tbuckley/cabot-search huggingface dataset:
Abdominal Computed Tomography Predicts Progression in Patients With Rai Stage 0 Chronic Lymphocytic Leukemia
Authors: Ana Muntañola, Francesc Bosch, Pedro Arguis, Eduardo Arellano-Rodrigo, Carmen Ayuso, Eva Giné, Marta Crespo, Pau Abrisqueta, Carol Moreno, Francesc Cobo, Armando López-Guillermo, Emili Montserrat
Journal: Journal of Clinical Oncology (2007)

Whether computed tomography (CT) should be routinely included in the diagnostic work-up in patients with chronic lymphocytic leukemia (CLL) has not yet been determined. The aim of this study was to analyze the prognostic significance of abdominal CT in patients with CLL in Rai clinical stage 0.Abdominal CT was performed at diagnosis in 140 patients consecutively diagnosed with CLL in Rai stage 0 disease.An abnormal abdominal CT was found in 38 patients (27%). Abnormal CT correlated with increased bone marrow infiltration (P = .024), high lymphocyte count (P = .001), increased ZAP-70 expression (P = .003), and short lymphocyte doubling time (LDT; P = .007). Patients with abnormal CT progressed more frequently and had a shorter time to progression than those with normal CT (median, 3.5 years v not reached, respectively; P < .001) and required earlier treatment intervention. In a multivariate analysis, only high ZAP-70 expression (relative risk = 3.60) and an abnormal abdominal CT (RR = 2.71) correlated with disease progression.In this series, an abnormal abdominal CT was a strong predictor of progression in patients with early-stage CLL. The inclusion of CT scans in the initial work-up of patients with early clinical stage on clinical grounds can, therefore, provide relevant clinical information.
The β-catenin pathway is activated in focal nodular hyperplasia but not in cirrhotic FNH-like nodules
Authors: Sandra Rebouissou, Gabrielle Couchy, Louis Libbrecht, Charles Balabaud, Sandrine Imbeaud, Charles Auffray, Tania Roskams, Paulette Bioulac-Sage, Jessica Zucman-Rossi
Journal: Journal of Hepatology (2008)
Omapatrilat Reduces Pulse Pressure and Proximal Aortic Stiffness in Patients With Systolic Hypertension
Authors: Gary F. Mitchell, Joseph L. Izzo, Yves Lacourcière, Jean-Pascal Ouellet, Joel Neutel, Chunlin Qian, Linda J. Kerwin, Alan J. Block, Marc A. Pfeffer
Journal: Circulation (2002)

Background — Increased pulse pressure, an indicator of conduit vessel stiffness, is a strong independent predictor of cardiovascular events in hypertensive cohorts, which suggests that reduction of conduit vessel stiffness may be desirable in hypertension. Methods and Results — We assessed changes in pulse pressure and conduit vessel stiffness in a 12-week double-blind, randomized clinical trial that compared monotherapy with the ACE inhibitor enalapril 40 mg daily (n=87) versus the vasopeptidase (dual ACE and neutral endopeptidase) inhibitor omapatrilat 80 mg daily (n=80) in patients with systolic hypertension. Patients were withdrawn from antihypertensive medications 1 to 2 weeks before enrollment, and systolic pressure was confirmed to be ≥160 mm Hg. With the use of calibrated tonometry and pulsed Doppler, pulsatile hemodynamics were assessed before randomization and at 12 weeks. Characteristic impedance (Z c ), a direct measure of the stiffness of the central aorta, was calculated from the ratio of changes in carotid pressure and aortic flow in early systole. Omapatrilat compared with enalapril produced greater reductions in peripheral (−8.2±12.2 versus −4.0±12.2 mm Hg, P &lt;0.05) and central (−10.2±16.2 versus −3.2±16.9 mm Hg, P &lt;0.01) pulse pressures and Z c (237±83 to 208±70 versus 225±87 to 231±94 dyne · s/cm 5 , P &lt;0.001); the latter remained significant ( P &lt;0.05) after adjusting for change in mean pressure. Conclusions — Greater reductions in pulse pressure and Z c in hypertensive subjects treated with omapatrilat compared with enalapril suggest that aortic stiffness is maintained by specific, partially reversible mechanisms and underscore a potential role for pharmacological modulation of natriuretic peptides in the treatment of hypertension.
Scope and Outcomes of Surrogate Decision Making Among Hospitalized Older Adults
Authors: Alexia M. Torke, Greg A. Sachs, Paul R. Helft, Kianna Montz, Siu L. Hui, James E. Slaven, Christopher M. Callahan
Journal: JAMA Internal Medicine (2014)

