tbuckley/cabot-search huggingface dataset:
Cardiac Mitochondria and Reactive Oxygen Species Generation
Authors: Yeong-Renn Chen, Jay L. Zweier
Journal: Circulation Research (2014)

Mitochondrial reactive oxygen species (ROS) have emerged as an important mechanism of disease and redox signaling in the cardiovascular system. Under basal or pathological conditions, electron leakage for ROS production is primarily mediated by the electron transport chain and the proton motive force consisting of a membrane potential (ΔΨ) and a proton gradient (ΔpH). Several factors controlling ROS production in the mitochondria include flavin mononucleotide and flavin mononucleotide-binding domain of complex I, ubisemiquinone and quinone-binding domain of complex I, flavin adenine nucleotide-binding moiety and quinone-binding pocket of complex II, and unstable semiquinone mediated by the Q cycle of complex III. In mitochondrial complex I, specific cysteinyl redox domains modulate ROS production from the flavin mononucleotide moiety and iron-sulfur clusters. In the cardiovascular system, mitochondrial ROS have been linked to mediating the physiological effects of metabolic dilation and preconditioning-like mitochondrial ATP-sensitive potassium channel activation. Furthermore, oxidative post-translational modification by glutathione in complex I and complex II has been shown to affect enzymatic catalysis, protein-protein interactions, and enzyme-mediated ROS production. Conditions associated with oxidative or nitrosative stress, such as myocardial ischemia and reperfusion, increase mitochondrial ROS production via oxidative injury of complexes I and II and superoxide anion radical-induced hydroxyl radical production by aconitase. Further insight into cellular mechanisms by which specific redox post-translational modifications regulate ROS production in the mitochondria will enrich our understanding of redox signal transduction and identify new therapeutic targets for cardiovascular diseases in which oxidative stress perturbs normal redox signaling.
Admitting to mistakes in the medical literature
Authors: Sarah Fox, Vidhya Nair, Nigel Dudley
Journal: Journal of the Royal Society of Medicine (2009)

We read with interest your comments facing the future of medical journals.1 Many of the lessons from patient safety are applicable to mistakes in the medical literature. Unintentional errors should be used as learning opportunities and editors (and authors) should welcome their detection. Retractions and corrections are rare2 and (as in clinical medicine) probably massively under-reported due to concerns about embarrassment and discomfort by authors.

Errors may vary in degree and type from minor typographical, system error (study design and execution) to the intentional acts of scientific misconduct (plagiarism, research fraud, duplication of publication). One study found that the highest number of retractions were in the following journals: Science; Proceedings of the National Academy of Sciences; and Nature.2

Perhaps differential corrections rates reflect the quality of postpublication scrutiny and the rigour of its readership. It has been suggested that corrections should be prominent, informative and citable, and mentioned within the table of contents.3

We conducted a study to assess the number of corrections in the following popular medical journals published in 2008: New England Journal of Medicine (NEJM); Journal of the Royal Society of Medicine (JRSM); Journal of the American Geriatrics Society (JAGS); British Medical Journal including Careers Focus (BMJ); Lancet; and Age & Ageing. We also looked at how each journal dealt with corrections, as summarized in Table 1.



Table 1

Corrections



We found that the journal with the most corrections was also one of the most regularly issued. The vast majority of corrections were typographical errors of minor significance.

It was interesting to compare how different editors treat corrections. JAGS appears to invite reader participation by starting its ‘Erratum’ page with ‘Dear Readers’, while Age & Ageing’s title of ‘Corrigendum’ highlights authority, severity and perhaps unintentionally hides its meaning to those unversed in Latin.

The publishing of corrections allows us to see what is perhaps only the tip of the iceberg of mistakes. We should anticipate more corrections as journal editors strive to demonstrate transparency and probity while at the same time readers strive to ensure that the scientific record is free from error.
Effects of food with two oral rehydration therapies: a randomised controlled clinical trial.
Authors: N H Alam, T Ahmed, M Khatun, A M Molla
Journal: Gut (1992)

