tbuckley/cabot-search huggingface dataset:
Endoscopic injection sclerotherapy vs. endoscopic variceal ligation in arresting acute variceal bleeding for patients with advanced hepatocellular carcinoma
Authors: Gin-Ho Lo, Kwok-Hung Lai, Chia-Fu Chang, Ming-Tse Shen, Jin-Shiung Jeng, Rong-Long Huang, Jia-Huey Hwu
Journal: Journal of Hepatology (1994)
Calcium plus Vitamin D Supplementation and the Risk of Fractures
Authors: Rebecca D. Jackson, Andrea Z. LaCroix, Margery Gass, Robert B. Wallace, John Robbins, Cora E. Lewis, Tamsen Bassford, Shirley A.A. Beresford, Henry R. Black, Patricia Blanchette, Denise E. Bonds, Robert L. Brunner, Robert G. Brzyski, Bette Caan, Jane A. Cauley, Rowan T. Chlebowski, Steven R. Cummings, Iris Granek, Jennifer Hays, Gerardo Heiss, Susan L. Hendrix, Barbara V. Howard, Judith Hsia, F. Allan Hubbell, Karen C. Johnson, Howard Judd, Jane Morley Kotchen, Lewis H. Kuller, Robert D. Langer, Norman L. Lasser, Marian C. Limacher, Shari Ludlam, JoAnn E. Manson, Karen L. Margolis, Joan McGowan, Judith K. Ockene, Mary Jo O'Sullivan, Lawrence Phillips, Ross L. Prentice, Gloria E. Sarto, Marcia L. Stefanick, Linda Van Horn, Jean Wactawski-Wende, Evelyn Whitlock, Garnet L. Anderson, Annlouise R. Assaf, David Barad
Journal: New England Journal of Medicine (2006)

The efficacy of calcium with vitamin D supplementation for preventing hip and other fractures in healthy postmenopausal women remains equivocal.We recruited 36,282 postmenopausal women, 50 to 79 years of age, who were already enrolled in a Women's Health Initiative (WHI) clinical trial. We randomly assigned participants to receive 1000 mg of elemental [corrected] calcium as calcium carbonate with 400 IU of vitamin D3 daily or placebo. Fractures were ascertained for an average follow-up period of 7.0 years. Bone density was measured at three WHI centers.Hip bone density was 1.06 percent higher in the calcium plus vitamin D group than in the placebo group (P<0.01). Intention-to-treat analysis indicated that participants receiving calcium plus vitamin D supplementation had a hazard ratio of 0.88 for hip fracture (95 percent confidence interval, 0.72 to 1.08), 0.90 for clinical spine fracture (0.74 to 1.10), and 0.96 for total fractures (0.91 to 1.02). The risk of renal calculi increased with calcium plus vitamin D (hazard ratio, 1.17; 95 percent confidence interval, 1.02 to 1.34). Censoring data from women when they ceased to adhere to the study medication reduced the hazard ratio for hip fracture to 0.71 (95 percent confidence interval, 0.52 to 0.97). Effects did not vary significantly according to prerandomization serum vitamin D levels.Among healthy postmenopausal women, calcium with vitamin D supplementation resulted in a small but significant improvement in hip bone density, did not significantly reduce hip fracture, and increased the risk of kidney stones. (ClinicalTrials.gov number, NCT00000611.).
<i>Mycobacterium tuberculosis</i> Expresses a Novel Ph-Dependent Divalent Cation Transporter Belonging to the Nramp Family
Authors: Daniel Agranoff, Irene M. Monahan, Joseph A. Mangan, Philip D. Butcher, Sanjeev Krishna
Journal: The Journal of Experimental Medicine (1999)

