tbuckley/cabot-search huggingface dataset:
Response to Letter Regarding Article, “Effect of Sulfaphenazole on Tissue Plasminogen Activator Release in Normotensive Subjects and Hypertensive Patients”
Authors: Chiara Giannarelli, Agostino Virdis, Ferdinando De Negri, Armando Magagna, Emiliano Duranti, Antonio Salvetti, Stefano Taddei
Journal: Circulation (2009)

We thank Drs Brown and Pretorius for their interest in our article about the effect of sulfaphenazole on tissue plasminogen activator (t-PA) release. 1 Drs Brown and Pretorius are correct in observing that the t-PA concentrations in Table 2 are reported as ng • min Ϫ1 • 100 mL Ϫ1 instead of ng/mL, which is a clear typographical error.In fact, the calculation of t-PA release (balance) was properly reported in the Methods, and t-PA release was calculated accordingly.We agree that t-PA release by bradykinin in our study is lower than that reported by other investigators with similar doses. 2 A possible explanation is that our study population is significantly older (42Ϯ6 years) than that of Brown et al (28.9Ϯ2.1 years). 2 Aging significantly reduces nitric oxide (NO) availability.Given that an NO pathway promotes t-PA release, an aging effect is conceivable.Moreover, we infused a single bradykinin dose (equivalent to 225 ng/min) for 10 minutes instead of cumulative doses (100 to 400 ng/mL) for 5 minutes each.The different methodological approach could explain the discrepancy.Conflicting results relative to the role of NO on stimulated t-PA release exist. 2,3Brown and Pretorius observed no effect of NO synthase inhibitor N ␣ -monomethyl-L-arginine (L-NMMA) on bradykinin-stimulated t-PA release. 2 A likely explanation is an insufficient endothelial NO synthase inhibition, as demonstrated by the concomitant lacking effect of L-NMMA on bradykinin-induced vasodilation.Available evidence clearly demonstrates that L-NMMA inhibits bradykinin-induced vasodilation in healthy subjects. 4DeSouza et al 3 reported an increase of bradykinin-induced t-PA release in the presence of L-NMMA, a finding possibly related to the higher dose used (5 mg/min) compared with the one we infused (1 mg/min).Moreover, the NO-clamp technique was not used.Because t-PA balance is a function of plasma flow, it is conceivable that the greater vasoconstriction induced by the higher dose of L-NMMA could account for the observed increase of t-PA release.Use of the NO clamp, which restores basal blood flow after L-NMMA-induced vasoconstriction, overwhelms this methodological limitation.Finally, sodium nitroprusside is an exogenous NO donor, acting directly on vascular smooth muscle cells. 5Our finding that this compound failed to stimulate t-PA release reinforces the concept that the relationship between NO and fibrinolysis mainly exists within endothelial cells.
Fixed drug eruption: ultrastructural study of dyskeratotic cells
Authors: G. DOBBELEER, G. ACHTEN
Journal: British Journal of Dermatology (1977)

Electron microscopic studies have been carried out on three cases of fixed drug eruption, with particular regard to the dyskeratotic cells. The authors have tried to show the sequence of events leading from a normal basal keratinocyte to a dyskeratotic body. Ribosomes were first increased in number; then the the tonofbrillar system looked thicker, cytoplasmic organelles degenerated and numerous melanosomes appeared. Many dyskeratotic bodies were later found in epidermal macrophages and in the intercellular space. Several intra-cytoplasmic desmosomes were found in the dyskeratotic cells and their evolution is discussed. The increased number of melanosomes seen in the dyskeratotic bodies could be due to injury to epidermal cell and thei evolution be due to injury to epidermal lysosomal catabolism or it could be due to an apparent increase in melanosome numbers, within cells whose volume has been reduced.
Randomized Comparison of ABVD Chemotherapy With a Strategy That Includes Radiation Therapy in Patients With Limited-Stage Hodgkin’s Lymphoma: National Cancer Institute of Canada Clinical Trials Group and the Eastern Cooperative Oncology Group
Authors: Ralph M. Meyer, Mary K. Gospodarowicz, Joseph M. Connors, Robert G. Pearcey, Andrea Bezjak, Woodrow A. Wells, Bruce F. Burns, Jane N. Winter, Sandra J. Horning, A. Rashid Dar, Marina S. Djurfeldt, Keyue Ding, Lois E. Shepherd
Journal: Journal of Clinical Oncology (2005)

