tbuckley/cabot-search huggingface dataset:
High Levels of Foot Ulceration and Amputation Risk in a Multiracial Cohort of Diabetic Patients on Dialysis Therapy
Authors: Agbor Ndip, Lawrence A. Lavery, Javier LaFontaine, Martin K. Rutter, Anand Vardhan, Loretta Vileikyte, Andrew J.M. Boulton
Journal: Diabetes Care (2010)

OBJECTIVE To evaluate the prevalence of lower-limb complications in a multiracial cohort of patients with diabetes receiving dialysis. RESEARCH DESIGN AND METHODS This work was a cross-sectional study of lower-limb complications in dialysis-treated patients with diabetes in the U.K. and U.S. RESULTS We studied 466 patients (139 U.K.; 327 U.S.). The prevalence of lower-limb complications was high (foot ulcers 12%, neuropathy 79%, peripheral arterial disease 57%, history of foot ulceration 34%, and prior amputation 18%), with no significant ethnic variation, except that foot ulcers were more common in whites than in patients of African descent (P = 0.013). Ninety-five percent of patients were at high risk of lower-limb complications. Prior amputation was related to foot ulcer history, peripheral arterial disease, and hemodialysis modality in multivariable analysis. Prevalent ulceration showed independent associations with foot ulcer history and peripheral arterial disease, but not with ethnicity. CONCLUSIONS All patients with diabetes receiving dialysis are at high risk of lower-limb complications independent of ethnic background.
Lysophosphatidic Acid Stimulates Ovarian Cancer Cell Migration via a Ras-MEK Kinase 1 Pathway
Authors: Dafang Bian, Shibing Su, Chitladda Mahanivong, Robert K. Cheng, Qiwei Han, Zhixing K. Pan, Peiqing Sun, Shuang Huang
Journal: Cancer Research (2004)

Abstract Lysophosphatidic acid (LPA) is present at high concentrations in ascites and plasma of ovarian cancer patients. Studies conducted in experimental models demonstrate that LPA promotes ovarian cancer invasion/metastasis by up-regulating protease expression, elevating protease activity, and enhancing angiogenic factor expression. In this study, we investigated the effect of LPA on ovarian cancer migration, an essential component of cancer cell invasion. LPA stimulates both chemotaxis and chemokinesis of ovarian cancer cells and LPA-stimulated cell migration is GI dependent. Moreover, constitutively active H-Ras enhances ovarian cancer cell migration, whereas dominant negative H-Ras blocks LPA-stimulated cell migration, suggesting that Ras works downstream of Gi to mediate LPA-stimulated cell migration. Interestingly, H-Ras mutants that specifically activate Raf-1, Ral-GDS, or phosphatidylinositol 3′-kinase are unable to significantly enhance ovarian cancer cell migration, suggesting that a Ras downstream effector distinct from Raf-1, Ral-GDS, and phosphatidylinositol 3′-kinase is responsible for LPA-stimulated cell migration. In this article, we demonstrate that LPA activates mitogen-activated protein kinase kinase 1 (MEKK1) in a Gi-Ras-dependent manner and that MEKK1 activity is essential for LPA-stimulated ovarian cancer cell migration. Inhibitors that block MEKK1 downstream pathways, including MEK1/2, MKK4/7, and nuclear factor-κB pathways, do not significantly alter LPA-stimulated cell migration. Instead, LPA induces the redistribution of focal adhesion kinase to focal contact regions of the cytoplasm membrane, and this event is abolished by pertussis toxin, dominant negative H-Ras, or dominant negative MEKK1. Our studies thus suggest that the Gi-Ras-MEKK1 signaling pathway mediates LPA-stimulated ovarian cancer cell migration by facilitating focal adhesion kinase redistribution to focal contacts.
Arterial Stiffness, Wave Reflections, and the Risk of Coronary Artery Disease
Authors: Thomas Weber, Johann Auer, Michael F. O’Rourke, Erich Kvas, Elisabeth Lassnig, Robert Berent, Bernd Eber
Journal: Circulation (2003)

