tbuckley/cabot-search huggingface dataset:
Phase II Study of Protracted Daily Temozolomide for Low-Grade Gliomas in Adults
Authors: Santosh Kesari, David Schiff, Jan Drappatz, Debra LaFrankie, Lisa Doherty, Eric A. Macklin, Alona Muzikansky, Sandro Santagata, Keith L. Ligon, Andrew D. Norden, Abigail Ciampa, Joanna Bradshaw, Brenda Levy, Gospova Radakovic, Naren Ramakrishna, Peter M. Black, Patrick Y. Wen
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Resistance to temozolomide chemotherapy is partly mediated by O6-methylguanine-DNA methlytransferase (MGMT). Protracted treatment with temozolomide potentially overcomes MGMT resistance and improves outcome. We conducted a phase II study of protracted daily temozolomide in adults with low-grade gliomas. Experimental Design: Patients with newly diagnosed oligodendroglioma or oligoastrocytoma with a MIB-1 index of &amp;gt;5% or recurrent low-grade gliomas received temozolomide (75 mg/m2/day in 11-week cycles of 7 weeks on/4 weeks off). Treatment continued for a total of six cycles or until tumor progression or unacceptable toxicity. Primary end point was best overall response rate; secondary end points were progression-free survival, overall survival, and toxicity. We correlated response with MGMT promoter methylation and chromosome 1p/19q deletion status. Results: Forty-four patients were treated (14 female, 30 male) with a median follow-up of 39.4 months. Median age was 43 years (range, 20-68 years) and median Karnofsky performance status was 90 (range, 70-100). The regimen was well tolerated. No patients had a complete response (0%), 9 had partial response (20%), 33 had stable disease (75%), and 2 had progressive disease (5%). A total of 21 patients eventually progressed with an overall median progression-free survival of 38 months. Patients with methylated MGMT promoter had a longer overall survival (P = 0.008). Deletion of either 1p or 19q chromosomes also predicted longer overall survival (hazard ratio, 0.17; 95% confidence interval, 0.03-0.93; log-rank P = 0.02). Conclusions: A protracted course of daily temozolomide is a well-tolerated regimen and seems to produce effective tumor control. This compares favorably with historical data on the standard 5-day temozolomide regimen.
Expression of major histocompatibility antigens in human chronic pancreatitis.
Authors: R P Jalleh, J A Gilbertson, R C Williamson, S D Slater, C S Foster
Journal: Gut (1993)

T-lymphocytic infiltration of the exocrine pancreas and liver in patients with chronic pancreatitis has suggested that cell mediated immune mechanisms may play a part in the pathogenesis of this disease. As expression of major histocompatibility (MHC) antigens is a prerequisite for organ specific autoimmunity, the expression of HLA class I (beta 2-microglobulin) and class II (HLA-DR) determinants have been analysed, together with the presence of T-lymphocytes, in 93 patients (64 men and 29 women, mean age 40.6 years) having an operation for chronic pancreatitis. Ethanol (63 patients), recurrent acute pancreatitis (12), congenital lesions (2), and unknown (16) were suggested to be the causes of the disease. Immunohistochemical staining of formalin fixed and paraffin wax embedded tissue sections used conventional immunohistochemical techniques with specific anti-serum samples. No MHC expression was identified in 10 histologically normal pancreatic control specimens or in four cases of chronic pancreatitis secondary to obstruction by neuroendocrine tumours within the head of the pancreas. beta 2-microglobulin expression by pancreatic exocrine epithelial cells was seen in 76 chronic pancreatitis specimens (82%) while HLA-DR was present in 61 (66%). Simultaneous expression of both class I and II determinants was seen in 53 (57%) of cases. MHC determinant expression was not found in 10 cases (11%) of chronic pancreatitis. In the positive specimens, expression was confined to ductal and ductular (interlobular and intralobular) epithelium with no staining of acinar cells. Staining was not related to the suspected cause of the disease or age. T-lymphocytes were more prominent in chronic pancreatitis mean (SEM) (131 (15) cells per high powered field) than controls (5 (1), p &lt; 0.01). Aberrant MHC expression by exocrine pancreatic epithelial cells occurring in the presence of an appreciable T-cell infiltration confirmed that the appropriate cellular conditions were present for cell mediated cytotoxicity to contribute to the pathogenesis of chronic pancreatitis.
Identification of a Molecular Signature Underlying Inhibition of Mammary Carcinoma Growth by Dietary N-3 Fatty Acids
Authors: Weiqin Jiang, Zongjian Zhu, John N. McGinley, Karam El Bayoumy, Andrea Manni, Henry J. Thompson
Journal: Cancer Research (2012)

