tbuckley/cabot-search huggingface dataset:
Highly Active Antiretroviral Therapy in a Large Urban Clinic: Risk Factors for Virologic Failure and Adverse Drug Reactions
Authors: Gregory M. Lucas, Richard E. Chaisson, Richard D. Moore
Journal: Annals of Internal Medicine (1999)

Background: In clinical trials, highly active antiretroviral therapy (HAART) reduces plasma HIV-1 RNA levels to less than 500 copies/mL in 60% to 90% of patients with HIV-1 infection. The performance of such therapy outside of the clinical trial setting is unclear. Objective: To determine factors associated with failure to suppress HIV-1 RNA levels and adverse drug reactions in a cohort of patients in whom protease inhibitor-containing therapy was begun in a large urban clinic. Design: Retrospective cohort study. Setting: Johns Hopkins HIV Clinic in Baltimore, Maryland. Patients: 273 protease inhibitor-naive patients began taking a protease inhibitor regimen containing at least one other antiretroviral drug to which the patients had not previously been exposed. Measurements: Demographic variables, plasma HIV-1 RNA levels, CD4+ lymphocyte counts, and adverse drug reactions. Results: Levels of HIV-1 RNA were undetectable in 42% of the cohort at 1 to 90 days, in 44% at 3 to 7 months, and in 37% at 7 to 14 months. Factors associated with failure to suppress viral load at two or more time points included higher rates of missed clinic appointments, nonwhite ethnicity, age 40 years or younger, injection drug use, lower baseline CD4+ lymphocyte count, and higher baseline viral load. In a multivariate model, only higher rates of missed clinic appointments were independently associated with viral suppression at 1 year. Ritonavir was associated with adverse drug reactions about twice as frequently as indinavir or nelfinavir, and women experienced significantly more adverse effects than men. Conclusions: Unselected patients in whom HAART is started in a clinic setting achieve viral suppression substantially less frequently than do patients in controlled clinical trials. Missed clinic visits were the most important risk factor for failure to suppress HIV-1 RNA levels. Studies are needed to identify interventions that maximize the performance of HAART in inner-city clinics.
Swallowed topical corticosteroids reduce the risk for long‐lasting bolus impactions in eosinophilic esophagitis
Authors: T. Kuchen, A. Straumann, E. Safroneeva, Y. Romero, C. Bussmann, S. Vavricka, P. Netzer, A. Reinhard, S. Portmann, A. M. Schoepfer
Journal: Allergy (2014)

Long-lasting food impactions requiring endoscopic bolus removal occur frequently in patients with eosinophilic esophagitis (EoE) and harbor a risk for severe esophageal injuries. We evaluated whether treatment with swallowed topical corticosteroids is able to reduce the risk of occurrence of this complication.We analyzed data from the Swiss EoE Cohort Study. Patients with yearly clinic visits, during which standardized assessment of symptoms, endoscopic, histologic, and laboratory findings was carried out, were included.A total of 206 patients (157 males) were analyzed. The median follow-up time was 5 years with a total of 703 visits (mean 3.41 visits/patient). During the follow-up period, 33 patients (16 % of the cohort) experienced 42 impactions requiring endoscopic bolus removal. We evaluated the following factors regarding the outcome 'bolus impaction' by univariate logistic regression modeling: swallowed topical corticosteroid therapy (OR 0.503, 95%-CI 0.255-0.993, P = 0.048), presence of EoE symptoms (OR 1.150, 95%-CI 0.4668-2.835, P = 0.761), esophageal stricture (OR 2.832, 95%-CI 1.508-5.321, P = 0.001), peak eosinophil count >10 eosinophils/HPF (OR 0.724, 95%-CI 0.324-1.621, P = 0.433), blood eosinophilia (OR 1.532, 95%-CI 0.569-4.118, P = 0.398), and esophageal dilation (OR 1.852, 95%-CI 1.034-3.755, P = 0.017). In the multivariate model, the following factors were significantly associated with bolus impaction: swallowed topical corticosteroid therapy (OR 0.411, 95%-CI 0.203-0.835, P = 0.014) and esophageal stricture (OR 2.666, 95%-CI 1.259-5.645, P = 0.01). Increasing frequency of use of swallowed topical steroids was associated with a lower risk for bolus impactions.Treatment of EoE with swallowed topical corticosteroids significantly reduces the risk for long-lasting bolus impactions.
Influence of indomethacin on extracellular calcium homeostasis.
Authors: J W Bijlsma, A J Rabelink
Journal: Annals of the Rheumatic Diseases (1990)

