tbuckley/cabot-search huggingface dataset:
Estrogen Receptor (<i>ESR1</i>) mRNA Expression and Benefit From Tamoxifen in the Treatment and Prevention of Estrogen Receptor–Positive Breast Cancer
Authors: Chungyeul Kim, Gong Tang, Katherine L. Pogue-Geile, Joseph P. Costantino, Frederick L. Baehner, Joffre Baker, Maureen T. Cronin, Drew Watson, Steven Shak, Olga L. Bohn, Debora Fumagalli, Yusuke Taniyama, Ahwon Lee, Megan L. Reilly, Victor G. Vogel, Worta McCaskill-Stevens, Leslie G. Ford, Charles E. Geyer, D. Lawrence Wickerham, Norman Wolmark, Soonmyung Paik
Journal: Journal of Clinical Oncology (2011)

Purpose Several mechanisms have been proposed to explain tamoxifen resistance of estrogen receptor (ER) –positive tumors, but a clinically useful explanation for such resistance has not been described. Because the ER is the treatment target for tamoxifen, a linear association between ER expression levels and the degree of benefit from tamoxifen might be expected. However, such an association has never been demonstrated with conventional clinical ER assays, and the ER is currently used clinically as a dichotomous marker. We used gene expression profiling and ER protein assays to help elucidate molecular mechanism(s) responsible for tamoxifen resistance in breast tumors. Patients and Methods We performed gene expression profiling of paraffin-embedded tumors from National Surgical Adjuvant Breast and Bowel Project (NSABP) trials that tested the worth of tamoxifen as an adjuvant systemic therapy (B-14) and as a preventive agent (P-1). This was a retrospective subset analysis based on available materials. Results In B-14, ESR1 was the strongest linear predictor of tamoxifen benefit among 16 genes examined, including PGR and ERBB2. On the basis of these data, we hypothesized that, in the P-1 trial, a lower level of ESR1 mRNA in the tamoxifen arm was the main difference between the two study arms. Only ESR1 was downregulated by more than two-fold in ER-positive cancer events in the tamoxifen arm (P &lt; .001). Tamoxifen did not prevent ER-positive tumors with low levels of ESR1 expression. Conclusion These data suggest that low-level expression of ESR1 is a determinant of tamoxifen resistance in ER-positive breast cancer. Strategies should be developed to identify, treat, and prevent such tumors.
Reduction in Stent and Vascular Graft Thrombosis and Enhancement of Thrombolysis by Recombinant Lys-Plasminogen in Nonhuman Primates
Authors: I. Birgitta Sundell, Ulla M. Marzec, Andrew B. Kelly, Nicolas A. F. Chronos, Lars C. Petersen, Stephen R. Hanson, Ulla Hedner, Laurence A. Harker
Journal: Circulation (1997)

Background To enhance thrombolytic responses without increasing hemorrhagic risks, the antithrombotic effects of recombinant Lys-plasminogen (r-LysPgn), a prothrombolytic plasminogen intermediate, were examined in baboon models of thrombus formation and dissolution. Methods and Results The dose-response effects of r-LysPgn, alone or in combination with subthreshold dosing of tissue plasminogen activator (TPA), were measured with respect to the accumulation of 111 In-labeled platelets and 125 I-fibrin in thrombus forming on endovascular metallic stents or thrombogenic segments of vascular graft interposed in exteriorized long-term arteriovenous (AV) femoral shunts. Thrombolytic losses have also been determined for preformed, stable, 111 In-platelet– and 125 I-fibrin–labeled graft thrombus and corresponding propagated thrombotic tails, together with changes in blood tests of thrombosis, thrombolysis, and hemostasis. Bolus intravenous r-LysPgn in escalating doses (2, 4, or 8 mg/kg) increased circulating plasminogen levels in a dose-dependent manner, was removed by log-linear clearance with a T 50 of 120 minutes, and reciprocally decreased the accumulating thrombus on metallic stents and segments of vascular graft ( P &lt;.001 in all cases for 8-mg/kg doses). r-LysPgn also impaired platelet aggregatory responses to physiological agonists in vitro but not ex vivo. Prethrombosis administration of low-dose r-LysPgn (2 mg/kg) greatly enhanced the lysis of radiolabeled nonoccluding thrombus by a subthreshold dose of TPA (0.1 mg/kg) compared with TPA-only controls ( P =.03). Conclusions Elective bolus injections of r-LysPgn before stent deployment decrease the amount of thrombus formed without compromising hemostasis by facilitating endogenous TPA thrombolysis. r-LysPgn may provide effective and safe antithrombotic therapy for interventional vascular procedures.
Non-tuberculous mycobacteria in cystic fibrosis
Authors: J K Torrens, P Dawkins, S P Conway, E Moya
Journal: Thorax (1998)

