tbuckley/cabot-search huggingface dataset:
Assessing the Diagnostic Properties of a Graded Oral Provocation Challenge for the Diagnosis of Immediate and Nonimmediate Reactions to Amoxicillin in Children
Authors: Christopher Mill, Marie-Noël Primeau, Elaine Medoff, Christine Lejtenyi, Andrew O’Keefe, Elena Netchiporouk, Alizee Dery, Moshe Ben-Shoshan
Journal: JAMA Pediatrics (2016)

<h3>Importance</h3> The diagnostic properties of a graded provocation challenge (PC) among children presenting with a rash in the course of amoxicillin treatment are currently unknown. <h3>Objective</h3> To assess the accuracy and the negative predictive value of the PC in a cohort of children referred with suspected allergy to amoxicillin. <h3>Design, Setting, and Participants</h3> A cohort study was conducted between March 1, 2012, and April 1, 2015, at the allergy clinic of the Montreal Children’s Hospital, Montreal, Quebec, Canada. All children referred with suspected allergy to amoxicillin were approached. In addition, 346 eligible children were followed up to assess reactions to subsequent use of amoxicillin at the time of illness in cases with negative PC results. Data were collected on clinical characteristics, suspected antibiotic exposure, personal and first-degree relatives’ comorbidities, and history of atopy and management of the reaction. Univariate and multivariate logistic regressions were compared to determine factors associated with immediate and nonimmediate reactions to the PC. <h3>Interventions</h3> All children had a graded PC. <h3>Main Outcomes and Measures</h3> Reactions to the graded PC, the negative predictive value of the PC for nonimmediate reactions, and factors associated with immediate and nonimmediate reactions to the PC. <h3>Results</h3> A total of 818 children were assessed (median age, 1.7 years [interquartile range, 1.0-3.9 years]; 441 [53.9%] male). Among all participants, 770 (94.1%) tolerated the PC, 17 (2.1%) developed mild immediate reactions, and 31 (3.8%) developed nonimmediate reactions. The graded PC had a specificity of 100.0% (95% CI, 90.9%-100.0%), a negative predictive value of 89.1% (95% CI, 77.1%-95.5%), and a positive predictive value of 100.0% (95% CI, 86.3%-100.0%). Among all 346 participants eligible for annual follow-up, 250 (72.3%; 95% CI, 67.2%-76.8%) responded, 55 of whom received subsequent full treatment with amoxicillin; 49 of these 55 participants (89.1%) reported tolerance to subsequent full treatment with amoxicillin, while 6 (10.9%) developed nonimmediate cutaneous reactions. History of a reaction occurring within 5 minutes of exposure was associated with immediate reactions to the PC (adjusted odds ratio = 9.6; 95% CI, 1.5-64.0), while a rash that lasted longer than 7 days (adjusted odds ratio = 4.8; 95% CI, 1.4-16.4) and parental history of drug allergy (adjusted odds ratio = 3.0; 95% CI, 1.3-6.8) were associated with nonimmediate reactions to the PC. <h3>Conclusions and Relevance</h3> Graded PCs provide an accurate and safe confirmatory test for skin-related reactions to amoxicillin. Further studies are required to assess factors associated with the PC outcome groups.
