tbuckley/cabot-search huggingface dataset:
Maternal Infection and Cerebral Palsy in Infants of Normal Birth Weight
Authors: Judith K. Grether
Journal: JAMA (1997)

<h3>Context.</h3> —Exposure to maternal or placental infection is related to risk of preterm birth and, in premature infants, of brain lesions predictive of cerebral palsy (CP). Few studies have investigated whether maternal infection is associated with risk of CP in children of normal birth weight. <h3>Objective.</h3> —To investigate maternal infection during the admission for delivery as a possible risk factor for CP in infants born weighing 2500 g or more. <h3>Design.</h3> —Population-based case-control study. <h3>Setting.</h3> —All hospitals in 4 northern California counties, 1983 through 1985. <h3>Participants.</h3> —A total of 46 children with disabling spastic CP who had no recognized prenatal brain lesions and 378 randomly selected control children weighing 2500 g or more at birth and surviving to age 3 years. <h3>Main Outcome Measures.</h3> —Disabling spastic CP and signs of neonatal morbidity. <h3>Results.</h3> —Maternal fever exceeding 38°C in labor was associated with increased risk of unexplained CP (odds ratio [OR], 9.3; 95% confidence interval [CI], 2.7-31.0), as was a clinical diagnosis of chorioamnionitis. One or more indicators of maternal infection were present in 2.9% of control children, 22% of children with CP (OR, 9.3; 95% CI, 3.7-23.0), and 37% of those with the spastic quadriplegic subtype of CP (OR, 19.0; 95% CI, 6.5-56.0). Newborns exposed to maternal infection, both cases and controls, had 5-minute Apgar scores below 6 more often than those unexposed. Among children with CP, those born to infected women were more often hypotensive, needed intubation, had neonatal seizures, and received a clinical diagnosis of hypoxic-ischemic encephalopathy. <h3>Conclusion.</h3> —Intrauterine exposure to maternal infection was associated with a marked increase in risk of CP in infants of normal birth weight. Maternal infection was also linked with low Apgar scores, other evidence of hypertension and need for resuscitation, and neonatal seizures—signs commonly attributed to birth asphyxia.
β-Adrenergic receptor blockade arrests myocyte damage and preserves cardiac function in the transgenic Gsα mouse
Authors: Kuniya Asai, Gui-Ping Yang, Yong-Jian Geng, Gen Takagi, Sanford Bishop, Yoshihiro Ishikawa, Richard P. Shannon, Thomas E. Wagner, Dorothy E. Vatner, Charles J. Homcy, Stephen F. Vatner
Journal: Journal of Clinical Investigation (1999)

Transgenic (TG) mice with cardiac G(salpha) overexpression exhibit enhanced inotropic and chronotropic responses to sympathetic stimulation, but develop cardiomyopathy with age. We tested the hypothesis that cardiomyopathy in TG mice with G(salpha) overexpression could be averted with chronic beta-adrenergic receptor (beta-AR) blockade. TG mice and age-matched wild-type littermates were treated with the beta-AR blocker propranolol for 6-7 months, starting at a time when the cardiomyopathy was developing but was not yet severe enough to induce significant cardiac depression (9.5 months of age), and ending at a time when cardiac depression and cardiomyopathy would have been clearly manifest (16 months of age). Propranolol treatment, which can induce cardiac depression in the normal heart, actually prevented cardiac dilation and the depressed left ventricular function characteristic of older TG mice, and abolished premature mortality. Propranolol also prevented the increase in myocyte cross-sectional area and myocardial fibrosis. Myocyte apoptosis, already apparent in 9-month-old TG mice, was actually eliminated by chronic propranolol. This study indicates that chronic sympathetic stimulation over an extended period is deleterious and results in cardiomyopathy. Conversely, beta-AR blockade is salutary in this situation and can prevent the development of cardiomyopathy.
Trusts' financial plans are "overly optimistic," warns watchdog
Authors: A. Gulland
Journal: BMJ (2009)

The financial plans submitted by NHS foundation trusts to their regulator, Monitor, may be “overly optimistic” in the current financial climate.

