勃脉力A注射液对体外循环心脏手术患者肝功能的影响

目的 探讨勃脉力A注射液对体外循环心脏手术患者肝功能的影响.方法 选择术前肝功能正常、无肝炎病史的行体外循环心脏手术患者60名,随机分为勃脉力A组(P组)和林格液组(R组).所有患者均在术前、术后2h、1d、3d、7d分别采肘正中静脉血和挠动脉血:静脉血分离血清后应用自动血生化分析仪检测血清中天冬氨酸转氨酶和丙氨酸氨基转移酶,以了解患者的肝脏功能改变;抽取动脉血查乳酸浓度.术中及术后密切观察患者血压、心率、中心静脉压、尿量等,观察并记录患者拔管及停留ICU时间.结果 与R组相比较,在术后各时间点P组ALT、AST及乳酸浓度均显著降低(P﹤0.05),并且拔除气管导管时间和停留ICU时间均有所缩短.结论 勃脉力A注射液能够显著降低体外循环术中乳酸浓度,并能改善患者肝功能,非常适用于体外循环手术.     

Assessment of myocardial triglyceride oxidation with PET and 11C-palmitate

Background  The goal of this study was to test whether myocardial triglyceride (TG) turnover including oxidation of TG-derived fatty acids (FA) could be assessed with PET and ¹¹C-palmitate. Methods and Results  A total of 26 dogs were studied fasted (FAST), during Intralipid infusion (IL), during a hyperinsulinemic-euglycemic clamp without (HIEG), or with Intralipid infusion (HIEG + IL). ¹¹C-palmitate was injected, and 45 minutes were allowed for labeling of myocardial TG pool. 3D PET data were then acquired for 60 minutes, with first 15 minutes at baseline followed by 45 minutes during cardiac work stimulated with constant infusion of either phenylephrine (FAST, n = 6; IL, n = 6; HIEG + IL, n = 6) or dobutamine (FAST, n = 4; HIEG, n = 4). Myocardial ¹¹C washout during adrenergic stimulation (AS) was fitted to a mono-exponential function (Km(PET)). To determine the source of this ¹¹C clearance, Km(PET) was compared to direct coronary sinus-arterial measurements of total ¹¹C activity, ¹¹C-palmitate, and ¹¹CO₂. Before AS, PET curves in all groups were flat indicating absence of net clearance of ¹¹C activity from heart. In both FAST groups, AS resulted in negligible net ¹¹C activity and ¹¹CO₂ production higher than net ¹¹C-palmitate uptake. AS with phenylephrine resulted in net myocardial uptake of total ¹¹C activity and ¹¹C-palmitate in IL and HIEG + IL, and ¹¹CO₂ production lower than ¹¹C-palmitate uptake. In contrast, AS with dobutamine in HIEG resulted in net clearance of all ¹¹C metabolites (total ¹¹C activity, ¹¹C-palmitate and ¹¹CO₂) with ¹¹CO₂ contributing 66% to endogenous FA oxidation. The AS resulted in significant Km(PET) in all the groups, except HIEG + IL. However, positive correlation between Km(PET) and ¹¹CO₂ was observed only in HIEG (R ² = 0.83, P = .09). Conclusions  This is the first study to demonstrate that using PET and pre-labeling of intracardiac TG pool with ¹¹C-palmitate, noninvasive assessment of myocardial TG use is feasible under metabolic conditions that favor endogenous TG use such as increased metabolic demand (β-adrenergic stimulation of cardiac work) with limited availability of exogenous substrate (HIEG).     

Time-dependent loss of surface complement regulatory activity during storage of donor blood

The survival of transfused red cells (RBCs) diminishes with time of in vitro storage in blood banks, but the molecular mechanisms underlying the slow but incessant deterioration are incompletely understood. To investigate the possibility that impaired resistance to autologous complement attack could play a role in this phenomenon, packed RBCs stored for variable periods were assayed for decay-accelerating factor (DAF) and CD59, two glycoinositol-phospholipid (GPI)-anchored, membrane- associated complement regulatory proteins that function physiologically to protect blood cells from autologous complement activation on their surfaces. Immunoradiometric and flow cytometric assays employing DAF and CD59 monoclonal antibodies showed that levels of both surface proteins gradually declined over 6 weeks. Digestion analyses with phosphatidylinositol-specific phospholipase C, an enzyme that releases GPI-anchored proteins from cell surfaces, showed that DAF and CD59 molecules with GPI anchors containing unacylated inositol were preferentially lost. These findings suggest: 1) that DAF and CD59 molecules with acylated GPI anchors are more stable in RBC membranes than are molecules with unacylated GPI anchors, and 2) that DAF and CD59 loss may participate with other membrane alterations that occur during in vitro storage in compromising the survival of transfused cells.     

Pharmacokinetic characterization in xenografted mice of a series of first-generation mimics for HLA-DR antibody, Lym-1, as carrier molecules to image and treat lymphoma.

