tbuckley/cabot-search huggingface dataset:
OP0319 Genetically Determined Mannose-Binding Lectin Deficiency Increases Risk of Nephritis in Danish Patients with Systemic Lupus Erythematosus
Authors: S. Jacobsen, N. Tanha, L. Troelsen, M.-L. F. Hermansen, L. Kjær, M. Faurschou, P. Garred
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Mannose-binding lectin (MBL) is involved in the processing of apoptotic debris; deficiencies in this mechanism are strongly associated with autoimmunity, including systemic lupus erythematosus (SLE) with nephritis, i.e. lupus nephritis (LN). <h3>Objectives</h3> To determine if the genetically determined state of MBL-deficiency confers an increased risk of LN in SLE. <h3>Methods</h3> SLE patients attending a Danish tertiary rheumatology center were genotyped in exon 1 of the MBL2 gene at codon 52, 54, and 57 for single-base substitutions named O versus the wildtype allele A. MBL2 genotype thus comprised genotypes <i>A/A</i>, <i>A/O</i>, and <i>O/O</i> (MBL deficient). Development and histological class of LN was looked for from the time fulfillment of the ACR 1987 classification criteria for SLE until end of follow-up. Development of end-stage renal disease (ESRD) was looked for from time of LN to end of follow-up. Cox regression analyses were controlled for gender, age, race, and immunosuppresants. <h3>Results</h3> Of the 171 patients included in the study, 91 percent were female and 92 percent of Caucasian descent. The median age at SLE onset was 29 years (range 11-72 years). The median follow-up from time of SLE classification to development of LN or end of follow-up was 5.7 years (range 0-34 years) with a total of 1165 patient-years. LN developed in 94 patients and among these ESRD developed in 16 patients during 1556 patient-years. The prevalence of <i>A/A</i>, <i>A/O</i>, and <i>O/O</i> MBL producers was 99 (58%), 60 (35%) and 12 (7.0%), respectively. <h3>Conclusions</h3> The finding of a 2.6-fold increased risk of LN among MBL deficient SLE patients supports the notion that deficiencies in innate immunity components involved in removal of apoptotic remnants may promote immunecomplex mediated manifestations of SLE. ESRD was not associated with MBL deficiency indicating its greater importance in early events of LN. These findings enhance our understanding of the pathogenesis of SLE. Furthermore, the relatively high background prevalence of MBL deficiency and the fact that 10 out of 12 such SLE patients eventually developed LN, also indicates that MBL genotyping may have a place in clinical risk stratification of SLE patients. <h3>Acknowledgements</h3> Danish Rheumatism Association, Novo Nordisk Foundation, Rigshospitalets Research Fund <h3>Disclosure of Interest</h3> None Declared
Gallium SPECT/CT for Permanent Catheter Infection
Authors: Tzyy-Ling Chuang, Yuh-Feng Wang
Journal: Clinical Nuclear Medicine (2013)

