tbuckley/cabot-search huggingface dataset:
Molecular prognostic factors of anaplastic oligodendroglial tumors and its relationship: a single institutional review of 77 patients from China
Authors: S. Li, C. Yan, L. Huang, X. Qiu, Z. Wang, T. Jiang
Journal: Neuro-Oncology (2011)

The increased chemosensitivity of oligodendroglial tumors has been associated with loss of heterozygosity (LOH) on chromosomes 1p and 19q. Other clinical and molecular factors have also been identified as being prognostic and predictive for treatment outcome. Seventy-seven patients with anaplastic oligodendroglioma (AO) or anaplastic oligoastrocytoma (AOA), treated in Beijing Tiantan Hospital from 2006 through 2008, were reviewed. LOH 1p, LOH 19q, IDH1 mutation, O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation, and protein expression level of MGMT, P53, EGFR, and Ki-67 were evaluated. Age at diagnosis, LOH 1p and 19q, IDH1 mutation, P53 expression level, reoperation when progression, and adjuvant chemotherapy were statistically significant factors for overall survival (OS) in univariate analysis. Further multivariate analysis showed that age at diagnosis (P = .010), LOH 1p and 19q (P = .016), IDH1 mutation (P = .011), and reoperation after progression (P = .048) were independent predictors for longer survival in these patients. Nonrandom associations were found between LOH 1p and LOH 19q, MGMT promoter methylation and LOH 1p or 19q, IDH1 mutation and LOH 1p and 19q, IDH1 mutation and MGMT promoter methylation, whereas mutual exclusion was found between MGMT promoter methylation and MGMT expression level. The present study confirmed that age at diagnosis, LOH 1p and 19q, IDH1 mutation, and reoperation after progression were independent significant prognostic factors for patients with anaplastic oligodendroglial tumors. Inter-relationship between LOH 1p, LOH 19q, IDH1 mutation, MGMT promoter methylation, and MGMT expression level were also revealed. Future clinical trials for AO and AOA should consider the molecular alterations of patients.
Selective Activation of Inflammatory Pathways by Intermittent Hypoxia in Obstructive Sleep Apnea Syndrome
Authors: Silke Ryan, Cormac T. Taylor, Walter T. McNicholas
Journal: Circulation (2005)

Obstructive sleep apnea syndrome (OSAS), characterized by intermittent hypoxia/reoxygenation (IHR), is an independent risk factor for cardiovascular disease. We investigated the underlying molecular mechanisms of this association in a translational study.In a novel in vitro model of IHR, we used HeLa cells transfected with reporter constructs and DNA binding assays for the master transcriptional regulators of the inflammatory and adaptive pathways (NFkappaB and HIF-1, respectively) to investigate underlying transcriptional events initiated by repeated cell exposure to IHR. Furthermore, we prospectively studied 19 male OSAS patients (median apnea-hypopnea frequency, 48.5 episodes per hour; interquartile range [IQR], 28.5 to 72.9) and 17 matched normal control subjects. Circulating levels of the proinflammatory cytokine tumor necrosis factor-alpha and the adaptive factor erythropoietin were assayed in all subjects at baseline and again after 6 weeks of continuous positive airway pressure therapy in patients. Full blood count was measured as part of a detailed baseline evaluation. HeLa cells exposed to IHR demonstrated selective activation of the proinflammatory transcription factor NFkappaB (P<0.001 by ANOVA), whereas the adaptive regulator HIF-1 was not activated, as demonstrated by luciferase reporter assays and DNA binding studies. Circulating tumor necrosis factor-alpha levels were higher in OSAS patients (2.56 pg/mL; IQR, 2.01 to 3.42 pg/mL) than in control subjects (1.25 pg/mL; IQR, 0.94 to 1.87; P<0.001) but normalized with continuous positive airway pressure therapy (1.24 pg/mL; IQR, 0.78 to 2.35 pg/mL; P=0.002). In contrast, erythropoietin levels were similar throughout. Furthermore, circulating neutrophil levels were higher in OSAS patients than in control subjects, whereas the hematocrit was unaltered.These data demonstrate selective activation of inflammatory over adaptive pathways in IHR and OSAS, which may be an important molecular mechanism of cardiovascular disease.
Mechanisms of hypoxemia and hypocapnia in pulmonary embolism.
Authors: A Santolicandro, R Prediletto, E Fornai, B Formichi, E Begliomini, A Giannella-Neto, C Giuntini
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Mechanisms of hypoxemia and hypocapnia in pulmonary embolism (PE) are incompletely understood. We studied 10 patients at diagnosis (D) and five of these again after 10 to 14 d of heparin treatment (T). Patients had right heart catheterization, assessment of ventilation-perfusion ratio (VA/Q) distribution by inert gas, radioisotopic perfusion and ventilation scans, and angiography. At D, two-thirds of the pulmonary circulation was obstructed, patients were hypoxemic (PaO2 = 63.0 +/- 11.7 mm Hg) and hypocapnic (PaCO2 = 30.0 +/- 4.1 mm Hg), mixed venous oxygen pressure (PvO2) was reduced (30.9 +/- 3.9 mm Hg), minute ventilation (VE) markedly increased (14.1 +/- 5.1 L/min), and cardiac output measured by applying the Fick principle to arteriovenous oxygen content difference (QT) slightly low (4.7 +/- 1.7 L/min). Hypoxemia was mainly explained by VA/Q inequality, reduced PvO2 also contributed. Hypocapnia was the result of hyperventilation. VA/Q inequality was characterized by shift of VA and Q distribution mean to regions with higher VA/Q ratio through a fraction of blood flow (19.0 +/- 24.3% of cardiac output) went to lung units with low VA/Q ratio. Log SDQ and log SDvA were increased. Shunt, diffusion limitation, or true alveolar dead space occurred in occasional patients but were generally insignificant. Regional ventilation and perfusion maps indicated that in the unperfused lung segments, ventilation was reduced. Furthermore, they disclosed overperfused lung segments. At T, hypoxemia and hypocapnia improved considerably. However, temporal imbalances in recovery between regional ventilation and perfusion occurred with the former normalizing sooner. However, perfusion recovered sooner than ventilation in some regions.
Role of the Autonomic Nervous System in Atrial Fibrillation
Authors: Peng-Sheng Chen, Lan S. Chen, Michael C. Fishbein, Shien-Fong Lin, Stanley Nattel
Journal: Circulation Research (2014)

