tbuckley/cabot-search huggingface dataset:
Parenteral Nutrition with Fish Oil Modulates Cytokine Response in Patients with Sepsis
Authors: Konstantin Mayer, Stephanie Gokorsch, Christine Fegbeutel, Katja Hattar, Simone Rosseau, Dieter Walmrath, Werner Seeger, Friedrich Grimminger
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Infusion of fish oil-based (n-3) lipids may influence leukocyte function and plasma lipids in critical care patients. Twenty-one patients with sepsis requiring parenteral nutrition were randomized to receive an n-3 lipid emulsion rich in eicosapentaenoic acid and docosahexaenoic acid or a conventional (n-6) lipid emulsion (index fatty acid: arachidonic acid) for 5 days. The impact on plasma-free fatty acids, mononuclear leukocyte cytokine generation, and membrane fatty acid composition was examined. Cytokine synthesis by isolated mononuclear leukocyte was elicited by endotoxin. Before the onset of lipid infusion therapy, plasma-free fatty acid concentrations were greatly increased in septic patients, with arachidonic acid by far surpassing eicosapentaenoic acid and docosahexaenoic acid, a feature maintained during conventional lipid infusion. Within 2 days of fish oil infusion, free n-3 fatty acids increased, and the n-3/n-6 ratio was reversed, with rapid incorporation of n-3 fatty acids into mononuclear leukocyte membranes. Generation of proinflammatory cytokines by mononuclear leukocytes was markedly amplified during n-6 and was suppressed during n-3 lipid application. After termination of lipid administration, free n-3 fatty acid concentrations and mononuclear leukocyte cytokine synthesis returned to preinfusion values. Use of lipid infusions might allow us to combine intravenous alimentation with differential impact on inflammatory events and immunologic functions in patients with sepsis.
Atrial fibrillation: effects beyond the atrium?
Authors: R. S. Wijesurendra, B. Casadei
Journal: Cardiovascular Research (2015)

Atrial fibrillation (AF) is the most common sustained clinical arrhythmia and is associated with significant morbidity, mostly secondary to heart failure and stroke, and an estimated two-fold increase in premature death. Efforts to increase our understanding of AF and its complications have focused on unravelling the mechanisms of electrical and structural remodelling of the atrial myocardium. Yet, it is increasingly recognized that AF is more than an atrial disease, being associated with systemic inflammation, endothelial dysfunction, and adverse effects on the structure and function of the left ventricular myocardium that may be prognostically important. Here, we review the molecular and in vivo evidence that underpins current knowledge regarding the effects of human or experimental AF on the ventricular myocardium. Potential mechanisms are explored including diffuse ventricular fibrosis, focal myocardial scarring, and impaired myocardial perfusion and perfusion reserve. The complex relationship between AF, systemic inflammation, as well as endothelial/microvascular dysfunction and the effects of AF on ventricular calcium handling and oxidative stress are also addressed. Finally, consideration is given to the clinical implications of these observations and concepts, with particular reference to rate vs. rhythm control.
Mobilizing Dendritic Cells for Tolerance, Priming, and Chronic Inflammation
Authors: Federica Sallusto, Antonio Lanzavecchia
Journal: The Journal of Experimental Medicine (1999)

M igration of Dendritic Cells from Blood to Tissues. A fundamental aspect of dendritic cell (DC) function is their capacity to migrate. It allows them to exert a continuous surveillance for incoming antigens in almost all body tissues and a prompt report to T cells in secondary lymphoid organs.
Prevalence of Obesity and Trends in the Distribution of Body Mass Index Among US Adults, 1999-2010
Authors: Katherine M Flegal, Margaret D Carroll, Brian K Kit, Cynthia L Ogden
Journal: JAMA (2012)

