tbuckley/cabot-search huggingface dataset:
A simple tool to predict hospital admissions in bronchiectasis
Authors: Waleed Salih, Lucy Popellwell, Richard Stretton, James Chalmers, Thomas Fardon
Journal: European Respiratory Journal (2013)

Introduction  Hospital admissions for bronchiectasis are increasing. Identifying patients at risk may help guide treatment and prevention strategies. Although diseases such as COPD have well established severity scores, there are no prognostic tools in bronchiectasis. The aim of this study was to identify risk factors predicting hospitalisation for severe exacerbations of bronchiectasis.  Methods  100 consecutive patients attending a specialist bronchiectasis clinic were studied. Variables recorded: FEV1, age, gender,sputum microbiology,MRC dysnoea score, smoking status,body mass index and the Reiff radiology severity score. Independent risk factors for hospitalisation during follow-up were identified.Data are presented as odds ratios(OR)with 95% confidence intervals.  Results  Patients9 median age was 66 years(IQR 58-73) with 27% of patients hospitalised during follow-up. Significant risk factors for hospitalisation were MRC dyspnoea score > 3 OR 2.9(1.7-7.2,p=0.02),FEV1  3 lobes involved on CT or cystic bronchiectasis OR 7.7(2.8-21.3,p  The area under the receiver operator characteristic curve for the score was 0.78(0.73-0.83),p  Conclusion  Bronchiectasis associated hospital admissions can be predicted using simple severity criteria.
A non-invasive test for prenatal diagnosis based on fetal DNA present in maternal blood: a preliminary study
Authors: Ravinder Dhallan, Xin Guo, Sarah Emche, Marian Damewood, Philip Bayliss, Michael Cronin, Julie Barry, Jordan Betz, Kara Franz, Katie Gold, Brett Vallecillo, John Varney
Journal: The Lancet (2007)
Overexpression of Hyaluronan in the Tunica Media Promotes the Development of Atherosclerosis
Authors: Song Chai, Qing Chai, Carl C. Danielsen, Peter Hjorth, Jene R. Nyengaard, Thomas Ledet, Yu Yamaguchi, Lars M. Rasmussen, Lise Wogensen
Journal: Circulation Research (2005)

The arterial content of hyaluronan (HA) undergoes diffuse changes as part of the diabetic macroangiopathy. Because HA influences the phenotype of vascular cells in vitro such as proliferation, migration, and secretion, it is tempting to speculate that diabetes-induced hastened cardiovascular disease may be linked to the increased amount of HA. To explore the pathophysiological role of altered HA content in the arterial wall in vivo, we created transgenic (Tg) mice with HA overexpression in smooth muscle cells (SMCs) in large and small vessels, targeted by the alpha smooth-muscle-cell-actin (alphaSMA) promoter fused to the human hyaluronan synthase 2 (hHAS2) cDNA. RT-PCR demonstrated hHAS2 mRNA expression in the tunica media of large and small vessels. In situ hybridization confirmed that hHAS2 mRNA was targeted to the SMCs. The aortic HA content was elevated in the Tg mice, and by immunohistochemistry, it was seen that HA accumulated in the tunica media. The secretory profile of high- and low-molecular HA was similar in wild-type and Tg animals. Overproduction of HA in the aorta resulted in thinning of the elastic lamellae in Tg mice. Our data suggest that this may lead to increased mechanical stiffness and strength, as determined by controlled stretching until failure. Finally, overproduction of HA on the genetic background of the ApoE-deficient mouse strain promoted atherosclerosis development in the aorta. These results indicate that a single component of the diabetic macroangiopathy, diffuse accumulation of HA, accelerates the progression of atherosclerosis.
THE USE OF PARNATE IN THE TREATMENT OF DEPRESSION
Authors: MILTON H. MILLER
Journal: American Journal of Psychiatry (1961)

Six months of clinical experience with a new antidepressant medication, Parnate (tranylcypromine), indicates that this compound is a very effective monoamine oxydase inhibitor. It appears to act fairly rapidly in a wide variety of depressive states and in this examiner's hands seemed to effect remission in several very refractory depressive illnesses. It would appear to be indicated in the treatment of any form of depression and warrants trial in some long depressive illnesses which had been nonresponsive to other therapies.
Chromium- and nickel-induced cytotoxicity in normal and transformed human keratinocytes: an investigation of pharmacological approaches to the prevention of Cr(VI)-induced cytotoxicity
Authors: M.C. LITTLE, D.J. GAWKRODGER, S. MACNEIL
Journal: British Journal of Dermatology (1996)

