tbuckley/cabot-search huggingface dataset:
ANTISEPTICS IN WAR
Authors: G. L. Cheatle
Journal: BMJ (1914)

ICAL l JO,,,< URNAL J only on righlt sidle aind witlh difficulty.Botlh cremasteric *etlexes weak.IPaini felt in back on passive movement of legs, wlhichl were mioderately flaccid.Zonie of hyperalgesia arou;ild l)ody oni I)otlh sides just above Poupart's ligamenit, but most acuite oni the left side.Lower abdominals weakenied on left si(le.1P'ain felt in lower )art of the abdomiien wlhen bladder Wa.Is ftll aldat tlle onset of micturitioin, buit no paini in peniis.
Functional Status of Elderly Adults before and after Initiation of Dialysis
Authors: Manjula Kurella Tamura, Kenneth E. Covinsky, Glenn M. Chertow, Kristine Yaffe, C. Seth Landefeld, Charles E. McCulloch
Journal: New England Journal of Medicine (2009)

It is unclear whether functional status before dialysis is maintained after the initiation of this therapy in elderly patients with end-stage renal disease (ESRD).Using a national registry of patients undergoing dialysis, which was linked to a national registry of nursing home residents, we identified all 3702 nursing home residents in the United States who were starting treatment with dialysis between June 1998 and October 2000 and for whom at least one measurement of functional status was available before the initiation of dialysis. Functional status was measured by assessing the degree of dependence in seven activities of daily living (on the Minimum Data Set-Activities of Daily Living [MDS-ADL] scale of 0 to 28 points, with higher scores indicating greater functional difficulty).The median MDS-ADL score increased from 12 during the 3 months before the initiation of dialysis to 16 during the 3 months after the initiation of dialysis. Three months after the initiation of dialysis, functional status had been maintained in 39% of nursing home residents, but by 12 months after the initiation of dialysis, 58% had died and predialysis functional status had been maintained in only 13%. In a random-effects model, the initiation of dialysis was associated with a sharp decline in functional status, indicated by an increase of 2.8 points in the MDS-ADL score (95% confidence interval [CI], 2.5 to 3.0); this decline was independent of age, sex, race, and functional-status trajectory before the initiation of dialysis. The decline in functional status associated with the initiation of dialysis remained substantial (1.7 points; 95% CI, 1.4 to 2.1), even after adjustment for the presence or absence of an accelerated functional decline during the 3-month period before the initiation of dialysis.Among nursing home residents with ESRD, the initiation of dialysis is associated with a substantial and sustained decline in functional status.
miR-296 Regulates Growth Factor Receptor Overexpression in Angiogenic Endothelial Cells
Authors: Thomas Würdinger, Bakhos A. Tannous, Okay Saydam, Johan Skog, Stephan Grau, Jürgen Soutschek, Ralph Weissleder, Xandra O. Breakefield, Anna M. Krichevsky
Journal: Cancer Cell (2008)
Cancer risk in chronic hepatitis B: Do genome-wide association studies hit the mark?
Authors: Markus Casper, Frank Grünhage, Frank Lammert
Journal: Hepatology (2011)

To identify susceptibility variants for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), we conducted a genome-wide association study by genotyping 440,794 SNPs in 355 chronic HBV carriers with HCC and 360 chronic HBV carriers without HCC, all of Chinese ancestry. We identified one intronic SNP (rs17401966) in KIF1B on chromosome 1p36.22 that was highly associated with HBV-related HCC and confirmed this association in five additional independent samples, consisting of 1,962 individuals with HCC, 1,430 control subjects and 159 family trios. Across the six studies, the association with rs17401966 was highly statistically significant (joint odds ratio = 0.61, P = 1.7 × 10-18). In addition to KIF1B , the association region tagged two other plausible causative genes, UBE4B and PGD . Our findings provide evidence that the 1p36.22 locus confers susceptibility to HBV-related HCC, and suggest that KIF1B-, UBE4B- or PGD-related pathways might be involved in the pathogenesis of this malignancy.
Cytotoxic T Lymphocyte Therapy for Epstein-Barr Virus+ Hodgkin's Disease
Authors: Catherine M. Bollard, Laura Aguilar, Karin C. Straathof, Benedikt Gahn, M. Helen Huls, Alexandra Rousseau, John Sixbey, M. Victoria Gresik, George Carrum, Melissa Hudson, Dagmar Dilloo, Adrian Gee, Malcolm K. Brenner, Cliona M. Rooney, Helen E. Heslop
Journal: The Journal of Experimental Medicine (2004)

