tbuckley/cabot-search huggingface dataset:
Interim Cosmetic and Toxicity Results From RAPID: A Randomized Trial of Accelerated Partial Breast Irradiation Using Three-Dimensional Conformal External Beam Radiation Therapy
Authors: Ivo A. Olivotto, Timothy J. Whelan, Sameer Parpia, Do-Hoon Kim, Tanya Berrang, Pauline T. Truong, Iwa Kong, Brandy Cochrane, Alan Nichol, Isabelle Roy, Isabelle Germain, Mohamed Akra, Melanie Reed, Anthony Fyles, Theresa Trotter, Francisco Perera, Wayne Beckham, Mark N. Levine, Jim A. Julian
Journal: Journal of Clinical Oncology (2013)

Purpose To report interim cosmetic and toxicity results of a multicenter randomized trial comparing accelerated partial-breast irradiation (APBI) using three-dimensional conformal external beam radiation therapy (3D-CRT) with whole-breast irradiation (WBI). Patients and Methods Women age &gt; 40 years with invasive or in situ breast cancer ≤ 3 cm were randomly assigned after breast-conserving surgery to 3D-CRT APBI (38.5 Gy in 10 fractions twice daily) or WBI (42.5 Gy in 16 or 50 Gy in 25 daily fractions ± boost irradiation). The primary outcome was ipsilateral breast tumor recurrence (IBTR). Secondary outcomes were cosmesis and toxicity. Adverse cosmesis was defined as a fair or poor global cosmetic score. After a planned interim cosmetic analysis, the data, safety, and monitoring committee recommended release of results. There have been too few IBTR events to trigger an efficacy analysis. Results Between 2006 and 2011, 2,135 women were randomly assigned to 3D-CRT APBI or WBI. Median follow-up was 36 months. Adverse cosmesis at 3 years was increased among those treated with APBI compared with WBI as assessed by trained nurses (29% v 17%; P &lt; .001), by patients (26% v 18%; P = .0022), and by physicians reviewing digital photographs (35% v 17%; P &lt; .001). Grade 3 toxicities were rare in both treatment arms (1.4% v 0%), but grade 1 and 2 toxicities were increased among those who received APBI compared with WBI (P &lt; .001). Conclusion 3D-CRT APBI increased rates of adverse cosmesis and late radiation toxicity compared with standard WBI. Clinicians and patients are cautioned against the use of 3D-CRT APBI outside the context of a controlled trial.
The Biomedical Challenges of Space Flight
Authors: David R. Williams
Journal: Annual Review of Medicine (2003)

Space medicine has evolved considerably through past U.S. missions. It has been proven that humans can live and work in space for long durations and that humans are integral to mission success. The space medicine program of the National Aeronautics and Space Administration (NASA) looks toward future long-duration missions. Its goal is to overcome the biomedical challenges associated with maintaining the safety, health, and optimum performance of astronauts and cosmonauts. This program investigates the health effects of adaptation to microgravity: the nature of their pathologies, the effects of microgravity on pathophysiology, and the alterations in pharmacodynamics and treatment. A critical capability in performing research is the monitoring of the health of all astronauts and of the spacecraft environment. These data support the evidence-based approach to space medicine, incorporating past studies of microgravity-related conditions and their terrestrial counterparts. This comprehensive approach will enable safe and effective exploration beyond low Earth orbit.
Bcl-2 Protects Endothelial Cells against γ-Radiation via a Raf-MEK-ERK-Survivin Signaling Pathway That Is Independent of Cytochrome <i>c</i> Release
Authors: Pawan Kumar, Ila K. Coltas, Bhavna Kumar, Douglas B. Chepeha, Carol R. Bradford, Peter J. Polverini
Journal: Cancer Research (2007)

