tbuckley/cabot-search huggingface dataset:
Risk of Human Papillomavirus–Associated Cancers Among Persons With AIDS
Authors: Anil K. Chaturvedi, Margaret M. Madeleine, Robert J. Biggar, Eric A. Engels
Journal: JNCI Journal of the National Cancer Institute (2009)

Although risk of human papillomavirus (HPV)–associated cancers of the anus, cervix, oropharynx, penis, vagina, and vulva is increased among persons with AIDS, the etiologic role of immunosuppression is unclear and incidence trends for these cancers over time, particularly after the introduction of highly active antiretroviral therapy in 1996, are not well described. Data on 499 230 individuals diagnosed with AIDS from January 1, 1980, through December 31, 2004, were linked with cancer registries in 15 US regions. Risk of in situ and invasive HPV-associated cancers, compared with that in the general population, was measured by use of standardized incidence ratios (SIRs) and 95% confidence intervals (CIs). We evaluated the relationship of immunosuppression with incidence during the period of 4–60 months after AIDS onset by use of CD4 T-cell counts measured at AIDS onset. Incidence during the 4–60 months after AIDS onset was compared across three periods (1980–1989, 1990–1995, and 1996–2004). All statistical tests were two-sided. Among persons with AIDS, we observed statistically significantly elevated risk of all HPV-associated in situ (SIRs ranged from 8.9, 95% CI = 8.0 to 9.9, for cervical cancer to 68.6, 95% CI = 59.7 to 78.4, for anal cancer among men) and invasive (SIRs ranged from 1.6, 95% CI = 1.2 to 2.1, for oropharyngeal cancer to 34.6, 95% CI = 30.8 to 38.8, for anal cancer among men) cancers. During 1996–2004, low CD4 T-cell count was associated with statistically significantly increased risk of invasive anal cancer among men (relative risk [RR] per decline of 100 CD4 T cells per cubic millimeter = 1.34, 95% CI = 1.08 to 1.66, P = .006) and non–statistically significantly increased risk of in situ vagina or vulva cancer (RR = 1.52, 95% CI = 0.99 to 2.35, P = .055) and of invasive cervical cancer (RR = 1.32, 95% CI = 0.96 to 1.80, P = .077). Among men, incidence (per 100 000 person-years) of in situ and invasive anal cancer was statistically significantly higher during 1996–2004 than during 1990–1995 (61% increase for in situ cancers, 18.3 cases vs 29.5 cases, respectively; RR = 1.71, 95% CI = 1.24 to 2.35, P < .001; and 104% increase for invasive cancers, 20.7 cases vs 42.3 cases, respectively; RR = 2.03, 95% CI = 1.54 to 2.68, P < .001). Incidence of other cancers was stable over time. Risk of HPV-associated cancers was elevated among persons with AIDS and increased with increasing immunosuppression. The increasing incidence for anal cancer during 1996–2004 indicates that prolonged survival may be associated with increased risk of certain HPV-associated cancers.
Mechanisms of Cancer Drug Resistance
Authors: Michael M. Gottesman
Journal: Annual Review of Medicine (2002)

▪ Abstract The design of cancer chemotherapy has become increasingly sophisticated, yet there is no cancer treatment that is 100% effective against disseminated cancer. Resistance to treatment with anticancer drugs results from a variety of factors including individual variations in patients and somatic cell genetic differences in tumors, even those from the same tissue of origin. Frequently resistance is intrinsic to the cancer, but as therapy becomes more and more effective, acquired resistance has also become common. The most common reason for acquisition of resistance to a broad range of anticancer drugs is expression of one or more energy-dependent transporters that detect and eject anticancer drugs from cells, but other mechanisms of resistance including insensitivity to drug-induced apoptosis and induction of drug-detoxifying mechanisms probably play an important role in acquired anticancer drug resistance. Studies on mechanisms of cancer drug resistance have yielded important information about how to circumvent this resistance to improve cancer chemotherapy and have implications for pharmacokinetics of many commonly used drugs.
Ready adsorption of medium chain triglyceride in the steatorrhoea syndrome.
Authors: B J Smits, P Wilding, W T Cooke
Journal: Gut (1968)

