tbuckley/cabot-search huggingface dataset:
MRP8 and MRP14, phagocyte-specific danger signals, are sensitive biomarkers of disease activity in cryopyrin-associated periodic syndromes
Authors: H. Wittkowski, J. B. Kuemmerle-Deschner, J. Austermann, D. Holzinger, R. Goldbach-Mansky, K. Gramlich, P. Lohse, T. Jung, J. Roth, S. M. Benseler, D. Foell
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Objectives</h3> To assess the sensitivity of the phagocyte-specific molecules myeloid-related protein (MRP) 8 and MRP14 (calprotectin) for monitoring disease activity during anti-interleukin (IL)-1 therapies in patients with cryopyrin-associated periodic syndromes (CAPS), including familial cold autoinflammatory syndrome (FCAS), Muckle–Wells syndrome (MWS) and chronic infantile neurological, cutaneous and articular (CINCA) syndrome. <h3>Methods</h3> A total of 39 patients with CAPS, including 5 FCAS, 16 MWS and 18 CINCA syndrome, received anti-IL-1 therapy. All patients with CINCA and 12 with MWS were treated with IL-1Ra (anakinra), 14 patients with MWS with a monoclonal anti-IL-1β antibody (canakinumab) and patients with FCAS received IL-1 Trap (rilonacept). During serial clinical visits serum amyloid A, C-reactive protein, erythrocyte sedimentation rate and MRP8/14 serum levels were analysed. <h3>Results</h3> Untreated patients with CAPS had significantly elevated MRP8/14 values. In response to treatment there was a significant reduction of MRP8/14 levels in CINCA (2,830 (range 690 – 8,480) ng/ml to 670 ng/ml, p &lt; 0.001) and MWS patients (anakinra-treated: 4,390 (1790 – 9780) ng/ml to 1,315 ng/ml (p = 0.003); canakinumab-treated: 3,000 (500 – 13060) ng/ml to 630 ng/ml (p=0.001)). However, in many patients with CAPS, MRP8/14 levels were still elevated compared with healthy individuals, reflecting residual disease activity. However, canakinumab-treated patients with CAPS showed normalised MRP8/14 levels, suggesting control of phagocyte activation. <h3>Conclusions</h3> Monitoring of cellular systems involved in inflammatory cascades of the innate immunity was successfully applied to the IL-1-driven CAPS diseases. This is the first study illustrating different states of subclinical disease activity in all types of CAPS depending on the type of anti-IL-1 therapy. MRP8/14 is a sensitive biomarker for monitoring disease activity, status of inflammation and response to IL-1 blockade in patients with CAPS.
P234 BLF and BTS "Ready for home" survey of the experiences of patients admitted to hospital with COPD. Pt2: the discharge process
Authors: J. E. Scullion, S. J. Singh, M. D. L. Morgan
Journal: Thorax (2010)

Introduction and Objectives A secure discharge from hospital following an admission for COPD is an important reflection of the quality of hospital care. Information about the discharge process will help inform strategies to prevent unnecessary re-admissions. Methods An 8-item questionnaire was sent to respiratory departments in all acute hospitals in the United Kingdom. Recipients were asked about their hospital's processes and the provision of information to patients at discharge. Results 68 hospitals returned the questionnaire. There was coverage of hospitals from all regions of England as well as Scotland and Wales. The majority (69%) of responses came from district general hospitals (DGHs). Catchment populations ranged from 100 000–1 million. Respiratory departments varied in size from <20 beds (10.3%) to >60 beds (11.8%). Almost half the departments (48.6%) have >70 COPD admissions per month. There was an early discharge service in many hospitals (71%), with most being based in the hospital (67%) vs the community. Only 52.9% patients were seen by a respiratory physician before discharge; the majority (69.1%) were seen by a specialist nurse. Most hospitals (52.9%) did not have a formal discharge check list or discharge pack (63.2%). Many hospitals (69%) give patients a copy of the discharge letter, and some refer patients directly to pulmonary rehabilitation (54%) or smoking cessation services (63%) on discharge. Follow-up appointments within primary or secondary care were not universally arranged and there was patchy coverage of educational advice to patients (range: 45%–75%), especially on return to work or sexual relationships. Conclusions Whilst admissions for exacerbations of COPD are common, preparation for discharge is unsatisfactory. Many patients do not see a specialist or have appropriate post-discharge advice or follow-up arrangements.
Failure of the Normal Ureagenic Response to Amino Acids in Organic Acid-loaded Rats
Authors: Peter M. Stewart, Mackenzie Walser
Journal: Journal of Clinical Investigation (1980)

