tbuckley/cabot-search huggingface dataset:
A randomized trial of minoxidil in chemotherapy-induced alopecia
Authors: Madeleine Duvic, Noreen A. Lemak, Vicente Valero, Sharon R. Hymes, Kathryn L. Farmer, Gabriel N. Hortobagyi, Ronald J. Trancik, Bruce A. Bandstra, Linda D. Compton
Journal: Journal of the American Academy of Dermatology (1996)
CARD 15 gene mutations in sarcoidosis
Authors: L-P Ho
Journal: Thorax (2005)

VEGF in idiopathic ILDSimler et al raise an interesting possibility of the prognostic value of plasma VEGF in interstitial lung disease. 1 Meyer et al 2 in a previous study did not find any difference in serum VEGF165 levels in patients with diffuse parenchymal lung disease.It would have been interesting to know the bronchoalveolar lavage (BAL) fluid levels of VEGF in these patients as Meyer et al 2 and Koyama et al 3 have shown reduced BAL fluid VEGF levels in interstitial lung disease.This might simply reflect damage to the alveolar epithelium (a known major source) in this disease or, indeed, VEGF may have an important role in the pathogenesis of interstitial disease.Interestingly, VEGF receptor blockade has been shown to lead to an induction of apoptosis and an emphysema-like histological appearance in rats but with no evidence of fibrosis or inflammatory cells. 4 In addition, it is interesting to speculate on the cellular source of the increased plasma levels of VEGF in the more fibrotic patients.Could this represent alveolar-capillary membrane damage with leakage of intra-alveolar VEGF which is known to be compartmentalised and hence lower BAL fluid levels as described in the previous studies? 5Or does it represent an inflammatory cell source of systemic VEGF correlating with an inflammatory response that is here associated with a poorer outcome?Or is there some other mechanism?Finally, Koyama et al 3 have shown that smokers also have reduced BAL fluid levels of VEGF and this may be of relevance (if intrapulmonary VEGF is postulated as having a role in this disease), given that the patients with desquamative interstitial pneumonia had all smoked compared with 50% of those with non-specific interstitial pneumonia and only 20% of the controls.
Predicting Adverse Events in Children With Fever and Chemotherapy-Induced Neutropenia: The Prospective Multicenter SPOG 2003 FN Study
Authors: Roland A. Ammann, Nicole Bodmer, Andreas Hirt, Felix K. Niggli, David Nadal, Arne Simon, Hulya Ozsahin, Udo Kontny, Thomas Kühne, Maja Beck Popovic, Annette Ridolfi Lüthy, Christoph Aebi
Journal: Journal of Clinical Oncology (2010)

Purpose To develop a score predicting the risk of adverse events (AEs) in pediatric patients with cancer who experience fever and neutropenia (FN) and to evaluate its performance. Patients and Methods Pediatric patients with cancer presenting with FN induced by nonmyeloablative chemotherapy were observed in a prospective multicenter study. A score predicting the risk of future AEs (ie, serious medical complication, microbiologically defined infection, radiologically confirmed pneumonia) was developed from a multivariate mixed logistic regression model. Its cross-validated predictive performance was compared with that of published risk prediction rules. Results An AE was reported in 122 (29%) of 423 FN episodes. In 57 episodes (13%), the first AE was known only after reassessment after 8 to 24 hours of inpatient management. Predicting AE at reassessment was better than prediction at presentation with FN. A differential leukocyte count did not increase the predictive performance. The score predicting future AE in 358 episodes without known AE at reassessment used the following four variables: preceding chemotherapy more intensive than acute lymphoblastic leukemia maintenance (weight = 4), hemoglobin ≥ 90 g/L (weight = 5), leukocyte count less than 0.3 G/L (weight = 3), and platelet count less than 50 G/L (weight = 3). A score (sum of weights) ≥ 9 predicted future AEs. The cross-validated performance of this score exceeded the performance of published risk prediction rules. At an overall sensitivity of 92%, 35% of the episodes were classified as low risk, with a specificity of 45% and a negative predictive value of 93%. Conclusion This score, based on four routinely accessible characteristics, accurately identifies pediatric patients with cancer with FN at risk for AEs after reassessment.
The WISDOM of inhaled corticosteroids in COPD
Authors: David M G Halpin, Jennifer K Quint
Journal: Thorax (2014)