Epstein Barr virus (EBV)+ Hodgkin's disease (HD) expresses clearly identified tumor antigens derived from the virus and could, in principle, be a target for adoptive immunotherapy with viral antigen–specific T cells. However, like most tumor-associated antigens in immunocompetent hosts, these potential targets are only weakly immunogenic, consisting primarily of the latent membrane protein (LMP)1 and LMP2 antigens. Moreover, Hodgkin tumors possess a range of tumor evasion strategies. Therefore, the likely value of immunotherapy with EBV-specific cytotoxic effector cells has been questioned. We have now used a combination of gene marking, tetramer, and functional analyses to track the fate and assess the activity of EBV cytotoxic T lymphocyte (CTL) lines administered to 14 patients treated for relapsed EBV+ HD. Gene marking studies showed that infused effector cells could further expand by several logs in vivo, contribute to the memory pool (persisting up to 12 mo), and traffic to tumor sites. Tetramer and functional analyses showed that T cells reactive with the tumor-associated antigen LMP2 were present in the infused lines, expanded in peripheral blood after infusion, and also entered tumor. Viral load decreased, demonstrating the biologic activity of the infused CTLs. Clinically, EBV CTLs were well tolerated, could control type B symptoms (fever, night sweats, and weight loss), and had antitumor activity. After CTL infusion, five patients were in complete remission at up to 40 mo, two of whom had clearly measurable tumor at the time of treatment. One additional patient had a partial response, and five had stable disease. The performance and fate of these human tumor antigen–specific T cells in vivo suggests that they might be of value for the treatment of EBV+ Hodgkin lymphoma.
Sodium modeling ameliorates intradialytic and interdialytic symptoms in young hemodialysis patients.
Authors: R H Sadowski, E N Allred, K Jabs
Journal: Journal of the American Society of Nephrology (1993)

Despite advances in the delivery of hemodialysis, significant dialytic morbidity persists. Sodium modeling in older adults has been shown to decrease some dialytic symptoms, but clear benefits in young patients without coexisting diabetes or advanced cardiovascular disease have not been shown. The effects of sodium modeling were evaluated in 16 adolescent and young adult hemodialysis patients (16 to 32 yr of age) treated with conventional hemodialysis for a median of 11.5 months. The 8-wk study was divided into four 2-wk blocks. During each block, one of three sodium programs or a constant (control) dialysate sodium of 138 mEq/L was used. During each sodium program, the initial dialysate sodium of 148 mEq/L was decreased by an exponential, linear, or step program to 138 mEq/L. Treatments with sodium modeling were significantly better than those with constant sodium dialysate. When all sodium programs were grouped and compared with constant dialysate sodium, the odds of improvement in dialytic cramps, headaches, and nausea were 1.8, 2.1, and 3.9, respectively (P < 0.05). Sodium modeling also significantly decreased the frequency of postdialysis hypotension and interdialytic fatigue, dizziness, and muscle cramping (P < 0.05). No differences were seen among the sodium protocols in the incidence of symptomatic hypotension, the amount of normal saline administered, the degree of hemo-concentration during treatments, or the decrease in serum osmolality. There was no increase in pretreatment or posttreatment serum sodium concentrations, interdialytic thirst, weight gain, or hypertension. Sodium modeling dramatically decreases both intradialytic and interdialytic morbidity in young hemodialysis patients. There was no increase in adverse events associated with sodium modeling.
Cutaneous Papillomavirus E6 Proteins Must Interact with p300 and Block p53-Mediated Apoptosis for Cellular Immortalization and Tumorigenesis
Authors: Peter Muench, Sonja Probst, Johanna Schuetz, Natalie Leiprecht, Martin Busch, Sebastian Wesselborg, Frank Stubenrauch, Thomas Iftner
Journal: Cancer Research (2010)

