tbuckley/cabot-search huggingface dataset:
ICAM-1 and VCAM-1 antisense oligonucleotides attenuate in vivo leucocyte adherence and inflammation in rat inflammatory bowel disease
Authors: E Rijcken
Journal: Gut (2002)

<b>Background:</b> Recruitment of circulating cells to the inflamed intestine is modulated by adhesion molecules expressed on the surface of both leucocytes and endothelial cells. <b>Aims:</b> The objective of this study was to test whether 2`-O-methoxyethyl chimeric antisense oligonucleotides directed against endothelial intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) can downregulate leucocyte-endothelial interactions and thereby attenuate inflammation in rat experimental ileitis. <b>Methods:</b> Indomethacin (7.5 mg/kg ) was injected subcutaneously into Sprague-Dawley rats 48 and 24 hours prior to intravital microscopy. Animals were treated with either ICAM-1 (ISIS 17470), VCAM-1 (ISIS 18155), or scrambled control antisense oligonucleotides administered subcutaneously or intravenously in parallel with indomethacin. Leucocyte trafficking was observed in ileal submucosal collecting venules. Macroscopic and histological grades of inflammation were measured 48 hours after the first indomethacin application. ICAM-1 and VCAM-1 expression in ileal submucosal venules was detected by immunohistochemistry. <b>Results:</b> Intravenous administration of ICAM-1 oligonucleotides 2 mg/kg (rolling leucocytes 5.7 (2.4)/0.01 mm<sup>2</sup> endothelial surface, adherent leucocytes 0.8 (1.1)) and VCAM-1 oligonucleotides 8 mg/kg (9.2 (4.4), 0.6 (0.8)) significantly reduced leucocyte adhesion compared with diseased controls (27.8 (5.3), 14 (4.4)) in a dose dependent manner whereas subcutaneous treatment did not. Correspondingly, macroscopic and histological inflammation was significantly decreased. ICAM-1 oligonucleotides markedly reduced endothelial ICAM-1 expression while VCAM-1 oligonucleotides clearly diminished endothelial VCAM-1 expression. <b>Conclusions:</b> Both ICAM-1 and VCAM-1 2`-O-methoxyethyl chimeric antisense oligonucleotides attenuate rat ileitis by downregulation of leucocyte adherence and thus are potential candidates for anti-inflammatory treatment in inflammatory bowel disease.
P53 The utility of PET-CT in detecting non-nodal extrathoracic metastases in lung cancer compared to the staging CT
Authors: JSZ Lee, KM Bradley, FV Gleeson
Journal: Thorax (2013)

<h3>Background</h3> NICE Lung Cancer Guidelines 2011 recommend performing a PET-CT in patients being considered for radical treatment after a staging CT of the neck, chest and liver has been performed. If mediastinal lymphadenopathy is detected by CT and the aetiology is determined by intervention, the true value of PET-CT is in the detection of non-nodal extrathoracic metastases. The yield of PET-CT in detecting non-nodal extrathoracic metastases has not previously been reported in comparison to that of reviewing the prior staging CT. <h3>Methods</h3> 235 consecutive lung cancer patients with no known extrathoracic metastases referred for a staging PET-CT scan prior to radical therapy were included. All patients underwent a contrast-enhanced CT of the neck, chest and liver and a whole body PET-CT. <h3>Results</h3> The median age at diagnosis was 72 years, 141 men (60%). Patients had stage Ia (16%), Ib (19%), IIa (6%), IIb (7%), IIIa (25%), IIIb (6%) and IV (20%) disease. The median interval between the CT and PET-CT scans was 25 days (IQR, 18 29). 21 (9%) patients had 25 extrathoracic and extra-cerebral metastases. 9 metastases were identified on the CT component of the PET-CT and review of the prior staging CT. 16 metastases were not visible on the staging CT scan; 4 (humeral and pelvic) bone metastases were outside the staging CT field of view, 6 metastases had developed since referral (median scan interval 28 days; IQR, 19 39), and 6 were only identified on PET-CT. <h3>Conclusion</h3> The addition of pelvic CT in patients referred for PET-CT staging prior to radical therapy may allow for increased detection of extrathoracic metastases. PET-CT detects extrathoracic metastases which were missed or invisible on the staging CT. Lung cancer patients should be offered a contrast-enhanced CT of the neck, chest, abdomen and pelvis at staging. Potentially, an interval CT scan should be performed if a delay of greater than 30 days has occurred prior to the PET-CT scan being performed.
Inhibition of Bone Matrix Formation, Mineralization, and Resorption in Thyroparathyroidectomized Rats
Authors: J. Wergedal, M. Stauffer, D. Baylink, C. Rich
Journal: Journal of Clinical Investigation (1973)