Propionic and methylmalonic acidemia are both known to be associated with hyperammonemia. Rats injected with 10 or 20 mmol/kg of propionate or 20 mmol/kg of methylmalonate, along with 1.5 g/kg of a mixture of amino acids, developed severe hyperammonemia, whereas rats administered the same dosages of acetate did not. In vitro, neither propionyl nor methylmalonyl CoA affected the activity of carbamyl phosphate synthetase I, ornithine transcarbamylase, nor the activation constant (KA) of carbamyl phosphate synthetase I for N-acetyl glutamate. Furthermore, rats injected with propionate showed no alteration of liver amino acid concentrations, which could explain impaired ureagenesis. Animals injected with methylmalonate showed an increase in both citrulline and aspartate, suggesting that argininosuccinic acid synthetase may also have been inhibited. Liver ATP levels were unchanged. Citrullinogenesis, measured in intact mitochondria from livers of injected animals, was reduced 20-25% by 20 mmol/kg of propionate or methylmalonate (compared with acetate). This effect was attributable to an impairment in the normal rise of liver N-acetyl glutamate content after amino acid injection. Thus, carbamyl phosphate synthetase I activation was reduced. Liver levels of acetyl CoA and free CoA were reduced. Levels of unidentified acyl CoA derivatives rose, presumably reflecting the accumulation of propionyl and methylmalonyl CoA. Thus, the principal mechanism for hyperammonemia induced by these acids is depletion of liver N-acetyl glutamate, which is in turn attributable to depletion of acetyl CoA and/or competitive inhibition by propionyl and methylmalonyl CoA of N-acetyl glutamate synthetase. Injection of methylmalonate may also have an additional inhibitory effect on argininosuccinic acid synthetase.
Intracellular Tumor-Associated Antigens Represent Effective Targets for Passive Immunotherapy
Authors: Takuro Noguchi, Takuma Kato, Linan Wang, Yuka Maeda, Hiroaki Ikeda, Eiichi Sato, Alexander Knuth, Sacha Gnjatic, Gerd Ritter, Shimon Sakaguchi, Lloyd J. Old, Hiroshi Shiku, Hiroyoshi Nishikawa
Journal: Cancer Research (2012)

Monoclonal antibody (mAb) therapy against tumor antigens expressed on the tumor surface is associated with clinical benefit. However, many tumor antigens are intracellular molecules that generally would not be considered suitable targets for mAb therapy. In this study, we provide evidence challenging this view through an investigation of the efficacy of mAb directed against NY-ESO-1, a widely expressed immunogen in human tumors that is expressed intracellularly rather than on the surface of cells. On their own, NY-ESO-1 mAb could neither augment antigen-specific CD8(+) T-cell induction nor cause tumor eradication. To facilitate mAb access to intracellular target molecules, we combined anti-NY-ESO-1 mAb with anticancer drugs to accentuate the release of intracellular NY-ESO-1 from dying tumor cells. Strikingly, combination therapy induced a strong antitumor effect that was accompanied by the development of NY-ESO-1-specific effector/memory CD8(+) T cells that were not elicited by single treatments alone. The combinatorial effect was also associated with upregulation of maturation markers on dendritic cells, consistent with the organization of an effective antitumor T-cell response. Administration of Fc-depleted F(ab) mAb or combination treatment in Fcγ receptor-deficient host mice abolished the therapeutic effect. Together, our findings show that intracellular tumor antigens can be captured by mAbs and engaged in an efficient induction of CD8(+) T-cell responses, greatly expanding the possible use of mAb for passive cancer immunotherapy.
Parvovirus associated antigen in the synovial membrane of patients with rheumatoid arthritis.
Authors: G Stierle, K A Brown, S G Rainsford, C A Smith, D Hamerman, H E Stierle, D C Dumonde
Journal: Annals of the Rheumatic Diseases (1987)

