tbuckley/cabot-search huggingface dataset:
Intensive Medical Therapy Versus Coronary Angioplasty for Suppression of Myocardial Ischemia in Survivors of Acute Myocardial Infarction
Authors: Habib A. Dakik, Neal S. Kleiman, John A. Farmer, Zuo-Xiang He, Juliet A. Wendt, Craig M. Pratt, Mario S. Verani, John J. Mahmarian
Journal: Circulation (1998)

Background —Patients who have inducible ischemia after acute myocardial infarction (AMI) generally undergo coronary angiography with the intent to revascularize. Whether this approach is superior to intensive treatment with anti-ischemic medications is unknown. Methods and Results —We performed a prospective, randomized pilot study comparing intensive medical therapy with coronary angioplasty (PTCA) for suppression of myocardial ischemia in 44 stable survivors of AMI. Myocardial ischemia was quantified with adenosine 201 Tl tomography (SPECT) performed 4.5±2.9 days after AMI. All patients at baseline had a large total (≥20%) and ischemic (≥10%) left ventricular perfusion defect size (PDS). SPECT was repeated at 43±26 days after therapy was optimized. The total stress-induced PDS was comparably reduced with medical therapy (from 38±13% to 26±16%; P &lt;0.0001) and PTCA (from 35±12% to 20±16%; P &lt;0.0001). The reduction in ischemic PDS was also similar ( P =NS) in both groups. Cardiac events occurred in 7 of 44 patients over 12±5 months. Patients who remained clinically stable had a greater reduction in ischemic PDS (−13±9%) than those who had a recurrent cardiac event (−5±7%; P &lt;0.02). Event-free survival was superior in the 24 patients who had a significant (≥9%) reduction in PDS (96%) compared with those who did not (65%; P =0.009). Conclusions —In this small pilot study, intensive medical therapy and PTCA were comparable at suppressing ischemia in stable patients after AMI. Sequential imaging with adenosine SPECT can track changes in PDS after anti-ischemic therapies and thereby predict subsequent outcome. Corroboration of these preliminary findings in a larger cardiac-event trial is warranted.
Abrogation of TGF-β signaling enhances chemokine production and correlates with prognosis in human breast cancer
Authors: Brian Bierie, Christine H. Chung, Joel S. Parker, Daniel G. Stover, Nikki Cheng, Anna Chytil, Mary Aakre, Yu Shyr, Harold L. Moses
Journal: Journal of Clinical Investigation (2009)

In human breast cancer, loss of carcinoma cell-specific response to TGF-beta signaling has been linked to poor patient prognosis. However, the mechanisms through which TGF-beta regulates these processes remain largely unknown. In an effort to address this issue, we have now identified gene expression signatures associated with the TGF-beta signaling pathway in human mammary carcinoma cells. The results strongly suggest that TGF-beta signaling mediates intrinsic, stromal-epithelial, and host-tumor interactions during breast cancer progression, at least in part, by regulating basal and oncostatin M-induced CXCL1, CXCL5, and CCL20 chemokine expression. To determine the clinical relevance of our results, we queried our TGF-beta-associated gene expression signatures in 4 human breast cancer data sets containing a total of 1,319 gene expression profiles and associated clinical outcome data. The signature representing complete abrogation of TGF-beta signaling correlated with reduced relapse-free survival in all patients; however, the strongest association was observed in patients with estrogen receptor-positive (ER-positive) tumors, specifically within the luminal A subtype. Together, the results suggest that assessment of TGF-beta signaling pathway status may further stratify the prognosis of ER-positive patients and provide novel therapeutic approaches in the management of breast cancer.
Hydroxychloroquine and visual screening in a rheumatology outpatient clinic
Authors: D J Grierson
Journal: Annals of the Rheumatic Diseases (1997)

