tbuckley/cabot-search huggingface dataset:
Pegylated Liposomal Doxorubicin, Rituximab, Cyclophosphamide, Vincristine, and Prednisone in AIDS-Related Lymphoma: AIDS Malignancy Consortium Study 047
Authors: Alexandra M. Levine, Ariela Noy, Jeannette Y. Lee, Wayne Tam, Juan Carlos Ramos, David H. Henry, Samir Parekh, Erin G. Reid, Ronald Mitsuyasu, Timothy Cooley, Bruce J. Dezube, Lee Ratner, Ethel Cesarman, Anil Tulpule
Journal: Journal of Clinical Oncology (2012)

Infusional chemotherapy is efficacious in patients with AIDS-related lymphoma, but it may be difficult to administer. We studied standard agents with rituximab plus pegylated liposomal doxorubicin (DR-COP) in an attempt to provide a more practical approach to therapy while ascertaining rates of response, potential infectious complications, and prognostic role of biologic markers.We conducted a prospective, multi-institutional phase II trial, employing (day 1) pegylated liposomal doxorubicin 40 mg/m(2), rituximab 375 mg/m(2), cyclophosphamide 750 mg/m(2), vincristine 1.4 mg/m(2) (not > 2 mg), and prednisone 100 mg orally on days 1 through 5, with concomitant antiretroviral therapy.In 40 evaluable patients, median CD4 cells was 114/μL (range, 5 to 1,026/μL), and median HIV-1 viral load (VL) was 25,000 copies/mL. High or intermediate/high age-adjusted International Prognostic Index was present in 28%. Overall response was 67.5%, with complete remission in 47.5% (95% CI, 31.5 to 63.9). Of 19 complete responders, 84% had extranodal disease, 47% had CD4 < 100/μL, and 47% had VL > 50,000 copies/mL; one relapsed. With 25.5-month median follow-up, 62% (95% CI, 44 to 75) of patients remain alive. Sixteen patients (40%) experienced 22 infections, with grade 4 in only two (5%). No patient died as a result of infection during treatment; one had opportunistic infection.Profound immunodeficiency and high HIV-1 viral load do not preclude attainment of complete response after DR-COP with highly active antiretroviral therapy. The regimen is tolerable, and use of rituximab was not associated with death as a result of infection during treatment. This approach may be useful in patients in whom the more intensive infusional regimens are impractical.
Amaranthus Pollen Extracts: Protein Diversity and Impact on Diagnosis
Authors: S.M. Hasnain, A. Alaiya, M. Gad El Rab, M. Al-Mohanna, H. Al Sini, A. Al Qassim, A. Al-Sobhi, M. Al Enazi
Journal: Journal of Allergy and Clinical Immunology (2009)
EUSTAR biobanking: recommendations for the collection, storage and distribution of biospecimens in scleroderma research
Authors: C. Beyer, J. H. W. Distler, Y. Allanore, M. Aringer, J. Avouac, L. Czirjak, M. Cutolo, N. Damjanov, F. Del Galdo, K. Fligelstone, S. Guiducci, O. Kowal-Bielecka, J. M. van Laar, M. Martucci-Cerinic, U. Muller-Ladner, G. Riemekasten, I. H. Tarner, A. Tyndall, A. T. Kennedy, G. Valentini, S. Vettori, U. A. Walker, C. Denton, O. Distler
Journal: Annals of the Rheumatic Diseases (2011)

