tbuckley/cabot-search huggingface dataset:
Low Hemoglobin, Chronic Kidney Disease, and Risk for Coronary Heart Disease–Related Death
Authors: Stephen R Leeder, Paul Mitchell, Gerald Liew, Elena Rochtchina, Wayne Smith, Jie Jin Wang
Journal: Journal of the American Society of Nephrology (2005)

A recent report found that chronic kidney disease (CKD) increased the risk for coronary heart disease (CHD) events in people with anemia but not in those without anemia. This study aimed to verify these findings in the Blue Mountains Eye Study cohort, a prospective Australian population-based study of 3654 residents aged 49 to 97 yr. Fasting blood samples were obtained at baseline and confirmed CHD-related deaths over 9 yr with the Australian National Death Index. "Low hemoglobin" was defined as levels in the lowest quintile of the cohort. Body surface area-adjusted GFR was estimated using a variety of methods (Cockcroft-Gault, abbreviated Modification of Diet in Renal Disease, and Bjornsson equations). People with CKD (GFR <60 ml/min per 1.73 m2 as estimated using the Cockcroft-Gault equation) and low hemoglobin (mean 13.2 g/dl; range 7.6 to 14.6 g/dl) had an increased risk for CHD-related death (multivariable-adjusted hazard risk ratio 1.49; 95% confidence interval 1.08 to 2.06) compared with people with CKD but in higher hemoglobin quintiles. This effect was not evident in people without CKD. The interaction between GFR and hemoglobin was significant (P = 0.05) when GFR was estimated using either the Cockcroft-Gault or Bjornsson equations or when serum creatinine instead of GFR was used in the analyses but not when GFR was estimated using the abbreviated Modification of Diet in Renal Disease equation. In conclusion, this study found that low hemoglobin, even within the normal range, together with CKD increased the risk for CHD-related death.
Glycogen Synthase Kinase-3β
Authors: Stefan E. Hardt, Junichi Sadoshima
Journal: Circulation Research (2002)

Glycogen synthase kinase-3beta (GSK-3beta) is a ubiquitously expressed constitutively active serine/threonine kinase that phosphorylates cellular substrates and thereby regulates a wide variety of cellular functions, including development, metabolism, gene transcription, protein translation, cytoskeletal organization, cell cycle regulation, and apoptosis. The activity of GSK-3beta is negatively regulated by protein kinase B/Akt and by the Wnt signaling pathway. Increasing lines of evidence show that GSK-3beta is an essential negative regulator of cardiac hypertrophy and that the inhibition of GSK-3beta by hypertrophic stimuli is an important mechanism contributing to the development of cardiac hypertrophy. GSK-3beta also plays an important role in regulating cardiac development. In this review, the role of GSK-3beta in cardiac hypertrophy and development and the potential underlying mechanisms are discussed.
Decreased Adenylate Cyclase Activity and Expression of G <sub>sα</sub> in Human Myocardium After Orthotopic Cardiac Transplantation
Authors: Evan Loh, Joey V. Barnett, Arthur M. Feldman, Gregory S. Couper, Dorothy E. Vatner, Wilson S. Colucci, Jonas B. Galper
Journal: Circulation Research (1995)

Abstract We studied several aspects of guanine nucleotide–stimulated adenylate cyclase function in patients after orthotopic cardiac transplantation. In 28 patients, adenylate cyclase activity was measured in endomyocardial biopsy samples obtained just before and at monthly intervals after cardiac transplantation. In biopsies obtained ≥6 months after transplantation, basal adenylate cyclase activity was decreased by 67% (n=12; P &lt;.05), GTPγS-stimulated adenylate cyclase activity was decreased by 78% (n=12; P &lt;.05), Mn +2 +forskolin–stimulated adenylate cyclase activity was decreased by 80% (n=8; P &lt;.05), and Mn +2 -stimulated adenylate cyclase activity (a measure of activity of the catalytic subunit of adenylate cyclase) was decreased by 83% (n=8, P &lt;.05). Western blot analysis demonstrated that 6 months after cardiac transplantation, the level of G sα protein was decreased by 61±12% (n=8; P &lt;.001). There was no change in the level of G iα as assessed by pertussis toxin–catalyzed ADP-ribosylation (n=4; P =NS). With the use of the quantitative polymerase chain reaction, a 50±10% (n=6; P &lt;.001) reduction in the steady-state level of G sα mRNA was observed. There was no change in the level of mRNA for G i-3α . Thus, after orthotopic cardiac transplantation in humans, guanine nucleotide–stimulated adenylate cyclase activity is decreased in parallel with decreased levels of G sα protein and mRNA.
Intravenous immunoglobulin versus intravenous methylprednisolone for chronic inflammatory demyelinating polyradiculoneuropathy: a randomised controlled trial
Authors: Eduardo Nobile-Orazio, Dario Cocito, Stefano Jann, Antonino Uncini, Ettore Beghi, Paolo Messina, Giovanni Antonini, Raffaella Fazio, Francesca Gallia, Angelo Schenone, Ada Francia, Davide Pareyson, Lucio Santoro, Stefano Tamburin, Roberta Macchia, Guido Cavaletti, Fabio Giannini, Mario Sabatelli
Journal: The Lancet Neurology (2012)
A REVIEW OF ONE HUNDRED CONSECUTIVE GALL-BLADDER OPERATIONS
Authors: J. M. Black
Journal: BMJ (1935)

