tbuckley/cabot-search huggingface dataset:
Efficacy of minocycline in patients with amyotrophic lateral sclerosis: a phase III randomised trial
Authors: Paul H Gordon, Dan H Moore, Robert G Miller, Julaine M Florence, Joseph L Verheijde, Carolyn Doorish, Joan F Hilton, G Mark Spitalny, Robert B MacArthur, Hiroshi Mitsumoto, Hans E Neville, Kevin Boylan, Tahseen Mozaffar, Jerry M Belsh, John Ravits, Richard S Bedlack, Michael C Graves, Leo F McCluskey, Richard J Barohn, Rup Tandan
Journal: The Lancet Neurology (2007)
Absence of central effects with levocabastine eye drops
Authors: F. Arriaga, N. Rombaut
Journal: Allergy (1990)

Twelve healthy volunteers were randomly allocated to receiving in a double‐blind cross‐over fashion levocabastine eye drops (0.5 mg/ml solution) and placebo. They were advised to instill 2 drops per eye, four times daily. Each treatment was administered for a period of 1 week. Before and after each treatment period psychomotor function was assessed using Critical Flicker Fusion Test and the Choice Reaction Time Test. At the same time intervals a subjective evaluation of sedation was given using a Visual Analogue of Sedation. Both objective and subjective measurements showed that no significant treatment effects could be detected. It is concluded that repeated instillations of levocabastine eye drops are devoid of any sedative side effects.
Increased antitumor activity, intratumor paclitaxel concentrations, and endothelial cell transport of cremophor-free, albumin-bound paclitaxel, ABI-007, compared with cremophor-based paclitaxel.
Authors: Neil Desai, Vuong Trieu, Zhiwen Yao, Leslie Louie, Sherry Ci, Andrew Yang, Chunlin Tao, Tapas De, Bridget Beals, Donald Dykes, Patricia Noker, Rosie Yao, Elizabeth Labao, Michael Hawkins, Patrick Soon-Shiong
Journal: Clinical Cancer Research (2006)

Abstract ABI-007, an albumin-bound, 130-nm particle form of paclitaxel, was developed to avoid Cremophor/ethanol-associated toxicities in Cremophor-based paclitaxel (Taxol) and to exploit albumin receptor-mediated endothelial transport. We studied the antitumor activity, intratumoral paclitaxel accumulation, and endothelial transport for ABI-007 and Cremophor-based paclitaxel. Antitumor activity and mortality were assessed in nude mice bearing human tumor xenografts [lung (H522), breast (MX-1), ovarian (SK-OV-3), prostate (PC-3), and colon (HT29)] treated with ABI-007 or Cremophor-based paclitaxel. Intratumoral paclitaxel concentrations (MX-1-tumored mice) were compared for radiolabeled ABI-007 and Cremophor-based paclitaxel. In vitro endothelial transcytosis and Cremophor inhibition of paclitaxel binding to cells and albumin was compared for ABI-007 and Cremophor-based paclitaxel. Both ABI-007 and Cremophor-based paclitaxel caused tumor regression and prolonged survival; the order of sensitivity was lung &amp;gt; breast congruent with ovary &amp;gt; prostate &amp;gt; colon. The LD(50) and maximum tolerated dose for ABI-007 and Cremophor-based paclitaxel were 47 and 30 mg/kg/d and 30 and 13.4 mg/kg/d, respectively. At equitoxic dose, the ABI-007-treated groups showed more complete regressions, longer time to recurrence, longer doubling time, and prolonged survival. At equal dose, tumor paclitaxel area under the curve was 33% higher for ABI-007 versus Cremophor-based paclitaxel, indicating more effective intratumoral accumulation of ABI-007. Endothelial binding and transcytosis of paclitaxel were markedly higher for ABI-007 versus Cremophor-based paclitaxel, and this difference was abrogated by a known inhibitor of endothelial gp60 receptor/caveolar transport. In addition, Cremophor was found to inhibit binding of paclitaxel to endothelial cells and albumin. Enhanced endothelial cell binding and transcytosis for ABI-007 and inhibition by Cremophor in Cremophor-based paclitaxel may account in part for the greater efficacy and intratumor delivery of ABI-007.
Sublingual immunotherapy with venom for patients with Hymenoptera venom allergy
Authors: Giampiero Patriarca, Eleonora Nucera, Chiara Roncallo, Arianna Aruanno, Carla Lombardo, Marzia Decinti, Lucilla Pascolini, Massimo Milani, Alessandro Buonomo, Domenico Schiavino
Journal: Journal of Allergy and Clinical Immunology (2009)
Role of anaerobic metabolism in the preservation of functional capacity and structure of anoxic myocardium
Authors: Arnold M. Weissler, Fred A. Kruger, Nobuhisa Baba, Dante G. Scarpelli, Richard F. Leighton, Judith K. Gallimore
Journal: Journal of Clinical Investigation (1968)