The daily diet in England contains 60 to 100 g. of fat, consisting mainly of triglycerides with fatty acid radicles of more than 10 carbon atoms and providing 25 to 40% of the calorie requirements.In an average hospital diet these include about 40% oleic acid, 20 to 25 % palmitic acid, and 10 to 12 % stearic acid; this composition is similar to that of the aver- age diet of the population (Osborn and Ohlson, 1963;Smits and Wilding, 1965).Long chain fatty acids are not well absorbed in disorders associated with steatorrhoea (Hoagland and Snider, 1943) although the unsaturated compounds are better assimilated than the saturated (Weijers and van de Kamer, 1953).Malabsorption increases with in- crease in chain length, particularly in conditions with cellular dysfunction of the intestinal mucosa such as coeliac disease and to a lesser degree in pancreatic disease where intraluminal lipolysis is defective (van de Kamer and Weijers, 1961; Fernandes, van de Kamer, and Weijers, 1962).The replacement of dietary long chain triglycerides by medium chain triglycerides, i.e., in which fatty acids have 8 to 10 carbon atoms, has been studied in a number of clinical conditions (Fernandes, van de
Time-course of antigen-induced airway inflammation in the guinea-pig and its relationship to airway hyperresponsiveness
Authors: S Underwood, M Foster, D Raeburn, S Bottoms, JA Karlsson
Journal: European Respiratory Journal (1995)

The causative relationship between airway inflammation and hyperreactivity is unclear, since inflammatory changes have been examined at one or, at most, a few time-points after antigen challenge in both human asthma and animal models. We have made a detailed investigation of inflammatory and functional changes in the airways up to 8 days after antigen challenge in guinea-pigs. In particular, we examined the hypothesis that eosinophil-derived mediators contribute to tissue damage and the development of airway hyperresponsiveness. Following antigen challenge, the influx of inflammatory cells and mediator release in airway tissue and bronchoalveolar lavage fluid were correlated temporally with histopathological changes in airway tissue and airway responsiveness. Eosinophil influx was demonstrable at 4 h. Eosinophilia peaked after 24 h and persisted for at least 8 days. Parallel increases in the concentrations of major basic protein and eosinophil cationic protein in bronchoalveolar lavage fluid indicated that the eosinophils were activated. Eosinophilia was accompanied by subepithelial oedema and epithelial damage co-localized with major basic protein immunoreactivity. A transient neutrophilia (< 48 h duration) and an increase in neutrophil elastase in bronchoalveolar lavage fluid peaked at 14 h. The proportion of airway macrophages with an activated morphology increased at 8 h and remained markedly elevated until 72 h. Airways were hyperresponsive to histamine at 4 h and for at least 8 days. The antigen-induced airway inflammation resemble in time-course and histopathology that seen in antigen-challenged asthmatics, and indicate that the eosinophil and its cytotoxic proteins may be major mediators of airway mucosal damage and airway hyperresponsiveness.
TIMP3 is the primary TIMP to regulate agonist-induced vascular remodelling and hypertension
Authors: Ratnadeep Basu, Jiwon Lee, Jude S. Morton, Abhijit Takawale, Dong Fan, Vijay Kandalam, Xiuhua Wang, Sandra T. Davidge, Zamaneh Kassiri
Journal: Cardiovascular Research (2013)

