tbuckley/cabot-search huggingface dataset:
Systemic hypotension and renal failure in obstructive jaundice-mechanistic and therapeutic aspects.
Authors: J Green, O S Better
Journal: Journal of the American Society of Nephrology (1995)

The association between obstructive jaundice and postoperative acute renal failure has been originally described more than eight decades ago and is now a well-established clinical phenomenon. Acute renal failure occurs in 8 to 10% of patients requiring surgery for relief of obstructive jaundice and contributes to eventual mortality in 70 to 80% of those who develop it. A major factor that may underlie the susceptibility to renal failure in patients with obstructive jaundice is cardiovascular instability manifested as systemic hypotension and defective vascular reactivity. This article outlines the scope of the clinical association between jaundice and renal failure and reviews the clinical and experimental studies that have contributed to our understanding of the underlying pathophysiologic mechanisms for this phenomenon. A growing body of evidence emanating from these studies indicates that bile constituents (e.g., bile acids, bilirubin, cholesterol) do not exert a direct nephrotoxic effect. Rather, the retention of bile during cholestatic jaundice has deleterious effects on cardiovascular function and on blood volume. This, in turn, sensitizes the kidney to prerenal failure and acute tubular necrosis in postsurgical patients with obstructive jaundice. The institution of prophylactic measures based on the appreciation of these underlying pathogenic mechanisms may result in an improvement in the overall prognosis of jaundiced patients undergoing surgery.
Infant Feeding and Childhood Cognition at Ages 3 and 7 Years
Authors: Mandy B. Belfort, Sheryl L. Rifas-Shiman, Ken P. Kleinman, Lauren B. Guthrie, David C. Bellinger, Elsie M. Taveras, Matthew W. Gillman, Emily Oken
Journal: JAMA Pediatrics (2013)

Breastfeeding may benefit child cognitive development, but few studies have quantified breastfeeding duration or exclusivity, nor has any study to date examined the role of maternal diet during lactation on child cognition.To examine relationships of breastfeeding duration and exclusivity with child cognition at ages 3 and 7 years and to evaluate the extent to which maternal fish intake during lactation modifies associations of infant feeding with later cognition.Prospective cohort study (Project Viva), a US prebirth cohort that enrolled mothers from April 22, 1999, to July 31, 2002, and followed up children to age 7 years, including 1312 Project Viva mothers and children.Duration of any breastfeeding to age 12 months.Child receptive language assessed with the Peabody Picture Vocabulary Test at age 3 years, Wide Range Assessment of Visual Motor Abilities at ages 3 and 7 years, and Kaufman Brief Intelligence Test and Wide Range Assessment of Memory and Learning at age 7 years.Adjusting for sociodemographics, maternal intelligence, and home environment in linear regression, longer breastfeeding duration was associated with higher Peabody Picture Vocabulary Test score at age 3 years (0.21; 95% CI, 0.03-0.38 points per month breastfed) and with higher intelligence on the Kaufman Brief Intelligence Test at age 7 years (0.35; 0.16-0.53 verbal points per month breastfed; and 0.29; 0.05-0.54 nonverbal points per month breastfed). Breastfeeding duration was not associated with Wide Range Assessment of Memory and Learning scores. Beneficial effects of breastfeeding on the Wide Range Assessment of Visual Motor Abilities at age 3 years seemed greater for women who consumed 2 or more servings of fish per week (0.24; 0.00-0.47 points per month breastfed) compared with less than 2 servings of fish per week (−0.01; −0.22 to 0.20 points per month breastfed) (P = .16 for interaction).Our results support a causal relationship of breastfeeding duration with receptive language and verbal and nonverbal intelligence later in life.
Rosiglitazone inhibits hypercholesterolaemia-induced myeloperoxidase upregulation--a novel mechanism for the cardioprotective effects of PPAR agonists
Authors: H.-R. Liu, L. Tao, E. Gao, Y. Qu, W. B. Lau, B. L. Lopez, T. A. Christopher, W. Koch, T.-L. Yue, X.-L. Ma
Journal: Cardiovascular Research (2008)

