tbuckley/cabot-search huggingface dataset:
A Vision for Patient-Centered Health Information Systems
Authors: Alex H. Krist
Journal: JAMA (2011)

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The Effect of Particulate Air Pollution on Emergency Admissions for Myocardial Infarction: A Multicity Case-Crossover Analysis
Authors: Antonella Zanobetti, Joel Schwartz
Journal: Environmental Health Perspectives (2005)

Recently, attention has focused on whether particulate air pollution is a specific trigger of myocardial infarction (MI). The results of several studies of single locations assessing the effects of ambient particular matter on the risk of MI have been disparate. We used a multicity case-crossover study to examine risk of emergency hospitalization associated with fine particulate matter (PM) with aerodynamic diameter < 10 microm (PM10) for > 300,000 MIs during 1985-1999 among elderly residents of 21 U.S. cities. We used time-stratified controls matched on day of the week or on temperature to detect possible residual confounding by weather. Overall, we found a 0.65% [95% confidence interval (CI), 0.3-1.0%] increased risk of hospitalization for MI per 10 microg/m3 increase in ambient PM10 concentration. Matching on apparent temperature yielded a 0.64% increase in risk (95% CI, 0.1-1.2%). We found that the effect size for PM10 doubled for subjects with a previous admission for chronic obstructive pulmonary disease or a secondary diagnosis of pneumonia, although these differences did not achieve statistical significance. There was a weaker indication of a larger effect on males but no evidence of effect modification by age or the other diagnoses. We also found that the shape of the exposure-response relationship between MI hospitalizations and PM10 is almost linear, but with a steeper slope at levels of PM10 < 50 microg/m3. We conclude that increased concentrations of ambient PM10 are associated with increased risk of MI among the elderly.
Lipid profiling identifies a triacylglycerol signature of insulin resistance and improves diabetes prediction in humans
Authors: Eugene P. Rhee, Susan Cheng, Martin G. Larson, Geoffrey A. Walford, Gregory D. Lewis, Elizabeth McCabe, Elaine Yang, Laurie Farrell, Caroline S. Fox, Christopher J. O’Donnell, Steven A. Carr, Ramachandran S. Vasan, Jose C. Florez, Clary B. Clish, Thomas J. Wang, Robert E. Gerszten
Journal: Journal of Clinical Investigation (2011)

Dyslipidemia is an independent risk factor for type 2 diabetes, although exactly which of the many plasma lipids contribute to this remains unclear. We therefore investigated whether lipid profiling can inform diabetes prediction by performing liquid chromatography/mass spectrometry-based lipid profiling in 189 individuals who developed type 2 diabetes and 189 matched disease-free individuals, with over 12 years of follow up in the Framingham Heart Study. We found that lipids of lower carbon number and double bond content were associated with an increased risk of diabetes, whereas lipids of higher carbon number and double bond content were associated with decreased risk. This pattern was strongest for triacylglycerols (TAGs) and persisted after multivariable adjustment for age, sex, BMI, fasting glucose, fasting insulin, total triglycerides, and HDL cholesterol. A combination of 2 TAGs further improved diabetes prediction. To explore potential mechanisms that modulate the distribution of plasma lipids, we performed lipid profiling during oral glucose tolerance testing, pharmacologic interventions, and acute exercise testing. Levels of TAGs associated with increased risk for diabetes decreased in response to insulin action and were elevated in the setting of insulin resistance. Conversely, levels of TAGs associated with decreased diabetes risk rose in response to insulin and were poorly correlated with insulin resistance. These studies identify a relationship between lipid acyl chain content and diabetes risk and demonstrate how lipid profiling could aid in clinical risk assessment.
Cysteine Protease Inhibitors Cure an Experimental <i>Trypanosoma cruzi</i> Infection
Authors: Juan C. Engel, Patricia S. Doyle, Ivy Hsieh, James H. McKerrow
Journal: The Journal of Experimental Medicine (1998)

