tbuckley/cabot-search huggingface dataset:
Precordial QT interval dispersion as a marker of torsade de pointes. Disparate effects of class Ia antiarrhythmic drugs and amiodarone.
Authors: J T Hii, D G Wyse, A M Gillis, H J Duff, M A Solylo, L B Mitchell
Journal: Circulation (1992)

BACKGROUND Patients with a history of class Ia drug-induced torsade de pointes have been treated with chronic amiodarone without recurrence of torsade de pointes despite comparable prolongation of the QT interval. We hypothesized that in such patients, class Ia drugs cause nonhomogeneous prolongation of cardiac repolarization times, whereas amiodarone causes homogeneous prolongation of cardiac repolarization times. METHODS AND RESULTS Thirty-eight consecutive patients who received both class Ia drug therapy and chronic amiodarone therapy were evaluated. Standard 12-lead ECGs at baseline and during each therapy were used to calculate precordial QT interval dispersion (maximum QT in leads V1 through V6 minus minimum QT leads V1 through V6) as a measure of regional variabilities in ventricular repolarization times. Nine of these patients had torsade de pointes during class Ia drug therapy. In these nine patients, class Ia drug therapy and amiodarone significantly prolonged the maximum QT interval to comparable extents. However, class Ia drug therapy but not amiodarone therapy significantly increased precordial QT interval dispersion (101 +/- 37 versus 49 +/- 26 msec; baseline, 44 +/- 12 msec; p = 0.002). In the 29 patients without class Ia drug-induced torsade de pointes, neither class Ia drug therapy nor amiodarone therapy significantly increased QT interval dispersion (50 +/- 6 versus 69 +/- 7 msec; baseline, 54 +/- 5 msec). None of the patients with class Ia drug-induced torsade de pointes had recurrent torsade de pointes during chronic amiodarone therapy. CONCLUSIONS An increase in regional QT interval dispersion during class Ia antiarrhythmic drug therapy is associated with torsade de pointes. Chronic amiodarone therapy in patients with a history of class Ia drug-induced torsade de pointes produces comparable maximum QT interval prolongation but does not increase QT interval dispersion. This characteristic may explain its apparent safe use in patients with a history of class Ia drug-induced torsade de pointes.
A Randomised, Placebo-Controlled Study to Assess the Efficacy of Twice-Daily Vardenafil in the Treatment of Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia
Authors: Christian G. Stief, Hartmut Porst, Dieter Neuser, Manfred Beneke, Ernst Ulbrich
Journal: European Urology (2008)
Experimental Models in Studies in the Pathogenesis of Fever.
Authors: Elisha Atkins
Journal: Annals of Internal Medicine (1964)

s1 April 1964Experimental Models in Studies in the Pathogenesis of Fever.Elisha Atkins, M.D.Elisha Atkins, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-60-4-732_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThough fever has played a prominent role in the history of medicine, little has been learned until recently about its pathogenesis.Various experimental models to investigate the cause of fever will be discussed. Most of these involve experimental infections or the intravenous injection of microbial materials into rabbits or dogs. In other instances, fevers of hypersensitivity have been induced by injection of antigen in specifically sensitized animals. On the basis of this work, it is postulated that most pyrogenic agents induce fever by releasing an intermediate circulating pyrogen from the tissues of the host. This pyrogen is believed to act... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: New Haven, Connecticut PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 April 1964Volume 60, Issue 4Page: 732-732KeywordsAntigensFeversHistory of medicineHypersensitivityIntravenous injectionsPathogenesisRabbits Issue Published: 1 April 1964 PDF DownloadLoading ...
Intramural Hemorrhage in Coronary Atherosclerosis
Authors: THOMAS M. BLAKE, PHILIP K. SPRINGER
Journal: Circulation (1958)

The mechanism of the development of acute occlusion of the coronary arteries is subject to considerable discussion. Intramural hemorrhage has been suggested as a cause of acute occlusion by the hematomatous enlargement of atheromata without associated thrombosis. By a systematic study of coronary arteries with a special technic of injection and clearing of the vessels the frequency of this mechanism was determined.
[135] EFFECTS OF PORTAL BLOOD ARTERIALIZATION WITH A NEW EXTRACORPOREAL DEVICE IN A MODEL OF TOXIC ACUTE LIVER FAILURE
Authors: D. Prezzi, M. Tsivian, F. Neri, L. Puviani, V. Facile, E. Bianchi, G.L. Piras, M. Pariali, S. Valentini, G. Spinella, B. Nardo
Journal: Journal of Hepatology (2007)
Rapid natural killer cell recovery determines outcome after T-cell-depleted HLA-identical stem cell transplantation in patients with myeloid leukemias but not with acute lymphoblastic leukemia
Authors: B N Savani, S Mielke, S Adams, M Uribe, K Rezvani, A S M Yong, J Zeilah, R Kurlander, R Srinivasan, R Childs, N Hensel, A J Barrett
Journal: Leukemia (2007)
P4-09-03: Clinical Significance of HER2+ and Triple-Negative Status in Patients with Tumor Size ≤ 1 cm and Node Negative Breast Cancer.
Authors: T Shao, SK Boolbol, K Boachie-Adjei, P Klein
Journal: Cancer Research (2011)