Homogenates of synovium from patients with rheumatoid arthritis (RA) and osteoarthritis (OA) were centrifuged on caesium chloride density gradients to obtain isolates of a density similar to that of parvoviruses. Six of 11 RA isolates and none of six OA isolates reacted with an antiserum raised against a rheumatoid associated, parvovirus-like agent (RA-1 virus). An anti-B19 parvovirus antiserum did not react with any of the isolates tested. Electron microscopy of negatively stained preparations of the isolates showed that small particles of diameter 10 nm were abundant in most of the RA isolates (11/13) but absent from all OA isolates. Such particles, whose identification is unknown, were also present in RA-1 positive lysates prepared from cultured RA synovial cells. These results suggest that the RA-1 virus can be directly identified in RA synovial tissue and that the virus appears to be unrelated to the human B19 parvovirus.
Endoscopic balloon dilatation versus endoscopic sphincterotomy for the removal of bile duct stones: a prospective randomised trial
Authors: P Vlavianos
Journal: Gut (2003)

<b>Background:</b> Endoscopic balloon dilatation (EBD) of the sphincter of Oddi has been proposed as an alternative therapy with possible advantages, as compared with endoscopic sphincterotomy (ES), for removal of bile duct stones. <b>Patients and methods:</b> In a randomised study, we compared the efficacy and complication rate of the two techniques in 202 patients with common bile duct stones. Patients were followed up for 12 months. <b>Results:</b> A total of 103 patients were randomised to the EBD group and 99 to the ES group. Overall duct clearance was 87.1% and did not differ between the two groups (EBD 87.4%; ES 86.9%). The complication rate at 24 hours was 6.8% in the EBD group and 3.0% in the ES group (NS). Complications during follow up were 11.7% and 15.2% respectively (NS). A multivariate logistic regression analysis showed only the size of the largest stone to be predictive of success for either technique. <b>Conclusion:</b> Endoscopic balloon dilatation offers no significant advantage over the well established technique of endoscopic sphincterotomy for the removal of bile duct stones.
Phase II Study of Weekly Vinblastine in Recurrent or Refractory Pediatric Low-Grade Glioma
Authors: Eric Bouffet, Regina Jakacki, Stewart Goldman, Darren Hargrave, Cynthia Hawkins, Manohar Shroff, Juliette Hukin, Ute Bartels, Nicholas Foreman, Stewart Kellie, Joanne Hilden, Michael Etzl, Beverly Wilson, Derek Stephens, Uri Tabori, Sylvain Baruchel
Journal: Journal of Clinical Oncology (2012)

To evaluate the efficacy of single-agent vinblastine in pediatric patients with recurrent or refractory low-grade glioma.Patients were eligible if they had experienced previous treatment failure (chemotherapy and/or radiation) for incompletely resected or unresectable low-grade glioma (LGG). Vinblastine (6 mg/m(2)) was administered weekly for 1 year unless unacceptable toxicity or progression (confirmed on two consecutive imaging studies) occurred.Fifty-one patients (age range, 1.4 to 18.2 years; median age, 7.2 years) were prospectively enrolled onto this phase II study. Fifty patients had previously received at least one prior regimen of chemotherapy, and 10 patients had previously received radiation treatment. Fifty patients were evaluable for response; 18 patients (36%) had a complete, partial, or minor response, and 31 patients completed 1 year of treatment. At a median follow-up of 67 months, 23 patients had not experienced progression; three patients have died. Five-year overall survival was 93.2% ± 3.8%, and 5-year progression-free survival was 42.3% ± 7.2%. Toxicity was manageable and mostly hematologic, although a few patients needed transfusions.Weekly vinblastine seems to be a reasonable alternative to radiation for pediatric patients with LGG who have experienced treatment failure with first-line chemotherapy. The 5-year progression-free survival observed in this phase II trial is comparable to results observed with first-line chemotherapy in chemotherapy-naive patients. The role of single-agent vinblastine and other vinca alkaloid in the management of pediatric LGGs deserves further investigation.
A Multicenter Randomized Trial of Breast Intensity-Modulated Radiation Therapy to Reduce Acute Radiation Dermatitis
Authors: Jean-Philippe Pignol, Ivo Olivotto, Eileen Rakovitch, Sandra Gardner, Katharina Sixel, Wayne Beckham, Thi Trinh Thuc Vu, Pauline Truong, Ida Ackerman, Lawrence Paszat
Journal: Journal of Clinical Oncology (2008)

