tbuckley/cabot-search huggingface dataset:
Adjuvant Intravesicular Pharmacotherapy for Superficial Bladder Cancer
Authors: B. L. Lum, F. M. Torti
Journal: JNCI Journal of the National Cancer Institute (1991)

In 1990, bladder cancer, excluding carcinoma in situ, was estimated to contribute 49,000 cases of cancer. In men 75 years old or older, it became the fifth leading cause of cancer deaths. Of patients with bladder cancer, 75%-80% initially present with superficial bladder tumors. Treatment of these tumors has three objectives: 1) to eradicate existing disease, 2) to provide prophylaxis against tumor recurrence, and 3) to avoid deep invasion into the muscle layers of the bladder. Transurethral resection is the primary treatment to eradicate superficial bladder tumors, but 40%-80% of these tumors recur. Because of these high recurrence rates, adjuvant intravesicular pharmacotherapy with cytotoxic and immunomodulatory drugs has gained widespread use. The past two decades of clinical investigations in superficial bladder cancer have provided valuable information on the biology and treatment of the disease. Multivariate analyses have indicated that tumor grade and stage are the most important prognostic variables commonly available to the clinician to identify the patient at greatest risk of developing muscle-invasive or metastatic bladder cancer. These studies have also identified groups at low risk for tumor recurrence and invasive bladder cancer. Randomized trials have shown that recurrence rates are decreased by adjuvant intravesicular pharmacotherapy with a number of drugs: bacillus Calmette-Guérin vaccine (BCG), doxorubicin, ethoglucid (Epodyl), mitomycin-C, teniposide, and thiotepa. However, few studies indicate that adjuvant intravesicular pharmacotherapy can prevent progression to invasive bladder cancer in the high-risk patient with superficial bladder cancer. Additional clinical trials are needed to determine whether such therapy can prevent invasive and metastatic bladder cancer and improve disease-free survival in this group. In addition, the identification of tests (e.g., monoclonal antibody tests, chromosomal analyses, and tumor marker assays) that can help to identify high-risk patients is needed to better develop therapeutic strategies for superficial bladder cancer.
Hypothalamic Orexin Stimulates Feeding-Associated Glucose Utilization in Skeletal Muscle via Sympathetic Nervous System
Authors: Tetsuya Shiuchi, Mohammad Shahidul Haque, Shiki Okamoto, Tsuyoshi Inoue, Haruaki Kageyama, Suni Lee, Chitoku Toda, Atsushi Suzuki, Eric S. Bachman, Young-Bum Kim, Takashi Sakurai, Masashi Yanagisawa, Seiji Shioda, Keiji Imoto, Yasuhiko Minokoshi
Journal: Cell Metabolism (2009)
Correction: Article on Diagnosis in Jaundice
Authors: JEFF WHITTLE
Journal: Annals of Internal Medicine (1983)

Letters and Corrections1 October 1983Correction: Article on Diagnosis in JaundiceJEFF WHITTLEJEFF WHITTLESearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-99-4-574_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: In the article by Richter and associates (1) there are discrepancies between the text, Figure 1, and Table 2. The text is correct in both cases. In Figure 1, the specificity is stated to be 97%; it is given as 99% in the Results section. In Table 2, at a prevalence of 0.60, the endoscopic retrograde cholangiopancreatographic and selective cholangiographic strategies each are assigned negative predictive values of 95%. The negative predictive value of each strategy is correctly given as 96% at the end of the Results section....Reference1. RICHTERSILVERSTEINSCHAPIRO JMR. Suspected obstructive jaundice: a decision analysis of diagnostic strategies. Ann Intern Med. 1983;99:46-51. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: 5015 North Woodburn Street; Whitefish Bay, WI 53217 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 October 1983Volume 99, Issue 4Page: 574-574KeywordsNegative predictive valueSpecificity ePublished: 1 December 2008 Issue Published: 1 October 1983 PDF downloadLoading ...
Drugs prescribed for self poisoners.
Authors: L F Prescott, M S Highley
Journal: BMJ (1985)