To evaluate the impact of food on the efficacy of oral rehydration solution (ORS), a randomised, controlled clinical trial was conducted in 182 adults with cholera. After initial rehydration with an intravenous polyelectrolyte solution for four hours, the patients were randomised to receive one of four rehydration therapies: glucose based ORS and no food for the first 24 hours (group A), glucose based ORS plus food from the beginning of treatment (group B), rice based ORS with no food for the first 24 hours (group C), and rice based ORS plus food from start of therapy (group D). Tetracycline was given after 72 hours to all patients. No significant differences in ORS intake, stool output, and duration of diarrhoea were noted between groups A and B and between groups C and D. A substantial and significant reduction in stool output was, however, shown in the groups who received rice based ORS irrespective of feeding. These results show that food does not potentiate the efficacy of either glucose based or rice based ORS in adults with cholera. Rice based ORS compared with glucose ORS substantially reduces purging in cholera patients.
Four Cases of Inversion of the Uterus: With Remarks
Authors: J. B. Hicks
Journal: BMJ (1872)

THE interest and anxiety attending the occurrence of inversion of the uterus after labour makes the record of cases always clinically useful, and this is my reason for occupying these pages with a narration of four, coupled with remarks.CASE I. -This has already been reported in Guly's Hospital Reports
Cervical cancer: a confidential enquiry is needed
Authors: A R Markos
Journal: Journal of the Royal Society of Medicine (2003)

Cervical cancer is in theory preventable yet the UK still sees about 3200 new cases every year. We do not know the amount of morbidity caused by this cancer, which may even have increased with the decline in mortality. Pessimists say that a further reduction in the incidence of cervical cancer is not practically possible. Before reaching any such conclusion, however, we need to look at avoidable and preventable causes; and the best way may be by individual case enquiries.1

Enquiries into medical care have helped to shape services, improve resources and reset standards. The Confidential Enquiry into Maternal Deaths (CEMD), begun in 1952, was a landmark in the development of maternity services and has been imitated in several other spheres (Box 1). The aim is to investigate areas of healthcare where trends are open to question, where avoidable or preventable factors need identification and where improvements are desirable.2 Some enquiries were national, others local.

There has been a notable reduction in the incidence of cervical cancer since the introduction of the national cervical cytology screening programme. The guidelines and quality assurance procedures for cytology and colposcopy provide support for service facilities, and the establishment of gynaecological cancer networks opens the way to local audits. But the national guidelines target the service as a whole. Even if the lessons from individual cases are shared locally through the specialist networks they do not necessarily filter through to other interested parties such as cytology programme managers and primary care physicians at either local or national level.
GSK-3β–Regulated N-Acetyltransferase 10 Is Involved in Colorectal Cancer Invasion
Authors: Hong Zhang, Wei Hou, Hua-Li Wang, Hai-Jing Liu, Xin-Ying Jia, Xing-Zheng Zheng, Yong-Xin Zou, Xin Li, Lin Hou, Michael A. McNutt, Bo Zhang
Journal: Clinical Cancer Research (2014)

Abstract Purpose: NAT10 (N-acetyltransferase 10) is a nucleolar protein, but may show subcellular redistribution in colorectal carcinoma. In this study, we evaluated membranous staining of NAT10 in colorectal carcinoma and its clinical implications, and explored the mechanism of regulation of NAT10 redistribution. Experimental Design: The expression and subcellular redistribution of NAT10, β-catenin, E-cadherin, and GSK-3β were evaluated by immunohistochemistry in 222 cases of colorectal carcinoma. Regulation of NAT10 and its influence on cell motility were analyzed with inhibitors of GSK-3β, transfection of wild-type or kinase-inactivated GSK-3β, or expression of various domains of NAT10, and evaluated with immunofluorescence, Western blotting, and Transwell assays. Results: NAT10 localized mainly in the nucleoli of normal tissues, and was redistributed to the membrane in cancer cells, particularly at the invasive “leading edge” of the tumor. This correlated well with nuclear accumulation of β-catenin (P &amp;lt; 0.001; χ2 = 68.213). In addition, NAT10 membrane staining reflected the depth of invasion and tendency to metastasize (all P values &amp;lt; 0.001), and was associated with a poorer prognosis (P = 0.023; χ2 = 5.161). Evaluation of the mechanism involved demonstrated that subcellular redistribution of NAT10 may result from its increased stability and nuclear export, which is brought about by inhibition of GSK-3β. Moreover, redistribution of NAT10 induces alteration of cytoskeletal dynamics and increases cancer cell motility. Conclusion: The subcellular redistribution of NAT10 can be induced by decreases in GSK-3β activity. This redistribution increases cancer cell motility, and is, thus, correlated with invasive potential and poorer clinical outcome. This finding suggests that NAT10 may be a useful prognostic marker and potential therapeutic target in colorectal carcinoma. Clin Cancer Res; 20(17); 4717–29. ©2014 AACR.
FLUCONAZOLE VERSUS KETOCONAZOLE IN OROPHARYNGEAL CANDIDIASIS IN AIDS
Authors: C.C. Kibbler, F.C. Odds, Geert Cauwenbergh, N. Clumeck, S. De Wit, H. Einsele, K. Jaschonek, D. Steinhilber, G. Ehninger, H.J. Roth, D.E. Smith, B.G. Gazzard
Journal: The Lancet (1989)
Autophagy in antigen-presenting cells results in presentation of citrullinated peptides to CD4 T cells
Authors: Jamie M. Ireland, Emil R. Unanue
Journal: The Journal of Experimental Medicine (2011)