We report results of a randomized trial comparing ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) chemotherapy alone with treatment that includes radiation therapy in patients with limited-stage Hodgkin's lymphoma.Patients with nonbulky clinical stage I to IIA Hodgkin's lymphoma were stratified into favorable and unfavorable risk cohorts. Patients allocated to radiation-containing therapy received subtotal nodal radiation if favorable risk or combined-modality therapy if unfavorable risk. Patients allocated to ABVD received four to six treatment cycles.We evaluated 399 patients. Median follow-up is 4.2 years. In comparison with ABVD alone, 5-year freedom from disease progression is superior in patients allocated to radiation therapy (P = .006; 93% v 87%); no differences in event-free survival (P = .06; 88% v 86%) or overall survival (P = .4; 94% v 96%) were detected. In a subset analyses comparing patients stratified into the unfavorable cohort, freedom from disease progression was superior in patients allocated to combined-modality treatment (P = .004; 95% v 88%); no difference in overall survival was detected (P = .3; 92% v 95%). Of 15 deaths observed, nine were attributed to causes other than Hodgkin's lymphoma or acute treatment-related toxicity.In patients with limited-stage Hodgkin's lymphoma, no difference in overall survival was detected between patients randomly assigned to receive treatment that includes radiation therapy or ABVD alone. Although 5-year freedom from disease progression was superior in patients receiving radiation therapy, this advantage is offset by deaths due to causes other than progressive Hodgkin's lymphoma or acute treatment-related toxicity.
Yellow nail syndrome: does protein leakage play a role?
Authors: A. D'Alessandro, G. Muzi, A. Monaco, S. Filiberto, A. Barboni, G. Abbritti
Journal: European Respiratory Journal (2001)

Yellow nail syndrome is characterized by primary lymphoedema, recurrent pleural effusion and yellow discoloration of the nails. Although mechanical lymphatic obstruction is assumed to be the underlying pathology, it cannot explain the common finding of high albumin concentration in the pleural space. This paper describes a case of yellow nail syndrome presenting with the classical triad of lymphoedema, recurrent pleural effusion and yellow discoloration of the nails, associated with persistent hypoalbuminaemia and increased enteric loss of albumin. Based on the findings in this case and those in the literature, it is speculated that increased microvascular permeability may contribute to the pathogenesis of this syndrome.
Haemodynamic effects of pressure support and PEEP ventilation by nasal route in patients with stable chronic obstructive pulmonary disease.
Authors: N Ambrosino, S Nava, A Torbicki, G Riccardi, C Fracchia, C Opasich, C Rampulla
Journal: Thorax (1993)

BACKGROUND--Intermittent positive pressure ventilation applied through a nasal mask has been shown to be useful in the treatment of chronic respiratory insufficiency. Pressure support ventilation is an assisted mode of ventilation which is being increasingly used. Invasive ventilation with intermittent positive pressure, with or without positive end expiratory pressure (PEEP), has been found to affect venous return and cardiac output. This study evaluated the acute haemodynamic support ventilation by nasal mask, with and without the application of PEEP, in patients with severe stable chronic obstructive pulmonary disease and hypercapnia. METHODS--Nine patients with severe stable chronic obstructive pulmonary disease performed sessions lasting 10 minutes each of pressure support ventilation by nasal mask while undergoing right heart catheterisation for clinical evaluation. In random order, four sessions of nasal pressure support ventilation were applied consisting of: (1) peak inspiratory pressure (PIP) 10 cm H2O, PEEP 0 cm H2O; (2) PIP 10 cm H2O, PEEP 5 cm H2O; (3) PIP 20 cm H2O, PEEP 0 cm H2O; (4) PIP 20 cm H2O, PEEP 5 cm H2O. RESULTS--Significant increases in arterial oxygen tension (Pao2) and saturation (Sao2) and significant reductions in arterial carbon dioxide tension (PaCO2) and changes in pH were observed with a PIP of 20 cm H2O. Statistical analysis showed that the addition of 5 cm H2O PEEP did not further improve arterial blood gas tensions. Comparison of baseline values with measurements performed after 10 minutes of each session of ventilation showed that all modes of ventilation except PIP 10 cm H2O without PEEP induced a small but significant increase in pulmonary capillary wedge pressure. In comparison with baseline values, a significant decrease in cardiac output and oxygen delivery was induced only by the addition of PEEP to both levels of PIP. CONCLUSIONS--In patients with severe stable chronic obstructive pulmonary disease and hypercapnia, pressure support ventilation with the addition of PEEP delivered by nasal mask may have short term acute haemodynamic effects in reducing oxygen delivery in spite of adequate levels of SaO2.
Chronic Kidney Disease, Cardiovascular Events, and the Effects of Perindopril-Based Blood Pressure Lowering
Authors: Vlado Perkovic, Toshiharu Ninomiya, Hisatomi Arima, Martin Gallagher, Meg Jardine, Alan Cass, Bruce Neal, Stephen MacMahon, John Chalmers
Journal: Journal of the American Society of Nephrology (2007)