The European League Against Rheumatism Scleroderma Trials and Research Group (EUSTAR) has established an online database with clinical data of currently more than 8200 patients with systemic sclerosis (SSc). In addition to clinical research, EUSTAR fosters biomolecular studies to develop novel biomarkers and therapies for SSc. High-quality biospecimens are the basis for successful biomolecular studies. The EUSTAR biobanking group has therefore developed recommendations to standardise the collection, storage and distribution of SSc biospecimens at EUSTAR centres. These recommendations consider the scientific challenges associated with biomolecular research in SSc and the organisational requirements of EUSTAR. They were approved by the EUSTAR executive committee as well as the EUSTAR board. Once they become effective, these recommendations will be the basis for international EUSTAR studies with large numbers of SSc biospecimens. These recommendations might also be followed by other SSc consortia to enable exchange of biosamples between different SSc initiatives and might serve as a template for biobanking initiatives in other rheumatic diseases.
Semantic sides of three-dimensional space representation
Authors: Arnaud Badets
Journal: Behavioral and Brain Sciences (2013)

In this commentary, I propose that horizontal and vertical dimensions of space are represented together inside a common metrics mechanism located in the parietal cortex. Importantly, this network is also involved in the processing of number magnitudes and environment-directed actions. Altogether, the evidence suggests that different magnitude dimensions could be intertwined with the horizontality and verticality of our world representation.
Regulation of cardiac contractile function by troponin I phosphorylation
Authors: J LAYLAND, R SOLARO, A SHAH
Journal: Cardiovascular Research (2005)

Cardiac troponin I (cTnI) is a key regulatory protein in cardiac muscle contraction and relaxation, linking Ca2+–troponin C binding with activation of crossbridge reactions with the thin filament. In recent years, it has become increasingly apparent that myofilament properties as well as changes in intracellular Ca2+have a major role in the dynamic modulation of contractile function. The phosphorylation of specific serine and threonine residues on cTnI by several different kinases represents a major physiological mechanism for alteration of myofilament properties. Furthermore, altered thin filament function plays an important role in the contractile dysfunction associated with heart failure. Modification of cTnI by protein kinases A and C has been extensively studied with especially useful information deriving from (a) in vitro studies in reconstituted detergent-skinned fibre bundles in which endogenous cTnI was replaced with various targeted cTnI mutants and (b) transgenic animals in which endogenous cTnI was similarly manipulated through overexpression of cardiomyocyte-targeted cTnI mutants. cTnI may also be specifically modified by protein kinase G, p21-activated kinases and by dephosphorylation. This review focuses on recent advances in understanding the mechanisms of cTnI modification by these kinases and the consequent functional effects both under physiological conditions and in pathophysiological settings.
Recurrent bullous erythema multiforme treated with topical tacrolimus 0·1% ointment
Authors: E. Higgins, P. Collins
Journal: British Journal of Dermatology (2010)

Funding sources: none. Conflicts of interest: none declared. Madam, Recurrent erythema multiforme, defined as ‘the presence of a symmetrically distributed, fixed eruption, including target lesions, with or without mucous membrane involvement, occurring on at least three occasions’, is a condition of substantial morbidity.1 Herpes simplex virus (HSV) has been implicated as a causative factor in recurrent erythema multiforme.2 Continuous antiviral therapy has been used to suppress recurrent erythema multiforme.3 Immunosuppressive agents are typically used for patients who do not respond to antiviral therapy, often with varied and suboptimal response.4 We report a 56‐year‐old woman with recurrent bullous erythema multiforme, which responded to treatment with topical tacrolimus 0·1% ointment. This patient presented to her family doctor in April 2007 with targetoid plaques and bullae affecting her forearms and chest. This was preceded by an episode of herpes labialis. She was treated with oral prednisolone 20 mg daily and the rash resolved over 3 weeks. She presented to our department 1 year later with target lesions consisting of plaques and bullae affecting her forearms and hands (Fig. 1a, b), knees and feet, and with three red macules on the hard palate. A skin biopsy from the palmar left hand confirmed the diagnosis of bullous erythema multiforme, with bulla formation along the dermoepidermal junction with confluent necrosis of the epidermis. Direct immunofluorescence demonstrated a granular deposition of complement C3 along the basement membrane (Fig. 2a, b). The diagnosis was bullous erythema multiforme secondary to HSV infection and she was commenced on valaciclovir 500 mg once daily. Subsequently she developed further episodes of bullous erythema multiforme at the same site, without evidence of herpes simplex infection and some were painful and unsightly, particularly on her hands. She was using topical clobetasol propionate 0·05% ointment daily, using approximately 30 g weekly, but this failed to control her disease and she had weekly flares. Topical tacrolimus 0·1% ointment once daily was commenced, which resulted in resolution of existing lesions over 1 month, and allowed discontinuation of topical steroids. Topical tacrolimus 0·1% has effectively suppressed the appearance of any new lesions over the last 4 months.
Source of hepatitis A outbreak in Europe may be frozen berries
Authors: A. O'Dowd
Journal: BMJ (2014)