Hypercholesterolaemia and myeloperoxidase (MPO) overexpression are two well-recognized risk factors for ischaemic heart disease. Peroxisome proliferator-activated receptor-gamma (PPARgamma) agonists have recently been shown to reduce ischaemic heart injury in hypercholesterolaemic animals. However, whether PPARgamma agonists may exert their cardioprotective effects by eliminating those risk factors that increase ischaemic injury remains unknown.Male New Zealand rabbits were fed with a normal or a high-cholesterol diet for 8 weeks, treated with vehicle or rosiglitazone (RSG, 3 mg/kg/day for the last 5 weeks) and subjected to myocardial ischaemia/reperfusion (1 h/4 h). MPO expression, activity, and distribution, cardiac caspase-3 activity, and myocardial infarct size were determined. Diet-induced hypercholesterolaemia caused a significant increase in neutrophil MPO expression/activity (7.2-/5.4-fold). Hypercholesterolaemia also tripled MPO activity in ischaemic/reperfused hearts when compared with rabbits fed with a normal diet. Surprisingly, MPO immunostaining was not only observed in perivascular and extracellular spaces in ischaemic/reperfused hearts, but also in cardiomyocytes. This intracardiomyocyte MPO staining was further intensified by hypercholesterolaemia. There is a strong positive correlation between cardiac MPO activity and caspase-3 activity, and treatment with an MPO inhibitor significantly reduced post-ischaemic caspase-3 activation. Treatment with RSG markedly inhibited hypercholesterolaemia-induced leucocyte MPO overexpression and activation, reduced MPO activity in ischaemic/reperfused hearts, decreased caspase-3 activity, and reduced myocardial infarct size (P < 0.01).Our results demonstrated that hypercholesterolaemia and MPO overexpression are causally related and that PPARgamma agonists may have great therapeutic value in ischaemic heart disease patients with multiple complications such as hypercholesterolaemia and diabetes.
Effects of Early and Late Intervention with Epoetin α on Left Ventricular Mass among Patients with Chronic Kidney Disease (Stage 3 or 4)
Authors: Simon D. Roger, Lawrence P. McMahon, Anthony Clarkson, Alex Disney, David Harris, Carmel Hawley, Helen Healy, Peter Kerr, Kelvin Lynn, Alan Parnham, Roess Pascoe, David Voss, Robert Walker, Adeera Levin
Journal: Journal of the American Society of Nephrology (2004)

It is not known whether prevention of anemia among patients with chronic kidney disease would affect the development or progression of left ventricular (LV) hypertrophy. A randomized controlled trial was performed with 155 patients with chronic kidney disease (creatinine clearance, 15 to 50 ml/min), with entry hemoglobin concentrations ([Hb]) of 110 to 120 g/L (female patients) or 110 to 130 g/L (male patients). Patients were monitored for 2 yr or until they required dialysis; the patients were randomized to receive epoetin alpha as necessary to maintain [Hb] between 120 and 130 g/L (group A) or between 90 and 100 g/L (group B). [Hb] increased for group A (from 112 +/- 9 to 121 +/- 14 g/L, mean +/- SD) and decreased for group B (from 112 +/- 8 to 108 +/- 13 g/L) (P < 0.001, group A versus group B). On an intent-to-treat analysis, the changes in LV mass index for the groups during the 2-yr period were not significantly different (2.5 +/- 20 g/m(2) for group A versus 4.5 +/- 20 g/m(2) for group B, P = NS). There was no significant difference between the groups in 2-yr mean unadjusted systolic BP (141 +/- 14 versus 138 +/- 13 mmHg) or diastolic BP (80 +/- 6 versus 79 +/- 7 mmHg). The decline in renal function in 2 yr, as assessed with nuclear estimations of GFR, also did not differ significantly between the groups (8 +/- 9 versus 6 +/- 8 ml/min per 1.73 m(2)). In conclusion, maintenance of [Hb] above 120 g/L, compared with 90 to 100 g/L, had similar effects on the LV mass index and did not clearly affect the development or progression of LV hypertrophy. The maintenance of [Hb] above 100 g/L for many patients in group B might have been attributable to the relative preservation of renal function.
Imager Evaluation of Diabetic Retinopathy at the Time of Imaging in a Telemedicine Program
Authors: Jerry D. Cavallerano, Paolo S. Silva, Ann M. Tolson, Taniya Francis, Dorothy Tolls, Bina Patel, Sharon Eagan, Lloyd M. Aiello, Lloyd P. Aiello
Journal: Diabetes Care (2012)