The 2009-10 annual risk assessment, published by Monitor, shows that the 115 NHS trusts registered with foundation status in March this year are forecasting …
Recurrent mutations in the U2AF1 splicing factor in myelodysplastic syndromes
Authors: Timothy A Graubert, Dong Shen, Li Ding, Theresa Okeyo-Owuor, Cara L Lunn, Jin Shao, Kilannin Krysiak, Christopher C Harris, Daniel C Koboldt, David E Larson, Michael D McLellan, David J Dooling, Rachel M Abbott, Robert S Fulton, Heather Schmidt, Joelle Kalicki-Veizer, Michelle O'Laughlin, Marcus Grillot, Jack Baty, Sharon Heath, John L Frater, Talat Nasim, Daniel C Link, Michael H Tomasson, Peter Westervelt, John F DiPersio, Elaine R Mardis, Timothy J Ley, Richard K Wilson, Matthew J Walter
Journal: Nature Genetics (2011)
Abstract 4151: A novel, fast, and efficient technology for the preparation of high quality NGS libraries.
Authors: Laurie Kurihara, Ron Beaubien, Jeff Perry, Vanessa Kelchner, Drew McUsic, Anjali Mishra, Julie Laliberte, Sergey Chupreta, Vladimir Makarov
Journal: Cancer Research (2013)

Abstract Today's next-generation sequencing (NGS) investigators and clinicians must extract and analyze complex sequence data from a wide range of sample types. Preparing fragment libraries from these samples for whole genome, exome or targeted gene panel sequencing by NGS is a laborious process, characterized by long prep times and sample compatibility constraints due to DNA input quantity, genomic complexity, and molecular integrity. The workflows for most commercially-available kits are variations on traditional modifications for the repair, adaptation, and selection of DNA fragments, requiring 2-4 hours of preparation time before sequencing. As a consequence, NGS users cite sample preparation as the second most time-consuming step and bottleneck in their NGS workflows (following data analysis and interpretation; Bioinformatics, Oct. 2011). We present a novel technology that enables faster and more efficient NGS fragment library preparation, which increases yield and is compatible with many sample types, including damaged, cross-linked samples derived from FFPE or ChIP or samples with limiting DNA quantity. This method conveys these advantages because it does not require intact, double-stranded DNA for adapter ligation, and the streamlined workflow results in significant time savings relative to the workflows of commercial products. Side-by-side comparisons of sequencing data from libraries prepared using this new technology versus those from existing commercial products demonstrates equivalent or improved genome coverage, and suitability for damaged or cross-linked samples. Citation Format: Laurie Kurihara, Ron Beaubien, Jeff Perry, Vanessa Kelchner, Drew McUsic, Anjali Mishra, Julie Laliberte, Sergey Chupreta, Vladimir Makarov. A novel, fast, and efficient technology for the preparation of high quality NGS libraries. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4151. doi:10.1158/1538-7445.AM2013-4151
Response of the intrarenal insulin-like growth factor-I axis to acute ischemic injury and treatment with growth hormone and epidermal growth factor
Authors: Fernando C. Fervenza, Tanny Tsao, Ralph Rabkin
Journal: Kidney International (1996)

