tbuckley/cabot-search huggingface dataset:
Intramyocardial Pressure and Strength of Left Ventricular Contraction
Authors: Peter F. Salisbury, Cecil E. Cross, P. Andre Rieben
Journal: Circulation Research (1962)

Intramyocardial pressure was followed with the Johnson-DiPalma method in isolated hearts and in hearts in situ. Systolic intramyocardial pressure curves from hearts in situ exhibited two pressure peaks which were believed to coincide with peak contractile tension and with myocardial fiber shortening, respectively. The following factors influenced intramyocardial pressure: ventricular cavity volume, heart rate, coronary perfusion pressure, outflow resistance, and "epicardial" compression. The contractile strength of the left ventricle varied in proportion with the intramyocardial pressure; it did not appear to be regulated primarily by diastolic volume or by metabolic support. Intramyocardial pressure was believed to determine the contractile strength of the heart by controlling the release of a potentiating substance.
Abstract 972: Direct activation of pro-apoptotic BAX as a novel strategy for cancer therapy
Authors: Evripidis Gavathiotis, James L. LaBelle, Denis Reyna, Joseph Bellairs, Loren D. Walensky
Journal: Cancer Research (2012)

Abstract BCL-2 family proteins are essential regulators of cellular life and death and, when deregulated, contribute to the development, maintenance, and chemoresistance of human cancer. Anti-apoptotic members contribute to cancer pathogenesis by sequestering the α-helical BH3 death domains of their pro-apoptotic counterparts such as BAX. The anti-apoptotic groove that binds and neutralizes BH3 helices has been successfully targeted by small molecules and stapled peptides in an effort to “inhibit the inhibitors” of apoptosis. Using a Stabilized Alpha-Helix of BCL-2 domain (SAHB) modeled after the BIM BH3 helix, we previously identified a geographically distinct BH3-binding groove that mediates the direct activation of BAX, suggesting a new strategy for inducing apoptosis by flipping BAX's “on switch”. Engagement of the novel site by BIM SAHB directly activates BAX (Gavathiotis et al. Nature, 2008), unleashing a succession of key conformational changes that culminates in the formation of toxic mitochondrial pores (Gavathiotis et al. Mol Cell, 2010). Here, we demonstrate that BIM SAHB effectively overcomes the apoptotic blockades of a series of diverse hematologic cancer cells by broadly targeting inhibitory anti-apoptotic complexes and directly activating BAX. Importantly, BIM SAHB induces dose-responsive caspase 3/7 activation and the morphologic features of apoptosis. To identify a BAX-selective agent, we further performed a computational screen to identify BAX activator molecules (BAMs) capable of directly engaging the BAX trigger site. We demonstrate by competitive fluorescence polarization binding assays and NMR analyses that BAM7 engages the BAX trigger site and, as a result, promotes the functional oligomerization of BAX. Strikingly, the molecule does not interact with the canonical BH3 binding pocket of anti-apoptotic proteins and induces cell death in a BAX-selective fashion. These first stapled peptide and small molecule gain-of-function modulators of a BCL-2 family protein highlight a new pharmacologic paradigm for induction of cancer cell apoptosis through direct activation of BAX. 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 972. doi:1538-7445.AM2012-972
Free smoke alarms: a fire officer responds
Authors: R. Greet
Journal: BMJ (2003)

EDITOR—As a professional fire officer I read with interest the article and ongoing debate on the issue of free smoke detectors and the suggested outcomes from the research.1 One element perhaps overlooked in the debate is ownership, which has two components.

The first is the gift of the smoke detector itself. Being given one doesn't bring with it the same sense of ownership as working for and buying one. It would not be appropriate …
Thyroid Disease: Endocrinology, Surgery, Nuclear Medicine, and Radiotherapy
Authors: Sheldon S. Stoffer
Journal: JAMA (1991)