<h3>Context</h3>Between 1980 and 1999, the prevalence of adult obesity (body mass index [BMI] ≥30) increased in the United States and the distribution of BMI changed. More recent data suggested a slowing or leveling off of these trends.<h3>Objective</h3>To estimate the prevalence of adult obesity from the 2009-2010 National Health and Nutrition Examination Survey (NHANES) and compare adult obesity and the distribution of BMI with data from 1999-2008.<h3>Design, Setting, and Participants</h3>NHANES includes measured heights and weights for 5926 adult men and women from a nationally representative sample of the civilian noninstitutionalized US population in 2009-2010 and for 22 847 men and women in 1999-2008.<h3>Main Outcome Measures</h3>The prevalence of obesity and mean BMI.<h3>Results</h3>In 2009-2010 the age-adjusted mean BMI was 28.7 (95% CI, 28.3-29.1) for men and also 28.7 (95% CI, 28.4-29.0) for women. Median BMI was 27.8 (interquartile range [IQR], 24.7-31.7) for men and 27.3 (IQR, 23.3-32.7) for women. The age-adjusted prevalence of obesity was 35.5% (95% CI, 31.9%-39.2%) among adult men and 35.8% (95% CI, 34.0%-37.7%) among adult women. Over the 12-year period from 1999 through 2010, obesity showed no significant increase among women overall (age- and race-adjusted annual change in odds ratio [AOR], 1.01; 95% CI, 1.00-1.03; P = .07), but increases were statistically significant for non-Hispanic black women (P = .04) and Mexican American women (P = .046). For men, there was a significant linear trend (AOR, 1.04; 95% CI, 1.02-1.06; P &lt; .001) over the 12-year period. For both men and women, the most recent 2 years (2009-2010) did not differ significantly (P = .08 for men and P = .24 for women) from the previous 6 years (2003-2008). Trends in BMI were similar to obesity trends.<h3>Conclusion</h3>In 2009-2010, the prevalence of obesity was 35.5% among adult men and 35.8% among adult women, with no significant change compared with 2003-2008.
Insidious bilateral infrapatellar tendon rupture in a patient with systemic lupus erythematosus.
Authors: L M Cooney, J M Aversa, J H Newman
Journal: Annals of the Rheumatic Diseases (1980)

A patient with systemic lupus erythematosus developed insidious bilateral infrapatellar tendon rupture initially diagnosed as steroid myopathy. Simultaneous loss of extension at the knee due to quadriceps or infrapatellar tendon ruptures is reviewed.
Toward an Improved Model of Treating Co-Occurring PTSD and Substance Use Disorders
Authors: Sudie E. Back
Journal: American Journal of Psychiatry (2010)

In this issue of the Journal, Hien and colleagues (1) utilized data from the National Institute on Drug Abuse (NIDA) Clinical Trials Network to examine the temporal association of improvements in co-occurring posttraumatic stress disorder (PTSD) and substance use disorders.Subjects were 353 women who received 12 weeks of either a trauma-focused intervention or health education.This study has important clinical relevance because of the high comorbidity of PTSD and substance use disorders (e.g., up to 43% of civilians with PTSD meet criteria for lifetime substance use disorders) (2).Over the last 20 years, evidence of the frequent co-occurrence of substance use disorders and other psychiatric disorders and the negative impact of comorbidity on treatment outcomes has increased (3).In spite of this acknowledgment, there are few controlled treatment trials to guide treatment.There are likely to be several reasons for this, including the fact that it is difficult for a single site to recruit a sufficient number of subjects to complete an adequately powered trial in individuals with co-occurring disorders within a reasonable time frame.The Hien et al. study utilized the NIDA-funded Clinical Trials Network, which allowed the investigators to recruit an adequate sample size to conduct an interesting and valuable set of analyses.
Tumor Angiogenesis Mediated by Myeloid Cells Is Negatively Regulated by CEACAM1
Authors: Rongze Lu, Maciej Kujawski, Hao Pan, John E. Shively
Journal: Cancer Research (2012)

Bv8 (prokineticin 2) expressed by Gr1(+)CD11b(+) myeloid cells is critical for VEGF-independent tumor angiogenesis. Although granulocyte colony-stimulating factor (G-CSF) has been shown to be a key inducer of Bv8 expression, the basis for Bv8 production in driving tumor angiogenesis is undefined. Because the cell adhesion molecule CEACAM1, which is highly expressed on Gr1(+)CD11b(+) myeloid cells, is known to regulate G-CSF receptor (G-CSFR) signaling, we hypothesized that CEACAM1 would regulate Bv8 production in these cells. In support of this hypothesis, we found that Bv8 expression was elevated in Gr1(+)CD11b(+) cells from Ceacam1-deficient mice implanted with B16 melanoma, increasing the infiltration of Gr1(+)CD11b(+) myeloid cells in melanoma tumors and enhancing their growth and angiogenesis. Furthermore, treatment with anti-Gr1 or anti-Bv8 or anti-G-CSF monoclonal antibody reduced myeloid cell infiltration, tumor growth, and angiogenesis to levels observed in tumor-bearing wild-type (WT) mice. Reconstitution of CEACAM1-deficient mice with WT bone marrow cells restored tumor infiltration of Gr1(+)CD11b(+) cells along with tumor growth and angiogenesis to WT levels. Treatment of tumor-bearing WT mice with anti-CEACAM1 antibody limited tumor outgrowth and angiogenesis, albeit to a lesser extent. Tumor growth in Ceacam1-deficient mice was not affected significantly in Rag(-/-) background, indicating that CEACAM1 expression in T and B lymphocytes had a negligible role in this pathway. Together, our findings show that CEACAM1 negatively regulates Gr1(+)CD11b(+) myeloid cell-dependent tumor angiogenesis by inhibiting the G-CSF-Bv8 signaling pathway.
Prospects for Gene Therapy for Heart Failure
Authors: Roger J. Hajjar, Federica del Monte, Takashi Matsui, Anthony Rosenzweig
Journal: Circulation Research (2000)