Trypanosoma cruzi is the causative agent of Chagas' disease. The major protease, cruzain, is a target for the development of new chemotherapy. We report the first successful treatment of an animal model of Chagas' disease with inhibitors designed to inactivate cruzain. Treatment with fluoromethyl ketone-derivatized pseudopeptides rescued mice from lethal infection. The optimal pseudopeptide scaffold was phenylalanine-homophenylalanine. To achieve cure of infection, this pseudopeptide scaffold was incorporated in a less toxic vinyl sulfone derivative. N-methyl piperazine-Phe-homoPhe-vinyl sulfone phenyl also rescued mice from a lethal infection. Six of the treated mice survived over nine months, three without further treatment. Three mice that had entered the chronic stage of infection were retreated with a 20-d regimen. At the conclusion of the experiments, five of the six mice had repeated negative hemacultures, indicative of parasitological cure. Studies of the effect of inhibitors on the intracellular amastigote form suggest that the life cycle is interrupted because of inhibitor arrest of normal autoproteolytic cruzain processing at the level of the Golgi complex. Parasites recovered from the hearts of treated mice showed the same abnormalities as those treated in vitro. No abnormalities were noted in the Golgi complex of host cells. This study provides proof of concept that cysteine protease inhibitors can be given at therapeutic doses to animals to selectively arrest a parasitic infection.
Through uncharted waters
Authors: T Greenway
Journal: BMJ (1994)

Contemporary general practice teaching encourages us to assess our patients' emotionalresponse to illness. As a profession our response is too often to medicalise feelings. Emotions are mistaken for psychopathology; fear and apprehension labelled as anxiety; sadness as depression. We compound matters by treating pharmacologically rather than reassuring. Reassurance is undervalued. If we explore our patients' fears and concerns, clarify their beliefs about their illness, if we can listen to them and given them time to talk we can begin to give them appropriate explanations about their illness and our proposed management. More importantly we allow the development of trust. I think it is this combination of addressing both intellectual and emotional issues that lessens fear and apprehensionand is the key to effective reassurance. Being a patient recently has been salutary. WhatI understood intellectually I have now experienced emotionally.

“He had used his skills to allow me to express my fears and reflect on the facts.”

Having had intermittent back pain for the past 10 years I dismissed another episode, this time with mild sciatica, brought on after a bout of winter digging. After two months,however, it was no better. I saw the physiotherapist. She cut through my self denial and said that it was a disc lesion. In spite of her treatment I got no better, probably because I declined her advice to take time off - I was a professional and indispensable. I hadpatients needing terminal care, …
Impaired oesophageal transit of capsule versus tablet formulations in the elderly.
Authors: A C Perkins, C G Wilson, P E Blackshaw, R M Vincent, R J Dansereau, K D Juhlin, P J Bekker, R C Spiller
Journal: Gut (1994)

Drug induced oesophageal injury is an important and preventable cause of iatrogenic injury. In most cases the injury is considered to be due to mucosal contact from formulations lodged in the oesophagus. A scintigraphic study was performed comparing the oesophageal transit of enteric coated tablets with similar sized and shaped gelatin capsules, using a population of elderly healthy volunteers similar in age (50-79 years) to the population most likely to be receiving regular treatment. Twenty three volunteers injected the radiolabelled tablet or capsule with 50 ml of water while sitting on two separate occasions according to a randomisation schedule. Oesophageal transit was assessed by gamma scintigraphy. Gastric residence was also assessed in 11 of 23 subjects. While the tablet was readily cleared from the oesophagus, mean transit time 4.3 seconds (range 1.0-14.0), the capsule often showed a comparatively prolonged holdup, mean transit time 20.9 seconds (range 1.5-174.5). Ten of 11 tablets emptied from the stomach intact, while all 11 capsules broke up in the stomach. Gelatin capsules showed a clear tendency to remain within the oesophagus of healthy elderly volunteers, while similar sized enteric coated tablets did not. These studies show the importance of assessing oesophageal transit when designing the formulation of drugs with a potential for oesophageal injury.
Mutations in CTC1, encoding conserved telomere maintenance component 1, cause Coats plus
Authors: Beverley H Anderson, Paul R Kasher, Josephine Mayer, Marcin Szynkiewicz, Emma M Jenkinson, Sanjeev S Bhaskar, Jill E Urquhart, Sarah B Daly, Jonathan E Dickerson, James O'Sullivan, Elisabeth Oppliger Leibundgut, Joanne Muter, Ghada M H Abdel-Salem, Riyana Babul-Hirji, Peter Baxter, Andrea Berger, Luisa Bonafé, Janice E Brunstom-Hernandez, Johannes A Buckard, David Chitayat, Wui K Chong, Duccio M Cordelli, Patrick Ferreira, Joel Fluss, Ewan H Forrest, Emilio Franzoni, Caterina Garone, Simon R Hammans, Gunnar Houge, Imelda Hughes, Sebastien Jacquemont, Pierre-Yves Jeannet, Rosalind J Jefferson, Ram Kumar, Georg Kutschke, Staffan Lundberg, Charles M Lourenço, Ramesh Mehta, Sakkubai Naidu, Ken K Nischal, Luís Nunes, Katrin Õunap, Michel Philippart, Prab Prabhakar, Sarah R Risen, Raphael Schiffmann, Calvin Soh, John B P Stephenson, Helen Stewart, Jon Stone, John L Tolmie, Marjo S van der Knaap, Jose P Vieira, Catheline N Vilain, Emma L Wakeling, Vanessa Wermenbol, Andrea Whitney, Simon C Lovell, Stefan Meyer, John H Livingston, Gabriela M Baerlocher, Graeme C M Black, Gillian I Rice, Yanick J Crow
Journal: Nature Genetics (2012)
Neurological Signs and the Heterogeneity of Schizophrenia
Authors: C Arango, B Kirkpatrick, R W Buchanan
Journal: American Journal of Psychiatry (2000)

