tbuckley/cabot-search huggingface dataset:
Early, short and long-term efficacy of the new American Academy Sleep Medicine (AASM) protocol for CPAP titration in patients with obstructive sleep apnea (OSA)
Authors: Luca Gadaleta, Paola Fulgoni, Onofrio Resta, Nadia D'artavilla Lupo, Irene Risi, Annalisa Carlucci, Marco Mancini, Francesco Fanfulla
Journal: European Respiratory Journal (2011)

CPAP titration is usually performed during attended polysomnography. CPAP is adjusted throughout the recording period to determine the optimal pressure for maintaining upper airway patency. The aim of the present study was to assess the efficacy in 3 different setting: night of titration, after 3 and l2 months. We enrolled 298 consecutive patients (M 205, age 57.7±12.4 yrs, baseline AHI 48.3±25.8). Once obtained a good acclimatization to mask, patients underwent manual CPAP titration according to new AASM protocol. Titration failed in 56 patients (TF). Baseline, in comparison with patients successfully titrated (ST), TF showed a lower sleep efficiency (80.9±13vs 74.9±18%, p<0.01), N3 (24.8±12.5 vs 20.3±16.5, p<0.05) and REM percentage (17.8±7.8 vs 14.1±8.9, p<0.01). During titration, TF presented a lower sleep efficiency (67.1±19.1 vs 75.6±13.7%, p<0.01), N3 (23.2±12.7 vs 27.8±10.7, p<0.01) and REM percentage (11.3±6 vs 16.7±7.9, p<0.01) than ST. ST and EF patients differs for the tolerance to CPAP at titration: 90% of ST patients reported optimal or good tolerance in comparison with 72.% of EF (χ2 15.4, p<0.01). 141 patients completed the short term follow-up and 76 the long term follow-up: 29 patients showed persistent OSA at 3 months and 13 at 1-year follow-up. No statistically significant differences were found between patients with or without persistent sleep apnea for age, baseline sleepiness, baseline or CPAP titration polysomnographic indices, tolerance to CPAP therapy or type of mask. We conclude that CPAP titration is more common in patients with more unstable sleep and with lower tolerance to ventilation.
Agnes Hallimond Wilkinson (née Crozier)
Authors: James Wilkinson
Journal: BMJ (2005)

Epidemiologist who showed that smoking caused cancer and heart disease Sir Richard Doll was the world's most distinguished medical epidemiologist.He established his reputation alongside Sir Austin Bradford Hill, showing that cigarette smoking caused lung cancer.He then went on to show it caused bladder and other cancers, and cardiovascular disease.He did seminal work with Richard Peto on the health of doctors and their families, demonstrating an increased incidence of suicide and liver disease.He also carried out major research on the risks and benefits of the contraceptive pill, on low level radiation, and the dietary treatment of gastric ulcers.Doll went to work with Bradford Hill at the Medical Research Council in January 1948.Government statisticians had drawn the MRC's attention to a huge recent increase in lung cancer deaths, and the MRC held a conference to decide whether the increase was real and, if so, whether a cause could be identified.
Clinical, but not oesophageal pH-impedance, profiles predict response to proton pump inhibitors in gastro-oesophageal reflux disease
Authors: Frank Zerbib, Kafia Belhocine, Mireille Simon, Maylis Capdepont, François Mion, Stanislas Bruley des Varannes, Jean-Paul Galmiche
Journal: Gut (2011)

