tbuckley/cabot-search huggingface dataset:
Glutaraldehyde-Fixed Bioprosthetic Heart Valve Conduits Calcify and Fail From Xenograft Rejection
Authors: Rizwan A. Manji, Lin F. Zhu, Nimrit K. Nijjar, David C. Rayner, Greg S. Korbutt, Thomas A. Churchill, Ray V. Rajotte, Arvind Koshal, David B. Ross
Journal: Circulation (2006)

Glutaraldehyde fixation (G-F) decreases but likely does not eliminate the antigenicity of bioprosthetic heart valves. Rejection (with secondary dystrophic calcification) may be why G-F xenograft valves fail, especially in young patients, who are more immunocompetent than the elderly. Therefore, we sought to determine whether rejection of G-F xenograft occurs and to correlate this with graft calcification.Ascending aortas/valves (from rats [syngeneic] or guinea pigs [xenogeneic]) were transplanted (fresh or after 48 hour of G-F) into the infrarenal aortas of young rat recipients for 20 days. A xenogeneic group was also treated with steroids until graft harvest. The valves and media/adventitia were scored blindly for inflammation (0 to 4). Percent graft infiltration by T cells/macrophages was determined (immunohistochemistry), and rat IgG ELISAs were performed. There was >3 times more valve inflammation, >10 times more valve T-cell/macrophage infiltrate, and >3 times antibody rise in the G-F xenogeneic groups compared with the fresh syngeneic or the G-F syngeneic groups (P<0.05). There was >2 times more adventitial inflammation and T-cell/macrophage infiltrate in the xenogeneic groups (P<0.05). Steroid treatment decreased inflammation and antibody rise in the xenogeneic groups (P<0.05). Correlation analysis revealed media/adventitia inflammation (P=0.02) and percent macrophage (P=0.01) infiltration to be predictors of calcification.G-F xenografts have cellular/humoral rejection and calcify secondarily.
A Randomized, Controlled Trial of Early versus Late Initiation of Dialysis
Authors: Bruce A. Cooper, Pauline Branley, Liliana Bulfone, John F. Collins, Jonathan C. Craig, Margaret B. Fraenkel, Anthony Harris, David W. Johnson, Joan Kesselhut, Jing Jing Li, Grant Luxton, Andrew Pilmore, David J. Tiller, David C. Harris, Carol A. Pollock
Journal: New England Journal of Medicine (2010)

In clinical practice, there is considerable variation in the timing of the initiation of maintenance dialysis for patients with stage V chronic kidney disease, with a worldwide trend toward early initiation. In this study, conducted at 32 centers in Australia and New Zealand, we examined whether the timing of the initiation of maintenance dialysis influenced survival among patients with chronic kidney disease.We randomly assigned patients 18 years of age or older with progressive chronic kidney disease and an estimated glomerular filtration rate (GFR) between 10.0 and 15.0 ml per minute per 1.73 m2 of body-surface area (calculated with the use of the Cockcroft-Gault equation) to planned initiation of dialysis when the estimated GFR was 10.0 to 14.0 ml per minute (early start) or when the estimated GFR was 5.0 to 7.0 ml per minute (late start). The primary outcome was death from any cause.Between July 2000 and November 2008, a total of 828 adults (mean age, 60.4 years; 542 men and 286 women; 355 with diabetes) underwent randomization, with a median time to the initiation of dialysis of 1.80 months (95% confidence interval [CI], 1.60 to 2.23) in the early-start group and 7.40 months (95% CI, 6.23 to 8.27) in the late-start group. A total of 75.9% of the patients in the late-start group initiated dialysis when the estimated GFR was above the target of 7.0 ml per minute, owing to the development of symptoms. During a median follow-up period of 3.59 years, 152 of 404 patients in the early-start group (37.6%) and 155 of 424 in the late-start group (36.6%) died (hazard ratio with early initiation, 1.04; 95% CI, 0.83 to 1.30; P=0.75). There was no significant difference between the groups in the frequency of adverse events (cardiovascular events, infections, or complications of dialysis).In this study, planned early initiation of dialysis in patients with stage V chronic kidney disease was not associated with an improvement in survival or clinical outcomes. (Funded by the National Health and Medical Research Council of Australia and others; Australian New Zealand Clinical Trials Registry number, 12609000266268.)
Microvascular exudative hyperresponsiveness in human coronavirus-induced common cold.
Authors: L Greiff, M Andersson, A Akerlund, P Wollmer, C Svensson, U Alkner, C G Persson
Journal: Thorax (1994)

