tbuckley/cabot-search huggingface dataset:
Recognition of Acute Cardiac Allograft Rejection From Serial Integrated Backscatter Analyses in Human Orthotopic Heart Transplant Recipients
Authors: Christiane E. Angermann, Kirsten Nassau, Hans-Ulrich Stempfle, Thomas M. Kru¨ger, Ralph Drewello, Reinhard Junge, Peter U¨berfuhr, Max Weiß, Karl Theisen
Journal: Circulation (1997)

Background Previous studies showed that moderate and severe acute cardiac rejection (AR) but not mild AR is associated with significant myocardial acoustic changes. This study examines whether serial measurements of end-diastolic two-dimensional integrated backscatter (2D-IB) enhance the diagnostic potential of ultrasonic tissue analysis in AR. Methods and Results Serial endomyocardial biopsies, conventional echocardiograms, and parasternal long-axis radiofrequency signals for determination of posterior wall and septal 2D-IB were performed in 52 transplant patients. Histology showed no AR in 155 biopsy samples, AR grade 1A in 25, AR grade 1B/2 in 27, and AR grade 3A/3B in 13. Whereas no significant 2D-IB changes occurred between AR-free studies and during AR grade 1A, posterior wall and septal 2D-IB increased during AR grade 1B/2 from −47.80±4.36 to −42.97±5.11 dB and from −36.72±7.45 to −32.52±7.98 dB ( P &lt;.001 and P &lt;.05, respectively) and during AR grade 3A/3B from −47.96±4.74 to −38.25±5.32 dB and from −37.92±5.87 to −31.01±4.62 dB ( P &lt;.001 and P &lt;.01, respectively). Changes in posterior wall and septal 2D-IB were greater during AR grade 3A/3B than during AR grade 1B/2 ( P &lt;.01 and P &lt;.05). Increases of 1.5 dB in posterior wall or septal 2D-IB indicated AR grades ≥1B with sensitivities of 88% and 83% and specificities of 89% and 85%; posterior wall and septal 2D-IB increases of 5.5 and 3.8 dB identified AR grades ≥3A with sensitivities of 92% and 79% and specificities of 90% and 84%. Although a weak inverse correlation between posterior wall and septal 2D-IB changes and posterior wall and septal thickening ( r =.41 and r =.39, both P &lt;.001) and fractional diameter shortening ( r =.35, P &lt;.001) was found, significant 2D-IB increases also occurred in some rejecting patients with unaltered contraction. Conclusions Increases in end-diastolic posterior wall and septal 2D-IB in serial studies permit reliable identification not only of moderate and severe AR but also of mild AR. Because 2D-IB increases significantly more in AR with myocyte damage than without such damage, an estimate of AR severity appears feasible. Significant myocardial acoustic changes during AR may occur independently of changes in contractile performance.
Abstract LB-181: The impact of Ras/MAPK/S6K signaling pathway on prediction of clinical outcome in metastatic Her-2 positive breast cancer patients treated with trastuzumab
Authors: Marek Svoboda, Marta Khoylou, Peter Grell, Jiri Navratil, Pavel Fabian, Jaroslav Juracek, Marketa Palacova, Rostislav Vyzula, Marian Hajduch
Journal: Cancer Research (2014)

