Auxiliary liver transplantation in jaundiced rats with UDP-glucuronyltransferase deficiency and defective hepatobiliary transport

In this study auxiliary liver transplantation (ALT) has been tested as a means of correcting the UDP-glucuronyltransferase deficiency in Gunn rats and the UDP-glucuronyltransferase deficiency and impaired hepatobiliary bilirubin transport in double mutant rats. In both groups serum bilirubin normalized and remained low until the end of the study at 12 weeks after transplantation in 4 out of 6 rats. Excretion of 99mTc-HIDA in non-transplanted double mutants was considerably slower than in Gunn rats (kel 0.9 x 10(-3) versus 4.3 x 10(-3) s-1). HIDA excretion by transplants in double mutants and Gunn rats was about equal (kel 1.6 x 10(-3) and 1.1 x 10(-3) s-1). Experiments with bile duct-cannulated transplants showed that in double mutants bile flow, bile acid and bilirubin excretion was 2-4 times higher than in Gunn rats. This study shows that auxiliary liver transplants can conjugate and excrete bilirubin when one of these or both functions are lacking in the recipient's liver.     

Leukocyte depletion of random single-donor platelet transfusions does not prevent secondary human leukocyte antigen-alloimmunization and refractoriness: a randomized prospective study

We studied the value of leukocyte depletion of platelet transfusions for the prevention of secondary human leukocyte antigen (HLA)- alloimmunization in patients with a high-risk of prior immunization induced by pregnancies. Seventy-five female patients with hematologic malignancies (mostly acute leukemia) and a history of pregnancy were randomized to receive either standard random single-donor platelet transfusions (mean leukocytes, 430 x 10(6) per transfusion) or leukocyte-depleted random single-donor platelet transfusions. Leukocyte depletion to less than 5 x 10(6) leukocytes per platelet transfusion (mean leukocytes, 2 x 10(6) per transfusion) was achieved by filtration. Of the 62 evaluable patients, refractoriness to random donor platelets occurred in 41% (14 of 34) of the patients in the standard group and in 29% (8 of 28) of the patients in the filtered group (P = .52); anti-HLA antibodies developed in 43% (9 of 21) of individuals in the standard group and 44% (11 of 25) of cases in the filtered group. The time toward refractoriness and development of anti- HLA antibodies was similar for both groups. We conclude that leukocyte depletion of random single-donor platelet products to less than 5 x 10(6) per transfusion does not reduce the incidence of refractoriness to random donor platelet transfusion because of boostering of anti-HLA antibodies.     

Radiolabelled interleukin-1 receptor antagonist for detection of synovitis in patients with rheumatoid arthritis

OBJECTIVES: To investigate the distribution of radiolabelled interleukin-1 receptor antagonist (IL-1ra) in patients with rheumatoid arthritis (RA) and to assess whether this cytokine is suitable for scintigraphic visualization of synovitis. METHODS: In patients with active RA, scintigraphy was performed after a single i. v. dose of [(123)I]IL-1ra. Clearance and organ distribution of radiolabelled IL-1ra were studied. To assess whether radiolabelled IL-1ra targets the synovial IL-1 receptors, the scintigraphic images obtained with IL-1ra were compared with those obtained by the use of a non-specific control agent. In addition, autoradiography was performed in mice with antigen-induced arthritis that were injected with either radiolabelled IL-1ra or a size-matched, non-receptor-binding protein. RESULTS: Radiolabelled IL-1ra allowed clear visualization of inflamed joints. Specificity in the detection of synovitis was high, whereas a number of painful and swollen joints were not visualized by scintigraphy. The procedure was well tolerated and [(123)I]IL-1ra was rapidly cleared from the circulation (t(1/2)alpha 11 min, t(1/2)beta 612 min) and excreted mainly in the urine. The definition of synovial contours by IL-1ra scintigraphy was not better than that observed with a non-specific agent. Although radiolabelled IL-1ra retained its affinity for IL-1 receptors, no binding to synovium was observed by autoradiography. CONCLUSIONS: Radiolabelled IL-1ra allows the visualization of synovitis in patients with RA. However, neither the imaging nor the autoradiographic studies indicate that joint accumulation of radiolabelled IL-1ra is due to specific IL-1 receptor targeting. IL-1ra has proved its therapeutic value in RA, but with the dose schedule in this study it does not behave as a specific radiopharmaceutical that is suitable for scintigraphic detection of inflammation.     