Abstract The Bcl-2 oncoprotein is a potent inhibitor of apoptosis and is overexpressed in a wide variety of malignancies. Until recently, it was generally accepted that Bcl-2 primarily mediates its antiapoptotic function by regulating cytochrome c release from mitochondria. However, more recent studies have shown that Bcl-2 is present on several intracellular membranes and mitochondria may not be the only site where Bcl-2 exercises its survival function. In this study, we investigated if Bcl-2 can protect endothelial cells against γ-radiation by a cytochrome c–independent signaling pathway. Human dermal microvascular endothelial cells (HDMEC), when exposed to γ-radiation, exhibited a time-dependent activation of caspase-3 that was associated with increased cytochrome c release from mitochondria. Bcl-2 expression in endothelial cells (HDMEC-Bcl-2) significantly inhibited irradiation-induced caspase-3 activation. However, Bcl-2–mediated inhibition of caspase-3 was significantly reversed by inhibition of the Raf-mitogen-activated protein kinase (MAPK)/extracellular signal–regulated kinase (ERK) kinase (MEK)-ERK pathway. Interestingly, caspase-3 activation in HDMEC-Bcl-2 cells was not associated with cytochrome c release. We also observed that endothelial cell Bcl-2 expression significantly increased the expression of survivin and murine double minute-2 (Mdm2) via the Raf-MEK-ERK pathway. Endothelial cells expressing Bcl-2 also inhibited γ-radiation–induced activation of p38 MAPK and p53 accumulation. Inhibition of p53 accumulation in HDMEC-Bcl-2 could be due to the enhanced expression of Mdm2 in these cells. Taken together, these results show three mechanisms by which Bcl-2 may mediate endothelial cell cytoprotection independently of cytochrome c release: (a) increased survivin expression, (b) inhibition of p53 accumulation, and (c) inhibition of p38 MAPK. [Cancer Res 2007;67(3):1193–202]
Ultrastructural study of two cases of -chain disease
Authors: J. Scotto, H. Stralin, J. Caroli
Journal: Gut (1970)

Intestinal biopsies of two patients with α heavy-chain disease were examined by electron microscopy. Except for a few differences, cells involved by the malignant neoplasia of the small intestine were similar and belonged to the plasma cell line and were, in fact, more like the cells observed in typical multiple myeloma. It is not surprising to find such cells in a disease which is characterized by the presence of α heavy chain in the serum since plasma cells are considered to be the main source of immunoglubulins. Moreover, the association of an intestinal plasmacytic neoplasia with the heavy chain of the immunoglobulin A in the serum agree with what is known of the normal synthesis by most of the plasma cells of the digestive tract of this immunoglobulin. Since lymphocytes can synthesize immunoglobulins and plasma cells probably originate from lymphocytes, too great an importance should not be attributed to morphological classification. Only an obvious, functional characteristic seems really useful for differentiation.
Elasticity of the Pulmonary Alveolar Microvascular Sheet in the Cat
Authors: SIDNEY S. SOBIN, Y. C. FUNG, HERTA M. TREMER, THOMAS H. ROSENQUIST
Journal: Circulation Research (1972)

The pulmonary interalveolar capillary bed of the cat has previously been shown to be consistent with a sheet-like endothelium-lined space bridged by avascular endothelium-covered posts. This was termed the sheet-flow model, and blood flow through that space is termed sheet flow. The initial formulation of the sheet-flow theory and model required that sheet thickness be the independent variable. Sheet thickness ( h ) was measured in vertical and horizontal silicone-elastomer-perfused cat lungs over the transmural (alveolar-capillary) pressure (Δ) range of 6.3 to 27 cm H 2 O. A plot of h vs. Δ for 2753 individual measurements is linear over the measured pressure range. The regression line is described by h = 4.28 + 0.2191 Δ. Sheet thickness of 4.28 µ at zero pressure is an extrapolated value. The value 0.2191 µ/cm H 2 O is the compliance coefficient (α) of the pulmonary capillary bed. Electron microscopic studies demonstrated that the capillary posts have a highly organized internal structure with abundant collagen and an elastin or elastinlike core. Collagen fibers originate from the alveolar-capillary basement membrane, emerge in a herringbone pattern, and sweep toward the center of the post in a helical array around the elastinlike amorphous and fibrillar core. The unusual compliance of the microvascular blood vessels in the lung can be correlated with the architectural organization within the posts.
Contribution of general practitioner hospitals in England and Wales.
Authors: A J Cavenagh
Journal: BMJ (1978)

A survey of a one-in-seven sample of general practitioner hospitals in England and Wales, performed to determine the contribution they make to overall hospital work load and the attitudes of the general practitioners working in them, showed that 3% of acute hospital beds in England and Wales were in general practitioner hospitals, which provided initial hospital care for up to 20% of the population. Altogether 16% of general practitioners and 22% of consultants were on the staffs, and they coped with more than 13% of all casualties, 6% of operations, and 4% of x-ray examinations. Nearly a million casualties were treated at no cost to the National Health Service. Twenty new district general hospitals would be needed to cope with the work load currently dealt with by general practitioner hospitals. The results of this survey indicate that these smaller hospitals deal efficiently and cheaply with their work load, and that morale is high. General practitioner hospitals could have an important part to play in providing certain types of care, but there are no financial incentives to enable general practitioners to realise this potential fully.
Acarbose in NIDDM Patients With Poor Control on Conventional Oral Agents: A 24-week placebo-controlled study
Authors: Karen SL Lam, SC Tiu, MW Tsang, TP Ip, Sidney CF Tam
Journal: Diabetes Care (1998)