Rheumatoid arthritis is associated with a generalised loss of bone mass. One of the factors that have been implicated in the pathogenesis of this bone loss is the chronic use of non-steroidal anti-inflammatory drugs (NSAIDs). These drugs are known to increase gastrointestinal permeability and may thus influence the absorption of calcium; they may also influence glomerular filtration rate and the renal excretion of calcium; in addition, NSAIDs may inhibit osteoblast function as well as osteoclastic bone resorption. Calcium homeostasis was studied in eight healthy volunteers during eight days' treatment with 150 mg indomethacin daily. No changes in serum concentration of calcium, phosphorus, parathyroid hormone, 25-hydroxyvitamin D3, and 1,25-dihydroxyvitamin D3 were found. The creatinine clearance and the urinary excretion of phosphorus and sodium did not change, but a decrease in calcium excretion was noted (mean (SEM) calcium/creatinine excretion 0.52 (0.05) v 0.28 (0.06)). This decrease is probably due to renal retention of calcium. Whether this decrease of urinary calcium excretion has a positive or a negative effect on bone is presently unknown.
We need more rationality around cancer
Authors: K. Patel
Journal: BMJ (2011)

“I can’t see why I’ve waited so long,” she said. “I’m a cancer patient.”

She had been seen sooner than most. I flicked through the notes to try to get a handle on what was going on. I quickly scanned the last letter from the oncologist, finding it in among a pile of paperwork relating to swabs for meticillin resistant Staphylococcus aureus , property receipts, and other rather unhelpful documents.

“But you’ve been cured,” I said. “That’s what your oncologist says.” …
Abstract MS3-3: Navigating the Genome: Quandaries and Approaches to Dealing with Genomic Information
Authors: JP Evans
Journal: Cancer Research (2012)

Abstract Recent technological advances have made large-scale DNA sequencing, including whole genome sequencing, a practical reality. The ability to sequence tumor genomes as well as the germ-line genome of individuals holds considerable promise for the practice of oncology. Broad assessment of cancer risk in individuals, identification of those at extreme risk for cancer who might benefit from specific interventions and pharmacogenomic guidance regarding therapy are possible benefits of assessing an individual's genome. Likewise, analysis of genomic information in tumors is poised to begin helping to guide highly specific treatment of cancer in an increasingly individualized manner. However, as the field of oncology begins to use genomic queries to assess patient risk, characterize disease and guide treatment, many challenges must be addressed. Purely technical issues include the suboptimal accuracy of current platforms for massively parallel sequencing, tumor heterogeneity and difficulties interpreting genomic risk information in a clinically relevant manner. Systemic challenges include how to interpret, store and present massive amounts of genomic data in the currently highly fragmented (and limited) electronic medical record. Finally, in the process of genome-scale sequencing vast numbers of incidental results are inevitably generated, which may have important ramifications for patients and providers but may be unwelcome. Such ethical, legal and social implications of whole genome sequencing raise significant questions about patient autonomy, the physician's duty to warn and the laboratory's duty to report a wide variety of highly heterogeneous genomic findings. In this presentation some of these salient issues and possible solutions will be explored. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr MS3-3.
Interaction of platelets with the vessel wall in the pathophysiology of sudden cardiac death.
Authors: J W Hammon, J A Oates
Journal: Circulation (1986)

The occurrence of ventricular fibrillation after occlusion of the circumflex coronary artery in the conscious dog was examined as one preparation for sudden cardiac death arising from coronary artery disease. The incidence of ventricular fibrillation after after circumflex occlusion was reduced from 53% to 6% (p less than .01) by the infusion of prostacyclin in doses that do not alter cardiac output or peripheral resistance. This effect of prostacyclin led to the evaluation of two structurally different inhibitors of thromboxane synthase in this preparation; RO 22-4679 and U-63557A reduced ventricular fibrillation by 82% and 100%, respectively (p less than .05). The inhibition of ventricular fibrillation by U-63557A was abrogated by pretreatment with indomethacin, suggesting that a metabolite of the endoperoxide that accumulated during thromboxane synthase inhibition was responsible for the protection from ventricular fibrillation.
Ulcerated Plaque With Lymphocutaneous Spread
Authors: Evan W. Piette, Karolyn A. Wanat, Douglas J. Pugliese
Journal: JAMA Dermatology (2015)

