tbuckley/cabot-search huggingface dataset:
Secondary Acute Myeloid Leukemia in Children Treated for Acute Lymphoid Leukemia
Authors: Ching-Hon Pui, Frederick G. Behm, Susana C. Raimondi, Richard K. Dodge, Stephen L. George, Gaston K. Rivera, Joseph Mirro, David K. Kalwinsky, Gary V. Dahl, Sharon B. Murphy, William M. Crist, Dorothy L. Williams
Journal: New England Journal of Medicine (1989)

We studied the risk of the development of acute myeloid leukemia (AML) during initial remission in 733 consecutive children with acute lymphoid leukemia (ALL) who were treated with intensive chemotherapy. This complication was identified according to standard morphologic and cytochemical criteria in 13 patients 1.2 to 6 years (median, 3.0) after the diagnosis of ALL. At three years of follow-up, the cumulative risk of secondary AML during the first bone marrow remission was 1.6 percent (95 percent confidence limits, 0.7 and 3.5 percent); at six years, it was 4.7 percent (2 and 10 percent). The development of secondary AML was much more likely among patients with a T-cell than a non-T-cell immunophenotype (cumulative risk, 19.1 percent [6 and 47 percent] at six years). Sequential cytogenetic studies in 10 patients revealed entirely different karyotypes in 9, suggesting the induction of a second neoplasm. In eight of these patients, the blast cells had abnormalities of the 11 q23 chromosomal region, which has been associated with malignant transformation of a pluripotential stem cell. There was no evidence of loss of DNA from chromosome 5 or 7, a karyotypic change commonly observed in cases of AML secondary to treatment with alkylating agents, irradiation, or both. We conclude that there is a substantial risk of AML in patients who receive intensive treatment for ALL, especially in those with a T-cell immunophenotype, and that 11q23 chromosomal abnormalities may be important in the pathogenesis of this complication. (N Engl J Med 1989;321:136–42.)
Altered sarcoplasmic reticulum Ca2(+)-ATPase gene expression in the human ventricle during end-stage heart failure.
Authors: J J Mercadier, A M Lompré, P Duc, K R Boheler, J B Fraysse, C Wisnewsky, P D Allen, M Komajda, K Schwartz
Journal: Journal of Clinical Investigation (1990)

A decrease in the myocardial level of the mRNA encoding the Ca2(+)-ATPase of the sarcoplasmic reticulum (SR) has been recently reported during experimental cardiac hypertrophy and failure. To determine if such a deficit occurs in human end-stage heart failure, we compared the SR Ca2(+)-ATPase mRNA levels in left (LV) and right ventricular (RV) specimens from 13 patients undergoing cardiac transplantation (6 idiopathic dilated cardiomyopathies; 4 coronary artery diseases with myocardial infarctions; 3 diverse etiologies) with control heart samples using a rat cardiac SR Ca2(+)-ATPase cDNA probe. We observed a marked decrease in the mRNA for the Ca2(+)-ATPase relative to both the 18S ribosomal RNA and the myosin heavy chain mRNA in LV specimens of patients with heart failure compared to controls (-48%, P less than 0.01 and -47%, P less than 0.05, respectively). The LV ratio of Ca2(+)-ATPase mRNA to 18S RNA positively correlated with cardiac index (P less than 0.02). The RV ratio correlated negatively with systolic, diastolic and mean pulmonary arterial pressures (P less than 0.02, P less than 0.02, and P less than 0.01, respectively). We suggest that a decrease of the SR Ca2(+)-ATPase mRNA in the myocardium plays an important role in alterations of Ca2+ movements and myocardial relaxation reported during human end-stage heart failure.
Abstract 3614: In vivo efficacy of the carbonic anhydrase IX (CA9)-targeted antibody-drug conjugate BAY 79-4620 is superior to that of microtubule inhibitors in preclinical models of NSCLC, gastric and colorectal cancer
Authors: Heike Petrul, Charlotte Kopitz, Christoph Schatz, Rudolf Beier, Miriam Zatovicova, Silvia Pastorekova, Bertolt Kreft, Karl Ziegelbauer
Journal: Cancer Research (2011)

