tbuckley/cabot-search huggingface dataset:
Spontaneous Breathing During Ventilatory Support Improves Ventilation–Perfusion Distributions in Patients with Acute Respiratory Distress Syndrome
Authors: CHRISTIAN PUTENSEN, NORBERT J. MUTZ, GABRIELE PUTENSEN-HIMMER, JÖRG ZINSERLING
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Ventilation–perfusion (V˙ a/Q˙) distributions were evaluated in 24 patients with acute respiratory distress syndrome (ARDS), during airway pressure release ventilation (APRV) with and without spontaneous breathing, or during pressure support ventilation (PSV). Whereas PSV provides mechanical assistance of each inspiration, APRV allows unrestricted spontaneous breathing throughout the mechanical ventilation. Patients were randomly assigned to receive APRV and PSV with equal airway pressure limits (Paw) (n = 12) or minute ventilation (V˙ e) (n = 12). In both groups spontaneous breathing during APRV was associated with increases (p < 0.05) in right ventricular end-diastolic volume, stroke volume, cardiac index (CI), PaO2 , oxygen delivery, and mixed venous oxygen tension (PvO2 ) and with reductions (p < 0.05) in pulmonary vascular resistance and oxygen extraction. PSV did not consistently improve CI and PaO2 when compared with APRV without spontaneous breathing. Improved V˙ a/Q˙ matching during spontaneous breathing with APRV was evidenced by decreases in intrapulmonary shunt (equal Paw: 33 ± 4 to 24 ± 4%; equal V˙ e: 32 ± 4 to 25 ± 2%) (p < 0.05), dead space (equal Paw: 44 ± 9 to 38 ± 6%; equal V˙ e: 44 ± 9 to 38 ± 6%) (p < 0.05), and the dispersions of ventilation (equal Paw: 0.96 ± 0.23 to 0.78 ± 0.22; equal V˙ e: 0.92 ± 0.23 to 0.79 ± 0.22) (p < 0.05), and pulmonary blood flow distribution (equal Paw: 0.89 ± 0.12 to 0.72 ± 0.10; equal V˙ e: 0.94 ± 0.19 to 0.78 ± 0.22) (p < 0.05). PSV did not improve V˙ a/Q˙ distributions when compared with APRV without spontaneous breathing. These findings indicate that uncoupling of spontaneous and mechanical ventilation during APRV improves V˙ a/Q˙ matching in ARDS presumably by recruiting nonventilated lung units. Apparently, mechanical assistance of each inspiration during PSV is not sufficient to counteract the V˙ a/Q˙ maldistribution caused by alveolar collapse in patients with ARDS.
Indicator-Dilution Studies with "Diffusible" Indicators
Authors: Francis P. Chinard, Theodore Enns, Mary F. Nolan
Journal: Circulation Research (1962)

Some of the applications and extensions of the indicator-dilution technics have been presented. The technics offer possibilities for the investigation of some of the parameters of the circulatory and respiratory systems. They also offer a means of studying some of the more rapid features of organ metabolism in vivo. Compared to the degree of sophistication achieved by the more conventional dye-dilution studies, these extensions with "diffusible" indicators are in an embryonic stage of development. It is believed that they have a future.
Expression of the peptide C4b-binding protein in the arthritic joint
Authors: O Sanchez-Pernaute
Journal: Annals of the Rheumatic Diseases (2006)

<b>Background:</b> C4b-binding protein (C4BP) is a plasma oligomeric glycoprotein that participates in the regulation of complement and haemostasis. Complement-regulatory activity depends on the C4BPα-polypeptide, whereas the C4BPβ-polypeptide inactivates protein S, interfering with the anti-coagulatory protein C-dependent pathway. <b>Objective:</b> To investigate the expression of C4BPβ in the rheumatoid joint. <b>Methods:</b> Expression of C4BP was studied in synovial explants from patients with rheumatoid arthritis, osteoarthritis and healthy controls, using immunohistochemistry and in situ hybridisation. C4BP isoforms and free C4BPβ were studied in synovial effusions from patients with rheumatoid arthritis, osteoarthritis and microcrystalline arthritis (MCA) by immunoblotting; total and free protein S levels were studied by enzyme immunoassay. <b>Results:</b> C4BPβ was overexpressed in the synovial membranes of patients with rheumatoid arthritis, in close association with the severity of synovitis and the extension of interstitial fibrin deposits. As many as 85% fluids from patients with rheumatoid arthritis contained free C4BPβ, whereas this unusual polypeptide was present in 50% fluids from patients with MCA and 40% fluids from patients with osteoarthritis. Free protein S at the effusions was pathologically reduced in patients with rheumatoid arthrits and MCA, and remained normal in patients with osteoarthritis. <b>Conclusion:</b> C4BPβ is expressed by the inflamed synovial tissue, where it can participate in processes of tissue remodelling associated with invasive growth.
Fibrinolytic and hemostatic abnormalities in gastroesophageal varicealbleeding in cirrhotic patients
Authors: M. Primignani, A. Dell'Era, P. Carnavale, P. Preatoni, M. Cattaneo, B. Bottasso, M.T. Bajetta, P. Bucciarelli, G. Scacchi, L. Tognini, E. Martino, R. de Franchis
Journal: Journal of Hepatology (2000)
Myocardial Potassium and Lactate Balance during Valve-Replacement Surgery
Authors: COLIN W. MCCORD, RICHARD S. CRAMPTON, MICHEL G. NASSER, ROBERT B. CASE, Anna Maria Wachter
Journal: Circulation (1969)