Awomaninher50sadmittedforbacterialpneumoniawasnotedtohave anulceratedplaqueontheforearm.Thepatienthadbeendischargedapproximately2weeksprior,afteranadmissionforcongestiveheart failure. A few days after that discharge, the patient noticedapainfululcerationontherightdistal forearm,at thesitewhereaperipheral intravenous catheter had been inserted during her initial hospitalization. On physicalexamination,thepatienthadanulceratedplaqueontherightforearm with 2 tender, 1to 2-cm red nodules in the right antecubital fossa (Figure,A).Onfurtherquestioning,thepatientnotedthatbetweenherhospitalizationsshehadgonehomeandcleanedherfishtank,playedwithher petcat,andgardenedinher indoorcactusgarden.Shesaidshehadnotrecentlytraveled,andwasnottakinganyimmunosuppressivemedications. Askinbiopsyandculturewereperformedfromtheforearmlesion(Figure, B andC). Quiz at jamadermatology.com A B
Recent Gene Conversions between Duplicated Glutamate Decarboxylase Genes (gadA and gadB) in Pathogenic Escherichia coli
Authors: T. M. Bergholz, C. L. Tarr, L. M. Christensen, D. J. Betting, T. S. Whittam
Journal: Molecular Biology and Evolution (2007)

Escherichia coli have evolved adaptive systems to resist strongly acidic habitats in part through the production of 2 biochemically identical isoforms of glutamate decarboxylase (GAD), encoded by the gadA and gadB genes. These genes occur in E. coli and other members of the genospecies (e.g., Shigella spp.) and originated as part of a genomic fitness island acquired early in Escherichia evolution. The present duplicated gad loci are widely spaced on the E. coli chromosome, and the 2 genes are 97% similar in sequence. Comparison of the nucleotide sequences of the gadA and gadB in 16 strains of pathogenic E. coli revealed 3.8% and 5.0% polymorphism in the 2 genes, respectively. Alignment of the homologous genes identified a total of 120 variable sites, including 21 fixed nucleotide differences between the loci within the first 82 codons of the genes. Twenty-three phylogenetically informative sites were polymorphic for the same nucleotides in both genes suggesting recent gene conversions or intergenic recombination. Phylogenetic analysis based on the synonymous substitutions per synonymous site indicated 2 cases in which specific gadA and gadB alleles were more closely related to one another than to other alleles at the corresponding locus. The results indicate that at least 3 gene conversion events have occurred after the gad gene duplication in the evolution of E. coli. Despite multiple gene conversion events, the upstream regulatory regions and the 5′ end of each gene remains distinct, suggesting that maintaining functionally different gad genes is important in this acid-resistance mechanism in pathogenic E. coli.
Abstract 4758: Self-assembled superparamagnetic iron oxide nanoparticles for targeted cancer therapy
Authors: G. S. Sailaja, Christopher S. Gondi, Praveen Bhoopathi, Bharathi Gorantla, Jasti S. Rao
Journal: Cancer Research (2012)

