tbuckley/cabot-search huggingface dataset:
A CYP3A4 Phenotype–Based Dosing Algorithm for Individualized Treatment of Irinotecan
Authors: Jessica M. van der Bol, Ron H.J. Mathijssen, Geert-Jan M. Creemers, André S.Th. Planting, Walter J. Loos, Erik A.C. Wiemer, Lena E. Friberg, Jaap Verweij, Alex Sparreboom, Floris A. de Jong
Journal: Clinical Cancer Research (2010)

Abstract Purpose: Irinotecan, the prodrug of SN-38, is extensively metabolized by cytochrome P450-3A4 (CYP3A4). A randomized trial was done to assess the utility of an algorithm for individualized irinotecan dose calculation based on a priori CYP3A4 activity measurements by the midazolam clearance test. Experimental Design: Patients were randomized to receive irinotecan at a conventional dose level of 350 mg/m2 (group A) or doses based on an equation consisting of midazolam clearance, γ-glutamyl-transferase, and height (group B). Pharmacokinetics and toxicities were obtained during the first treatment course. Results: Demographics of 40 evaluable cancer patients were balanced between both groups, including UGT1A1*28 genotype and smoking status. The absolute dose of irinotecan ranged from 480 to 800 mg in group A and 380 to 1,060 mg in group B. The mean absolute dose and area under the curve of irinotecan and SN-38 were not significantly different in either group (P &amp;gt; 0.18). In group B, the interindividual variability in the area under the curve of irinotecan and SN-38 was reduced by 19% and 25%, respectively (P &amp;gt; 0.22). Compared with group A, the incidence of grades 3 to 4 neutropenia was &amp;gt;4-fold lower in group B (45 versus 10%; P = 0.013). The incidence of grades 3 to 4 diarrhea was equal in both groups (10%). Conclusions: Incorporation of CYP3A4 phenotyping in dose calculation resulted in an improved predictability of the pharmacokinetic and toxicity profile of irinotecan, thereby lowering the incidence of severe neutropenia. In combination with UGT1A1*28 genotyping, CYP3A4 phenotype determination should be explored further as a strategy for the individualization of irinotecan treatment. Clin Cancer Res; 16(2); 736–42
Epidemiological, clinical and therapeutic associations of hepatitis C types in western European patients
Authors: Peter Simmonds, Janet Mellor, Antonio Craxi, Jose-Maria Sanchez-Tapias, Alfredo Alberti, Jesus Prieto, Massimo Colombo, Maria Grazia Rumi, Oreste Lo Iacano, Sergi Ampurdanes-Mingall, Xavier Forns-Bernhardt, Liliane Chemello, Maria-Pilar Civeira, Christopher Frost, Geoffrey Dusheiko
Journal: Journal of Hepatology (1996)
Acute Fulminating Neurogenic Hypertension Produced by Brainstem Lesions in the Rat
Authors: NOBUTAKA DOBA, DONALD J. REIS
Journal: Circulation Research (1973)

Bilateral electrolytic lesions of the nucleus tractus solitarii in the rat at the level of the obex abolished baroreceptor reflexes and resulted in an immediate, marked elevation in systemic blood pressure without a change in heart rate. In unanesthetized rats the hypertension was associated with a marked increase in total peripheral resistance, a reduction in blood flow in the abdominal aorta, and an increase in central venous pressure. The cardiac output was reduced to 62% of control as a consequence of reduced stroke volume, which was reflected, in turn, by increased end-diastolic pressure. The hypertension was abolished and the end-diastolic pressure lowered by blockade of alpha receptors with phentolamine. The hypertension was not due to changes in blood gases or to release of agents from the kidneys or the adrenal glands; it was very sensitive to anesthetics and was abolished or aborted by midcollicular decerebration. Within hours after lesioning, the rats developed progressive congestive heart failure and died in shock, often in association with pulmonary edema. We concluded that the fulminating hypertension evoked by lesions of the nucleus tractus solitarii was due to the increased vasoconstriction caused by the augmented discharge of sympathetic nerves in response to central deafferentation of baroreceptor reflexes; the hypertension was mediated by alpha receptors and depended on the integrity of structures lying above the midbrain.
Technique of on-line analysis of diaphragmatic electromyogram activity in the newborn
Authors: B Chambille, G Vardon, J P Monrigal, M Dehan, C Gaultier
Journal: European Respiratory Journal (1989)