To evaluate the ability of certified retinal imagers to identify presence versus absence of sight-threatening diabetic retinopathy (stDR) (moderate nonproliferative diabetic retinopathy or worse or diabetic macular edema) at the time of retinal imaging in a telemedicine program.Diabetic patients in a primary care setting or specialty diabetes clinic received Joslin Vision Network protocol retinal imaging as part of their care. Trained nonphysician imagers graded the presence versus absence of stDR at the time of imaging. These gradings were compared with masked gradings of certified readers.Of 158 patients (316 eyes) imaged, all cases of stDR (42 eyes [13%]) were identified by the imagers at the time of imaging. Six eyes with mild nonproliferative diabetic retinopathy were graded by the imagers to have stDR (sensitivity 1.00, 95% CI 0.90-1.00; specificity 0.97, 0.94-0.99).Appropriately trained imagers can accurately identify stDR at the time of imaging.
Prognostic factors for survival of patients with glioblastoma: Recursive partitioning analysis
Authors: Kathleen R. Lamborn, Susan M. Chang, Michael D. Prados
Journal: Neuro-Oncology (2004)

Survival for patients with glioblastoma multiforme is short, and current treatments provide limited benefit. Therefore, there is interest in conducting phase 2 trials of experimental treatments in newly diagnosed patients. However, this requires historical data with which to compare the experimental therapies. Knowledge of prognostic markers would also allow stratification into risk groups for phase 3 randomized trials. In this retrospective study of 832 glioblastoma multiforme patients enrolled into prospective clinical trials at the time of initial diagnosis, we evaluated several potential prognostic markers for survival to establish risk groups. Analyses were done using both Cox proportional hazards modeling and recursive partitioning analyses. Initially, patients from 8 clinical trials, 6 of which included adjuvant chemotherapy, were included. Subsequent analyses excluded trials with interstitial brachytherapy, and finally included only nonbrachytherapy trials with planned adjuvant chemotherapy. The initial analysis defined 4 risk groups. The 2 lower risk groups included patients under the age of 40, the lowest risk group being young patients with tumor in the frontal lobe only. An intermediate-risk group included patients with Karnofsky performance status (KPS) >70, subtotal or total resection, and age between 40 and 65. The highest risk group included all patients over 65 and patients between 40 and 65 with either KPS < 80 or biopsy only. Subgroup analyses indicated that inclusion of adjuvant chemotherapy provides an increase in survival, although that improvement tends to be minimal for patients over age 65, for patients over age 40 with KPS less than 80, and for those treated with brachytherapy.
Candida Precipitins as a Diagnostic Aid in Candida Endocarditis
Authors: Paul B. lannini
Journal: JAMA (1976)

We report a case of aortic valve homograft endocarditis secondary to preoperative contamination of the homograft.<i>Candida</i>precipitins, determined by double immunodiffusion, were an invaluable aid in diagnosis in the presence of negative venous blood cultures. (<i>JAMA</i>236:2518-2520, 1976)
Prevalence of obstructive sleep apnoea in children with Down syndrome
Authors: Mieke Maris, Stijn Verhulst, Marek Wojciechowski, Paul Van de Heyning, An Boudewyns
Journal: European Respiratory Journal (2014)

Aim: Obstructive sleep apnea (OSA) is a complex and multifactorial condition in children with Down syndrome (DS) with prevalence rates between 30 and 60%. We aimed to investigate the prevalence of OSA in a large cohort of DS children and to investigate which patient related factors correlated with disease severity.

Methods: All children enrolled in our multidisciplinary Down team were referred for polysomnography (PSG) when there was a positive history for OSA (snoring, witnessed apneas) (group A) or as part of “good clinical practice” to screen for OSA in this high risk population (group B) (Shott et al. 2006). A diagnosis of OSA is established at an obstructive apnea/hypopnea index (oAHI) ≥ 2/hr. Values are presented as mean ± standard deviation.

Results: Polysomnographic data are available for 93 children: 48 boys and 45 girls, age 7.1 ± 5.1years, BMI 19. 2 ± 4.6 kg/m2. The prevalence of OSA was 66.7% with an oAHI 10.2 ±16.8/h, mean oxygen saturation 96,34 ± 1,38 % and minimum saturation 85,85 ± 9,98%. Moderately severe OSA (oAHI >5 and <10/h) was found in 22.5% and severe OSA (≥10/h) in 45.2%. OSA was significantly more common for group A (74,1%) compared to group B (54,1%) (p=0.048). Multiple linear regression analysis showed a significant relationship (p=0,001) between oAHI and BMI but not with age or sex.

