tbuckley/cabot-search huggingface dataset:
Enhancement of Platelet Deposition by Cross-Linked Hemoglobin in a Rat Carotid Endarterectomy Model
Authors: Stephen B. Olsen, Douglas B. Tang, Mark R. Jackson, Edward R. Gomez, Benjamin Ayala, Barbara M. Alving
Journal: Circulation (1996)

Purified human cross-linked hemoglobin, which is now being used in clinical trials, increases mean arterial pressure through binding of nitric oxide (NO). We postulated that binding of NO by cross-linked hemoglobin (alpha alpha Hb) could also increase platelet deposition at sites of subintimal injury.Male Sprague-Dawley rats were infused with alpha alpha Hb (0.88 g/kg, n = 8) or with the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA, 30 mg/kg, n = 7) before undergoing microsurgical carotid endarterectomy. 111In-labeled platelets were infused after endarterectomy, and platelet deposition was measured 20 minutes later. In control endarterectomized rats (n = 8), mean platelet deposition was 7.7 +/- 0.7 x 10(6)/mm2. Platelet deposition was significantly increased above controls in rats that received alpha alpha Hb (13.2 +/- 0.9 x 10(6)/mm2, P = .0004) and in rats infused with L-NMMA (13.9 +/- 1.0 x 10(6)/mm2, P = .0002). The increase was prevented by infusion of L-arginine (150 mg/kg) immediately after alpha alpha Hb or L-NMMA. To determine whether aspirin (ASA) blocked the increased deposition induced by alpha alpha Hb, rats received oral ASA (10 mg/kg) 18 hours before endarterectomy. Platelet deposition in animals receiving ASA alone was 6.4 +/- 0.9 x 10(6)/mm2 (n = 8). This was significantly increased to 10.8 +/- 0.8 x 10(6)/mm2 (P = .002) for the ASA-treated group that received alpha alpha Hb at the time of endarterectomy (n = 8). The prolonged bleeding times induced by ASA were unaffected by the infusion of alpha alpha Hb.These data suggest that in a rat endarterectomy model, alpha alpha Hb increases platelet deposition at sites of subintimal injury by binding NO. Increased deposition induced by alpha alpha Hb can be prevented by administration of L-arginine but not by pretreatment with aspirin.
Depot Fluphenazines: 12 Years' Experience
Authors: J. Raymond DePaulo
Journal: JAMA (1978)

This little book comprises the 11 papers presented at a symposium held in August 1977. Compared with most published symposiums, this book is a pleasant surprise. It is up to date and clearly written. The chapters complement each other to produce a coherent view of research and clinical practice with this subgroup of neuroleptic drugs. Much of the credit must go to the editor. The chapters cover, among other topics, the clinical response and plasma levels of fluphenazine, the comparison of the long-acting depot neuroleptics with short-acting oral preparations, and the safety of highdose depot fluphenazine. Dr Ayd's overview in the last chapter indicates the consensus that long-acting depot fluphenazines are still most useful for patients with schizophrenia who have florid symptoms, reasonably intact affective responsiveness, and "who are either unreliable consumers of oral medications or poor responders to oral neuroleptics because of unknown obstacles of absorption or metabolism." The
I. ANTIGENICITY OF OXYPOLYGELATIN AND GELATIN IN MAN
Authors: Paul H. Maurer
Journal: The Journal of Experimental Medicine (1954)

It has been demonstrated that there are normally occurring antibodies to gelatin in human sera. Immunization with gelatin can in many cases increase the antibody level. The presence of these antibodies does not result in cutaneous reactions of the wheal and erythema type after injection of antigen. Many of the properties of the gelatin-antigelatin reaction and the precipitates formed are those of a truly specific antigen-antibody aggregate. Explanations have been advanced both as to the possible sources of the gelatin antibody and its significance.
Poorest areas have best smoking cessation services, report shows
Authors: Zosia Kmietowicz
Journal: BMJ (2006)

The quality of smoking cessation services provided by the 303 primary care trusts in England is variable, with services in deprived areas outperforming those in richer parts of the country, says a report from the health service watchdog.

