tbuckley/cabot-search huggingface dataset:
Risk of Herpes Zoster in Patients With Rheumatoid Arthritis Treated With Anti–TNF-α Agents
Authors: Anja Strangfeld
Journal: JAMA (2009)

The risk of bacterial infection is increased in patients treated with drugs that inhibit tumor necrosis factor alpha (TNF-alpha). Little is known about the reactivation of latent viral infections during treatment with TNF-alpha inhibitors.To investigate whether TNF-alpha inhibitors together as a class, or separately as either monoclonal anti-TNF-alpha antibodies (adalimumab, infliximab) or a fusion protein (etanercept), are related to higher rates of herpes zoster in patients with rheumatoid arthritis.Patients were enrolled in the German biologics register RABBIT, a prospective cohort, between May 2001 and December 2006 at the initiation of treatment with infliximab, etanercept, adalimumab, or anakinra, or when they changed conventional disease-modifying antirheumatic drug (DMARD). Treatment, clinical status, and adverse events were assessed by rheumatologists at fixed points during follow-up.Hazard ratio (HR) of herpes zoster episodes following anti-TNF-alpha treatment. Study aims were to detect a clinically significant difference (HR, 2.0) between TNF-alpha inhibitors as a class compared with DMARDs and to detect an HR of at least 2.5 for each of 2 types of TNF-alpha inhibitors, the monoclonal antibodies or the fusion protein, compared with conventional DMARDs.Among 5040 patients receiving TNF-alpha inhibitors or conventional DMARDs, 86 episodes of herpes zoster occurred in 82 patients. Thirty-nine occurrences could be attributed to treatment with anti-TNF-alpha antibodies, 23 to etanercept, and 24 to conventional DMARDs. The crude incidence rate per 1000 patient-years was 11.1 (95% confidence interval [CI], 7.9-15.1) for the monoclonal antibodies, 8.9 (95% CI, 5.6-13.3) for etanercept, and 5.6 (95% CI, 3.6-8.3) for conventional DMARDs. Adjusted for age, rheumatoid arthritis severity, and glucocorticoid use, a significantly increased risk was observed for treatment with the monoclonal antibodies (HR, 1.82 [95% CI, 1.05-3.15]), although this risk was lower than the threshold for clinical significance. No significant associations were found for etanercept use (HR, 1.36 [95% CI, 0.73-2.55]) or for anti-TNF-alpha treatment (HR, 1.63 [95% CI, 0.97-2.74]) as a class.Treatment with monoclonal anti-TNF-alpha antibodies may be associated with increased risk of herpes zoster, but this requires further study.
Heat-Induced Perturbations of DNA Damage Signaling Pathways are Modulated by Molecular Chaperones
Authors: Andrei Laszlo, Ilona Fleischer
Journal: Cancer Research (2009)

Heat is one of the most potent radiosensitizers known. Several randomized trials have shown that hyperthermia is a good adjuvant for radiotherapy at several different cancer sites. However, the mechanism(s) involved in the interaction of heat and radiation that lead to radiosensitization remain to be elucidated. In this report, we have determined that heat induces perturbations in some of the earliest events in the cellular response to DNA damage induced by ionizing radiation. We studied the effect of heat on the formation of complexes containing gamma-H2AX/MDC1/53BP1 in heated-irradiated cells. We found that the formation of this complex was delayed in heated-irradiated cells, in a heat but not radiation dose-dependent manner. The length of the heat-induced delay of complex formation was attenuated in thermotolerant and heat radiosensitization-resistant cells. The length of the delay of gamma-H2AX/MDC1/53BP1 complex formation correlated with the magnitude of heat radiosensitization and was modulated by the molecular chaperone Hsc70. Heat radiosensitization was attenuated in 53BP1-null cells, implying that the delay of the formation of the gamma-H2AX/MDC1/53BP1 complex plays a role in heat radiosensitization. Heat also induced a delay of events in the DNA damage response that are downstream from 53BP1. Our results support the notion that heat-induced perturbations in the earliest events of the cellular response to ionizing radiation-induced DNA damage play a role in heat radiosensitization.
NOVEL 19F MRI AND CT TRACKABLE MICROENCAPSULATED MESENCHYMAL STEM CELLS FOR TREATING PERIPHERAL ARTERIAL DISEASE
Authors: Yingli Fu, Dorota Kedziorek, Steven Shea, Ronald Ouwerkerk, Gary Huang, Tina Ehtiati, Robert Krieg, Jeff WM Bulte, Dara L. Kraitchman
Journal: Journal of the American College of Cardiology (2010)
P1-235: Once a day (QD) thoracic 3D conformal radiotherapy (XRT) for patients with limited stage small-cell lung cancer (SCLC) treated concurrently with etoposide and cisplatin (EP): results of a single institution retrospective experience.
Authors: Sebastien Couraud, Ana Direito, Isabelle Martel Lafay, Dominique Arpin, Corinne Depagne, Pascale Nesme, Jean-Claude Guerin, Maurice Perol
Journal: Journal of Thoracic Oncology (2007)
Abstract 999: Potential role of reactive oxygen species in mediating glioblastoma stem cell differentiation
Authors: Feng Wang, Shuqiang Yuan, Gan Chen, Sangbae Kim, Naima Hammoudi, Li Feng, Weiqin Lu, Ju-Seog Lee, Peng Huang
Journal: Cancer Research (2012)