Coronary venous drainage was isolated, and arterial and coronary venous lactate and potassium concentrations were determined during valve-replacement surgery in 15 patients. Coronary flow was measured in seven. Fourteen had diminished lactate uptake during control periods of normothermic bypass whereas potassium uptake or loss was variable. The recovery period after intermittent anoxic cardiac arrest for 10 to 20 minutes at 28° C (five patients) and 4° C (seven patients) was associated with lactate production and large potassium losses. Continuous coronary perfusion at 28° C and 150 to 250 ml/min flow (three patients) was associated with continuous lactate production and potassium loss. Total myocardial potassium loss averaged 1.15 mEq. In most patients lactate production diminished and rapid potassium uptake occurred when normal coronary perfusion was reestablished while still on bypass. In spite of these shifts in potassium balance, myocardial function was regained promptly upon defibrillation without serious arrhythmias.
Report calls for clinical networks to improve babies' survival
Authors: S. Mayor
Journal: BMJ (2003)

Guidelines and clinical networks should be established in England and Wales to improve the quality of care for premature babies, says a report published this week by the Confidential Enquiry into Stillbirths and Deaths in Infancy.

The report aimed to identify patterns of practice or service provision that might have contributed to the deaths of premature babies born at 27 or 28 weeks.

The inquiry included 3522 babies …
Antimyeloma Activity of the Orally Bioavailable Dual Phosphatidylinositol 3-Kinase/Mammalian Target of Rapamycin Inhibitor NVP-BEZ235
Authors: Douglas W. McMillin, Melissa Ooi, Jake Delmore, Joseph Negri, Patrick Hayden, Nicolas Mitsiades, Jana Jakubikova, Sauveur-Michel Maira, Carlos Garcia-Echeverria, Robert Schlossman, Nikhil C. Munshi, Paul G. Richardson, Kenneth C. Anderson, Constantine S. Mitsiades
Journal: Cancer Research (2009)

Abstract The phosphatidylinositol 3-kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR) pathway mediates proliferation, survival, and drug resistance in multiple myeloma (MM) cells. Here, we tested the anti-MM activity of NVP-BEZ235 (BEZ235), which inhibits PI3K/Akt/mTOR signaling at the levels of PI3K and mTOR. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric survival assays showed that MM cell lines exhibited dose- and time-dependent decreased viability after exposure to BEZ235 (IC50, 25–800 nmol/L for 48 hours). MM cells highly sensitive (IC50, &amp;lt;25 nmol/L) to BEZ235 (e.g., MM.1S, MM.1R, Dox40, and KMS-12-PE) included both lines sensitive and resistant to conventional (dexamethasone, cytotoxic chemotherapeutics) agents. Pharmacologically relevant BEZ235 concentrations (25–400 nmol/L) induced rapid commitment to and induction of MM.1S and OPM-2 cell death. Furthermore, normal donor peripheral blood mononuclear cells were less sensitive (IC50, &amp;gt;800 nmol/L) than the majority of MM cell lines tested, suggesting a favorable therapeutic index. In addition, BEZ235 was able to target MM cells in the presence of exogenous interleukin-6, insulin-like growth factor-1, stromal cells, or osteoclasts, which are known to protect against various anti-MM agents. Molecular profiling revealed that BEZ235 treatment decreased the amplitude of transcriptional signatures previously associated with myc, ribosome, and proteasome function, as well as high-risk MM and undifferentiated human embryonic stem cells. In vivo xenograft studies revealed significant reduction in tumor burden (P = 0.011) and survival (P = 0.028) in BEZ235-treated human MM tumor-bearing mice. Combinations of BEZ235 with conventional (e.g., dexamethasone and doxorubicin) or novel (e.g., bortezomib) anti-MM agents showed lack of antagonism. These results indicate that BEZ235 merits clinical testing, alone and in combination with other agents, in MM. [Cancer Res 2009;69(14):5835–42]
E-cigarettes and the marketing push that surprised everyone
Authors: M. McKee
Journal: BMJ (2013)