The review, from the Healthcare Commission, shows that half of the trusts in the poorest parts of England scored “excellent” in their efforts to reduce the impact of smoking, with only 2% of trusts being graded as “fair,” the lowest grade. Of trusts in wealthier areas less than 20% were graded as excellent, and a quarter were rated …
Accenture withdraws from NHS IT contract
Authors: Michael Cross
Journal: BMJ (2006)

Accenture withdraws from NHS IT contract 167accentshortThe £12bn (€18bn; $23bn) programme to computerise the NHS in England has lost its second largest contractor.Accenture, a consulting and information technology (IT) services company that is based mainly in the United States but registered in Bermuda, last week announced that it is withdrawing from contracts worth some £2bn to create electronic health records in the northeast and east of England.Although expected, the move rekindled speculation about the future of the world's largest civil IT programme.Accenture was one of four firms awarded contracts in 2003 worth £5bn for packages of work to install standard IT systems across regional clusters of health authorities in England.The other three were BT, Fujitsu, and Computer Sciences Corporation (CSC), which is to take over Accenture's two regions.The Department of Health drew up the contracts on a scale that would attract global companies prepared to accept tough contracting terms, including payment on delivery.Accenture's departure may mean that it found the terms too tough.Earlier this year it set aside £257m in its accounts for losses on the programme, for which it blamed delays caused by the late delivery of clinical software being developed by the UK specialist firm iSOFT, a subcontractor to Accenture and CSC.
Drug-Resistant Tuberculosis, Clinical Virulence, and the Dominance of the Beijing Strain Family in Russia
Authors: Francis Drobniewski
Journal: JAMA (2005)

Tuberculosis and multidrug-resistant tuberculosis is a serious public health problem in Russia.To address the extent of "Beijing strain" transmission in the prison/civil sectors and the association of drug resistance, clinical, and social factors with the Beijing genotype.Cross-sectional population-based molecular epidemiological study of all civilian and penitentiary tuberculosis facilities in the Samara region, Russia.Consecutively recruited patients with bacteriologically proven tuberculosis (n = 880).Proportion of Beijing strains and association with drug resistance, human immunodeficiency virus infection, imprisonment, radiological, clinical, and other social factors.Beijing-family strains (identified by spoligotyping and composed of 2 main types by mycobacterial interspersed repetitive unit analysis) were predominant: 586/880 (66.6%; 95% confidence interval [CI], 63.4%-69.7%) with a significantly higher prevalence in the prison population (rate ratio [RR], 1.3; 95% CI, 1.2-1.5) and those aged younger than 35 years (RR, 1.2; 95% CI, 1.0-1.3). Comparable proportions were co-infected with the human immunodeficiency virus ( approximately 10%), concurrent hepatitis B and C (21.6%), drank alcohol ( approximately 90%), smoked ( approximately 90%), and had a similar sexual history. Drug resistance was nearly 2-fold higher in patients infected with Beijing strains compared with non-Beijing strains: multidrug resistance (RR, 2.4; 95% CI, 1.9-3.0), for isoniazid (RR, 1.8; 95% CI, 1.5-2.1), for rifampicin (RR, 2.2; 95% CI, 1.7-2.7), for streptomycin (RR, 1.9; 95% CI, 1.5-2.3), and for ethambutol (RR, 2.2; 95% CI, 1.6-3.2). Univariate analysis demonstrated that male sex (odds ratio [OR], 1.5; 95% CI, 1.1-1.9), advanced radiological abnormalities (OR, 3.3; 95% CI, 1.3-8.4), homelessness (OR, 5.6; 95% CI, 1.1-6.3), and previous imprisonment (OR, 2.0; 95% CI, 1.5-2.7) were strongly associated with Beijing-strain family disease. Multivariate analysis supported previous imprisonment to be a risk factor (OR, 2.0; 95% CI, 1.4-3.3) and night sweats to be less associated (OR 0.7; 95% CI, 0.5-1.0) with Beijing-strain disease.Drug resistance and previous imprisonment but not human immunodeficiency virus co-infection were significantly associated with Beijing-strain infection. There was evidence that Beijing isolates caused radiologically more advanced disease.
Local regulation of subcutaneous forefoot blood flow during orthostatic changes in normal subjects, in sympathetically denervated patients and in patients with occlusive arterial disease
Authors: J. H EICKHOFF, A. O. HENRIKSEN
Journal: Cardiovascular Research (1985)

