tbuckley/cabot-search huggingface dataset:
Gadolinium blocks rat kupffer cell calcium channels: Relevance to calcium-dependent prostaglandin E2 synthesis and septic mortality
Authors: Claude R. Roland, Bashoo Naziruddin, T. Mohanakumar, Wayne M. Flye
Journal: Hepatology (1999)

Hepatic Kupffer cells (KC), the major tissue macrophage population, produce the septic response mediators, tumor necrosis factor α (TNF–α) and prostaglandin E 2 (PGE 2 ), and have been shown to internalize gadolinium chloride (GD), a rare earth metal of the lanthanide series. Because GD pretreatment of rats has been shown to inhibit the mortality of sepsis, we studied the secretory response to lipopolysaccharide (LPS) by KC isolated from rats injected with either saline or GD (7 mg/kg, intravenously) on the 2 days before KC isolation. Using culture conditions modified to reflect the intrasinusoidal milieu of arginine (RPMI–1640 media with 10 or 100 μmol/L arginine), KC from GD–treated rats responded to LPS (0.0025 μg/mL) with significantly ( P &lt; .01) reduced PGE 2 release. In contrast, TNF–α release by treated KC was significantly ( P &lt; .05) enhanced, consistent with the loss of PGE 2 autocoid inhibition of TNF–α. Calcium flux is an early signaling event in eicosanoid synthesis, and GD is known to block calcium channels. Therefore, KC were loaded with fura–2–AM to study the effect of GD on KC calcium flux. GD prevented ionomycin and platelet–activating factor (PAF)–mediated [Ca ++ ] i increase and calcium–dependent PGE 2 synthesis, while GD did not affect PGE 2 synthesis when protein kinase C (PKC) was directly activated with tetradecanoylphorbolacetate (TPA). The inhibition of calcium flux and calcium–dependent PGE 2 synthesis in the major cell of the monocytic phagocytic system by GD may explain the previously reported ability of this lanthanide to prevent the mortality of endotoxemia.
Relationship Between the Magnitude of Reduction in Mitral Regurgitation Severity and Left Ventricular and Left Atrial Reverse Remodeling After MitraClip Therapy
Authors: Paul A. Grayburn, Elyse Foster, Chithra Sangli, Neil J. Weissman, Joseph Massaro, Donald G. Glower, Ted Feldman, Laura Mauri
Journal: Circulation (2013)

Background— MitraClip has been shown to reduce mitral regurgitation (MR) severity safely but to a lesser degree than surgery. No data exist on the magnitude of MR reduction necessary to reverse left ventricular (LV) and left atrial (LA) dilation in patients with severe MR. Therefore, an analysis was performed to evaluate the relationship between MR reduction and LV and LA volumes after MitraClip therapy. Methods and Results— A total of 801 patients treated with MitraClip and 80 patients treated surgically were included. All patients had severe (3–4+) MR. MR severity, LV volumes at end-diastole and end-systole, and LA volumes were measured at baseline, discharge, 30 days, 6 months, and 1 year by an independent echocardiographic core laboratory. A linear repeated measures model was developed to determine the relationship between MR severity and time of measurement postindex procedure on longitudinal LV and LA volumes. Separate models were fit for functional MR and degenerative MR. In both degenerative and functional MR, reduction in LV volumes at end-diastole was associated with degree of residual MR at 12 months ( P &lt;0.0001). LV volumes at end-systole was significantly reduced in functional MR but not degenerative MR. LA volumes were significantly related to reduction of MR severity in both groups. Conclusions— Reduction of LV volumes at end-diastole and LA volumes, but not LV volumes at end-systole in degenerative MR, is consistent with correction of volume overload from primary MR. Reduction of all 3 measurements in functional MR demonstrates reverse remodeling when MR severity is reduced to either 1+ or 2+ by MitraClip therapy. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00209274.
The effect of intralesional 5-Fluorouracil Therapeutic Implant (MPI 5003) for treatment of basal cell carcinoma
Authors: E K Orenberg, B H Miller, H T Greenway, J A Koperski, N Lowe, T Rosen, D M Brown, M Inui, A G Korey, E E Luck
Journal: Journal of the American Academy of Dermatology (1992)
Away with all application forms
Authors: R T. Jones
Journal: BMJ (1981)