We present a case of permanent catheter infection demonstrated by gallium SPECT/CT. The patient is a 71-year-old woman with a history of end-stage renal disease under hemodialysis via permanent catheter due to arteriovenous graft occlusion. This time, she had fever, chills, and leukocytosis. Whole-body gallium scan showed uptake to the right clavicular region, and the SPECT/CT study showed that the uptake area was localized to the catheter line of the right neck permanent catheter. Culture of the removed catheter grew coagulase-negative staphylococci.
FRI0109 Disease Activity is Strongly Associated with Work Productivity and Physical Health-Related Quality of Life in Patients with Early Axial Spondyloarthritis in the Space-Cohort
Authors: A. Roeterink, M. de Hooge, J. vd Vijver, R. vd Berg, H. Dagfinrud, R. Landewe, M. van Oosterhout, R. Ramonda, T. Huizinga, D. vd Heijde, F. van Gaalen
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Work productivity loss (WPL) and decreased health-related quality of life (HRQoL) are important problems for patients (pts) with chronic back pain. Not much is known about the relation between disease activity and WPL and HRQoL in pts with early onset axial SpondyloArthritis (axSpA). <h3>Objectives</h3> To assess the relationship between disease activity and WPL and HRQoL in early axSpA. <h3>Methods</h3> The SPACE cohort recruited pts (n=345) with chronic back pain (≥3 months, ≤2 years, onset &lt;45 years) in 5 European centers. In pts fulfilling the ASAS axSpA criteria (n=131), the following assessments were done: ASDAS and BASDAI (disease activity), BASFI (functional ability), SF-36 (HRQoL) and Work Productivity and Activity Impairment (WPAI). Pts were grouped according to ASDAS: inactive disease (&lt;1.3), moderate disease (1.3-2.1), high disease (2.1-3.5) and very high disease activity (&gt;3.5). BASDAI and BASFI scores ≥4 were considered as high disease activity and impaired function, respectively. HRQoL was reported as the SF-36 physical (PCS) and mental component summary (MCS) scores (score of 50 (general population) ±10 (standard deviation; SD)). Impact of disease on work productivity (WP) was defined as percentage of absenteeism (absence from work due to illness), presenteeism (reduced productivity while at work) and WPL (combines absenteeism and presenteeism) in the past 7 days, with greater scores indicating greater impairment. <h3>Results</h3> Figure 1a (n=122) shows that PCS score decreases significantly with increasing ASDAS state. PCS scores had a similar association when looking at low and high BASDAI (19.6 vs. 36.1, <i>P</i>&lt;0.001) and BASFI scores (32.7 vs. 12.6, <i>P</i>&lt;0.001). MCS is not influenced by disease activity (ASDAS states; <i>P</i>=0.97, low vs. high BASDAI; 45.9 vs. 48.0, <i>P</i>=0.37) or functional ability (low vs. high BASFI; 46.3 vs. 47.2, <i>P</i>=0.76). Figure 1b (n=100) shows that absenteeism (<i>P</i>=0.02), presenteeism (<i>P</i>&lt;0.001) and WPL (<i>P</i>&lt;0.001) increases as ASDAS increases. Similar findings are found when looking at pts with low vs. high BASDAI (absenteeism; 3.9% vs. 19.5%, presenteeism; 19.4% vs. 51.2%, WPL; 20.6% vs. 57.5%, all <i>P</i>-value&lt;0.001) and BASFI (WPL; 30.9% vs. 66.7%, absenteeism; 7.1% vs. 24.9%, presenteeism; 28.9% vs. 61.1%, all <i>P</i>-value&lt;0.001). <h3>Conclusions</h3> In early axial SpA disease activity has a major impact on physical HRQoL and on work productivity. These findings support aiming for clinical remission in patients with early axial SpA. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2259
Abstract 3007: Hsa-miR-9 expression patterns are associated with metastatic recurrence in patients with clear cell renal cell carcinoma through hypermethylation of the gene in tumor tissue
Authors: Michelle A.T. Hildebrandt, Jian Gu, Jie Lin, Yuanqing Ye, Weiqi Tan, Pheroze Tamboli, Christopher G. Wood, Xifeng Wu
Journal: Cancer Research (2010)

Abstract The long-term prognosis for patients with clear cell renal cell carcinoma (ccRCC) is dramatically altered by the development of metastatic recurrence. However, there are very few indicators that can predict which patient will develop a recurrence. MicroRNA gene expression has been shown to be associated with RCC development, and here we show that it can also help to identify patients at increased recurrence risk. We utilized genome-wide microRNA arrays to measure expression levels in tumors from 74 ccRCC patients and identified hsa-miR-9 as a candidate for recurrence risk (Hazard Ratio: 2.6, 95% Confidence Interval: 1.55-4.38) resulting in a reduction in median time to recurrence by 30 months (P-value = 0.0038). This observation was validated in a replication sample of an additional 254 ccRCC tumors. We further showed that the genes encoding for hsa-miR-9 were significantly hypermethylated in tumors compared to adjacent normal tissues (P-value &amp;lt; 0.001 for both miR-9-1 and miR-9-3) resulting in decreased expression, and that the methylation of these genes was more significant in tumor DNA obtained from patients who developed a recurrence (P-value = 0.012 and 0.009 for miR-9-1 and miR-9-3, respectively). Furthermore, methylation of miR-9-1 and miR-9-3 were independently associated with a reduction in time to recurrence. Hsa-miR-9 has been shown to play a role in tumor development for other cancers, and our results demonstrate that it has similar functions in ccRCC while also playing a role in the development of metastatic recurrence. 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 3007.
P3-06-05: Comparison of Oncotype DX® Recurrence Scores between Surgical and Core Biopsy Specimens in Breast Cancer Patients.
Authors: TS Stull, MC Goodwin, JM Anderson, FL Baehner, AP Sing, CN Yoshizawa, AV Barrio, TG Frazier
Journal: Cancer Research (2011)

