tbuckley/cabot-search huggingface dataset:
The Treatment of Pain in The Patient with Cancer
Authors: K. M. Foley
Journal: CA A Cancer Journal for Clinicians (1986)

Advances in the diagnosis and treatment of cancer, coupled with an expanded understanding of the physiology, pharma cology, and psychology of pain perception, have led to improved care of the patient with pain from cancer.' Improved methods of cancer diagnosis and treatment provide the best approach to managing pain by treating its cause.Before the start of an titumor therapy, or when such therapy is unsuccessful or when irreversible injury to bone, soft tissue, or nerve has occurred, however, adequate pain control is essen tial.Management of pain in patients with cancer requires specific expertise that in cludes a knowledge of the clinical pain syndromes that are common in cancer and
The integrated exposure uptake biokinetic model for lead in children: independent validation and verification.
Authors: L Zaragoza, K Hogan
Journal: Environmental Health Perspectives (1998)

The U.S. Environmental Protection Agency employs a model, the integrated exposure biokinetic (IEUBK) model for lead in children, for the assessment of risks to children posed by environmental lead at hazardous waste sites. This paper describes results of an effort to verify the consistency of the documentation with the computer model and to test the computer code using a group that is independent from those involved in the model development. This review concluded that the IEUBK model correctly calculates the equations specified in the IEUBK model theory documentation. However, several issues were identified on model documentation, model performance, and the C++ programming language code (i.e., IEUBK model source code) documentation. These issues affect the ability of an independent reviewer to understand the workings of the IEUBK model but not the model's reliability. As a result of these findings, recommendations have been provided for updating documentation to the model as well as associated adjustments to the model documentation.
Tamiflu and neuropsychiatric disturbance in adolescents
Authors: Simon R J Maxwell
Journal: BMJ (2007)

The authors examined the association of total plasma homocysteine (Hcy) levels with measures of atrophy and white matter disease on MRI scans in 36 healthy elderly individuals. Hcy had a significant positive relationship with lateral ventricle–brain ratios in the anterior (<i>r</i> = 0.49) and middle (<i>r</i> = 0.43) ventricular regions as measures of central atrophy, but not with cortical atrophy or white matter hyperintensities. In a logistic regression analysis, elevated Hcy was a significant determinant of increased anterior ventricle–brain ratio (≥0.34) after controlling for age, folate, B12, creatinine, and white matter disease (OR = 2.3; CI, 1.03–5.09).
Abstract 1537: Characterization of tumor-infiltrating macrophages in humanized mouse model of prostate cancer.
Authors: Vladimir Ryabov, David Kim, Rikka Saito, Richard B. Alexander, Elena Klyushnenkova
Journal: Cancer Research (2013)

Abstract Macrophage infiltration is observed in many types of human and mouse malignant tumors. Though some studies reported anti-tumor activity of tumor-associated macrophages (TAM) the majority of reports revealed contribution of TAM to tumor growth, invasion and metastasis. The phenotype and functions of TAM in prostate cancer are not well known. However, their abundance in the tumor suggests an important role in the course of malignant progression. In our novel humanized mouse model of prostate cancer, the expression of human HLA-DR*1501 (DR2b) transgene drastically impairs immune response to prostate tumor and induces excessive accumulation of TAM, which predominate in tumor tissue. In parallel, substantial accumulation of CD4+CD25+FOXP3+ T cells is observed in the tumor mass. The initial gene expression profiling of TAM in DR2b+ mice revealed their mixed M1/M2 phenotype since these cells expressed typical M2-associated genes TGFβ, IL10, arginase I, stabilin-1 and M1-associated genes IL1β, TNFα and IL6. Moreover, TAM strongly expressed chemokines CCL2, CCL3, CCL4, CCL5 and CXCL10, which are capable to recruit myeloid, NK and T cells as well as immune checkpoint receptor PDL-1. Interestingly, compared to DR2b- mice, TAM from DR2b+ animals had reduced expression of important NK and T cell survival factor IL15. Immunohistochemical investigation of the tumor tissue revealed that CD68+ TAM co-localized with T cells on the periphery of the tumor and expressed M2-associated marker stabilin-1. Moreover, T cells were found exclusively on the tumor periphery, whereas TAM were observed inside tumor mass. Altogether, present data suggest that TAM in DR2b model of prostate cancer have potential to recruit various immune cells to the tumor mass. However, elevated expression of immunosuppressive factors TGFβ, IL10, arginase I, PDL-1 and close association between TAM and T cells on tumor periphery may impair T cell activation and induce generation of Tregs. Citation Format: Vladimir Ryabov, David Kim, Rikka Saito, Richard B. Alexander, Elena Klyushnenkova. Characterization of tumor-infiltrating macrophages in humanized mouse model of prostate cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1537. doi:10.1158/1538-7445.AM2013-1537
Expression of Sorafenib Targets in Melanoma Patients Treated with Carboplatin, Paclitaxel and Sorafenib
Authors: Lucia Jilaveanu, Christopher Zito, Sandra J. Lee, Katherine L. Nathanson, Robert L. Camp, David L. Rimm, Keith T. Flaherty, Harriet M. Kluger
Journal: Clinical Cancer Research (2009)

