tbuckley/cabot-search huggingface dataset:
TCT-36 Circumferential distribution of the neointima tissue at 6 months and 2 at years follow-up after a bioresorbable scaffold implantation. A serial optical coherence tomography study
Authors: Christos Bourantas, Vasim Farooq, Hector M. Garcia-Garcia, Yoshinobu Onuma, Patrick Serruys, Yaojun Zhang
Journal: Journal of the American College of Cardiology (2012)
Platelet C1- inhibitor. A secreted alpha-granule protein.
Authors: A H Schmaier, P M Smith, R W Colman
Journal: Journal of Clinical Investigation (1985)

In order to characterize which proteins of the contact phase of coagulation interact with platelets, human platelets were studied immunochemically and functionally to determine if they contain C1- inhibitor. By means of monospecific antibody to C1- inhibitor, a competitive enzyme-linked immunosorbent assay (CELISA) was developed to measure directly platelet C1- inhibitor. With the CELISA, from 33 to 115 ng of C1- inhibitor antigen per 10(8) platelets from 15 normal donors was quantified in lysates of washed human platelets solubilized in nonionic detergent. The mean concentration in 10(8) platelets was 62 +/- 33 ng (SD). Plasma C1- inhibitor either in the platelet suspension medium or on the surface of the platelets could account for only from 6.5 to 16% of the total antigen measured in the solubilized platelets. Upon functional studies, platelets contained 84 +/- 36 ng (SD) of C1- inhibitor activity in 10(8) platelets. As assessed by the CELISA, platelet C1- inhibitor antigen was immunochemically identical to plasma and purified C1- inhibitor. In contrast, the mean concentration of platelet C1- inhibitor antigen in platelets from four patients with classical hereditary angioedema was 8.3 ng/10(8) platelets (range, 5.3 to 11.3 ng/10(8) platelets). 25 and 31% of the total platelet C1- inhibitor was secreted without cell lysis from normal platelets after exposure to collagen (20 micrograms/ml) and thrombin (1 U/ml), respectively, and this secretion was blocked by metabolic inhibitors. Platelet subcellular fractionation showed that platelet C1- inhibitor resided mostly in alpha-granules, similar to the location of platelet fibrinogen. Thus, human platelets contained C1- inhibitor, which became available by platelet secretion. The identification of platelet C1- inhibitor suggests that platelets may modulate the activation of the proteins of early blood coagulation and the classical complement pathways.
Transport of Gentamicin Into Synovial Fluid
Authors: Denver C. Marsh
Journal: JAMA (1974)

RAPID transport of antibiotics into the synovial space is critical in the treatment of septic arthritis. Most antibiotics have been studied,<sup>1</sup>with the exception of the aminoglycoside, gentamicin sulfate. We have had the opportunity to study the transport of this agent into the synovial cavity in a patient with<i>Serratia marcescens</i>arthritis. Our findings demonstrate that gentamicin rapidly gains entrance into synovial fluid and reaches concentrations approaching those in serum. <h3>Report of a Case</h3> A 57-year-old white male farmer with a 30-year history of ankylosing spondylitis was hospitalized at the Bexar County Hospital for care of quadriplegia caused by trauma to his fused cervical spine. The patient was immobilized and treated initially with dexamethasone, 4 mg administered intravenously every six hours, to reduce cervical cord edema. On the 36th hospital day he developed a temperature of 38.9 C (102 F), and urine and blood cultures were obtained.<i>Serratia marcescens</i>
The Chronic Sequelae of Non-A, Non-B Hepatitis
Authors: M. BERMAN
Journal: Annals of Internal Medicine (1979)

Twenty-six of 388 patients (6.7%) followed prospectively after open-heart surgery developed non-A, non-B hepatitis. Of these 26,12 had an elevated (often fluctuating) serum alanine aminotransferase (SGPT) for greater than 1 year. Liver biopsy, done in eight of 12, showed chronic active hepatitis in six and chronic persistent hepatitis in two; one patient with chronic active hepatitis had early cirrhosis. Anicteric patients with peak SGPT greater then 300 IU/L were at greatest risk of developing chronic hepatitis. Chronic non-A, non-B hepatitis was symptomatically mild and unaccompanied by physical signs or laboratory evidence of autoimmune disease or severe chronic liver disease. In all 12 patients there was spontaneous improvement in serum transaminase over a period of 1 to 3 years, and four patients had sustained normalization of SGPT. Thus chronic active hepatitis is a common sequela of acute non-A, non-B hepatitis but may have a better prognosis than chronic active hepatitis of other causes.
Studies in porphyria. IV. Expression of the gene defect of acute intermittent porphyria in cultured human skin fibroblasts and amniotic cells: prenatal diagnosis of the porphyric trait.
Authors: S Sassa, G Solish, R D Levere, A Kappas
Journal: The Journal of Experimental Medicine (1975)