Autonomic nervous system activation can induce significant and heterogeneous changes of atrial electrophysiology and induce atrial tachyarrhythmias, including atrial tachycardia and atrial fibrillation (AF). The importance of the autonomic nervous system in atrial arrhythmogenesis is also supported by circadian variation in the incidence of symptomatic AF in humans. Methods that reduce autonomic innervation or outflow have been shown to reduce the incidence of spontaneous or induced atrial arrhythmias, suggesting that neuromodulation may be helpful in controlling AF. In this review, we focus on the relationship between the autonomic nervous system and the pathophysiology of AF and the potential benefit and limitations of neuromodulation in the management of this arrhythmia. We conclude that autonomic nerve activity plays an important role in the initiation and maintenance of AF, and modulating autonomic nerve function may contribute to AF control. Potential therapeutic applications include ganglionated plexus ablation, renal sympathetic denervation, cervical vagal nerve stimulation, baroreflex stimulation, cutaneous stimulation, novel drug approaches, and biological therapies. Although the role of the autonomic nervous system has long been recognized, new science and new technologies promise exciting prospects for the future.
A tale of two cities: comparing lung cancer outcomes in Teesside, UK and Varese, Italy
Authors: G A Silvestri
Journal: Thorax (2006)

The study and publication of health outcomes has become increasingly common over the past decade. Providers of health care want assurance that they get what they pay for. In an increasingly consumer driven society, patients want to receive the best health care they can and feel they should have the opportunity to compare the performance of physicians and hospitals for any given illness. This can lead to the publication in the lay press of sensational articles which, for example, reveal that the mortality for heart bypass surgery is twice as high in one hospital as in another. Predictably, this is followed by physician outrage as they believe that their patients are somehow different, older, sicker, and at higher risk for a poor outcome. In some institutions the result is that surgeons no longer perform difficult cases for fear that they will be labelled as having poorer results. This may have had the unintentional consequence of less choice for patients.