Abstract BAY 79-4620 is a novel antibody drug conjugate (ADC) consisting of a fully human monoclonal antibody directed against carbonic anhydrase IX (CA9) conjugated to the auristatin derivative monomethyl auristatin E (MMAE) and is currently in Phase I clinical testing. CA9 is overexpressed in a range of tumor types, including gastric cancer, non-small cell lung cancer (NSCLC), pancreatic cancer and colorectal cancer. CA9 is a hypoxia-inducible protein regulated by HIF-1α, and its expression has been linked to higher aggressiveness of tumors and is predictive of poor prognosis in several cancers. In this study, we first compared the internalization rates of the ADC BAY 79-4620 and of the naked antibody, which were found to be similar in several cell lines, indicating that CA9 internalization in vitro is not affected by the conjugated toxophore. It has previously been shown that the cytotoxicity of BAY 79-4620 depends on both CA9 expression and sensitivity of tumor cells to tubulin inhibitors. The anti-tumor efficacy of BAY 79-4620 was therefore compared to that of free toxophore MMAE as well as paclitaxel. At cumulative doses corresponding to a fraction of that of paclitaxel (calculated as toxophore equivalents), BAY 79-4620 showed equivalent or superior efficacy to paclitaxel and MMAE in xenograft models of human NSCLC and gastric carcinoma. Cumulative BAY 79-4620 doses corresponding to only 30% of the highest dose of free MMAE given showed equivalent or superior efficacy in xenograft models of non-small cell lung carcinoma. Moreover, BAY 79-4620 also showed efficacy in patient-derived NSCLC models that are resistant to paclitaxel and/or cisplatin. Finally, regrowing CRC tumors after an initial response to BAY 79-4620 responded well to a second cycle of BAY 79-4620 treatment. This indicates that no resistance through clonal selection of CA9 negative tumor cells was induced and that repeated treatment cycles should be possible for cancer patients. These results show the superiority of the CA9-targeted approach over the systemic administration of tubulin inhibitors, component of treatment regimens commonly used for the treatment of NSCLC and gastric cancer. Efficacy of BAY 79-4620 was particularly high in models expressing high levels of CA9, making BAY 79-4620 a promising agent for the treatment of CA9-positive NSCLC and gastric cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3614. doi:10.1158/1538-7445.AM2011-3614
The inability to process a self-peptide allows autoreactive T cells to escape tolerance.
Authors: M J Mamula
Journal: The Journal of Experimental Medicine (1993)

It is now clear that antigen presenting cells (APCs) do not present all the possible peptides of self-proteins to the immune system. When then, is the fate of T cells specific for those self-peptides that escape processing? In this study, the COOH-terminal peptide (residues 81-104) of self cytochrome c (cyt c) elicited strong autoimmune T cells, as well as autoantibodies specific for this immunogen. These T cells did not respond to stimulation with the whole self cyt c molecule, demonstrating that APCs cannot process and present the self 81-104 peptide. Whereas mice were unresponsive to immunization with the whole mouse cyt c molecule, the mouse 81-104 fragment together with the whole self-molecule induced and amplified the autoimmune T cell response to sites within the 1-80 peptide. T cells that never contact the relevant self-peptide are functionally ignorant. They do not become tolerized or deleted, nor do they normally participate in immune responses to the native whole self-protein, since APCs cannot present the 81-104 peptide.
Measurement of cardioversion/defibrillation thresholds in man by a truncated exponential waveform and an apical patch-superior vena caval spring electrode configuration.
Authors: R A Winkle, E B Stinson, S M Bach, D S Echt, P Oyer, K Armstrong
Journal: Circulation (1984)

Defibrillation/cardioversion thresholds were measured in 33 patients undergoing defibrillator implants. Each patient had a 12 cm2 patch placed near the left ventricular apex via a thoracotomy and a 10 cm2 spring lead placed pervenously at the right atrial-superior vena caval junction. Ventricular tachycardia of stable morphology, polymorphic ventricular tachycardia, or ventricular fibrillation was induced four times in each patient and 1, 5, 10, and 25 J truncated exponential shocks with 60% tilt were given in a random sequence. The conversion rate was constant (77%, 86%, 87%, 85%) with increasing energy for ventricular tachycardia but progressively increased for polymorphic ventricular tachycardia and ventricular fibrillation (8%, 33%, 58%, 92%). The ventricular tachycardia acceleration rates for 1, 5, 10, and 25 J were 23%, 14%, 10%, and 15%. Patients not reliably converted with 25 J may require repositioning of leads or two patches. We conclude that for the spring-patch electrodes, increasing energy from 1 to 25 J improves the conversion rate for polymorphic ventricular tachycardia and ventricular fibrillation; the ventricular tachycardia conversion rate is constant. Acceleration of ventricular tachycardia occurs at all energies. Defibrillator implantation requires extensive intraoperative electrophysiologic testing to ensure safe and reliable termination of ventricular tachycardia and fibrillation.
PROGRESS IN CARE AND EDUCATION OF CRIPPLED CHILDREN IN OHIO UNDER NEW LAWS
Authors: BURT G. CHOLLETT
Journal: JAMA (1922)

