tbuckley/cabot-search huggingface dataset:
Is it more effective for highly trained swimmers to live and train at 1200 m than at 1850 m in terms of performance and haematological benefits?
Authors: B Roels, P Hellard, L Schmitt, P Robach, J-P Richalet, G P Millet
Journal: British Journal of Sports Medicine (2006)

Objectives: The effects of living and training have not been compared at different altitudes in well trained subjects. Methods: Nine international swimmers lived and trained for 13 days similarly at 1200 m (T1200) and 1850 m (T1850). The two altitude training periods were separated by six weeks of sea level training. Before and after each training trip, subjects performed, at an altitude of 1200 m, an incremental exercise test to exhaustion of 5 × 200 m swims and a maximal test over 2000 m. Results: There was no difference in V˙ o 2 max after each training trip: the before values were 58.5 (5.6) and 60.4 (6.7) ml/kg/min and the after values were 56.2 (5.2) and 57.1 (4.7) ml/kg/min for T1200 and T1850 respectively. The 2000 m performance had improved during T1200 (1476 (34) to 1448 (45) seconds) but not during T1850 (1458 (35) v 1450 (33) seconds). Mean cell volume increased during T1850 (86.6 (2.8) to 88.7 (2.9) µm 3 ) but did not change during T1200 (85.6 (2.9) v 85.7 (2.9) µm 3 ). The proportion of reticulocytes decreased during T1200 (15.2 (3.8)% to 10.3 (3.4)%) and increased during T1850 (9.3 (1.6)% to 11.9 (3.5)%). Conclusions: The short term effects of 13 days of training at 1200 m on swimming performance appear to be greater than the same type of training for the same length of time at 1850 m. As mean cell volume and proportion of reticulocytes only increased during training at 1850 m, the benefits of training at this altitude may be delayed and appear later on.
Consequences of opiate agonist and antagonist in myocardial ischaemia suggest a role of endogenous opioid peptides in ischaemic heart disease
Authors: A. Y.-S. Lee, Y.-T. Chen, M.-N. Kan, F.-K. P'eng, C.-Y. Chai, J.-S. Kuo
Journal: Cardiovascular Research (1992)

The aim was to evaluate the effects of an opiate agonist (U50,488H) and an opiate antagonist (naloxone) in myocardial ischaemia.A left thoracotomy was performed and the left coronary artery was ligated in adult Sprague-Dawley rats of either sex (350-400 g). Blood pressure, heart rate and electrocardiogram were measured before and after injections of U50,488H or naloxone and throughout the 30 min postligation period.Following coronary artery occlusion, all rats in the control group developed arrhythmias, bradycardia, and hypotension. U50,488H potentiated and naloxone attenuated the ischaemia induced arrhythmias, bradycardia, and hypotension.The potentiating and blocking effects of U50,488H and naloxone, respectively, suggest that endogenous opioid peptides are involved in the pathophysiology of myocardial ischaemia and play an important role in ischaemic heart disease.
Randomised comparison of morbidity after D1 and D2 dissection for gastric cancer in 996 Dutch patients
Authors: J.J. Bonenkamp, I. Songun, K. Welvaart, C.J.H. van de Velde, J. Hermans, M. Sasako, J.T.M. Plukker, P. van Elk, H. Obertop, D.J. Gouma, C.W. Taat, J. van Lanschot, S. Meyer, P.W. de Graaf, M.F. von Meyenfeldt, H. Tilanus
Journal: The Lancet (1995)
Relation between Urinary Hydroxyproline and Parathyroid Function*
Authors: Harry R. Keiser, John R. Gill, Albert Sjoerdsma, Frederic C. Bartter
Journal: Journal of Clinical Investigation (1964)