Lost in this debate are the …
Prospective Study of Serum Selenium Levels and Incident Esophageal and Gastric Cancers
Authors: S. D. Mark
Journal: JNCI Journal of the National Cancer Institute (2000)

Background: From March 1986 through May 1991, we conducted a randomized nutritional intervention trial, the General Population Trial, in Linxian, China, a region with epidemic rates of squamous esophageal and adenomatous gastric cardia cancers. We found that participants who received selenium, β-carotene, and vitamin E had significantly lower cancer mortality rates than those who did not. In the current study, we examined the relationship between selenium levels measured in pretrial (1985) sera from participants and the subsequent risk of developing squamous esophageal, gastric cardia, and gastric non-cardia cancers during the trial. Methods: This study was designed and analyzed in accord with a stratified case–cohort sampling scheme, with the six strata defined by sex and three age categories. We measured serum selenium levels in 590 case subjects with esophageal cancer, 402 with gastric cardia cancers, and 87 with gastric non-cardia cancers as well as in 1062 control subjects. Relative risks (RRs), absolute risks, and population attributable risk for cancers were estimated on the basis of the Cox proportional hazards models. All statistical tests are two-sided. Results: We found highly significant inverse associations of serum selenium levels with the incidence of esophageal (P for trend <10−4) and gastric cardia (P for trend <10−6) cancers. The RR and 95% confidence interval (CI) for comparison of highest to lowest quartile of serum selenium was 0.56 (95% CI = 0.44–0.71) for esophageal cancer and 0.47 (95% CI = 0.33–0.65) for gastric cardia cancer. The population proportion of these cancers that is attributable to low selenium levels was 26.4% (95% CI = 14.45–38.36). We found no evidence for a gradient of serum selenium associated with incidence of gastric non-cardia cancer (P for trend = .96), with an RR of 1.07 (95% CI = 0.55–2.08) for the highest to lowest quartile of serum selenium. Conclusions: Our study supports findings from previous prospective studies and randomized trials that variations in selenium levels affect the incidence of certain cancers. In the United States, where intervention trials of selenium are in the planning stages, consideration should be given to including populations at high risk for squamous esophageal and gastric cardia cancers.
THE TRANSFORMATION OF PNEUMOCOCCAL TYPES
Authors: Martin H. Dawson
Journal: The Journal of Experimental Medicine (1930)

R forms of Pneumococcus may be converted into S forms of the homologous Type. In addition to the methods previously reported,-(1) animal passage and (2) growth in anti-R sera,-conversion may be effected by the following procedures as employed by Griffith; (1) The subcutaneous injection, in white mice, of large amounts of living R organisms. (2) The subcutaneous injection, in white mice, of small amounts of living R organisms together with the heat-killed bacteria from large amounts of homologous S cultures. There are "varying degrees of constancy of the R variant"; but by these means it has been possible to effect conversion of all R forms selected. Attempts to cause a further "degradation" of R organisms by continued growth in homologous immune serum have been unsuccessful. Type II S and III S vaccines are equally effective in producing conversion when heated for 15' at 60 degrees C., or for 15' at 100 degrees C. Type I S vaccine, however, while effective in causing conversion when heated for 15' at 60 degrees C., apparently loses this property when heated for 15' at 100 degrees C. R vaccines, and vaccines of other organisms, when injected together with live R cultures, have always failed to produce conversion. The causes responsible for conversion under these experimental conditions are discussed and the possibility of the occurrence of a similar process under natural conditions in human beings is indicated.
Time of Day and the Decision to Prescribe Antibiotics
Authors: Jeffrey A. Linder, Jason N. Doctor, Mark W. Friedberg, Harry Reyes Nieva, Caroline Birks, Daniella Meeker, Craig R. Fox
Journal: JAMA Internal Medicine (2014)

Clinicians make many patient care decisions each day. The cumulative cognitive demand of these decisions may erode clinicians’ abilities to resist making potentially inappropriate choices. Psychologists, who refer to the erosion of self-control after making repeated decisions as decision fatigue,1,2 have found evidence that it affects nonmedical professionals. For example, as court sessions wear on, judges are more likely to deny parole, the “easier” or “safer” option.3
Gemcitabine and oxaliplatin for metastatic pancreatic adenocarcinoma: a North Central Cancer Treatment Groupphase II study
Authors: S.R. Alberts, P.M. Townley, R.M. Goldberg, S.S. Cha, D.J. Sargent, D.F. Moore, J.E. Krook, H.C. Pitot, T.R. Fitch, M. Wiesenfeld, J.A. Mailliard
Journal: Annals of Oncology (2003)
Chemotaxis of primitive hematopoietic cells in response to stromal cell–derived factor-1
Authors: Deog-Yeon Jo, Shahin Rafii, Tsuneyoshi Hamada, Malcolm A.S. Moore
Journal: Journal of Clinical Investigation (2000)