Mammalian natural resistance–associated macrophage protein (Nramp) homologues are important determinants of susceptibility to infection by diverse intracellular pathogens including mycobacteria. Eukaryotic Nramp homologues transport divalent cations such as Fe2+, Mn2+, Zn2+, and Cu2+. Mycobacterium tuberculosis and Mycobacterium bovis (bacillus Calmette-Guérin [BCG]) also encode an Nramp homologue (Mramp). RNA encoding Mramp induces ∼20-fold increases in 65Zn2+ and 55Fe2+ uptake when injected into Xenopus laevis oocytes. Transport is dependent on acidic extracellular pH and is maximal between pH 5.5 and 6.5. Mramp-mediated 65Zn2+ and 55Fe2+ transport is abolished by an excess of Mn2+ and Cu2+, confirming that Mramp interacts with a broad range of divalent transition metal cations. Using semiquantitative reverse transcription PCR, we show that Mramp mRNA levels in M. tuberculosis are upregulated in response to increases in ambient Fe2+ and Cu2+ between &amp;lt;1 and 5 μM concentrations and that this upregulation occurs in parallel with mRNA for y39, a putative metal-transporting P-type ATPase. Using a quantitative ratiometric PCR technique, we demonstrate a fourfold decrease in Mramp/y39 mRNA ratios from organisms grown in 5–70 μM Cu2+. M. bovis BCG cultured axenically and within THP-1 cells also expresses mRNA encoding Mramp. Mramp exemplifies a novel prokaryotic class of metal ion transporter. Within phagosomes, Mramp and Nramp1 may compete for the same divalent cations, with implications for intracellular survival of mycobacteria.
Aetiology and outcome of severe community-acquired pneumonia in Singapore
Authors: YK Tan, KL Khoo, SP Chin, YY Ong
Journal: European Respiratory Journal (1998)

The aim of this study was to determine the aetiology and outcome of severe community-acquired pneumonia, and to assess whether the existing guidelines for initial antimicrobial therapy are being applied. The records of 57 consecutive nonimmunocompromised patients admitted to the medical intensive care unit (ICU) between January 1989 and May 1993 with this diagnosis were reviewed. The microbiological data, chest radiographic changes and outcome were analysed. Nine (16%) of the 57 patients had pulmonary tuberculosis. When these patients were excluded from further analysis, a microbiological diagnosis was made in 41 (72%) cases. The most commonest pathogens were Burkholderia pseudomallei (n=10), Klebsiella spp. (n=5) and Staphylococcus aureus (n=5), Mycoplasma pneumoniae (n=4) and Streptococcus pneumoniae (n=2) were less common. This microbiological spectrum was quite different from that in the West, where the incidence of S. pneumoniae was higher. Also, when pulmonary tuberculosis was excluded, the mortality (67%) was much higher than that in other series. This was attributed to the high incidence of unrecognized B. pseudomallei infection, which is associated with a very high mortality in the region under study. In addition to applying published guidelines on severe community-acquired pneumonia, the endemicity of certain organisms such as Mycobacterium tuberculosis and Burkholderia pseudomallei in different geographical regions needs to be considered when choosing initial empirical antimicrobial therapy.
Hemodynamic Responses to Rapid Saline Loading
Authors: Naoki Fujimoto, Barry A. Borlaug, Gregory D. Lewis, Jeffrey L. Hastings, Keri M. Shafer, Paul S. Bhella, Graeme Carrick-Ranson, Benjamin D. Levine
Journal: Circulation (2012)