Hypertension is accompanied by structural remodelling of vascular extracellular matrix (ECM). Tissue inhibitor of metalloproteinases (TIMPs) inhibits matrix metalloproteinases (MMPs) that degrade the matrix structural proteins. In response to a hypertensive stimulus, the balance between MMPs and TIMPs is altered. We examined the role of TIMPs in agonist-induced hypertension. We subjected TIMP-knockout mice to angiotensin II (Ang II) infusion, and found that Ang-II-induced hypertension in TIMP1−/−, TIMP2−/−, and TIMP4−/− mice was comparable to wild-type (WT) mice, but significantly suppressed in TIMP3−/− mice. Ex vivo pressure myography analyses on carotid and mesenteric arteries revealed that Ang-II-infused TIMP3−/− arteries were more distensible with impaired elastic recoil compared with the WT group. The acute response to vasoconstriction and vasodilation was intact in TIMP3−/− mesenteric and carotid arteries. Mesenteric arteries from TIMP3−/−-Ang II mice exhibited a reduced media-to-lumen ratio, suppressed collagen and elastin levels, elevated elastase and gelatinase proteolytic activities compared with WT-Ang II. TIMP3−/−-Ang II carotid arteries also showed adverse structural remodelling. Treatment of mice with doxycycline, a matrix metalloproteinase inhibitor, improved matrix integrity in mesenteric and carotid arteries in TIMP3−/−-Ang II and differentially regulated elastin and collagen levels in WT-Ang II vs. TIMP3−/−-Ang II. Our study demonstrates a critical role for TIMP3, among all TIMPs, is preserving arterial ECM in response to Ang II. It is critical to acknowledge that the suppressed Ang-II-induced hypertension in TIMP3−/− mice is not a protective mechanism but owing to adverse remodelling in arterial matrix.
Blood tests in tired elite athletes: expectations of athletes, coaches and sport science/sports medicine staff
Authors: K E Fallon
Journal: British Journal of Sports Medicine (2006)

Background: The issue of the expectations of elite athletes, their coaches and non-medically qualified athlete support staff of consultations with sports physicians has not been previously dealt with in the sports medicine literature. As fulfilment of expectations of the content of a consultation may influence patient’s satisfaction and clinical outcome, it is important to assess the expectations of athletes and, most importantly, coaches. Objective: To assess the expectations and beliefs about fatigue, particularly in relation to blood tests, of athletes, their coaches and support staff in the specific context of tiredness of &lt;7 days’ duration. Subjects: 28 senior sports science or non-medically qualified sports medicine staff, 22 elite coaches and 62 elite athletes from the Australian Institute of Sport were included in this study. Methods: A single questionnaire. Results: The expectation for a blood test at the initial consultation for short-term fatigue was particularly high among athletes (81%) and coaches (91%). This expectation increased in athletes if their performance was worsening. All groups unanimously suggested that a blood test be performed in cases of more prolonged fatigue. Increase in total training load was perceived to be the most important cause of fatigue, but issues relating to sleep were also thought to be highly relevant. All groups suggested that blood tests provide some degree of reassurance, and all groups suggested that the most important blood tests that might be performed related to exclusion of iron deficiency, anaemia and infection. Conclusion: Athletes and their coaches generally expect that blood tests will be performed even when fatigue has been present for &lt;1 week. This is at odds with currently available evidence of the diagnostic utility of these tests. Despite the current evidence base, individual factors in the athletes, coaches and doctors need to be considered when deciding on whether such testing has to be performed.
TESTOSTERONE REPLACEMENT ATTENUATES CONTRACTILE DYSFUNCTION, INFARCT SIZE AND FATAL ARRHYTHMIAS CAUSED BY ISCHEMIA-REPERFUSION INJURY IN TESTOSTERONE-DEPRIVED RATS
Authors: Wanpitak Pongkan, Krekwit Shinlapawittayatorn, Siriporn Chattipakorn, Nipon Chattipakorn
Journal: Journal of the American College of Cardiology (2014)
Retropharyngeal Lymph Node Metastasis in Nasopharyngeal Carcinoma: Prognostic Value and Staging Categories
Authors: Jun Ma, Lizhi Liu, Linglong Tang, Jingfeng Zong, Aihua Lin, Taixiang Lu, Nianji Cui, Chunyan Cui, Li Li
Journal: Clinical Cancer Research (2007)

