tbuckley/cabot-search huggingface dataset:
Fetal rights and abortion laws.
Authors: S F O'Beirn
Journal: BMJ (1973)

A leading article (January 27, p. 191) and your medicolegal expert (p. 244) both record that the Law Commission has expressed its provisional view that a child with injury or deformity caused by somebody's neglience before birth could sue that person for damages. The same principle is being supported in the course of the thalidomide case and it is a principle with which nobody can seriously disagree. When one looks at it, however, in the context of the present abortion laws, it is clear that either this principle or the abortion laws must be wrong. According to the abortion laws a fetus has no separate existence apart from its mother and in certain circumstances can be killed. If this "thing" which has not and never had an existence of its own also has no legal right to live, how can it have legal rights of any kind?
MHC Class II–Transduced Tumor Cells Originating in the Immune-Privileged Eye Prime and Boost CD4+ T Lymphocytes that Cross-react with Primary and Metastatic Uveal Melanoma Cells
Authors: Jacobus J. Bosch, James A. Thompson, Minu K. Srivastava, Uzoma K. Iheagwara, Timothy G. Murray, Michal Lotem, Bruce R. Ksander, Suzanne Ostrand-Rosenberg
Journal: Cancer Research (2007)

Abstract Uveal melanoma, the most common malignancy of the eye, has a 50% rate of liver metastases among patients with large primary tumors. Several therapies prolong survival of metastatic patients; however, none are curative and no patients survive. Therefore, we are exploring immunotherapy as an alternative or adjunctive treatment. Uveal melanoma may be particularly appropriate for immunotherapy because primary tumors arise in an immune-privileged site and may express antigens to which the host is not tolerized. We are developing MHC class II (MHC II)–matched allogeneic, cell-based uveal melanoma vaccines that activate CD4+ T lymphocytes, which are key cells for optimizing CD8+ T-cell immunity, facilitating immune memory, and preventing tolerance. Our previous studies showed that tumor cells genetically modified to express costimulatory and MHC II molecules syngeneic to the recipient are potent inducers of antitumor immunity. Because the MHC II–matched allogeneic vaccines do not express the accessory molecule, Invariant chain, they present MHC II–restricted peptides derived from endogenously encoded tumor antigens. We now report that MHC II–matched allogeneic vaccines, prepared from primary uveal melanomas that arise in the immune-privileged eye, prime and boost IFNγ-secreting CD4+ T cells from the peripheral blood of either healthy donors or uveal melanoma patients that cross-react with primary uveal melanomas from other patients and metastatic tumors. In contrast, vaccines prepared from metastatic cells in the liver are less effective at activating CD4+ T cells, suggesting that tumor cells originating in immune-privileged sites may have enhanced capacity for inducing antitumor immunity and for serving as immunotherapeutic agents. [Cancer Res 2007;67(9):4499–506]
Digoxin partly restores the abnormal circadian pattern of autonomic control during daytime but not during nighttime in patients with congestive heart failure
Authors: Jan Brouwer, Dirk J. van Veldhuisen, Arie J. Man in 't Veld, Peter H.J.M. Dunselman, Jaap Haaksma, K.I. Lie
Journal: Journal of the American College of Cardiology (1996)
Quality assurance in the treatment of colorectal cancer: the EURECCA initiative
Authors: A.J. Breugom, P.G. Boelens, C.B.M. van den Broek, A. Cervantes, E. Van Cutsem, H.J. Schmoll, V. Valentini, C.J.H. van de Velde
Journal: Annals of Oncology (2014)
Ca <sup>2+</sup> /Calmodulin-Dependent Protein Kinase II Phosphorylation Regulates the Cardiac Ryanodine Receptor
Authors: Xander H.T. Wehrens, Stephan E. Lehnart, Steven R. Reiken, Andrew R. Marks
Journal: Circulation Research (2004)

The cardiac ryanodine receptor (RyR2)/calcium release channel on the sarcoplasmic reticulum is required for muscle excitation-contraction coupling. Using site-directed mutagenesis, we identified the specific Ca2+/calmodulin-dependent protein kinase II (CaMKII) phosphorylation site on recombinant RyR2, distinct from the site for protein kinase A (PKA) that mediates the "fight-or-flight" stress response. CaMKII phosphorylation increased RyR2 Ca2+ sensitivity and open probability. CaMKII was activated at increased heart rates, which may contribute to enhanced Ca2+-induced Ca2+ release. Moreover, rate-dependent CaMKII phosphorylation of RyR2 was defective in heart failure. CaMKII-mediated phosphorylation of RyR2 may contribute to the enhanced contractility observed at higher heart rates. The full text of this article is available online at http://circres.ahajournals.org.
Effect of nitrogen dioxide and ozone on the risk of dying in patients with severe asthma
Authors: J Sunyer
Journal: Thorax (2002)

