tbuckley/cabot-search huggingface dataset:
Services with excessive delays in delivering carotid endarterectomy should close, recommends audit
Authors: S. Mayor
Journal: BMJ (2012)

People with symptoms of stroke or transient ischaemic attack (TIA) are having carotid endarterectomy to reduce their risk of severe stroke within an average of 15 days from onset of symptoms, show latest results from a regular UK audit.1 But the report shows considerable variation and recommends moving surgery from poorly performing trusts to those that meet guidelines.

The UK carotid endarterectomy audit collects information to assess the speed and quality of care of patients with carotid stenosis who undergo preventive surgery or endovascular stenting. The latest audit analysed data for 5543 patients who had carotid endarterectomy between 1 August 2010 and 30 September 2011.

Results showed that the median time between onset of symptoms and undergoing surgery was 15 days, which was less than the …
Settling in for a Long Debate
Authors: John K. Iglehart
Journal: New England Journal of Medicine (2009)

With virtually all Republicans in opposition and public opinion sharply divided, the Senate opened debate on a Democratic health care reform bill that would greatly expand insurance coverage and, its leadership hopes, reverse the erosion of the party's standing in the electorate's eyes. Prospects seem dim that the Democrats will be able to enact their proposal without scaling down its scope to accommodate the more conservative Democratic senators and two independents. Nevertheless, Majority Leader Harry Reid (D-NV) opened floor debate on December 1 by saying that “the next weekends, plural, we will be working” on the reform bill, because there . . .
Urinary Porphyrin Excretion in Neurotypical and Autistic Children
Authors: James S. Woods, Sarah E. Armel, Denise I. Fulton, Jason Allen, Kristine Wessels, P. Lynne Simmonds, Doreen Granpeesheh, Elizabeth Mumper, J. Jeffrey Bradstreet, Diana Echeverria, Nicholas J. Heyer, James P.K. Rooney
Journal: Environmental Health Perspectives (2010)

BackgroundIncreased urinary concentrations of pentacarboxyl-, precopro- and copro-porphyrins have been associated with prolonged mercury (Hg) exposure in adults, and comparable increases have been attributed to Hg exposure in children with autism (AU).ObjectivesThis study was designed to measure and compare urinary porphyrin concentrations in neurotypical (NT) children and same-age children with autism, and to examine the association between porphyrin levels and past or current Hg exposure in children with autism.MethodsThis exploratory study enrolled 278 children 2–12 years of age. We evaluated three groups: AU, pervasive developmental disorder-not otherwise specified (PDD-NOS), and NT. Mothers/caregivers provided information at enrollment regarding medical, dental, and dietary exposures. Urine samples from all children were acquired for analyses of porphyrin, creatinine, and Hg. Differences between groups for mean porphyrin and Hg levels were evaluated. Logistic regression analysis was conducted to determine whether porphyrin levels were associated with increased risk of autism.ResultsMean urinary porphyrin concentrations are naturally high in young children and decline by as much as 2.5-fold between 2 and 12 years of age. Elevated copro- (p &lt; 0.009), hexacarboxyl- (p &lt; 0.01) and pentacarboxyl- (p &lt; 0.001) porphyrin concentrations were significantly associated with AU but not with PDD-NOS. No differences were found between NT and AU in urinary Hg levels or in past Hg exposure as determined by fish consumption, number of dental amalgam fillings, or vaccines received.ConclusionsThese findings identify disordered porphyrin metabolism as a salient characteristic of autism. Hg exposures were comparable between diagnostic groups, and a porphyrin pattern consistent with that seen in Hg-exposed adults was not apparent.
Observations on the Vasodilator Properties of Urine
Authors: S. J. SARNOFF, R. B. CASE, R. MACRUZ, L. C. SARNOFF, K. E. SUSSMAN, J. V. PIERCE
Journal: Circulation Research (1958)