Abstract Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor with poor prognosis due in part to drug resistance and high incidence of tumor recurrence. The drug resistant and cancer recurrence phenotype may be ascribed to the presence of cancer stem cells, which seem to reside in special stem-cell niches in vivo and require special culture conditions including certain growth factors and serum-free medium to maintain their stemness in vitro. In this study, we used several stem-like glioblastoma cell lines (GSC11, GSC23 and GBM3752) derived from patients’ tissues by typical neurosphere culture system, and showed that addition of fetal bovine serum (FBS) to the medium induced an increase of ROS, leading to aberrant differentiation and decreases of stem cell markers such as CD133. We found that exposure of glioblastoma stem cells (GSCs) to serum induces their differentiation through activation of mitochondrial respiration, leading to an increase in superoxide (O2−) generation and a profound reactive oxygen species (ROS) stress response manifested by upregulation of oxidative stress response pathway. This increase in mitochondrial ROS leads to a down-regulation of molecules including SOX2, and Olig2, and Notch1 that are important for stem cell function and an upregulation of mitochondrial superoxide dismutase SOD2 that converts O2− to H2O2. Neutralization of ROS by antioxidant N-acetylcysteine in the serum-treated GSCs suppresses the increase of superoxide and largely rescues the expression of SOX2, Olig2, and Notch1, and prevents the serum-induced differentiation phenotype. Upregulation of ROS by chemical disruption of mitochondrial electron respiration chain induced further decrease of CD133. Our study suggests that mitochondrial function and cellular redox status may profoundly affect the fates of glioblastoma stem cells, and that modulation of ROS generation may be an effective way to impact CSCs, which may provide a new basis for developing novel therapeutic approaches. 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 999. doi:1538-7445.AM2012-999
Points from Letters: Seniority Payments
Authors: G. Cameron-Mowat
Journal: BMJ (1964)

BRITIH 845£4,000 or more.This is a far greater differ- ential than that said to exist between the " average " general practitioner and the fulltime consultant.The remedy for the ills of general practice may well lie in better conditions of service, and in a fairer distribution of the Pool, what- ever the future size of the latter.-Iam, etc., Cardiff.N. G. SANERKIN.SIR,-Before we have the spectacle of our learned and erstwhile dignified profession indulging in intramural arguments of our relative worths, let us quickly stop the correspondence along the lines of Drs. A. P.
EPIDEMIOLOGY OF PULMONARY ARTERIAL HYPERTENSION IN CONGENITAL HEART DISEASE; NATIONWIDE PREVALENCE AND IMPACT ON SOCIOECONOMIC STATUS
Authors: Annelieke CMJ van Riel, A. Zomer, Mark Schuuring, Lia JM Engelfriet-Rijk, Maurice Langemeijer, Aeilko Zwinderman, Elke Hoendermis, Arie Van Dijk, Hubert Vliegen, Berto Bouma, Barbara Mulder
Journal: Journal of the American College of Cardiology (2012)
National Trends in Heart Failure Hospitalization After Acute Myocardial Infarction for Medicare Beneficiaries
Authors: Jersey Chen, Angela Fu-Chi Hsieh, Kumar Dharmarajan, Frederick A. Masoudi, Harlan M. Krumholz
Journal: Circulation (2013)

