tbuckley/cabot-search huggingface dataset:
Potential approach to immunotherapy of chronic lymphocytic leukemia (CLL): enhanced immunogenicity of CLL cells via infection with vectors encoding for multiple costimulatory molecules
Authors: Claudia Palena, Kenneth A. Foon, Dennis Panicali, Alicia Gómez Yafal, Jarasvech Chinsangaram, James W. Hodge, Jeffrey Schlom, Kwong Y. Tsang
Journal: Blood (2005)
Metronidazole and Dark Urine
Authors: John W. Torrance
Journal: JAMA (1972)

<h3>To the Editor.—</h3> Your correspondent Bruce (<b>218</b>:1832, 1971) appears not to have read his<i>Physician's Desk Reference</i>(PDR) very carefully. The 1971 edition of PDR devotes ten lines (p 1208, col 2) to a discussion of darkened urine following administration of metronidazole (Flagyl). Moreover, the effect was mentioned in the first article on metronidazole to appear in PDR in 1964. Curiously, a considerable part of Bruce's LETTER repeats word for word the phraseology of the article in PDR: "Although the pigment which is responsible for the phenomenon has not been positively identified, it is almost certainly a metabolite of metronidazole. It seems certain that it is of no clinical significance." More curious still, the information does not appear in this form in the source he cites for it (Goodman LS, Gilman A:<i>The Pharmacological Basis of Therapeutics. New York, Macmillan Co, 1970, p 1151)</i>.
Personalized Medicine and Inhibition of<i>EGFR</i>Signaling in Lung Cancer
Authors: Adi F. Gazdar
Journal: New England Journal of Medicine (2009)

The concept underlying much of cancer therapy is that patients with specific types and stages of cancer should be treated according to standardized, predetermined protocols.However, recent advances in drug development, pharmacogenomics, and the molecular characterization of tumors -including genomewide RNA expression, DNA copy-number and sequence analyses, and micro-RNA and proteomic profiling -have the potential to allow individualized selection of treatment as determined by the characteristics of the patient and the tumor.In principle, targeted therapies attack cancer-cell-specific attributes that are essential for growth or survival ("oncogene addiction") and avoid the potentially severe side effects of conventional cytotoxic treatments.Successful examples of targeted therapy include imatinib for the treatment of BCR-ABL-positive chronic myeloid leukemia and the reversible tyrosine kinase inhibitors, erlotinib and gefitinib, for blocking the gene that encodes epidermal growth factor receptor (EGFR) in subgroups of patients with non-small-cell lung cancer.
Abstract 4903: Oxidative DNA damage and its relationship with GSTP1 methylation in prostate cancer
Authors: Rajnee Fnu, Haripaul Sharma, Sanjay Gupta
Journal: Cancer Research (2010)

Abstract Prostate cancer is the most common cancer diagnosed in men and is the second leading cause of cancer-related death in the United States. The risk factor for prostate cancer includes both genetic and epigenetic modifications. Growing evidence suggests that epigenetic mechanisms such as DNA methylation affect gene expression in tissue-specific manner. The most frequent epigenetic alteration observed in human prostate cancer is hypermethylation of gluthathione-S-transferase-pi class (GSTP1) in the promoter region which causes loss or its decrease expression. Inactivation of GSTP1 renders prostate epithelial cells vulnerable to oxidative DNA damage from both oxidants and electrophile carcinogens to acquire relevant genetic alteration and neoplastic transformation. Extensive observations suggest that reactive oxygen species may cause accumulated DNA damage which might contribute to increased incidence of prostate cancer. However, the role of GSTP1 and its correlation with DNA damage has not been studied. Based on the assumption that DNA damage is prevalent in cancer cells compared to nontumorous tissue, we took a panel of 24 human prostate specimens obtained after surgery which comprised of matched primary tumor and adjacent nontumorous (benign) prostate tissues. Oxidative DNA damage was measured by 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels through highly sensitive and quantitative ELISA assay. GSTP1 methylation was determined by methyl-specific PCR and 5-methylcytosine estimation was performed by HPLC analysis. The 8-OHdG levels were higher in cancer specimen compared to their benign counterparts. The 8-OHdG levels in DNA of prostate cancer tissues ranged from 0.151 to 0.616ng/μg DNA, whereas the levels in benign tissue range from 0.149 to 0.318ng/μg DNA, respectively. The increase in 8-OHdG levels correlate with GSTP1 methylation which was higher in cancer specimens compared to the benign counterparts. Furthermore, levels of 5-methylcytosine were higher in tumor specimens compared to benign tissue. Taken together, our studies suggest that there is a link between GSTP1 methylation and DNA damage which correlates to epigenetic modification in prostate cancer. Our results are in agreement with the prediction that positive relationship occur between GSTP1 inactivation and DNA damage in prostate cancer. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4903.
Integrity and characteristics of secondary oesophageal peristalsis in patients with gastro-oesophageal reflux disease.
Authors: M N Schoeman, R H Holloway
Journal: Gut (1995)