The present study provides an on-line analysis of diaphragmatic electromyographic activity (EMGdi) in newborns. EMGdi was recorded using surface electrodes. EMGdi signals were processed using a microcomputer (Apple IIe). The centroid frequency (Fc) and the high over low (H/L) frequencies ratio of the power spectrum were calculated. Furthermore the model frequency (Fo) was computed by an autoregressive model of the EMG signal. EMGdi analysis was performed in seven healthy spontaneously breathing preterm newborns. Fc ranged from 46-62 Hz. Fc was significantly lower than Fo in four of the seven preterm newborns. The coefficient of variation for Fc was significantly lower than for the H/L ratio (p less than 0.001). The coefficients of variation for Fo and Fc were not significantly different, but the percentage of rejected calculations for Fo was significantly higher than for Fc (p less than 0.01). Therefore, in healthy preterm newborns, Fc appears to be the best index of EMGdi analysis.
Treatment of Nocturnal Airway Obstruction Improves Daytime Cognitive Performance in Asthmatics
Authors: ELS J. M. WEERSINK, ED H. van ZOMEREN, GERARD H. KOËTER, DIRKJE S. POSTMA
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

It has been shown that asthmatics have nocturnal symptoms associated with impaired cognitive performance. We explored more carefully different therapeutic approaches on this performance in relation to lung function in 46 atopics with mild to moderate asthma and with a circadian variation in peak expiratory flow (PEF) ⩾ 15%. In a double-blind, parallel study they inhaled salmeterol 50 μ g or fluticasone 250 μ g or a combination of both twice daily for 6 wk. The psychometric tests used informed about focused attention, mental flexibility, concentration, and attention. The results of the psychometric tests were compared with those in healthy control subjects. The PASAT score and the finishing time of the color-word chart subtest were significantly lower in these asthmatics than in the control subjects. Circadian PEF variation was the only independent factor significantly associated with impaired cognitive performance before the treatment period. The three treatment groups were equally effective in reducing circadian PEF variation below 10% and in improving FEV1 and bronchial hyperresponsiveness to methacholine (MCh) both day and night. After 6 wk of therapy, the daytime cognitive performance was improved to levels comparable to those of the healthy control subjects no matter which drug was inhaled. We conclude that a high level of circadian PEF variation ( ⩾ 20%) has been associated with lower daytime cognitive performance in asthmatics. Reduction of circadian PEF variation to below 10% is an important goal of treatment in asthmatics.
Polarized Dendritic Transport and the AP-1 μ1 Clathrin Adaptor UNC-101 Localize Odorant Receptors to Olfactory Cilia
Authors: Noelle D. Dwyer, Carolyn E. Adler, Justin Gage Crump, Noelle D. L'Etoile, Cornelia I. Bargmann
Journal: Neuron (2001)
Molecular Epidemiology of Haemophilus ducreyi Infections
Authors: H. HUNTER HANDSFIELD
Journal: Annals of Internal Medicine (1981)

Haemophilus ducreyi was isolated with an enriched chocolate agar containing vancomycin from seven patients with clinical evidence of chancroid. Four cases were imported from outside the United States; the other three cases were acquired in the United States from one of the imported cases. All strains of H. ducreyi contained ampicillin-resistance plasmids with molecular weights of 7.3, 5.7, or 3.6 megadaltons. Plasmid molecular weights were identical for isolates from the epidemiologically linked cases and differed according to the geographic origins of the strains. Findings of this study confirm that H. ducreyi is sexually transmitted and suggest that clinical chancroid develops frequently after acquisition of H. ducreyi.
Quake: quality-aware detection and correction of sequencing errors
Authors: David R Kelley, Michael C Schatz, Steven L Salzberg
Journal: Genome biology (2010)

Abstract We introduce Quake, a program to detect and correct errors in DNA sequencing reads. Using a maximum likelihood approach incorporating quality values and nucleotide specific miscall rates, Quake achieves the highest accuracy on realistically simulated reads. We further demonstrate substantial improvements in de novo assembly and SNP detection after using Quake. Quake can be used for any size project, including more than one billion human reads, and is freely available as open source software from http://www.cbcb.umd.edu/software/quake .
Pharmacokinetics and bioequivalence of a combined oral formulation of eniluracil, an inactivator of dihydropyrimidine dehydrogenase, and 5-fluorouracil in patients with advanced solid malignancies
Authors: L. Ochoa, H.I. Hurwitz, G. Wilding, D. Cohen, J.P. Thomas, G. Schwartz, P. Monroe, W.P. Petros, V.Ph. Ertel, A. Hsieh, C. Hoffman, R. Drengler, S. Magnum, E.K. Rowinsky
Journal: Annals of Oncology (2000)
HIV-1 envelope protein binds to and signals through integrin α4β7, the gut mucosal homing receptor for peripheral T cells
Authors: James Arthos, Claudia Cicala, Elena Martinelli, Katilyn Macleod, Donald Van Ryk, Danlan Wei, Zhen Xiao, Timothy D Veenstra, Thomas P Conrad, Richard A Lempicki, Sherry McLaughlin, Massimiliano Pascuccio, Ravindra Gopaul, Jonathan McNally, Catherine C Cruz, Nina Censoplano, Eva Chung, Kristin N Reitano, Shyam Kottilil, Diana J Goode, Anthony S Fauci
Journal: Nature Immunology (2008)
Rapid detection of Mycoplasma pneumoniae IgM antibodies using ImmunoCard Mycoplasma kit compared with complement fixation (CF) tests and clinical application
Authors: Ryuta Ueda, Juri Okamura, Yasushi Inoue, Taichi Mochizuki, Tetsuo Sato
Journal: European Respiratory Journal (2012)