Chronic kidney disease (CKD) is associated with a high risk of cardiovascular disease, but evidence regarding the effectiveness of interventions to reduce that risk is lacking. The Perindopril Protection against Recurrent Stroke Study (PROGRESS) study enrolled 6105 participants with cerebrovascular disease and randomly allocated them to perindopril-based blood pressure-lowering therapy or placebo. Individuals with CKD were at approximately 1.5-fold greater risk of major vascular events, stroke, and coronary heart disease, and were more than twice as likely to die (all P< or =0.002). Perindopril-based treatment reduced the risk of major vascular events by 30% and stroke by 35% among subjects with CKD, and the absolute effects of treatment were 1.7-fold greater for those with CKD than for those without. Considering patients with CKD and a history of cerebrovascular disease, perindopril prevented one stroke or other cardiovascular event among every 11 patients treated over five years. In conclusion, kidney function should be considered when determining the need for blood pressure lowering therapy in patients with cerebrovascular disease.
Ultrasonic delivery of silica–gold nanoshells for photothermolysis of sebaceous glands in humans: Nanotechnology from the bench to clinic
Authors: Dilip Paithankar, Byeong Hee Hwang, Girish Munavalli, Arielle Kauvar, Jenifer Lloyd, Richard Blomgren, Linda Faupel, Todd Meyer, Samir Mitragotri
Journal: Journal of Controlled Release (2015)
Prophylaxis of Graft-Versus-Host Disease in Unrelated Donor Transplantation With Pentostatin, Tacrolimus, and Mini-Methotrexate: A Phase I/II Controlled, Adaptively Randomized Study
Authors: Simrit Parmar, Borje S. Andersson, Daniel Couriel, Mark F. Munsell, Marcelo Fernandez-Vina, Roy B. Jones, Elizabeth J. Shpall, Uday Popat, Paolo Anderlini, Sergio Giralt, Amin Alousi, Pedro Cano, Doyle Bosque, Chitra Hosing, Leandro de Padua Silva, Michael Westmoreland, J. Kyle Wathen, Donald Berry, Richard E. Champlin, Marcos J. de Lima
Journal: Journal of Clinical Oncology (2010)

Acute graft-versus-host disease (aGVHD) is a major cause of morbidity and mortality after matched unrelated, related, or mismatched related donor hematopoietic stem-cell transplantation (HSCT). Improved GVHD prevention methods are needed. Pentostatin, an adenosine deaminase inhibitor, leads to lymphocyte depletion with low risk of myelosuppression. We hypothesized that addition of pentostatin to GVHD prophylaxis with tacrolimus and mini-methotrexate may improve outcomes, and we conducted a Bayesian adaptively randomized, controlled, dose-finding study, taking into account toxicity and efficacy.Success was defined as the patient being alive, engrafted, in remission, without GVHD 100 days post-HSCT and no grade ≥ 3 GVHD at any time. Patients were randomly assigned to pentostatin doses of 0, 0.5, 1.0, 1.5, and 2.0 mg/m(2) with drug administered on HSCT days 8, 15, 22, and 30. Eligible patients were recipients of mismatched related (n = 10) or unrelated (n = 137) donor HSCT.Median age was 47 years. Thirty-seven, 10, 29, 61, and 10 patients were assigned to the control and four treatment groups, respectively, with comparable baseline characteristics. Pentostatin doses of 1.0 and 1.5 mg/m(2) had the highest success rates (69.0% and 70.5%) versus control (54.1%). The posterior probabilities that the success rates were greater with 1.5 mg/m(2) or 1.0 mg/m(2) versus control are 0.944 and 0.821, respectively. Hepatic aGVHD rates were 0%, 17.2%, and 11.1%, respectively, for 1.5 mg/m(2), 1.0 mg/m(2), and control groups. No grades 3 to 4 aGVHD occurred in 11 HLA-mismatched recipients in the 1.5 mg/m(2) group.Pentostatin increased the likelihood of success as defined here, and should be further investigated in larger randomized, confirmatory studies.
Caring for the brain tumor patient: Family caregiver burden and unmet needs
Authors: Jane R. Schubart, Mable B. Kinzie, Elana Farace
Journal: Neuro-Oncology (2007)