An Outbreak of Herpes Gladiatorum at a High-School Wrestling Camp
Authors: Edward A. Belongia, Jesse L. Goodman, Edward J. Holland, Charles W. Andres, Scott R. Homann, Robert L. Mahanti, Martin W. Mizener, Alejo Erice, Michael T. Osterholm
Journal: New England Journal of Medicine (1991)

Herpes simplex virus type 1 (HSV-1) has been identified as a cause of cutaneous or ocular infection among athletes involved in contact sports; in this context it is known as herpes gladiatorum. In July 1989, we investigated an outbreak among 175 high-school wrestlers attending a four-week intensive-training camp. Cases of infection were identified by review of medical records, interview and examination of the wrestlers, and culture of skin lesions. Oropharyngeal swabs were obtained for HSV-1 culture, and serum samples for HSV-1 serologic studies. HSV-1 isolates were compared by restriction-endonuclease analysis.HSV-1 infection was diagnosed in 60 wrestlers (34 percent). The lesions were on the head in 73 percent of the wrestlers, the extremities in 42 percent, and the trunk in 28 percent. HSV-1 was isolated from 21 wrestlers (35 percent), and in 39 (65 percent) infection was identified by clinical criteria. Five had conjunctivitis or blepharitis; none had keratitis. Constitutional symptoms were common, including fever (25 percent), chills (27 percent), sore throat (40 percent), and headache (22 percent). The attack rate varied significantly among the three practice groups, ranging from 25 percent for practice group 1 (lightweights) to 67 percent for group 3 (heavyweights). Restriction-endonuclease analysis identified four strains of HSV-1 among the 21 isolates. All 10 isolates from practice group 3 were identical (strain A), and 5 of 7 isolates from practice group 2 (middleweights) were identical (strain B), which suggested concurrent transmission of different strains within different groups. HSV-1 was not isolated from any oropharyngeal swabs.Herpes gladiatorum may cause substantial morbidity among wrestlers, and it is primarily transmitted by direct skin-to-skin contact. Prompt identification and exclusion of wrestlers with skin lesions may reduce transmission.
The Course of Rheumatoid Arthritis in Patients Receiving Simple Medical and Orthopedic Measures
Authors: Charles L. Short, Walter Bauer
Journal: New England Journal of Medicine (1948)

NO METHOD of treatment thus far employed in rheumatoid arthritis can justly be considered "specific" — a term that implies a rapid and complete reversal of subjective and objective manifestations of the disease, whether localized in the skeletal system or in other parts of the body. Such a therapeutic principle, of course, is constantly effective and leaves no doubt of its value in the minds of either patient or physician. Pending the discovery of this long-awaited advance, the treatment of rheumatoid arthritis is necessarily confined to measures believed to be useful but of unproved value. Furthermore, the assessment of newer . . .
A prospective, randomized, double-blind, controlled trial on the efficacy of carbon dioxide insufflation in gastric endoscopic submucosal dissection
Authors: Y. Maeda, D. Hirasawa, N. Fujita, T. Obana, T. Sugawara, T. Ohira, Y. Harada, T. Yamagata, K. Suzuki, Y. Koike, J. Kusaka, M. Tanaka, Y. Noda
Journal: Endoscopy (2013)

<b>Background and study aims</b>: Carbon dioxide (CO<sub>2</sub>) insufflation is expected to be safe and effective in endoscopic submucosal dissection (ESD) as well as in other endoscopic procedures. The present study aimed to clarify the usefulness and safety of CO<sub>2</sub> insufflation in gastric ESD. <b>Patients and methods:</b> A total of 102 consecutive patients were randomly assigned to CO<sub>2</sub> insufflation (CO<sub>2</sub> group, n = 54) or air insufflation (Air group, n = 48). Abdominal pain and distension were chronologically recorded on a 100-mm visual analog scale (VAS). The volume of residual gas in the digestive tract was measured by computed tomography performed immediately after ESD. <b>Results: </b>Abdominal pain on a 100-mm VAS in the CO<sub>2</sub> vs. Air group was 4 vs. 3 immediately after ESD, 4 vs. 4 one hour after the procedure, 3 vs. 3 three hours after the procedure, and 1 vs. 4 the next morning, showing no difference between the groups. In addition, there was no difference in abdominal distension on the 100-mm VAS over the time course of the study. The volume of residual gas in the digestive tract in the CO<sub>2</sub> group was significantly smaller than that in the Air group (643 mL vs. 1037 mL, <i>P</i> < 0.001). The dose of sedative drugs did not differ between the groups. Neither the incidences of complications nor clinical courses differed between the groups. <b>Conclusions:</b> Compared with air insufflation, CO<sub>2</sub> insufflation during gastric ESD significantly reduced the volume of residual gas in the digestive tract but not the VAS score of abdominal pain and distension.