rMTHEBRJOTISUA 1 ConclusionThe results of thoracic surgery are most encouraging and the work must be supported, but there is no iieed to be carried away in our enthusiasm to provide surplus possibilities for the treatment of one case while there are not adequate facilities for treatment of the ninety-nine others.In conclusion, I wish to state that the above views are my own personal opinions, and have no bearing on, or connexion with, the scheme or work of any public authority, and that I have brought them forward merely with a view to promote discussion on what I conmider an interesting and important problem.
Development and application of triage and medical evacuation system for casualties at sea
Authors: Tai Xie, Xiao-Rong Liu, Guo-Liang Chen, Liang Qi, Zhi-Yin Xu, Xu-Dong Liu
Journal: Military Medical Research (2014)

Traditional triage could not meet the needs of battlefield casualties’ care in modern warfare. This paper designs of triage and medical evacuation system for casualties at sea that can quickly address mass-casualty triage, and store and transmit medical information during battlefield treatment and medical evacuation. This system consists of a high-capacity medical information card, a simulated patient generator, a triage classifier and a multifunctional airbag triage vest.
Formation of calcium pyrophosphate crystals in vitro: implications for calcium pyrophosphate crystal deposition disease (pseudogout)
Authors: P. R. Hearn, R. G. G. Russell
Journal: Annals of the Rheumatic Diseases (1980)

Little is known about how calcium pyrophosphate dihydrate (CaPPD) crystals form in vivo and give rise to chondrocalcinosis or pseudogout (pyrophosphate arthropathy or calcium pyrophosphate crystal deposition disease). In this study a simple method has been devised to define the conditions necessary for the deposition of crystals in vitro. Crystal formation is monitored by <sup>45</sup>Ca in the presence of 1·5 mmol/l Ca and increasing concentrations of inorganic pyrophosphate (PPi) under simulated physiological conditions of pH and ionic strength. Concentrations of PPi required to initiate crystal formation were about 40 mmol/l in the absence and 175 mmol/l in the presence of 0·5 mmol/l Mg<sup>2+</sup> at pH 7·4. Less PPi was required at higher pH values. The naturally occurring monoclinic and triclinic forms of CaPPD were produced after prolonged incubation in vitro, but the initial deposits were amorphous or orthorhombic. The physiological significance of these observations is discussed. Since much higher concentrations of PPi are required to form crystals in vitro than are found to occur naturally in synovial fluids from patients with pyrophosphate arthropathy, it is suggested that crystals are more likely to deposit initially within cartilage and that nucleating mechanisms may be important in vivo. Since other workers have observed a slow interconversion of other calcium pyrophosphate crystal forms into monoclinic and triclinic allomorphs under laboratory conditions, the reason why only these 2 forms occur under clinical conditions may reflect the long time available in vivo for the formation of crystals.
A stem cell–like chromatin pattern may predispose tumor suppressor genes to DNA hypermethylation and heritable silencing
Authors: Joyce E Ohm, Kelly M McGarvey, Xiaobing Yu, Linzhao Cheng, Kornel E Schuebel, Leslie Cope, Helai P Mohammad, Wei Chen, Vincent C Daniel, Wayne Yu, David M Berman, Thomas Jenuwein, Kevin Pruitt, Saul J Sharkis, D Neil Watkins, James G Herman, Stephen B Baylin
Journal: Nature Genetics (2007)
A patient with Ehlers-Danlos syndrome type VI is a compound heterozygote for mutations in the lysyl hydroxylase gene.
Authors: V T Ha, M K Marshall, L J Elsas, S R Pinnell, H N Yeowell
Journal: Journal of Clinical Investigation (1994)

