tbuckley/cabot-search huggingface dataset:
Impact of Diabetes on Coronary Stenosis and Coronary Artery Calcification Detected by Electron-Beam Computed Tomography in Symptomatic Patients
Authors: Masayuki Hosoi, Toshihiko Sato, Keiko Yamagami, Takanori Hasegawa, Tetsuya Yamakita, Masafumi Miyamoto, Katsunobu Yoshioka, Tsunehiko Yamamoto, Tomofusa Ishii, Shiro Tanaka, Akira Itoh, Kazuo Haze, Satoru Fujii
Journal: Diabetes Care (2002)

OBJECTIVE—Ischemic heart disease is a pivotal complication for diabetic patients. Electron-beam computed tomography (EBCT) represents the only noninvasive method that allows for accurate quantification of coronary artery calcification that reflects underlying atherosclerotic disease. Although coronary calcium score (CCS) cut points that predict the presence of angiographic stenosis have been established in nondiabetic individuals, it is not known whether coronary calcifications in diabetic patients are associated with the presence of significant coronary stenoses. In this study, we evaluated the relationship between coronary calcifications and angiographic stenosis in symptomatic patients with or without type 2 diabetes. RESEARCH DESIGN AND METHODS—In this study, 282 patients (204 men and 78 women) with chest pain, including 101 diabetic patients and 181 nondiabetic patients (mean age 63 ± 9.6 years), underwent coronary angiography and EBCT with determination of CCS using Agatston’s method. Luminal stenosis ≥ 50% was defined as significant coronary stenosis. RESULTS—Angiography identified 205 patients with significant stenoses (89 of 101 diabetic patients, 114 of 181 nondiabetic patients). The sensitivity and specificity of EBCT to detect significant coronary stenosis were not significantly different between diabetic and nondiabetic patients. In diabetic patients, a CCS ≥90 was associated with 75% sensitivity and 75% specificity, whereas a CCS ≥200 was associated with 64% sensitivity and 83% specificity. CONCLUSIONS—We demonstrated that calcification of the coronary arteries in symptomatic diabetic patients is well associated with severity of coronary stenosis, as in nondiabetic patients.
Further studies on the composition of human femoral head cartilage.
Authors: A Maroudas, M T Bayliss, M F Venn
Journal: Annals of the Rheumatic Diseases (1980)

This report continues our previous studies on the composition and swelling of articular cartilage. When the protein part of the proteoglycan moiety has been taken into consideration, there is no longer a large fraction of the tissue which is not accounted for. In fact, the collagen, proteoglycans, and free electrolyte represent over 92% of the dry weight of adult femoral head cartilage, the remainder consisting most probably of other glycoproteins. Once the composition of cartilage had been well defined, it was possible to calculate the overall wet volume of tissue per unit weight of collagen for both normal and osteoarthritic cartilage. This is an important parameter, as it constitutes a direct measure of the extensibility of the collagen network. By determining the fixed charge density profile close to the articular surface, we have also been able to estimate the swelling pressure due to the proteoglycans in this region of the tissue, and to show that there is a gentle grading of osmotic stresses.
Measurement of Local Blood Flow with Hydrogen Gas
Authors: KNUR AUKLAND, BRUCE F. BOWER, ROBERT W. BERLINER
Journal: Circulation Research (1964)

