tbuckley/cabot-search huggingface dataset:
Protection of ischemic hearts perfused with an anion exchange inhibitor, DIDS, is associated with beneficial changes in substrate metabolism
Authors: R Ramasamy
Journal: Cardiovascular Research (2001)

Objective: Metabolic interventions that promote glucose use during ischemia have been shown to protect the myocardium and improve functional recovery on reperfusion. In this study we evaluated if cardioprotection can be accomplished by inhibiting fatty acid uptake, which would be expected to increase glycolytic metabolism. Methods: Diisothiocyanostilbene sulfonic acid (DIDS), commonly used to inhibit Band-3 mediated anion exchanger, and has also been demonstrated to inhibit fatty acid transport in adipocytes, was used to inhibit fatty acid uptake prior to ischemia. Isolated rat hearts were perfused with buffer containing 5 mM glucose, 70 mU/l insulin, 0.4 mM palmitate, and 0.4 mM albumin, paced at 300 beats/min, and subjected to 50 min of low-flow ischemia followed by 60 min of reperfusion. Results: Ischemic injury, as assessed by creatine kinase release, was diminished in hearts perfused with DIDS (334±72 in DIDS vs. 565±314 IU/g dry wt in controls, P<0.04). Increases in LVEDP during ischemia were attenuated (8±3 mmHg in DIDS vs. 15±18 mmHg in controls, P<0.03) and the % recovery of LV function with reperfusion was enhanced in DIDS-treated hearts (78±10% of baseline in DIDS vs. 62±19% of baseline in controls, P<0.04). These beneficial effects of DIDS were associated with increased glucose metabolism and ATP content during ischemia and reperfusion. Furthermore, treatment with DIDS lowered the accumulation of long chain acyl carnitines. Conclusions: This study demonstrates that DIDS protects ischemic myocardium, and is associated with inhibition of fatty acid uptake, improved glucose metabolism, and enhanced functional recovery on reperfusion. The data presented here suggest a potential role for therapeutic agents that lower fatty acid uptake as a metabolic adjunct in the treatment of myocardial ischemia.
Persistently Perplexing Purpuras: Thrombotic Thrombocytopenic Purpura and Immune Thrombocytopenic Purpura
Authors: Raphael B. Stricker
Journal: Annals of Internal Medicine (1994)

Letters1 November 1994Persistently Perplexing Purpuras: Thrombotic Thrombocytopenic Purpura and Immune Thrombocytopenic PurpuraRaphael B. Stricker, MDRaphael B. Stricker, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-121-9-199411010-00031 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Olenich and Schattner [1] report a case of postpartum TTP complicating pregnancy-associated ITP. The authors state that “the coexistence of these two disorders has not been previously reported in the English-language literature.”Although coexistent TTP and ITP may not have been reported during pregnancy, the association between these two diseases has previously been described in various settings. Elevated levels of platelet-associated antibodies have been noted in patients with TTP [2, 3], and the sequential development of TTP and ITP has been described in several cases, including one after pregnancy [4]. Further, the association between TTP and ITP ...References1. Olenich M, Schattner E. Postpartum thrombotic thrombocytopenic purpura (TTP) complicating pregnancy-associated immune thrombocytopenic purpura (ITP). Ann Intern Med. 1994; 120:845-7. Google Scholar2. Bodensteiner D, Rosenfeld C. Elevated platelet-surface-bound IgM in thrombotic thrombocytopenic purpura. South Med J. 1988; 81:81-3. Google Scholar3. Stricker RB, Davis JA, Gershow J, Yamamoto K, Kiprov DD. Thrombotic thrombocytopenic purpura complicating systemic lupus erythematosus: report of a case and review of the literature from the plasmapheresis era. J Rheumatol. 1992; 19:1469-73. Google Scholar4. Stein RS, Flexner JM. Idiopathic thrombocytopenic purpura during remission of thrombotic thrombocytopenic purpura. South Med J. 1984; 77:1599-601. Google Scholar5. Routy JP, Beaulieu R, Monte M, Saint-Louis J, Sauvageau G, Toma E. Immunologic thrombocytopenia followed by thrombotic thrombocytopenic purpura in two HIV1 patients. Am J Hematol. 1991; 38:327-8. Google Scholar Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 November 1994Volume 121, Issue 9Page: 720-721KeywordsAntibodiesDatabasesHIVIdiopathic thrombocytopenic purpuraPregnancyThrombotic thrombocytopenic purpura ePublished: 15 August 2000 Issue Published: 1 November 1994 Copyright & PermissionsCopyright © 1994 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
The waiting time paradox: population based retrospective study of treatment delay and survival of women with endometrial cancer in Scotland
Authors: S. C Crawford
Journal: BMJ (2002)