Of 230 adults admitted for self poisoning over two months, 153 (67%) had previously been taking a total of 309 prescribed drugs. Of these patients, 119 (78%) had been given psychotropic drugs (usually benzodiazepines), 81 (53%) obtained them on repeat prescription, and 47 (31%) had been prescribed multiple psychotropic drugs, often in seemingly illogical combinations. The use of these drugs increased progressively with age and most patients took the same drugs in overdosage as they had been prescribed. Psychotropic drugs were prescribed for more than a third of patients with no psychiatric illness and a normal personality, nearly half of those with existing alcohol or drug abuse problems, and for most of the unemployed. Fewer than a third of the patients suffering from depression were prescribed antidepressants but half had been given benzodiazepines and other potentially depressing drugs. Psychotropic drug use, psychotropic polypharmacy, and the repeat prescribing of these drugs were strongly associated with repeated overdosage and, under certain circumstances, with personality disorder, alcohol or drug abuse, unemployment, and conflict with the law. In the long term psychotropic drugs are unlikely to benefit most self poisoners, and they may do positive harm by inducing apathy and depression and predisposing to self poisoning. The incidence of self poisoning (and repeat overdosage in particular) might be reduced by more care and restraint in the prescribing of these drugs.
EFFECTS OF CHRONIC EXCESS SALT FEEDING
Authors: Lewis K. Dahl, Martha Heine
Journal: The Journal of Experimental Medicine (1961)

Female rats were fed diets containing either excess sea salt or excess sodium chloride for periods up to 14 months. The hypertension produced by sea salt was more pronounced than that caused by sodium chloride alone, although the average amount of sodium chloride contained in the sea salt feeding was slightly less. The ions involved in this incremental effect of sea salt were not identified.
Correction of the disease phenotype in canine leukocyte adhesion deficiency using ex vivo hematopoietic stem cell gene therapy
Authors: Thomas R. Bauer, Mehreen Hai, Laura M. Tuschong, Tanya H. Burkholder, Yu-chen Gu, Robert A. Sokolic, Cole Ferguson, Cynthia E. Dunbar, Dennis D. Hickstein
Journal: Blood (2006)
A Phase 3, Double-blind, Randomised, Parallel-group, Placebo-controlled Study of Oral Weekly Alendronate for the Prevention of Androgen Deprivation Bone Loss in Nonmetastatic Prostate Cancer: The Cancer and Osteoporosis Research with Alendronate and Leuprolide (CORAL) Study
Authors: Laurence H. Klotz, Irene Y. McNeill, Marlene Kebabdjian, Liying Zhang, Joseph L. Chin
Journal: European Urology (2012)
Corticosteroid-Responsive Intestinal Lymphangiectasia Secondary to an Inflammatory Process
Authors: Thomas A. Fleisher, Warren Strober, Andrew V. Muchmore, Samuel Broder, Edward L. Krawitt, Thomas A. Waldmann
Journal: New England Journal of Medicine (1979)

PROTEIN-losing enteropathy can be associated with a disorder of the gastrointestinal lymphatics termed intestinal lymphangiectasia.1 The three patients with protein-losing enteropathy and abnormal intestinal lymphatics described below manifested findings differentiating them from patients with primary intestinal lymphangiectasia: elevated sedimentation rates, normal or slightly elevated immunoglobulin levels and variable features of inflammatory disease.Case ReportsCase 1. A 22-year-old woman had facial edema, increasing abdominal girth and fatigue. Laboratory studies revealed an albumin of 1.3 g per deciliter, a sedimentation rate of 80 mm per hour, lymphocytopenia (count of 693 per cubic millimeter), normal immunoglobulin levels (Table 1), negative serologic test . . .
Abstract A52: Paracrine apoptotic effect of the tumor suppressor p53 is mediated by secreted Par-4
Authors: Tripti Shrestha-Bhattarai, Ravshan Burikhanov, Nikhil Hebbar, Shirley Qiu, Yanming Zhao, Gerard P. Zambetti, Vivek M. Rangnekar
Journal: Cancer Research (2015)