Despite their large size, antibodies (Abs) are suitable carriers to deliver systemic radiotherapy, often molecular image-based, for lymphoma and leukemia. Lym-1 Ab has proven to be an effective radioisotope carrier, even in small amounts, for targeting human leukocyte antigen DR (HLA-DR), a surface membrane protein overexpressed on B-cell lymphoma. Pairs of molecules (referred to as ligands), shown by computational and experimental methods to bind to each of 2 sites within the Lym-1 epitopic region, have been linked to generate small (<2 kDa) molecules (referred to as selective high-affinity ligands [SHALs]) to mimic the targeting properties of Lym-1 Ab. METHODS: A lysine-polyethylene glycol (PEG) backbone was used to synthetically link 2 of the following ligands: deoxycholate, 5-leuenkephalin, triiodothyronine, thyronine, dabsyl-L-valine, and N-benzoyl-L-arginyl-4-amino-benzoic acid to generate a series of 13 bidentate SHALs with a biotin or 1,4,7,10-tetraazacyclododecane-N,N',N',N'-tetraacetic acid (DOTA) chelate attached to the linker. These SHALs have been assessed for their selectivity in binding to HLA-DR10-expressing cells and for their pharmacokinetics and tissue biodistribution in mice. Biotinylated versions of these SHALs discriminated cell lines positive for HLA-DR10 expression with near-nanomolar affinity. The DOTA versions of 4 SHALs were labeled with (111)In for pharmacokinetic studies in mice with HLA-DR10-expressing malignant Raji xenografts. RESULTS: The bidentate, biotinylated, and DOTA-SHALs were synthesized in high-purity, multimilligram amounts. Mean radiochemical and product yields and purities were 90%, 75%, and 90% at mean specific activities of 3.9 MBq/microg (105 microCi/microg) for the (111)In-labeled SHALs. As expected, rapid blood clearance and tumor targeting were observed. The pharmacokinetics of the SHALs was influenced by the component ligands. Biliary clearance, kidney localization, and serum receptor binding contributed to less favorable tumor targeting. CONCLUSION: A series of SHALs was readily synthesized in multimilligram amounts and showed the expected selective binding in vitro. Better selection of the SHAL components should provide second-generation SHALs with improved properties to fulfill the substantial potential of these novel molecular carriers for targeting.     

Thermal dosimetry predictive of efficacy of 111In-ChL6 nanoparticle AMF--induced thermoablative therapy for human breast cancer in mice.

Antibody (mAb)-linked iron oxide nanoparticles (bioprobes) provide the opportunity to develop tumor specific thermal therapy (Rx) for metastatic cancer when inductively heated by an externally applied alternating magnetic field (AMF). To evaluate the potential of this Rx, in vivo tumor targeting, efficacy, and predictive radionuclide-based heat dosimetry were studied using (111)In-ChL6 bioprobes (ChL6 is chimeric L6) in a human breast cancer xenograft model. METHODS: Using carbodiimide, (111)In-DOTA-ChL6 (DOTA is dodecanetetraacetic acid) was conjugated to polyethylene glycol-iron oxide-impregnated dextran 20-nm particles and purified as (111)In-bioprobes. (111)In doses of 740-1,110 kBq (20-30 muCi) (2.2 mg of bioprobes) were injected intravenously into mice bearing HBT3477 human breast cancer xenografts. Pharmacokinetic (PK) data were obtained at 1, 2, 3, and 5 d. AMF was delivered 72 h after bioprobe injection at amplitudes of 1,410 (113 kA/m), 1,300 (104 kA/m), and 700 (56 kA/m) oersteds (Oe) at 30%, 60%, and 90% "on" time (duty), respectively, and at 1,050 Oe (84 kA/m) at 50% and 70% duty over the 20-min treatment. Treated and control mice were monitored for 90 d. Tumor total heat dose (THD) from activated tumor bioprobes was calculated for each Rx group using (111)In-bioprobe tumor concentration and premeasured particle heat response to AMF amplitudes. Tumor growth delay was analyzed by Wilcoxon rank sum comparison of time to double, triple, and quintuple tumor volume in each group, and all groups were compared with the controls. RESULTS: Mean tumor concentration of (111)In-bioprobes at 48 h was 14 +/- 2 percentage injected dose per gram; this concentration 24 h before AMF treatment was used to calculate THD. No particle-related toxicity was observed. Toxicity was observed at the highest AMF amplitude-duty combination of 1,300 Oe and 60% over 20 min; 6 of 10 mice died acutely. Tumor growth delay occurred in all of the other groups, correlated with heat dose and, except for the lowest heat dose group, was statistically significant when compared with the untreated group. Electron microscopy showed (111)In-bioprobes on tumor cells and cell death by necrosis at 24 and 48 h after AMF. CONCLUSION: mAb-guided bioprobes (iron oxide nanoparticles) effectively targeted human breast cancer xenografts in mice. THD, calculated using empirically observed (111)In-bioprobe tumor concentration and in vitro nanoparticle heat induction by AMF, correlated with tumor growth delay.     

Delayed hepatic CT scanning: increased confidence and improved detection of hepatic metastases

Fifty oncologic patients with suspected hepatic metastases were prospectively evaluated by dynamic sequential hepatic computed tomography (DSHCT) and by delayed iodine hepatic computed tomography (DICT) scanning. DICT scanning was performed 4-6 hours following administration of 60 g of intravenous iodine. Both techniques were evaluated for lesion definition relative to the adjacent hepatic parenchyma and for numbers of metastases detected. Metastases were detected by both techniques in 26 patients. Fifteen patients (58%) had lesions better defined by DICT. DICT scanning detected more metastases in seven of these 15 patients. In eight patients (31%), there was no difference between the two techniques in numbers of masses detected or lesion definition. In three cases (11%), metastases were more confidently identified on the initial or DSHCT scan. DICT scanning, as described, is useful in defining and detecting hepatic metastases, especially where there is questionable hepatic involvement or better quantification of size is necessary.