Abstract Purpose: To investigate the incidence, prognostic value, and staging categories of retropharyngeal lymph node (RLN) metastasis in nasopharyngeal carcinoma (NPC). Experimental Design: We did a retrospective review of the data from 749 biopsy-proved nonmetastatic NPC patients. All patients had undergone contrast-enhanced computed tomography and had radiotherapy as their primary treatment. Results: The incidence of RLN metastasis was 51.5%. After adjusting for tumor (T) and node (N) classifications, a borderline significant difference of distant metastasis-free survival (DMFS) rates was observed between patients with or without RLN metastasis. In N0 disease, the presence of RLN metastasis was a significant independent predictor for overall survival (OS), loco-regional relapse-free survival, and DMFS in multivariate Cox modeling analysis. No significant difference was observed in all end points between patients with unilateral and bilateral RLN metastasis. The hazard ratios of death and distant failure for N0 with RLN metastasis were similar to N1. The survival curve of OS and DMFS for N0 disease with RLN metastasis had approximated that of N1 disease. The survival curve of OS for T1 disease with RLN metastasis was approximately the same as T2 disease. However, the survival curve of DMFS for T1 disease with RLN metastasis was approximately the same as in T3 disease. Conclusions: RLN metastasis has a tendency to affect the DMFS rates of patients with NPC. Retropharyngeal node involvement has a negative effect on the prognosis of N0 disease. RLN metastasis should be classified as N1.
Peroxiredoxin 2 Deficiency Exacerbates Atherosclerosis in Apolipoprotein E–Deficient Mice
Authors: Jong-Gil Park, Ji-Young Yoo, Se-Jin Jeong, Jae-Hoon Choi, Mi-Ran Lee, Mi-Ni Lee, Jeong Hwa Lee, Hyoung Chin Kim, Hanjoong Jo, Dae-Yeul Yu, Sang Won Kang, Sue Goo Rhee, Mun-Han Lee, Goo Taeg Oh
Journal: Circulation Research (2011)

Rationale: Peroxiredoxin 2 (Prdx2), a thiol-specific peroxidase, has been reported to regulate proinflammatory responses, vascular remodeling, and global oxidative stress. Objective: Although Prdx2 has been proposed to retard atherosclerosis development, no direct evidence and mechanisms have been reported. Methods and Results: We show that Prdx2 is highly expressed in endothelial and immune cells in atherosclerotic lesions and blocked the increase of endogenous H 2 O 2 by atherogenic stimulation. Deficiency of Prdx2 in apolipoprotein E–deficient (ApoE −/− ) mice accelerated plaque formation with enhanced activation of p65, c-Jun, JNKs, and p38 mitogen-activated protein kinase; and these proatherogenic effects of Prdx2 deficiency were rescued by administration of the antioxidant ebselen. In bone marrow transplantation experiments, we found that Prdx2 has a major role in inhibiting atherogenic responses in both vascular and immune cells. Prdx2 deficiency resulted in increased expression of vascular adhesion molecule-1, intercellular adhesion molecule-1, and monocyte chemotactic protein-1, which led to increased immune cell adhesion and infiltration into the aortic intima. Compared with deficiency of glutathione peroxidase 1 or catalase, Prdx2 deficiency showed a severe predisposition to develop atherosclerosis. Conclusions: Prdx2 is a specific peroxidase that inhibits atherogenic responses in vascular and inflammatory cells, and specific activation of Prdx2 may be an effective means of antiatherogenic therapy.
Influence of uvulopalatopharyngoplasty on alpha-EEG arousals in nonapnoeic snorers
Authors: A Boudewyns, W De Cock, M Willemen, M Wagemans, W De Backer, PH Van de Heyning
Journal: European Respiratory Journal (1997)