We previously reported that following bilateral acute tubular necrosis (ATN) profound changes in the intrarenal insulin-like growth factor-I axis occurs which are unrelated to altered nutritional intake. In this current report we studied rats with unilateral ATN to assess whether these changes reflect a response to acute injury or the accompanying uremia. Compared to the contralateral kidney, the injured kidney showed an increase in IGF-I receptor number without a change in IGF-I receptor mRNA levels, a decrease in IGF-I mRNA and IGF-I protein levels, a decrease in growth hormone (GH) receptor mRNA abundance and receptor binding. There was also a decrease in IGF binding protein-2, -3 and -5 mRNA levels together with a fall in protein products. Since this unilateral ATN model excludes the influence of uremia and reduced nutritional intake, we surmised that these changes reflect a direct response to injury. Next, because of the reduced GH receptor binding noted above and the reported decrease in epidermal growth factor (EGF) expression in ATN, we tested the thesis that the low kidney IGF-I mRNA levels in ATN are partly due to a relative or absolute deficiency of these hormones. Administration of EGF or GH promptly increased ATN kidney IGF-I mRNA levels to control kidney values, lending support to the thesis. The response to EGF also suggests that the salutary effect of EGF treatment in ATN may partly be mediated by stimulating IGF-I production.
From the outside in
Authors: D. Spence
Journal: BMJ (2009)

Distracted by the old black and white photos of my family on the walls, I was struggling to concentrate. The compulsory online module on “ethnicity and diversity” was difficult, for the questions seemed so obvious that they must be a trick. My grandfather, born in Berlin to a South African father and a Latvian mother, smiled down at me. My grandmother’s expression conveyed her ever reproachful “get on with your work”—she was born into a military family in what is now Pakistan. But the war changed everything for them; my …
Aspirin-Stimulated Nitric Oxide Production by Neutrophils After Acute Myocardial Ischemia in Rabbits
Authors: Antonio Lo´pez-Farre´, Amparo Riesco, Enzo Digiuni, Juan R. Mosquera, Carlos Caramelo, Lourdes S. de Miguel, Inmaculada Milla´s, Trinidad de Frutos, Maria R. Cernadas, Mercedes Monto´n, Javier Alonso, Santos Casado
Journal: Circulation (1996)

Background In recent studies, it has been hypothesized that the protective anti-ischemic effects of aspirin outweigh the effects of inhibition of platelet thromboxane A 2 synthesis. Recently, we have found that the antiaggregating effects of aspirin significantly affect nitric oxide (NO) generation by neutrophils. Methods and Results The present study used circulating neutrophils from myocardial ischemic rabbits to assess the effect of aspirin on the circulating neutrophil–derived NO production and, subsequently, on the modulation of platelet activation. Neutrophils were obtained after 60 minutes of coronary artery occlusion followed by 60 minutes of reperfusion. Sham-operated animals were used as controls. The results demonstrated that aspirin stimulated the production of NO by neutrophils obtained from both sham-operated rabbits and rabbits with myocardial ischemia. However, neutrophils isolated from animals with myocardial ischemia showed an enhanced ability to generate NO in the presence of aspirin. As a functional in vitro marker, we observed that neutrophils had a NO-dependent, platelet-antiactivating effect in the presence of aspirin. In the absence of aspirin, ischemic neutrophils did not modify platelet activation, even though they produced increased amounts of NO. An inhibitory role of superoxide anion on the neutrophil-related antiplatelet effect was suggested because superoxide dismutase induced significant platelet inhibition by myocardial ischemic neutrophils in the absence of aspirin. Conclusions Our results show that myocardial ischemia/reperfusion stimulates production of NO by circulating neutrophils, an effect that was enhanced in the presence of aspirin. These results suggest a novel interpretation of the protective effect of aspirin on myocardial ischemia damage.
Unnecessary Time Pressure in Refusal of Life-Sustaining Therapies: Fear of Missing the Opportunity to Die
Authors: Thomas I. Cochrane
Journal: The American Journal of Bioethics (2009)

During an illness requiring brief use of life-sustaining therapy (LST), patients and surrogates sometimes feel that LST must be withdrawn before it becomes unnecessary to avoid later being stuck living in a debilitated condition that the patient considers worse than death. This fear depends on the belief that the patient can legitimately refuse only artificial LST, so that if such therapies are no longer required, he or she will have missed the 'opportunity to die.' This fear of being stuck with life can lead to premature decisions to terminate LST and is unfounded because adequate ethical and moral justification exists for refusal of not just artificial LST, but also for refusal of natural LST, including oral hydration and nutrition.
Systemic, pulmonary and mesenteric perfusion and oxygenation effects of dopamine and epinephrine.
Authors: P Y Cheung, K J Barrington, R J Pearson, D L Bigam, N N Finer, J E Van Aerde
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