When a platinized platinum electrode is polarized at the potential of the standard calomel electrode, the current generated is proportional to the concentration of dissolved hydrogen gas. The effects of physiological variations in oxygen tension, pH, temperature, and ascorbic acid concentration were found to be negligible. Although absolute calibration in vivo is not possible, the rate of tissue hydrogen saturation or desaturation can be measured by needle-shaped electrodes inserted into the tissue. Arterial and venous concentration can be measured with catheter electrodes. Solubility of hydrogen gas in kidney slices was found to be the same as in blood. With the assumption that tissue is in instantaneous diffusion equilibrium with local venous blood with respect to hydrogen, the local blood flow per volume of tissue can be calculated according to the Fick principle from the rate of tissue desaturation when arterial concentration is lowered to zero. The method was tested on dogs in myocardium, kidney, and skeletal muscle. Hydrogen was administered by respiration or by intra-arterial infusion of hydrogen-saturated saline, giving an arterial concentration of 3% to 5% saturation. Tissue desaturation curves were recorded simultaneously from two to three tissue electrodes. Good agreement with flow measured simultaneously with other methods was obtained in myocardium and renal cortex, while the data on skeletal muscle do not permit any definite conclusion. The main virtue of this method lies in the fact that repeated measurements of local blood flow can be obtained without access to arterial or local venous blood. Reliable measurements of regional blood flow were also obtained from continuously recorded venous desaturation curves, which also provide information on the distribution of blood flow.
Antiretroviral Prophylaxis for HIV Prevention in Heterosexual Men and Women
Authors: Jared M. Baeten, Deborah Donnell, Patrick Ndase, Nelly R. Mugo, James D. Campbell, Jonathan Wangisi, Jordan W. Tappero, Elizabeth A. Bukusi, Craig R. Cohen, Elly Katabira, Allan Ronald, Elioda Tumwesigye, Edwin Were, Kenneth H. Fife, James Kiarie, Carey Farquhar, Grace John-Stewart, Aloysious Kakia, Josephine Odoyo, Akasiima Mucunguzi, Edith Nakku-Joloba, Rogers Twesigye, Kenneth Ngure, Cosmas Apaka, Harrison Tamooh, Fridah Gabona, Andrew Mujugira, Dana Panteleeff, Katherine K. Thomas, Lara Kidoguchi, Meighan Krows, Jennifer Revall, Susan Morrison, Harald Haugen, Mira Emmanuel-Ogier, Lisa Ondrejcek, Robert W. Coombs, Lisa Frenkel, Craig Hendrix, Namandjé N. Bumpus, David Bangsberg, Jessica E. Haberer, Wendy S. Stevens, Jairam R. Lingappa, Connie Celum
Journal: New England Journal of Medicine (2012)

Antiretroviral preexposure prophylaxis is a promising approach for preventing human immunodeficiency virus type 1 (HIV-1) infection in heterosexual populations.We conducted a randomized trial of oral antiretroviral therapy for use as preexposure prophylaxis among HIV-1-serodiscordant heterosexual couples from Kenya and Uganda. The HIV-1-seronegative partner in each couple was randomly assigned to one of three study regimens--once-daily tenofovir (TDF), combination tenofovir-emtricitabine (TDF-FTC), or matching placebo--and followed monthly for up to 36 months. At enrollment, the HIV-1-seropositive partners were not eligible for antiretroviral therapy, according to national guidelines. All couples received standard HIV-1 treatment and prevention services.We enrolled 4758 couples, of whom 4747 were followed: 1584 randomly assigned to TDF, 1579 to TDF-FTC, and 1584 to placebo. For 62% of the couples followed, the HIV-1-seronegative partner was male. Among HIV-1-seropositive participants, the median CD4 count was 495 cells per cubic millimeter (interquartile range, 375 to 662). A total of 82 HIV-1 infections occurred in seronegative participants during the study, 17 in the TDF group (incidence, 0.65 per 100 person-years), 13 in the TDF-FTC group (incidence, 0.50 per 100 person-years), and 52 in the placebo group (incidence, 1.99 per 100 person-years), indicating a relative reduction of 67% in the incidence of HIV-1 with TDF (95% confidence interval [CI], 44 to 81; P<0.001) and of 75% with TDF-FTC (95% CI, 55 to 87; P<0.001). Protective effects of TDF-FTC and TDF alone against HIV-1 were not significantly different (P=0.23), and both study medications significantly reduced the HIV-1 incidence among both men and women. The rate of serious adverse events was similar across the study groups. Eight participants receiving active treatment were found to have been infected with HIV-1 at baseline, and among these eight, antiretroviral resistance developed in two during the study.Oral TDF and TDF-FTC both protect against HIV-1 infection in heterosexual men and women. (Funded by the Bill and Melinda Gates Foundation; Partners PrEP ClinicalTrials.gov number, NCT00557245.).
Unexpected Erythroid and Cytogenetic Responses After Discontinuation of a Short Course of Lenalidomide As a Result of Severe Skin Rash in a Patient With 5q Syndrome
Authors: Massimo Breccia, Laura Cannella, Roberto Latagliata, Giuseppina Loglisci, Adriano Salaroli, Michelina Santopietro, Esther N. Oliva, Giuliana Alimena
Journal: Journal of Clinical Oncology (2011)
The long-term effect of lifestyle interventions to prevent diabetes in the China Da Qing Diabetes Prevention Study: a 20-year follow-up study
Authors: Guangwei Li, Ping Zhang, Jinping Wang, Edward W Gregg, Wenying Yang, Qiuhong Gong, Hui Li, Hongliang Li, Yayun Jiang, Yali An, Ying Shuai, Bo Zhang, Jingling Zhang, Theodore J Thompson, Robert B Gerzoff, Gojka Roglic, Yinghua Hu, Peter H Bennett
Journal: The Lancet (2008)
Projecting the need for hip replacement over the next three decades: influence of changing demography and threshold for surgery
Authors: F. Birrell, O. Johnell, A. Silman
Journal: Annals of the Rheumatic Diseases (1999)