The inflammatory response of the airway microcirculation in rhinitis and asthma may be recorded as luminal entry of plasma macromolecules (mucosal exudation). This study examines the exudative responsiveness of the subepithelial microvessels in subjects with and without common cold after inoculation with coronavirus.The airway mucosa was exposed to exudative concentrations of histamine (40 and 400 micrograms/ml) before and six days after inoculation. To assess whether mucosal penetration of a topically applied agent was altered, nasal absorption of chromium-51 labelled ethylene diamine tetraacetic acid (51Cr-EDTA, MW 372) was also examined. A nasal pool technique kept the challenge and tracer solutes in contact with the same ipsilateral mucosal surface. Concentrations of albumin in lavage fluids were measured as an index of mucosal exudation of plasma. Nasal absorption of 51Cr-EDTA was determined by the cumulated 24 hour urinary excretion of radioactivity.Nine subjects developed common cold after coronavirus inoculation and 10 remained healthy. Histamine produced concentration dependent mucosal exudation of plasma in all subjects before and after coronavirus inoculation. In subjects with common cold, however, the histamine-induced mucosal exudation was significantly augmented compared with the group without common cold. This exudative hyperresponsiveness is not explained by an increased baseline exudation because the lavage regimen used produced comparably low baseline exudation in both groups of subjects, nor is it explained by an increased penetration of topical histamine because the ability of the nasal mucosa to absorb 51Cr-EDTA was not significantly increased in the subjects with common cold.An increased proclivity of the airway subepithelial microcirculation to respond with plasma exudation develops during coronavirus-induced common cold. This specific exudative hyperresponsiveness may be a feature of inflammatory airway diseases.
Prospects for Vaccine Protection Against HIV-1 Infection and AIDS
Authors: Norman L. Letvin, Dan H. Barouch, David C. Montefiori
Journal: Annual Review of Immunology (2002)

The rapid and devastating spread of the AIDS epidemic in the developing world as well as the difficulties associated with delivering antiretroviral drugs in affected countries underscore the urgent need for the development of a safe and effective AIDS vaccine. In this review, we discuss recent advances in our understanding of the cellular and humoral immune responses to human immunodeficiency virus type 1 (HIV-1) infection. We then describe vaccine strategies that have been explored and discuss the evidence suggesting that cellular immune responses elicited by novel vaccine modalities may attenuate clinical disease caused by HIV-1.
Recognition, referral, diagnosis, and management of adults with autism: summary of NICE guidance
Authors: S. Pilling, S. Baron-Cohen, O. Megnin-Viggars, R. Lee, C. Taylor
Journal: BMJ (2012)

Autism is a lifelong condition characterised by difficulties in social interaction and communication and by rigid or repetitive behaviours; it affects about 1.1% of adults.1 Although some people’s autism is diagnosed in childhood, for every three known cases, there are two individuals without a diagnosis who might need assessment, support, and interventions for autism at some point in their lives.2 Four out of five adults with autism find that obtaining a diagnosis in adulthood is difficult or not possible,3 and many who have all the core symptoms do not receive a formal diagnosis.4 Particular problems arise in identifying high functioning autism (Asperger’s syndrome), which may not be recognised until adulthood5 or may be misdiagnosed as depression, personality disorder, or a psychotic illness. Inadequate identification and assessment of adults with autism not only leads to inadequate care but can also result in inadequate recognition and treatment of coexisting mental and physical health problems. Whereas care for children and young people is relatively well coordinated6 this is often not the case for adults. Falling between and being passed around services is a particular problem for adults with autism who have an IQ over 70 and do not have severe and enduring mental illness, as they may be excluded from both learning disabilities and mental health services.3 Social and economic exclusion affects a large proportion of adults with autism. Unemployment or underemployment is a considerable problem for adults with autism, including the 44% of those who do not have a learning disability,7 with almost 90% of this group unemployed.8

This article summarises the most recent recommendations from the National Institute for Health and Clinical Excellence (NICE) on autism in adults.9

