tbuckley/cabot-search huggingface dataset:
Repeated Sequences and Large-Scale Size Variation of Mitochondrial DNA: A Common Feature among Scallops (Bivalvia: Pectinidae)
Authors: B Gjetvaj, DI Cook, E Zouros
Journal: Molecular Biology and Evolution (1992)

The mitochondrial genomes of seven species of scallops were examined for the presence of repeated sequences and within-species size variation.The mtDNA of one species, Argopecten irradians, shows a typical 16.2-kb invariant size and ap parently lacks repeated sequences.The mtDNA of another species, Placopecten mageilanicus, is known to be very large (>3 1 kb), to contain a tandemly repeated sequence, and to vary widely in size among individuals.The mtDNAs of five other species (Pecten maximus, Crassadoma gigantea, Aequipecten opercularis, Chlamys hastata, and Chlamys isfandica) represent intermediate cases: all are larger than typical animal mtDNA (>20 kb), contain repeated sequences, and exhibit abundant intraspecific size polymorphism.When the cloned repeated sequence of P. magellanicus was used as a probe, no sequence similarity was seen with fragments containing the repeated sequence of other species.The same results were obtained when those other fragments were used as probes, suggesting that the repeated sequences of the various scallop species do not share extensive sequence similarity.Our findings support the increasingly accepted view that the normally observed conservatism of animal mtDNA size and organization is not universal.Invertebrates and poikilotherm vertebrates may contain large-scale intraspecific size variation whose origin and fate is, most likely, determined by nonselective forces of repeatedsequence-mediated mutational or recombination mechanisms and by subsequent random drift in the resulting germ-cell lineages.Such size polymorphism can be so extensive that each individual may have a unique RFLP profile (mtDNA fingerprint), but the suspected high turnover rate of the number of repeated sequences may restrict the application of this polymorphism to population genetic studies.1.
Refining the Mantle Cell Lymphoma Paradigm: Impact of Novel Therapies on Current Practice
Authors: Irit Avivi, Andre Goy
Journal: Clinical Cancer Research (2015)

Although mantle cell lymphoma (MCL) is a rare subtype of non-Hodgkin lymphoma, proactive research efforts fueled by challenges in the management of MCL have led to an increase in median overall survival (OS) of 2.5 years in the mid 1990s to beyond 5 years nowadays. This improvement is due mostly to the use of dose-intensive strategies, particularly cytarabine-containing regimens [with or without high-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) consolidation], which are associated with deeper remission (and higher molecular complete response rate), as well as better salvage therapies. Along this line, MCL became the first lymphoma for which four novel agents have been approved in the relapsed/refractory setting: temsirolimus, lenalidomide, ibrutinib, and bortezomib (the last agent approved both in relapsed/refractory disease and in first-line combination therapy). In addition, the use of rituximab maintenance has helped reduce relapse rates and improve outcome. However, in routine practice (i.e., outside clinical trials), the outcome of MCL remains overall unchanged with standard immunochemotherapy, and even after HDT-ASCT, most patients still relapse and frequently develop chemoresistance. The persistent lack of consensus for the treatment of MCL explains the rather impressive variability in management of these patients. The integration of newer therapies, either in combination with immunochemotherapy or as consolidation/maintenance postinduction, offers new opportunities for patients with MCL. This review highlights how such developments can help refine the current MCL paradigm.
Late-breaking abstract: p-STAT6 and PU.1 are involved in IL-9 production by Th9 cells during allergen-induced late phase airway inflammation in asthma patients
Authors: Deimante Hoppenot, Kestutis Malakauskas, Simona Lavinskiene, Raimundas Sakalauskas
Journal: European Respiratory Journal (2014)