The clinical significance of the presence of non-tuberculous mycobacteria in the sputum of patients with cystic fibrosis is unclear. A retrospective case-control study was performed to assess possible risk factors for non-tuberculous mycobacteria and its impact on clinical status in patients with cystic fibrosis.The records of all patients attending the Leeds cystic fibrosis clinics who were positive for non-tuberculous mycobacteria were examined. Each case was matched with two controls for sex, age, and respiratory function at the time of the first non-tuberculous mycobacteria isolate. Details of respiratory function, nutritional status, antibiotic and corticosteroid therapy, Shwachman-Kulczycki (S-K) score, Northern chest radiographic score, and the frequency of isolation of other bacteria and fungi were collected from two years before to two years after the first non-tuberculous mycobacteria isolate. The patients' genotype and the presence of diabetes mellitus were also recorded.Non-tuberculous mycobacteria were isolated from 14 patients out of a cystic fibrosis population of 372 (prevalence = 3.8%). No significant effect of non-tuberculous mycobacteria was seen on respiratory function, nutritional status, or S-K score. There was a significant association with the number of intravenous antibiotic courses received before the first isolate with cases receiving, on average, twice as many courses as controls (cases 6.64, controls 2.86, 95% CI for difference 1.7 to 5.9). No significant difference was seen between cases and controls for Northern scores, previous steroid therapy, or the incidence of diabetes mellitus.Non-tuberculous mycobacteria infection in patients with cystic fibrosis is uncommon and its clinical impact appears to be minimal over a two year period. Frequent intravenous antibiotic usage is a possible risk factor for colonisation with non-tuberculous mycobacteria.
Upper arm circumference is associated with race performance in ultra-endurance runners
Authors: B Knechtle, P Knechtle, I Schulze, G Kohler
Journal: British Journal of Sports Medicine (2007)

To investigate the association of anthropometric parameters to race performance in ultra-endurance runners in a multistage ultra-endurance run.Descriptive field study.The Deutschlandlauf 2006 race in Germany, where athletes had to run 1200 km within 17 consecutive days. There were no interventions.In total, there were 19 male Caucasian ultra-endurance runners (mean (SD) 46.2 (9.6) years, 71.8 (5.2) kg, 179 (6) cm, BMI 22.5 (1.9) kg/m(2)).Determination of body mass, body height, length of lower limbs, skin-fold thicknesses, circumference of limbs, body mass index (BMI), percentage skeletal muscle mass (%SM), and percentage body fat (%BF) in 19 successful finishers in order to correlate anthropometric parameters with running performance.A significant association of upper arm circumference with the total running time was found (p<0.05, r2 = 0.26). No significant association was found with the directly measured anthropometric properties body height, body mass, average skin-fold thickness and the circumference of thigh and calf (p>0.05). Furthermore, no significant association was observed between the running time and the calculated parameters BMI, %BF, and %SM (p>0.05).In an ultra-endurance run over 1200 km within 17 consecutive days, circumference of the upper arm was the only factor associated with performance in well-experienced ultra-endurance runners. Body mass, BMI, body height, length of limbs, skin-fold thicknesses, circumference of limbs and the calculated percentage body composition of skeletal muscle mass and body fat showed no association with running performance.
Therapeutic potential of new B cell-targeted agents in the treatment of elderly and unfit patients with chronic lymphocytic leukemia
Authors: Kanti R. Rai
Journal: Journal of Hematology & Oncology (2015)

