tbuckley/cabot-search huggingface dataset:
Population-Based Study of the Risk of Second Primary Contralateral Breast Cancer Associated With Carrying a Mutation in <i>BRCA1</i> or <i>BRCA2</i>
Authors: Kathleen E. Malone, Colin B. Begg, Robert W. Haile, Ake Borg, Patrick Concannon, Lina Tellhed, Shanyan Xue, Sharon Teraoka, Leslie Bernstein, Marinela Capanu, Anne S. Reiner, Elyn R. Riedel, Duncan C. Thomas, Lene Mellemkjær, Charles F. Lynch, John D. Boice, Hoda Anton-Culver, Jonine L. Bernstein
Journal: Journal of Clinical Oncology (2010)

Purpose Women with breast cancer diagnosed early in life comprise a substantial portion of those tested for BRCA1/BRCA2 mutations; however, little information is available on the subsequent risks of contralateral breast cancer in mutation carriers. This study assessed the risk of subsequent contralateral breast cancer associated with carrying a BRCA1 or BRCA2 mutation. Patients and Methods In this nested case-control study, patients with contralateral breast cancer diagnosed 1 year or more after a first primary breast cancer (n = 705) and controls with unilateral breast cancer (n = 1,398) were ascertained from an underlying population-based cohort of 52,536 women diagnosed with a first invasive breast cancer before age 55 years. Interviews and medical record reviews were used to collect risk factor and treatment histories. All women were tested for BRCA1/BRCA2 mutations. Relative (rate ratios) and absolute (5- and 10-year cumulative) risks of developing contralateral breast cancer following a first invasive breast cancer were computed. Results Compared with noncarriers, BRCA1 and BRCA2 mutation carriers had 4.5-fold (95% CI, 2.8- to 7.1-fold) and 3.4-fold (95% CI, 2.0- to 5.8-fold) increased risks of contralateral breast cancer, respectively. The relative risk of contralateral breast cancer for BRCA1 mutation carriers increased as age of first diagnosis decreased. Age-specific cumulative risks are provided for clinical guidance. Conclusion The risks of subsequent contralateral breast cancer are substantial for women who carry a BRCA1/BRCA2 mutation. These findings have important clinical relevance regarding the assessment of BRCA1/BRCA2 status in patients with breast cancer and the counseling and clinical management of patients found to carry a mutation.
Biochemistry of protein tyrosine nitration in cardiovascular pathology
Authors: G PELUFFO, R RADI
Journal: Cardiovascular Research (2007)

Several pathologies of the cardiovascular system are associated with an augmented production of nitric oxide and/or superoxide-derived oxidants and/or alteration in the antioxidant detoxification pathways that lead to nitroxidative stress. One important consequence of these reactive intermediates at the biochemical level is the nitration of protein tyrosines, which is performed through either of two of the relevant nitration pathways that operate in vivo, namely peroxynitrite and heme peroxidase-dependent nitration. Proteins nitrated at tyrosine residues have been detected in several compartments of the cardiovascular system. In this review a selection of nitrated proteins in plasma (fibrinogen, plasmin, Apo-1), vessel wall (Apo-B, cyclooxygenase, prostaglandin synthase, Mn-superoxide dismutase) and myocardium (myofibrillar creatine kinase, alpha-actinin, sarcoplasmic reticulum Ca(2+) ATPase) are analyzed in the context of cardiovascular disease. Nitration of tyrosine can affect protein function, which could directly link nitroxidative stress to the molecular alterations found in disease. While some proteins are inactivated by nitration (e.g. Mn-SOD) others undergo a gain-of-function (e.g. fibrinogen) that can have an ample impact on the pathophysiology of the cardiovascular system. Nitrotyrosine is also emerging as a novel independent marker of cardiovascular disease. Pharmacological strategies directed towards inhibiting protein nitration will assist to shed light on the relevance of this post-translational modification to human cardiovascular pathology.
Comprehensive geriatric assessment predicts tolerance to chemotherapy and survival in elderly patients with advanced ovarian carcinoma: a GINECO study
Authors: G. Freyer, J.-F. Geay, S. Touzet, J. Provencal, B. Weber, J.-P. Jacquin, G. Ganem, N. Tubiana-Mathieu, O. Gisserot, E. Pujade-Lauraine
Journal: Annals of Oncology (2005)
Effect of Risedronate on Bone in Renal Transplant Recipients
Authors: Maria Coco, James Pullman, Hillel W. Cohen, Sally Lee, Craig Shapiro, Clemencia Solorzano, Stuart Greenstein, Daniel Glicklich
Journal: Journal of the American Society of Nephrology (2012)