Abstract Background Data regarding the clinical significance of HER2 and triple negative status in patients with small node negative tumors is limited. Several small case series have suggested an increased risk of recurrence in patients with T 1abN0M0 HER2+ or triple negative (TN) tumors. Conversely, a recent study reported that the recurrence risk for T1abN0M0 HER2+ tumors was too low to justify any adjuvant chemotherapy or trastuzumab. Therefore it remains unclear who among those with small lesions might possibly benefit from more aggressive adjuvant therapy. Methods: We identified all node negative breast cancer patients with tumor size ≤ 1 cm diagnosed between 1/1/1995 and 12/21/2008 through our institutional breast service database. Patients were classified according to their receptor status into three groups: 1) Hormone receptor (HR)+ (ER or PR positive, HER2 negative); 2) HER2+ (IHC 3+ or FISH ≥2); and 3) TN (ER, PR, and HER2 negative). Disease-free survival (DFS) was calculated using KaplanMeier methods. Cox proportional hazards models were used to estimate the association between breast cancer subtypes with DFS adjusting for patient and disease characteristics. Results: Among 658 patients with tumor ≤ 1 cm, 494 (75%) of the patients were HR+, 109 (17%) were HER2+, and 55 (8%) were TN. Two hundred thirty-two tumors were classified as T1a, and 426 were classified as T1b. Median age was 58 years (27-92). Median follow-up was 3.5 years. The 5-year DFS rates were 97.9%, 95.6%, 93.5% in patients with HR+, HER2+, and TN tumors, respectively (p=0.026). In multivariate analysis, TN status was associated with worse DFS (HR 3.13, 95% CI 1.26−7.73), while HER2+ was not (HR 1.64, 95% CI 0.73−3.69). In the HER2+ group, 5-year DFS was also not different between patients who received chemotherapy +/− trastuzumab (32%) and those who did not (p=0.588). We also analyzed T1aN0 and T1bN0 patients separately in order to differentiate the sub-populations of patients more likely to benefit from systemic adjuvant chemotherapy. TN status remains an independent risk factor for worse DFS in T1bN0 (HR 3.68, 95% CI 1.17−11.6), but not in T1aN0 patients. Conclusion: TN, but not HER2+ status was associated with worse DFS in patients with T1abN0M0 tumors, and adjuvant chemotherapy should be considered in TN breast cancer patients who have T1bN0 tumors. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-09-03.
An Assessment of the Role of Redox Cycling in Mediating the Toxicity of Paraquat and Nitrofurantoin
Authors: Aishah Adam, Lewis L. Smith, Gerald M. Cohen
Journal: Environmental Health Perspectives (1990)

The abilities of paraquat, diquat, and nitrofurantoin to undergo cyclic oxidation and reduction with rat microsomal systems have been assessed and compared to that of the potent redox cycler, menadione. Diquat and menadione were found to be potent redox cyclers with comparable abilities to elicit a nonstoichiometric increase in both the consumption of O2 and the oxidation of NADPH, compared to the amounts of substrate added. In contrast, paraquat and nitrofurantoin redox cycled poorly, being an order of magnitude less potent than either diquat or menadione. This was reflected in kinetic studies using lung and liver microsomes, which showed that NADPH-cytochrome P-450 reductase had a lower affinity (Km) for paraquat and nitrofurantoin than for menadione and diquat, although values of Vmax were comparable for all the substrates except nitrofurantoin, which was lower. In order to assess redox cycling of the substrates in an intact lung system, the O2 consumption of rat lung slices was measured in the presence of all four compounds. A small increase in lung slice O2 uptake was observed with paraquat (10(-5) M) in the first 2.5 hr of incubation, possibly because of redox cycling of a high intracellular concentration of paraquat resulting from active accumulation into target cells. This stimulation in O2 uptake was no longer observed when slices were incubated for a longer period or with higher paraquat concentrations (10(-4) M), possibly because of toxic effects in target cells. High concentrations of diquat (10(-5) M) had no effect on O2 consumption of lung slices.(ABSTRACT TRUNCATED AT 250 WORDS)
559. Potentiation of DNA Vaccination Using an Integrated Application System for Electroporation-Mediated Intramuscular Delivery
Authors: Alain Luxembourg, Drew Hannaman, Steve Masterson, Barry Ellefsen, Gerald Nakamura, Robert Bernard
Journal: Molecular Therapy (2005)