These experiments trace the recent interest in the vasodilator properties of urine. This interest was triggered by the incidental observation of a potent coronary dilator influence when urine was introduced into the reservoir of the isolated supported heart preparation. A comparison of human urine with nitroglycerin then revealed that 10 ml. of urine had 2 to 3 times the dilator potency of 0.6 mg. nitroglycerin. Neither agent altered myocardial oxygen consumption or efficiency at the peak of their effect. The development of a simple, rapid and reproducible bioassay technic which would permit the comparative examination of numerous samples in the same preparation was a necessary precursor to realizing the broader objective of ascertaining whether the vasodilator substance in urine has physiologic significance for circulatory regulation. Accordingly, a re-examination was made of the limitations of the femoral arterial flow technic. The irregularity in the amplitude and contour of sequential responses to the same test substance in spite of an apparently steady hemodynamic state suggested the possibility of inadequate mixing after injections into the external circuit. Model studies with blue dye confirmed this impression and a magnetic mixer was therefore introduced into the external circuit in order to thoroughly mix the injected material. This resulted in substantially improved reproducibility and the obtaining of satisfactory dose-response curves. This technic was then used to assay the 24 hour output of vasodilator activity in the urine of 5 hypotensive patients and 5 normal individuals. The hypotensive group exhibited something less than 15 per cent of that secreted by the control group. The substance under examination is non-dialyzable and, chemically, resembles callicrein. The urines from 9 mammalian species all exhibited high activity. These observations were construed as being compatible with the hypothesis that the vasodilator agent under examination is, in some way, associated with autonomic function and/or the regulation of arterial pressure. This view was supported by the observation of a diminished vasodilator output in the sheep while under the influence of ganglionic blockade with hexamethonium.
Vitamin A and zinc therapy in primary biliary cirrhosis
Authors: H. Franklin Herlong, Robert M. Russell, Willis C. Maddrey
Journal: Hepatology (1981)

Eleven patients with primary biliary cirrhosis were surveyed for evidence of vitamin A and zinc deficiencies. Vitamin A deficiency manifested as a low serum vitamin A concentration and abnormal dark adaptation was present in 9 of the 11 patients. A low serum zinc level was present in four patients who were also vitamin A deficient. All seven patients who received p.o. vitamin A therapy with 25,000 to 50,000 units per day for 4 to 12 weeks achieved normal vitamin A levels. Normalization of serum vitamin A was associated with significant improvement in dark adaptation (p less than 0.01). In three patients, normalization of serum vitamin A level did not correct the abnormal dark adaptation. These three patients also had decreased serum zinc levels and dark adaptation abnormalities were corrected following p.o zinc supplementation. These studies suggest high dose and long term p.o. vitamin A and zinc therapy may be required to correct abnormalities in dark adaptation in patients with primary biliary cirrhosis.
Treatment of paroxysmal supraventricular tachycardia in infancy with digitalis, adenosine-5'-triphosphate, and verapamil: a comparative study.
Authors: R Greco, B Musto, V Arienzo, A Alborino, S Garofalo, F Marsico
Journal: Circulation (1982)

The treatment of paroxysmal supraventricular tachycardia (PSVT) in infancy with digitalis, adenosine triphosphate (ATP) and verapamil is reported. Treatment was successful in about 90% of the patients treated with ATP and verapamil and in 61--71% of the patients treated with digitalis (Lanatoside C). Verapamil terminated the tachycardia within 2 minutes of administration in most instances and ATP in less than 1 minute. Digitalis, however, took as long as 2 hours; it was therefore excluded as the drug of first choice in emergencies, and is better suited for treating patients with poor hemodynamics. Side effects with ATP are common but short-lived. With verapamil, side effects are rare, but may be serious if certain contraindications are not taken into account. Digitalis in the dose used in this trial rarely produced side effects. We conclude that ATP or verapamil is the drug of first choice for quick termination of PSVT in infancy.
CONTAGION AS A FACTOR IN THE SPREAD OF TYPHOID FEVER IN THE MILITARY SERVICE.
Authors: CHARLES F. MASON
Journal: JAMA (1907)

