tbuckley/cabot-search huggingface dataset:
Sensitivity to Gemcitabine and Its Metabolizing Enzymes in Neuroblastoma
Authors: Masahiro Ogawa, Hiroki Hori, Takuya Ohta, Kaori Onozato, Masazumi Miyahara, Yoshihiro Komada
Journal: Clinical Cancer Research (2005)

Abstract Purpose: We examined the activity of gemcitabine against neuroblastoma in vitro and in vivo. In addition, we investigated the cellular mechanisms of high sensitivity to the agent in neuroblastoma cells. Experimental Design: We examined 11 neuroblastoma cell lines for sensitivity to gemcitabine and other chemotherapeutic agents used clinically for neuroblastoma. The in vivo sensitivity of neuroblastoma to gemcitabine was determined in xenograft models. Furthermore, the major metabolic enzymes of gemcitabine were assessed and compared in leukemia and carcinoma cells. Apoptosis and mitochondrial membrane potentials were also evaluated. Results: The IC50s for gemcitabine in 11 neuroblastoma lines ranged between 3 nmol/L and 4 μmol/L. The high activity of gemcitabine against neuroblastoma was confirmed in animal models. Interestingly, enzymes in neuroblastoma cells involved in the metabolism of deoxycytidine analogue have unique characteristics among solid tumors. The median of deoxycytidine kinase activity in neuroblastoma lines was similar to that in leukemia lines, which have low IC50s for cytarabine. Cytidine deaminase (CDA) activity in neuroblastoma was hardly detectable and significantly lower than that in carcinoma. The defect of CDA activity was associated with negative expression of mRNA. Furthermore, gemcitabine-induced apoptosis was observed irrespective of the caspase-8 status of neuroblastoma cells, which indicates that apoptosis depends on the mitochondrial pathway. Conclusions: Neuroblastoma is highly sensitive to gemcitabine. Although the cellular mechanism involved in sensitivity to gemcitabine is multifactorial, low CDA activity may contribute high sensitivity in neuroblastoma cells. These results suggest that clinical application of gemcitabine to the treatment of neuroblastoma is warranted.
Temporal changes in canine right ventricular volume, mass, cell size, and sarcomere length after banding the pulmonary artery
Authors: M. M. LAKS, F. MORADY, D. GARNER, H. J. C. SWAN
Journal: Cardiovascular Research (1974)

The interrelation of sarcomere length, cell length, ventricular volume, and weight was determined in the right ventricle of normal and pulmonary arterial banded dogs; a temporal model of the acute and chronic compensatory changes of the myocardium is presented. These changes include an early increase in end-diastolic sarcomere length and the occurrence of fibre slippage. Although myocardial hypertrophy diminishes ventricular volume, the ventricle does not completely compensate; therefore, the volume of the ventricle does not return to normal.
Sinus node function and conduction system after complete repair of tetralogy of Fallot.
Authors: H Niederhauser, P Simonin, B Friedli
Journal: Circulation (1975)

Twenty-three children underwent electrophysiological studies during routine postoperative catheterization two months to five years after complete correction of tetralogy of Fallot. The aim of the study was to investigate the whole conduction system, including sinus node function, suing His bundle recordings and atrial pacing. H-V intervals were normal at rest and with pacing in twenty-two patients, including four patients with evidence of bifascicular block on the surface ECG. One patient with cardiomegaly and evidence of diffuse myocardial damage had a prolonged H-V interval but did not develop a block at this level during pacing A-H interval was slightly prolonged in four patients and normal in all others. The threshold of pacing-induced atrioventricular block ranged from 75 to 240/min and was somewhat age dependent (r = -0.55). Two patients fell below the 95% confidence limit of this regression and are considered abnormal. One returned to normal after intravenous injectionof atropine. Corrected sinus node recovery time ranged from 60 to 2000 msec. Three patients had values above 500 msec which are considered abnormal. These patients had other minor signs of sinus node dysfunction, i.e., episodes of sino-atrial block at rest or intermittent sinus bradycardia. Thus, while the His Purkinje system performed satisfactorily in all patients, sinus node dysfunctional and A-V node dysfunction were demonstrated in a few patients after correction of tetralogy of Fallot.
Liver Transplantation With Hepatitis C Virus–Infected Graft: Interaction Between Donor and Recipient Viral Strains
Authors: Xiaofeng Fan, Dorothy M. Lang, Yanjuan Xu, Andre C. Lyra, Karina Yusim, James E. Everhart, Bette T.M. Korber, Alan S. Perelson, Adrian M. Di Bisceglie
Journal: Hepatology (2003)

