tbuckley/cabot-search huggingface dataset:
OC-146 Outcome of endoscopic submucosal dissection (ESD) for superficial oesophageal neoplasm: a UK pilot series
Authors: T P George, R Shakespeare, M Collins, A Burdge
Journal: Gut (2012)

<h3>Introduction</h3> In Japan endoscopic submucosal dissection (ESD) is accepted as a safe and effective treatment for early oesophageal cancer. Experience in the UK remains limited and oesophagectomy is still the gold standard. The aim of this prospective single centre pilot study was to evaluate the safety and clinical outcomes of oesophageal ESD in a UK setting. <h3>Methods</h3> Between July 2008 and November 2011 the regional upper GI MDT for North Wales and Cheshire considered 14 patients with early oesophageal cancer (T1N0M0) (n=11) and high grade dysplasia (n=3) for ESD after full staging. All patients underwent trimodal endoscopy (autofluorescence, narrow band imaging, magnification, and chromoendoscopy) to assess the lesion and depth of invasion. Informed consent was obtained after full discussion and counselling as to alternative treatment options. Standard ESD technique was used, whereby the lesion was isolated by circumferential cutting using a flush and IT2 knife after marking the edges and raising with submucosal injection; followed by dissection. Specimens were staged according to the Kikuchi classification. Patients with residual Barrett9s (n=5) had radio-frequency ablation after ESD to reduce the risk of metachronous cancer. Data were collected prospectively and audited by an independent group. <h3>Results</h3> Of the 14 cases (nine male, five female; mean age 73 years), two were excluded as trimodal endoscopy showed evidence of deep submucosal infiltration and one patient declined treatment. Mean specimen size was 16 mm. Procedure time ranged from 120 to 210 min. Enbloc resection rate was 91%. R0 resection rate of the lateral and deep margins were 82% and 64% respectively (Abstract OC-146 table 1). There were no major complications, although one procedure was abandoned as the endoscopic field of view was obscured by bleeding. Mean hospital stay was 72 h. Procedure and disease specific mortality was zero. Over a median follow-up period of 20.5 months there was one recurrence. This occurred in a patient with incomplete resection of both lateral and deep margins at ESD. Those with R1 resection of the deep margins showed no evidence of recurrence. <h3>Conclusion</h3> ESD is a safe and effective treatment with high cure rate for early oesophageal neoplasm, even when the endoscopist is in the steep part of the learning curve. ESD has the advantage of high enbloc resection rates and low risk of recurrence. In our opinion all patients in the UK with early oesophageal cancer and high grade dysplasia should have access to ESD as a standard treatment option. <h3>Competing interests</h3> None declared.
Studies of marmoset megakaryocytopoiesis in vitro
Authors: Samuel A. Burstein, Janine Breton‐Gorius, Laurence A. Harker
Journal: American Journal of Hematology (1980)

Abstract Liquid culture of the mononuclear fraction of the blood of marmosets without any added stimulator resulted in the appearance of megakaryocytes. These cells could not be identified by light microscopy or by indirect immunofluorescence using antiplatelet antiserum. Ultrastructural idetification was made using platelet peroxidase. Some megakaryocytes demonstrated sparse but detectable demarcation membranes, early granule formation, and platelet formation. The results indicate that marmoset megakaryocytic progenitor cells circulate and can begin to differentiate in vitro, although unstimulated liquid culture conditions do not promote the development of the usual light‐microscopic features of differentiation.
Dispersion of ventricular repolarization and refractory period
Authors: F Burton
Journal: Cardiovascular Research (2001)

Time for primary review 34 days. 

In their classic studies published in 1964, Han, Moe and co-workers [1,2] established an association between nonuniform recovery of excitability and lowered fibrillation threshold. They concluded that “those agencies known to favour the development of ventricular fibrillation were found to increase the temporal dispersion of recovery of excitability, whether the average refractory period was reduced … or increased…. The results emphasise the importance of nonuniformity of excitability and conduction velocity during the relative refractory period in the induction of turbulent impulse propagation.” The purpose of this review is to describe the basis of dispersion in recovery of excitability in the ventricle and its association with arrhythmogenesis.