Stromal cell–derived factor-1 (SDF-1) provides a potent chemotactic stimulus for CD34+ hematopoietic cells. We cultured mobilized peripheral blood (PB) and umbilical cord blood (CB) for up to 5 weeks and examined the migratory activity of cobblestone area–forming cells (CAFCs) and long-term culture–initiating cells (LTC-ICs) in a transwell assay. In this system, SDF-1 or MS-5 marrow stromal cells placed in the lower chamber induced transmembrane and transendothelial migration by 2- and 5-week-old CAFCs and LTC-ICs in 3 hours. Transmigration was blocked by preincubation of input CD34+ cells with antibody to CXCR4. Transendothelial migration of CB CAFCs and LTC-ICs was higher than that of PB. We expanded CD34+ cells from CB in serum-free medium with thrombopoietin, flk-2 ligand, and c-kit ligand, with or without IL-3 and found that CAFCs cultured in the absence of IL-3 had a chemotactic response equivalent to noncultured cells, even after 5 weeks. However, addition of IL-3 to the culture reduced this response by 20–50%. These data indicate that SDF-1 induces chemotaxis of primitive hematopoietic cells signaling through CXCR4 and that the chemoattraction could be downmodulated by culture ex vivo.
Validation of ATS cut-off points for FeNO in a clinical unselected population of subjects with possible asthma
Authors: Maria Vestergaard, Asger Sverrild, Vibeke Backer, Celeste Porsbjerg
Journal: European Respiratory Journal (2014)

Background and objective:   The American Thoracic society (ATS) suggests fractional exhaled nitric oxide (FeNO) as a marker of eosinophilic airway inflammation. FeNO 50 indicates that eosinophilia is likely. The present study aimed to validate these cut-off values in a non-selected clinical population.   Methods:   All patients referred consecutively over a 12-months period for specialist assessment of asthma at the Respiratory Outpatient Clinic at Bispebjerg Hospital in Copenhagen were examined with FeNO and induced sputum, among others. Eosinophilia was defined as >3% eosinophils in sputum. Sensitivity, specificity and predictive values were assessed for the cut-off values of FeNO. A ROC curve was constructed.   Results:   Of 155 subjects with asthma, 107 were able to produce induced sputum (62% females, mean age 31.7(±14.3). 28 asthmatics had >3% sputum eosinophils. The PPV for FeNO  50ppb was 15.6%, 33.3% and 61.5% respectively. The NPV was 84.4%, 66.8% and 28.5% in the corresponding FeNO groups. The sensitivity of the 50 ppb cut-off was 28.6%, increasing to 64.3% at the 25ppb cut-off, whereas the specificity was 93.7% at the 50 ppb cut-off, decreasing to 68.4% at the 25 ppb cut-off. The area under the ROC curve was 0.73.   Conclusion:   Increasing values of PPV was found with increasing cut-off values, indicating the higher FeNO, the greater is the likelihood of eosinophilic inflammation. This supports the proposed cut-points. However, the low sensitivity of the 50ppb cut-off indicates that the 25ppb cut-off should be used when a high sensitivity is required clinically.
Characterization of the incorporation of woodchuck hepatitis virus surface antigen into hepatocyte plasma membrane in woodchuck hepatitis and in the virus-induced hepatocellular carcinoma
Authors: Tomasz I. Michalak, Robert L. Snyder, Norma D. Churchill
Journal: Hepatology (1989)

Interaction between woodchuck hepatitis virus surface antigen and proteins of hepatocyte plasma membranes were examined in the course of woodchuck hepatitis virus infection. Membranes purified from animals with histologically confirmed acute hepatitis, active or persistent chronic hepatitis and the virus-related hepatocellular carcinoma were evaluated for the virus surface antigen contents, treated with agents eluting plasma membrane-bound antigen to test the extent of the antigen-membrane associations and incubated with purified, particulate woodchuck hepatitis virus surface antigen to determine membrane potential for the antigen adsorption. Hepatocyte plasma membranes originating from woodchucks chronically infected with the virus showed the highest quantities of the incorporated virus surface antigen among membranes studied, the behavior of bound antigen as an integral and a peripheral membrane protein and the resistance to bind an exogenous antigen. Similar properties were expressed by plasma membranes prepared from hepatocytes of nontumor parenchyma displaying chronic active hepatitis of a woodchuck hepatitis virus carrier with hepatoma. Furthermore, plasma membranes originating from animals with active or persistent chronic hepatitis demonstrated identical properties, implicating that histologic activity of the chronic liver inflammatory process is not dependent on the quantity of the virus surface antigen insertion into the membrane. In contrast, hepatocyte plasma membranes from animals with acute hepatitis showed significantly lower antigen quantities, presence of the antigen specificity exclusively behaving as an integral membrane protein and noticeable ability to bind an exogenous surface antigen of the virus. Comparable, but not identical, features were observed for hepatocyte membranes purified from nodules of hepatocellular carcinoma, suggesting that neoplastic transformation of infected hepatocytes is associated with loss of the membrane-bound antigen and with simultaneous, partial recovery of the membrane potential for the antigen binding. Comparative analysis of the properties on the woodchuck hepatitis virus surface antigen incorporation into hepatocyte plasma membranes in studied cases indicated that sustained infection with woodchuck hepatitis virus leads to an increase in the quantity of the membrane-incorporated antigen and to the appearance of the virus surface antigen specificity behaving as a peripheral membrane protein. In conclusion, this study demonstrated that the extent and the character of the antigen interaction with hepatocyte plasma membranes undergoes significant variations in the natural course of hepadna viral infection in woodchucks and that histologically distinct forms of the virus-induced liver disease express specific properties on the association.
Changes in the intragastric distribution of Helicobacter pylori during treatment with omeprazole.
Authors: R P Logan, M M Walker, J J Misiewicz, P A Gummett, Q N Karim, J H Baron
Journal: Gut (1995)