More than 20 studies of schizophrenia have found a three-factor model of symptom complexes or syndromes consisting of hallucinations/delusions, disorganization of thought and behavior, and negative symptoms. Several lines of evidence suggest that these syndromes relate to neurobiological differences. We examined the relationship of these three syndromes to neurological signs.The relationships among the subscales of the Neurological Evaluation Scale and hallucinations/delusions, disorganization, and the deficit syndrome were examined in 83 clinically stable outpatients with schizophrenia. Patients with the deficit syndrome have enduring, idiopathic (or primary) negative symptoms.Each of the three syndromes had a distinctive pattern of relationships to neurological signs. Disorganization was significantly related to the total score on the Neurological Evaluation Scale, to sensory integration, and to the sequencing of complex motor acts. The deficit syndrome was significantly related to sensory integration only. Neither hallucinations/delusions nor a continuous measure of negative symptoms derived from the Brief Psychiatric Rating Scale (that measured both primary and secondary negative symptoms, as well as enduring and transient symptoms) was related to any of the Neurological Evaluation Scale subscales or total score. Drug treatment was not related to neurological impairment.The results further support the neurobiological significance of the three clinical syndromes of schizophrenia. Ratings on a scale measuring negative symptoms appear to be less sensitive to neurobiological correlates than is the categorization of the presence or absence of the deficit syndrome.
Evaluation of physiological standard pressures of the forearm flexor muscles during sport specific ergometry in sport climbers
Authors: V Schoeffl, S Klee, W Strecker
Journal: British Journal of Sports Medicine (2004)

Background: Chronic exertional compartment syndromes (CECS) are well known in sports medicine. Most commonly affected is the tibialis anterior muscle compartment in runners and walkers. Only a few cases of CECS of the forearm flexor muscles have been reported. Objectives: To determine pressure levels inside the deep flexor compartment of the forearms during a sport specific stress test. Method: Ten healthy, high level climbers were enrolled in a prospective study. All underwent climbing specific ergometry, using a rotating climbing wall (step test, total climbing time 9–15 minutes). Pressure was measured using a slit catheter placed in the deep flexor compartment of the forearm. Pressure, blood lactate, and heart rate were recorded every three minutes and during recovery. Results: In all the subjects, physical exhaustion of the forearms defined the end point of the climbing ergometry. Blood lactate increased with physical stress, reaching a mean of 3.48 mmol/l. Compartment pressure was related to physical stress, exceeding 30 mm Hg in only three subjects. A critical pressure of more than 40 mm Hg was never observed. After the test, the pressure decreased to normal levels within three minutes in seven subjects. The three with higher pressure levels (&gt;30 mm Hg) required a longer time to recover. Conclusions: For further clinical and therapeutic consequences, an algorithm was derived. Basic pressure below 15 mm Hg and stress pressure below 30 mm Hg as well as pressures during the 15 minute recovery period below 15 mm Hg are physiological. Pressures of 15–30 mm Hg during recovery suggest high risk of CECS, and pressures above 30 mm Hg confirm CECS.
Combination chemotherapy with gemcitabine, oxaliplatin, and paclitaxel in patients with cisplatin-refractory or multiply relapsed germ-cell tumors: a study of the German Testicular Cancer Study Group
Authors: C. Bokemeyer, K. Oechsle, F. Honecker, F. Mayer, J.T. Hartmann, C.F. Waller, I. Böhlke, C. Kollmannsberger
Journal: Annals of Oncology (2007)
Inhaled Flunisolide for Acute Severe Asthma
Authors: GUSTAVO RODRIGO, CARLOS RODRIGO
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