<h3>Importance</h3> Hospitalized older adults often lack decisional capacity, but outside of the intensive care unit and end-of-life care settings, little is known about the frequency of decision making by family members or other surrogates or its implications for hospital care. <h3>Objective</h3> To describe the scope of surrogate decision making, the hospital course, and outcomes for older adults. <h3>Design, Setting, and Participants</h3> Prospective, observational study conducted in medicine and medical intensive care unit services of 2 hospitals in 1 Midwestern city in 1083 hospitalized older adults identified by their physicians as requiring major medical decisions. <h3>Main Outcomes and Measures</h3> Clinical characteristics, hospital outcomes, nature of major medical decisions, and surrogate involvement. <h3>Results</h3> According to physician reports, at 48 hours of hospitalization, 47.4% (95% CI, 44.4%-50.4%) of older adults required at least some surrogate involvement, including 23.0% (20.6%-25.6%) with all decisions made by a surrogate. Among patients who required a surrogate for at least 1 decision within 48 hours, 57.2% required decisions about life-sustaining care (mostly addressing code status), 48.6% about procedures and operations, and 46.9% about discharge planning. Patients who needed a surrogate experienced a more complex hospital course with greater use of ventilators (2.5% of patients who made decisions and 13.2% of patients who required any surrogate decisions;<i>P</i> &lt; .001), artificial nutrition (1.7% of patients and 14.4% of surrogates;<i>P</i> &lt; .001), and length of stay (median, 6 days for patients and 7 days for surrogates;<i>P</i> &lt; .001). They were more likely to be discharged to an extended-care facility (21.2% with patient decisions and 40.9% with surrogate decisions;<i>P</i> &lt; .001) and had higher hospital mortality (0.0% patients and 5.9% surrogates;<i>P</i> &lt; .001). Most surrogates were daughters (58.9%), sons (25.0%), or spouses (20.6%). Overall, only 7.4% had a living will and 25.0% had a health care representative document in the medical record. <h3>Conclusions and Relevance</h3> Surrogate decision making occurs for nearly half of hospitalized older adults and includes both complete decision making by the surrogate and joint decision making by the patient and surrogate. Surrogates commonly face a broad range of decisions in the intensive care unit and the hospital ward setting. Hospital functions should be redesigned to account for the large and growing role of surrogates, supporting them as they make health care decisions.
The effect of nonvisible sleep fragmentation on daytime function.
Authors: S E Martin, P K Wraith, I J Deary, N J Douglas
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Patients with sleep apnea/hypopnea syndrome (SAHS) suffer from impaired daytime function that correlates with hypoxemia and visible electroencephalographic (EEG) arousals. However, not all breathing irregularities during sleep terminate with visible EEG arousal. We hypothesized that sleep disturbance without visible EEG change may impair daytime function. Twelve normal subjects spent two pairs of 2 nights each in the laboratory. The first night of each pair was for acclimatization. On the second night, subjects either slept undisturbed or had sleep fragmented every minute to cause a transient increase in arterial blood pressure or increase in heart rate without visible EEG arousal. We tested daytime function after each study night. We presented 253 +/- 23 tones (mean +/- SD), 79 +/- 7% of which did not cause visible EEG arousals. Fragmentation did not alter total sleep time (undisturbed: 419 +/- 27 min; fragmented: 414 +/- 32 min; p = 0.5) or arousal frequency (undisturbed: 22 +/- 4/h; fragmented: 25 +/- 6/h; p = 0.4). Fragmentation reduced slow-wave sleep (undisturbed: 24 +/- 5%; fragmented: 20 +/- 4%; p < 0.01), mean sleep onset latency on the multiple sleep latency test (MSLT) (undisturbed: 8.0 +/- 3.1; fragmented: 6.2 +/- 2.1 min; p = 0.01) and the maintenance of wakefulness test (MWT) (undisturbed: 29.0 +/- 10.0 min; fragmented 25.7 +/- 9.7 min; p = 0.04). Fragmentation decreased hedonic tone at 7 A.M. (27 +/- 4, 25 +/- 6; p = 0.03). Nonvisible (autonomic) sleep fragmentation makes normal subjects sleepier and impairs their mood.
Fake artesunate in southeast Asia
Authors: Paul Newton, Stephane Proux, Michael Green, Frank Smithuis, Jan Rozendaal, Sompol Prakongpan, Kesinee Chotivanich, Mayfong Mayxay, Sornchai Looareesuwan, Jeremy Farrar, Francois Nosten, Nicholas J White
Journal: The Lancet (2001)
Activity of the Estrogen-Metabolizing Enzyme Cytochrome P450 1B1 Influences the Development of Pulmonary Arterial Hypertension
Authors: Kevin White, Anne Katrine Johansen, Margaret Nilsen, Loredana Ciuclan, Emma Wallace, Leigh Paton, Annabel Campbell, Ian Morecroft, Lynn Loughlin, John D. McClure, Matthew Thomas, Kirsty M. Mair, Margaret R. MacLean
Journal: Circulation (2012)