Current national and international guidelines recommend the use of inhaled corticosteroids (ICS) in addition to long-acting bronchodilators in people with more severe COPD to reduce the risk of exacerbations. Opinions on the benefits and role of ICS in COPD have changed considerably over the last 25 years. In the 1980s, they were widely used in Europe by extrapolation from their role in asthma. Indeed, it was thought that they might have long-term disease modifying potential and the ISOLDE study was undertaken to investigate this.1 ISOLDE showed no overall effect on the rate of decline in FEV1, but did for the first time raise the possibility that ICS had an effect on the occurrence of exacerbations.

Perhaps surprisingly, some long-acting bronchodilators were also found to reduce the risk of moderate and severe exacerbations compared with placebo. In a meta-analysis, this reduction in severe exacerbations requiring hospitalisation was over 25% in the long-acting β agonist (LABA) group compared with placebo.2 Some evidence suggests that long-acting antimuscarinics (LAMAs) are even more effective than LABAs at reducing exacerbations compared with placebo.3 ,4

Subsequently, studies investigated the effect of combinations of ICS with LABA bronchodilators and showed that the rate of exacerbations was reduced by both ICS and LABA but that the combination was more effective.5 The effect appeared to be most marked in people with an FEV1 less than 50% predicted. Recognition of the importance of exacerbations as key events in the course of COPD was also growing at this time, with studies showing that they were key determinants of health status and associated with a faster decline in lung function. Both from a patient and a health service perspective, prevention of exacerbations became a key objective of COPD management.

Unlike asthma management, COPD pharmacotherapy has largely …
Cerebrovascular disease in Dumas' The Count of Monte Cristo
Authors: A N Williams
Journal: Journal of the Royal Society of Medicine (2003)

Alexandre Dumas' famous novel The Count of Monte Cristo (1844-1845) tells of the unjust imprisonment of Edmond Dantes, his escape and revenge. An incidental feature of this novel is the description of two cases of cerebrovascular disease, with expression of contemporary opinion on pathology and treatment. Earlier readers of the work in English may have missed this since most versions are based on an 1846 translation that has substantial omissions. A retranslation of the unexpurgated text provides access to the original novel in English.1 This gripping tale includes drug-taking, a serial female poisoner, lesbianism and two cases of infanticide. (The quotations in this paper refer to this translation by Buss, as do the page numbers.) It is far from the children's novel that most people perceive it to be.
Hyperoxic sheep pulmonary microvascular endothelial cells generate free radicals via mitochondrial electron transport.
Authors: S P Sanders, J L Zweier, P Kuppusamy, S J Harrison, D J Bassett, E W Gabrielson, J T Sylvester
Journal: Journal of Clinical Investigation (1993)

Free radical generation by hyperoxic endothelial cells was studied using electron paramagnetic resonance (EPR) spectroscopy and the spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). Studies were performed to determine the radical species produced, whether mitochondrial electron transport was involved, and the effect of the radical generation on cell mortality. Sheep pulmonary microvascular endothelial cell suspensions exposed to 100% O2 for 30 min exhibited prominent DMPO-OH and, occasionally, additional smaller DMPO-R signals thought to arise from the trapping of superoxide anion (O2-.), hydroxyl (.OH), and alkyl (.R) radicals. Superoxide dismutase (SOD) quenched both signals suggesting that the observed radicals were derived from O2-.. Studies with deferoxamine suggested that the generation of .R occurred secondary to the formation of .OH from O2-. via an iron-mediated Fenton reaction. Blocking mitochondrial electron transport with rotenone (20 microM) markedly decreased radical generation. Cell mortality increased slightly in oxygen-exposed cells. This increase was not significantly altered by SOD or deferoxamine, nor was it different from the mortality observed in air-exposed cells. These results suggest that endothelial cells exposed to hyperoxia for 30 min produce free radicals via mitochondrial electron transport, but under the conditions of these experiments, this radical generation did not appear cause cell death.
Phase II Study of Alisertib, a Selective Aurora A Kinase Inhibitor, in Relapsed and Refractory Aggressive B- and T-Cell Non-Hodgkin Lymphomas
Authors: Jonathan W. Friedberg, Daruka Mahadevan, Erin Cebula, Daniel Persky, Izidore Lossos, Amit B. Agarwal, JungAh Jung, Richard Burack, Xiaofei Zhou, E. Jane Leonard, Howard Fingert, Hadi Danaee, Steven H. Bernstein
Journal: Journal of Clinical Oncology (2013)