Secondary peristalsis contributes to oesophageal acid clearance. The aim of the study was to evaluate the integrity and characteristics of secondary peristalsis in patients with gastro-oesophageal reflux disease. Studies were performed in 22 patients with reflux disease and 20 age matched controls. Oesophageal motility was recorded at 3 cm intervals along the oesophageal body. Primary peristalsis was tested with 5 ml water swallows. Secondary peristalsis was stimulated with 10 ml boluses of air and water injected in the mid-oesophagus and by 5 second distensions with a 3 cm balloon at the same level. It was found that primary peristalsis was normal in 19 of 20 control subjects and in 14 of 22 patients with reflux disease. In patients with reflux disease, intact secondary peristalsis was triggered infrequently by air and water distension (median success rate of 0% for both stimuli) and occurred significantly less frequently than in control subjects (50% and 30% respectively). The frequency of balloon induced secondary peristalsis, however, was similar in the two groups (0% controls, 20% reflux disease). The major pattern of failure of secondary peristalsis was the complete absence of any oesophageal secondary peristaltic response. The amplitudes of the intact secondary peristaltic responses were not significantly different for the two groups. Peristaltic velocity for air and balloon induced secondary peristalsis was also similar in control subjects and patients with reflux disease whereas water induced secondary peristalsis was slower in the reflux patients. In conclusion, patients with reflux disease exhibit a pronounced defect in the triggering of secondary peristalsis.
Acute Pulmonary Edema
Authors: A. A. LUISADA, L. CARDI
Journal: Circulation (1956)

Acute pulmonary edema may be associated with the most varied clinical conditions including cardiovascular, renal, cerebral, and pulmonary diseases, trauma to the skull or chest, infections, and shock. Many drugs and physical means have been employed in the treatment of this syndrome. Two main clinical types of pulmonary edema may be differentiated because of the different effect of therapy in each of them. Antifoaming therapy, a purely symptomatic method of treatment, tends to break a vicious circle and may be lifesaving. It should be employed initially while the patient is being examined and drugs or other remedies are being selected for possible additional treatment.
Abstract 2430: Gastric cancer cell lines with c-Met gene amplification are sensitive to growth inhibition by the bivalent c-Met antibody LA480
Authors: Jonathan Tetreault, Jinqi Xia, Wei Zeng, Mark Wortinger, Jason Cunningham, Farhana Mohammed Feroze, Kun Yu, Chi-Kin Chow, Jirong Lu, Irene Denning, Peter Vaillancourt, Julian Davies, Ling Liu
Journal: Cancer Research (2010)

Abstract Gastric cancer is common in Asia, and advanced disease is typically incurable. Development of effective treatments for gastric cancer is thus a high priority to address this highly unmet clinical need. c-Met gene amplification resulting in c-Met overexpression and pathway activation has been highly linked to tumor progression and metastasis. It has been reported that approximately 10-20% of gastric tumors have increased copy numbers of the MET gene. c-Met- amplified gastric cancer cell lines that are dependent on an activated c-Met pathway for cell growth have been reported to be highly sensitive to growth inhibition by small molecule inhibitors of c-Met. We report that LA480, a humanized monoclonal antibody specific for c-Met, can directly inhibit HGF-independent in vitro cell proliferation of three c-Met- amplified Asian gastric cell lines (MKN45, SNU-5, and NUGC-4), in a dose-dependent manner. After 48 hours of treatment with LA480, 60-70% percent inhibition of 3H-thymidine incorporation was observed. For one of these gastric lines (NUGC-4), sensitivity to LA480 increases with continuous passage of the culture. This increased sensitivity to LA480 over time appears to be associated with increased expression of cell surface c-Met and increased constitutive phospho-Met expression. In addition to inhibiting proliferation of c-Met- amplified Asian gastric lines, LA480 also directly inhibited proliferation of a c-Met- amplified gastric cell line (Hs 746T) from a Caucasian patient. These data suggest that targeting c-Met amplification with LA480 may be a promising treatment for gastric cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2430.
Ticrynafen-Associated Hepatic Injury: Analysis of 340 Cases
Authors: Hyman J. Zimmerman, James H. Lewis, Kamal G. Ishak, Willis C. Maddrey
Journal: Hepatology (1984)