<h3>OBJECTIVES</h3> To estimate the requirement for total hip replacement in the United Kingdom over the next three decades <h3>METHODS</h3> Projection of age and sex specific hip replacements in the UK over 10 year intervals taking account of demographic change and the extrapolation of arthroplasty rates from Sweden; a country with recently introduced guidelines. <h3>RESULTS</h3> Assuming no change in the age and sex specific arthroplasty rates, the estimated number of hip replacements will increase by 40% over the next 30 year period because of demographic change alone. The proportionate change will be substantially higher in men (51%) than women (33%), with a doubling of the number of male hip replacements in those aged over 85. Changes in the threshold for surgery may increase this further—up to double the current number. <h3>CONCLUSION</h3> A sharp rise in hip replacements will be needed to satisfy needs in the UK population over the next 30 years.
Neurooncology clinical trial design for targeted therapies: Lessons learned from the North American Brain Tumor Consortium
Authors: Susan M. Chang, Kathleen R. Lamborn, John G. Kuhn, W.K. Alfred Yung, Mark R. Gilbert, Patrick Y. Wen, Howard A. Fine, Minesh P. Mehta, Lisa M. DeAngelis, Frank S. Lieberman, Timothy F. Cloughesy, H. Ian Robins, Lauren E. Abrey, Michael D. Prados
Journal: Neuro-Oncology (2008)

The North American Brain Tumor Consortium (NABTC) is a multi-institutional consortium with the primary objective of evaluating novel therapeutic strategies through early phase clinical trials. The NABTC has made substantial changes to the design and methodology of its trials since its inception in 1994. These changes reflect developments in technology, new types of therapies, and advances in our understanding of tumor biology and biological markers. We identify the challenges of early clinical assessment of therapeutic agents by reviewing the clinical trial effort of the NABTC and the evolution of the protocol template used to design trials. To better prioritize effort and allocation of patient resources and funding, we propose an integrated clinical trial design for the early assessment of efficacy of targeted therapies in neurooncology. This design would mandate tissue acquisition prior to therapeutic intervention with the drug, allowing prospective evaluation of its effects. It would also include a combined phase 0/I pharmacokinetic study to determine the safety and biologically optimal dose of the agent and to verify successful modulation of the target prior to initiating a larger, phase II efficacy study.
Interstitial Fluid Pressure as a Prognostic Factor in Cervical Cancer Following Radiation Therapy
Authors: Seung-Gu Yeo, Jun-Sang Kim, Moon-June Cho, Ki-Hwan Kim, Jae-Sung Kim
Journal: Clinical Cancer Research (2009)

Abstract Purpose: To investigate tumor interstitial fluid pressure as a prognostic factor for recurrence-free survival in patients with cervical cancer following radiation therapy. Experimental Design: Tumor interstitial fluid pressure was measured in 55 cervical cancer patients who received radiation therapy between August 1998 and September 2002. Interstitial fluid pressure measurements were made before radiation therapy (pre–radiation therapy interstitial fluid pressure) and after a median of 28.8 Gy in 16 fractions (range, 25.2-30.6 Gy in 14-17 fractions) of radiation therapy (mid–radiation therapy interstitial fluid pressure), using a modified wick-in-needle technique. Median follow-up was 74 months (range, 2-118 months). The Kaplan-Meier method with the log-rank test and Cox's proportional hazard model were used in univariate and multivariate analyses, respectively, of prognostic factors for recurrence-free survival. Results: Median pre–radiation therapy and mid–radiation therapy interstitial fluid pressure were 29.0 mm Hg (range, 4.0-93.9 mm Hg) and 20.0 mm Hg (range, −1.2 to 29.6 mm Hg), respectively (P = 0.001). Pre–radiation therapy interstitial fluid pressure was significantly higher in adenocarcinomas than squamous cell carcinomas (P = 0.028). Significant reduction of interstitial fluid pressure was noted only in patients with complete responses (P = 0.002), and mid–radiation therapy interstitial fluid pressure was significantly lower in patients with complete responses (P = 0.036). In the multivariate analysis including interstitial fluid pressures and clinical variables, pre–radiation therapy interstitial fluid pressure was an independent prognostic factor for local and distant recurrence-free survival (P = 0.001 and 0.027, respectively). Conclusions: Mid–radiation therapy interstitial fluid pressure measurement may be useful in predicting radiation therapy responses, and pre–radiation therapy interstitial fluid pressure was a significant prognostic factor for local and distant relapse-free survival in patients with cervical cancer after radiation therapy. (Clin Cancer Res 2009;15(19):6201–7)
Gene Expression Signature With Independent Prognostic Significance in Epithelial Ovarian Cancer
Authors: Dimitrios Spentzos, Douglas A. Levine, Marco F. Ramoni, Marie Joseph, Xuesong Gu, Jeff Boyd, Towia. A. Libermann, Stephen A. Cannistra
Journal: Journal of Clinical Oncology (2004)

