tbuckley/cabot-search huggingface dataset:
The Staging of Cancer: A Retrospective and Prospective Appraisal
Authors: F. L. Greene, L. H. Sobin
Journal: CA A Cancer Journal for Clinicians (2008)

The tumor-node-metastasis (TNM) classification describes the anatomic extent of cancer. The ability to separately classify the individual T, N, and M elements and then group them into stages differs from other cancer staging classifications, which are primarily concerned with summarized groups. The objectives of the TNM system are to aid clinicians and investigators in planning treatment, assessing prognosis, stratifying patients for therapeutic studies, evaluating the results of treatment, and facilitating communication. The most important challenge facing TNM is how to interface the current taxonomy with the numerous nonanatomic prognostic factors currently in use or under study. As nonanatomic prognostic factors become widely used, TNM will remain a solid foundation on which to build prognostic classifications. There is, however, a risk that this system will be corrupted by a variety of irrelevant prognostic data. An anatomic extent of disease classification is needed to provide a standard against which to measure the importance of nonanatomic factors. Methods are needed to express overall prognosis without losing the vital anatomic content of TNM. These methods should be able to integrate multiple prognostic factors, including TNM, yet permit TNM to remain intact and distinct.
Stimulation of intestinal mucosal adenyl cyclase by cholera enterotoxin and prostaglandins
Authors: Daniel V. Kimberg, Michael Field, Judith Johnson, Antonia Henderson, Elaine Gershon
Journal: Journal of Clinical Investigation (1971)

The effects of several prostaglandins (PG) and a highly purified preparation of cholera enterotoxin (CT) on intestinal mucosal adenyl cyclase activity and the effect of CT on intestinal mucosal cyclic 3',5'-adenosine monophosphate concentration were determined in guinea pig and rabbit small intestine and were correlated with the effects of the same agents on ion transport. Adenyl cyclase activity, measured in a crude membrane fraction of the mucosa, was found at all levels of the small intestine with the highest activity per milligram protein in the duodenum. The prostaglandins, when added directly to the assay, increased adenyl cyclase activity; the greatest effect (2-fold increase) was obtained with PGE(1) (maximal effect at 0.03 mM) and PGE(2). The prostaglandins also increased short-circuit current (SCC) in isolated guinea pig ileal mucosa, with PGE(1) and PGE(2) again giving the greatest effects. The prior addition of theophylline (10 mM) reduced the subsequent SCC response to PGE(1) and vice versa. It was concluded, therefore, that the SCC response to PGE(1), like the response to theophylline, represented active Cl secretion. CT increased adenyl cyclase activity in guinea pig and rabbit ileal mucosa when preincubated with the mucosa from 1 to 2.5 hr in vitro or for 2.5 hr in vivo but not when added directly to the assay. The increments in activity caused by PGE(1) and NaF were the same in CT-treated and control mucosa. Cyclic 3',5'-AMP concentration in rabbit ileal mucosa was increased 3.5-fold after a 2 hr preincubation with CT in vitro. Phosphodiesterase activity in the crude membrane fraction of the mucosa was unaffected by either CT or PGE(1). A variety of other agents including insulin, glucagon, parathormone, thyroid-stimulating hormone, L-thyroxine, thyrocalcitonin, vasopressin, and epinephrine all failed to change adenyl cyclase activity. It is concluded that CT and certain prostaglandins produce small intestinal fluid secretion by increasing mucosal adenyl cyclase activity, thereby stimulating an active secretory process.
Molecular Diagnosis of Activating EGFR Mutations in Non–Small Cell Lung Cancer Using Mutation-Specific Antibodies for Immunohistochemical Analysis
Authors: Akihiko Kawahara, Chizuko Yamamoto, Kazutaka Nakashima, Koichi Azuma, Satoshi Hattori, Masaki Kashihara, Hisamichi Aizawa, Yuji Basaki, Michihiko Kuwano, Masayoshi Kage, Tetsuya Mitsudomi, Mayumi Ono
Journal: Clinical Cancer Research (2010)