The gene lesion of the porphyrin-heme synthetic pathway in acute intermittent porphyria (AIP) is reflected in a deficient level of activity of the cytosol enzyme uroporphyrinogen I synthetase (URO-S). A marked URO-S deficiency has been demonstrated in the liver and in circulating erythrocytes of individuals with both active and latent AIP. This enzymic abnormality accounts for the excessive production and excretion into urine of the porphyrin precursors, lamda-aminolevulinic acid (ALA) and porphobilinogen (PBG) in AIP subjects. In this study, utilizing cell culture techniques, a marked URO-S deficiency has also been demonstrated in skin fibroblasts from AIP patients and in cells derived through aminocentesis from an approximately 17-wk old fetus. The prenatal diagnosis of the AIP trait in this fetus was confirmed postnatally by the demonstration in the child of a deficient level of erythrocyte URO-S activity which was comparable to those found in her AIP mother and affected sibling and which was approximately one-half the levels characterizing her normal father and aunt and a second unaffected sibling. The identification of the URO-S deficiency in cultured human fibroblasts from AIP patients was facilitated by a newly developed, sensitive assay for the enzyme activity. In this assay, the ability of such cells to convert ALA to protoporphyrin was quantitated; in the sequence of reactions involved in this transformation, URO-S is limiting so that the gene defect of AIP could be simply and precisely determined by appropriate spectrofluorometry of cell extracts. The technique described has distinct advantages over the direct enzymatic assay for URO-S activity in cultured human skin fibroblasts and permits clear differentiation of AIP carrier from normal individuals.
Multiple Combination Bactericidal Antibiotic Testing for Patients with Cystic Fibrosis Infected with <i>Burkholderia cepacia</i>
Authors: SHAWN D. AARON, WENDY FERRIS, DEBORAH A. HENRY, DAVID P. SPEERT, NONI E. MacDONALD
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Most Burkholderia cepacia strains are resistant to many, or all, of the antibacterial agents commonly used in cystic fibrosis (CF), and selection of appropriate antibiotics for treatment of pulmonary exacerbations is therefore difficult. We developed a technique for rapid in vitro testing of multiple antibiotic combinations for B. cepacia isolates. For each of 119 multi-drug-resistant isolates of B. cepacia, our multiple combination bactericidal test (MCBT) studied the bactericidal activity of 10 to 15 antimicrobial agents using 225 ± 97 single, double, and triple antibiotic combinations. Of the 119 isolates, 50% were resistant to all single antibiotics tested, 8% were resistant to all two-drug antibiotic combinations, but all were inhibited by at least one bactericidal triple-drug combination. When used alone, meropenem, ceftazidime and high-dose tobramycin (200 μ g/ml) were bactericidal against only 47, 15, and 14% of in vitro isolates, respectively. Using a double antibiotic combination improved bactericidal activity; meropenem-minocycline, meropenem-amikacin, and meropenem-ceftazidime combinations were bactericidal against 76, 73, and 73% of isolates, respectively. However, 47% of isolates demonstrated antagonism (growth of an organism when a second antibiotic was added to a bactericidal single antibiotic). Triple antibiotic combinations that contained tobramycin, meropenem, and an additional antibiotic were most effective, and were bactericidal against 81 to 93% of isolates. We conclude that triple-antibiotic combinations are more likely than double and single antibiotic combinations to be bactericidal against B. cepacia in vitro. MCBT testing is a useful technique to help clinicians decide on appropriate nonantagonistic combination antibiotic therapy for patients with CF infected with B. cepacia.
Glasgow Medical Women 1951-4: Their Contribution and Attitude to Medical Work
Authors: M. C. Timbury, M. A. Ratzer
Journal: BMJ (1969)

A questionary sent to 137 women who qualified in Glasgow during 1951–4 showed that of the 106 respondents 24% of the married women were unemployed and only 31% were working full-time. The married women had fewer qualifications than a matched group of male contemporaries, and fewer of those in hospital work were consultants. The married women in full-time work had fewer children and showed some differences in their background compared with those working part-time or unemployed. Most part-time workers were satisfied with their present posts and did not wish to work more.
Bone Mineral Density After Resumption of Menses in Amenorrheic Athletes
Authors: Barbara L. Drinkwater
Journal: JAMA (1986)

