tbuckley/cabot-search huggingface dataset:
Expression of biosynthetic enzymes for leukotrienes B4 and C4 in tonsillar tissue of children with OSA
Authors: Marina Tsaoussoglou, Souzana Hatzinikolaou, Loukia Lianou, Panagiotis Maragozidis, Nikolaos Balatsos, Polytimi Panaghiotopoulou-Gartagani, George Chrousos, Athanasios Kaditis
Journal: European Respiratory Journal (2013)

Objective: Cysteinyl leukotrienes potentially promote adenotonsillar hypertrophy in children with obstructive sleep apnea (OSA). In adults, 5-lipoxygenase (5-LO) is expressed by tonsillar B-lymphocytes, but conflicting data have been presented regarding 5-LO in T-lymphocytes. We hypothesized that in children with OSA, leukotriene biosynthetic enzymes [5-LO; 5-LO activating protein (FLAP); LTA4 hydrolase (LTA4H); and leukotriene C4 synthase (LTC4S)] are expressed by both T- and B-tonsillar lymphocytes. Study design: Tonsillar tissue from children with OSA or controls with recurrent tonsillitis (RT) was studied for expression of biosynthetic enzymes by RT-PCR and flow cytometry (FC). Results: Thirteen children with OSA and 12 subjects with RT were included. mRNA for all enzymes was detected in both T- and B-lymphocytes. Children with OSA had higher LTC4S mRNA copies obtained from CD19+ B-lymphocytes than subjects with RT (RT-PCR: 1.72 ± 0.14 vs. 1.14 ± 0.92; p=0.04). There were no other differences in mRNA copies for the other enzymes from T- or B-lymphocytes. In OSA participants, LTC4S + fractions of CD3+ T-lymphocytes or CD19+ B-lymphocytes were significantly higher than in children with RT (FC: 22.5 ± 13.8% vs. 11.8 ± 6.7% or 28.9 ± 18% vs. 14.5 ± 11%, respectively; p<0.05). The two groups were similar regarding T- or B-lymphocytes fractions expressing other enzymes. Conclusions: Enzymes of the leukotriene biosynthetic pathway are detected in both T- and B-tonsillar lymphocytes. Children with sleep apnea and hypertrophic tonsils have enhanced expression of LTC4S, a key enzyme for cysteinyl leukotriene synthesis.
Bisphosphonate therapy requirement during adjuvant aromatase inhibitor therapy in early breast cancer patients according to UK bone health guidelines
Authors: M. Moe, M. Almatari, P. Ali, P. Willshaw
Journal: Journal of Clinical Oncology (2009)