To determine the efficacy of acarbose, compared with placebo, on the metabolic control of NIDDM patients inadequately controlled on maximal doses of conventional oral agents.In this three-center double-blind study, 90 Chinese NIDDM patients with persistent poor glycemic control despite maximal doses of sulfonylurea and metformin were randomly assigned to receive additional treatment with acarbose 100 mg thrice daily or placebo for 24 weeks, after 6 weeks of dietary reinforcement. Efficacy was assessed by changes in HbA1c, fasting and 1-h postprandial plasma glucose and insulin levels, and fasting lipid levels.Acarbose treatment was associated with significantly greater reductions in HbA1c (-0.5 +/- 0.2% vs. placebo 0.1 +/- 0.2% [means +/- SEM], P = 0.038), 1-h postprandial glucose (-2.3 +/- 0.4 mmol/l vs. placebo 0.7 +/- 0.4 mmol/l, P < 0.001) and body weight (-0.54 +/- 0.32 kg vs. placebo 0.42 +/- 0.29 kg, P < 0.05). There was no significant difference between the two groups regarding changes in fasting plasma glucose and lipids or fasting and postprandial insulin levels. Flatulence was the most common side effect (acarbose vs. placebo: 28/45 vs. 11/44, P < 0.05). One patient on acarbose had asymptomatic elevations in serum transaminases that normalized in 4 weeks after acarbose withdrawal. Another patient on acarbose developed severe hypoglycemia; glycemic control was subsequently maintained on half the baseline dosage of sulfonylurea.In NIDDM patients inadequately controlled on conventional oral agents, acarbose in moderate doses resulted in beneficial effects on glycemic control, especially postprandial glycemia, and mean body weight. Additional use of acarbose can be considered as a useful alternative in such patients if they are reluctant to accept insulin therapy.
Nasal continuous positive airway pressure in stroke patients with sleep apnoea: a randomized treatment study
Authors: O. Sandberg, K.A. Franklin, G. Bucht, S. Eriksson, Y. Gustafson
Journal: European Respiratory Journal (2001)

The authors have investigated whether treatment of sleep apnoea with nasal continuous positive airway pressure (nCPAP) improves depressive symptoms, personal activities of daily living (ADL), cognitive functioning and delirium in patients that have suffered a stroke. Sixty-three patients consecutively admitted to a stroke rehabilitation unit 2-4 weeks after a stroke, with an apnoea/hypopnoea index > or =15, were randomized to either nCPAP treatment (n=33) or a control group (n=30). Four patients dropped out after randomization. Both groups were assessed at baseline and after 7 and 28 nights using the Montgomery-Asberg Depression Rating Scale (MADRS), Barthel-ADL index, and the Mini-Mental State Examination (MMSE) scale. Compared to the control group, depressive symptoms (MADRS total score) improved in patients randomized to nCPAP treatment (p=0.004). No significant treatment effect was found with regard to delirium, MMSE or Barthel-ADL index. Delirium and low cognitive level (MMSE score) explained poor compliance with nCPAP. Depressive symptoms are reduced through nasal continuous positive airway pressure treatment in patients with severe stroke and sleep apnoea. Compliance with nasal continuous positive airway pressure treatment is a problem in stroke patients, especially when delirium and severe cognitive impairment occur.
Morphological and molecular characteristics of living human fetuses between Carnegie stages 7 and 23: ultrasound scanning and direct measurements
Authors: L. Harkness
Journal: Human Reproduction Update (1997)

