tbuckley/cabot-search huggingface dataset:
Sustained Hemodynamic Effects of Intravenous Levosimendan
Authors: Matti Kivikko, Lasse Lehtonen, Wilson S. Colucci
Journal: Circulation (2003)

Background— The short-term infusion of levosimendan (Levo) improves hemodynamic function in patients with decompensated heart failure. The metabolites of Levo have a prolonged half-life, and one is hemodynamically active. The goal of this study was to determine whether the hemodynamic effects of Levo are sustained during a long-term infusion and beyond the discontinuation of drug infusion. Methods and Results— Patients with decompensated heart failure received escalating infusion rates of intravenous Levo (n=98) or placebo (n=48) for 6 hours. At the end of 6 hours, 85 of the Levo-treated patients were continued on open-label drug for a total of 24 hours, at which time they were randomized 1:1 to an additional 24 hours of Levo (n=43) or placebo (n=42).The hemodynamic effects observed at 24 hours were maintained at 48 hours in both the continuation and withdrawal groups and did not differ between groups. Although the plasma concentration of Levo decreased rapidly in the withdrawal group, concentrations of the active metabolite OR-1896 were similar in the continuation and withdrawal groups at 24 hours and increased further (3.5-fold to 4-fold) and to a similar extent in both groups at 48 hours. Conclusions— The hemodynamic effects of Levo were maintained during a 48-hour continuous infusion and for at least 24 hours after discontinuation of a 24-hour infusion. The active metabolite OR-1896 increased for at least 24 hours after cessation of drug infusion and may account for the prolonged hemodynamic effects of Levo.
Lead, Diabetes, Hypertension, and Renal Function: The Normative Aging Study
Authors: Shirng-Wern Tsaih, Susan Korrick, Joel Schwartz, Chitra Amarasiriwardena, Antonio Aro, David Sparrow, Howard Hu
Journal: Environmental Health Perspectives (2004)

In this prospective study, we examined changes in renal function during 6 years of follow-up in relation to baseline lead levels, diabetes, and hypertension among 448 middle-age and elderly men, a subsample of the Normative Aging Study. Lead levels were generally low at baseline, with mean blood lead, patella lead, and tibia lead values of 6.5 microg/dL, 32.4 microg/g, and 21.5 microg/g, respectively. Six percent and 26% of subjects had diabetes and hypertension at baseline, respectively. In multivariate-adjusted regression analyses, longitudinal increases in serum creatinine (SCr) were associated with higher baseline lead levels but these associations were not statistically significant. However, we observed significant interactions of blood lead and tibia lead with diabetes in predicting annual change in SCr. For example, increasing the tibia lead level from the midpoints of the lowest to the highest quartiles (9-34 microg/g) was associated with an increase in the rate of rise in SCr that was 17.6-fold greater in diabetics than in nondiabetics (1.08 mg/dL/10 years vs. 0.062 mg/dL/10 years; p < 0.01). We also observed significant interactions of blood lead and tibia lead with diabetes in relation to baseline SCr levels (tibia lead only) and follow-up SCr levels. A significant interaction of tibia lead with hypertensive status in predicting annual change in SCr was also observed. We conclude that longitudinal decline of renal function among middle-age and elderly individuals appears to depend on both long-term lead stores and circulating lead, with an effect that is most pronounced among diabetics and hypertensives, subjects who likely represent particularly susceptible groups.
Pigmented nodular melanoma: the predictive value of dermoscopic features using multivariate analysis
Authors: M.A. Pizzichetta, H. Kittler, I. Stanganelli, R. Bono, S. Cavicchini, V. De Giorgi, G. Ghigliotti, P. Quaglino, P. Rubegni, G. Argenziano, R. Talamini
Journal: British Journal of Dermatology (2015)