This randomized, double-blind trial was designed to determine the benefit of high and cumulative doses of flunisolide added to salbutamol in patients with acute asthma in the emergency room (ER). Ninety-four patients who presented to an ER for treatment of an acute exacerbation of asthma were assigned in a randomized, double-blind fashion to receive salbutamol and placebo (n = 47) or salbutamol combined with flunisolide (n = 47). Both drugs were administered successively through a metered-dose inhaler and spacer at 10-min intervals for 3 h (400 μ g of salbutamol and 1 mg of flunisolide every 10 min). In both groups, FEV1 and peak expiratory flow rate (PEFR) improved significantly over baseline values (p < 0.01). Results in the flunisolide group were significantly different from those in the placebo group at 90, 120, 150, and 180 min. Data analyzed separately in accord with the duration of the attack before presenting at the ER ( < 24 or ⩾ 24 h) showed that the placebo ⩾ 24 h group produced a significantly lower FEV1 at 120, 150, and 180 min (p = 0.041) than did the remaining groups. Our data support the theory that high and cumulative doses of inhaled flunisolide administered by metered-dose inhaler with spacer and added to salbutamol are an effective therapy for patients with acute asthma and a prolonged duration of symptoms before ER presentation.
Inhibition of the p110α isoform of PI 3-kinase stimulates nonfunctional tumor angiogenesis
Authors: Adriana Soler, Helena Serra, Wayne Pearce, Ana Angulo, Julie Guillermet-Guibert, Lori S. Friedman, Francesc Viñals, Holger Gerhardt, Oriol Casanovas, Mariona Graupera, Bart Vanhaesebroeck
Journal: The Journal of Experimental Medicine (2013)

Understanding the direct, tumor cell–intrinsic effects of PI 3-kinase (PI3K) has been a key focus of research to date. Here, we report that cancer cell–extrinsic PI3K activity, mediated by the p110α isoform of PI3K, contributes in an unexpected way to tumor angiogenesis. In syngeneic mouse models, inactivation of stromal p110α led to increased vascular density, reduced vessel size, and altered pericyte coverage. This increased vascularity lacked functionality, correlating with enhanced tumor hypoxia and necrosis, and reduced tumor growth. The role of p110α in tumor angiogenesis is multifactorial, and includes regulation of proliferation and DLL4 expression in endothelial cells. p110α in the tumor stroma is thus a regulator of vessel formation, with p110α inactivation giving rise to nonfunctional angiogenesis, which can stunt tumor growth. This type of vascular aberration differs from vascular endothelial growth factor–centered antiangiogenesis therapies, which mainly lead to vascular pruning. Inhibition of p110α may thus offer a new antiangiogenic therapeutic opportunity in cancer.
Brain tumour necrosis factor- modulates neurotransmitters in hypothalamic paraventricular nucleus in heart failure
Authors: Y.-M. Kang, R.-L. He, L.-M. Yang, D.-N. Qin, A. Guggilam, C. Elks, N. Yan, Z. Guo, J. Francis
Journal: Cardiovascular Research (2009)