e11612 Background: Adjuvant aromatase inhibitor (AI) therapy increases bone loss and incidence of bone fracture. Recently published UK bone health guidelines recommend to prescribe bisphosphonate (BPN) during adjuvant AI therapy for T score of -2 or less, or annual loss of bone density &gt;4%, or known vertebral fracture, or patients over the age of 75 with one or more clinical risk factors (previous low-trauma fracture after age 50, previous hip fracture, alcohol intake of &gt;4 units/ day, diseases associated with secondary osteoporosis, prior corticosteroids for &gt;6 months, BMI &lt;22). We evaluated the impact of BPN therapy requirement using UK guidelines on adjuvant AI therapy patients. Methods: Patients who were commencing adjuvant AI therapy for early breast cancer underwent Dual energy X-ray Absorptiometry (DXA) bone density assessment, with a baseline scan and 2 subsequent scans. Results: A total of 91 patients were eligible and included in this study (median age 59). Different AIs included anastrozole(68), exemestane (7) and letrozole (16). Patients received AI therapy in up-front (56), sequential (15) and extended adjuvant (20) therapy settings. Median duration of AI therapy was 35 months, with 85 patients having received therapy for more than 24 months. BPN was prescribed to 35 patients during AI therapy as per local practice. According to WHO classification, 11 patients were found to have osteoporosis at the 1 st scan, and 4 &amp; 2 patients were found to develop osteoporosis at 2 nd &amp; 3 rd scans, respectively. According to UK guidelines, however, BPN therapy would be indicated in 56 patients (62%): after 1 st scan 22 patients, after 2 nd scan another 26 patients and following the 3 rd scan an additional 8 patients. Factors predictive of BPN indication during AI therapy are hyperthyroidism (p = 0.009), previous fracture (p = 0.001) and smoking (p = &lt;0.001). Patients who took tamoxifen for more than one year are less likely to require BPN compared to those who did not take tamoxifen (p = 0.028) Conclusions: Majority of patients (up to 62% in our study) will require BPN during adjuvant AI for breast cancer. Therefore the cost of BPN and potential drug side effects need to be taken into account in the use of adjuvant AI, and it's health economic analysis. No significant financial relationships to disclose.
Surgical approach to mediastinal goiter: An update based on a retrospective cohort study
Authors: Andrea Polistena, Alessandro Sanguinetti, Roberta Lucchini, Sergio Galasse, Massimo Monacelli, Stefano Avenia, Roberta Triola, Walter Bugiantella, Fabio Rondelli, Roberto Cirocchi, Nicola Avenia
Journal: International Journal of Surgery (2015)
More doctors charged with manslaughter are being convicted, shows analysis
Authors: Philip White
Journal: BMJ (2015)

More doctors in the United Kingdom who are charged with medical manslaughter and whose cases reach court are being convicted and sent to jail, data indicate, though overall numbers are too small for statistical analysis.

Searches of news, legal, and medical databases, together with a request to the General Medical Council made under freedom of information legislation, found that 11 doctors had been charged with medical (gross negligence) manslaughter in the UK between 2006 and the end of 2013. Of these, six (55%) were convicted.

The last three doctors convicted in 2012-13 all received custodial sentences rather than the usual suspended sentence (box). Before that the previous doctor to get a custodial sentence for medical manslaughter was in 2004.1

Since December 2014 four more doctors have been charged with medical manslaughter and are awaiting trial.

The 55% conviction rate was …
Abstract 21449: Control of Hif1 and Hif2 in Smooth Muscle is Crucial for Normal Development and Survival
Authors: Li Lei, Dingang Liu, Wedong Jiang, Yan Huang, Frank J Giordano
Journal: Circulation (2010)

Objective: To investigate the role of the VHL-HIF1-HIF2 axis in smooth muscle. Methods: VHL, HIF1alpha, and HIF2alpha floxed allele mice in a C57BL6 background were crossed with SM22alpha-Cre mice ...
Entrenching an association between Islam, fear, and violence
Authors: Salman Waqar
Journal: BMJ (2015)

Gardham’s analysis begins with questions about the teaching and entry standards of medical schools overseas—namely, in Muslim majority nations bearing the brunt of terrorism—and their accreditation by the General Medical Council.1 On its own this argument may have merit, but Gardham’s attempt to link this as a material threat is unfounded and poorly constructed. The insinuation of guilt in the …
Myeloid but not lymphoid cells carry the 5q deletion: polymerase chain reaction analysis of loss of heterozygosity using mini-repeat sequences on highly purified cell fractions
Authors: MJ Kroef, WE Fibbe, R Mout, RP Jansen, HL Haak, JW Wessels, H Van Kamp, R Willemze, JE Landegent
Journal: Blood (1993)
ADHD and Obesity
Authors: J.J. Sandra Kooij
Journal: American Journal of Psychiatry (2016)