Many important conversations at the European Regional Committee of the World Health Organization take place in the corridors.This year, at its meeting in Izmir, Turkey, a common topic was the dramatic rise in the marketing of e-cigarettes now being seen in many countries.Where they are allowed, advertisements seem to be appearing everywhere.New outlets are also appearing, in some cases beside schools, as in Slovenia.Governments that had imposed restrictions have been coming under pressure to relax them from manufacturers and, in some cases, from groups portraying e-cigarettes as an effective means of harm reduction.Many in Izmir wondered whether this intense activity was confined to their own country, but it was soon clear that this was something affecting all of Europe.But why now?The e-cigarette, a battery powered device designed to mimic smoking and to deliver a dose of nicotine without many nasty cancer producing substances in conventional cigarettes, has been around for a long time.The first patent was in 1963, and China has been exported e-cigarettes since 2005.Nobody had seen the big marketing push coming.
Improving outcomes in social anxiety disorder
Authors: Pim Cuijpers, Annemieke van Straten
Journal: The Lancet Psychiatry (2014)

Social anxiety disorder is increasingly recognised as a highly prevalent and debilitating disorder, with huge costs in terms of personal distress of patients and economic costs to society.1 A substantial number of randomised controlled trials have examined the effects of treatments for social anxiety disorders, and although both psychological and pharmacological treatments are effective, there is still a lot we do not know.
Vagal function in relation to gastro-oesophageal reflux and associated motility changes.
Authors: R V Heatley, R J Collins, P D James, M Atkinson
Journal: BMJ (1980)

Vagal function in 28 patients with gastro-oesophageal reflux was examined by determining gastric secretory response to insulin-induced hypoglycaemia and pulse-rate variation with respiration. Gastric secretory studies were also performed on 13 patients with duodenal ulcer who had not undergone operations. In all patients the presence and degree of oesophagitis were determined endoscopically and mucosal biopsy and oesophageal manometry were performed. Seven of the 28 patients with gastro-oesophageal reflux showed evidence of impaired vagal efferent function in the upper alimentary tract. No such impairment was found in those patients who showed manometric evidence of oesophageal spasm secondary to gastro-oesophageal reflux. Low pulse-rate variation with respiration was found in 12 of 27 patients with gastro-oesophageal reflux, suggesting dysfunction of cardiac vagal fibres. Impairment of efferent vagal supply may be a causative factor in some patients with gastr-oesophageal reflux but does not seem to be important in oesophageal spasm secondary to gastro-oesophageal reflux.
Antigen nonspecific effect of major histocompatibility complex haplotype on autoantibody levels in systemic lupus erythematosus-prone lpr mice.
Authors: P L Cohen, E Creech, D Nakul-Aquaronne, R McDaniel, S Ackler, R G Rapoport, E S Sobel, R A Eisenberg
Journal: Journal of Clinical Investigation (1993)

MHC-linked genes strongly influence susceptibility to autoimmune diseases and also regulate responses to exogenous antigens. To begin to understand the mechanism of this MHC effect on disease, we have investigated MHC-congenic mouse strains that develop spontaneous autoimmunity because of the lpr gene. C57BL6/lpr (B6/lpr) mice (H-2b) are known to have substantial levels of autoantibodies to chromatin, single stranded DNA (ssDNA3), and IgG of different murine subclasses (rheumatoid factor). We have crossed the H-2d and the H-2bm12 (la mutant) haplotypes onto the B6/lpr background. Surprisingly, levels of all the autoantibodies were markedly lower in B6/lpr.H-2d, but levels in B6/lpr.H-2bm12 were no different from those in B6/lpr mice. The downregulating influence of the H-2d allele was dominant, and there was no effect on autoantibody fine specificities. The genetics of the H-2d effect and its diffuse influence on multiple autoantibody specificities, in addition to the lack of effect of the bm12 mutation, which modifies the peptide-binding groove of I-A, together raise the question of whether MHC-linked genes other than classical (IR) genes may be responsible for MHC disease associations in this model.
Clinical Management of Gene Expression
Authors: Edward J. Benz
Journal: New England Journal of Medicine (1982)