Local blood flow regulation was studied on the forefoot by the 133-Xenon wash-out method. In 21 normal limbs blood flow decreased 36% when the foot was lowered 40 cm below heart (local vasoconstrictor response). During elevation blood flow was constant to 20 cm, and flow decreased only 10% at further elevation to 40 cm, corresponding to a drop in vascular resistance of 15% (autoregulation of blood flow). In six sympathetically denervated limbs blood flow decreased only 6%, significantly less than in the normal limbs. Autoregulation of blood flow was preserved in these limbs. In 22 limbs with intermittent claudication blood flow decreased only 19%, significantly less than in the normal limbs. However, taking into account the additional increase in arterial pressure that occurs, when a limb with arterial occlusion is lowered there was no significant difference (p = 0.26) in the increase in vascular resistance between the two groups. During elevation vascular resistance decreased significantly in the claudicants indicating preservation of autoregulation. In limbs with rest pain blood flow increased 28% during lowering, and when the additional increase in arterial blood pressure was accounted for, a significant increase in vascular resistance of 21% was noted. During elevation blood flow decreased significantly, and the estimated vascular resistance in this group did not decrease significantly. The study suggests that the increase in blood flow and the relief of ischaemic rest pain induced by lowering are due to an additional increase in arterial pressure rather than due to dilatation of arterioles.
Banning trans fatty acids will reduce risk of heart attacks, study says
Authors: David Spurgeon
Journal: BMJ (2006)

Virtually eliminating the amount of trans fatty acids in industrially produced food could avert between 72 000 (6% of the total) and 228 000 (19%) coronary heart events each year in the United States, a new US and Dutch review study concludes ( N Engl J Med 354;1601-13).

The amount of trans fats in packaged snack foods, bakery products, deep fried fast food, margarine, and packaged snacks such as tortilla chips increases consumers' risk of cardiovascular disease, coronary heart disease, and sudden death from cardiac causes, say the researchers, from Brigham and Women's Hospital and Harvard Medical School and the Harvard School of Public Health in …
Platelet-derived LIGHT induces inflammatory responses in endothelial cells and monocytes
Authors: Kari Otterdal, Camilla Smith, Erik Øie, Turid M. Pedersen, Arne Yndestad, Espen Stang, Knut Endresen, Nils O. Solum, Pål Aukrust, Jan K. Damås
Journal: Blood (2006)
Mitochondrial gene rearrangement in the sea cucumber genus Cucumaria
Authors: A. Arndt, M. J. Smith
Journal: Molecular Biology and Evolution (1998)

A novel mitochondrial tRNA gene arrangement is described for two species of sea cucumber. The mitochondrial tRNA gene cluster common to sea stars, sea urchins, and the sea cucumber Parastichopus californicus has been significantly modified in the genus Cucumaria as a result of dispersal of the tRNA genes into two separate areas of the genome. The tRNA genes in the novel clusters are interspersed with short unassigned sequences (UASs). Alignment of the two separated novel clusters indicates that the rearrangement was most likely the result of a tandem duplication of approximately 7 kb, encompassing the putative control region, the tRNA cluster, NADH dehydrogenase subunits 1 and 2, the large ribosomal RNA (lrRNA), cytochrome oxidase subunit I, and tRNAArg. Subsequently, deletion of the duplicated lrRNA and protein-coding genes occurred. In addition, the degeneration of one of each of the duplicated tRNA gene pairs has resulted in the interspersed UAS segments observed in each cluster. In contrast, the second copy of the putative control region has been maintained with a very high degree of sequence conservation, suggesting either some functional constraint or concerted evolution for the duplicated element. Analysis of gene organization in other sea cucumber species may provide (1) important insights into the mechanism of mitochondrial gene rearrangements and (2) an informative character set for deep-level phylogenetic analysis of this echinoderm class.
Thrombomodulin modulates growth of tumor cells independent of its anticoagulant activity.
Authors: Y Zhang, H Weiler-Guettler, J Chen, O Wilhelm, Y Deng, F Qiu, K Nakagawa, M Klevesath, S Wilhelm, H Böhrer, M Nakagawa, H Graeff, E Martin, D M Stern, R D Rosenberg, R Ziegler, P P Nawroth
Journal: Journal of Clinical Investigation (1998)

Thrombomodulin (TM), recognized as an essential vessel wall cofactor of the antithrombotic mechanism, is also expressed by a wide range of tumor cells. Tumor cell lines subcloned from four patients with malignant melanoma displayed a negative correlation between TM expression and cell proliferation in vitro and in vivo. Overexpression of wild-type TM decreased cell proliferation in vitro and tumor growth in vivo. TM mutants with altered protein C activation capacity lead to a similar effect. In contrast, transfection of melanoma cells with mutant TM constructs, in which a portion of the cytoplasmic or lectin domain was deleted, abrogated the antiproliferative effect associated with overexpression of wild-type TM. Experiments performed with either peptide agonists/antagonists of the thrombin receptor, with hirudin, or with inhibitors of thrombin-TM interaction did not alter the growth inhibitory effect of TM overexpression. These data suggest that TM exerts an effect on cell proliferation independent of thrombin and the thrombin receptor, possibly related to the binding of novel ligands to determinants in the lectin domain which might trigger signal transduction pathways dependent on the cytoplasmic domain.
Effects of cortisol deficiency on the electrocardiogram.
Authors: M. Hartog, G. F. Joplin
Journal: BMJ (1968)