Employing an isolated perfused rat heart preparation, we investigated the contribution of anaerobic metabolic energy to the performance, recoverability, and ultrastructure of the heart perfused at 32 degrees C in 5% albumin in Krebs-Ringer Bicarbonate solution. During exposure to anoxia for 30 min, inclusion in the perfusate of the anaerobic substrate, glucose, resulted in marked improvement in electrical and mechanical performance of the heart and in enhanced recovery during the subsequent period of reoxygenation. Lactate production was fivefold greater in the glucose-supported anoxic heart than in the anoxic heart without glucose. Electron microscope sections of the hearts exposed to anoxia in the absence of glucose revealed alterations in mitochondrial morphology and dilatation of the longitudinal tubules. These morphologic changes during anoxia were averted by inclusion of glucose in the perfusion fluid. The data are consistent with the hypothesis that anaerobic energy generation plays a significant role in preserving myocardial function and structure and in promoting recoverability of the anoxic mammalian heart.
Reciprocal Limbic-Cortical Function and Negative Mood: Converging PET Findings in Depression and Normal Sadness
Authors: Helen S. Mayberg, Mario Liotti, Stephen K. Brannan, Scott McGinnis, Roderick K. Mahurin, Paul A. Jerabek, J. Arturo Silva, Janet L. Tekell, Charles C. Martin, Jack L. Lancaster, Peter T. Fox
Journal: American Journal of Psychiatry (1999)

Theories of human behavior from Plato to Freud have repeatedly emphasized links between emotion and reason, a relationship now commonly attributed to pathways connecting phylogenetically "old" and "new" brain regions. Expanding on this theory, this study examined functional interactions between specific limbic and neocortical regions accompanying normal and disease-associated shifts in negative mood state.Regions of concordant functional change accompanying provocation of transient sadness in healthy volunteers and resolution of chronic dysphoric symptoms in depressed patients were examined with two positron emission tomography techniques: [15O]water and [18F]fluorodeoxyglucose, respectively.With sadness, increases in limbic-paralimbic blood flow (subgenual cingulate, anterior insula) and decreases in neocortical regions (right dorsolateral prefrontal, inferior parietal) were identified. With recovery from depression, the reverse pattern, involving the same regions, was seen--limbic metabolic decreases and neocortical increases. A significant inverse correlation between subgenual cingulate and right dorsolateral prefrontal activity was also demonstrated in both conditions.Reciprocal changes involving subgenual cingulate and right prefrontal cortex occur with both transient and chronic changes in negative mood. The presence and maintenance of functional reciprocity between these regions with shifts in mood in either direction suggests that these regional interactions are obligatory and probably mediate the well-recognized relationships between mood and attention seen in both normal and pathological conditions. The bidirectional nature of this limbic-cortical reciprocity provides additional evidence of potential mechanisms mediating cognitive ("top-down"), pharmacological (mixed), and surgical ("bottom-up") treatments of mood disorders such as depression.
Myocardial Infarction Enhances Progressive Renal Damage in an Experimental Model for Cardio-Renal Interaction
Authors: Richard P.E. van Dokkum, Wouter B.A. Eijkelkamp, Alex C.A. Kluppel, Rob H. Henning, Harry van Goor, Marin Citgez, Willemijn A.K.M. Windt, Dirk J. van Veldhuisen, Pieter A. de Graeff, Dick de Zeeuw
Journal: Journal of the American Society of Nephrology (2004)