Conclusions: 

We found an overall 66.7% prevalence of OSA in children with Down syndrome and a significant correlation between OSA severity and BMI. Even with a negative history for OSA, the prevalence was 54,1%. This figure is much higher than in the normally developing paediatric population. Our data support the notion that PSG should be part of the routine care for children with Down syndrome.
RSV bronchiolitis and risk of wheeze and allergic sensitisation in the first year of life
Authors: U. Schauer, S. Hoffjan, J. Bittscheidt, A. Köchling, S. Hemmis, S. Bongartz, V. Stephan
Journal: European Respiratory Journal (2002)

Severe respiratory syncytial virus (RSV) infection has been hypothesised to be a risk factor for the development of allergy and asthma, but epidemiological studies in older children have been inconclusive. The current study hypothesises that the effect of RSV bronchiolitis might be most prominent during the first year after bronchiolitis. Forty-two infants had experienced RSV bronchiolitis severe enough to cause hospitalisation. For each child with RSV infection, two controls were acquired from a birth cohort and matched for date of birth and sex. All the children were followed prospectively and underwent a follow-up examination at a mean age of 1 yr, which included physical examination, and serum immunoglobulin (Ig) E tests for common food and inhaled allergens. Risk factors for the development of recurrent wheezing and IgE antibodies were analysed for the whole group of 126 children. A positive test for IgE antibodies was noted in 14 of 42 (33%) RSV children and in 2 of 84 (2.3%) children in the control group. RSV bronchiolitis was the most important risk factor for allergic sensitisation. Likewise, 13 children (15.5%) of the RSV group and three (3.6%) children of the control group suffered from recurrent wheezing, and RSV bronchiolitis posed a considerable risk for recurrent wheezing. Severe respiratory syncytial virus bronchiolitis during the first year of life is an important risk factor for the development of recurrent wheezing and sensitisation to common allergens during the subsequent year.
HLA-DQβ Typing and Non-Asp57 Alleles in IDDM and Nondiabetic Subjects in New Zealand
Authors: Louisa V Forbes, Laurie J Brown, Russell S Scott
Journal: Diabetes Care (1993)

OBJECTIVE To determine the frequency of IDDM risk-associated HLA-DQβ alleles in New Zealanders with IDDM and nondiabetic control subjects, and to examine these as susceptibility markers in relation to IDDM incidence. RESEARCH DESIGN AND METHODS HLA-DQβ typing was conducted in 55 juvenile-onset IDDM subjects diagnosed between 1990 and 1992, and 53 nondiabetic control subjects. Allele typing was conducted by a polymerase chain reaction-restriction fragment-length polymorphism technique. All subjects were residents of Canterbury, New Zealand. IDDM incidence data were obtained from the Canterbury, New Zealand, Diabetes Registry. RESULTS The frequency of the susceptibility genotype DQβ*0201/0302 was 43.6 and 5.7% in the IDDM and control groups, respectively, reflecting the increased prevalence of allele 0302 in the IDDM group. Alleles 0301, 0501, and 0602.3 were more prevalent in the control group than the IDDM group. The frequency of non-Asp57 alleles was 90.9 and 61.3% in the IDDM and control groups, respectively. Overall, the HLA-DQβ allele distribution was similar to reports from other Caucasian populations. The 0- to 19-yr age-specific IDDM incidence rate over the period in which the diabetic subjects were diagnosed was 19.5/100,000 person-yr, the highest levels observed in Canterbury over the last decade. Our relatively high background prevalence of non-Asp57 alleles and high IDDM incidence rates were similar to results from some Scandinavian and other hotspot populations. CONCLUSIONS HLA-DQβ alleles are genetic susceptibility markers in New Zealand, and other Caucasian populations. Peak IDDM incidence levels observed in 1990–1992 in our population are in accordance with a high background population prevalence of non-Asp57 alleles. These results suggest that the high Canterbury incidence rates may be due to a large HLA-DQβ non-Asp57 at-risk population.
Transcriptional Control of Cellular Metabolism by mTOR Signaling
Authors: Jessica L. Yecies, Brendan D. Manning
Journal: Cancer Research (2011)

