residual confounding by indication or severity (3). For example, this study did not measure or adjust for levels of glycemia, a known risk factor for CHF in diabetes …
Massive Resection of the Small Intestine after Occlusion of the Superior Mesenteric Artery
Authors: R. J. Harrison, C. C. Booth
Journal: Gut (1960)

Resection of all the small intestine but the proximal 8 in. of jejunum was performed in an elderly woman. Intestinal function tests revealed an extensive defect of absorption. The patient died nine months after the operation in a state of extreme emaciation. Necropsy revealed hypertrophy of the remnant of small intestine and intense fatty degeneration of the liver.
Better access to health care facilities is needed to further reduce malaria
Authors: J. Zarocostas
Journal: BMJ (2009)

The prevalence of malaria in more than a third of the 108 countries affected by the disease halved between 2000 and 2008, thanks largely to increased aid aimed at prevention, said the World Health Organization.

Margaret Chan, WHO director general, said in a foreword to the World Malaria Report 2009, “that the tremendous increase in funding for malaria control is resulting in the rapid scale up of today’s control tools.” In particular she singled out the increased use of insecticide treated mosquito nets.

However, the report found that cases fell least in countries with the highest incidence rates—for example, Uganda, Burkina Faso, Kenya, Congo, Malawi, Pakistan, and Nigeria.

These countries …
TLR2 ligands induce cardioprotection against ischaemia/reperfusion injury through a PI3K/Akt-dependent mechanism
Authors: T. Ha, Y. Hu, L. Liu, C. Lu, J. R. McMullen, J. Kelley, R. L. Kao, D. L. Williams, X. Gao, C. Li
Journal: Cardiovascular Research (2010)

Toll-like receptor (TLR)-mediated signalling pathways have been implicated in myocardial ischaemia/reperfusion (I/R) injury. Activation of the phosphoinositide 3-kinase (PI3K)/Akt pathway protects the myocardium from ischaemic injury. We hypothesized that the modulation of TLR2 would induce cardioprotection against I/R injury via activation of the PI3K/Akt signalling. Mice were treated with TLR2 ligands, peptidoglycan (PGN) or Pam3CSK4, respectively, 1 h before the hearts were subjected to ischaemia (1 h), followed by reperfusion (4 h). Infarct size was determined by triphenyltetrazolium chloride staining. Cardiac function and haemodynamic performance were evaluated. Infarct size was significantly reduced in PGN- or Pam3CSK4-treated mice compared with untreated I/R mice. Administration of TLR2 ligands improved cardiac function following I/R. PGN treatment increased the levels of phospho-Akt and phospho-GSK-3β (glycogen synthase kinase-3β), compared with untreated I/R hearts. PGN stimulation increased TLR2 tyrosine phosphorylation and association of the p85 subunit of PI3K with TLR2. To investigate the role of PI3K/Akt signalling in PGN-induced cardioprotection, we administered the PI3K inhibitor, Wortmannin, to the mice 15 min before PGN treatment. We also administered PGN to kinase-deficient Akt (kdAkt) transgenic mice 1 h before myocardial I/R. Both PI3K inhibition and kdAkt mice abolished the cardioprotection induced by PGN. To examine the role of TLR2 in PGN-induced cardioprotection, we administrated PGN to TLR2 knockout mice 1 h before the hearts were subjected to I/R. PGN-induced cardioprotection was lost in TLR2-deficient mice. These results demonstrate that TLR2 ligands induced cardioprotection, which is mediated through a TLR2/PI3K/Akt-dependent mechanism.
Time-Limited vs Unlimited Physician Certification
Authors: Paul Friedmann
Journal: JAMA (2015)

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
Authors' reply to Davies
Authors: K. H. Thomas, R. M. Martin, N. M. Davies, C. Metcalfe, F. Windmeijer, D. Gunnell
Journal: BMJ (2013)

We agree with Davies that further studies are needed before psychiatric safety concerns about varenicline can be laid to rest.1 2

We believe that our study provides reassuring evidence because we used validated outcomes for reporting suicide and non-fatal self harm and assessed the impact of confounding by indication using new and conventional methods. Because of its large …
No short cuts to science
Authors: Bruce G. Charlton
Journal: Behavioral and Brain Sciences (1999)