The art of the molecular geneticist is no longer confined to the elegant but arcane domain of simple microbial genomes. Recombinant-DNA technology has rendered equally susceptible to his wizardry the several billion base pairs of DNA present in each human cell.Recent events have demonstrated the rapidity with which molecular genetics is achieving clinical relevance. For example, direct molecular analysis of DNA is now used as a diagnostic tool for the definitive antenatal detection of hemoglobinopathies,1 , 2 for investigating infections,3 , 4 and for classifying leukemias.5 Ley et al., in this issue of the Journal,6 and Dover et al., in a recent . . .
Octreotide and Graves' ophthalmopathy.
Authors: P. Perros, R. A. James, P. Kendall-Taylor
Journal: BMJ (1992)

time to take effect.Our patients described their recovery in terms of a "cracked mirror" 10-15 minutes after the injection.Angiography was performed 60 minutes after injection and showed complete reopening.With regard to the adverse side effects mentioned by Pandit and Tiamiyu, cardiac arrhythmias were reported after longer administra- tion of higher doses of steroids (4x 30 mg/kg daily),' not after a single 1000 mg bolus, which is not a massive dose.Steroids are an effective measure against anaphylactic shock.4Are anaphy- lactoid reactions to steroids really common?We tried to show the effect of steroids on vessel walls and offered angiographic evidence that occluded vessels became completely perfused 60 minutes later.A steroid bolus seems to us to be a suitable emergency treatment that does not inter- fere with other drugs for this condition.Any other treatment may be given simultaneously or after- wards.
Letter: Muscle cramps during maintenance haemodialysis.
Authors: G R Catto, F W Smith, M MacLeod
Journal: BMJ (1973)

In 1970 340 of strains were resistant to tetracycline, in 1971 46%, in 1972 54%, and in 1973 to date 35°%.It would seem there- fore that in this area, at least, there has been no fall in the level of tetracycline-resistant Strep.pyogenes over the past four years.The majority of strains isolated continue to come from throat swabs, though many also come from skin sepsis and abscesses.Group B haemolytic streptococci show an even higher prevalence of tetracycline resistance- 580% of 74 strains isolated so far this year (mainly from vaginal swabs) were resistant to this drug.Whether the difference between Dr. Robertson's findings and mine is due to differences in the usage of tetracyclines in the two areas is something on which I cannot comment, but our results illustrate how widely divergent antibiotic sensitivity patterns may 'be observed in different areas of the couniry.-Iam, etc.,
Meta-analysis of increased dose of inhaled steroid or addition of salmeterol in symptomatic asthma (MIASMA)
Authors: S Shrewsbury, S Pyke, M Britton
Journal: BMJ (2000)

To examine the benefits of adding salmeterol compared with increasing dose of inhaled corticosteroids.Systematic review of randomised, double blind clinical trials. Independent data extraction and validation with summary data from study reports and manuscripts. Fixed and random effects analyses.EMBASE, Medline, and GlaxoWellcome internal clinical study registers.Efficacy and exacerbations.Among 2055 trials of treatment with salmeterol, there were nine parallel group trials of >/=12 weeks with 3685 symptomatic patients aged >/=12 years taking inhaled steroid in primary or secondary care. Compared with response to increased steroids, in patients receiving salmeterol morning peak expiratory flow was greater at three months (difference 22.4 (95% confidence interval 15.0 to 30.0) litre/min, P<0.001) and six months (27.7 (19.0 to 36.4) litre/min, P<0.001). Forced expiratory volume in one second (FEV(1)) was also increased at three months (0.10 (0.04 to 0.16) litres, P<0.001) and six months (0.08 (0.02 to 0.14) litres, P<0.01), as were mean percentage of days and nights without symptoms (three months: days-12% (9% to 15%), nights-5% (3% to 7%); six months: days-15% (12% to 18%), nights-5% (3% to 7%); all P<0.001) and mean percentage of days and nights without need for rescue treatment (three months: days-17% (14% to 20%), nights-9% (7% to 11%); six months: days-20% (17 to 23%), nights-8% (6% to 11%); all P<0.001). Fewer patients experienced any exacerbation with salmeterol (difference 2.73% (0.43% to 5.04%), P=0. 02), and the proportion of patients with moderate or severe exacerbations was also lower (2.42% (0.24% to 4.60%), P=0.03).Addition of salmeterol in symptomatic patients aged 12 and over on low to moderate doses of inhaled steroid gives improved lung function and increased number of days and nights without symptoms or need for rescue treatment with no increase in exacerbations of any severity.
New evidence on the impact of China's New Rural Cooperative Medical Scheme and its implications for rural primary healthcare: multivariate difference-in-difference analysis
Authors: K. S. Babiarz, G. Miller, H. Yi, L. Zhang, S. Rozelle
Journal: BMJ (2010)

