tbuckley/cabot-search huggingface dataset:
PMO-045 Perioperative dietetic consultation leads to improved nutritional status at 2 week follow-up in patients with oesphagogastric cancer
Authors: L Bakewell, F Noble, V Lam, E Walters, T Underwood
Journal: Gut (2012)

<h3>Introduction</h3> Patients with oesophagogastric cancer are at high risk of malnutrition.<sup>1</sup> The aim of this study was to assess the effect of advice provided by a dietitian peri-operatively on nutritional status at first surgical follow-up. The period studied was prior to specialist dietetic services being funded, resulting in lack of capacity to see all patients referred. <h3>Methods</h3> Consecutive records (n=60) of patients who underwent oesophagogastric resection between August 2010 and November 2011 and referred to the dietetic service were reviewed. Jejunally (n=19) and parenterally fed (n=4), palliative (n=3), stromal tumour resection (n=1), peri-operative deaths (n=1) and incomplete records (n=1) were excluded. Anthropometrics were collected on admission and at first surgical outpatient follow-up. Number of consultations and time spent with a dietitian was recorded. Data for patients referred but not seen was compared to those who received dietetic input. Effect was measured as percentage weight loss. Tests for normality were performed. T-test was used to determine significance. <h3>Results</h3> 31 patients were included in the study. All were initiated on oral nutrition post-operatively. n=21 received dietetic input and n=10 did not. Patient characteristics were similar between both groups apart from tumour differentiation (p=0.046), sex (p=0.023) and weight loss on admission (p=0.148). Mean length of stay=12.8 days (SE 1.1) and time to follow-up= 22.8 days (SE 2.2) (p=ns). Weight loss percentage at follow-up between patients seen and not seen by a dietitian was 7.87 (SE 0.70) and 11.66 (SE 1.24) respectively (p=0.008). Adjusting for sex, tumour differentiation and weight loss on admission did not effect the result (6.88 (SE 0.93), 11.49 (SE 1.07) p=0.005). In the intervention group mean reviews by a dietitian=2.4 (SE 0.3) and time spent=138 min (SE 14). Regression analysis showed a tendency for attenuation of percentage weight loss on increasing time with a dietitian (r=0.33; p=0.142). <h3>Conclusion</h3> Dietetic advice peri-operatively significantly attenuates weight loss at first outpatient follow-up. This effect may improve with increasing time spent with a dietitian. The data supports the Improving Outcomes Guidance on access to dietetic expertise. Although not found in this study, malnutrition is known to increase readmission and hospital stay.<sup>2</sup> <h3>Competing interests</h3> None declared. <h3>References</h3> 1. <b>Bozzetti F.</b> Screening the nutritional status in oncology: a preliminary report on 1000 outpatients. <i>Support Care Cancer</i> 2009;<b>17</b>:279–84. 2. <b>Correia MI,</b> Waitberg DL. The impact of malnutruition on morbidity, mortality, length of stay and costs evaluated through a multivariate model analysis. <i>Clin Nutr</i> 2003;<b>22</b>:235–9.
Influence of Environmental Concentrations of NO on the Exhaled NO Test
Authors: GIORGIO L. PIACENTINI, ALESSANDRO BODINI, LIDIA VINO, LUISA ZANOLLA, SILVIA COSTELLA, LUCIA VICENTINI, ATTILIO L. BONER
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Measurement of levels of exhaled nitric oxide (NO) has been proposed as a noninvasive method for evaluating the degree of airway inflammation in asthmatic patients. Some concern in the interpretation of results of such measurement may arise from possible interference by high environmental concentrations of NO inhaled by these patients. The aim of this study was to verify whether environmental concentrations of NO in the range from 0 to 150 ppb can influence levels of exhaled NO. We tested two groups of subjects. The first group, consisting of 16 subjects, was tested when environmental levels of NO were from 0 to 3 ppb and from 20 to 60 ppb, and exhaled NO mean ppb (+/- SEM) levels were 9.81 +/- 1.43 and 9.78 +/- 1.47 (p = ns) (mean +/- SEM), respectively. The second group, consisting of 30 subjects, was tested at ambient NO concentrations of 0 to 3 ppm, 80 to 100 ppm, and 120 to 150 ppb, and for 18 of these subjects who underwent testing under all three conditions investigated, the mean levels of exhaled NO were 9.23 +/- 1.51, 7.78 +/- 1.19, and 9.33 +/- 1.55 ppb (p = ns), respectively. The results of this study suggest that significantly different ambient levels of NO have no effect on levels of exhaled NO.
