tbuckley/cabot-search huggingface dataset:
Less than 0.5% of safety incidents reported in 2008-9 came from general practice
Authors: J. Wise
Journal: BMJ (2010)

General practice lacks a safety reporting culture with less than 0.5% of mistakes and near misses reported to the NHS safety watchdog coming from this sector, says the health and social care regulator.

In its first annual report to parliament on the state of health care and adult social care in England the Care Quality Commission says that although 90% of patient contacts take place at GP practices, only 3417 (0.3%) incidents (out of a total 1 061 934) were reported from this sector in the year to July 2009 compared with 693 700 from hospitals. The commission says it is crucial that organisations report incidents so that they can learn and put things right. 

The overall reporting of serious incidents to the National Patient Safety Agency has improved greatly from 922 552 incidents in 2007-8 to 1 061 934 in 2008-9. But the reporting rate continues to vary across organisations. For example, reporting from primary care trusts with hospital beds varies more than 20-fold.

Maggie Kemmner, head …
Molecular mechanism of copper transport in Wilson disease.
Authors: Negah Fatemi, Bibudhendra Sarkar
Journal: Environmental Health Perspectives (2002)

Wilson disease is an autosomal recessive disorder of copper metabolism. The Wilson disease protein is a putative copper-transporting P-type ATPase, ATP7B, whose malfunction results in the toxic accumulation of copper in the liver and brain, causing the hepatic and/or neurological symptoms accompanying this disease. The cytosolic N-terminal domain (approximately 70 kDa) of this ATPase comprises six heavy metal-associated domains, each of which contains the conserved metal-binding motif GMTCXXC. The N-terminal domain (Wilson disease copper-binding domain [WCBD]) has been expressed, purified, and characterized using various techniques. The WCBD binds six atoms of copper in the +1 oxidation state competitively, and with a greater affinity than all other metals. The copper atom is coordinated by two cysteines in a distorted linear geometry. Copper binds the WCBD in a cooperative manner and induces secondary and tertiary conformation changes. Zinc binding to the WCBD has also been characterized by circular dichroism spectroscopy and shown to produce conformational changes that are completely different from those induced by copper. The phosphorylation/nucleotide-binding domain of ATP7B has also been expressed and characterized and shown to be capable of binding ATP but lacking ATPase activity. A peptide corresponding to the sixth transmembrane domain of ATP7B has been constructed and shown to undergo secondary conformational changes upon binding a single atom of copper. Finally, a chimeric protein consisting of the WCBD and truncated ZntA, a zinc-transporting ATPase lacking the N-terminal domain, has been constructed and analyzed for metal ion selectivity. These results suggest that the core determines the metal ion specificity of P-type ATPases, and the N-terminal metal-binding domain may play a regulatory role.
Hemolytic Transfusion Reactions Associated with the Kidd Antibody (Jk<sup>A</sup>)
Authors: Thomas A. Rauner, Kouichi R. Tanaka
Journal: New England Journal of Medicine (1967)

ALTHOUGH the Kidd antibody (Jka) was originally described as a cause of hemolytic disease in the newborn,1 a few well documented cases of hemolytic transfusion reactions secondary to anti-Jka have been reported.2 3 4 5 6 7 These are of clinical importance because anti-Jka is frequently difficult to detect in the recipient's blood, and the crossmatch can appear to be normal.This report describes 2 patients with hemolytic reactions secondary to anti-Jka that followed transfusions with apparently compatible blood.Case ReportsCase 1. C.H., a 50-year-old man, was first seen at Harbor General Hospital on November 21, 1965, with a diagnosis of Hodgkin's disease. . . .
Is Type 2 Diabetes a Different Disease in Obese and Nenobese Patients?
Authors: Romano Prando, Valeria Cheli, Pierluigi Melga, Roberta Giusti, Emanuela Ciuchi, Patrizio Odetti
Journal: Diabetes Care (1998)