The response of the systemic, pulmonary, hepatic and portal circulations to infusion of dopamine and epinephrine was studied in newborn piglets 1 to 3 d of age. Anesthetized animals were instrumented to measure cardiac index (CI), hepatic arterial flow, and portal venous blood flow. Catheters were inserted for measurement of systemic arterial pressure (SAP), pulmonary arterial pressure (PAP), and for sampling of arterial, portal venous, and mixed venous oxygen saturations and plasma lactate levels. Systemic, pulmonary and mesenteric vascular resistance indices (SVRI, PVRI, MVRI), and systemic and mesenteric oxygen extraction were calculated. Dopamine and epinephrine were infused in doses of 2, 10, 32 microg/kg/min and 0.2, 1.0, 3.2 microg/kg/min respectively, given in random order. Significant increases in SAP, PAP, and CI were demonstrated with 32 microg/kg/min of dopamine and the two higher doses (1.0 and 3.2 microg/kg/min) of epinephrine. There were no significant changes in SVRI and PVRI with dopamine infusions. Epinephrine at 3.2 microg/kg/min significantly elevated SVRI and PVRI. The SAP/PAP ratio was decreased with 32 microg/kg/min of dopamine whereas epinephrine did not affect the ratio. Dopamine had no significant effect on hepatic arterial flow, portal venous flow, or mesenteric vascular resistance. Epinephrine infusion at 3.2 microg/kg/min decreased portal venous blood flow, total hepatic blood flow, and hepatic oxygen delivery with an increase in calculated mesenteric vascular resistance. Systemic and mesenteric oxygen extraction were not affected by dopamine or epinephrine infusions. Plasma lactate levels were significantly elevated with epinephrine infusion 3.2 microg/kg/min. The differential responses of dopamine and epinephrine on pulmonary and mesenteric circulations may be significant in the pathophysiology and management of persistent fetal circulation and necrotizing enterocolitis.
Potential role for interleukin-10 in the immunosuppression associated with kala azar.
Authors: B J Holaday, M M Pompeu, S Jeronimo, M J Texeira, A de A Sousa, A W Vasconcelos, R D Pearson, J S Abrams, R M Locksley
Journal: Journal of Clinical Investigation (1993)

Patients with acute kala azar are generally nonreactive in a number of immunologic assays, including T cell proliferation and generation of macrophage-activating cytokines, principally IFN-gamma, in response to leishmania antigens in vitro. To test for potential immunosuppressive factors, a series of T cell lines and clones were established from patients with acute kala azar, from patients after chemotherapy for kala azar, and from skin test-positive adults from the same endemic region. Although CD4+ T cell lines and clones could be readily established from the skin test-positive adults, lines and clones from acute or treated patients were heavily biased in expression of CD8+. The CD8+ cells from acute patients did not themselves release cytokines in response to leishmania antigens in vitro, but markedly affected the cytokine profile of peripheral blood mononuclear cells isolated 1 yr later after recovery. Addition of the CD8+ cells caused inhibition of lymphoproliferation and IFN-gamma release, with augmentation of IL-6 and IL-10 release. The inhibitory effects of the CD8+ cells could be partially abrogated by antibodies to IL-10 but not by antibodies to IL-4. Analysis of four patients with acute kala azar demonstrated release of IL-10 that could not be demonstrated in supernatants from asymptomatic skin test-positive individuals. Generation of IL-10 may contribute to the profound suppression of IFN-gamma release that occurs during kala azar due to Leishmania chagasi.
Tc-99m-GALACTOSYL-NEOGLYCOALBUMIN (Tc-NGA) LIVER IMAGING
Authors: E Steve Woodle, Richard E Ward, David R Vera, Robert C Stadalnik
Journal: Clinical Nuclear Medicine (1984)