to high concentrations of oxygen as under a general anaesthetic.2Haemorrhage may be present in the thrombocytopenic patient.3The clinical importance of this is obvious.Steroids will improve the drug-induced change but encourage infection.Antibiotics will treat an infection but have no effect on disease infiltrates.Cytotoxic drugs will improve disease infiltrates but worsen drug-induced change.It is interesting to note the work of Phillips et al.1 They obtained a histological diagnosis with transbronchial lung biopsy in 26 out of 42 patients with Hodgkin's disease, lymphoma, or leukaemia who had pulmonary disease that failed to respond to antibiotics.Perhaps the current practice of putting diagnosis before treatment is incorrect in these patients as diagnosis represents a relatively hazardous procedure.Empirical use of anti- biotics to exclude infection may be the first step in management.It is uncertain how long a trial of antibiotics should be continued before further investigation is initiated.
<i>In Situ</i> Tumor PD-L1 mRNA Expression Is Associated with Increased TILs and Better Outcome in Breast Carcinomas
Authors: Kurt A. Schalper, Vamsidhar Velcheti, Daniel Carvajal, Hallie Wimberly, Jason Brown, Lajos Pusztai, David L. Rimm
Journal: Clinical Cancer Research (2014)

Blockade of the PD-1/PD-L1 axis emerged as a promising new therapeutic option for cancer that has resulted in lasting responses in metastatic renal, lung carcinomas, and melanomas. Tumor PD-L1 protein expression may predict response to drugs targeting this pathway. Measurement of PD-L1 protein is limited by the lack of standardized immunohistochemical methods and variable performance of antibodies. Our goal was to correlate PD-L1 mRNA expression with clinical variables in primary breast carcinomas.The fluorescent RNAscope paired-primer assay was used to quantify in situ PD-L1 mRNA levels in 636 stage I-III breast carcinomas on two sets of tissue microarrays [YTMA128 (n = 238) and YTMA201 (n = 398)]. Tumor-infiltrating lymphocytes (TIL) were assessed by hematoxylin/eosin stain and quantitative fluorescence.On YTMA128 and YTMA201, 55.7% and 59.5% of cases showed PD-L1 mRNA expression, respectively. Higher PD-L1 mRNA expression was significantly associated with increased TILs (P = 0.04) but not with other clinical variables. Elevated TILs (scores 2 and 3+) occurred in 16.5% on YTMA128 and 14.8% on YTMA201 and was associated with estrogen receptor-negative status (P = 0.01 on YTMA128 and 0.0001 on YTMA201). PD-L1 mRNA expression was associated with longer recurrence-free survival (log-rank P = 0.01), which remained significant in multivariate analysis including age, tumor size, histologic grade, nodal metastasis, hormone receptor, HER2 status, and the extent of TILs (HR, 0.268; CI, 0.099-0.721; P = 0.009).PD-L1 mRNA expression is identified in nearly 60% of breast tumors and it is associated with increased TILs and improved recurrence-free survival. These observations support the evaluation of PD-1/PD-L1-targeted therapies in breast cancer.
Minor Histocompatibility Antigens and Marrow Transplantation
Authors: Nancy A. Kernan, Bo Dupont
Journal: New England Journal of Medicine (1996)

Acute graft-versus-host disease (GVHD) and graft rejection are the principal obstacles to successful allogeneic bone marrow transplantation. Even among recipients of transplants from HLA-identical siblings, the incidence of severe acute GVHD ranges from 20 to 50 percent, depending on the type of immunosuppressive prophylaxis given after transplantation.1 Among recipients of apparently HLA-identical marrow from unrelated donors, the incidence of acute GVHD can reach 64 percent.2 The frequent occurrence of GVHD and graft rejection after the transplantation of marrow from HLA-identical siblings underscores the importance of factors other than HLA antigens. Two articles in this issue of the Journal address possible . . .
Relation between free triiodothyronine/free thyroxine ratio, echocardiographic parameters and mortality in dilated cardiomyopathy
Authors: Guliz Kozdag, Dilek Ural, Ahmet Vural, Aysen Agacdiken, Goksel Kahraman, Tayfun Sahin, Ertan Ural, Baki Komsuoglu
Journal: European Journal of Heart Failure (2004)
β lactam monotherapy versus β lactam-aminoglycoside combination therapy for sepsis in immunocompetent patients: systematic review and meta-analysis of randomised trials
Authors: Mical Paul, Ishay Benuri-Silbiger, Karla Soares-Weiser, Leonard Leibovici
Journal: BMJ (2004)

