tbuckley/cabot-search huggingface dataset:
Effect of dietary composition on the unconjugated hyperbilirubinaemia of Gilbert's syndrome.
Authors: J L Gollan, C Bateman, B H Billing
Journal: Gut (1976)

The influence of dietary composition on the unconjugated hyperbilirubinaemia of Gilbert's syndrome was studied in 29 patients. After a period on a normal diet (10 MJ) an intravenous infusion of 40% glucose (8-4 MJ) together with a 1-6 MJ oral diet for two days resulted in an increment in plasma bilirubin concentration of 127 +/- 18% (mean +/- SEM) above the basal level. Both the administration of intravenous Intralipid 20% and the return to a normal diet caused a prompt reversal of this glucose effect. An increment of 135 +/- 10% in plasma bilirubin concentration was obtained when a standard "fasting" diet (1-6 MJ) was given for two days. When the lipid content of this "fasting" diet was increased from 33% to 85%, the rise in plasma bilirubin was only 49 +/- 19%. A 10 MJ oral diet for three days, which contained most of its energy content as carbohydrate and only 0-6% as lipid, produced a 76 +/- 12% increase in plasma bilirubin concentration. When the lipid content of the diet was increased to 9% of the energy intake no significant change from the basal level was observed. These findings support the hypothesis that the hyperbilirubinaemia associated with both carbohydrate feeding and fasting is attributable, at least in part, to lipid withdrawal. Although a restricted dietary intake or the parenteral administration of lipid-free solutions has a marked effect on the hyperbilirubinaemia of patients with Gilbert's syndrome, normal daily variation in dietary composition is unlikely to cause a significant change. The influence of different feeding regimes on neonatal hyperbilirubinaemia requires investigation.
Coronary Artery Calcification in Older Adults to Age 99
Authors: Anne B. Newman, Barbara L. Naydeck, Kim Sutton-Tyrrell, Adam Feldman, Daniel Edmundowicz, Lewis H. Kuller
Journal: Circulation (2001)

Background Coronary artery calcification has been proposed as a noninvasive method to assess cardiovascular disease (CVD) risk. However, the prevalence and risk factors for coronary artery calcification in populations &gt;65 years have not been well studied. Methods and Results Electron beam tomography was performed to assess coronary artery calcium (CAC) in 614 older adults aged, on average, 80 years (range, 67 to 99 years); 367 (60%) were women, and 143 (23%) were black. Calcium scores ranged from 0 to 5459. Median scores were 622 for men and 205 for women. Scores increased by age and were lower in blacks than in whites. Nine percent of subjects (n=57) had no CAC, and 31% (n=190) had a score lower than 100. A history of CVD was associated with calcium score. Age, male sex, white race, CVD, triglyceride level, pack-years of smoking, and asthma, emphysema, or bronchitis (chronic obstructive pulmonary disease) were independently associated with CAC score in the fourth quartile. Conclusions A wide range of CAC scores was observed, suggesting adaptation with aging. CAC may have potential to predict CVD in older adults, but this remains to be determined.
Rates of virological failure in patients treated in a home-based versus a facility-based HIV-care model in Jinja, southeast Uganda: a cluster-randomised equivalence trial
Authors: Shabbar Jaffar, Barbara Amuron, Susan Foster, Josephine Birungi, Jonathan Levin, Geoffrey Namara, Christine Nabiryo, Nicaise Ndembi, Rosette Kyomuhangi, Alex Opio, Rebecca Bunnell, Jordan W Tappero, Jonathan Mermin, Alex Coutinho, Heiner Grosskurth
Journal: The Lancet (2009)
Phase I/II trial of imatinib and temozolomide in advanced unresectable melanoma
Authors: L. A. Fecher, K. Nathanson, K. T. Flaherty, R. Amaravadi, L. Giles, S. McGettigan, M. Carberry, D. Elder, L. Schuchter
Journal: Journal of Clinical Oncology (2008)