Steven Rose regards oversimplification of biology as the supreme sin, inevitably leading to evil consequences, and requiring an unique distortion of scientific practice to avoid it. To avoid this, he proposes a short-cut to scientific knowledge by defining certain areas of biology that are intrinsically flawed. But this achieves only a subordination of science to politics. There are no general-purpose shortcuts for evaluating the validity of theories, and no substitutes for testing specific theories using relevant evidence.
Key and Critical Objectives for The Journal
Authors: George D. Lundberg
Journal: JAMA (1987)

Since 1980, the masthead ofTHE JOURNALhas carried a mission statement that reads as follows: "The Journal is a forum for open and responsible discussion of matters relevant to the field of medicine. Its mission is education: to inform its readers of progress in clinical medicine, medical research, and of developments in other fields of interest to physicians." Shortly after becoming the Editor in 1982,I discovered thatTHE JOURNALdid not have a set of written goals or objectives in addition to the mission statement. Believing such to be important for strategic planning, I used a modified Delphi process involving the editorial staff and the Editorial Board to establish a set of 13 goals. These were approved by American Medical Association (AMA) senior management and subsequently published as an editorial entitled "Goals forTHE JOURNAL"1 on Aug 6, 1982. The editors have functioned under those goals since that time
Statistical inference: Why wheels spin
Authors: William S. Verplanck
Journal: Behavioral and Brain Sciences (1998)

NHSTP is embedded in the research of “cognitive science.” Its use is based on unstated assumptions about the practices of sampling, “operationalizing,” and using group data. NHSTP has facilitated both research and theorizing – research findings of limited interest – diverse theories that seldom complement one another. Alternative methods are available for data acquisition and analysis, and for assessing the “truth- value” of generalizations.
The Physician as an Educated Person
Authors: James L. Harper
Journal: JAMA (1983)

To the Editor.—  As a first-year medical student, I believe I am in a unique position to respond to the commentary by Dr Rhoads.  In the commentary, Dr Rhoads joins the ranks of those who decry the heavy emphasis on the sciences in premedical education. He also joins the ranks of those who suggest that the way to solve this problem is to suddenly shift gears and start overemphasizing humanities in the premedical curriculum.  I see this as simplistic and perilous. There are three perils of overemphasizing humanities in premedical training. First, by increasing the amount of humanities studied, by necessity you decrease the amount of science taken. (There are only so many credit hours to be used.) This leads to the second problem of a weakened background for the clinical years. Problem one also leads indirectly to problem 3—the sciences and the humanities require a different type of study.
Severe Pelvic Infection From Chlamydia trachomatis After Cesarean Section
Authors: Arthur Cytryn
Journal: JAMA (1982)

A severe pelvic infection developed in a 17-year-old primigravida after a cesarean section. Multiple antibiotics were administered for presumed mixed aerobic and anaerobic infections, without improvement. Subsequently, total hysterectomy and bilateral salpingo-oophorectomy were performed. Despite negative standard cultures, her condition continued to deteriorate and she required two more exploratory laparotomies for suspected intra-abdominal abscesses. Chlamydia trachomatis and, subsequently, Candida albicans were recovered from cultures of peritoneal fluid obtained after the third operation. Serological tests confirmed the presence of acute chlamydial infection. Marked clinical improvement occurred after doxycycline hyclate administration. Although genitourinary and acute pelvic inflammatory diseases due to chlamydiae have been reported previously, no case of severe pelvic infection due to this agent after cesarean section had been described, to our knowledge. Specimens should be studied specifically for chlamydiae when standard cultures demonstrate no pathogens in women suffering from documented pelvic infection.
Pretreatment viral load and response to prolonged interferon-α course for chronic hepatitis C
Authors: Nobukazu Yuki, Norio Hayashi, Akinori Kasahara, Hideki Hagiwara, Tetsuo Takehara, Masahide Oshita, Kazuhiro Katayama, Hideyuki Fusamoto, Takenobu Kamada
Journal: Journal of Hepatology (1995)
Absence of a Relationship between Tumor 18F-fluorodeoxyglucose Standardized Uptake Value and Survival in Patients Treated with Definitive Radiotherapy for Non–Small-Cell Lung Cancer
Authors: Ming-Yin Lin, Muzo Wu, Sinead Brennan, Marie-Pierre Campeau, David Sidney Binns, Michael MacManus, Benjamin Solomon, Rodney J. Hicks, Richard John Fisher, David Lee Ball
Journal: Journal of Thoracic Oncology (2014)