CNT1 Expression Influences Proliferation and Chemosensitivity in Drug-Resistant Pancreatic Cancer Cells
Authors: Yangzom D. Bhutia, Sau Wai Hung, Bhavi Patel, Dylan Lovin, Rajgopal Govindarajan
Journal: Cancer Research (2011)

Overcoming the inherent chemoresistance of pancreatic cancers remains a major goal of therapeutic investigations in this disease. In this study, we discovered a role for the human concentrative nucleoside transporter-1 (hCNT1; SLC28A1), a high-affinity pyrimidine nucleoside transporter, in determining the chemosensitivity of human pancreatic cancer cells to gemcitabine, the drug used presently as a standard of care. Compared with normal pancreas and pancreatic ductal epithelial cells, hCNT1 expression was frequently reduced in pancreatic tumors and tumor cell lines. In addition, hCNT1-mediated (3)H-gemcitabine transport was lower in pancreatic cancer cell lines and correlated with cytotoxic IC(50) estimations of gemcitabine. In contrast to gemcitabine-sensitive pancreatic cancer cell lines, MIA PaCa-2, a gemcitabine-resistant pancreatic cancer cell line, exhibited relatively restrictive, cell cycle-dependent hCNT1 expression and transport. hCNT1 translation was suppressed in the late G1-enriched MIA PaCa-2 cell population possibly in an miRNA-dependent manner, which corresponded with the lowest hCNT1-mediated gemcitabine transport during this phase. Although hCNT1 protein was induced during G1/S transition, increased hCNT1 trafficking resulted in maximal cell surface recruitment and transport-overshoot in the G2/M phase-enriched cell population. hCNT1 protein was directed predominantly to proteasomal or lysosomal degradation in S or G2/M phase MIA PaCa-2 cells, respectively. Pharmacological inhibition of hCNT1 degradation moderately increased cell surface hCNT1 expression and cellular gemcitabine transport in MIA PaCa-2 cells. Constitutive hCNT1 expression reduced clonogenic survival of MIA PaCa-2 cells and steeply augmented gemcitabine transport and chemosensitization. In addition to supporting a putative tumor suppressor role for hCNT1, our findings identify hCNT1 as a potential candidate to render drug-resistant pancreatic cancer cells amenable to chemotherapy.
Treatment of verapamil toxicity in intact dogs.
Authors: R Gay, S Algeo, R Lee, M Olajos, E Morkin, S Goldman
Journal: Journal of Clinical Investigation (1986)

The treatment of verapamil toxicity was examined in lightly sedated dogs. Verapamil, administered as a bolus (0.72 mg/kg) followed by a continuous infusion (0.11 mg/kg per min), decreased cardiac output (CO) from 3.1 +/- 0.1 to 1.7 +/- 0.1 liter/min (P less than 0.001), heart rate (HR) from 85 +/- 4 to 57 +/- 3 beats/min (P less than 0.001), left ventricular derivative of pressure with respect to time (LV dP/dt) from 2,085 +/- 828 to 783 +/- 78 mm Hg/s (P less than 0.001), mean aortic pressure (AO) from 77 +/- 4 to 38 +/- 2 mm Hg (P less than 0.001) and stroke volume from 39 +/- 3 to 28 +/- 2 ml/beat (P less than 0.01). In verapamil-toxic animals isoproterenol increased HR, CO, LV dP/dt, and AO; calcium chloride increased LV dP/dt and AO; norepinephrine, epinephrine, and dopamine increased CO, AO, and LV dP/dt, atropine increased HR, CO, and AO. Phenylephrine (13-55 micrograms/kg per min) produced no changes except a small increase in AO while very high dose phenylephrine (300 micrograms/kg per min) increased AO, CO, and LV dP/dt. 4-Aminopyridine (4-AP) increased HR, CO, LV dP/dt, and AO. When administered prior to verapamil, 4-AP prevented the development of verapamil toxicity as shown by the significantly higher AO (P less than 0.001), CO (P less than 0.01), and LV dP/dt (P less than 0.01) when 4-AP followed by verapamil was compared to verapamil alone. In conclusion, there does not appear to be a single specific therapy for verapamil toxicity, however it can be partially corrected by presently available pharmacologic therapy and 4-AP.