Amenorrheic athletes have been found to have a lower vertebral bone mineral density (BMD) than matched groups of eumenorrheic athletes. This study reports changes in BMD over a 15.5-month period in athletes who regained menses, athletes who remained amenorrheic, and athletes with regular cycles. The BMD was measured at two sites on the radius and at the lumbar vertebrae (L-1 through L-4), using single- and dual-photon densitometry, respectively. Changes in vertebral BMD were significant for the amenorrheic group (+6.3%), but not for cyclic women (—0.3%). A slight increase in radial density at S-1 and S-2 was not significant for either group. Two athletes who remained amenorrheic during this period continued to lose bone (—3.4%). We conclude that resumption of menses was the primary factor for the significant increase in the vertebral BMD of the formerly amenorrheic athletes. (<i>JAMA</i>1986;256:380-382)
Surveillance Intervals after Colonoscopic Polypectomy
Authors: J.D. Waye, S. Braunfeld
Journal: Endoscopy (1982)

Two hundred and twenty seven patients had multiple follow-up total colonoscopies after initial endoscopic polypectomy. All adenomas were removed at the initial examination ('clean colon') in those patients who had no history of colon cancer, inflammatory bowel disease or polyposis coli; when re-endoscoped within one year 56% of them were found to have further adenomas. Nine percent had adenomas over 10 mm diameter which are presumed to have been missed during the index colonoscopy. Patients with single or multiple adenomas had an equal likelihood of being found to have further lesions on a one-year follow-up colonoscopy. With an apparent chance of missing a significant-size polyp at colonoscopy of at least 10% we recommend that all patients have a follow-up colonoscopy within one year after polypectomy. 133 Patients in whom no adenomas were found at the one year colonoscopy ('negative colonoscopy') were followed up. The incidence of new adenomas occurring within four years of 'negative colonoscopy' was 35% for those with a single adenoma at the index examination and twice as high for patients with multiple adenomas. If no polyp is found at one year, we recommend that interval follow-up colonoscopies should be performed every two years if more than one adenoma was removed during the initial examination, and every three years if only one was removed.
ECG Abnormalities And the Barium Enema
Authors: Ronald A. Andree
Journal: JAMA (1972)

<h3>To the Editor.—</h3> I was very interested to see the paper by Gregory L. Eastwood on ECG abnormalities associated with barium enema in the Feb 7,1972 issue ofThe JournalThis is because his observations have confirmed one of my pet clinical impressions. Often, when called upon by my surgical colleagues to render an opinion concerning the fitness of an aged patient for anesthesia, I take particular note of the radiologic procedures he has had. From noting his survival without complications of one or more barium enemas within the not-too-distant past, I think one can gain a crude assessment of the patient's ability to tolerate the stresses we impose upon him during the induction of an anesthetic—a period which is likewise fraught with a high incidence of cardiac arrhythmias.
Expression and localization of endothelin-1 and endothelin receptors in human meningiomas. Evidence for a role in tumoral growth.
Authors: U Pagotto, T Arzberger, U Hopfner, J Sauer, U Renner, C J Newton, M Lange, E Uhl, A Weindl, G K Stalla
Journal: Journal of Clinical Investigation (1995)

In addition to its well-known homoeostatic actions in the cardiovascular system, ET-1 has been shown to constitute a potent growth regulatory peptide in various tissues. We have studied the expression of ET-1 and its receptors (ET-Ar and ET-Br) in human meningiomas (n = 35) as well as their involvement in cellular growth. By PCR of reverse-transcribed RNA we detected ET-1 mRNA in 91% (32 of 35), ET-Ar mRNA in 82% (29 of 35), and ET-Br mRNA in 42% (15 of 35) of human meningiomas examined. The localization of ET-1 mRNA, ET-Ar mRNA, and ET-1 peptide in tumoral cells was observed by in situ hybridization and immunohistochemistry, whereas ET-Br mRNA was expressed at low level only in cells belonging to blood vessels. In addition, we found that ET-1 stimulated [3H] thymidine incorporation in primary cell cultures of 20 meningiomas and that this effect could be blocked by BQ-123, a specific antagonist for ET-Ar. In contrast, RES-701-3, an antagonist of ET-Br, did not block the proliferative effect of ET-1. In conclusion, our data provide evidence that ET-1 constitutes an important growth factor for meningiomas acting via ET-Ar. We can hypothesize that ET-1, acting in concert with other growth factors and cytokines, is involved in the meningioma tumorigenesis.
Innovation in the pharmaceutical industry
Authors: R Sykes
Journal: BMJ (1994)

The pharmaceutical industry today is operating in an environment whose main feature is an unprecedented pace of change. In most markets the rising costs of health care are of increasing concern, and the medicines bill is being targeted for savings. New constraints are limiting the medicines that can be used and paid for in the system. In the United States health maintenance organisations use formularies, while European governments are resorting to various measures to control the pricing and prescribing of medicines and are increasing the range of medicines available over the counter. Medical practice is also changing for demographic reasons, and the health problems of elderly people are attracting increasing attention.