An increased ratio of dietary n-3 relative to n-6 fatty acids has been shown to inhibit the development of mammary cancer in animal models. However, the molecular mechanisms by which n-3 fatty acids affect tumor growth remain unknown. Here, we investigated the effects of varying dietary ratios of n-3:n-6 fatty acids on cell signaling in a rat model of chemically induced mammary carcinoma. Cell proliferation was reduced by 60% in carcinomas from the high n-3:n-6 treatment group compared with the low n-3:n-6 treatment group. These changes were associated with decreased cyclin-D1 and phospho-retinoblastoma protein expression and increased levels of cyclin-dependent kinase inhibitors, CIP1 (p21) and KIP1 (p27). In addition, the apoptotic index was increased in carcinomas from the high n-3:n-6 group and was associated with elevated apoptotic protease-activating factor 1 and a higher ratio of Bax/Bcl-2. Interestingly, changes in protein expression were consistent with reduced inflammation and suppressed mTOR activity, and the molecular signature associated with high n-3:n-6 treatment revealed changes in PPARγ activation and suppression of lipid synthesis. Together, our findings indicate that the molecular effects of high dietary n-3 to n-6 ratios are heterogeneous in nature but point to consistent changes in lipid metabolism pathways, which may serve as potential therapeutic targets for cancer prevention and control. This study identifies the pathways modulated by dietary fatty acid ratios in a rat model of breast cancer, with implications for cancer prevention.
Low-Dose Aspirin for Prevention of Morbidity and Mortality From Preeclampsia: A Systematic Evidence Review for the U.S. Preventive Services Task Force
Authors: Jillian T. Henderson, Evelyn P. Whitlock, Elizabeth O’Connor, Caitlyn A. Senger, Jamie H. Thompson, Maya G. Rowland
Journal: Annals of Internal Medicine (2014)

Preeclampsia is a leading cause of maternal and perinatal morbidity and mortality.To systematically review benefits and harms of low-dose aspirin for preventing morbidity and mortality from preeclampsia.MEDLINE, Database of Abstracts of Reviews of Effects, PubMed, and Cochrane Central Register of Controlled Trials (January 2006 to June 2013); previous systematic reviews, clinical trial registries, and surveillance searches for large studies (June 2013 to February 2014).Randomized, controlled trials (RCTs) to assess benefits among women at high preeclampsia risk and RCTs or large cohort studies of harms among women at any risk level. English-language studies of fair or good quality were included.Dual quality assessment and abstraction of studies.Two large, multisite RCTs and 13 smaller RCTs of high-risk women (8 good-quality) were included, in addition to 6 RCTs and 2 observational studies of average-risk women to assess harms (7 good-quality). Depending on baseline risk, aspirin use was associated with absolute risk reductions of 2% to 5% for preeclampsia (relative risk [RR], 0.76 [95% CI, 0.62 to 0.95]), 1% to 5% for intrauterine growth restriction (RR, 0.80 [CI, 0.65 to 0.99]), and 2% to 4% for preterm birth (RR, 0.86 [CI, 0.76 to 0.98]). No significant perinatal or maternal harms were identified, but rare harms could not be ruled out. Evidence on long-term outcomes was sparse, but 18-month follow-up from the largest trial found no developmental harms.Benefits may have been overestimated due to small-study effects. Predictive intervals were not statistically significant. Future studies could shift findings toward the null.Daily low-dose aspirin beginning as early as the second trimester prevented clinically important health outcomes. No harms were identified, but long-term evidence was limited.
Cluster of human tuberculosis caused by Mycobacterium bovis: evidence for person-to-person transmission in the UK
Authors: Jason T Evans, E Grace Smith, Ashis Banerjee, Robert MM Smith, James Dale, John A Innes, David Hunt, Alan Tweddell, Annette Wood, Charlotte Anderson, R Glyn Hewinson, Noel H Smith, Peter M Hawkey, Pam Sonnenberg
Journal: The Lancet (2007)
Central neural activation of hyperdynamic circulation in portal hypertensive rats depends on vagal afferent nerves
Authors: H Liu, N Schuelert, J J McDougall, S S Lee
Journal: Gut (2008)

