tbuckley/cabot-search huggingface dataset:
Accuracy and reproducibility of new M-mode echocardiographic recommendations for measuring left ventricular dimensions.
Authors: M H Crawford, D Grant, R A O'Rourke, M R Starling, B M Groves
Journal: Circulation (1980)

In order to assess the accuracy and reproducibility of the proposed American Society of Echocardiography (ASE) method for measuring left ventricular dimensions on M-mode echocardiograms, we measured the end-diastolic (Dd) and end-systolic (Ds) dimensions by the ASE method and our current technique in 50 normal subjects and 24 patients without coronary artery disease who had symmetrically contracting ventricles on cineangiography. Dd and Ds were significantly greater by the proposed ASE method than by our current technique (p less than 0.001), but the correlation between the two was good (r = 0.93 and 0.83, respectively). In 10 of the normal subjects, the interobserver variability of both methods was excellent. In the 24 patients, the proposed method consistently overestimated the angiographic left ventricular volumes compared with our current technique and occasionally the discrepancies were quite large. Therefore, the proposed ASE method for measuring left ventricular dimensions is not clearly superior to other currently available techniques.
Continua outperform dichotomies
Authors: John D. Baldwin
Journal: Behavioral and Brain Sciences (1995)

Abstract Mealey's data do not support her dichotomous model of primary and secondary sociopathy; this data supports the view that there is a continuum of degrees of sociopathy, from zero to the maximal manifestation. There are multitudes of factors that can contribute to sociopathy – from both genetic and environmental sources – and the countless different mixes of them can produce multiple degrees and variations of sociopathic behavior.
Alport familial nephritis. Absence of 28 kilodalton non-collagenous monomers of type IV collagen in glomerular basement membrane.
Authors: M M Kleppel, C E Kashtan, R J Butkowski, A J Fish, A F Michael
Journal: Journal of Clinical Investigation (1987)

Alport-type familial nephritis (FN), a genetic disorder, results in progressive renal insufficiency and sensorineural hearing loss. Immunochemical and biochemical analyses of the non-collagenous (NC1) domain of type IV collagen isolated from the glomerular basement membranes (GBM) of three males with this disease demonstrate absence of the normally occurring 28-kilodalton (kD) NC1 monomers, but persistence of the 26- and 24-kD monomeric subunits derived from alpha 1 and 2 (both type IV) collagen chains, respectively.
Acute Reversible Hypoxemia in Systemic Lupus Erythematosus
Authors: Steven B. Abramson, Jeffrey Dobro, Mark A. Eberle, Marc Benton, Joan Reibman, Hadassah Epstein, David M. Rapoport, H. Michael Belmont, Roberta M. Goldring
Journal: Annals of Internal Medicine (1991)

To determine the frequency of unexplained reversible hypoxemia in patients with systemic lupus erythematosus and to assess the relation between hypoxemia and elevated plasma levels of complement split products.Cohort study.Inpatient and outpatient facilities of the New York University Medical Center/Bellevue Hospital and the Hospital for Joint Diseases.Case patients were 22 patients hospitalized with disease exacerbation and no evidence of parenchymal lung disease on chest roentgenogram. Four patients with stable disease were followed in the outpatient clinic, and five healthy normal volunteers served as controls.Plasma levels of complement split products (C3a, factor Bb fragment), alveolar-arterial (A-a) Po2 gradients, and pulmonary function were measured.Nine episodes of hypoxemia or hypocapnia (mean A-a gradient, 30.4 +/- 4.8 mm Hg) or both (despite normal chest roentgenogram results) were noted in six hospitalized patients (group 1). Gas exchange improved within 72 hours of steroid therapy (mean A-a gradient, 11.6 +/- 4.3 mm Hg; P less than 0.01). These patients had an elevated initial mean C3a level (938.4 +/- 246.8 ng/mL) that decreased within 72 hours (407.8 +/- 80.9 ng/mL; P less than 0.01), concomitant with improved oxygenation. Ventilation-perfusion scans, obtained for four of six group 1 patients, excluded pulmonary emboli. Four hospitalized patients (group 2) had a normal A-a gradient (mean, 7.5 +/- 2.7 mm Hg). The mean C3a level of this group (358.3 +/- 39.2 ng/mL) was lower than that of group 1 (P less than 0.05). Four patients with stable disease (group 3) had a mean A-a gradient and a mean C3a level of 3.3 +/- 2.7 mm Hg and 237.8 +/- 105.7 ng/mL, respectively, similar to values found in five normal volunteers, in whom the mean A-a gradient was 3.7 +/- 1.7 mm Hg and the mean C3a level was 124.8 +/- 9.2 ng/mL.A syndrome of reversible hypoxemia, unassociated with parenchymal lung disease, is unexpectedly common in acutely ill, hospitalized patients with systemic lupus erythematosus. The pathogenesis of this syndrome is unclear, although the data are compatible with the hypothesis that hypoxemia may be related to pulmonary leukoaggregation.
Depletion of cell surface CD44 in nonmelanoma skin tumours is associated with increased expression of matrix metalloproteinase 7
Authors: S. Hartmann-Petersen, R.H. Tammi, M.I. Tammi, V.-M. Kosma
Journal: British Journal of Dermatology (2009)