The developmental age of an embryo in the first trimester of pregnancy is generally determined by ultrasound scanning and/or by calculation from menstrual age. In the original studies, validation of the estimate of gestational age by ultrasound was not possible as the exact date of conception was unknown. Variation in growth rates of identically aged fetuses has previously been reported after assisted conception and with the use of ultrasound scanning. As these pregnancies were ongoing the accuracy of the scanning results could not be determined. Comparison of scanning and direct measurements after termination of pregnancy and menstrual age were carried out to determine the accuracy in fetal dating. The results suggest that the use of ultrasound scanning to determine gestational age is of less use than previously thought, and that the use of menstrual age is severely limited.
Loss of Mismatched HLA in Leukemia after Stem-Cell Transplantation
Authors: Luca Vago, Serena Kimi Perna, Monica Zanussi, Benedetta Mazzi, Cristina Barlassina, Maria Teresa Lupo Stanghellini, Nicola Flavio Perrelli, Cristian Cosentino, Federica Torri, Andrea Angius, Barbara Forno, Monica Casucci, Massimo Bernardi, Jacopo Peccatori, Consuelo Corti, Attilio Bondanza, Maurizio Ferrari, Silvano Rossini, Maria Grazia Roncarolo, Claudio Bordignon, Chiara Bonini, Fabio Ciceri, Katharina Fleischhauer
Journal: New England Journal of Medicine (2009)

Transplantation of hematopoietic stem cells from partially matched family donors is a promising therapy for patients who have a hematologic cancer and are at high risk for relapse. The donor T-cell infusions associated with such transplantation can promote post-transplantation immune reconstitution and control residual disease.
Signal Transducer and Activator of Transcription (Stat)-Induced Stat Inhibitor 1 (Ssi-1)/Suppressor of Cytokine Signaling 1 (Socs1) Inhibits Insulin Signal Transduction Pathway through Modulating Insulin Receptor Substrate 1 (Irs-1) Phosphorylation
Authors: Yoshinori Kawazoe, Tetsuji Naka, Minoru Fujimoto, Hidetsugu Kohzaki, Yoshiaki Morita, Masashi Narazaki, Kohichi Okumura, Hiroshi Saitoh, Reiko Nakagawa, Yasuo Uchiyama, Shizuo Akira, Tadamitsu Kishimoto
Journal: The Journal of Experimental Medicine (2001)

Signal transducer and activator of transcription (STAT)-induced STAT inhibitor 1 (SSI-1) is known to function as a negative feedback regulator of cytokine signaling, but it is unclear whether it is involved in other biological events. Here, we show that SSI-1 participates and plays an important role in the insulin signal transduction pathway. SSI-1–deficient mice showed a significantly low level of blood sugar. While the forced expression of SSI-1 reduced the phosphorylation level of insulin receptor substrate 1 (IRS-1), SSI-1 deficiency resulted in sustained phosphorylation of IRS-1 in response to insulin. Furthermore, SSI-1 achieves this inhibition both by binding directly to IRS-1 and by suppressing Janus kinases. These findings suggest that SSI-1 acts as a negative feedback factor also in the insulin signal transduction pathway through the suppression of IRS-1 phosphorylation.
393 Impaired trail-dependent cytotoxicity of CD1C-positive dendritic cells in chronic hepatitis C virus infection
Authors: S. Ciesek, J. Hadem, H. Liermann, T. Greten, N. Aslan, H.L. Tillmann, M. Cornberg, M.P. Manns, H. Wedemeyer
Journal: Journal of Hepatology (2004)
Taking airway disease seriously
Authors: Pierre Ernst
Journal: Thorax (2014)

Sadatsafavi and colleagues address the question of the safety of long-acting β-agonists (LABA) in asthma with and without the concomitant use of inhaled corticosteroids (ICS).1 They carried out a study within the administrative healthcare databases of the province of British Columbia, Canada. The universal healthcare system provides healthcare for all residents of the province and includes coverage of prescription drugs. The results of the study are therefore based on a complete population avoiding the exaggeration of benefit and the minimisation of harm that may result in randomised controlled trials (RCTs) which often exclude those with comorbid disease. Within a cohort of more than 120 000 subjects, aged between 12 years and 45 years at study initiation, who were users of asthma medications, they identified more than 3000 hospitalisations for asthma. They then compared the medication used in the 12 months prior to the asthma hospitalisation with the use of asthma medications among control subjects with similar asthma severity that had not been hospitalised at that time.

Several of the results reported are of interest. First, irregular use of maintenance asthma therapy with ICS or the combination ICS/LABA is substantially more common than regular use. This is not new,2 but is particularly troublesome for the ICS/LABA combination since it is only clearly indicated in subjects who do not achieve control of their asthma with regular ICS use. Second, the risk of an asthma hospitalisation, …
Serum Myeloperoxidase Levels Independently Predict Endothelial Dysfunction in Humans
Authors: Joseph A. Vita, Marie-Luise Brennan, Noyan Gokce, Shirley A. Mann, Marlene Goormastic, Mehdi H. Shishehbor, Marc S. Penn, John F. Keaney, Stanley L. Hazen
Journal: Circulation (2004)