<b>Background:</b> A study was performed to assess the acute association between air pollution, pollen and spores, and mortality in a population based cohort of subjects with asthma recruited from emergency room admissions for an asthma exacerbation using a case crossover design. <b>Methods:</b> Patients in Barcelona aged over 14 years who died during the period 1985–95 who had visited the emergency department of one of the four largest hospitals in the city for asthma during 1985–9 were included in the study (a total of 467 men and 611 women). Deaths were identified by record linkage of the cohort individuals with the Catalonia mortality registry. Causes of death were based on the underlying cause on the death certificate. Air pollution, pollen and spore levels were measured at the city monitoring stations which provide an average for the entire city. <b>Results:</b> Nitrogen dioxide was associated with mortality for all causes of death (adjusted odds ratio (OR) for an increase of the interquartile range = 1.50, 95% confidence interval (CI) 1.09 to 2.64) in asthmatic patients with more than one emergency room admission for asthma. The association was particularly strong for respiratory causes (OR 1.63, 95% CI 0.93 to 2.86). Ozone also increased the risk of death in asthmatic patients (OR 1.90, 95% CI 1.09 to 3.30) during spring and summer. The association with particles, pollen, and spores was not significant, and no interactions between air pollutants and pollen and spores were found. <b>Conclusion:</b> Nitrogen dioxide and ozone may exacerbate severe asthma and even cause death among asthmatic subjects.
THE RELATIONSHIP OF MENTAL AND PHYSICAL STATUS IN INSTITUTIONALIZED AGED PERSONS
Authors: R. L. KAHN, A. I. GOLDFARB, M. POLLACK, I. E. GERBER
Journal: American Journal of Psychiatry (1960)

Our results show that the mental and physical functional status of institutionalized aged persons are highly interrelated. The relationship is seen within each of the 3 types of institutions studied, and for all age groups. In the different types of institutions it was found that persons tended to have disabilities consistent with the type of services to be expected in the institution. Thus, patients in state hospitals had the largest number with poor mental functional status, while there was predominance of persons with poor physical functional status found in the nursing homes. Nevertheless, institutions of a given type differed widely from each other. Some homes for the aged and nursing homes had a larger proportion of persons with poor mental status than did some state hospitals, while some state hospitals and homes for the aged had more persons with poor physical functional status than did some nursing homes. Therefore, it is possible to make a more accurate prediction of a person's mental status on the basis of his physical status, or of his physical status by his mental status, than on the basis of the type of institution in which he is residing. Physical functional status is not significantly related to chronologic age in nursing homes or state hospitals. In homes for the aged the relationship is significant, but even then mental status is better than chronologic age in predicting the physical status. A person 85 years of age or over with good mental status is much more likely to have a good physical functional status than a person 74 or younger who is in poor mental condition. It is concluded that physical and mental aspects of functioning cannot be compartmentalized in aged persons; impairment of either can be regarded as indicating a need for comprehensive medical care. Recent trends in the development of special medical facilities in state hospitals, and both medical and psychiatric services in homes for the aged are apparent recognition of this phenomenon.
Airway function at one year: association with premorbid airway function, wheezing, and maternal smoking
Authors: C Dezateux
Journal: Thorax (2001)

Impaired growth and development of the respiratory system during fetal and early postnatal life may have important implications for lung development and later lung health. The aim of this study was to examine the association of diminished premorbid airway function, prior wheezing, and maternal smoking with airway function at 1 year of age.Respiratory function was measured at the end of the first year in 100 of 108 healthy term infants (93%) in whom similar measurements had been undertaken prior to any respiratory illness at 8 weeks. Physician diagnosed wheezing episodes were identified retrospectively from medical records.At 1 year specific airway conductance during end expiration (sGawEE; /s/kPa) was significantly diminished in those infants with prior wheezing (95% CI wheeze/no wheeze -0.76 to -0.14), mothers who smoked (95% CI smoke/no smoke -0.81 to -0.27), a family history of asthma (95% CI family history/no family history -0.62 to 0.00), or diminished premorbid sGawEE (95% CI -0.13 to -0.43/s/kPa per unit reduction sGawEE at 8 weeks). In a multivariate model only maternal smoking and diminished premorbid sGawEE were independently associated with diminished sGawEE at 1 year.Diminished airway function at the end of the first year appears to be mediated by impaired airway development during early life as well as by exposure to maternal smoking. These findings are consistent with the hypothesis that, at a population level, diminished premorbid airway function provides the link between wheezing lower respiratory illness and diminished airway function at 1 year. Maternal smoking remains an important and avoidable cause of impaired airway development and function in infancy.
THE DISTRIBUTION OF IRON INJECTED INTRAPERITONEALLY. EVIDENCE OF SEROSAL “ABSORPTION” BY THE SMALL INTESTINE
Authors: Phairojana Thirayothin, William H. Crosby
Journal: Journal of Clinical Investigation (1962)