Abstract Objective To compare β lactam monotherapy with β lactam-aminoglycoside combination therapy for severe infections. Data sources Medline, Embase, Lilacs, Cochrane Library, and conference proceedings, to 2003; references of included studies; contact with all authors. No restrictions, such as language, year of publication, or publication status. Study selection All randomised trials of β lactam monotherapy compared with β lactam-aminoglycoside combination therapy for patients without neutropenia who fulfilled criteria for sepsis. Data selection Two reviewers independently applied selection criteria, performed quality assessment, and extracted the data. The primary outcome assessed was all cause fatality by intention to treat. Relative risks were pooled with the random effect model (relative risk &lt; 1 favours monotherapy). Results 64 trials with 7586 patients were included. There was no difference in all cause fatality (relative risk 0.90, 95% confidence interval 0.77 to 1.06). 12 studies compared the same β lactam (1.02, 0.76 to 1.38), and 31 studies compared different β lactams (0.85, 0.69 to 1.05). Clinical failure was more common with combination treatment overall (0.87, 0.78 to 0.97) and among studies comparing different β lactams (0.76, 0.68 to 0.86). There was no advantage to combination therapy among patients with Gram negative infections (1835 patients) or Pseudomonas aeruginosa infections (426 patients). There was no difference in the rate of development of resistance. Nephrotoxicity was significantly more common with combination therapy (0.36, 0.28 to 0.47). Heterogeneity was not significant for these comparisons. Conclusions In the treatment of sepsis the addition of an aminoglycoside to β lactams should be discouraged. Fatality remains unchanged, while the risk for adverse events is increased.
Severity of Airflow Limitation Is Associated with Severity of Airway Inflammation in Smokers
Authors: ANTONINO DI STEFANO, ARMANDO CAPELLI, MIRCO LUSUARDI, PIERO BALBO, CINZIA VECCHIO, PIERO MAESTRELLI, CRISTINA E. MAPP, LEONARDO M. FABBRI, CLAUDIO F. DONNER, MARINA SAETTA
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

To investigate the relationship between airflow limitation and airway inflammation in smokers, we examined paraffin-embedded bronchial biopsies obtained from 30 smokers: 10 with severe airflow limitation, eight with mild/moderate airflow limitation, and 12 control smokers with normal lung function. Histochemical and immunohistochemical methods were performed to assess the number of inflammatory cells in the subepithelium and the expression of CC chemokines macrophage inflammatory protein (MIP)-1 α and -1 β in the bronchial mucosa. Compared with control smokers, smokers with severe airflow limitation had an increased number of neutrophils (p < 0.02), macrophages (p < 0.03), and NK lymphocytes (p < 0.03) in the subepithelium, and an increased number of MIP-1 α+ epithelial cells (p < 0.02). When all smokers were considered together, the value of FEV1 was inversely correlated with the number of neutrophils (r = − 0.59, p < 0.002), macrophages (r = − 047, p < 0.012), NK-lymphocytes (r = − 0.51, p < 0.006) in the subepithelium, and with the number of MIP-1 α+ epithelial cells (r = − 0.61, p < 0.003). We conclude that in smokers the severity of airflow limitation is correlated with the severity of airway inflammation and that severe airflow limitation is associated with an increased number of neutrophils, macrophages, NK lymphocytes, and MIP-1 α+ cells in the bronchial mucosa.
Aortic root dilatation and mitral valve prolapse in Marfan's syndrome: an ECHOCARDIOgraphic study.
Authors: O R Brown, H DeMots, F E Kloster, A Roberts, V D Menashe, R K Beals
Journal: Circulation (1975)

Echocardiographic and phonocardiographic findings in 35 patients with Marfan's Syndrome and ten patients without Marfan's or other clinically apparent connective tissue disorders but with angiographic and echocardiographic evidence of mitral prolapse are reported and compared. Echocardiography revealed aortic root dilatation and/or mitral valve prolapse in 97% of the patients with Marfan's Syndrome. Aortic root dilatation was found in 60% of this group (74% of males, 33% of females) while mitral valve prolapse was found in 91% (87% of males, 100% of females). The incidence of aortic dilatation and mitral prolapse in patients with Marfan's syndrome was essentially equal in children and adults of the same sex. None of the nine adults or one child with mitral prolapse but without evidence of Marfan's Syndrome or other clinically apparent connective tissue disorder had aortic root enlargement. Ausculatory examination and phnocardiography revealed abnormalities in 54% of the patients with Marfan's Syndrome. Aortic regurgitation was found in 23% of this group (35% of males, 0% of females) while mitral regurgitation and/or mitral clicks were found in 46% (39% of males, 58% of females). Aortic regurgitation was much more frequent in adult males with Marfan's Syndrome (7/14, 50%) than male children (1/9, 11%), while the incidence of abnormal mitral sounds was essentially the same in adults (33% of males, 60% of females) and children (43% of males, 57% of females) of the same sex with Marfan's Syndrome. Abnormal mitral sounds were more frequent in patients without Marfan's who had mitral prolapse (90%) than in those with Marfan's (46%). It appears that cardiac abnormalities are a consistent manifestation of Marfan's Syndrome and that ultrasound is a more sensitive indicator of these abnormalities in such patients than ausculation or phonocardiography.
The use and abuse of ethnography
Authors: Tim Ingold
Journal: Behavioral and Brain Sciences (2001)