Bisphosphonates may prevent or treat the bone loss promoted by the immunosuppressive regimens used in renal transplantation. Risedronate is a commonly used third-generation amino-bisphosphonate, but little is known about its effects on the bone health of renal transplant recipients. We randomly assigned 42 new living-donor kidney recipients to either 35 mg of risedronate weekly or placebo for 12 months. We obtained bone biopsies at the time of renal transplant and after 12 months of protocol treatment. Treatment with risedronate did not affect bone mineral density (BMD) in the overall cohort. In subgroup analyses, it tended to preserve BMD in female participants but did not significantly affect the BMD of male participants. Risedronate did associate with increased osteoid volume and trabecular thickness in male participants, however. There was no evidence for the development of adynamic bone disease. In summary, further study is needed before the use of prophylactic bisphosphonates to attenuate bone loss can be recommended in renal transplant recipients.
Association of Unconscious Race and Social Class Bias With Vignette-Based Clinical Assessments by Medical Students
Authors: Adil H. Haider, Janel Sexton, N. Sriram, Lisa A. Cooper, David T. Efron, Sandra Swoboda, Cassandra V. Villegas, Elliott R. Haut, Morgan Bonds, Peter J. Pronovost, Pamela A. Lipsett, Julie A. Freischlag, Edward E. Cornwell
Journal: JAMA (2011)

Studies involving physicians suggest that unconscious bias may be related to clinical decision making and may predict poor patient-physician interaction. The presence of unconscious race and social class bias and its association with clinical assessments or decision making among medical students is unknown.
Catatonia Induced in Monkeys by Antibrain Antibody
Authors: ROBERT G. HEATH, IRIS M. KRUPP
Journal: American Journal of Psychiatry (1967)

Antibody against specific regions of monkey and human brains was produced by these investigators by inoculating sheep with homogenates of brain parts, fortified with an adjuvant. Observations made in the experiments indirectly support the hypothesis that schizophrenic serum contains antibody against the brain and that symptoms of schizophrenia are the result of an immune process.
Health utilities in evaluating intervention in the sleep apnoea/hypopnoea syndrome
Authors: I. Chakravorty, R.M. Cayton, A. Szczepura
Journal: European Respiratory Journal (2002)

Formulating a rational health policy necessitates the ability to compare between different healthcare interventions and disease scenarios. Continuous positive airway pressure (CPAP) therapy with a conservative lifestyle strategy in sleep apnoea/hypopnoea syndrome (SAHS) was evaluated using health utility and quality-adjusted life years (QALYs) as outcome measures. A total 71 SAHS (apnoea/hypopnoea index =15 h -1 ) patients completed a randomised, parallel group study over 3 months using utilities derived by the standard gamble approach (U sg ) and European quality of life questionnaire (Euroqol) (U eq ). The severely impaired health status at baseline improved by 23% (U sg 0.32 to 0.55) adding 8 QALYs in the CPAP group, compared to a 4% improvement with 4.7 QALYs added in the lifestyle group (U sg 0.31 to 0.35). The U eq showed a marginal change with CPAP (0.73 to 0.77) but did not demonstrate any improvement with lifestyle intervention. The health status impairment in sleep apnoea/hypopnoea syndrome patients is markedly improved by continuous positive airway pressure compared to a modest improvement with conservative lifestyle strategies using the standard gamble utility, which may be incorporated in effectiveness and economic analyses. The European quality of life questionnaire did not reflect a similar degree of impact and is probably not useful in this population.
Recent Chronic Beryllium Disease in Residents Surrounding a Beryllium Facility
Authors: Lisa A. Maier, John W. Martyny, Jing Liang, Milton D. Rossman
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