The systematic review and meta-analysis by Cortese and colleagues, published in this issue of the Journal (1), shows a clear association between attention deficit hyperactivity disorder (ADHD) and obesity in more than 700,000 children and adults, of whom 48,161 had ADHD.Strengths of the study are that the finding was validated in both children and adults separately.The findings were also similar in both epidemiological and clinical populations.The association between ADHD and obesity remained significant after controlling for confounding factors such as gender, study setting, study country, and study quality.The association between ADHD and obesity also remained significant when investigating only studies that had adjusted for possible confounding factors such as depression, when restricted to diagnoses of ADHD by direct interview (instead of rating scales), and when using directly measured height and weight (instead of self-reported height and weight).The risk of obesity was higher in adult ADHD compared with childhood ADHD, pointing to an obesity risk that increases over time.Interestingly, individuals medicated for ADHD were not at higher risk for obesity.Many unpublished studies were included, but a limitation of the study is that data from some unpublished studies were not available or otherwise included.
Response to “Insulin-like growth factor 1 receptor signaling via Akt: a general therapeutic target in neurocutaneous melanocytosis?”
Authors: Yibing Ruan, Aru Narendran
Journal: Neuro-Oncology (2015)

those seen in skin fibroblasts.However, we could not detect any significant difference in expression levels compared with normal epidermal melanocytes isolated from newborn foreskin (Fig. 1A).No significant difference was observed in IGFBP3 expression between NRAS and BRAF mutated cells (Fig. 1B); neither did we find any disparity between NCM and non-NCM nevus cells (Fig. 1C).These data indicate that lower IGFBP expression could be a general characteristic of cells of melanocytic lineage that depend on IGF signaling for their survival, and not a function of their oncogenic status.Consistent with this idea, the IGF1R blocker AEW-541 could reduce cell viability in NRAS and BRAF mutant cells, albeit to different degrees (Fig. 1D).The reduced cell viability observed by Ruan and colleagues was associated with decreased Akt phosphorylation, which was interpreted as a downstream effect due to pharmacological blockade of IGF1R.Recently, we reported a similar reduction in phospho-Akt, due to a dual inhibition of phosphatidylinositol-3 kinase and mammalian target of rapamycin (PI3K-mToR) in NRAS mutant NCM cells. 5Based on these observations, it appears that Akt could be considered a major nodal point of signal convergence for IGF1R and oncogenic NRAS and an important mediator of cell survival in NCM cells.In conclusion, we present evidence in support of IGF1R as a general therapeutic target in NCM irrespective of oncogenic status.
Membrane Translocation of 15-Lipoxygenase in Hematopoietic Cells Is Calcium-Dependent and Activates the Oxygenase Activity of the Enzyme
Authors: Roland Brinckmann, Kerstin Schnurr, Dagmar Heydeck, Thomas Rosenbach, Gerhard Kolde, Hartmut Kühn
Journal: Blood (1998)
Phase II study of vincristine sulfate liposomes injection in patients with metastatic uveal melanoma
Authors: A. Y. Bedikian, T. Sato, K. B. Kim, N. E. Papadopoulos, W. Hwu, J. Homsi, M. Davies, C. Cheung, S. M. Imperiale, P. Prasad, P. Hwu
Journal: Journal of Clinical Oncology (2009)