Pericarditis-Robinsonz and Brigden BRITSH 275 ciated with the post-infarction syndrome and post-cardiotomy syndrome.The problems of differential diagnosis are discussed.Cardiac tamponade was the most serious complication ; but this was uncommon and was rapidly relieved by aspiration of peri- cardial fluid.No patients required pericardectomy, possibly because corticosteroids brought rapid resolution or possibly because constriction is so rare that it was not encountered in any one of these 41 patients.Furthermore, corticosteroid therapy effectively prevents recurrences, which are common in all forms of "benign " pericarditis." Antiheart" antibodies were detected in almost all of the post-infarction and post-cardiotomy cases and in one-third of the idiopathic group.It is concluded that recurrent pericarditis may be provoked by a variety of noxious agents, which lead, in susceptible individuals, to an abnormal immune reaction independcnt of the primary cause.
Left Ventricular Systolic Function and Outcome After In-Hospital Cardiac Arrest
Authors: Maria M. Gonzalez, Robert A. Berg, Vinay M. Nadkarni, Caio B. Vianna, Karl B. Kern, Sergio Timerman, Jose A. Ramires
Journal: Circulation (2008)

The effect of prearrest left ventricular ejection fraction (LVEF) on outcome after cardiac arrest is unknown.During a 26-month period, Utstein-style data were prospectively collected on 800 consecutive inpatient adult index cardiac arrests in an observational, single-center study at a tertiary cardiac care hospital. Prearrest echocardiograms were performed on 613 patients (77%) at 11+/-14 days before the cardiac arrest. Outcomes among patients with normal or nearly normal prearrest LVEF (> or = 45%) were compared with those of patients with moderate or severe dysfunction (LVEF < 45%) by chi(2) and logistic regression analyses. Survival to discharge was 19% in patients with normal or nearly normal LVEF compared with 8% in those with moderate or severe dysfunction (adjusted odds ratio, 4.8; 95% confidence interval, 2.3 to 9.9; P<0.001) but did not differ with regard to sustained return of spontaneous circulation (59% versus 56%; P=0.468) or 24-hour survival (39% versus 36%; P=0.550). Postarrest echocardiograms were performed on 84 patients within 72 hours after the index cardiac arrest; the LVEF decreased 25% in those with normal or nearly normal prearrest LVEF (60+/-9% to 45+/-14%; P<0.001) and decreased 26% in those with moderate or severe dysfunction (31+/-7% to 23+/-6%, P<0.001). For all patients, prearrest beta-blocker treatment was associated with higher survival to discharge (33% versus 8%; adjusted odds ratio, 3.9; 95% confidence interval, 1.8 to 8.2; P<0.001).Moderate and severe prearrest left ventricular systolic dysfunction was associated with substantially lower rates of survival to hospital discharge compared with normal or nearly normal function.
Accelerated progression of coronary artery disease.
Authors: R J Vecht, E P Nicolaides, A Duffett, D C Cumberland
Journal: BMJ (1987)

<b>Introduction: </b>Nasal NO (nNO) is used to screen for Primary Ciliary Dyskinesia (PCD). nNO and exhaled NO (FENO) are low in PCD and cystic fibrosis (CF), but nothing is known about nNO in patients with humoral immunodeficiencies (HID). We want to study the discriminate validity of nNO and FENO or composite scores for the diagnosis of PCD. <b>Methods: </b>157 patients between 5 and 25 years old performed nNO and FENO measurements using the chemiluminescence analyzer Spiroware 3.0® (Eco Medics): 27 with PCD, 28 with CF, 32 with asthma (A), 30 with HID and 40 healthy controls (C). 6 nNO measurements were performed during slow exhalation against a fixed resistance. For FENO, 2 measurements were done conform ATS/ERS guidelines. <b>Results: </b>For nNO, median coefficient of variation (CV) was 7.2% (P25 4.1%, P75 19.7%, range 1 to 92%), despite perfect test performance. nNO differed significantly between PCD and no PCD and between PCD and CF, A, HID and C individually. nNO &lt; 270 ppb had a sensitivity of 92.6 % and a specificity of 89.2 % to diagnose PCD. Area under the curve (AUC) for the ROC curve was 0.978. However, some overlap exists between PCD and CF, HID and A. FENO was significantly lower in PCD versus no PCD and in PCD versus CF, A, HID and C. FENO &lt; 7.1 ppb had a sensitivity of 92%, but only a specificity of 71.6% (AUC 0.833). The composite scores nNO + FENO, nNO * FENO, nNO * FENO² all had a lower AUC for the ROC curve, only the composite score nNO² * FENO had an equal AUC and a slightly higher specificity (93.1% for a sensitivity of 92.0%) than nNO measurement alone. <b>Conclusion: </b>Both nNO and FENO are useful screening tests for PCD: using the composite score nNO² * FENO increases the specificity with stable sensitivity.
Abstract LB-401: Functional impact bias reveals cancer drivers
Authors: Abel Gonzalez-Perez, Nuria Lopez-Bigas
Journal: Cancer Research (2012)