Antibody responses to citrullinated self-proteins are found in autoimmunities, particularly in rheumatoid arthritis, where they serve as a diagnostic indicator. We show here that processing of the protein hen egg-white lysozyme (HEL) resulted in citrullination of peptides presented on class II MHC molecules by antigen-presenting cells. The presentation of the citrullinated peptides but not of the unmodified peptides was associated with autophagy. Dendritic cells (DCs), macrophages, and thymic DCs presented citrullinated peptides constitutively. Their treatment with 3-methyladenine (3MA) blocked presentation of citrullinated HEL peptides, but presentation of unmodified peptides was not affected. Presentation of citrullinated peptides was not detected on B cells or B lymphoma cells under normal culture conditions. In B cells, engagement of the B cell antigen receptor was required for presentation of the citrullinated peptides, also inhibited by 3MA. B lymphoma–expressing HEL cells presented citrullinated peptides only after brief serum starvation. This presentation was reduced by 3MA or by reduction in Atg5 expression. Presentation of the unmodified peptides was not changed. The findings indicate a linkage between autophagy and autoreactivity through the generation of this neo-epitope.
Cardiac mucosa: the heart of the problem
Authors: Stuart Jon Spechler
Journal: Gut (2015)

Traditional teaching holds that the normal stomach has three types of mucosae. The oxyntic mucosa of the gastric body and fundus has glands with parietal cells that secrete acid, and chief cells that secrete digestive enzymes. The mucosa of the antrum is comprised of mucus-secreting cells and endocrine cells that produce gastrin, which regulates acid production by the oxyntic mucosa. Finally, the most proximal portion of the stomach (the gastric cardia), a region with ill-defined borders, allegedly is lined by ‘cardiac mucosa’ comprised almost exclusively of mucus-secreting cells. Cardiac mucosa has been assumed to function as a buffer zone, preventing the damage that might result if the acid-sensitive, squamous mucosa of the oesophagus joined directly with the acid-secreting oxyntic mucosa of the gastric body. This dogma went unchallenged until 1997, when Chandrasoma proposed that cardiac mucosa is not a normal structure, but rather is acquired when GORD causes columnar metaplasia of squamous epithelium in the distal oesophagus.1 Furthermore, he contended that cardiac mucosa evolves into the intestinal metaplasia of Barrett's oesophagus in the setting of persistent GORD. Recent studies by investigators in Glasgow provide support for Chandrasoma's proposals.

In an earlier investigation, the Glasgow group studied the gastro-oesophageal junction (GOJ) region of 51 healthy volunteers.2 No subject had abnormal acid reflux by conventional pH monitoring in which a pH electrode was positioned 5 cm above the lower oesophageal sphincter (LOS). Using pH electrodes positioned within the LOS, however, significant differences …
How Long Should Insulin Be Used Once a Vial Is Started?
Authors: Martin M. Grajower, Charles G. Fraser, John H. Holcombe, Marci L. Daugherty, William C. Harris, Michael R. De Felippis, Olga M. Santiago, Nathaniel G. Clark
Journal: Diabetes Care (2003)

Editor’s comment : The commentary by Dr. Grajower has such important clinical relevance that responses were invited from the three pharmaceutical companies that supply insulin in the U.S. and the American Diabetes Association, and all of these combined in this commentary. The commenting letter and individual responses were authored separately and are completely independent of each other. 