Long-Term Histologic Improvement and Loss of Detectable Intrahepatic HCV RNA in Patients with Chronic Hepatitis C and Sustained Response to Interferon-α Therapy
Authors: Patrick Marcellin
Journal: Annals of Internal Medicine (1997)

Background: Less than 20% of patients with chronic hepatitis C have a sustained response to interferon-α therapy. The long-term benefit of interferon-α with regard to hepatic viral clearance and histologic improvement remains unknown. Objective: To determine the long-term biochemical, virologic, and histologic outcomes in patients with chronic hepatitis C who have a sustained response to interferon-α therapy. Design: Prospective cohort study. Setting: University hospital. Patients: 80 patients who had chronic hepatitis C, had a sustained biochemical and virologic response to interferon-α therapy, and were followed for at least 12 months. Measurements: Serum hepatitis C virus (HCV) RNA detected by polymerase chain reaction (PCR); HCV genotyping determined by line probe assay; liver histologic studies; liver HCV RNA detected by PCR on frozen liver tissue samples (in 27 patients); and repeated measurements of serum alanine aminotransferase (ALT) levels. Liver biopsy was done before treatment in all 80 patients, and at least one biopsy was done in 69 patients 1 to 6 years after treatment. Results: The 80 patients had follow-up 1 to 7.6 years (mean ±SD, 4.0 ± 2.0 years) after interferon-α treatment. The follow-up period was 1, 2, 3, 4, 5, 6, and more than 6 years in 11, 13, 14, 18, 10, 12, and 2 patients, respectively, after the end of therapy. During the entire follow-up period, 93% (95% CI, 84% to 97%) of patients had persistently normal serum ALT levels. Serum HCV RNA remained undetectable in 96% (CI, 89% to 99%) of patients. A comparison of liver histologic findings before and 1 to 6.2 years after interferon-α treatment showed a clear improvement in 94% (CI, 83% to 99%) of patients. In 62% of patients, the last biopsy done showed normal or nearly normal histologic findings. Liver HCV RNA was detectable before treatment in all 13 patients tested and was undetectable 1 to 5 years after treatment in all 27 patients tested. Conclusions: In patients with chronic hepatitis C who have persistently normal serum ALT levels and no detectable serum HCV RNA 6 months after interferon-α therapy, a long-term sustained biochemical and virologic response is generally seen. This response is associated with an absence of detectable intrahepatic HCV RNA and marked histologic improvement.