Abstract Background: The overexpression of Her-2 (c-erbB2/Neu) in breast cancer is associated with poor prognosis, tumor recurrence and shortened survival. The administration of the trastuzumab significantly improves patients prognosis. However, in spite of these successful results, trastuzumab is effective only in 30-50% of cases. PI3K/Akt and Ras/MAPK signaling pathways are activated through Her-2 receptor and other growth factors’ receptors and both play important role in tumor behavior. Methods: The study included 76 women with verified Her-2+ metastatic breast cancer (MBC) who were treated with trastuzumab based palliative chemotherapy. Immunohistochemistry was performed on formalin fixed, paraffin embedded tissue sections with antibodies against S6K, p-S6K-Ser235/236, MAPK, p-MAPK-Thr202/Tyr204, GSK3β, p-GSK3β-Ser9, mTOR, p-mTOR-Ser2448. The cytoplasmatic and nuclear fractions of the staining were assessed separately. Results: Patients whose tumors showed cytoplasmic (c) and nuclear (n) expression of p- GSK3β-Ser9 exhibited worse PFS compared to tumors with negative p-GSK3β-Ser9 (PFS 5,1 vs 9,1 months; P=0,006). Similar results were also found in p-S6K kinase activity, with the difference that it was possible to observe the dependence on the p-S6K kinase compartmentalization. Patients whose tumors showed p-S6K-Ser235/236 expression accompanied with only cytoplasmatic (c) or nuclear and cytoplasmatic (n+c) staining exhibited worse PFS compared to tumors with negative p-S6K-Ser235/236 expression (negat) (c vs negat: 6,3 vs 16,1 months, P=0,006; n+c vs negat: 7,8 vs 16,1 months, P=0,025). Of the remaining kinases, we showed no effect of their expression on treatment outcome. Conclusions: This study confirms that prediction of the response or resistance to trastuzumab treatment depends on the S6K and GSK3β kinase activity. Patients, whose tumors had high level of p-S6K or p-GSK3β, had poorer benefit from trastuzumab based therapy. These patients are candidates for targeted blockade of PI3K/Akt and/or RAS/MAPK signaling pathways. Supported by the Internal Grant Agency of Ministry of Health, Czech Republic, No.NT/14599 and Biomedreg CZ.1.05/2.1.00/01.0030. Citation Format: Marek Svoboda, Marta Khoylou, Peter Grell, Jiri Navratil, Pavel Fabian, Jaroslav Juracek, Marketa Palacova, Rostislav Vyzula, Marian Hajduch. The impact of Ras/MAPK/S6K signaling pathway on prediction of clinical outcome in metastatic Her-2 positive breast cancer patients treated with trastuzumab. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-181. doi:10.1158/1538-7445.AM2014-LB-181
An expansible cannula: a new technique for chest drain insertion.
Authors: S S Gill, U U Nkere, R K Walesby
Journal: Thorax (1992)

The insertion of a chest drain into the pleural space is a common procedure used by many specialties. The commonly used device is a prepacked, sterile plastic tube with its own central metal trocar. Complications may arise during its insertion, with the occasional penetration of intrathoracic and upper abdominal organs. As most chest drains are inserted by junior and relatively inexperienced doctors, it is therefore imperative that a simple, safe, and effective technique of insertion is found. A device has been developed that consists of a 5 cm conical length of an expansible cannula, made from rolled metal foil, which when inserted into the chest reaches only a few millimetres within the pleura. When an expander tube, 10 mm in diameter, is passed through the device from its proximal end the conical tube is distended into a hollow cylindrical one, through which a standard Portex chest catheter is passed. The whole appliance is then removed over the end of the tube, leaving the drain in situ. The efficacy of this unique device has been tested in a pilot study in 22 patients. There have been no complications.
Short-Acting Barbiturate Overdosage
Authors: Margaret M. McCarron
Journal: JAMA (1982)

The only consistent clinical features in 1,140 cases of short-acting barbiturate overdosage were CNS depression with and without respiratory depression, hypotension, and hypothermia. Seven states of intoxication were defined and then scored, using a modification of the Glasgow coma scale. There was a linear correlation between the "intoxication score" and the mean serum short-acting barbiturate concentration in 688 cases tested. The following serum short-acting barbiturate concentrations may be expected for nonaddicted patients having no medical complications contributing to cerebral depression and intoxicated with only short-acting barbiturate: less than 6 μg/mL, alert; 8+/-2 μg/mL, drowsy; 14+/-3 μg/mL, stuporous; 18+/-2 μg/mL, coma 1; 22+/-2 μg/mL, coma 2; 26+/-2 μg/mL, coma 3; and 34+/-6 μg/mL, coma 4. The serum concentrations will be lower if the patient has ingested an additional sedative or has a complication contributing to cerebral depression, and higher if the patient is addicted to a sedative-hypnotic drug. (<i>JAMA</i>1982;248:55-61)
Meta-analysis: Potentials and promise
Authors: M. Egger, G. D. Smith
Journal: BMJ (1997)

