tbuckley/cabot-search huggingface dataset:
Gene Expression Profiles of Multiple Breast Cancer Phenotypes and Response to Neoadjuvant Chemotherapy
Authors: Holly K. Dressman, Christopher Hans, Andrea Bild, John A. Olson, Eric Rosen, P. Kelly Marcom, Vlayka B. Liotcheva, Ellen L. Jones, Zeljko Vujaskovic, Jeffrey Marks, Mark W. Dewhirst, Mike West, Joseph R. Nevins, Kimberly Blackwell
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Breast cancer is a heterogeneous disease, and markers for disease subtypes and therapy response remain poorly defined. For that reason, we employed a prospective neoadjuvant study in locally advanced breast cancer to identify molecular signatures of gene expression correlating with known prognostic clinical phenotypes, such as inflammatory breast cancer or the presence of hypoxia. In addition, we defined molecular signatures that correlate with response to neoadjuvant chemotherapy. Experimental Design: Tissue was collected under ultrasound guidance from patients with stage IIB/III breast cancer before four cycles of neoadjuvant liposomal doxorubicin paclitaxel chemotherapy combined with local whole breast hyperthermia. Gene expression analysis was done using Affymetrix U133 Plus 2.0 GeneChip arrays. Results: Gene expression patterns were identified that defined the phenotypes of inflammatory breast cancer as well as tumor hypoxia. In addition, molecular signatures were identified that predicted the persistence of malignancy in the axillary lymph nodes after neoadjuvant chemotherapy. This persistent lymph node signature significantly correlated with disease-free survival in two separate large populations of breast cancer patients. Conclusions: Gene expression signatures have the capacity to identify clinically significant features of breast cancer and can predict which individual patients are likely to be resistant to neoadjuvant therapy, thus providing the opportunity to guide treatment decisions.
Genetic Engineering of Glomerular Sclerosis in the Mouse via Control of Onset and Severity of Podocyte-Specific Injury
Authors: Taiji Matsusaka, Jing Xin, Suguri Niwa, Kazuto Kobayashi, Akira Akatsuka, Hiroomi Hashizume, Qing-Cheng Wang, Ira Pastan, Agnes B Fogo, Iekuni Ichikawa
Journal: Journal of the American Society of Nephrology (2005)

This study aimed to generate a mouse model of acquired glomerular sclerosis. A model system that allows induction of podocyte injury in a manner in which onset and severity can be controlled was designed. A transgenic mouse strain (NEP25) that expresses human CD25 selectively in podocytes was first generated. Injection of anti-Tac (Fv)-PE38 (LMB2), an immunotoxin with specific binding to human CD25, induced progressive nonselective proteinuria, ascites, and edema in NEP25 mice. Podocytes showed foot process effacement, vacuolar degeneration, detachment and downregulation of synaptopodin, WT-1, nephrin, and podocalyxin. Mesangial cells showed matrix expansion, increased collagen, mesangiolysis, and, later, sclerosis. Parietal epithelial cells showed vacuolar degeneration and proliferation, whereas endothelial cells were swollen. The severity of the glomerular injury was LMB2 dose dependent. With 1.25 ng/g body wt or more, NEP25 mice developed progressive glomerular damage and died within 2 wk. With 0.625 ng/g body wt of LMB2, NEP25 mice survived >4 wk and developed focal segmental glomerular sclerosis. Thus, the study has established a mouse model of acquired progressive glomerular sclerosis in which onset and severity can be preprogrammed by experimental maneuvers.
Cell Adhesion to Fibronectin (CAM-DR) Influences Acquired Mitoxantrone Resistance in U937 Cells
Authors: Lori A. Hazlehurst, Raul F. Argilagos, Michael Emmons, David Boulware, Craig A. Beam, Dan M. Sullivan, William S. Dalton
Journal: Cancer Research (2006)