Depot iron is normally held in the body as a combination with ferritin, the iron-storage protein. A study of normal rats was undertaken concerning the deposition of iron in ferritin after the animals were given a large intraperitoneal dose of iron. A peculiarity of behavior of ferritin in the small intestine after such injection led to the observation that the intestine is able to incorporate ferritin iron through its serosal surface.
Combined Molecular and Clinical Prognostic Index for Relapse and Survival in Cytogenetically Normal Acute Myeloid Leukemia
Authors: Friederike Pastore, Annika Dufour, Tobias Benthaus, Klaus H. Metzeler, Kati S. Maharry, Stephanie Schneider, Bianka Ksienzyk, Gudrun Mellert, Evelyn Zellmeier, Purvi M. Kakadia, Michael Unterhalt, Michaela Feuring-Buske, Christian Buske, Jan Braess, Maria Cristina Sauerland, Achim Heinecke, Utz Krug, Wolfgang E. Berdel, Thomas Buechner, Bernhard Woermann, Wolfgang Hiddemann, Stefan K. Bohlander, Guido Marcucci, Karsten Spiekermann, Clara D. Bloomfield, Eva Hoster
Journal: Journal of Clinical Oncology (2014)

Cytogenetically normal (CN) acute myeloid leukemia (AML) is the largest and most heterogeneous cytogenetic AML subgroup. For the practicing clinician, it is difficult to summarize the prognostic information of the growing number of clinical and molecular markers. Our purpose was to develop a widely applicable prognostic model by combining well-established pretreatment patient and disease characteristics.Two prognostic indices for CN-AML (PINA), one regarding overall survival (OS; PINAOS) and the other regarding relapse-free survival (RFS; PINARFS), were derived from data of 572 patients with CN-AML treated within the AML Cooperative Group 99 study (www.aml-score.org).On the basis of age (median, 60 years; range, 17 to 85 years), performance status, WBC count, and mutation status of NPM1, CEBPA, and FLT3-internal tandem duplication, patients were classified into the following three risk groups according to PINAOS and PINARFS: 29% of all patients and 32% of 381 responding patients had low-risk disease (5-year OS, 74%; 5-year RFS, 55%); 56% of all patients and 39% of responding patients had intermediate-risk disease (5-year OS, 28%; 5-year RFS, 27%), and 15% of all patients and 29% of responding patients had high-risk disease (5-year OS, 3%; 5-year RFS, 5%), respectively. PINAOS and PINARFS stratified outcome within European LeukemiaNet genetic groups. Both indices were confirmed on independent data from Cancer and Leukemia Group B/Alliance trials.We have developed and validated, to our knowledge, the first prognostic indices specifically designed for adult patients of all ages with CN-AML that combine well-established molecular and clinical variables and that are easily applicable in routine clinical care. The integration of both clinical and molecular markers could provide a basis for individualized patient care through risk-adapted therapy of CN-AML.
The International Prognostic Factors Project score for advanced Hodgkin’s disease is useful for predicting outcome of autologous hematopoietic stem cell transplantation
Authors: P.J. Bierman, J.C. Lynch, R.G. Bociek, V.L. Whalen, A. Kessinger, J.M. Vose, J.O. Armitage
Journal: Annals of Oncology (2002)
Discovery of a novel class of highly conserved vaccine antigens using genomic scale antigenic fingerprinting of pneumococcus with human antibodies
Authors: Carmen Giefing, Andreas L. Meinke, Markus Hanner, Tamás Henics, Duc Bui Minh, Dieter Gelbmann, Urban Lundberg, Beatrice M. Senn, Michael Schunn, Andre Habel, Birgitta Henriques-Normark, Åke Örtqvist, Mats Kalin, Alexander von Gabain, Eszter Nagy
Journal: The Journal of Experimental Medicine (2007)