Abstract Background: Sorafenib, a multitarget kinase inhibitor, inhibits members of the mitogen-activated protein kinase (MAPK) pathway and receptor tyrosine kinases, including vascular endothelial growth factor receptor 2 (VEGF-R2). Sorafenib, carboplatin, and paclitaxel (SCP) has antitumor activity in melanoma patients, but no association was found between response and activating B-Raf V600E mutations. We assessed the expression of sorafenib targets in SCP-treated patient specimens and evaluated the association with response and progression-free survival. Experimental Design: Using automated quantitative analysis, we quantified the expression of VEGF-R1, VEGF-R2, VEGF-R3, fibroblast growth factor receptor 1, platelet-derived growth factor receptor β, c-Kit, B-Raf, C-Raf, meiosis-specific serine/threonine protein kinase 1, and extracellular regulated kinase 1/2 (ERK1/2) in pretreatment specimens from 46 patients. Furthermore, we assessed ERK1/2 expression in 429 archival melanomas. Results: VEGF-R2 expression was significantly higher in patients with a complete or partial response (P = 0.0435), whereas ERK1/2 was higher in patients who did not respond (P = 0.0417). High ERK1/2 was an independent predictor of poor survival. High ERK1/2 was associated with decreased survival in the archival melanoma cohort, suggesting that high ERK1/2-expressing tumors are biologically more aggressive. All of the six patients with both high VEGF-R2 and low ERK1/2 responded to SCP. Conclusions: High VEGF-R2 expression is associated with response to SCP in melanoma, whereas high ERK1/2 is associated with resistance. Collection of specimens from SCP-treated melanoma patients in a cooperative group phase III trial comparing this regimen with the chemotherapy alone is ongoing, and confirmation of these findings is necessary. These markers might be useful for predicting response to sorafenib when given with other chemotherapies and in other diseases, resulting in the possible elimination of unnecessary treatment of patients unlikely to respond.
Doctors, their wellbeing, and their stress
Authors: J. Firth-Cozens
Journal: BMJ (2003)

Countless studies of the levels and sources of stress in doctors have taken place in the UK over the past 20 years. My own longitudinal study, begun with students in 1983,1 was in response to two registrars asking me if someone could do something on the stress and depression that they saw around them. Two of their house officers had killed themselves in the last month, and no one had discussed or mentioned it within the teams. It was unmentionable. Over the years some things have changed, and some have stayed the same. This week's theme issue in Career Focus concentrates on ill and stressed doctors.

The proportion of doctors and other health professionals showing above threshold levels of stress has stayed remarkably constant at around 28%, whether the studies are cross sectional or longitudinal, compared with around 18% in the general working population. 1 2 What has changed over the years is that, contrary to the …
Effects of continuous positive airway pressure on cardiac output in normal and hypervolemic unanesthetized pigs.
Authors: J Genovese, M Moskowitz, A Tarasiuk, L M Graver, S M Scharf
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