9067 Background: Preclinical and clinical studies showed that liposomal encapsulation of vincristine sulfate (VCR) results in increased drug circulation time and accumulation of VCR at the tumor site. Marqibo has been administered safely at 2.25 mg/m2, a dose exceeding that typically employed for VCR ( dose capped at 2 mg), with tolerable clinical toxicities consistent with VCR. Of the 27 previously treated patients with metastatic melanoma in the Marqibo pharmacokinetic studies, 3 patients had a tumor response, including one patient with uveal melanoma metastatic to the lung that experienced a complete response. Methods: Patients with metastatic uveal melanoma with no more than one prior systemic therapy were enrolled. Patients with controlled brain metastases were allowed. Marqibo (2.25 mg/m2 by 1-hour intravenous infusion, no dose capping) was administered every 14 days until tumor progression. Responses were assessed every 6 weeks using the Response Evaluation Criteria in Solid Tumors (RECIST). Toxicity was assessed at least as frequently as before each dose. Results: Preliminary data is available for 22 enrolled patients (73% female). Median age was 65 years (range 38–79), 23% were previously treated with systemic chemotherapy, 86% had liver metastasis and 96% had M1c disease. Baseline serum LDH levels were elevated in 73% and were more than 2 × ULN in 37% of the patients. Twenty-one patients were evaluable for response; one patient discontinued the treatment after a single dose of therapy for toxicity without tumor progression. No patients died of drug toxicity while on the study. Twelve patients (57%) had stable disease. Estimated median survival is 6.4 months. Fourteen patients are alive, 2 for more than 12 months. Treatment related side effects were mostly grade 1 or 2; peripheral neuropathy was the only grade 3 toxicity, seen in 18% of the patients. The hematologic toxicities were minor; no neutropenia or thrombocytopenia was seen. Conclusions: Marqibo is well tolerated as single agent therapy in patients with advanced stage IV uveal melanoma. Its impact on the progression-free and overall survival of these critically ill patients will be presented. No significant financial relationships to disclose.
The Authors' reply
Authors: A. Cardenas, P. Gines
Journal: Gut (2011)

We thank Dr Hutchinson and Dr Davies for their comments1 regarding the use of alternative options in patients with cirrhosis and refractory ascites. The use of other potential therapies for patients with refractory ascites is attractive and should perhaps be considered in selected cases. Therapies such as clonidine, a centrally acting α2-agonist and sympatholytic agent, and the use of vasoconstrictors such as midodrine have been …
Sorafenib Inhibition of Mcl-1 Accelerates ATRA-Induced Apoptosis in Differentiation-Responsive AML Cells
Authors: Rui Wang, Lijuan Xia, Janice Gabrilove, Samuel Waxman, Yongkui Jing
Journal: Clinical Cancer Research (2015)

Abstract Purpose: All trans-retinoic acid (ATRA) is successful in treating acute promyelocytic leukemia (APL) by inducing terminal differentiation-mediated cell death, but it has limited activity in non-APL acute myeloid leukemia (AML). We aim to improve ATRA therapy of AML by enhancing apoptosis through repression of the antiapoptotic proteins Bcl-2 and Mcl-1. Experimental Design: APL and AML cell lines, as well as primary AML samples, were used to explore the mechanisms regulating differentiation and apoptosis during ATRA treatment. Stable transfection and gene silencing with siRNA were used to identify the key factors that inhibit apoptosis during induction of differentiation and drugs that accelerate apoptosis. Results: In differentiation-responsive AML cells, ATRA treatment induces long-lasting repression of Bcl-2 while first upmodulating and then reducing the Mcl-1 level. The Mcl-1 level appears to serve as a gatekeeper between differentiation and apoptosis. During differentiation induction, activation of MEK/ERK and PI3K/Akt pathways by ATRA leads to activation of p90RSK and inactivation of glycogen synthase kinase 3β (GSK3β), which increase Mcl-1 levels by increasing its translation and stability. Sorafenib blocks ATRA-induced Mcl-1 increase by reversing p90RSK activation and GSK3β inactivation, maintains the repressed Bcl-2 level, and enhances ATRA induced apoptosis in non-APL AML cell lines and in primary AML cells. Conclusions: Inhibition of Mcl-1 is required for apoptosis induction in ATRA differentiation-responsive AML cells. ATRA and sorafenib can be developed as a novel drug combination therapy for AML patients because this drug combination augments apoptosis by inhibiting Bcl-2 and Mcl-1. Clin Cancer Res; 22(5); 1211–21. ©2015 AACR.
Corrigendum to “Environmental pH-sensitive polymeric nano-carriers for targeted tumor delivery” [J. Control. Release 213 (2015) e46–e47]
Authors: Shih-Han Kao, Kuo-Yen Huang, Hsin-Jung Li, S.-Ja Tseng, Zi-Xian Liao, Ivan Kempson
Journal: Journal of Controlled Release (2015)
Reply from Authors re: Camillo Porta, Chiara Paglino. Experience Gathered from Retrospective Series on Renal Cell Carcinoma Is Useful, But Now It Is Time for a Global Claim for Academically Driven Prospective Studies. Eur Urol 2013;64:71–2
Authors: Steffen Weikert, Viktor Grünwald
Journal: European Urology (2012)
Changes in Needle Sharing and Syringe Cleaning among San Francisco Drug Abusers
Authors: J L Sorensen, J Guydish, M Costantini, S L Batki
Journal: New England Journal of Medicine (1989)