The abstract of the report on the origin and spread of typhoid fever in the United States military camps during the Spanish War of 1898, by Majors Reed, Vaughan and Shakespeare showed conclusively that personal contact was a most important factor in the spread of typhoid fever in military camps. The lesson of that experience was thoroughly taken to heart by the medical department of the army, and on request of the Surgeon General the attention of all officers and men was called to the importance of this method of infection and to the means of preventing it by the following circular: [CircularNo. 62.] HEADQUARTERS OF THE ARMY, Adjutant General's Office, Washington, Dec. 24, 1902. By direction of the Secretary of War, the following memorandum, prepared by the Surgeon General of the Army, on the subject of typhoid fever contagion and the means of preventing it is published to
Reversal of Ethanol and Indomethacin–Induced Suppression of Hepatic Dna Synthesis by 16,16–Dimethyl Prostaglandin E2
Authors: Gloria E. McNeil, Thomas S. Chen, Carroll M. Leevy
Journal: Hepatology (1985)

Investigations were undertaken to determine effectiveness of 16,16-dimethyl prostaglandin E2 (dmPGE2) in overcoming the suppressive effects of ethanol and/or indomethacin on hepatic DNA synthesis. Adult litter mate Sprague-Dawley rats were subjected to sham operation or partial hepatectomy. Immediately after partial hepatectomy, and at 8-hr intervals for 24 hr, the rats were given: (a) ethanol with and without dmPGE2 or (b) indomethacin with and without ethanol and/or dmPGE2. DmPGE2 produced a significant increase in DNA synthesis in sham-operated (p less than 0.001) and untreated partially hepatectomized animals (p less than 0.025). Ethanol and indomethacin caused a 6- and 18-fold reduction, respectively, in hepatic DNA synthesis following partial hepatectomy. DmPGE2 overcame the inhibitory effect of ethanol (p less than 0.005) and indomethacin (p less than 0.0005) in partially hepatectomized animals. Mitoses were decreased concomitantly with ethanol and/or indomethacin-induced reduction in DNA synthesis and increased with administration of dmPGE2. It is concluded that dmPGE2 increases hepatic DNA synthesis and regeneration in normal rat liver and overcomes their inhibition when ethanol and/or indomethacin is given after partial hepatectomy. Timing of dmPGE2 administration is crucial. When given 30 min before ethanol, it completely inhibits suppression of regenerative activity; omission of this "priming" dmPGE2 dose results in only 44% of DNA synthesis obtained in control animals.
Fibronectin deposition in delayed-type hypersensitivity. Reactions of normals and a patient with afibrinogenemia.
Authors: R A Clark, C R Horsburgh, A A Hoffman, H F Dvorak, M W Mosesson, R B Colvin
Journal: Journal of Clinical Investigation (1984)

During development of delayed hypersensitivity (DH) skin reactions, fibronectin accumulates in two distinct sites: (a) the dermal interstitium in a pattern similar to fibrin and with a time course similar to that of fibrin deposition and mononuclear cell infiltration, and (b) blood vessel walls in a pattern suggestive of basement membrane staining and with a time course similar to that of endothelial cell proliferation. In vitro fibronectin can bind to monocytes or endothelial cells and simultaneously bind to fibrin or collagen matrices; by such interaction in vivo it may affect cell migration or proliferation. Thus, fibronectin deposition in DH reactions may facilitate cell-matrix interactions; however, the possibility exists that extravascular fibronectin accumulation may be only secondary to interstitial fibrin clot formation, and that blood vessel-associated fibronectin may be only a function of adsorption onto basement membrane (type IV) collagen. To address these possibilities, we investigated the association of fibronectin with fibrin, type IV collagen, and mononuclear cell infiltrates in DH reactions. Skin sites of DH reactions in normal volunteers were biopsied at 24, 48, and 72 h after intradermal challenge and examined by immunofluorescence technique. At all time points most of the interstitial fibronectin coincided with fibrin; however, some interstitial fibronectin was coincident with mononuclear cells positive for HLA-DR or monocyte-specific antigen. The coincidence of fibronectin with mononuclear cells was more apparent in a 48-h DH reaction from a patient with congenital afibrinogenemia. Vessel wall fibronectin was increased by 48 h after challenge and appeared as a fine linear band on the luminal side of a much thicker band of type IV collagen. Thus, the coincidence of extravascular fibronectin with mononuclear cells, its appearance without fibrin in the site from a patient with afibrinogenemia, and incomplete correspondence of vessel wall fibronectin with type IV collagen suggest that fibronectin localization in DH reactions involves endothelial cell and mononuclear cell binding as well as adsorption to fibrin and/or type IV collagen.
Neuromedin U: A Candidate Biomarker and Therapeutic Target to Predict and Overcome Resistance to HER-Tyrosine Kinase Inhibitors
Authors: Sweta Rani, Claire Corcoran, Liam Shiels, Serena Germano, Susan Breslin, Stephen Madden, Martina S. McDermott, Brigid C. Browne, Norma O'Donovan, John Crown, Martina Gogarty, Annette T. Byrne, Lorraine O'Driscoll
Journal: Cancer Research (2014)