Abstract The guardian of the genome, p53, is mutated or functionally inactivated in a majority of human cancers. However, p53 in normal cells is intact and functional. In the present study, we tested the potential of wild-type p53 in normal tissues to inhibit the growth of p53-deficient cancer cells. Co-culture experiments of normal fibroblasts with cancer cells revealed that specific activation of p53 in normal fibroblasts selectively induced apoptosis in p53-deficient cancer cells. Moreover, this paracrine apoptotic effect of p53 was attributed to an enhanced secretion of the tumor suppressor Par-4 in response to p53 activation. Mechanistically, p53 represses the expression of UACA, a binding partner of Par-4, by directly binding to its signature motif in the UACA gene. Down-regulation of UACA expression liberates Par-4 from sequestration, and thus induces its secretion. Consistent with our cell culture studies, animal experiments also show that activation of p53 results in an elevation of systemic Par-4 levels in p53+/+ mice, which can induce apoptosis in p53-deficient cancer cells in ex vivo experiments. By contrast, p53 activators failed to induce this paracrine effect in p53-/- or Par-4-/- mice. Thus, by activating wild-type p53, normal cells can be empowered to inhibit tumor growth, progression, and metastasis. Citation Format: Tripti Shrestha-Bhattarai, Ravshan Burikhanov, Nikhil Hebbar, Shirley Qiu, Yanming Zhao, Gerard P. Zambetti, Vivek M. Rangnekar. Paracrine apoptotic effect of the tumor suppressor p53 is mediated by secreted Par-4. [abstract]. In: Abstracts: AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment; 2014 Feb 26-Mar 1; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(1 Suppl):Abstract nr A52. doi:10.1158/1538-7445.CHTME14-A52
Genital Chlamydia trachomatis infections in primary care
Authors: J. D C Ross, S. Sutherland, J. Coia
Journal: BMJ (1996)

The size of the differences we observed was surprising and, along with the inverse relation we have described between quality of service provision and practice catchment area, suggests that the time may have come to re-examine the geographical distribution of general medi- cal practices.Optimal practice list size has not yet been defined, although larger practice lists have been suggested to be disadvantageous to patients.'7Larger practice catchment areas may also be associated with disadvantages to patient care, and further research is needed into this neglected but important area of health care planning.We thank all the practices who participated in this study and Ashley Cohen, Peter Holland, and John Sandhu of Lambeth, Southwark and Lewisham Family Health Services Authority for their help in providing data.
Discontinuing venom immunotherapy: Outcome after five years
Authors: David B.K. Golden, Kathleen A. Kwiterovich, Anne Kagey-Sobotka, Martin D. Valentine, Lawrence M. Lichtenstein
Journal: Journal of Allergy and Clinical Immunology (1996)

BACKGROUND: The clinical and immunologic consequences of discontinuing venom immunotherapy are not well-defined. To determine which patients can safely stop treatment, we accepted all volunteers who had completed at least 5 years of maintenance venom immunotherapy regardless of the severity of the historical sting reaction, the persistence of venom skin test sensitivity, or any other variable. METHODS: Sting challenge was performed every 1 to 2 years after therapy was stopped; and venom-specific skin tests were performed, and IgE antibody levels were measured. RESULTS: Systemic symptoms occurred after challenge in eight of 270 stings (3%), in seven of 74 patients (10%); only two reactions were clinically significant. Venom skin test results became negative in 28% after 5 years of venom immunotherapy (at the time of discontinuation) and were negative in 56% to 67% of patients after 2 to 4 years without venom immunotherapy. There was a parallel decrease in the venom-specific IgE antibody levels. Challenge stings did not prevent the progressive decline in sensitivity, nor did they increase the risk of sting reaction even after two sequential stings 1 month apart. CONCLUSIONS: Venom immunotherapy can be safely discontinued after 5 years of maintenance therapy in virtually all patients, with the possible exception of those in whom the level of venom sensitivity has not declined during therapy. Venom sensitivity decreases with time even after venom therapy is stopped. Insect stings do not cause re-sensitization, and there was no increased risk from sequential stings. There appears to be a late-onset, non-IgG-mediated mechanism for long-term suppression of allergic sensitivity by prolonged high-dose venom immunotherapy. (J ALLERGY CLIN IMMUNOL 1996;97:579-87.)
Abnormal FDG PET Imaging in Tuberculosis Appearing Like Mesothelioma
Authors: Chia-Lu Yeh, Liang-Kuang Chen, Shih-Wei Chen, Yen-Kung Chen
Journal: Clinical Nuclear Medicine (2009)