Abstract The binding of the papillomavirus E6 protein to E6AP and the induction of p53 degradation are common features of high-risk genital human papillomaviruses (HPV); cutaneous HPVs, on the other hand, lack these capacities. Nevertheless, several cutaneous HPV types of the β-genus, such as HPV38 are associated with tumor formation when combined with genetic predisposition, immunosuppression, or UV exposure. In an animal model system, the cottontail rabbit papillomavirus (CRPV) rapidly induces skin cancer without additional cofactors, and CRPVE6 and E7 immortalize rabbit keratinocytes in vitro. However, CRPVE6 neither interacts with E6AP and p53 nor does it induce p53 degradation. In this study, we show that the interaction of CRPVE6, or HPV38E6, with the histone acetyltransferase p300 is crucial to inhibit the ability of p53 to induce apoptosis. Strikingly, E6 mutants deficient for p300 binding are incapable of preventing p53 acetylation, p53-dependent transcription, and apoptosis induction. Moreover, E6 mutants deficient for p300 binding cannot contribute to HPV38-induced immortalization of human keratinocytes or CRPV-induced tumor formation. Our findings highlight changes in the p53 acetylation status mediated by the viral E6 protein as a crucial requirement in the ability of high-risk cutaneous papillomaviruses to immortalize primary keratinocytes and induce tumors. Cancer Res; 70(17); 6913–24. ©2010 AACR.
Symptom Improvement in Lung Cancer Patients Treated With Erlotinib: Quality of Life Analysis of the National Cancer Institute of Canada Clinical Trials Group Study BR.21
Authors: Andrea Bezjak, Dongsheng Tu, Lesley Seymour, Gary Clark, Aleksandra Trajkovic, Mauro Zukin, Joseph Ayoub, Sergio Lago, Ronaldo de Albuquerque Ribeiro, Alexandra Gerogianni, Arnold Cyjon, Jonathan Noble, Francis Laberge, Raymond Tsz-Tong Chan, David Fenton, Joachim von Pawel, Martin Reck, Frances A. Shepherd
Journal: Journal of Clinical Oncology (2006)

Purpose This report describes the quality of life (QOL) findings of a randomized placebo controlled study of erlotinib, an epidermal growth factor receptor inhibitor, in patients with non–small-cell lung cancer (NSCLC). Patients and Methods This double-blind phase III trial randomly assigned 731 patients with NSCLC who had progressed after prior chemotherapy to erlotinib 150 mg daily or placebo, with survival as the primary study outcome. QOL was assessed by European Organisation for Research and Treatment of Cancer QLQ-C30 and the lung cancer module QLQ-LC13. The primary end points for QOL analysis were time to deterioration of three common lung cancer symptoms: cough, dyspnea, and pain. Results Survival was significantly longer (hazard ratio, 0.70; P &lt; .0001) in the erlotinib arm. Compliance with QOL was 87% at baseline and more than 70% during treatment. Patients receiving erlotinib had significantly longer median time to deterioration for all three symptoms (4.9 v 3.7 months for cough [P = .04]; 4.7 v 2.9 months for dyspnea [P = .04], and 2.8 v 1.9 months for pain [P = .03]). QOL response analyses showed that 44%, 34%, and 42% of patients receiving erlotinib had improvement in these three symptoms, respectively. This was accompanied by a significant improvement in the physical function (31% erlotinib v 19% placebo, P = .01), and global QOL (35% v 26%, P &lt; .0001). Patients with complete or partial response were more likely to have improvement in the QOL response than patients with stable or progressive disease (P &lt; .01). Conclusion Erlotinib not only improves survival in previously treated patients with NSCLC, but also improves tumor-related symptoms and important aspects of QOL.
Integrated Care for Management of Ventricular Arrhythmias
Authors: Roderick Tung, Kalyanam Shivkumar
Journal: Circulation (2013)

I n 1962, the term coronary care unit was first coined by a Kansas City cardiologist, Hughes Day, to describe a centralized unit with a specialized team trained to rapidly identify and resuscitate patients admitted with acute myocardial infarction. 1,2With the dedicated critical care, improved reperfusion strategies, evidence-based medical therapy, and implantable cardioverter-defibrillators, survival from myocardial infarction in the acute and healed stages has significantly improved over the past 50 years.At the present time, the spectrum of patients with ventricular arrhythmias in the coronary care unit includes an increasing number of patients with scar-mediated reentrant ventricular tachycardia (VT) seen late after infarct remodeling and from noncoronary causes of cardiomyopathy. Article see p 1359Catheter ablation of VT is perhaps one of the most challenging and complex procedures in interventional cardiology.Catheter ablation of scar-mediated VT requires preprocedural imaging, the ability to perform specialized procedures such as electroanatomic mapping, and, in select cases, percutaneous access into the pericardial space.These techniques allow the operator to explore the complex scar architecture that typically supports multiple morphologies of VT that are hemodynamically unstable in the vast majority of present-day cases.It is also not surprising that the average procedural duration is >5 hours, 3 but what is most relevant to the morbidity and mortality associated with the procedure is the severity of the disease in the patients who develop recurrent VT.The clinical context and the backdrop of this disease state mandates a team approach to care (Figure ).Patients presenting with VT have multiple comorbid conditions including heart failure, coronary artery disease, peripheral vascular disease, and renal dysfunction.Heart failure specialists typically are involved early on in the care of these patients to establish up-front optimization and backup options in the event that VT ablation is only partially effective.Pulmonary artery catheterization to guide hemodynamic optimization and mechanical support (ie, intra-aortic balloon pump, extracorporeal membrane oxygenation, left ventricular assist device) are
Overexpression of c-Maf Contributes to T-Cell Lymphoma in Both Mice and Human
Authors: Naoki Morito, Keigyou Yoh, Yuki Fujioka, Takako Nakano, Homare Shimohata, Yuko Hashimoto, Akiko Yamada, Atsuko Maeda, Fumihiko Matsuno, Hiroyuki Hata, Atsushi Suzuki, Shigehiko Imagawa, Hiroaki Mitsuya, Hiroyasu Esumi, Akio Koyama, Masayuki Yamamoto, Naoyoshi Mori, Satoru Takahashi
Journal: Cancer Research (2006)