Introduction: Previously vitro studies demonstrated that transcription factors STAT6 and PU.1 are required to induce IL-9 secretion by Th9 cells. The importance of STAT6 and PU.1 in human acute allergic asthma (AA) has not yet been well studied.  The aim: Evaluate p-STAT6 and PU.1 expression in peripheral blood Th9 cells during allergen-induced late phase airway inflammation in AA patients.  Material and Methods: 14 patients with intermittent/mild persistent AA and 11 healthy subjects (HS) were examined. Peripheral blood was collected 24 h before (baseline) and 24 h after bronchial allergen challenge. Th9 cells were defined by flow cytometry as CD4+IL-9+IFNγ-TGFβ1-IL-4-IL17-. p-STAT6 and PU.1 expression was obtained as mean fluorescence intensity (MFI) in Th9 cells. Serum IL-9 estimated by ELISA.  Results: There was no significant difference on p-STAT6 and PU.1 expression at baseline in AA and HS. P-STAT6 significantly increased in AA group 24 h after bronchial allergen challenge comparing with baseline: 81.8, range 67.2-90.5 MFI vs. 29.4, range 21.1-37.1 MFI; p=0.0001, accordingly. Same tendency was observed for PU.1 (99.5, range 68.9-112.8 MFI vs. 61.2, range 49.9-71.2 MFI; p=0.002, accordingly). After bronchial allergen challenge increased serum IL-9 level correlated with increased Th9 cells count (r=0.74, p=0.003) as well as with MFI of PU.1 (r=0.65, p=0.013) and STAT6 (r=0.56, p=0.041) in AA. In HS neither transcription factors nor IL-9 and Th9 cell count has changed after bronchial allergen challenge.  Conclusion: p-STAT6 and PU.1 are required for IL-9 production by Th9 cells in allergen-induced late phase airway inflammation in asthma patients.
Association Between Narrow Pharmacy Networks and Medication Adherence
Authors: Jennifer M. Polinski, Olga S. Matlin, Christine Sullivan, Michael Gagnon, Troyen A. Brennan, William H. Shrank
Journal: JAMA Internal Medicine (2015)

Disclaimer: Sedasys is the manufacturer of the SEDASYS Computer-Assisted Personalized System.The system is intended to allow trained physician-led teams to deliver minimal-to-moderate sedation with propofol to patients at low risk of complications during
Pharmacodynamic analysis of target inhibition and tumor endothelial cell death in biopsies obtained from patients treated with the VEGF receptor antagonists SU5416 or SU6668
Authors: Francis Y. Lee, Louis Lombardo, Robert Borzilleri, Amy Camuso, Stephen Castaneda, Nicholas Donato, Krista Fager, Christine Flefleh, Hilary Gray, Ivan Inigo, David Kan, Roger Luo, Suhong Pang, Mei-Li Wen, Robert Wild, Tai W. Wong, Moshe Talpaz, Robert Kramer
Journal: Cancer Research (2004)

3988   Preclinical studies with small molecule VEGF receptor tyrosine kinase inhibitors have suggested that this receptor is a viable therapeutic target for solid tumors. However, clinical results with SU6668 or SU5416 VEGF receptor antagonists have been disappointing. In this study, we determined the effects of SU6668 or SU5416 on receptor phosphorylation and biological surrogates of angiogenesis inhibition in paired tumor biopsies obtained within the context of 3 separate clinical trials (one with SU6668 and two with SU5416) in patients with advanced solid malignancies. Excisional or 18 g core biopsies were obtained before and after therapy with SU5416 (145 mg/m 2 / twice weekly) or SU6668 (200 mg/m 2 /day) delivered i.v. via continuous infusion. Tumor tissue sections were stained for immunofluorescence and laser scanning cytometry (LSC)-mediated analysis was used to quantify phosphorylated and total VEGF and PDGF receptor levels, tumor microvessel densities (MVDs), and endothelial and tumor cell apoptosis. Baseline levels of phosphorylated VEGFR-2, MVD, and apoptosis were highly variable in the tumor cohort (n = 11). Levels of phosphorylated VEGFR-2 were lower in 6/11 of the matched tissue sections obtained after SU-5416 or SU-6668, but these decreases were substantial (>50%) in only two of them. Although microvessel densities were also lower in most of the post-treatment biopsies compared to pretreatment controls (7/11), substantial decreases were only observed in the same 2 biopsies that displayed the greatest decreases in phosphorylated VEGFR-2. Substantial increases in apoptosis were observed in only 1 of the 11 tumors. Thus, both VEGFR-2 inhibitors displayed some biological activity at the concentrations achieved in patients. However, their effects on receptor phosphorylation were inconsistent and did not usually translate into sufficient increases in endothelial or tumor cell death, which probably accounted for their failure to produce significant clinical activity.
An Evaluation of the Royal Air Force Helicopter Search and Rescue Services in Britain with Reference to Royal Air Force Valley 1980–1989
Authors: W J Liskiewicz
Journal: Journal of the Royal Society of Medicine (1992)