To review 10 years' data relating to visual screening of patients taking hydroxychloroquine.Following baseline visual assessment, ophthalmic monitoring was carried out at six monthly intervals on 758 patients while on hydroxychloroquine. This consisted of corrected visual acuity, central field screening with a red Amsler grid, slit lamp examination, and retinoscopy.None of the patients suffered visual impairment from retinal toxicity, though 12 reported visual disturbance. This was related to ocular muscle imbalance in four. In the remainder, none of the ocular findings was directly attributable to hydroxychloroquine. Ten patients reported defects when tested with a red Amsler grid. None was related to retinal toxicity. Seven patients developed corneal drug deposits which cleared on stopping or reducing the dose of hydroxy-chloroquine.The findings support the view that following baseline ophthalmic examination for patients receiving hydroxychloroquine, regular ophthalmic screening is not required if the daily dose is less than 6.5 mg kg-1 and the cumulative dose is less than 200 g.
Mouse Models of Lung Cancer
Authors: Amit Dutt, Kwok-Kin Wong
Journal: Clinical Cancer Research (2006)

Abstract Human lung cancer is responsible for ∼30% of all cancer deaths worldwide with &amp;gt;160,000 deaths in the United States alone annually. Recent advances in the identification of novel mutations relevant to lung cancer from a myriad of genomic studies might translate into meaningful diagnostic and therapeutic progress. Towards this end, a genetic model animal system that can validate the oncogenic roles of these mutations in vivo would facilitate the understanding of the pathogenesis of lung cancer as well as provide ideal preclinical models for targeted therapy testing. The mouse is a promising model system, as complex human genetic traits causal to lung cancer, from inherited polymorphisms to somatic mutations, can be recapitulated in its genome via genetic manipulation. We present here a brief overview of the existing mouse models of lung cancers and the challenges and opportunities for building the next generation of lung cancer mouse models.
High-resolution narrow band imaging endoscopy
Authors: A Larghi, P G Lecca, G Costamagna
Journal: Gut (2008)

Oesophageal, gastric and colorectal neoplasms made up 24% of worldwide cancer mortality in 2002.1 Early detection of these neoplasms or their precursors may be the only chance to reduce this high mortality. Endoscopy is currently the initial procedure used for early detection of gastrointestinal (GI) cancers worldwide. The endoscopic appearance of early cancers is described as 9superficial9, and was first described in Japan for gastric cancer. The Japanese Gastric Cancer Association divides these superficial lesions into three types: type I polypoid, type II non-polypoid and nonexcavated, and type III non-polypoid with an ulcer (Figure 1).2  The type I is further divided into Ip for pedunculated lesions and Is for sessile lesions, while type II is subdivided into IIa for slightly elevated lesions, IIb for completely flat lesions, and IIc for slightly depressed lesions.2 This classification is the result of meticulous work by Japanese endoscopists who were facing with the high burden of gastric cancer, which develops almost exclusively from flat precursors.3 Thus, learning to identify subtle superficial abnormalities, such as discoloration of the mucosa (pale or red), helped to increase the recognition of mucosal and submucosal lymph node-negative gastric cancers (from 25% in 1975-1977 to 50% in 1993-1995)4 and improved survival in this patient population.5
The Effect of Real-Time Continuous Glucose Monitoring in Pregnant Women With Diabetes
Authors: Anna L. Secher, Lene Ringholm, Henrik U. Andersen, Peter Damm, Elisabeth R. Mathiesen
Journal: Diabetes Care (2013)

OBJECTIVE To assess whether intermittent real-time continuous glucose monitoring (CGM) improves glycemic control and pregnancy outcome in unselected women with pregestational diabetes. RESEARCH DESIGN AND METHODS A total of 123 women with type 1 diabetes and 31 women with type 2 diabetes were randomized to use real-time CGM for 6 days at 8, 12, 21, 27, and 33 weeks in addition to routine care, including self-monitored plasma glucose seven times daily, or routine care only. To optimize glycemic control, real-time CGM readings were evaluated by a diabetes caregiver. HbA1c, self-monitored plasma glucose, severe hypoglycemia, and pregnancy outcomes were recorded, with large-for-gestational-age infants as the primary outcome. RESULTS Women assigned to real-time CGM (n = 79) had baseline HbA1c similar to that of women in the control arm (n = 75) (median 6.6 [range 5.3–10.0] vs. 6.8% [5.3–10.7]; P = 0.67) (49 [34–86] vs. 51 mmol/mol [34–93]). Forty-nine (64%) women used real-time CGM per protocol. At 33 weeks, HbA1c (6.1 [5.1–7.8] vs. 6.1% [4.8–8.2]; P = 0.39) (43 [32–62] vs. 43 mmol/mol [29–66]) and self-monitored plasma glucose (6.2 [4.7–7.9] vs. 6.2 mmol/L [4.9–7.9]; P = 0.64) were comparable regardless of real-time CGM use, and a similar fraction of women had experienced severe hypoglycemia (16 vs. 16%; P = 0.91). The prevalence of large-for-gestational-age infants (45 vs. 34%; P = 0.19) and other perinatal outcomes were comparable between the arms. CONCLUSIONS In this randomized trial, intermittent use of real-time CGM in pregnancy, in addition to self-monitored plasma glucose seven times daily, did not improve glycemic control or pregnancy outcome in women with pregestational diabetes.
Decision Aids and Breast Cancer: Do They Influence Choice for Surgery and Knowledge of Treatment Options?
Authors: Jennifer F. Waljee, Mary A.M. Rogers, Amy K. Alderman
Journal: Journal of Clinical Oncology (2007)