Fluoro-deoxy-glucose/positron emission tomography (FDG PET/CT) imaging has an established role in the evaluation of many malignancies. However, FDG also can be accumulated intensely by inflammatory lesions. We report a case of a 75-year-old man with recent fever and chronic cough for years. Chest radiograph showed multiple nodules in bilateral lung fields and pleural effusion on the left side, suspicious for lung metastases. Whole body FDG PET/CT scan demonstrated diffusely intense FDG uptake in the left thickened pleura and multiple focal areas of intense FDG uptake scattered in bilateral lungs. FDG PET/CT images in conjunction with anatomic delineation of coregistration CT were suspicious for active pulmonary tuberculosis with left tuberculous pleuritis, although the distribution of abnormal FDG uptake mimicked malignant pleural mesothelioma with lung metastases. Pulmonary tuberculosis was subsequently confirmed by sono-guided needle biopsy of the left pleura and sputum culture. In this case, anatomic features provided by CT can help for image interpretation.
Fetoscopic Transesophageal Electrocardiography and Stimulation in Fetal Sheep
Authors: Thomas Kohl, Paulus F. Kirchhof, Wiebke Gogarten, Julia Reckers, Boulos Asfour, Ralf Witteler, Wilhelm Haverkamp, Lars Eckardt, Abraham E. Marcus, Hugo VanAken, Günter Breithardt, Johannes Vogt, Hans H. Scheld
Journal: Circulation (1999)

Therapy-refractory supraventricular tachycardia commonly results in hydrops and death in human fetuses. The purpose of this study in fetal sheep was to assess the feasibility of a minimally invasive fetoscopic approach for fetal transesophageal electrocardiography and stimulation aimed at diagnosis and termination of these tachycardias.We studied a total of 10 fetal sheep (87 to 103 days of gestation; term=145 days). We entered the amniotic cavity using a percutaneous fetoscopic approach and placed various electrophysiology catheters into the fetal esophagus. We recorded the number of animals in which fetoscopic transesophageal electrocardiography and stimulation were successful and assessed pacing success and thresholds for different catheters. In addition, we monitored for potential adverse effects from stimulation and for other complications of the operation. Recording of transesophageal electrocardiograms was successful in all fetal sheep. Capture during stimulation was successfully documented by additional fetal bipolar surface electrocardiograms in 7 fetuses. In fetuses in which fetal surface electrocardiograms were not recorded, pacing stimulus artifacts interfered with documentation of capture. Although stimulation thresholds were high, the maternal rhythm was not affected by fetal stimulation.Fetoscopic fetal transesophageal electrocardiography and stimulation are feasible in fetal sheep. This minimally invasive approach might have the potential to improve diagnosis and management of therapy-refractory supraventricular tachycardias in human fetuses.
Leishmania Evades Host Immunity by Inhibiting Antigen Cross-Presentation through Direct Cleavage of the SNARE VAMP8
Authors: Diana Matheoud, Neda Moradin, Angélique Bellemare-Pelletier, Marina Tiemi Shio, Wan Jin Hong, Martin Olivier, Étienne Gagnon, Michel Desjardins, Albert Descoteaux
Journal: Cell Host & Microbe (2013)

Highlights•The Leishmania metalloprotease GP63 cleaves phagosomal SNAREs, notably VAMP8•GP63-mediated VAMP8 cleavage inhibits phagolysosome biogenesis and cross-presentation•VAMP8 controls the proteolytic activity of phagosomesSummaryDuring phagocytosis, microorganisms are taken up by immune cells into phagosomes. Through membrane-trafficking events mediated by SNARE proteins, phagosomes fuse with lysosomes, generating degradative phagolysosomes. Phagolysosomes contribute to host immunity by linking microbial killing within these organelles with antigen processing for presentation on MHC class I or II molecules to T cells. We show that the intracellular parasite Leishmania evades immune recognition by inhibiting phagolysosome biogenesis. The Leishmania cell surface metalloprotease GP63 cleaves a subset of SNAREs, including VAMP8. GP63-mediated VAMP8 inactivation or Vamp8 disruption prevents the NADPH oxidase complex from assembling on phagosomes, thus altering their pH and degradative properties. Consequently, the presentation of exogenous Leishmania antigens on MHC class I molecules, also known as cross-presentation, is inhibited, resulting in reduced T cell activation. These findings indicate that Leishmania subverts immune recognition by altering phagosome function and highlight the importance of VAMP8 in phagosome biogenesis and antigen cross-presentation.
Human autoantibody to a novel protein of the nuclear coiled body: immunological characterization and cDNA cloning of p80-coilin.
Authors: L E Andrade, E K Chan, I Raska, C L Peebles, G Roos, E M Tan
Journal: The Journal of Experimental Medicine (1991)