Delay in the delivery of treatment for gynaecological cancers has been previously investigated. 1 2In some cases, the delay reflects the illness behaviour of women; in others, it was inherent in the system for delivering health care.Few studies have linked delay in treatment with survival, although a study from Israel found that survival from endometrial cancer was not affected by a delay in treatment of four months. 3 We investigated links between delays in treatment and survival, using a recently completed audit of endometrial cancer treatment in Scotland.
A 75-Year-Old Man with Fever, Diarrhea, Weight Loss and a Mid-Esophageal Mass
Authors: T. Weber, A. Kirchgatterer, G. Kronabethleitner, W. Höbling, C. Mannhalter, A. Chott, P. Knoflach
Journal: Endoscopy (2002)

A 75-year old man was admitted due to a 6-month history of 15 kg weight loss, diarrhea and fever. The physical examination showed cachexia. Important pathological laboratory values were: erythrocyte sedimentation rate (ESR) 87/96 mm, lactate dehydrogenase (LDH) 597 U/l (rising to 2030 U/l within 20 days), and albumin 2.2 g/dl. The patient had macrocytic anemia, and gliadin and endomysial antibody tests were positive.
Metformin: An Update
Authors: Dmitri Kirpichnikov, Samy I. McFarlane, James R. Sowers
Journal: Annals of Internal Medicine (2002)

Metformin is an insulin-sensitizing agent with potent antihyperglycemic properties. Its efficacy in reducing hyperglycemia in type 2 diabetes mellitus is similar to that of sulfonylureas, thiazolidinediones, and insulin. Metformin-based combination therapy is often superior to therapy with a single hypoglycemic agent. The antihyperglycemic properties of metformin are mainly attributed to suppressed hepatic glucose production, especially hepatic gluconeogenesis, and increased peripheral tissue insulin sensitivity. Although the precise mechanism of hypoglycemic action of metformin remains unclear, it probably interrupts mitochondrial oxidative processes in the liver and corrects abnormalities of intracellular calcium metabolism in insulin-sensitive tissues (liver, skeletal muscle, and adipocytes) and cardiovascular tissue.
Hypersensitivity to antigen derived from brain tissue in patients with Huntington's disease and in individuals at risk.
Authors: R S Walls, A Ruwoldt
Journal: Journal of Clinical Investigation (1984)

The hypothesis that an immune response is directed to components of brain tissue in Huntington's disease (HD) was examined. 27 patients with HD, 21 children of affected parents who showed no signs of disease, 6 spouses of HD patients, and 40 patients with other neurologic diseases were investigated. Leukocyte migration inhibition to antigens prepared from brain tissue was demonstrated in 26 HD patients and in 9 children. None of the six spouses reacted. 13 patients with other neurologic conditions (including 60% of patients after cerebrovascular accidents) reacted to rat brain extract. Fractionation of brain tissue indicated that the material responsible for reactions in these patients differed from that in HD. The material that elicited hypersensitivity in HD was not species specific, since it was found in rat, calf, human, and rabbit brain. It was not present in rat kidney, liver, or heart. Preliminary characterization showed that the material was protein in nature, contained sugar and lipid, and was heat labile. The finding of hypersensitivity in about half the unaffected children of HD parents suggests that it may precede the clinical onset of disease and serve as a marker for the gene.
In vivo, in vitro correlation of acetylcholine airway responsiveness in sensitized guinea pigs. The role of modified epithelial functions.
Authors: Y Masaki, M Munakata, M Amishima, Y Homma, Y Kawakami
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