Chromium and nickel compounds cause irritancy but can also induce allergic contact dermatitis. The aims of this study were to characterize the direct cytotoxic effects of Cr(VI), Cr(III) and Ni(II) salts on keratinocytes, and to investigate pharmacological strategies to protect cells against Cr(VI)-induced cytotoxicity. Normal human keratinocytes and the HaCaT keratinocyte cell line were used. Cell viability was assessed by neutral red dye uptake, the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) eluted stain assay and measurement of lactate dehydrogenase (LDH) activity in the medium. The assays varied slightly in their sensitivities (neutral red > MTT > LDH) although all three gave similar results. In both cell types, the relative order of cytotoxicity of the salts was Cr(VI) >> Ni(II) > Cr(III). There were no major differences between chromium salts of a common valency. Normal human keratinocytes showed a much greater variability in their response to Cr(VI) and Ni(II) salts than HaCaT cells and were generally more resistant to Cr(VI)- and Ni(II)-induced cytotoxicity. Several drugs were screened for their potential to protect both cell types against the cytotoxic effects of Cr(VI), specifically the reducing agents ascorbic acid, cysteine and glutathione, and the Cr(VI) cellular uptake inhibitors 4,4'-diisothiocyanato-2,2'-stilbenedisulphonic acid (DIDS) and 4-acetamido-4'-isothiocyanato-2,2'-stilbenedisulphonic acid (SITS). All five drugs provided concentration-dependent protection against Cr(VI)-induced cytotoxicity but only ascorbic acid offered complete protection. Several of these pharmacological approaches to the prevention of Cr(VI) cytotoxicity confirm previous clinical studies on the inactivation of Cr(VI), while the clinical potential of others has yet to be investigated.
Initial Molecular Response at 3 Months May Predict Both Response and Event-Free Survival at 24 Months in Imatinib-Resistant or -Intolerant Patients With Philadelphia Chromosome–Positive Chronic Myeloid Leukemia in Chronic Phase Treated With Nilotinib
Authors: Susan Branford, Dong-Wook Kim, Simona Soverini, Ariful Haque, Yaping Shou, Richard C. Woodman, Hagop M. Kantarjian, Giovanni Martinelli, Jerald P. Radich, Giuseppe Saglio, Andreas Hochhaus, Timothy P. Hughes, Martin C. Müller
Journal: Journal of Clinical Oncology (2012)

Purpose The association between initial molecular response and longer-term outcomes with nilotinib was examined. Patients and Methods Patients with imatinib-resistant or -intolerant chronic myeloid leukemia in chronic phase from the phase II nilotinib registration study with available postbaseline BCR-ABL1 transcript assessments were included (N = 237). Results BCR-ABL1 transcript levels (International Scale [IS]) at 3 months correlated with complete cytogenetic response (CCyR) by 24 months. Patients with BCR-ABL1 (IS) of &gt; 1% to ≤ 10% at 3 months with nilotinib had higher cumulative incidence of CCyR by 24 months than patients with BCR-ABL1 (IS) of &gt; 10% (53% v 16%). BCR-ABL1 (IS) at 3 months predicted major molecular response (MMR) by 24 months. Cumulative incidence of MMR by 24 months for patients with BCR-ABL1 (IS) of &gt; 0.1% to ≤ 1%, &gt; 1% to ≤ 10%, and &gt; 10% was 65%, 27%, and 9%, respectively. These differences were observed for patients with or without baseline BCR–ABL1 mutations and for those with imatinib resistance or intolerance. Estimated event-free survival (EFS) rates at 24 months decreased with higher transcript levels at 3 months; patients with BCR-ABL1 (IS) of ≤ 1% had an estimated 24-month EFS rate of 82%, compared with 70% for patients with BCR-ABL1 (IS) of &gt; 1% to ≤ 10% and 48% for patients with BCR-ABL1 (IS) of &gt; 10%. Conclusion Patients with BCR-ABL1 (IS) of &gt; 10% at 3 months had a lower cumulative incidence of CCyR and MMR and lower rates of EFS versus patients with BCR-ABL1 (IS) of ≤ 10%. Prospective studies may determine whether close monitoring or alternative therapies are warranted for patients with minimal initial molecular response.
Feed-Forward Loop Circuits as a Side Effect of Genome Evolution
Authors: Otto X. Cordero, Paulien Hogeweg
Journal: Molecular Biology and Evolution (2006)