9059 Background: Imatinib mesylate (I) is a selective tyrosine kinase inhibitor targeting c-KIT, PDGFR, and others. Preclinical studies suggest activity against melanoma (M). Recent data showed c-KIT mutations or increased copy number in mucosal, acral, ocular, and chronic sun damaged (CSD) M, but not in non-CSD M. Methods: This ongoing phase I/II study was initiated to define safety and MTD of I in combination with temozolomide (T) in pts with unresectable, stage III/IV M and to determine preliminary efficacy. I is given daily from D1 and T is given daily on D1–5, every 28 days. Responses assessed every 2 cycles per RECIST. No prior treatment with T allowed. Correlative studies: c-KIT expression and genotyping on pre-treatment tumor samples. As trial was ongoing when c-KIT data became available, pts with acral, mucosal, ocular, and CSD M were preferentially enrolled onto phase II portion. Results: To date, 24 pts enrolled and 23 treated; phase I: 16 with cutaneous M treated in 5 dose level cohorts and phase II: 7 (1 CSD, 1 non-CSD, 1 mucosal, 2 acral, 2 ocular). Observed side effects: (T) - N/V, myelosuppression, fatigue; (I) - fluid retention. G4 (1) toxicities attributable to study treatment: neutropenia/ thrombocytopenia. G3 toxicities (8) attributable to study treatment: edema, fatigue, rash, diarrhea, N/V. MTD established at dose level 4: I- 600mg and T-1,000mg/m2, given DLT (G3 rash) at dose level 5. Phase II: 1 pt demonstrated a CR (CSD M), 6 had PD. Tumor samples are being collected for correlative studies. Conclusions: MTD of combination I and T is 600mg and 1,000mg/m2, respectively. Combination therapy is well tolerated and has anti-tumor activity in melanoma. Accrual continues and updated results will be presented including correlation between c-KIT expression and mutation status, clinicopathologic subtype of melanoma, and treatment response. Dose level Imatinib mg QD Temozolomide mg/m2 /5 days No. of pts Total No. of cycles DLT (Cycle 1 only) 1 300 750 3 11 No 2 400 750 3 9 No 3 400 1000 3 8 No 4 600 1000 4 9 No 5 800 1000 4 12 Yes-rash Phase II 600 1000 7 24 No No significant financial relationships to disclose.
Interaction between transcription factors Iroquois proteins 4 and 5 controls cardiac potassium channel Kv4.2 gene transcription
Authors: Wenjie He, Ying Jia, Koichi Takimoto
Journal: Cardiovascular Research (2008)

The homeobox transcription factor, Iroquois protein 5 (Irx5), plays an essential role in the generation of region-selective expression of Kv4.2 gene across the left ventricular wall of rodent hearts. Here, we analyse molecular mechanisms underlying the Irx5-induced regulation of the rat Kv4.2 promoter. The mRNA levels for Irx members in various heart regions were assessed by RT–PCR. A luciferase reporter gene with the rat Kv4.2 promoter was used to test the effects of Irx members on channel promoter activity. Irx3 and Irx5 mRNAs were differentially distributed across the left ventricular wall, whereas Irx4 message was equally abundant in various ventricular regions. Irx5, but not Irx3 or Irx4, increased Kv4.2 promoter activity in 10T1/2 fibroblasts, whereas the transcription factor decreased promoter activity in neonatal ventricular myocytes. These effects were mediated by the C-terminal portion of Irx5. Irx4 appeared to inhibit the Irx5-induced increase in channel promoter activity in 10T1/2 cells. The N-terminal region of Irx4 was necessary and sufficient for this inhibition. Furthermore, when endogenous Irx4 expression was suppressed with siRNA, Irx5 increased channel promoter activity in neonatal myocytes. These results indicate that Irx5 possesses the ability to activate the Kv4.2 promoter. The abundant Irx4 expression throughout the rat ventricle may play a role in the inverse relationship between Irx5 and Kv4.2 levels across the left ventricular wall.
Diagnostic accuracy of clinical tests for ankle syndesmosis injury
Authors: Amy D Sman, Claire E Hiller, Katherine Rae, James Linklater, Deborah A Black, Leslie L Nicholson, Joshua Burns, Kathryn M Refshauge
Journal: British Journal of Sports Medicine (2013)