Dermatitis is a frequent adverse effect of adjuvant breast radiotherapy. It is more likely in full-breasted women and when the radiation is distributed nonhomogeneously in the breast. Breast intensity-modulated radiation therapy (IMRT) is a technique that ensures a more homogeneous dose distribution.A multicenter, double-blind, randomized clinical trial was performed to test if breast IMRT would reduce the rate of acute skin reaction (notably moist desquamation), decrease pain, and improve quality of life compared with standard radiotherapy using wedges. Patients were assessed each week during and up to 6 weeks after radiotherapy.A total of 358 patients were randomly assigned between July 2003 and March 2005 in two Canadian centers, and 331 were included in the analysis. Breast IMRT significantly improved the dose distribution compared with standard radiation. This translated into a lower proportion of patients experiencing moist desquamation during or up to 6 weeks after their radiation treatment; 31.2% with IMRT compared with 47.8% with standard treatment (P = .002). A multivariate analysis found the use of breast IMRT (P = .003) and smaller breast size (P < .001) were significantly associated with a decreased risk of moist desquamation. The use of IMRT did not correlate with pain and quality of life, but the presence of moist desquamation did significantly correlate with pain (P = .002) and a reduced quality of life (P = .003).Breast IMRT significantly reduced the occurrence of moist desquamation compared with a standard wedged technique. Moist desquamation was correlated with increased pain and reduction in the quality of life.
Collegiate rugby union injury patterns in New England: A prospective cohort study
Authors: Hamish A. Kerr, Christine M. Curtis, Lyle J. Micheli, Mininder S. Kocher, David Zurakowski, John H.M. Brooks, Simon P.T. Kemp
Journal: British Journal of Sports Medicine (2008)

To establish injury profile of collegiate rugby union in the USA. DESIGN/ SETTING: 31 men's and 38 women's collegiate rugby union teams prospectively recorded injuries during games and practice during the 2005-06 season. Three teams withdrew before data collection. An injury was defined as one: (1) occurring in an organised intercollegiate game or practice; and (2) requiring medical attention during or after the game or practice, or (3) resulting in any restriction of the athletes' participation for >or=1 day(s) beyond the day of injury, or in a dental injury.In total, 847 injuries (447 in men; 400 in women) during 48,026 practice (24,280 in men; 23,746 in women) and 25,808 game (13,943 in men; 11,865 in women) exposures were recorded.During games, injury rates of 22.5 (95% CI 20.2 to 25.0) and 22.7 (20.2 to 25.5) per 1000 game athletic exposures or 16.9 (15.1 to 18.9) and 17.1 (15.1 to 19.1) per 1000 player game hours were recorded for men and women, respectively. Over half of all match injuries were of major severity (>7 days' absence) (men 56%; women 51%) and the tackle was the game event most often associated with injury (men 48%; women 53%).Collegiate game injury rates for rugby were lower than rates recorded previously in men's professional club and international rugby and lower than reported by the National Collegiate Athletic Association Injury Surveillance System for American football, but similar to rates reported for men's and women's soccer in 2005-06.
Ways to shorten the lung clearance index measurement I - Are three measurements needed?
Authors: Sophie Yammine, Florian Singer, Chiara Abbas, Philipp Latzin
Journal: European Respiratory Journal (2012)