Studies conducted from 1985-1987 indicated that most intravenous drug users in San Francisco were attempting to reduce their risks of infection with HIV by cleaning their syringes with bleach but these studies found only small changes in the reported frequency of needle sharing.  Recent analyses of patient reports in our San Francisco drug- abuse clinic reveal considerable decreases in needle sharing as well.  All clients entering the outpatients heroin detoxification clinic of San Francisco General Hospital from 1986-1988 answered questions about the number of times they had shared needles in the previous month and the number of people who had shared each needle.  To assess the change in such statistics over time we selected all clinical admission (n=313) in June of each of the 3 years.  The results are shown in Figure 1.  The proportion of patients sharing needles decreased from 55% to 28% (p<0.001).  However the decrease is accounted for by patients reporting 1 needle-sharing partner which decreased from 37% to 15%.  The proportion of patients who reported sharing a needle with 2 or more partners decreased only 5%--from 18% in 1986 to 13% in 1988.  In a multiple logistic regression analysis controlling for age sex race and previous treatment cocaine use was significantly (p<0.05) associated with needle sharing with multiple partners in the month before admission.  In addition patients have reported using condoms in the syringe-cleaning process.  The rubber plunger becomes stiff when the syringe is repeatedly sterilized with bleach.  Several patients have reported lubricating the plunger by inserting it into the packet of a lubricated condom thus restoring its smooth action.  The use of condoms to lubricate syringes may have some value if the lubricant contains sufficient nonoxynol 9 and provided it does not contribute to irritation or infection.  This practice also provides drug users with a reason to carry condoms eliminating 1 reason for not using them during sexual activity.  (full text)
Abstract 4484: Predictors of Early vs. Late Stent Thrombosis after Drug Eluting vs. Bare Metal Stent Implantation: A Protective Effect of High Dose Statin Therapy?
Authors: Raban Jeger, Hanspeter Brunner-La Rocca, Gregor Leibundgut, Fabian Nietlispach, Michael Handke, Christoph Kaiser, Matthias Pfisterer
Journal: Circulation (2008)