Preclinical studies in animal models indicate that the intramuscular administration of plasmid DNA (pDNA) encoding antigenic sequences is an effective immunization strategy. Vaccines based on pDNA represent an appealing immunization strategy since such vaccines would be easy to produce, standardize and store, would raise fewer safety concerns than viral vectors, and would be suitable for multiple immunizations (in distinction with viral vectors). However, it has been more difficult to induce immune responses to pDNA vaccines in larger animals and humans than in mice. As a result, an effective delivery method is generally considered necessary for the clinical development of pDNA vaccines usable in humans. Electroporation (EP), a potent non-viral delivery technique utilizing the in vivo application of electrical fields dramatically enhances intracellular uptake of nucleic acids and ensuing gene expression. This technique might provide a means to overcome some of the traditional hurdles associated with the use of pDNA vaccines in larger species.
The Impact of Peer Review of Volume Delineation in Stereotactic Body Radiation Therapy Planning for Primary Lung Cancer: A Multicenter Quality Assurance Study
Authors: Andrea C. Lo, Mitchell Liu, Elisa Chan, Chad Lund, Pauline T. Truong, Shaun Loewen, Jeffrey Cao, Devin Schellenberg, Hannah Carolan, Tanya Berrang, Jonn Wu, Eric Berthelet, Robert Olson
Journal: Journal of Thoracic Oncology (2014)
B-TYPE NATRIURETIC PEPTIDE AND THE RISK OF CONTRAST INDUCED NEPHROPATHY IN STEMI: ANALYSIS FROM THE HORIZONS-AMI TRIAL
Authors: Rudolf Jarai, George Dangas, Kurt Huber, Ke Xu, Roxana Mehran, Gregg Stone, Bimmer E. Claessen
Journal: Journal of the American College of Cardiology (2012)
Thyroid Neoplasia, Autoimmune Thyroiditis, and Hypothyroidism in Persons Exposed to Iodine 131 From the Hanford Nuclear Site
Authors: Scott Davis
Journal: JAMA (2004)

ContextApproximately 740 000 Ci (2.73 × 1016 Bq) of iodine 131 (131I) were released to the atmosphere from the Hanford Nuclear Site in Washington State from 1944 through 1957. The risk of thyroid disease resulting from prolonged environmental 131I exposure is poorly understood.ObjectiveThe Hanford Thyroid Disease Study (HTDS) was conducted to determine if thyroid disease is increased among persons exposed as children to atmospheric releases of 131I from Hanford.DesignRetrospective cohort study. Exposure could have occurred from December 1944 through 1957. Follow-up occurred until the time of the HTDS examination (December 1992–September 1997). Participants’ thyroid radiation doses from Hanford’s 131I releases were estimated from interview data regarding residence and dietary histories.SettingThe cohort included a sample of all births from 1940 through 1946 to mothers with usual residence in 1 of 7 counties in eastern Washington State.ParticipantsOf 5199 individuals identified, 4350 were located alive and 3440 were evaluable; ie, had sufficient data for dose estimation and received an HTDS evaluation for thyroid disease, including a thyroid ultrasound, physical examination, and fine needle biopsy if required to evaluate thyroid nodularity.Main Outcome MeasuresThyroid cancer, benign thyroid nodules, total neoplasia, any thyroid nodules, autoimmune thyroiditis, and hypothyroidism.ResultsThere was no evidence of a relationship between Hanford radiation dose and the cumulative incidence of any of the outcomes. These results remained unchanged after taking into account several factors that might confound the relationship between radiation dose and the outcomes of interest.ConclusionThese results do not support the hypothesis that exposure during infancy and childhood to 131I at the dose levels (median, 97 mGy; mean, 174 mGy) and exposure circumstances experienced by our study participants increases the risk of the forms of thyroid disease evaluated in this study.
Socioeconomic Impact of Seasonal (Epidemic) Influenza and the Role of Over-the-Counter Medicines
Authors: Michael E. Klepser
Journal: Drugs (2014)