Aurora A kinase (AAK) is overexpressed in aggressive lymphomas and can correlate with more histologically aggressive forms of disease. We therefore designed a phase II study of alisertib, a selective AAK inhibitor, in patients with relapsed and refractory aggressive non-Hodgkin lymphomas.Patients age ≥ 18 years were eligible if they had relapsed or refractory diffuse large B-cell lymphoma (DLBCL), mantle-cell lymphoma (MCL), transformed follicular lymphoma, Burkitt's lymphoma, or noncutaneous T-cell lymphoma. Alisertib was administered orally at 50 mg twice daily for 7 days in 21-day cycles.We enrolled 48 patients. Histologies included DLBCL (n = 21), MCL (n = 13), peripheral T-cell lymphoma (n = 8), transformed follicular lymphoma (n = 5), and Burkitt's (n = 1). Most common grade 3 to 4 adverse events were neutropenia (63%), leukopenia (54%), anemia (35%), thrombocytopenia (33%), stomatitis (15%), febrile neutropenia (13%), and fatigue (6%). Four deaths during the study were attributed to progressive non-Hodgkin lymphoma (n = 2), treatment-related sepsis (n = 1), and unknown cause (n = 1). The overall response rate was 27%, including responses in three of 21 patients with DLBCL, three of 13 with MCL, one of one with Burkitt's lymphoma, two of five with transformed follicular lymphoma, and four of eight with noncutaneous T-cell lymphoma. The alisertib steady-state trough concentration (n = 25) revealed the expected pharmacokinetic variability, with a trend for higher incidence of adverse event-related dose reductions at higher trough concentrations. Analysis for AAK gene amplification and total AAK protein revealed no differences between histologies or correlation with clinical response.The novel AAK inhibitor alisertib seems clinically active in both B- and T-cell aggressive lymphomas. On the basis of these results, confirmatory single-agent and combination studies have been initiated.
Efficacy of Labeling of Foods and Pharmaceuticals
Authors: W K Viscusi
Journal: Annual Review of Public Health (1994)

Over the past several decades, the US Congress and regulatory agencies have developed a complex system of informational regulations for food and drugs that goes far beyond indications such as USDA pproved. Individual states have also begun to display increasing interest in this issue. California, for instance, has adopted its own warning system for risks of cancer and reproductive toxicity, and many other states are also considering warning measures. These efforts have diverse objectives. One function is to provide information about beneficial features, such as information about the nutritional value of foods and the medical conditions that pharmaceutical products can address. A second function is to alert the consumers to possible adverse effects of the product, for instance sodium labels for foods, health warnings for cigarettes, and information about adverse reactions to drugs. A third function of warnings is to indicate the particular types of precautions, that should be exercised, e.g. cautioning against driving after drinking alcoholic beverages, and against adverse drug interactions. Examination of food and drug warnings is instructive more generally since these warnings embody all the functions of risk communication mechanisms. Moreover, the presence of the learned intermediary--the physician in the case of prescription medications--provides an interesting variation on the context of risk communication.
Functional Impairment in Patients With Schizotypal, Borderline, Avoidant, or Obsessive-Compulsive Personality Disorder
Authors: Andrew E Skodol, John G Gunderson, Thomas H McGlashan, Ingrid R Dyck, Robert L Stout, Donna S Bender, Carlos M Grilo, M Tracie Shea, Mary C Zanarini, Leslie C Morey, Charles A Sanislow, John M Oldham
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: The purpose of this study was to compare psychosocial functioning in patients with schizotypal, borderline, avoidant, or obsessive-compulsive personality disorder and patients with major depressive disorder and no personality disorder. METHOD: Patients (N=668) were recruited by the four clinical sites of the Collaborative Longitudinal Personality Disorders Study. The carefully diagnosed study groups were compared on an array of domains of psychosocial functioning, as measured by the Longitudinal Interval Follow-Up Evaluation—Baseline Version and the Social Adjustment Scale. RESULTS: Patients with schizotypal personality disorder and borderline personality disorder were found to have significantly more impairment at work, in social relationships, and at leisure than patients with obsessive-compulsive personality disorder or major depressive disorder; patients with avoidant personality disorder were intermediate. These differences were found across assessment modalities and remained significant after covarying for demographic differences and comorbid axis I psychopathology. CONCLUSIONS: Personality disorders are a significant source of psychiatric morbidity, accounting for more impairment in functioning than major depressive disorder alone.
Expression of Mesenchymal and α-Cell Phenotypic Markers in Islet β-Cells in Recently Diagnosed Diabetes
Authors: Michael G. White, Helen L. Marshall, Rebecca Rigby, Guo Cai Huang, Aimen Amer, Trevor Booth, Steve White, James A.M. Shaw
Journal: Diabetes Care (2013)