The number of papers published on meta-analyses in medical research has increased sharply in the past 10 years (fig 1). The merits and perils of the somewhat mysterious procedure of meta-analysis, however, continue to be debated in the medical community.1 23 What, then, is meta-analysis? A useful definition was given by Huque: "A statistical analysis that combines or integrates the results of several independent clinical trials considered by the analyst to be 'combinable.'" 4 The terminology, however, is still debated, and expressions used concurrently include "overview," "pooling," and "quantitative synthesis." We believe that the term meta-analysis should be used to describe the statistical integration of separate studies, whereas "systematic review" is most appropriate for denoting any review of a body of data that uses clearly defined methods and criteria (box). Systematic reviews can include meta-analyses, appraisals of single trials, and other sources of evidence.6 In this article we examine the potentials and promise of meta-analysis of randomised controlled trials. In later articles of this series we will consider the practical steps involved in meta-analysis,7 examine various extensions beyond the calculation of a combined estimate,8 address potential biases and discuss strategies to detect and minimise the influence of these in meta-analysis of randomised trials9 and of observational studies.10 We will conclude with a discussion of unresolved issues and future developments.11 Details of relevant software will appear on the BMJ's website at the end of the series. Fig 1 Number of publications about meta-analysis, 1987–96 (results from Medline search using text word and medical subject heading "meta-analysis") #### What's in a name? The case for "meta-analysis" The term meta-analysis for statistically combining and analysing data from separate studies is appropriate because:
Beta-blockade and ischaemic injury: effects of partial agonist activity
Authors: A. S MANNING, J. M KEOGH, D. J HEARSE, D J. COLTART
Journal: Cardiovascular Research (1980)

In this study we have attempted: firstly to assess the extent to which the presence of partial agonist activity in a beta-blocking compound and /or sympathetic drive, influence ischaemic injury, and secondly to determine if any of the observed differences are due to changes in contractile activity. In the isolated, globally ischaemic (low flow) rat heart, oxprenolol (which possesses partial agonist activity) did not reduce creatine kinase leakage to the same extent as propranolol (no partial agonist activity) regardless of the background level of catecholamine drive. However, increasing background catecholamine drive increased the relative protection against enzyme leakage, of both beta-blockers. Under conditions of zero contractile activity (high K+ - medium) neither beta-blocker reduced enzyme leakage. Thus at equi-blocking doses oxprenolol and propranolol reduce enzyme leakage to different extents and the lesser protection afforded by oxprenolol is likely to be attributed to the presence of partial agonist activity. In addition, the reduction in enzyme leakage caused by both these compounds is due to reductions in contractile activity.
Frequency of Myocardial Infarction and Its Relationship to Angiographic Collateral Flow in Territories Supplied by Chronically Occluded Coronary Arteries
Authors: Jin-Ho Choi, Sung-A Chang, Jin-Oh Choi, Young Bin Song, Joo-Yong Hahn, Seung Hyuk Choi, Sang-Chol Lee, Sang-Hoon Lee, Jae K. Oh, YeonHyeon Choe, Hyeon-Cheol Gwon
Journal: Circulation (2013)

Despite complete interruption of antegrade coronary artery flow in the setting of a chronic total occlusion (CTO), clinical recognition of myocardial infarction is often challenging. Using cardiac MRI, we investigated the frequency and extent of myocardial infarction in patients with CTO, and assessed their relationship with regional systolic function and the extent of angiographic collateral flow.We included 170 consecutive patients (median age, 62 years) with angiographically documented CTO. Regional late gadolinium enhancement and wall motion score index were assessed by cardiac MRI with the use of a 17-segment model. Angiographic collateral flow was assessed by the collateral connection grade and the Rentrop score. Evidence of previous myocardial infarction was found in 25% of patients by ECG Q waves, in 69% by regional wall motion abnormality, and in 86% of patients by late gadolinium enhancement. Increased angiographic collateral flow was associated with a lower frequency of Q waves on ECG, and a lower regional wall motion score index, late gadolinium enhancement volume (%), and degree of late gadolinium enhancement transmurality (all P<0.001), as well.The frequency of myocardial infarction in territories subtended by CTO is significantly higher than previously recognized. The degree of myocardial injury downstream epicardial CTO is inversely correlated with the degree of angiographic collaterals.
Cardiovascular effects of air pollution: what to measure in ECG?
Authors: W Zareba, A Nomura, J P Couderc
Journal: Environmental Health Perspectives (2001)