Introduction:A recent meta-analysis suggested that patients with non–small-cell lung cancer (NSCLC) whose primary tumors have a higher standardized uptake value (SUV) derived from 18F-fluorodeoxyglucose positron emission tomography (PET) have a worse prognosis in comparison with those with tumors with lower values. However, previous analyses have had methodological weaknesses. Furthermore, the prognostic significance over the full range of SUV values in patients treated nonsurgically remains unclear. The aim of this retrospective study was to investigate the relationship between survival and maximum SUV (SUVmax) analyzed as a continuous variable, in patients with NSCLC, staged using PET/computed tomography (CT) and treated with radiotherapy with or without chemotherapy.Methods:Eligible patients had a histological diagnosis of NSCLC, were treated with radical radiotherapy with or without chemotherapy as their primary treatment, and had pretreatment PET/CT scans. SUVmax, defined as the maximum pixel SUV value retrieved from the primary tumor, was analyzed primarily as a continuous variable for overall survival.Results:Eighty-eight patients met eligibility criteria: stage I, 19; stage II, 10; and stage III, 59. Median SUVmax was 15.0 (range, 2.5–56). Higher stage was associated with higher SUVmax values (p = 0.048). In univariate analysis, there was no evidence of a prognostic effect of SUVmax (hazard ratio per doubling = 0.83; 95% confidence interval, 0.62–1.11; p = 0.22). Analyzing SUVmax as a dichotomous variable (median cut point = 15.0), the hazard ratio (high: low) for risk of death was 0.71, with p = 0.18 (95% confidence interval, 0.44–1.15).Conclusions:In this cohort of patients, increasing SUVmax derived from 18F-fluorodeoxyglucose–PET/CT was associated with increasing tumor, node, metastasis (TNM) stage. We found no evidence of an association of increasing SUVmax with a shorter survival. Previous reports of an association between prognosis and SUVmax may partly be the result of methodological differences between this study and previous reports and an association between stage and SUVmax.
Firearm Violence and Public Health
Authors: Paul H. Blackman
Journal: JAMA (1994)

<h3>To the Editor.</h3> —The Commentary on firearms<sup>1</sup>presented no factual or scientific justification for the legislative policies advocated. None of the 10 sources cited in the article tested the effectiveness of any gun law. Most of the statistics cited were true a decade ago, such as the increase in suicide among the young and its second-place ranking as a cause of death. Those limited data may support the Commentary's call for better data on firearm-related morbidity and mortality, but normally, data are collected and analyzed first, with policy recommendations following that. Here, the call to collect data was introduced as the last legislative proposal, with the admitted ultimate goal of banning the private possession of handguns. No basis was given to support the other proposals, partly because they were preceded by the misleading statement that national standards were needed because "guns are carried across state lines." The existing national
Angiographic and Scintigraphic Findings in Fibrosing Mediastinitis
Authors: ALBERT J. MORENO, IDELLE WEISMANN, JEROME L. BILLINGSLEY, MICHAEL N. LUNDY, JERRY M. BROWN, GORDON D. GRAHAM, TOMMY J. BROWN
Journal: Clinical Nuclear Medicine (1983)