Relative contributions of reversible β-cell dysfunction and true decrease in β-cell mass in type 2 diabetes remain unclear. Definitive rodent lineage-tracing studies have identified β-cell dedifferentiation and subsequent reprogramming to α-cell fate as a novel mechanism underlying β-cell failure. The aim was to determine whether phenotypes of β-cell dedifferentiation and plasticity are present in human diabetes.Immunofluorescence colocalization studies using classical endocrine and mesenchymal phenotypic markers were undertaken using pancreatic sections and isolated islets from three individuals with diabetes and five nondiabetic control subjects.Intraislet cytoplasmic coexpression of insulin and vimentin, insulin and glucagon, and vimentin and glucagon were demonstrated in all cases. These phenotypes were not present in nondiabetic control subjects.Coexpression of mesenchymal and α-cell phenotypic markers in human diabetic islet β-cells has been confirmed, providing circumstantial evidence for β-cell dedifferentiation and possible reprogramming to α-cells in clinical diabetes.
The longitudinal relationship between common comorbidities: Breathing disorders, back pain and incontinence
Authors: Paul Hodges, Michelle Smith, Anne Russell
Journal: European Respiratory Journal (2013)

Respiratory disorders, back pain and incontinence commonly present together as comorbid conditions. Coexistence of these conditions complicates the clinical management of patients and highlights possible shared mechanisms for some of the presenting symptoms. However, causality is difficult to infer. This longitudinal study aimed to determine whether the presence or development of one disorder increases risk for the development of another. Women from the Australian Longitudinal Study on Women’s Health were divided into subgroups; those with no back pain (n=7,259), no breathing problems (including allergy) (n=15,096), no incontinence (n=18,480), and no gastrointestinal symptoms (n=17,623). Each subgroup was analysed to determine the relationship between the development of the absent condition and the presence or development of the other conditions. Potential confounders were included in the analysis. Women with pre-existing and/or newly developed breathing problems (prevalence ratio (PR): 1.38 -2.11) or incontinence (PR: 1.26-2.12) had an increase risk for the development of back pain, and women with pre-existing and newly developed back pain were more likely to develop breathing problems and incontinence (PR: 1.53-2.62 and 1.18-2.44, respectively). Presence of gastrointestinal symptoms was also a risk factor for the development of these conditions. These longitudinal data show the presence of one symptom is associated with the greater prevalence of development of another. Common factors may contribute to the development of symptoms across this range of conditions and this may include the conflicting mechanical demands of these conditions on the trunk muscle system.
Prognostic factors in acute pancreatitis.
Authors: S L Blamey, C W Imrie, J O'Neill, W H Gilmour, D C Carter
Journal: Gut (1984)

Prognostic factor scoring systems provide one method of predicting severity of acute pancreatitis. This paper reports the prospective assessment of a system using nine factors available within 48 hours of admission. This assessment does not include patient data used to compile the system. Of 405 episodes of acute pancreatitis occurring in a seven year period, 72% had severity correctly predicted by the system; 31% of 131 episodes with three or more factors present were severe and 8% of 274 episodes with less than three factors were severe. Assessment of individual factors revealed only one which did not predict severity. A scoring system based on the other eight factors correctly predicted severity in 79% of episodes. Prognostic factor scoring systems (i) alert the clinician to potentially severe disease, (ii) allow comparison of severity within and between patient series and (iii) will allow rational selection of patients for trials of new treatment.
Asymptomatic Atrial Fibrillation
Authors: S. Ben Freedman, Nicole Lowres
Journal: JAMA (2015)