Diabetic patients treated with insulin, whether for type 1 or type 2 diabetes, are prone to often unexplained swings in their blood glucose. These swings can vary from dangerously low to persistently high levels. Most diabetic patients, and most physicians, will adjust insulin regimens so as to avoid hypoglycemia at the expense of hyperglycemia. Among the “textbook” reasons for variable glucose responses to any given insulin regimen are 1 ) site of administration, 2 ) exercise, 3 ) bottles not adequately mixed before drawing the insulin (for NPH, Lente, or Ultralente), and 4 ) duration of treatment with insulin (1).

A new insulin was marketed by Aventis Pharmaceuticals about 1 year ago, insulin glargine (Lantus). The manufacturer seemed to stress that patients not use a started bottle of this insulin for >28 days (2). Two patients of mine highlighted this point.

L.K. is a 76-year-old woman with type 2 diabetes, diagnosed at 55 years of age, and treated with insulin since age 56. Her insulin regimen was changed to Lantus at night together with Novolog before meals. She monitors her blood glucose four times a day. She used a bottle of Lantus until it ran out; therefore, a bottle lasted for 2 months. Her recent HbA1c was 7.6%. I retrospectively analyzed her home glucose readings by averaging her fasting blood glucose levels for the first 15 days of a new bottle and the last 15 days of that same bottle. The results were 137 ± …
Prognostic Performance of Metabolic Indexes in Predicting Onset of Type 1 Diabetes
Authors: Ping Xu, Yougui Wu, Yiliang Zhu, Getachew Dagne, Giffe Johnson, David Cuthbertson, Jeffrey P. Krischer, Jay M. Sosenko, Jay S. Skyler
Journal: Diabetes Care (2010)

OBJECTIVE In this investigation we evaluated nine metabolic indexes from intravenous glucose tolerance tests (IVGTTs) and oral glucose tolerance tests (OGTTs) in an effort to determine their prognostic performance in predicting the development of type 1 diabetes in those with moderate risk, as defined by familial relation to a type 1 diabetic individual, a positive test for islet cell antibodies and insulin autoantibody, but normal glucose tolerance. RESEARCH DESIGN AND METHODS Subjects (n = 186) who had a projected risk of 25–50% for developing type 1 diabetes within 5 years were followed until clinical diabetes onset or the end of the study as part of the Diabetes Prevention Trial–Type 1. Prognostic performance of the metabolic indexes was determined using receiver operating characteristic (ROC) curve and survival analyses. RESULTS Two-hour glucose from an OGTT most accurately predicted progression to disease compared with all other metabolic indicators with an area under the ROC curve of 0.67 (95% CI 0.59–0.76), closely followed by the ratio of first-phase insulin response (FPIR) to homeostasis model assessment of insulin resistance (HOMA-IR) with an area under the curve value of 0.66. The optimal cutoff value for 2-h glucose (114 mg/dl) maintained sensitivity and specificity values &amp;gt;0.60. The hazard ratio for those with 2-h glucose ≥114 mg/dl compared with those with 2-h glucose &amp;lt;114 mg/dl was 2.96 (1.67–5.22). CONCLUSIONS The ratio of FPIR to HOMA-IR from an IVGTT provided accuracy in predicting the development of type 1 diabetes similar to that of 2-h glucose from an OGTT, which, because of its lower cost, is preferred. The optimal cutoff value determined for 2-h glucose provides additional guidance for clinicians to identify subjects for potential prevention treatments before the onset of impaired glucose tolerance.
Periarticular and generalised bone loss in patients with early rheumatoid arthritis: influence of alendronate and intra-articular glucocorticoid treatment. Post hoc analyses from the CIMESTRA trial
Authors: T W Jensen, M S Hansen, K Hørslev-Petersen, L Hyldstrup, B Abrahamsen, B Langdahl, B Zerahn, J Pødenphant, K Stengaard-Petersen, P Junker, M Østergaard, T Lottenburger, T Ellingsen, L S Andersen, I Hansen, H Skjødt, J K Pedersen, U B Lauridsen, A J Svendsen, U Tarp, H Lindegaard, Anne Grethe Jurik, Aage Vestergaard, M L Hetland
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> The aims of this study were to investigate the influence of alendronate and intra-articular betamethasone treatment on bone mineral density (BMD) changes in hand, lumbar spine and femoral neck during 1 year of a treat-to-target study (Cyclosporine, Methotrexate, Steroid in RA (CIMESTRA)). <h3>Patients and methods</h3> A hundred and sixty patients with early, active rheumatoid arthritis (RA) received methotrexate, intra-articular betamethasone and ciclosporin /placebo-ciclosporin. Patients with Z-score ≤0 also started alendronate 10 mg/day. BMD of the hand (digital x-ray radiogrammetry (DXR-BMD<sub>hand</sub>)), BMD of lumbar spine and femoral neck (dual x-ray absorptiometry (DXA-BMD<sub>lumbar spine</sub> and DXA-BMD<sub>femoral neck</sub>)) and x-rays of hands, wrists and forefeet (modified Sharp-van der Heijde score) were measured at baseline and 1 year, with complete data available in 107 patients. <h3>Results</h3> The change in BMD in hand, lumbar spine and femoral neck was negatively associated with the dose of intra-articular betamethasone (p&lt;0.01 for all), but the bone loss in hand was modest and in the axial skeleton comparable with that of healthy individuals. Alendronate did not influence changes in DXR-BMD<sub>hand</sub>, which averaged −2.8%, whereas significant changes were observed in DXA-BMD<sub>lumbar spine</sub> and DXA-BMD<sub>femoral neck</sub> in alendronate-treated patients (1.8% and 0.8%) compared with untreated patients (–1.8% and –2.2%) (p&lt;0.01 and 0.02). Alendronate did not affect the radiographic progression (alendronate-treated patients: 0 (range 0–19), non-alendronate: 0 (0–18)). <h3>Conclusions</h3> In early active RA, intra-articular betamethasone injections added to disease-modifying antirheumatic drug (DMARD) treatment led to minimal loss of hip and lumbar BMD, and the loss could be prevented by treatment with alendronate. Alendronate treatment did not affect radiographic progression.
Ossification of the ligamentum teres as a possible mechanism of lateral subluxation in coxopathy associated with ankylosing spinal hyperostosis.
Authors: K Inoue, K Schichikawa, Y Takenaka, E Yamauchi, J Nishioka, S Hukuda
Journal: Annals of the Rheumatic Diseases (1993)