OBJECTIVE The main purpose of this work was to study the possible differences in insulin secretion in a large group of type 2 diabetic patients in relation to diabetes duration, obesity, and the presence of secondary failure after treatment with oral hypoglycemic agents. RESEARCH DESIGN AND METHODS There were 147 nonobese and 215 obese type 2 diabetic subjects, aged 35–80 years, investigated in a cross-sectional descriptive study. Subjects were grouped according to whether glycemic control was good (mean blood glucose &amp;lt;8.5 mmol/l) or poor. β-Cell function was assessed by measuring meal-stimulated insulin and C-peptide concentrations, as the mean of the three postprandial increments above the premeal value. RESULTS Basal C-peptide concentrations were significantly higher in obese than nonobese patients of both groups. The mean of meal-stimulated C-peptide concentrations was also significantly higher in obese than nonobese patients with good glycemic control, but not in the secondary failure groups. In nonobese and obese patients considered separately, a significant negative correlation between the mean of daily blood glucose and meal-stimulated C-peptide was observed (r = −0.705 and r = −0.679, respectively, P &amp;lt; 0.001) and the residual β-cell function was significantly correlated with the known duration of diabetes and metabolic control, but not with BMI, in both groups. CONCLUSIONS On average, obese diabetic subjects showed higher meal-stimulated Cpeptide than nonobese subjects only in well-controlled groups. In both obese and nonobese patients, an inverse association between meal-stimulated insulin secretion and duration of diabetes was observed. In obese patients, as in nonobese patients, the lower β-cell function seems likely to be the major pathogenetic factor in the appearance of secondary failure, while being overweight plays only a minor role, thus showing that type 2 diabetes is the same disease in obese and nonobese patients.
EXTERNAL CARDIAC MASSAGE
Authors: Alfred Blalock
Journal: JAMA (1961)

The discovery by Kouwenhoven, Knickerbacker, and Jude of the value of external cardiac massage in the treatment of cardiac arrest is an important one. Although some slight pulmonary ventilation is usually caused by properly performed external massage, it is not sufficient; and the procedure should be supplemented by positive-pressure ventilation, such as mouth-to-mouth or other available means. Furthermore, if ventricular fibrillation is present, equipment should be available for performing external defibrillation. Fortunately, defibrillation may be accomplished many minutes after its onset, provided that external massage and positive-pressure ventilation have been used during the interval. It has been found that upon application of the defibrillating shock the heart will usually resume normal rhythm. The underlying principle of external cardiac massage is that the heart is more or less anchored between the sternum and the vertebral column, and its lateral motion is limited by the pericardium. Therefore, the heart may be effectively
THE TREATMENT OF BURNS AND SKIN GRAFTING.
Authors: HALDOR SNEVE
Journal: JAMA (1905)

There is perhaps no more frightful accident than a severe burn of large area. The intense suffering of the patient, and, in case of recovery, the hideous deformity left, render these accidents peculiarly distressing. In spite of all our pastes and powders, salves and solutions, the mortaltiy in burns involving more than one-third of the body surface is nearly 100 per cent., and in many cases the agony of redressing these wounds is so great as to lead physician and patient alike to pray for a merciful termination by death. Dupuytren's classification of burns into six degrees was cumbersome, and modern writers have adopted Boyer's and speak only of three degrees. In the following description, hyperemia of the skin will be considered a burn of the first degree, destruction of the epidermis shown by vesication, second degree, destruction of the derma, third degree, and of the deeper tissues, fourth degree.
Abstract 4089: Differential regulation of androgen receptor by PIM-1 kinases via phosphorylation-dependent recruitment of distinct ubiquitin E3 ligases.
Authors: Douglas Linn, Xi Yang, Yingqiu Xie, Alan Alfano, Dhanraj Deshmukh, Xin Wang, Hermela Shimelis, Hegang Chen, Wei Li, Kexin Xu, Mingyuan Chen, Yun Qiu
Journal: Cancer Research (2013)