Background— Pulmonary arterial hypertension (PAH) is a hyperproliferative vascular disorder observed predominantly in women. Estrogen is a potent mitogen in human pulmonary artery smooth muscle cells and contributes to PAH in vivo; however, the mechanisms attributed to this causation remain obscure. Curiously, heightened expression of the estrogen-metabolizing enzyme cytochrome P450 1B1 (CYP1B1) is reported in idiopathic PAH and murine models of PAH. Methods and Results— Here, we investigated the putative pathogenic role of CYP1B1 in PAH. Quantitative reverse transcription–polymerase chain reaction, immunoblotting, and in situ analysis revealed that pulmonary CYP1B1 is increased in hypoxic PAH, hypoxic+SU5416 PAH, and human PAH and is highly expressed within the pulmonary vascular wall. PAH was assessed in mice via measurement of right ventricular hypertrophy, pulmonary vascular remodeling, and right ventricular systolic pressure. Hypoxic PAH was attenuated in CYP1B1 −/− mice, and the potent CYP1B1 inhibitor 2,3′,4,5′-tetramethoxystilbene (TMS; 3 mg · kg −1 · d −1 IP) significantly attenuated hypoxic PAH and hypoxic+SU5416 PAH in vivo. TMS also abolished estrogen-induced proliferation in human pulmonary artery smooth muscle cells and PAH–pulmonary artery smooth muscle cells. The estrogen metabolite 16α-hydroxyestrone provoked human pulmonary artery smooth muscle cell proliferation, and this mitogenic effect was greatly pronounced in PAH–pulmonary artery smooth muscle cells. ELISA analysis revealed that 16α-hydroxyestrone concentration was elevated in PAH, consistent with CYP1B1 overexpression and activity. Finally, administration of the CYP1B1 metabolite 16α-hydroxyestrone (1.5 mg · kg −1 · d −1 IP) caused the development of PAH in mice. Conclusions— Increased CYP1B1-mediated estrogen metabolism promotes the development of PAH, likely via the formation of mitogens, including 16α-hydroxyestrone. Collectively, this study reveals a possible novel therapeutic target in clinical PAH.
Accidental Communities: Race, Emergency Medicine, and the Problem of PolyHeme<sup>®</sup>
Authors: Karla F. C. Holloway
Journal: The American Journal of Bioethics (2006)

This article focuses on emergency medical care in black urban populations, suggesting that the classification of a “community” within clinical trial language is problematic. The article references a cultural history of black Americans with pre-hospital emergency medical treatment as relevant to contemporary emergency medicine paradigms. Part I explores a relationship between “autonomy” and “community.” The idea of community emerges as a displacement for the ethical principle of autonomy precisely at the moment that institutionalized medicine focuses on diversity. Part II examines a clinical trial for the blood substitute PolyHeme® (Northfield Laboratories, Inc., Evanston, IL). It illustrates the ways in which bias in research paradigms and Institutional Review Board decisions attach to the notion and utility of the language of “community.” The conclusion's contemporary anecdote makes apparent the vitality of the issues of prehospital emergency medical care and the ways in which decisions and practices fall too easily into a narrative of culturally biased treatment.
Altered Neuroendocrine Sleep Architecture in Patients With Type 1 Diabetes
Authors: Kamila Jauch-Chara, Sebastian M. Schmid, Manfred Hallschmid, Jan Born, Bernd Schultes
Journal: Diabetes Care (2008)