Occurrence of allogeneic HLA and non-HLA antibodies after transfusion of prestorage filtered platelets and red blood cells: a prospective study [see comments]

The incidence and consequences of HLA and non-HLA immunization were evaluated in 229 patients with aplastic thrombocytopenia. All patients were transfused with prestorage filtered red blood cells and platelets. On admission, 29 patients presented with HLA antibodies due to prior immunization by pregnancy and/or blood transfusions. Of the 200 patients showing no detectable HLA antibodies on admission, 164 could be evaluated. HLA antibodies developed in 2.7% (3 of 112) of the patients with a negative risk history of prior immunization. The occurrence of HLA antibodies in patients with a history of previous pregnancies or prior non-leukocyte-depleted blood transfusions (risk history positive) was 31% (16 of 52). Of the total of 48 patients who were or became alloimmunized, 92% (44 of 48) had a positive risk history. Ten patients with broad multispecific HLA antibodies with a panel reactivity (PRA) of greater than 70% required transfusions with HLA-matched platelets. Patients with HLA antibodies with lower PRA could be supported by random donor platelets. Two patients developed platelet-specific antibodies, causing transfusion refractoriness that necessitated selecting platelets by the absence of a platelet-specific antigen. Using prestorage leukocyte depletion of red cells and platelets with less than 5 x 10(6) residual leukocytes, 95% of the patients, including patients with a previous risk history or with HLA antibodies with low PRA, can be supported with random donor transfusions for the entire duration of their thrombocytopenic periods.     

Software package for integrated data processing for internal dose assessment in nuclear medicine (SPRIND)

Purpose Internal radiation dose calculations are normally carried out using the Medical Internal Radiation Dose (MIRD) schema. This requires residence times of radiopharmaceutical activity and S-values for all organs of interest. Residence times can be obtained by quantitative nuclear imaging modalities. For dealing with S-values, the freeware packages MIRDOSE and, more recently, OLINDA/EXM are available. However, these software packages do not calculate residence times from image data. Methods and results For this purpose, we developed an IDL-based software package for integrated data processing for internal dose assessment in nuclear medicine (SPRIND). SPRIND allows reading and viewing of planar whole-body scintigrams. Organ and background regions of interest (ROIs) can be drawn and are automatically mirrored from the anterior to the posterior view. ROI statistics are used to obtain anterior-posterior averaged counts for each organ, corrected for background activity and attenuation. Residence times for each organ are calculated based on effective decay. The total body biological half-time is calculated for use in the voiding bladder model. Red bone marrow absorbed dose can be calculated using bone regions in the scintigrams or by a blood-derived method. Finally, the results are written to a file in MIRDOSE-OLINDA/EXM format. Using scintigrams in DICOM, the complete analysis is gamma camera vendor independent, and can be performed on any computer using an IDL virtual machine. Conclusion SPRIND is an easy-to-use software package for radiation dose assessment studies. It has made these studies less time consuming and less error prone.     

Characterization of human skeletal stem and bone cell populations using dielectrophoresis

Dielectrophoresis (DEP) is a non‐invasive cell analysis method that uses differences in electrical properties between particles and surrounding medium to determine a unique set of cellular properties that can be used as a basis for cell separation. Cell‐based therapies using skeletal stem cells are currently one of the most promising areas for treating a variety of skeletal and muscular disorders. However, identifying and sorting these cells remains a challenge in the absence of unique skeletal stem cell markers. DEP provides an ideal method for identifying subsets of cells without the need for markers by using their dielectric properties. This study used a 3D dielectrophoretic well chip device to determine the dielectric characteristics of two osteosarcoma cell lines (MG‐63 and SAOS‐2) and an immunoselected enriched skeletal stem cell fraction (STRO‐1 positive cell) of human bone marrow. Skeletal cells were exposed to a series of different frequencies to induce dielectrophoretic cell movement, and a model was developed to generate the membrane and cytoplasmic properties of the cell populations. Differences were observed in the dielectric properties of MG‐63, SAOS‐2 and STRO‐1 enriched skeletal populations, which could potentially be used to sort cells in mixed populations. This study provide evidence of the ability to characterize different human skeletal stem and mature cell populations, and acts as a proof‐of‐concept that dielectrophoresis can be exploited to detect, isolate and separate skeletal cell populations from heterogeneous bone marrow cell populations. Copyright © 2012 John Wiley & Sons, Ltd.     

阻塞性睡眠呼吸暂停低通气综合征患者的内皮细胞凋亡与内皮功能异常有关

背景与目的：阻塞性睡眠呼吸暂停低通气综合征（OSAHS）患者罹患心血管疾病的危险性增加。内皮细胞损伤被认为是动脉硬化的始动机制之一。本研究观察了OSAHS患者循环中凋亡的内皮细胞与血管收缩功能异常的关系。方法：研究对象包括14例确诊OSAHS患者和10例健康对照。在基线以及持续气道内正压（CPAP）治疗8周后测定臂动脉血流介导扩张（反映内皮依赖臂动脉扩张的指标）。采用流式细胞术测量循环中凋亡的内皮细胞。结果：