<h3>Background:</h3> Hyperdynamic circulation in portal hypertensive rats depends on central neural c-<i>fos</i> gene expression, but how the portal hypertensive signal activates central c-<i>fos</i> expression remains obscure. <h3>Aim:</h3> To elucidate the afferent pathway from the gut to the central cardiovascular regulatory nuclei in portal hypertensive rats. <h3>Methods:</h3> Cervical vagus nerves and the coeliac ganglion were treated with topical capsaicin to denervate the sensory afferents. Surgical portal vein stenosis (PVS) was performed 3 weeks after denervation. Effectiveness of vagal afferent denervation was confirmed by absent oesophagus to brainstem transfer of the neural tracer cholera toxin-conjugated horseradish peroxidase. Fos, the protein product of the c-<i>fos</i> gene, was detected by immunohistochemistry in central cardiovascular regulatory nuclei. Vagal nerve activity was measured after acute portal hypertension induced by an inflatable cuff around the portal vein. Cardiac output and mean arterial pressure were recorded. <h3>Results:</h3> In vagal capsaicin-treated rats, no horseradish peroxidase was detected in the brainstem after oesophageal injection. In vagal capsaicin-treated rats subjected to PVS, Fos expression was significantly decreased in both the solitary tract nucleus and paraventricular nucleus compared with untreated PVS rats. Acute portal hypertension stimulated vagal nerve electrical activity. The hyperdynamic circulation was completely abrogated in vagal capsaicin-treated PVS rats. Capsaicin induced no neural or haemodynamic changes in either sham-operated controls or coeliac ganglion-treated PVS rats. <h3>Conclusion:</h3> In portal hypertensive rats, central cardiovascular regulatory nuclei initiate hyperdynamic circulation in response to a gut signal associated with portal hypertension. Portal hypertension signals to the central nuclei via capsaicin-sensitive vagal afferent nerves.
Heavy cigarette smoking is strongly associated with rheumatoid arthritis (RA), particularly in patients without a family history of RA
Authors: D Hutchinson
Journal: Annals of the Rheumatic Diseases (2001)

To investigate the potential relation between cumulative exposure to cigarette smoking in patients with or without rheumatoid arthritis (RA) and a positive family history of the disease.239 outpatient based patients with RA were compared with 239 controls matched for age, sex, and social class. A detailed smoking history was recorded and expressed as pack years smoked. Conditional logistic regression was used to calculate the association between RA and pack years smoked. The patients with RA were also interviewed about a family history of disease and recorded as positive if a first or second degree relative had RA. The smoking history at the time of the study of the patients with RA with or without a family history of the disease was compared directly with that of their respective controls. Patients with RA with or without a family history of the disease were also compared retrospectively for current smoking at the time of disease onset.An increasing association between increased pack years smoked and RA was found. There was a striking association between heavy cigarette smoking and RA. A history for 41-50 pack years smoked was associated with RA (odds ratio (OR) 13.54, 95% confidence interval (95% CI) 2.89 to 63.38; p<0.001). The association between ever having smoked and RA was modest (OR 1.81, CI 1.22 to 2.19; p=0.002). Furthermore, cigarette smoking in the patients with RA without a positive family history of RA was more prevalent than in the patients with a positive family history of RA for ever having smoked (72% v 54%; p=0.006), the number of pack years smoked (median 25.0 v 4.0; p<0.001), and for smoking at the time of disease onset (58% v 39%; p=0.003).Heavy cigarette smoking, but not smoking itself, is strongly associated with RA requiring hospital follow up and is markedly more prevalent in patients with RA without a family history of RA.
Long-term follow-up of children with congenital chylothorax
Authors: Bernhard Resch, Melanie Halmer, Wilhelm D. Müller, Ernst Eber
Journal: European Respiratory Journal (2012)

To the Editors:

Congenital chylothorax, defined as the accumulation of lymphatic fluid in the pleural cavity, is a rare neonatal disorder. Nevertheless, congenital chylothorax represents the most common cause of pleural effusion in fetuses and newborns [1]. Due to the rarity of this disorder only a few case series are reported in the literature and current treatment recommendations are based on individual case reports or case series only [2–5]. The diagnosis of chylothorax is considered when pleural fluid triglyceride levels are >1.1 mmol·L−1 and total cell counts are >1,000 cells per mL with >80% lymphocytes. Without oral fat intake chylomicrons, which are often an indication for the diagnosis of chylothorax, are absent in the pleural fluid and distinction between chylous and non-chylous effusion might be difficult [6]. Long-term follow-up of children with congenital chylothorax, however, was documented in only four studies [7–10] and none included pulmonary function testing. We describe the clinical course and long-term outcome of infants with congenital chylothorax including neurodevelopmental follow-up and pulmonary function testing.