Between 1948 and 1969, cases of community-acquired chronic beryllium disease (CA-CBD) were reported in neighborhoods surrounding beryllium facilities. Further surveillance was not performed in these communities, and additional cases have not been reported.To increase awareness of recently diagnosed cases of CA-CBD in residents surrounding a beryllium facility.Medical records were reviewed from individuals in a community surrounding a beryllium manufacturing facility in Reading, Pennsylvania. Definite cases of CBD required (1) an abnormal beryllium lymphocyte proliferation test in blood or bronchoalveolar lavage and (2) biopsy evidence of granulomatous inflammation. Probable cases of CBD either displayed an abnormal blood test to beryllium and radiographic evidence consistent with disease, or met epidemiologic criteria for CBD based on the Beryllium Case Registry criteria. Cases with occupational or potential paraoccupational exposure were excluded.Sixteen cases of potential community-acquired CBD were evaluated. From these, eight cases of community-acquired CBD were identified (five definite and three probable). The cases' initial year of residence began between 1943 and 1953 and continued until 1956-2001. Six of the eight cases required medical treatment and three of the cases died since diagnosis.Cases of CBD meeting current immunologic diagnostic criteria and attributable to industry-associated environmental exposure were detected among residents of a community surrounding a beryllium manufacturing facility. Most were diagnosed years after exposure cessation. The frequency and extent of beryllium disease in this community are unknown. We anticipate that not only have cases been misdiagnosed in this community but that more cases of CBD will be diagnosed in the future.
Doctors' input is sought as NHS approaches "perfect storm" of funding cuts and rising demand
Authors: A. O'Dowd
Journal: BMJ (2009)

Health service leaders must engage more with clinicians to find ways for the NHS to survive impending financial difficulties, says a report published by a leading health policy think tank.

NHS managers should involve staff members more in developing solutions for “worst case scenarios” by using their knowledge of local circumstances to make decisions, says the report from the King’s Fund.

The report emphasises that local and national NHS leaders must be honest about the scale of financial challenges ahead and how they will maintain quality of services during the current economic recession.

The report details the findings of a two day simulation event held in July, which …
Mortality After Major Surgery for Urologic Cancers in Specialized Urology Hospitals: Are They Any Better?
Authors: Badrinath R. Konety, Veerasathpurush Allareddy, Sanjukta Modak, Brian Smith
Journal: Journal of Clinical Oncology (2006)

Specialty-specific hospitals and hospitals with a high volume of complex procedures have been shown to have better outcomes. We sought to determine whether a high volume of unrelated complex procedures or procedures in the same specialty area (urology) could translate into better outcomes after major urologic cancer surgery.We performed a cross-sectional analysis of administrative discharge abstract data from the Nationwide Inpatient Sample of the Health Care Utilization Project for years 1998 to 2002. Comparison of outcome after three major urologic cancer-related surgical procedures (radical cystectomy [RC], radical nephrectomy [RN], and radical prostatectomy [RP]) at hospitals by procedure-specific volume, specialized urology status, and Leapfrog criteria was obtained to determine in-hospital mortality after the procedure. All patients in the database with a diagnosis of bladder, kidney, or prostate cancer being admitted for RC, RN, or RP between 1998 and 2002 were included.Neither specialized urology status nor meeting Leapfrog volume criteria for unrelated procedures was associated with lower odds of in-hospital mortality after any of the procedures examined. High-volume hospitals (for RC and RP) and moderate-volume hospitals (for RP) were associated with lower odds of mortality. None of the examined hospital volume-related factors was associated with lower odds of mortality after RN.In-hospital mortality after two of three major urologic cancer procedures is affected only by procedure-specific volumes. Generalized process measures existing in hospitals performing a high volume of general urologic procedures or unrelated complex procedures may be less important determinants of procedure-specific outcomes in patients.
Why Won't Our Patients Stop Smoking?
Authors: David M. Mannino
Journal: Diabetes Care (2009)

Health risks related to tobacco use have been well established for >50 years, with diseases including lung cancer, other malignancies, and cardiovascular diseases linked to smoking and causing early mortality in current and former smokers (1–4). Yet cigarette smoking remains highly prevalent in both the developing and developed worlds (5). Smoking uptake typically occurs in the teenage years, when risk-taking behavior is the norm and peer pressure is a powerful predictor of behavior. The prevalence of chronic diseases, such as hypertension, diabetes, respiratory disease, arthritis, and cardiovascular disease, is low in teenagers and young adults but increases into middle-age and older adulthood (6–9). Conversely, in developed countries like the U.S., smoking prevalence peaks in young adults and decreases as the population ages, because people stop smoking or die (with current smokers dying at a faster rate than former or never smokers) (10). Most of the adult population in the developed world who are current smokers grew up in an environment where the risks of smoking were well established and well known to the public. So why do our adult patients, many of whom have diseases either related to tobacco smoking or complicated by smoking, find it difficult to quit?