Drug regulation is both costly and time consuming, particularly in the clinical phases. Now, in addition to the stringent demands for safety and efficacy, the need to show the economic benefits of a new medicine is increasingly emphasised. Although these changes may well sink some pharmaceutical companies, they should be seen as challenges to be met to ensure the future of both the industry and the communities who benefit from its activities. Undoubtedly, the pharmaceutical industry's future success will depend on innovative medicines that meet unmet clinical needs and provide genuine therapeutic advance.

Fortunately, other …
Cyclosporin A levels in suction-blister fluid of patients with psoriasis treated systemically
Authors: M.M.H.M. MEINARDI, J.P. EENDENBURG, J. OOSTING, C.J. BOXTEL, M.A. RIE, J.D. BOS
Journal: British Journal of Dermatology (1990)

Oral cyclosporin A (CyA) is highly effective in the treatment of psoriasis. The long-term use is limited by dose-dependent side-effects, and the local concentration of CyA is a determining factor in treatment. The concentration of CyA in suction-blister fluid (SBF) and in whole blood was assessed using a polyclonal radioimmunoassay (RIA). This was carried out in patients with psoriasis following a single dose of CyA and while on adequate oral treatment with the drug. Peak blister fluid levels ranged from 32 to 170 ng/ml, and whole blood levels from 1250 to 2540 ng/ml. CyA trough levels (12 h following taking the drug) in the blister fluid ranged from 22 to 113 ng/ml, and in whole blood from 148 to 935 ng/ml. The trough concentrations in SBF were approximately 10% of whole blood trough levels.
Abstract IA6: Genetic strategies for next generation of breast cancer therapies
Authors: Jose M. Silva
Journal: Cancer Research (2012)

Abstract One of the major challenges for modern cancer treatments is the ability to eliminate tumor cells without affecting normal cell homeostasis. We propose to identify the “Achilles' heel” of cancer cells using the novel concept of the “noncancer addition.” Additionally to alterations in bona-fide cancer genes, in a tumor cell, multiple normal regulatory networks have been rearranged in order to adapt to the tumorigenic state. As consequence of this divergence, survival of cancer cells also depends on noncancer genes that are essential to maintain the tumor homeostasis. Therefore, we postulate that interfering with these noncancer dependencies will result in system failure, that is, the cessation of the tumorigenic state. We are combining the power of interactome-prediction models with the state-of-the-art RNAi-genetic approaches to block the function of every gene in the entire genome to find genetic synthetic lethal interactions between noncancer genes and bona-fide cancer genes. Recently, we have applied this strategy searching for novel therapeutic alternatives for ErbB2 positive breast cancer patients. ErbB2 is a receptor tyrosine kinase found overexpressed in 20-40% of breast tumors (ErbB2+ tumors) and correlates with poor prognosis. Different targeted therapies have been developed to specifically inhibit its activity. Unfortunately, the majority of these patient tumors eventually progress acquiring resistance. Thus, there is the need to find alternative tumor targets to develop specific, more efficient, treatments for these patients. By combining genome-wide RNAi loss-of-function screens with system biology interactome models we have recently found that the JAK/STAT3 pathway is activated in ErbB2 overexpressing breast cancers through an autocrine loop mediated by the secretion of Interleukin-6 (IL-6). Importantly, blockage of this pathway strongly reduced the viability of ErbB2+ cancer cells. The identification of Stat3 as a tumor target in ErbB2+ tumors opens new avenues for patients which tumors have become refractory to standard protocols. Citation Format: Jose M. Silva. Genetic strategies for next generation of breast cancer therapies [abstract]. In: Proceedings of the AACR Special Conference on Chemical Systems Biology: Assembling and Interrogating Computational Models of the Cancer Cell by Chemical Perturbations; 2012 Jun 27-30; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2012;72(13 Suppl):Abstract nr IA6.
In the Face of Uncertainty About the Risks of Low-Level Drinking, Abstinence Is Prudent, Not Misogynistic, Advice
Authors: Brad Partridge, Jayne Lucke, Wayne Hall
Journal: The American Journal of Bioethics (2011)