1). 1 Eli Lilly & Co., Indianapolis, Ind. received constant diets containing at most 120 g of lean, red meat daily, but no fish, Jello, ice cream, or other gelatin-rich foods.PTE was given intramuscularly at a dosage of 600 U a day for 10 to 12 days.Urine was collected in 24-hour pools under toluene and stored in a cold room at 4°C.Feces were collected in 4-or 6-day pools.2) Four-hour calcium infusion.Calcium glucohepto-
Antiarrhythmic drug use in the implantable defibrillator arm of the antiarrhythmics vs implantable defibrillators (AVID) study
Authors: J.S. Steinberg, J.B. Martins, M. Domanski, P. Foster, B. Goldner, H.L. Greene, E. Monchavez-Tan, C. Rizo-Patron, A. Russo, N. Tullo, R. Moore, A. Hallstrom
Journal: Journal of the American College of Cardiology (1998)
Assessment of the 12-Lead ECG as a Screening Test for Detection of Cardiovascular Disease in Healthy General Populations of Young People (12–25 Years of Age)
Authors: Barry J. Maron, Richard A. Friedman, Paul Kligfield, Benjamin D. Levine, Sami Viskin, Bernard R. Chaitman, Peter M. Okin, J. Philip Saul, Lisa Salberg, George F. Van Hare, Elsayed Z. Soliman, Jersey Chen, G. Paul Matherne, Steven F. Bolling, Matthew J. Mitten, Arthur Caplan, Gary J. Balady, Paul D. Thompson
Journal: Circulation (2014)
Changes in biomarkers after therapeutic intervention in temporal arteries cultured in Matrigel: a new model for preclinical studies in giant-cell arteritis
Authors: Marc Corbera-Bellalta, Ana García-Martínez, Ester Lozano, Ester Planas-Rigol, Itziar Tavera-Bahillo, Marco A Alba, Sergio Prieto-González, Montserrat Butjosa, Georgina Espígol-Frigolé, José Hernández-Rodríguez, Pedro L Fernández, Pascale Roux-Lombard, Jean-Michel Dayer, Mahboob U Rahman, Maria C Cid
Journal: Annals of the Rheumatic Diseases (2013)

Background Search for therapeutic targets in giant-cell arteritis (GCA) is hampered by the scarcity of functional systems. We developed a new model consisting of temporal artery culture in tri-dimensional matrix and assessed changes in biomarkers induced by glucocorticoid treatment. Methods Temporal artery sections from 28 patients with GCA and 22 controls were cultured in Matrigel for 5 days in the presence or the absence of dexamethasone. Tissue mRNA concentrations of pro-inflammatory mediators and vascular remodelling molecules was assessed by real-time RT-PCR. Soluble molecules were measured in the supernatant fluid by immunoassay. Results Histopathological features were exquisitely preserved in cultured arteries. mRNA concentrations of pro-inflammatory cytokines (particularly IL-1β and IFNγ), chemokines (CCL3/MIP-1α, CCL4/MIP-1β, CCL5/RANTES) and MMP-9 as well as IL-1β and MMP-9 protein concentrations in the supernatants were significantly higher in cultured arteries from patients compared with control arteries. The culture system itself upregulated expression of cytokines and vascular remodelling factors in control arteries. This minimised differences between patients and controls but underlines the relevance of changes observed. Dexamethasone downregulated pro-inflammatory mediator (IL-1β, IL-6, TNFα, IFNγ, MMP-9, TIMP-1, CCL3 and CXCL8) mRNAs but did not modify expression of vascular remodelling factors (platelet derived growth factor, MMP-2 and collagens I and III). Conclusions Differences in gene expression in temporal arteries from patients and controls are preserved during temporal artery culture in tri-dimensional matrix. Changes in biomarkers elicited by glucocorticoid treatment satisfactorily parallel results obtained in vivo. This may be a suitable model to explore pathogenetic pathways and to perform preclinical studies with new therapeutic agents.
Milder Presentation of Recessive Polycystic Kidney Disease Requires Presence of Amino Acid Substitution Mutations
Authors: Laszlo Furu, Luiz F. Onuchic, Ali Gharavi, Xiaoying Hou, Ernie L. Esquivel, Yasuyuki Nagasawa, Carsten Bergmann, Jan Senderek, Ellis Avner, Klaus Zerres, Gregory G. Germino, Lisa M. Guay-Woodford, Stefan Somlo
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Autosomal recessive polycystic kidney disease (ARPKD; MIM 263200) is a hereditary and severe form of polycystic disease affecting the kidneys and biliary tract with an estimated incidence of 1 in 20,000 live births. The clinical spectrum is widely variable: up to 50% of affected neonates die shortly after birth, whereas others survive to adulthood. Mutations at a single locus, polycystic kidney and hepatic disease 1 (PKHD1), are responsible for all typical forms of ARPKD. Mutation detection was performed in PKHD1 by DHPLC in 85 affected, unrelated individuals. Seventy-four amplicons were amplified and analyzed from the PKHD1 genomic locus. Sequence variants were considered pathogenic when they were not observed in 160 control individuals (320 chromosomes). For purposes of genotype-phenotype comparisons, families were stratified by clinical presentation into two groups: the severe perinatal group, in which at least one affected child presented with perinatal disease and neonatal demise, and the less severe, nonperinatal group, in which none of the affected children died in the neonatal period. Forty-one mutations were found in 55 affected disease chromosomes; 32 of these mutations have not been reported previously. Mutations were distributed throughout the portions of gene encoding the predicted extracellular portion of the protein product. The most commonly encountered mutation, T36M, was found in 8 of 55 disease chromosomes. Amino acid substitutions were found to be more commonly associated with a nonlethal presentation, whereas chain terminating mutations were more commonly associated with neonatal demise (χ2 = 11.54, P = 0.003). All patients who survive the neonatal period have at least one amino acid substitution mutation, suggesting that such substitutions produce milder disease through production of partially functional protein products. The nature of the germline mutations in ARPKD plays a significant role in determining clinical outcome. E-mail: [email protected]
Detrimental role for CD4+ T lymphocytes in murine diffuse peritonitis due to inhibition of local bacterial elimination
Authors: M Busse, T Traeger, C Potschke, A Billing, A Dummer, E Friebe, C Kiank, U Grunwald, R S Jack, C Schutt, C-D Heidecke, S Maier, B M Broker
Journal: Gut (2007)