Abstract Purpose: Therapeutic responses of non–small cell lung carcinoma (NSCLC) to epidermal growth factor receptor (EGFR)–targeted drugs, such as gefitinib and erlotinib, are closely associated with activating EGFR mutations. The most common mutations are delE746-A750 in exon 19 and L858R in exon 21, accounting for ∼90% of all EGFR mutations. Recently, EGFR mutation-specific antibodies were developed and did well in immunohistochemical analysis, giving a sensitivity of ∼90%. We have investigated whether this method detects activating EGFR mutations with sensitivity comparable with direct DNA sequencing, which is used to detect these mutations in NSCLC. Experimental Design: We used antibodies specific for the E746-A750 deletion mutation in exon 19 and the L858R point mutation in exon 21 in Western blot analysis and immunohistochemistry to determine the presence of these mutations in NSCLC cell lines. We also examined these EGFR mutations in NSCLC tumor samples from 60 patients by immunohistochemically and direct DNA sequencing. Results: We were able to identify EGFR mutations in NSCLC tumor samples immunohistochemically with a sensitivity of 79% using the anti–delE746-A750 antibody and 83% using the anti-L858R antibody. Additional DNA sequencing markedly improved the sensitivity obtained by immunohistochemistry. Conclusions: This simple and rapid assay for detecting EGFR mutations, even in the small bronchial biopsies obtained in stage IV NSCLC patients, will be useful for diagnosing responsiveness to EGFR-targeted drugs in patients with NSCLC. Combining this with DNA sequencing is recommended for the development of improved personalized EGFR-targeted therapeutics. Clin Cancer Res; 16(12); 3163–70. ©2010 AACR.
Regulation of polyethylene glycol 400 intestinal permeability by endogenous and exogenous prostanoids. Influence of non-steroidal anti-inflammatory drugs.
Authors: P Krugliak, D Hollander, K Le, T Ma, V D Dadufalza, K D Katz
Journal: Gut (1990)

Polyethylene glycol 400 (PEG 400) is a clinically useful intestinal permeability probe whose rate of intestinal permeation is influenced in part by solvent drag. As mucosal prostanoids are increased in inflammatory bowel disease and affect water transport we examined the possible relationship between prostaglandin E2 (PGE2) and the inhibitors of endogenous prostaglandins--the non-steroidal anti-inflammatory drugs (NSAIDS)--on PEG 400 absorption in vivo using segmental perfusion of rat small intestine. We found that the addition of exogenous PGE2 in concentrations of 0.5, 1.0, and 1.5 micrograms/ml significantly (p less than 0.01) decreased PEG 400 and water absorption. Addition of 5 mmol/l of the cyclooxygenase inhibitors acetylsalicylic acid (ASA) or indomethacin in concentrations 2.5 or 5.0 mmol/l to the perfusate significantly (p less than 0.01) increased PEG 400 and water absorption. The simultaneous addition of 1.0 micrograms/ml of exogenous PGE2 to the perfusate with 5 mmol/l of ASA or with 2.5 mmol/l of indomethacin reversed the increase of PEG 400 and water transport (p less than 0.01). There were no differences in PEG 400 and water absorption when PGE2 was given alone or in combination with ASA or indomethacin. This study suggests that endogenous or exogenous prostanoids play an important role in the regulation of PEG 400 permeation. PGE2 and NSAIDS modify PEG 400 permeation in parallel with changes in water transport indicating that their effect on permeability is through changes in solvent drag. These findings provide a mechanism which might explain the increase in PEG 400 intestinal permeability in Crohn9s disease patients and the increase in intestinal permeability found in patients receiving NSAIDS.
Population-based study of lung function and incidence of heart failure hospitalisations
Authors: G. Engstrom, O. Melander, B. Hedblad
Journal: Thorax (2010)