Many attempts have failed to correlate in vivo airway responsiveness with in vitro airway smooth muscle functions. We have reexamined this relation by taking account of airway epithelial functions in guinea pigs sensitized with inhaled ovalbumin (OA). In vivo responses were assessed by the provocative concentration of acetylcholine (ACh) required to double the airway opening pressure (PC200) under mechanical ventilation. In vitro responses were measured in a perfused whole-tracheal preparation. The negative logarithm of the molar concentration of ACh required to produce a 10% reduction in diameter was calculated both for epithelial-side stimulation (PC10(in)) and for serosal-side stimulation (PC10(out)). OA-sensitized guinea pigs showed significantly smaller log PC200 than control animals (0.51 +/- 0.07 and 0.81 +/- 0.10, respectively, p < 0.01). In in vitro study, there were variable differences in PC10(in) and PC10(out) in each animal. The difference in sensitivity between epithelial- and serosal-side stimulation (PC10(in-out)) showed a significant correlation in PC10(in) (r = 0.82, n = 9, p < 0.01) but not to PC10(out) (r = 0.39, p > 0.1), indicating that the variation in PC10(in-out) resulted from the changes in PC10(in). For in vivo-in vitro correlation, log PC200 correlated significantly with PC10(in) (r = 0.68, n = 9, p < 0.05) but not with PC10(out) (r = 0.18, p > 0.1). These results indicate that the sensitization by inhalation of OA produces increased airway responsiveness to ACh in vivo and that this airway responsiveness may be related, at least in part, to the altered airway epithelial functions.
CHEMO-IMMUNOLOGICAL STUDIES ON CONJUGATED CARBOHYDRATE-PROTEINS
Authors: Walther F. Goebel, Frank H. Babers, Oswald T. Avery
Journal: The Journal of Experimental Medicine (1934)

The chemical and immunological properties of the acetylated and unacetylated forms of the p-aminophenol beta-glucoside of glucose have been described. The serological specificity of these beta-glucosides in combination with protein has been correlated with known changes in chemical structure and has been compared with the immunological properties of the alpha-glucoside of the same hexose.
Abstract 5166: Tumor adiponectin signaling underlies the association between obesity and lethal outcome in prostate cancer
Authors: Neil E. Martin, Travis Gerke, Massimo Loda, Meir Stampfer, Stephen Finn, Jennifer Rider, Lorelei A. Mucci
Journal: Cancer Research (2012)

Abstract Background: Obesity is associated with poor outcomes in men with prostate cancer. The biologic drivers of this relationship are poorly understood. Adiponectin is produced by adipose tissue and has been shown to regulate multiple pathways including inflammation, angiogenisis and insulin sensitivity. Low circulating levels are associated both with obesity and with lethal prostate cancer. Here we investigate whether adiponectin signaling has a differential effect on cancer outcomes in the tumors of obese compared to healthy weight men. Methods: The study cohort consisted of men diagnosed with prostate cancer from the Physicians’ Health Study (1982-2004) and the Health Professionals Follow Up Study (1986-2004) for whom archival tumor specimens were available. Follow-up data for development of metastases and cancer-specific mortality (defined as lethal prostate cancer) was available through 2010. Gene set analyses was undertaken for 116 men using gene expression profiling data from cDNA-mediated annealing, selection, extension, and ligation (DASL) assay of 6000 genes. Genes differentially expressed between lethal (n=30 lethal events) and indolent disease among the obese and healthy weight men were explored. Immunohistochemistry for adiponectin receptor 2 (ADIPOR2) protein expression in tumors and adjacent normal was performed on tissue microarrays representing tumor tissue from 1017 patients (n=98 lethal events). Anthropometric measures were obtained from validated questionnaires. Results: Gene set analysis identified distinct gene sets that were enriched in the comparison of lethal to indolent among the obese and healthy weight men. In the obese men, five gene sets were enriched in the lethal cases with a false discovery rate &amp;lt;0.1. The second most enriched set associated with lethality was the KEGG adiponectin signaling pathway. We found that protein expression of ADIPOR2 in prostate tumors, but not normal prostate, was higher among obese compared to healthy weight men. Moreover, high expression of ADIPOR2 protein expression was associated with a 3-fold greater risk of lethal outcomes. Conclusion: Tumor adiponectin signaling appears to be key pathway underlying lethal outcomes in obese men with prostate cancer. This work supports the hypothesis that there are unique drivers of poor outcome among obese men with prostate cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5166. doi:1538-7445.AM2012-5166
Active modification of host inflammation by<i>Salmonella</i>
Authors: Ana Victoria C. Pilar, Sarah A. Reid-Yu, Colin A. Cooper, David T. Mulder, Brian K. Coombes
Journal: Gut Microbes (2013)