spoken of, they do require preoperative and postoperative medical treatment.At least three of the men present who are doing a large number of goiter operations have a printed outline as to follow-up treatment of patients after they return to their homes.Follow-up care of these people with hearts more or less crippled, and who always will be more or less crippled, is of special importance, in order to put them in the best condition possible.They feel well enough, but unless they are taken care of and take care of themselves, they do not get along very well.Dr. Crile and Dr. Mayo emphasized the fact that goiter is a surgical disease.A very distin¬ guished physician, Dr. O'sler, emphasized this point twenty years ago when he said that, after the patient has been unsuc¬ cessfully handled for three months, he should be referred to the surgeon.Another point which deserves to be mentioned in this connection is that no matter how simple and how safe the proposition may seem, a man must be prepared to handle almost anything, when he goes into the neck of a patient with goiter.We are not able to tell always when we are going to encounter malignancy, or deep thoracic goiter, or when the toxemia may be a very much graver element than seems at first.Dr. J. Earl Else, Portland, Ore. : I want to emphasize two things : first, I hope that no one goes away with the idea that all goiter cases are surgical cases.The majority of cases do not require surgical treatment.Colloid goiters, for the most part, are not surgical cases, and only rarely does a goiter patient in the adolescent age require operation.Goiter accompanied by hyperthyroidism, however, is another matter.The toxic exophthalmic goiters are practically all surgical.The other thing I wish to mention is the relationship of tonsillitis to goiter.If tonsillitis is a direct etiologic factor in goiter, I do not understand why the majority of cases appear in females, because there are probably more cases of infected tonsils in the male than in the female.In view of this fact, it would appear that the relationship, if there be one, is an indirect one.Personally, I am inclined to think that at least in the majority of cases, the relationship is merely coincidental.
Mitral Valvular Disease: Hemodynamic Studies of the Consequences for the Circulation
Authors: Robert L. Grissom
Journal: JAMA (1964)

In this book Dr. Werkö presents clinical studies on 250 patients, most with mild mitral stenosis, whom he and his colleagues personally studied in Sweden over a 15-year period from 1948 through 1962. The particular value of the data relates to stressful procedures such as exercise; the response of the rheumatic heart to medication such as antihypertensive drugs; simultaneous renal function testing; the effect of mitral stenosis as measured by cardiac catheterization; and the long-term course of the patient's illness. Hemodynamic studies before and after operation were carried out on 38 patients, but in the majority, no operation was performed. In each section, Dr. Werkö succinctly evaluates previously published information before he presents his own data. Many excellent graphs are shown, which are well labelled. For the most part, the pressure tracings are clearly reproduced. Often representative examples are discussed in detail. One stressful procedure having real pertinence to patient
894 COMBINED GLUTATHIONE-S-TRANSFERASE M1 AND T1 GENETIC POLYMORPHISM AND SUSCEPTIBILITY TO DEVELOP DRUG-INDUCED IDIOSYNCRATIC LIVER INJURY (DILI)
Authors: R.J. Andrade, C. Martinez, E. Ulzurrun, E. Garcia-Martin, J. Agundez, Y. Borraz, S. Lopez-Ortega, A. Fernandez-Castaner, G. Pelaez, M. Romero-Gomez, A. Madrazo, A. Castiella, R. Planas, J.M. Navarro, J. Salmeron
Journal: Journal of Hepatology (2008)
WILLIAM STEWART HALSTED, AN APPRECIATION ON THE CENTENARY OF HIS BIRTH
Authors: Alfred Blalock
Journal: JAMA (1952)