Abstract Tumor cells are characterized by adaptations in cellular metabolism that afford growth and proliferative advantages over normal cells and, thus, contribute to cancer pathophysiology. There is an increasing appreciation of the fact that oncogenic signaling controls the metabolic reprogramming of cancer cells; however, the mechanisms and critical players are only beginning to be elucidated. Recent studies have revealed that mTOR complex 1 (mTORC1), a master regulator of cell growth and proliferation downstream of oncogenic signaling pathways, controls specific aspects of cellular metabolism through the induction of metabolic gene expression. mTORC1 activation is sufficient to promote flux through glycolysis and the oxidative branch of the pentose phosphate pathway, as well as to stimulate de novo lipogenesis, all processes that are important in tumor biology. As mTORC1 signaling is aberrantly elevated in the majority of genetic tumor syndromes and sporadic cancers, this pathway is poised to be a major driver of the metabolic conversion of tumor cells. Cancer Res; 71(8); 2815–20. ©2011 AACR.
Epidermal Growth Factor Receptor Mutation Detection Using High-Resolution Melting Analysis Predicts Outcomes in Patients with Advanced Non–Small Cell Lung Cancer Treated with Gefitinib
Authors: Toshimi Takano, Yuichiro Ohe, Koji Tsuta, Tomoya Fukui, Hiromi Sakamoto, Teruhiko Yoshida, Ukihide Tateishi, Hiroshi Nokihara, Noboru Yamamoto, Ikuo Sekine, Hideo Kunitoh, Yoshihiro Matsuno, Koh Furuta, Tomohide Tamura
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Epidermal growth factor receptor (EGFR) mutations, especially deletional mutations in exon 19 (DEL) and L858R, predict gefitinib sensitivity in patients with non–small cell lung cancer (NSCLC). In this study, we validated EGFR mutation detection using high-resolution melting analysis (HRMA) and evaluated the associations between EGFR mutations and clinical outcomes in advanced NSCLC patients treated with gefitinib on a larger scale. Experimental Design: The presence of DEL or L858R was evaluated using HRMA and paraffin-embedded tissues and/or cytologic slides from 212 patients. In 66 patients, the results were compared with direct sequencing data. Results: HRMA using formalin-fixed tissues had a 92% sensitivity and a 100% specificity. The analysis was successfully completed in 207 patients, and DEL or L858R mutations were detected in 85 (41%) patients. The response rate (78% versus 8%), time-to-progression (median, 9.2 versus 1.6 months), and overall survival (median, 21.7 versus 8.7 months) were significantly better in patients with EGFR mutations (P &amp;lt; 0.001). Even among the 34 patients with stable diseases, the time-to-progression was significantly longer in patients with EGFR mutations. Patients with DEL (n = 49) tended to have better outcomes than those with L858R (n = 36); the response rates were 86% and 67%, respectively (P = 0.037), and the median time-to-progression was 10.5 and 7.4 months, respectively (P = 0.11). Conclusions: HRMA is a precise method for detecting DEL and L858R mutations and is useful for predicting clinical outcomes in patients with advanced NSCLC treated with gefitinib.
Upregulation of Id1 by Epstein-Barr Virus-encoded LMP1 confers resistance to TGFβ-mediated growth inhibition
Authors: Angela KF Lo, Christopher W Dawson, Kwok W Lo, Yanxing Yu, Lawrence S Young
Journal: Molecular Cancer (2010)

Epstein-Barr virus (EBV)-encoded LMP1 protein is commonly expressed in nasopharyngeal carcinoma (NPC). LMP1 is a prime candidate for driving tumourigenesis given its ability to activate multiple signalling pathways and to alter the expression and activity of variety of downstream targets. Resistance to TGFβ-mediated cytostasis is one of the growth transforming effects of LMP1. Of the downstream targets manipulated by LMP1, the induction of Id1 and inactivation of Foxo3a appear particularly relevant to LMP1-mediated effects. Id1, a HLH protein is implicated in cell transformation and plays a role in cell proliferation, whilst Foxo3a, a transcription factor controls cell integrity and homeostasis by regulating apoptosis. The mechanism(s) by which LMP1 induces these effects have not been fully characterised. In this study, we demonstrate that the ability of LMP1 to induce the phosphorylation and inactivation of Foxo3a is linked to the upregulation of Id1. Furthermore, we show that the induction of Id1 is essential for the transforming function of LMP1 as over-expression of Id1 increases cell proliferation, attenuates TGFβ-SMAD-mediated transcription and renders cells refractory to TGFβ-mediated cytostasis. Id1 silencing in LMP1-expressing epithelial cells abolishes the inhibitory effect of LMP1 on TGFβ-mediated cell growth arrest and reduces the ability of LMP1 to attenuate SMAD transcriptional activity. In response to TGFβ stimulation, LMP1 does not abolish SMAD phosphorylation but inhibits p21 protein expression. In addition, we found the induction of Id1 in LMP1-expressing cells upon stimulation by TGFβ. We provide evidence that LMP1 suppresses the transcriptional repressor ATF3, possibly leading to the TGFβ-induced Id1 upregulation. The current data provide novel information regarding the mechanisms by which LMP1 suppresses TGFβ-induced cytostasis, highlighting the importance of Id1 in LMP1 mediated cell transformation