In this article, we establish a connection between the mechanics of genome evolution and the topology of gene regulation networks, focusing in particular on the evolution of the feed-forward loop (FFL) circuits. For this, we design a model of stochastic duplications, deletions, and mutations of binding sites and genes and compare our results with yeast network data. We show that the mechanics of genome evolution may provide a mechanism of FFL circuit generation. Our simulations result in overrepresentation of FFL circuits as well as in their clustering around few regulator pairs, in concordance with data from transcription networks. The mechanism here proposed and the analysis of the yeast data show that regulator duplication could have played an important role in FFL evolution.
Blood flow suppresses vascular Notch signalling via dll4 and is required for angiogenesis in response to hypoxic signalling
Authors: Oliver Watson, Peter Novodvorsky, Caroline Gray, Alexander M.K. Rothman, Allan Lawrie, David C. Crossman, Andrea Haase, Kathryn McMahon, Martin Gering, Fredericus J.M. Van Eeden, Timothy J.A. Chico
Journal: Cardiovascular Research (2013)

The contribution of blood flow to angiogenesis is incompletely understood. We examined the effect of blood flow on Notch signalling in the vasculature of zebrafish embryos, and whether blood flow regulates angiogenesis in zebrafish with constitutively up-regulated hypoxic signalling. Developing zebrafish (Danio rerio) embryos survive via diffusion in the absence of circulation induced by knockdown of cardiac troponin T2 or chemical cardiac cessation. The absence of blood flow increased vascular Notch signalling in 48 h post-fertilization old embryos via up-regulation of the Notch ligand dll4. Despite this, patterning of the intersegmental vessels is not affected by absent blood flow. We therefore examined homozygous vhl mutant zebrafish that have constitutively up-regulated hypoxic signalling. These display excessive and aberrant angiogenesis from 72 h post-fertilization, with significantly increased endothelial number, vessel diameter, and length. The absence of blood flow abolished these effects, though normal vessel patterning was preserved. We show that blood flow suppresses vascular Notch signalling via down-regulation of dll4. We have also shown that blood flow is required for angiogenesis in response to hypoxic signalling but is not required for normal vessel patterning. These data indicate important differences in hypoxia-driven vs. developmental angiogenesis.
How Good Is “Good Enough”? The Case for Varying Standards of Evidence According to Need for New Interventions in HIV Prevention
Authors: Bridget Haire, John Kaldor, Christopher FC Jordens
Journal: The American Journal of Bioethics (2012)

In 2010, randomized controlled trials (RCTs) of two different biomedical strategies to prevent HIV infection had positive findings. However, despite ongoing very high levels of HIV infection in some countries and population groups, it has been made clear by regulatory authorities that the evidence remains insufficient to support either product being made available outside of research contexts in the developing world for at least two years. In addition, prevention trials in endemic areas will continue to test new interventions against placebo. But the judgments of evidentiary standards are never value-neutral. Using the recent trials and their contexts as case studies, we examine the basis for these decisions, which will potentially delay access to scientific innovation to the people who are most urgently in need of it.
Circulating MicroRNAs in Patients With Coronary Artery Disease
Authors: Stephan Fichtlscherer, Salvatore De Rosa, Henrik Fox, Thomas Schwietz, Ariane Fischer, Christoph Liebetrau, Michael Weber, Christian W. Hamm, Tino Röxe, Marga Müller-Ardogan, Angelika Bonauer, Andreas M. Zeiher, Stefanie Dimmeler
Journal: Circulation Research (2010)