Superinfection of different viral strains within a single host provides an opportunity for studying host-virus and virus-virus interactions, including viral interference and genetic recombination, which cannot be studied in infections with single viral strains. Hepatitis C virus (HCV) is a positive single-strand RNA virus that establishes persistent infection in as many as 85% of infected individuals. However, there are few reports regarding coinfection or superinfection of HCV. Because of the lack of tissue culture systems and small animal models supporting efficient HCV replication, we explored these issues in the setting of liver transplantation where both recipient and donor were infected with different HCV strains and therefore represent a distinct model for HCV superinfection. Serial serum samples collected at multiple time points were obtained from 6 HCV-positive liver donor/recipient pairs from the National Institute of Diabetes and Digestive and Kidney Diseases liver transplantation database. At each time point, HCV genotype was determined by both restriction fragment length polymorphism analysis and phylogenetic analysis. Furthermore, we selectively sequenced 3 full-length HCV isolates at the earliest time points after liver transplantation, including both 5' and 3' ends. Detailed genetic analyses showed that only one strain of HCV could be identified at each time point in all 6 cases. Recipient HCV strains took over in 3 cases, whereas donor HCV strains dominated after liver transplantation in the remaining 3 cases. In conclusion, in all 6 cases studied, there was no genetic recombination detected among HCV quasispecies or between donor and recipient HCV strains.
Graduates from different UK medical schools vary in postgraduate exam performance
Authors: Susan Mayor
Journal: BMJ (2008)

Graduates from some UK medical schools consistently perform better than others in postgraduate medical exams, says a study published this week.The authors say that their finding supports the introduction of a national licensing examination for doctors.The study retrospectively analysed the performance from 2003 to 2005 of 5827 doctors from 19 UK medical schools in one or more of the three examinations required for membership of the Royal College of Physicians.This is an international postgraduate assessment that is important for career progression and is attempted by about 30% of all UK medical graduates.The research group looked at performance in parts 1 and 2 of the written examination, which are multiple choice assessments, and in part 2 of the practical examination of clinical assessment skills (PACES), which uses real and simulated patients to test clinical examination and communication skills.A further analysis involved data on performance in the part 1 examination over a much longer timeframe, from 1989 to 2002.The results showed that graduates from Oxford, Cambridge, and Newcastle upon Tyne performed significantly better than average in part 1 and part 2 of the written examination (BMC Medicine 2008;6:5).Those from Liverpool, Dundee, Belfast, and Aberdeen showed significantly below average performance.Ninety one per cent of Oxford students, 76% from Cambridge, and 67% from Newcastle passed part 1 at their first attempt, whereas the figures were 32% for Liverpool, 38% for Dundee, 37% for Belfast, and 41% for Aberdeen.The overall relation between medical school and exam performance was highly significant (χ 2 =300, df=6, P<0.001).About 60% of the variance between medical schools was explained by differences in pre-admission qualifications (according to number of points gained, but not subjects taken, in A level examinations or in the Scottish highers).However, the remaining portion of the variance was still significant. Doctors from different schools vary in later postgraduate examsUK NEWS BMA advises GPs on longer opening hours, p 351 World NEWS Inquiry finds scientists collaborated with Nazis, p 353 bmj.comCharity is set up to improve adolescents' health care newS
Irradiation for Inoperable Carcinoma of the Lung and High Performance Status
Authors: James D. Cox, Ritsuko Komaki, Donald R. Eierst
Journal: JAMA (1980)

Disagreement continues about the role of immediate irradiation of asymptomatic patients with inoperable lung cancer. Information pertaining specifically to irradiation of asymptomatic patients is scarce. The Medical College of Wisconsin, Milwaukee, reported that survival two years after irradiation was affected by control of the intrathoracic tumor. Ninety-two patients from that study with high performance status (80 to 100 on the Karnofsky scale) were evaluated for long-term survival. Of 54 patients (59%) whose tumors were controlled locally by irradiation, 22% survived five years. None of the 38 patients with uncontrolled thoracic disease lived beyond 27 months. Eight patients are alive and well 53 to 100 months after treatment. No specific late complications of irradiation have been seen. Patients having few symptoms with inoperable bronchial carcinoma can live many years if the tumor is controlled by irradiation. (<i>JAMA</i>244:1931-1933, 1980)
Immunodeficiency Associated with Loss of T4<sup>+</sup>Inducer T-Cell Function
Authors: Ellis L. Reinherz, Raif Geha, Mary Ellen Wohl, Chikao Morimoto, Fred S. Rosen, Stuart F. Schlossman
Journal: New England Journal of Medicine (1981)