Background— Hemodynamic assessment after volume challenge has been proposed as a way to identify heart failure with preserved ejection fraction. However, the normal hemodynamic response to a volume challenge and how age and sex affect this relationship remain unknown. Methods and Results— Sixty healthy subjects underwent right heart catheterization to measure age- and sex-related normative responses of pulmonary capillary wedge pressure and mean pulmonary arterial pressure to volume loading with rapid saline infusion (100–200 mL/min). Hemodynamic responses to saline infusion in heart failure with preserved ejection fraction (n=11) were then compared with those of healthy young (&lt;50 years of age) and older (≥50 years of age) subjects. In healthy subjects, pulmonary capillary wedge pressure increased from 10±2 to 16±3 mm Hg after ~1 L and to 20±3 mm Hg after ~2 L of saline infusion. Older women displayed a steeper increase in pulmonary capillary wedge pressure relative to volume infused (16±4 mm Hg·L −1 ·m 2 ) than the other 3 groups ( P ≤0.019). Saline infusion resulted in a greater increase in mean pulmonary arterial pressure relative to cardiac output in women compared with men regardless of age. Subjects with heart failure with preserved ejection fraction exhibited a steeper increase in pulmonary capillary wedge pressure relative to infused volume (25±12 mm Hg·L −1 ·m 2 ) than healthy young and older subjects ( P ≤0.005). Conclusions— Filling pressures rise significantly with volume loading, even in healthy volunteers. Older women and patients with heart failure with preserved ejection fraction exhibit the largest increases in pulmonary capillary wedge pressure and mean pulmonary arterial pressure.
Textbook of Pediatric Rheumatology
Authors: B. M. Ansell
Journal: Annals of the Rheumatic Diseases (1984)

<h3>Background and objectives</h3> Alemtuzumab is a humanized anti-CD52 monoclonal antibody used as induction in kidney transplantation (KTX) since 2003. Few studies have evaluated long-term outcomes of this agent or changes in outcomes over time. <h3>Design, setting, participants, &amp; measurements</h3> A retrospective cohort study was performed examining United States registry data from 2003 to 2014 of primary KTX recipients receiving induction with alemtuzumab (AZ; <i>n</i>=5521) or antithymocyte globulin (ATG; <i>n</i>=8504) and maintenance immunosuppression with tacrolimus and mycophenolate mofetil and early withdrawal of steroids. The primary outcome was overall death-censored graft survival (DCGS), and secondary outcomes were overall patient survival and 1-year acute rejection. Multivariate models were fit with donor, recipient, and transplant covariates. Because poorer outcomes with AZ may occur from a learning curve impact with the use of a new medication, transplant year was categorized into three time periods to evaluate outcomes over time (2003–2005, 2006–2008, ≥2009), and an interaction term of induction type with transplant year category was included in all models to test for era impacts. <h3>Results</h3> On multivariate analysis of DCGS there was a significant interaction between AZ and era (<i>P</i>&lt;0.001). AZ was significantly associated with inferior DCGS in the earliest 2003–2005 era (adjusted hazard ratio [aHR], 2.21; 95% confidence interval [95% CI], 1.72 to 2.84) but not in the middle 2006–2008 era (aHR, 1.14; 95% CI, 0.96 to 1.36) or the most recent 2009–2014 era (aHR, 1.08; 95% CI, 0.90 to 1.29) compared with ATG. Risk-adjusted patient survival (aHR, 1.32; 95% CI, 1.08 to 1.61; aHR, 1.26; 95% CI, 1.09 to 1.46; and aHR, 1.10; 95% CI, 0.93 to 1.29 by era, respectively) and acute rejection (adjusted odds ratio [aOR], 1.17; 95% CI, 0.96 to 1.42; aOR, 0.94; 95% CI, 0.82 to 1.07; aOR, 0.89; 95% CI, 0.81 to 0.98 by era, respectively) with AZ was comparable with ATG in the most recent era; however, there was no significant interaction with time (<i>P</i>=0.13 and <i>P</i>=0.06, respectively). <h3>Conclusions</h3> Current alemtuzumab utilization is associated with comparable graft and patient survival and acute rejection compared with ATG. Graft survival with alemtuzumab has improved over time.
Angiopoietin-2–Induced Arterial Stiffness in CKD
Authors: Fan-Chi Chang, Wen-Chih Chiang, Ming-Hsuan Tsai, Yu-Hsiang Chou, Szu-Yu Pan, Yu-Ting Chang, Pei-Ying Yeh, Yi-Ting Chen, Chih-Kang Chiang, Yung-Ming Chen, Tzong-Shinn Chu, Kwan-Dun Wu, Shuei-Liong Lin
Journal: Journal of the American Society of Nephrology (2014)