Ventricular tachyarrhythmias are readily generated not only in acute ischaemia/infarction but also in hearts that have undergone remodelling following myocardial infarction [3–5]. Life-threatening arrhythmias are commonly seen in patients with previous myocardial infarction in the absence of new ischaemic events, as evidenced by the ability to initiate sustained ventricular tachycardia by programmed stimulation [6]. The risk of ventricular arrhythmias and sudden death in heart failure is inversely proportional to the left ventricular ejection fraction [7]. However, the Veterans Heart Failure Trial and other studies suggest that the proportion of deaths that are sudden is higher in patients with less severe LV dysfunction [8]. Such individuals are less likely to die from pump failure, hence they are at greater relative (but not absolute) risk of sudden death in comparison with patients with advanced heart failure.

The classical prerequisites for the development of reentry are the presence of a potential circuit around an anatomical obstacle, unidirectional block, and sufficiently slow conduction to enable recovery of excitability in time for reexcitation by the depolarizing wavefront [9]. A feature of this type of reentry is the presence … 

* Corresponding author. Tel.: +44-141-211-4722; fax: +44-141-552-4683 stuart.cobbe{at}clinmed.gla.ac.uk
Size variation of the M protein in group A streptococci.
Authors: V A Fischetti, K F Jones, J R Scott
Journal: The Journal of Experimental Medicine (1985)

In addition to the type-specific antigenic variation that is a well-known characteristic for the group A streptococcal M protein, we have now found that the M molecules vary with respect to their molecular size, both between M types and within an M type. By the use of an M6 monoclonal antibody, which crossreacts with 20 different M protein types, and antibodies to the N-acetyl glucosamine determinant of the cell wall, we have been able to identify the M protein molecules released from the streptococcal cell wall with muralytic enzymes, particularly group C phage-associated lysin. Immunoblot analysis of the cell extract identified M protein molecules bound to various cell wall fragments, suggesting a peptidoglycan linkage for the M molecule. M protein extracted from 20 different streptococcal serotypes revealed size variations from 41,000 to 80,000 in molecular weight. This extreme variation is unusual for related proteins. Similar size variations in the M molecule were also found in random clinical isolates of type 6 streptococci. No size change was seen in M6 protein isolated from: (a) strains within a limited epidemic, (b) a strain passaged in mice 192 times, and (c) a strain passaged in the laboratory for 156 generations, suggesting that the observed variation is not a rapid process. The results indicate that, within the broad limits observed in this study, the size of the M protein may not be critical to the antiphagocytic activity of the molecule.
Change in Sleep Duration and Type 2 Diabetes: The Whitehall II Study
Authors: Jane E. Ferrie, Mika Kivimäki, Tasnime N. Akbaraly, Adam Tabak, Jessica Abell, George Davey Smith, Marianna Virtanen, Meena Kumari, Martin J. Shipley
Journal: Diabetes Care (2015)

OBJECTIVE Evidence suggests that short and long sleep durations are associated with a higher risk of type 2 diabetes. Using successive data waves spanning &amp;gt;20 years, we examined whether a change in sleep duration is associated with incident diabetes. RESEARCH DESIGN AND METHODS Sleep duration was reported at the beginning and end of four 5-year cycles: 1985–1988 to 1991–1994 (n = 5,613), 1991–1994 to 1997–1999 (n = 4,193), 1997–1999 to 2002–2004 (n = 3,840), and 2002–2004 to 2007–2009 (n = 4,195). At each cycle, change in sleep duration was calculated for participants without diabetes. Incident diabetes at the end of the subsequent 5-year period was defined using 1) fasting glucose, 2) 75-g oral glucose tolerance test, and 3) glycated hemoglobin, in conjunction with diabetes medication and self-reported doctor diagnosis. RESULTS Compared with the reference group of persistent 7-h sleepers, an increase of ≥2 h sleep per night was associated with a higher risk of incident diabetes (odds ratio 1.65 [95% CI 1.15, 2.37]) in analyses adjusted for age, sex, employment grade, and ethnic group. This association was partially attenuated by adjustment for BMI and change in weight (1.50 [1.04, 2.16]). An increased risk of incident diabetes was also seen in persistent short sleepers (average ≤5.5 h/night; 1.35 [1.04, 1.76]), but this evidence weakened on adjustment for BMI and change in weight (1.25 [0.96, 1.63]). CONCLUSIONS This study suggests that individuals whose sleep duration increases are at an increased risk of type 2 diabetes. Greater weight and weight gain in this group partly explain the association.
Dying with Dignity in the Intensive Care Unit
Authors: Deborah Cook, Graeme Rocker
Journal: New England Journal of Medicine (2014)