Currently available clinical and molecular prognostic factors provide an imperfect assessment of prognosis for patients with epithelial ovarian cancer (EOC). In this study, we investigated whether tumor transcription profiling could be used as a prognostic tool in this disease.Tumor tissue from 68 patients was profiled with oligonucleotide microarrays. Samples were randomly split into training and validation sets. A three-step training procedure was used to discover a statistically significant Kaplan-Meier split in the training set. The resultant prognostic signature was then tested on an independent validation set for confirmation.In the training set, a 115-gene signature referred to as the Ovarian Cancer Prognostic Profile (OCPP) was identified. When applied to the validation set, the OCPP distinguished between patients with unfavorable and favorable overall survival (median, 30 months v not yet reached, respectively; log-rank P = .004). The signature maintained independent prognostic value in multivariate analysis, controlling for other known prognostic factors such as age, stage, grade, and debulking status. The hazard ratio for death in the unfavorable OCPP group was 4.8 (P = .021 by Cox proportional hazards analysis).The OCPP is an independent prognostic determinant of outcome in EOC. The use of gene profiling may ultimately permit identification of EOC patients appropriate for investigational treatment approaches, based on a low likelihood of achieving prolonged survival with standard first-line platinum-based therapy.
Nature and standards of gastrointestinal and liver services in the United Kingdom.
Authors: M J Farthing, R Williams, C H Swan, A Burroughs, R C Heading, J A Dodge, R I Russell, C W Venables, R Dick, R Burnham
Journal: Gut (1993)

1. Purpose of the working party: 1.1 To describe the scope of major digestive and liver disorders and identify changes in patterns of disease. 1.2 To identify diagnostic and therapeutic services required to manage these disorders in the United Kingdom. 1.3 To describe the facilities and staffing required to provide these services. 1.4 To examine the training requirements for medical, nursing, and other support staff. 1.5 To define the part that audit and research should play in the provision and maintenance of high quality gastrointestinal and liver services.
Mechanism of biphasic contractions in strontium-treated ventricular muscle.
Authors: B W King, D Bose
Journal: Circulation Research (1983)

Biphasic contractions were produced in dog trabeculae by replacing 90-95% of the calcium in the bathing solution with strontium. These conditions produced prolonged action potentials accompanied by contractions with two distinct phasic components. The early component disappeared slowly when the remaining Ca++ was removed, whereas the late component was eliminated quickly when Sr++ was removed. Manganese ion (0.25 mM) preferentially decreased the late component without changing the action potential, whereas caffeine and ryanodine decreased or eliminated the early component. Ryanodine did not alter the action potential. Isoproterenol rapidly increased the early component and, more slowly and to a lesser degree, increased the late component. The results suggest that the early component is caused by intracellular release of activator cation, probably from the sarcoplasmic reticulum, whereas the late component is the result of Sr++ entry across the sarcolemma, possibly by way of the slow inward current.
Multiple human beta interferon genes.
Authors: A D Sagar, P B Sehgal, D L Slate, F H Ruddle
Journal: The Journal of Experimental Medicine (1982)

Analysis of human beta interferon (IFN) mRNA preparations obtained from poly(I) . poly (C)-induced human diploid fibroblasts (FS-4) and from several similarly induced human-mouse somatic cell hybrids by electrophoresis through agarose-CH3HgOH tube gels led to the detection of at least five translationally active human IFN-beta mRNA species. The results obtained are consistent with the existence of IFN-beta genes on different human chromosomes. Marked cell-dependent variability in the expression of these IFN mRNA species was observed.
Role of tumour necrosis factor- receptor p75 in cigarette smoke-induced pulmonary inflammation and emphysema
Authors: A. I. D'hulst, K. R. Bracke, T. Maes, J. L. De Bleecker, R. A. Pauwels, G. F. Joos, G. G. Brusselle
Journal: European Respiratory Journal (2006)