At present, criteria for patient selection in liver transplantation (L/T) are poorly defined, and are based largely on clinically oriented, subjective evaluation of the patient. Tc-NGA is a new liver imaging agent which binds to a hepatocyte specific membrane receptor. Because hepatic uptake of Tc-NGA is dependent on hepatic blood flow and the hepatic receptor concentration, Tc-NGA liver imaging provides a means for evaluating liver function. The purpose of the present study was to determine the potential of Tc-GNA imaging as an objective means for selecting patients for L/T. Studies were performed in 9 patients undergoing evaluation for L/T. The Tc-NGA dose was standardized according to each patient's dry weight (1.8 nmole/kg, 0.04 mCi/nmole). A 30-minute dynamic imaging study was performed immediately after Tc-NGA injection. Diagnoses included: cirrhosis (5), hepatoma (3), and fulminant nonA-nonB hepatitis (1). Of these 9 patients 3 are alive, 3 died awaiting L/T, and 3 underwent orthotopic L/T. Two patients with hepatomas and otherwise normal liver function demonstrated prompt hepatic uptake of Tc-NGA. The 3 nonsurvivors demonstrated poor hepatic uptake, which was evidenced by marked flattening of the hepatic time-activity curve and significant retention of activity in the peripheral blood. The two patients in whom minimal hepatic uptake of Tc-NGA was seen had rapid, progressive deterioration in hepatic function resulting in coma and death. Although the results of these studies are not conclusive, they indicate that Tc-NGA liver imaging is a promising objective means for evaluating patients for L/T.
In vivo action of 15-lipoxygenase in early stages of human atherogenesis.
Authors: H Kühn, D Heydeck, I Hugou, C Gniwotta
Journal: Journal of Clinical Investigation (1997)

Oxidative modification of low density lipoprotein has been suggested as patho-physiologically relevant process in atherogenesis and the lipid peroxidizing enzyme 15-lipoxygenase may be involved. For experimental evidence on the in vivo action of this enzyme in the time course of plaque formation we analyzed the lipid extracts of lesional areas representing various stages of human atherogenesis for the occurrence of specific 15-lipoxygenase products. In advanced human lesions the degree of oxygenation of the lesion lipids measured as hydroxy linoleic acid/linoleic acid ratio varied between 0.2 and 3.2%. Here an unspecific pattern of oxygenated lipids that did not differ from the pattern formed during copper-catalyzed LDL oxidation was detected. In both cases an enantiomer ratio (S/R-ratio) of 13-hydroxy-9Z,11E-octadecadienoic acid (13-HODE) of approximately 1:1 was found. In young human lesions which were obtained from the collection of the pathological determinants of atherosclerosis in youth (PDAY) program the hydroxy linoleic acid/linoleic acid ratio was much smaller (variation between 0.05 and 0.6%), and a significant share of specific 15-lipoxygenase products was detected (S/R-ratio of 13-hydroxy linoleic acid of 54 +/- 3.1/46 +/- 3.1 [mean +/- SD]). These data suggest that the 15-lipoxygenase is enzymatically active on endogenous substrates in young human lesions and thus, may be of patho-physiological importance for early atherogenesis. In advanced human plaques the 15-lipoxygenase may be functionally silent and specific lipoxygenase products formed in earlier stages may be decomposed or superimposed by large amounts of nonenzymatic lipid peroxidation products.
Adding serial N‐terminal pro brain natriuretic peptide measurements to optimal clinical management in outpatients with systolic heart failure: a multicentre randomized clinical trial (NorthStar monitoring study)
Authors: Morten Schou, Finn Gustafsson, Lars Videbaek, Helge Andersen, Jens Toft, Ole Nyvad, Henrik Ryde, Lars Fog, Jens C.H. Jensen, Olav W. Nielsen, Soren Lind‐Rasmussen, Jawdat Abdulla, Per R. Hildebrandt
Journal: European Journal of Heart Failure (2013)
Treatment of accidental hypothermia: a prospective clinical study.
Authors: I M Ledingham, J G Mone
Journal: BMJ (1980)