The dampening of host immune responses is a critical aspect of pathogenesis for the enteropathogen Salmonella enterica. Our laboratory has recently described a role for the secreted effector GogB in disruption of NFκB activation and limitation of the host inflammatory response to infection. GogB alters the NFκB pathway by preventing IκB degradation by the host SCF E3 ubiquitin ligase, through an interaction with Skp1 and FBXO22. The prevention of NFκB activation through this interaction dampens the host inflammatory response in the gut, which in turn limits the damage to host tissues during chronic infection. In this addendum, we summarize these recent findings and discuss their implications and impact in the area of host-pathogen interactions.
Overexpression of Smad2 Drives House Dust Mite–mediated Airway Remodeling and Airway Hyperresponsiveness via Activin and IL-25
Authors: Lisa G. Gregory, Sara A. Mathie, Simone A. Walker, Sophie Pegorier, Carla P. Jones, Clare M. Lloyd
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Airway hyperreactivity and remodeling are characteristic features of asthma. Interactions between the airway epithelium and environmental allergens are believed to be important in driving development of pathology, particularly because altered epithelial gene expression is common in individuals with asthma.To investigate the interactions between a modified airway epithelium and a common aeroallergen in vivo.We used an adenoviral vector to generate mice overexpressing the transforming growth factor-beta signaling molecule, Smad2, in the airway epithelium and exposed them to house dust mite (HDM) extract intranasally.Smad2 overexpression resulted in enhanced airway hyperreactivity after allergen challenge concomitant with changes in airway remodeling. Subepithelial collagen deposition was increased and smooth muscle hyperplasia was evident resulting in thickening of the airway smooth muscle layer. However, there was no increase in airway inflammation in mice given the Smad2 vector compared with the control vector. Enhanced airway hyperreactivity and remodeling did not correlate with elevated levels of Th2 cytokines, such as IL-13 or IL-4. However, mice overexpressing Smad2 in the airway epithelium showed significantly enhanced levels of IL-25 and activin A after HDM exposure. Blocking activin A with a neutralizing antibody prevented the increase in lung IL-25 and inhibited subsequent collagen deposition and also the enhanced airway hyperreactivity observed in the Smad2 overexpressing HDM-exposed mice.Epithelial overexpression of Smad2 can specifically alter airway hyperreactivity and remodeling in response to an aeroallergen. Moreover, we have identified novel roles for IL-25 and activin A in driving airway hyperreactivity and remodeling.
ON ABSORPTION FROM INTRAMUSCULAR TISSUE
Authors: J. Auer, S. J. Meltzer
Journal: The Journal of Experimental Medicine (1911)

Injections of adrenalin or other substances into the lumbar muscles of rabbits are followed by a rapid absorption in whole or in part of these substances. The rapid absorption is not due to the needle being within a vein or to the tearing of veins by the needle during its insertion. Similar injections into gluteal muscles fail to give reliable results.
Recurrent Bacterial Infections in Children
Authors: Richard B. Johnston
Journal: New England Journal of Medicine (1984)

THE presence of recurrent bacterial infections in a child raises the discomforting possibility of some type of underlying immunodeficiency disease. None of these diseases is common, and the money spent and blood withdrawn searching for them can be excessive.1 Yet the consequences of allowing such a disorder to go undiagnosed, even for days or weeks, can be grave indeed. Thus, careful physicians must entertain the possibility of an immunodeficiency disease much more frequently than they expect to diagnose one.How can this process of diagnostic exploration be accomplished efficiently? Beginning the process by selecting laboratory tests from the long complicated . . .
Avascular necrosis of bone caused by combination chemotherapy without corticosteroids.
Authors: P G Harper, C Trask, R L Souhami
Journal: BMJ (1984)

Avascular necrosis of bone is sometimes a complication of cancer chemotherapy that includes corticosteroids but generally occurs at a single site. A patient with testicular teratoma who received chemotherapy that did not include steroids developed avascular necrosis of the left femoral head, left scaphoid, and both medial femoral condyles. Symptoms were relieved with anti-inflammatory drugs and physiotherapy. This case indicates that avascular necrosis may be caused by cancer chemotherapy that does not include steroids.
“Drink plenty of fluids”: Authors' reply
Authors: Michelle P B Guppy, Sharon M Mickan, Chris B Del Mar
Journal: BMJ (2004)

EDITOR—We carefully worded our systematic review: there is no direct empirical evidence to support or refute the advice; we ask only that more research is undertaken, and that in the meantime we exercise caution with the age old advice. That the press has run away with …
Venlafaxine for major depression
Authors: Andrea Cipriani, John R Geddes, Corrado Barbui
Journal: BMJ (2007)

More evidence that risks outweigh benefits for most patients?