Intrapleural Use of Tissue Plasminogen Activator and DNase in Pleural Infection
Authors: Najib M. Rahman, Nicholas A. Maskell, Alex West, Richard Teoh, Anthony Arnold, Carolyn Mackinlay, Daniel Peckham, Chris W.H. Davies, Nabeel Ali, William Kinnear, Andrew Bentley, Brennan C. Kahan, John M. Wrightson, Helen E. Davies, Clare E. Hooper, Y.C. Gary Lee, Emma L. Hedley, Nicky Crosthwaite, Louise Choo, Emma J. Helm, Fergus V. Gleeson, Andrew J. Nunn, Robert J.O. Davies
Journal: New England Journal of Medicine (2011)

More than 30% of patients with pleural infection either die or require surgery. Drainage of infected fluid is key to successful treatment, but intrapleural fibrinolytic therapy did not improve outcomes in an earlier, large, randomized trial.We conducted a blinded, 2-by-2 factorial trial in which 210 patients with pleural infection were randomly assigned to receive one of four study treatments for 3 days: double placebo, intrapleural tissue plasminogen activator (t-PA) and DNase, t-PA and placebo, or DNase and placebo. The primary outcome was the change in pleural opacity, measured as the percentage of the hemithorax occupied by effusion, on chest radiography on day 7 as compared with day 1. Secondary outcomes included referral for surgery, duration of hospital stay, and adverse events.The mean (±SD) change in pleural opacity was greater in the t-PA-DNase group than in the placebo group (-29.5±23.3% vs. -17.2±19.6%; difference, -7.9%; 95% confidence interval [CI], -13.4 to -2.4; P=0.005); the change observed with t-PA alone and with DNase alone (-17.2±24.3 and -14.7±16.4%, respectively) was not significantly different from that observed with placebo. The frequency of surgical referral at 3 months was lower in the t-PA-DNase group than in the placebo group (2 of 48 patients [4%] vs. 8 of 51 patients [16%]; odds ratio for surgical referral, 0.17; 95% CI, 0.03 to 0.87; P=0.03) but was greater in the DNase group (18 of 46 patients [39%]) than in the placebo group (odds ratio, 3.56; 95% CI, 1.30 to 9.75; P=0.01). Combined t-PA-DNase therapy was associated with a reduction in the hospital stay, as compared with placebo (difference, -6.7 days; 95% CI, -12.0 to -1.9; P=0.006); the hospital stay with either agent alone was not significantly different from that with placebo. The frequency of adverse events did not differ significantly among the groups.Intrapleural t-PA-DNase therapy improved fluid drainage in patients with pleural infection and reduced the frequency of surgical referral and the duration of the hospital stay. Treatment with DNase alone or t-PA alone was ineffective. (Funded by an unrestricted educational grant to the University of Oxford from Roche UK and by others; Current Controlled Trials number, ISRCTN57454527.).
Relations of ethnicity and vascular parameters to left ventricular structure in hypertensive adults
Authors: Jorge R. Kizer, Donna K. Arnett, Jonathan N. Bella, Mary Paranicas, D.C. Rao, Michael A. Province, Albert Oberman, Dalane W. Kitzman, Paul N. Hopkins, Mary J. Roman, Richard B. Devereux
Journal: Journal of the American College of Cardiology (2003)
Immune response inversion after hyperimmunisation. Possible mechanism in the pathogenesis of HLA-linked diseases.
Authors: C.R Young, A Ebringer, J.R Archer
Journal: Annals of the Rheumatic Diseases (1978)

The crosstolerance hypothesis suggests that animals sharing antigens with some microorganisms will produce low antibody levels in the early part and high levels in the latter part of an infection. Antibody responses have been measured in high responder B10.M and B10.D2 mice and low responder C3H and A.Thy-1.1, as well as F1 hybrids (B10.M X A.Thy-1.1) and (B10.M X C3H/He), after repeated immunisation with the antigen ferritin, involving altogether 483 mice. An inversion in the immune response was found to occur and similar delayed high antibody responses have been described in rheumatic fever. It is suggested a mechanism of immune inversion may operate in the pathogenesis of HLA and blood group-linked diseases.