Omeprazole is a powerful inhibitor of gastric acid and may suppress Helicobacter pylori by effecting the pKa of H pylori urease, by altering the pattern of infection, or by promoting overgrowth of other bacteria. At routine endoscopy H pylori was detected by histology and culture before and after four weeks9 treatment with omeprazole, 40 mg each morning. A 13C-urea breath test was also done at t = 0, 2, 4, and 6 weeks. Thirty nine patients with duodenal ulcer (n = 25) or reflux oesophagitis (n = 14) were studied, of whom 29 of 39 had H pylori infection. During omeprazole treatment, 13C-urea breath test values fell significantly--mean (SEM) values before treatment and at four weeks were 23.0 (2.1) and 15.5 (2.7) per mil respectively, p &lt; 0.001. Before treatment H pylori was seen in 28 of 29 antral, 29 of 29 corpus, and 28 of 29 fundic biopsy specimens. After four weeks of omeprazole treatment, the histological density of H pylori in the antrum and corpus was reduced (p &lt; 0.001), while that in the fundus was increased. The migration of H pylori from the antrum to the fundus was associated with a corresponding decrease in the activity of antral gastritis. H pylori was not seen in antral biopsy specimens from 12 of 29 patients whose median excess delta 13CO2 excretion fell from 23.0 to 9.9 per mil. In the body mucosa, 26 of 29 specimens were still positive for H pylori and there was no significant change in the gastritis type. Two weeks after finishing treatment, the mean (SEM) excess delta 13CO2 excretion returned to levels before treatment. Omeprazole decreases antral H pylori colonisation but increases that in the fundus. The changes in the intragastric distribution of the organism are associated with concomitant changes in the activity of gastritis and are matched by a progressive fall in the excretion of delta 13CO2.
Clinical Predictors of Disease Progression and Medication Initiation in Untreated Patients With Type 2 Diabetes and A1C Less Than 7%
Authors: Lydie Nkwimi Pani, David Matthew Nathan, Richard William Grant
Journal: Diabetes Care (2008)

Many patients with early diabetes remain untreated. Our objectives were to identify clinical predictors of 1) worsening glycemic control and 2) medical treatment initiation in response to worsening glycemic control among patients with type 2 diabetes.We identified 5,804 type 2 diabetic patients seen at least twice between June 2005 and June 2006 within our 12-clinic primary care network. We examined predictors of diabetes progression (A1C >or=7% or initiation of hypoglycemic agent) over a 1-year follow-up period in 705 patients who had A1C <7% and were not on glucose-lowering medications at baseline. In the 200 patients in this group who progressed, we examined predictors of medical therapy initiation.In multivariate analyses, baseline A1C (P < 0.0001), younger age (P = 0.04), and weight gain (P = 0.03) were independent predictors of progression after adjusting for race, sex, and baseline HDL levels. Each decade of increasing age reduced the risk of progression by 15%. Each 1-lb increase in weight was associated with a 2% increased odds of progression. Likelihood of medication initiation among progressors decreased by 40% (P = 0.02) with every decade of age and decreased by 2.3% (P = 0.02) with each 1-mg/dl decrease in LDL level from baseline after adjusting for race, sex, and weight change.Among untreated primary care patients with type 2 diabetes and A1C <7%, younger patients and those with weight gain were more likely to have diabetes progression and should be the focus of aggressive diabetes management.