Chronic lymphocytic leukemia (CLL), the most common adult leukemia in the Western world, is primarily a disease of the elderly, with most patients ≥65 years of age and having at least one major comorbidity. Aggressive chemoimmunotherapy regimens recommended to achieve remission and improve survival in young, fit patients are often poorly tolerated in elderly and/or less physiologically fit ("unfit") patients, necessitating alternative treatment options. Although patient age, fitness, and comorbidities are key considerations in the selection of a treatment regimen, historically, clinical trials have been limited to young, fit patients by virtue of the ethical concerns associated with potential end organ toxic effects that could worsen comorbidities. However, the availability of new therapies promises a shift to a research paradigm that encompasses the identification of optimal treatments for elderly and unfit patients. Anti-CD20 monoclonal antibody therapy, which overall has improved response rates and survival in patients with CLL, has only recently been evaluated elderly and unfit patients. B cell-targeted agents such as the Bruton's tyrosine kinase inhibitor ibrutinib and the phosphatidylinositol 3-kinase inhibitor idelalisib are the first of a new generation of oral agents for CLL. Available clinical data suggest that these therapies have the potential to address the unmet need in elderly and unfit patients with CLL and result in clinical remission, and not merely symptom palliation and improved quality of life, which, by themselves, are also a reasonable goal.
Risk of Aborted Cardiac Arrest or Sudden Cardiac Death During Adolescence in the Long-QT Syndrome
Authors: Jenny B. Hobbs, Derick R. Peterson, Arthur J. Moss, Scott McNitt, Wojciech Zareba, Ilan Goldenberg, Ming Qi, Jennifer L. Robinson, Andrew J. Sauer, Michael J. Ackerman, Jesaia Benhorin, Elizabeth S. Kaufman, Emanuela H. Locati, Carlo Napolitano, Silvia G. Priori, Jeffrey A. Towbin, G. Michael Vincent, Li Zhang
Journal: JAMA (2006)

Analysis of predictors of cardiac events in hereditary long-QT syndrome (LQTS) has primarily considered syncope as the predominant end point. Risk factors specific for aborted cardiac arrest and sudden cardiac death have not been investigated.To identify risk factors associated with aborted cardiac arrest and sudden cardiac death during adolescence in patients with clinically suspected LQTS.The study involved 2772 participants from the International Long QT Syndrome Registry who were alive at age 10 years and were followed up during adolescence until age 20 years. The registry enrollment began in 1979 at 5 cardiology centers in the United States and Europe.Aborted cardiac arrest or LQTS-related sudden cardiac death; follow-up ended on February 15, 2005.There were 81 patients who experienced aborted cardiac arrest and 45 who had sudden cardiac death; 9 of the 81 patients who had an aborted cardiac arrest event experienced subsequent sudden cardiac death. Significant independent predictors of aborted cardiac arrest or sudden cardiac death during adolescence included recent syncope, QTc interval, and sex. Compared with those with no syncopal events in the last 10 years, patients with 1 or 2 or more episodes of syncope 2 to 10 years ago (but none in the last 2 years) had an adjusted hazard ratio (HR) of 2.7; (95% confidence interval [CI], 1.3-5.7; P<.01) and an adjusted HR of 5.8 (95% CI, 3.6-9.4; P<.001), respectively, for life-threatening events; those with 1 syncopal episodes in the last 2 years had an adjusted HR of 11.7 (95% CI, 7.0-19.5; P<.001) and those with 2 or more syncopal episodes in the last 2 years had an adjusted HR of 18.1 (95% CI, 10.4-31.2; P<.001). Irrespective of events occurring more than 2 years ago, QTc of 530 ms or longer was associated with increased risk (adjusted HR, 2.3; 95% CI, 1.6-3.3; P<.001) compared with those having a shorter QTc. Males between the ages of 10 and 12 years had higher risk than females (HR, 4.0; 95% CI, 1.8-9.2; P = .001), but there was no significant risk difference between males and females between the ages of 13 and 20 years. Among individuals with syncope in the past 2 years, beta-blocker therapy was associated with a 64% reduced risk (HR, 0.36; 95% CI, 0.18-0.72; P<.01).In LQTS, the timing and frequency of syncope, QTc prolongation, and sex were predictive of risk for aborted cardiac arrest and sudden cardiac death during adolescence. Among patients with recent syncope, beta-blocker treatment was associated with reduced risk.
Gene expression profiling of epithelial ovarian tumours correlated with malignant potential.
Authors: Susanne Warrenfeltz, Stephen Pavlik, Susmita Datta, Eileen T Kraemer, Benedict Benigno, John F McDonald
Journal: Molecular Cancer (2004)

