tbuckley/cabot-search huggingface dataset:
Low cardiac output predicts development of hepatorenal syndrome and survival in patients with cirrhosis and ascites
Authors: A Krag, F Bendtsen, J H Henriksen, S Moller
Journal: Gut (2009)

Recent studies suggest that cardiac dysfunction precedes development of the hepatorenal syndrome. In this follow-up study, we aimed to investigate the relation between cardiac and renal function in patients with cirrhosis and ascites and the impact of cardiac systolic function on survival.Twenty-four patients with cirrhosis and ascites were included. Cardiac function was investigated by gated myocardial perfusion imaging (MPI) for assessment of cardiac index (CI) and cardiac volumes. The renal function was assessed by determination of glomerular filtration rate (GFR) and renal blood flow (RBF) and the patients were followed up for 12 months.In patients with a CI below 1.5 l/min/m(2) on MPI, GFR was lower (39 (SD 24) vs 63 (SD 23) ml/min, p = 0.03), RBF was lower (352 (SD 232) vs 561 (SD 229) ml/min, p = 0.06), and serum creatinine was higher (130 (SD 46) vs 78 (SD 29) mumol/l, p<0.01). The number of patients who developed hepatorenal syndrome type 1 within 3 months was higher in the group with low CI than in the high CI group (43% vs 5%, p = 0.04). Patients with the lowest CI (N = 8) had significantly poorer survival at 3, 9, and 12 months compared to those with a higher CI (N = 16), p<0.05. In contrast, the Model for End-stage Liver Disease (MELD) score failed to predict mortality in these patients.The development of renal failure and poor outcome in patients with advanced cirrhosis and ascites seem to be related to a cardiac systolic dysfunction. Other parameters may be more important than MELD score to predict prognosis.
Infectivity-Enhanced Adenoviruses Deliver Efficacy in Clinical Samples and Orthotopic Models of Disseminated Gastric Cancer
Authors: Lotta Kangasniemi, Tuula Kiviluoto, Anna Kanerva, Mari Raki, Tuuli Ranki, Merja Sarkioja, Hongju Wu, Frank Marini, Krister Höckerstedt, Helena Isoniemi, Henrik Alfthan, Ulf-Håkan Stenman, David T. Curiel, Akseli Hemminki
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Metastatic gastric cancer remains a common and devastating disease without curative treatment. Recent proof-of-concept clinical trials have validated gene therapy with adenoviruses as an effective and safe modality for the treatment of cancer. However, expression of the primary coxsackie-adenovirus receptor is variable in advanced cancers, and therefore, the use of heterologous receptors could be advantageous. Experimental Design: Here, we used capsid-modified adenoviruses for increasing the transduction and subsequent antitumor efficacy. 5/3 chimeric viruses have a serotype 3 knob which allows binding to a receptor distinct from coxsackie-adenovirus receptor. The fiber of Ad5lucRGD is modified with an integrin-targeted motif. Polylysine motifs, pK7 and pK21, bind to heparan sulfates. Oncolytic adenoviruses replicate in and kill tumor cells selectively. Gastric cancer cell lines and fresh clinical samples from patients were infected with transductionally targeted viruses. Capsid-modified oncolytic adenoviruses were used in cell killing experiments. To test viral transduction and therapeutic efficacy in vivo, we developed orthotopic mouse models featuring i.p. disseminated human gastric cancer, which allowed the evaluation of biodistribution and antitumor efficacy in a system similar to humans. Results: Capsid modifications benefited gene transfer efficiency and cell killing in gastric cancer cell lines and clinical samples in vitro and in vivo. Modified oncolytic adenoviruses significantly increased the survival of mice with orthotopic gastric cancer. Conclusions: These preclinical data set the stage for the clinical evaluation of safety and efficacy in patients with disease refractory to current modalities.
A phase 2, single-arm study of an autologous dendritic cell treatment against mucin 1 in patients with advanced epithelial ovarian cancer
Authors: Paul LR Mitchell, Michael A Quinn, Peter T Grant, David G Allen, Thomas W Jobling, Shane C White, Anne Zhao, Vaios Karanikas, Hilary Vaughan, Geoffrey Pietersz, Ian FC McKenzie, Sharron E Gargosky, Bruce E Loveland
Journal: Journal for ImmunoTherapy of Cancer (2014)