Intrinsic and acquired resistance to HER-targeting drugs occurs in a significant proportion of HER2-overexpressing breast cancers. Thus, there remains a need to identify predictive biomarkers that could improve patient selection and circumvent these types of drug resistance. Here, we report the identification of neuromedin U (NmU) as an extracellular biomarker in cells resistant to HER-targeted drugs. NmU overexpression occurred in cells with acquired or innate resistance to lapatinib, trastuzumab, neratinib, and afatinib, all of which displayed a similar trend upon short-term exposure, suggesting NmU induction may be an early response. An analysis of 3,489 cases of breast cancer showed NmU to be associated with poor patient outcome, particularly those with HER2-overexpressing tumors independent of established prognostic indicators. Ectopic overexpression of NmU in drug-sensitive cells conferred resistance to all HER-targeting drugs, whereas RNAi-mediated attenuation sensitized cells exhibiting acquired or innate drug resistance. Mechanistic investigations suggested that NmU acted through HSP27 as partner protein to stabilize HER2 protein levels. We also obtained evidence of functional NmU receptors on HER2-overexpressing cells, with the addition of exogenous NmU eliciting an elevation in HER2 and EGFR expression along with drug resistance. Finally, we found that NmU seemed to function in cell motility, invasion, and anoikis resistance. In vivo studies revealed that NmU attenuation impaired tumor growth and metastasis. Taken together, our results defined NmU as a candidate drug response biomarker for HER2-overexpressing cancers and as a candidate therapeutic target to limit metastatic progression and improve the efficacy of HER-targeted drugs.
Ischemic Optic Neuropathy Decompression Trial
Authors: Don B. Smith
Journal: JAMA (1995)

<h3>To the Editor.</h3> —Regarding the publication by the Ischemic Optic Neuropathy Decompression Trial (IONDT) Research Group,<sup>1</sup>it seems noteworthy that 72% of the surgically treated patients in this trial were treated more than a week after onset of symptoms. No one was treated within the first 24 hours. Given that the window of opportunity for treatment of acute ischemic cerebrovascular disease is probably 6 hours or less, one wonders whether the treatment is truly ineffective or whether it was simply applied much too late.
Let the Experiment Be Fairly Made
Authors: Marlys Hearts Witte
Journal: JAMA (1978)

In 1869, Edward Clarke, MD, professor of materia medica at Harvard, publicly denounced male medical students in Philadelphia for chasing women out of the classroom with tobacco quid and tinfoil and pleaded that aspiring women be given the chance free of harrassment to prove their worth in medicine: "Let the experiment be fairly made and in 50 years we will get the answer."<sup>1</sup> Reluctantly set into motion more than a century ago and involving generations of eager research subjects (female medical students) who followed the protocol unswervingly, the experiment has produced little in the way of hard scientific data. The discovery that gender does not influence performance in a general medicine clerkship at the University of Kansas, as reported by Holmes et al in this issue ofThe Journal(p 2259), is in keeping with earlier studies demonstrating that men and women score equivalently on parts 1 and 2
Obesity and Heart Failure — Risk Factor or Mechanism?
Authors: Barry M. Massie
Journal: New England Journal of Medicine (2002)

As has been noted repeatedly by expert panels and the lay press, nearly 60 percent of the adult population of the United States is overweight or obese, with substantial resulting morbidity and mortality.1 Since obesity increases the risk of the most frequent causes of heart failure, an association between these conditions is to be expected. Indeed, an increased risk of heart failure has previously been noted in the Framingham Heart Study and in other cohort studies.24 However, controversy has persisted with regard to whether obesity is an independent risk factor for heart failure or even coronary heart disease. For . . .
Skeletal Muscle Involvement in Systemic Sclerosis
Authors: J. M. Thompson, R. Bluestone, E. G. L. Bywaters, J. Dorling, M. Johnson
Journal: Annals of the Rheumatic Diseases (1969)