Abstract Surface engineered iron oxide nanoparticles offer greater potential for targeted gene therapy as compared to many of the current treatment modalities for cancer. The intrinsic superparamagnetism of iron oxide nanoparticles along with a bio-inspired coating to circumvent the physiological and cellular barriers suggests their usefulness as an efficient non-invasive therapeutic option to invoke the desired response at the tumor site. In the present study, a novel functionalized iron oxide nanoparticle based polyplex system that explores the greater potentials of self-assembly together with magnetic targeting is employed for “smart targeting” and to improve therapeutic index. Poly (L-glutamic acid) functionalized iron oxide nanoparticles (Feg) were synthesized and complexed with plasmid DNA containing the gene of interest in the presence of carboxymethyl chitosan (CMCS). The preliminary characterization of the nanoparticles was performed by X-ray diffraction and FT-IR analysis. The formation and the internalization of Feg-CMCS-DNA polyplex occurred irrespective of the type of DNA as illustrated by gel retardation assay and Prussian blue staining, respectively. The Feg-CMCS nanoparticles, when conjugated with secreted protein acidic and rich in cysteine (SPARC)-overexpressing plasmid, showed excellent cytocompatibility (evident from MTT assay, morphology and organization of cytoskeleton) with comparable in vitro biofunctionality (illustrated by western blot analysis) as that of a commonly used transfection agent. The supramolecular assembly of the (Feg-CMCS-SPARC) polyplex system was manifested by scanning and transmission electron micrographs. The mechanism of internalization of the polyplex system and the role of magnetic field in enhancing the internalization were observed by transmission electron microscopy. Further, Feg-CMCS-SPARC polyplex transfection resulted in significant inhibition of in vitro tumor angiogenesis. This study highlights the superior efficacy of Feg-CMCS-SPARC self-assembled polyplex system for use as a localized therapeutic drug in vivo at the tumor site. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4758. doi:1538-7445.AM2012-4758
Allergens of Arizona cypress (Cupressus arizonica) pollen: Characterization of the pollen extract and identification of the allergenic components
Authors: Gabriella Di Felicea, Maria Filomena Caiaffab, Giuseppe Barilettob, Claudia Affernia, Roberto Di Paolab, Adriano Maria, Sabrina Palumboa, Raffaella Tinghinoa, Federica Sallustoa, Alfredo Tursib, Luigi Macchiab, Carlo Pinia
Journal: Journal of Allergy and Clinical Immunology (1994)
Evidence of Independent Origin of Multiple Tumors From Patients With Prostate Cancer
Authors: Liang Cheng, Thomas G. Pretlow, Fadi W. Abdul-Karim, Hsing-Jien Kung, Min-Lung Tsai, Deborah V. Dawson, W. Marston Linehan, Sang-Yong Song, Won-Sang Park, Young-Wan Moon, Michael R. Emmert-Buck, Lance A. Liotta, Zhengping Zhuang
Journal: JNCI Journal of the National Cancer Institute (1998)

Background: In men with prostate cancer, the gland usually contains two or more widely separate tumors. A critical issue of prostatic carcinogenesis is whether these multiple tumors are independent in origin. Molecular analysis of microsatellite (i.e., highly repeated, short nucleotide sequences) alterations in the DNA from separate tumors in the same prostate can be used to determine whether or not these separate tumors arise independently. Methods: Four microsatellite polymorphic markers (D8S133, D8S136, and D8S137, for a putative tumor suppressor gene on chromosome 8p, and D17S855, for the BRCA1 gene on chromosome 17q) were used to examine the pattern of allelic loss in prostate cancer from 19 patients who had two or more distantly separate tumors (i.e., located on contralateral sides or separated by at least half the anterior-posterior diameter of the prostate). Forty distantly separate tumors were microdissected, DNA samples were prepared from formalinfixed, paraffin-embedded wholemount prostate tissue section, and the overall frequencies of loss of heterozygosity at the four loci were determined. Results: The pattern of allelic loss was compatible with independent tumor origin in 15 of 18 informative cases. A random discordant pattern of allelic deletion was observed in distantly separate tumors, whereas the same allele was consistently lost in cells from different regions of the same tumor. For three patients, the results were compatible with either intraglandular dissemination or independent origin of prostate cancer. Conclusions: Our data suggest that multiple tumors in some patients with prostate cancer have independent origin.
The use of a gold nanoparticle-based adjuvant to improve the therapeutic efficacy of hNgR-Fc protein immunization in spinal cord-injured rats
Authors: Yong-Tang Wang, Xiu-Min Lu, Feng Zhu, Peng Huang, Ying Yu, Lin Zeng, Zai-Yun Long, Ya-Min Wu
Journal: Biomaterials (2011)
Registration of Foreign Physicians
Authors: D. Nathan
Journal: JAMA (1910)

To the Editor:—  Having read the letters of Drs. Hoenes and McReynolds inThe Journalon this subject, I beg leave to make a few remarks. By way of criticism I will add that there was an air of sentiment about them that interested me. If candidates for license to practice medicine in Canada will comply with the various provincial laws, they will have no difficulty. Of course, if one has, up to a few years ago, carried the hod and later, by way of recreation, obtained a degree or license to practice medicine either by serving apprenticeship for a year as office boy to some poorly trained practitioner, or attending one, two, or even three, five or six-month courses at some diploma mill, one will be blocked at the start. I am surrounded by physicians who have spent, at most, two six-month terms at college, hardly enough time to
Effect of aspirin in "aspirin sensitive" patients.
Authors: S I Asad, D M Kemeny, L J Youlten, A W Frankland, M H Lessof
Journal: BMJ (1984)