Human beings grow into cultural knowledge, within a social and environmental context, rather than receiving it ready made. This seems also to be true of cetaceans. Rendell and Whitehead invoke a notion of culture long since rejected by anthropologists, and fundamentally misunderstand the nature of ethnography. A properly ethnographic study of cetaceans would directly subvert their positivist methodology and reductionist assumptions.
Reversibility of exogenous corticosteroid-induced bone loss
Authors: G Rizzato, L Montemurro
Journal: European Respiratory Journal (1993)

Osteoporosis is not usually considered to be reversible, as it is a consequence of the ageing process. However, an improvement of bone mineral density after successful surgery in Cushing's syndrome has been shown in several reports. The question of reversibility of exogenous corticosteroid-induced osteoporosis is, as yet, unanswered, possibly because of the difficulty in discontinuing steroids after long-term use. We describe six patients, all under 45 yrs of age, with chronic long-standing sarcoidosis, in whom long-term prednisone therapy resulted in 15 +/- 7% bone loss, as evaluated by quantitative computed tomography. This side-effect appeared fully reversible after prednisone withdrawal. This report of the reversibility of exogenous corticosteroid-induced bone loss needs confirmation in elderly people, where the capacity for recovery of bone mass could be reduced. Such potential for recovery may have implications for the pattern of use of corticosteroids.
Replacement of methicillin-resistant Staphylococcus aureus clones in Hungary over time: a 10-year surveillance study
Authors: T. Conceição, M. Aires-de-Sousa, M. Füzi, Á. Tóth, J. Pászti, E. Ungvári, W.B. van Leeuwen, A. van Belkum, H. Grundmann, H. de Lencastre
Journal: Clinical Microbiology and Infection (2007)
Translymphatic Chemotherapy by Intrapleural Placement of Gelatin Sponge Containing Biodegradable Paclitaxel Colloids Controls Lymphatic Metastasis in Lung Cancer
Authors: Jiang Liu, Dale Meisner, Elizabeth Kwong, Xiao Y. Wu, Michael R. Johnston
Journal: Cancer Research (2009)

Abstract As a means of treating lymphatic metastasis from lung cancer, the pharmacokinetics and therapeutic effects of an intrapleural (ipl) implantable drug delivery system consisting of a gelatin sponge impregnated with polylactide-co-glycolide paclitaxel (PLGA-PTX) microspheres were studied. PLGA-PTX with 7% (w/w) drug loading were incorporated into gelatin matrix. The pharmacokinetics were studied in rats with one of the following regimens: (a) Taxol 8 mg/kg by i.v. injection; (b) Taxol 8 mg/kg ipl; (c) PLGA-PTX (100 mg/kg) ipl; (d) sponge containing PLGA-PTX (100 mg/kg) ipl. PTX concentrations in lymph node and plasma were determined by liquid chromatography mass spectrometry, and the area under the curve (AUC) was calculated. Therapeutic efficacy was assessed in an orthotopic lung cancer model with tumor resection 14 days following tumor implantation. Animals were randomized to ipl placement of PLGA-PTX sponge, placebo sponge, or no treatment. Lymph node metastases were examined at 32 d. The results show that the mediastinal lymph node AUC was significantly higher with ipl. placement of PLGA-PTX sponge compared with i.v. and ipl administration of Taxol. This represents 100- to 400-fold increase of lymphatic drug exposure compared with i.v. dosing. Peak plasma concentration was significantly reduced in the PLGA-PTX sponge group compared with i.v. dosing. PLGA-PTX particles were microscopically identified in lymphatic tissue and resulted in an 80% reduction of lymphatic metastasis compared with controls. Translymphatic-targeted drug delivery significantly decreases lymphatic metastasis in an orthotopic lung cancer model. This effect may be attributable to the improved distribution of PTX to the lymphatic system. [Cancer Res 2009;69(3):1174–81]
NAD(P)H Oxidase–Dependent Self-Propagation of Hydrogen Peroxide and Vascular Disease
Authors: Hua Cai
Journal: Circulation Research (2005)