Epidemiologic evidence indicates that air pollution adversely affects the cardiovascular system, leading to increased cardiovascular morbidity and mortality. However, the mechanisms of such an association are unknown. Although potential mechanisms of deleterious effects of air pollution may involve response of the respiratory system, immunologic response, or coagulation abnormalities, the cardiovascular system seems to be the common end point of these pathways. Cardiovascular response to any stress (which may include air pollution) is a consequence of a complex interplay between the autonomic nervous system governing centrally mediated control of the cardiovascular system, a myocardial substrate (current state of the myocardium) altered in the course of disease processes, and myocardial vulnerability leading to arrhythmogenic or ischemic response. Through the use of standard electrocardiograms (ECGs), exercise ECG testing, and long-term ambulatory ECG monitoring, modern electrocardiology makes a valuable contribution to understanding the different mechanistic factors involved in the increase in adverse cardiovascular events due to air pollution. Heart rate variability analysis can provide quantitative insight into the autonomic response of the cardiovascular system to air pollution. Analysis of ventricular repolarization in an ECG (both duration and morphology) gives valuable information about the status and dynamic behavior of myocardium, reflecting myocardial substrate and vulnerability. ST-segment analysis of ECGs is used routinely to monitor the magnitude of ischemia and could be used to monitor subtle changes in the myocardium in subjects exposed to air pollution. Comprehensive analysis of ECG parameters describing the influence of the autonomic nervous system, the role of myocardial substrate, and the contribution of myocardial vulnerability could and should be employed in air pollution studies, especially as those mechanistic components have been proven to contribute to increased cardiovascular morbidity and mortality in general.
Increased IgM-Type Betalactoglobulin Antibodies in Children with Recurrent Otitis Media
Authors: ULLA M. SAARINEN, ERKKI SAVILAHTI, PIRKKO ARJOMAA
Journal: Allergy (1983)

Total concentrations of IgA, IgG, IgM and IgE, precipitating antibodies to cow milk, milk-specific IgE, as well as anti-milk antibodies and betalactoglobulin antibodies of the IgA, IgG and IgM classes determined by the ELISA method were studied and compared in children with recurrent otitis media, and children who had never had otitis. The children with recurrent otitis had a higher total IgE at 1 year of age and a higher total IgM at 3 years. The only difference in milk-specific antibodies was an increased titre of betalactoglobulin antibodies of IgM type in children with recurrent otitis. This new finding suggests that immunological mechanisms might play a part in recurrent otitis, which has been shown to be more common in bottle-fed than in breast-fed infants. So far, the role of betalactoglobulin antibodies in the pathogenesis of otitis media remains uncertain.
Cryoglobulinemia in chronic liver diseases: role of hepatitis C virus and liver damage Lunel F, Mussel L, Cacoub P, Frangeul, Cresta P, Perrin M, Grippon P, Hoang C, Piette JC, Huraux JH, Opolon P. Gastroenterology 1994;106:1291?1300
Authors: J LEVEY
Journal: Hepatology (1995)
Trastuzumab wins backing of European drug regulator
Authors: Clare Dyer
Journal: BMJ (2006)

Trastuzumab (Herceptin), the breast cancer drug at the centre of a row over rationing in the NHS, last week won the first stage of approval by the European drug regulator for use in treating early stage cancer.

A committee of the European Medicines Agency, which licenses drugs for European Union countries, backed the extension of the drug's licence to include early stage disease in a record 10 weeks from application.

The recommendation, from the agency's committee for medicinal products for human use, is for the use of trastuzumab after surgery and …
Precancerous Lesions of the Colon and Rectum
Authors: Basil C. Morson
Journal: JAMA (1962)

A plea is made for greater precision in the use of the word polyp, which has, unfortunately, become increasingly used as synonymous with adenoma. There are many different pathological varieties of benign intestinal polyp. The classification here presented emphasizes that the only precancerous polyps are the adenoma, papillary adenoma, and villous papilloma. The distinction between the different histological types of intestinal polyp is discussed with particular reference to adenomas of the colon and rectum in children and young adults and the hamartomatous group of polyps including the Peutz-Jeghers and juvenile types. The pathology of carcinoma in association with ulcerative colitis is described and an explanation offered for these unusual pathological appearances. The value of a careful follow-up of every patient with ulcerative colitis for an indefinite period of time is emphasized.
FcgRIIIA (CD16)-expressing monocytes mediate the depletion of tumor-infiltrating Tregs via Ipilimumab-dependent ADCC in melanoma patients
Authors: Emanuela Romano, Monika Kusio-Kobialka, Periklis G Foukas, Helene Bichat, Petra Baumgaertner, Christiane Meyer, Pierluigi Ballabeni, Olivier Michielin, Benjamin Weide, Pedro Romero, Daniel E Speiser
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts Enhancing immune responses with immune-modulatory monoclonal antibodies (mAbs) directed to inhibitory immune-receptors is a promising modality in cancer therapy. Clinical efficacy has been demonstrated with antibodies blocking inhibitory immune checkpoints such as CTLA-4 or PD-1/
Expression of miR-15/107 Family MicroRNAs in Human Tissues and Cultured Rat Brain Cells
Authors: Wang-Xia Wang, Robert J. Danaher, Craig S. Miller, Joseph R. Berger, Vega G. Nubia, Bernard S. Wilfred, Janna H. Neltner, Christopher M. Norris, Peter T. Nelson
Journal: Genomics Proteomics & Bioinformatics (2014)