Antibodies producing an unusual immunofluorescent pattern were identified in the sera of patients with diverse autoimmune features. This pattern was characterized by the presence of up to six round discrete nuclear bodies in interphase cell nuclei. Immunoblotting analysis showed that these sera recognized an 80-kD nuclear protein, and affinity-purified anti-p80 antibody from the protein band reproduced the fluorescent staining of nuclear bodies. Colloidal gold immunoelectron microscopy showed that the affinity-purified anti-p80 antibody recognized the coiled body, an ultramicroscopic nuclear structure probably first described by the Spanish cytologist Ramon y Cajal. Five cDNA clones were isolated from a MOLT-4 cell lambda gt-11 expression library using human antibody and oligonucleotide probes. The longest cDNA insert was 2.1 kb and had an open reading frame of 405 amino acids. A clone encoding a 14-kD COOH-terminal region of the protein was used for expression of a beta-galactosidase fusion protein. An epitope was present in this COOH-terminal 14-kD region, which was recognized by 18 of 20 sera with anti-p80 reactivity, and affinity-purified antibody from the recombinant protein also reacted in immunofluorescence to show specific staining of the coiled body. This is the first demonstration and molecular cloning of a protein that appears to have particular identification with the coiled body, and it was designated p80-coilin. Autoantibody to p80-coilin may be useful for the elucidation of the structure and function of the coiled body, and the availability of a cDNA sequence could be helpful in further studies to clarify the clinical significance of this autoantibody response.
Vodka Consumption Leads to High Risk of Premature Death in Russian Men
Authors: M. J. Friedrich
Journal: JAMA (2014)

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Characterization of ornidazole metabolites in human bile after intraveneous doses by ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry
Authors: Jiangbo Du, Pan Deng, Xiaoyan Chen, Haidong Wang, Tiangeng You, Dafang Zhong
Journal: Acta Pharmaceutica Sinica B (2012)

Ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS) was used to characterize ornidazole metabolites in human bile after intravenous doses. A liquid chromatography tandem mass spectrometry (LC–MS/MS) assay was developed for the determination of the bile level of ornidazole. Bile samples, collected from four patients with T-tube drainage after biliary tract surgery, were prepared by protein precipitation with acetonitrile before analysis. A total of 12 metabolites, including 10 novel metabolites, were detected and characterized. The metabolites of ornidazole in human bile were the products of hydrochloride (HCl) elimination, oxidative dechlorination, hydroxylation, sulfation, diastereoisomeric glucuronation, and substitution of NO2 or Cl atom by cysteine or N-acetylcysteine, and oxidative dechlorination followed by further carboxylation. The bile levels of ornidazole at 12 h after multiple intravenous infusions were well above its minimal inhibitory concentration for common strains of anaerobic bacteria.
Tumoricidal activity of TLR7/8-activated inflammatory dendritic cells
Authors: Georg Stary, Christine Bangert, Martina Tauber, Robert Strohal, Tamara Kopp, Georg Stingl
Journal: The Journal of Experimental Medicine (2007)

Imiquimod (IMQ), a synthetic agonist to Toll-like receptor (TLR) 7, is being successfully used for the treatment of certain skin neoplasms, but the exact mechanisms by which this compound induces tumor regression are not yet understood. While treating basal cell carcinoma (BCC) patients with topical IMQ, we detected, by immunohistochemistry, sizable numbers of both myeloid dendritic cells (mDCs) and plasmacytoid DCs (pDCs) within the inflammatory infiltrate. Surprisingly, peritumoral mDCs stained positive for perforin and granzyme B, whereas infiltrating pDCs expressed tumor necrosis factor–related apoptosis-inducing ligand (TRAIL). The biological relevance of this observation can be deduced from our further findings that peripheral blood–derived CD11c+ mDCs acquired antiperforin and anti–granzyme B reactivity upon TLR7/8 stimulation and could use these molecules to effectively lyse major histocompatibility complex (MHC) class Ilo cancer cell lines. The same activation protocol led pDCs to kill MHC class I–bearing Jurkat cells in a TRAIL-dependent fashion. While suggesting that mDCs and pDCs are directly involved in the IMQ-induced destruction of BCC lesions, our data also add a new facet to the functional spectrum of DCs, ascribing to them a major role not only in the initiation but also in the effector phase of the immune response.