Chronic obstructive pulmonary disease (COPD) is characterised by a local pulmonary inflammatory response to respiratory pollutants and by systemic inflammation. Tumour necrosis factor (TNF)-α has been implicated in systemic effects of COPD and operates by binding the p55 (R1) and p75 (R2) TNF-α receptors. To investigate the contribution of each TNF-α receptor in the pathogenesis of COPD, the present study examined the effects of chronic air or cigarette smoke (CS) exposure in TNF-α R1 knockout (KO) mice, TNF-α R2 KO mice and wild type (WT) mice. CS was found to significantly increase the protein levels of soluble TNF-α R1 (by four-fold) and TNF-α R2 (by 10-fold) in the bronchoalveolar lavage of WT mice. After 3 months, CS induced a prominent pulmonary inflammatory cell influx in WT and TNF-α R1 KO mice. In TNF-α R2 KO mice, CS-induced pulmonary inflammation was clearly attenuated. After 6 months, no emphysema was observed in CS-exposed TNF-α R2 KO mice in contrast to WT and TNF-α R1 KO mice. CS-exposed WT and TNF-α R1 KO mice failed to gain weight, whereas the body mass of TNF-α R2 KO mice was not affected. These current findings suggest that both tumour necrosis factor-α receptors contribute to the pathogenesis of chronic obstructive pulmonary disease, but tumour necrosis factor-α receptor-2 is the most active receptor in the development of inflammation, emphysema and systemic weight loss in this murine model of chronic obstructive pulmonary disease.
Genetical control of B-cell responses. IV. Inheritance of the unresponsiveness to lipopolysaccharides.
Authors: A Coutinho, G Moller, E Gronowicz
Journal: The Journal of Experimental Medicine (1975)

The inheritance of B-cell responsiveness to lipopolysaccharide (LPS) was studied in 55 crosses between mice of the low-responder strain C3H/HeJ and the high-responder strains B10.5M and C3H/Tif. F1 hybrid mice between the low-and the high-responder strains, showed in every case responses which were intermediate between the responses obtained with each parent. The responsiveness among F2 hybrid and backcross mice to either high- or low-responder parents, segregated into intermediate, high, or low categories, respectively. The present results are compatible with the hypothesis that responsiveness to LPS is determined by one single, codominantly expressed, autosomal gene. The capacity to develop a specific thymus-independent response to a hapten-LPS conjugate, also under genetical control, was found to segregate together with the capacity to develop polyclonal responses to LPS.
Phase III Randomized Trial of Intravenous Cisplatin Plus a 24- or 96-Hour Infusion of Paclitaxel in Epithelial Ovarian Cancer: A Gynecologic Oncology Group Study
Authors: David R. Spriggs, Mark F. Brady, Luis Vaccarello, Daniel L. Clarke-Pearson, Robert A. Burger, Robert Mannel, John F. Boggess, Roger B. Lee, Mark Hanly
Journal: Journal of Clinical Oncology (2007)

This study was undertaken to assess if prolonged paclitaxel administration in combination with cisplatin improves overall survival (OS) in epithelial ovarian cancer (EOC).Eligible patients with suboptimal stage III or IV EOC, fallopian tube, or primary peritoneal cancer were randomly allocated to receive six cycles of cisplatin 75 mg/m2 and either paclitaxel 135 mg/m2 during 24 hours (arm 1) or paclitaxel 120 mg/m2 during 96 hours (arm 2).Planned accrual was 324 patients; 293 were enrolled before the study was closed as a result of a scheduled interim futility analysis. There were 13 ineligible patients; thus, 140 patients in each arm were assessable. In arm 1, 80% of patients completed all six cycles compared with 83% of patients in arm 2. Grade 4 granulocytopenia was more common in arm 1 (79% v 54%; P < .001) whereas grade 3 or worse anemia was more severe in arm 2 (6% v 18%; P < .003). The median progression-free survival was 1.03 years for arm 1 versus 1.05 years for arm 2. The median OS was 2.49 and 2.54 years for arms 1 and 2, respectively. There have been 237 reported deaths. The relative death rate was approximately 12% greater in arm 2 (hazard ratio, 1.12; 95% CI, 0.860 to 1.45).Patients with advanced EOC have a relatively poor prognosis. The results of treatment with cisplatin and paclitaxel are not significantly improved by prolonging the paclitaxel infusion from 24 to 96 hours.