Abstract 181: Biological and clinical relevance of quantitative global methylation in repetitive DNA sequences in B-cell chronic lymphocytic leukemia
Authors: Valentina Bollati, Sonia Fabris, Fortunato Morabito, Luca Agnelli, Valeria Motta, Giovanna Cutrona, Massimo Gentile, Giorgio Lambertenghi Deliliers, Pier Alberto Bertazzi, Manlio Ferrarini, Antonino Neri, Andrea Baccarelli
Journal: Cancer Research (2010)

Abstract Background: B-cell chronic lymphocytic leukemia (B-CLL) is characterized by highly clinical heterogeneity; the identification of reliable prognostic factors useful in predicting patient outcome and planning therapeutic strategies represent a crucial task. Global DNA hypomethylation affecting repeat sequences, such as long interspersed nuclear elements-1 (LINE-1), Alu and satellite α DNA (SAT-α DNA), has been reported in different cancer types and associated with chromosomal instability. Aim: In order to investigate the role of global DNA methylation in B-CLL we quantified the methylation levels of Alu, LINE-1 and SAT-α repetitive in B-CLL patients and correlated them with the major cytogenetic and molecular features and clinical relevance in predicting therapy-free survival (TFS). Patients and methods: A quantitative bisulfite-PCR Pyrosequencing method was used to evaluate methylation of Alu, LINE-1, and SAT-α in a panel of highly purified (&amp;gt;90%) peripheral mononuclear CD19+ cells from 7 healthy donors and 77 B-CLL untreated well-characterized patients in early stage disease (Binet stage A). Results: Forty-eight patients had unmutated IgVH genes; ZAP-70 and CD38 were positive in 28 and 35 cases, respectively; 13q14.3 deletion was present as a sole abnormality in 21/33 patients while in the remaining cases it was combined with 17p13.1 (4 pts) or 11q22.3 deletions (7 pts) or both (1 pt). The 11q22.3 and 17p13.1 deletions were detected as sole abnormality in 6 and 7 patients, respectively. Trisomy 12 occurred in 17 patients, as a sole abnormality in all cases. Methylation levels (median %5mC) were lower in B-CLLs compared with controls (21.4 vs. 25.9; 66.8 vs. 85.7; and 84.0, vs. 88.2; for Alu, LINE-1 and SAT-α, respectively). A significant association was observed with 17p13.1 deletion (15.4 vs. 22.4; 42.9 vs. 68.5; 32.7 vs. 85.0, for Alu, LINE-1 and SAT-α) but not with other major genetic lesions, IgVH mutation status, CD38 or ZAP-70 expression. Notably, lower SAT-α methylation levels appeared to be an independent prognostic marker significantly associated with a shorter TFS. Conclusion: Our study extended limited evidence in methylation of repetitive sequences in B-CLL suggesting an important biological and clinical relevance in the disease. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 181.