Studied were the effects of myocardial infarction (MI) on mild renal function loss in unilateral nephrectomized (UnX) rats. UnX was performed, followed after 1 wk by a variable MI (UnX + MI; n = 24). Rats with only UnX (n = 15) or MI (n = 9) and double sham animals (CON, n = 15) served as controls. Renal outcome was measured by proteinuria and plasma creatinine. Focal glomerulosclerosis (FGS) incidence was evaluated by renal histology. Cardiac function and systolic BP were measured. A division into small and large infarcts after UnX was made a priori, resulting in two groups, one with a mild MI (<20%; n = 15) and one with a moderate MI (>20%; n = 9). Mild proteinuria up to 55.5 mg/d was observed in the UnX + mild MI group, whereas proteinuria rose significantly higher to 124.5 mg/d in the UnX + moderate MI group. Incidence of FGS was significantly increased in both UnX + MI groups compared with all other groups. The average MI size was 18%, 17%, and 25% in the MI, UnX + mild MI, and UnX + moderate MI group, respectively. LVP in both UnX + MI groups was correlated with proteinuria, indicative of a cardio-renal interaction. Clinically, these data imply that more patients are at risk for cardiovascular events and that after such an event, their chance of more renal function loss increases. Finding the underlying mechanism will enable improved protection for both kidneys and heart.
Trends in hip and knee joint replacement: socioeconomic inequalities and projections of need
Authors: T Dixon
Journal: Annals of the Rheumatic Diseases (2004)

To examine trends in primary and revision joint (hip and knee) replacement in England between 1991 and 2000.Analysis of hospital episodes statistics between 1 April 1991 and 30 March 2001 for total hip replacement (THR) and total knee replacement (TKR). Descriptive statistics and regression modelling were used to summarise patients' demographic and clinical characteristics and to explore variations in joint surgery rates by age, sex, and deprivation.Between 1991 and 2000, the incidence of primary THR increased by 18%, while the incidence of revision THR more than doubled. The incidence of primary TKR doubled, with revision TKR increasing by 300%. Over the 10 year period, the proportion of THR episodes that involved revision operations rose from 8% to 20%. Substantial variations in operation rates by socioeconomic status were seen, with the most deprived fifth of the population experiencing significantly lower rates. Projections estimate that primary THR numbers could rise by up to 22% by the year 2010, with primary TKR numbers rising by up to 63%.Provision of joint replacement surgery in English NHS hospitals has increased substantially over the past decade. Revision operations in particular have increased markedly. The growth in primary operations has mostly occurred among those aged 60 years and over; rates among young people have changed very little. There is a significant deprivation based gradient in rates. If current trends continue there would be almost 47 000 primary hip and 54 000 primary knee operations annually by 2010.
Telomere length and outcomes in ischaemic heart failure: data from the <scp>COntrolled ROsuvastatin multiNAtional</scp> Trial in Heart Failure (<scp>CORONA</scp>)
Authors: Vincent G. Haver, Irene Mateo Leach, John Kjekshus, Jayne C. Fox, Hans Wedel, John Wikstrand, Rudolf A. de Boer, Wiek H. van Gilst, John J.V. McMurray, Dirk J. van Veldhuisen, Pim van der Harst
Journal: European Journal of Heart Failure (2015)
After a long wait, two arrive, one after the other!
Authors: Kevin W Southern, Pamela McCormack, Paul S McNamara
Journal: Thorax (2013)