The modulatory influence of nocturnal sleep on neuroendocrine secretory activity is increasingly recognized as a factor critical to health. Disturbances of sleep may arise from and contribute to the disease process in chronically ill patients with type 1 diabetes.Using standard polysomnography and repetitive blood sampling, neuroendocrine sleep architecture was assessed under well-controlled nonhypoglycemic conditions in 14 type 1 diabetic patients and 14 healthy control subjects matched for age, sex, and BMI.As expected, plasma glucose (P = 0.02) and serum insulin (P < 0.001) levels were constantly higher in type 1 diabetic patients than in healthy subjects throughout the night. Beside these characteristic alterations of glucose metabolism, type 1 diabetic patients displayed higher blood levels of growth hormone (P = 0.001) and epinephrine (P = 0.02) during the entire night and higher levels of ACTH (P = 0.01) as well as a tendency toward higher cortisol levels (P = 0.072) during the first night-half, compared with healthy control subjects. Patients spent slightly less time in slow wave sleep (P = 0.09) during the first night-half (where this sleep stage predominates), and overall exhibited an increased proportion of stage 2 sleep (P = 0.01). Correspondingly, assessment of mood and symptoms after sleep revealed that subjective sleep was less restorative in type 1 diabetic patients than in healthy subjects.Our data indicate distinct alterations in the neuroendocrine sleep architecture of patients with type 1 diabetes, which add to the generally adverse impact of the disease on the patients' health.
Continuous high-dose vancomycin combination therapy for methicillin-resistant staphylococcal prosthetic hip infection: a prospective cohort study
Authors: V. Dubée, V. Zeller, L. Lhotellier, M.-D. Kitzis, J.-M. Ziza, P. Mamoudy, N. Desplaces
Journal: Clinical Microbiology and Infection (2012)
IGF activation in a molecular subclass of hepatocellular carcinoma and pre-clinical efficacy of IGF-1R blockage
Authors: Victoria Tovar, Clara Alsinet, Augusto Villanueva, Yujin Hoshida, Derek Y. Chiang, Manel Solé, Swan Thung, Susana Moyano, Sara Toffanin, Beatriz Mínguez, Laia Cabellos, Judit Peix, Myron Schwartz, Vincenzo Mazzaferro, Jordi Bruix, Josep M. Llovet
Journal: Journal of Hepatology (2010)
Multiple Roles for Neutrophils in Atherosclerosis
Authors: Oliver Soehnlein
Journal: Circulation Research (2012)

Because of their rare detection in atherosclerotic lesions, the involvement of neutrophils in the pathophysiology of atherosclerosis has been largely denied. However, over the past couple of years, studies have provided convincing evidence for the presence of neutrophils in atherosclerotic plaques and further revealed the causal contribution of neutrophils during various stages of atherosclerosis. This review describes mechanisms underlying hyperlipidemia-mediated neutrophilia and how neutrophils may enter atherosclerotic lesions. It also highlights possible mechanisms of neutrophil-driven atherogenesis and plaque destabilization. Knowledge of the contribution of neutrophils to atherosclerosis will allow for exploration of new avenues in the treatment of atherogenesis and atherothrombosis.
Extragonadal Germ Cell Tumors of the Mediastinum and Retroperitoneum: Results From an International Analysis
Authors: Carsten Bokemeyer, Craig R. Nichols, Jean-P. Droz, Hans-J. Schmoll, Alan Horwich, Arthur Gerl, Sophie D. Fossa, Jörg Beyer, Jörg Pont, Lothar Kanz, Lawrence Einhorn, Jörg T. Hartmann
Journal: Journal of Clinical Oncology (2002)

To characterize the clinical and biologic features of extragonadal germ cell tumor (EGCT) and to determine the overall outcome with currently available treatment strategies.Of an unselected population of 635 consecutive patients treated from 1975 through 1996 at 11 cancer centers, 341 patients (54%) had primary mediastinal EGCT, and 283 patients (45%) had retroperitoneal EGCT. Five hundred twenty-four patients (83%) had a nonseminomatous germ cell tumor (GCT), and 104 patients (16%) had a seminomatous histology.After platinum-based induction chemotherapy with or without secondary surgery, 141 patients (49%) with mediastinal nonseminomas (median follow-up, 19 months; range, 1 to 178 months) and 144 patients (63%) with retroperitoneal nonseminoma (median follow-up, 29 months; range, 1 to 203 months) are alive (P =.0006). In contrast, the overall survival rate for patients with a seminomatous EGCT is 88%, with no difference between patients with mediastinal or retroperitoneal tumor location (median follow-up, 49 months; range, 4 to 193 months; respective 70 months; range, 1 to 211 months). A significantly lower progression-free survival rate was found in seminoma patients treated with initial radiotherapy alone compared with chemotherapy. Nonseminomatous histology, presence of nonpulmonary visceral metastases, primary mediastinal GCT location, and elevated beta-human chorionic gonadotropin were independent prognostic factors for shorter survival. Hematologic malignancies (n = 17) occurred without exception in patients with primary mediastinal nonseminoma. Sixteen patients developed a metachronous testicular cancer despite the use of platinum-based chemotherapy.Whereas patients with pure seminomatous EGCT histology have a long-term chance of cure of almost 90% irrespective of the primary tumor site, 45% of patients with mediastinal nonseminomas are alive at 5 years. This outcome is clearly inferior compared with patients with nonseminomatous retroperitoneal primary tumors.
NSIP in a curry sauce factory worker
Authors: S Ando, T Arai, Y Inoue, M Kitaichi, M Sakatani
Journal: Thorax (2006)

Curry powder and ground pepper are commonly used spices in many countries of the world. Although a case of bronchiolitis obliterans organising pneumonia has been reported in a worker who inhaled spice dust in a potato chip factory,1 we report the first case of non-specific interstitial pneumonia (NSIP)2 with bronchiolar lesions associated with curry powder and ground pepper.