Excessive production of reactive oxygen species in the vasculature contributes to cardiovascular pathogenesis. Among biologically relevant and abundant reactive oxygen species, superoxide (O2*-) and hydrogen peroxide (H2O2) appear most important in redox signaling. Whereas O2*- predominantly induces endothelial dysfunction by rapidly inactivating nitric oxide (NO*), H2O2 influences different aspects of endothelial cell function via complex mechanisms. This review discusses recent advances establishing a critical role of H2O2 in the development of vascular disease, in particular, atherosclerosis, and mechanisms whereby vascular NAD(P)H oxidase-derived H2O2 amplifies its own production. Recent studies have shown that H2O2 stimulates reactive oxygen species production via enhanced intracellular iron uptake, mitochondrial damage, and sources of vascular NAD(P)H oxidases, xanthine oxidase, and uncoupled endothelial nitric oxide synthase (eNOS). This self-propagating phenomenon likely prolongs H2O2-dependent pathological signaling in vascular cells, thus contributing to vascular disease development. The latest progress on Nox functions in vascular cells is also discussed [Nox for NAD(P)H oxidases, representing a family of novel NAD(P)H oxidases].
Prognostic and predictive role of ESR1 status for postmenopausal patients with endocrine-responsive early breast cancer in the Danish cohort of the BIG 1-98 trial
Authors: B. Ejlertsen, J. Aldridge, K.V. Nielsen, M.M. Regan, K.L. Henriksen, A.E. Lykkesfeldt, S. Müller, R.D. Gelber, K.N. Price, B.B. Rasmussen, G. Viale, H. Mouridsen
Journal: Annals of Oncology (2011)
Quality of life assessment in patients receiving adjuvant therapy for breast cancer: The IBCSG approach
Authors: J. Bernhard, C. Hürny, A.S. Coates, H.F. Peterson, M. Castiglione-Gertsch, R.D. Gelber, A. Goldhirsch, H.-J. Senn, C.-M. Rudenstam
Journal: Annals of Oncology (1997)
Bridging Dermatologists With Patient Advocacy Organizations Through Smartphones
Authors: A. Shadi Kourosh, Evan D. Schoenberg, Jean M. Dejace, Paul R. Bergstresser
Journal: JAMA Dermatology (2014)

Patient advocacy organizations seek to increase their benefits for patients with skin disease; low awareness and patient referrals among dermatologists have presented an obstacle to this.To determine whether the Skin Advocate iPhone App would increase awareness and referrals to patient advocacy organizations in the Coalition of Skin Diseases (CSD) among Texas dermatologists and dermatology residents and patient registrations among CSD member organizations.We present results of an institutional review board-exempted investigation conducted among member organizations of the CSD and among dermatologists and dermatology residents in Texas from April 1, 2011, through March 31, 2013. Effects were measured in a blinded fashion subjectively through pre-intervention and post-intervention surveys and objectively through internal analytics that tracked downloads and use of the iPhone app, as well as pre-intervention and post-intervention numbers of registrations for CSD member organizations.The Skin Advocate iPhone App.Awareness and referrals to patient advocacy organizations in the CSD among Texas dermatologists and dermatology residents and patient registrations among CSD member organizations.Throughout the study, mean app use ranged from 3.3 to 3.6 uses per user per month, maintaining the 3-fold improvement compared with self-reported referral for 90% of the study population and a 12-fold improvement for 64% of the study population. Our data revealed substantial improvement in self-reported physician awareness and referrals, and increased patient registrations for CSD organizations.The Skin Advocate iPhone App improved physician awareness and subsequent referrals to CSD member organizations.
Correlation of structure with T cell responses of the three members of the HLA-DRw52 allelic series.
Authors: J Gorski, C Irle, E M Mickelson, M J Sheehy, A Termijtelen, C Ucla, B Mach
Journal: The Journal of Experimental Medicine (1989)

A third allele at the DRB3 locus, DRw52c, represents an intermediate sequence between DRw52a and DRw52b and may have arisen by a gene conversion-like event. The recognition of cells bearing these molecules by a number of alloreactive and antigen-specific DR-restricted T cell clones was analyzed. On the basis of a theoretical model of HLA class II structure, distinct amino acid clusters have been identified as motifs controlling TCR recognition. These are located both in the cleft and in the alpha-helical edge of the MHC class II recognition platform. Motifs shared between two alleles may restrict public T cell clones.