In previous work we found that vitamin D-deficient and also calcium-deficient rats developed hypocalcemia and an impairment of bone formation and mineralization. The present study of thyroparathyroidectomized (TPTX) rats was undertaken to determine the effect of hypocalcemia without secondary hyperparathyroidism. TPTX rats fed a normal diet developed hypocalcemia and hyperphosphatemia in association with impairment of osteoblastic bone matrix formation and of mineralization of newly formed matrix. The serum calcium × phosphorus product was not decreased. The decreased formation was largely due to a reduction in matrix apposition indicating decreased synthetic activity of individual ostcoblasts. In contrast to the above results, when TPTX rats were fed a high-calcium diet to prevent hypocalcemia, no impairment of either formation or mineralization was found. From the results of these two experiments, it is reasonably certain that hypocalcemia was responsible for the inhibition of formation and mineralization. Moreover, based on the magnitude of the changes in serum calcium and bone parameters in TPTX rats, hypocalcemia could have accounted for the inhibition of formation and mineralization in calcium-deficient as well as vitamin D-deficient rats.
A Double-blind, Placebo-Controlled Trial of Desipramine for Primary Alcohol Dependence Stratified on the Presence or Absence of Major Depression
Authors: B J Mason, J H Kocsis, E C Ritvo, R B Cutler
Journal: JAMA (1996)

To assess the use of desipramine for secondary depression in primary alcohol dependence and its effect on abstinence.Randomized, double-blind, placebo-controlled trial, with stratification on the presence of secondary depression.Seventy-one volunteer and referred patients with primary alcohol dependence, abstinent a median of 8 days before randomization. A subset of 28 patients had major depression secondary to alcoholism.The outpatient psychiatry departments of two urban medical centers.Six months of a clinically determined dose of desipramine.Hamilton Depression Rating Scale, and Time Line Follow Back Interview, with breath alcohol concentrations and collateral verification.Hamilton Depression scores of desipramine-treated depressed alcoholics decreased significantly, controlling for baseline Hamilton Depression scores (P=.04). Overall, patients were abstinent significantly longer when receiving desipramine (P=.03). Rates of relapse of depressed vs nondepressed patients, analyzed separately, were not significant, although the survival function approached significance for the depressed subgroup (P=.09). Desipramine-treated depressed patients were more satisfied and were rated as more improved.Major depression secondary to alcohol dependence that is diagnosed after at least 1 week of abstinence can remain stable in some placebo-treated alcoholics and can respond to desipramine. Treating depression secondary to alcoholism may reduce risk for drinking relapse in some patients. Use of desipramine to reduce relapse in nondepressed alcoholics is not supported.
Macrophage-dependent nitric oxide expression regulates tumor cell detachment and metastasis after IL-2/anti-CD40 immunotherapy
Authors: Jonathan M. Weiss, Lisa A. Ridnour, Tim Back, S. Perwez Hussain, Peijun He, Anna E. Maciag, Larry K. Keefer, William J. Murphy, Curtis C. Harris, David A. Wink, Robert H. Wiltrout
Journal: The Journal of Experimental Medicine (2010)

Using an orthotopic model of renal cell carcinoma, we showed previously that IL-2/anti-CD40 immunotherapy resulted in synergistic anti-tumor responses, whereas IL-2 or α-CD40 alone mediated partial transient anti-tumor effects. We now show that treatment of tumor-bearing mice with IL-2/α-CD40, but not IL-2 or α-CD40, induced significant nitric oxide synthase (NOS) 2 expression in tumor-associated macrophages. In control-treated mice (low NO), NOS2 inhibition reduced tumor burden. However, during immunotherapy (high NO), NOS2 inhibition or macrophage depletion reversed the ability of IL-2/α-CD40 treatment to reduce lung metastases but had no effect on primary tumor burden. Furthermore, IL-2/α-CD40 induced the IFN-γ– and NO-dependent decrease in matrix metalloproteinase (MMP) expression and activity, concomitant with increases in tissue inhibitor of metalloproteinase (TIMP) 1 and E-cadherin expression within tumors. Finally, treatment of tumor-bearing mice with the NO donor JS-K significantly reduced metastases. These data differentiate the mechanism for primary anti-tumor effects of IL-2/α-CD40 immunotherapy, which are independent of NO, from the NO-dependent inhibition of metastases. Furthermore, reduced MMP9 activity implicates M1-polarized macrophages within the tumor microenvironment as critical components of therapeutic response. Our data demonstrate the mechanistic basis for IL-2/α-CD40–mediated control of metastases and suggest that the context-dependent application of NO donors may hold promise for prevention of metastatic disease.
SURFACE TENSION OF SERUM
Authors: P. Lecomte du Noüy
Journal: The Journal of Experimental Medicine (1924)