Objective Our aim was to investigate the diagnostic accuracy of the clinical presentation of ankle syndesmosis injury and four common clinical diagnostic tests. Design Cross-sectional diagnostic accuracy study. Setting 9 clinics in two Australian cities. Participants 87 participants (78% male) with an ankle sprain injury presenting to participating clinics within 2 weeks of injury were enrolled. Methods Clinical presentation, dorsiflexion-external rotation stress test, dorsiflexion lunge with compression test, squeeze test and ankle syndesmosis ligament palpation were compared with MRI results (read by a blinded radiologist) as a reference standard. Tests were evaluated using diagnostic accuracy, sensitivity, specificity and likelihood ratios (LRs). A backwards stepwise Cox regression model determined the combined value of the clinical tests. Results The clinical presentation of an inability to perform a single leg hop had the highest sensitivity (89%) with a negative LR of 0.37 (95% CI 0.13 to 1.03). Specificity was highest for pain out of proportion to the apparent injury (79%) with a positive LR of 3.05(95% CI 1.68 to 5.55). Of the clinical tests, the squeeze test had the highest specificity (88%) with a positive LR of 2.15 (95% CI 0.86 to 5.39). Syndesmosis ligament tenderness (92%) and the dorsiflexion-external rotation stress test (71%) had the highest sensitivity values and negative LR of 0.28 (95% CI 0.09 to 0.89) and 0.46 (95% CI 0.27 to 0.79), respectively. Syndesmosis injury was four times more likely to be present with positive syndesmosis ligament tenderness (OR 4.04, p=0.048) or a positive dorsiflexion/external rotation stress test (OR 3.9, p=0.004). Conclusions Although no single test is sufficiently accurate for diagnosis, we recommend a combination of sensitive and specific signs, symptoms and tests to confirm ankle syndesmosis involvement. An inability to hop, syndesmosis ligament tenderness and the dorsiflexion-external rotation stress test (sensitive) may be combined with pain out of proportion to injury and the squeeze test (specific).
Cholesteryl Ester Transfer Protein Inhibitor Torcetrapib and Off-Target Toxicity
Authors: Menno Vergeer, Michiel L. Bots, Sander I. van Leuven, Dick C. Basart, Eric J. Sijbrands, Gregory W. Evans, Diederick E. Grobbee, Frank L. Visseren, Anton F. Stalenhoef, Erik S. Stroes, John J.P. Kastelein
Journal: Circulation (2008)

Torcetrapib, an inhibitor of cholesteryl ester transfer protein, has been shown to increase the cardiovascular event rate despite conferring a significant high-density lipoprotein cholesterol increase. Using data from the Rating Atherosclerotic Disease Change by Imaging with a New CETP Inhibitor [corrected] (RADIANCE) trials, which assessed the impact of torcetrapib on carotid intima-media thickness (cIMT), we sought to explore potential mechanisms underlying this adverse outcome.Data from the RADIANCE 1 and 2 studies, which examined cIMT in 904 subjects with familial hypercholesterolemia and in 752 subjects with mixed dyslipidemia, were pooled. Subjects were randomized to either atorvastatin or torcetrapib combined with atorvastatin. Mean common cIMT progression was increased in subjects receiving torcetrapib plus atorvastatin compared with subjects receiving atorvastatin alone (0.0076+/-0.0011 versus 0.0025+/-0.0011 mm/y; P=0.0014). Subjects treated with torcetrapib plus atorvastatin displayed higher postrandomization systolic blood pressure and plasma sodium and bicarbonate levels in conjunction with lower potassium levels. The decrease in potassium levels was associated with the blood pressure increase. Markedly, the use of renin-angiotensin-aldosterone system inhibitors tended to aggravate the blood pressure increase. Subjects receiving torcetrapib plus atorvastatin with the strongest low-density lipoprotein cholesterol reduction showed the smallest cIMT progression, whereas subjects with the highest systolic blood pressure increase showed the largest cIMT progression. High-density lipoprotein cholesterol increase was not associated with cIMT change.These analyses support mineralocorticoid-mediated off-target toxicity in patients receiving torcetrapib as a contributing factor to an adverse outcome. The absence of an inverse relationship between high-density lipoprotein cholesterol change and cIMT progression suggests that torcetrapib-induced high-density lipoprotein cholesterol increase does not mediate atheroprotection. Future studies with cholesteryl ester transfer protein inhibitors without off-target toxicity are needed to settle this issue.
Breast Milk Jaundice in the Newborn
Authors: A. Patrick Schneider
Journal: JAMA (1986)