NICE recommendations are based on systematic reviews of best available evidence and explicit …
Ibsen's play and Meissner's story
Authors: D. Greaves
Journal: BMJ (1990)

sixfold to eightfold increase in the prevalence of coronary heart disease and peripheral vascular disease in 187 subjects examined during the recall phase of the Islington diabetes survey, associations that seemed to be independent of hypertension and diabetes.'During the three and a half years of follow up microalbuminuric subjects had an excess mortality of about 24-fold compared with those with normal urinary albumin excretion.'It is possible, therefore, that screening for microalbuminuria, rather than proteinuria, would be preferable if the test is to be used as a prognostic indicator, but in the absence of evidence of benefit from intervention this type of information may be of greater interest to life insurance companies than to the medical profession.It must be said, however, that lack of evidence of benefit has never previously constrained this government in its efforts to introduce change and innovation in the NHS.
Patient Preferences for Axillary Dissection in the Management of Early-Stage Breast Cancer
Authors: S. R. Galper
Journal: JNCI Journal of the National Cancer Institute (2000)

Background: Recent data on the value of adjuvant therapy in lymph node-negative breast cancer and promising early data on less invasive strategies for managing the axilla have raised questions about the appropriate role of axillary lymph node dissection (ALND) in the management of early-stage breast cancer. We sought to evaluate how women weigh potential benefits of ALND—prognostic information, enhanced local control, and tailored therapy—against the risks of long-term morbidity that are associated with the procedure. Methods: We used hypothetical scenarios to survey 82 randomly selected women with invasive breast cancer who had been treated with ALND and 62 women at risk for invasive breast cancer by virtue of a history of ductal carcinoma in situ (DCIS) who had not undergone ALND. Results: Women in both the invasive cancer and the DCIS groups required substantial improvements in local control of the cancer (5% and 15%, respectively) and overall survival (3% and 10%, respectively) before they would opt for this procedure. Women with invasive cancer would choose ALND if it had only a 1% chance of altering treatment recommendations, whereas DCIS subjects required a 25% chance. Sixty-eight percent and 29% of women in the invasive cancer and DCIS groups, respectively, would accepted a 40% risk of arm dysfunction to gain prognostic information that would not change treatment. Conclusions: For most subjects treated previously for invasive breast cancer and almost half those at risk of the disease, the potential benefits of ALND, particularly the value of prognostic information, were sufficient to outweigh the risks of morbidity. However, women varied considerably in their preferences, highlighting the need to tailor decisions regarding management of the axilla to individual patients' values.
Clinical Implications of Old and New Genes for Open-Angle Glaucoma
Authors: Wishal D. Ramdas, Leonieke M.E. van Koolwijk, Angela J. Cree, A. Cecile J.W. Janssens, Najaf Amin, Paulus T.V.M. de Jong, Roger C.W. Wolfs, Jane Gibson, James F. Kirwan, Albert Hofman, Fernando Rivadeneira, Ben A. Oostra, André G. Uitterlinden, Sarah Ennis, Andrew J. Lotery, Hans G. Lemij, Caroline C.W. Klaver, Johannes R. Vingerling, Nomdo M. Jansonius, Cornelia M. van Duijn
Journal: Ophthalmology (2011)
Intestinal permeability in patients with coeliac disease and relatives of patients with coeliac disease.
Authors: R M van Elburg, J J Uil, C J Mulder, H S Heymans
Journal: Gut (1993)

The functional integrity of the small bowel is impaired in coeliac disease. Intestinal permeability, as measured by the sugar absorption test probably reflects this phenomenon. In the sugar absorption test a solution of lactulose and mannitol was given to the fasting patient and the lactulose/mannitol ratio measured in urine collected over a period of five hours. The sugar absorption test was performed in nine patients with coeliac disease with an abnormal jejunum on histological examination, 10 relatives of patients with coeliac disease with aspecific symptoms but no villous atrophy, six patients with aspecific gastrointestinal symptoms but no villous atrophy, and 22 healthy controls to determine whether functional integrity is different in these groups. The lactulose/mannitol ratio (mean (SEM) is significantly higher in both coeliac disease (0.243 (0.034), p < 0.0001)) and relatives of patients with coeliac disease (0.158 (0.040), p < 0.005)) v both healthy controls (0.043 (0.006)) and patients with aspecific gastrointestinal symptoms (0.040 (0.011)). The lactulose/mannitol ratio in relatives of coeliac disease patients was significantly lower than in the coeliac disease patient group (p = 0.04). The lactulose/mannitol ratio was the same in healthy controls and patients with aspecific gastrointestinal symptoms. It is concluded that the sugar absorption test is a sensitive test that distinguishes between patients with coeliac disease and healthy controls. The explanation for the increased permeability in relatives of patients with coeliac disease is uncertain. Increased intestinal permeability may be related to constitutional factors in people susceptible to coeliac disease and may detect latent coeliac disease. The sugar absorption test may therefore be helpful in family studies of coeliac disease.
Platelet Cyclooxygenase Inhibition by Low-Dose Aspirin Is Not Reflected Consistently by Platelet Function Assays
Authors: Francesca Santilli, Bianca Rocca, Raimondo De Cristofaro, Stefano Lattanzio, Laura Pietrangelo, Aida Habib, Caterina Pettinella, Antonio Recchiuti, Elisabetta Ferrante, Giovanni Ciabattoni, Giovanni Davì, Carlo Patrono
Journal: Journal of the American College of Cardiology (2009)
Intramuscular viral delivery of paraplegin rescues peripheral axonopathy in a model of hereditary spastic paraplegia
Authors: Marinella Pirozzi, Angelo Quattrini, Gennaro Andolfi, Giorgia Dina, Maria Chiara Malaguti, Alberto Auricchio, Elena I. Rugarli
Journal: Journal of Clinical Investigation (2014)