Arousals are more numerous in heavy snorers than in nonsnorers and might be a cause of excessive daytime sleepiness (EDS) in these patients. The present study investigated whether treatment of snoring by uvulopalatopharyngoplasty (UPPP) had an influence on sleep microstructure in nonapnoeic snorers. The polysomnographic records of 10 nonapnoeic snorers were reviewed retrospectively and arousals scored according to the American Sleep Disorders Association (ASDA) 3 s definition. Scores for snoring, EDS and polysomnographic data were compared before and after UPPP (mean (+/-SD) time interval 249 +/- 183 days). UPPP resulted in a subjective improvement of snoring and a significant decrease in the arousal index (mean 14.6, 95% confidence interval (95% CI) 8.5-20.8 vs mean 9.1, 95% CI 6.6-11.5) (p = 0.01). EDS and the amount of slow-wave sleep remained unchanged. Uvulopalatopharyngoplasty resulted in an improvement of subjective snoring and a significant decrease of arousals in nonapnoeic snorers. Although these data do not provide any insight into whether the improvement observed can be maintained on a long-term basis, uvulopalatopharyngoplasty can be considered as a useful treatment modality to reduce sleep fragmentation and snoring in nonapnoeic snorers.
Progranulin protects against osteoarthritis through interacting with TNF-α and β-Catenin signalling
Authors: Yun-peng Zhao, Ben Liu, Qing-yun Tian, Jian-lu Wei, Brendon Richbourgh, Chuan-ju Liu
Journal: Annals of the Rheumatic Diseases (2014)

Objective Progranulin (PGRN) was previously isolated as an osteoarthritis (OA)-associated growth factor. Additionally, PGRN was found to play a therapeutic role in inflammatory arthritis mice models through antagonising tumour necrosis factor α (TNF-α). This study was aimed at investigating the role of PGRN in degradation of cartilage and progression of OA. Methods Progression of OA was analysed in both spontaneous and surgically induced OA models in wild type and PGRN-deficient mice. Cartilage degradation and OA were evaluated using Safranin O staining, immunohistochemistry and ELISA. Additionally, mRNA expression of degenerative factors and catabolic markers known to be involved in cartilage degeneration in OA were analysed. Furthermore, the anabolic effects and underlying mechanisms of PGRN were investigated by in vitro experiments with primary chondrocytes. Results Here, we found that deficiency of PGRN led to spontaneous OA-like phenotype in ‘aged’ mice. Additionally, PGRN-deficient mice exhibited exaggerated breakdown of cartilage structure and OA progression, while local delivery of recombinant PGRN protein attenuated degradation of cartilage matrix and protected against OA development in surgically induced OA models. Furthermore, PGRN activated extracellular signal-regulated kinases (ERK) 1/2 signalling and elevated the levels of anabolic biomarkers in human chondrocyte, and the protective function of PGRN was mediated mainly through TNF receptor 2. Additionally, PGRN suppressed inflammatory action of TNF-α and inhibited the activation of β-Catenin signalling in cartilage and chondrocytes. Conclusions Collectively, this study provides new insight into the pathogenesis of OA, and also presents PGRN as a potential target for the treatment of joint degenerative diseases, including OA.
Functional Consequences of Integrin Gene Mutations in Mice
Authors: Daniel Bouvard, Cord Brakebusch, Erika Gustafsson, Attila Aszódi, Therese Bengtsson, Alejandro Berna, Reinhard Fässler
Journal: Circulation Research (2001)

Integrins are cell-surface receptors responsible for cell attachment to extracellular matrices and to other cells. The application of mouse genetics has significantly increased our understanding of integrin function in vivo. In this review, we summarize the phenotypes of mice carrying mutant integrin genes and compare them with phenotypes of mice lacking the integrin ligands.
Drugs and cardiovascular risk in inflammatory arthritis: another case of glucocorticoid-bashing?
Authors: Maarten Boers
Journal: Annals of the Rheumatic Diseases (2015)