Expression of matrix metalloproteinase (MMP)-7 and MMP-9 is low in the normal epidermis and is induced by physiological processes such as wound healing, but also malignant transformation of epidermal cells. The activity of both MMPs has been associated with the hyaluronan (HA) receptor CD44. We previously reported that the levels of CD44 and HA differ between the two types of epidermal tumours, basal (BCC) and squamous cell carcinoma (SCC), as well as between different grades of SCC.To investigate if the immunostaining patterns of MMP-7 and MMP-9 correlate to those of CD44 and HA in BCC and SCC.Paraffin sections from 71 BCCs, 21 in situ SCCs and 27 SCCs were immunostained for MMP-7 and -9.Positive immunostaining for MMP-7 and MMP-9 was found in tumour cells of both BCC and SCC, while the staining intensity tended to be stronger in SCC. The staining intensity of MMP-7 was inversely correlated with that of CD44 in both tumour types. In well-differentiated SCC, the intensity of MMP-7 was generally weak, while CD44 staining was strong and homogeneously distributed. In poorly differentiated SCC, an increase in MMP-7 was seen, and the staining intensity of CD44 became weak and was locally absent. No correlation was seen between MMP-9 and CD44 or either of the two MMPs and HA.Our results show that in nonmelanoma skin tumours MMP-7 and -9 are present in the tumour cells, and suggest a link between MMP-7 activity and the depletion of cell surface CD44.
OxDONS syndrome: the inevitable disease of the NHS reforms
Authors: C B T Adams
Journal: BMJ (1995)

The financial demise of Oxford's department of neurosurgery (OxDONS) was precipitated by the financial rules of the reformed NHS. In particular it was produced by the failure of "resources to follow patients"; the requirement that "prices have to follow costs"; and the use of private income for revenue expenditure, not capital expenditure. This process will eventually affect all hospital departments, but it affected the unit in Oxford sooner as it started as "efficient"--that is, underresourced--and has depended on income from extracontractual referrals and private work. Current NHS accounting rules act as a disincentive to private income being generated in NHS hospitals, and consultants should be aware of this.
Working with Dangerous People: The Psychotherapy of Violence
Authors: Gwen Adshead
Journal: BMJ (2004)

Iread this book on a recent trip to New York. On a beautiful spring day in Manhattan's upper east side, it is hard to believe that the annual rate of homicide in the city is the same as theannual rate for the whole of England and Wales. It doesn't take a minute in New York to work outthat reducing violence is an urgent political priority; so a book about an unusual approach to treating violent men should be of interest.

Ed David Jones

Radcliffe Medical Press,

£24.95,

pp 212

ISBN 1857758242 …
Vacuolation of the Nuclei of Nerve Cells in the Cortex
Authors: Fred. M.T. Skae
Journal: BMJ (1894)

the increased blood pressure against whichli its work is directed.It is a well-known pliysiolotgieal fact tli-it ill cases of sylncope due to loss of blood, the injection of a nieutrall fluid into the main arterial system will cause the flaccid heart to recommence its pulsations, simiiply mechanically, by giving the lheart a heavier column to beat against.
Abstract 821: Subgroups of urothelial carcinoma of the bladder defined by genomic analysis.
Authors: Carolyn D. Hurst, Fiona M. Platt, Claire F. Taylor, Margaret A. Knowles
Journal: Cancer Research (2013)