The Royal Air Force (RAF) operates a helicopter Search and Rescue (SAR) service in the United Kingdom and territorial waters; it also provides a similar service in several locations abroad. A 10-year retrospective study of the SAR helicopter service operating from the RAF base at Valley on the island of Anglesey in North Wales is presented, with national SAR statistics over a similar period provided for comparison. Analysis of records kept by SAR aircrew at RAF Valley shows that their assistance had been requested on 1490 occasions during the 10-year period studied; most of these requests were the result of incidents involving holidaymakers, particularly in the mountains or along the coast. The results illustrate the versatility and life-saving potential of a highly skilled and motivated service able to work in adverse weather and dangerous locations. In the light of current debate, the value of aeromedical evacuation of seriously ill patients using helicopters is discussed.
Pfizer loses UK patent for blockbuster pain drug after threats to doctors
Authors: Zosia Kmietowicz
Journal: BMJ (2015)

The drug company Pfizer made unjustifiable threats when it said earlier this year that prescribing generic versions of pregabalin, which it markets as Lyrica, for pain control could leave doctors open to litigation, the High Court has ruled.

Mr Justice Richard Arnold said, in the course of a judgment in which he also overturned Pfizer’s UK patent for pregabalin for pain control, that the company made “groundless claims” that its patent for Lyrica would be infringed if doctors did not specify Lyrica as opposed to a generic alternative when prescribing pregabalin for pain.

Pfizer has said that it will appeal the ruling.

NHS England responded by saying that its current advice to doctors to prescribe Lyrica by brand name for use in pain control still stood and would not change until a court order giving effect to the judgment had been received.

Andrew Green, chairman of the BMA’s clinical and prescribing subcommittee for GPs, said that Pfizer should refund what the NHS has spent on branded Lyrica for pain. 

The …
Is a double 6-minute walk test (6MWT) required as part of the routine assessment of pulmonary rehabilitation (PR) in COPD patients?
Authors: Silke Wingart, Nicola Lehbert, Benjamin Krämer, Veronika Huber, Sebastian Fuchs, Michael Wittmann, Danijel Jelusic, Michael Schuler, Konrad Schultz
Journal: European Respiratory Journal (2014)

Background:  The 6MWT is a central diagnostic assessment tool within PR. The 6-minute walk distance (6MWD) forms a basis for training regulation, is a parameter of overall load capacity and is considered one of the best predictors in the prognosis of survival and the morbidity rate of COPD patients.  In the literature a 2. 6MWT is, increasingly, required at the beginning and end of PR to minimize learning effect & incorrect conclusions. Here, the best test is used as a basis for the evaluation.  The aim of the study was to examine whether there is a marked difference between the results of a double test & those of a single test.   Methods:  In 306 consecutive COPD patients (GOLD II-IV) a double 6MWT was made at the beginning (T0) and end (T1) of PR, with an interval of 1 hour between the tests.   Results:  The mean improvement after PR in the 6MWD at T1 was 81.7m, if in each case the best result was used for T0 & T1, and 80.0m if only the 1. test at T0 & T1 was taken into account  (1.7m=2.1%, p=0.6 Wilcoxontest). At T0 14.7% of patients achieved a difference in 6MWD of >10% between the walk tests, at T1 10.8% of patients.   Conclusion:  A “double walk test”, applying the best values, shows in the medium with regard to the improvement of the 6MWD after PR no relevant change compared to a single 6MWT. But in up to 15% of patients, the difference between the 2 tests was above 10%.
HHV-6 infection after allogeneic hematopoietic stem cell transplantation: From chromosomal integration to viral co-infections and T-cell reconstitution patterns
Authors: Adrien Quintela, Vanessa Escuret, Sandrine Roux, Pascale Bonnafous, Lila Gilis, Fiorenza Barraco, Hélène Labussière-Wallet, Sophie Duscastelle-Leprêtre, Franck-Emmanuel Nicolini, Xavier Thomas, Christian Chidiac, Tristan Ferry, Emilie Frobert, Stéphane Morisset, Françoise Poitevin-Later, Guillaume Monneret, Mauricette Michallet, Florence Ader, F. Ader, E. Bachy, M. Balsat, F. Barraco, A.L. Bienvenu, G. Billaud, F. Biron, A. Boibieux, C. Chidiac, A. Conrad, S. Ducastelle-Leprêtre, O. Dumitrescu, D. Dupont, V. Escuret, T. Ferry, E. Frobert, L. Gilis, A. Grateau, M. Heiblig, H. Labussière-Wallet, M. Le Maréchal, L. Lebras, B. Lina, G. Lina, A. Quintela, P. Miailhes, A.-S. Michallet, M. Michallet, M.-C. Michallet, G. Monneret, F. Morfin-Sherpa, F.E. Nicolini, T. Perpoint, M. Peyrouse de Montclos, S. Picot, F. Poitevin-Later, A.G. Ranc, S. Roux, G. Salles, J. Saison, A. Sénéchal, M. Sobh, X. Thomas, F. Valour, E. Wattel
Journal: Journal of Infection (2015)
Use of increase in esophageal FDG SUV during radiotherapy to predict radiation esophagitis.
Authors: S. Yuan, R. Brown, L. Zhao, M. Gross, J. Hayman, N. Ramnath, K. B. Cease, G. P. Kalemkerian, F. Kong
Journal: Journal of Clinical Oncology (2010)