[Purpose] Mycoplasma pneumoniae  is a leading cause of community-acquired pneumonia. For a rapid diagnosis of  M. pneumoniae  infection, we often use ImmunoCard  Mycoplasma  kit (IC), a 10-min-card-based enzyme-linked immunosorbent assay (ELISA) of IgM antibodies to  M. pneumonia . However, widespread clinical application of this test is hampered by an inability to identify pathogen directly with adequate sensitivity and specificity. Therefore, we examined the clinical usefulness of IC test retrospectively.  [Method]We evaluated 316 samples which are measured by IC from October,2008 to March,2009. We also compared IC with the complement fixation (CF) test, and estimated false positive and negative rate based on the clinical course and other laboratory findings.  [Results]Among 316 samples, 69 (21.8%) were positive of IC and 247 (78.2%) negative. Sixteen cases were also measured by CF test with the paired serum, and in 5 (31.3%) cases of these, there was a discrepancy between the result of IC and that of CF test. On the basis of a clinical diagnosis, IC gave the false positive rate of 80.0%, false negative rate of 31.3%.  [Conclusion]IC has so far been attributed to the rapid diagnosis of  M.  pneumoniae  infection because it is unnecessary to use paired serum and possible to judge the infection rapidly. But a positive result of IC does not always indicate acute infection because the result of IC were not always concordant with that of CF test. According to our results, it seems that the interpretation of the result of IC is very difficult in order to use it clinically.
T-Cell Homeostasis in Breast Cancer Survivors With Persistent Fatigue
Authors: J. E. Bower, P. A. Ganz, N. Aziz, J. L. Fahey, S. W. Cole
Journal: JNCI Journal of the National Cancer Institute (2003)

Approximately 30% of women successfully treated for breast cancer suffer persistent fatigue of unknown origin. Recent studies linking inflammatory processes to central nervous system–mediated fatigue led us to examine cellular immune system status in 20 fatigued breast cancer survivors and 19 matched non-fatigued breast cancer survivors. Fatigued survivors, compared with non-fatigued survivors, had statistically significantly increased numbers of circulating T lymphocytes (mean 31% increase, 95% confidence interval [CI] = 6% to 56%; P = .015 by two-sided analysis of variance [ANOVA]), with pronounced elevation in the numbers of CD4+ T lymphocytes (mean 41% increase, 95% CI = 15% to 68%; P = .003 by two-sided ANOVA) and CD56+ effector T lymphocytes (mean 52% increase, 95% CI = 4% to 99%; P = .027 by two-sided ANOVA). These changes were independent of patient demographic and treatment characteristics. Absolute numbers of B cells, natural killer cells, granulocytes, and monocytes were not altered. The increased numbers of circulating T cells correlated with elevations in the level of serum interleukin 1 receptor antagonist (for CD3+ cells, r = .56 and P = .001; for CD3+/CD4+ cells, r = .68 and P<.001, by Spearman rank correlation). Results of this study suggest that persistent fatigue in breast cancer survivors might be associated with a chronic inflammatory process involving the T-cell compartment. These results require confirmation in a larger study that is specifically designed to address this hypothesis.
Recurrent cough in childhood and its relation to asthma.
Authors: A L Wright, C J Holberg, W J Morgan, L M Taussig, M Halonen, F D Martinez
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