Ticrynafen, a uricosuric diuretic, was withdrawn from clinical use in the United States in 1980 after having been implicated as the cause of a number of instances of serious hepatic injury. In this report, we analyze 340 cases of ticrynafen-associated hepatic disease reported to the manufacturer from the time of initial marketing until shortly after the drug had been recalled. Jaundice was recorded in 246 of 287 patients with sufficient clinical information, and 25 (10.2%) of these icteric patients died. The high levels of serum aminotransferase and the case fatality rate are consistent with the hepatocellular injury that was evident in all of the histologic material. In three-fourths of the cases available to us for histologic study, the lesion was that of acute hepatocellular injury. In the remaining cases there was evidence of chronic active hepatitis and/or cirrhosis. Comparison of demographic characteristics of the total population exposed to ticrynafen with the subset developing hepatic injury suggests a proportionately higher risk of injury for females over the age of 60 years. The variable and unusually prolonged latent period and lack of reported eosinophilia or rash generally suggest a mechanism other than hypersensitivity. However, the recurrence of hepatic injury in 15 of the 16 patients challenged with the drug and the prominence of eosinophils in hepatic tissue in some of the cases suggests that hypersensitivity may also play a pathogenetic role. Accordingly, there is reason to incriminate both metabolic idiosyncrasy and hypersensitivity in the mechanism of injury.
Monocyte activation in angiogenesis and collateral growth in the rabbit hindlimb.
Authors: M Arras, W D Ito, D Scholz, B Winkler, J Schaper, W Schaper
Journal: Journal of Clinical Investigation (1998)

We have previously shown that monocytes adhere to the vascular wall during collateral vessel growth (arteriogenesis) and capillary sprouting (angiogenesis). In this study we investigated the association of monocyte accumulation with both the production of the cytokines-basic fibroblast growth factor (bFGF) and TNF-alpha-and vessel proliferation in the rabbit after femoral artery occlusion. In particular, we studied the effects of an increase in monocyte recruitment by LPS on capillary density as well as collateral and peripheral conductance after 7 d of occlusion. Monocytes accumulated around day 3 in collateral arteries when maximal proliferation was observed, and stained strongly for bFGF and TNF-alpha. In the lower limb where angiogenesis was shown to be predominant, macrophage accumulation was also closely associated with maximal proliferation (around day 7). LPS treatment significantly increased capillary density (424+/-26.1 n/mm2 vs. 312+/-20.7 n/mm2; P < 0.05) and peripheral conductance (109+/-33.8 ml/min/100 mmHg vs. 45+/-6.8 ml/min/100 mmHg; P < 0.05) as compared with untreated animals after 7 d of occlusion. These results indicate that monocyte activation plays a major role in angiogenesis and collateral artery growth.
HIGH RISK ANATOMY IS FREQUENT IN ANOMALOUS AORTIC ORIGIN OF CORONARY ARTERY
Authors: Maciej Krupinski, Tomasz Miszalski, Beata Rog, Bartosz Laskowicz, Wojciech Mazur, Malgorzata Urbanczyk, Magdalena Kostkiewicz
Journal: Journal of the American College of Cardiology (2012)
CLINICAL USEFULNESS AND SAFETY EVALUATION OF INTRACORONARY ACETYLCHOLINE PROVOCATION TESTING AMONG 1000 CONSECUTIVE CAUCASIAN PATIENTS WITH ANGINAL SYMPTOMS AND UNOBSTRUCTED CORONARY ARTERIES
Authors: Peter Ong, Anastasios Athanasiadis, Gabor Borgulya, Heiko Mahrholdt, Udo Sechtem
Journal: Journal of the American College of Cardiology (2012)
Phylogenetic tests of the sensory exploitation model of sexual selection
Authors: Kerry Shaw
Journal: Trends in Ecology & Evolution (1995)