Abstract —Heart failure represents an enormous clinical challenge in need of effective therapeutic approaches. The possibility of gene therapy for heart failure merits consideration at this time because of improvements in vector technology; cardiac gene delivery; and, most importantly, our understanding of the molecular pathogenesis of heart failure. We will first review recent advances in cardiac gene delivery in animal models and then examine several targets being considered for therapeutic intervention. In this context, gene transfer provides not only a potential therapeutic modality but also an important tool to help validate specific targets. Several interventions, particularly those enhancing sarcoplasmic calcium transport, show promise in animal models of heart failure and in myopathic cardiomyocytes derived from patients. However, bridging the gap between these basic investigative studies and clinical gene therapy remains a formidable task. Early experiments in rodents will need to be extended to large-animal models with clinical-grade vectors and delivery systems to assess both efficacy and safety. On the basis of a foundation of rigorous science and a growing understanding of heart failure pathogenesis, there is reason for cautious optimism for the future.
Our experience of glycopyrrolate 2% cream for axillary hyperhidrosis
Authors: D.R. Hale, A.I. MacKenzie, G.M. Kavanagh
Journal: British Journal of Dermatology (2014)

Funding sources: none. Conflicts of interest: none declared. Dear Editor, First‐line treatment of axillary hyperhidrosis (HH) is usually with aluminium chloride preparations. Their potential irritancy may be reduced significantly by the addition of aloe vera and camphor, which can be purchased via http://www.sweat-stop.com (personal communication from Julie Halford, who runs the Hyperhidrosis U.K. website with some 18 000 members). We were interested to read Baker's reported positive experience of treating axillary HH with twice‐daily glycopyrrolate 2% spray (glycopyrronium bromide).1 Topical glycopyrrolate in our experience is most effective for HH of the head and neck2 and gustatory sweating (diabetic and Frey),3 4 perhaps explaining why the literature on its use is predominantly in diabetes and ear–nose–throat journals. European Pharmacopeia‐ and US Pharmacopeia‐grade glycopyrrolate powder can be imported, and the desired formulation prepared by special‐order manufacturers in a cream formulation with an acidic base, cetomacrogol cream BP, to reduce drug hydrolysis and extend stability to 3 months.
Randomized Phase III Intergroup Trial of Etoposide and Cisplatin With or Without Paclitaxel and Granulocyte Colony-Stimulating Factor in Patients With Extensive-Stage Small-Cell Lung Cancer: Cancer and Leukemia Group B Trial 9732
Authors: Harvey B. Niell, James E. Herndon, Antonius A. Miller, Dorothy M. Watson, Alan B. Sandler, Karen Kelly, Randolph S. Marks, Micheal C. Perry, Rafat H. Ansari, Grefory Otterson, John Ellerton, Everett E. Vokes, Mark R. Green
Journal: Journal of Clinical Oncology (2005)