<h3>Background</h3> Mucin 1 antigen, highly expressed by epithelial ovarian cancer (EOC), is a potential target for immunotherapy. A previous successful phase 1 trial was conducted in patients with adenocarcinoma who were injected with Cvac, autologous monocyte-derived dendritic cells (DCs) incubated with mannosylated mucin 1 protein (M-FP). The present study was a phase 2 trial of Cvac in patients with advanced EOC. <h3>Methods</h3> Eligible patients had EOC with progressive disease, defined as an increase in CA125 of ≥ 25% in 1&nbsp;month. The primary endpoint was CA125 response or stabilization. Peripheral blood mononuclear cells were collected by leukapheresis and cultured to generate DCs. The DC were incubated with M-FP, and after washing were prepared for injection into the patient intradermally every 4&nbsp;weeks for 3 doses, then every 10&nbsp;weeks for up to 12&nbsp;months. <h3>Results</h3> All 28 patients recruited were evaluable for safety and 26 for efficacy. All had undergone surgery and platinum-based chemotherapy, and 57% of patients received ≥ 3 chemotherapy regimens. There were no Grade 3 or 4 toxicities considered related to Cvac. Four patients showed CA125 response or stabilization (2 patients with major responses, 1 minor response, 1 stabilization) of median duration 10.3&nbsp;months (5.3–16.3&nbsp;months). An additional patient had &gt; 25% CA125 reduction (not confirmed). <h3>Conclusions</h3> Cvac immunotherapy was well tolerated. Clinical activity in EOC was evident based on decline or stabilization of CA125 in some patients, supporting ongoing development of Cvac in ovarian carcinoma and planning of additional trials of patients in remission is currently underway.
Changes in the use of anti-asthmatic medication in an international cohort
Authors: C. Janson
Journal: European Respiratory Journal (2005)

The aim of this study was to describe changes in pharmacotherapy for asthma since the early 1990s in an international cohort of young and middle-aged adults. A total of 28 centres from 14 countries participated in a longitudinal study. The study included 8,829 subjects with a mean follow-up time of 8.7 yrs. Change in the prevalence of use for medication was expressed as absolute net change (95% confidence interval) standardised to a 10-yr period. The use of anti-asthmatics was found to have increased by 3.1% (2.4–3.7%) and the prevalence of symptomatic asthma by 4.0% (3.5–4.5%). In the sample with asthma in both surveys (n = 423), the use of inhaled corticosteroids increased by 12.2% (6.6–17.8%). Despite this, only 17.2% were using inhaled corticosteroids on a daily basis at follow-up. Females with continuous asthma were more likely, compared with males, and smokers with asthma, to have started using inhaled corticosteroids since the first survey. The use of anti-asthmatics has increased in a pattern consistent with current consensus on treatment. However, despite increased use of inhaled corticosteroids, a large majority of subjects with symptomatic asthma do not use this treatment on a daily basis, particularly males and smokers with asthma.
MIXED LYMPHOCYTE REACTIVITY AGAINST NORMAL CELLS BY SPLENIC LYMPHOCYTES FROM TUMOR-BEARING MICE
Authors: R. G. Devlin, J. D. McCurdy, P. E. Baronowsky
Journal: The Journal of Experimental Medicine (1974)

A possible consequence of an antilymphocytic autoimmune process would be serious impairment of an animal's ability to destroy tumor cells. One measure of autoimmune reactivity of this type would be the demonstration of cellular immune responsiveness by cells from tumor-bearing mice against syngeneic normal cells. These experiments demonstrate that spleen cells from mice bearing a lymphocytic leukemia of identical histocompatability type as the host mounted a vigorous immune response against normal syngeneic cells in a mixed lymphocyte reaction (MLR). Moreover, ascitic cells from leukemic mice responded significantly to normal syngeneic spleen cells in MLR's. The former reactions are usually much more vigorous than the responses of normal to malignant cells. These results are discussed in terms of the relationship between autoimmunity and neoplasia. Alternative explanations necessitated by the dangers involved in the interpretation of the immunology of transplantable tumors are considered.
Pressure/volume curves and lung computed tomography in acute respiratory distress syndrome
Authors: J‐J. Rouby, Q. Lu, S. Vieira
Journal: European Respiratory Journal (2003)