The diverse characteristics among closely related species are often involved in communication between the sexes. The traditional view that intersexual communication behaviors evolve in a complementary way is called into question by the sensory exploitation hypothesis. By predicting a lack of coordinated evolution between signals and preferences, the sensory exploitation hypothesis is distinct from other mechanisms of sexual selection. Tests of sensory exploitation have taken a multi-disciplinary approach, with insights from sensory physiology, behavior and phylogenetic comparisons. By demonstrating that signals and receivers are not closely coupled, and that signal preference pre-dates signal origin, proponents of the model argue that sensory exploitation is an evolutionary force responsible for the diversification of intersexual communication signals.
Estimated GFR and Risk of Death — Is Cystatin C Useful?
Authors: Julie R. Ingelfinger, Philip A. Marsden
Journal: New England Journal of Medicine (2013)

Current estimates suggest that as many as one in six persons in North America have chronic kidney disease,1 a condition that may worsen over time and signal the need for continuous monitoring. Knowing which patient with chronic kidney disease is at risk for end-stage kidney disease or death could tell us who needs intensive monitoring or intervention.The glomerular filtration rate (GFR), the classic measure of kidney function, describes the amount of plasma that is cleared of an endogenous or exogenous marker filtered by the glomeruli per unit of time. Direct measurement of endogenous clearance is difficult, since it requires . . .
A nurse‐based strategy reduces heart failure morbidity in patients admitted for acute decompensated heart failure in Brazil: the <scp>HELEN‐II</scp> clinical trial
Authors: Emiliane Nogueira de Souza, Luis Eduardo Rohde, Karen Brasil Ruschel, Cláudia Mota Mussi, Luis Beck‐da‐Silva, Andréia Biolo, Nadine Clausell, Eneida Rejane Rabelo‐Silva
Journal: European Journal of Heart Failure (2014)
Academic medicine: who is it for?
Authors: Birte Twisselmann
Journal: BMJ (2005)

The opening salvo of the webchat on academic medicine was whether a definition of academic medicine was needed.1 No, it made the whole thing hopeless from the start. Yes, it helped to set a framework.

Thereon the main strands of the webchat were dominated by a negative view of the status quo: academic medicine is a giant industry perpetuating its own power and influence rather than serving the public. Medicine has become a source of profit for commerce and is now so intertwined with industry that the threads cannot be untied (although the BMJ campaign has made the links between academia and the pharmaceutical industry one of its research targets).

Vioxx and Seroxat were supposed to be triumphs of academic medicine. But, although the problems were recognised in academic circles, academics lack the power to communicate to wider society and effect change. Academic medicine has to change and start anew. To have any legitimacy it must address the problems of individuals in society—which it clearly is not doing. Another perceived problem was that government research allocations inevitably create priorities.

Ideas to identify areas for improvement tried to counter this negativity. Academic medicine should serve the interests of society as a whole, filling the gap between university education and everyday medical practice. It is primarily about people, teachers, students, and the public. Academics should be leaders in their field with special expertise; principles should be stated, relevant research conducted and published, and human resources rethought. Academics should define research priorities, proving to governments and society that academic doctors are a force to be reckoned with.

Teaching is a problem. Perhaps it should be left to those with a gift for it, and be taken out of the universities and into other work settings. This would help the interdisciplinarian approach to working that several participants desired (“academics on child health talking with schoolteachers”). International collaborations are to be encouraged, as is integrating students into the campaign from the outset.

The reason teaching is a problem may be the emphasis on publishing research in journals with high impact factors and on developing new methodologies, as determined by the UK government's research assessment exercise, for example. Creating new teaching materials would not improve a researcher's publications list and therefore not move him or her up the ladder, although it benefits both researcher and students.