<h3>Background</h3> Reduced forced expiratory volume (FEV<sub>1</sub>) and forced vital capacity (FVC) are risk factors for myocardial infarction (MI) and stroke. However, the relationship with incidence of heart failure (HF) is incompletely known. This population-based study explored whether reduced FEV<sub>1</sub> or FVC is associated with the incidence of hospitalisation for HF. <h3>Methods</h3> 20 998 men (mean age 43 years) with no history of MI or stroke were examined with spirometry in 1974–84. The incidence of hospitalisation due to HF was studied over a mean follow-up of 23 years in relation to age- and height-adjusted FEV<sub>1</sub> and FVC. <h3>Results</h3> 725 incident HF hospitalisations occurred during the follow-up period, 503 of them without a previous or concurrent diagnosis of MI. In non-smokers the risk factor-adjusted hazard ratio (HR) for HF hospitalisation was 1.25 (95% CI 1.11 to 1.40) and 1.26 (95% CI 1.13 to 1.42), respectively, per 1SD lower FEV<sub>1</sub> and FVC. The corresponding risk factor-adjusted HRs in smokers were 1.32 (95% CI 1.21 to 1.45) and 1.22 (95% CI 1.11 to 1.33), respectively, for FEV<sub>1</sub> and FVC. This relationship was consistent in men with and without hypertension, in men above and below the median age of 44 years and for HF events without previous or concurrent MI. Exclusion of cases with a diagnosis of chronic obstructive pulmonary disease during the follow-up period did not substantially change the results. <h3>Conclusion</h3> In this long-term population-based study of men, moderately reduced FEV<sub>1</sub> and FVC were associated with an increased incidence of hospitalisations due to HF.
Human gonadotrophin preparations May cause allergic reaction
Authors: P C Dore, C Rice, S Killick, S Vine, L Gregory, D Chui, C Wells, M Rumington, S Walker
Journal: BMJ (1994)

Ellis and Cunningham cite a study in which patients were randomised to fluorouracildoxorubicin-methotrexate or to best supportive care.2They comment that randomisation was stopped in mid-study because of the apparent survival benefit in the chemotherapy arm.Subse- quent patients recruited to the study were assigned only to the chemotherapy arm.Only 10 patients had been accrued in the control group and 12 in the treatment arm when randomisation was stopped.No formal assessment of quality of life was included.
Aspirin in Patients Undergoing Noncardiac Surgery
Authors: P J Devereaux, Marko Mrkobrada, Daniel I Sessler, Kate Leslie, Pablo Alonso-Coello, Andrea Kurz, Juan Carlos Villar, Alben Sigamani, Bruce M Biccard, Christian S Meyhoff, Joel L Parlow, Gordon Guyatt, Andrea Robinson, Amit X Garg, Reitze N Rodseth, Fernando Botto, Giovanna Lurati Buse, Denis Xavier, Matthew T V Chan, Maria Tiboni, Deborah Cook, Priya A Kumar, Patrice Forget, German Malaga, Edith Fleischmann, Mohammed Amir, John Eikelboom, Richard Mizera, David Torres, C Y Wang, Tomas VanHelder, Pilar Paniagua, Otavio Berwanger, Sadeesh Srinathan, Michelle Graham, Laura Pasin, Yannick Le Manach, Peggy Gao, Janice Pogue, Richard Whitlock, André Lamy, Clive Kearon, Colin Baigent, Clara Chow, Shirley Pettit, Susan Chrolavicius, Salim Yusuf
Journal: New England Journal of Medicine (2014)

There is substantial variability in the perioperative administration of aspirin in patients undergoing noncardiac surgery, both among patients who are already on an aspirin regimen and among those who are not.Using a 2-by-2 factorial trial design, we randomly assigned 10,010 patients who were preparing to undergo noncardiac surgery and were at risk for vascular complications to receive aspirin or placebo and clonidine or placebo. The results of the aspirin trial are reported here. The patients were stratified according to whether they had not been taking aspirin before the study (initiation stratum, with 5628 patients) or they were already on an aspirin regimen (continuation stratum, with 4382 patients). Patients started taking aspirin (at a dose of 200 mg) or placebo just before surgery and continued it daily (at a dose of 100 mg) for 30 days in the initiation stratum and for 7 days in the continuation stratum, after which patients resumed their regular aspirin regimen. The primary outcome was a composite of death or nonfatal myocardial infarction at 30 days.The primary outcome occurred in 351 of 4998 patients (7.0%) in the aspirin group and in 355 of 5012 patients (7.1%) in the placebo group (hazard ratio in the aspirin group, 0.99; 95% confidence interval [CI], 0.86 to 1.15; P=0.92). Major bleeding was more common in the aspirin group than in the placebo group (230 patients [4.6%] vs. 188 patients [3.8%]; hazard ratio, 1.23; 95% CI, 1.01, to 1.49; P=0.04). The primary and secondary outcome results were similar in the two aspirin strata.Administration of aspirin before surgery and throughout the early postsurgical period had no significant effect on the rate of a composite of death or nonfatal myocardial infarction but increased the risk of major bleeding. (Funded by the Canadian Institutes of Health Research and others; POISE-2 ClinicalTrials.gov number, NCT01082874.).
Factors Influencing Indoor Concentrations of Nitric Oxide in a Parisian Intensive Care Unit
Authors: ERIC MOURGEON, ERIC LEVESQUE, CLAIRE DUVEAU, JEAN-DOMINIQUE LAW-KOUNE, BENNY CHARBIT, ELISABETH TERNISSIEN, PIERRE CORIAT, JEAN-JACQUES ROUBY
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