Abdominal sepsis due to intestinal leakage of endogenous gut bacteria is a life-threatening condition. In healthy individuals, T lymphocytes have essential functions in balancing the immune response to the commensal gut flora.To determine how T lymphocytes shape the process of diffuse faecal peritonitis.In colon ascendens stent peritonitis (CASP), a clinically relevant mouse model of diffuse peritonitis, the kinetics of systemic T cell activation were investigated by assessment of activation markers. CD4(+) T cells were then depleted with monoclonal antibodies, and survival, bacterial dissemination and cytokine concentrations were measured. T cell receptor signalling was blocked with tacrolimus.In diffuse peritonitis, CD4(+) T cells, both Foxp3(-) and Foxp3(+), became systemically involved within hours and upregulated CTLA-4 and other activation markers. Depletion of the CD4(+) T cells enhanced local bacterial clearance from the peritoneal cavity, reduced bacterial dissemination and improved survival. This was accompanied by increased immigration of granulocytes and macrophages into the peritoneum, indicating that CD4(+) T cells inhibit the local innate immune response. Blockade of T cell receptor (TCR) signalling by tacrolimus did not influence the survival in this peritonitis model, showing that the inhibitory effects of the CD4(+) T lymphocytes were independent of TCR-mediated antigen recognition.In diffuse peritonitis caused by commensal gut bacteria the CD4(+) T lymphocytes exert a net negative effect on the local anti-bacterial defence, and thereby contribute to bacterial dissemination and poor outcome.
Immunologically induced purulent anterior segment inflammation of the guinea pig eye
Authors: D. Sompolinsky, L. Lundberg, J. U. Prause
Journal: Allergy (1992)

A single conjunctival application of ovalbumin to inbred guinea pigs (IMM/S 209) immunized with the same antigen in Freund's complete adjuvant provoked an acute purulent inflammation of the anterior segment of the eyes with a duration of up to 1 week. Intense conjunctival injection and chemosis were followed by a purulent discharge. A corneal haze was observed regularly, and a considerable proportion of the animals developed a pronounced pannus and corneal ulcers. Tear fluid cytology revealed a rapid increase in cell concentration, from the normal level (&lt; 10 8 /1) to &gt; 10 11 /1.Seventy to 95% of the cells were polymorphonuclear leukocytes. Histological examination revealed an acute inflammatory reaction which radiated from the conjunctival fornices to the entire anterior segments of the eyes. The process was characterized by an intense oedema, vasodilation and perivascular aggregations of polymorphonuclear leukocytes, and to a lesser extent eosinophilic granulocytes which characteristically infiltrated and penetrated the epithelial layers. Ncovascularization could be observed early after challenge in the stroma of all parts of the outer eye. Ulcerations of the conjunctival and corneal epithelia were observed frequently. After a number of reiterations of the antigenic challenge, a marked infiltration with lymphocytes and basophils/mast cells was observed, and significant scarring of the conjunctival mucosa developed. In several animals, a slight, but significant co‐reaction of the contra‐lateral, non‐challenged eye was observed.
Effect of negative pressure ventilation on arterial blood gas pressures and inspiratory muscle strength during an exacerbation of chronic obstructive lung disease.
Authors: J. M. Montserrat, J. A. Martos, A. Alarcon, R. Celis, V. Plaza, C. Picado
Journal: Thorax (1991)