Abstract Androgen receptor (AR) plays a pivotal role in prostate cancer. Regulation of AR transcriptional activity by post-translational modifications, such as phosphorylation by multiple kinases, is well documented. Here, we report that two PIM-1 kinase isoforms which are upregulated during prostate cancer progression, namely PIM-1S and PIM-1L, modulate AR stability and transcriptional activity through differentially phosphorylating AR at Serine 213 (S213) and Threonine 850 (T850). Although both kinases are capable of interacting with and phosphorylating AR at S213, only PIM-1L could phosphorylate T850. We also showed that PIM-1S induced S213 phosphorylation destabilizes AR by recruiting the ubiquitin E3 ligase Mdm2 and promotes AR degradation in a cell cycle dependent manner, while PIM-1L-induced T850 phosphorylation stabilizes AR by recruiting the ubiquitin E3 ligase RNF6 and promotes AR-mediated transcription under low-androgen conditions. Furthermore, both PIM-1 isoforms could promote prostate cancer cell growth under low-androgen conditions. Our data suggest that these kinases regulate AR stability and transcriptional activity through recruitment of different functional partners in a phosphorylation-dependent manner. As AR turnover has been previously shown to be critical for cell cycle progression in prostate cancer cells, PIM-1 kinase isoforms may promote prostate cancer cell growth, at least in part, through modulating AR activity via distinct mechanisms. Citation Format: Douglas Linn, Xi Yang, Yingqiu Xie, Alan Alfano, Dhanraj Deshmukh, Xin Wang, Hermela Shimelis, Hegang Chen, Wei Li, Kexin Xu, Mingyuan Chen, Yun Qiu. Differential regulation of androgen receptor by PIM-1 kinases via phosphorylation-dependent recruitment of distinct ubiquitin E3 ligases. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4089. doi:10.1158/1538-7445.AM2013-4089
Relationship of thyroid function to post-traumatic S-100b serum levels in survivors of severe head injury: preliminary results
Authors: Ioanna Dimopoulou, Stylianos Tsagarakis, Stefanos Korfias, Dimitrios Zervakis, Evangelia Douka, Nikolaos Thalassinos, Damianos E Sakas, Charis Roussos
Journal: Intensive Care Medicine (2004)
Induced Pluripotent Stem Cells
Authors: Katja Schenke-Layland, W. Robb MacLellan
Journal: Circulation (2009)

E mbryonic stem cells (ESCs) were first derived in the early 1980s simultaneously by 2 independent groups, 1,2 and because of their plasticity and potentially unlimited capacity for self-renewal, they were predicted to transform research in mammalian development, genetics, stem cell biology, and regenerative medicine.However, it quickly became apparent that although ESCs would become an invaluable tool to study development and stem cell biology, translating their promise into the clinics would be problematic.Twenty-eight years after the first report describing mouse ESCs and 10 years after the successful derivation of human ESCs, the US Food and Drug Administration approved the first human ESC-related clinical trial for spinal cord injuries this year; however, it is now on its second clinical hold, and no subjects have yet been enrolled.Although this delay in translation to human trials is likely multifactorial, major obstacles remain with the clinical use of ESCs over ethical issues, oncogenic risk, and the fact that ESC derivatives for tissue repair involve the use of allogeneic cells that can lead to rejection of mismatched cellular grafts.The oncogenic risk associated with stem cell therapies is no longer just theoretical.This year, the first report of a patient who developed multiple tumors in his brain and spinal cord after receiving fetal neural stem cells was published. 3Thus, therapeutic application of pluripotent stem cells (PSCs), particularly in the cardiovascular field, requires further advancement and new approaches such as that described by Zwi et al 4 in this issue of Circulation.
Bullous pemphigoid in infancy: Clinical and epidemiologic characteristics
Authors: Orith Waisbourd-Zinman, Dani Ben-Amitai, Arnon D. Cohen, Meora Feinmesser, Daniel Mimouni, Ayelet Adir-Shani, Marina Zlotkin, Alex Zvulunov
Journal: Journal of the American Academy of Dermatology (2007)
Increased Extracellular Volume and Altered Mechanics Are Associated With LVH in Hypertensive Heart Disease, Not Hypertension Alone
Authors: Sujith Kuruvilla, Rajesh Janardhanan, Patrick Antkowiak, Ellen C. Keeley, Nebiyu Adenaw, Jeremy Brooks, Frederick H. Epstein, Christopher M. Kramer, Michael Salerno
Journal: JACC. Cardiovascular imaging (2015)
Relapse after autologous hematopoietic stem cell transplantation in acute myeloid leukemia, a single center experience over 13 years
Authors: Vincent Lévy, Zora Marjanovic, Anne Vekhoff, Ramdam Belhocine, Jean Pierre Marie, Alain Delmer, Florence Ajchenbaum‐Cymbalista, Robert Zittoun, Bernard Rio
Journal: American Journal of Hematology (2000)
Author's reply to Cox and to McIntyre and colleagues
Authors: M. McCartney
Journal: BMJ (2014)

Although I respect Cox’s view that regulation of herbal drugs may help protect the public from fundamentally dangerous preparations,1 2 such regulation causes confusion. Herbal preparations of no proved efficacy are presented on pharmacy shelves with the Medicines and Healthcare Products Regulatory Agency (MRHA) stamp and the promise that they are approved for “traditional” use. What does this mean to prospective customers? …
Rapid one step urine tests in early pregnancy
Authors: G. Jones, I Scudamore, P N Bamford
Journal: BMJ (1991)