Pressure/volume ( P / V ) curves can be measured by static methods, constant or sinusoidal flow methods and the dynostatic method that allows a breath-to-breath determination of P / V curves. Recent ventilators are equipped with specific flow generators and software aimed at obtaining P / V curves without disconnecting the patient from the ventilator. The most recent generation of computed tomography scanners allows the quantitative determination of lung aeration, lung volumes (gas and tissue), alveolar recruitment and lung overinflation of the whole lung. In the supine position, the acute respiratory distress syndrome (ARDS) lung is characterised by an increase in lung tissue that predominates in upper lobes and a massive loss of aeration that predominates in lower lobes. In a minority of ARDS patients, the loss of aeration is homogeneously distributed. The overall lung volume of upper lobes is preserved suggesting an alveolar flooding-induced loss of aeration. In contrast, the overall lung volume of lower lobes is reduced because the heart and the abdomen exert an external compression that contributes to the loss of aeration. The P / V curve is a lung recruitment curve and the chord compliance indicates the potential for recruitment. In such patients, alveolar recruitment resulting from positive end-expiratory pressure is not accompanied by lung overinflation. In a majority of acute respiratory distress syndrome patients, upper lobes remain partially or totally aerated despite a marked regional increase in lung tissue. The upper lobes' overall lung volume is either normal or increased, suggesting that the lung does not collapse under its own weight as generally believed. In lower lobes, the overall lung volume is reduced because the heart and the abdomen exert an external compression that contributes to the loss of aeration. The pressure/volume curve is influenced by the recruitment of poorly and nonaerated lung regions and by the mechanical properties of the part of the lung remaining aerated. In such patients, alveolar recruitment resulting from positive end-expiratory pressure &gt;10 cmH 2 O is preceded and accompanied by lung overinflation.
Hypoxia-Induced SUMOylation of E3 Ligase HAF Determines Specific Activation of HIF2 in Clear-Cell Renal Cell Carcinoma
Authors: Mei Yee Koh, Vuvi Nguyen, Robert Lemos, Bryant G. Darnay, Galina Kiriakova, Mena Abdelmelek, Thai H. Ho, Jose Karam, Federico A. Monzon, Eric Jonasch, Garth Powis
Journal: Cancer Research (2014)

Abstract Clear-cell renal cell cancer (CRCC) is initiated typically by loss of the tumor-suppressor VHL, driving constitutive activation of hypoxia-inducible factor-1 (HIF1) and HIF2. However, whereas HIF1 has a tumor-suppressor role, HIF2 plays a distinct role in driving CRCC. In this study, we show that the HIF1α E3 ligase hypoxia-associated factor (HAF) complexes with HIF2α at DNA to promote HIF2-dependent transcription through a mechanism relying upon HAF SUMOylation. HAF SUMOylation was induced by hypoxia, whereas HAF-mediated HIF1α degradation was SUMOylation independent. HAF overexpression in mice increased CRCC growth and metastasis. Clinically, HAF overexpression was associated with poor prognosis. Taken together, our results show that HAF is a specific mediator of HIF2 activation that is critical for CRCC development and morbidity. Cancer Res; 75(2); 316–29. ©2014 AACR.
Inhibition of cellular DNA synthesis by reovirus occurs through a receptor-linked signaling pathway that is mimicked by antiidiotypic, antireceptor antibody.
Authors: G N Gaulton, M I Greene
Journal: The Journal of Experimental Medicine (1989)

Mammalian reovirus type 3 binds to a 67-kD surface glycoprotein on the membrane of neuronal cells. This interaction initiates the infective reovirus cycle. The physiological function of this virus receptor is not known, however, initial studies illustrate a striking structural and antigenic homology to the beta adrenergic receptor family. The earliest known pathologic effect of reovirus type 3 is an inhibition of host cell DNA synthesis within 8-10 h after virus attachment. The studies reported here demonstrate that binding and aggregation of reovirus receptor molecules provides the signal for this inhibitory process. Inhibition of DNA synthesis in the neuroblastoma cell line B104.G4 was unaffected by using replication-defective virus or when lysosomal processing of normal virus was blocked. Inhibition was mimicked by an antiidiotypic, antireceptor mAb. Inhibition was not observed when monovalent mAb fragments were bound to receptors, but was reconstituted when these fragments were aggregated by the addition of anti-Ig. The signal for the inhibitory effect was generated within the first 60 min after mAb binding. These observations demonstrate that reovirus and antiidiotypic pathogenicity can result from the perturbation of membrane proteins that may perform normal physiological functions.
Superiority of tacrolimus 0·1% ointment compared with fluticasone 0·005% in adults with moderate to severe atopic dermatitis of the face: results from a randomized, double-blind trial
Authors: N. Doss, S. Reitamo, L. Dubertret, G.L. Fekete, M.-R. Kamoun, M. Lahfa, J.-P. Ortonne
Journal: British Journal of Dermatology (2009)