Continuous positive airway pressure (CPAP) has been used to increase cardiac index (CI) in patients with congestive cardiomyopathy in the presence of elevated pulmonary wedge pressure. We hypothesized that with normovolemia, CPAP would decrease CI because of decreased left ventricular (LV) preload, whereas in hypervolemia CPAP would increase CI because of a decrease in afterload. We tested this hypothesis on nine sedated, unanesthetized pigs instrumented 5 to 10 d before study. We measured CI, heart rate, stroke volume, LV end-diastolic and end-systolic pressures, and LV dimensions at CPAP levels 0, 5, 10, 15, and 20 cm H2O before and after volume expansion with hetastarch (35 ml/kg). From LV dimensions, LV end-diastolic (LVEDV) and LV end-systolic volumes (LVESV) and LV ejection fraction (LVEF) were calculated. With normovolemia, CI and LVEDV decreased with increased CPAP. Volume infusion produced mild cardiac dysfunction as evidenced by increased LV volumes, decreased LVEF, and decreased contractility. With hypervolemia, CPAP produced an increase in CI, decrease in LVEDV and LVESV, and an increase in LVEF. At higher values of CPAP, we observed decreased CI and LVEDV as with normovolemia. We conclude that with normovolemia, CPAP's effects are mainly related to changes in preload. Hypervolemia produced mild cardiac dysfunction. The improvement in CI with CPAP appears predominantly to be secondary to decrease in LV afterload, but a mild preload effect, which parallels the effect seen with normovolemia, was superimposed on afterload changes at higher CPAP values.
Cytotoxicity of human eosinophil granule major basic protein to human nasal sinus mucosa in vitro
Authors: Ken-ichi Hisamatsu, Tetsuya Ganbo, Tsutomu Nakazawa, Yoshihiko Murakami, Gerald J. Gleich, Kiyoshi Makiyama, Hideaki Koyama
Journal: Journal of Allergy and Clinical Immunology (1990)
PTH-010 Rises In both White Cell Count and Crp at Day 3 Predict Failure of Treatment with Metronidazole in C.Difficile Infection: Abstract PTH-010 Table 1
Authors: N M Joshi, K Kok, W Alazawi, J Goodhand, S S Das, D S Rampton
Journal: Gut (2013)

<h3>Introduction</h3> <i>C.difficile</i> infection (CDI) is the most serious cause of hospital-acquired diarrhoea. Factors predicting outcome are unclear. We have assessed possible biomarkers of failure to respond to metronidazole in a prospective series of 43 inpatients with CDI. <h3>Methods</h3> At diagnosis (T<sup>1</sup>) and after 3 days (T<sup>2</sup>) of metronidazole 400mg tds po (n = 33) or 500mg tds iv (n = 10), we assessed haemoglobin, white cell count (WCC), platelet count, C-reactive protein (CRP), creatinine, albumin, pulse, BP, temperature, stool frequency and Bristol score. Cure was defined as formed stool on 2 consecutive days within 7 days of starting metronidazole; failure was clinical deterioration needing treatment with vancomycin, colectomy and/or death within 28 days. Positive and negative predictive values (PPV, NPV) for failure of metronidazole were calculated. <h3>Results</h3> 17 patients failed metronidazole: 7 needed vancomycin and 10 died. Regardless of outcome, there were significant falls in CRP, pulse, stool frequency between T<sup>1</sup> and T<sup>2</sup>; however, neither WCC and Bristol stool score did not fall in treatment failures (Table). The other measures did not change in either group (data not shown). PPV for treatment failure of increases in WCC and CRP (as separate variables) between T<sup>1</sup> and T<sup>2</sup> were 67% and 57%, with NPV 75% and 65% (accuracies 72% and 63%), respectively. However, PPV and NPV for treatment failure of increases in both WCC and CRP between T<sup>1</sup> and T<sup>2</sup> were 100% and 62% (accuracy 75%). Table. Mean (SEM); <sup>*</sup>p &lt; 0.05, <sup>*</sup><sup>*</sup>p &lt; 0.001 from T<sup>1</sup> <h3>Conclusion</h3> No single measure predicted failure to respond to metronidazole. However, all patients showing a rise in both WCC <i>and</i> CRP after 3 days of metronidazole failed treatment (PPV 100%). This simple predictive combination needs confirmation in a validation cohort, but should alert clinicians to the need for prompt escalation of therapy <h3>Disclosure of Interest</h3> None Declared.
Unwanted reflex-like saccades in visual extinction patients
Authors: Alessandra Fanini, Carlo Alberto Marzi
Journal: Behavioral and Brain Sciences (1999)

We studied patients with left visual extinction following right hemisphere damage in a simple manual reaction time task using brief visual stimuli. With unilateral lateralized stimuli the patients showed a high proportion of unwanted, reflex-like saccades to either side of stimulation. In contrast, with bilateral stimuli there was an overall decrease in the proportion of unwanted saccades, and the vast majority of them were directed toward the ipsilesional side. The implications of these results for the Findlay &amp; Walker model are discussed.
Immunoglobulin E is not required for but enhances airway inflammation and hyperresponsiveness
Authors: D. M. Itami, D. Latinne, H. Bazin, M. L. B. Garcia, A. Perini, M. A. Martins, M. S. Macedo, M. F. Macedo‐Soares
Journal: Allergy (2003)