Nodular melanoma (NM), representing 10-30% of all melanomas, plays a major role in global mortality related to melanoma. Nonetheless, the literature on dermoscopy of NM is scanty.To assess odds ratios (ORs) to quantify dermoscopic features of pigmented NM vs. pigmented superficial spreading melanoma (SSM), and pigmented nodular nonmelanocytic and benign melanocytic lesions.To assess the presence or absence of global patterns and dermoscopic criteria, digitized images of 457 pigmented skin lesions from patients with a histopathological diagnosis of NM (n = 75), SSM (n = 93), and nodular nonmelanocytic and benign melanocytic lesions (n = 289; namely, 39 basal cell carcinomas, 85 seborrhoeic keratoses, 81 blue naevi, and 84 compound/dermal naevi) were retrospectively collected and blindly evaluated by three observers.Multivariate analysis showed that ulceration (OR 4.07), homogeneous disorganized pattern (OR 10.76), and homogeneous blue pigmented structureless areas (OR 2.37) were significantly independent prognostic factors for NM vs. SSM. Multivariate analysis of dermoscopic features of NM vs. nonmelanocytic and benign melanocytic lesions showed that the positive correlating features leading to a significantly increased risk of NM were asymmetric pigmentation (OR 6.70), blue-black pigmented areas (OR 7.15), homogeneous disorganized pattern (OR 9.62), a combination of polymorphous vessels and milky-red globules/areas (OR 23.65), and polymorphous vessels combined with homogeneous red areas (OR 33.88).Dermoscopy may be helpful in improving the recognition of pigmented NM by revealing asymmetric pigmentation, blue-black pigmented areas, homogeneous disorganized pattern and abnormal vascular structures, including polymorphous vessels, milky-red globules/areas and homogeneous red areas.
Inhibition of ALK Signaling for Cancer Therapy
Authors: Yael P. Mossé, Andrew Wood, John M. Maris
Journal: Clinical Cancer Research (2009)

Paradigm shifting advances in cancer can occur after discovering the key oncogenic drivers of the malignant process, understanding their detailed molecular mechanisms, and exploiting this transdisciplinary knowledge therapeutically. A variety of human malignancies have anaplastic lymphoma kinase (ALK) translocations, amplifications, or oncogenic mutations, including anaplastic large cell lymphoma, inflammatory myofibroblastic tumors, non-small cell lung cancer, and neuroblastoma. This finding has focused intense interest in inhibiting ALK signaling as an effective molecular therapy against diseases with ALK-driven pathways. Recent progress in the elucidation of the major canonical signaling pathways postulated to be activated by NPM-ALK signaling has provided insight into which pathways may present a rational therapeutic approach. The identification of the downstream effector pathways controlled by ALK should pave the way for the rational design of ALK-inhibition therapies for the treatment of a subset of human cancers that harbor ALK aberrations.
Intensive Chemotherapy for Acute Myelogenous Leukemia
Authors: ROBERT PETER GALE
Journal: Annals of Internal Medicine (1981)

A complete remission rate of 82% was obtained in a group of 68 patients with acute myelogenous leukemia treated with a high-dose induction chemotherapy (TAD) consisting of 7-day courses of 6-thioguanine, cytarabine, and daunorubicin. The patients who achieved remission received intensive consolidation chemotherapy and were randomized to receive maintenance chemotherapy with or without immunotherapy. Median remission duration was 13 months and median survival, 21 months. Neither central nervous system prophylaxis nor the addition of immunotherapy to the maintenance regimen prolonged remissions or improved survival. Age, sex, and subclassification of acute myelogenous leukemia had no effect on the remission rate or survival. These data indicate that a large proportion of patients with acute myelogenous leukemia can achieve remission with intensive induction chemotherapy. Attempts to prolong remission have been less successful.
Spinal Epidural Hematoma during Anticoagulant Therapy
Authors: BERTRAM M. WINER, SIMON HORENSTEIN, ALBERT M. STARR
Journal: Circulation (1959)

Spinal epidural hematoma complicated the course of anticoagulant therapy of cerebrovascular disease in a patient in whom observations of multiple aspects of coagulation had been obtained. Examination of this case and a review of the literature allow delineation of a syndrome that should aid in early diagnosis of spinal epidural hematoma. It is clear that coumarin derivatives induce multiple coagulation defects, which vary quantitatively and qualitatively with time. Contemporary evaluation of the benefits and risks of long-term anticoagulants is beset by many problems that have not been fully resolved.
Renal Gluconeogenesis
Authors: John E. Gerich, Christian Meyer, Hans J. Woerle, Michael Stumvoll
Journal: Diabetes Care (2001)