Background  Inert gas multiple-breath washout (MBW) derived lung clearance index (LCI) is a sensitive lung function parameter in subjects with mild cystic fibrosis (CF) lung disease, but rarely measured in clinical routine due to lack of available equipment and lengthy protocols. Using an available nitrogen (N 2 ) MBW setup (Exhalyzer D, Eco Medics, Switzerland) we assessed shortened N 2 MBW protocols for LCI.   Methods  We determined whether the LCI from the 1 st  (LCI 1 ) and the mean LCI of the 1 st  and 2 nd  valid N 2 MBW (LCI 2 ), respectively, are comparable to the averaged information obtained from three N 2 MBW (LCI 3 ). We analyzed data of 33 school-aged children with CF and 10 controls performing triplicate N 2 MBW.   Results  LCI 1 , LCI 2 , and LCI 3  differed significantly between healthy and CF children. LCI 1  and LCI 2  were strongly associated with LCI 3  (R 2  = 0.98 for both), took less time, and were of similar diagnostic value. Comparing LCI 1  and LCI 2  with LCI 3 , mean (range) test duration was 2.2 (0.5-5.2), 6.6 (3.6-12.7), and 11.1 (8.0-17.1) min, and upper limits of normal LCI (8.3, 8.3, and 8.4) all correctly classified 71% of children, respectively. Bland-Altman analysis of LCI 1  and LCI 2  showed good agreement with LCI 3 : Mean difference was -1.1% and -0.7%, limits of agreement were 6.8 to -9.0% and 5.9 to -7.3%, respectively.   Conclusion  In the current study population, the 1 st  LCI or the mean of the 1 st  and 2 nd  LCI take less time and predict the mean LCI of three N 2 MBW within physiological measurement variability. Using less N 2 MBW measurements seems promising for time-saving LCI measurement in clinical routine.
Identification of a subpopulation of metastatic breast cancer patients with very high HER2 expression levels and possible resistance to trastuzumab
Authors: M. Bates, J. Sperinde, W.J. Köstler, S.M. Ali, K. Leitzel, E.M. Fuchs, A. Paquet, Y. Lie, T. Sherwood, R. Horvat, C.F. Singer, J. Winslow, J.M. Weidler, W. Huang, A. Lipton
Journal: Annals of Oncology (2011)
The Anatomy of Health Care in the United States
Authors: Hamilton Moses, David H. M. Matheson, E. Ray Dorsey, Benjamin P. George, David Sadoff, Satoshi Yoshimura
Journal: JAMA (2013)

Health care in the United States includes a vast array of complex interrelationships among those who receive, provide, and finance care. In this article, publicly available data were used to identify trends in health care, principally from 1980 to 2011, in the source and use of funds ("economic anatomy"), the people receiving and organizations providing care, and the resulting value created and health outcomes. In 2011, US health care employed 15.7% of the workforce, with expenditures of $2.7 trillion, doubling since 1980 as a percentage of US gross domestic product (GDP) to 17.9%. Yearly growth has decreased since 1970, especially since 2002, but, at 3% per year, exceeds any other industry and GDP overall. Government funding increased from 31.1% in 1980 to 42.3% in 2011. Despite the increases in resources devoted to health care, multiple health metrics, including life expectancy at birth and survival with many diseases, shows the United States trailing peer nations. The findings from this analysis contradict several common assumptions. Since 2000, (1) price (especially of hospital charges [+4.2%/y], professional services [3.6%/y], drugs and devices [+4.0%/y], and administrative costs [+5.6%/y]), not demand for services or aging of the population, produced 91% of cost increases; (2) personal out-of-pocket spending on insurance premiums and co-payments have declined from 23% to 11%; and (3) chronic illnesses account for 84% of costs overall among the entire population, not only of the elderly. Three factors have produced the most change: (1) consolidation, with fewer general hospitals and more single-specialty hospitals and physician groups, producing financial concentration in health systems, insurers, pharmacies, and benefit managers; (2) information technology, in which investment has occurred but value is elusive; and (3) the patient as consumer, whereby influence is sought outside traditional channels, using social media, informal networks, new public sources of information, and self-management software. These forces create tension among patient aims for choice, personal care, and attention; physician aims for professionalism and autonomy; and public and private payer aims for aggregate economic value across large populations. Measurements of cost and outcome (applied to groups) are supplanting individuals' preferences. Clinicians increasingly are expected to substitute social and economic goals for the needs of a single patient. These contradictory forces are difficult to reconcile, creating risk of growing instability and political tensions. A national conversation, guided by the best data and information, aimed at explicit understanding of choices, tradeoffs, and expectations, using broader definitions of health and value, is needed.