The mechanism of vascular calcification in CKD is not understood fully, but may involve collagen deposition in the arterial wall upon osteo/chondrocytic transformation of vascular smooth muscle cells (VSMCs). Increased levels of circulating angiopoietin-2 correlate with markers of CKD progression and angiopoietin-2 regulate inflammatory responses, including intercellular and vascular adhesion and recruitment of VSMCs. Here, we investigate the potential role of angiopoietin-2 in the pathogenesis of arterial stiffness associated with CKD. In a cohort of 416 patients with CKD, the plasma level of angiopoietin-2 correlated independently with the severity of arterial stiffness assessed by pulse wave velocity. In mice subjected to 5/6 subtotal nephrectomy or unilateral ureteral obstruction, plasma levels of angiopoietin-2 also increased. Angiopoietin-2 expression markedly increased in tubular epithelial cells of fibrotic kidneys but decreased in other tissues, including aorta and lung, after 5/6 subtotal nephrectomy. Expression of collagen and profibrotic genes in aortic VSMCs increased in mice after 5/6 subtotal nephrectomy and in mice producing human angiopoietin-2. Angiopoietin-2 stimulated endothelial expression of chemokines and adhesion molecules for monocytes, increased Ly6C(low) macrophages in aorta, and increased the expression of the profibrotic cytokine TGF-β1 in aortic endothelial cells and Ly6C(low) macrophages. Angiopoietin-2 blockade attenuated expression of monocyte chemokines, profibrotic cytokines, and collagen in aorta of mice after 5/6 subtotal nephrectomy. This study identifies angiopoietin-2 as a link between kidney fibrosis and arterial stiffness. Targeting angiopoietin-2 to attenuate inflammation and collagen expression may provide a novel therapy for cardiovascular disease in CKD.
The Childhood Cancer Survivor Study: A National Cancer Institute–Supported Resource for Outcome and Intervention Research
Authors: Leslie L. Robison, Gregory T. Armstrong, John D. Boice, Eric J. Chow, Stella M. Davies, Sarah S. Donaldson, Daniel M. Green, Sue Hammond, Anna T. Meadows, Ann C. Mertens, John J. Mulvihill, Paul C. Nathan, Joseph P. Neglia, Roger J. Packer, Preetha Rajaraman, Charles A. Sklar, Marilyn Stovall, Louise C. Strong, Yutaka Yasui, Lonnie K. Zeltzer
Journal: Journal of Clinical Oncology (2009)

Survival for childhood cancer has increased dramatically over the last 40 years with 5-year survival rates now approaching 80%. For many diagnostic groups, rapid increases in survival began in the 1970s with the broader introduction of multimodality approaches, often including combination chemotherapy with or without radiation therapy. With this increase in rates of survivorship has come the recognition that survivors are at risk for adverse health and quality-of-life outcomes, with risk being influenced by host-, disease-, and treatment-related factors. In 1994, the US National Cancer Institute funded the Childhood Cancer Survivor Study, a multi-institutional research initiative designed to establish a large and extensively characterized cohort of more than 14,000 5-year survivors of childhood and adolescent cancer diagnosed between 1970 and 1986. This ongoing study, which reflects the single most comprehensive body of information ever assembled on childhood and adolescent cancer survivors, provides a dynamic framework and resource to investigate current and future questions about childhood cancer survivors.
Therapeutic targets in osteoarthritis: from today to tomorrow with new imaging technology
Authors: J-P Pelletier
Journal: Annals of the Rheumatic Diseases (2003)

Over the last decade, there have been several interesting advances in the treatment of osteoarthritis (OA). A clearer understanding of the pathophysiology of this disease1 has facilitated the development of new approaches for treatments aimed at specifically and effectively retarding disease progress. New classes of molecules that inhibit one or more OA catabolic processes are under evaluation for their potential to alter the degenerative process.