<h3>Objective</h3> Approximately 30% of patients with gastro-oesophageal reflux disease (GORD) do not achieve adequate symptom control with proton pump inhibitors (PPIs). The aim of this study was to determine whether any symptom profile or reflux pattern was associated with refractoriness to PPI therapy. <h3>Design</h3> Patients with typical GORD symptoms (heartburn and/or regurgitation) were included and had 24 h pH-impedance monitoring off therapy. Patients were considered to be responders if they had fewer than 2 days of mild symptoms per week while receiving a standard or double dose of PPI treatment for at least 4 weeks. Both clinical and reflux parameters were taken into account for multivariate analysis (logistic regression). <h3>Results</h3> One hundred patients were included (median age 50 years, 42 male), 43 responders and 57 non-responders. Overall, multivariate analysis showed that the factors associated with the absence of response were absence of oesophagitis (p=0.050), body mass index (BMI) ≤25 kg/m<sup>2</sup> (p=0.002) and functional dyspepsia (FD) (p=0.001). In patients who reported symptoms during the recording (n=85), the factors associated with PPI failure were BMI ≤25 kg/m<sup>2</sup> (p=0.004), FD (p=0.009) and irritable bowel syndrome (p=0.045). In patients with documented GORD (n=67), the factors associated with PPI failure were absence of oesophagitis (p=0.040), FD (p=0.003), irritable bowel syndrome (p=0.012) and BMI ≤25 kg/m<sup>2</sup> (p=0.029). <h3>Conclusion</h3> No reflux pattern demonstrated by 24 h pH-impedance monitoring is associated with response to PPIs in patients with GORD symptoms. In contrast, absence of oesophagitis, presence of functional digestive disorders and BMI ≤25 kg/m<sup>2</sup> are strongly associated with PPI failure.
Ten-year results of a strategy combining three cycles of ABVD and high-dose extended irradiation for treating Hodgkin’s disease at advanced stages
Authors: J.-M. Andrieu, J.-P. Jais, P. Colonna, B. Desablens, J. Brière, S. François, J.-L. Harousseau, P. Casassus, A. Lemevel, P.-Y. Le Prisé, C. Ghandour, F. Guilhot, F. Lejeune
Journal: Annals of Oncology (1998)
Racial and Ethnic Differences in Wait-List Outcomes in Patients Listed for Heart Transplantation in the United States
Authors: Tajinder P. Singh, Christopher S. Almond, David O. Taylor, Carly E. Milliren, Dionne A. Graham
Journal: Circulation (2012)

Racial differences in long-term survival after heart transplant (HT) are well known. We sought to assess racial/ethnic differences in wait-list outcomes among patients listed for HT in the United States in the current era.
Targeting Ras in Myeloid Leukemias
Authors: Benjamin S. Braun, Kevin Shannon
Journal: Clinical Cancer Research (2008)

Abstract Ras proteins normally relay growth-promoting signals from many activated cell surface receptors, and they are altered by oncogenic point mutations in ∼30% of human cancers. Activating KRAS and NRAS mutations are especially common in malignancies of the pancreas, lung, and colon, and in myeloid leukemia. Here, we discuss general strategies for targeting hyperactive Ras signaling in cancer cells with specific reference to myeloid malignancies.
Uncertainty and Relative Risks of Radiation Exposure
Authors: S. James Adelstein
Journal: JAMA (1987)

Exposure to ionizing radiation in a nonmilitary emergency is likely to alarm those persons exposed and their families. Not only is the outcome uncertain, but the risks are difficult to convey. This communication discusses uncertainties in short-term outcome and long-term effects, as well as means of conveying the magnitude of risks to patients and their families. It emphasizes that the perception of radiation hazards is contextual. It offers three ways of presenting the prognostic long-term risks of accidental radiation exposure by comparing them with the incidence of cancer and genetic abnormalities in unexposed persons, the hazards of everyday living, and the level of natural and medical exposures to ionizing radiation.
Hepatitis B virus infection: Precore mutants and its relation to viral genotypes and core mutations
Authors: Francisco Rodriguez-Frias, Maria Buti, Rosendo Jardi, Montserrat Cotrina, Luis Viladomiu, Rafael Esteban, Jaime Guardia
Journal: Hepatology (1995)

The precore-core gene of hepatitis B virus (HBV) was directly sequenced from serum samples of 42 patients with chronic B hepatitis (19 hepatitis B e antigen [HBeAg]+ and 23 anti-HBe+). Viral genotypes were determined by comparison with 11 reference sequences and by restriction analysis. Genotype A was identified in 16 cases, genotype D in 24 cases, and other genotypes in 2 cases. Precore mutations, mainly M1 (stop at codon 28), were differently distributed among the viral genotypes: 3 cases (18.8%) with genotype A and 18 cases (75%) with genotype D. In sequences with precore mutants, the encapsidation signal was more stable (negative stabilization energy) than in sequences without precore mutants. In genotype A, the M1 mutation coexisted with a second mutation (C → T at position 1858 in codon 15), and both mutations were paired in the secondary structure of the RNA encapsidation signal, which justified the rare presence of precore mutants in this genotype. The analysis showed different distribution of mutations depending on the viral genotype; patients with genotype D were more likely to have persistent HBV infection by selection of precore mutants. Multiple amino acid substitutions were detected in the core region, mainly in two subsequences that have been previously described as epitopes (flanked by codons 11 to 27 and 74 to 83); the presence of these mutations was significantly related to the presence of precore variants which abolished the expression of HBeAg. The study of viral genotypes in chronic HBV infection may be valuable in predicting the persistence of viral replication after seroconversion to anti-HBe and suggest that the outcome of chronic infection may be affected by the HBV variability. (Hepatology 1995; 22:1641-1647).
Randomized study of vinorelbine and cisplatin versus vindesine and cisplatin versus vinorelbine alone in advanced non-small-cell lung cancer: results of a European multicenter trial including 612 patients.
Authors: T Le Chevalier, D Brisgand, J Y Douillard, J L Pujol, V Alberola, A Monnier, A Riviere, P Lianes, P Chomy, S Cigolari
Journal: Journal of Clinical Oncology (1994)