Background: Several predictors of stent thrombosis (ST) after implantation of drug-eluting stents (DES) have been identified. However, no data is available on the differences between early vs. late ST despite their different pathophysiology. In addition, a direct comparison of predictors of ST after DES vs. bare metal stent (BMS) implantation is lacking. Methods: Baseline clinical and angiographic parameters and 3-year follow-up data of the Basel Kosten Effektivitäts Trial (BASKET; 826 patients randomized 2:1 to DES vs. BMS) were analyzed in univariate and multivariate models regarding early ST, i.e., ST on dual antiplatelet therapy with aspirin and clopidogrel in the first 6 months, and late ST, i.e., ST on aspirin only after the first 6 months (definite, probable, and possible). Separate analyses were done for DES and BMS. Results: Overall, there were 51 (9.0%) vs. 21 (7.5%) ST in DES vs. BMS treated patients (p=0.51). Multivariate predictors of early ST in DES (n=16) were the use of glycoprotein IIb/IIIa inhibitors (OR 6.65, 95% CI 1.80 –24.57; p=0.005), type C lesions (OR 5.46, 95% CI 1.73–17.23; p=0.004), 3-vessel disease (OR 4.77, 95% CI 1.49 –15.26; p=0.009), statin dose (OR 0.37 per quintile increase, 95% CI 0.19 – 0.74; p=0.005), and intervention in the right coronary artery (OR 0.14, 95% CI 0.03– 0.69; p=0.016), whereas the only multivariate predictor of early ST in BMS (n=11) was age (OR 1.05 per year increase, 95% CI 1.005–1.092; p=0.029). The only multivariate predictor of late ST in DES (n=35) was saphenous vein graft intervention (OR 6.74, 95% CI 2.85–15.85; p&lt;0.0001), whereas multivariate predictors of late ST in BMS (n=10) were saphenous vein graft intervention (OR 5.23, 95% CI 0.92–29.75; p=0.062) and age (OR 1.098 per year increase, 95% CI 1.021–1.18; p=0.011). Conclusion: Early ST after DES implantation mainly depends on the complexity of the disease and the intervention, with the use of a higher statin dose possibly having a protective effect against early ST. The observation of a strong dose-dependent protective effect of statins to prevent early ST after DES is new, hypothesis-generating, and should be evaluated in an adequately powered prospective randomized trial.
Radioimmunotherapy of interleukin-2R alpha-expressing adult T-cell leukemia with Yttrium-90-labeled anti-Tac [see comments]
Authors: TA Waldmann, JD White, JA Carrasquillo, JC Reynolds, CH Paik, OA Gansow, MW Brechbiel, ES Jaffe, TA Fleisher, CK Goldman
Journal: Blood (1995)
Influence of Sex on Mortality and Perioperative Outcomes in Patients Undergoing TAVR
Authors: Loïc Bière, Marie Launay, Frédéric Pinaud, Jean-François Hamel, Hélène Eltchaninoff, Bernard Iung, Marc Laskar, Alain Leguerrier, Martine Gilard, Alain Furber
Journal: Journal of the American College of Cardiology (2015)
Selective versus routine use of pegfilgrastim in dose-dense chemotherapy.
Authors: Alexandra R. Pass, Caylin Lo, Jennifer Bishop, K. M. Steve Lo
Journal: Journal of Clinical Oncology (2014)

149 Background: ASCO recommends CSFs such as pegfilgrastim for dose dense doxorubicin cyclophosphamide paclitaxel (ddACT) in breast cancer. It is unclear whether dose dense paclitaxel requires pegfilgrastim, and some community oncologists use pegfilgrastim selectively with the dose dense paclitaxel portion of ddACT. We reviewed the results of pegfilgrastim use based on physician preference within a single breast oncology community-based practice. Methods: This is a single-center, single-practice retrospective cohort study of adjuvant ddACT for breast cancer patients identified from the pharmacy database between 1/2010 and 6/2014. Patient demographics, stage, chemotherapy and pegfilgrastim use, chemotherapy delays, febrile neutropenic (FN) events, and pain records including narcotic use were collected from patient charts. Patients receiving pegfilgrastim routinely at cycle 1 were compared to those within the practice given pegfilgrastim selectively for ANC &lt; 1.5 on day of treatment or nadir ANC &lt; 1.0 during the preceding cycle. Differences between groups were analyzed using the Mann-Whitney test, with significance at the p &lt; 0.05 level. Results: The two groups were balanced with regard to age and number of cycles. There were no significant differences in cycle delay, and FN. Routine pegfilgrastim resulted in more bone pain and higher cost. Conclusions: The selective use of pegfilgrastim during the paclitaxel portion of ddACT did not result in chemotherapy delay, more infections or FN. It did decrease painful myalgia and arthralgias, and dramatically lowered treatment cost. These retrospective data, although limited by participant number, question the need for the routine use of pegfilgrastim for the paclitaxel portion of ddACT and require prospective validation. [Table: see text]