The influence of liver dysfunction on cyclosporine pharmacokinetics -A comparison between 70 per cent hepatectomy and complete bile duct ligation in dogs-

The influence of experimentally induced hepatic dysfunction on the pharmacokinetics of Cyclosporine A (CsA) was determined in dogs. The pharmacokinetics of oral (PO) and intravenous (IV) CsA were studied before and after 70 per cent hepatectomy or complete bile duct ligation (CBDL). Changes in liver function were monitored by serial measurements of serum bilirubin, and by the maximum removal rate (Rmax) and plasma disappearance rate (ICG-K) of indocyanine green (ICG). Concentrations of CsA in whole blood were measured by HPLC. Seventy per cent hepatectomy caused significant liver dysfunction: the ICG-Rmax decreased by 47.7±7.1 per cent (mean±SD) and the ICG-K decreased by 61.3±9.7 per cent during the first week after hepatectomy. At the same time, the systemic clearance (CLs) of IV-CsA decreased by 43.9±8.2 per cent, the area under the concentration curve (AUC) of IV-CsA increased by 35.4±20.8 per cent and the bioavailability of CsA decreased by 26.4±14.8 per cent. CBDL also induced significant liver dysfunction: the ICG-Rmax decreased by 39.1±12.8 per cent and the ICG-K decreased by 65.6±3.6 per cent in the second week after the operation. During the same period, the AUC of PO-CsA decreased by 69.9±10.7 per cent and the bioavailability of CsA also decreased markedly by 73.9±15.6 per cent. These data indicate that hepatic impairment significantly influences the pharmacokinetics of CsA, not only by the changes in intestinal absorption, but also by those in hepatic, metabolism. Dose adjustment is therefore necessary in the presence of hepatic dysfunction in order to maintain an adequate blood concentration of CsA without causing side effects. © 1989 The Japan Surgical Society

Low heat-gain cryogenic-liquid transfer system

Cryogenic-liquid transfer system, containing a ring structure with tensioned small diameter, high strength wires, provides adequate physical support for the piping, minimizes the conductive heat paths between the piping and jacket, and allows for thermal expansion and contraction of the piping

Review of Web Mapping: Eras, Trends and Directions

Web mapping and the use of geospatial information online have evolved rapidly over the past few decades. Almost everyone in the world uses mapping information, whether or not one realizes it. Almost every mobile phone now has location services and every event and object on the earth has a location. The use of this geospatial location data has expanded rapidly, thanks to the development of the Internet. Huge volumes of geospatial data are available and daily being captured online, and are used in web applications and maps for viewing, analysis, modeling and simulation. This paper reviews the developments of web mapping from the first static online map images to the current highly interactive, multi-sourced web mapping services that have been increasingly moved to cloud computing platforms. The whole environment of web mapping captures the integration and interaction between three components found online, namely, geospatial information, people and functionality. In this paper, the trends and interactions among these components are identified and reviewed in relation to the technology developments. The review then concludes by exploring some of the opportunities and directions

Alkylating chemotherapeutic agents cyclophosphamide and melphalan cause functional injury to human bone marrow-derived mesenchymal stem cells

The adverse effects of melphalan and cyclophosphamide on hematopoietic stem cells are well-known; however, the effects on the mesenchymal stem cells (MSCs) residing in the bone marrow are less well characterised. Examining the effects of chemotherapeutic agents on patient MSCs in vivo is difficult due to variability in patients and differences in the drug combinations used, both of which could have implications on MSC function. As drugs are not commonly used as single agents during high-dose chemotherapy (HDC) regimens, there is a lack of data comparing the short- or long-term effects these drugs have on patients post treatment. To help address these problems, the effects of the alkylating chemotherapeutic agents cyclophosphamide and melphalan on human bone marrow MSCs were evaluated in vitro. Within this study, the exposure of MSCs to the chemotherapeutic agents cyclophosphamide or melphalan had strong negative effects on MSC expansion and CD44 expression. In addition, changes were seen in the ability of MSCs to support hematopoietic cell migration and repopulation. These observations therefore highlight potential disadvantages in the use of autologous MSCs in chemotherapeutically pre-treated patients for future therapeutic strategies. Furthermore, this study suggests that if the damage caused by chemotherapeutic agents to marrow MSCs is substantial, it would be logical to use cultured allogeneic MSCs therapeutically to assist or repair the marrow microenvironment after HDC. © 2011 Springer-Verlag