Epithelial ovarian tumours exhibit a range of malignant potential, presenting distinct clinical phenotypes. Improved knowledge of gene expression changes and functional pathways associated with these clinical phenotypes may lead to new treatment targets, markers for early detection and a better understanding of disease progression. Gene expression profiling (Affymetrix, U95Av2) was carried out on 18 ovarian tumours including benign adenomas, borderline adenocarcinomas of low malignant potential and malignant adenocarcinomas. Clustering the expression profiles of samples from patients not treated with chemotherapy prior to surgery effectively classified 92% of samples into their proper histopathological group. Some cancer samples from patients treated with chemotherapy prior to surgery clustered with the benign adenomas. Chemotherapy patients whose tumours exhibited benign-like expression patterns remained disease free for the duration of this study as indicated by continued normal serum CA-125 levels. Statistical analysis identified 163 differentially expressed genes: 61 genes under-expressed in cancer and 102 genes over-expressed in cancer. Profiling the functional categories of co-ordinately expressed genes within this list revealed significant correlation between increased malignant potential and loss of both IGF binding proteins and cell adhesion molecules. Interestingly, in several instances co-ordinately expressed genes sharing biological function also shared chromosomal location. Our findings indicate that gene expression profiling can reliably distinguish between benign and malignant ovarian tumours. Expression profiles of samples from patients pre-treated with chemotherapy may be useful in predicting disease free survival and the likelihood of recurrence. Loss of expression of IGF binding proteins as well as specific cell adhesion molecules may be a significant mechanism of disease progression in ovarian cancer. Expression levels in borderline tumours were intermediate between benign adenomas and malignant adenocarcinomas for a significant portion of the differentially expressed genes, suggesting that borderline tumours are a transitional state between benign and malignant tumours. Finally, genes displaying coordinated changes in gene expression were often genetically linked, suggesting that changes in expression for these genes are the consequence of regional duplications, deletions or epigenetic events.
Microvascular and C-Fiber Function in Diabetic Charcot Neuroarthropathy and Diabetic Peripheral Neuropathy
Authors: Neil Baker, Alistair Green, Singhan Krishnan, Gerry Rayman
Journal: Diabetes Care (2007)

Sympathetic denervation and hyperemia are implicated in the pathogenesis of Charcot neuroarthropathy (CN) but are also features of diabetic peripheral neuropathy (DPN). Differences in these physiological parameters were sought by determining C-fiber function (laser Doppler imager [LDI]flare technique) and maximum microvascular hyperemia (MMH) in 13 subjects with diabetic CN (DCN), 10 subjects with DPN, and 10 healthy control subjects. Additionally, unaffected limbs of the nine DCN subjects with unilateral CN (UCN) were studied to determine whether any observed differences precede CN.LDIflare area was reduced in DPN (mean +/- SD 1.41 +/- 0.51 cm(2)) and DCN (1.42 +/- 0.37) groups compared with the healthy control group (5.24 +/- 1.33; P < 0.0001). MMH was higher in DCN (432 +/- 88 PU [perfusion units]) than in DPN (262 +/- 71; P = 0.001) subjects but lower than in the control group (564 +/- 112; P < 0.01). LDIflare area and MMH were similar in the UCN and DCN groups.C-fiber function is equally impaired in neuropathic patients with and without CN; however, a higher MMH distinguishes those with CN. Unaffected and affected limbs of those with unilateral CN have the same neurovascular abnormalities, suggesting that these abnormalities precede CN and are not a result of CN.
Effects of air quality on chronic respiratory symptoms adjusted for allergy among preadolescent children
Authors: W Jedrychowski, E Flak
Journal: European Respiratory Journal (1998)

The aim of this study was to assess the respiratory effects of outdoor air pollution after correcting for allergy and indoor air quality. The respiratory health survey targeted 1,129 schoolchildren, 9 yrs of age, attending schools in Krakow located in city areas differing in outdoor air pollution levels. Chronic phlegm as a unique symptom was related neither to allergy nor to indoor variables, but was associated with the outdoor air pollution level (odds ratio (OR): 4.2; 95% confidence interval (CI): 1.1-16.9). The same relationship has been confirmed for the self-reported local sources of industrial air pollution in the area of residence (OR: 4.2; 95% CI: 1.5-11.7). Hay fever appeared to be related to outdoor air pollution level (OR: 1.43; 95% CI: 1.1-2.0) and self-reported heavy traffic (OR: 1.3; 95% CI: 1.0-1.7). In the total sample, wheezing was connected exclusively to allergy and parental atopy, while attacks of dyspnoea with wheezing and asthma diagnosed by physician only were associated with allergy. Since the effect of outdoor pollutants on chronic cough and wheezing (odds ratio: 1.85; 95% confidence interval: 1.03-3.33) was only shown to be significant in the subsample of children without allergy and parental atopy, it may be postulated that either allergy is predisposing to respiratory reactions, or outdoor air pollution is coinvolved in an allergization process of the preadolescent children. Consequently, allergy should be considered as an important confound in epidemiological studies on the respiratory effects of air pollution.
Football for life versus antidoping for the masses: ethical antidoping issues and solutions based on the extenuating experiences of an elite footballer competing while undergoing treatment for metastatic testicular cancer
Authors: Richard Weiler, Dylan Tombides, Jon Urwin, Jane Clarke, Michele Verroken
Journal: British Journal of Sports Medicine (2014)