To describe the effect of decision aids on the choice for surgery and knowledge of surgical therapy among women with early-stage breast cancer.A systematic review was conducted between years 1966 to 2006 of all studies designed to assess the effect of decision aids on surgical therapy. MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health (CINAHL), the Cochrane Network, HAPI databases, and bibliographies were searched. Of the 123 studies screened, 11 studies met criteria. Meta-analyses were performed to assess the pooled relative risk for surgical choice and the pooled mean difference in patient knowledge.Results from randomized controlled trials indicated that women who used a decision aid were 25% more likely to choose breast-conserving surgery over mastectomy (risk ratio, 1.25; 95% CI, 1.11 to 1.40). Decision aids significantly increased patient knowledge by 24% (P = .024). The data also suggested that decision aids decreased decisional conflict and increased satisfaction with the decision-making process. Decision aids were well received by surgeons and patients, facilitated patients' desire for shared decision making, and were feasible to implement into practice.Decision aids are important adjuncts for counseling women with early-stage breast cancer. Their use increases the likelihood that women will choose breast-conserving surgery, and enhances patient knowledge of treatment options.
Evolution of Promoter Affinity for Transcription Factors in the Human Lineage
Authors: I. Molineris, E. Grassi, U. Ala, F. Di Cunto, P. Provero
Journal: Molecular Biology and Evolution (2011)

Changes in gene regulation are believed to play an important role in the evolution of animals. It has been suggested that changes in cis-regulatory regions are responsible for many or most of the anatomical and behavioral differences between humans and apes. However, the study of the evolution of cis-regulatory regions is made problematic by the degeneracy of transcription factor (TF) binding sites and the shuffling of their positions. In this work, we use the predicted total affinity of a promoter for a large collection of TFs as the basis for studying the evolution of cis-regulatory regions in mammals. We introduce the human specificity of a promoter, measuring the divergence between the affinity profile of a human promoter and its orthologous promoters in other mammals. The promoters of genes involved in functional categories such as neural processes and signal transduction, among others, have higher human specificity compared with the rest of the genome. Clustering of the human-specific affinities (HSAs) of neural genes reveals patterns of promoter evolution associated with functional categories such as synaptic transmission and brain development and to diseases such as bipolar disorder and autism.
Hearing loss in patients on treatment for drug-resistant tuberculosis
Authors: James A. Seddon, Peter Godfrey-Faussett, Kayleen Jacobs, Adam Ebrahim, Anneke C. Hesseling, H. Simon Schaaf
Journal: European Respiratory Journal (2012)

The treatment of drug-resistant (DR)-tuberculosis (TB) necessitates the use of second-line injectable anti-TB drugs which are associated with hearing loss. Hearing loss affects communication and the development of language and social skills in children. This review describes the pathophysiology of hearing loss and the testing methodologies that can be employed. It is the first paper to systematically review the literature regarding hearing loss in those treated for DR-TB. In the studies identified, the methodology used to test for and to classify hearing loss is inconsistent and children and those with HIV are poorly represented. This review describes existing guidelines and suggests management strategies when hearing loss is found. It describes the challenges of testing hearing in the developing world contexts where the majority of patients with DR-TB are treated. Finally it makes the recommendation that a standardised testing methodology and classification system should be used.
Tight Blood Glucose Control Is Renoprotective in Critically Ill Patients
Authors: Miet Schetz, Ilse Vanhorebeek, Pieter J. Wouters, Alexander Wilmer, Greet Van den Berghe
Journal: Journal of the American Society of Nephrology (2008)