Cystic fibrosis (CF) airways disease is unique, with chronic infection causing a localised but intense inflammatory process, acute in nature, but lasting for years. 1 Prevention, eradication and suppression of airway infection have been the cornerstones of CF management, and success with these strategies has been a key factor in improving the outlook for people with CF. 2 An armamentarium is available to achieve this goal, including a variety of aerosolised therapies.The evidence base to support these therapies ranges from good to poor. 3 4 Individual patients respond
Creatinine Production, Nutrition, and Glomerular Filtration Rate Estimation
Authors: Srinivasan Beddhu, Matthew H. Samore, Mark S. Roberts, Gregory J. Stoddard, Lisa M. Pappas, Alfred K. Cheung
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. This study examined the validity and clinical implications of the assumption of the Modification of Diet in Renal Disease Study (MDRD) formula that age, gender, race, and BUN account for creatinine production (CP). The relationships of MDRD GFR, CP, and nutrition were examined in 1074 Dialysis Morbidity and Mortality Study Wave II patients with reported measured creatinine clearances at initiation of dialysis. Age, gender, race, BUN, and serum creatinine (Scr) were used to calculate MDRD GFR. The measured 24-h urinary creatinine was used to estimate CP. In linear regression, Scr positively correlated with CP independent of age, gender, race, and BUN. Compared with the highest CP quartile, the lowest CP quartile had lower creatinine clearance (5.8 ± 2.9 <i>versus</i> 11.3 ± 3.4 ml/min, <i>P</i> &lt; .01) despite lower Scr (5.8 ± 2.6 <i>versus</i> 8.6 ± 3.1 mg%, <i>P</i> &lt; .01). There was an excellent correlation between the reciprocal of Scr and the MDRD GFR (<i>r</i> = 0.90). As a result, the MDRD GFR was higher in the lowest CP quartile (10.9 ± 4.6 <i>versus</i> 7.6 ± 2.4 ml/min, <i>P</i> &lt; .01). Malnutrition (48% <i>versus</i> 26%, <i>P</i> &lt; .01) was more common in the lowest CP quartile. Each 5-ml/min increase in MDRD GFR was associated with 21% higher odds of malnutrition (<i>P</i> = 0.046) in a multivariable logistic regression, which was abolished by controlling for CP. The fundamental assumption of the MDRD formula is invalid in patients with advanced renal failure, and the use of this formula in these patients might introduce biases. srinivasan.beddhu@hsc.utah.edu
Home-Based Resistance Training Is Not Sufficient to Maintain Improved Glycemic Control Following Supervised Training in Older Individuals With Type 2 Diabetes
Authors: David W. Dunstan, Robin M. Daly, Neville Owen, Damien Jolley, Elena Vulikh, Jonathan Shaw, Paul Zimmet
Journal: Diabetes Care (2005)

OBJECTIVE—To examine whether improvements in glycemic control and body composition resulting from 6 months of supervised high-intensity progressive resistance training could be maintained after an additional 6 months of home-based resistance training. RESEARCH DESIGN AND METHODS—We performed a 12-month randomized controlled trial in 36 sedentary, overweight men and women with type 2 diabetes (aged 60–80 years) who were randomly assigned to moderate weight loss plus high-intensity progressive resistance training (RT&amp;WL group) or moderate weight loss plus a control program (WL group). Supervised gymnasium-based training for 6 months was followed by an additional 6 months of home-based training. Glycemic control (HbA1c), body composition, muscle strength, and metabolic syndrome abnormalities were assessed at 0, 3, 6, 9, and 12 months. RESULTS—Compared with the WL group, HbA1c decreased significantly more in the RT&amp;WL group (−0.8%) during 6 months of supervised gymnasium-based training; however, this effect was not maintained after an additional 6 months of home-based training. In contrast, the greater increase in lean body mass (LBM) observed in the RT&amp;WL group compared with the WL group (0.9 kg, P &amp;lt; 0.05) after the gymnasium-based training tended to be maintained after the home-based training (0.8 kg, P = 0.08). Similarly, the gymnasium-based increases in upper body and lower body muscle strength in the RT&amp;WL group were maintained over the 12 months (P &amp;lt; 0.001). There were no between-group differences for changes in body weight, fat mass, fasting glucose, or insulin at 6 or 12 months. CONCLUSIONS—In older adults with type 2 diabetes, home-based progressive resistance training was effective for maintaining the gymnasium-based improvements in muscle strength and LBM but not glycemic control. Reductions in adherence and exercise training volume and intensity seem to impede the effectiveness of home-based training for maintaining improved glycemic control.
CD8 T cells primed in the gut-associated lymphoid tissue induce immune-mediated cholangitis in mice
Authors: Daniel Seidel, Ira Eickmeier, Anja A. Kühl, Alf Hamann, Christoph Loddenkemper, Eckart Schott
Journal: Hepatology (2013)