Initially, editor Stephen Falk was asked to assemble a text concerned with thyroid surgery. Some time later, the focus changed so that physicians from many types of disciplines were invited to participate in this book. Included were the disciplines of endocrinology, otolaryngology, head and neck surgery, pathology, nuclear medicine, radiation and medical oncology, diagnostic radiology, ophthalmology, pediatrics, anesthesiology, and others. It was hoped that an integrated approach would provide a unique textbook for all physicians interested in thyroid disease. Falk has indeed assembled an eminent cast of physicians, and most of this book is very well written and chock-full of useful information. There are numerous excellent illustrations, and most chapters re amply supported by abundant references. Unfortunately, this ambitious undertaking is hampered by uneven quality and reliability. In chapter 14, "Management of Graves' Ophthalmopathy," Fig 1D is a photograph of a 67-year-old woman with asymmetrical exophthalmos. The legend states, "The
S81. Proffered paper: A new PD1-CD28 chimeric receptor overcomes PD-1-mediated immunosuppression in adoptive T cell therapy
Authors: S Grassmann, P Peters, Y Zeng, J Schmollinger, S Endres, S Kobold
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts Although tumour-specific cytotoxic T cells are capable of killing tumour cells both in vitro and in vivo , treatment with adoptive T cell transfer does not lead to sufficient tumour regression without adjuvant therapy. Tumour-promoted T cell exhaustion and anergy have been
A7.10 Genetic Variants in the<i>IL-4</i>and<i>IL-4</i>Receptor Genes in Association with the Severity of Joint Damage in Rheumatoid Arthritis: A Study in Seven Cohorts
Authors: A Krabben, AG Wilson, DPC de Rooy, A Zhernakova, E Brouwer, E Lindqvist, T Saxne, G Stoeken, JAB van Nies, R Knevel, TWJ Huizinga, B Koeleman, R Toes, PK Gregersen, AHM van der Helm-van Mil
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objective</h3> The progression of joint destruction in rheumatoid arthritis (RA) is determined by genetic factors. Changes in <i>IL-4</i> and <i>IL-4R</i> genes have been associated with RA severity but not replicated. We studied the association between <i>IL-4</i> and <i>IL-4R</i> tagging SNPs and progression rate of joint damage in RA in a multi-cohort candidate gene study. <h3>Methods</h3> <i>IL-4</i> and <i>IL-4R</i> tagging SNPs (8 and 39, respectively) were genotyped in 600 RA-patients of whom 2,846 sets of hands and feet X-rays were collected during 7 years follow-up. Subsequently, significantly associated SNPs were genotyped and studied in relation to 3,415 X-rays of 1,953 RA-patients; these included data-sets from Groningen (NL), Lund (SE), Sheffield (UK), NARAC (USA), Wichita (USA) and NDB (USA). The relative increase in progression rate per year in the presence of a genotype was determined in each cohort. An inverse variance weighting meta-analysis was done on the six datasets that together formed the replication-phase. <h3>Results</h3> In the discovery-phase none of the <i>IL-4</i> SNPs and seven of the <i>IL-4R</i> SNPs were significantly associated with joint damage progression rate. In the replication-phase, two SNPs in <i>IL-4R</i> gene were significantly associated with joint damage progression rate (Rs1805011, p = 0.02 and Rs1119132, p = 0.001). <h3>Conclusions</h3> Genetic variants in <i>IL-4R</i> were identified and independently replicated to associate with progression rate of joint damage in RA.
There must be cost effective private health care
Authors: C. M Barron
Journal: BMJ (1996)

“Take me to Colin's hospital,” said my dying father as he lay slumped on the couch. My mother wiped the tears from her eyes and telephoned me immediately. In fact the “hospital” was a private nursing home which I ran with my business partner, but “hospital” was the best word my sick father could find as he struggled to cope with dementia.

Four months later he was dead. I could not sleep the night he died; some hours before he died I saw him and just knew that I would never see him again. Early next morning I got the telephone call and instantly felt relieved that my father's suffering was over. Three days later I spoke at his funeral and payed tribute to his many personal qualities. Like my mother, sister, and uncle he was a doctor; a former general practitioner in Greenock and Port Glasgow. I too had followed in his footsteps and studied medicine.