William Stewart Halsted, who was destined to work and to produce in a golden era in medicine, was born in New York City in 1852. He was graduated from Yale University in arts in 1874 and from the College of Physicians and Surgeons in medicine in 1877. It was while serving an internship at Bellevue that he first met William H. Welch, who had just returned from Germany where he had been working in the basic sciences in the laboratories of Julius Cohnheim and others. At that time medical education in this country was in a deplorable state. There were many medical schools, none of university caliber, and all proprietary, whereas there were about 20 university medical schools in Germany. About this time Johns Hopkins, a Baltimore merchant and banker, left his fortune for the establishment of a university and a hospital, the latter to be a part of the
Further Studies of the Cerebral Chemoreceptor Buffers as Influenced by Vasoconstrictor and Vasodilator Drugs and Veratrum Viride
Authors: ROBERT D. TAYLOR, IRVINE H. PAGE
Journal: Circulation (1951)

These experiments extend our studies on the newly described cerebral chemoreceptors to show that most pressor drugs cause peripheral hypotension when perfused through the brain of the animal isolated except for nervous connections with its body. Depressor drugs usually act oppositely and cause hypertension. The cerebral chemoreceptors thus seem to act as a buffer mechanism. The receptors may be inactivated to some drugs without blocking the neurogenic hypertension response elicited by cerebral ischemia. Veratrum viride is shown to be such a drug. Besides initiating the von Bezold reflex, veratrum lowers blood pressure by direct central action.
Redesign and modernisation of an NHS cataract service (Fife 1997-2004): multifaceted approach
Authors: Adrian Tey, Barbara Grant, Dawn Harbison, Shona Sutherland, Patrick Kearns, Roshini Sanders
Journal: BMJ (2007)

A Scottish national health service ophthalmic facility was unable to cope with increasing demand for cataract surgery.Multifaceted approach to redesign hospital space to accommodate a cataract unit; to invest in cataract nursing staff to allow more operations under local anaesthesia and as day cases; and to enhance input by general practitioners and optometrists to streamline and reduce false positive cataract referrals. A prospective audit for productivity was undertaken in 2004 (two years after the redesign) and compared against the national cataract surgery audit data for Fife from 1997.District general hospital serving a population of 400,000 in south east Scotland.Increasing throughput of cataract surgery while assessing quality of care provided against predefined evidence and Royal College of Ophthalmologists' guidelines, and evaluating training standards for ophthalmic surgical trainees against higher surgical training requirements.Cataract services were redesigned to increase throughput and to reduce waiting times while preserving the quality of patient care. A secondary end point was to maintain surgical case load mix thus allowing trainees to continue to fulfil the number of operations required to acquire higher surgical training standards.In the same three month period 237 cataract operations were carried out in 1997 and 374 in 2004, representing an increase of productivity by 60%. The waiting time for surgery decreased from more than one year to three months. The redesign resulted in almost complete preoperative and postoperative assessment by nursing staff, thus freeing medical time and allowing for more operations. Optometrists' referrals with reports increased significantly (P<0.0001). The number of operations carried out as day cases under local anaesthesia increased, with fewer intraoperative complications and postoperative visits (P<0.0001). The number of operations carried out by trainees more than doubled, from 43 to 100 cases, thus improving training opportunities.Modest capital investment in rebuilding space and in staff for cataract services can improve the quality and volume of cataract surgery. Enhancing existing NHS services provides for future need while maintaining training standards, thus potentially obviating the need for independent treatment centres. This model could be used throughout the United Kingdom.
CENTRAL OBESITY SEEMS TO HAVE THE HIGHEST PREDICTIVE VALUE AMONG ALL OTHERS ANTHROPOMETRIC INDICES FOR THE FIVE-YEAR INCIDENCE OF HYPERTENSION IN APPARENTLY HEALTHY INDIVIDUALS: THE ATTICA STUDY
Authors: Christina A. Chrysohoou, Demosthenes B. Panagiotakos, Christos Pitsavos, John Skoumas, Yannis Lentzas, Anastasia Katinioti, Constantina Masoura, Akis Zeibekis, Lambros Papadimitriou, Manolis Kambaxis, Vasiliki Metaxa
Journal: Journal of the American College of Cardiology (2010)
Emerging Technologies in Screening for Colorectal Cancer: CT Colonography, Immunochemical Fecal Occult Blood Tests, and Stool Screening Using Molecular Markers
Authors: B. Levin, D. Brooks, R. A. Smith, A. Stone
Journal: CA A Cancer Journal for Clinicians (2003)