The assumption has been made in preceding papers that, at a given concentration of 1:10,000, in the vessels used in our experiments, a monomolecular oriented layer was formed. Such a layer might be supposed to prevent the free escape of water molecules from the surface into the air, at least to a certain extent. In order to check this assumption, the rate of evaporation of solutions of serum at different concentrations was measured. It was found that, under the conditions of the experiments, in a progression of dilutions from 10(-1) to 10(-6), the slowest evaporation took place at a concentration of 1:10,000. In a few cases (less than 20 per cent), evaporation was slower at a different concentration, but always within the same range (between 10(-3) and 10(-5)), not far from 10(-4).
Topotecan Is Active Against Wilms’ Tumor: Results of a Multi-Institutional Phase II Study
Authors: Monika L. Metzger, Clinton F. Stewart, Burgess B. Freeman, Catherine A. Billups, Fredric A. Hoffer, Jianrong Wu, Max J. Coppes, Ronald Grant, Murali Chintagumpala, Elizabeth A. Mullen, Carlos Alvarado, Najat C. Daw, Jeffrey S. Dome
Journal: Journal of Clinical Oncology (2007)

Purpose A phase II study was conducted to evaluate the activity and safety of topotecan in pediatric patients with recurrent Wilms' tumor. Patients and Methods Patients with favorable histology Wilms' tumor (FHWT) and recurrence after at least one salvage chemotherapy regimen or with anaplastic histology Wilms' tumor (AHWT) in first or subsequent recurrence were eligible. Patients were stratified according to histology, with statistical considerations based on the FHWT stratum. Topotecan was administered intravenously over 30 minutes for 5 days on 2 consecutive weeks. Treatment dosages were adjusted to achieve a target area under the curve (AUC) of 80 ± 10 ng/mL*h. Tumor responses were measured after two cycles of treatment. Results Thirty-seven patients (26 patients with FHWT) were enrolled and received a total of 94 cycles of topotecan (range, one to six cycles). The median topotecan dosage required to achieve the target AUC was 1.8 mg/m 2 (range, 0.7 to 3.2 mg/m 2 ). Of 25 assessable patients with FHWT, 12 had partial response (PR), six had stable disease (SD), and seven had progressive disease (PD), for an overall response rate of 48% (95% CI, 27.8% to 68.7%). Of 11 assessable patients with AHWT, two had PR, one had SD, and eight had PD. The main toxicities were grade 3 and 4 neutropenia (median duration, 13 days) and thrombocytopenia (median duration, 7.5 days). Conclusion Topotecan administered on a protracted schedule is active against recurrent FHWT. Inclusion of topotecan in front-line clinical trials for patients with recurrent Wilms' tumor should be considered.
Why have UK doctors been deterred from prescribing Avastin?
Authors: D. Cohen
Journal: BMJ (2015)

Doctors in England's NHS have been left seemingly unable to prescribe a cheap, safe, and effective drug despite its flourishing use elsewhere in Europe and the US. In the first of a two part investigation <b>Deborah Cohen </b>examines which agencies are responsible, whether commissioners and prescribers actually have more freedom to use intravitreal bevacizumab than might at first seem to be the case, and whether the UK's drug marketing authorisation system really acts in the best interests of public health
On a New Double Stethoscope: The Head-Spring Stethoscope
Authors: R. H. Hilliard
Journal: BMJ (1875)

ignited, charcoal-points, and electric heat, all of which either have some disadv'antage or are ineffectual.I believe nitric acid to possess these advantages as a caustic in uterine practice.It requires no special pre- parmition, and is always at hand; it cannot affect the system as may a salt of mercury; it does not spread like potassa cum calce, nor is its ac.tion so deep; it produces little or no pain, and no htemor-rhage.
Comparison of induced sputum with bronchial wash, bronchoalveolar lavage and bronchial biopsies in COPD
Authors: SR Rutgers, W Timens, HF Kaufmann, TW van der Mark, GH Koeter, DS Postma
Journal: European Respiratory Journal (2000)