In this study the data of all children who were documented in the local database of the Division of Neonatology (Paediatric Dept, Medical University of Graz, Graz, Austria) with the diagnosis of congenital chylothorax between January 1, 1995 and December …
Immunochemotherapy and Autologous Stem-Cell Transplantation for Untreated Patients With Mantle-Cell Lymphoma: CALGB 59909
Authors: Lloyd E. Damon, Jeffrey L. Johnson, Donna Niedzwiecki, Bruce D. Cheson, David D. Hurd, Nancy L. Bartlett, Ann S. LaCasce, Kristie A. Blum, John C. Byrd, Michael Kelly, Wendy Stock, Charles A. Linker, George P. Canellos
Journal: Journal of Clinical Oncology (2009)

PURPOSE Mantle-cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin's lymphoma with a poor prognosis. We explored the feasibility, safety, and effectiveness of an aggressive immunochemotherapy treatment program that included autologous stem-cell transplantation (ASCT) for patients up to age 69 years with newly diagnosed MCL. PATIENTS AND METHODS The primary end point was 2-year progression-free survival (PFS). A successful trial would yield a 2-year PFS of at least 50% and an event rate (early progression plus nonrelapse mortality) less than 20% at day +100 following ASCT. Seventy-eight patients were treated with two or three cycles of rituximab combined with methotrexate and augmented CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone). This treatment was followed by intensification with high doses of cytarabine and etoposide combined with rituximab and filgrastim to mobilize autologous peripheral-blood stem cells. Patients then received high doses of carmustine, etoposide, and cyclophosphamide followed by ASCT and two doses of rituximab. Results There were two nonrelapse mortalities, neither during ASCT. With a median follow-up of 4.7 years, the 2-year PFS was 76% (95% CI, 64% to 85%), and the 5-year PFS was 56% (95% CI, 43% to 68%). The 5-year overall survival was 64% (95% CI, 50% to 75%). The event rate by day +100 of ASCT was 5.1%. CONCLUSION The Cancer and Leukemia Group B 59909 regimen is feasible, safe, and effective in patients with newly diagnosed MCL. The incorporation of rituximab with aggressive chemotherapy and ASCT may be responsible for the encouraging outcomes demonstrated in this study, which produced results comparable to similar treatment regimens.
NICE guidance on place of birth falls short of neutrality
Authors: A. L. O'Brien, M. Chandiramani, C. C. Lees
Journal: BMJ (2014)

The title of the news item on the National Institute for Health and Care Excellence (NICE) guidance on intrapartum care—“Midwife led units safest for straightforward births”—and the guideline itself, belie the evidence.1 Birth can be considered straightforward only in retrospect—classification beforehand implies a predictive accuracy that neither obstetricians nor midwives possess.

It is not immediately obvious from the guideline that “the …
PTU-133 Goblet Cell Carcinoma of the Appendix: Acute vs Chronic Presentations
Authors: R Basuroy, A Ngu, L Mills, H El-Mahallawi, T Cecil, J K Ramage
Journal: Gut (2013)

<h3>Introduction</h3> Goblet Cell Carcinomas (GCC) are a rare neuroendocrine tumour (NET) of the appendix. The experience of a National Specialist Centre’s for pseudomyxoma peritonei (cytoreductive surgery) and two regional NET services with patients with GCC are presented. <h3>Methods</h3> A retrospective audit was performed of patients with histologically proven GCC collated from histology, NET and cytoreductive surgery databases. Mortality rates (%) for subgroups were calculated. <h3>Results</h3> 16 patients (female = 9) were included for analysis with median age at diagnosis of 58 years (range, 25.5–71.8). The mortality rate was 25% (n = 4) associated with median survival of 22 months (range, 9–72) following diagnosis. The most common symptoms were acute appendicitis-like (62.5%), chronic abdominal pain (50%), bowel obstruction (25%) and chronic diarrhoea (12.5%). Patients presenting with acute appendicitis-like symptoms had the lowest mortality rate at 10%. Bowel obstruction, chronic abdominal pain and chronic diarrhoea were associated with mortality rates of 50%, 38% and 50% respectively. Completion right hemicolectomy (n = 10) was associated with decreased mortality (22% vs 40%). Bilateral salphingo-oophrectomy (n = 5) was associated with increased mortality (66% vs 0%). The mortality rate associated with chemotherapy (n = 6) and cytoreductive surgery (n = 4) was 17% and 50% respectively. <h3>Conclusion</h3> Patients with GCC who present acutely have better outcomes than those with chronic symptoms suggesting different disease processes. Performing a completion right hemicolectomy is associated with benefit, while the role of BSO is less clear. <h3>Disclosure of Interest</h3> None Declared
CORRECTION
Authors: D J Armstrong, A D Crockard, E M Whitehead, A L Bell
Journal: Annals of the Rheumatic Diseases (2005)