After a few years as a hospital doctor …
Measurement of flow through perfused bronchial segments: optimization of flow head resistance
Authors: P K McFawn, M P Sparrow, H W Mitchell
Journal: European Respiratory Journal (1995)

Techniques for measuring flow, for example through perfused bronchial segments, frequently use a flow head as the sensing device. The sensitivity of these instruments to changes in airway resistance is dependent on the flow head resistance. This study aims to quantify the effect of flow head resistance on sensitivity and flow, allowing optimization of flow head resistance. A mathematical model of the perfused bronchial segment preparation was constructed and used to explore the effect of flow head resistance on sensitivity. The model's assumptions were experimentally tested using segments of pig bronchus, perfused through the lumen with Krebs solution. The model suggests a complex relationship between flow head resistance and sensitivity that has a distinct maximum when approximately half of the total resistance is present in the flow head. Furthermore, the maximum sensitivity was found to be proportional to the resting flow. Regression between experimentally derived sensitivities and modelled predictions was linear, with a correlation coefficient of 0.93. We have defined the optimum recording conditions for study of flow through isolated bronchial segments.
Iatrogenic Foreign Bodies of the Urinary Bladder
Authors: Karl R. Herwig
Journal: JAMA (1969)

Retention of ruptured fragments of catheter in the urinary bladder occurs infrequently. Three cases were seen in a six-month period. Diagnosis depends upon observation and awareness that the catheter has ruptured. Removal at endoscopy is the treatment of choice although prevention is best accomplished by the use of new catheters.
Identification by cell electrophoresis of a subpopulation of polymorphonuclear cells which is increased in patients with rheumatoid arthritis and certain other rheumatological disorders.
Authors: K A Brown, J D Perry, C Black, D C Dumonde
Journal: Annals of the Rheumatic Diseases (1988)

Two and occasionally three electrophoretic subpopulations of polymorphonuclear cells (PMNs) were identified in the blood of normal healthy subjects and patients with rheumatoid arthritis (RA). Most of the PMNs from both groups of subjects were found in the population with the highest surface charge; the remainder being in the other distributions, which were collectively termed the slow cell population. There was a significant increase in the percentage of rheumatoid PMNs (mean 42%) ascribed to the slow population when compared with PMNs from normal subjects (mean 17%). A similar increase in the slow cell population was also seen in patients with Felty's syndrome (mean 38%) and scleroderma (mean 51%), but not in patients with Behçet's syndrome (mean 18%). Synovial fluid aspirated from the knee joints of patients with RA contained PMNs with the lowest surface charge. With nylon fibre as an adherence substrate cells of a low surface charge were found to be more adherent than those of a high surface charge. An alteration in the electrophoretic distribution of PMNs may represent changes that are related to the expression of functionally related membrane ionogenic groups.
P72 ORAL TREATMENT WITH PBI-4050, A NOVEL FIRST-IN-CLASS ANTI-FIBROTIC COMPOUND, REDUCES HEPATIC FIBROSIS AND HEPATOCELLULAR CARCINOMA
Authors: L. Gagnon, L. Geerts, A. Doucet, F. Sarra-Bournet, M. Tremblay, K. Hince, S. Abbott, J.-S. Duceppe, B. Zacharie, C. Penney, P. Laurin, B. Grouix
Journal: Journal of Hepatology (2014)
The Use of Serum Digoxin Levels in Clinical Practice
Authors: Robert H. Goldman
Journal: JAMA (1974)

THE need for an accurate and simple method of monitoring digitalis dosage is clearly evident from recent studies showing that 30% of patients admitted to a medical service had evidence of toxic effects from digitalis, while 11% of patients were "under-digitalized." Studies in experimental animals indicate that 60% of a lethal dose has been given when cardiac arrhythmias first appear, ie, at the point of maximal therapeutic effect. In addition, with the exception of the patient with atrial fibrillation in whom the ventricular rate usually can be used as a guide to further digitalis therapy, heretofore there has been no accurate, safe, and reliable clinical means to determine optimal digitalis therapy. To complicate matters further, there is no specific cardiac arrhythmia due to digitalis that cannot also be due to a patient's underlying heart disease. Hence, the clinician is often presented with the therapeutic choice of either increasing his patient's
18F-fluorodeoxyglucose PET scans in lung cancer.
Authors: J M Hughes
Journal: Thorax (1996)