Several participants agreed that new structures should be developed outside the mainstream, with new approaches to education, research, leadership, clinical care, publications, and all the things that currently constitute a successful career in academic medicine. The clarion call was be brave. Forget your reputation. Forget your status. Just act. Do it differently. Ignore authority. Reject conformity. Be you—the webchat's closing rally.
Assessment of residual tissue viability by exercise testing in recent myocardial infarction: Comparison of the electrocardiogram and myocardial perfusion scintigraphy
Authors: Alberto Margonato, Carlo Ballarotto, Fabrizio Bonetti, Alberto Cappelletti, Maria Sciammarella, Domenico Cianflone, Sergio Lorenzo Chierchia
Journal: Journal of the American College of Cardiology (1992)
Influence of Graft Characteristics on the Outcome of Kidney Transplantation
Authors: Jean-Paul Soulillou, Magali Giral
Journal: New England Journal of Medicine (2006)

The characteristics of renal allografts before transplantation present a multifaceted puzzle that in large part predetermines the outcome of kidney transplantation. Compatibility at the major-histocompatibility-complex (MHC) loci, the age of the donor, cold-ischemia times, and nephron mass1,2 all contribute to long-term results through interacting effects involving initial damage to parenchymal or vascular cells and possible hyperfiltration. Many factors are involved in chronic allograft dysfunction, in which immune-mediated lesions caused by chronic rejection are only one component.3 In this issue of the Journal, Brown et al.4 report on a newly identified donor factor, an allotype of the C3 complement molecule . . .
Differences in late fetal death rates in association with determinants of small for gestational age fetuses: population based cohort study
Authors: S. Cnattingius, B. Haglund, M. S Kramer
Journal: BMJ (1998)

To examine differences in late fetal death rates in association with determinants of small for gestational age fetuses.Population based cohort study.1 026 249 pregnancies without congenital malformations.Sweden 1983-92.Late fetal death rate.Depending on underlying determinants late fetal death rates were greatly increased in extremely small for gestational age fetuses (range 16 to 45 per 1000) compared with non-small for gestational age fetuses (1.4 to 4.6). In extremely small for gestational age fetuses late fetal death rates were increased from 31 per 1000 in mothers aged less than 35 years to 45 per 1000 in older mothers, and from 22 per 1000 in women <155 cm in height to 33 per 1000 in women >=175 cm tall. Late fetal death rates were also higher in extremely small for gestational age fetuses in singleton compared with twin pregnancies and in non-hypertensive pregnancies compared with pregnancies complicated by severe pre-eclampsia or other hypertensive disorders. Slightly higher late fetal death rates were observed in nulliparous compared with parous women and in non-smokers compared with smokers.Although the risk of late fetal death is greatly increased in fetuses that are extremely small for gestational age the risk is strongly modified by underlying determinants-for example, there is a lower risk of late fetal death in a small for gestational age fetus if the mother is of short stature, has a twin pregnancy, or has hypertension.
Some More Costs of Managed Care
Authors: William D. Loeser
Journal: New England Journal of Medicine (1993)

To the Editor: I wish to comment on an interesting new phenomenon, the extraordinary acceleration in the cost of continuing education for those engaged in managed care. After a 40-year medical career, 31 in internal medicine, 6 in medical education, and the most recent 3 in managed care, I hope I can report on this new trend fairly and objectively. If a total of 50 hours of continuing education is required annually for licensure (as in Ohio) and for updating an internist's medical knowledge, I could make a good start on obtaining these credit hours by taking a three-day course . . .
Xylose Absorption and Duodenal Diverticula
Authors: C. S. Reusch
Journal: JAMA (1967)

<h3>To the Editor:—</h3> Numerous investigators<sup>1-4</sup>have reported that the measurement of the urinary excretion of xylose after the oral administration of the sugar is a reliable means of testing the absorption of carbohydrates. Xylose is not metabolized by the body but is excreted unchanged in the urine. We used this test to establish whether patients with duodenal diverticula had demonstrable evidence of malabsorption. Serum carotene levels have also been found useful in screening patients from malabsorption.<sup>3</sup> Most of the individuals with duodenal diverticula were over 50 years old. None had diverticula of the ileum or jejunum. As we took data on these patients, we became aware that the lowest xylose excretion values were in the oldest patients. Texter<sup>3</sup>reports a decrease in xylose excretion after the sixth decade. However, our data were inadequate to allow statistical evaluation of our patient group. <h3>Methods and Materials:—</h3> Food was withheld