It is thankfully rare for extenuating circumstances to fully test the processes and procedures enshrined in national and world antidoping authorities' rules and laws. It is also thankfully very rare that a failed drugs test can have some positive implications. Antidoping laws are undoubtedly focused on ensuring fair competition, however, there are occasions when honest athletes discover medical diagnoses through failed antidoping tests. The purpose of this paper is to broadly discuss antidoping considerations encountered, based on the four principles of medical ethics and to propose simple solutions to these problems. Unfortunately, extreme medical circumstances will often test the limits of antidoping and medical processes and with open channels for feedback, these systems can improve. Performance enhancement seems an illogical concept if an athlete's medical treatment and disease are more inherently performance harming than unintended potential doping, but needs to be carefully managed to maintain fair sport.
Circulating endothelial giant cells permissive for human cytomegalovirus (HCMV) are detected in disseminated HCMV infections with organ involvement.
Authors: E Percivalle, M G Revello, L Vago, F Morini, G Gerna
Journal: Journal of Clinical Investigation (1993)

Giant cells fully permissive for human cytomegalovirus (HCMV) were found to circulate, at a variable proportion, in peripheral blood of 21 out of 25 immunocompromised patients with disseminated HCMV infection. Circulating endothelial giant cells (EGC) were identified by a specific monoclonal antibody of endothelial origin and shown to express immediate-early, early, and late viral proteins. Immunostaining patterns of different viral proteins were comparable to those detected in vitro in cultured human umbilical vein endothelial cells. EGC counts > 10 were associated with high levels (> 100) of HCMV viremia and antigenemia, as well as with an overt clinical syndrome in transplanted patients, and to an untreated long lasting organ localization in AIDS patients. On the other hand, EGC counts were < 10 during disseminated HCMV infections of both transplant recipients with no apparent organ syndrome and AIDS patients with recent organ involvement. In tissue sections from AIDS patients, infected endothelial cells were found to progressively enlarge till detaching from the small vessel wall and entering blood stream. HCMV-infected EGC represent a new systemic parameter suitable for the diagnosis of HCMV organ involvement and for the study of the pathogenesis of disseminated infections.
Is the Impact of Hospital and Surgeon Volumes on the In-Hospital Mortality Rate for Coronary Artery Bypass Graft Surgery Limited to Patients at High Risk?
Authors: Chuntao Wu, Edward L. Hannan, Thomas J. Ryan, Edward Bennett, Alfred T. Culliford, Jeffrey P. Gold, O. Wayne Isom, Robert H. Jones, Barbara McNeil, Eric A. Rose, Valavanur A. Subramanian
Journal: Circulation (2004)

Background— Restriction of volume-based referral for CABG surgery to high-risk patients has been suggested, and earlier studies have reached different conclusions regarding volume-based referral for low-risk patients. Methods and Results— Patients who underwent isolated CABG surgery in New York from 1997 through 1999 (n=57 150) were separated into low-risk and moderate-to-high-risk groups with a predicted probability of in-hospital death of 2% as the cutoff point. The provider volume-mortality relationship was examined for both groups. For annual hospital volume thresholds between 200 and 600 cases, the adjusted ORs of in-hospital mortality for high-volume to low-volume hospitals ranged from 0.45 to 0.77 and were all significant for the low-risk group; for the moderate-to-high-risk group, ORs ranged from 0.62 to 0.91, and most were significant. The number needed to treat at higher-volume hospitals to avoid 1 death was greater for the low-risk group (a range of 114 to 446 versus 37 to 184). As the annual surgeon volume threshold increased from 50 to 150 cases, the ORs for high- to low-volume surgeons increased from 0.43 to 0.74 for the low-risk group; for the moderate-to-high-risk group, ORs ranged from 0.79 to 0.86. Compared with patients treated by surgeons with volumes of &lt;125 in hospitals with volumes of &lt;600, patients treated by higher-volume surgeons in higher-volume hospitals had a significantly lower risk of death; in particular, the OR was 0.52 for the low-risk group. Conclusions— For both low-risk and moderate-to-high-risk patients, higher provider volume is associated with lower risk of death.