Abstract Introduction: The Oncotype DX® 21 gene assay is usually performed on surgical resection specimens (SRx) for patients (pts) with early stage, estrogen receptor positive (ER+) breast cancer to predict the risk of recurrence and likelihood of benefit from adjuvant chemotherapy (CT) and hormonal therapy (HT). Using the Recurrence Score (RS) to aid in making a decision to administer preoperative CT requires assaying the core biopsy specimen (CBx). The objective of this study is to compare the RS obtained from paired CBx and SRx specimens. Methods: 25 pts with invasive breast cancer diagnosed by CBx with a subsequent Oncotype DX® 21 gene assay performed on the SRx were identified. Fixed, paraffin embedded tissue from these paired CBx were sent to Genomic Health. The H&amp;E slide from the paired SRx sample sent for the RS was used to compare the histology with the paired CBx. The RS from the CBx and SRx pairs were examined descriptively with scatterplots and Pearson correlation coefficients. Results: Median age of diagnosis was 64 (range 39–78). Sufficient RNA was obtained from all but 1 of the CBx. H&amp;E from CBx and SRx were histologically dissimilar for 3 of 24 pairs with RT-PCR data. The Pearson correlation for RS between CBx and SRx was 0.83 (95% CI 0.64, 0.92) for all 24 pairs. The distribution of RS groups from CBx was 19 low (RS&amp;lt;18), 3 intermediate (RS 18–30), 2 high (RS&amp;gt;31). The RS group from SRx was unchanged for 22 (92%) pts. Two pts switched RS groups, CBx RS 5 to SRx RS 18 and CBx RS 8 to SRx RS 24; only the latter is clinically meaningful because the former straddles the low-intermediate cutpoint. Correlations between CBx and SRx for individual single gene scores were 0.84 (95% CI 0.65, 0.93) for ER, 0.83 (95% CI 0.64, 0.92) for PR, and 0.82 (95% CI 0.61, 0.92) for HER2. Similar results were obtained excluding the 3 histologically dissimilar pairs. Conclusion: The RS's obtained from CBx's were consistently similar to the RS's obtained from the paired SRx. Using an RS obtained from a CBx in pts with ER+ disease to make a decision regarding neoadjuvant CT or HT is clinically acceptable, thus, giving physicians an additional tool to improve pt care and outcomes. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-06-05.
A Reference Hand-Book of Gynecology for Nurses.
Journal: JAMA (1928)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Hepatobiliary (HB) safety of eltrombopag administered after carboplatin+paclitaxel (Carb+Pac) in patients (pts) with solid tumors
Authors: A. Kellum, A. Jagiello-Gruszfeld, I. Bondarenko, R. Rafi, P. Giangiulio, C. Messam, Y. Mostafa Kamel
Journal: Journal of Clinical Oncology (2009)

e20667 Background: Eltrombopag is an oral, small molecule, non-peptide, TPO-receptor agonist studied for the treatment of thrombocytopenia (TCP) due to various causes, including chemotherapy (CT)-induced TCP and is approved for the treatment of chronic ITP in the US. Since eltrombopag is excreted primarily through the liver and liver function is an important safety parameter, HB lab values and AEs were analyzed in a double-blind, placebo (pbo)-controlled, multicenter ph II study. Methods: The safety of eltrombopag was evaluated in adults with advanced solid tumors (mainly NSCLC and ovarian). Pts received up to 8 cycles of Carb (AUC 5–6 IV) + Pac (175–225 mg/m 2 IV), both administered on day 1 q 21 days. 183 pts were randomized to eltrombopag 50, 75, 100mg, or pbo (1:1:1:1). Eltrombopag or pbo were taken from Day 2 - 11 in each cycle of CT. Results: Baseline characteristics, prior medical conditions and number of CT cycles during the study were similar between the treatment groups. At baseline, one pt reported liver metastases (75mg group). Similar numbers of pts had HB lab abnormalities in all groups ( table ). Additionally, HB AEs (34 AEs) occurred in 15 pts across all treatment groups ( table ). Conclusions: In this study, eltrombopag did not increase the incidence of HB AEs or HB lab abnormalities compared to pbo. [Table: see text] [Table: see text]
Abstract 4750: Clinical and Immune Data From an Ongoing Phase II Trial of an Adenovirus/PSA Vaccine for Prostate Cancer
Authors: David M. Lubaroff, Richard D. Williams, Daniel Vaena, Fadi Joudi, Mark Smith, Pamela Zehr, Erica Flanders, Julie Eastman, Karen Griffith, Tammy Madsen, Christine Johnson
Journal: Cancer Research (2010)