In vitro and animal studies demonstrate that myeloperoxidase catalytically consumes nitric oxide as a substrate, limiting its bioavailability and function. We therefore hypothesized that circulating levels of myeloperoxidase would predict risk of endothelial dysfunction in human subjects.Serum myeloperoxidase was measured by enzyme-linked immunoassay, and brachial artery flow-mediated dilation and nitroglycerin-mediated dilation were determined by ultrasound in a hospital-based population of 298 subjects participating in an ongoing study of the clinical correlates of endothelial dysfunction (age, 51+/-16; 61% men, 51% with cardiovascular disease). A strong inverse relation between brachial artery flow-mediated dilation and increasing quartile of serum myeloperoxidase level was observed (11.0+/-6.0%, 9.4+/-5.3%, 8.6+/-5.8%, and 6.4+/-4.5% for quartiles 1 through 4, respectively; P<0.001 for trend). Using the median as a cut point to define endothelial dysfunction, increasing quartile of myeloperoxidase predicted endothelial dysfunction after adjustment for classic cardiovascular disease risk factors, C-reactive protein levels, prevalence of cardiovascular disease, and ongoing treatment with cardiovascular medications (OR, 6.4; 95% CI, 2.6 to 16; P=0.001 for highest versus lowest quartile).Serum myeloperoxidase levels serve as a strong and independent predictor of endothelial dysfunction in human subjects. Myeloperoxidase-mediated endothelial dysfunction may be an important mechanistic link between oxidation, inflammation, and cardiovascular disease.
Increasing Incidence of and Increased Mortality Associated With<i>Clostridium difficile</i>–Associated Megacolon
Authors: SreyRam Kuy, Peter Jenkins, Ramon A. L. Romero, Navdeep Samra, SreyReath Kuy
Journal: JAMA Surgery (2015)

The symptoms of Clostridium difficile infection range from diarrhea to the rare, but potentially fatal, toxic megacolon.The aim of this study is to determine the changes in the incidence and outcomes of C difficile-associated megacolon over a 10year period.Methods | Using the Nationwide Inpatient Sample (2000-2010) and International Classification of Diseases, Ninth Revision (ICD-9) codes, we identified patients with both C difficile infection and megacolon.Patients without both diagnoses were excluded.The study cohort included patients who were managed with surgery and those who were managed without surgery.This study used deidentified data and is exempt from institutional review board approval.The outcome measures were length of stay, inflation-adjusted cost of hospitalization, transitional care needs, and in-hospital mortality. 1Analyses were performed with χ 2 tests and analysis of variance.P > .05 was considered statistically significant.
NKp46+ expression on NK cells as a biomarker for liver pathology and IFN-responiveness in HCV infection
Authors: Robert Thimme
Journal: Gut (2013)

Natural killer (NK) cells are large granular lymphocytes that play an important role in the control of viral infections. NK cells do have direct antiviral effects, mediated by cytolytic (eg, TNF-related apoptosis inducing ligand (TRAIL) or perforin mediated) or non-cytolytic (eg, IFN-γ mediated) effector functions as well as regulatory effects.1––3 The latter may be mediated by lysing of virus-infected antigen-presenting cells, activated CD4 T cells or virus-specific CD8 T cells.4

Several lines of evidence support an important role of NK cells in hepatitis C virus (HCV) infection. First, genetic studies have demonstrated that genes encoding the inhibitory NK cell receptor KIR2DL3 and its human leukocyte antigen C group 1 (HLA-C1) ligand directly influence resolution of HCV infection.5 Second, an activated multifunctional NK cell response (cytotoxicity and IFN-γ production) is detectable early after HCV exposure in healthcare workers and injecting drug users who do not develop acute infection suggesting an important contribution to the prevention of high-level viremia.6 ,7 Third, highly activated NK cells with increased degranulation and significant cytokine production are present during acute HCV infection although irrespective of the outcome of infection.8 ,9 Fourth, NK cells can inhibit HCV replication in vitro by IFN-γ mediated non-cytoytic and by perforin/granzyme and TRAIL-mediated cytotoxic mechanisms.1 In this context, it is interesting to note that HCV-infected hepatocytes upregulate expression of TRAIL receptors.10 Fifth, in chronic HCV infection, NK cells are activated and may display alterations in phenotype and function.1 ,2 Finally, upon initiation of antiviral IFN-based therapy, NK cells are further activated and may contribute to HCV clearance by primarily cytotoxic TRAIL-mediated effector functions.11 Interestingly, …