REPLY,-It is important that epileptic women who are pregnant should continue with some anticonvulsant treatment as if they do not the incidence of fetal abnormalities is higher than normal.Advice from the neurologist and obstetrician should be coordinated, and it is wise to use only one therapeutic agent, not several-on all these matters Dr Orrell and I agree.However, Dr Orrell also cites data on the risks of abnormalities of the central nervous system associated with sodium valproate.The teratogenic effects of various therapeutic regimens and their relation with background diseases is still mostly unproved.One recent review warned of the teratogenic effects of phenytoin, hydantoin, troxidone (trimethadione), primidone, ethosuximide, and carbamazepine as well as the possible risks of sodium valproate.'No anticonvulsants can be proved to be completely free of teratogenic associations, and Dr Orrell is probably right that sodium valproate should not be given to women in early pregnancy because of its teratogenic associations.It may be possible either to reduce the dose in the first trimester or to substitute another anticonvulsant that currently is thought to be less teratogenic.I disagree with the action recommended in his letter for a woman who has been taking valproate inadvertently in early pregnancy.She does not need to have her ca fetoprotein concentration measured; this is only a screening test, and by current thinking this woman is already at higher risk of an abnormality.She needs detailed ultra- sound scanning.If for some reason this is not available amniocentesis may be offered.
Fractional Exhaled Nitric Oxide (FeNO) is Elevated in School Aged Children who have Culture-Documented Frequent Viral Respiratory Illnesses during Infancy
Authors: L.E. Salazar, M.D. Evans, E.L. Anderson, D.F. DaSilva, R.A. Grabher, T.E. Pappas, K.A. Roberg, K. Sullivan Dillie, C.J. Tisler, R.E. Gangnon, J.E. Gern, R.F. Lemanske
Journal: Journal of Allergy and Clinical Immunology (2007)
Morphology of the Anterior Cingulate Gyrus in Patients With Schizophrenia: Relationship to Typical Neuroleptic Exposure
Authors: Alison Kopelman, Nancy C. Andreasen, Peg Nopoulos
Journal: American Journal of Psychiatry (2005)

The anterior cingulate gyrus is a pivotal component of brain networks directing affective and cognitive functions, and abnormalities of the anterior cingulate gyrus may be involved in the pathophysiology of schizophrenia. However, magnetic resonance imaging studies of the morphology of this region have been few and the results inconsistent. Many of the studies have not accounted for confounding factors such as gender, handedness, or clinical variables such as neuroleptic exposure.The morphology and clinical correlates of the anterior cingulate gyrus were evaluated in a group of 30 right-handed male subjects with schizophrenia and a comparison group matched for age, sex, and handedness. The patient group was specifically designed to provide measures of multiple phenomenological differences such as severity of illness, duration of illness, and exposure to typical neuroleptics.The patient group had a significantly larger left anterior cingulate gyrus volume relative to comparison subjects, whereas right anterior cingulate gyrus volume did not differ between groups. Depth of the left anterior cingulate gyrus was significantly correlated with neuroleptic exposure, indicating that greater exposure to neuroleptics was associated with greater cortical depth of this region. There was no significant relationship between anterior cingulate gyrus morphology and duration of illness or severity of symptoms.Anterior cingulate gyrus depth in subjects with schizophrenia is directly related to typical medication exposure (the greater the exposure, the thicker the anterior cingulate gyrus) but not to other clinical variables such as length of illness or symptom severity. Future research is needed to determine the functional consequences of these changes and relationship to atypical neuroleptic use.
Cowpox Treated with Marboran (Methisazone)
Authors: W. F. T. McMath, H. T. H. Wilson
Journal: BMJ (1965)