Previous studies have reported conflicting findings regarding how the incidence of heart failure (HF) after acute myocardial infarction (AMI) has changed over time, and data on contemporary national trends are sparse.Using a complete national sample of 2 789 943 AMI hospitalizations of Medicare fee-for-service beneficiaries from 1998 through 2010, we evaluated annual changes in the incidence of subsequent HF hospitalization and mortality using Poisson and survival analysis models. The number of patients hospitalized for HF within 1 year after AMI declined modestly from 16.1 per 100 person-years in 1998 to 14.2 per 100 person years in 2010 (P<0.001). After adjusting for demographic factors, a relative 14.6% decline for HF hospitalizations after AMI was observed over the study period (incidence risk ratio, 0.854; 95% confidence interval, 0.809-0.901). Unadjusted 1-year mortality following HF hospitalization after AMI was 44.4% in 1998, which decreased to 43.2% in 2004 to 2005, but then increased to 45.5% by 2010. After adjusting for demographic factors and clinical comorbidities, this represented a 2.4% relative annual decline (hazard ratio, 0.976; 95% confidence interval, 0.974-0.978) from 1998 to 2007, but a 5.1% relative annual increase from 2007 to 2010 (hazard ratio, 1.051; 95% confidence interval, 1.039-1.064).In a national sample of Medicare beneficiaries, HF hospitalization after AMI decreased from 1998 to 2010, which may indicate improvements in the management of AMI. In contrast, survival after HF following AMI remains poor, and has worsened from 2007 to 2010, demonstrating that challenges still remain for the treatment of this high-risk condition after AMI.
Diagnosis of Insulinomas
Authors: LARRY B. BALLONOFF
Journal: Annals of Internal Medicine (1974)

Comments and Correction1 October 1974Diagnosis of InsulinomasLARRY B. BALLONOFF, M.D., THOMAS J. HANSON, M.D.LARRY B. BALLONOFF, M.D.Search for more papers by this author, THOMAS J. HANSON, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-81-4-565 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The paper by Kumar, Mehtalia and Miller (1) suggests that the insulin response to glucagon administration be used as a screening test in patients in whom "the clinical features suggest an insulinoma." We feel this test offers no advantage over the determination of plasma insulin and glucose after an overnight fast.Pooling the data from this article and that of Marks and Samols (2), 20 of 21 patients had abnormal fasting insulins or amended insulin to glucose ratios (3) at the start of the glucagon tolerance test and thus did not require any further diagnostic study. Obesity,...References1. KUMARMEHTALIAMILLER DSL: Diagnostic use of glucagon-induced insulin response. Ann Intern Med 80:697-701, 1974 LinkGoogle Scholar2. MARKSSAMOLS VE: Glucagon test for insulinoma, a chemical study in 25 cases. J Clin Pathol 21:346-352, 1968 CrossrefMedlineGoogle Scholar3. TURNEROAKLYNABARRO RNJ: Control of basal insulin secretion, with special reference to the diagnosis of insulinomas. Br Med J 2:132-135, 1971 CrossrefMedlineGoogle Scholar4. ALSEVERSTJERNHOLM RM: Current concepts in diagnosis of insulinoma. Rocky Mt Med J 71:209-212, 1974 MedlineGoogle Scholar1. SHERMANPEKFAJANS BSS: Plasma proinsulin in patients with functioning pancreatic islet cell tumors. J Clin Endocrinol Metab 35:271-280, 1972 CrossrefMedlineGoogle Scholar2. SCHEINDELELLISKHAN PRC: Islet cell tumors: current concepts and management. Ann Intern Med 79:239-257, 1973 LinkGoogle Scholar3. GORDENSHERMANROTH PBJ: Proinsulin-like component of circulating insulin in the basal state in patients and hamsters with islet cell tumors. J Clin Invest 50:2113-2122, 1971 CrossrefMedlineGoogle Scholar4. GUTMANLAZARUSPENHOS RNJ: Circulating proinsulin-like material in patients with functioning insulinomas. N Engl J Med 284:1003-1008, 1971 CrossrefMedlineGoogle Scholar5. SCHMIDTLEVEYMINITZ WGD: Various tests in the evaluation of islet cell adenomas. J Fla Med Assoc 60:21-24, 1973 Google Scholar6. ALSEVERSTJERNHOLMMAKO RMM: Is endogenous human proinsulin-like material biologically active? Abstract No. 237. Presented at the 56th Annual Meeting of the Endocrine Society, Atlanta, Georgia, June 1974 Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: University of Colorado Medical Center Denver, Colorado 80220 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 October 1974Volume 81, Issue 4Page: 565-566KeywordsBlood plasmaGlucagonGlucoseInsulinInsulinomaObesityPatients Issue Published: 1 October 1974 PDF downloadLoading ...
Diabetic Foot Syndrome
Authors: Lawrence A. Lavery, David G. Armstrong, Robert P. Wunderlich, Jeffrey Tredwell, Andrew J.M. Boulton
Journal: Diabetes Care (2003)