To determine, in a randomized comparison, whether the addition of paclitaxel to etoposide and cisplatin improves the time to progression and overall survival in patients with extensive small-cell lung cancer (SCLC) compared with standard etoposide and cisplatin and to compare the regimens' toxicity.Eligible patients (N=587) with untreated extensive SCLC were randomly assigned to receive either cisplatin 80 mg/m2 on day 1 and etoposide 80 mg/m2 on days 1 through 3 administered every 3 weeks for six cycles (EP) or cisplatin 80 mg/m2 on day 1, paclitaxel 175 mg/m2 over 4 hours on day 1, and etoposide 80 mg/m2 on days 1 to 3 followed by recombinant human granulocyte colony-stimulating factor on days 4 to 18 administered every 3 weeks for six cycles (PET).Reporting of demographics, response, and survival included 565 patients, of whom 282 were randomly assigned to receive EP and 283 were assigned to receive PET. Overall response rates were 68% for the EP arm and 75% for the PET arm. Median failure-free survival time was 5.9 months for the EP arm and 6 months for the PET arm (P = .179). Median overall survival time was 9.9 months for patients on EP and 10.6 months for patients on PET (P = .169). Toxic deaths occurred in 2.4% of the patients on EP and 6.5% of patients on PET.PET did not improve the time to progression or survival in patients with extensive SCLC compared with EP alone and was associated with unacceptable toxicity.
Relations between transit time, fermentation products, and hydrogen consuming flora in healthy humans.
Authors: L El Oufir, B Flourie, S Bruley des Varannes, J L Barry, D Cloarec, F Bornet, J P Galmiche
Journal: Gut (1996)

BACKGROUND/AIMS: To investigate whether transit time could influence H2 consuming flora and certain indices of colonic bacterial fermentation. METHODS: Eight healthy volunteers (four methane excretors and four non-methane excretors) were studied for three, three week periods during which they received a controlled diet alone (control period), and then the same diet with cisapride or loperamide. At the end of each period, mean transit time (MTT) was estimated, an H2 lactulose breath test was performed, and stools were analysed. RESULTS: In the control period, transit time was inversely related to faecal weight, sulphate reducing bacteria counts, concentrations of total short chain fatty acids (SCFAs), propionic and butyric acids, and H2 excreted in breath after lactulose ingestion. Conversely, transit time was positively related to faecal pH and tended to be related to methanogen counts. Methanogenic bacteria counts were inversely related to those of sulphate reducing bacteria and methane excretors had slower MTT and lower sulphate reducing bacteria counts than non-methane excretors. Compared with the control period, MTT was significantly shortened (p &lt; 0.05) by cisapride and prolonged (p &lt; 0.05) by loperamide (73 (11) hours, 47 (5) hours and 147 (12) hours for control, cisapride, and loperamide, respectively, mean (SD)). Cisapride reduced transit time was associated with (a) a significant rise in faecal weight, sulphate reducing bacteria, concentrations of total SCFAs, and propionic and butyric acids and breath H2 as well as (b) a significant fall in faecal pH and breath CH4 excretion, and (c) a non-significant decrease in the counts of methanogenic bacteria. Reverse relations were roughly the same during the loperamide period including a significant rise in the counts of methanogenic bacteria and a significant fall in those of sulphate reducing bacteria. CONCLUSIONS: Transit time differences between healthy volunteers are associated with differences in H2 consuming flora and certain indices of colonic fermentation. Considering the effects of some fermentation products on intestinal morphology and function, these variations may be relevant to the pathogenesis of colorectal diseases.
Taurocholate transport by rat intestinal basolateral membrane vesicles. Evidence for the presence of an anion exchange transport system.
Authors: S L Weinberg, G Burckhardt, F A Wilson
Journal: Journal of Clinical Investigation (1986)

The transport of bile acid was studied in basolateral membrane vesicles isolated from rat small intestine. Taurocholate transport into an osmotically reactive intravesicular space was Na+ independent. The uptake of taurocholate in jejunal and ileal vesicles preloaded with sulfate was stimulated with respect to uptake in unpreloaded vesicles. Glycocholate inhibited the transstimulation of taurocholate uptake by sulfate. Sulfate and taurocholate uptake in ileal vesicles preloaded with bicarbonate was stimulated with respect to uptake in unpreloaded vesicles. Taurocholate inhibited the transstimulation of sulfate uptake by bicarbonate. When ileal vesicles were loaded with p-aminohippurate, an early transstimulation of taurocholate was found that exceeded equilibrium uptake, was insensitive to a K+ diffusion potential, and was cis-inhibited by taurocholate, glycocholate, pyruvate, p-aminohippurate, probenecid, chloride, sulfate, and bicarbonate. These data indicate the presence of an anion exchanger in intestinal basolateral membrane vesicles that may be involved in the exit of bile acids from the enterocyte.
Rituximab Plus Fludarabine and Cyclophosphamide Prolongs Progression-Free Survival Compared With Fludarabine and Cyclophosphamide Alone in Previously Treated Chronic Lymphocytic Leukemia
Authors: Tadeusz Robak, Anna Dmoszynska, Philippe Solal-Céligny, Krzysztof Warzocha, Javier Loscertales, John Catalano, Boris V. Afanasiev, Loree Larratt, Christian H. Geisler, Marco Montillo, Ilya Zyuzgin, Peter S. Ganly, Caroline Dartigeas, András Rosta, Jörg Maurer, Myriam Mendila, M. Wayne Saville, Nancy Valente, Michael K. Wenger, Sergey I. Moiseev
Journal: Journal of Clinical Oncology (2010)