It is unclear how cellular and soluble inflammatory markers in induced sputum relate to markers in lavage fluid and biopsies in chronic obstructive pulmonary disease (COPD). This was investigated and also the possible differences between subjects with COPD and healthy controls assessed. Eighteen nonatopic subjects with COPD and 11 healthy controls were studied. Sputum was induced by inhalation of hypertonic saline. The airways were lavaged, using the first 50 mL for bronchial wash (BW) and the subsequent 150 mL for bronchoalveolar lavage (BAL), and biopsies were taken from subsegmental carinae. Neutrophils were the predominant cell type in sputum in COPD (median 77.3%) but not in BW (5.5%) and BAL fluid (1.7%). Differential cell counts in sputum did not correlate with the counts in BW or BAL fluid or biopsies, whereas sputum eosinophil cationic protein (ECP) levels correlated with BW fluid ECP levels (p=0.66, p=0.007) and sputum interleukin-8 (IL-8) concentration with BAL fluid IL-8 concentration (p= 0.52, p=0.026). Subjects with COPD had a higher percentage of sputum neutrophils and eosinophils and higher concentrations of ECP and IL-8 than healthy controls. The higher percentages of eosinophils and concentrations of ECP were also seen in BW and BAL fluid. Finally, higher numbers of macrophages and eosinophils were found in biopsies. In conclusion, induced sputum is derived from a different compartment from BW and BAL fluid and biopsies. Induced sputum may be useful for studying the contribution of luminal neutrophils and eosinophils in chronic obstructive pulmonary disease.
Clinical Relevance of a Pharmacogenetic Approach Using Multiple Candidate Genes to Predict Response and Resistance to Imatinib Therapy in Chronic Myeloid Leukemia
Authors: Dong Hwan (Dennis) Kim, Lakshmi Sriharsha, Wei Xu, Suzanne Kamel-Reid, Xiangdong Liu, Katherine Siminovitch, Hans A. Messner, Jeffrey H. Lipton
Journal: Clinical Cancer Research (2009)

Imatinib resistance is major cause of imatinib mesylate (IM) treatment failure in chronic myeloid leukemia (CML) patients. Several cellular and genetic mechanisms of imatinib resistance have been proposed, including amplification and overexpression of the BCR/ABL gene, the tyrosine kinase domain point mutations, and MDR1 gene overexpression.We investigated the impact of 16 single nucleotide polymorphisms (SNP) in five genes potentially associated with pharmacogenetics of IM, namely ABCB1, multidrug resistance 1; ABCG2, breast-cancer resistance protein; CYP3A5, cytochrome P450-3A5; SLC22A1, human organic cation transporter 1; and AGP, alpha1-acid glycoprotein. The DNAs from peripheral blood samples in 229 patients were genotyped.The GG genotype in ABCG2 (rs2231137), AA genotype in CYP3A5 (rs776746), and advanced stage were significantly associated with poor response to IM especially for major or complete cytogenetic response, whereas the GG genotype at SLC22A1 (rs683369) and advanced stage correlated with high rate of loss of response or treatment failure to IM therapy.We showed that the treatment outcomes of imatinib therapy could be predicted using a novel, multiple candidate gene approach based on the pharmacogenetics of IM.
Autoimmunity and Pregnancy Loss
Authors: D. Ware Branch
Journal: JAMA (1990)

The spontaneous loss of a clinically recognized pregnancy is the most common complication of human gestation and is a significant emotional disappointment for the involved couple. Recurrent pregnancy loss (traditionally defined as three consecutive losses) occurs in 0.5% to 1% of women, an incidence equal to or exceeding that of most major medical problems. Genetic, anatomic, hormonal, and infectious factors have each been implicated as causing some spontaneous abortion, but even when taken together they do not explain the majority of losses. Within the last 10 years several maternal autoimmune conditions have been linked to pregnancy loss. Although these autoimmune conditions do not appear to explain a large proportion of losses, they are as important numerically as uterine malformations and parental chromosome abnormalities. A few maternal autoimmune conditions cause pregnancy loss through the transplacental passage of maternal autoantibodies that act on the fetus through classic autoantibody-mediated mechanisms. The best example
Alternative-Site Blood Glucose Measurement at the Abdomen
Authors: Paul R. van der Valk, Irene van der Schatte Olivier-Steding, Klaas-Jan C. Wientjes, Adelbert J. Schoonen, Klaas Hoogenberg
Journal: Diabetes Care (2002)

Alternative sites for self-monitoring of blood glucose (SMBG) (e.g., forearm, abdomen, calf, or thigh) are currently being introduced in clinical practice (1). However, blood glucose (BG) concentrations by these methods may differ from those by traditional fingertip pricking (2–4). In an elegant study, Jungheim and Koschinski (3) demonstrated that BG measurements, at the forearm by three commercially available devices, showed a less steep increase after an oral glucose load and a delayed decline after insulin administration. In addition, Ellison et al. (4) showed similar findings, which were less adequately followed at the forearm after a standardized meal.