This question has been a vexing one to both clinicians and public health practitioners since the adverse affects of smoking became known to us. There are divergent truths. On one hand, in most developed countries, the majority of people who have ever smoked in their lifetime have successfully quit (11). On the other hand, many people with chronic diseases that are clearly worsened by cigarette smoking are unable to quit. So why can some patients quit quickly and easily while other patients smoke right …
Noninvasive ventilation for acute respiratory failure. Quite low time consumption for nurses
Authors: G. Hilbert, D. Gruson, F. Vargas, R. Valentino, L. Portel, G Gbikpi-Benissan, J.P Cardinaud
Journal: European Respiratory Journal (2000)

Methods of noninvasive pressure support ventilation (NIPSV) are not always easy to apply in patients with acute exacerbations of chronic obstructive pulmonary disease (COPD). The assistance time spent by nurses in relation to ventilatory time was prospectively studied, when NIPSV was used, in a sequential mode, in COPD patients with either acute exacerbations (58 patients, group I) or postextubation hypercapnic respiratory insufficiency (42 patients, group II) in a medical intensive care unit. During the first 24 h after enrolment, NIPSV was used for 6.7+/-3.2 h (mean+/-SD) in group I and 5.6+/-3.1 h in group II; the duration of NIPSV sessions and the nurse time consumption per session were respectively 47+/-12 and 11+/-7 min in group 1, and 46+/-12 and 11+/-6 min in group II. After the first 24 h of the study, the duration of NIPSV was 4.7+/-3.2 h x day(-1) in group I and 4.9+/-3.5 h x day(-1) in group II, and the nurse time consumption dropped significantly: the duration of NIPSV sessions and the nurse time consumption per session were respectively 44+/-10 and 7+/-4 min in group I, and 47+/-14 and 7+/-3 min in group II. Between the first 24 h and the subsequent period of 24 h, the nursing time dropped significantly (98 versus 59 min in group I (p<0.05), and 85 versus 52 min in group II (p<0.05)). There was no difference in the duration of NIPSV sessions, or in the overall assistance time per session, between the two groups of patients. In conclusion, the study seems to favour a quite low assistance time spent by nurses in relation to ventilatory time when noninvasive pressure support ventilation is used in chronic obstructive pulmonary disease patients with either acute exacerbations or postextubation hypercapnic respiratory insufficiency.
Abundant progenitor cells in the adventitia contribute to atherosclerosis of vein grafts in ApoE-deficient mice
Authors: Yanhua Hu, Zhongyi Zhang, Evelyn Torsney, Ali R. Afzal, Fergus Davison, Bernhard Metzler, Qingbo Xu
Journal: Journal of Clinical Investigation (2004)