Pneumococcus is one of the most important human pathogens that causes life-threatening invasive diseases, especially at the extremities of age. Capsular polysaccharides (CPSs) are known to induce protective antibodies; however, it is not feasible to develop CPS-based vaccines that cover all of the 90 disease-causing serotypes. We applied a genomic approach and described the antibody repertoire for pneumococcal proteins using display libraries expressing 15–150 amino acid fragments of the pathogen's proteome. Serum antibodies of exposed, but not infected, individuals and convalescing patients identified the ANTIGENome of pneumococcus consisting of ∼140 antigens, many of them surface exposed. Based on several in vitro assays, 18 novel candidates were preselected for animal studies, and 4 of them showed significant protection against lethal sepsis. Two lead vaccine candidates, protein required for cell wall separation of group B streptococcus (PcsB) and serine/threonine protein kinase (StkP), were found to be exceptionally conserved among clinical isolates (&amp;gt;99.5% identity) and cross-protective against four different serotypes in lethal sepsis and pneumonia models, and have important nonredundant functions in bacterial multiplication based on gene deletion studies. We describe for the first time opsonophagocytic killing activity for pneumococcal protein antigens. A vaccine containing PcsB and StkP is intended for the prevention of infections caused by all serotypes of pneumococcus in the elderly and in children.
The effect of CYP2C19 polymorphism on the safety, tolerability, and pharmacokinetics of tivantinib (ARQ 197): results from a phase I trial in advanced solid tumors
Authors: N. Yamamoto, H. Murakami, T. Nishina, T. Hirashima, K. Sugio, K. Muro, T. Takahashi, T. Naito, H. Yasui, S. Akinaga, Y. Koh, N. Boku
Journal: Annals of Oncology (2013)
Bacterial invasion of the biliary system by way of the portal-venous system
Authors: Joseph Y. Sung, Eldon A. Shaffer, Merle E. Olson, Joseph W. C. Leung, Kan Lam, William J. Costerton
Journal: Hepatology (1991)

It has been suggested that bacteria in the intestine gain access into the biliary tract by entering the portal-venous blood. We have tested the hypothesis of hematogenous infection of the biliary system in cats. The animals were treated in three different groups: group A (no biliary obstruction), group B (acute biliary obstruction) and group C (chronic biliary obstruction). A mutant strain of Escherichia coli was infused into the splenic vein of cats at three different dosages (10(7), 10(5) and 10(3) with sham controls. In the unobstructed biliary system, the mutant E. coli was isolated from the bile 30 min and 90 min after the infusion of 10(7) and 10(5) E. coli, respectively. No bacteria were found in the bile with the infusion of 10(3) E. coli and in the control animals. Bile flow was significantly reduced with the infusion of bacteria. The biliary excretion of E. coli in group B was similar to that in group A. In group C, the bile output in the first hour was very high but declined rapidly. E. coli was excreted into the bile at all three dosages of infusion after 30 min. Histological sections of the liver showed that the infused bacteria entered the sinusoidal blood and that some were phagocytosed by Kupffer cells. The portal-venous blood was considered an important route of bacterial invasion into the biliary system, and the penetration of bacteria was facilitated in biliary obstruction.
Mechanoelectric contributions to sudden cardiac death
Authors: D Babuty
Journal: Cardiovascular Research (2001)

Time for primary review 28 days. 

Sudden death, a major problem in developed countries and increasingly so in some underdeveloped countries, justifies research on the mechanisms and identification of patients at high risk of sudden death. Most sudden deaths are secondary to ventricular tachyarrhythmias [1,2]. Primary electrical disturbances, such as Brugada syndrome, long QT syndrome, are rare and account for few sudden deaths. Sudden death as a rule complicates the situation with an underlying cardiac disease with different classes of heart failure [2]. The alteration of the cardiac mechanical properties developing early in heart failure is accompanied by action potential lengthening [3], which is modulated by acute stretch [4–6].

The English theologian and philosopher William of Occam (1280–1349) stated: ‘Entia non sunt multiplicanda praeter necessitatum’. This is recognised as Occam's Razor. Roughly interpreted, it proposes that it is better to have one hypothesis to explain five observations than five hypotheses to explain each one. The cardiovascular clinical parameters used for predicting sudden arrhythmic death ranging through indices of neurohormonal status (i.e. heart rate variability) to indices of electrophysiological substrate (i.e. late potentials, QT dispersion, alternans) are influenced by and associated with mechanical disturbances in heart. Although some of these issues have been related to mechanical factors in previous reviews [6–12], this review describes the possibility that many of the mechano-arrhythmic factors affect a common pathway. Moreover, several arrhythmic mechanisms and their clinical correlates infringe such a pathway. That is, we will try to apply the Occam's Razor principle to this problem.