In this week's BMJ Rubino and colleagues provide new evidence that informs the debate about whether antidepressants increase the risk of suicide.1 The study, a retrospective observational analysis of the General Practice Research Database, found that patients prescribed venlafaxine were more likely to attempt or complete suicide than patients prescribed citalopram, fluoxetine, or dothiepin. Adjustment for possible confounders, however, greatly reduced the excess risk. 

Venlafaxine is a serotoninergic and noradrenergic reuptake inhibitor, and it may be more effective than selective serotonin inhibitors for major depression.2 3 However, patients often discontinue treatment because of side effects.4 

The database analysed is the world's largest computerised database of anonymised longitudinal medical records from primary care (more than 3.4 million active patients, about 13 million in total since 1987, from around 450 primary care practices throughout the United Kingdom; www.gprd.com). The database has been used extensively for pharmacoepidemiological research, including previous studies examining the possible association between …
A Randomized Trial of Bevacizumab, an Anti–Vascular Endothelial Growth Factor Antibody, for Metastatic Renal Cancer
Authors: James C. Yang, Leah Haworth, Richard M. Sherry, Patrick Hwu, Douglas J. Schwartzentruber, Suzanne L. Topalian, Seth M. Steinberg, Helen X. Chen, Steven A. Rosenberg
Journal: New England Journal of Medicine (2003)

Mutations in the tumor-suppressor gene VHL cause oversecretion of vascular endothelial growth factor by clear-cell renal carcinomas. We conducted a clinical trial to evaluate bevacizumab, a neutralizing antibody against vascular endothelial growth factor, in patients with metastatic renal-cell carcinoma.A randomized, double-blind, phase 2 trial was conducted comparing placebo with bevacizumab at doses of 3 and 10 mg per kilogram of body weight, given every two weeks; the time to progression of disease and the response rate were primary end points. Crossover from placebo to antibody treatment was allowed, and survival was a secondary end point.Minimal toxic effects were seen, with hypertension and asymptomatic proteinuria predominating. The trial was stopped after the interim analysis met the criteria for early stopping. With 116 patients randomly assigned to treatment groups (40 to placebo, 37 to low-dose antibody, and 39 to high-dose antibody), there was a significant prolongation of the time to progression of disease in the high-dose--antibody group as compared with the placebo group (hazard ratio, 2.55; P<0.001). There was a small difference, of borderline significance, between the time to progression of disease in the low-dose--antibody group and that in the placebo group (hazard ratio, 1.26; P=0.053). The probability of being progression-free for patients given high-dose antibody, low-dose--antibody, and placebo was 64 percent, 39 percent, and 20 percent, respectively, at four months and 30 percent, 14 percent, and 5 percent at eight months. At the last analysis, there were no significant differences in overall survival between groups (P>0.20 for all comparisons).Bevacizumab can significantly prolong the time to progression of disease in patients with metastatic renal-cell cancer.
CATHETER-BASED LEFT ATRIAL APPENDAGE (LAA) LIGATION FOR THE PREVENTION OF EMBOLIC EVENTS ARISING FROM THE LAA
Authors: Randall J. Lee, Steven J. Yakubov, Krzysztof Bartus, Jacek Bednarek, Boguslaw Kapelak, Jerzy Sadowski
Journal: Journal of the American College of Cardiology (2010)
Treatment for Rheumatic Disorders
Authors: Elizabeth A. Tindall, David A. Fox
Journal: New England Journal of Medicine (2006)

Lentigo Maligna and RadiotherapyTo the Editor: Imiquimod has recently been shown to be effective in the management of lentigo maligna, as demonstrated in Images in Clinical Medicine (Nov.17 issue) 1 and in other reports.The authors correctly suggest that imiquimod may be effective for lentigo maligna, but readers are subsequently led to believe that perhaps this is the only alternative to surgery.Although imiquimod may be a promising nonsurgical alternative for the treatment of lentigo maligna, radiotherapy has been clinically successful, with excellent cosmesis.In one series of 101 patients with either lentigo maligna or lentigo maligna melanoma who were treated with radiotherapy and followed for a minimum of 2 years (mean, 8 years), the mean time to recurrence was 45.6 months, with a recurrence rate of 7 percent. 2Although radiotherapy may not be as convenient as treatment with a self-administered topical agent, it should be recognized as a potential therapeutic choice for patients with lentigo maligna.Radiotherapy can provide excellent cosmesis and local control.