In low concentrations, inhaled nitric oxide (NO) increases arterial oxygenation in patients with severe acute respiratory distress syndrome. When present in the ambient atmosphere, NO and its oxidative derivate, nitrogen dioxide (NO2), are considered pollutants. The aim of this study was to assess whether the administration of inhaled NO to mechanically ventilated patients was associated with an increased risk of exposure to NO and NO2 for medical and paramedical staff. During a 1-yr period, indoor and outdoor NO and NO2 concentrations were measured using chemiluminescence in a 14-bed intensive care unit (ICU) to assess the possible influence of therapeutic NO administration on indoor pollution. Ambient concentrations of NO within the ICU were 237 ± 147 parts per billion (ppb) during periods of NO administration and 289 ± 147 ppb during periods without NO administration (mean ± SD, NS). Indoor concentrations of NO and NO2 were entirely dependent on outdoor concentrations and were mainly influenced by climatic conditions such as atmospheric pressure, mass of clouds, and speed of the wind. Therapeutic administration of concentrations of inhaled NO ⩽ 5 ppm to critically ill patients did not affect the ambient concentration of NO and NO2 within the ICU, which was mainly dependent on the outdoor air pollution. As a consequence, scavenging of exhaust NO from the breathing circuit in the ventilator does not appear mandatory in ICUs located in areas with significant urban pollution when NO concentrations ⩽ 5 ppm are administered.
A systematic review of physical activity promotion strategies.
Authors: M Hillsdon, M Thorogood
Journal: British Journal of Sports Medicine (1996)

We have reviewed randomised controlled trials of physical activity promotion to provide recent and reliable information on the effectiveness of physical activity promotion. Computerised databases and references of references were searched. Experts were contacted and asked for information about existing work. Studies assessed were randomised controlled trials of healthy, free living, adult subjects, where exercise behaviour was the dependent variable. Eleven trials were identified. No United Kingdom based studies were found. Interventions that encourage walking and do not require attendance at a facility are most likely to lead to sustainable increases in overall physical activity. Brisk walking has the greatest potential for increasing overall activity levels of a sedentary population and meeting current public health recommendations. The small number of trials limits the strength of any conclusions and highlights the need for more research.
Emerging Roles for Ubiquitin and Protein Degradation in Neuronal Function
Authors: Jason J. Yi, Michael D. Ehlers
Journal: Pharmacological Reviews (2007)

Alterations in cellular structure and synapse composition are central to proper nervous system function. Recent work has identified the ubiquitin-proteasome system (UPS) as a key regulator of neuronal biology. The UPS is essential for the growth and development of immature neurons and is a criticalmediator of synaptic adaptability in mature neurons. Furthermore, proteinaceous deposits that accumulate in diverse neurodegenerative disorders are enriched in components of the UPS, suggesting that UPS dysfunction may be pivotal for pathogenesis. Here, we summarize existing knowledge about the role of the UPS in brain function, highlighting recent work delineating its importance in neuronal development, plasticity, and degeneration.
Radiographic features of lumbar disc degeneration and bone mineral density in men and women
Authors: S R Pye
Journal: Annals of the Rheumatic Diseases (2005)

<b>Objectives:</b> To determine the association between individual radiographic features of lumbar disc degeneration and bone mineral density (BMD) at the spine and hip. <b>Methods:</b> Subjects were recruited from a population register for a screening survey of vertebral osteoporosis. BMD was assessed at the spine and hip using dual energy <i>x</i> ray absorptiometry. Lateral spinal radiographs were evaluated for features of lumbar disc degeneration. Each vertebral level from L1/2 to L4/5 was assessed for the presence and severity of osteophytes, end plate sclerosis, and disc space narrowing. Linear regression was used to determine the association between each of these features and BMD at the spine and hip, with adjustments for age, body mass index, and levels of physical activity. Analyses were done separately in men and women. <b>Results:</b> 250 women and 256 men (mean age around 65 years) were studied. At the lumbar spine, after age adjustment there was an increase in BMD with increasing grade for all radiographic features of disc degeneration in both men and women. At the femoral neck, after age adjustment there was an increase in BMD with increasing osteophyte and end plate sclerosis grade though not disc space narrowing. Adjusting for body mass index and physical activity did not influence the strength of the associations. <b>Conclusions:</b> Radiographic features of lumbar disc degeneration are associated with an increase in BMD at the spine. Osteophytes and end plate sclerosis, but not disc space narrowing, are associated with an increase in BMD at the hip.
Effect of ultramarathon cycling on the heart rate in elite cyclists
Authors: G Neumayr, R Pfister, G Mitterbauer, A Maurer, H Hoertnagl
Journal: British Journal of Sports Medicine (2004)