"In the Face of Uncertainty About the Risks of Low-Level Drinking, Abstinence Is Prudent, Not Misogynistic, Advice." The American Journal of Bioethics, 11(12), pp. 66–67
The NAD+ Precursor Nicotinamide Riboside Enhances Oxidative Metabolism and Protects against High-Fat Diet-Induced Obesity
Authors: Carles Cantó, Riekelt H. Houtkooper, Eija Pirinen, Dou Y. Youn, Maaike H. Oosterveer, Yana Cen, Pablo J. Fernandez-Marcos, Hiroyasu Yamamoto, Pénélope A. Andreux, Philippe Cettour-Rose, Karl Gademann, Chris Rinsch, Kristina Schoonjans, Anthony A. Sauve, Johan Auwerx
Journal: Cell Metabolism (2012)
AB0217 Biomarkers of Inflammation in Juvenile Idiopathic Arthritis (JIA)
Authors: J. Brunner, T. Giner, G. Weiss, D. Fuchs
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Juvenile idiopathic arthritis (JIA) is a relevant autoimmune disease in children. T cells, B cells, and damage-associated molecular patterns (DAMPS) are involved in the pathogenesis of the disease. Biomarkers for JIA and its subtypes are not established. Pro-inflammatory pathways activate enzyme indoleamine 2,3-dioxygenase (IDO) which enhances tryptophan (Trp) conversion to kynurenine (Kyn). Thus, in conditions of chronic immune activation reduced Trp availability and production of Kyn and its down-stream metabolites may inhibit cell proliferation. In rheumatoid arthritis (RA) Trp concentrations are lower in patients than in controls and the Kyn/Trp ratios are higher and correlate with neopterin concentrations [1-3]. <h3>Objectives</h3> To evaluate Tryptophan as Biomarker in JIA <h3>Methods</h3> In this study, Trp and Kyn metabolism was investigated in children with JIA and compared to serum neopterin concentrations. Fifty-four sera of 25 JIA patients and 10 samples of synovial fluid were examined with HPLC (Trp and Kyn) and Elisa (Neopterin, BRAHMS, Hennigsdorf, Germany). Eighteen sera from 18 children with non-inflammatory diseases were used as controls. <h3>Results</h3> Trp in the sera of patients was mean 57.2 + SD 19.0 μmol/L and Kyn was mean 2.40 + SD 0.81 μmol/L). Serum neopterin was 5.69 + SD 1.72 nmol/L. In the synovial fluid, neopterin was mean 10.5 + SD 7.41 nmol/L), Trp was 36.7 + SD 17.4 μmol/L and Kyn was 2.13 + SD 0.75 μmol/L). In control patients, neopterin was 6.93 + SD 3.10), Trp was 57.6 + SD 14.8) and Kyn was 2.60 + SD 1.60 μmol/L. <h3>Conclusions</h3> Serum Trp concentrations showed no relevant difference in JIA patients vs. controls. IDO activity reduces Trp primarily in the synovial fluid in JIA patients. <h3>References</h3> Schroecksnadel K, et al. Increased degradation of tryptophan in blood of patients with rheumatoid arthritis. J Rheumatol 2003;30:1935-9. Fagerer N. et al. Expression of neopterin and chemokines in rheumatoid arthritis and cardiovascular disease. Pteridines 2011;22:7-12. Kurz K, et al. Effects of adalimumab therapy on disease activity and interferon-γ-mediated biochemical pathways in patients with rheumatoid arthritis. Autoimmunity 2011;44:235-42. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4864
Telling Him He Has Cancer of the Lung
Authors: Eric L. Dyer
Journal: Annals of Internal Medicine (1997)

Ad Libitum15 January 1997Telling Him He Has Cancer of the LungEric L. Dyer, MDEric L. Dyer, MDNashville, TN 37203Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-126-2-199701150-00002 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail sculpting the pink cloud in ... Author, Article, and Disclosure InformationAffiliations: Nashville, TN 37203Corresponding Author: Eric L. Dyer, MD, Suite 500, 2400 Patterson Street, Nashville, TN 37203. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 January 1997Volume 126, Issue 2Page: 106KeywordsLung and intrathoracic tumorsThorax Issue Published: 15 January 1997 Copyright & PermissionsCopyright © 1997 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...