Rationale: MicroRNAs are small RNAs that control gene expression. Besides their cell intrinsic function, recent studies reported that microRNAs are released by cultured cells and can be detected in the blood. Objective: To address the regulation of circulating microRNAs in patients with stable coronary artery disease. Methods and Results: To determine the regulation of microRNAs, we performed a microRNA profile using RNA isolated from n=8 healthy volunteers and n=8 patients with stable coronary artery disease that received state-of-the-art pharmacological treatment. Interestingly, most of the highly expressed microRNAs that were lower in the blood of patients with coronary artery disease are known to be expressed in endothelial cells (eg, miR-126 and members of the miR-17∼92 cluster). To prospectively confirm these data, we detected selected microRNAs in plasma of 36 patients with coronary artery disease and 17 healthy volunteers by quantitative PCR. Consistent with the data obtained by the profile, circulating levels of miR-126, miR-17, miR-92a, and the inflammation-associated miR-155 were significantly reduced in patients with coronary artery disease compared with healthy controls. Likewise, the smooth muscle–enriched miR-145 was significantly reduced. In contrast, cardiac muscle–enriched microRNAs (miR-133a, miR-208a) tend to be higher in patients with coronary artery disease. These results were validated in a second cohort of 31 patients with documented coronary artery disease and 14 controls. Conclusions: Circulating levels of vascular and inflammation-associated microRNAs are significantly downregulated in patients with coronary artery disease.
A heterophilic adhesion mechanism for platelet/endothelial cell adhesion molecule 1 (CD31).
Authors: W A Muller, M E Berman, P J Newman, H M DeLisser, S M Albelda
Journal: The Journal of Experimental Medicine (1992)

The molecular nature of cell adhesion mediated by platelet/endothelial cell adhesion molecule 1 (PECAM-1; CD31) was examined using stably transfected L cells in a PECAM-dependent aggregation assay. This adhesion was temperature sensitive and divalent cation dependent, with Mg2+ supporting aggregation to a greater degree than Ca2+. PECAM-dependent aggregation was heterophilic: PECAM-1 transfectants bound as readily to control-transfected L cells as to other PECAM-1 transfectants, demonstrating that a molecule endogenously expressed on the L cells serves as the ligand for PECAM in this system and presumably substitutes for the natural human ligand.
Trajectories of endurance activity following pulmonary rehabilitation in COPD patients
Authors: J.E. Soicher, N.E. Mayo, L. Gauvin, J.A. Hanley, S. Bernard, F. Maltais, J. Bourbeau
Journal: European Respiratory Journal (2011)

Maintenance of physical activity following pulmonary rehabilitation remains a challenge for patients with chronic obstructive pulmonary disease (COPD). The objectives of this study were to identify patterns of endurance activity after completion of pulmonary rehabilitation and to characterise people who succeed and those who have difficulty maintaining endurance activity. In a longitudinal study embedded within a randomised clinical trial, 206 individuals with COPD underwent a 3-month pulmonary rehabilitation programme. Weekly duration of endurance activity was assessed at 4, 6, 8 and 12 months after the start of rehabilitation. Trajectory modelling was used to determine the most common patterns of activity during the post-rehabilitation phase from 4-12 months. Three distinct patterns were identified, two of which indicated difficulty in maintaining endurance activity: 61 individuals reported a high activity level at 4 months (2.7 h·week(-1)) and stayed high; 114 individuals started at a low activity level (mean 1.0 h·week(-1)) and stayed low; and 31 individuals started high (3.0 h·week(-1)) and declined. The low activity group was characterised by more severe disease and greater respiratory impairment. The high and declined group had less severe disease and respiratory impairment, but reported greater barriers to exercise. Pulmonary rehabilitation should include interventions aimed at minimising barriers, in order to induce long-term behaviour change.
Exercise-induced haemoptysis: a thoroughbred cause?
Authors: James H Hull, Andrew Menzies-Gow, Andrew G Nicholson, Raad H Mohiaddin, Toby M Maher
Journal: Thorax (2013)

The authors report a novel case of exercise-induced haemoptysis with an unexpected underlying pathology. The report discusses the case and provides a pragmatic overview of the diagnosis and management of the pulmonary vein stenosis.
LACTIC ACID IN DYSPEPSIA
Authors: C. H. Jones
Journal: BMJ (1854)

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Comparison of the efficacy of levocetirizine 5 mg and desloratadine 5 mg in chronic idiopathic urticaria patients
Authors: P. C. Potter, A. Kapp, M. Maurer, G. Guillet, A. M. Jian, P. Hauptmann, A. Y. Finlay
Journal: Allergy (2008)