We have to satisfy several criteria to support this contention (Fig. 1). First, the currently accepted situation (Fig. 1A). The black arrows represent the paths taken by the conventional dogma. The etiological factors (Fig. 1A top centre), through a variety of mechanisms act via … 

*Corresponding author. Tel.: +33-2-4747-4687; fax: +33-2-4747-5919 d.babuty{at}chu.med.univ-tours.fr
Mixture of N-carbamoyl-l-glutamate plus l-arginine can protect rats with liver cirrhosis from acute ammonia intoxication
Authors: Wook-Hwan Kim, Hyelee Park, Chawon Yun, Hyeseong Cho, Sangduk Kim, Woon Ki Paik, Soung-Hoo Jeon, Jae-Ho Lee
Journal: Journal of Hepatology (2001)
P46 * THE KI-67 LABELLING INDEX WITH MAXIMALLY SELECTED CUT-OFFS IS BETTER AT PREDICTING RECURRENCE THAN THE WHO GRADING SYSTEM OF MENINGIOMAS
Authors: R. Laxton, L. Doey, A. Murphy-Stout, E. Davis, R. Bhangoo, R. Gullan, K. Ashkan, S. Al-Sarraj
Journal: Neuro-Oncology (2014)

INTRODUCTION: Meningiomas are principally benign tumours curable by resection. Many studies have shown a link between Ki-67 labelling indices (LI) and recurrence. Here we seek to improve the grading of meningioma through the use of LI with maximally selected cut points. METHOD: 285 adult meningiomas seen between 1999 and 2004 were examined immunohistochemically using the Ki-67/Mib-1 monoclonal antibody. Statistical analyses, were performed using R-Stats v2.15.1 and the R-Coin package. RESULTS: LI is associated with recurrence free survival (RFS) hazard ratio (HR) (1.09 p = 1.6x10−10). LI is correlated with tumour grade, there were significant differences between the LI means of each WHO grade (I - 4.9%, II - 12.3%, III - 28.7%; p = 2x10−16). Maximal selection of a cut point for RFS using multiple parameters revealed a cut point of LI 10%. Obtaining a further cut point on meningiomas with LI >10% gave the higher cut point of 27%. Kaplan-Meier (KM) analysis of WHO I - III showed a median RFS of 20.28, 8.79, & 1.14 years respectively (p = 3.7x10−8). KM analysis of cut point groups LI 1-10 (LI_A), 11-27 (LI_B), & >27 (LI_C) showed median RFS of 20.28, 7.96, & 1.99 years respectively (p = 6.9x10−13). Cox regression for RFS adjusting for age, gender, WHO grade & LI(A,B,&C) showed that with reference to WHO I, WHO II had a HR of 1.99 p = 0.03, grade III 4.25 p = 0.04; with reference to LI_A, LI_B had a HR of 2.3(1.15 - 4.7) p = 0.02 and LI_C a HR of 10.2(4 - 26) p = 1.2x10−6. CONCLUSION: These results demonstrated stratification, based solely upon the Ki67 labelling index, better predicting recurrence than the current WHO grading. This emphasises the need for LI to be fully incorporated into the grading system of meningiomas.
Gestational Diabetes Mellitus
Authors: Mukesh M. Agarwal, Gurdeep S. Dhatt, Syed M. Shah
Journal: Diabetes Care (2010)

OBJECTIVE To determine the impact of the International Association of Diabetes and Pregnancy Study Group (IADPSG) criteria on 1) gestational diabetes mellitus (GDM) diagnosis compared with the American Diabetes Association (ADA) criteria and 2) the fasting plasma glucose (FPG) to predict GDM. RESEARCH DESIGN AND METHODS In 10,283 pregnant women undergoing a 75-g oral glucose tolerance test (OGTT) for universal screening of GDM, two FPG thresholds (of the OGTT) were used to rule in and to rule out GDM. RESULTS The IADPSG and ADA criteria identified GDM in 3,875 (37.7%) women and 1,328 (12.9%) women, respectively (P &amp;lt; 0.0005). FPG thresholds of ≥5.1 mmol/l ruled in GDM in 2,975 (28.9%) women with 100% specificity, while &amp;lt;4.4 mmol/l ruled out GDM in 2,228 (21.7%) women with 95.4% sensitivity. FPG independently could have avoided the OGTT in 5,203 (50.6%) women. CONCLUSIONS The IADPSG criteria increased GDM prevalence nearly threefold. By circumventing a significant number of OGTTs, an initial FPG can greatly simplify the IADPSG diagnostic algorithm.