The substantial economic impact of influenza on society results primarily from lost work time and reduced productivity of patients and caregivers and increased use of medical resources. Additionally, since the 1980s, aging of the US population has meant rising influenza-related morbidity and mortality. According to the most current published data on this topic, in 2003 the total economic burden of influenza epidemics in the USA across all age groups was US$87.1 billion. As of February 2013, overall vaccine effectiveness for the 2012/2013 season was estimated to be 56 %. The Centers for Disease Control and Prevention’s National Center for Immunization and Respiratory Diseases has concluded that more effective vaccines and vaccination strategies are needed. Moderate efficacy of the influenza vaccine, continued questions regarding the value of treatment with antivirals, and a growing self-care movement have led to increased use of over-the-counter (OTC) medicines, which play a vital role in managing symptoms associated with mild to moderate influenza and provide an estimated US$102 billion in annual savings for the US healthcare system. A primary benefit to society of using OTC medicines to manage influenza is decreased use of the healthcare system, thereby mitigating the socioeconomic burden of influenza. Considering the stresses placed on the US healthcare system and the substantial productivity losses resulting from seasonal influenza as well as the growing self-care movement, OTC medicines will play an important role in the course of future influenza epidemics.
The arthropathy of cystic fibrosis.
Authors: J Dixey, A N Redington, R C Butler, M J Smith, J R Batchelor, D F Woodrow, M E Hodson, J C Batten, D A Brewerton
Journal: Annals of the Rheumatic Diseases (1988)

Musculoskeletal symptoms are frequent in cystic fibrosis (CF). Here the clinical features of 29 patients with CF who had significant arthropathy are described. Twelve had episodic arthritis (EA) characterised by repeated short attacks of severe, incapacitating polyarthritis, which in seven was associated with fever and erythema nodosum. Ten patients had hypertrophic pulmonary osteoarthropathy (HPOA). The onset of symptoms in the group with HPOA was usually later (mean age 20 years v 16 years for EA) and was associated with significantly worse lung function than in patients with CF, either without arthropathy or with EA. Seven patients had arthropathies which could not be classified as EA or HPOA.
Abstract 199: HPV-16 E6 silencing of p16INK4a in human cervical cancer cells
Authors: Chi Lam Au Yeung, Tsun Yee Tsang, Ngai Na Co, Pak Lun Yau, Tim Tak Kwok
Journal: Cancer Research (2010)

Abstract Aberrant promoter methylation and silencing of tumor suppressor genes such as p16INK4a were reported in association with cervical carcinogenesis. Persistent infection with high-risk human papillomavirus (HPVs), such as HPV-16, contributes significantly towards the cervical cancer development. One of the HPV-16 early proteins E6 is considered to function as an oncoprotein. In the present study, the role of HPV-16 E6 in the regulation of p16INK4a silencing was investigated. Knockdown of E6 in HPV-16 positive human cervical carcinoma SiHa cells by the technique of small interfering RNA (siRNA) led to an increase in p16INK4a mRNA expression as assessed by quantitative RT-PCR analysis. Addition of DNA demethylating agent, 5-aza-2’-deoxyctidine, also had similar effect. Moreover, by methylation-specific PCR analysis, hypo-methylation of p16INK4a promoter was detected in HPV-16 E6 knockdown SiHa cells. The results indicated that HPV-16 E6 may regulate the expression of p16INK4a through promoter methylation. By Western blot analysis, the expression of DNA methyltransferase DNMT1 was repressed in HPV-16 E6 knockdown SiHa cells while it was induced in HPV-16 E6 over-expressed cells. In addition, decrease in p16INK4a mRNA expression and hyper-methylation of its promoter were observed in SiHa cells upon DNMT1 cDNA transfection. To sum up, HPV-16 E6 silencing of p16INK4a may be through the upregulation of DNMT1 which in turn induces the hyper-methylation of p16INK4a promoter and thus suppresses p16INK4a expression. This pathway may be one of the possible mechanisms for the oncogenic function of HPV-16 E6 in human cervical cancer development. 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 199.
Relapse and Reinfection in Chronic Bacteriuria
Authors: Marvin Turck, Allan R. Ronald, Robert G. Petersdorf
Journal: New England Journal of Medicine (1968)

To examine the relation between the pattern of recurrence and the site of chronic bacteriuria, 54 patients with well documented recurrent infections were studied by bilateral ureteral catheterizations. Twenty-nine had renal bacteriuria, and in 25 infection was confined to the bladder. Fifty-two of 65 recurrences in patients with renal bacteriuria were due to relapse with the same species and strain of micro-organism that was present before therapy. In contrast, 27 of 38 recurrent infections among 25 patients with bladder bacteriuria were characterized by reinfection with new organisms. These data indicate that the pattern of recurrence after seemingly effective chemotherapy is of prognostic importance and is helpful in localizing the site of chronic bacteriuria and in guiding further treatment.
Pericarditis Infection due to Coxsackie B, Virus
Authors: T. d. S. Monaldi, A. Benedetto, T. T. Montalto
Journal: BMJ (1963)