The rapid onset and progression of a brain tumor, cognitive and behavioral changes, and uncertainty surrounding prognosis are issues well known to health practitioners in neuro-oncology. We studied the specific challenges that family caregivers face when caring for patients experiencing the significant neurocognitive and neurobehavioral disorders associated with brain tumors. We selected 25 family caregivers of adult brain tumor patients to represent the brain tumor illness trajectory (crisis, chronic, and terminal phases). Interviews documented caregiving tasks and decision-making and information and support needs. Themes were permitted to emerge from the data in qualitative analysis. We found that the family caregivers in this study provided extraordinary uncompensated care involving significant amounts of time and energy for months or years and requiring the performance of tasks that were often physically, emotionally, socially, or financially demanding. They were constantly challenged to solve problems and make decisions as care needs changed, yet they felt untrained and unprepared as they struggled to adjust to new roles and responsibilities. Because the focus was on the patient, their own needs were neglected. Because caregiver information needs are emergent, they are not always known at the time of a clinic visit. Physicians are frequently unable to address caregiver questions, a situation compounded by time constraints and cultural barriers. We provide specific recommendations for (1) improving the delivery of information; (2) enhancing communication among patients, families, and health care providers; and (3) providing psychosocial support for family caregivers.
Regional Arterial Stiffness in Patients with Type 2 Diabetes and Chronic Kidney Disease
Authors: Eiji Kimoto, Tetsuo Shoji, Kayo Shinohara, Sawako Hatsuda, Katsuhito Mori, Shinya Fukumoto, Hidenori Koyama, Masanori Emoto, Yasuhisa Okuno, Yoshiki Nishizawa
Journal: Journal of the American Society of Nephrology (2006)

Increased arterial stiffness is an independent predictor of death from cardiovascular disease, and aortic stiffness is more predictive than stiffness of other arterial regions. Because little is known about the effect of chronic kidney disease (CKD) on regional arterial stiffness, pulse wave velocity (PWV) of four different arterial segments was measured in patients who had type 2 diabetes with and without various stages of CKD. A total of 434 patients had type 2 diabetes, and there were 192 healthy control subjects who were comparable in age and gender. GFR was estimated by the abbreviated Modification of Diet in Renal Disease equation. The patients with diabetes were classified into CKD stages by the definition of the Kidney Disease Outcomes Quality Initiative guidelines. PWV was measured in the heart-femoral, heart-carotid, heart-brachial, and femoral-ankle segments simultaneously using an automatic pulse wave analyzer. PWV of each arterial region was increased in patients who had diabetes without kidney damage and was increased further in a stepwise manner with the advanced stages of CKD. The increase in PWV was greater in the heart-femoral and heart-carotid regions than in the heart-brachial and femoral-ankle segments. However, after adjustment for age, BP, and other confounding factors using a multiple regression model, decreased GFR was independently associated with increased PWV of the heart-femoral region but not with PWV of other arterial segments. In type 2 diabetes, CKD was associated with increased stiffness of arteries, particularly of the aorta. The cross-sectional result may explain the increased risk for cardiovascular disease in CKD, although longitudinal studies are needed to confirm it.
Phase I and Pharmacokinetic Study of Weekly Docetaxel, Cisplatin, and Daily Capecitabine in Patients with Advanced Solid Tumors
Authors: Marwan G. Fakih, Patrick J. Creaven, Nithya Ramnath, Donald Trump, Milind Javle, Sandra Strychor, Trisha V.W. Repinski, Beth A. Zamboni, James K. Schwarz, Renee A. French, William C. Zamboni
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Docetaxel, cisplatin, and capecitabine are three active chemotherapeutic agents with different mechanisms of action. This phase I study investigated the feasibility and pharmacokinetics of this combination given on a weekly schedule. Experimental Design: Docetaxel and cisplatin were given i.v. over 30 minutes on days 1 and 8 and capecitabine was given orally bid on days 1 to 14 (every 21 days). Escalation occurred in cohorts of three patients until the maximum tolerated dose was defined. Pharmacokinetics studies of docetaxel and total and ultrafiltrate platinum after cisplatin administration were done on cycle 1 (with capecitabine) and cycle 2 (without capecitabine). Results: Twenty-five patients were enrolled. Two of six patients at dose level 5 had a dose-limiting infection and diarrhea. One of six evaluable patients at dose level 4 (27 mg/m2 docetaxel, 27 mg/m2 cisplatin, 825 mg/m2 capecitabine) had a dose-limiting hypomagnesemia. Pharmacokinetics of docetaxel were similar on cycles 1 and 2. Area under the plasma concentrations versus time curves of total platinum was significantly greater in cycle 2 compared with cycle 1 (P = 0.001). There was no difference in the disposition of docetaxel on cycles 1 and 2. Conclusions: The recommended docetaxel, cisplatin, and capecitabine dose for phase II studies is 27/27/825 mg/m2. The alteration in total and ultrafiltrate platinum disposition on cycle 2 compared with cycle 1 may be inherent to sequential cisplatin administration; however, prior treatment with capecitabine cannot be ruled out as a factor.
Murine Cutaneous Mastocytosis and Epidermal Melanocytosis Induced by Keratinocyte Expression of Transgenic Stem Cell Factor
Authors: Takahiro Kunisada, Shu-Zhuang Lu, Hisahiro Yoshida, Satomi Nishikawa, Shin-ichi Nishikawa, Masako Mizoguchi, Shin-ichi Hayashi, Lynda Tyrrell, David A. Williams, Xiaomei Wang, B. Jack Longley
Journal: The Journal of Experimental Medicine (1998)