We investigated the immune function of a patient with anergy and acquired hypogammaglobulinemia. Despite normal numbers of B cells and T4+ inducer and T5+ suppressor T cells, this patient's lymphocytes did not produce immunoglobulin, proliferate in response to soluble antigens, or generate helper factors in vitro. In addition, her T4+ T cells did not express la molecules after stimulation by soluble antigen. In mixing experiments, her T cells did not induce immunoglobulin secretion by B cells from a normal, HLA-D-identical sibling; this failure was not due to excessive suppression, since the patient's T cells did not abrogate immunoglobulin production by the normal sibling's T and B cells. Moreover, the patient's B cells secreted immunoglobulin in the presence of the sibling's T4+ cells. In contrast to the deficient inducer cells, the patient's T5+ T cells were capable of expressing suppressor-cell functions. These results indicate that immunodeficiency may occur because of a selective loss of T4+ inducer function. (N Engl J Med. 1981; 304:811–6.)
Arthralgia and Rubella Immunization
Authors: Stephen J. Lerman, Marcia R. Silver, George A. Nankervis
Journal: Annals of Internal Medicine (1978)

Letters and Corrections1 January 1978Arthralgia and Rubella ImmunizationSTEPHEN J. LERMAN, M.D., MARCIA R. SILVER, M.D., GEORGE A. NANKERVIS, PH.D., M.D.STEPHEN J. LERMAN, M.D.Search for more papers by this author, MARCIA R. SILVER, M.D.Search for more papers by this author, GEORGE A. NANKERVIS, PH.D., M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-88-1-131_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: In a paper on our 1969 clinical trial of HPV-77:DE-5 live attenuated rubella virus vaccine in adolescent girls and young women (1), we described in detail a 17-year-old vaccinee (subject #281) who developed moderate arthralgia of her knees and hips, moderate-to-severe arthritis of her fingers, and a painful ganglion. We noted that intermittent arthralgia of her knees and hips had persisted for a year after vaccination. We report here an 8-year follow-up.Subject #281 is now a 25-year-old resident in internal medicine. At 2-to-3-month intervals and in association with the onset of cool, damp weather, she experiences...References1. LERMAN S, NANKERVIS G, HEGGIE A, and GOLD E: Immunologic response, virus excretion, and joint reactions with rubella vaccine. A study of adolescent girls and young women given live attenuated virus vaccine (HPV-77:DE-5). Ann Intern Med 74:67-73, 1971 LinkGoogle Scholar2. KANTOR T and TANNER M: Rubella arthritis and rheumatoid arthritis. Arthritis Rheum 5:378-383, 1962 CrossrefMedlineGoogle Scholar3. SPRUANCE S, KLOCK L, and BAILEY A: Recurrent joint symptoms in children vaccinated with HPV-77:DK-12 rubella vaccine. J Pediatr 80:413-417, 1972 CrossrefMedlineGoogle Scholar4. THOMPSON G, WEISS J, and ELOISE M: Intermittent arthritis following rubella vaccination. A three-year follow-up. Am J Dis Child 125:526-530, 1973 CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: STEPHEN J. LERMAN, M.D.; MARCIA R. SILVER, M.D.; GEORGE A. NANKERVIS, PH.D., M.D.Affiliations: Pediatric Infectious Disease Unit University of Nebraska Medical Center Omaha, NE 68105 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 January 1978Volume 88, Issue 1Page: 131-131KeywordsAdolescentsArthralgiaArthritisClinical trialsDeoxyadenosine monophosphateHipKneesRubellaVaccines ePublished: 1 December 2008 Issue Published: 1 January 1978 PDF downloadLoading ...
EVIPAN SODIUM IN GENERAL PRACTICE
Authors: C. M. Douglas
Journal: BMJ (1935)