I have reviewed clinical trials that provide data relative to the comparative rates, means, or odds ratio of jaundiced normal breast-fed newborns vs jaundiced normal formula-fed newborns. A pooled analysis of 12 studies revealed moderate jaundice (serum bilirubin level, greater than or equal to 12 mg/dL) in 514 of 3,997 breast-fed vs 172 of 4,255 formula-fed newborns. An analysis of six of these 12 studies demonstrated severe jaundice (serum bilirubin level, greater than or equal to 15 mg/dL) in 54 of 2,655 breast-fed vs ten of 3,002 formula-fed newborns. Eleven of 13 studies found breast-fed newborns to have a higher mean serum bilirubin level. One study of 12,023 newborns found a significant (odds ratio, 1.80) relationship between breast-feeding and jaundice of the newborn. In conclusion, breast-feeding is one common cause of jaundice in normal newborns in the first week of life and beyond.
Venous Distension in the Diabetic Neuropathic Foot (Physical Sign of Arteriovenous Shunting)
Authors: J D Ward, A J M Boulton, J M Simms, D A Sandler, G Knight
Journal: Journal of the Royal Society of Medicine (1983)

A new physical sign is described in the feet of a group of diabetic patients with ulcerating neuropathic problems, in which major venous distension of the veins on the dorsum of the foot and lower calf is seen. Elevation of the leg is required to an average height of 32.3 cm to cause collapse of these distended veins. It is suggested that this clinical sign indicates the presence of arteriovenous shunting in such neuropathic legs, and as such is a simple and useful measure of this abnormality.
THE INTERACTION IN VITRO BETWEEN POLYMORPHONUCLEAR LEUKOCYTES AND MYCOPLASMA
Authors: Michael S. Simberkoff, Peter Elsbach
Journal: The Journal of Experimental Medicine (1971)

The interaction, between mycoplasma (PPLO) and human or rabbit leukocytes was examined in vitro. Upon incubation of M. hominis or M. arthritidis for 2 hr with rabbit peritoneal exudate granulocytes or leukocytes from human peripheral blood, no killing of mycoplasma was observed either in the presence or absence of type-specific antiserum. However, (14)CO(2) production from glucose-1-(14)C was stimulated up to 10-fold in the presence of live or heat-killed PPLO. The extent of stimulation depended upon the number of organisms and the presence of type-specific antiserum. The stimulation of (14)CO(2) production seems not because of tight adherence of PPLO to the leukocytes, since PPLO were quantitatively recovered in the medium after sedimenting the granulocytes. The enhanced conversion of medium lysolecithin to cellular lecithin that accompanies phagocytosis of polystyrene particles was significantly reduced when PPLO were also present. Mycoplasma alone elicited no stimulation of lecithin formation. Killing of E. coli, a microorganism readily engulfed and killed by leukocytes in vitro, was diminished when the leukocytes were preincubated with mycoplasma. These findings indicate that M. hominis and M. arthritidis are not ingested by granulocytes to any detectable extent, but that these organisms affect the leukocytes' metabolism and also impair phagocytosis of E. coli.
Validation of the ASAS criteria and definition of a positive MRI of the sacroiliac joint in an inception cohort of axial spondyloarthritis followed up for 8 years
Authors: Sibel Z Aydin, W P Maksymowych, A N Bennett, D McGonagle, P Emery, H Marzo-Ortega
Journal: Annals of the Rheumatic Diseases (2011)