Molecular Evolution of the Drosophila Retinome: Exceptional Gene Gain in the Higher Diptera
Authors: R. Bao, M. Friedrich
Journal: Molecular Biology and Evolution (2009)

Using genomic information from mosquito, red flour beetle, honeybee, mouse, and sea anemone, we have studied the molecular evolution of 91 Drosophila genes involved in eye primordium determination, retinal differentiation, and phototransduction. Our results show that the majority of these gene sequences predate the diversification of endopterygote insects. However, all three functional groups contain a conspicuous fraction of evolutionarily younger genes, which originated by tandem duplication in the lineage leading to Drosophila, whereas gene duplications are rare in other insect lineages. We conclude that the retention of duplicated genes spiked during the early diversification of the higher Diptera possibly due to an extended period of exceptional population size reduction. Genetic data suggest that gene duplication played an important role in the evolution of visual performance in the fast flying higher Diptera by spatial or intracellular subfunctionalization. Developmental gene duplications, by contrast, predominantly retained overlapping expression patterns and preserved partial to complete redundancy consistent with a role in boosting developmental robustness.
Role of protein kinase C in bradykinin-induced increases in microvascular permeability.
Authors: M A Murray, D D Heistad, W G Mayhan
Journal: Circulation Research (1991)

The goal of this study was to determine whether protein kinase C mediates bradykinin-induced increases in microvascular permeability. Permeability of the hamster cheek pouch was evaluated using intravital fluorescent microscopy and fluorescein isothiocyanate (FITC)-dextran (MW 70,000). We examined effects of sphingosine, a protein kinase C inhibitor, on bradykinin-induced increases in permeability. Increases in permeability were quantitated by counting the number of leaky sites and calculating the clearance of FITC-dextran. During bradykinin (10(-6) M), leaky sites increased from 0 to 40 +/- 4 (mean +/- SEM) sites/0.11 cm2, and clearance increased from 1.7 +/- 1.0 to 22 +/- 9 ml/sec x 10(-6). The bradykinin type-2 receptor antagonist D-Arg,[Hyp3,Thi5,8,D-Phe7]-bradykinin virtually abolished formation of leaky sites in response to bradykinin. To determine whether changes in microvascular pressure contribute to the increase in leaky sites, venular pressure was measured using a micropipette and survo-null device. Increases in cheek pouch venular pressure were similar during application of bradykinin and adenosine, which increased permeability, and isoproterenol, which did not increase permeability in the cheek pouch. Thus, increases in permeability were not linked to changes in microvascular pressure. The protein kinase C inhibitor, sphingosine (10(-6) M), markedly attenuated responses to bradykinin. Leaky sites increased from 0 to only 2 +/- 1 sites/0.11 cm2, and clearance increased from 3.9 +/- 1.4 to only 6.7 +/- 2.2 ml/sec x 10(-6). To test the specificity of sphingosine, we examined effects of adenosine (10(-6) M). Sphingosine did not significantly alter increases in microvascular permeability in responses to adenosine. We also examined effects of 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7), another protein kinase C inhibitor, on responses to bradykinin and adenosine. H-7 greatly attenuated formation of leaky sites during stimulation with bradykinin and did not alter the number of leaky sites produced during adenosine. The findings suggest that protein kinase C may mediate increases in vascular permeability in response to bradykinin.
Interleukin 10 (IL-10) upregulates IL-1 receptor antagonist production from lipopolysaccharide-stimulated human polymorphonuclear leukocytes by delaying mRNA degradation.
Authors: M A Cassatella, L Meda, S Gasperini, F Calzetti, S Bonora
Journal: The Journal of Experimental Medicine (1994)

Polymorphonuclear leukocytes (PMN) have been identified as cells capable of producing a number of pro- and antiinflammatory cytokines in response to specific agonists. Previously, we showed that tumor necrosis factor (TNF), interleukin-1 beta (IL-1 beta), and IL-8, are produced by PMN after stimulation with agonists, such as lipopolysaccharide (LPS). In this study, we demonstrate that LPS is also a potent stimulus for the mRNA expression and release of the IL-1 receptor antagonist (IL-1ra). In addition, we show that the release of IL-1ra from LPS-stimulated PMN is markedly potentiated in the presence of IL-10 (from two to threefold after 18 h of stimulation). Moreover, we observed that this upregulation of IL-1ra production by IL-10 in LPS-stimulated PMN took place through IL-1ra mRNA stabilization. Indeed, the half-life of IL-1ra mRNA was prolonged in PMN stimulated in the presence of IL-10 and LPS, as compared with cells stimulated with LPS alone. That IL-10 selectively upregulates IL-1ra production in LPS-activated PMN, while it inhibits the production of IL-1 beta, TNF, and IL-8 under the same conditions, suggests that IL-10 may be an important physiologic regulator of cytokine production from PMN, and emphasizes the potential role of IL-10 in inflammatory responses.