Eighteen patients with a history of urticaria or asthma, or both, induced by aspirin were studied before and after provocation of symptoms with aspirin. The plasma prostaglandin F2 alpha concentration, which was characteristically raised before challenge, fell significantly at the time of adverse reactions. Repeated administration of aspirin up to a dose of 650 mg daily induced tolerance in most of the patients, and several developed bronchodilator responses to aspirin. Although median total IgE concentrations may be raised in patients with aspirin sensitivity, it appears likely that pharmacological rather than immunological mechanisms are chiefly responsible for the phenomena of aspirin sensitivity and desensitisation.
Amino acid modulation of renal phosphatidylcholine biosynthesis in the rat.
Authors: L J Havener, F G Toback
Journal: Journal of Clinical Investigation (1980)

The hypothesis that amino acids act as modifiers of phospholipid biosynthesis was tested in renal cortical cells from normal rats. The rate of [14C]-choline incorporation into phospholipid in cortical slices was enhanced by the addition of lysine or arginine to the incubation medium, and reduced by phenylalanine, aspartic acid, or four other amino acids. Lysine and aspartic acid appeared to modify the cholinephosphotransferase reaction in which cytidine 5'-diphosphocholine (CDP-choline) and 1,2-diacylglycerol react to form phosphatidylcholine, the major phospholipid of renal membranes. Since this enzymatic reaction takes place in the endoplasmic reticulum, the effect of single amino acids on microsomal preparations was examined. Lysine increased CDP-choline:1,2-diacylglycerol cholinephosphotransferase activity by 95%, whereas aspartic acid reduced activity by 65%, in a concentration-dependent manner. For both substrates in the reaction, amino acids modulated enzyme activity by altering the maximum velocity without changing the apparent Km. These observations in intact renal cells and in microsomal preparations indicate that changes in cellular amino acid concentrations could modify the biosynthetic rate of phosphatidylcholine, and suggest a mechanism that could coordinate the biosynthesis of phospholipid and protein.
cAMP-dependent phosphorylation of PTB1 promotes the expression of insulin secretory granule proteins in β cells
Authors: Klaus-Peter Knoch, Ronny Meisterfeld, Stephan Kersting, Hendrik Bergert, Anke Altkrüger, Carolin Wegbrod, Melanie Jäger, Hans-Detlev Saeger, Michele Solimena
Journal: Cell Metabolism (2006)
Abstract LB-69: Novel WBC gene expression assay for prostate cancer detection.
Authors: Amin I. Kassis, Qi Wu, Maliackal Poulo Joy, Pichumani Balagurumoorthy, Massimo Loda, Carolyn Evan, Gillian Petrozziello, Philip W. Kantoff, S. James Adelstein
Journal: Cancer Research (2013)

Abstract In recent studies, we showed that several oncogenes and cancer-associated genes and proteins are differentially expressed in phagocytic WBCs of tumor-bearing mice (colon, lung, melanoma, and prostate), compared to non-phagocytic WBCs from the same mice as well as to phagocytic WBCs obtained from non-tumor-bearing mice. Prompted by the translational potential of these findings, we carried out whole genome microarray analysis of total RNA samples isolated from peripheral blood phagocytic (macrophages and neutrophils) and nonphagocytic (T cells) WBCs of prostate cancer patients (n = 58) and blood donors (n = 36). Comparison of the genomic expression profiles of macrophages vs. T cells or neutrophils vs. T cells of these patients to those identified in blood donors revealed the presence of gene signatures that are unique to the patient population. These differentially expressed genes were used to generate receiver operating characteristic curves. The area under the curve was 1.000 for macrophages and 0.980 for neutrophils, indicating the high accuracy of the assay. While the PSA cutoff of 4 ng/mL failed to identify 14 of the 58 patients, the assay reported herein correctly identified 57 out of the 58 patients and all 36 controls (sensitivity = 0.983; specificity = 1.000) when macrophages were used; with neutrophils, there were 7 false negatives (sensitivity = 0.879; Specificity = 1.000). These promising results suggest that the approach lays the foundation for a next generation diagnostic blood test for prostate-cancer. Citation Format: Amin I. Kassis, Qi Wu, Maliackal Poulo Joy, Pichumani Balagurumoorthy, Massimo Loda, Carolyn Evan, Gillian Petrozziello, Philip W. Kantoff, S. James Adelstein. Novel WBC gene expression assay for prostate cancer detection. [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 LB-69. doi:10.1158/1538-7445.AM2013-LB-69 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.