The aim of this study was to investigate the role of immunoglobulin E (IgE) in the late phase reaction (LPR) of murine experimental asthma. Our model consisted of an implant of DNP-conjugated, heat-coagulated hen's egg white (DNP-EWI), followed 14 days later by an intratracheal challenge with aggregated DNP-ovalbumin. Airway inflammation was analyzed 48 h after challenge and compared with a similarly immunized group of mice with highly suppressed humoral response due to anti-micro and anti-delta antibody treatment. Total number of cells in the bronchoalveolar lavage (BAL) (with predominance of eosinophils) and EPO activity in the lung homogenate were increased in the DNP-EWI-immunized group compared with immunosuppressed or nonimmunized mice. However, the cellular infiltration and EPO activity observed in the immunosuppressed group were still significantly above those obtained in the nonimmunized group, indicating that inhibition of antibody production did not completely prevent the inflammatory manifestations in BAL and lung. Airway hyperresponsiveness to methacoline was obtained in DNP-EWI-immunized mice, but the respiratory mechanical parameters returned to normal levels in the immunosuppressed group. When these mice were reconstituted with monoclonal anti-DNP antibodies, only IgE, but not IgG1, restored lung inflammation and decreased the conductance of the respiratory system, therefore, increasing hyperresponsiveness. These results indicate that antibodies are not essential for induction of LPR in the lung. However, IgE enhances pulmonary inflammation and hyperresponsiveness.
Learning to Accentuate the Positive in Managed Care
Authors: P R Alper
Journal: New England Journal of Medicine (1997)

Managed care scares me, but with patients enrolled in health maintenance organizations (HMOs) now making up a quarter of my internal-medicine practice, I've found it essential to think positive thoughts. This often means discerning silver linings where others see only clouds.Flexibility is essential. Once, I believed that only the physicians treating patients should define and take charge of their care. Managed care has successfully challenged this philosophy by showing that patients (and doctors) are more similar than they are different. Also, I have learned that an obsessive concentration on the doctor–patient relationship distracts me from attending to the needs . . .
Visual-Field Impairment Related to Football Headgear and Face Guards
Authors: Richard C. Schneider
Journal: JAMA (1965)

Clear and unobstructed vision is essential for any athlete participating in a contact sport so he may function at his best and with the greatest degree of safety. 1-3 This is particularly important in football where speed and heavy impact blocking are such vital factors in the proper execution of the plays. 4 The rigid plastic helmet and the plastic face  have done much to protect the player from severe facial injuries and have permitted a more fearless type of tackling and blocking. This paper treats only the effect of the face  on the players' field of vision; it purposely avoids, in general, elaboration on the advantages or disadvantages of the rigid helmet or face mask .  It has been some years since Coach Paul Brown abandoned the old nose guard and provided the first protruding bar face  for the protection of one of his star players. This
805-2 Faster but not more Complete Thrombolysis with Tissue Plasminogen Activator than with Streptokinase in Massive Pulmonary Embolism
Authors: Nicolas Meneveau, François Schiele, François Barthès, Alain Vuillemenot, Thierry Anguenot, Benoit Valette, Gilles Grollier, Yvette Bernard, Jean-Pierre Bassand
Journal: Journal of the American College of Cardiology (1995)
Influence of Payor on Use of Invasive Cardiac Procedures and Patient Outcome After Myocardial Infarction in the United States
Authors: Mark J. Sada, William J. French, David M. Carlisle, Nisha C. Chandra, Joel M. Gore, William J. Rogers
Journal: Journal of the American College of Cardiology (1998)

