tbuckley/cabot-search huggingface dataset:
Monoclonal antibody-based therapy as a new treatment strategy in multiple myeloma
Authors: N W C J van de Donk, S Kamps, T Mutis, H M Lokhorst
Journal: Leukemia (2011)

The introduction of autologous stem cell transplantation combined with the introduction of immunomodulatory drugs (IMiDs) and proteasome inhibitors has significantly improved survival of multiple myeloma patients. However, ultimately the majority of patients will develop refractory disease, indicating the need for new treatment modalities. In preclinical and clinical studies, promising results have been obtained with several monoclonal antibodies (mAbs) targeting the myeloma tumor cell or the bone marrow microenvironment. The mechanisms underlying the therapeutic efficacy of these mAbs include direct induction of tumor cell apoptosis via inhibition or activation of target molecules, complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity (ADCC). The capability of IMiDs to enhance ADCC and the modulation of various important signaling cascades in myeloma cells by both bortezomib and IMiDs forms the rationale to combine these novel agents with mAbs as new treatment strategies for myeloma patients. In this review, we will give an overview of various mAbs directly targeting myeloma tumor cells or indirectly via effects on the bone marrow microenvironment. Special focus will be on the combination of these mAbs with IMiDs or bortezomib.
P120 Comparison of cellular inflammation and TLR expression profiles between healthy and COPD subjects
Authors: A. Keys, T. Wilkinson, K. J. Staples, M. North, S. Pink, S. Wilson, I. Kilty, R. Djukanovic, B. Nicholas
Journal: Thorax (2011)

<h3>Introduction and Objectives</h3> Chronic obstructive pulmonary disease (COPD) is a complex inflammatory disease of the lungs Initiated by inhalation of toxic particles or gases. Periodic exacerbations triggered by respiratory pathogens are a major cause of morbidity/mortality in these patients. Microbial pathogens are recognised by pattern recognition receptors such as the toll-like receptors (TLRs), initiating innate immune defences. We hypothesised that abnormal TLR expression, and not resident inflammatory cell load in the lung parenchyma, contributes to exacerbation in COPD. <h3>Methods</h3> Human lung tissue, distant from tumour margins, was taken from ex-smoker patients undergoing lobectomy for lung cancer. Patients were classified according to GOLD guidelines as healthy control subjects (HC) or those with COPD. Resected tissue was digested and cells analysed by flow cytometry for phenotypic markers of epithelial cells and inflammatory cell subtypes (macrophages, CD8+ and CD8− T lymphocytes) and the TLR2 and four expressions on these subtypes. Quantitative data of cell numbers and TLR staining intensity were compared using Mann–Whitney U tests. <h3>Results</h3> Seven COPD patients and nine age-matched HC were analysed. No significant differences in the numbers of inflammatory or epithelial cells in the parenchymal tissue of these groups were observed, although a trend was observed to a reduction in macrophage numbers in the COPD group (median HC=4.2, median COPD=3.2 p=0.17). Similarly, no significant difference was found in the level ofTLR2 or TLR4 expression on any of the cell types examined. However, a trend was observed towards a decrease in TLR2 expression on epithelial cells in the COPD patients (median sMFI 3399 (HC) vs 2462 (COPD), p=0.094). <h3>Conclusions</h3> This preliminary analysis has demonstrated that, as hypothesised, there was no significant difference in inflammatory cell load in parenchymal tissue between the two groups. The trend towards a reduced expression of TLR2 in the epithelial cells may reflect an abnormal down regulation of this receptor due to constant exposure to bacterial pathogens. The lack of surveillance of microbial pathogens by TLRs is a potential mechanism by which patients with COPD are more susceptible to infection by new bacterial strains and thus could contribute to exacerbation frequency.
Review: Topical nitroglycerin reduces pain during ADL in patients with chronic tendinopathies
Authors: Owen D. Williamson
Journal: Annals of Internal Medicine (2011)

Source Citation Gambito ED, Gonzalez-Suarez CB, Oquinena TI, Agbayani RB. Evidence on the effectiveness of topical nitroglycerin in the treatment of tendinopathies: a systematic review and meta-analysis. Arch Phys Med Rehabil. 2010;91:1291-305. 20684913
Noradrenaline in Artery Walls and its Dispersal by Reserpine
Authors: J. H. Burn, M. J. Rand
Journal: BMJ (1958)