Given the patients’ preference for alternative-site SMBG, an appreciation mainly based on the avoidance of painful fingertip pricking (1), clinical application will certainly ensue and, thereby, will introduce a new …
Managed Care and Oncology: The Quality Debate
Authors: Joseph Bailes
Journal: Journal of Clinical Oncology (2000)

Article Tools EDITORIAL Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2000.18.4.705 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 10673510 Managed Care and Oncology: The Quality Debate Joseph Bailes, MDxJoseph BailesSearch for articles by this author Show More President, American Society of Clinical Oncology https://doi.org/10.1200/JCO.2000.18.4.705 First Page Full Text PDF Figures and Tables © 2000 by American Society of Clinical Oncology
Dietary supplements and asthma: another one bites the dust
Authors: J. Feary, J. Britton
Journal: Thorax (2007)

is evidence that tissue neutrophilia is more frequent in severe asthma. 22espite these unavoidable limitations, the report by Qiu et al is important because it promotes a better understanding of the events contributing to the development of severe exacerbations.Indeed, this study provides the framework for the cellular changes occurring in the airway tissue and the molecular mechanisms responsible for inflammatory cell recruitment.As a consequence, these observations will encourage new research into therapeutic strategies to prevent exacerbations, one of the most important aims of asthma management.
A very strange tail
Authors: Ambika Talwar, Anne McGown, Tracy Langham, Muhammad Abid, John Pilling
Journal: Thorax (2014)

A young couple both presented in the autumn of 2013 with a protracted flu-like illness, right-sided pleuritic chest pain and night sweats. Neither had any significant past illnesses nor had they travelled abroad recently.

Patient X (aged 18 years) was systemically well with no extrapulmonary abnormalities on examination. Her C-reactive protein was elevated at 46 with a normal white cell count and negative blood cultures. She was not immunocompromised. Chest X-ray and thoracic ultrasound revealed a small right-sided pleural effusion. She was extremely needle phobic, and so pleural aspiration was not performed. She was treated for pneumonia with a 4-week course of oral antibiotics and clinically improved.

Patient Y (aged 20 years) presented to chest clinic 1 month later. On examination, he was septic. Chest X-ray, thoracic ultrasound and pleural aspiration confirmed that he had a right-sided empyema. He was admitted and treated with intravenous antibiotics and an intercostal …
Sites of action and active forms of lidocaine and some derivatives on cardiac Purkinje fibers.
Authors: J I Gliklich, B F Hoffman
Journal: Circulation Research (1978)

We have compared the effects of lidocaine (L) to those of several derivatives in an attempt to determine the sites of action and active forms of the molecules. We studied cardiac Purkinje fibers with intracellular microelectrodes, and drugs were administered by superfusion or by iontophoretic intracellular injection. We compared to L the effects of QX-314 and QX-572, two quaternary derivatives, and also compound 6603, a tertiary analogue with a pKa of 9.81. When administered by superfusion in concentrations of 10(-5) and 10(-4) M, all four agents exerted qualitatively similar effects on the transmembrane action potential. The rate of onset of action of the quaternary derivatives was considerably slower than that of L and their actions were not reversed by superfusion for 1 hour with drug-free solution. Comparison of effects of L and QX-314 after intracellular injection showed that attenuation of Vmax, and thus of the fast inward current, results from interaction of the charged form acting form acting from the inner surface of the sarcolemma. After intracellular injection, QX-314 diffused readily along the long axis of fiber bundles, and it was thus possible to expose the inner surface of a large number of contiguous cells to drug. Comparison of results of extracellular and intracellular application suggests that effects on the voltate during phase 2 result from the charged form acting from the inner surface, but effects on total action potential duration result only from drug acting from the outer surface of the sarcolemma. Unlike L, the three derivatives did not decrease the slope of normal phase 4 depolarization. The results may help relate antiarrhythmic action to specific effects on transmembrane potentials.