Abstract 2969: A Wee1 kinase inhibitor, MK-1775, sensitizes cervical carcinoma cell lines to cisplatin and topotecan
Authors: Stuart D. Shumway, Jamie L. Kubica, Amy D. Guertin, Melissa S. Hurd, Roseanne S. Wexler, Tim Demuth, Carlo Toniatti
Journal: Cancer Research (2011)

Abstract The Wee1 tyrosine kinase plays a key role in checkpoint arrest by phosphorylating and inhibiting cyclin-dependent kinases 1 and 2, two CDKs that drive S-phase and G2- to M-phase transitions, respectively. Interfering with Wee1 leads to elevated CDK1 and 2 activity, which in turn overcomes checkpoint arrest and causes cells to progress through the cell cycle in the presence of DNA damage. Wee1 inhibitors are therefore expected to sensitize cancer cells to DNA damaging chemotherapeutics. In particular, p53-deficient cells are postulated to be particularly sensitive to Wee1 inhibition because they lack a G1-checkpoint and rely more on S- and G2-phase checkpoints where Wee1 activity is critical. The p53 pathway is frequently inactivated in cervical carcinoma either through TP53 mutation or through functional inactivation by Human PapillomaVirus (HPV) gene products. We thus investigated the capability of MK-1775, a selective and potent inhibitor of Wee1, to sensitize cervical cancer cell lines to cisplatin and topotecan. We have evaluated the potential of the Wee1 inhibitor MK-1775 to sensitize cervical cancer cells to standard-of-care treatments both in vitro and in vivo. Using a panel of cervical cancer cell lines, we demonstrated that MK-1775 at clinically relevant concentrations potentiates the cytotoxic activity of cisplatin and topotecan in vitro as indicated by the average 3-fold and 2-fold shift in the CC50s for cisplatin and topotecan, respectively. Chemosenstization was observed in both HPV-negative/p53 mutant and HPV-positive p53/wild-type cervical cancer cell lines. Finally, we have demonstrated that MK-1775 significantly increases the in vivo efficacy of a cisplatin-topotecan combination therapy in xenograft models of HPV+ cervical carcinoma. Based on these data, MK-1775 is currently undergoing clinical evaluation in a phase 1b/2 trial in platinum combination for the treatment of cervical carcinoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2969. doi:10.1158/1538-7445.AM2011-2969
Abstract 3852: Bcl-xL and IL-6 act independently and synergistically to accelerate plasmacytopoiesis and plasma cell tumor formation in Balb/c mice.
Authors: Tomomi Sakai, Alexander L. Kovalchuk, Herbert Morse
Journal: Cancer Research (2013)

Abstract Accelerated development of spontaneous plasma cell tumors (PCT) occurs in mucosal-associated lymphoid tissues of mice bearing both IL-6 and BCL-XL transgenes (double transgenic (dTg)). 91% of dTG mice developed PCTs at a mean age of 89 days. In contrast, 53% of the IL-6 Tg mice developed PCTs at a mean age of 301 days and 12% BCL-XL Tg mice developed PCTs with a mean age of 433 days. The PCTs formed primarily in Peyer's Patches, medullary cords of the mesenteric lymph node and/or the lamina propria of small intestinal villi where they were preceded by massive plasma cell hyperplasia. To investigate the molecular basis of the cooperation between IL-6 and BCL-xL transgenes to accelerate PCT development we performed detailed analysis of cell lines developed from dTG mice and and spontaneous or pristane-induced tumors of Bcl-xL TG mice. All the tumors carry Ig/Myc-deregulating chromosomal translocations, which are thought to be the initiating event of PCT development. Therefore we focused on finding possible differences in secondary alterations. Although the subsets were poorly distinguished by microarray-based gene expression profiling, there were significant differences in the expression of p21, p19ARF, p53, HUWE1 and pRb as determined by western blotting and qPCR. DTG tumors were characterized by alterations in pathways governing expression of pRb that included increased expression of INK4A and down regulation of pRb itself as well as down regulation of p19ARF. Most notably we discovered discordance between protein and mRNA levels for pRb and p19Arf. Efforts to understand the molecular basis for these distinctions and their contributions to the biology of these PCT subsets are in progress. Citation Format: Tomomi Sakai, Alexander L. Kovalchuk, Herbert Morse. Bcl-xL and IL-6 act independently and synergistically to accelerate plasmacytopoiesis and plasma cell tumor formation in Balb/c mice. [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 3852. doi:10.1158/1538-7445.AM2013-3852
Infection in Organ-Transplant Recipients
Authors: Jay A. Fishman, Robert H. Rubin
Journal: New England Journal of Medicine (1998)

A primary goal in organ transplantation is the prevention or effective treatment of infection, the most common life-threatening complication of long-term immunosuppressive therapy. The challenges involved in achieving this goal are several: a broad range of potential sources of infection ranging from latent viruses to pathogens of both community and hospital origin; immunosuppression-induced impairment of the inflammatory response, which attenuates the signs and symptoms of invasive infection; and the adverse effects of the antimicrobial drugs used for prophylaxis and therapy, which result both from the duration of therapy required and from interactions with the immunosuppressive drugs cyclosporine and tacrolimus. Our . . .