Background The new Assessment of SpondyloArthritis international Society (ASAS) criteria classify axial spondyloarthritis (SpA) into human leucocyte antigen-B27 and/or imaging-based arms. To aid implementation, ASAS has proposed a definition of a positive MRI for active sacroiliitis. Objective The authors aimed to test the diagnostic and predictive value of the ASAS criteria and definition of a ‘positive’ MRI. Methods Baseline MRI scans on 29 patients with early inflammatory back pain and 18 controls were read independently by four experienced rheumatologists. Both arms of the criteria were tested against a ‘gold standard’ of physician diagnosis of SpA. MRI abnormalities were assessed according to a global assessment of MRI and the ASAS definition. Sensitivity, specificity and likelihood ratios for individual and concordant reader data were calculated for axial SpA diagnosis at baseline and the development of radiographic sacroiliitis, fulfilling the modified New York criteria at 8 years. Results All patients were classified as having axial SpA, with more patients fulfilling the imaging arm (83%, n=24/29) than the human leucocyte antigen B27 arm (62%, n=18/29). Concordant reader data showed that the baseline MRI had high diagnostic utility for SpA according to global assessment (sensitivity/specificity: 66%/94%, LR+ (positive likelihood ratio) 11.8, LR− (negative likelihood ratio) 0.4) and ASAS definition (sensitivity/specificity: 79%/89%, LR+ 7.1, LR− 0.2). Likewise, a positive baseline MRI had 100% sensitivity for subsequent radiographic sacroiliitis by either assessment, although specificity was lower (56% for global assessment and 33% for ASAS definition). Conclusion Both arms of the ASAS criteria have good diagnostic utility in early SpA, although they are of limited value for the prediction of radiographic progression. This may be due to the definition of a positive MRI for sacroiliitis that lacks specificity at baseline.
The EGFR mutation and its correlation with response of gefitinib in previously treated Chinese patients with advanced non-small-cell lung cancer
Authors: X.-T. Zhang, L.-Y. Li, X.-L. Mu, Q.-C. Cui, X.-Y. Chang, W. Song, S.-L. Wang, M.-Z. Wang, W. Zhong, L. Zhang
Journal: Annals of Oncology (2005)
<i>N</i> -Acetylcysteine Treatment Normalizes Serum Tumor Necrosis Factor-α Level and Hinders the Progression of Cardiac Injury in Hypertensive Rats
Authors: Marie Bourraindeloup, Christophe Adamy, Gabriele Candiani, Michel Cailleret, Marie-Claude Bourin, Thierry Badoual, Jin Bo Su, Sylviane Adubeiro, Françoise Roudot-Thoraval, Jean-Luc Dubois-Rande, Luc Hittinger, Françoise Pecker
Journal: Circulation (2004)

Studies in isolated cardiomyocytes showed that replenishment in cellular glutathione, achieved with the glutathione precursor N-acetylcysteine (NAC), abrogated deleterious effects of tumor necrosis factor-alpha (TNF-alpha).We examined the ability of NAC to limit the progression of cardiac injury in the rat model of hypertension, induced by the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) (50 mg/kg per day SC) and high-salt diet (HS) (8% NaCl). Four-week HS/L-NAME administration induced hypertension (193+/-8 versus 122+/-4 mm Hg for low-salt diet [LS] group) and left ventricular (LV) dysfunction, revealed by echocardiography and characterized by decreased LV shortening fraction (38+/-2% versus 49+/-4% for LS group; P<0.05) and decreased LV posterior wall thickening (49+/-3% versus 70+/-4% for LS group; P<0.05). LV dysfunction worsened further after 6-week HS/L-NAME administration. Importantly, increase in serum TNF-alpha level was strongly correlated with shortening fraction decrease and cardiac glutathione depletion. NAC (75 mg/d) was given as a therapeutic treatment in a subgroup of HS/L-NAME animals during weeks 5 and 6 of HS/L-NAME administration. NAC treatment, which replenished cardiac glutathione, had no effect on hypertension but reduced LV remodeling and dysfunction, normalized serum TNF-alpha level, and limited activation of matrix metalloproteinases -2 and -9 and collagen deposition in LV tissues.These findings suggest that glutathione status determines the adverse effects of TNF-alpha in cardiac failure and that TNF-alpha antagonism may be achieved by glutathione supplementation.
Regional bone mineral density in male athletes: a comparison of soccer players, runners and controls
Authors: Michael Fredericson, Kelvin Chew, Jessica Ngo, Tammy Cleek, Jenny Kiratli, Kristin Cobb
Journal: British Journal of Sports Medicine (2007)