Increased arterial stiffness, determined invasively, has been shown to predict a higher risk of coronary atherosclerosis. However, invasive techniques are of limited value for screening and risk stratification in larger patient groups.We prospectively enrolled 465 consecutive, symptomatic men undergoing coronary angiography for the assessment of suspected coronary artery disease. Arterial stiffness and wave reflections were quantified noninvasively using applanation tonometry of the radial artery with a validated transfer function to generate the corresponding ascending aortic pressure waveform. Augmented pressure (AP) was defined as the difference between the second and the first systolic peak, and augmentation index (AIx) was AP expressed as a percentage of the pulse pressure. In univariate analysis, a higher AIx was associated with an increased risk for coronary artery disease (OR, 4.06 for the difference between the first and the fourth quartile [1.72 to 9.57; P<0.01]). In multivariate analysis, after controlling for age, height, presence of hypertension, HDL cholesterol, and medications, the association with coronary artery disease risk remained significant (OR, 6.91; P<0.05). The results were exclusively driven by an increase in risk with premature vessel stiffening in the younger patient group (up to 60 years of age), with an unadjusted OR between AIx quartiles I and IV of 8.25 (P<0.01) and a multiple-adjusted OR between these quartiles of 16.81 (P<0.05).AIx and AP, noninvasively determined manifestations of arterial stiffening and increased wave reflections, are strong, independent risk markers for premature coronary artery disease.
Neuroanatomic Alterations and Social and Communication Deficits in Monozygotic Twins Discordant for Autism Disorder
Authors: Shanti R. Mitchell, Allan L. Reiss, Danielle H. Tatusko, Ichiro Ikuta, Dana B. Kazmerski, Jo-Anna C. Botti, Courtney P. Burnette, Wendy R. Kates
Journal: American Journal of Psychiatry (2009)

Objective: Investigating neuroanatomic differences in monozygotic twins who are discordant for autism can help unravel the relative contributions of genetics and environment to this pervasive developmental disorder. The authors used magnetic resonance imaging (MRI) to investigate several brain regions of interest in monozygotic twins who varied in degree of phenotypic discordance for narrowly defined autism. Method: The subjects were 14 pairs of monozygotic twins between the ages of 5 and 14 years old and 14 singleton age- and gender-matched typically developing comparison subjects. The monozygotic twin group was a cohort of children with narrowly defined autistic deficits and their co-twins who presented with varying levels of autistic deficits. High-resolution MRIs were acquired and volumetric/area measurements obtained for the frontal lobe, amygdala, and hippocampus and subregions of the prefrontal cortex, corpus callosum, and cerebellar vermis. Results: No neurovolumetric/area differences were found between twin pairs. Relative to typically developing comparison subjects, dorsolateral prefrontal cortex volumes and anterior areas of the corpus callosum were significantly altered in autistic twins, and volumes of the posterior vermis were altered in both autistic twins and co-twins. Intraclass correlation analysis of brain volumes between children with autism and their co-twins indicated that the degree of within-pair neuroanatomic concordance varied with brain region. In the group of subjects with narrowly defined autism only, dorsolateral prefrontal cortex, amygdala, and posterior vermis volumes were significantly associated with the severity of autism based on scores from the Autism Diagnostic Observation Schedule—Generic. Conclusions: These findings support previous research demonstrating alterations in the prefrontal cortex, corpus callosum, and posterior vermis in children with autism and further suggest that alterations are associated with the severity of the autism phenotype. Continued research involving twins who are concordant and discordant for autism is essential to disentangle the genetic and environmental contributions to autism.
Encoding of Oscillations by Axonal Bursts in Inferior Olive Neurons
Authors: Alexandre Mathy, Sara S.N. Ho, Jenny T. Davie, Ian C. Duguid, Beverley A. Clark, Michael Häusser
Journal: Neuron (2009)