Rituximab, a monoclonal antibody that targets the CD20 cell surface antigen, has clinical activity in patients with non-Hodgkin's lymphoma and other B-lymphocyte disorders when administered alone or in combination with chemotherapy. Promising results have previously been reported in nonrandomized studies in patients with chronic lymphocytic leukemia (CLL). This trial was designed to compare chemoimmunotherapy with chemotherapy alone in patients with previously treated CLL.This international, multicenter, randomized trial compared six cycles of rituximab plus fludarabine and cyclophosphamide (R-FC) with six cycles of fludarabine and cyclophosphamide alone (FC) in patients with previously treated CLL. A total of 552 patients with Binet stage A (1%), B (59%), or C (31%) disease entered the study and were randomly assigned to receive R-FC (n = 276) or FC (n = 276).After a median follow-up time of 25 months, rituximab significantly improved progression-free survival in patients with previously treated CLL (hazard ratio = 0.65; P < .001; median, 30.6 months for R-FC v 20.6 months for FC). Event-free survival, response rate, complete response rate, duration of response, and time to new CLL treatment or death were also significantly improved. Although the rates of adverse events, grade 3 or 4 events, and serious adverse events were slightly higher in the R-FC arm, R-FC was generally well tolerated, with no new safety findings and no detrimental effect on quality of life.R-FC significantly improved the outcome of patients with previously treated CLL.
Wing-Beating Tremor
Authors: Ramit Mahajan, Uday Zachariah
Journal: New England Journal of Medicine (2014)

An 18-year-old man presented with tremor in the right arm that had begun 2 years earlier and had progressed to the other arm, the head, and the legs. Examination revealed dysarthria, generalized hypertonia, and a “wing-beating” tremor. A video is available at NEJM.org.
Continuous positive airway pressure improves vascular function in obstructive sleep apnoea/hypopnoea syndrome: a randomised controlled trial
Authors: M D Cross, N L Mills, M Al-Abri, R Riha, M Vennelle, T W Mackay, D E Newby, N J Douglas
Journal: Thorax (2008)

<h3>Background:</h3> The obstructive sleep apnoea/hypopnoea syndrome (OSAHS) is associated with hypertension and increased cardiovascular risk, particularly when accompanied by marked nocturnal hypoxaemia. The mechanisms of these associations are unclear. We hypothesised that OSAHS combined with severe nocturnal hypoxaemia causes impaired vascular function that can be reversed by continuous positive airways pressure (CPAP) therapy. <h3>Methods:</h3> We compared vascular function in two groups of patients with OSAHS: 27 with more than 20 4% desaturations/h (desaturator group) and 19 with no 4% and less than five 3% desaturations/h (non-desaturator group). In a randomised, double blind, placebo controlled, crossover trial, the effect of 6 weeks of CPAP therapy on vascular function was determined in the desaturator group. In all studies, vascular function was assessed invasively by forearm venous occlusion plethysmography during intra-arterial infusion of endothelium dependent (acetylcholine 5–20 μg/min and substance P 2–8 pmol/min) and independent (sodium nitroprusside 2–8 μg/min) vasodilators. <h3>Results:</h3> Compared with the non-desaturator group, patients with OSAHS and desaturations had reduced vasodilatation to all agonists (p = 0.007 for all). The apnoea/hypopnoea index and desaturation frequency were inversely related to peak vasodilatation with acetylcholine (r = −0.44, p = 0.002 and r = −0.43, p = 0.003) and sodium nitroprusside (r = −0.42, p = 0.009 and r = −0.37, p = 0.02). In comparison with placebo, CPAP therapy improved forearm blood flow to all vasodilators (p = 0.01). <h3>Conclusions:</h3> Patients with OSAHS and frequent nocturnal desaturations have impaired endothelial dependent and endothelial independent vasodilatation that is proportional to hypoxaemia and is improved by CPAP therapy. Impaired vascular function establishes an underlying mechanism for the adverse cardiovascular consequences of OSAHS.