Acute-phase response predicts erythropoietin resistance in hemodialysis and peritoneal dialysis patients

We defined erythropoietin (EPO) resistance by the ratio of the weekly EPO dose to hematocrit (Hct), yielding a continuously distributed variable (EPO/Hct). EPO resistance is usually attributed to iron or vitamin deficiency, hyperparathyroidism, aluminum toxicity, or inflammation. Activation of the acute-phase response, assessed by the level of the acute-phase C-reactive protein (CRP), correlates strongly with hypoalbuminemia and mortality in both hemodialysis (HD) and peritoneal dialysis (PD) patients. In this cross-sectional study of 92 HD and 36 PD patients, we examined the contribution of parathyroid hormone (PTH) levels, iron indices, aluminum levels, nutritional parameters (normalized protein catabolic rate [PCRn]), dialysis adequacy (Kt/V), and CRP to EPO/Hct. Albumin level serves as a measure of both nutrition and inflammation and was used as another independent variable. Serum albumin level (deltaR2 = 0.129; P < 0.001) and age (deltaR2 = 0.040; P = 0.040) were the best predictors of EPO/Hct in HD patients, and serum albumin (deltaR2 = 0.205; P = 0.002) and ferritin levels (deltaR2 = 0.132; P = 0.015) in PD patients. When albumin was excluded from the analysis, the best predictors of EPO/Hct were CRP (deltaR2 = 0.105; P = 0.003) and ferritin levels (deltaR2 = 0.051; P = 0.023) in HD patients and CRP level (deltaR2 = 0.141; P = 0.024) in PD patients. When both albumin and CRP were excluded from analysis in HD patients, low transferrin levels predicted high EPO/Hct (deltaR2 = 0.070; P = 0.011). EPO/Hct was independent of PTH and aluminum levels, PCRn, and Kt/V. High EPO/Hct occurred in the context of high ferritin and low transferrin levels, the pattern expected in the acute-phase response, not in iron deficiency. In well-dialyzed patients who were iron replete, the acute-phase response was the most important predictor of EPO resistance.     

Effects of temperature on radiochemical purity and immunoreactivity of radiolabeled monoclonal antibody 1H10

OBJECTIVE: This study was undertaken to investigate the effects of temperature on preserving the radiochemical purity and immunoreactivity of 125I- and 131I-labeled monoclonal antibody (MAb) 1H10--an antibody against human cervical carcinoma cell-surface antigen. METHODS: An antibody-irrelevant human melanoma cell line, H2269, served as the control group. Iodine-125 and 131I radiolabeling of MAbs 1H10 and H2669 was performed by the chloramine-T method. All the prepared MAbs were divided into aliquots and stored at 4, -20, and -70 degrees C for 2-14 d. The radiochemical purity and immunoreactivity of the labeled antibodies in set conditions were measured by thin-layer chromatography and a modified index, respectively, after a single freeze-and-thaw cycle. RESULTS: Reduced release of free radioiodide and better preservation of immunoreactivity were observed in the radiolabeled MAbs stored at -70 degrees C than in those stored at -20 degrees C or 4 degrees C. The extent of free iodide dissociation and immunologic binding degradation of 125I-labeled MAb 1H10 appeared milder than that of 131I-labeled MAb under the same conditions. However, both 125I- and 131I-labeled MAb stored at -70 degrees C or -20 degrees C retained more than 90% radiochemical purity for at least 3d. CONCLUSION: Freezing provides an appropriate alternative for reducing radiolysis and preserving immunoreactivity of radioiodinated MAbs. MAb 1H10, labeled with either 125I or 131I and stored at temperatures of -20 degrees C or below for 3 d after labeling, appeared stable in both radiolabeling and binding studies in vitro and was still acceptable for in vivo use.     

Detection of multiple myeloma by PET/CT in a patient with colon cancer

A 76-year-old man with previous sigmoid colon resection for adenocarcinoma had low back pain for 2 months. Whole-body bone scintigraphy showed multiple focal Tc-99m methylene diphosphonate (MDP)-avid lesions in both rib cages and 3 lumbar vertebrae, indicating metastases. F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) imaging was performed for further evaluation of this possible metastatic disease and demonstrated the lumbar and costal metastases and several hypermetabolic areas in the pelvic bones, multiple thoracic vertebrae, both shoulders, and the right femur. Histopathologic examination of the right-sided iliac crest, however, revealed multiple myeloma.     