Studies conducted over the last 60 years in animals and in vitro have provided considerable evidence that the mammalian kidney can make glucose and release it under various conditions. Until quite recently, however, it was generally believed that the human kidney was not an important source of glucose except during acidosis and after prolonged fasting. This review will summarize early work in animals and humans, discuss methodological problems in assessing renal glucose release in vivo, and present results of recent human studies that provide evidence that the kidney may play a significant role in carbohydrate metabolism under both physiological and pathological conditions.
Abstract LB-236: Patient derived xenografts as high-fidelity genomic models for advanced breast cancer.
Authors: Shunqiang Li, Dong Shen, Ding Li, Tao Yu, Jingqin Luo, Jeremy Hoog, Joshua McMichael, Chris Miller, Dave Larson, Ron Bose, Bob Fulton, Rick Wilson, Charles Perou, Elaine Mardis, Matthew Ellis
Journal: Cancer Research (2013)

Abstract A limitation of recent genome studies is that they have almost exclusively focused on early stage untreated samples. Consequently the genomic landscape of advanced and treatment-resistant disease is poorly documented, even though Stage 4 patients stand to benefit most from new therapeutic approaches. To address this issue we developed a panel of patient-derived xenografts (PDX) from Stage 3 and 4 patients with treatment-resistant disease to create a platform for detailed molecular and pharmacological investigation. Recently we reported a whole genome sequencing study of a single example of a breast cancer primary, brain metastasis and PDX “trio” demonstrating that the PDX model efficiently captured almost all of the genome-wide variants observed in the tumor and was enriched for mutations present in the metastatic sample (Ding, Ellis et al., Nature 2010). We now extend these findings by conducting massively parallel sequencing of 13 additional PDX models from a diverse set of locally- advanced or Stage 4 breast cancers, all of whom subsequently died from their disease. Structural variants (deletions, inversions and translocations) were remarkably stable and although new single nucleotide variants were observed post-engraftment, most were either non-coding or not expressed and only one had established functionality (K-RAS). PDX models are therefore high-fidelity genomic models for the biological and pharmacological study of complex, often tumor-unique somatic events responsible for lethal drug-resistant advanced breast cancer. Citation Format: Shunqiang Li, Dong Shen, Ding Li, Tao Yu, Jingqin Luo, Jeremy Hoog, Joshua McMichael, Chris Miller, Dave Larson, Ron Bose, Bob Fulton, Rick Wilson, Charles Perou, Elaine Mardis, Matthew Ellis. Patient derived xenografts as high-fidelity genomic models for advanced breast cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-236. doi:10.1158/1538-7445.AM2013-LB-236
Role of the renin-angiotensin system in the systemic vasoconstriction of chronic congestive heart failure.
Authors: C Curtiss, J N Cohn, T Vrobel, J A Franciosa
Journal: Circulation (1978)