Objectives. We sought to determine the influence of payor status on the use and appropriateness of cardiac procedures. Background. The use of invasive procedures affects the cost of cardiovascular care and may be influenced by payor status. Methods. We compared treatment and outcomes of myocardial infarction among four payor groups: fee for service (FFS), health maintenance organization (HMO), Medicaid and uninsured. Multivariate comparison was performed on the use of invasive cardiac procedures, length of hospital stay and in-hospital mortality in 17,600 patients <65 years old enrolled in the National Registry of Myocardial Infarction from June 1994 to October 1995. To determine the appropriateness of coronary angiography, we compared its use in patients at low and high risk for cardiac events. Results. Angiography was performed in 86% of FFS, 80% of HMO, 61% of Medicaid and 75% of uninsured patients. FFS patients were more likely to undergo angiography than HMO (odds ratio [OR] 1.27, 95% confidence interval [CI] 1.13 to 1.42), Medicaid (OR 2.43, 95% CI 2.11 to 2.81) and uninsured patients (OR 1.99, 95% CI 1.76 to 2.25). Similar patterns for the use of coronary revascularization were found. Among those at low risk, FFS patients were as likely to undergo angiography as HMO patients but more likely than Medicaid and uninsured patients. For those at high risk, FFS patients were more likely to undergo angiography than patients in other payor groups. Adjusted mean length of stay (7.3 days) was similar among all payor groups, but adjusted mortality was higher in the Medicaid group (Medicaid vs. FFS: OR 1.55, 95% CI 1.19 to 2.01). Conclusions. Payor status is associated with the use and appropriateness of invasive cardiac procedures but not length of hospital stay after myocardial infarction. The higher in-hospital mortality in the Medicaid cohort merits further study.
Reversible binding of 5- and 8-methoxypsoralen to human serum proteins (albumin) and to epidermis in vitro
Authors: M. ARTUC, G. STUETTGEN, W. SCHALLA, H. SCHAEFER, J. GAZITH
Journal: British Journal of Dermatology (1979)

Binding of the two photosensitizers, 8-methoxypsoralen (8-MOP) and 5-methoxypsoralen (5-MOP), to serum proteins and to epidermis was measured. 8-MOP binds to serum proteins with an apparent dissociation constant (Kd) of 4 x 10(-5) M. Under conditions of oral therapy, serum concentrations of the photosensitizer 2 h after administration are usually in the range of 100-1000 ng per ml serum. In this concentration range, 75-80% of the drug was found to be reversibly bound to serum proteins. 5-MOP shows a higher binding affinity to serum proteins and 98-99% of the drug is protein bound. The binding of both psoralen derivatives appears to take place mainly to serum albumin. 5-MOP and 8-MOP bind to different and non-interacting sites on serum proteins and the binding of the one has no effect on the binding of the other methoxypsoralen. Both photosensitizers bind reversibly to human epidermis. 8-MOP concentration in the epidermis is increased by ten to twenty fold compared with the equilibrium buffer. 5-MOP shows a higher binding affinity, resulting in a higher tissue concentration of the photosensitizer. As in serum, the two drugs appear to be bound in the epidermis to independent and non-interacting sites. No binding competition was found between the two methoxypsoralens and hydrocortisone, fluocinonide and acetyl salicylic acid, either in serum or in epidermis, using up to 1000 fold higher concentrations as compared with those of 5-MOP and 8-MOP.
Tolerance to repeat exposure of inhaled endotoxin: an observation in healthy humans
Authors: L. C. Loh
Journal: European Respiratory Journal (2005)

overall population.In order to reveal a lower, but still significant difference in the cystic fibrosis transmembrane regulator DF508 allele prevalence, the number of patients should be increased dramatically.Hopefully, the worldwide existing large collections of DNA specimens from osteoporotic patients will provide an opportunity to enlighten the possible implication of a cystic fibrosis transmembrane regulator mutation in the development of osteoporosis.
Isocitrate dehydrogenase 1 and 2 mutations induce BCL-2 dependence in acute myeloid leukemia
Authors: Steven M Chan, Daniel Thomas, M Ryan Corces-Zimmerman, Seethu Xavy, Suchita Rastogi, Wan-Jen Hong, Feifei Zhao, Bruno C Medeiros, David A Tyvoll, Ravindra Majeti
Journal: Nature Medicine (2015)
Familial Hemochromatosis
Authors: Edward R. Feller, Allan Pont, Jack R. Wands, Edward A. Carter, Gerald Foster, Ione A. Kourides, Kurt J. Isselbacher
Journal: New England Journal of Medicine (1977)

We studied 12 members of a family with precirrhotic hemochromatosis to define the physiologic abnormalities in the asymptomatic phase of the disease. Six of 12 had increased iron stores; the mode of inheritance was consistent with an autosomal dominant trait. Serum ferritin levels were no more predictive of tissue iron levels than measurements of serum iron, transferrin saturation or chelatable iron excretion. In three affected family members intestinal iron content was normal. Liver proline hydroxylase activity and urinary hydroxyproline excretion did not correlate with tissue iron content, suggesting that, in addition to the possible role of tissue iron, hepatic fibrosis may involve other factors. "Borderline diabetes mellitus" was present in three affected family members, but extensive studies revealed that pituitary dysfunction is uncommon in early hemochromatosis. Increased levels of liver iron proved to be the most reliable marker for the disease.