To analyse the heart rate (HR) response and estimate the ultraendurance threshold-the optimum maintainable exercise intensity of ultraendurance cycling-in ultraendurance elite cyclists competing in the Race across the Alps.HR monitoring was performed in 10 male elite cyclists during the first Race across the Alps in 2001 (distance: 525 km; cumulative altitude difference: 12 600 m) to investigate the exercise intensity of a cycle ultramarathon and the cardiopulmonary strains involved. Four different exercise intensities were defined as percentages of maximal HR (HR(max)) as follows: recovery HR (HR(re)), <70% of HR(max); moderate aerobic HR (HR(ma)), 70-80%; intense aerobic HR (HR(ia)), 80-90%; and high intensity HR (HR(hi)), >90%.All athletes investigated finished the competition. The mean racing time was 27 hours and 25 minutes, and the average speed was 18.6 km/h. The mean HR(max) was 186 beats/min, and the average value of measured HRs (HR(average)) was 126 beats/min resulting in a mean HR(average)/HR(max) ratio of 0.68, which probably corresponds to the ultraendurance threshold. The athletes spent 53% (14 hours 32 minutes) of total race time within HR(re), 25% (6 hours 51 minutes) within HR(ma), 19% (5 hours 13 minutes) within HR(ia), and only 3% (49 minutes) within HR(hi), which shows the exercise intensity to be predominantly moderate (HR(re) + HR(ma) = 78% or 21 hours 23 minutes). The HR response was influenced by the course profile as well as the duration. In all subjects, exercise intensity declined significantly during the race, as indicated by a decrease in HR(average)/HR(max) of 23% from 0.86 at the start to 0.66 at the end.A substantial decrease (10% every 10 hours) in the HR response is a general cardiovascular feature of ultramarathon cycling, suggesting that the ultraendurance threshold lies at about 70% of HR(max) in elite ultramarathon cyclists.
Circulating albumin messenger RNA in hepatocellular carcinoma: Results of a multicenter prospective study
Authors: V Barbu, A Bonnand, S Hillaire, T Coste, O Chazouilleres, J Gugenheim, E Boucher, R Poupon, R E Poupon
Journal: Hepatology (1997)

The presence of circulating tumor cells might be an indicator of hematogenous spread of tumor cells leading to extrahepatic metastasis. Messenger RNA (mRNA) expression of human albumin, as a liver specific cell marker, has been proposed for this purpose in hepatocellular carcinoma. We conducted a multicenter prospective study in 101 patients with biopsy-proven hepatocellular carcinoma followed-up every 3 months for 1 year or until death. At entry into the study, albumin mRNA was detected in the blood by reverse transcription-polymerase chain reaction (RT-PCR). At entry into the study, 45% of the patients had a positive albumin mRNA test, 53% a single tumor, 16% a portal or venous hepatic thrombosis, and 16% had proven metastasis. After 1 year, there was no significant difference in survival of patients with positive or negative albumin mRNA at entry ( P = .16, log-rank test). When patients with metastasis at entry were excluded, again survival did not differ between the two groups ( P = .20). Independent prognostic factors of survival were radical therapeutic procedures, metastasis, number of tumors, Child-Pugh score, and thrombosis, but not the albumin mRNA test. Taking the presence of metastasis as a reference, the specificity of the test was 56%, its sensitivity 50%, and its negative predictive value 85%. The present study shows that circulating albumin mRNA detected by means of RT-PCR fails to provide significant information in the diagnosis and prognosis of hepatocellular carcinoma. Further studies are needed to determine whether the use of specific tumor markers could have clinical relevance in this setting.
A Treatise on Regional Surgery.
Authors: John Fairbairn Binnie
Journal: JAMA (1918)

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