The number of cases of hepatitis A in 11 European countries has risen to 1315 since January 2013, show new figures from the European Food Safety Authority.

In a newly updated rapid outbreak assessment,1 the authority said that of the 1315 cases 240 were confirmed cases related to an ongoing outbreak of the infection.

The authority …
Impact of the Extent of Surgery and Postoperative Chemoradiotherapy on Recurrence Patterns in Gastric Cancer
Authors: Johan L. Dikken, Edwin P.M. Jansen, Annemieke Cats, Berdine Bakker, Henk H. Hartgrink, Elma Meershoek-Klein Kranenbarg, Henk Boot, Hein Putter, Koen C.M.J. Peeters, Cornelis J.H. van de Velde, Marcel Verheij
Journal: Journal of Clinical Oncology (2010)

The Intergroup 0116 trial has demonstrated that postoperative chemoradiotherapy (CRT) improves survival in gastric cancer. We retrospectively compared survival and recurrence patterns in two phase I/II studies evaluating more intensified postoperative CRT with those from the Dutch Gastric Cancer Group Trial (DGCT) that randomly assigned patients between D1 and D2 lymphadenectomy.Survival and recurrence patterns of 91 patients with adenocarcinoma of the stomach who had received surgery followed by radiotherapy combined with fluorouracil and leucovorin (n = 5), capecitabine (n = 39), or capecitabine and cisplatin (n = 47) were analyzed and compared with survival and recurrence patterns of 694 patients from the DGCT (D1, n = 369; D2, n = 325). For both groups, the Maruyama Index of Unresected Disease (MI) was calculated and correlated with survival and recurrence patterns.With a median follow-up of 19 months in the CRT group, local recurrence rate after 2 years was significantly higher in the surgery only (DGCT) group (17% v 5%; P = .0015). Separate analysis of CRT patients who underwent a D1 dissection (n = 39) versus DGCT-D1 (n = 369) showed fewer local recurrences after chemoradiotherapy (2% v 8%; P = .001), whereas comparison of CRT-D2 (n = 25) versus DGCT-D2 (n = 325) demonstrated no significant difference. CRT significantly improved survival after a microscopically irradical (R1) resection. The MI was found to be a strong independent predictor of survival.After D1 surgery, the addition of postoperative CRT had a major impact on local recurrence in resectable gastric cancer.
The effect of aerosol ipratropium bromide and salbutamol on exercise tolerance in chronic bronchitis.
Authors: A G Leitch, J M Hopkin, D A Ellis, S Merchant, G J McHardy
Journal: Thorax (1978)

In a double-blind placebo controlled trial in 24 patients fulfilling the MRC criteria for chronic bronchitis, ipratropium bromide 40 microgram and salbutamol 200 microgram produced similar and significant (P less than 0.001) increases in forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). A greater increase in FEV1 and FVC was seen when both drugs were used together, but this increase did not differ significantly from that produced by either drug alone. Salbutamol increased 12-minute walking distance significantly (P less than 0.001) by 62 +/- 15 metres, whereas the increase of 43 +/- 15 metres observed after ipratropium was not significant (P less than 0.05). With both drugs in combination 12-minute walking distance increased by 72 +/- 15 metres, but this change was not significantly different from that observed with salbutamol alone. If aerosol bronchodilators in the doses used in this study are to be given with a view to improving exercise tolerance in such patients than salbutamol would appear to be the aerosol of choice.
Localization and Pyrazinamide Inhibition of Distal Transtubular Movement of Uric Acid-2-C14 with a Modified Stop-Flow Technique*
Authors: Bernard B. Davis, James B. Field, Gerald P. Rodnan, Laurence H. Kedes
Journal: Journal of Clinical Investigation (1965)

