tbuckley/cabot-search huggingface dataset:
Use of Gallium Scanning in Predicting Resolution of Legionnaires?? Pneumonia
Authors: LOUIS J. IMBRIANO, PERRY R. MANDEL, ANTHONY F. CORDARO
Journal: Clinical Nuclear Medicine (1983)

The value of Ga-67 scanning to detect acute infectious lung disease has been described. We present a patient who apparently improved both clinically and radiographically after acute Legionnaires' pneumonia. Five months later a relapse developed. During his relapse the pulmonary uptake of Ga-67 and the appearance of chest x-rays were disparate. We suggest that pulmonary Ga-67 uptake may be a more sensitive indicator of the resolution of pneumonia than is chest radiography. Therapeutic success may be assumed when pulmonary Ga-67 uptake is absent.
Tell Me Not
Authors: Tzvi Shlitner
Journal: Annals of Internal Medicine (2012)

On Being a Doctor1 May 2012Tell Me NotTzvi Shlitner, MDTzvi Shlitner, MDFrom The Ruth & Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Clalit Health Services, Haifa and Western Galilee District, Haifa 35152, Israel.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-156-9-201205010-00014 Audio Reading - “Tell Me Not” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "Tell Me Not," by T. Shlitner. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Fifty-six. What does it feel like? Stop for a moment and count the stones in front of your feet. The stones are always there. Sometimes it's hard to see their shape or color, but if you gaze long enough, they become clear, distilled beneath the cold water of the childhood spring that carries away your unsteady reflection. Reach 56 and wait. Don't go any further, do not succumb to the temptation to keep counting—just wait ….I came to Yoram's house in the early afternoon of a hot, sunny day in the middle of May—a small country house, neat garden, ... Author, Article, and Disclosure InformationAffiliations: From The Ruth & Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Clalit Health Services, Haifa and Western Galilee District, Haifa 35152, Israel.Note: The author confirms that all identifiers have been removed or disguised so that the persons described are not identifiable and cannot be identified through the details of the story.Corresponding Author: Tzvi Shlitner, MD, Kfar Hayam 5605, Hadera 38100, Israel; e-mail, dr.[email protected]com. PreviousarticleNextarticle Advertisement Audio Reading - “Tell Me Not” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "Tell Me Not," by T. Shlitner. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics 1 May 2012Volume 156, Issue 9Page: 666-667KeywordsBreadBreathingCancer treatmentDrugsDustEmotionsHeartSaltsSleepSmell ePublished: 1 May 2012 Issue Published: 1 May 2012 Copyright & PermissionsCopyright © 2012 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
International consumer group slates drug companies' marketing practices
Authors: Michael Day
Journal: BMJ (2006)

Drug companies continue to pull the wool over the eyes of patients and doctors, concludes a new report from Consumers International. The report lambasts the industry for its lack of transparency and unscrupulous marketing.

Consumers International has called on governments to rein in the industry's practices that “misinform consumers about the benefits of the drugs they are buying.”

It warns that drug companies are adopting new ways to influence consumers, such as sponsoring patients' groups and funding disease awareness campaigns, as well as using old methods such as offering hospitality to medical experts or “opinion leaders.”

Richard Lloyd, the …
Biennial report on carcinogens. A work in progress.
Authors: K G Thigpen
Journal: Environmental Health Perspectives (1995)

Research ArticleOpen AccessBiennial report on carcinogens. A work in progress. K G Thigpen K G Thigpen Search for more papers by this author Published:1 September 1995https://doi.org/10.1289/ehp.95103806AboutSectionsPDF ToolsDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InReddit "Biennial report on carcinogens. A work in progress.." Environmental Health Perspectives, 103(9), pp. 806–807FiguresReferencesRelatedDetails Vol. 103, No. 9 September 1995Metrics About Article Metrics Publication History Originally published1 September 1995Published in print1 September 1995 Financial disclosuresPDF download License information EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted. Note to readers with disabilities EHP strives to ensure that all journal content is accessible to all readers. However, some figures and Supplemental Material published in EHP articles may not conform to 508 standards due to the complexity of the information being presented. If you need assistance accessing journal content, please contact [email protected]. Our staff will work with you to assess and meet your accessibility needs within 3 working days.
Mechanism underlying inhibition of intestinal apical Cl–/OH– exchange following infection with enteropathogenic E. coli
Authors: Ravinder K. Gill, Alip Borthakur, Kim Hodges, Jerrold R. Turner, Daniel R. Clayburgh, Seema Saksena, Ayesha Zaheer, Krishnamurthy Ramaswamy, Gail Hecht, Pradeep K. Dudeja
Journal: Journal of Clinical Investigation (2007)

