Impact of graft preservation solutions for liver transplantation on early cytokine release and postoperative organ dysfunctions. A pilot study.

INTRODUCTION: During liver transplantation, graft ischemia-reperfusion injury leads to a systemic inflammatory response producing postoperative organ dysfunctions. The aim of this observational and prospective study was to compare the impact of Solution de conservation des organes et tissus (SCOT) 15 and University of Wisconsin (UW) preservation solutions on early cytokine release, postreperfusion syndrome and postoperative organ dysfunctions. METHODS: Thirty-seven liver transplantations were included: 21 in UW Group and 16 in SCOT 15 group. Five cytokines were measured in systemic blood after anesthetic induction, 30minutes after unclamping portal vein and on postoperative day 1. RESULTS: Following unclamping portal vein, cytokines were released in systemic circulation. Systemic cytokine concentrations were higher in UW than in SCOT 15 group: Interleukin-10, Interleukine-6. In SCOT 15 group, significant reduction of postreperfusion syndrome incidence and acute kidney injury were observed. Alanine and aspartate aminotransferase peak concentrations were higher in SCOT 15 group than in UW group. However, from postoperative day 1 to day 10, aminotransferase returned to normal values and did not differ between groups. CONCLUSIONS: Compared to UW, SCOT 15 decreases systemic cytokine release resulting from graft ischemia-reperfusion injury and reduces incidence of postreperfusion syndrome and postoperative renal failure.

Future Direction of IMIA Standardization. Report from the IMIA Standardization Working Group.

OBJECTIVES: Standardization in the field of health informatics has increased its importance and global alliance for establishing interoperability and compatibility internationally. Standardization has been organized by standard development organizations (SDOs) such as ISO (International Organization for Standardization), CEN (European Committee for Standardization), IHE (Integrating the Healthcare Enterprise), and HL7 (Health Level 7), etc. This paper reports the status of these SDOs' activities. METHODS: In this workshop, we reviewed the past activities and the current situation of standardization in health care informatics with the standard development organizations such as ISO, CEN, IHE, and HL7. Then we discussed the future direction of standardization in health informatics toward "future medicine" based on standardized technologies. RESULTS: We could share the status of each SDO through exchange of opinions in the workshop. Some WHO members joined our discussion to support this constructive activity. CONCLUSION: At this meeting, the workshop speakers have been appointed as new members of the IMIA working groups of Standards in Health Care Informatics (WG16). We could reach to the conclusion that we collaborate for the international standardization in health informatics toward "future medicine".

Binding of artemether and lumefantrine to plasma proteins and erythrocytes.

The serum/plasma protein binding and blood distribution of artemether and lumefantrine was studied in vitro. The techniques used were the erythrocyte partitioning and ultrafiltration methods with 1499%, respectively. Under physiological protein concentrations, the distribution in blood showed that 33% of artemether was bound to alpha(1)-acid glycoprotein, 17% to albumin, 12% to high density lipoproteins (HDL), 9.3% to low density lipoproteins (LDL) and 12% to very low density lipoproteins (VLDL), with binding capacities (nKa) of 3.2 x 10(5), 6.2 x 10(3), 2.1 x 10(5), 1.7 x 10(6) and 2.0 x 10(7) lmol(-1), respectively. 77% of lumefantrine was bound to HDL, 7.3% to LDL and 6.6% to VLDL, with binding capacities of 2.7 x 10(7), 2. 6 x 10(7) and 2.4 x 10(8) lmol(-1), respectively. A negligible fraction of lumefantrine was bound to albumin and alpha(1)-acid glycoprotein. The fraction in erythrocytes was around 10% for both artemether and lumefantrine.

Binding of iralukast to serum proteins and erythrocytes: measurements using ultrafiltration and an erythrocyte partitioning method.

The binding of iralukast to plasma (or serum) proteins and to erythrocytes was studied in vitro, at +37 degrees C, using the erythrocyte partitioning method (EPM) and/or ultrafiltration (UF) with 14C-labelled iralukast. Iralukast was highly bound in human and animal serum (>99%). Similar bound fraction values were obtained with the two methods: in whole human plasma (or serum) 99.8% (EPM) and 99.9% (UF), in albumin solution 99.8% (EPM and UF), in high density lipoprotein solution 97.3% (EPM) and 98.3% (UF), and in low density lipoprotein solution 97.2% (EPM) and 98.8% (UF). Moreover, the erythrocyte partitioning method allowed the evaluation of other binding parameters. The binding capacity (l/micromol) of proteins equalled 35 for low density lipoproteins, 3.6 for high density lipoproteins, 1.0 for albumin, 0.78 for alpha-1-acid glycoprotein, and 0.03 for gamma globulins. In whole blood, iralukast was distributed between plasma and erythrocytes in the proportion (%) 90/10. At physiological protein concentrations, iralukast was primarily bound to albumin (79%).