Inferior olive neurons regulate plasticity and timing in the cerebellar cortex via the climbing fiber pathway, but direct characterization of the output of this nucleus has remained elusive. We show that single somatic action potentials in olivary neurons are translated into a burst of axonal spikes. The number of spikes in the burst depends on the phase of subthreshold oscillations and, therefore, encodes the state of the olivary network. These bursts can be successfully transmitted to the cerebellar cortex in vivo, having a significant impact on Purkinje cells. They enhance dendritic spikes, modulate the complex spike pattern, and promote short-term and long-term plasticity at parallel fiber synapses in a manner dependent on the number of spikes in the burst. Our results challenge the view that the climbing fiber conveys an all-or-none signal to the cerebellar cortex and help to link learning and timing theories of olivocerebellar function.
Institutional facilities in national health research systems in sub-Saharan African countries: results of a questionnaire-based survey
Authors: Derege Kebede, Chris Zielinski, Peter Ebongue Mbondji, Issa Sanou, Wenceslas Kouvividila, Paul-Samson Lusamba-Dikassa
Journal: Journal of the Royal Society of Medicine (2014)

To describe the current status of institutional facilities and the supporting research infrastructure of surveyed health research institutions in Africa, including information on communication technologies and connectivity, library resources, and laboratory operations and resources.A structured questionnaire was used to solicit information on institutional facilities at health research institutions.Health research institutions in 42 sub-Saharan African countries.Key informants from 847 health research institutions.The availability of laboratory, information and communication, and library facilities in health research institutions.Less than half of the respondent health research institutions had computer laboratories (49%), network computers (50%) and information technology support (38%). More than two-thirds (67%) had a library. Electronic subscriptions to international journals were observed to be very low, with an average of three subscriptions per institution. Almost two-thirds of the surveyed institutions (69%) reported having laboratories, about half of which (55%) were accredited nationally. Linkages and research collaborations were generally weak, particularly those with other laboratories in the Region. Challenges included financial and human resource constraints and the inability to communicate effectively with partners.Health research institutions in the Region have insufficient access to essential facilities such as laboratories, libraries, computers and the Internet to generate, access and share information.
Anaerobic Metabolism of Heart
Authors: Walter F. Ballinger, Heinz Vollenweider
Journal: Circulation Research (1962)

Calculation of excess lactate removal and production, together with the arteriovenous difference of oxygen and carbon dioxide content of the coronary circulation, was performed during normal ventilation, induced hypoxia, and apnea in dogs. During ventilation with 100 per cent oxygen or room air, excess lactate was removed by the canine heart and continued to be removed until the arterial oxygen content fell to an average level of 9 ml./100 ml. of arterial blood. Below this level, excess lactate was produced by the heart, indicating a shift to anaerobic metabolism. The heart continued to work anaerobically, and its efficiency was increased since little, if any, oxygen was utilized. During severe hypoxia, the oxygen equivalent of the excess lactate produced was equal to the carbon dioxide produced. The heart, still performing work, was functioning completely anaerobically.
Neurodevelopmental Outcomes of Preterm Infants Fed High-Dose Docosahexaenoic Acid
Authors: Maria Makrides, Robert A. Gibson, Andrew J. McPhee, Carmel T. Collins, Peter G. Davis, Lex W. Doyle, Karen Simmer, Paul B. Colditz, Scott Morris, Lisa G. Smithers, Kristyn Willson, Philip Ryan
Journal: JAMA (2009)

Uncertainty exists about the benefit of dietary docosahexaenoic acid (DHA) on the neurodevelopment of preterm infants.To determine the effect of meeting the estimated DHA requirement of preterm infants on neurodevelopment at 18 months' corrected age.Randomized, double-blind controlled trial enrolling infants born at less than 33 weeks' gestation from April 2001 to October 2005 at 5 Australian tertiary hospitals, with follow-up to 18 months.High-DHA (approximately 1% total fatty acids) enteral feeds compared with standard DHA (approximately 0.3% total fatty acids) from day 2 to 4 of life until term corrected age.Bayley Mental Development Index (MDI) at 18 months' corrected age. A priori subgroup analyses were conducted based on randomization strata (sex and birth weight < 1250 g vs > or = 1250 g).Of the 657 infants enrolled, 93.5% completed the 18-month follow-up. Bayley MDI scores did not differ between the high- and standard-DHA groups (mean difference, 1.9; 95% confidence interval [CI], -1.0 to 4.7). The MDI among girls fed the high-DHA diet was higher than girls fed standard DHA in unadjusted and adjusted analyses (unadjusted mean difference, 4.7; 95% CI, 0.5-8.8; adjusted mean difference, 4.5; 95% CI, 0.5-8.5). The MDI among boys did not differ between groups. For infants born weighing less than 1250 g, the MDI in the high-DHA group was higher than with standard DHA in the unadjusted comparison (mean difference, 4.7; 95% CI, 0.2-9.2) but did not reach statistical significance following adjustment for gestational age, sex, maternal education, and birth order (mean difference, 3.8; 95% CI, -0.5 to 8.0). The MDI among infants born weighing at least 1250 g did not differ between groups.A DHA dose of approximately 1% total fatty acids in early life did not increase MDI scores of preterm infants overall born earlier than 33 weeks but did improve the MDI scores of girls.anzctr.org.au Identifier: ACTRN12606000327583.
Mass isolation and culture of rat kupffer cells.
Authors: A C Munthe-Kaas, T Berg, P O Seglen, R Seljelid
Journal: The Journal of Experimental Medicine (1975)