Abstract Introduction and Objectives: Our Phase I adenovirus/PSA vaccine trial has proved that this vaccine is safe. We are conducting a Phase II clinical trial with two separate protocols for patients with recurrent or hormone refractory prostate cancer assessing toxicity, immune responses, and changes in PSA levels. Methods: In Protocol #1 men with recurrent prostate cancer following definitive initial treatment for their disease were placed in one of two arms: Arm A; men receive the vaccine alone at days 0, 30, and 60; Arm B; men receive the vaccine 14 days after the initiation of androgen deprivation therapy (ADT). In Protocol #2 men with hormone refractory disease receive the vaccine alone using the same 3 injection schedule. Each injection consists of 108 pfu of the Ad/PSA vaccine suspended in a collagen matrix. All patients return at regular intervals for physical, chemical, radiologic, and immunologic evaluations. Results: To date fifteen patients have been enrolled and have been followed a median of 10.5 months. The patients have a median age of 70 years, and median enrollment PSA levels of 1.67 ng/ml in Protocol #1 and 8.70 ng/ml in Protocol #2. In our preliminary results at this early stage of the trial, seventy seven percent of the patients in both protocols demonstrated anti-PSA T cell responses above preinjection levels. Sixty four percent of the patients demonstrated an increase in PSA doubling time (PSADT). Conclusions: In an attempt to follow up on the success of our Phase I clinical trial of the Ad/PSA vaccine we have initiated a Phase II trial to investigate the therapeutic efficacy of the vaccine in men with recurrent prostate cancer, either following definitive therapy prior to other treatments or hormone refractory. Early results from the first fifteen patients demonstrate the induction of anti-PSA T cells responses in a high percentage of the vaccinated patients and increase in PSADT in more than half of the patients. No serious vaccine-related toxicities have been identified in the patients. 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 4750.
Abstract 2781: Expression patterns of the <i>ERBB2</i> gene and its splice variant in mammary tissues and their associations with breast risk and survival
Authors: Chuanzhong Ye, Xiao-Ou Shu, Wanqing Wen, Shimian Qu, Regina Courtney, Yu-Tang Gao, Wei Zheng, Qiuyin Cai
Journal: Cancer Research (2010)

Abstract Alternative splicing generates different transcripts from the same precursor mRNA. ERBB2 proto-oncogene is involved in the growth, invasion, and prognosis of breast cancer. The ERBB2-sp is a splice variant of ERBB2 that lacks the intracellular and transmembrane domains, which may alter the function of the ERBB2 gene. We hypothesize that the ERBB2-sp and the wild type ERBB2 gene may play a different role in the development and prognosis of breast cancer, and thus compared ERBB2 and ERBB2-sp mRNA expression in tumor tissue and adjacent non-tumor tissue in both breast cancer patients and benign breast disease (BBD) patients. Included in the study were 515 patients diagnosed with breast cancer and 206 patients diagnosed with BBD. These women were recruited as part of the Shanghai Breast Cancer Study and they provided samples of tumor tissue and adjacent non-tumor tissue to the study. Tumor tissues from patients with breast cancer had substantially higher levels of ERBB2 expression than those from patients with BBD (81vs 37, P &amp;lt; 0.0001). On the other hand, adjacent non-tumor tissues from patients with breast cancer had substantially lower levels of ERBB2 expression than those from patients with BBD (20 vs 34, p=0.0254). In breast cancer cases, ERBB2 expression in tumor tissue was significantly higher than that in their paired adjacent non-tumor tissue (p=0.0028). No significant difference of ERBB-sp expression levels was found in any of the following comparisons, tumor tissues or adjacent normal tissues between breast cancer patients and BBD controls as well as between the tumor tissues and adjacent normal tissues in both breast cancer and BBD patients. In the comparison of tumor tissues between breast cancer patients and BBD controls, the ratio of ERBB2 to ERBB2-sp expression levels (ERBB2 /ERBB2-sp index) in tumor tissue was associated with a significantly increased breast cancer risk in a linear manner, with adjusted odds ratios (95% CI) increased from 1.00 (reference) to 1.33 (0.84-2.13), 1.82 (1.13-2.94), and 2.63(1.55-4.43) (P for trend &amp;lt;0.001) from the lowest to the highest quintiles of expression groups. However, there were no apparent associations of expressions of ERBB2 and ERBB2-sp, or ERBB2/ERBB2-sp index in cancer tissue with either overall survival or disease-free survival. Our findings suggest that the expression of ERBB2 and its splice variant ERBB2-sp may play a different role in the development, but not prognosis, of breast cancer. 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 2781.
Renal cell carcinoma with direct colonic invasion
Authors: E. Paine, S. Daram, F. Bhaijee, C. Lahr, N. Ahmed, T. Abell, S. Tang
Journal: Endoscopy (2012)