Abstract Urothelial carcinoma (UC) of the bladder is a heterogeneous disease and presents a significant challenge in disease management. The divergence in clinical behaviour of tumors of similar stage and grade indicates the presence of molecular subgroups. In this study we aimed to identify novel genomic subgroups of UC to provide improved subclassification at diagnosis. We assessed 160 bladder tumors comprising all stages and grades and including 49 high-stage T1 (T1G3) tumors for genome-wide copy number alterations and mutations in 8 key genes (AKT1, FGFR3, HRAS, KRAS, NRAS, PIK3CA, TP53, TSC1) implicated in UC. This revealed the existence of potential genomic subclasses of the “gold-standard” stage/grade groups of UC. The clinical management of patients with T1G3 tumors is particularly challenging as this subset of tumors exhibit highly divergent behaviour. Three major subgroups of T1G3 tumors were identified that differed with respect to copy number alterations and to FGFR3 and TP53 mutation status. One of these, which showed a prevalence of copy number losses, had the highest rate of stage progression/metastasis. We also identified novel regions of copy number alteration, concomitant molecular events, and relationships between molecular events and clinico-pathological features. Tumors harbouring FGFR3 mutations were found to be more chromosomally stable than their wild-type counterparts and FGFR3 mutation was mutually exclusive with overrepresentation of 8q in non-muscle-invasive tumors. In muscle-invasive (MI) tumors, losses of regions on 10q (including PTEN), 16q and 22q and gains on 10q, 11p, 12p, 19p and 19q were positively associated with metastasis. TP53 mutation in MI tumors was positively associated with losses on 16p, 2q, 4q, 11p, 10q, 13q, 14q, 16q and 19p and gains on 1p, 8q, 10q and 12q. Molecular alterations involving chromosome 9 were highly complex and copy number loss in the CDKN2A region was positively associated with deletions on 6p, 6q, 9p, 9q, 11p, 13q and 17p, and gains on 1q, 4q, 7p, 7q, 8p, 17q and 20q in MI tumors. Our findings add information to conventional histopathological classification and may lead to improved biological understanding and the development of robust prognostic biomarkers. Studies of larger numbers of tumors are underway to confirm the subgroups and relate findings to clinico-pathological data. Citation Format: Carolyn D. Hurst, Fiona M. Platt, Claire F. Taylor, Margaret A. Knowles. Subgroups of urothelial carcinoma of the bladder defined by genomic analysis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 821. doi:10.1158/1538-7445.AM2013-821
Nifedipine for Hypertensive Emergencies
Authors: John M. DiMichele
Journal: JAMA (1997)

<h3>To the Editor.</h3> —The article by Dr Grossman and colleagues<sup>1</sup>raises a critical issue that all physicians must face in sciencebased practice: are we basing our clinical and therapeutic decisions on our best sound logic and proven fact? The issue becomes especially critical when the risks of our actions might become life-threatening. However, I pause at the conclusion that we must abandon outright the practice of using nifedipine for the treatment of hypertensive emergencies. The authors cite the lack of data proving the benefit of this intervention, but lack of data is not equivalent to negative data. Is not the decision to abandon a practice based on the absence of data proving its benefit equivalent to endorsing a practice without supporting data? Significant morbidity is often an acceptable cost if we know that the therapeutic risk is outweighed by the benefit of therapy. Of note, both deaths reported secondary
TREATMENT OF TUBERCULOUS AFFECTIONS BY INFLATION WITH OXYGEN
Authors: R. Purves, E. J. Bilcliffe
Journal: BMJ (1924)

JORRIreally necessary?With the exception of Moiison's recur- renit case anid Wauglh's case, they were perfonmed in only one of the other eight cases mentioned-aanother reasoni for the performanice being given.They were not performed in aniy of Dr. Still's cases, and though "the ear-liest was nearly eight year-s ago anid the latest a year ago "2 none had recuiirred.My best tlhanks are due to Dr. G. F.
Increased Generation of Leukotriene C<sub>4</sub> from Eosinophils in Asthmatic Patients
Authors: N. Taniguchi, H. Mita, H. Saito, Y. Yui, T. Kajita, T. Shida
Journal: Allergy (1985)