Abstract c-Maf translocation or overexpression has been observed in human multiple myeloma. Although c-maf might function as an oncogene in multiple myeloma, a role for this gene in other cancers has not been shown. In this study, we have found that mice transgenic for c-Maf whose expression was direct to the T-cell compartment developed T-cell lymphoma. Moreover, we showed that cyclin D2, integrin β7, and ARK5 were up-regulated in c-Maf transgenic lymphoma cells. Furthermore, 60% of human T-cell lymphomas (11 of 18 cases), classified as angioimmunoblastic T-cell lymphoma, were found to express c-Maf. These results suggest that c-Maf might cause a type of T-cell lymphoma in both mice and humans and that ARK5, in addition to cyclin D2 and integrin β7, might be downstream target genes of c-Maf leading to malignant transformation. (Cancer Res 2006; 66(2): 812-9)
Diffusion Bypass of Xenon in Brain Circulation
Authors: POUL BRODERSEN, PER SEJRSEN, NIELS A. LASSEN
Journal: Circulation Research (1973)

The diffusion bypass of 133 Xe between arteries and veins was studied in the brains of anesthetized dogs. A mixture of 51 Cr-labeled red cells and 133 Xe was injected as a bolus into the internal carotid artery. Gas-tight venous samples were taken every 0.4-0.8 seconds from the superior sagittal sinus. An excess of 133 Xe in the early venous blood samples over that expected from blood-tissue equilibration considerations was demonstrated in all the experiments. The excess was most marked in the first samples, and it was enhanced by lowering cerebral blood flow by decreasing the cerebral perfusion pressure to 20-30 mm Hg. We concluded that diffusion bypass of the tissue by 133 Xe is the most likely explanation for these experimental findings. The fraction of the bolus which appeared to bypass the tissue amounted to about 2-3% at the normal perfusion pressure (i.e., normal blood flow) and about 10% at a reduced cerebral perfusion pressure of 20-30 mm Hg (i.e., about half of normal blood flow). We concluded that measurement of cerebral blood flow by a bolus injection of 133 Xe in the internal carotid artery and external detection of the washout is not influenced significantly by the diffusion bypass of 133 Xe in the normal flow range.
Adipocyte fatty acid binding protein levels relate to inflammation and fibrosis in nonalcoholic fatty liver disease
Authors: Kerry‐Lee Milner, David van der Poorten, Aimin Xu, Elisabetta Bugianesi, James G. Kench, Karen S. L. Lam, Donald J. Chisholm, Jacob George
Journal: Hepatology (2009)

Several circulating cytokines are increased with obesity and may combine with the influence of visceral fat to generate insulin resistance, inflammation, and fibrosis in nonalcoholic fatty liver disease (NAFLD). Little information exists in NAFLD about three recently recognized tissue-derived cytokines that are all lipid-binding and involved in inflammation, namely adipocyte fatty acid–binding protein (AFABP), lipocalin-2, and retinol-binding protein 4 (RBP4). We examined the association of these three peptides with hepatic steatosis, inflammation, and fibrosis plus indices of adiposity, insulin resistance, and dyslipidaemia in 100 subjects with NAFLD and 129 matched controls. Levels of AFABP and lipocalin-2, but not RBP4, were significantly elevated in NAFLD versus control (AFABP, 33.5 ± 14.4 versus 23.1 ± 12.1 ng/mL [P < 0.001]; lipocalin-2, 63.2 ± 26 versus 48.6 ± 20 ng/mL [P < 0.001]) and correlated with indices of adiposity. AFABP correlated with indices of subcutaneous rather than visceral fat. AFABP alone distinguished steatohepatitis from simple steatosis (P= 0.02). Elevated AFABP independently predicted increasing inflammation and fibrosis, even when insulin resistance and visceral fat were considered; this applied to lobular inflammation and ballooning (odds ratio 1.4, confidence interval 1.0-1.8) and fibrosis stage (odds ratio 1.3, confidence interval 1.0-1.7) (P ≤ 0.05 for all). None of the cytokines correlated with steatosis grade. AFABP levels correlated with insulin resistance (homeostasis model assessment of insulin resistance) in controls and NAFLD, whereas lipocalin-2 and RBP4 only correlated positively with insulin resistance in controls. Conclusion: Circulating AFABP, produced by adipocytes and macrophages, and lipocalin-2, produced by multiple tissues, are elevated and may contribute to the metabolic syndrome in NAFLD. AFABP levels, which correlate with subcutaneous, but not visceral fat, independently predict inflammation and fibrosis in NAFLD and may have a direct pathogenic link to disease progression. (HEPATOLOGY 2009;49:1926–1934.)
Radiologic Imaging of Human Diseases in Exotic Animals
Authors: A. Everette James
Journal: JAMA (1976)