The pathogenesis of primary sclerosing cholangitis (PSC) remains poorly understood. Since PSC predominantly occurs in patients with inflammatory bowel disease, autoimmunity triggered by activated T cells migrating from the gut to the liver is a possible mechanism. We hypothesized that T cells primed in the gut-associated lymphoid tissue (GALT) by a specific antigen migrate to the liver and cause cholangitis when they recognize the same antigen on cholangiocytes. We induced ovalbumin-dependent colitis in mice that express ovalbumin in biliary epithelia (ASBT-OVA mice) and crossed ASBT-OVA mice with mice that express ovalbumin in enterocytes (iFABP-OVA mice). We analyzed T-cell activation in the GALT and crossreactivity to the same antigen in the liver as well as the effects of colitis per se on antigen-presentation and T-cell activation in the liver. Intrarectal application of ovalbumin followed by transfer of CD8 OT-I T cells led to antigen-dependent colitis. CD8 T cells primed in the GALT acquired effector function and the capability to migrate to the liver, where they caused cholangitis in a strictly antigen-dependent manner. Likewise, cholangitis developed in mice expressing ovalbumin simultaneously in biliary epithelia and enterocytes after transfer of OT-I T cells. Dextran sodium sulfate colitis led to increased levels of inflammatory cytokines in the portal venous blood, induced activation of resident liver dendritic cells, and promoted the induction of T-cell-dependent cholangitis. Conclusion : Our data strengthen the notion that immune-mediated cholangitis is caused by T cells primed in the GALT and provide the first link between colitis and cholangitis in an antigen-dependent mouse model. (Hepatology 2014;59:601–611)
Pten Loss Causes Hypertrophy and Increased Proliferation of Astrocytes <b> <i>In vivo</i> </b>
Authors: Melissa M. Fraser, Xiaoyan Zhu, Chang-Hyuk Kwon, Erik J. Uhlmann, David H. Gutmann, Suzanne J. Baker
Journal: Cancer Research (2004)

Abstract Somatic mutations of PTEN are found in many types of cancers including glioblastoma, the most malignant astrocytic tumor. PTEN mutation occurs in 25 to 40% of glioblastomas but is rarely observed in low-grade glial neoplasms. To determine the role of Pten in astrocytes and glial tumor formation, we inactivated Pten by a Cre-loxP approach with a GFAP-cre transgenic mouse that induced Cre-mediated recombination in astrocytes. Pten conditional knockout mice showed a striking progressive enlargement of the entire brain. Increased nuclear and soma size was observed in both astrocytes and neurons, which contributed in part to the increase in brain size. Pten-deficient astrocytes showed accelerated proliferation in vitro and aberrant ongoing proliferation in adult brains in vivo. In contrast, neurons lacking Pten did not show alterations in proliferation. This study shows cell-type dependent effects of Pten loss in the adult brain, including increased astrocyte proliferation that may render astroglial cells susceptible to neoplastic transformation or malignant progression.
Thoracic duct changes in schistosomal hepatic fibrosis
Authors: A. M. Sadek, A. Aboul-Enein, E. Hassenein, A. Ismail
Journal: Gut (1970)