In 15 patients with severe chronic left ventricular failure, plasma renin activity (PRA) ranged widely, from 0.2--39 ng/ml/hr. The level of PRA was unrelated to cardiac output (CO) or pulmonary artery wedge pressure (PWP), but was slightly negatively correlated with mean arterial pressure (MAP) (r = -0.45) and systemic vascular resistance (SVR) (r = -0.40). After infusion of the angiotensin converting enzyme inhibitor teprotide (SQ 20,881) PWP fell from 26.3 +/- 1.3 (SEM) to 20.3 +/- 1.4 mm Hg (P less than 0.001), CO rose from 3.94 +/- 0.23 to 4.75 +/- 0.31 l/min (P less than 0.001), MAP fell from 87.5 +/- 3.8 to 77.9 +/- 4.1 mm Hg (P less than 0.001) and SVR from 1619 +/- 148 to 1252 +/- 137 dyne-sec-cm-5 (P less than 0.001). The fall in MAP and in SVR was significantly correlated with control PRA (r = 0.68 and r = 0.58, respectively). When subjects were divided on the basis of control PRA the hemodynamic response to teprotide was greatest in the high renin group. PRA rose after teprotide (8.7 +/- 3.4 to 37.9 +/- 7.7 ng/ml/hr, P less than 0.05) but plasma norepinephrine fell (619.1 +/- 103.6 to 449.7 +/- 75.7, P less than 0.05). The renin-angiotensin system thus appears to have an important role in the elevated SVR in some patients with heart failure. Chronic inhibition of converting enzyme should be explored as a possible therapeutic approach.
938 GLUCOSYLCERAMIDE INHIBIT IL-6/STAT3 SIGNALING PATHWAY AND LEADS TO AN IMPAIRMENT OF LIVER REGENERATION
Authors: I. Gretchen, R. Sandhoff, M. Gonzalez-Carmona, S. Weber, R. Büttner, F. Lammert, T. Sauerbruch, Y. Yildiz
Journal: Journal of Hepatology (2010)
Abstract 5268: CXCR4 and P-glycoprotein N-glycan patterning in developing cancer cells
Authors: Stan Ivey, Yufei Shan, Tori A. Owens
Journal: Cancer Research (2011)

Abstract Human CXCR4 and P-glycoprotein (Pgp) are N-glycosylated membrane proteins overexpressed in cancer cells. CXCR4 is thought to be an initiator of neuroblastoma metastasis to bone tissue and is overexpressed in neuroblastomas. Pgp is a heavily glycosylated, ATP-dependent drug efflux pump overexpressed in uterine sarcomas. Pgp is responsible for multidrug resistance in some tumors. Our lab is studying the N-glycan profiles of CXCR4 and Pgp in neuroblastoma (IMR-32) and uterine sarcoma cells (MES-SA and MES-SA/Dx5). We believe CXCR4 and Pgp are closely involved in metastasis. To better understand the molecular mechanisms of the metastatic roles of CXCR4 and Pgp, we are characterizing their respective complements of N-glycans. CXCR4 contains a N-linked oligosaccharide on two separate extracellular loops; moreover, Pgp has 3 N-glycans present on a 9 amino acid stretch near its N-terminus. We believe both protein N-glycan moieties are differentially glycosylated enough to act as markers for identifying and staging cancer cells. Our previous studies have shown that Pgp overexpressed in MES-SA/Dx5 cells contains at least two different complex N-glycans; a high mannose tree and a hybrid, sialic acid-capped oligosaccharide. To build on our previous studies, we have developed a novel approach to further characterize CXCR4 and Pgp N-glycans using polyclonal antibodies (pAbs) raised to the specific amino acid sequences containing the sugars in both cancer proteins. We are using these inimitable pAbs to aid in the isolation, sequencing, and profiling of specific N-glycan changes that are associated with the stage of each of the cancer cell lines mentioned above. Our pAb panels bind the native, expressed glycoforms of CXCR4 and Pgp in cells and on Western blots. We are using pAb affinity columns to capture protease-released glycopeptides. Once captured, we intend to sequence each of the released glycopeptides’ oligosaccharides to verify their saccharide sequences in the different cancer cell stages. Furthermore, we predict that the resultant glycopeptide gel and blot patterns will ‘bar code’ the specific cancer stage of the cells lines studied. We envision that these glycopeptide patterns can be used to identify and catalog the various stages of developing cancer cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5268. doi:10.1158/1538-7445.AM2011-5268
Intracellular cystine loading inhibits transport in the rabbit proximal convoluted tubule.
Authors: R F Salmon, M Baum
Journal: Journal of Clinical Investigation (1990)