Degeneration of peripheral motor axons is a common feature of several debilitating diseases including complicated forms of hereditary spastic paraplegia. One such form is caused by loss of the mitochondrial energy-dependent protease paraplegin. Paraplegin-deficient mice display a progressive degeneration in several axonal tracts, characterized by the accumulation of morphological abnormal mitochondria. We show that adenoassociated virus-mediated (AAV-mediated) intramuscular delivery of paraplegin halted the progression of neuropathological changes and rescued mitochondrial morphology in the peripheral nerves of paraplegin-deficient mice. One single injection before onset of symptoms improved the motor performance of paraplegin-deficient mice for up to 10 months, indicating that the peripheral neuropathy contributes to the clinical phenotype. This study provides a proof of principle that gene transfer may be an effective therapeutic option for patients with paraplegin deficiency and demonstrates that AAV vectors can be successfully employed for retrograde delivery of an intracellular protein to spinal motor neurons, opening new perspectives for several hereditary axonal neuropathies of the peripheral nerves.
Dexrazoxane-Associated Risk for Acute Myeloid Leukemia/Myelodysplastic Syndrome and Other Secondary Malignancies in Pediatric Hodgkin's Disease
Authors: Cameron K. Tebbi, Wendy B. London, Debra Friedman, Doojduen Villaluna, Pedro A. De Alarcon, Louis S. Constine, Nancy Price Mendenhall, Richard Sposto, Allen Chauvenet, Cindy L. Schwartz
Journal: Journal of Clinical Oncology (2007)

Purpose Pediatric Oncology Group (POG) studies 9426 and 9425 evaluated dexrazoxane (DRZ) as a cardiopulmonary protectant during treatment for Hodgkin's disease (HD). We evaluated incidence and risk factors of acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) and second malignant neoplasms (SMNs). Patients and Methods Treatment for low- and high-risk HD with doxorubicin, bleomycin, vincristine, and etoposide (ABVE) or dose-intensified ABVE with prednisone and cyclophosphamide (ABVE-PC), respectively, was followed by low-dose radiation. The number of chemotherapy cycles was determined by rapidity of the initial response. Patients were assigned randomly to receive DRZ (n = 239) or no DRZ (n = 239) concomitantly with chemotherapy to evaluate its potential to decrease adverse cardiopulmonary outcomes. Results Ten patients developed SMN. Six of eight patients developed AML/MDS, and both solid tumors (osteosarcoma and papillary thyroid carcinoma) occurred in recipients of DRZ. Eight patients with SMN were first events. With median 58 months' follow-up, 4-year cumulative incidence rate (CIR) for AML/MDS was 2.55% ± 1.0% with DRZ versus 0.85% ± 0.6% in the non-DRZ group (P = .160). For any SMN, the CIR for DRZ was 3.43% ± 1.2% versus CIR for non-DRZ of 0.85% ± 0.6% (P = .060). Among patients receiving DRZ, the standardized incidence rate (SIR) for AML/MDS was 613.6 compared with 202.4 for those not receiving DRZ (P = .0990). The SIR for all SMN was 41.86 with DRZ versus 10.08 without DRZ (P = .0231). Conclusion DRZ is a topoisomerase II inhibitor with a mechanism distinct from etoposide and doxorubicin. Adding DRZ to ABVE and ABVE-PC may have increased the incidence of SMN and AML/MDS.
Time for tea, anyone?
Authors: M Turner, P McCrory, A Johnston
Journal: British Journal of Sports Medicine (2005)