Enteropathogenic E. coli (EPEC) is a major cause of infantile diarrhea, but the pathophysiology underlying associated diarrhea is poorly understood. We examined the role of the luminal membrane Cl(-)/OH(-) exchange process in EPEC pathogenesis using in vitro and in vivo models. Cl(-)/OH(-) exchange activity was measured as OH(-) gradient-driven (36)Cl(-) uptake. EPEC infection (60 minutes-3 hours) inhibited apical Cl(-)/OH(-) exchange activity in human intestinal Caco-2 and T84 cells. This effect was dependent upon the bacterial type III secretory system (TTSS) and involved secreted effector molecules EspG and EspG2, known to disrupt the host microtubular network. The microtubule-disrupting agent colchicine (100 muM, 3 hours) also inhibited (36)Cl(-) uptake. The plasma membrane expression of major apical anion exchanger DRA (SLC26A3) was considerably reduced in EPEC-infected cells, corresponding with decreased Cl(-)/OH(-) exchange activity. Confocal microscopic studies showed that EPEC infection caused a marked redistribution of DRA from the apical membrane to intracellular compartments. Interestingly, infection of cells with an EPEC mutant deficient in espG significantly attenuated the decrease in surface expression of DRA protein as compared with treatment with wild-type EPEC. EPEC infection in vivo (1 day) also caused marked redistribution of surface DRA protein in the mouse colon. Our data demonstrate that EspG and EspG2 play an important role in contributing to EPEC infection-associated inhibition of luminal membrane chloride transport via modulation of surface DRA expression.
Tories extend general practice fundholding
Authors: L Beecham
Journal: BMJ (1994)

General practices will be able to become fundholders with 5000 patients, Virginia Bottomley, the health secretary, told the Conservative party conference last week (see editorial p1032). Reducing the minimum list size from 7000 will draw in an additional 18% of the population. The government has decided that fundholders will now be able to purchase all elective …
Renal Insufficiency as a Predictor of Cardiovascular Outcomes and the Impact of Ramipril: The HOPE Randomized Trial
Authors: Johannes F.E. Mann, Hertzel C. Gerstein, Janice Pogue, Jackie Bosch, Salim Yusuf
Journal: Annals of Internal Medicine (2001)

Background: The cardiovascular risk associated with early renal insufficiency is unknown. Clinicians are often reluctant to use angiotensin-converting enzyme inhibitors in patients with renal insufficiency. Objective: To determine whether mild renal insufficiency increases cardiovascular risk and whether ramipril decreases that risk. Design: Post hoc analysis. Setting: The Heart Outcomes and Prevention Evaluation (HOPE) study, a randomized, double-blind, multinational trial involving 267 study centers. Patients: 980 patients with mild renal insufficiency (serum creatinine concentration ≥ 124 µmol/L [≥ 1.4 mg/dL]) and 8307 patients with normal renal function (serum creatinine concentration < 124 µmol/L [<1.4 mg/dL]) Patients with a baseline serum creatinine concentration greater than 200 µmol/L (2.3 mg/dL) were excluded. Measurements: The primary outcome measure was incidence of cardiovascular death, myocardial infarction, or stroke. Results: Cumulative incidence of the primary outcome was higher in patients with renal insufficiency than in those without (22.2% vs. 15.1%; P < 0.001) and increased with serum creatinine concentration. Patients with renal insufficiency had a substantially increased risk for cardiovascular death (11.4% vs. 6.6%) and total mortality (17.8% vs. 10.6%) (P < 0.001 for both comparisons). The effect of renal insufficiency on the primary outcome (adjusted hazard ratio, 1.40 [95% CI, 1.16 to 1.69]) was independent of known cardiovascular risks and treatment. Ramipril reduced the incidence of the primary outcome in patients with and those without renal insufficiency (hazard ratio, 0.80 vs. 0.79; P > 0.2 for the difference). Conclusions: In patients who had preexisting vascular disease or diabetes combined with an additional cardiovascular risk factor, mild renal insufficiency significantly increased the risk for subsequent cardiovascular events. Ramipril reduced cardiovascular risk without increasing adverse effects.
Medicines out of Control? Antidepressants and the Conspiracy of Goodwill
Authors: Sean A Spence
Journal: BMJ (2004)

T he treatment of depression has seldom been more controversial. The safety of new antidepressants is subject to radical reappraisal, while an unpleasant question looms: can we really trust scientific evidence? Medawar and Hardon give a detailed analysis of this quagmire, massively annotated with footnotes and verbatim quotations.