Human eosinophils with a density of over 1.095 were isolated from peripheral blood by dextran sedimentation, centrifugation with Lymphoprep and density gradients with Percoll. After the cells (1 × l0 5 ml) were incubated with 1 μg/ml calcium ionophore A23187 for 20 min, leukotriene C 4 (LTC 4 ) content in the supernatant was measured by radioimmunoassay. The generation of LTC 4 was significantly higher in the cells from extrinsic asthmatics (23.5 ± 14.8 ng/l0 6 cells, mean ± SD, n = 26, P &lt; 0.01) and intrinsic asthmatics (24.6 ± 20.6 ng/10 6 cells, n = 27, P &lt; 0.01) as compared with normal healthy subjects (8.3 ± 7.7 ng/10 6 cells, n = 10). There was no significant difference in the generation of LTC 4 between intrinsic and extrinsic asthmatics. These observations indicate that eosinophils from asthmatic patients have increased ability to release LTC 4 .
1161-172 Upregulation of Akt and endothelial nitric oxide synthase induces vascular smooth muscle cell differentiation in hypertension in vivo
Authors: Shinji Kawahara, Seiji Umemoto, Masakazu Tanaka, Kyoko Umeji, Ryo Hashimoto, Susumu Matsuda, Masunori Matsuzaki
Journal: Journal of the American College of Cardiology (2004)
Recent Declines in Hospitalizations for Acute Myocardial Infarction for Medicare Fee-for-Service Beneficiaries
Authors: Jersey Chen, Sharon-Lise T. Normand, Yun Wang, Elizabeth E. Drye, Geoffrey C. Schreiner, Harlan M. Krumholz
Journal: Circulation (2010)

Amid recent efforts to reduce cardiovascular risk, whether rates of acute myocardial infarction (AMI) in the United States have declined for elderly patients is unknown.
The death of biomedical journals
Authors: R. E LaPorte, E. Marler, S. Akazawa, F. Sauer, C. Gamboa, C. Shenton, C. Glosser, A. Villasenor, M. Maclure
Journal: BMJ (1995)

<h3>Abstract</h3> Kinase inhibitors are one of the largest classes of FDA-approved drugs and are major targets in oncology. Although kinase inhibitors have played an important role in improving cancer outcomes, major challenges still exist, including the development of resistance and failure to respond to treatments. Improvements for tumor profiling of kinase activity would be an important step in improving treatment outcomes and identifying effective kinase targets. Here, we present a graph- and statistics-based algorithm, called KSTAR, which harnesses the phosphoproteomic profiling of human cells and tissues by predicting kinase activity profiles from the observed phosphorylation of kinase substrates. The algorithm is based on the hypothesis that the more active a kinase is, the more of its substrates will be observed in a phosphoproteomic experiment. This method is error- and bias-aware in its approach, overcoming challenges presented by the variability of phosphoproteomic pipelines, limited information about kinase-substrate relationships, and limitations of global kinase-substrate predictions, such as training set bias and high overlap between predicted kinase networks. We demonstrate that the predicted kinase activities: 1) reproduce physiologically-relevant expectations and generates novel hypotheses within cell-specific experiments, 2) improve the ability to compare phosphoproteomic samples on the same tissues from different labs, and 3) identify tissue-specific kinase profiles. Global benchmarking and comparison to other algorithms demonstrates that KSTAR is particularly superior for predicting tyrosine kinase activities and, given its focus on utilizing more of the available phosphoproteomic data, significantly less sensitive to study bias. Finally, we apply the approach to complex human tissue biopsies in breast cancer, where we find that KSTAR activity predictions complement current clinical standards for identifying HER2-status – KSTAR can identify clinical false positives, patients who will fail to respond to inhibitor therapy, and clinically defined HER2-negative patients that might benefit from HER2-targeted therapy. KSTAR will be useful for both basic biological understanding of signaling networks and for improving clinical outcomes through improved clinical trial design, identification of new and/or combination therapies, and for identifying the failure to respond to targeted kinase therapies.
Screening for abdominal aortic aneurysms.
Authors: J. S. Rose
Journal: BMJ (1992)