The American Cancer Society's (ACS) Colorectal Cancer Advisory Group held a workshop on new technologies for the early detection of colorectal cancer and adenomatous polyps as part of a regular review of ACS guidelines for colorectal cancer screening. The Advisory Group formally reviewed CT colonography, immunochemical fecal occult blood tests (FOBT), and stool screening using molecular markers, and also addressed other technologies including capsule video endoscopy. With the exception of immunochemical stool testing, the ACS has determined that at this time there is insufficient evidence to recommend these technologies for routine colorectal cancer screening. Based on recommendations of the Advisory Group, only a minor modification has been made to the ACS's Recommendations for Screening and Surveillance of the Early Detection of Adenomatous Polyps and Colorectal Cancer.
Changing Incidence and Survival for Heart Failure in a Well-Defined Older Population, 1970–1974 and 1990–1994
Authors: William H. Barker, John P. Mullooly, William Getchell
Journal: Circulation (2006)

Background— An epidemic increase in heart failure (HF) mortality, hospitalization, and prevalence rates has been observed among older persons in recent years. It is unclear whether this reflects an increase in incidence or survival. Methods and Results— We conducted a retrospective cohort study comparing HF in 1970 to 1974 and 1990 to 1994 among persons ≥65 years old belonging to a large, well-defined population with complete medical records available for research. Using Framingham clinical criteria, we identified incident cases of HF in the respective periods. Age-specific and age-adjusted incidence, mortality, and survival rates were compared. Cox proportional-hazards models were used to assess association of comorbidities and medications with survival. During 38 800 and 127 419 person-years for 1970 to 1974 and 1990 to 1994, respectively, 387 and 1555 confirmed incident cases were identified. When adjusted for age, incidence increased by 14% (95% CI 2% to 28%). Increased incidence tended to be greater for older persons and for men. Based on 5-year follow-up and adjustment for age and comorbidities, the mortality hazards decreased 33% (95% CI 14% to 48%) among men and 24% (95% CI −1% to 43%) among women. Conclusions— The epidemic increase in HF among the older population between the 1970s and 1990s is associated with increased incidence and improved survival, with both of these effects being greater in men.
Acute coronary syndrome patients with ST-segment depression have substantial mortality rates but undergo less aggressive management strategies: Insights from the global registry of acute coronary events (GRACE)
Authors: Shaun G. Goodman, Christopher B. Granger, Kami White, David Brieger, Andrzej Budaj, Omar H. Dabbous, Philippe Gabriel Steg
Journal: Journal of the American College of Cardiology (2003)
Screening for fragile X syndrome: a model for genetic disorders?
Authors: A. Barnicoat
Journal: BMJ (1997)

The fragile X syndrome is often cited as the commonest inherited cause of mental handicap. It was described after the finding that a fragile site at the distal end of the X chromosome was associated with mental handicap. The X linked inheritance pattern is atypical; female carriers may show some features, and males may also occasionally be asymptomatic carriers. Fragile X syndrome was the first of an increasing number of neurological genetic conditions in which a dynamic mutation of a triplet repeat was identified, where instability between generations explained the unusual inheritance pattern.1 The documentation of the molecular pathology in fragile X allowed confirmation of carrier status in both male and female family members. The growth in understanding of the condition led to early calls for screening,2 proposed both to implement early therapy and to reduce the birth prevalence.

Several approaches to screening are possible, broadly divided into either case finding with cascade screening (of relatives at risk in the extended family) or population …
Staphylococcal Food Poisoning in the United States
Authors: Scott D. Holmberg
Journal: JAMA (1984)

To determine the current epidemiologic characteristics of staphylococcal food-borne disease (SFD), we reviewed 131 outbreaks reported to the Centers for Disease Control, Atlanta, from 1977 through 1981. Staphylococcal food-borne disease was the second most common cause of reported food-borne illness, affecting more than 7,000 persons during the five-year period; 10% of these patients visited or were admitted to hospitals for their illnesses. The proportion of outbreaks attributable to<i>Staphylococcus aureus</i>enterotoxins A through E has changed, with enterotoxin A being the only toxin incriminated during the last three years of this review. Milk—the most common source of enterotoxin C- and D-producing strains—and commercially packed foods are less common causes of SFD outbreaks now than they were before 1960. However, previously cooked, proteinaceous foods remain preeminent in causing SFD. The presence or absence of fever in infected persons, skin lesions in food handlers, or large numbers of staphylococci in food were unreliable as diagnostic criteria. Thorough epidemiologic investigation remains crucial to identifying SFD and its sources. (<i>JAMA</i>1984;251:487-489)