The cases are reported of two patients with coxopathy associated with ankylosing spinal hyperostosis who showed ossification of the ligamentum teres. It is suggested that considerable ossification at the medial acetabular floor including the ligamentum teres can explain the mechanism of development of coxopathy with lateral subluxation of the femoral head which is often seen in patients with ankylosing spinal hyperostosis.
MELD scoring system is useful for predicting prognosis in patients with liver cirrhosis and is correlated with residual liver function: a European study
Authors: F Botta
Journal: Gut (2002)

<b>Background:</b> Indices for predicting survival are essential for assessing prognosis and assigning priority for liver transplantation in patients with liver cirrhosis. The model for end stage liver disease (MELD) has been proposed as a tool to predict mortality risk in cirrhotic patients. However, this model has not been validated beyond its original setting. <b>Aim:</b> To evaluate the short and medium term survival prognosis of a European series of cirrhotic patients by means of MELD compared with the Child-Pugh score. We also assessed correlations between the MELD scoring system and the degree of impairment of liver function, as evaluated by the monoethylglycinexylidide (MEGX) test. <b>Patients and methods:</b> We retrospectively evaluated survival of a cohort of 129 cirrhotic patients with a follow up period of at least one year. The Child-Pugh score was calculated and the MELD score was computed according to the original formula for each patient. All patients had undergone a MEGX test. Multivariate analysis was performed on all variables to identify the parameters independently associated with one year and six month survival. MELD values were correlated with both Child-Pugh scores and MEGX test results. <b>Results:</b> Thirty one patients died within the first year of follow up. Child-Pugh and MELD scores, and MEGX serum levels were significantly different among patients who survived and those who died. Serum creatinine, international normalised ratio, and MEGX<sub>60</sub> were independently associated with six month mortality while the same variables and the presence of ascites were associated with one year mortality. MELD scores showed significant correlations with both MEGX values and Child-Pugh scores. <b>Conclusions:</b> In a European series of cirrhotic patients the MELD score is an excellent predictor of both short and medium term survival, and performs at least as well as the Child-Pugh score. An increase in MELD score is associated with a decrease in residual liver function.