In the present study, we have isolated and sequenced the complementary DNAs of two mutant alleles for lysyl hydroxylase (LH) in fibroblasts from one patient (AT750) with Ehlers-Danlos syndrome type VI (EDS VI). We have identified a putative mutation in each allele which may be responsible for the patient's decreased LH (normalized to prolyl hydroxylase) activity (24% of normal). Intermediate levels of LH activity were measured in the patient's parents, who are clinically normal (father 52%; mother 86%). After the cloning of cDNAs and amplification by PCR, sequence analysis revealed two equally distributed populations of cDNAs for LH in the AT750 cell line. Each allele revealed different but significant changes from the normal sequence. In one allele (allele 1), the most striking change was a triple base deletion that would result in the loss of residue Glu532. The most significant difference in the other allele (allele 2) was a G-->A change which would produce a Gly678-->Arg codon change in a highly conserved region of the enzyme. Restriction analysis identified that allele 1 was inherited from the proband's mother and allele 2 from the father. This study represents the first example of compound heterozygosity for the LH gene in an EDS VI patient, and it appears that there is an additive effect of each mutant allele on clinical expression in this patient.
Dialysis Modality and Delayed Graft Function after Cadaveric Renal Transplantation
Authors: ANTHONY J. BLEYER, JOHN M. BURKART, GREGORY B. RUSSELL, PATRICIA L. ADAMS
Journal: Journal of the American Society of Nephrology (1999)

Abstract. The purpose of this investigation was to compare outcomes in the immediate posttransplant period for hemodialysis (HD) and peritoneal (PD) dialysis patients who received cadaveric renal transplantation. Data were obtained from the United Network of Organ Sharing on all cadaveric graft recipients who were dialysis-dependent at the time of transplantation between April 1994 and December 1995. Baseline characteristics were compared between groups, and multivariate logistic regression was performed with outcome measures including urine production in the first 24 h posttransplantation (U24), requirement for dialysis in the first week posttransplant (FWDIAL), and treatment for acute rejection during the initial hospitalization. The odds of oliguria (not producing urine in the first 24 h) were 1.49 (1.28 to 1.74) times higher in HD versus PD patients. After adjustment for other comorbid conditions including age, gender, race, HLA mismatch, time on dialysis, panel-reactive antibodies, and cold and warm ischemia time, the odds of oliguria were 1.60 (1.14 to 2.25) times higher in black HD patients compared with PD patients and 1.29 (1.06 to 1.57) times higher in white HD patients. In a similar manner, after adjustment for significant comorbid conditions, the odds of requiring dialysis in the first week were 1.56 (1.22 to 2.0) times higher in black HD patients versus PD patients and 1.40 (1.21 to 1.60) times higher in white HD patients. The rate of acute rejection was similar during the first hospitalization. These results suggest that there is an association between hemodialysis and delayed graft function. Differences in biocompatibility between the two modalities could potentially be responsible.
Bortezomib As Induction Before Autologous Transplantation, Followed by Lenalidomide As Consolidation-Maintenance in Untreated Multiple Myeloma Patients
Authors: Antonio Palumbo, Francesca Gay, Patrizia Falco, Claudia Crippa, Vittorio Montefusco, Francesca Patriarca, Fausto Rossini, Simona Caltagirone, Giulia Benevolo, Norbert Pescosta, Tommasina Guglielmelli, Sara Bringhen, Massimo Offidani, Nicola Giuliani, Maria Teresa Petrucci, Pellegrino Musto, Anna Marina Liberati, Giuseppe Rossi, Paolo Corradini, Mario Boccadoro
Journal: Journal of Clinical Oncology (2010)