It is understandable that the references sometimes get lost or the argument wanders, for the problem is not focal but pervasive. Theirs is an indictment of “big pharma” (the drug industry), doctors (both as prescribers and researchers), the regulatory authorities, politicians, and, ultimately, the values of society itself. Building on the evidence that earlier treatments of “distress” (such as opium, barbiturates, and benzodiazepines) initially seemed benign, only to wreak havoc later, the authors locate a similar optimism among early accounts of some antidepressants (particularly the selective serotonin reuptake inhibitors or SSRIs).

However, they suggest that there is something different about the current debate—something that is about precision, semantics, or sleight of hand, depending on your viewpoint. The authors argue …
Automated, Quantitative Screening Assay for Antiangiogenic Compounds Using Transgenic Zebrafish
Authors: T. Cameron Tran, Blossom Sneed, Jamil Haider, Delali Blavo, Audrey White, Temitope Aiyejorun, Timothy C. Baranowski, Amy L. Rubinstein, Thanh N. Doan, Raymond Dingledine, Eric M. Sandberg
Journal: Cancer Research (2007)

Abstract Pathologic angiogenesis has emerged as an important therapeutic target in several major diseases. Zebrafish offer the potential for high-throughput drug discovery in a whole vertebrate system. We developed the first quantitative, automated assay for antiangiogenic compound identification using zebrafish embryos. This assay uses transgenic zebrafish with fluorescent blood vessels to facilitate image analysis. We developed methods for automated drugging and imaging of zebrafish in 384-well plates and developed a custom algorithm to quantify the number of angiogenic blood vessels in zebrafish. The assay was used to screen the LOPAC1280 compound library for antiangiogenic compounds. Two known antiangiogenic compounds, SU4312 and AG1478, were identified as hits. Additionally, one compound with no previously known antiangiogenic activity, indirubin-3′-monoxime (IRO), was identified. We showed that each of the hit compounds had dose-dependent antiangiogenic activity in zebrafish. The IC50 of SU4312, AG1478, and IRO in the zebrafish angiogenesis assay was 1.8, 8.5, and 0.31 μmol/L, respectively. IRO had the highest potency of the hit compounds. Moreover, IRO inhibited human umbilical vein endothelial cell tube formation and proliferation (IC50 of 6.5 and 0.36 μmol/L, respectively). It is therefore the first antiangiogenic compound discovered initially in a zebrafish assay that also has demonstrable activity in human endothelial cell-based angiogenesis assays. [Cancer Res 2007;67(23):11386–92]
Phase 2 study of rituximab in newly diagnosed stage IA nodular lymphocyte-predominant Hodgkin lymphoma: a report from the German Hodgkin Study Group
Authors: Dennis A. Eichenauer, Michael Fuchs, Annette Pluetschow, Beate Klimm, Teresa Halbsguth, Boris Böll, Bastian von Tresckow, Lucia Nogová, Peter Borchmann, Andreas Engert
Journal: Blood (2011)
The Harveian Oration ON THE PASSING OF MORBID ANATOMY: Delivered at the Royal College of Physicians of London on St. Luke's Day, October 18th, 1912
Authors: J. Goodhart
Journal: BMJ (1912)