e17509 Background: Esophageal uptake of FDG is commonly seen in patients with non-small cell lung cancer (NSCLC), but the relationship of the uptake to radiation esophagitis has not been delineated. Since esophageal mucosa is sensitive to the effect of radiation, we hypothesized that: (1) esophageal FDG activity changes during fractionated radiotherapy (RT), (2) these changes are associated with radiation esophagitis. Methods: Patients with stage I-III NSCLC were prospectively enrolled and received >60 Gy RT. FDG-PET/CT scans were acquired prior to and during RT after the delivery of 45 Gy. Normalized standardized uptake values (NSUV), defined by the esophageal maximum SUV relative to intravascular background within the aortic arch, were measured at the levels of the primary tumor, sternal notch, aortic arch, carina, and gastro-esophageal junction. Grade ≥2 radiation esophagitis was defined as an event. Results: 16 of 50 patients had radiation esophagitis event. Clinical stage, concurrent chemotherapy, maxium, and mean esophageal dose all correlated with esophagitis. Compared to baseline, esophageal NSUV increased significantly during-RT at the level of the primary tumor (1.09 ± 0.05 vs. 1.28 ± 0.06, p=0.001), but did not change significantly at other levels. The time from during-RT PET to the development of clinical esophgitis was 11.6 ± 1.4 days. Patients with esophagitis had a higher during-RT to baseline NSUV ratio than those without (1.46 ± 0.12, 95% CI 1.20-1.71; vs. 1.11 ± 0.05, 95% CI 1.01-1.21, p=0.002). On logistic regression analysis, during- RT to baseline esophageal NSUV ratio and maximum esophageal dose were independent predictive factors for radiation esophagitis and areas under curve were 0.84 and 0.80 (p<0.001), respectively. The predictive sensitivity, specificity, accuracy, negative and positive predictive values for esophageal NSUV ratio ≥ 1.20 were 94%, 71%, 78%, 96%, and 60%; for maximum esophageal dose ≥ 65Gy, 75%, 77%, 76%, 87%, and 67%, and for the combination of both factors, 69%, 94%, 86%, 85% and 87%, respectively. Conclusions: Increases in esophageal SUV during RT may predict radiation esophagitis. A model combining the esophageal SUV ratio and the maximum esophageal dose may improve the predictive power. No significant financial relationships to disclose.
Some Effects of the Administration of Endotoxin in Mice
Authors: Peter D. Gorevic, Yoram Levo, Prem C. Chatpar, Blas Frangione, E. C. Franklin
Journal: Journal of Clinical Investigation (1979)

Endotoxin has been shown to induce amyloidosis in mice and to result in the appearance in serum of large amounts of amyloidrelated protein (SAA). After injection of 300 μg lipopolysaccharide Escherichia coli, SAA behaves as an acute phase reactant with levels reaching a peak of >600 μg/ml at 18-22 h and returning to base line (<50 μg/ml) by 48 h in each of four strains tested; only the endotoxin-resistant C3H/HeJ strain showed a smaller response. Lesser, though significant, elevations were also found after subcutaneous injection of 25 mg of casein, bovine serum albumin, ovalbumin, or monomeric immunoglobulin G, whereas pyrogen-free human serum albumin/U. S. Pharmacopeia failed to raise SAA levels. SAA generation may thus be a result of endotoxin contamination of these protein preparations.
Factors Associated With Response to High-Dose Interleukin-2 in Patients With Metastatic Melanoma
Authors: Giao Q. Phan, Peter Attia, Seth M. Steinberg, Donald E. White, Steven A. Rosenberg
Journal: Journal of Clinical Oncology (2001)