OA can be described as the degradation and loss of articular cartilage accompanied by subchondral bone remodelling, osteophyte formation, and synovial membrane inflammation. This is clinically reflected by gradual development of fluctuating joint pain, swelling, stiffness, and loss of motion. Pharmacological interventions have focused on treating pain, primarily using non-steroidal anti-inflammatory drugs (NSAIDs), analgesics, and, more recently, specific cyclo-oxygenase-2 (COX-2) inhibitors. The rationale behind this was to inhibit COX, the key enzymes that metabolise arachidonic acid to prostaglandins.

Clinical studies to date have focused on the alleviation of signs and symptoms, for which comparable efficacy has generally been found for NSAIDs and acetaminophen in stable cohorts of patients with mild to moderate OA.2,3 Published data on the use of intra-articular corticosteroids for OA have shown short term (up to four weeks) improvement in signs and symptoms compared with placebo.2,4 The comparative efficacy of these agents in the treatment of episodic crystal induced inflammatory exacerbations superimposed on chronic OA in selected patients,5 for which one might predict the superior efficacy of NSAIDs or corticosteroids over acetaminophen, has not been studied. However, the main objectives in the management of OA are not only to reduce symptoms and minimise functional disability, but also to limit progression of structural changes.

As there are in vitro data to indicate that corticosteroids inhibit synoviocytes and chondrocyte production of interleukin 1 (IL1), COX-2, and tumour necrosis …
The antiangiogenic protein kinase inhibitors SU5416 and SU6668 inhibit the SCF receptor (c-kit) in a human myeloid leukemia cell line and in acute myeloid leukemia blasts
Authors: Beverly D. Smolich, Helene A. Yuen, Kristina A. West, Francis J. Giles, Maher Albitar, Julie M. Cherrington
Journal: Blood (2001)
Physiological effects of flow and pressure triggering during non- invasive mechanical ventilation in patients with chronic obstructive pulmonary disease
Authors: S. Nava, N. Ambrosino, C. Bruschi, M. Confalonieri, C. Rampulla
Journal: Thorax (1997)

BACKGROUND: The effect of the type of trigger system on inspiratory effort has been studied in intubated patients, but no data are available in non-invasive mechanical ventilation where the "trigger variable" may be even more important since assisted modes of ventilation are often employed from the beginning of mechanical ventilation. METHODS: The effect of flow triggering (1 and 5 1/min) and pressure triggering (-1 cm H2O) on inspiratory effort during pressure support ventilation (PSV) and assisted controlled mode (A/C) delivered non-invasively with a full face mask were compared in patients with chronic obstructive pulmonary disease (COPD) recovering from an acute exacerbation. The patients were studied during randomised 15 minute runs at zero positive end expiratory pressure (ZEEP). The oesophageal pressure time product (PTPoes), dynamic intrinsic PEEP (PEEPi,dyn), fall in maximal airway pressure (delta Paw) during inspiration, and ventilatory variables were measured. RESULTS: Minute ventilation, respiratory pattern, dynamic lung compliance and resistances, and changes in end expiratory lung volume (delta EELV) were the same with the two triggering systems. The total PTPoes and its pre-triggering phase (PTP due to PEEPi and PTP due to valve opening) were significantly higher during both PSV and A/C with pressure triggering than with flow triggering at both levels of sensitivity. delta Paw was larger during pressure triggering, and PEEPi,dyn was significantly reduced during flow triggering in the A/C mode only. CONCLUSIONS: In patients with COPD flow triggering reduces the inspiratory effort during both PSV and A/C modes compared with pressure triggering. These findings are likely to be due to a reduction in PEEPi,dyn and in the time of valve opening with a flow trigger.
Population-Based Study of Human Papillomavirus Infection and Cervical Neoplasia in Rural Costa Rica
Authors: Rolando Herrero, Allan Hildesheim, Concepcion Bratti, Mark E. Sherman, Martha Hutchinson, Jorge Morales, Ileana Balmaceda, Mitchell D. Greenberg, Mario Alfaro, Robert D. Burk, Sholom Wacholder, Martyn Plummer, Mark Schiffman
Journal: JNCI Journal of the National Cancer Institute (2000)