Adherent PericardiumAdherent pericardium hardly comes into our subject, as the deficiencies arising from this condition are those associated with its chronic effect on the heart.Many cases of pericarditis are followed by some degree of adherence between the visceral and parietal pericardium, but this is not enough to be very important in itself, or sufficiently widespread to prevent subsequent attacks of pericarditis and even of pericardial effusion.But the term is more often applied to the more extreme condition, where both layers of the pericardium are fixed to the sur- rounding mediastinum as the result of an old extensive mediastino-pericarditis.This adds a good deal to the work of the heart, and is known to be frequently associated with a very high degree of cardiac hypertrophy.No satisfactory local treatment has been devised, and the correct treatment is that of the underlying damaged heart muscle.
Response to Letter Regarding Article, “Relationship Between Homocysteine and Mortality in Chronic Kidney Disease”
Authors: Vandana Menon, Mark J. Sarnak, Arema A. Pereira, Andrew S. Levey, Tom Greene, Xuelei Wang, Gerald J. Beck, John W. Kusek, Jacob Selhub, Allan J. Collins, Michael G. Shlipak
Journal: Circulation (2006)
Residual HIV-1 Disease in the Era of Highly Active Antiretroviral Therapy
Authors: Roger J. Pomerantz
Journal: New England Journal of Medicine (1999)

Over the past 18 years the human immunodeficiency virus type 1 (HIV-1) epidemic has evolved, with the disease shifting from a syndrome whose cause was undefined to one in which the etiologic agent of AIDS was isolated and identified, but for which therapeutic options were limited. We are now in a new era characterized by efficient therapeutic agents to combat HIV-1 in many patients. This progress has been based on the development of highly active antiretroviral therapy in which combinations of agents are given that inhibit HIV-1 replication in vivo. Although vaccines are still under development and critical issues such . . .
AZD9291, an Irreversible EGFR TKI, Overcomes T790M-Mediated Resistance to EGFR Inhibitors in Lung Cancer
Authors: Darren A.E. Cross, Susan E. Ashton, Serban Ghiorghiu, Cath Eberlein, Caroline A. Nebhan, Paula J. Spitzler, Jonathon P. Orme, M. Raymond V. Finlay, Richard A. Ward, Martine J. Mellor, Gareth Hughes, Amar Rahi, Vivien N. Jacobs, Monica Red Brewer, Eiki Ichihara, Jing Sun, Hailing Jin, Peter Ballard, Katherine Al-Kadhimi, Rachel Rowlinson, Teresa Klinowska, Graham H.P. Richmond, Mireille Cantarini, Dong-Wan Kim, Malcolm R. Ranson, William Pao
Journal: Cancer Discovery (2014)

First-generation EGFR tyrosine kinase inhibitors (EGFR TKI) provide significant clinical benefit in patients with advanced EGFR-mutant (EGFRm(+)) non-small cell lung cancer (NSCLC). Patients ultimately develop disease progression, often driven by acquisition of a second T790M EGFR TKI resistance mutation. AZD9291 is a novel oral, potent, and selective third-generation irreversible inhibitor of both EGFRm(+) sensitizing and T790M resistance mutants that spares wild-type EGFR. This mono-anilino-pyrimidine compound is structurally distinct from other third-generation EGFR TKIs and offers a pharmacologically differentiated profile from earlier generation EGFR TKIs. Preclinically, the drug potently inhibits signaling pathways and cellular growth in both EGFRm(+) and EGFRm(+)/T790M(+) mutant cell lines in vitro, with lower activity against wild-type EGFR lines, translating into profound and sustained tumor regression in EGFR-mutant tumor xenograft and transgenic models. The treatment of 2 patients with advanced EGFRm(+) T790M(+) NSCLC is described as proof of principle.We report the development of a novel structurally distinct third-generation EGFR TKI, AZD9291, that irreversibly and selectively targets both sensitizing and resistant T790M(+) mutant EGFR while harboring less activity toward wild-type EGFR. AZD9291 is showing promising responses in a phase I trial even at the first-dose level, with first published clinical proof-of-principle validation being presented.
Risk Factors for Sudden Cardiac Death in Middle-Aged British Men
Authors: Goya Wannamethee, A. G. Shaper, P. W. Macfarlane, Mary Walker
Journal: Circulation (1995)