OBJECTIVE—To report the incidence of diabetes-related lower-extremity complications in a cohort of patients enrolled in a diabetes disease management program. RESEARCH DESIGN AND METHODS—We evaluated screening results and clinical outcomes for the first 1,666 patients enrolled in a disease management program for a period of 24 months (50.3% men, aged 69.1 ± 11.1 years). RESULTS—The incidence of ulceration, infection, amputation, and lower-extremity bypass was 68.4, 36.5, 5.9, and 7.7 per 1,000 persons with diabetes per year. Amputation incidence was higher in Mexican Americans than in non-Hispanic whites (7.4/1,000 vs. 4.1/1,000; P = 0.003, odds ratio [OR] 1.8, 95% CI 1.2–2.7). The amputation-to-ulcer ratio was 8.7%. The incidence of Charcot arthropathy was 8.5/1,000 per year. Charcot was more common in non-Hispanic whites than in Mexican Americans (11.7/1,000 vs. 6.4/1,000; P = 0.0001, 1.8, 1.3–2.5). The prevalence of peripheral vascular disease was 13.5%, with no significant difference based on ethnicity (P = 0.3). There was not a significant difference in incidence of foot infection (P = 0.9), lower-extremity bypass (P = 0.3), or ulceration (P = 0.1) based on ethnicity. However, there were more failed bypasses in Mexican Americans (33%) than in non-Hispanic whites (7.1%). Mexican Americans were 3.8 times more likely to have a failed bypass (leading to an amputation) or be diagnosed as “nonbypassable” than non-Hispanic whites (75.0 vs. 44.0%; P = 0.01, 3.8, 1.2–11.8). CONCLUSIONS—The incidence of amputation is higher in Mexican Americans, despite rates of ulceration, infection, vascular disease, and lower-extremity bypass similar to those of non-Hispanic whites. There may be factors associated with failed or failure to bypass that mandate further investigation.
Drug-Induced Blood Disorders.
Authors: D A Danielson, S W Douglas, P Herzog, H Jick, J B Porter
Journal: Annals of Internal Medicine (1976)

A case-history study of drug-induced blood disorders (pancytopenia, hemolytic anemia, thrombocytopenia, and granulocytopenia) was carried out at the Group Health Cooperative of Puget Sound, a health maintenance organization with more than 200,000 members, for the ten-year period from 1972 through 1981. During this time, only 26 instances of hospitalization for such disorders were thought to be definitely, probably, or possibly due to drugs other than antitumor agents. The rate was of the order of one per 100,000 person-years at risk. Only quinidine/quinine and sulfa-containing drugs were implicated in more than one case.
A Kinetic Evaluation of Hemostasis in Renal Disease
Authors: C. R. P. George, Sherrill J. Slichter, Leonard J. Quadracci, Gary E. Striker, Laurence A. Harker
Journal: New England Journal of Medicine (1974)

Abstract To clarify the pathogenic role of microvascular thrombosis in renal disease, platelet, fibrinogen and plasminogen survivals were measured in 78 patients. Selective platelet consumption occ...
Adolescents and Children Injured or Killed in Drive-By Shootings in Los Angeles
Authors: H. Range Hutson, Deirdre Anglin, Michael J. Pratts
Journal: New England Journal of Medicine (1994)

Drive-by shootings by violent street gangs contribute to early morbidity and mortality among adolescents and children in Los Angeles. This study attempted to determine the frequency of this problem and the population at greatest risk. We also studied the most frequently injured areas of the body, the seasons in which the most shootings occurred, the most common sites for drive-by shootings, and the types of firearms used.We retrospectively reviewed the files of the Gang Information Section of the Los Angeles Police Department to identify all drive-by shootings in Los Angeles in 1991 in which a child or adolescent under the age of 18 was shot at, injured, or killed.A total of 677 adolescents and children were shot at, among whom 429 (63 percent) had gunshot wounds and 36 (5.3 percent) died from their injuries. Three hundred three of those with gunshot wounds (71 percent) were gang members. Arms and legs were the areas of the body most commonly injured. Handguns were the most frequently used type of firearm. All the homicide victims were African American or Hispanic, and 97 percent were boys. African American and Hispanic children and adolescents, especially male gang members, had a significantly higher risk than their Asian and white counterparts of injury and death from drive-by shootings in Los Angeles (P < 0.001).Drive-by shootings involving adolescents and children are frequent in Los Angeles. Although Los Angeles may be an atypical case, understanding why violent street gangs form, preventing causes of violence, and limiting access to firearms are essential steps in preventing this serious problem.
Reply to “Diminishing Role of Platinum-Sensitivity Status in Patients with Small Cell Lung Cancer”
Authors: Primo N. Lara, David R. Gandara, Mary W. Redman
Journal: Journal of Thoracic Oncology (2015)