Risk factors for recurrent cough (RC) in childhood, and its relation to asthma were investigated as part of the prospective, longitudinal Tucson Children's Respiratory Study. RC, defined as > or = 2 episodes of cough without a cold in the past year, was assessed by questionnaire in 987 children at age 6. Children having RC without wheeze (n = 154) did not differ from children with neither symptom (n = 610) in serum IgE levels, skin test response, size-corrected forced expiratory flow, or percentage of decline following cold air challenge. In contrast, children with both RC and wheeze (n = 116) had significantly more respiratory illness, more atopy, lower flow at end-tidal expiration (V'maxFRC), and greater declines in lung function following cold air challenge than children with neither symptom. Current parental smoking was a risk for RC without wheeze, whereas male gender, maternal allergy, wheezing lower respiratory tract illness (LRI) in early life, and high IgE were significant risks for RC with wheeze, compared with children having neither symptom. RC early in life resolved in the majority of children, between ages 2-3 yr and age 6, and between age 6 and age 11. High IgE and positive skin prick test were associated with persistence of RC to age 6 among children who wheezed, and markers of allergy were associated with persistence of RC between 6 and 11 yr. These findings suggest that recurrent cough in the absence of wheeze differs in important respects from classic asthma, and using the same label to refer to these distinct syndromes may obscure their diverse pathophysiologies.
Reply to F. Tomao et al
Authors: Polly A. Newcomb, Michael N. Passarelli
Journal: Journal of Clinical Oncology (2015)

We thank Tomao et al for their correspondence in reference to our article, in particular, for suggesting biases that may have arisen because of factors related to a lower risk of endometrial cancer among patients using bisphosphonates. Common hormonal medications that have been shown to reduce endometrial cancer risk, specifically oral contraceptives and progestin, were, in fact, included in our statistical models. Use of gonadotropin-releasing hormone agonists for the treatment of endometriosis or other benign gynecologic diseases was not yet common, particularly among postmenopausal women, when the Women’s Health Initiative (WHI) investigators began recruiting in 1993. Therefore, we do not believe our inability to adjust for their use distorted our results. Statins have been associated with a reduced risk of endometrial cancer in previous reports, and an analysis of this association in the WHI is forthcoming. During the early years of follow-up, however, statins were not as frequently prescribed as they are today, and previous WHI analyses have not shown statin use to be related to the risk of other hormonal cancers or indications for bisphosphonate use. As we noted, our study had an observational design, and therefore, a causal relationship between bisphosphonate use and endometrial cancer remains to be established.
Predictors of Contralateral Prophylactic Mastectomy in Women With a <i>BRCA1</i> or <i>BRCA2</i> Mutation: The Hereditary Breast Cancer Clinical Study Group
Authors: Kelly A. Metcalfe, Jan Lubinski, Parviz Ghadirian, Henry Lynch, Charmaine Kim-Sing, Eitan Friedman, William D. Foulkes, Susan Domchek, Peter Ainsworth, Claudine Isaacs, Nadine Tung, Jacek Gronwald, Shelly Cummings, Teresa Wagner, Siranoush Manoukian, Pål Møller, Jeffrey Weitzel, Ping Sun, Steven A. Narod
Journal: Journal of Clinical Oncology (2008)

Purpose To evaluate the rate of prophylactic contralateral mastectomy in an international cohort of women with hereditary breast cancer and to evaluate the predictors of uptake of preventive surgery. Patients and Methods Women with a BRCA1 or BRCA2 mutation who had been diagnosed with unilateral breast cancer were followed prospectively for a minimum of 1.5 years. Information was collected on prophylactic surgery, tamoxifen use, and the occurrence of contralateral breast cancer. Results Nine hundred twenty-seven women were included in the study; of these, 253 women (27.3%) underwent a contralateral prophylactic mastectomy after the initial diagnosis of breast cancer. There were large differences in uptake of contralateral prophylactic mastectomy by country, ranging from 0% in Norway to 49.3% in the United States. Among women from North America, those who had a prophylactic contralateral mastectomy were significantly younger at breast cancer diagnosis (mean age, 39 years) than were those without preventive surgery (mean age, 43 years). Women who initially underwent breast-conserving surgery were less likely to undergo contralateral prophylactic mastectomy than were women who underwent a mastectomy (12% v 40%; P &lt; 10 −4 ). Women who had elected for a prophylactic bilateral oophorectomy were more likely to have had their contralateral breast removed than those with intact ovaries (33% v 18%; P &lt; 10 −4 ). Conclusion Age, type of initial breast cancer surgery, and prophylactic oophorectomy are all predictive of prophylactic contralateral mastectomy in women with breast cancer and a BRCA mutation. The acceptance of contralateral preventive mastectomy was much higher in North America than in Europe.
Inverse ratio ventilation (I/E = 2/1) in acute respiratory distress syndrome: a six-hour controlled study.
Authors: A Mercat, M Titiriga, N Anguel, C Richard, J L Teboul
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