<h3>Objective:</h3> N/A. <h3>Background:</h3> West Nile virus (WNV) first emerged in the late 1990s in the United States. Since then upwards of 23,000 cases have been reported. Presentation of WNV varies from West Nile fever in approximately 20% of patients to West Nile neuroinvasive disease in less than 1% of infected individuals. Here we present a patient with neuroinvasive West Nile encephalitis who presented with Anton-Babinski syndrome (ABS). <h3>Design/Methods:</h3> A 55-year-old female with a past medical history of hypertension, hypothyroidism, hyperlipidemia and CKD presented to a community hospital in the Summer with sudden acute onset of fevers, chills, and altered mental status. Vital signs were significant for a fever of 39.0 C, and blood pressure 180/112. Laboratory results were significant for elevated white blood cell count of 22,000/ul. Neurologic exam was significant for altered mental status (oriented only to self). MRI brain revealed T2/FLAIR hyperintensities in the fontal, temporal, and occipital cortices. A lumbar puncture was completed with concern for autoimmune encephalitis which had returned negative. A preliminary diagnosis of posterior-reversible encephalopathy syndrome (PRES) was made. After 8 weeks with no significant improvement the patient was transferred to a tertiary care center. Physical exam was notable for no response to visual threat, equal and reactive pupils, and visual anosognosia with confabulations. A repeat MRI showed interval progression of the previously defined lesions. A repeat LP with clear CSF was obtained and serum blood test revealed an elevated WNV IgG, CSF and serum of 1.89 and 2.62 respectively. Based on clinical progression and prognosis of WNV the patient was referred to a long term care facility. <h3>Results:</h3> N/A. <h3>Conclusions:</h3> Neuroinvasive West Nile disease remains to be a rare diagnosis and it’s radiographic and clinical presentation vary. This case aims to highlight the importance of early diagnosis and recognition of symptoms to improve clinical outcomes. <b>Disclosure:</b> Dr. Srichawla has nothing to disclose. Dr. Min has nothing to disclose.
Abstract P5-20-01: A randomized double-blind phase II study of the combination of oral WX-671 plus capecitabine vs. capecitabine monotherapy in first-line HER2− negative metastatic breast cancer (MBC).
Authors: LJ Goldstein, CT Oliveria, B Heinrich, SM Stemmer, C Mala, S Selder, P Bevan, N Harbeck
Journal: Cancer Research (2012)

Abstract Background: uPA and its inhibitor PAI-1 play a key role in tumor invasion, metastasis and tumor growth. High levels of uPA and PAI-1 in breast tumors are statistically significant prognostic factors of disease-free (DFS) and overall survival (OS), which were validated at the highest level of evidence, as well as predictors for benefit of adjuvant chemotherapy. WX-UK1 is an active site competitive inhibitor of uPA with an inhibition constant in the submicromolar range. WX-671 (upamostat) is an oral prodrug of WX-UK1. In preclinical animal tumor models, both WX-UK1 and WX-671 have been shown to reduce the growth rate of implanted tumors, to inhibit invasion, and reduce metastases. This current proof of concept study is designed to substantiate the anti-metastatic properties of upamostat for patients appropriate for first line therapy for MBC. Methods: Female patients aged &amp;gt;18, with HER2 negative MBC appropriate for first line monotherapy with capecitabine, with adequate performance status, organ function, bone marrow reserve without brain metastases were eligible. Patients were randomized in a double-blind fashion to receive upamostat (200mg orally daily for 21 days) plus capecitabine (1000 mg/m2 orally twice daily for 14 days) vs. capecitabine (1000 mg/m2 orally twice daily for 14 days) in 3 week treatment cycles until progressive disease or unacceptable toxicity. The primary endpoint is to evaluate the efficacy of the combination of upamostat plus capecitabine compared to monotherapy as assessed by comparison of progression free survival. The secondary objectives are OS, objective response rates, safety and tolerability, and to assess the pharmacokinetics (PK) of upamostat and capecitabine when combined. Results: Between August 2008 and April 2011,132 patients were enrolled. 17 patients are still receiving treatment. 26% of the patients are characterized as triple negative, 13% as only Estrogen Receptor (ER) positive and 4% as only Progesteron Receptor (PR) positive. 57 % of the patients are ER and PR positive. Conclusions: Progression free survival, response rates and safety will be reported. This abstract is being submitted as a placeholder. A completed abstract will be submitted when the analyses are completed. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-20-01.
Diagnostic Value of Peroral Biopsy of the Proximal Small Intestine
Authors: Jerry S. Trier
Journal: New England Journal of Medicine (1971)