P3-01-02: EC 304: A Novel Progesterone Receptor (PR) Antagonist Inhibits Transcription and Induces Cell Cycle Arrest in T47D Breast Cancer Cells.
Authors: SS Bhaskaran, N Kesavaram, KJ Nickisch, JL VandeBerg, HB Nair
Journal: Cancer Research (2011)

Abstract Progesterone receptor (PR) is a ligand activated transcription factor which plays a crucial role in female reproduction. PR antagonists have been shown to repress estrogen dependent proliferation in the uterus and mammary gland. Even though PR antagonists are potent therapeutic candidates for breast cancer, partial agonism towards glucocorticoid receptor (GR) and androgen receptor (AR) lead to undesirable side effects. Evestra's rational design and development approach in the synthesis of EC304 was aimed at minimizing these side effects as well as to deliver more potent and selective antiprogestins. We used select screen® (Invitrogen) to determine relative binding affinity of EC304 with AR,GR and PR. The binding affinity of EC304 showed strong antagonism towards PR with mild or negligible agonism with AR or GR. PR transactivation was inhibited by EC304 with IC50 of 0.04nM in the presence of progesterone (5nM). EC304 showed superior cytotoxicity over known antiprogestins ZK230211, ORG33628, CDB2914, CDB4124 and RU486 in T47D cells. IC50 of EC304 was found to be 0.5nM in a 6-day cytotoxicity assay (MTT) in T47D cells stimulated with 1nM estrogen (E2). In a 21-day in vitro tumorigenicity assay, EC304 inhibited 80 and 100% of colony formation of T47D cells in the presence of E2 at 1 and 10 nM respectively. Further studies revealed that EC304 induced apoptosis and G1-phase arrest in cell cycle progression when co-incubated with E2 for 24 h. Treatment with EC304 down regulated PR target genes and up regulated cell cycle dependent kinase (CDK) inhibitor P21 in vitro. Ongoing studies address whether EC304 is specifically acting on PR-A or PR-B isoform at gene expression, protein levels and PR isoform specific knockdowns in T47D and other metastatic breast cancer cells. Considered together, these data indicate that EC304 might be a safer but efficacious novel antiprogestin for hormone sensitive postmenopausal breast cancer patients. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-01-02.
AB0547 Bone mineral density (bmd) assessment in patients with symptoms suggestive of spondyloarthritis: an accurate tool for diagnosis
Authors: M. Forien, A. Molto, S. Paternotte, M. Dougados, C. Roux, K. Briot
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Several diseases can mimick spondyloarthritis (SpA) symptoms. Patients may be overdiagnosed in the presence of HLA B27. Patients with spondyloarthritis (SpA) have an increased risk of osteoporosis which can be observed in the early stages of the disease, related to a systemic bone effect of inflammation. Our hypothesis is that BMD is lower in patients with SpA than in patients without this diagnosis. <h3>Objectives</h3> The aim of the study was to assess the performances of BMD for the diagnosis of SpA. <h3>Methods</h3> Patients who consulted in a tertiary Department of Rheumatology for symptoms suggestive of SpA suspicion between January 2008 and December 2012 were included; exclusion criteria were biological therapies and antiosteoporotic treatment intake. Demographic data, disease duration, activity disease (BASDAI, CRP), presence of HLA B27 were assessed. Bone mineral density (BMD) measurements at lumbar spine and hip were performed using DXA; low BMD was defined by a T score ≤-2 (at at least one site). The diagnosis of confirmed SpA was the one done by the rheumatologist. Comparisons of BMD measurements between patients with or without SpA, and performance of BMD (sensibility, specificity, positive