Increasing low-carbon energy in Scottish agriculture through a whole systems approach

The Climate Change Plan update sets out targets to reduce emissions from the agriculture sector. Carbon dioxide emissions associated with stationary combustion sources and off-road machinery use in agriculture contribute significantly to agricultural emissions and have increased between 2020 and 2021. The impact of agriculture’s energy use can be difficult to account for, with emissions being captured within grouped sectors (electricity, gas and other) of the GHG inventory. This report examines the energy use and associated emissions baseline on farms and crofts in Scotland, and explores the potential for efficiency measures and new, low-carbon technologies to support energy emissions reductions in the longer term

Hematopoietic stem cell transplantation in children with acute leukemia: similar outcomes in recipients of umbilical cord blood versus marrow or peripheral blood stem cells from related or unrelated donors

PurposeThis study compared outcomes in children with acute leukemia who underwent transplantations with umbilical cord blood (UCB), bone marrow, or peripheral blood stem cells from a human leukocyte antigen (HLA)-matched related donor (MRD) or an unrelated donor (URD).MethodsThis retrospective study included consecutive acute leukemia patients who underwent their first allogeneic hematopoietic stem cell transplantation (HSCT) at Samsung Medical Center between 2005 and 2010. Patients received stem cells from MRD (n=33), URD (n=46), or UCB (n=41).ResultsNeutrophil and platelet recovery were significantly longer after HSCT with UCB than with MRD or URD (P<0.01 for both). In multivariate analysis using the MRD group as a reference, the URD group had a significantly higher risk of grade III to IV acute graft-versus-host disease (GVHD; relative risk [RR], 15.2; 95% confidence interval [CI], 1.2 to 186.2; P=0.03) and extensive chronic GVHD (RR, 6.9; 95% CI, 1.9 to 25.2; P<0.01). For all 3 donor types, 5-year event-free survival (EFS) and overall survival were similar. Extensive chronic GVHD was associated with fewer relapses (RR, 0.1; 95% CI, 0.04 to 0.6; P<0.01). Multivariate analysis showed that lower EFS was associated with advanced disease at transplantation (RR, 3.2; 95% CI, 1.3 to 7.8; P<0.01) and total body irradiation (RR, 2.1; 95% CI, 1.0 to 4.3; P=0.04).ConclusionSurvival after UCB transplantation was similar to survival after MRD and URD transplantation. For patients lacking an HLA matched donor, the use of UCB is a suitable alternative

Endocrine Complications after Hematopoietic Stem Cell Transplantation during Childhood and Adolescence

Long-term survivors of hematopoietic stem cell transplantation (HSCT) during childhood and adolescence are at risk of developing endocrine complications. The purpose of this study was to evaluate the long-term endocrine complications and their associated risk factors among such patients. We reviewed the data from 111 patients (59 males and 52 females) who underwent HSCT at the mean age of 8.3±4.1 yr. Thirty patients (27.0%) had growth impairment, and seven (21.2%) out of 33 patients who attained final height reached final height below 2 standard deviation (SD). The final height SD score of the patients conditioned with total body irradiation (TBI) was significantly lower than that of the patients conditioned without TBI (-1.18±1.14 vs. -0.19±0.78, P=0.011). Thirteen patients (11.7%) developed hypothyroidism (11 subclinical, 2 central) 3.8±1.8 (range 1.6-6.2) yr after HSCT. Nineteen (65.5%) out of 29 females had evidence of gonadal dysfunction, and 18 (64.3%) out of 28 males had evidence of gonadal dysfunction. The risk for gonadal dysfunction was significantly higher in females conditioned with busulfan/cyclophosphamide (P=0.003). These results suggest that the majority of patients treated with HSCT during childhood and adolescence have one or more endocrine complications. Therefore, multiple endocrine functions should be monitored periodically after HSCT until they reach adult age