Abstract Cell adhesion to fibronectin is known to confer a temporally related cell adhesion–mediated drug resistance (CAM-DR). However, it is unknown whether cell adhesion during drug selection influences the more permanent form of acquired drug resistance. To examine this question, we compared the acquisition of mitoxantrone resistance in U937 cells adhered to fibronectin versus cells selected in a traditional suspension culture. Our data show that acquired drug resistance levels of resistance to mitoxantrone are 2- to 3-fold greater for cells adhered to fibronectin compared with cells in suspension culture. We also compared mechanism(s) of resistance associated with drug selection in suspension versus fibronectin-adherent cultures. Drug resistance in both suspension and fibronectin-adhered cultures correlated with reduced drug-induced DNA damage and diminished topoisomerase II levels and activity; however, mechanisms regulating topoisomerase II levels differed depending on culture conditions. In suspension cultures, a reduction in topoisomerase IIβ levels was detected at both RNA and protein levels. Furthermore, the decreased expression of topoisomerase IIβ mRNA levels correlated with decreased expression of NF-YA. In contrast, in spite of no changes in NF-YA or topoisomerase IIβ RNA expression, topoisomerase IIβ protein levels were decreased in fibronectin-adherent, drug-resistant cells. In addition, topoisomerase IIα protein levels (but not RNA levels) were reduced in drug resistance cells selected on fibronectin; however, no change in topoisomerase IIα was observed in cells selected with mitoxantrone in suspension culture. Taken together, our results suggest that the development of drug resistance models must consider interactions with the microenvironment to identify clinically relevant targets and mechanisms associated with acquired drug resistance. (Cancer Res 2006; 66(4): 2338-45)
Reactive Hyperemia in the Human Finger
Authors: DALI J. PATEL, ALAN C. BURTON
Journal: Circulation Research (1956)

Reactive hyperemia in the finger was investigated in 16 experiments on 5 normal subjects, using venous occlusion plethysmography. Since the flow is so variable from moment to moment, the simultaneous "corrected" flow in a control finger, not occluded, was subtracted from the flow in the test finger, so the difference gave the effect of occlusion free from fluctuations of central origin. The absolute amount and the duration of extra blood flow increased with the period of occlusion. The percentage of the calculated "blood flow debt" repaid was variable, with a mean of 51 percent ± 36. S.D. (σM ± 6 per cent). This is greatly in excess of nutritional debt of the skin.
Idiopathic Pericarditis Without Symptoms
Authors: M. Mirowski
Journal: JAMA (1967)

PATIENTS with idiopathic pericarditis usually complain of chest pain, dyspnea, fever, and malaise. Although the intensity of these symptoms may vary and may in fact be very low,1no report of a completely asymptomatic case was found in the literature.  Recently, one such patient has been observed, and because of the case's apparent rarity and eventual implications it was considered to be worthwhile reporting.  Report of a Case  An 8 1/2-year-old boy was referred to the pediatric department on Dec 22, 1965, because of a marked enlargement of the heart incidentally discovered at a routine x-ray examination. The patient, one of probably homozygous twins, had nothing of significance in his or his family's history except that he was prone to repeated upperrespiratory tract infections. He was suffering from enlarged adenoids, and prior to their removal, a routine chest roentgenogram was made.  Physical examination revealed a well-developed, wellnourished, active, and
Effect of Small Degrees of Venous Distension on the Apparent Inflow Rate of Blood to the Human Calf
Authors: D. R. COLES, B. S. L. KIDD
Journal: Circulation Research (1957)

The apparent blood flow through the human calf has been measured by venous occlusion plethysmography in the horizontal subject both at rest, and while the volume of the calf was increased by up to 3 per cent by venous congestion. When this degree of venous distension was continued for 5 min., the apparent blood flow through the calf was not altered significantly. Since the perfusion pressure is presumably reduced, this suggests that the vessels of the calf offering resistance to flow are slightly dilated.
Whistleblowing and patient safety: the patient's or the profession's interests at stake?
Authors: Stephen Bolsin, Rita Pal, Peter Wilmshurst, Milton Pena
Journal: Journal of the Royal Society of Medicine (2011)

Whistleblowing has a tortured history in the NHS although it has been recognized by authoritative reviewers as making an important contribution to patient safety.1,2

In a highly critical 6th Report the House of Commons Health Committee stated ‘The NHS remains largely unsupportive of whistleblowing, with many staff fearful about the consequences of going outside official channels to bring unsafe care to light. We recommend that the Department of Health (DH) bring forward proposals on how to improve this situation.’3