Objectives: To investigate the association of soccer playing and long-distance running with total and regional bone mineral density (BMD). Design: Cross-sectional study. Setting: Academic medical centre. Participants: Elite male soccer players (n = 15), elite male long-distance runners (n = 15) and sedentary male controls (n = 15) aged 20–30 years. Main outcome measurements: BMD (g/cm 2 ) of the lumbar spine (L1–L4), right hip, right leg and total body were assessed by dual-energy x -ray absorptiometry, and a scan of the right calcaneus was performed with a peripheral instantaneous x -ray imaging bone densitometer. Results: After adjustment for age, weight and percentage body fat, soccer players had significantly higher whole body, spine, right hip, right leg and calcaneal BMD than controls (p = 0.008, p = 0.041, p&lt;0.001, p = 0.019, p&lt;0.001, respectively) and significantly higher right hip and spine BMD than runners (p = 0.012 and p = 0.009, respectively). Runners had higher calcaneal BMD than controls (p = 0.002). Forty percent of the runners had T-scores of the lumbar spine between −1 and −2.5. Controls were similar: 34% had T-scores below −1 (including 7% with T-scores lower than −2.5). Conclusions: Playing soccer is associated with higher BMD of the skeleton at all sites measured. Running is associated with higher BMD at directly loaded sites (the calcaneus) but not at relatively unloaded sites (the spine). Specific loading conditions, seen in ball sports or in running, play a pivotal role in skeletal adaptation. The importance of including an appropriate control group in clinical studies is underlined.
A functional genomic screen reveals novel host genes that mediate interferon-alpha’s effects against hepatitis C virus
Authors: Hong Zhao, Wenyu Lin, Kattareeya Kumthip, Du Cheng, Dahlene N. Fusco, Oliver Hofmann, Nikolaus Jilg, Andrew W. Tai, Kaku Goto, Leiliang Zhang, Winston Hide, Jae Young Jang, Lee F. Peng, Raymond T. Chung
Journal: Journal of Hepatology (2011)
Mesenteric lymph node B lymphoblasts which home to the small intestine are precommitted to IgA synthesis.
Authors: M McWilliams, J M Phillips-Quagliata, M E Lamm
Journal: The Journal of Experimental Medicine (1977)

The fate of mesenteric lymph node lymphoblasts labeled with either [125I]iododeoxyuridine or [3H]thymidine can be studied after intravenous transfer into syngeneic mice both by measurement of radioactivity in various organs and by combined immunofluorescence and autoradiography of recipient tissues. Many of the lymphoblasts home to the lamina propria of the small intestine within hours of transfer; of these, many visibly secrete IgA. To determine whether the cells that will ultimately secrete IgA are already committed to IgA synthesis before their arrival in the gut, mesenteric lymph node cell populations were treated with various class-specific antisera to mouse immunoglobulins before transfer. Treatment with antiserum to IgA, plus complement, reduced the fraction of injected label recovered from the recipients' intestines, and also reduced the proportion of donor (labeled) cells containing IgA. We conclude that mesenteric lymph nodes are probably the principal source of IgA-secreting plasma cells in the lamina propria of the gut, and that the cells become committed to IgA synthesis and develop cell surface IgA before emigrating. This IgA is apparently synthesized by the cells that bear it since it is not removed by extensive rinsing at 37 degrees C, a maneuver that elutes passively adsorbed immunoglobulin.