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The Accuracy of the Ottawa Knee Rule To Rule Out Knee Fractures
Authors: Lucas M. Bachmann, Sophie Haberzeth, Johann Steurer, Gerben ter Riet
Journal: Annals of Internal Medicine (2004)

Background: The Ottawa knee rule is a clinical decision aid that helps rule out fractures and avoid unnecessary radiography. Purpose: To summarize evidence about the accuracy of the Ottawa knee rule. Data Sources: Relevant English- and non–English-language articles were identified from PreMEDLINE and MEDLINE (1966–2003), EMBASE (1980–2003), CINAHL (1982–2003), BIOSIS (1990–2003), the Cochrane Library (2002, Issue 3), the Science Citation Index database, reference lists of included studies, and experts. Study Selection: Articles were included if they reported enough information to determine the sensitivity and specificity of the Ottawa knee rule for detecting fractures confirmed either radiologically or in combination with follow-up. Data Extraction: Two reviewers independently extracted data on study samples, the ways that the Ottawa knee rule was used, and methodologic characteristics of studies. Data Synthesis: Of 11 identified studies, 6 involving 4249 adult patients were considered appropriate for pooled analysis. The pooled negative likelihood ratio was 0.05 (95% CI, 0.02 to 0.23), the pooled sensitivity was 98.5% (CI, 93.2% to 100%), and the pooled specificity was 48.6% (CI, 43.4% to 51.0%). Conclusion: A negative result on an Ottawa knee rule test accurately excluded knee fractures after acute knee injury. However, because the rule is calibrated toward 100% sensitivity and actual fracture prevalences are usually low, large-scale, multicentered studies are still needed to establish the cost-effectiveness of routinely implementing the rule.
Clinical and bacteriological outcomes in hospitalised patients with community-acquired pneumonia treated with azithromycin plus ceftriaxone, or ceftriaxone plus clarithromycin or erythromycin: a prospective, randomised, multicentre study
Authors: M. Tamm, T. Todisco, C. Feldman, J. Garbino, F. Blasi, P. Hogan, P.J. de Caprariis, I.M. Hoepelman
Journal: Clinical Microbiology and Infection (2006)
Cellular Injury Associated with Renal Thrombotic Microangiopathy in Human Immunodeficiency Virus–Infected Macaques
Authors: Stephan Segerer, Frank Eitner, Yan Cui, Kelly L. Hudkins, Charles E. Alpers
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Pigtailed macaques infected with a virulent human immunodeficiency virus-2 (HIV-2) strain develop renal thrombotic microangiopathy (TMA), which morphologically resembles aspects of human HIV-associated TMA. Apoptotic cell death of microvascular endothelial cells might be a pathogenetic clue to this disease. For defining further the pattern of cellular injury in this model, serial kidney sections of 58 macaques infected with HIV-2 and 7 uninfected controls were studied by routine microscopy, terminal deoxynucleotidyl-transferase-mediated dUTP nick-end labeling (TUNEL), 4′,6-diamidino-2-phenylindole staining, and immunohistochemistry for single-stranded DNA, p53, the Wilms’ tumor suppressor gene-1 peptide product, caspase-3, and the proliferation marker Ki67. Selected cases were further evaluated by in situ end labeling and transmission electron microscopy. Kidneys of 13 HIV-2–infected animals contained a pattern of cellular injury, which was characterized by (1) nuclear swelling with an ultrastructural morphology different from apoptotic nuclei, (2) sharply demarcated areas of renal cells with chromatin nicks (TUNEL positive) and single-stranded DNA, (3) absence of an inflammatory or proliferative response, (4) upregulation of p53 and loss of at least one cellular differentiation marker (Wilms’ tumor suppressor gene-1), (5) a tight correlation with the diagnosis of renal TMA, and (6) a contrast between profound changes in the renal cellular morphology and the apparently unaffected clinical condition of the host. This pattern of injury, which shares some features of both apoptotic and oncotic necrosis, might be involved in the pathogenesis of HIV-associated renal TMA in this model.