The growth and differentiation of mast cells and melanocytes require stem cell factor (SCF), the ligand for the kit receptor tyrosine kinase. SCF may exist as a membrane-bound or soluble molecule. Abnormalities of the SCF-kit signaling pathway, with increased local concentrations of soluble SCF, have been implicated in the pathogenesis of the human disease cutaneous mastocytosis, but have not yet been shown to play a causal role. To investigate both the potential of SCF to cause mastocytosis and its role in epidermal melanocyte homeostasis, we targeted the expression of SCF to epidermal keratinocytes in mice with two different transgenes controlled by the human keratin 14 promoter. The transgenes contained cDNAs that either produced SCF, which can exist in both membrane-bound and soluble forms, or SCF, which remains essentially membrane bound. Murine epidermal keratinocyte expression of membrane-bound/ soluble SCF reproduced the phenotype of human cutaneous mastocytosis, with dermal mast cell infiltrates and epidermal hyperpigmentation, and caused the maintenance of a population of melanocytes in the interadnexal epidermis, an area where melanocytes and melanin are found in human skin but where they are not typically found in murine skin. Expression of membrane-bound SCF alone resulted in epidermal melanocytosis and melanin production, but did not by itself cause mastocytosis. We conclude, first, that a phenotype matching that of human mastocytosis can be produced in mice by keratinocyte overproduction of soluble SCF, suggesting a potential cause of this disease. Second, we conclude that keratinocyte expression of membrane-bound SCF results in the postnatal maintenance of epidermal melanocytes in mice. Since the resulting animals have skin that more closely approximates human skin than do normal mice, their study may be more relevant to human melanocyte biology than the study of skin of normal mice.
Identification of a New Panel of Serum Autoantibodies Associated with the Presence of <i>In situ</i> Carcinoma of the Breast in Younger Women
Authors: Caroline Desmetz, Caroline Bascoul-Mollevi, Philippe Rochaix, Pierre-Jean Lamy, Andrew Kramar, Philippe Rouanet, Thierry Maudelonde, Alain Mangé, Jerome Solassol
Journal: Clinical Cancer Research (2009)

We examined the feasibility of using a panel of autoantibodies to multiple tumor-associated proteins as a method for early detection of breast cancer and, more particularly, carcinoma in situ (CIS).PPIA, PRDX2, and FKBP52 were identified as early-stage breast cancer autoantigens by proteomic approaches. The seroreactivity of a panel of antibodies consisting of these three antigens and two previously described autoantigens, HSP60 and MUC1, was tested on 235 samples (60 from primary breast cancer patients, 82 from CIS patients, and 93 from healthy controls) with the use of specific ELISAs. FKBP52, PPIA, and PRDX2 mRNA and protein expression levels were evaluated by reverse transcription-PCR and immunohistochemistry in early-stage breast tumors.Three of five autoantibodies, FKBP52, PPIA, and PRDX2, showed significantly increased reactivity in primary breast cancer and CIS compared with healthy controls. When combined, the five markers significantly discriminated primary breast cancer [receiver operating characteristic area under the curve, 0.73; 95% confidence interval (95% CI), 0.60-0.79] and CIS (receiver operating characteristic area under the curve, 0.80; 95% CI, 0.71-0.85) from healthy individuals. Importantly, the receiver operating characteristic-area under the curve value of the autoantibody panel was able to distinguish CIS, including high grades, from healthy controls in women under the age of 50 years (receiver operating characteristic area under the curve, 0.85; 95% CI, 0.61-0.92). Finally, only FKBP52 mRNA and protein levels were found to be increased in CIS and primary breast cancer compared with healthy breast tissue.This autoantibody assay against a panel of five antigens allows for an accurate discrimination between early-stage breast cancer, especially CIS, and healthy individuals. These results could be of interest in detecting early breast cancer as an aid to mammography, especially in women under the age of 50 years with aggressive cancers.