To determine the usefulness of positron emission tomography with fluoro-2-deoxyglucose (PET-FDG) in assessing mediastinal disease in patients with non-small-cell lung cancer (NSCLC) and to compare its yield to that of computed tomography (CT), we performed a prospective consecutive sample investigation in a university hospital and its related clinics.In 30 patients with NSCLC with clinical stage I (T1-2, NO, MO) disease, we compared the results of chest CT and PET-FDG with the findings at surgical exploration of the mediastinum.Seven (77%) of nine patients with surgically proven mediastinal metastasis were identified by the PET-FDG results, with four false-positives in 21 patients with negative lymph-node dissections (P=0 004).Using the results of pathologic examination of mediastinal lymph nodes as the criterion standard, the diagnostic sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) for PET-FDG imaging of mediastinal metastases were 78%, 81%, 80%, 64%, and 89%, respectively.The sensitivity, specificity, accuracy, PPV and NPV for chest CT in the detection of mediastinal metastasis were 56%, 86%, 77%, 63%, and 87%, respectively.CT and PET- FDG results agreed in 21 patients.The diagnostic accuracy of the combined imaging modalities was 90%.We concluded that mediastinal uptake ofFDG correlates with the extent of mediastinal involvement of NSCLC and may contribute to preoperative staging.PET-FDG imaging complements chest CT in the noninvasive evaluation of NSCLC, and strategies for its use merit further investigation.(
Measurement of end-systolic pressure-volume relations by intra-aortic balloon occlusion.
Authors: K B Gupta, J E Bavaria, M B Ratcliffe, L H Edmunds, D K Bogen
Journal: Circulation (1989)

A new situ technique has been developed for measuring peak end-systolic elastance, Emax, that does not alter intrinsic or reflex-stimulated cardiac contractility. Afterload is varied by the inflation of an intra-aortic balloon catheter positioned in the ascending aorta. Balloon inflation is timed to interrupt ventricular ejection transiently at different times during the ejection phase, therefore, producing contraction at different ventricular volumes. Simultaneous measurement of left ventricular pressure and aortic flow during the occlusion sequence allows pressure versus ejected volume loops to be generated, from which the end-systolic pressure-volume relation is determined. End-systolic pressure-volume relation (ESPVR) was measured in six anesthetized Dorsett sheep with normal and enhanced contractile states. ESPVR was analyzed using both linear and nonlinear techniques. Although nonlinear components were seen in ESPVR, for the pressure-volume data range produced by the transient occlusions, linear approximations of ESPVR fit the end-systolic data points well. In the normal state, Emax, the slope of the linear ESPVR, was 1.01-5.08 mm Hg/ml in animals with body weights of 23-32 kg. After epinephrine infusion, Emax increased from 3.07 +/- 1.49 to 5.79 +/- 1.97 mm Hg/ml, which is consistent with previous investigations. Linear and nonlinear volume intercepts had a small increase with positive inotropic stimulation. Furthermore, serial measurements of Emax tracked cardiac function in depressed hearts with rapidly changing contractility.
CDC Program for Diagnosis of Gonorrhea
Authors: Albert Balows
Journal: JAMA (1972)

<h3>To the Editor.—</h3> Within the next four months an extensive nationwide program designed to provide laboratory services to all physicians for the diagnosis of gonorrheal infection will be in operation. (In some states, this activity is already under way.) This program, operated by the individual state health departments through funding from the Center for Disease Control (CDC), will emphasize routine screening for gonorrhea of all female patients in the reproductive age group. The screening will be done with "appropriate" laboratory techniques. Appropriate in this sense means abbreviated cultural techniques leading to a presumptive laboratory identification. We wish to clarify any misunderstanding regarding the application of these presumptive laboratory identifications to the diagnosis of gonorrhea. To enhance the validity of the rapid results obtained with these streamlined bacteriologic procedures, it is imperative that the physician identify accurately for the laboratory the anatomical site(s) of the specimen(s) being cultured. Direct inoculation of
The photosensitivity dermatitis and actinic reticuloid syndrome: no association with lymphoreticular malignancy
Authors: D. BILSLAND, I.K. CROMBIE, J. FERGUSON
Journal: British Journal of Dermatology (2006)