Collagenase perfusion of the liver followed by pronase treatment of the cell suspension thus obtained gave a quantitative recovery of viable nonparenchymal liver cells (NPC). From these NPC, Kupffer (K) cells can be purified by attachment to tissue culture dishes. Tail vein injection of carbon 1-2 h before liver perfusion permitted stepwise calculation as well as visualization of carbon-containing K cells. When these K cells have been put into tissue culture medium with serum and incubated overnight, they exhibit typical macrophage characteristics. Phase-contrast and transmission electron microscopy showed typical macrophage morphology and scanning electron microscopy revealed well-spread cells with cytoplasmic projections and ruffled membranes. Endocytosis studies using radioactive colloidal gold and inert latex particles also indicated that these cells are highly active in pinocytosis and phagocytosis. Further characterization of K cells is the identification of Fc receptor on their membranes. Studies on lysosomal enzymes showed that purified K cells possess higher specific activities in beta-glucuronidase, acid DNase, and cathepsin D than in purified parenchymal cells.
Clinical Effects of β-Adrenergic Blockade in Chronic Heart Failure
Authors: Philippe Lechat, Milton Packer, Stephan Chalon, Michel Cucherat, Tarek Arab, Jean-Pierre Boissel
Journal: Circulation (1998)

Background —β-Blockers have improved symptoms and reduced the risk of cardiovascular events in studies of patients with heart failure, but it is unclear which end points are most sensitive to the therapeutic effects of these drugs. Methods and Results —We combined the results of all 18 published double-blind, placebo-controlled, parallel-group trials of β-blockers in heart failure. From this combined database of 3023 patients, we evaluated the strength of evidence supporting an effect of treatment on left ventricular ejection fraction, NYHA functional class, hospitalizations for heart failure, and death. β-Blockers exerted their most persuasive effects on ejection fraction and on the combined risk of death and hospitalization for heart failure. β-Blockade increased the ejection fraction by 29% ( P &lt;10 −9 ) and reduced the combined risk of death or hospitalization for heart failure by 37% ( P &lt;0.001). Both effects remained significant even if &gt;90% of the trials were eliminated from the analysis or if a large number of trials with a neutral result were added to the analysis. In contrast, the effect of β-blockade on NYHA functional class was of borderline significance ( P =0.04) and disappeared with the addition or removal of only 1 moderate-size study. Although β-blockade reduced all-cause mortality by 32% ( P =0.003), this effect was only moderately robust and varied according to the type of β-blocker tested, ie, the reduction of mortality risk was greater for nonselective β-blockers than for β 1 -selective agents (49% versus 18%, P =0.049). However, selective and nonselective β-blockers did not differ in their effects on other measures of clinical efficacy. Conclusions —These analyses indicate that there is persuasive evidence supporting a favorable effect of β-blockade on ejection fraction and the combined risk of death and hospitalization for heart failure. In contrast, the effect of these drugs on other end points requires additional study.
Challenges for the functional diffusion map in pediatric brain tumors
Authors: M. Grech-Sollars, D. E. Saunders, K. P. Phipps, R. Kaur, S. M. L. Paine, T. S. Jacques, J. D. Clayden, C. A. Clark
Journal: Neuro-Oncology (2013)