TWENTY-SEVEN years ago, in delivering the Bradsbaw Lecture before our College, I stood in the place of a much regretted Fellow dead in his early prime, when, in a retro- spect of his wvork on arterial tension, I had the more easy task of recalling still recent memories.To-day, when in pursuance of the honourable duty that you, Sir, in your kindness, have imposed upon me, I try to look back into the mists of centuries to the full life and ever-to-be- revered memory of Harvey, no longer can one appeal to those personal recollections in which we all could share and sympathize; in place thereof is an influence, a resurrection, and my outlook becomes essentially prospective.sHarvey's influence as it is permeating the avenues of timeI What a subject, what an opportunity!Yet, when some 256 years have come and gone since this annual commemoration of our benefactors was instituted by Harvey himself, what an impossibility, in any but the most spectral formI
Abstract 4173: IKBKE/IKKα is a prognostic marker and is required for KRAS-driven tumorigenecity in non-small cell lung cancer
Authors: Donghwa Kim, Jian-Ping Guo, Jingchun Gao, Catherine Yu, John Park, Domenico Coppola, Eric Haura, Jin Q. Cheng
Journal: Cancer Research (2012)

Abstract IKBKE (IKKα) is a serine/threonine protein kinase that belongs to the IKK kinase family. Here we demonstrated that IKKα is frequently overexpressed and activated in NSCLC. Elevated protein levels of IKKα were detected in 16/30 (52.6%) cell lines and 91/176 (51.7%) primary tumors. Alterations of IKBKE are associated with overall survival but not tumor stage and grade. Enforcing expression of IKBKE decreases whereas knockdown of IKBKE increases the apoptosis induced by chemotherapeutic agents. Notably, suppression of IKBKE selectively induced cell death and inhibited tumor growth in NSCLC cell lines that depend on oncogenic K-Ras expression. Mechanistically, knockdown of IKBKE largely abrogated activating mutation of K-Ras-induced NFκB activation. These data suggest that IKBKE could be a poor prognostic marker and mediates K-Ras oncogenic function and signaling to NFκB. 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 4173. doi:1538-7445.AM2012-4173
Study of an inhibiting factor of epidermal proliferation in plucked skin and various tumours of mice
Authors: M. GUIGON, E. FRINDEL, J. HEWITT, M. TUBIANA
Journal: British Journal of Dermatology (1976)

The aim of our research was to investigate, by autoradiographic methods, the presence of an inhibitory factor (IF) in normal skin, in plucked skin and in five experimental skin tumors of the mouse, capable of inhibiting epidermal proliferation. The experimental model used was that of Bullough & Laurence (1960), i.e. a wound in the ear of a mouse. After tritiated thymidine administration the measurement of the labelling index confirmed the existence of an inhibitory substance in normal skin. The plucked skin had no inhibitory effect when it was taken 24 h after plucking, but after 4 days its effect had returned to normal. The skin tumours, whether epithelial or mesenchymal, showed the same inhibitory effect as normal skin whereas a non-cutaneous tumour tested had no inhibitory effect.
The Born-Again Spleen
Authors: Howard A. Pearson, Dorothy Johnston, Karen A. Smith, Robert J. Touloukian
Journal: New England Journal of Medicine (1978)

We assessed splenic activity after splenectomy by interference phase microscopical examination of circulating red cells. Normal eusplenic children had a low number (<1 per cent) of red cells with surface indentations or "pits." About 20 per cent of red cells of children who had electively been subjected to splenectomy for hematologic indications were "pitted." Thirteen of 22 children who had had emergency splenectomy because of traumatic injury had a low percentage of "pitted" red cells, suggesting a return of splenic function. In five of these children a 99mTc sulfur colloid scan demonstrated multiple nodules of recurrent splenic tissue. In contrast to the prevailing opinion that splenosis is rare, we have found it to be a frequent occurrence. Return of splenic function may, in part, account for the low frequency with which overwhelming bacterial sepsis and meningitis have been documented after splenectomy for traumatic indications. (N Engl J Med 298:1389–1392, 1978)
CD4 Count and the Risk for Death in Patients Infected with HIV Receiving Antiretroviral Therapy
Authors: Robert Yarchoan, David J. Venzon, James M. Pluda, Jill Lietzau, Kathleen M. Wyvill, Anastasios A. Tsiatis, Seth M. Steinberg, Samuel Broder
Journal: Annals of Internal Medicine (1991)