In the management of photosensitivity dermatitis/actinic reticuloid syndrome (PD/AR) (syn.chronic actinic dermatitis), a chronic and often severe photodermatosis, there has been concern that patients may be predisposed to the development of lymphoreticular malignancy. A follow-up study of 231 patients with PD/AR who had been investigated at the Photobiology Unit, Ninewells Hospital, Dundee, between 1971 and 1991, was undertaken to determine (i) the incidence and type of malignancies (ii) the causes of any deaths. This information was obtained from three sources: (a) National Cancer Registry data, (b) death certificates, (c) when possible or practical, by casenote review. Thirty-eight malignancies had occurred (in 37 of the 231 patients). Although six of the 38 malignancies were lymphoma registrations, it emerged from a review of casenotes, pathology reports and death certificates that five of the six were incorrect: two were labelled 'mycosis fungoides' prior to diagnosis of PD/AR; a case of dermatopathic lymphadenopathy was initially reported as Hodgkin's disease; clerical errors had occurred in two cases. The remaining case was a true B-cell lymphoma. The occurrence of one lymphoreticular malignancy is not significantly different from the number expected in a normal population (0.96), when applying 5-year age-, sex-, and site-specific incidence rates to the cumulative patient years of risk [standardized incidence ratio 1.04 (95% CI 0.03–5.79)]. There was also no significant increase in the risk of non-lymphoma malignancies in the PD/AR subjects. Since diagnosis, 83 patients have died, the majority from cardiorespiratory or cerebrovascular diseases, or the reported malignancies, a pattern expected in an elderly population. This study indicates that PD/AR patients are not at an increased risk of developing lymphoreticular or other malignancies. When the diagnosis is made, specific lymphoma screening measures are not indicated.
Echocardiographic evaluation of fixed left ventricular outlet obstruction in children. Pre and postoperative outlet obstruction in children.
Authors: G L Johnson, R A Meyer, D C Schwartz, J Korfhagen, S Kaplan
Journal: Circulation (1977)

Rencently, several investigators have utilized the echographically determined magnitude of relative left ventricular posterior wall hypertrophy as a reflection of normalized systolic wall stress to estimate left ventricular systolic pressure noninvasively. In this study, relative wall thickness determined echographically was compared to peak systolic pressure measured at catheterization in 20 children without obstruction to left ventricular outflow and with normal left ventricular function. From these data a relationship, pressure = 225 X left ventricular systolic wall thickness/left ventricular end-systolic internal dimension, was derived. The relationship was then applied to 57 children with fixed aortic stenosis. Left ventricular pressure estimated echographically compared well with that demonstrated at cardiac catheterization (r = 0.89). Twenty-one patients had further echographic studies following surgical relief of outlet obstruction. Estimated left ventricular pressure fell to normal values within two months following surgery in over half the patients with good surgical relief of obstruction, and was normal at subsequent studies up to 22 months postoperatively in all but one patient with good surgical relief. In patients in whom outlet obstruction was not adequately relieved at surgery, echographically estimated left ventricular pressure remained persistently elevated.
Standardising Outcomes in Paediatric Clinical Trials
Authors: Mike Clarke
Journal: PLoS Medicine (2008)

Whether decisions about the health care of children are made by parents, carers, health practitioners, or children themselves, ideally these decisions will be informed by the results of systematic reviews of previous clinical trials. Unfortunately, drawing on research from the past when making these decisions is not straightforward, even with the advent of systematic reviews, because different trials have used different outcome measures. Indeed, systematic reviews have helped to highlight the problems that arise when researchers from different times and places—sometimes even in the same times and places—use a variety of health outcomes and outcome measures to assess the effect of interventions [1].

In a new systematic review published in this issue of PLoS Medicine, Ian Sinha and colleagues examined studies that involved the selection of outcomes for use in paediatric clinical trials [2]. As they say in their report, the choice of outcome is important because choosing inappropriate outcomes may lead to “wasted resources or misleading information which either overestimates, underestimates or completely misses the potential benefits of an intervention.”
When sleeping beauty wakes up and jumps into a cancer-minded environment
Authors: Ralf Weiskirchen, Christian Liedtke, Christian Trautwein, Kris Kowdley, Geoffrey McCaughan, Christian Trautwein
Journal: Hepatology (2009)

We describe a system that permits conditional mobilization of a Sleeping Beauty (SB) transposase allele by Cre recombinase to induce cancer specifically in a tissue of interest. To demonstrate its potential for developing tissue-specific models of cancer in mice, we limit SB transposition to the liver by placing Cre expression under the control of an albumin enhancer/promoter sequence and screen for hepatocellular carcinoma (HCC)-associated genes. From 8,060 nonredundant insertions cloned from 68 tumor nodules and comparative analysis with data from human HCC samples, we identify 19 loci strongly implicated in causing HCC. These encode genes, such as EGFR and MET, previously associated with HCC and others, such as UBE2H, that are potential new targets for treating this neoplasm. Our system, which could be modified to drive transposon-based insertional mutagenesis wherever tissue-specific Cre expression is possible, promises to enhance understanding of cancer genomes and identify new targets for therapeutic development.