Nonsedating H(1)-antihistamines are recommended for the treatment of urticaria by the recent EAACI/GA(2)LEN/EDF guidelines. The aim of this study was to compare the efficacy, after 4 weeks of treatment, with levocetirizine 5 mg and desloratadine 5 mg, both once daily in the morning, in symptomatic chronic idiopathic urticaria (CIU) patients.This multi-center, randomized, double-blind study involved 886 patients (438 on levocetirizine and 448 on desloratadine). The primary objective was to compare their efficacy on the mean pruritus severity score after 1 week of treatment. Mean pruritus severity score over 4 weeks and pruritus duration score, number and size of wheals, mean CIU composite score (sum of the scores for pruritus severity and numbers of wheals), quality of life, and the patient's and investigator's global satisfaction with treatment, were secondary efficacy measures.Levocetirizine led to a significantly greater decrease in pruritus severity than desloratadine over the first treatment week; mean pruritus severity scores of 1.02 and 1.18 for levocetirizine and desloratadine, respectively (P < 0.001). The result was similar for the entire 4-week treatment period (P = 0.004). In addition, levocetirizine decreased pruritus duration and the mean CIU composite scores to a significantly greater extent than desloratadine during the first week (P = 0.002 and 0.005, respectively) and over the entire study (P = 0.009 and P < 0.05, respectively). Similarly, levocetirizine increased the patients' global satisfaction after one and 4 weeks (P = 0.012 and 0.021, respectively), compared with desloratadine. Safety and tolerability were similar in both groups.Levocetirizine 5 mg was significantly more efficacious than desloratadine 5 mg in the treatment of CIU symptoms.
Systematic Review: Nonoperative and Operative Treatments for Rotator Cuff Tears
Authors: Jennifer C. Seida
Journal: Annals of Internal Medicine (2010)

Background: Many approaches exist for managing rotator cuff tears. Purpose: To compare the benefits and harms of nonoperative and operative interventions on clinically important outcomes in adults with rotator cuff tears. Data Sources: 12 electronic databases (1990 to September 2009), gray literature, trial registries, and reference lists were searched. Study Selection: Controlled and uncontrolled studies that assessed nonoperative or operative treatments or postoperative rehabilitation for adults with confirmed rotator cuff tears were included. Operative studies in English-language publications and nonoperative and postoperative rehabilitation studies in English, French, or German were considered. Studies were assessed in duplicate. Data Extraction: 2 reviewers assessed risk for bias by using the Cochrane Risk of Bias tool and the Newcastle–Ottawa Scale. One reviewer rated the evidence by using a modified GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. Data were extracted by one reviewer and verified by another. Data Synthesis: 137 studies met eligibility criteria. All trials had high risk for bias. Cohort and uncontrolled studies were of moderate quality. Reported functional outcomes did not differ between open versus mini-open repair, mini-open versus arthroscopic repair, arthroscopic repair with versus without acromioplasty, or single-row versus double-row fixation. Earlier return to work was reported for mini-open repair versus open repair and for continuous passive motion with physical therapy versus physical therapy alone. Open repairs showed greater improvement in function than did arthroscopic debridement. Complication rates were low across all interventions. Limitations: Limited evidence, which was often of low quality, precluded conclusions for most comparisons. Language restrictions may have excluded some relevant studies, and selective outcome reporting may have introduced bias. Conclusion: Evidence on the comparative effectiveness and harms of various operative and nonoperative treatments for rotator cuff tears is limited and inconclusive. Primary Funding Source: Agency for Healthcare Research and Quality.
Pressure of intraoesophageal varices assessed by fine needle puncture: its relation to endoscopic signs and severity of liver disease in patients with cirrhosis.
Authors: G Kleber, T Sauerbruch, G Fischer, G Paumgartner
Journal: Gut (1989)

In 40 patients with cirrhosis and oesophageal varices transmural variceal pressure was assessed endoscopically by fine needle puncture and related to endoscopic signs as well as to the severity of liver disease. Transmural pressure was significantly (p less than 0.01) higher in the presence of a red colour sign (26.7 (7.8) cm H2O) than in its absence (19.1 (6.6) cm H2O). Transmural pressure, however, was not significantly related to diameter or number of varices (diameter greater than 5 mm: 23.7 (8.4), diameter less than or equal to 5 mm: 22.2 (7.9) cm H2O; number greater than 3: 23.2 (8.0), number less than or equal to 3: 22.2 (7.8) cm H2O). The Child status (Child A: 23.9 (8.0), Child B/C: 21.3 (8.1) cm H2O) and individual Child-Pugh parameters including ascites (ascites present: 23.2 (8.3) cm H2O ascites absent: 22.8 (8.1) cm H2O) were not significantly related to transmural variceal pressure. We conclude that the endoscopic visibility of a red colour sign on the varices is associated with a high transmural oesophageal variceal pressure. Our results favour the hypothesis that variceal pressure may be of major importance for the development of the red colour sign.