PURPOSE We designed a prospective randomized trial to compare vinorelbine and cisplatin (NVB-P) with vindesine and cisplatin (VDS-P) and to evaluate whether the best of these regimens affords a survival benefit compared with vinorelbine alone (NVB), an outpatient regimen, in patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Forty-five centers included 612 patients in this study: 206 on NVB-P, 200 on VDS-P, and 206 on NVB. Vinorelbine was administered at a dose of 30 mg/m2 weekly, cisplatin at 120 mg/m2 on days 1 and 29 and then every 6 weeks, and vindesine at 3 mg/m2 weekly for 6 weeks and then every other week. Treatment was continued until progression or toxicity. Four percent of the patients entered were ineligible and 59% had metastatic disease. RESULTS An objective response rate was observed in 30% of patients in the NVB-P arm versus 19% in the VDS-P arm (P = .02) and 14% in the NVB arm (P &lt; .001). The median duration of survival was 40 weeks in the NVB-P arm, compared with 32 weeks in the VDS-P arm and 31 weeks in the NVB arm. Comparison of survival among the three groups demonstrated an advantage for NVB-P compared with VDS-P (P = .04) and NVB (P = .01). Neutropenia was significantly higher in the NVB-P group (P &lt; .001), and neurotoxicity was more frequent with VDS-P (P &lt; .004). CONCLUSION Since our results have demonstrated that NVB-P yields a longer survival duration and a higher response rate than VDS-P or NVB alone, with acceptable toxicity, this combination should be considered a relevant regimen in advanced NSCLC.
Effect of alterations of arterial blood pressure and heart rate on segmental dyskinesis during acute myocardial ischemia and following coronary reperfusion.
Authors: R E Kerber, F M Abboud
Journal: Circulation Research (1975)

The effect of alterations of blood pressure and heart rate on segmental dyskinesis induced by coronary artery ligation and the influence of such manipulations on the magnitude of recovery of the syskinetic segment during subsequent coronary artery reperfusion were evaluated in 77 open-chest dogs. Wall motion was recorded by ultrasound reflected directly from the ischemic myocardial segment. Acute ischemia produced characteristic regional abnormalities in wall motion: aneurysmal bulging occurred during isometric contraction and wall velocity was markedly reduced during ventricular ejection. During 69 minutes of ischemia, a control group of dogs underwent no interventions and showed no further changes in wall motion. Tachycardia induced by atrial pacing during ischemia had no significant effect. Arterial hypertension during ischemia caused a marked reduction in wall velocity when methoxamine was used: 14 plus or minus 2 (SE) mm/sec (ischemia alone) to 6 plus or minus 1 mm/sec (ischemia + drug). In contrast, norepinephrine improved wall velocity: 11 plus or minus 2 mm/sec (ischemia alone) to 25 plus or minus 4 mm/sec (ischemia + drug). Hypertension caused by infusion of phenylephrine gave intermediate results, as did hypotension induced by either nitroprusside or hemorrhage during the ischemic period. After 60 minutes the drugs were stopped, the coronary ligation released, and the ischemic myocardium reperfused. The relative order of improvement of wall velocity with reperfusion was 11 plus or minus 2 mm/sec (ischemia alone) to 24 plus or minus 3 mm/sec (reperfusion) in the group that received norepinephrine, 12 plus or minus 3 mm/sec to 20 plus or minus 3 mm/sec in the control group with no intervention durin ischemia, 13 plus or minus 2 mm/sec to 20 plus or minus 1 mm/sec in the nitroprusside group, 9 plus or minus 2 mm/sec in the phenylephrine group, and 14 plus or minus 2 mm/sec to 12 plus or minus 1 mm/sec in the methoxamine group. The aneurysmal bulging during isometric contraction also was reduced to a greater degree by reperfusion in the group that received norepinephrine during the ischemic period than it was in the groups undergoing other interventions during ischemia. We conclude that drug-induced elevations in arterial blood pressure can have different effects on the syskinetic motion of acutely ischemic myocardium and on the degree of recovery following reperfusion depending on the particular agent used.
Measuring Tissue-Based Biomarkers by Immunochromatography Coupled with Reverse-Phase Lysate Microarray
Authors: Martin J. Romeo, John Wunderlich, Lien Ngo, Steven A. Rosenberg, Seth M. Steinberg, David M. Berman
Journal: Clinical Cancer Research (2006)