The changes in the thoracic duct were studied in schistosomatic hepatic fibrosis, particularly in cases with ascites. The postmortem findings, lymphangiography, and clinical thoracic duct cannulation showed that, particularly in cases with ascites, the thoracic duct is dilated, pressure within is raised, and the lymph flow is increased. The significance of these findings is discussed in relation to the site and the treatment of ascites.
The Problem of Chest "Pain"
Authors: J. Willis Hurst
Journal: JAMA (1976)

THE ALGORITHM presented here emphasizes the workup of a patient who has chest "pain" whose clinical features might be associated with myocardial ischemia caused by coronary atherosclerosis. Note that the arrows in the algorithm are numbered and correspond to related numbered paragraphs in the discussion. The discussion highlights some of the variables one needs to consider in order to move from one place in the algorithm to another. The physician whose goal is to give comprehensive care should define in advance the items in the history, physical examination, and laboratory workup (which includes a chest roentgenogram and ECG) that should be done on every patient. Items done occasionally are not included in the initial data-gathering process. With this approach, the physician should be able to identify the cause of the chest discomfort in the majority of instances without resorting to additional diagnostic studies. More often than not, the chest pain
P17.52 * ANALYSIS OF RISK AND PROGNOSIS FACTORS IN GLIOBLASTOMA - OUR EXPERIENCE IN 104 PATIENTS
Authors: C. L. Zaruma, E. Arregui, J. M. Cano, J. Gonzalez, M. Amo-Salas, C. Lopez, J. M. B. Moreno
Journal: Neuro-Oncology (2014)

Comite de Neuro-Oncologia, Hospital General Universitario de Ciudad Real, Spain OBJECTIVE: Glioblastoma multiforme (GBM), is the most common and most aggressive malignant primary brain tumor in humans. These tumors are typically associated with a dismal prognosis and poor quality of life. Our objective is analyze both the overall survival (OS) and progression-free survival (PFS) based on different potentially prognostic and risk factors. MATERIALS AND METHODS: We have analyzed 104 patients diagnosed with GBM in our center between 2006 and 2013. The standard scheme that we used was the STUPP scheme, of which 59 patients have benefited. Variables used include age, the diameter of the tumor at onset and the presence of necrosis, and have been evaluated different treatment schemes. RESULTS: In terms of age, it was statistically significant for both the OS (p = 0.0026) and the PFS (p = 0.002). We did not see differences nor in the size of tumor at the diagnosis nor in the presence of necrosis. No differences were seen in OS or PFS with the degree of surgical resection according to STUPP scheme. Patients who have made a complete treatment with surgery, radiotherapy and chemotherapy, have presented an OS of 17.2 months, while PFS was 10.9 months. If we compare these patients with those who have only been operated, survival is statistically significant (p = 0.00015 and p = 0.0013 respectively). CONCLUSIONS: After analyzing our series, we see that the only prognostic factor is age, with strong statistical significance. In our 104 patients, there are no significant differences in regard to the size and the presence of necrosis at diagnosis. Regarding the treatment, the OS nearly 18 months that present our patients treated with STUPP scheme is superior than in other series. We need to expand our database to improve both diagnosis and treatment and the subsequent impact on OS and PFS.
Derivation of Lymphoma Variants With Reduced Sensitivity to Plant Lectins2
Authors: Robert Hyman, Monique Lacorbiere, Suzan Stavarek, Garth Nicolson
Journal: JNCI Journal of the National Cancer Institute (1974)

Variant murine lymphoma cell lines no longer sensitive to the cytotoxic action of lectin antilectin and complement were selected. Lectins were affinity-purified Ricinus communis and wheat germ agglutinins. The variant cell lines expressed 0.5–0.7 of the parental amount of total lectin-binding sites and showed a 10- to 100-fold decrease in sensitivity to the direct cytotoxic action of the lectin. There were no significant changes in other cellsurface determinants.