Biological markers in human lung carcinoma: an immunopathological study of six antigens.
Authors: H R Harach, M Skinner, A R Gibbs
Journal: Thorax (1983)

Immunohistological methods were used to investigate the presence of calcitonin, thyrotrophin, carcinoembryonic antigen, beta pregnancy specific glycoprotein, human placental lactogen, and the beta subunit of human chorionic gonadotrophin in formalin fixed lung tumour tissue sections. Carcinoembryonic antigen was observed in 71% of 101 tumours studied (70%), beta 1 pregnancy specific glycoprotein in 66 of 97 tumours (68%), beta subunit of human chorionic gonadotrophin in 35 of 97 (36%), human placental lactogen in 19 of 97 (20%), calcitonin in 10 of 71 (14%), and thyrotrophin in one of 27 lung tumours studied. There appeared to be no direct association between the presence of any given marker and the presence of any other. Similarly, the association between the presence of a tumour marker and histological type was poor. This study shows that the presence of tumour markers is relatively common in human lung tumours.
Low Tonicity Mediates a Downregulation of Cyclooxygenase-1 Expression by Furosemide in the Rat Renal Papilla
Authors: Hayo Castrop, Helga Vitzthum, Karl Schumacher, Frank Schweda, Armin Kurtz
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. It is well known that loop diuretics enhance the renal excretion of prostanoids; therefore, this study aimed to characterize the influence of loop diuretics on the intrarenal expression of cyclooxygenases, which are the key enzymes for prostanoid formation. Male Sprague-Dawley rats were infused with furosemide (12 mg/kg per d) for 6 d, and the expression of cyclooxygenase-1 and -2 (Cox-1 and Cox-2) was analyzed in the different kidney zones. Furosemide increased Cox-2 mRNA expression approximately twofold in the cortex, but it left Cox-1 mRNA expression unaltered there. In the outer medulla, furosemide changed neither Cox-1 nor Cox-2 mRNA expression. In the inner medulla, however, furosemide decreased Cox-1 and Cox-2 mRNA levels to approximately 30% and 60% of their control levels, respectively. The downregulation of mRNA was paralleled by a decrease of Cox protein in the collecting ducts and interstitial cells. Moreover, tissue prostaglandin E 2 (PGE 2 ) concentrations in the papilla were markedly decreased by furosemide to about 30% of the control level. Furosemide lowered urine osmolality from 1550 mosmol/kg to 480 mosmol/kg; therefore, further consideration was given to the influence of tonicity as a possible mediator of the effects of furosemide on the Cox expression. Water loading was therefore used to reduce the medullary tonicity by a second maneuver. Water loading led to a similar reduction in papillary Cox mRNA expression and PGE 2 content like furosemide. To investigate the influence of the osmolarity on the expression of Cox and the production of PGE 2 under defined in vitro conditions, inner medullary collecting duct cells were incubated with culture medium containing graded amounts of NaCl ranging from 200 mmol/L to 600 mmol/L, and Cox-1 and Cox-2 mRNA abundance were determined after 24 h an 48 h. Cox-1 and Cox-2 mRNA abundance changed in parallel with the osmolarity. The data suggest that loop diuretics decrease the expression of cyclooxygenases and consequently tissue PGE 2 concentrations in the kidney inner medulla. This effect could be related to the breakdown of the papillary osmotic gradient induced by loop diuretics.