T he traditional goals of intensive care are to reduce the morbidity and mortality associated with critical illness, maintain organ function, and restore health.Despite technological advances, death in the intensive care unit (ICU) remains commonplace.Death rates vary widely within and among countries and are influenced by many factors. 1 Comparative international data are lacking, but an estimated one in five deaths in the United States occurs in a critical care bed. 2 In this review, we address the concept of dignity for patients dying in the ICU.When the organ dysfunction of critical illness defies treatment, when the goals of care can no longer be met, or when life support is likely to result in outcomes that are incongruent with patients' values, ICU clinicians must ensure that patients die with dignity.The definition of "dying with dignity" recognizes the intrinsic, unconditional quality of human worth but also external qualities of physical comfort, autonomy, meaningfulness, preparedness, and interpersonal connection. 3Respect should be fostered by being mindful of the "ABCDs" of dignity-conserving care (attitudes, behaviors, compassion, and dialogue) 4 (Table 1).Preserving the dignity of patients, avoiding harm, and preventing or resolving conflict are conditions of the privilege and responsibility of caring for patients at the end of life.In our discussion of principles, evidence, and practices, we assume that there are no extant conflicts between the ICU team and the patient's family.Given the scope of this review, readers are referred elsewhere for guidance on conflict prevention and resolution in the ICU. 5,6he concept of dying with dignity in the ICU implies that although clinicians may forgo some treatments, care can be enhanced as death approaches.Fundamental to maintaining dignity is the need to understand a patient's unique perspectives on what gives life meaning in a setting replete with depersonalizing devices.The goal is caring for patients in a manner that is consistent with their values at a time of incomparable vulnerability, when they rarely can speak for themselves. 7For example, patients who value meaningful relationships may decline life-prolonging measures when such relationships are no longer possible.Conversely, patients for whom physical autonomy is not crucial may accept technological dependence if it confers a reasonable chance of an acceptable, albeit impaired, outcome. 8At issue is what each patient would be willing to undergo for a given probability of survival and anticipated quality of life. On the Need for Pa lli ati v e C a r eThe coexistence of palliative care and critical care may seem paradoxical in the technological ICU.However, contemporary critical care should be as concerned with palliation as with the prevention, diagnosis, monitoring, and treatment of lifethreatening conditions.
STUDIES ON EASTERN EQUINE ENCEPHALOMYELITIS
Authors: Lester S. King
Journal: The Journal of Experimental Medicine (1940)

In mice affected with equine encephalomyelitis, the first pathological disturbance in infant animals is an inflammatory reaction, which is usually less pronounced in adult animals. A characteristic type of parenchymal damage appears to be independent of the inflammation. In such foci of injury there is initially a vacuolation of intercellular tissue. Neurones in such areas are at first intact, later show cytoplasmic changes, and finally nuclear alterations. Complete disintegration of tissue and all its elements may be the end result.
Estimating Treatment Benefits for the Elderly: The Effect of Competing Risks
Authors: H. Gilbert Welch
Journal: Annals of Internal Medicine (1996)

To fully involve patients in treatment decisions, physicians need to communicate future health prospects that patients will have both with and without newly diagnosed disease.These prospects depend not only on the risks patients face from the new disease but also on the risks they face from other causes. Nowhere is an understanding of these competing risks more relevant than in the care of the elderly. In this study, we use the declining exponential approximation for life expectancy (DEALE) to provide a framework to help clinicians gauge the effect of competing risks as a function of age.Because older patients have many competing risks for death, the absolute effect of a new diagnosis on life expectancy is often relatively small. Consequently, the potential gain in survival even from perfect therapy may also be small. Moreover, no therapy is perfect, and the risks of therapy often increase with age. In the elderly, the combination of a high burden of competing risks and high rates of treatment-related complications conspires to reduce the net benefit of numerous interventions. We conclude that, compared with younger patients, the elderly should request only the more clearly effective treatments and should be willing to tolerate fewer associated complications before they agree to initiate therapy.
AROMATIC-INDUCED PREVENTION OF FATAL TOXICITY OF 7,12-DIMETHYLBENZ[<i>a</i>]ANTHRACENE
Authors: Charles Huggins, Elizabeth Ford, Ryo Fukunishi, E. V. Jensen
Journal: The Journal of Experimental Medicine (1964)