MmwU#a lOUmA pressure of about 2 atmospheres absolute appears to be the lowest at which measurable changes in mental effi- ciency are likely to be found.It is also the lowest pressure at which type I "bends " are normally reported (Pawon and Walder, 1954).A fuller account of this work is to be published.
Medulloblastoma subgroup-specific outcomes in irradiated children: who are the true high-risk patients?
Authors: Vijay Ramaswamy, Marc Remke, Jennifer Adamski, Ute Bartels, Uri Tabori, Xin Wang, Annie Huang, Cynthia Hawkins, Donald Mabbott, Normand Laperriere, Michael D. Taylor, Eric Bouffet
Journal: Neuro-Oncology (2015)

The advent of integrated genomics has fundamentally changed our understanding of medulloblastoma. Although survival differences exist among the 4 principal subgroups, this has yet to be elucidated in a North American cohort of irradiated patients. Ninety-two consecutive patients between the ages of 3 and 17 treated with surgery, craniospinal irradiation, and chemotherapy were identified at the Hospital for Sick Children. Molecular subgrouping was performed using nanoString. Two treatment periods were identified: prior to 2006 as per the protocols of the Children's Oncology Group, and after 2006 per the St Jude Medulloblastoma 03 protocol. Five-year progression-free survival (PFS) over the entire cohort was 0.801 (95% CI: 0.692–0.875) with no significant difference between treatment protocols. Strikingly, we found that Group 4 patients had excellent 5-year PFS of 0.959 (95% CI: 0.744–0.994) for average risk and 0.887 (95% CI: 0.727–0.956) across all Group 4 patients. Group 3 patients had 5-year PFS of 0.733 (95% CI: 0.436–0.891). Sonic hedgehog patients did poorly across both treatment protocols, with 5-year PFS of 0.613 (95% CI: 0.333–0.804), likely owing to a high proportion of TP53 mutated patients in this age group. In a cohort of irradiated patients over 3 years of age, PFS for Group 4 patients was significantly improved compared with initial reports. The impact of subgroup affiliation in these children needs to be assessed in large prospectively treated cooperative protocols to determine if more than just WNT patients can be safely selected for de-escalation of therapy.
Prize winner to donate funds from Israeli university to Arab researchers
Authors: J. Siegel-Itzkovich
Journal: BMJ (2003)

Sir John Sulston, the British winner of the 2002 Nobel prize in genetics, has donated almost a third of prize money he received last year to advance joint Israeli-Palestinian research on genes that cause deafness in both populations.

Scientific cooperation between the two peoples has floundered since the intifada began …
Chimeric antigen receptor-redirected CD45RA-negative T cells have potent antileukemia and pathogen memory response without graft-versus-host activity
Authors: W K Chan, D Suwannasaen, R E Throm, Y Li, P W Eldridge, J Houston, J T Gray, C-H Pui, W Leung
Journal: Leukemia (2014)

Chimeric antigen receptor (CAR)-redirected cellular therapy is an attractive modality for cancer treatment. We hypothesized that allogeneic CAR-engineered CD45RA-negative T cells can control cancer and infection without the risk of graft-versus-host disease (GVHD). We used CD19+ MLL-rearranged leukemia as prototype because it is an aggressive and generally drug-resistant malignancy. CD45RA– cells that were transduced with anti-CD19 CAR containing 4-1BB and CD3ζ signaling domains effectively lysed MLL-rearranged leukemia cell lines and primary blasts in vitro. In a disseminated leukemia mouse model, CAR+CD45RA– cells significantly reduced leukemia burdens and prolonged overall survival without GVHD. CAR+ cells were sustainable in blood, and all the treated mice remained leukemia-free even after they were re-challenged with leukemia cells. Despite the transduction process, CD45RA– cells retained recall activity both in vitro and in vivo against human pathogens commonly found in cancer patients. In comparison with CD45RA+ cells, CD45RA– cells showed less allogeneic activity in mixed leukocyte reactions and in mouse models. Thus, the use of CAR+CD45RA– cells can separate GVHD from graft-versus-malignancy effect and infection control. These cells should also be useful in nontransplant settings and may be administered as off-the-shelf third-party cells.