The effects of intermittent negative pressure ventilation have been studied in 20 patients with chronic obstructive pulmonary disease during an exacerbation of their disease. Measurements of arterial blood gas tensions and maximal inspiratory pressure (MIP) were performed before and after six hours of negative pressure ventilation or standard treatment (control day) given in random order on two consecutive days. After negative pressure ventilation the mean (SD) value of MIP increased from 68.1 (21.5) to 74.8 (20) cm H2O;* arterial oxygen tension (PaCO2) fell from 60.6 (12.2) to 50.9 (8.9) mm Hg* but PaO2 changed little (from 48.4 (7.4) to 47.6 (8.2) mm Hg). There were no significant changes on the control day in arterial blood gas tensions (PaO2 47.8 (8.1) and 48.9 (9.4) and Paco2 59.8 (10.9) and 57.5 (8.06) mm Hg) or in MIP (69.4 (22.4) and 70.9 (22.9) cm H2O). Six patients tolerated negative pressure ventilation poorly and these patients showed less improvement after negative pressure ventilation. Our results suggest that intermittent negative pressure ventilation can increase alveolar ventilation in patients with an exacerbation of chronic obstructive lung disease, particularly in those who tolerate the procedure well. Most subjects showed a fall in PaCO2 and an increase in MIP. The fact that PaO2 was unchanged despite the fall in PaCO2 suggests that gas exchange may deteriorate with negative pressure ventilation in these patients.
Decision Analysis of Hematopoietic Growth Factor Use in Patients Receiving Cancer Chemotherapy
Authors: G. H. Lyman, C. G. Lyman, R. A. Sanderson, L. Balducci
Journal: JNCI Journal of the National Cancer Institute (1993)

Hematopoietic growth factors (HGFs) have been shown to reduce the incidence of neutropenia and fever in patients receiving cancer chemotherapy.This cost analysis was designed to determine the conditions in which use of HGFs in patients receiving cancer chemotherapy is cost-effective.We used a standard model based on decision theory; the model assumes that all patients experiencing neutropenia and fever will be hospitalized and treated with intravenous antibiotics. Data from a prospective, randomized clinical trial of granulocyte colony-stimulating factor in small-cell lung cancer treated with combination chemotherapy were used to determine baseline probabilities for control hospitalization risk and survival; proportional hospitalization risk with prophylactic HGF; and median durations of hospitalization and prophylactic HGF use. The model was analyzed by one-way and multivariate sensitivity analyses, with estimation of threshold values at which the expected cost is the same for either of two treatment options. One or more of the specific costs and durations and the probability for each group of threshold curves were varied in a sensitivity analysis that generated variable thresholds. Use of Monte Carlo analysis based on the available distributions of the main variables provided 90% confidence limits and an inference method for comparing decision options.The expected excess cost per treatment cycle, based on hospitalization for neutropenic fever and/or HGF administration, was $5500 for no HGF, $4750 for prophylactic HGF, and $6875 for therapeutic HGF. Sensitivity analysis provided the following thresholds for no HGF versus prophylactic HGF: control risk of hospitalization, 0.40; risk of hospitalization with HGF as a proportion of control, 0.64; total daily cost of hospitalization, $727; total daily cost of HGF, $344; duration of hospitalization, 7.3 days; and duration of HGF use, 11.0 days. Multivariate analysis revealed that conditions favoring the use of HGF on a cost basis become greater (a) as risk of hospitalization, total daily hospital cost, and duration of hospitalization increase and (b) as the proportional risk of hospitalization with HGF, daily cost of HGF, and duration of HGF treatment decrease.The major determinants of total excess cost were the control risk of hospitalization, the proportional reduction in risk with HGF, and the average daily hospital cost.Use of HGFs should be based on the risk of hospitalization for neutropenic fever and consideration of the patient population and institutional costs.
Skin irritation thresholds in hairdressers: implications for the development of hand dermatitis
Authors: H.R. Smith, D.K.B. Armstrong, D. Holloway, L. Whittam, D.A. Basketter, J.P. Mcfadden
Journal: British Journal of Dermatology (2002)

Individuals vary in their ability to react to irritants.To observe the development of clinical hand dermatitis and sensitization prospectively in trainee hairdressers and to compare this with their irritant threshold to sodium lauryl sulphate (SLS).Subjects were patch tested to a limited series of occupational importance and their irritant threshold to SLS was determined; patch testing was repeated 6 months later and subjects were assessed for hand dermatitis.The development of hand dermatitis was associated with a lower irritant threshold. A similar association was not found for sensitization.The development of clinical dermatitis in prospectively followed subjects with greater irritant reactivity has not previously been identified. The association of greater irritant reactivity with a proinflammatory cytokine polymorphism may partly explain this. Further development of the irritant threshold test could contribute to the identification of non-atopic subjects at risk of occupational skin disease.
Pneumonia classification and healthcare-associated pneumonia: a new avenue or just a cul-de-sac?
Authors: Mark Woodhead
Journal: Thorax (2013)