There is a need for new technologies to study tissue-based biomarkers. The current gold standard, immunohistochemistry, is compromised by variability in tissue processing and observer bias. Reverse transcription-PCR (RT-PCR), immunocytochemistry, and reverse-phase lysate microarrays (RPM) are promising alternative technologies but have not yet been validated, or correlated, on the same patient-derived tissues. Furthermore, RPM is currently limited by time-consuming microdissection and low amounts of evaluable protein lysates.Metastatic melanoma was surgically excised from 30 patients and macroscopically dissected from surrounding stroma. Each specimen was processed by formalin-fixation (immunohistochemistry), cytospin (immunocytochemistry), or disaggreagation and enrichment (RT-PCR and RPM). The latter protocol uses immunochromatography to remove hematopoetic-derived cells, thus enriching for melanoma cells. Each sample was measured for the expression of gp100 or MART-1 normalized to actin.Immunochromatography coupled with RPM (I-RPM) is reproducible (r >/= 0.70) and, for gp100, correlates strongly with immunohistochemistry and immunocytochemistry (r = 0.78 and 0.76, respectively) and moderately with transcript levels, measured by RT-PCR (r = 0.61). In contrast, for MART-1, I-RPM correlates strongly with transcript level (r = 0.78) but only moderately strong correlations are noted with immunohistochemistry and immunocytochemistry (r = 0.64 and 0.59, respectively). In general, transcript levels show only moderately strong correlations with immunohistochemistry and immunocytochemistry (r = 0.41-0.64).I-RPM is a promising technology for quantitative grading of tissue biomarkers; however, antigen-dependent correlations are noted.
Metabotropic Glutamate Receptor 4-Mediated 5-Fluorouracil Resistance in a Human Colon Cancer Cell Line
Authors: Byong Chul Yoo, Eunkyung Jeon, Sung-Hye Hong, Young-Kyoung Shin, Hee Jin Chang, Jae-Gahb Park
Journal: Clinical Cancer Research (2004)

Abstract Purpose: 5-Fluorouracil (5-FU) has been the mainstay treatment for colorectal cancer for the past few decades. However, as with other cancers, development of 5-FU resistance has been a major obstacle in colorectal cancer chemotherapy. The purpose of this study was to gain further understanding of the mechanisms underlying 5-FU resistance in colorectal cancer cells. Experimental Design: A 5-FU-resistant cell line was established from the human colon cancer cell line SNU-769A. Protein extracts from these two cell lines (parent and resistant) were analyzed using comparative proteomics to identify differentially expressed proteins. Results: 5-FU-resistant human colon cancer cells were found to overexpress metabotropic glutamate receptor 4 (mGluR4). Other experiments showed cellular resistance to 5-FU (i.e., cell survival) was altered by the mGluR4 agonist l-2-amino-4-phosphonobutyric acid (L-AP 4), and by the mGluR4 antagonist (S)-amino-2-methyl-4-phosphonobutanoic acid (MAP 4), in that L-AP 4 increased 5-FU resistance in SNU-769A cells, whereas MAP 4 ablated 5-FU resistance in 5-FU-resistant cells. However, there was no significant effect of L-AP 4 or MAP 4 on basal cAMP and thymidylate synthase levels. Interestingly, 5-FU down-regulated mGluR4 expression, and MAP 4 suppressed proliferation in both cell lines. Conclusions: We here report mGluR4 expression in human colon cancer cell line, which provides further evidence for extra-central nervous system expression of glutamate receptors. Overexpression of mGluR4 may tentatively be responsible for 5-FU resistance and, although activation by agonist promotes cell survival in the presence of 5-FU, decreased mGluR4 expression or inactivation by antagonist contributes to cell death.
Ongoing research in Europe: Alpha One International Registry (AIR) objectives and development
Authors: R. A. Stockley, M. Luisetti, M. Miravitlles, E. Piitulainen, P. Fernandez
Journal: European Respiratory Journal (2007)