No specific data are available on tacrolimus ointment as a second-line treatment in adults with facial eczema.To compare tacrolimus 0.1% and fluticasone 0.005% ointments in adults with moderate to severe atopic dermatitis (AD) of the face in whom conventional treatment was ineffective or poorly tolerated.Patients were randomized to double-blind treatment of facial AD with twice-daily tacrolimus ointment (n = 288) or fluticasone ointment (n = 280) for 3 weeks or until clearance. After day 21, patients could continue without the study treatment, apply the same ointment once daily, or switch to the other medication twice daily, depending on lesion clearance and patient/physician satisfaction. The primary endpoint was the day-21 response [> or = 60% reduction in the modified Local Eczema and Severity Index (mLEASI) score]. Secondary endpoints included facial erythema and pruritus, global clinical response, treatment switching at day 21 and safety. RESULTS Response with tacrolimus ointment (93%) was superior to that with fluticasone (88%; P = 0.026). Improvements in mLEASI components were also greater with tacrolimus ointment. Facial erythema and pruritus improved in both groups. Global clinical response was rated 'marked improvement' or better in 88% and 79% of patients in the tacrolimus ointment and fluticasone groups, respectively. At day 21, 9% of patients switched from fluticasone to tacrolimus ointment, while 4.5% switched from tacrolimus ointment to fluticasone. Adverse events were more frequent with tacrolimus ointment as a result of the higher incidence of application-site skin burning sensation. Safety of both drugs was in line with their respective summary of product characteristics.Tacrolimus 0.1% ointment has superior efficacy to fluticasone 0.005% ointment for twice-daily treatment of adults with moderate to severe facial AD in whom conventional therapy was inadequately effective or not tolerated. Tacrolimus 0.1% ointment is a safe and effective second-line treatment for the control of moderate to severe AD of the face.
Dietary Therapy Slows the Return of Hypertension After Stopping Prolonged Medication
Authors: Herbert G. Langford, M. Donald Blaufox, Albert Oberman, C. Morton Hawkins, J. David Curb, Gary R. Cutter, Sylvia Wassertheil-Smoller, Sara L Pressel, Connie Babcock, John D. Abernethy, Jeanne Hotchkiss, Myra Tyler
Journal: JAMA (1985)

This study asks whether prolonged antihypertensive therapy will "cure" a substantial percent of rigorously treated hypertensive patients and whether nutritional change will add an antihypertensive effect and reduce the relapse rate. Of 584 eligible patients normotensive while receiving therapy, 496 were randomized into control and discontinued-medication groups with and without dietary intervention. At 56 weeks, 50% of those who were no longer receiving medication remained normotensive by study criteria. Randomization either to weight-loss group (mean loss of 4.5 kg [10 lb]) or to sodium-restriction group (mean reduction of 40 mEq/day) increased the likelihood of remaining without drug therapy, with an adjusted odds ratio of 2.17 for the sodium group and 3.43 for the weight group. Highest success rates were in the nonoverweight mild hypertensives with sodium restriction (78%) and the overweight mild hypertensives who were reducing their weight (72%). These data demonstrate that weight loss or sodium restriction, in hypertensives controlled for five years, more than doubles success in withdrawal of drug therapy.
A Quantitative Map of the Liver Mitochondrial Phosphoproteome Reveals Posttranslational Control of Ketogenesis
Authors: Paul A. Grimsrud, Joshua J. Carson, Alex S. Hebert, Shane L. Hubler, Natalie M. Niemi, Derek J. Bailey, Adam Jochem, Donald S. Stapleton, Mark P. Keller, Michael S. Westphall, Brian S. Yandell, Alan D. Attie, Joshua J. Coon, David J. Pagliarini
Journal: Cell Metabolism (2012)
Early-onset phenytoin toxicity mimicking a renopulmonary syndrome
Authors: AJ Polman, TS van der Werf, AT Tiebosch, JG Zijlstra
Journal: European Respiratory Journal (1998)

Phenytoin is a commonly used anti-epileptic drug. Adverse reactions including fever, skin reactions and lymphadenopathy are well known but atypical reactions can also occur. A patient is described with a lag time of only 4 days between onset of phenytoin and the development of a syndrome with acute lung injury and renal failure. The symptoms mimicked a renopulmonary syndrome, and resolved completely after cessation of phenytoin and addition of steroids.
Hypothenar hammer syndrome in a middle blocker - case report and brief review
Authors: M Massada, R Aido, C Magalhaes, N Puga
Journal: British Journal of Sports Medicine (2011)