SINCE its introduction over 15 years ago,1 , 2 peroral biopsy of the small intestine has become established as a valuable procedure in the evaluation of patients with malabsorption.3 Only with biopsy can the physician establish or exclude with certainty diffuse disease of the mucosa of the small intestine as the cause of malabsorption, diarrhea and associated nutritional deficiencies.The technic of peroral biopsy is simple and safe. Two rare but serious complications, bleeding4 and perforation,5 have been reported. The frequency of these complications can be minimized by correction of deficiencies of blood-clotting factors before biopsy and by selection of an instrument . . .
High‐frequency ultrasonography but not 930‐nm optical coherence tomography reliably evaluates melanoma thickness <i>in vivo</i> : a prospective validation study
Authors: N. Meyer, V. Lauwers‐Cances, S. Lourari, J. Laurent, M.‐P. Konstantinou, J.‐M. Lagarde, B. Krief, H. Batatia, L. Lamant, C. Paul
Journal: British Journal of Dermatology (2014)

Early diagnosis and rapid surgical excision are essential for improving the prognosis of patients with melanoma. Reflectance confocal microscopy has been validated as a feasible procedure for in vivo diagnosis of melanoma but cannot be used to measure tumour thickness. However, ultrasonography and optical coherence tomography may allow melanoma thickness to be measured in vivo.To validate the accuracy and reliability of high-frequency ultrasonography (HFUS) and optical coherence tomography for assessing melanoma thickness in vivo.We conducted a prospective study on 131 patients with at least one equivocal melanocytic lesion. Each lesion underwent optical coherence tomography and HFUS assessment, followed by excision and pathological examination. Histopathology was considered to be the gold standard for assessing melanoma thickness. Repeatability, inter- and intrarater reproducibility and reliability were evaluated for each imaging procedure.Ultrasonography showed a good level of agreement with histology [intraclass correlation coefficient (ICC) 0.807; 95% confidence interval (CI) 0.703-0.877] and excellent inter-rater reproducibility (G = 0.97), resulting in reliable in vivo assessment of melanoma thickness. The 930-nm optical coherence tomography showed a poor level of agreement with histopathology (ICC 0.0; 95% CI -0.2-0.2) and the inter-rater reproducibility was null (G = 0.00).HFUS is a reliable and reproducible noninvasive method for assessing melanoma thickness. Routine use of HFUS may allow single-step excision of equivocal melanocytic lesions, with surgical margins determined by in vivo assessment of tumour thickness.
Up‐regulation of IL‐18 in allergic rhinitis
Authors: B. Verhaeghe, P. Gevaert, G. Holtappels, K. F. Lukat, B. Lange, P. Van Cauwenberge, C. Bachert
Journal: Allergy (2002)

This paper reports a study on the concentrations of the pro-inflammatory cytokines IL-18 and IL-1beta in nasal secretions of allergic rhinitis patients in relation to ECP and nasal symptoms.We measured IL-18 and IL-1beta concentrations using ELISA, and eosinophilic cationic protein (ECP) using the CAP system, in nasal secretions of 15 seasonal allergic rhinitis (SAR) patients at six visits throughout the pollen season. Pollen exposure, nasal and ocular symptoms were monitored daily. Furthermore, we measured IL-18, IL-1beta and ECP concentrations in nasal secretions of 19 controls and 20 symptomatic persistent allergic rhinitis (PAR) patients with house dust mite allergy.In SAR, the increase of IL-18, IL-1beta and ECP paralleled the pollen flight with a time delay. IL-18 and IL-1beta significantly increased during the pollen season compared to baseline, and differently from ECP, remained elevated until 4 weeks after the season. In PAR, the concentrations of IL-18 and ECP, but not IL-1beta, were significantly higher compared to controls, with IL-18 concentrations also being significantly higher than in SAR.This is the first study to demonstrate the up-regulation of IL-18 in nasal secretions in allergic rhinitis. The persistence of elevated IL-18 concentrations until after the season and the high concentrations in PAR compared to SAR suggests its role in persistent allergic inflammation.
Relation of sputum inflammatory markers to symptoms and lung function changes in COPD exacerbations
Authors: A. Bhowmik
Journal: Thorax (2000)