Background Risk factors specific to sudden cardiac death (SCD), ie, death within 1 hour after onset of symptoms, have been poorly identified, although recent findings from the present study incriminate heavy drinking and elevated heart rate. This paper examines the relations between a wide range of established and potential risk factors for ischemic heart disease (IHD) and SCD to identify independent risk factors for SCD and factors that might particularly or specifically relate to SCD. Methods and Results We present a prospective study of a cohort that was drawn from general practices in 24 British towns of 7735 middle-aged men who were followed up for 8 years. During 8 years of follow-up, the men experienced 488 major IHD events (nonfatal and fatal), of which 117 (24%) were classified as SCD. Age, preexisting IHD, arrhythmia, systolic blood pressure, blood cholesterol, elevated heart rate (≥90 beats per minute), physical activity (all, P &lt;.05), and, to a lesser extent, smoking ( P =.06), HDL cholesterol ( P &lt;.07), and elevated hematocrit (≥46%, P &lt;.09) emerged as independent risk factors for SCD after adjustment for a wide range of factors. Diabetes was not found to be associated with SCD, and forced expiratory volume in 1 second, body mass index, white blood cell count, and antihypertensive drugs were not associated with risk of SCD after adjustment. When examined in relation to non–sudden IHD deaths and nonfatal myocardial infarction, elevated heart rate, heavy drinking, and arrhythmia emerged as factors that appear to be specific or particular to SCD. These three factors and age and blood cholesterol were associated with an increased risk of SCD in men both with and without preexisting IHD. Physical activity, systolic blood pressure, and current smoking were associated with SCD only in men without preexisting IHD. HDL cholesterol and hematocrit were strong predictors of SCD only in men with preexisting IHD. Conclusions Three risk factors appear to be specific or particular to the risk of SCD, and these and other risk factors operate differently in patients with versus those without preexisting IHD. These findings have implications for the causes and prevention of SCD.
Initial antiretroviral regimens
Authors: C. Carpenter
Journal: BMJ (2002)

Papers p 757 

In this issue Rachel Jordan and colleagues have provided a meta-analysis of published controlled clinical trials, which provide significant information relevant to the initial treatment of established HIV infection in adults and adolescents (p 757).1 Their analyses are based on a large number of well conducted clinical trials. The data largely confirm earlier observations, often from relatively small studies, which have shown that dual nucleoside antiretroviral regimens are significantly more effective than single nucleoside therapy, and that three drug antiretroviral regimens are significantly better than two drug regimens for initial therapy of HIV infection.

The conclusions of the meta-analysis are entirely consistent with current consensus recommendations that initial therapy for established HIV infection in adults and adolescents should include a combination of three potent antiretroviral …
Mechanical properties of human pericardium. Differences in viscoelastic response when compared with canine pericardium.
Authors: J M Lee, D R Boughner
Journal: Circulation Research (1985)

Whereas most experiments on the mechanical function of the pericardium have been performed on dogs, very little is known about the applicability of those data to humans. To examine the tensile viscoelastic properties of fresh human pericardium, we have used the methods from our previous study of canine pericardium. Although the mechanical responses of canine and human pericardium were qualitatively similar, human pericardium displayed a significantly greater viscous character. Human pericardium was 7.3 times thicker than canine pericardium, but was more extensible in stress-strain tests, with lower stiffness at a given strain. The static (elastic) stiffness of human pericardium seems identical to that of canine pericardium; lower stiffness per unit thickness of the human tissue at predicted physiological stresses was almost exactly compensated by the greater wall thickness. This effect was also seen in data on fracture strength and stiffness. However, human pericardium displayed greater viscous responses than the canine tissue. This was seen in doubled cyclic hysteresis losses, and greater stress relaxation and creep. Our results suggest that experiments on the viscoelastic properties of canine pericardium may not be directly applicable to humans, especially where dynamic mechanical properties are most important: i.e., in studies of ventricular function and the time-course of pericardial effusions.
Thalidomide arm of Total Therapy 2 improves complete remission duration and survival in myeloma patients with metaphase cytogenetic abnormalities
Authors: Bart Barlogie, Mauricio Pineda-Roman, Frits van Rhee, Jeff Haessler, Elias Anaissie, Klaus Hollmig, Yazan Alsayed, Sarah Waheed, Nathan Petty, Joshua Epstein, John D. Shaughnessy, Guido Tricot, Maurizio Zangari, Jerome Zeldis, Sol Barer, John Crowley
Journal: Blood (2008)