61, 62, and 63). Also, three of our patients who were operated on had small aneurysms initially that grew by over 1 cm in six months, a far quicker rate of growth than that described by others in nonhypertensive patients.On the basis of our initial findings we believe that screening should be offered to male hypertensive patients from the age of 60 and should be done regularly-for example, every three to five years-in this group.In the 388 women we have screened eight aneurysms have been detected (only two over 3 5 cm), confirming the low incidence ofaneurysms in women described by others.3One woman, aged 72, has required an elective repair of an aneurysm of 6 1 cm.Many more hypertensive women will require screening to determine more precisely the lower incidence of aneurysms in this group.Offering screening in some form to this group may well, however, prove to be just as economical as breast cancer screening, in terms of quality adjusted life years at least.Numerous studies have suggested an association between hypertension and abdominal aortic aneurysms.We believe that hypertensive people also "require special provision for screening irrespective of any plans to screen apparently healthy people."
Protumorigenic overexpression of stathmin/Op18 by gain-of-function mutation in p53 in human hepatocarcinogenesis
Authors: Stephan Singer, Volker Ehemann, Antje Brauckhoff, Martina Keith, Sebastian Vreden, Peter Schirmacher, Kai Breuhahn
Journal: Hepatology (2007)

The microtubule (MT)-destabilizing protein stathmin/Op18 has previously been described to be negatively regulated by p53 and to be highly expressed in several tumor entities. However, little is known about its expression profile, functional or therapeutic relevance, and regulation in human hepatocarcinogenesis. Here we demonstrate cytoplasmic overexpression of stathmin in premalignant lesions (dysplastic nodules; DNs) and hepatocellular carcinomas (HCCs), which significantly correlated with tumor progression, proliferation, and activation of other protumorigenic factors (e.g., nuclear p53). Inhibition of stathmin expression by gene-specific short interfering RNA (siRNA) was associated with a significant reduction of MT-dependent cellular functions such as tumor cell viability, proliferation, migration, and increased apoptosis in HCC cells. Loss of stathmin expression increased responsiveness of tumor cells to the treatment with cytostatic drugs targeting MT-stability (paclitaxel, vinblastine) and to DNA cross-linking agents (cisplatin). Surprisingly, inducible expression of p53(wt) in p53-negative HCC cells as well as a reduction of p53(wt) by siRNA in p53(wt)-positive cells did not alter stathmin expression. However, stathmin was down-regulated after siRNA-based reduction of p53(mut/Y220C) and p53(mut/R213Q) expression in different tumor cell types.Our results demonstrate that overexpression of stathmin is an early protumorigenic event in human hepatocarcinogenesis, and its up-regulation can be mediated by gain-of-function mutations in p53. Thus, stathmin represents a potential therapeutic target, for example, by increasing responsiveness of tumor cells to treatment with chemotherapeutic agents after reduction of stathmin bioactivity.
Effective strategies for managing new <i>Pseudomonas</i> cultures in adults with cystic fibrosis
Authors: Haider Ali, Christopher Orchard, Myril Mariveles, Sandra Scott, Khalid Alshafi, Diana Bilton, Nicholas Simmonds
Journal: European Respiratory Journal (2015)

Pseudomonas aeruginosa is a common chronic pulmonary infection in cystic fibrosis (CF). It is associated with poor outcomes and new detection should prompt an early eradication attempt [1–3]. Sputum can be rendered P. aeruginosa culture-negative in adults with CF, although recurrence within 2 years is high <http://ow.ly/KPBsY>
The oncoprotein NPM-ALK of anaplastic large-cell lymphoma induces JUNB transcription via ERK1/2 and JunB translation via mTOR signaling
Authors: Philipp B. Staber, Paul Vesely, Naznin Haq, Rene G. Ott, Kotaro Funato, Isabella Bambach, Claudia Fuchs, Silvia Schauer, Werner Linkesch, Andelko Hrzenjak, Wilhelm G. Dirks, Veronika Sexl, Helmut Bergler, Marshall E. Kadin, David W. Sternberg, Lukas Kenner, Gerald Hoefler
Journal: Blood (2007)
Allopurinol-Associated Hand and Foot Deformities in Chronic Tophaceous Gout
Authors: Norman L. Gottlieb
Journal: JAMA (1977)

Telescoped digits of the hands and feet developed in a 69-year-old male with severe chronic tophaceous gout during allopurinol treatment. Extensive osseous tophi, resorbed rapidly during therapy with this xanthine oxidase inhibitor and not replaced by new bone matrix, were responsible for the deformity. Several hypotheses are advanced to explain the failure of bone erosions to heal. (<i>JAMA</i>238:1663-1664, 1977)