<h3>BACKGROUND</h3> Although it is presumed that exacerbations of chronic obstructive pulmonary disease (COPD) are associated with increased airway inflammation, there is little information available on inflammatory markers during an exacerbation and the relationship with severity or time course of recovery. A study was undertaken to investigate the sputum cell and cytokine characteristics of COPD when stable and during an exacerbation. <h3>METHODS</h3> Induced sputum samples from 57 patients with moderate to severe COPD were analysed (44 samples were taken during a stable period and 37 during an exacerbation). The patients recorded daily symptoms on diary cards. Cell counts and sputum levels of interleukin (IL)-6 and IL-8 were measured. <h3>RESULTS</h3> Patients with ⩾3 exacerbations/year had higher median stable sputum levels of IL-6 (110 (95% CI 11 to 215) pg/ml) and IL-8 (6694 (95% CI 3120 to 11995) pg/ml) than those with ⩽2 exacerbations/year (22 (95% CI 12 to 93) and 1628 (95% CI 607 to 4812) pg/ml, respectively). Median IL-6 levels were increased during exacerbations compared with stable conditions. The levels of IL-6 during exacerbations were related to the presence of a cold and to the total cell count and eosinophil and lymphocyte numbers, while IL-8 was positively correlated with all sputum cell counts. Sputum cell counts and cytokine levels during an exacerbation did not predict the size and duration of lung function changes in the exacerbation. <h3>CONCLUSIONS</h3> Patients with more frequent exacerbations have higher baseline sputum cytokine levels, which may predict the frequency of future exacerbations.
THE INFLUENCE OF PLASMA PROTEIN ON THE CHLORIDE CONTENT OF THE CEREBROSPINAL FLUID
Authors: Herbert I. Coombs, Kenneth Wade Thompson
Journal: The Journal of Experimental Medicine (1932)

1. When the plasma protein of dogs is lowered by plasmapheresis, the concentration of chloride and sodium in the plasma and the cerebrospinal fluid tends to become the same, a diminishing of the usual disparity which exists in the presence of a normal plasma protein. 2. This is in accord with the theory that the cerebrospinal fluid is a dialysate, with the choroid plexus acting as a simple dialyzing membrane.
Cerebral herniation in patients with acute E liver failure is correlated with arterial ammonia concentration
Authors: Jens Otto Clemmesen, Fin Stolze Larsen, Jens Kondrup, Bent Adel Hansen, Peter Ott
Journal: Hepatology (1999)

Cerebral edema leading to cerebral herniation (CH) is a common cause of death in acute liver failure (ALF). Animal studies have related ammonia with this complication. During liver failure, hepatic ammonia removal can be expected to determine the arterial ammonia level. In patients with ALF, we examined the hypotheses that high arterial ammonia is related to later death by CH, and that impaired removal in the hepatic circulation is related to high arterial ammonia. Twenty-two patients with ALF were studied retrospectively. In addition, prospective studies with liver vein catheterization were performed after development of hepatic encephalopathy (HE) in 22 patients with ALF and 9 with acute on chronic liver disease (AOCLD). Cerebral arterial-venous ammonia difference was studied in 13 patients with ALF. In all patients with ALF (n = 44), those who developed CH (n = 14) had higher arterial plasma ammonia than the non-CH (n = 30) patients (230 +/- 58 vs. 118 +/- 48 micromol/L; P <. 001). In contrast, galactose elimination capacity, bilirubin, creatinine, and prothrombin time were not different (NS). Cerebral arterial-venous differences increased with increasing arterial ammonia (P <.001). Arterial plasma ammonia was lower than hepatic venous in ALF (148 +/- 73 vs. 203 +/- 108 micromol/L; P <.001). In contrast, arterial plasma ammonia was higher than hepatic venous in patients with AOCLD (91 +/- 26 vs. 66 +/- 18 micromol/L; P <.05). Net ammonia release from the hepatic-splanchnic region was 6.5 +/- 6. 4 mmol/h in ALF, and arterial ammonia increased with increasing release. In contrast, there was a net hepatic-splanchnic removal of ammonia (2.8 +/- 3.3 mmol/h) in patients with AOCLD. We interpret these data that in ALF in humans, vast amounts of ammonia escape hepatic metabolism, leading to high arterial ammonia concentrations, which in turn is associated with increased cerebral ammonia uptake and CH.
Prevalence and impact of GBV-C, SEN-V and HBV occult infections in HIV–HCV co-infected patients on HCV therapy
Authors: Lionel Piroth, Fabrice Carrat, Sylvie Larrat, Isabelle Goderel, Benoit Martha, Christopher Payan, Françoise Lunel-Fabiani, Firouze Bani-Sadr, Christian Perronne, Patrice Cacoub, Stanislas Pol, Patrice Morand
Journal: Journal of Hepatology (2008)
Cryopyrin-associated autoinflammatory syndrome: a new mutation
Authors: A. Zeft, J. F Bohnsack
Journal: Annals of the Rheumatic Diseases (2007)