Renal tubular secretion of uric acid has been demonstrated in several mammalian species in- cluding the rabbit (1), mongrel and Dalmatian dog (24), and man (7).Although secretion was easily delineated in the Dalmatian coach hound (4-6), special experimental conditions were neces- sary for its substantiation in other species.Uric acid clearance in excess of simultaneous creatinine clearance, indicative of tubular secretion of urate, was noted by Poulsen and Praetorius in rabbits made hyperuricemic by the intravenous infu- sion of urate (1).In 1959, Gutman, Yfi, and Berger (7) documented tubular secretion of uric acid in patients with reduced glomerular filtra- tion, who were given infusions of uric acid and mannitol and treated with large doses of sulfinpyrazone in order to suppress tubular reabsorption.One year later tubular secretion of urate was reported in the mongrel dog under similar conditions of an osmotic diuresis and an intravenous infusion of uric acid (2,3).Efforts to localize the site of tubular urate se- cretion in the mongrel dog by stop-flow analysis have yielded conflicting results.Yu and his col- leagues (3, 8) reported peak net tubular secretion in the distal segment of the nephron.However, Kessler, Hierholzer, and Gurd (6), utilizing the same experimental procedure except for the ad- ministration of probenecid, found no evidence for distal tubular secretion of urate.
Prediction of post-remission survival in acute myeloid leukaemia: a post-hoc analysis of the AML96 trial
Authors: Markus Pfirrmann, Gerhard Ehninger, Christian Thiede, Martin Bornhäuser, Michael Kramer, Christoph Röllig, Joerg Hasford, Markus Schaich
Journal: The Lancet Oncology (2011)
Fatal consequences of freshwater pearl diving
Authors: Nguyen Hoan Phu, Nguyen Thi Hoang Mai, Ho Dang Trung Nghia, Tran Thi Hong Chau, Pham Phu Loc, Le Hong Thai, Tran My Phuong, Cao Quang Thai, Dinh Nguyen Huy Man, Nguyen Van Vinh Chau, Tran Vu Thieu Nga, James Campbell, Stephen Baker, James Whitehorn
Journal: The Lancet (2013)
Increased frequency of asymptomatic bronchial hyperresponsiveness in nonasthmatic patients with food allergy
Authors: A. Thaminy, C. Lamblin, T. Perez, C. Bergoin, A.b Tonnel, B Wallaert
Journal: European Respiratory Journal (2000)

Subclinical inflammation in gut mucosa has been demonstrated in bronchial asthma suggesting the whole mucosal system is involved in allergic diseases. The presence of subclinical bronchial involvement was assessed by nonspecific bronchial hyperresponsiveness (BHR) in nonasthmatic patients with food allergy (FA). BHR was studied in 35 patients with various manifestations of FA without food-induced asthma. Sixteen had a previous history of asthma and/or rhinitis to aeroallergens (group A), whereas 19 patients (group B) did not. BHR was defined by a provocative dose causing a 20% fall in forced expiratory volume in one second of (PC20) &lt;8 mg.mL(-1) of methacholine. Asymptomatic BHR occurred frequently in nonasthmatic patients with FA (10 of 19, 53%); this did not significantly differ from patients with FA and a previous history of asthma and/or rhinitis to aeroallergens (13 of 16, 81%). PC20 was significantly lower in group A (1.84+/-0.53 mg.mL(-1)) than in group B (3.35+/-0.74 mg.mL(-1); p&lt;0.05). The number of patients with positive skin tests to aeroallergens was similar between groups. Sequential evaluation, performed 1 year after initial evaluation, in 7 nonasthmatic patients (group B) demonstrated a similar level of BHR. The present study demonstrated that BHR is a frequent finding in nonasthmatic patients with food allergy which may be due, at least in part, to a subclinical inflammatory process in the bronchi.
Association of patient-perceived COPD symptoms & activity limitations with comorbidities: The "COPD language" study
Authors: Epaminondas Kosmas, Petros Bakakos, Nikos Nikas, Elena Panitti, Paschalis Steiropoulos, Nikos Tzanakis, Michalis Toumbis
Journal: European Respiratory Journal (2013)