Large doses of 7,12-dimethylbenz[a]anthracene (7,12-DMBA) caused the death of rats within 1 day. A small amount of any of 5 polynuclear aromatic hydrocarbons or of an aromatic amine given before the highly toxic dose of 7,12-DMBA resulted in survival for more than 2 months and the specific atrophy of testis which follows 7,12-DMBA was largely prevented. Among the protective aromatics is 7,12-DMBA itself; a small dose of 7,12-DMBA given in advance induced protection of life against an otherwise lethal dose of 7,12-DMBA but only in a proportion of the animals, and testis was not protected from injury. The highly efficient inducers of protection were condensed aromatics composed of 4 or 5 rings. Protection of life against toxicity of big doses of 7,12-DMBA by pretreatment with small doses of aromatics required time (ca. 5 to 8 hours) for its induction. Ethionine given a few minutes after a highly efficient inducer of protection, 3-methylcholanthrene (3-MC), abolished induction of protection; ethionine given 8 hours after 3-MC exerted no influence on its protective effect. A lethal dose of 7,12-DMBA resulted in a considerable reduction in incorporation of tritium in DNA from tritiated thymidine while at the same time synthesis of menadione reductase was induced in liver. A small dose of 3-MC given prior to 7,12-DMBA was advantageous in partially protecting DNA synthesis.
Maintenance of anal continence: a review of pelvic floor physiology.
Authors: V A Dickinson
Journal: Gut (1978)

Progress reportMaintenance of anal continence: a review of pelvic floor physiology The activity of the external sphincter and puborectalis is maintained as part of a spinal reflex, as it is present (although slightly modified) in patients with complete transection of the spinal cord3'5"5.Patients with tabes dor- 1163 on August 20,
Metabolic evidence of inadequate coronary blood flow during closed-chest resuscitation in dogs
Authors: R. V DITCHEY, L. D HORWITZ
Journal: Cardiovascular Research (1985)

Closed-chest cardiopulmonary resuscitation (CPR) produces only small pressure differences across the coronary circulation and relatively little coronary blood flow in dogs with ventricular fibrillation. To determine whether coronary flow during experimental resuscitation is sufficient to maintain aerobic myocardial metabolism, we measured left ventricular adenosine triphosphate (ATP) and lactate concentrations before and immediately after a 20 min period of CPR in six fibrillating dogs. The mean aortic-right atrial pressure difference generated during CPR averaged 5.4 +/- 2.6 mmHg (SEM) and 3.2 +/- 2.6 mmHg at the beginning and end of the 20 min period, respectively. Left ventricular myocardial blood flow (measured with radioactive microspheres) averaged 16.7 +/- 5.7% of prearrest values during the first 10 min of CPR, and 8.5 +/- 4.8% of prearrest values during the second 10 min of CPR. Biopsies after CPR contained less ATP (3.3 +/- 0.1 vs 4.7 +/- 0.5 nmol.mg-1, p less than 0.05) and more than seven times more lactate (14.7 +/- 3.1 vs 1.9 +/- 0.2 nmol.mg-1, p less than 0.01) than control biopsies. We conclude that coronary blood flow during CPR is inadequate relative to myocardial oxygen demands during ventricular fibrillation in dogs. The techniques developed in this study provide a potential means of assessing the effects of experimental interventions on myocardial oxygenation during CPR.
Growth of Human Melanoma in Nude Mice: Suppression by T-Lymphocytes From the Tumor Donor: Brief Communication 2
Authors: A. S. Coates, Marjorie Crawford
Journal: JNCI Journal of the National Cancer Institute (1977)

Human malignant melanoma cell lines established in tissue culture were successfully transplanted sc into BALB/c nude mice. The growth rate of the resulting tumors was significantly suppressed when lymphocytes from the patient in whom the tumor arose were injected iv into BALB/c nude mice at the same time as sc tumor transplantation, but inoculation with lymphocytes from a person without a tumor was ineffective. Cell separation identified T-lymphocytes as the active subpopulation. Growth of the tumors was also significantly suppressed by reconstitution of the mice with normal BALB/c lymphocytes; lymphocytes from BALB/c mice previously immunized against the melanoma line were not more effective than nonimmune lymphocytes in preventing tumor growth. Sera from normal BALB/c mice or BALB/c mice immunized against a human melanoma cell line effectively suppressed growth of that cell line in BALB/c nude mice if given at the time of tumor transplant. The results suggested that, whereas murine lymphocytes reconstitute the ability of nude mice to react to xenogeneic antigens on the human tumor, human lymphocytes showed greater specificity to autologous human melanoma-associated antigens.
Bone Marrow-Derived Endothelial Progenitor Cells Participate in Cerebral Neovascularization After Focal Cerebral Ischemia in the Adult Mouse
Authors: Zheng Gang Zhang, Li Zhang, Quan Jiang, Michael Chopp
Journal: Circulation Research (2002)