Objective: To investigate the relation between CD4 count and the immediate hazard of dying in patients receiving zidovudine (azidothymidine [AZT])-based antiretroviral therapy. Setting: A research hospital that recruits patients from the entire United States. Design: Retrospective analysis of a cohort of patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex participating in longterm zidovudine-based antiretroviral protocols. Patients: Fifty-five patients with human immunodeficiency virus (HIV) infection and either AIDS or severe AIDS-related complex who were followed for as many as 4 years while they received antiretroviral therapy. Measurements: CD4 counts were measured. Main Results: Ten patients are known to be alive and 1 was lost to follow-up. Of the 44 patients who are known to have died, the CD4 range was known within 6 months of death in 41. All but 1 of these 41 assessable deaths occurred in patients whose CD4 counts were known to have fallen below 50 CD4 cells/mm3 (P < 10-10). The hazard of dying in the cohort ranged from 0 deaths/patient-month (95% Cl, 0 to 0.008 deaths/ patient-month) in patients with 200 or more CD4 cells/ mm3 to 0.07 deaths/patient-month (Cl, 0.050 to 0.094 deaths/patient-month) in patients with fewer than 50 CD4 cells/mm3. For the patients who died and whose cases were assessable, the mean of the last three CD4 counts obtained before death was 7.7 CD4 cells/mm3 (Cl, 0.9 to 63.3 cells/mm3). The median survival of patients once their CD4 counts fell below 50 CD4 cells/mm3 was 12.1 months (Cl, 7.2 to 19.4 months). Conclusions: In a carefully followed cohort treated with zidovudine-based antiretroviral therapy, nearly all deaths occurred in patients with fewer than 50 CD4 cells/mm3. These findings may have implications in the monitoring of patients with AIDS and in the use of CD4 count as a clinical trials end point for the antiretroviral therapy of HIV infection.
Abstract 1047: AKT inhibitor MK-2206 induces necrotic cell death of uterine leiomyoma cells in vitro and reduces tumor volume in vivo.
Authors: Elizabeth Sefton, Wenan Qiang, Vanida Serna, Takeshi Kurita, Julie Kim
Journal: Cancer Research (2013)

Abstract Uterine leiomyomas (UL), benign tumors of the myometrium, are the number one indication for hysterectomies in the U.S. due to a lack of effective therapy. ULs show increased phosphorylation of the pro-survival protein AKT compared to normal myometrium indicating that AKT signaling is increased in UL. However, substantial data directly linking AKT to UL cell survival is lacking. We hypothesized that AKT promotes UL cell survival and that it is a viable drug target for inhibiting UL growth. We utilized the AKT inhibitor MK-2206 (MK), currently in phase II trials, on cultured primary human UL cells. MK-2206 effectively reduced phosphorylation of AKT and PRAS40, an AKT substrate. MK-2206 did not affect cell proliferation but caused cell death. We observed a lack of apoptosis in dead UL cells by Annexin V staining. Additionally, MK-2206 was able to induce UL cell death in the presence of pan-caspase inhibitor, Z-VAD-FMK, indicating that MK-2206 mediated cell death is caspase independent and non-apoptotic. Given that caspases did not modulate cell death, we explored necrosis. MK-2206 induced HMGB1 cytoplasmic localization and mitochondrial disruption indicating possible leiomyoma necrosis. We next explored programmed necrosis, a form of non-apoptotic cell death mediated by RIP kinases (RIPK). However, MK-2206 was able to induce cell death in the presence of RIPK inhibitors, necrostatin-1 and necrosulfonamide, indicating that programmed necrosis is not the mechanism of MK-2206 mediated UL cell death. We are actively exploring alternate necrotic cell death pathways as the mechanisms of MK-2206 induced UL cell death. Lastly, in-vivo MK-2206 treatments reduced tumor volume of human UL cells implanted under the kidney capsule of NSG mice. Xenograft sections from mice treated with MK-2206-2206 contained dying cells in the absence of cleaved caspase 3 supporting the in-vitro results. This is the first report of non-apoptotic cell death in UL and the first time that AKT has been targeted in-vivo for UL therapy. Our data provides molecular evidence for the involvement of AKT in UL cell survival and suggest that AKT inhibition by MK-2206 may be a viable option for the future treatment of UL. This work was funded by NIH P01HD057877. Citation Format: Elizabeth Sefton, Wenan Qiang, Vanida Serna, Takeshi Kurita, Julie Kim. AKT inhibitor MK-2206 induces necrotic cell death of uterine leiomyoma cells in vitro and reduces tumor volume in vivo. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1047. doi:10.1158/1538-7445.AM2013-1047