Background:  Comorbidities are common in COPD patients and may impact patient-perceived symptoms and disease management.   Objectives:  To evaluate the association of the words and phrases most frequently used by patients to express COPD symptoms and activity limitations with comorbidities.   Methods:  The “COPD Language” study (NCT01219946) was a cross-sectional survey of stable COPD patients under LAMA/LABA±ICS treatment. Investigators and patients chose words describing COPD symptoms and activity limitations from 2 identical lists.   Results : Of the 700 patients enrolled, 72% had ≥1 comorbidity, with hypertension(HTN)/diabetes being the most prevalent (57%/20% respectively). The words and phrases most frequently chosen by patients to describe COPD symptoms were “cough” (39%), “shortness of breath” (34%), “phlegm” (32%) and “chest sounds” (24%), whereas “walking uphill” (62%), “stair climbing” (59%), “brisk walking” (48%) and “can9t do what I want” (22%) most commonly described activity limitations. Positive associations were found for “shortness of breath” with heart failure (HF; p=0.012); “walking uphill” with HTN (p   Conclusions : Significant associations were found between patient comorbidities and certain patient-perceived COPD symptoms and activity limitations, implying that clinical presentation is not COPD-specific and could be attributed to comorbidities as well.
Informed Decision Making for Percutaneous Coronary Intervention for Stable Coronary Disease
Authors: Michael B. Rothberg, Senthil K. Sivalingam, Reva Kleppel, Marc Schweiger, Bo Hu, Karen R. Sepucha
Journal: JAMA Internal Medicine (2015)

IMPORTANCEPatients with stable coronary disease undergoing percutaneous coronary intervention (PCI) are frequently misinformed about the benefits of PCI.Little is known about the quality of decision making before angiography and possible PCI.OBJECTIVE To assess the quality of informed decision making and its association with patient decisions. DESIGN, SETTING, AND PARTICIPANTSWe performed a cross-sectional analysis of recorded conversations between August 1, 2008, and August 31, 2012, among adults with known or suspected stable coronary disease at outpatient cardiology practices.MAIN OUTCOMES AND MEASURES Presence of 7 elements of informed decision making and the decision to undergo angiography and possible PCI. RESULTSOf 59 conversations conducted by 23 cardiologists, 2 (3%) included all 7 elements of informed decision making; 8 (14%) met a more limited definition of procedure, alternatives, and risks.Specific elements significantly associated with not choosing angiography and possible PCI included discussion of uncertainty (odds ratio [OR], 20.5; 95% CI, 2.3-204.9),patient's role (OR, 5.3; 95% CI, 1.3-21.3),exploration of alternatives (OR, 9.5; 95% CI, 2.5-36.5),and exploration of patient preference (OR, 4.8; 95% CI, 1.2-19.4).Neither the presence of angina nor severity of symptoms was associated with choosing angiography and possible PCI.In a multivariable analysis using the total number of elements as a predictor, better informed patients were less likely to choose angiography and possible PCI (OR per additional element, 3.2; 95% CI, 1.4-7.1;P = .005). CONCLUSIONS AND RELEVANCEIn conversations between cardiologists and patients with stable angina, informed decision making is often incomplete.More complete discussions are associated with patients choosing not to undergo angiography and possible PCI.
Myocardin Is a Key Regulator of CArG-Dependent Transcription of Multiple Smooth Muscle Marker Genes
Authors: Tadashi Yoshida, Sanjay Sinha, Frédéric Dandré, Brian R. Wamhoff, Mark H. Hoofnagle, Brandon E. Kremer, Da-Zhi Wang, Eric N. Olson, Gary K. Owens
Journal: Circulation Research (2003)