Background Hypothenar hammer syndrome (HHS) is an uncommon vascular overuse syndrome caused by trauma to the palmar portion of the ulnar artery. Objective In this report, we describe a representative case in the volleyball player as well as a brief approach to clinical features, pathogenesis, diagnosis, imaging and management. Design Case report. Setting Volleyball National Team. Methods The athlete is a 22-year-old right-hand dominant male, national team middle blocker, who presented to the Medical Department for evaluation of painful and paresthetic fourth and fifth digits. He described the affected fingertips and hypothenar region as being tender and sensitive to touch. When queried, he stated that he would use the hypothenar portion of his right hand to spike and block. There was an abnormal Allen test in the right hand with refill of the palmar vasculature with release of the radial artery but no refill with release of the ulnar artery, consistent with a diagnosis of HHS. He started a platelet aggregation inhibitor and was instructed and trained to change his hitting technique. Results On follow-up the athlete's remaining symptom was mild cold sensitivity. He was able to perform his usual sports activities without impairment. Conclusions Typically, HHS occurs in men in their 40s involving the dominant hand and in occupational settings where the workers use the hypothenar portion of the hand as a tool to hammer, push or squeeze hard objects (metal workers, machinists, brick layers, carpenters, etc.). It is a curable and preventable cause of upper extremity digital ischemia, rarely seen in volleyball.
Dietary factors associated with wheezing and allergic rhinitis in children
Authors: S. Farchi, F. Forastiere, N. Agabiti, G. Corbo, R. Pistelli, C. Fortes, V. Dell'Orco, C.A. Perucci
Journal: European Respiratory Journal (2003)

The effect of dietary factors on asthma is controversial. This study examined food consumption and the use of fats in relation to wheezing and allergic rhinitis in children. Baseline questionnaire data on individual and family characteristics were recorded by parents of 5,257 children aged 6–7 yrs living in central Italy participating in the International Study on Asthma and Allergies in Childhood study. A total of 4,104 children (78.1%) were reinvestigated after 1 yr using a second parental questionnaire to record occurrence of respiratory symptoms over the intervening 12 months. Consumption of foods rich in antioxidants, such as vitamins C and E, animal fats, and food containing omega‐3 fatty acids were investigated using a food-frequency questionnaire. Frequency of use of fats was also evaluated. Wheezing, shortness of breath with wheeze, and symptoms of allergic rhinitis in the past 12 months were considered. Intake of cooked vegetables, tomatoes, and fruit were protective factors for any wheeze in the last 12 months and shortness of breath with wheeze. Consumption of citrus fruit had a protective role for shortness of breath with wheeze. Consumption of bread and margarine was associated with an increased risk of wheeze, while bread and butter was associated with shortness of breath with wheeze. Dietary antioxidants in vegetables may reduce wheezing symptoms in childhood, whereas both butter and margarine may increase the occurrence of such symptoms.
Surgical Stress Promotes Tumor Growth in Ovarian Carcinoma
Authors: Jeong-Won Lee, Mian M.K. Shahzad, Yvonne G. Lin, Guillermo Armaiz-Pena, Lingegowda S. Mangala, Hee-Dong Han, Hye-Sun Kim, Eun Ji Nam, Nicholas B. Jennings, Jyotsnabaran Halder, Alpa M. Nick, Rebecca L. Stone, Chunhua Lu, Susan K. Lutgendorf, Steve W. Cole, Anna E. Lokshin, Anil K. Sood
Journal: Clinical Cancer Research (2009)

Surgical stress has been suggested to facilitate the growth of preexisting micrometastases as well as small residual tumor postoperatively. The purpose of this study was to examine the effects of surgical stress on ovarian cancer growth and to determine underlying mechanisms responsible for increased growth.To mimic the effects of surgery, we did a laparotomy or mastectomy under isoflurane inhalation on athymic nude mice 4 days after i.p. tumor cell injection. Propranolol infusion via Alzet pumps was used to block the influence of sympathetic nervous system activation by surgical stress.In both HeyA8 and SKOV3ip1 models, the mice in the laparotomy and mastectomy groups had significantly greater tumor weight (P < 0.05) and nodules (P < 0.05) compared with anesthesia only controls. There was no increase in tumor weight following surgery in the beta-adrenergic receptor-negative RMG-II model. Propranolol completely blocked the effects of surgical stress on tumor growth, indicating a critical role for beta-adrenergic receptor signaling in mediating the effects of surgical stress on tumor growth. In the HeyA8 and SKOV3ip1 models, surgery significantly increased microvessel density (CD31) and vascular endothelial growth factor expression, which were blocked by propranolol treatment.These results indicate that surgical stress could enhance tumor growth and angiogenesis, and beta-blockade might be effective in preventing such effects.