Human papillomavirus (HPV) is the main cause of cervical neoplasia. Because few population-based studies have investigated the prevalence of type-specific infection in relation to cervical disease, we studied a high-risk population, estimating the prevalence of HPV infection and the risk associated with various HPV types.We screened 9175 women in Guanacaste, Costa Rica, to obtain a referent standard final diagnosis, and tested 3024 women for more than 40 types of HPV with a polymerase chain reaction-based system.Among women with normal cytology, HPV infections peaked first in women younger than 25 years, and they peaked again at age 55 years or older with predominantly non-cancer-associated types of HPV and uncharacterized HPV types. Low-grade squamous intraepithelial lesions (LSILs) (n = 189) decreased consistently with age. The prevalence of high-grade squamous intraepithelial lesions (HSILs) (n = 128) peaked first around age 30 years and again at age 65 years or older. Seventy-three percent of LSILs were HPV positive, with HPV16 being the predominant type (16% of positive subjects). HPV was found in 89% of HSILs and 88% of cancers, with HPV16 being strongly predominant (51% and 53% of positive subjects). Virtually all HSILs and cancers had cancer-associated HPV types, with high odds ratios (ORs) and attributable fractions around 80%. Risk for HPV16 was particularly high (OR for HSILs = 320, 95% confidence interval [CI] = 97-1000; OR for cancer = 710, 95% CI = 110-4500).We confirm the early decline of HPV infection with age but note increased prevalence after menopause, which could be related to a second peak of HSILs, an observation that warrants further investigation. At least 80% of HPVs involved in cervical carcinogenesis in this population have been characterized. Polyvalent vaccines including the main cancer-associated HPV types may be able to prevent most cases of cervical disease in this region.
Brief Report: Distinct Dysregulation of the Small Leucine‐Rich Repeat Protein Family in Osteoarthritic Acetabular Labrum Compared to Articular Cartilage
Authors: Nele Juchtmans, Aad A. M. Dhollander, Julie Coudenys, Emmanuel A. Audenaert, Christophe Pattyn, Stijn Lambrecht, Dirk Elewaut
Journal: Arthritis & Rheumatology (2014)

Articular cartilage is well studied in osteoarthritis (OA). However, the role of supporting structures, such as the acetabular labrum, a sealing structure surrounding the hip joint, has been investigated much less. We recently showed that fibrochondrocytic labrum cells are metabolically active. This study was undertaken to investigate hip OA–associated changes in human acetabular labrum cells.Microarray analysis was performed to compare OA labrum cells to healthy labrum cells cultured in a 3-dimensional alginate bead system. Data were analyzed by cluster analysis using gene set enrichment analysis software and by gene list analysis using PANTHER gene family tools. Selected candidates were validated by quantitative polymerase chain reaction analysis on labrum and cartilage samples and by immunohistochemistry. The functional impacts of the genes identified were investigated by in vitro stimulation experiments in labrum cells.Pathway analysis revealed increased cytokine and chemokine signaling in OA labrum cells, whereas reduced extracellular matrix interactions and transforming growth factor β signaling were observed. Several genes were significantly differentially expressed in OA compared to healthy labrum. We specifically focused on 3 small leucine-rich repeat proteins (SLRPs), osteomodulin, osteoglycin, and asporin, that appeared to be distinctly regulated in OA labrum compared to OA cartilage. SLRPs were strongly down-regulated in OA labrum but up-regulated in OA articular chondrocytes. Moreover, in vitro stimulation with osteomodulin increased aggrecan expression in OA labrum cells.OA labrum fibrochondrocytes have several features similar to OA chondrocytes. However, SLRP expression seems to be differentially influenced by degeneration in OA labrum compared to cartilage, suggesting a specific role for this supporting structure in OA. The functional impact of SLRPs on labrum cells makes them interesting targets for further studies in hip OA.