Encouraging the medical profession to report poor care and to report incidents that occur in their practice has been problematical in modern healthcare although there are notable exceptions.4 This article discusses why a change in the attitude of the profession is required, what the benefits will be and how it can be achieved.
Pruritus. A manifestation of iron deficiency
Authors: E. M. Lewiecki
Journal: JAMA (1976)

PRURITUS as a manifestation of iron deficiency, to the best of our knowledge, has not been described. The following report presents such a case. <h3>Report of a Case</h3> A 62-year-old woman was seen in the outpatient clinic in August 1975, with a six-month history of generalized itching that had recently become more severe. Her only medications were conjugated estrogens and occasional aspirin. Results of a physical examination and a dermatological examination were normal. She was treated with diphenhydramine hydrochloride, with no relief of itching. At a follow-up clinic visit, psychogenic itching was diagnosed, and her medication was changed to meprobamate. In December 1975, she was seen again complaining of unrelieved itching, shortness of breath, and chest pain characteristic of angina pectoris. She had stopped taking meprobamate a few weeks previously, since it did not relieve her pruritus. Present medications were conjugated estrogens and aspirin. Findings from a physical examination showed
Current Controversies and Future Perspectives in Chronic Obstructive Pulmonary Disease
Authors: Alvar Agustí, Jørgen Vestbo
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Section:ChooseTop of pageAbstract <<Natural HistoryPathogenic MechanismsDiagnosisAssessmentTherapyConclusionsReferencesCITING ARTICLES
MR889, a neutrophil elastase inhibitor, in patients with chronic obstructive pulmonary disease: a double-blind, randomized, placebo-controlled clinical trial
Authors: M. Luisetti, C. Sturani, D. Sella, E. Madonini, V. Galavotti, G. Bruno, V. Peona, U. Kucich, G. Dagnino, J. Rosenbloom, B. Starcher, C. Grassi
Journal: European Respiratory Journal (1996)

We investigated whether MR889, a synthetic cyclic thiolic elastase inhibitor, administered for a period of 4 weeks to chronic obstructive pulmonary disease (COPD) patients, is well-tolerated, and whether it modifies biochemical indices of lung destruction. The study was a double-blind, randomized, placebo-controlled clinical trial in COPD patients. Thirty subjects were administered MR889 orally at a dose of 500 mg b.i.d. for 4 weeks, and 30 received placebo following the same schedule. In addition to safety parameters, MR889 efficacy was checked by a pretreatment/postreatment evaluation of levels of plasma elastin-derived peptides and urinary desmosine. There were no statistically significant differences between pretreatment and posttreatment efficacy parameter levels either in the control group or in the treated group. However, in a subset of treated patients with a short disease duration, the level of urinary desmosine dropped significantly with respect to pretreatment values (p = 0.004). We conclude that MR889 is safe to administer to COPD patients for a period of at least 4 weeks. During this time, MR889 does not modify biochemical markers of lung destruction in unselected COPD patients. Nevertheless, a subset of treated patients with fairly short disease duration showed a post-treatment reduction of desmosine urine levels, thus justifying the need for further studies to prove the efficacy of MR889 in modulating indices of lung destruction in COPD.
New Insights on the Risk for Cardiovascular Disease in African Americans
Authors: Karim R Saab, Jessica Kendrick, Joseph M Yracheta, Miguel A Lanaspa, Maisha Pollard, Richard J Johnson
Journal: Journal of the American Society of Nephrology (2014)

African Americans are at increased risk for cardiovascular and metabolic diseases, including obesity, high BP, diabetes, CKD, myocardial infarction, and stroke. Here we summarize the current risks and provide an overview of the underlying risk factors that may account for these associations. By reviewing the relationship between cardiovascular and renal diseases and the African-American population during the early 20th century, the historic and recent associations of African heritage with cardiovascular disease, and modern population genetics, it is possible to assemble strong hypotheses for the primary underlying mechanisms driving the increased frequency of disease in African Americans. Our studies suggest that underlying genetic mechanisms may be responsible for the increased frequency of high BP and kidney disease in African Americans, with particular emphasis on the role of APOL1 polymorphisms in causing kidney disease. In contrast, the Western diet, particularly the relatively high intake of fructose-containing sugars and sweetened beverages, appears to be the dominant force driving the increased risk of diabetes, obesity, and downstream complications. Given that intake of added sugars is a remediable risk factor, we recommend clinical trials to examine the reduction of sweetened beverages as a primary means for reducing cardiovascular risk in African Americans.
Expression of the Caudal-Type Homeodomain Transcription Factors <i>CDX</i> 1/2 and Outcome in Carcinomas of the Ampulla of Vater
Authors: Donna E. Hansel, Anirban Maitra, John W. Lin, Michael Goggins, Pedram Argani, Charles J. Yeo, Steven Piantadosi, Steven D. Leach, Andrew V. Biankin
Journal: Journal of Clinical Oncology (2005)