hospital to control relapses with intravenous pulsed methylprednisolone.Sustained high daily prednisolone doses led to the development of Cushing's syndrome in patients 1, 2 and 3, a side effect that promptly subsided after the fast steroid tapering, achieved after the introduction of anakinra.Despite the lack of randomised controlled trials, the impressive efficacy, the steroid-sparing effect and the good tolerance of anakinra in cases of refractory AOSD, combined with the limited efficacy and/or intolerance of anti-tumour necrosis factor-a regimens, 5 suggest that interleukin 1R antagonism may represent a preferred treatment for patients with refractory AOSD.The steroid-sparing effect of anakinra in our patients represents a notable advantage of this treatment.We report, for the first time, such a striking steroid-sparing effect of anakinra treatment in patients with AOSD.Our study, although limited to four patients, adds to the similarly limited existing published literature. 3 6 7Despite rarity of AOSD, we suggest that larger clinical trials are important to evaluate the role of anakinra in the treatment of this disease.
Anesthesia and Recent
Authors: John G. Fraser
Journal: JAMA (1967)

A review has been made of mortality statistics associated with surgery in patients with recent myocardial infarction. The overall mortality figures compare closely with those of coronary-disease patients not involved in surgery or anesthesia. Our findings support the concept that elective surgery should be postponed until the end of the healing stage (three months). Essential surgery performed during the early postinfarction period carried a very high risk. The prognosis following surgery performed after the first 15 days postinfarction was significantly improved.
Characteristics of Hodgkin's Lymphoma after Infectious Mononucleosis
Authors: Henrik Hjalgrim, Johan Askling, Klaus Rostgaard, Stephen Hamilton-Dutoit, Morten Frisch, Jin-Song Zhang, Mette Madsen, Nils Rosdahl, Helle Bossen Konradsen, Hans H. Storm, Mads Melbye
Journal: New England Journal of Medicine (2003)

Infectious mononucleosis-related Epstein-Barr virus (EBV) infection has been associated with an increased risk of Hodgkin's lymphoma in young adults. Whether the association is causal remains unclear.We compared the incidence rates of Hodgkin's lymphoma in two population-based Danish cohorts of patients who were tested for infectious mononucleosis: 17,045 with serologic evidence of having had acute EBV infection, and 24,614 with no such evidence. We combined the cohort of patients who had serologically verified infectious mononucleosis with a cohort of 21,510 Swedish patients with infectious mononucleosis (combined total, 38,555). Biopsy specimens of Hodgkin's lymphomas occurring during follow-up in this combined cohort were tested serologically for the presence of EBV. Using this information, we modeled the relative risk of EBV-negative and EBV-positive Hodgkin's lymphoma in different periods after the diagnosis of infectious mononucleosis and estimated the median incubation time for mononucleosis-related EBV-positive Hodgkin's lymphoma.Only serologically confirmed infectious mononucleosis was associated with a persistently increased risk of Hodgkin's lymphoma. Sixteen of 29 tumors (55 percent), obtained from patients with infectious mononucleosis, had evidence of EBV. There was no evidence of an increased risk of EBV-negative Hodgkin's lymphoma after infectious mononucleosis. In contrast, the risk of EBV-positive Hodgkin's lymphoma was significantly increased (relative risk, 4.0; 95 percent confidence interval, 3.4 to 4.5). The estimated median incubation time from mononucleosis to EBV-positive Hodgkin's lymphoma was 4.1 years (95 percent confidence interval, 1.8 to 8.3).A causal association between infectious mononucleosis-related EBV infection and the EBV-positive subgroup of Hodgkin's lymphomas is likely in young adults.
The Patient Package Insert
Authors: Richard Dorsey
Journal: JAMA (1977)

ON MARCH 31, 1975, a group of consumer organizations petitioned the Food and Drug Administration to require that written warning information be provided to patients along with certain prescription drugs. The stated rationale was that physicians fail to inform their patients adequately about drug effects or that patients fail to comprehend or remember these warnings. Meetings were subsequently held by the FDA with a number of professional associations, including the American Medical Association. On Nov 7, 1975, the FDA published a<i>Federal Register</i>notice requesting comments on the "Patient Prescription Drug Labeling Project."1 Legislation introduced in both Houses during the last session of Congress advocated the patient package insert (PPI) concept, and similar bills introduced during the current session retain the same provision. Thus, while some Washingtonians are advocating the PPI as "an idea whose time has come," one could say more fairly that the time for close scrutiny of
Immunoglobulin E Signal Inhibition during Allergen Ingestion Leads to Reversal of Established Food Allergy and Induction of Regulatory T Cells
Authors: Oliver T. Burton, Magali Noval Rivas, Joseph S. Zhou, Stephanie L. Logsdon, Alanna R. Darling, Kyle J. Koleoglou, Axel Roers, Hani Houshyar, Michael A. Crackower, Talal A. Chatila, Hans C. Oettgen
Journal: Immunity (2014)