In 1997, the World Health Organization recommended establishing an international registry of alpha1-antitrypsin deficiency. The objective of the present article is to describe the organisation of an international network of registries, the Alpha One International Registry (AIR), and the processes of enrolling and entering data. By the end of 2005, the registry included individuals from 21 countries (from four continents). The inclusion criterion was either phenotypes PiZZ, PiSZ or other severely deficient variants. Demographic and clinical information have been collected by a standardised questionnaire, translated for each country. Data are transferred to the AIR database at the Dept of Respiratory Medicine, University Hospital, Malmö, Sweden, either by e-mail or via two web-enabled questionnaires in HTML. All data are merged and checked for consistency and missing values. Collection of data started in 1999 and, by September 2005, data on 2,150 individual patients (1,180 male) had been submitted. Of these, 1,855 (84%) have phenotype PiZ, 181 (8%) PiSZ and 114 (5%) other rare Pi phenotypes. The mean age at inclusion was 49.8 yrs (SD = 13.3) and the majority were index cases (64.1%). The Alpha One International Registry is the largest specific alpha1-antitrypsin deficiency registry, fulfilling a major World Health Organization recommendation. The success related to the convergence of national registries into a common database creating a unique registry beyond geographic boundaries and encompassing alpha1-antitrypsin deficiency from various ethnic groups.
Regulation of Renal Urea Transportersa
Authors: JEFF M. SANDS
Journal: Journal of the American Society of Nephrology (1999)

Abstract. Urea is important for the conservation of body water due to its role in the production of concentrated urine in the renal inner medulla. Physiologic data demonstrate that urea is transported by facilitated and by active urea transporter proteins. The facilitated urea transporter (UT-A) in the terminal inner medullary collecting duct (IMCD) permits very high rates of transepithelial urea transport and results in the delivery of large amounts of urea into the deepest portions of the inner medulla where it is needed to maintain a high interstitial osmolality for concentrating the urine maximally. Four isoforms of the UT-A urea transporter family have been cloned to date. The facilitated urea transporter (UT-B) in erythrocytes permits these cells to lose urea rapidly as they traverse the ascending vasa recta, thereby preventing loss of urea from the medulla and decreasing urine-concentrating ability by decreasing the efficiency of countercurrent exchange, as occurs in Jk null individuals (who lack Kidd antigen). In addition to these facilitated urea transporters, three sodium-dependent, secondary active urea transport mechanisms have been characterized functionally in IMCD subsegments: ( 1 ) active urea reabsorption in the apical membrane of initial IMCD from low-protein fed or hypercalcemic rats; ( 2 ) active urea reabsorption in the basolateral membrane of initial IMCD from furosemide-treated rats; and ( 3 ) active urea secretion in the apical membrane of terminal IMCD from untreated rats. This review focuses on the physiologic, biophysical, and molecular evidence for facilitated and active urea transporters, and integrative studies of their acute and long-term regulation in rats with reduced urine-concentrating ability.
Anxiety and Depression in Later Life: Co-Occurrence and Communality of Risk Factors
Authors: Aartjan T.F. Beekman, Edwin de Beurs, Anton J.L.M. van Balkom, Dorly J.H. Deeg, Richard van Dyck, Willem van Tilburg
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: The purpose of this study was to examine the comorbidity of and communality of risk factors associated with major depressive disorder and anxiety disorders in later life. METHOD: A random age- and sex-stratified community-based sample (N=3,056) of the elderly (age 55–85 years) in the Netherlands was studied. A two-stage screening design was used, with the Center for Epidemiologic Studies Depression Scale as a screening instrument and the National Institute of Mental Health Diagnostic Interview Schedule as a criterion instrument. Risk factors were measured with well-validated instruments and represented a broad range of vulnerability and stress-related factors associated with anxiety and depression. Multivariate analyses examined risk factors associated with pure major depressive disorder, pure anxiety disorders, and comorbid conditions. RESULTS: Comorbidity was highly prevalent: 47.5% of those with major depressive disorder also met criteria for anxiety disorders, whereas 26.1% of those with anxiety disorders also met criteria for major depressive disorder. While the only variables associated with pure major depressive disorder were younger age and external locus of control, risk factors representing a wide range of both vulnerability and stress were associated with pure anxiety disorders. External locus of control was the only common factor. The group with anxiety disorders plus major depressive disorder had a distinct risk factor profile and may represent those with a more severe disorder. CONCLUSIONS: Although high levels of comorbidity between major depressive disorder and anxiety disorders were found, comparing risk factors associated with pure major depressive disorder and pure anxiety disorders revealed more differences than similarities. Anxiety disorders in later life merit separate study.