To determine whether China's New Rural Cooperative Medical Scheme (NCMS), which aims to provide health insurance to 800 million rural citizens and to correct distortions in rural primary care, and the individual policy attributes have affected the operation and use of village health clinics.We performed a difference-in-difference analysis using multivariate linear regressions, controlling for clinic and individual attributes as well as village and year effects.100 villages within 25 rural counties across five Chinese provinces in 2004 and 2007. Participants 160 village primary care clinics and 8339 individuals.Clinic outcomes were log average weekly patient flow, log average monthly gross income, log total annual net income, and the proportion of monthly gross income from medicine sales. Individual outcomes were probability of seeking medical care, log annual "out of pocket" health expenditure, and two measures of exposure to financial risk (probability of incurring out of pocket health expenditure above the 90th percentile of spending among the uninsured and probability of financing medical care by borrowing or selling assets).For village clinics, we found that NCMS was associated with a 26% increase in weekly patient flow and a 29% increase in monthly gross income, but no change in annual net revenue or the proportion of monthly income from drug revenue. For individuals, participation in NCMS was associated with a 5% increase in village clinic use, but no change in overall medical care use. Also, out of pocket medical spending fell by 19% and the two measures of exposure to financial risk declined by 24-63%. These changes occurred across heterogeneous county programmes, even in those with minimal benefit packages.NCMS provides some financial risk protection for individuals in rural China and has partly corrected distortions in Chinese rural healthcare (reducing the oversupply of specialty services and prescription drugs). However, the scheme may have also shifted uncompensated new responsibilities to village clinics. Given renewed interest among Chinese policy makers in strengthening primary care, the effect of NCMS deserves greater attention.
Scan the legs, not the lungs, in low risk patients with suspected pulmonary embolism
Authors: J. R. Benger
Journal: BMJ (2013)

The BMJ ’s Too Much Medicine campaign is welcome,1 although the challenges associated with overinvestigation and overdiagnosis in suspected pulmonary embolism have long been familiar to emergency physicians.2 In patients with possible pulmonary embolism and normal vital signs, the pulmonary embolism rule-out criteria identify a group of patients at …
Phase II trial of preirradiation and concurrent temozolomide in patients with newly diagnosed anaplastic oligodendrogliomas and mixed anaplastic oligoastrocytomas: RTOG BR0131
Authors: Michael A. Vogelbaum, Brian Berkey, David Peereboom, David Macdonald, Caterina Giannini, John H. Suh, Robert Jenkins, James Herman, Paul Brown, Deborah T. Blumenthal, Christopher Biggs, Christopher Schultz, Minesh Mehta
Journal: Neuro-Oncology (2008)

The primary objectives of this phase II study were to evaluate the use of preirradiation temozolomide followed by concurrent temozolomide and radiotherapy (RT) in patients with newly diagnosed anaplastic oligodendroglioma (AO) and mixed anaplastic oligoastrocytoma (MOA). Preirradiation temozolomide (150 mg/m(2)/day) was given on a 7-day-on/7-day-off schedule for up to six cycles. The primary end point was the response rate during the 6-month, pre-RT chemotherapy. Tumor tissue was analyzed for the presence of chromosomal deletions on 1p and 19q and for MGMT-promoter methylation. Forty-two patients were enrolled; 39 were eligible. The objective response rate was 32% (6% [complete response, CR], 26% [partial response PR]), and the rate of progression during pre-RT chemotherapy was 10%. The worst nonhematological toxicity was grade 4 in three patients (8%). Twenty-two patients completed concurrent chemotherapy and RT. There were no grade 4 nonhematological toxicities during the concurrent chemotherapy and RT. Seventeen of 28 (60.7%) evaluable cases had codeletion of 1p/19q; all 17 were free from progression at 6 months. Sixteen of 20 (80%) evaluable cases had MGMT-promoter methylation; all 16 were free from progression at 6 months. In conclusion, the rate of progression of 10% during pre-RT temozolomide chemotherapy for newly diagnosed AO and MAO compared favorably with prior experience with pre-RT PCV chemotherapy (20% in RTOG 9402). The toxicity of the dose-intense pre-RT regimen used in this study may warrant evaluation of other, less intense dosing strategies. Future studies will need to prospectively stratify patients according to the presence of deletions of chromosomes 1p and 19q.