predictive value PPV, negative predictive value NPV and positive likelihood ratio) were performed. <h3>Results</h3> Among the 237 patients included (57.8% male, mean age of 40.5±12.0 years), 169 (71%) patients (mean age of 40±12.3 years) had confirmed SpA. Compared to patients without the diagnosis of confirmed SpA (n=44), patients with SpA were more frequently male (64.5% vs 40.9% p=0.005), with positive HLA B27 (80.9% vs 48.8%, p&lt;0.0001) and higher CRP (11.5±15.9mg/l vs 2.8±3.4mg/l, p&lt;0.0001). No differences were found with regard to the disease duration (11.3±9.9 vs 8.2±6.1 y (p=0.163)), BASDAI (39.5±20.9 vs. 48.0±20.7 (p=0.062)) or BASFI (29.3±23.3 vs 27.8±26.1 p=0.586) for the confirmed SpA and non confirmed SpA groups, respectively. Mean lumbar spine BMD was significantly lower in patients with SpA than in patients without (0.99 ±0.16 vs 1.06 ±0.16, p=0.013) without any differences for hip BMD (0.81g/cm<sup>2</sup> vs 0.82±0.13, p=0.25). Low BMD tended to be more frequent in patients with SpA than without (38.2% vs 22.5%, p=0.065). Performances of BMD are in table: low BMD had a high specificity (78% and 90%) and a high PPV (87% and 90%) for low T score at at least one site and at lumbar spine, respectively. <h3>Conclusions</h3> In patients having symptoms suggestive of SpA, a low BMD is an additional tool for the diagnosis of SpA. <h3>Disclosure of Interest</h3> None Declared
Ledipasvir and Sofosbuvir for HCV in Patients Coinfected with HIV-1
Authors: Susanna Naggie, Curtis Cooper, Michael Saag, Kimberly Workowski, Peter Ruane, William J. Towner, Kristen Marks, Anne Luetkemeyer, Rachel P. Baden, Paul E. Sax, Edward Gane, Jorge Santana-Bagur, Luisa M. Stamm, Jenny C. Yang, Polina German, Hadas Dvory-Sobol, Liyun Ni, Phillip S. Pang, John G. McHutchison, Catherine A.M. Stedman, Javier O. Morales-Ramirez, Norbert Bräu, Dushyantha Jayaweera, Amy E. Colson, Pablo Tebas, David K. Wong, Douglas Dieterich, Mark Sulkowski
Journal: New England Journal of Medicine (2015)

Effective treatment for hepatitis C virus (HCV) in patients coinfected with human immunodeficiency virus type 1 (HIV-1) remains an unmet medical need.We conducted a multicenter, single-group, open-label study involving patients coinfected with HIV-1 and genotype 1 or 4 HCV receiving an antiretroviral regimen of tenofovir and emtricitabine with efavirenz, rilpivirine, or raltegravir. All patients received ledipasvir, an NS5A inhibitor, and sofosbuvir, a nucleotide polymerase inhibitor, as a single fixed-dose combination for 12 weeks. The primary end point was a sustained virologic response at 12 weeks after the end of therapy.Of the 335 patients enrolled, 34% were black, 55% had been previously treated for HCV, and 20% had cirrhosis. Overall, 322 patients (96%) had a sustained virologic response at 12 weeks after the end of therapy (95% confidence interval [CI], 93 to 98), including rates of 96% (95% CI, 93 to 98) in patients with HCV genotype 1a, 96% (95% CI, 89 to 99) in those with HCV genotype 1b, and 100% (95% CI, 63 to 100) in those with HCV genotype 4. Rates of sustained virologic response were similar regardless of previous treatment or the presence of cirrhosis. Of the 13 patients who did not have a sustained virologic response, 10 had a relapse after the end of treatment. No patient had confirmed HIV-1 virologic rebound. The most common adverse events were headache (25%), fatigue (21%), and diarrhea (11%). No patient discontinued treatment because of adverse events.Ledipasvir and sofosbuvir for 12 weeks provided high rates of sustained virologic response in patients coinfected with HIV-1 and HCV genotype 1 or 4. (Funded by Gilead Sciences; ION-4 ClinicalTrials.gov number, NCT02073656.).