AimsIncreased proinflammatory cytokines after myocardial infarction augment the progression of heart failure (HF) and are of prognostic significance. Recently, we demonstrated that increased proinflammatory cytokines in the brains of HF rats increased paraventricular nucleus (PVN) superoxide and down-regulated neuronal nitric oxide synthase (nNOS), contributing to sympathoexcitation. In this study, we explored the possible roles of brain proinflammatory cytokines and their effects on modulating PVN neurotransmitters in the exaggerated sympathetic activity in HF.
Analysis of major histocompatibility complex haplotypes of t-chromosomes reveals that the majority of diversity is generated by recombination.
Authors: K Artzt, H S Shin, D Bennett, A Dimeo-Talento
Journal: The Journal of Experimental Medicine (1985)

t-chromosomes are natural polymorphisms in feral populations of mice that are thought to be descended from a single ancestral chromosome. They carry an inversion of at least 10 cM surrounding the major histocompatibility complex (MHC) that effectively prevents recombination between a t-bearing chromosome and wild type chromosomes. However, on the rare occasion when two different t-chromosomes meet in a wild female, recombination occurs at an apparently normal rate. Since they contain the highly polymorphic MHC, their limited origin and restricted chances for recombination make t-chromosomes a valuable tool for studying the relative contributions of mutation and recombination to the generation of diversity. Using 13 different serological reagents to class I antigens, and studying restriction enzyme polymorphisms detected with three molecular probes for class II genes examined with three endonucleases, we present data indicating that the major factor responsible for the diversity of class I antigens is recombination, but that for class II genes, mutation must play an important role in addition to recombination.
Simvastatin for cognitive deficits and behavioural problems in patients with neurofibromatosis type 1 (NF1-SIMCODA): a randomised, placebo-controlled trial
Authors: Thijs van der Vaart, Ellen Plasschaert, André B Rietman, Marleen Renard, Rianne Oostenbrink, Annick Vogels, Marie-Claire Y de Wit, Mie-Jef Descheemaeker, Yvonne Vergouwe, Coriene E Catsman-Berrevoets, Eric Legius, Ype Elgersma, Henriëtte A Moll
Journal: The Lancet Neurology (2013)
THE LONDON SKULL
Authors: G. E. Smith
Journal: BMJ (1925)

I AM very grateful to Mr. Bromehead for directing my attention to the evidence for identifying the London Terraces. In reply to his query on what grounds I assign the deposit at Lloyd's to the Low Terrace instead of the Middle, I can only say that I have never claimed any competence to decide the geological points at issue; but, as I have already stated in public and in print on several occasions, have taken the opinions expressed when the ulna of the woolly rhinoceros (from the same level in the blue clay at Lloyd's) was exhibited at a meeting of the Zoological Society last March.
Antibody activity in ankylosing spondylitis sera to two sites on HLA B27.1 at the MHC groove region (within sequence 65-85), and to a Klebsiella pneumoniae nitrogenase reductase peptide (within sequence 181-199).
Authors: C Ewing, R Ebringer, G Tribbick, H M Geysen
Journal: The Journal of Experimental Medicine (1990)

74 overlapping peptides of varying lengths from Klebsiella pneumoniae nitrogenase reductase (residues 181-199) and from the HLA B27.1 molecule (residues 65-85) were synthesized and tested by ELISA against sera from HLA B27+ ankylosing spondylitis (AS) patients, and sera from HLA B27+ and HLA B27- healthy first-degree relatives. Antibody activity in AS sera to Klebsiella peptides of four to eight amino acids was maximal with the peptide NSRQTDR. Activity to HLA B27 peptides was maximal with the peptide KAKAQTDR (named epitope I). These peptides overlap with, but are proximal to the NH2 terminus from QTDRED, which is homologous in HLA B27.1 and K. pneumoniae nitrogenase reductase. A second weaker reactive site was noted in the HLA B27.1 peptides, proximal to the COOH terminus from the homologous sequence, namely peptide REDLRTLL (named epitope II). Little activity was seen against peptides that included the entire homologous sequence. Sera from 50 AS patients showed higher total Ig activity against peptides KAKAQTDR (p less than 0.001) and NSRQTDR (p less than 0.02) than did sera from 22 B27+ and 22 B27- healthy controls. These data indicate that AS patient sera contain antibodies that bind to K. pneumoniae nitrogenase peptides and HLA B27.1 peptides, and that there are at least two epitopes on HLA B27.1 in the alpha 1 domain, at the MHC groove region, that are autoantigenic in AS patients. Epitope I may be a site for crossreactivity between HLA B27 and Klebsiella.