The functional diffusion map (fDM) has been suggested as a tool for early detection of tumor treatment efficacy. We aim to study 3 factors that could act as potential confounders in the fDM: areas of necrosis, tumor grade, and change in tumor size. Thirty-four pediatric patients with brain tumors were enrolled in a retrospective study, approved by the local ethics committee, to examine the fDM. Tumors were selected to encompass a range of types and grades. A qualitative analysis was carried out to compare how fDM findings may be affected by each of the 3 confounders by comparing fDM findings to clinical image reports. Results show that the fDM in areas of necrosis do not discriminate between treatment response and tumor progression. Furthermore, tumor grade alters the behavior of the fDM: a decrease in apparent diffusion coefficient (ADC) is a sign of tumor progression in high-grade tumors and treatment response in low-grade tumors. Our results also suggest using only tumor area overlap between the 2 time points analyzed for the fDM in tumors of varying size. Interpretation of fDM results needs to take into account the underlying biology of both tumor and healthy tissue. Careful interpretation of the results is required with due consideration to areas of necrosis, tumor grade, and change in tumor size.
Permanent alopecia after busulfan chemotherapy
Authors: A. Tosti, B.M. Piraccini, C. Vincenzi, C. Misciali
Journal: British Journal of Dermatology (2005)

Journal Article Permanent alopecia after busulfan chemotherapy Get access A. Tosti, A. Tosti Department of Dermatology, University of Bologna, Via Massarenti 1, 40138 Bologna, Italy Antonella Tosti. E‐mail: tosti@med.unibo.it Search for other works by this author on: Oxford Academic Google Scholar B.M. Piraccini, B.M. Piraccini Department of Dermatology, University of Bologna, Via Massarenti 1, 40138 Bologna, Italy Search for other works by this author on: Oxford Academic Google Scholar C. Vincenzi, C. Vincenzi Department of Dermatology, University of Bologna, Via Massarenti 1, 40138 Bologna, Italy Search for other works by this author on: Oxford Academic Google Scholar C. Misciali C. Misciali Department of Dermatology, University of Bologna, Via Massarenti 1, 40138 Bologna, Italy Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 152, Issue 5, 1 May 2005, Pages 1056–1058, https://doi.org/10.1111/j.1365-2133.2005.06469.x Published: 01 May 2005 Article history Accepted: 23 October 2003 Published: 01 May 2005
Radiofrequency ablation must be assessed by pathological methods
Authors: Juan C. Rodríguez-Sanjuán, Francisco González, Manuel Gómez-Fleitas
Journal: Hepatology (2009)

We read with interest the article by N'Kontchou et al.1 concerning hepatocellular carcinoma treatment by radiofrequency ablation (RFA). They report an excellent series with impressive results in terms of both very low major complication and tract seeding rates as well as a considerable long-term survival. Their complete response rate is 94.7%. However, this was assessed by radiological methods (magnetic resonance imaging and computed tomography) and not by pathological examination. As a result, the true response rate could be lower. Our modest experience with 30 hepatocellular carcinoma nodules treated by RFA before liver transplant was recently published.2 We performed a pathological analysis of the explanted liver and found that only 14 nodules (46.7%) showed complete tumor destruction. In our study, the detection of RFA incomplete response by means of computed tomography scan had a 50% sensitivity and 100% specificity. The reported rates of complete pathological response in other works were variable but lower than those reported by N'Kontchou et al.: 20%,3 34.2%,4 37.5%,5 46.7%,6 55%,7 70.3%,8 and 75%.9 In these studies, as in ours, pathological examination was performed using hematoxylin-eosin stains. Although RFA cannot be considered as a radical or curative treatment, and the ideal situation would be complete tumor destruction, partial destruction is probably enough to increase long-term survival and, especially, to avoid patient drop-out from liver transplant waiting lists. Juan C. Rodríguez-Sanjuán M.D., Ph.D.*, Francisco González M.D.*, Manuel Gómez-Fleitas M.D., Ph.D.*, * Departments of General Surgery and Radiology, University Hospital Marqués de Valdecilla, University of Cantabria, Santander, Spain.