Two large, prospective, randomized, controlled trials have shown a beneficial effect of intensive insulin therapy (IIT) on the kidney function of critically ill patients. The data from these trials were combined for performance of a more detailed analysis of the renoprotective effect of IIT. After exclusion of 41 patients with preadmission ESRD, the study sample comprised 2707 critically ill patients who were randomly assigned to conventional or IIT. A modified risk-injury-failure-loss-ESRD (mRIFLE) system was used to classify acute kidney injury such that mRIFLE-Injury and -Failure (mR-IF) corresponded to peak serum creatinine levels >/=2x and >/=3x the admission levels, respectively. IIT significantly reduced the incidence of mR-I or -F from 7.6 to 4.5% (P = 0.0006), and this renoprotective effect was most pronounced in patients who achieved strict normoglycemia. In surgical patients, IIT also significantly reduced oliguria (from 5.6 to 2.6%; P = 0.004) and the need for renal replacement therapy (from 7.4 to 4.0%; P = 0.008). In medical patients, the incidence of mR-I or -F decreased to a lesser extent, perhaps because a greater severity of illness at admission may have rendered preventive therapies less effective. In conclusion, this secondary analysis of two large, randomized, controlled trials suggests that IIT, with a goal of achieving normoglycemia, protects the renal function of critically ill patients.
The Effect of Acute Respiratory Distress Syndrome on Long-term Survival
Authors: TIMOTHY A. DAVIDSON, GORDON D. RUBENFELD, ELLEN S. CALDWELL, LEONARD D. HUDSON, KENNETH P. STEINBERG
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Despite a great deal of information about the risk factors, prognostic variables, and hospital mortality in the acute respiratory distress syndrome (ARDS), very little is known about the long-term outcomes of patients with this syndrome. We conducted a prospective, matched, parallel cohort study with the goals of describing the survival of patients with ARDS after hospital discharge and comparing the long-term survival of patients with ARDS and that of a group of matched controls. The study involved 127 patients with ARDS associated with trauma or sepsis and 127 controls matched for risk factor (trauma or sepsis) and severity of illness who survived to hospital discharge. Time until death was used as the outcome measure. Survival was associated with age, risk factor for ARDS, and comorbidity. There was no difference in the long-term mortality rate for ARDS patients and that of matched controls (hazard ratio for ARDS: 1.00; 95% confidence interval: 0.47 to 2.09) after controlling for age, risk factor for ARDS, comorbidity, and severity of illness. We conclude that if sepsis or trauma patients survive to hospital discharge, ARDS does not increase their risk of subsequent death. Older patients, patients with sepsis, and patients with comorbidities, regardless of the presence of ARDS, have a higher risk of death after hospital discharge. For the purposes of clinical prognosis and cost-effectiveness analysis, the long-term survival of patients with ARDS can be modeled on the basis of age, underlying risk factor for ARDS, and comorbidity. Davidson TA, Rubenfeld GD, Caldwell ES, Hudson LD, Steinberg KP. The effect of acute respiratory distress syndrome on long-term survival.
Commentary: but what should journals actually do to keep industry sponsored research unbiased?
Authors: C. Del Mar
Journal: BMJ (2010)

A timely paper from Robert Steinbrook and Jerome P Kassirer (doi:10.1136/bmj.c5391) takes the position that journals should increase the rigour required to address bias in data offered for publication from industry sponsored trials. In particular (1) the definition (currently ambiguous) of “full access to data” for the authors should be cleared up; (2) one author in the team should be truly independent of any pecuniary interest in the product and act as guarantor; (3) data must be available to editors in case of future concern, (something hopefully rarely exercised); and finally (4) there would be consequences after publication if data were found to have been …
Evaluation of an [<sup>18</sup>F]AlF-NOTA Analog of Exendin-4 for Imaging of GLP-1 Receptor in Insulinoma
Authors: Dale O. Kiesewetter, Ning Guo, Jinxia Guo, Haokao Gao, Lei Zhu, Ying Ma, Gang Niu, Xiaoyuan Chen
Journal: Theranostics (2012)