A 15-year prospective study was carried out of 44 patients with accidental hypothermia (mean age 60 years) admitted to an intensive therapy unit. The lowest core temperature recorded in each patient ranged from 20.0 to 34.3 degrees C. The precipitating factors were poisoning (by drugs, alcohol, or coal gas) in 25 cases and various illnesses in 19. Rewarming was achieved in 42 patients by applying a radiant heat cradle over the torso, and in two patients by mediastinal irrigation with warmed fluids. Twelve patients died, but only two during the period of rewarming. Thus rewarming may be consistently and safely achieved irrespective of the cause of hypothermia, and normal body temperature may be regained as rapidly as is compatible with adequate tissue perfusion and oxygenation. Surface rewarming of the torso is perhaps the simplest technique available, but internal rewarming procedures may be desirable or essential in the presence of, for example, profound hypothermia, severe hypotension, or ventricular fibrillation. Mortality was attributable to underlying factors or disease and not to hypothermia.
THE "MOUSE" APPEARANCE OF A VERTEBRA IS MORE SUGGESTIVE OF PAGET'S DISEASE THAN METASTASIS EVEN IN PATIENTS WITH CANCER
Authors: CK Kim, N. Pandit, WN Estrada, D. Religioso, M. Lorberboym, A Alavi
Journal: Clinical Nuclear Medicine (1996)

Kim, CK; Pandit, N.; Estrada, WN; Religioso, D.; Lorberboym, M.; Alavi, A Author Information
Promoter Hypermethylation of the Bone Morphogenetic Protein-6 Gene in Malignant Lymphoma
Authors: Masanori Daibata, Yuiko Nemoto, Kentaro Bandobashi, Norihiro Kotani, Masayuki Kuroda, Mutsumi Tsuchiya, Heiwa Okuda, Tetsuya Takakuwa, Shosuke Imai, Taro Shuin, Hirokuni Taguchi
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Bone morphogenetic proteins (BMP), belonging to the transforming growth factor-β superfamily, are important regulators of cell growth, differentiation, and apoptosis. The biological effects of BMPs on malignant lymphoma, however, remain unknown. Promoter methylation of the BMP-6 gene in lymphomas was investigated. Experimental Design: We investigated BMP-6 promoter methylation and its gene expression in various histologic types of 90 primary lymphomas and 30 lymphoma cell lines. The effect of BMP-6 promoter hypermethylation on clinical outcome was also evaluated. Results: BMP-6 was epigenetically inactivated in subsets of lymphomas. The silencing occurred with high frequency in diffuse large B-cell lymphoma (DLBCL) and Burkitt's lymphoma in association with aberrant BMP-6 promoter methylation. The methylation was observed in 60% (21 of 35) of DLBCL cases and 100% (7 of 7) of DLBCL cell lines, and in 83% (5 of 6) of Burkitt's lymphoma cases and 86% (12 of 14) of Burkitt's lymphoma cell lines. In contrast, other histologic types of primary lymphomas studied had little or no detectable methylation (1 of 49; 2%). The presence of BMP-6 promoter hypermethylation in DLBCL statistically correlated with a decrease in disease-free survival (P = 0.014) and overall survival (P = 0.038). Multivariate analysis showed that the methylation profile was an independent prognostic factor in predicting disease-free survival (P = 0.022) and overall survival (P = 0. 046). Conclusion: BMP-6 promoter was hypermethylated more often in aggressive types of lymphomas, and the hypermethylation is likely to be related to the histologic type of lymphomas. BMP-6 promoter methylation may be a potential new biomarker of risk prediction in DLBCL.