Abstract Currently, one of the main challenges in cancer genomics is the identification of driver genes and pathways among all the altered genes in a cohort of tumors. Typically, tests of recurrence are applied to identify significantly mutated genes, which are candidates to cancer drivers. These methods assess the probability to observe by chance the number of somatic single nucleotide variants (SNVs) found across a number of tumor samples. Some known limitations of these methods include the difficulty in correctly assessing background mutation rate, as all parameters that affect it are not well-understood, and the fact that they usually fail to identify lowly recurrently mutated driver genes. In addition, methods that compute recurrence treat all observed somatic SNVs equally when clearly their impact on protein function varies widely. We have developed a method which can complement the analysis of recurrence of SNVs across several tumor samples to detect candidate driver genes by taking advantage of the information provided by the analysis of functional impact of SNVs and short frameshift indels. The method is based on the assumption that any bias towards the accumulation of variants with high functional impact (FM bias) is an indication of positive selection and can thus be used to detect candidate driver genes or gene modules. We have called it Oncodrive-fm. We have applied the Oncodrive-fm approach to two datasets of genes with variants in samples of different tumor types: Chronic Lymphocytic Leukemia (cll: from Spanish ICGC Group) and Glioblastoma datasets (gbm: from TCGA). Most of the genes detected by recurrence analysis (i.e MutSig) also show significant FM bias (eg. TP53, EGFR, PTEN in gbm and SF3B1 in cll), we call these clear drivers. However, Oncodrive-fm can also detect lowly recurrent likely driver genes that are overlooked by recurrence analysis (eg. IDH1, FGFR1 and FGFR3 in gbm and CDH9 and CHD2 in cll), and identify genes with high number of mutations that do not show FM bias, which we term as candidate false positives. The application of Oncodrive-fm to the analysis of pathways reveals several pathways with FM bias, such as MAPK and mTOR pathways in gbm and mRNA splicing pathway in cll. In summary we show that FM bias helps to uncover drivers and recommend its computation in conjunction with the analysis of recurrence in a cohort of tumor samples to identify candidate driver genes and gene modules. Oncodrive-fm method is available at http://bg.upf.edu/oncodrive. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-401. doi:1538-7445.AM2012-LB-401
Pooled cataract waiting lists: views of hospital consultants, general practitioners and patients
Authors: M. Ramchandani, S. Mirza, A. Sharma, G. Kirkby
Journal: Journal of the Royal Society of Medicine (2002)

In the National Health Service general practitioners (GPs) usually refer patients to named consultants; thus, waiting times for a particular procedure can vary greatly even within a single centre. An alternative is to pool the waiting list, with patients treated in turn by the consultant available. We sought opinions on this strategy, from patients, GPs, and consultants, in relation to cataract surgery. Questionnaires were sent to 776 consultant ophthalmologists; telephone interviews were conducted with 50 randomly selected Birmingham GPs; and 85 Birmingham patients listed for cataract surgery were asked whether they would change consultant to be operated on sooner. 503 (64%) of the consultants responded. Of consultants, 30% favoured pooled lists and 67% were against. Of patients, 82% favoured pooled lists and 18% were against. Of GPs, 92% favoured pooled lists and 8% were against. Some consultants thought that pooled lists were suitable for routine cases but not for more complex cases. 82% of patients expressed willingness to change consultant in order to get an earlier operation. In units with surgeons whose cataract-surgery practices are similar, pooled lists are one way to maximize theatre use and equalize waiting times for routine cases. The model could be applied to other routine surgical procedures such as hip replacement, herniorrhaphy and prostatectomy.