We investigated whether circulating endothelial progenitor cells contribute to neovascularization after stroke. Donor bone marrow cells obtained from transgenic mice constitutively expressing beta-galactosidase transcriptionally regulated by an endothelial-specific promoter, Tie2, were injected into adult mice. Focal cerebral ischemia was induced by embolic middle cerebral artery (MCA) occlusion and changes of cerebral blood flow (CBF) were measured by perfusion-weighted magnetic resonance imaging (MRI). Laser scanning confocal microscopy (LSCM), immunohistochemistry and X-gal staining were performed. Perfusion-weighted MRI demonstrated increases in CBF around the boundary of an infarct area 1 month after ischemia. Morphological and 3-dimensional image analyses revealed enlarged and thin-walled blood vessels with sprouting or intussusception at the boundary of the ischemic lesion, which closely corresponded to elevated CBF areas detected on perfusion-weighted MRI, indicating the presence of neovascularization. X-gal and double immunostaining demonstrated that Tie2-lacZ-positive cells incorporated into sites of neovascularization at the border of the infarct, and these cells exhibited an endothelial antigenic marker (von Willebrand factor). In addition, bone marrow recipient mice without ischemia showed incorporation of Tie2-lacZ-expressing cells into vessels of the choroid plexus. These data suggest that formation of new blood vessels in the adult brain after stroke is not restricted to angiogenesis but also involves vasculogenesis and that circulating endothelial progenitor cells from bone marrow contribute to the vascular substructure of the choroid plexus.
The practice of cardiothoracic surgeons in the perioperative staging of non-small cell lung cancer.
Authors: G M Tsang, D C Watson
Journal: Thorax (1992)

BACKGROUND: The treatment and prognosis of non-small cell lung cancer, and assessment of the results of treatment, depend on accurate perioperative staging. The extent to which this is carried out in the United Kingdom is unknown. METHODS: A postal questionnaire survey was undertaken in 1990 to determine the perioperative staging practices of cardiothoracic surgeons in the United Kingdom. RESULTS: Replies from 77 surgeons, who between them performed about 4833 pulmonary resections a year for lung cancer, were analysed. Forty four per cent of surgeons, operating on 43% of the patients, do not perform computed tomography of the thorax or mediastinal exploration before surgery. They may therefore embark on a thoracotomy for stage III disease. At thoracotomy 45% of surgeons, operating on 40% of patients, do not sample macroscopically normal lymph nodes. They may therefore understage cases as N0/N1 when there is at least microscopic disease in mediastinal lymph nodes. CONCLUSIONS: The staging of lung cancer in the United Kingdom in 1990 appears in many instances to be inadequate. There should be a more organised approach to perioperative staging so that prognosis may be assessed and comparisons between groups of patients can be made.
The Future of Cancer Care: Are We Ready For Personalized Value?
Authors: Jonas A. de Souza, Colleen Kelly, Chadi Nabhan
Journal: Journal of the National Comprehensive Cancer Network (2015)

Tremendous advances have been achieved in the understanding of cancer biology, with cancer researchers extolling the potential of precision medicine in tailoring treatment to specific tumor markers.However, instead of feeling empowered, patients often have difficulty comparing and selecting among various treatment options. 1 Compounding this perplexity is the rising cost of cancer therapies coupled with continued concerns about side effects and their impact on quality of life (QOL).Although incremental improvements in overall survival remain the most important consideration when selecting a particular treatment, additional critical considerations are needed for proper therapeutic choosing.This delicate balance has recently been translated into so-called "value" in cancer care.Although frameworks to better understand and practice "value in cancer care" have been developed, 2 these tools have not actively involved patients.To create an effective model of value in oncology care, the views and needs of all stakeholders must be aligned with those of the patients.To that end, we propose a patient-centered value framework as a mechanism of optimizing cancer care moving forward (Figure 1).