We were pleased to see that our recent article questioning the continued relevance of platinum-sensitivity status in relapsed small cell lung cancer (SCLC) in the modern era has stimulated a healthy debate on this issue. In our report, we highlighted our collective experience within Southwest Oncology Group (SWOG) trials of noncytotoxic molecular-targeted therapies in the platinum-treated SCLC population. We reported that in our pooled database, platinum sensitivity status was no longer as strongly associated with subsequent survival after treatment with newer noncytotoxic agents, in contrast with what had been previously described with second-line cytotoxic therapies. Tiseo et al. point to their own meta-analysis of six trials of second line therapy as evidence that platinum-sensitivity status should continue to be considered for SCLC treatment planning and study stratification. However, we must point out that this meta-analysis was solely confined to trials of the cytotoxic topoisomerase inhibitor topotecan whereas our analysis was based on trials that predominantly evaluated noncytotoxic targeted agents. In fact, we agree with Kim and Mishima when they articulately emphasize this point by stating that our conclusions are correct “when noncytotoxic agents, such as molecularly targeted agents, are used for second line chemotherapy.” We, therefore, believe that our data set is even more relevant to modern-day clinical trial design and planning of novel SCLC therapeutics beyond that of cytotoxics. Finally, we must emphasize that SWOG has done a remarkable job of consistently collecting the same data elements in its SCLC trials through the years. The availability of high quality, consistent data allows us to confidently pool our SWOG trials and expect that each data element is available for evaluation in our bivariate and multivariate models. Other pooled datasets or meta-analyses collect information from disparate trials that do not consistently share the same data elements, thus reducing confidence in the subsequent prognostic models.
Coronary Microvascular Dysfunction Induced by Primary Hyperparathyroidism is Restored After Parathyroidectomy
Authors: Elena Osto, Francesco Fallo, Maria Rosa Pelizzo, Anna Maddalozzo, Nadia Sorgato, Francesco Corbetti, Roberta Montisci, Giulia Famoso, Roberto Bellu, Thomas F. Lüscher, Sabino Iliceto, Francesco Tona
Journal: Circulation (2012)

Symptomatic primary hyperparathyroidism (PHPT) is associated with increased cardiovascular mortality. However, data on the association between asymptomatic PHPT and cardiovascular risk are lacking. We assessed coronary flow reserve (CFR) as a marker of coronary microvascular function in asymptomatic PHPT of recent onset.We studied 100 PHPT patients (80 women; age, 58±12 years) without cardiovascular disease and 50 control subjects matched for age and sex. CFR in the left anterior descending coronary artery was detected by transthoracic Doppler echocardiography, at rest, and during adenosine infusion. CFR was the ratio of hyperemic to resting diastolic flow velocity. CFR was lower in PHPT patients than in control subjects (3.0±0.8 versus 3.8±0.7; P<0.0001) and was abnormal (≤2.5) in 27 patients (27%) compared with control subjects (4%; P=0.0008). CFR was inversely related to parathyroid hormone (PTH) levels (r=-0.3, P<0.004). In patients with CFR ≤2.5, PTH was higher (26.4 pmol/L [quartiles 1 and 3, 16 and 37 pmol/L] versus 18 [13-25] pmol/L; P<0.007), whereas calcium levels were similar (2.9±0.1 versus 2.8±0.3 mmol/L; P=0.2). In multivariable linear regression analysis, PTH, age, and heart rate were the only factors associated with CFR (P=0.04, P=0.01, and P=0.006, respectively). In multiple logistic regression analysis, only PTH increased the probability of CFR ≤2.5 (P=0.03). In all PHPT patients with CFR ≤2.5, parathyroidectomy normalized CFR (3.3±0.7 versus 2.1±0.5; P<0.0001).PHPT patients have coronary microvascular dysfunction that is completely restored after parathyroidectomy. PTH independently correlates with the coronary microvascular impairment, suggesting a crucial role of the hormone in explaining the increased cardiovascular risk in PHPT.