MANY DISEASES seen in humans also occur in animals. Their diagnosis often proves more difficult, especially in the exotic species. Pathologic abnormalities may therefore remain unchanged for long periods of time, allowing the radiologic manifestations to be more pronounced in these animals.<sup>1-3</sup>We have found the ability to depict derangements of structure and function helpful in caring for the population of animals at the National Zoological Park. <h3>Techniques</h3> Conventional and magnification radiography, angiography, xeroradiography, radioisotope studies, and ultrasound have been shown to be useful diagnostic aids in these exotic animals.<sup>4-6</sup>Often, these imaging studies have allowed us to make specific diagnoses or have provided information that resulted in the appropriate diagnostic sequence, leading to a proper clinical evaluation. In some regards, the most common circumstance in which we find ourselves is analogous to that encountered in acute pediatric problems or emergency room practice in human medicine. We are
Letter by Fayssoil Regarding Article, “Early Treatment With Lisinopril and Spironolactone Preserves Cardiac and Skeletal Muscle in Duchenne Muscular Dystrophy Mice”
Authors: Abdallah Fayssoil
Journal: Circulation (2012)

I read with great interest the article by Rafael-Fortney et al 1 about the effect of early treatment with lisinopril and spironolactone on cardiac and skeletal muscle in Duchenne muscular dystrophy mice.This article raised the concerns stated below.The authors have tested the 2 drugs lisinopril and spironolactone in utrn(Ϯ);mdx mice, and we cannot analyze the only effect of spironolactone.Bauer et al 2 demonstrated afterload reduction, lower end-systolic pressures in 16-week-old mdx mice treated with captopril, an angiotensin-converting enzyme inhibitor, during 8 weeks with an increase of the end-systolic elastance in the group mdx mice treated with captopril.Because no difference in fibrosis was noted in angiotensin-converting enzyme I group in comparison with untreated mice, we can postulate antifibrotic effects of spironolactone in Duchenne muscular dystrophy mice treated with spironolactone and angiotensin-converting enzyme inhibitors.The rationale of aldosterone antagonism in heart failure relies on the upregulation of the renin angiotensin aldosterone system that plays a role in the development of heart failure. 3It would be interesting to check the level of activation of this system in Duchenne muscular dystrophy mice at early stage that have normal left ventricular function, even if abnormalities of circumferential strain rate have been reported.
Novel approaches in the management of pancreatic ductal adenocarcinoma: potential promises for the future
Authors: Gaurav Goel, Weijing Sun
Journal: Journal of Hematology & Oncology (2015)

Despite a few breakthroughs in therapy for advanced disease in the recent years, pancreatic ductal adenocarcinoma continues to remain one of the most challenging human malignancies to treat. The overall prognosis for the majority of patients with pancreatic cancer is rather dismal, and therefore, more effective treatment options are being desperately sought. The practical goals of management are to improve the cure rates for patients with resectable disease, achieve a higher conversion rate of locally advanced tumor into potentially resectable disease, and finally, prolong the overall survival for those who develop metastatic disease. Our understanding of the complex genetic alterations, the implicated molecular pathways, and the role of desmoplastic stroma in pancreatic cancer tumorigenesis has increased several folds in the recent years. This has facilitated the development of novel therapeutic strategies against pancreatic cancer, some of which are currently under evaluation in ongoing preclinical and clinical studies. This review will summarize the existing treatment approaches for this devastating disease and also discuss the promising therapeutic approaches that are currently in different stages of clinical development.