Cystinosis is an autosomal recessive disorder characterized by a high intracellular cystine concentration. To establish an in vitro model of this disorder and examine the mechanism of the proximal tubule transport defect seen with elevated intracellular cystine concentrations, rabbit proximal convoluted tubules (PCT) were perfused in vitro. PCTs were loaded with cystine using cystine dimethyl ester, a permeative methyl ester derivative. Bath cystine dimethyl ester (0.5 mM) reduced volume absorption (Jv) (0.67 +/- 0.07 to 0.15 +/- 0.09 nl/mm.min, P less than 0.01), bicarbonate transport (JTCO2) (47.2 +/- 4.9 to 11.1 +/- 2.8 pmol/mm.min, P less than 0.001) and glucose transport (JGLU) (34.1 +/- 1.5 to 19.7 +/- 1.5 pmol/mm.min, P less than 0.001). The methyl esters of leucine (0.5 mM), and tryptophan (0.5 and 2.0 mM) had no effect on these parameters. To examine if intracellular reduction of cystine to cysteine could contribute to the inhibition in transport, the effect of bath cysteine methyl ester on proximal tubular transport was examined. Bath cysteine methyl ester (2 but not 0.5 mM) resulted in an inhibition in Jv, JGLU, and JTCO2. Cystine dimethyl ester had no effect on mannitol or bicarbonate permeability. These data are consistent with intracellular proximal tubular cystine accumulation resulting in an inhibition of active transport.
Participation of HIV-Infected Patients in Autologous Blood Programs
Authors: Paul D. Mintz
Journal: JAMA (1993)

CONSIDER two patients scheduled for elective surgery at the same time in adjacent operating rooms served by the same blood storage refrigerator. Two units of blood have been collected recently from each patient for autologous transfusion. One of the patients is known to be infected with human immunodeficiency virus type 1 (HIV-1). The patient who is not infected with HIV-1 does not want blood from the infected patient on the operating room refrigerator shelf next to his uninfected blood while both patients undergo surgery, during which a single oversight could result in transfusion of the wrong blood. The patient who is infected wants to receive autologous blood and not risk exposure to other transfusion-transmitted viruses that could pose a particular threat to him. He wants the identical care as the patient in the next room. How should the conflict created by these competing interests be resolved? Physicians responsible for blood
Feasible HCV targets in Egypt – Authors' reply
Authors: Romulus Breban, Arnaud Fontanet
Journal: The Lancet Global Health (2014)

www.thelancet.com/lancetgh Vol 2 December 2014 e688 maintained their injection practices for 8–10 years. Hence, evidence from field investigations supports our assumptions about frequent injectors. We did not validate our assumptions for the general population. Conceivably, individuals change their frequencies of undergoing medical procedures on the basis of age. However, these changes are not likely to substantially aff ect the frequency of HCV transmission, unless individuals are frequent injectors. In conclusion, exclusion of age structure is not a major limitation of our modelling work. Interventions that target the top 2–5% of frequent injectors seems like a feasible approach, would be much more effective at reducing R0 than would untargeted interventions, and would not depend on substantial increases in logistical and financial resources beyond those already deployed for the existing national strategy.
Hematology for Practitioners
Authors: Marvin Lewis
Journal: JAMA (1979)

Hematology for Practitioners , edited by Marshall Lichtman, was written to help primary physicians evaluate hematologic signs. It is not written for the hematologist, medical student, or physician seeking a description of a hematologic disease process or the latest information on therapy. By starting with common laboratory abnormalities such as anemia, hyperglobulinemia, splenomegaly, or neutropenia, specific outlines for evaluation with a few well-selected tests are described in detail. The book is well written and has adequate illustrations and flowcharts. The book is an outgrowth of a course offered by the faculty of the University of Rochester in 1976. Almost all references seem to be prior to that year.  The chapters on surgical management, radiotherapeutic considerations, and psychological issues are not written in sufficient depth and seem out of context for this book. Chapters on cytogenetics and genetic considerations are well written but do not seem to fit into the goal of
QCM-D studies of attachment and differential spreading of pre-osteoblastic cells on Ta and Cr surfaces
Authors: Charlotte Modin, Anne-Louise Stranne, Morten Foss, Mogens Duch, Jeannette Justesen, Jacques Chevallier, Lars K. Andersen, Anne G. Hemmersam, Finn S. Pedersen, Flemming Besenbacher
Journal: Biomaterials (2005)