Plasma protein binding of letrozole, a new nonsteroidal aromatase enzyme inhibitor.

The protein binding characteristics of the nonsteroidal aromatase inhibitor letrozole were determined using 14C-labeled letrozole. The binding of letrozole in human serum was 60.1 +/- 2.9% as a mean obtained in six individual sera and was similar in human plasma. The binding in human serum remained constant at concentrations of letrozole ranging from 10 to 500 ng/mL. A similar binding value in human serum was obtained using equilibrium dialysis and ultrafiltration technique. Albumin (binding 55.1 +/- 1.4%) is the main protein involved in the drug binding to plasma proteins. Increases in letrozole concentration (10-500 ng/mL) had no effect on binding. Albumin binding appeared to be nonsaturable with a binding capacity of 2 L/mmol. Binding to alpha1-acid glycoprotein and to gamma globulins was lower than 10%. The fraction in erythrocytes with a hematocrit of 0.4 was found to be 35.2 +/- 2.7%. Letrozole binding to serum proteins of rat, dog, mouse, and rabbit was approximately 10% lower than that in human serum and approximately 20% lower than that in baboons. Tamoxifen (100-1,500 ng/mL) had no effect on the in vitro binding of letrozole. Ex vivo binding in plasma from patients after repeated administration of letrozole alone (61.4 +/- 2.6%) was the same as after combined administration of letrozole and tamoxifen (60.0 +/- 3.2%).

Protein binding in plasma of valsartan, a new angiotensin II receptor antagonist.

The protein-binding characteristics of the angiotensin II receptor antagonist valsartan were determined in vitro by equilibrium dialysis, using 14C-labeled valsartan with serum from healthy donors, plasma from patients who had received valsartan, serum or plasma from animals, and purified human plasma proteins. The binding of valsartan was high (96 +/- 2%) in human serum at concentrations ranging from 0.05 micrograms/mL to 5 micrograms/mL. A comparable extent of binding (85-99%) was recorded in plasma from patients after repeated administration of valsartan. Albumin (binding 92%) is the main protein involved in the binding to plasma proteins, while the binding to alpha 1-acid glycoprotein was low (22%) and to gamma globulins, negligible. Although highly bound, valsartan was not displaced in vitro by hydrochlorothiazide, diclofenac, furosemide, and warfarin. A high extent of binding was found in rat, dog, and rabbit serum and in marmoset plasma, while a lower binding was found in mouse serum.

The DICOM standard. A breakthrough for digital information exchange in cardiology.

The DICOM Standard for network communication has been approved by ACR and NEMA in October 1993. The ACC has joined the effort in 1992 and drives the extension of DICOM for Media Interchange with a focus on defining a digital recording standard for communication between catheterisation laboratories. This is a necessary foundation towards cinefilm replacement. DICOM networking is being adopted as a European Standard called MEDICOM and the increasing interest of the ESC is likely to result in the adoption of DICOM Media Storage and interchange as an extension of MEDICOM in 1995. This represents a major breakthrough in the communication of medical images in electronic form. DICOM has been designed to offer an integrated approach to the increasing use of high speed computer networks in health care as well as larger and higher throughput storage media. This article focuses on the network communication as well as introduces the extension of DICOM for Media interchange which has been approved early 1995.

PAPYRUS 3.0: DICOM-compatible file format.

This paper describes the PAPYRUS 3.0 file format based on the new DICOM 3.0 Standard which addresses the open interchange of medical images in files or on removable storage media. This specific implementation of the DICOM standard is intended as a generic solution for interchange of multi-modality medical images on removable media. It can also be used for convenient exchange of image data between different computer systems through industry standard file transfer mechanisms. Finally it can also be used for storage and archiving of medical image data in a DICOM-compatible format.

High performance liquid chromatographic determination of nicotine and cotinine in plasma and nicotine and cotinine, simultaneously, in urine.

Three analytical procedures were developed to determine nicotine in plasma, cotinine in plasma and, simultaneously, nicotine and cotinine in urine. After liquid or solid-phase extraction, the purified aqueous phase is injected into a high performance liquid chromatograph equipped with an ultra-violet detector using a CN Spheri-5 micron cartridge-column with an inner diameter of 4.6 mm and a length of 10 or 22 cm. The limit of quantitation for nicotine in plasma was around 8 to 15 ng/ml, that of cotinine in plasma around 50 ng/ml and that of nicotine and cotinine in urine around 170 ng/ml and 70 ng/ml, respectively. The limit of detection of nicotine in plasma was around 1 ng/ml and that of nicotine and cotinine in urine around 20 ng/ml and 10 ng/ml, respectively. The passive exposure to cigarette smoke by non-smokers and the "resting levels" of nicotine in plasma and urine of smokers were studied. The analytical methods were set up to study the pharmacokinetics and bioavailability of nicotine in healthy volunteers following single and repeated administrations of different doses of transdermal nicotine systems.