Peripneumony, peripleumoniacon and pleurisy were all terms used by the ancient Greeks and Romans to refer to illnesses which include the condition we now know as pneumonia. In the early 19th century, Laennec separated ‘pleurisy’ from pneumonia, and later that century, Rokitansky was probably the first to recognise bronchopneumonia and lobar pneumonia as separate pathological entitities. In 1938, Reimann1 introduced the term ‘atypical pneumonia’ for a group of pneumonias with a slower evolution and later link with mycoplasma aetiology (although subsequent studies suggest that such a clinical distinction is difficult and not useful in routine practice). The late 19th and 20th centuries were those of microbial discovery and the multiplicity of microbial pathogens that commonly cause pneumonia were recognised. It was only later in the 20th century, with alterations in the structure of society and healthcare facilities, that different patterns of microbial aetiology linked to social and population factors started to be detected, particularly in the USA. A high frequency of pneumonia associated with Gram-negative bacilli was found in a population with a high frequency of alcoholism.2 In a US study published in 1973, Gram-negative bacteria were found, perhaps for the first time, to be associated with pneumonia arising in those in institutional residence,3 and similar findings were found in patients with pneumonia developing in nursing homes—nursing home-acquired pneumonia (NHAP).4 This was the precursor to the current internationally recognised classification of pneumonia by site of origin into either hospital acquired pneumonia (HAP) or community acquired pneumonia (CAP)—a classification that is easy to apply at patient presentation, and which links to a different spectrum …
Prospective cohort study to determine if trial efficacy of anticoagulation for stroke prevention in atrial fibrillation translates into clinical effectiveness
Authors: L. Kalra
Journal: BMJ (2000)

<h3>Abstract</h3> <b>Objective:</b> To determine whether trial efficacy of prophylaxis with warfarin for patients with atrial fibrillation at high risk of stroke translates into effectiveness in clinical practice. <b>Design:</b> Two year prospective cohort study. <b>Setting:</b> District general hospital. <b>Participants:</b> 167 patients with atrial fibrillation and at high stroke risk who were eligible for anticoagulation <b>Interventions:</b> Long term anticoagulation with warfarin at adjusted doses to maintain an international normalised ratio of 2.0-3.0 <b>Main outcome measures:</b> Comparison of patient characteristics, comorbidity, anticoagulation control, stroke rate, and haemorrhagic complications with pooled data from five randomised controlled trials. <b>Results:</b> Patients in the study group were seven years older (95% confidence interval 4 to 10) and comprised 33% more women than patients in the pooled trials. The international normalised ratio was in the target range for 61% of the time (range 37%-85%), below for 26% of the time (range 8%-32%), and above for 13% of the time (range 6%-26%). The time that patients in the study group spent in the target range was significantly less than in the pooled analysis. The incidence of stroke in the study group (2.0% per year, 0.7% to 4.4%) was comparable to that of patients receiving warfarin in pooled studies (1.4%, 0.8% to 2.3%). Per year the incidence of major (1.7% v 1.6%) and minor (5.4% v 9.2%) bleeding complications was also similar. <b>Conclusion:</b> Rates of stroke and major haemorrhage after anticoagulation in clinical practice were comparable to those obtained from pooled data from randomised controlled studies for patients with atrial fibrillation at high risk of stroke
mRNA Splicing Variants: Exploiting Modularity to Outwit Cancer Therapy
Authors: Scott M. Dehm
Journal: Cancer Research (2013)

Systemic cancer therapy has traditionally exploited vulnerabilities in cancer cells, a strategy which has become more precise with the identification and targeting of driver oncogenes. However, persistent tumor growth due to primary (de novo) or secondary (acquired) resistance limits therapeutic efficacy for many patients. Alternative splicing is important for increasing the diversity of the cellular proteome, and is a process frequently deregulated during cancer development and progression. In cancer cells, diverse splicing alterations have been identified that eliminate protein domains or enzymatic activities required for efficacy of cancer therapies, promote gain of novel signaling functions that circumvent cancer therapies, and uncouple signaling pathways from upstream regulatory points that are blocked by cancer therapies. The mechanisms underlying these splicing changes range from stable alterations in gene sequence/structure to deregulation of splicing regulatory factors. In this review, the role of splice variants in cancer therapy resistance will be discussed, with examples of how mechanistic understanding of these processes has led to the development of novel strategies for therapy resensitization.