PURPOSE: The present study attempted to identify characteristics that correlated with clinical response to interleukin (IL)-2 therapy in patients with metastatic melanoma. PATIENTS AND METHODS: We retrospectively evaluated laboratory and clinical characteristics of 374 consecutive patients with metastatic melanoma treated with high-dose intravenous bolus IL-2 (720,000 IU/kg) from July 1, 1988, to December 31, 1999, at the Surgery Branch of the National Cancer Institute. RESULTS: The overall objective response rate was 15.5%. Pretreatment parameters such as patient demographics, laboratory values, and prior therapy did not correlate with response; however, 53.6% of patients with only subcutaneous and/or cutaneous metastases responded, compared with 12.4% of patients with disease at other sites (P 2 = .000001). During therapy, patients who were responders tended to have received more doses during course 1 (16.2 ± 0.3 doses v 14.5 ± 0.2 doses; P 2 = .0095); however, when limited to patients who were able to complete both cycles of course 1, there was no statistically significant difference (P 2 = .27). Responders had a higher maximum lymphocyte count immediately after therapy compared with nonresponders (P 2 = .0026). The development of abnormal thyroid function tests and vitiligo after therapy was associated with response (thyroid-stimulating hormone, P 2 = .01; free T4, P 2 = .0049; vitiligo, P 2 &lt; 10 −6 ), although thyroid dysfunction may have been related more to the length of IL-2 therapy than to response. CONCLUSION: The presence of metastases only to subcutaneous and/or cutaneous sites, lymphocytosis immediately after treatment, and long-term immunologic side effects, especially vitiligo, were associated with antitumor response to IL-2 therapy.
ABPA syndrome (ABPAs) in CF: FEV1 decline, infectious exacerbations and BMI before and after the year of diagnosis (index year), a case control study
Authors: Frans De Baets, Simeon Wanyana, Linde De Keyzer, Petra Schelstraete, Filomeen Haerynck, Muriel Thomas, Sabine Van daele
Journal: European Respiratory Journal (2014)

ABPAs is a complication occurring in 10 to 15% of the CF patients. In case of late diagnosis bronchial damage can be considerably. A high degree of suspicion is mandatory and indicators of ABPAs must be followed carefully. We intend to study facilitators and consequences of ABPAs.  Methods:  We performed a case control study relying on data from the Belgian CF register. One hundred and fifty five ABPAs patients matched for age, gender and  P. aeruginosa  colonisation were compared to 356 controls. FEV1 decline, infectious exacerbations and BMI were studied over a period of 10 years before and 10 years after the index year.  Results :  Before the index year mean cumulative FEV1values are significantly lower in the ABPAs group (p  Before the index year ABPAs patients spent significantly more days in hospital for IV antibiotic treatment (p  BMI is significantly lower in the ABPAs patient group, both before and after the index year (p  Conclusions:  Lower FEV1, lower BMI and increased need for IV antibiotics seems to facilitate the development of ABPAs. ABPAs favours accelerated bronchial damage leading to a further increased need for IV antibiotics and a steeper decline in FEV1.
Three Simple Methods of Detecting Malnutrition on Medical Wards
Authors: J M D Nightingale, N Walsh, M E Bullock, A C Wicks
Journal: Journal of the Royal Society of Medicine (1996)

Malnutrition in hospital is often unrecognized. A nutrition team aims to teach simple methods of detecting malnutrition. On a single day all medical in-patients underwent a nutritional assessment. Eighty-four patients (43 men), median age 71 years (range 28–97), were assessed. The most common diagnoses were cardiac disease (26), stroke/dementia (12), non-malignant lung disease (9) and malignancy (6). A weight loss of more than 10% (%WL) was found in 17/65 (26%) and a body mass index (BMI) of less than 19kg/m 2 in 13/69 (19%). A mid-arm muscle circumference (MAMC) less than the fifth percentile occurred in 16/83 (19%) patients. Percentage weight loss alone detected seven patients of whom four were overweight (BMI &gt; 25 kg/m 2 ), BMI alone detected three patients, and MAMC alone eight patients of whom three could not be weighed and three had fluid retention. There was fluid retention in 35/84 (42%) patients of whom nine were malnourished (six detected by BMI and/or %WL, and three by MAMC alone). All three measurements were made in 64 patients, six (9%) of whom were detected as malnourished by all three methods. Combining the three measurements 29/84 (35%) of patients were malnourished and only 28% of these patients had been assessed by a dietitian. BMI and %WL detect most patients but fluid retention may limit their accuracy. MAMC is useful in those who cannot be weighed or who have fluid retention.