Adenocarcinomas of the ampulla of Vater demonstrate a characteristic histology but vary significantly in outcome. As a consequence, prognostic factors for these cancers are poorly defined. The caudal-type homeodomain transcription factors 1 (CDX1) and 2 (CDX2) regulate axial development and intestinal differentiation. We assessed the expression of these putative intestinal epithelial-specific transcription factors and their influence on patient outcome.Fifty-three resected carcinomas of the ampulla of Vater, 31 pancreatic ductal adenocarcinomas, and 15 extrahepatic biliary carcinomas were analyzed for CDX1 and CDX2 expression using immunohistochemistry.Forty percent of carcinomas of the ampulla of Vater but less than 5% of pancreatic and biliary adenocarcinomas expressed CDX. Expression of CDX was associated with a better prognosis (P = .0009). Individually, both CDX1 (P = .02) and CDX2 (P = .02) expression were associated with a survival advantage on univariate analysis. Advanced T stage (P = .02), lymph node metastases (P = .004), and vascular space invasion (P = .0009) were associated with a poor prognosis. Multivariate analysis revealed vascular space invasion (P = .01) and CDX expression (P = .01) to be independent prognostic factors.Expression of CDX was an independent marker of outcome in patients with resected adenocarcinoma of the ampulla of Vater. Expression of CDX may distinguish good prognosis intestinal-like tumors, which potentially arise within intestinal epithelium, from poorer prognosis pancreatobiliary tumors, which arise in adjacent pancreatic and/or biliary ductal epithelium.
Cardiovascular and biochemical changes in dogs during etomidate-nitrous oxide anaesthesia
Authors: A A VAN LAMBALGEN, W BRONSVELD, G C VAN DEN BOS, L G THIJS, G J J TEULE
Journal: Cardiovascular Research (1982)

Etomidate was infused in dogs to test whether the drug could be used for long-lasting stable anaesthesia. In six dogs anaesthesia was induced with pentothal (20 mg·kg−1) and continued with a constant infusion of etomidate (4 mg·kg−1·h−1). The animals were ventilated with a mixture of O2 and N2O (1:2). Several haemodynamic (heart rate, arterial pressure, central venous pressure, pulmonary artery pressure, left ventricular end-diastolic pressure, dP/dtLV, cardiac output, systemic vascular resistance) and biochemical (pO2, pCO2, pH, O2 content, lactate, glucose) variables together with the distribution of cardiac output (radioactive microsphere method) were studied for four and a half hours. In the course of the experiment cardiac output (thermodilution), stroke volume and dP/dtLV (catheter tip manometer) decreased by 38, 40 and 25% respectively while systemic vascular resistance increased (38%); the pH in mixed venous blood fell from 7.31 to 7.26. Blood flow to gastrointestinal tract, pancreas, skin and muscle decreased in proportion with the fall in cardiac output. Myocardial, renal, adrenal and splenic blood flow did not change. Hepatic artery flow decreased (67%). Liver perfusion was thus severely affected since portal blood flow also decreased. Oxygen consumption in the systemic, myocardial and splanchnic bed was not affected. In four other dogs blood etomidate levels were also measured. They rose gradually in the course of the experiment even though concentration and infusion rate of etomidate were kept constant throughout the four and a half hour experiment in these and all other dogs. Etomidate thus caused cardiovascular depression when it was used as long-lasting anaesthetic. Insufficient clearance of etomidate by the liver through deficient hepatic blood flow may be a causative factor.
Graft-Versus-Lymphoma Effect in Relapsed Peripheral T-Cell Non-Hodgkin's Lymphomas After Reduced-Intensity Conditioning Followed by Allogeneic Transplantation of Hematopoietic Cells
Authors: Paolo Corradini, Anna Dodero, Francesco Zallio, Daniele Caracciolo, Marco Casini, Marco Bregni, Franco Narni, Francesca Patriarca, Mario Boccadoro, Fabio Benedetti, A. Rambaldi, Alessandro M. Gianni, Corrado Tarella
Journal: Journal of Clinical Oncology (2004)