假细锥香茶菜新二萜成分——假细锥甲素的结构

从假细锥香茶菜(Rabdosia coetsoides C.Y.Wu)叶分离得到新二萜成分,根据紫外光谱、红外光谱、质谱、核磁共振氢谱及碳谱等分析,推定了化学结构,并经X-射线衍射确证,命名为假细锥甲素。     

Coinduction of granulocyte-macrophage colony-stimulating factor release and lymphokine-activated killer cell susceptibility in monocytes by interleukin-2 via interleukin-2 receptor beta

Human monocytes express interleukin-2 receptor beta (IL-2R beta) constitutively; however, the function of these receptors has not been fully delineated. We discovered that IL-2R beta directs two biologic activities in human monocytes, the release of granulocyte-macrophage colony-stimulating factor (GM-CSF) and increased susceptibility to lysis by lymphokine-activated killer cells (LAK) cells. Human monocytes were purified from peripheral blood mononuclear cells by plastic adherence and anti-CD2 plus complement lysis. By a 5-hour 51Cr-release assay, monocytes cultured in IL-2 were found to gain increasing susceptibility to LAK cells with time and this effect was dose dependent. Maximal susceptibility was obtained with a 4-day culture in 1,000 U/mL of IL-2. Monocytes were also found to release GM-CSF in response to IL-2 using a CSF-dependent cell line, Mo7e. Because IL-2- induced GM-CSF release coincides with LAK lysis of IL-2-cultured monocytes, we treated monocytes with anti-GM-CSF and anti-IL-2R beta to determine whether GM-CSF release and LAK susceptibility were dependent or independent events. We found that both phenomena were inhibited by either antibody. Therefore, we conclude that IL-2-induced release of GM- CSF is mediated by IL-2R beta, which then acts to modulate the susceptibility of monocytes to lysis by LAK cells.     

Large right atrial thrombus with pulmonary embolism

We present the cases of two patients, aged 67 and 77 years, who were admitted for the evaluation of rapidly progressive dyspnea and syncope, respectively. Both patients developed large right atrial thrombi with pulmonary embolism. The first patient received recombinant tissue plasminogen activator and survived with an uneventful result, whereas the second patient received operative thrombectomy followed by intravenous heparin and died 15 days later of pulmonary infarction with pulseless electrical activity. Data from these limited experiences suggest that thrombolytic therapy might be considered in patients with right heart thrombi with pulmonary embolism.     

Combination of quinine as a potential reversing agent with mitoxantrone and cytarabine for the treatment of acute leukemias: a randomized multicenter study

A phase III prospective randomized multicenter study was performed to determine whether quinine could improve the response rate of poor-risk acute leukemias (ALs) to standard chemotherapy including a multidrug resistance (MDR)-related cytotoxic agent. The rationale of the study was based on the negative prognostic value of MDR phenotype in ALs and the ability of quinine to reverse this phenotype both in vitro and ex vivo. Three hundred fifteen patients (median age, 49 years; range, 16 to 65) with relapsed (n = 108) or refractory (n = 32) acute myeloblastic leukemia (AML), relapsed (n = 27) or refractory (n = 9) acute lymphoblastic leukemia (ALL), secondary AL (n = 22) or blastic transformation of myelodysplastic syndrome ([MDS] n = 74) or myeloproliferative syndrome ([MPS] n = 43) were randomly assigned to receive mitoxantrone ([MXN] 12 mg/m2/d, days 2 to 5) and cytarabine ([Ara-C] 1 g/m2/12 h, days 1 to 5) alone or in combination with quinine (30 mg/kg/d, days 1 to 5; continuous intravenous infusion beginning 24 hours before MXN infusion). Side effects of quinine were observed in 56 of 161 quinine-treated patients and disappeared in all but four cases after one or two 20% dose decreases. Sera from quinine-treated patients showed increased MXN uptake in an MDR-positive cell line compared with matched sera obtained before quinine infusion. Quinine induced a significant increase in the incidence of nausea, vomiting, mucositis, and cardiac toxicity. A complete response (CR) was observed in 85 of 161 patients (52.8%) from the quinine-treated group versus 70 of 154 patients (45.5%) in the control group (P = .19). The most important differences between quinine and control group CR rates were observed in patients with refractory AMLs and blastic transformation of MDS and MPS. The CR rate was higher in P-glycoprotein-positive cases, although the difference was not significant. Failure of the regimen due to blastic persistence or blast number increase was higher in the control group (61 of 154 patients) than in the quinine group (45 of 161, P = .04). Early death was observed in eight cases (four in each arm) and death in aplasia in 27 cases (20 in quinine group v seven in control group, P = .01). The significant increase of toxicity in the quinine arm could have masked the clinical benefit of MDR reversion in poor- risk ALs.