Fifteen unselected patients (13 women, 2 men) aged from 28 to 72 years (mean 48 6) with systemic sclerosis were studied.In addition to evaluation of skeletal muscle, appropriate investigations to characterize 281 copyright.
Defective splicing of mRNA from one COL1A1 allele of type I collagen in nondeforming (type I) osteogenesis imperfecta.
Authors: M L Stover, D Primorac, S C Liu, M B McKinstry, D W Rowe
Journal: Journal of Clinical Investigation (1993)

Osteogenesis imperfecta (OI) type I is the mildest form of heritable bone fragility resulting from mutations within the COL1A1 gene. We studied fibroblasts established from a child with OI type I and demonstrated underproduction of alpha 1 (I) collagen chains and alpha 1 (I) mRNA. Indirect RNase protection suggested two species of alpha 1 (I) mRNA, one of which was not collinear with fully spliced alpha 1 (I) mRNA. The noncollinear population was confined to the nuclear compartment of the cell, and contained the entire sequence of intron 26 and a G-->A transition in the first position of the intron donor site. The G-->A transition was also identified in the genomic DNA. The retained intron contained an in-frame stop codon and introduced an out-of-frame insertion within the collagen mRNA producing stop codons downstream of the insertion. These changes probably account for the failure of the mutant RNA to appear in the cytoplasm. Unlike other splice site mutations within collagen mRNA that resulted in exon skipping and a truncated but inframe RNA transcript, this mutation did not result in production of a defective collagen pro alpha 1 (I) chain. Instead, the mild nature of the disease in this case reflects failure to process the defective mRNA and thus the absence of a protein product from the mutant allele.
Metastatic Lymph Node and Osteolytic Skeletal Metastasis Detected by FDG-PET in an Endoscopy-Diagnosed Early-Stage Esophageal Cancer
Authors: Tay-Jiunn Lee, Horng-Yuan Lou, Chi-Ming Lee, Chung-Huei Hsu
Journal: Clinical Nuclear Medicine (2005)

A 50-year-old man who had chronic peptic ulcer disease with an early-stage squamous cell carcinoma in the lower third of the esophagus. The primary tumor was not visualized on an FDG-PET study. However, a paraaortic lymph node metastasis in the upper abdomen was demonstrated in this initial staging. The patient underwent an operation at another hospital. The postoperative staging was classified as stage I (T1N0M0: tumor invasion limited to submucosa, no regional lymph node metastasis 0/47, no distant metastais). One year later, a protruding firm mass developed over the sternum. Follow-up FDG-PET showed foci with intense activity in the sternal and epigastric regions. Although conventional MDP bone scan did not clearly show the lesion, an osteolytic skeletal metastasis to the sternum and progressive enlargement of the metastatic paraaortic lymph node were identified by PET.
60 Analysis of HBV-specific T-cell responses in patients with occult HBV infection
Authors: A. Zerbini, M. Pilli, C. Boni, P. Fisicaro, A. Penna, D. Laccabue, P. Di Vincenzo, T. Giuberti, G. Raffa, T. Pollicino, G. Raimondo, C. Ferrari, G. Missale
Journal: Journal of Hepatology (2006)
THE ETIOLOGY OF ACUTE ARTICULAR RHEUMATISM.
Authors: GEORGE W. WEBSTER
Journal: JAMA (1903)

At the outset, while it may seem trite, it may be well to define the sense in which the term etiology is used as well as to indicate what is meant by the term rheumatism. We here employ the term cause in the same sense as we do in typhoid fever, pneumonia, pulmonary tuberculosis, etc., in which we recognize that aside from the infective agent there must be what some have called the soil, susceptibility to infection varying from extreme susceptibility on the one hand to complete immunity on the other; and that the latter may for certain animals and diseases be variable in degree and also either hereditary or acquired. In order to limit discussion the term rheumatism will be confined to those cases of non-suppurative arthritis occurring especially in children, but which also occur in the adult. This is the view of Poynton and Paine<sup>1</sup>They say: "All suppurative arthritis must, we think,