cases to a surgical unit at the West Middlesex Hospital over a period of four years.There were 408 patients, of whom 118 had retention of urine and 20 had non-malignant intestinal obstruction other than by hernia incarceration.There was no case of acute intestinal obstruction due to compression by a distended bladder.Surgical textbooks in common use-for example, Ian Aird (1958), Souttar and Goligher (1958), and Bailey and Love (1959) -do not mention compression obstruction of the large bowel by a distended bladder.Because a previous reference to this condition could not be found, it was thought worth while to report this case.It is probable that in most patients with obstruction to the bladder outlet the distended bladder rises easily into the abdomen and does not compress the bowel to any great extent.Some degree of compression may, however, occur, and may be a contributory factor to the constipation that is often present in elderly patients admitted with retention of urine.In the above case the small size of the pelvic cavity caused the distended bladder to impact at the pelvic brim and compress the pelvirectal junction.This resulted in acute large-bowel obstruction.I would like to thank Mr. E. B. Z. Masterman, under whose care this patient was treated, for his encouragement and advice, and for permission to report the case ; Dr. A. H. Morris and the staff of the x-ray department for the x-ray films
Murine atopic dermatitis responds to peroxisome proliferator-activated receptors α and β/δ (but not γ) and liver X receptor activators
Authors: Yutaka Hatano, Mao-Qiang Man, Yoshikazu Uchida, Debra Crumrine, Theodora M. Mauro, Kenneth R. Feingold, Peter M. Elias, Walter M. Holleran
Journal: Journal of Allergy and Clinical Immunology (2009)
Use of flow-volume curves in detecting secretions in ventilator-dependent patients.
Authors: A Jubran, M J Tobin
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

A noninvasive means of detecting airway secretions in ventilator-dependent patients is desirable because endotracheal suctioning can result in life-threatening complications. In a patient who had copious secretions, we observed a sawtooth pattern on his flow-volume curve that disappeared after suctioning. Accordingly, we systematically examined the usefulness of a sawtooth pattern on flow-volume curves in detecting secretions in ventilator-dependent patients and compared its accuracy with clinical examination. Flow-volume curves were recorded in 50 ventilator-dependent patients over 1 min of spontaneous breathing. In 15 of these patients, clinical examination was performed by three clinicians to determine its accuracy in detection of secretions. Endotracheal suctioning was then performed to determine the presence or absence of secretions. Subsequently, the flow-volume curves of all 50 patients were played back on a video screen, and three observers, who were unaware of the results of suctioning, made a decision regarding the presence or absence of a sawtooth pattern. The sensitivity of the sawtooth pattern in detecting secretions ranged from 0.76 to 0.86, and specificity ranged from 0.86 to 0.90. The likelihood ratio of a positive test ranged from 5.55 to 7.97, whereas the likelihood ratio of a negative test ranged from 0.16 to 0.27. Interobserver agreement, assessed by the kappa statistic, was excellent: 0.76, 0.76, and 0.84. In the subgroup of patients evaluated by both clinical examination and flow-volume curve analysis, clinical examination was less accurate in 11 of the 15 patients. In conclusion, detection of a sawtooth pattern strongly suggests the presence of secretions, and the absence of this pattern suggests that secretions are unlikely to be present.
Estimating Absolute Rates of Molecular Evolution and Divergence Times: A Penalized Likelihood Approach
Authors: Michael J. Sanderson
Journal: Molecular Biology and Evolution (2002)

Rates of molecular evolution vary widely between lineages, but quantification of how rates change has proven difficult. Recently proposed estimation procedures have mainly adopted highly parametric approaches that model rate evolution explicitly. In this study, a semiparametric smoothing method is developed using penalized likelihood. A saturated model in which every lineage has a separate rate is combined with a roughness penalty that discourages rates from varying too much across a phylogeny. A data-driven cross-validation criterion is then used to determine an optimal level of smoothing. This criterion is based on an estimate of the average prediction error associated with pruning lineages from the tree. The methods are applied to three data sets of six genes across a sample of land plants. Optimally smoothed estimates of absolute rates entailed 2- to 10-fold variation across lineages.
Pathologists shed new light on Sally Clark case
Authors: Clare Dyer
Journal: BMJ (2005)

The evidence for a double homicide in the case of Sally Clark, the solicitor convicted and later cleared on appeal of killing her two baby sons, was “overwhelming,” the General Medical Council was told last week.

Alison Armour, a consultant pathologist, said she did not believe that either death was natural. She would not exclude shaken baby syndrome or smothering as the cause of death of Mrs Clark's second son, Harry. Her first son, Christopher, had marks of violence on his body, and she would describe the cause of death as “unascertained.”

Dr Armour, a consultant pathologist for Lancashire Teaching Hospitals NHS Trust and a pathologist for the Home Office, was giving evidence on behalf of Dr Alan Williams, the pathologist who …