The interactions between serum response factor (SRF) and CArG elements are critical for smooth muscle cell (SMC) marker gene transcription. However, the mechanisms whereby SRF, which is expressed ubiquitously, contributes to SMC-specific transcription are unknown. Myocardin was recently cloned as a coactivator of SRF in the heart, but its role in regulating CArG-dependent expression of SMC differentiation marker genes has not been clearly elucidated. In this study, we examined the expression and the function of myocardin in SMCs. In adult mice, myocardin mRNA was expressed in multiple smooth muscle (SM) tissues including the aorta, bladder, stomach, intestine, and colon, as well as the heart. Myocardin was also expressed in cultured rat aortic SMCs and A404 SMC precursor cells. Of particular interest, expression of myocardin was induced during differentiation of A404 cells, although it was not expressed in parental P19 cells from which A404 cells were derived. Cotransfection studies in SMCs revealed that myocardin induced the activity of multiple SMC marker gene promoters including SM α-actin, SM-myosin heavy chain, and SM22α by 9- to 60-fold in a CArG-dependent manner, whereas myocardin short interfering RNA markedly decreased activity of these promoters. Moreover, adenovirus-mediated overexpression of a dominant-negative form of myocardin significantly suppressed expression of endogenous SMC marker genes, whereas adenovirus-mediated overexpression of wild-type myocardin increased expression. Taken together, results provide compelling evidence that myocardin plays a key role as a transcriptional coactivator of SMC marker genes through CArG-dependent mechanisms.
The specificity of ultrasound-detected bone erosions for rheumatoid arthritis
Authors: Ahmed S Zayat, Karen Ellegaard, Philip G Conaghan, Lene Terslev, Elizabeth M A Hensor, Jane E Freeston, Paul Emery, Richard J Wakefield
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Bone erosion is one of the hallmarks of rheumatoid arthritis (RA), but also seen in other rheumatic diseases. The objective of this study was to determine the specificity of ultrasound (US)-detected bone erosions (including their size) in the classical 'target' joints for RA. <h3>Methods</h3> Patients fulfilling the diagnostic criteria for RA, psoriatic arthritis, osteoarthritis or gout in addition to healthy volunteers were included. The following areas were examined by US: distal radius and ulna, 2nd, 3rd and 5th metacarpophalangeal (MCP), 2nd and 3rd proximal interphalangeal (PIP) and 1st and 5th metatarsophalangeal (MTP) joints. All joints were scanned in four quadrants using both semiquantitative (0–3) and quantitative (erosion diameter) scoring systems. <h3>Results</h3> 310 subjects were recruited. The inter-reader and intrareader agreements were good to excellent. US-detected bone erosions were more frequent but not specific for RA (specificity 32.9% and sensitivity 91.4%). The presence of erosions with semiquantitative score ≥2 in four target joints (2nd, 5rd MCP, 5th MTP joints and distal ulna) was highly specific for RA (specificity 97.9% and sensitivity 41.4%). Size of erosion was found to be associated with RA. Erosions of any size in the 5th MTP joint were both specific and sensitive for RA (specificity 85.4% and sensitivity 68.6%). <h3>Conclusions</h3> The presence of US-detected erosions is not specific for RA. However, larger erosions in selected joints, especially 2nd and 5rd MCP, 5th MTP joints and distal ulna, were highly specific for and predictive of RA.