There have been suggestions that urine samples positive for benzoylecognine, the diagnostic metabolite of cocaine, may be the result of consumption Mate de Coca, a commercially available tea made from coca ( Erythroxylon coca ) leaves. The Jockey Club in Great Britain commissioned research into this subject as several jockeys have tested positive for benzoylecognine over the past few years. Urine samples collected at various time points within 24 h after ingestion of a 250 ml infusion of Mate de Coca tea were analysed using three different methods. All samples tested positive for benzoylecognine.
Validation of a Novel Staging System for Disease-Specific Survival in Patients With Breast Cancer Treated With Neoadjuvant Chemotherapy
Authors: Elizabeth A. Mittendorf, Jacqueline S. Jeruss, Susan L. Tucker, Aparna Kolli, Lisa A. Newman, Ana M. Gonzalez-Angulo, Thomas A. Buchholz, Aysegul A. Sahin, Janice N. Cormier, Aman U. Buzdar, Gabriel N. Hortobagyi, Kelly K. Hunt
Journal: Journal of Clinical Oncology (2011)

We previously described a novel breast cancer staging system for assessing prognosis after neoadjuvant chemotherapy on the basis of pretreatment clinical stage (CS), estrogen receptor status (E), grade (G), and post-treatment pathologic stage (PS). This clinical-pathologic stage (CPS) + EG staging system assigned and summed points for each factor, allowing for better determination of breast cancer-specific survival than CS or PS alone. The current study was undertaken to validate this staging system using internal and external cohorts.We identified an internal cohort of 804 patients treated with neoadjuvant chemotherapy at our institution from 2003 to 2005 and an external cohort of 165 patients treated at another institution. Clinicopathologic characteristics, treatment regimens, and patient outcomes were assessed. Outcomes were stratified by CPS + EG score.Five-year disease-specific survival (DSS) for the internal cohort was 77% (95% CI, 72 to 82) at a median follow-up of 3.4 years (range, 0.3 to 5.9 years). Five-year DSS for the external cohort was 86% (95% CI, 79 to 91) at a median follow-up of 4.7 years (range, 0.5 to 10.5 years). The ability of the CPS + EG score to stratify outcomes was confirmed in both the internal and external cohorts. Application of the CPS + EG staging system facilitated more refined categorization of patients into prognostic subgroups by outcome than presenting CS or final PS as defined by the American Joint Committee on Cancer (AJCC) staging system.The current study validates the CPS + EG staging system in two independent cohorts. We recommend that biologic markers and response to treatment be incorporated into revised versions of the AJCC staging system for patients receiving neoadjuvant chemotherapy.
Systematized porokeratotic eccrine and hair follicle naevus: report of a case and review of the literature
Authors: G. Kroumpouzos, C.M. Stefanato, C.S. Wilkel, H. Bogaars, J. Bhawan
Journal: British Journal of Dermatology (1999)

We report a unique case of a congenital keratinocytic naevus associated with severe alopecia, onychodysplasia and palmoplantar involvement in a 13-year-old girl. The lesions, consisting of scaly, spinous and verrucous papules and plaques, mainly followed Blaschko’s lines and have remained unchanged since birth. The predominant histopathological picture was that of a column of parakeratosis overlying the eccrine ostia and hair follicles. This is the first case of a systematized keratinocytic naevus characterized by histopathology of eccrine and hair follicle porokeratosis and a widespread bilateral involvement. This may be a distinct entity to be included in the differential diagnosis of linear, hyperkeratotic dermatoses. We suggest its classification as systematized porokeratotic eccrine and hair follicle naevus.
Cotransfection of Vascular Endothelial Growth Factor-A and Platelet-Derived Growth Factor-B Via Recombinant Adeno-Associated Virus Resolves Chronic Ischemic Malperfusion
Authors: Christian Kupatt, Rabea Hinkel, Achim Pfosser, Chiraz El-Aouni, Alexander Wuchrer, Andrea Fritz, Franziska Globisch, Michael Thormann, Jan Horstkotte, Corinna Lebherz, Eckart Thein, Andrea Banfi, Peter Boekstegers
Journal: Journal of the American College of Cardiology (2010)