The clinical and morphologic findings in the case of a 47-year-old man with fibrosing mediastinitis, most probably due to histoplasmosis, are described. Radionuclide angiography demonstrated obstruction of the superior vena cava with collateral vascularization. Computed tomography demonstrated a large calcific mass interposed between the pulmonary artery and superior vena cava suggesting potential pulmonary vasculature involvement. For this reason, pulmonary scintigraphy was performed which showed right lung perfusion and ventilation defects. Radionuclide angiography and pulmonary scintigraphy complement each other in determining the extent of vascular involvement with fibrosing mediastinitis. However, contrast venography is necessary to correctly delineate the anatomy of the obstructed superior vena cava and its collaterals.
709 FACTORS INFLUENCING THE ACCURACY OF LIVER STIFFNESS MEASUREMENTS BY TRANSIENT ELASTOGRAPHY (TE) AND BY ACOUSTIC RADIATION FORCE IMPULSE (ARFI) ELASTOGRAPHY FOR LIVER FIBROSIS EVALUATION
Authors: S. Bota, I. Sporea, M. Peck-Radosavljevic, R. Sirli, H. Saito, H. Ebinuma, M. Lupsor, R. Badea, M. Friedrich-Rust, C. Sarrazin, F. Piscaglia, S. Marinelli, P. Salzl, A. Popescu, M. Danila
Journal: Journal of Hepatology (2013)
291 Effect of chronic administration of ursodeoxycholic acid on a gastrointestinal motility in gallstones and healthy controls
Authors: A. Colecchia, L. Sandri, P. Simoni, F. Azzaroli, A. Vestito, G. Mazzella, A. Roda, E. Roda, D. Festi
Journal: Journal of Hepatology (2004)
Varieties in the Distribution of Vessels Interesting to the Surgeon
Authors: None Hyrtl
Journal: BMJ (1841)

should it be brought forward by the Secretary of State for the Homne Department.Still, from the declaration of Mr. Geithrie, that there was no grievance which the college was not anxious to see remloved, and the assertion of Mr. White, that they were surgeons, an(d ha(l nothing to do witlh medicine or l
Alistair John Gordon
Authors: J. Kirkham
Journal: BMJ (2009)

<h3>Purpose</h3> Pulmonary arterial hypertension (PAH) has been reported with several rheumatologic diseases; however, it is not common in adult-onset Still9s disease (ASD). We describe a patient with ASD who developed PAH. <h3>Case Report</h3> A 29-year-old female with a 9-year history of ASD was admitted in July 2005 with 3 months of progressive exertional dyspnea, orthopnea, cough, and lower extremity edema. Her Still9s disease was characterized by periods of remissions and exacerbations, manifested by high spiking fevers, polyarthritis, evanescent maculopapular rash, leukocytosis, elevated ESR and ferritin, treated with corticosteroids, NSAIDs, hydroxychloroquine, and sulfasalazine. She never had dysphagia, GE reflex, Raynaud9s phenomenon, sleep-related breathing problems, use of tobacco, or anorexigens. Her physical exam was significant for heart rate of 120 beats per minute, respiration rate of 28 per minute, and blood pressure of 139/99 mm Hg, clear lungs, right parasternal heave, an accentuated pulmonary second heart sound, a 2/6 systolic murmur at left lower sternal border, elevated jugular venous pressure of 7 cm, mild hepatomegaly, ascites, 2+ dependent edema, and wrist and ankle joint synovitis. There was no skin tightness or telangiectasias. Laboratory testing on admission included WBC 19.2 k/μL, hemoglobin 9.6 g/dL, platelet count 552 k/μL, ESR 64 mm/hour, AST 221U/L, ALT 354 U/L, ferritin 1270 ng/mL (&lt; 132). Tests for ANA, RF, and HIV were negative. A CT of the chest as well as a ventilation perfusion scintigraphy showed no evidence of thromboembolic or lung parenchymal disease. Echocardiogram revealed right atrial and right ventricular dilatation, tricuspid regurgitation, and pulmonary artery systolic pressure of 61 mm Hg. Right heart catheterization showed pulmonary artery pressure of 50/24 mm Hg (mean 33, normal &lt; 25), capillary wedge pressure of 8 mm Hg, cardiac output 5.7 liters/minute, and cardiac index 2.8 liters/minute/m<sup>2</sup>. There was a good response to vasodilator infusion. The patient was treated with nifedipine and anakinra. Her systemic and arthritic symptoms improved; however, her right ventricular failure worsened, and she expired after 21/2 months. <h3>Discussion and Conclusion</h3> Pulmonary manifestations of ASD include aseptic pneumonitis, pleural effusions, rarely acute respiratory distress syndrome, and restrictive lung disease. PAH has been reported in patients with scleroderma, SLE, MCTD, dermatomyositis, polymyositis, and RA. However, this condition has only been reported once in a Japanese patient with ASD in 1990. We describe this patient with ASD with PAH without any other obvious cause; thus, we conclude it is likely secondary to pulmonary vascular changes related to ASD.