I read with interest the meta-analysis by Roubille et al ,1 especially for the adverse effects noted with glucocorticoids (GCs). The data appear to confirm the risk of GC, which is surprising in view of the stated objective to include evidence from clinical trials. In a recent meta-analysis of randomised controlled trials (RCTs) that I participated in, no increased cardiovascular risk was found in 66 comparisons and a total …
Long Term Follow-Up of National Surgical Adjuvant Breast and Bowel Project Trial B-31: How Well Can We Predict Cardiac Toxicity With Trastuzumab?
Authors: Erica L. Mayer, Nancy U. Lin
Journal: Journal of Clinical Oncology (2012)

The physician must be able to tell the antecedents, know the present, and foretell the future-must mediate these things, and have two special objects in view … to do good or to do no harm.The art consists in three things-the disease, the patient, and the physician.
Insulin Autoimmune Syndrome Induced by α–Lipoic Acid in a Caucasian Woman: Case Report
Authors: Enrico Bresciani, Anna Bussi, Elena Bazzigaluppi, Gianpaolo Balestrieri
Journal: Diabetes Care (2011)

Insulin autoimmune syndrome (IAS) is a rare cause of hypoglycemia characterized by the production of autoantibodies to insulin in individuals without prior insulin administration. Drugs containing the sulfydryl group are known to be associated with this syndrome (1). IAS induced by α-lipoic acid (ALA) (a popular health supplement containing a sulfydryl group) has been described only in Japanese patients (2–4). We report on the first case of IAS likely induced by ALA in a Caucasian patient.

A 70-year-old Italian woman was referred to our hospital on 21 October 2010 because of recurrent episodes of sweating, weariness, and fainting occurring both fasting and postprandial. Her symptoms began 3 days before she entered the hospital. The patient, a …
MRI assessment of early response to certolizumab pegol in rheumatoid arthritis: a randomised, double-blind, placebo-controlled phase IIIb study applying MRI at weeks 0, 1, 2, 4, 8 and 16
Authors: M Østergaard, L T H Jacobsson, C Schaufelberger, M Sejer Hansen, J W J Bijlsma, A Dudek, M Rell-Bakalarska, F Staelens, R Haake, B Sundman-Engberg, H Bliddal
Journal: Annals of the Rheumatic Diseases (2014)

Objectives To identify the first time point of an MRI-verified response to certolizumab pegol (CZP) therapy in patients with rheumatoid arthritis (RA). Methods Forty-one patients with active RA despite disease-modifying antirheumatic drug therapy were randomised 2:1 to CZP (CZP loading dose 400 mg every 2 weeks at weeks 0–4; CZP 200 mg every 2 weeks at weeks 6–16) or placebo→CZP (placebo at weeks 0–2; CZP loading dose at weeks 2–6; CZP 200 mg every 2 weeks at weeks 8–16). Contrast-enhanced MRI of one hand and wrist was acquired at baseline (week 0) and weeks 1, 2, 4, 8 and 16. All six time points were read simultaneously, blinded to time, using the Outcome Measures in Rheumatology Clinical Trials RA MRI scoring system. Primary outcome was change in synovitis score in the CZP group; secondary outcomes were change in bone oedema (osteitis) and erosion scores and clinical outcome measures. Results Forty patients were treated (27 CZP, 13 placebo→CZP), and 36 (24 CZP, 12 placebo→CZP) completed week 16. In the CZP group, there were significant reductions from baseline synovitis (Hodges–Lehmann estimate of median change, −1.5, p=0.049) and osteitis scores (−2.5, p=0.031) at week 16. Numerical, but statistically insignificant, MRI inflammation reductions were observed at weeks 1–2 in the CZP group. No significant change was seen in bone erosion score. Improvements across all clinical outcomes were seen in the CZP group. Conclusions CZP reduced MRI synovitis and osteitis scores at week 16, despite small sample size and the technical challenge of reading six time points simultaneously. This study provides essential information on optimal MRI timing for subsequent trials. Trial registration number ClinicalTrials.gov, NCT01235598 .