Introduction:The GLP-1 receptor plays an important role in glucose homeostasis and thus is a very important target for diabetes therapy.The receptor is also overexpressed in insulinoma, a tumor of pancreatic beta-cells.We previously evaluated two fluorine-18-labeled analogs of exendin-4 prepared by conjugation with [ 18 F]FBEM (N-[2-(4-[ 18 F]fluorobenzamide) ethyl]maleimide).Both compounds demonstrated good tumor uptake, but the synthesis of the radiotracers was time consuming.To overcome this challenge, we developed a NOTA analog and performed radiolabeling using aluminum [ 18 F]fluoride complexation.Methods: Cys 40 -exendin-4 was conjugated with NOTA mono N-ethylmaleimide.[ 18 F]AlF conjugation was conducted and the radiolabeled product purified by preparative HPLC.Dynamic and static PET imaging scans were conducted on nude mice with established INS-1 xenografts.Uptake of tumor and other major organs in static images was quantitated (%ID/g) and comparison with blocking studies was made.PET quantification was also compared with ex vivo biodistribution results.Results: The radiosynthesis provided [ 18 F]AlF-NOTA-MAL-cys 40 -exendin-4 in 23.6 ± 2.4 % radiochemical yield (uncorrected, n = 3) after HPLC; the process required about 55 min.The specific activity at time of injection ranged from 19.6 to 31.4 GBq (0.53-0.85 Ci)/µmol.Tumor uptake had reached its maximum (16.09 ± 1.18% ID/g, n = 4) by 5 min and remained nearly constant for the duration of the study.Kidney uptake continued to increase throughout the entire one hour time course.Pre-injection of exendin-4 caused a marked reduction in tissue uptake with the major exception of liver and kidneys, in which uptake was not affected.HPLC analysis of the radioactive components in extracts of the tumor and plasma showed primarily parent compound at 60 min post-injection, whereas extracts of kidney and urine contained exclusively one polar radioactive component. Conclusion:The radiotracer is prepared in a simple one-step procedure and obtained in high specific activity after HPLC purification.[ 18 F]AlF-NOTA-MAL-exendin-4 shows high tumor uptake and highly selective GLP-1 tissue uptake (INS-1 tumor, lung, pancreas), but still suffers from high kidney uptake.
Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial
Authors: Helen M Colhoun, D John Betteridge, Paul N Durrington, Graham A Hitman, H Andrew W Neil, Shona J Livingstone, Margaret J Thomason, Michael I Mackness, Valentine Charlton-Menys, John H Fuller
Journal: The Lancet (2004)
Intratumoral Therapy of Glioblastoma Multiforme Using Genetically Engineered Transferrin for Drug Delivery
Authors: Dennis J. Yoon, Byron H. Kwan, Felix C. Chao, Theodore P. Nicolaides, Joanna J. Phillips, Gretchen Y. Lam, Anne B. Mason, William A. Weiss, Daniel T. Kamei
Journal: Cancer Research (2010)

Abstract Glioblastoma multiforme (GBM) is the most common and lethal primary brain tumor with median survival of only 12 to 15 months under the current standard of care. To both increase tumor specificity and decrease nonspecific side effects, recent experimental strategies in the treatment of GBM have focused on targeting cell surface receptors, including the transferrin (Tf) receptor, that are overexpressed in many cancers. A major limitation of Tf-based therapeutics is the short association of Tf within the cell to deliver its payload. We previously developed two mutant Tf molecules, K206E/R632A Tf and K206E/K534A Tf, in which iron is locked into each of the two homologous lobes. Relative to wild-type Tf, we showed enhanced delivery of diphtheria toxin (DT) from these mutants to a monolayer culture of HeLa cells. Here, we extend the application of our Tf mutants to the treatment of GBM. In vitro treatment of Tf mutants to a monolayer culture of glioma cells showed enhanced cellular association as well as enhanced delivery of conjugated DT. Treatment of GBM xenografts with mutant Tf-conjugated DT resulted in pronounced regression in vivo, indicating their potential use as drug carriers. Cancer Res; 70(11); 4520–7. ©2010 AACR.