Recent evidence indicates that vascular progenitor cells may be the source of smooth muscle cells (SMCs) that accumulate in atherosclerotic lesions, but the origin of these progenitor cells is unknown. To explore the possibility of vascular progenitor cells existing in adults, a variety of tissues from ApoE-deficient mice were extensively examined. Immunohistochemical staining revealed that the adventitia in aortic roots harbored large numbers of cells having stem cell markers, e.g., Sca-1+ (21%), c-kit+ (9%), CD34+ (15%), and Flk1+ cells (4%), but not SSEA-1+ embryonic stem cells. Explanted cultures of adventitial tissues using stem cell medium displayed a heterogeneous outgrowth, for example, islands of round-shaped cells surrounded by fibroblast-like cell monolayers. Isolated Sca-1+ cells were able to differentiate into SMCs in response to PDGF-BB stimulation in vitro. When Sca-1+ cells carrying the LacZ gene were transferred to the adventitial side of vein grafts in ApoE-deficient mice, β-gal+ cells were found in atherosclerotic lesions of the intima, and these cells enhanced the development of the lesions. Thus, a large population of vascular progenitor cells existing in the adventitia can differentiate into SMCs that contribute to atherosclerosis. Our findings indicate that ex vivo expansion of these progenitor cells may have implications for cellular, genetic, and tissue engineering approaches to vascular disease.
Latent Tuberculosis Infection Treatment and T-Cell Responses to <i>Mycobacterium tuberculosis</i>–specific Antigens
Authors: Cynthia B. E. Chee, Kyi W. KhinMar, Suay H. Gan, Timothy M. S. Barkham, Mariappan Pushparani, Yee T. Wang
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Rationale: There is currently no available test for monitoring the effect of treatment of latent tuberculosis infection (LTBI) to indicate cure or predict risk of subsequent progression to disease.Objective: We used the T-SPOT.TB assay, which measures T-cell interferon-γ responses to the Mycobacterium tuberculosis–specific peptides early secretory antigenic target 6-kD protein (ESAT-6) and culture filtrate protein 10 (CFP-10), to determine the effect of LTBI treatment on these responses.Methods: A total of 226 tuberculosis contacts with positive T-SPOT.TB results underwent repeat testing on LTBI treatment completion. The majority (96%) received 6 months of isoniazid. The pre- and post-treatment T-SPOT.TB results were analyzed according to the combined and separate responses to ESAT-6 and CFP-10 antigens.Results: The T-SPOT.TB reverted to negative in 85 (37.6%) contacts at treatment completion. Treatment had a significant effect on the response to CFP-10 (p < 0.001; reversion rate, 48.6%), but not on the response to ESAT-6 (p = 0.081; reversion rate, 21.6%). The median number of spot-forming cells (SFCs)/2.5 × 105 peripheral blood mononuclear cells (PBMCs) pre- and post-treatment was 6 versus 4.5 for ESAT-6 (p = 0.116) and 11 versus 4 for CFP-10 (p < 0.001). There was a significant difference between the change (fall) in the pre- and post-treatment responses to CFP-10 (6 SFCs/2.5 × 105 PBMCs) and ESAT-6 (0 SFCs/2.5 × 105 PBMCs; p < 0.001). Significantly different age-related T-cell responses to the two antigens were found.Conclusion: LTBI treatment had a differential effect on T-cell responses to ESAT-6 and CFP-10 as measured by the T-SPOT.TB. The quantitative response to CFP-10 may be a useful LTBI treatment–monitoring tool.
Meta-analysis: Intravenous Immunoglobulin in Critically Ill Adult Patients with Sepsis
Authors: Alexis F. Turgeon, Brian Hutton, Dean A. Fergusson, Lauralyn McIntyre, Alan A. Tinmouth, D. William Cameron, Paul C. Hébert
Journal: Annals of Internal Medicine (2007)

Background: Intravenous immunoglobulin therapy has been proposed as an adjuvant treatment for sepsis. Yet, its benefit remains unclear, and its use is not currently recommended. Purpose: To evaluate the effect of polyclonal intravenous immunoglobulin therapy on death in critically ill adult patients with sepsis. Data Sources: MEDLINE (1966 to May 2006) and the Cochrane Central Register of Controlled Trials (May 2006 edition). Study Selection: All randomized, controlled trials of critically ill adult patients with sepsis, severe sepsis, or septic shock who received polyclonal intravenous immunoglobulin therapy or placebo or no intervention were selected. No restrictions were made for study language or type of publication. Data extraction: Data were independently extracted by 2 investigators using a standardized form. Data Synthesis: The literature search identified 4096 articles, of which 33 were deemed to be potentially eligible. Twenty trials (n = 2621) met eligibility criteria and were included in the analysis. Polyclonal intravenous immunoglobulin therapy was associated with an overall survival benefit (risk ratio, 0.74 [95% CI, 0.62 to 0.89]) compared with placebo or no intervention. In sensitivity analyses, documented survival improved when the analysis was limited to published, peer-reviewed trials (risk ratio, 0.72 [CI, 0.58 to 0.89]) (17 trials [n = 1865]) and blinded trials (risk ratio, 0.61 [CI, 0.40 to 0.93) (7 trials [n = 896]). Severe sepsis or septic shock (risk ratio, 0.64 [CI, 0.52 to 0.79]) (11 trials [n = 689]), receiving a total dose regimen of 1 gram or more per kilogram of body weight (risk ratio, 0.61 [CI, 0.40 to 0.94]) (7 trials [n = 560]), and receiving therapy for longer than 2 days (risk ratio, 0.66 [CI, 0.53 to 0.82]) (17 trials [n = 1847]) were strongly associated with this survival benefit. Limitations: Most trials were published before new developments modifying the care and outcome of critically ill patients with sepsis including early goal-directed therapy and activated protein C treatment, were introduced. Conclusions: A survival benefit was observed for patients with sepsis who received polyclonal intravenous immunoglobulin therapy compared with those who received placebo or no intervention. A large, randomized, controlled trial of polyclonal intravenous immunoglobulin therapy should be performed on the basis of the methodological limitations of the current literature, the potential benefit from this therapy in more severely ill patients, and the potential effect of dosage and duration of this therapy.