Abstract The miR-15/107 family comprises a group of 10 paralogous microRNAs (miRNAs), sharing a 5′ AGCAGC sequence. These miRNAs have overlapping targets. In order to characterize the expression of miR-15/107 family miRNAs, we employed customized TaqMan Low-Density micro-fluid PCR-array to investigate the expression of miR-15/107 family members, and other selected miRNAs, in 11 human tissues obtained at autopsy including the cerebral cortex, frontal cortex, primary visual cortex, thalamus, heart, lung, liver, kidney, spleen, stomach and skeletal muscle. miR-103, miR-195 and miR-497 were expressed at similar levels across various tissues, whereas miR-107 is enriched in brain samples. We also examined the expression patterns of evolutionarily conserved miR-15/107 miRNAs in three distinct primary rat brain cell preparations (enriched for cortical neurons, astrocytes and microglia, respectively). In primary cultures of rat brain cells, several members of the miR-15/107 family are enriched in neurons compared to other cell types in the central nervous system (CNS). In addition to mature miRNAs, we also examined the expression of precursors (pri-miRNAs). Our data suggested a generally poor correlation between the expression of mature miRNAs and their precursors. In summary, we provide a detailed study of the tissue and cell type-specific expression profile of this highly expressed and phylogenetically conserved family of miRNA genes.
Diabetes Treated by Saccharine Food
Authors: G. Corfe
Journal: BMJ (1858)

the postscript to a paper lately read before the Bath and Bristol Branch on Diabetes, by Dr. W. Budd, the following judicious remark is made by that gentleman:-" There are few maxims in philosophy which are entitled to more respect, than that which inculcates caution in drawing deductions from single instances."In the spirit of that suggestion I beg leave to communicate the following particulars to the profession.When I perused the details of the case which forms the subject of Dr. Budd's paper, I felt satisfied that the views incul- cated were based on a safe principle, and that they were not " meteoric," although they came upon Dr. T. Williams " with con- vulsive and startling effect," which seems to have been commu- nicated to his two diabetic patients, on whom Dr. Williams made a short trial of the saccharine treatment.The following case was under my care at the period when Dr. Budd's remarks were published, Nov. 14th, 1857.A tradesman in an adjoining county, aged 40, married, with seven children, tall, dark and spare, with black eyes and hair, and a tawny skin, evincing the true phosphatic diathesis, com- plained, October 1st, 1857, of weakness in knees, dryness of the throat and tongue, which was covered with a dirty fur, and so clammy that he was unable to eat solids; also of thirst, with ema- ciation, and frequent desire to pass uline.These symptoms had been creeping on him five or six weeks, prior to which period he had enjoyed excellent health.On desiring him to pass some urine, it was ascertained to be loaded with sugar, was amber-coloured, and of specific gravity 1042.There was un- equivocal evidence of solidification of the apex of the upper lobe of the right lung.The patient had lost one brother, at the age of 25, with tuberculosis, and a sister, aged 40, with diabetes.His father died at 75, and his mother is still living, aged 85.The patient is the youngest of eight children.He was immediately put under the following treatment:- Creasoti miv; mist.acac.5 ss; aquoe carui 3i.M. Fiat haustus ter in die sumendus.In additiont to the above, he was directed to take a table- spoonful of cod-liver oil in milkl after each meal.The usual diabetic diet, consisting of underdone meat, greens, eggs, milk, and bran biscuits, was prescribed, together with a total absti- nence from saccharine, farinaceous, and amylaceous substances.The nrine voided averaged five pints in twenty-four hours.I was enabled to test the urine of six of the children, and found them all free from sugar except irn one, a boy, 51 years old, where the quantity was small, but marked by the usual tests.From this pei-iod to December 1st (two months) the patient became more or less dispirited at the manifest downward course the disease was assuming.The urine gradually increased in quantity, and the specific gravity ranged from 46 to 52, his vigour was fast waning, the disease assumed a most formidable character and threatened to cut short his life in a few weeks.