A 50 year old male smoker (20 pack-years) developed a cough with sputum and shortness of breath on both working days and non-working days and was admitted to our hospital 1 month after developing the symptoms. He had worked in a factory that produced curry sauce for 13 years. His job was to carry sacks filled with curry powder (containing a mix of ground spices) and ground pepper on his shoulders and to empty …
Biosimilar epoetins and other “follow‐on” biologics: Update on the European experiences
Authors: Wolfgang Jelkmann
Journal: American Journal of Hematology (2010)

Abstract After the patents of biopharmaceuticals have expired, based on specific regulatory approval pathways copied products (“biosimilars” or “follow‐on biologics”) have been launched in the EU. This article summarizes experiences with hematopoietic medicines, namely the epoetins (two biosimilars traded under five different brand names) and the filgrastims (two biosimilars, six brand names). Physicians and pharmacists should be familiar with the legal and pharmacological specialities of biosimilars: The production process can differ from that of the original, clinical indications can be extrapolated, glycoproteins contain varying isoforms, the formulation may differ from the original, and biopharmaceuticals are potentially immunogenic. Only on proof of quality, efficacy and safety, biosimilars are a viable option because of their lower costs. Am. J. Hematol. 2010. © 2010 Wiley‐Liss, Inc.
Prevention by selenium supplementation of cyclosporin-A-induced vascular toxicity
Authors: G BERKENBOOM, D BREKINE, Z FANG, J NEVE, J FONTAINE
Journal: Cardiovascular Research (1997)

Objective: The aim was to determine whether selenium supplementation, an important component of glutathione peroxidase, might attenuate cyclosporin (Cx)-induced vascular toxicity. Methods: Four groups of rats were treated in parallel: the first group was supplemented with selenium (sodium selenite, 0.5 mg · kg −1 ) orally (p.o.) for 5 weeks and the same dose of selenium plus Cx 20 mg · kg −1 (i.m.) during the 6th week; group 2 received Cx only (20 mg · kg −1 i.m. for 1 week); group 3 was supplemented with selenium (0.5 mg · kg −1 p.o., for 6 weeks) and group 4 served as control. Thoracic aortas isolated from these various groups were studied in organ baths. Results: In comparison with the control group, selenium supplementation did not modify acetylcholine (Ach)- and nitroprusside-induced relaxations. In group 2, endothelium-dependent relaxations (Ach) were markedly impaired and endothelium-independent relaxations (nitroprusside) were shifted to the right; with selenium supplementation (group 1), the responses to Ach were partially restored whereas the rightward shift of the concentration-response curves to nitroprusside persisted. Incubation with superoxide dismutase (SOD, 150 IU · ml −1 ) or selenium (1 μg · ml −1 ) (but not with selenium plus an inhibitor of the glutathione redox cycle) improved the relaxations to Ach in group 2. Conclusions: The vascular toxicity of Cx seems related to generation of oxygen-derived radicals promoting EDRF destruction and is attenuated by selenium supplementation.
Failure of D- and L-Thyroxine to Protect Cholesterol and Oil Fed Cockerels Against Coronary Atherogenesis
Authors: Savitri Jain, Ruth Pick, Philip J. Johnson, Louis N. Katz
Journal: Circulation Research (1966)

In cockerels, L-thyroxine was significantly more active biologically than an equivalent dose of D-thyroxine, or even four times the dose, as demonstrated by the effects on body weights, organ weights and comb index. In cockerels fed an atherogenic diet, the plasma cholesterol concentrations in all the thyroxine-treated groups were significantly lower than in the control groups. No consistent effect of D-thyroxine on thoracic aorta atherosclerosis was observed. However, L-thyroxine had some protective action in the one experiment done. Despite suppression of hypercholester-olemia, no protection against coronary atherosclerosis was seen with the administration of either L- or D-thyroxine. In fact, with an increase in dose of D-thyroxine to 4 mg, there developed actually an increase in the percentage of coronary vessels showing atherosclerosis. These observations confirm once again the importance of avoiding reliance exclusively on blood cholesterol levels when judging the effects of hormones on atherogenesis.