Renal cell carcinoma (RCC) is a fairly uncommon malignancy, comprising only 3 % of malignancies in adults [1]. Symptoms related to gastrointestinal involvement of this tumor rarely present, although up to 4 % of patients with RCC have small-bowel metastases. Direct colonic invasion by RCC is extremely rare due to the retroperitoneal location of the kidneys and mesocolon. A thorough search of the English medical literature revealed only three reported cases of RCC with direct invasion into the colon [2] [3] [4]. Here, we present another case with a brief literature review.
National guidance is neededfor Viagra
Authors: R. Harling
Journal: BMJ (1998)

The government should urgently review the mechanism for introducing newly licensed expensive drugs into clinical practice, doctors urged at the BMA's annual representative meeting last week.

Major concerns were raised about the introduction of sildenafil (Viagra), which is expected to be licensed for use in Britain in September. Tessa Jowell, the minister for public health, has stated that …
Abstract 5223: Elucidating the complex cross-talk between the MAPK and PIK3 pathways.
Authors: Megan E. Egbert, Michelle L. Wynn, Zhi Fen Wu, Santiago Schnell, Sofia D. Merajver
Journal: Cancer Research (2013)

Abstract Targeted molecular inhibitors have emerged as a leading anti-cancer strategy; however, despite promising pre-clinical data, many targeted inhibitors induce undesirable off-target effects in the clinic. The large number of off-target effects associated with molecular inhibitors was recently termed the ‘‘whack a mole problem’’ because inhibiting one molecular target often unintentionally activates another molecule. It is increasingly clear that the high incidence of off-target effects associated with targeted inhibitors is related to the complex interactions and emergent behaviors inherent to the highly complex and dysregulated intracellular networks of cancer. Both the mitogen activated protein kinase (MAPK) and phosphatidylinositol-3 kinase (PI3K) pathways are known to be dysregulated in cancer. In previous work, we and others have demonstrated that the MAPK pathway promotes motility, invasion, and angiogenic factors while the PI3K pathway plays an important role in controlling anchorage independent growth. In addition, the PI3K pathway plays an essential role in stimulating glucose metabolism and the Warburg effect. We hypothesize that robust interactions exist between these two pathways that influence efficacy and potentially also acquired resistance to targeted therapies. Using a combination of experimental and theoretical techniques, we developed a predictive network model linking growth factor signaling to the MAPK and PI3K pathways as well as to glucose metabolism. Specifically, we constructed a logic-based network of the cross-talk between MAPK and PI3K signaling that relied on a detailed literature survey to identify known molecular interactions as well as proposed interactions and regulatory feedback connections in the literature. We next performed a set of experiments using a normal-like breast epithelial cell line and a series of pathway specific inhibitors with and without growth factor stimulation to validate our model. Finally, we repeated these experiments using a diverse set of breast cancer cell lines and integrated this data to produce a series of cancer networks representative of different stages of breast cancer progression. Our model was able to recapitulate both our own experimental data and published data in the literature using a smaller subset of regulatory feedback mechanisms than we started with. Together, our results suggest that some proposed interactions and feedback mechanisms attributed to MAPK and PI3K cross-talk in the literature may not be valid. Citation Format: Megan E. Egbert, Michelle L. Wynn, Zhi Fen Wu, Santiago Schnell, Sofia D. Merajver. Elucidating the complex cross-talk between the MAPK and PIK3 pathways. [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 5223. doi:10.1158/1538-7445.AM2013-5223