To assess the cardiorespiratory effects of a prolonged application of inverse ratio ventilation (IRV), we compared IRV (I/E = 2) with conventional ventilation (CV) (I/E = 0.5), applied for 6 h each in a randomized order, with constant tidal volume (VT) and total positive end-expiratory pressure (PEEP(tot)) in eight patients with acute respiratory distress syndrome (ARDS). After 1 h, IRV resulted in a lower peak inspiratory pressure (PIP) (28.2 +/- 1.5 versus 35.6 +/- 1.7 cm H2O, p < 0.05), an unchanged plateau pressure, and a higher mean airway pressure (MAP) (17.8 +/- 0.8 versus 15.6 +/- 0.5 cm H2O, p < 0.05) than CV. No significant difference in Pa(O2) and shunt fraction (QS/QT) was observed (83 +/- 7 mm Hg and 40 +/- 4% in CV versus 92 +/- 14 mm Hg and 35 +/- 3% in IRV, respectively). The Pa(CO2) was lower in IRV (48 +/- 3 versus 55 +/- 5 mm Hg, p < 0.05). Cardiac index (CI) and oxygen delivery (D(O2)) were lower in IRV (3.7 +/- 0.4 L/min/m2 and 500 +/- 61 ml/min/m2 versus 4.6 +/- 0.5 L/min/m2 and 617 +/- 80 ml/min/m2, respectively, p = 0.05 for both). Regardless of the considered parameter, no significant difference was observed between results after 1, 2, 4, and 6 h in each mode. We conclude that IRV at a ratio that results in a significant intrinsic PEEP does not improve Pa(O2), enhances CO2 elimination, decreases cardiac output (CO), and does not exert any time-dependent effect.
Evaluating Antiangiogenesis Agents in the Clinic
Authors: Joseph A. Sparano, Robert Gray, Bruce Giantonio, Peter O’Dwyer, Robert L. Comis
Journal: Clinical Cancer Research (2004)

Abstract Recent evidence indicates that treatment with a humanized monoclonal antibody (bevacizumab) directed at vascular endothelial growth factor improves response and survival in metastatic colorectal cancer when added to standard chemotherapy, validating angiogenesis as a therapeutic target. Investigators from the Eastern Cooperative Oncology Group (ECOG) have initiated a number of Phase III studies that will help further define the role of antiangiogenic agents for the treatment of breast, colon, lung, renal, and head and neck cancer, as well as melanoma and myeloma. The agents being evaluated target various biological functions involved in angiogenesis, including vascular endothelial growth factor (bevacizumab), endothelial cell proliferation (thalidomide, IFN-α), and matrix metalloproteinases (marimastat). These clinical trials include correlative laboratory studies aimed at elucidating how these agents may exert their clinical effects. The portfolio of Eastern Cooperative Oncology Group studies will serve to further define the role of this therapeutic strategy for patients with advanced cancer.
Role of leukotrienes in bronchial hyperresponsiveness and cellular responses in airways
Authors: A. R Leff
Journal: Thorax (2000)

Among constitutively present cells, bronchoactive leukotrienes are produced predominantly by mast cells1 and macrophages.2 A unique characteristic of asthmatic inflammation is the migration of leukocytes from the peripheral blood to the conducting airways of the lung. This is especially true of the eosinophil, which is not present in the airways of normal individuals, but may be found in massive numbers during periods of airway hyperresponsiveness in asthmatic individuals (fig1).3-5 Most experimental models indicate that eosinophils are an invariable component of asthmatic hyperresponsiveness, although some studies suggest that bronchoconstriction can occur in the relative absence of these cells.



Figure 1 
Effect of eosinophil infiltration into human airways. At later stages a cytotoxic effect probably accounts for the epithelial denudation found in human asthma. (A) Histological section of the airway of a patient with asthma (stain: haematoxylin-eosin; original magnification ×160). (B) Same section stained with fluorescent monoclonal antibody for the eosinophil major basic protein (MBP; magnification ×160). (C) Higher power view of the desquamated epithelium in (A) (basal magnification ×400). (D) Localisation of MBP in cells (arrowheads); these cells correspond directly to the cells marked in (C). MBP is also localised outside cells in association with epithelial desquamation (arrow; original transformation ×400). (C) and (D) illustrate the identical area; this section was first stained for MBP by immunofluorescence and subsequently stained with haematoxylin-eosin. Reprinted with permission from Gleich.5 



For the purposes of this discussion, the eosinophil will be viewed as a leukotriene transport system capable of providing a substantial reservoir of bronchoactive leukotrienes to airways in relatively short time. They may be delivered to conducting airways in large numbers and have the capacity to produce cysteinyl leukotrienes (LTC4) which cannot be produced by neutrophils, but also migrate into conducting airways in some circumstances.6 7 This discussion …