PURPOSE To evaluate the effect of bortezomib as induction therapy before autologous transplantation, followed by lenalidomide as consolidation-maintenance in myeloma patients. PATIENTS AND METHODS Newly diagnosed patients age 65 to 75 years were eligible. Induction (bortezomib, doxorubicin, and dexamethasone [PAD]) included four 21-day cycles of bortezomib (1.3 mg/m(2) on days 1, 4, 8, and 11), pegylated liposomal doxorubicin (30 mg/m(2) on day 4), and dexamethasone (40 mg/d; cycle 1: days 1 to 4, 8 to 11, and 15 to 18; cycles 2 to 4: days 1 to 4). Autologous transplantation was tandem melphalan 100 mg/m(2) (MEL100) and stem-cell support. Consolidation included four 28-day cycles of lenalidomide (25 mg/d on days 1 to 21 every 28 days) plus prednisone (50 mg every other day), followed by maintenance with lenalidomide (LP-L; 10 mg/d on days 1 to 21) until relapse. Primary end points were safety (incidence of grade 3 to 4 adverse events [AEs]) and efficacy (response rate). Results A total of 102 patients were enrolled. In a per-protocol analysis, after PAD, 58% of patients had very good partial response (VGPR) or better, including 13% with complete response (CR); after MEL100, 82% of patients had at least VGPR and 38% had CR; and after LP-L, 86% of patients had at least VGPR and 66% had CR. After median follow-up time of 21 months, the 2-year progression-free survival rate was 69%, and the 2-year overall survival rate was 86%. During induction, treatment-related mortality was 3%; grade 3 to 4 AEs included thrombocytopenia (17%), neutropenia (10%), peripheral neuropathy (16%), and pneumonia (10%). During consolidation-maintenance, grade 3 to 4 AEs were neutropenia (16%), thrombocytopenia (6%), pneumonia (5%), and cutaneous rash (4%). CONCLUSION Bortezomib as induction before autologous transplantation, followed by lenalidomide as consolidation-maintenance, is an effective regimen.
The Phosphorylation of EphB2 Receptor Regulates Migration and Invasion of Human Glioma Cells
Authors: Mitsutoshi Nakada, Jared A. Niska, Hisashi Miyamori, Wendy S. McDonough, Jie Wu, Hiroshi Sato, Michael E. Berens
Journal: Cancer Research (2004)

Abstract Eph receptor tyrosine kinases and their ligands, ephrins, mediate neurodevelopmental processes such as boundary formation, axon guidance, vasculogenesis, and cell migration. We determined the expression profiles of the Eph family members in five glioma cell lines under migrating and nonmigrating conditions. EphB2 mRNA was overexpressed in all five during migration (1.2–2.8-fold). We found abundant EphB2 protein as well as strong phosphorylation of EphB2 in migrating U87 cells. Confocal imaging showed EphB2 localized in lamellipodia of motile U87 cells. Treatment with ephrin-B1/Fc chimera stimulated migration and invasion of U87, whereas treatment with a blocking EphB2 antibody significantly inhibited migration and invasion. Forced expression of EphB2 in U251 cells stimulated cell migration and invasion and diminished adhesion concomitant with the tyrosine phosphorylation of EphB2. U251 stably transfected with EphB2 showed more scattered and more pronounced invasive growth in an ex vivo rat brain slice. In human brain tumor specimens, EphB2 expression was higher in glioblastomas than in low-grade astrocytomas or normal brain; patterns of phosphorylated EphB2 matched the expression levels. Laser capture microdissection of invading glioblastoma cells revealed elevated EphB2 mRNA (1.5–3.5-fold) in 7 of 7 biopsy specimens. Immunohistochemistry demonstrated EphB2 localization primarily in glioblastoma cells (56 of 62 cases) and not in normal brain. This is the first demonstration that migrating glioblastoma cells overexpress EphB2 in vitro and in vivo; glioma migration and invasion are promoted by activation of EphB2 or inhibited by blocking EphB2. Dysregulation of EphB2 expression or function may underlie glioma invasion.
Antisense Oligonucleotide Inhibition of Apolipoprotein C-III Reduces Plasma Triglycerides in Rodents, Nonhuman Primates, and Humans
Authors: Mark J. Graham, Richard G. Lee, Thomas A. Bell, Wuxia Fu, Adam E. Mullick, Veronica J. Alexander, Walter Singleton, Nick Viney, Richard Geary, John Su, Brenda F. Baker, Jennifer Burkey, Stanley T. Crooke, Rosanne M. Crooke
Journal: Circulation Research (2013)