We read with interest the report of Marto et al 1 on the occurrence of anti-C1q antibodies in systemic lupus erythematosus (SLE), particularly their finding of anti-C1q in 39.8% of patients with SLE without renal disease, 27.3% of whom went on to develop nephritis.

We recently tested for anti-C1q antibodies using an enzyme linked immunosorbent assay (ELISA) kit (Buhlmann Laboratories, Basel) in the sera …
Application of High-Density DNA Microarray to Study Smoke- and Hydrogen Peroxide–Induced Injury and Repair in Human Bronchial Epithelial Cells
Authors: Ken Yoneda, Mary Mann-Jong Chang, Ken Chmiel, Yin Chen, Reen Wu
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Recent advances in high-density DNA microarray technique allow the possibility to analyze thousands of genes simultaneously for their differential gene expression patterns in various biologic processes. Through clustering analysis and pattern recognition, the significance of these differentially expressed genes can be recognized and correlated with the biologic events that may take place inside the cell and tissue. High-density DNA microarray nylon membranes were used to explore gene expression and regulation associated with smoke- and hydrogen peroxide–induced injury and repair in differentiated human bronchial epithelial cells in vitro. At least three phases of change in gene expression could be recognized. The first phase seems to be an immediate event in response to oxidant injury. This phase includes the induction of bcl-2 and mdm2 genes that are involved in the regulation of apoptosis, and the mitogen-activated protein kinase phosphatase 1 that functions as a regulator for various mitogen-activated protein kinase activities. The second phase, usually 5 h later, includes the induction of various stress proteins and ubiquitin, which are important in providing the chaperone mechanism and the turnover of damaged macromolecules. The third phase, which is 5 to 10 h later, includes the induction of genes that seem to be involved in reducing oxidative stress by metabolizing the cellular level of reactive oxygen species. In this phase, enzymes associated with tissue and cell remodeling are also elevated. These results demonstrated a complex gene expression array by bronchial epithelial cells in response to a single insult of oxidants that are relevant to environmental pollutants. E-mail: [email protected]
Body weight and weight gain related to pulmonary function decline in adults: a six year follow up study.
Authors: Y Chen, S L Horne, J A Dosman
Journal: Thorax (1993)

BACKGROUND--Obesity increases the risk of cardiovascular disease, hypertension, diabetes, digestive diseases, and some cancers. Several studies have shown that excess weight or weight gain is related to pulmonary dysfunction, but this issue needs to be further clarified. METHODS--The analysis was based on data of the Humboldt cohort study which was conducted in the town of Humboldt, Saskatchewan, Canada. The baseline survey in 1977 included 1202 adults, comprising 94% of all residents aged 25-59 years. Of these, 709 (59%) were followed up in 1983. Pulmonary function (forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and maximal mid expiratory flow rate (MMFR) and weight were measured in both surveys. Weight gain was determined by subtracting weight at baseline from weight at follow up. A residual analysis was used to examine the relationship between body mass index (BMI) at baseline, weight gain, and pulmonary function decline. RESULTS--Both BMI at baseline and weight gain were significantly related to pulmonary function at follow up. The effect of weight gain during the study period, however, was more prominent. The results showed that both mean residual FVC and FEV1 were highest in the group that gained &lt; 1.0 kg, lowest in the group that gained &gt; or = 4.0 kg, and intermediate in the group that gained 1.0-3.9 kg in both men and women after taking age, BMI at baseline, and smoking into account. The effect of weight gain on pulmonary function was greater in men than in women. Multiple regression analysis showed that each kilogram of weight gain was associated with an excess loss of 26 ml in FVC and 23 ml in FEV1 in men, and 14 ml and 9 ml respectively in women. CONCLUSIONS--Weight gain is significantly related to lung dysfunction. The effect of weight gain on pulmonary function is greater in men than in women.