Purpose Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of malignancies characterized by a poor prognosis. We performed a pilot study to investigate the role of reduced-intensity conditioning (RIC) followed by allogeneic stem-cell transplantation in relapsed or refractory PTCLs. Patients and Methods We have conducted a phase II trial on 17 patients receiving salvage chemotherapy followed by RIC and allogeneic transplantation of hematopoietic cells. The RIC regimen consisted of thiotepa, fludarabine, and cyclophosphamide. The acute graft-versus-host disease prophylaxis consisted of cyslosporine and short course methotrexate. Results Patients had a median age of 41 years (range, 23 to 60 years). Two patients were primary chemorefractory, and 15 had relapsed disease; eight patients (47%) had a disease relapse after an autologous transplantation. After a median follow-up of 28 months from the day of study entry (range, 3 to 57 months), 14 of 17 patients were alive (12 in complete remission, one in partial remission, and one with stable disease), two died as a result of progressive disease, and one died as a result of sepsis concomitant to acute graft-versus-host disease. The estimated 3-year overall and progression-free survival rates were 81% (95% CI, 62% to 100%) and 64% (95% CI, 39% to 89%), respectively. The estimated probability of nonrelapse mortality at 2 years was 6% (95% CI, 1% to 17%). Donor lymphocyte infusions induced a response in two patients progressing after allografting. Conclusion RIC followed by allogeneic stem-cell transplantation is feasible, has a low treatment-related mortality, and seems to be a promising salvage treatment for relapsed PTCL. These findings suggest that the existence of a graft-versus-T-cell lymphoma effect.
General practitioner knowledge of prohibited substances in sport.
Authors: P Thomas
Journal: British Journal of Sports Medicine (1997)

sider it in the same way as any other health problem.This would mean taking into account the factors that encourage it as well as the clinical symptoms, desired effects, immediate or delayed complications, thera- peutic acceptance, and social implications.In other words, doctors must change their attitude to doping in order not to limit this subject merely to a question of a list of banned substances.Moreover, doping should form an integral and specialised part of the studies undertaken by every medical student.This is urgently required considering the fact that doping agents such as anabolic steroids, human growth hormones, and stimulants are also used by people not taking part in sports.
Synovial biopsy in arthritis research: five years of concerted European collaboration
Authors: B. Bresnihan
Journal: Annals of the Rheumatic Diseases (2000)

The term rheumatoid arthritis (RA) was first proposed by Garrod in 1859.1 By 1959, the histopathological features of synovitis, the proliferating pannus, and cartilage degradation in longstanding RA had been well described.2 Early histopathological studies were based on tissue samples obtained at surgery or at postmortem examinations. Occasionally, biopsy samples were obtained for analysis from patients with arthritis undergoing open arthrotomy.

The initial interest in developing synovial biopsy techniques was to aid the differential diagnosis of joint diseases. In 1932 Forestier described a technique for obtaining synovial tissue with a dental nerve extractor that was introduced into the joint through a large calibre needle.3 He never published his results. Early experience with needle biopsy of the synovium was described in the 1950s.4 5 It was concluded that if strict aseptic techniques were employed, the procedure was safe and practical for use in both hospital wards and outpatient clinics. However, the biopsy needles tended to cause considerable trauma to the penetrated tissues owing to their wide bore and the requirement for an incision. In 1963 Parker and Pearson developed a simplified 14-gauge biopsy needle that did not require a skin incision.6 They described their experience of 125 procedures, almost all from the suprapatellar pouch of the knee joint, of which only five failed to yield adequate tissue for analysis. No serious complications were encountered. The potential of needle biopsy as a research tool in arthritis was highlighted in 1970 by Kinsella et al in their study of synovial lining layer cells in RA,7 and in 1972 by Schumacher and Kitridou in their clinicopathological study of the early features of synovitis.8 

Arthroscopy was also initially developed as a diagnostic instrument. It was used primarily by orthopaedic surgeons.9 In the 1970s and 1980s a number …