Rationale: Elevated plasma triglyceride levels have been recognized as a risk factor for the development of coronary heart disease. Apolipoprotein C-III (apoC-III) represents both an independent risk factor and a key regulatory factor of plasma triglyceride concentrations. Furthermore, elevated apoC-III levels have been associated with metabolic syndrome and type 2 diabetes mellitus. To date, no selective apoC-III therapeutic agent has been evaluated in the clinic. Objective: To test the hypothesis that selective inhibition of apoC-III with antisense drugs in preclinical models and in healthy volunteers would reduce plasma apoC-III and triglyceride levels. Methods and Results: Rodent- and human-specific second-generation antisense oligonucleotides were identified and evaluated in preclinical models, including rats, mice, human apoC-III transgenic mice, and nonhuman primates. We demonstrated the selective reduction of both apoC-III and triglyceride in all preclinical pharmacological evaluations. We also showed that inhibition of apoC-III was well tolerated and not associated with increased liver triglyceride deposition or hepatotoxicity. A double-blind, placebo-controlled, phase I clinical study was performed in healthy subjects. Administration of the human apoC-III antisense drug resulted in dose-dependent reductions in plasma apoC-III, concomitant lowering of triglyceride levels, and produced no clinically meaningful signals in the safety evaluations. Conclusions: Antisense inhibition of apoC-III in preclinical models and in a phase I clinical trial with healthy subjects produced potent, selective reductions in plasma apoC-III and triglyceride, 2 known risk factors for cardiovascular disease. This compelling pharmacological profile supports further clinical investigations in hypertriglyceridemic subjects.
Intra-aortic balloon counterpulsation in acute myocardial infarction complicated by cardiogenic shock (IABP-SHOCK II): final 12 month results of a randomised, open-label trial
Authors: Holger Thiele, Uwe Zeymer, Franz-Josef Neumann, Miroslaw Ferenc, Hans-Georg Olbrich, Jörg Hausleiter, Antoinette de Waha, Gert Richardt, Marcus Hennersdorf, Klaus Empen, Georg Fuernau, Steffen Desch, Ingo Eitel, Rainer Hambrecht, Bernward Lauer, Michael Böhm, Henning Ebelt, Steffen Schneider, Karl Werdan, Gerhard Schuler
Journal: The Lancet (2013)
Trends in physical activity and sedentary behaviour in adolescence: ethnic and socioeconomic differences
Authors: Naomi Henning Brodersen, Andrew Steptoe, David R Boniface, Jane Wardle
Journal: British Journal of Sports Medicine (2006)

Objective: To assess developmental trends in physical activity and sedentary behaviour in British adolescents in relation to sex, ethnicity and socioeconomic status (SES). Design: A 5-year longitudinal study of a diverse cohort of students aged 11–12 years at baseline in 1999. Setting: 36 London schools sampled using a stratified random sampling procedure. Participants: A total of 5863 students categorised as white, black or Asian, and stratified for SES using the Townsend Index. Main outcome measures: Number of days per week of vigorous activity leading to sweating and breathing hard. Hours of sedentary behaviour, including watching television and playing video games. Data were analysed using multilevel, linear, mixed models. Results: Marked reductions in physical activity and increases in sedentary behaviour were noticed between ages 11–12 and 15–16 years. Boys were more active than girls, and the decline in physical activity was greater in girls (46% reduction) than in boys (23%). Asian students were less active than whites, and this was also true of black girls but not boys. Black students were more sedentary than white students. Levels of sedentary behaviour were greater in respondents from lower SES. Most differences between ethnic and SES groups were present at age 11 years, and did not evolve over the teenage years. Conclusions: Physical activity declines and sedentary behaviour becomes more common during adolescence. Ethnic and SES differences are observed in physical activity and sedentary behaviour in British youth that anticipate adult variations in adiposity and cardiovascular disease risk. These are largely established by age 11–12 years, so reversing these patterns requires earlier intervention.
Construction of a high-resolution genetic linkage map and comparative genome analysis for the reef-building coral Acropora millepora
Authors: Shi Wang, Lingling Zhang, Eli Meyer, Mikhail V Matz
Journal: Genome biology (2009)

Worldwide, coral reefs are in decline due to a range of anthropogenic disturbances, and are now also under threat from global climate change. Virtually nothing is currently known about the genetic factors that might determine whether corals adapt to the changing climate or continue to decline. Quantitative genetics studies aiming to identify the adaptively important genomic loci will require a high-resolution genetic linkage map. The phylogenetic position of corals also suggests important applications for a coral genetic map in studies of ancestral metazoan genome architecture.We constructed a high-resolution genetic linkage map for the reef-building coral Acropora millepora, the first genetic map reported for any coral, or any non-Bilaterian animal. More than 500 single nucleotide polymorphism (SNP) markers were developed, most of which are transferable in populations from Orpheus Island and Great Keppel Island. The map contains 429 markers (393 gene-based SNPs and 36 microsatellites) distributed in 14 linkage groups, and spans 1,493 cM with an average marker interval of 3.4 cM. Sex differences in recombination were observed in a few linkage groups, which may be caused by haploid selection. Comparison of the coral map with other metazoan genomes (human, nematode, fly, anemone and placozoan) revealed synteny regions.Our study develops a framework that will be essential for future studies of adaptation in coral and it also provides an important resource for future genome sequence assembly and for comparative genomics studies on the evolution of metazoan genome structure.
On the Death of a Child
Authors: C. M. Parkes
Journal: BMJ (1994)

Celia Hindmarch Radcliffe, £ 12.50, pp 133 ISBN 1 870905 19 9

The death of a child is traumatic to medical staff as well as to the families who are bereaved. This is recognised with sympathy and understanding by Celia Hindmarch in her short book of …