Serum BLyS levels increase after rituximab as initial therapy in patients with follicular grade 1 non‐Hodgkin lymphoma

Serum B‐lymphocyte stimulator (BLyS) levels are elevated in a subset of non‐Hodgkin lymphoma (NHL) patients, particularly those with a family history of B‐cell malignancies or a polymorphism in the BLyS gene. BLyS promotes growth of malignant B‐cells and increased serum BLyS levels are associated with a poor clinical outcome. In this study, BLyS levels were measured before and after 4 weekly doses of rituximab in 30 patients with previously untreated follicular Grade 1 NHL. A significant increase was seen in the serum levels of BLyS (P = 0.0001) after rituximab therapy. The increase was independent of genetic variability in the BLyS gene. Am. J. Hematol., 2009. © 2008 Wiley‐Liss, Inc.     

Panniculitis–an unusual cutaneous manifestation of systemic sclerosis

Systemic sclerosis (SSc) is an autoimmune systemic disease characterized by small vessel involvement that leads to tissue ischemia and fibroblast stimulation resulting in accumulation of collagen (fibrosis) in the skin and internal organs. Lipomembranous panniculitis is a peculiar type of fat necrosis and has been reported with clinical conditions, commonly with peripheral vascular diseases. We describe a case of a 43‐year‐old woman with SSc manifestations, who presented with black scaly skin plaques, associated with thickening of the subcutaneous fat tissue, on the lateral surface of her thighs, her calves, gluteal area and lower abdomen. Biopsy revealed lipomembranous panniculitis. Lipomembranous changes have been seen in connective tissue disorders such as lupus profundus, morphea, systemic sclerosis and panniculitis associated with dermatomyositis, but rarely in thighs, calves, gluteal area and lower abdomen. Almeida MSTM, Lima SCB, Carvalho LL, Almeida JVM, Santos LG, Rolim JRA, Rocha TE. Panniculitis–An unusual cutaneous manifestation of systemic sclerosis.     

加替沙星无菌检查方法的建立与标准操作探讨

目的:建立加替沙星原料及制剂无菌检查法及标准操作方法。方法:按2005年版中国药典无菌检查法验证实验的有关要求,通过接种阳性代表菌株,对薄膜过滤、添加中和剂等去除加替沙星抗菌活性的实验方法和条件进行验证,逐步建立加替沙星原料及制剂无菌检查的标准操作方法。结果:在对加替沙星不同原料及制剂样品适当的处理基础上,采用薄膜过滤法,以0.1%蛋白胨水溶液作为冲洗液,约每滤筒300 mL 的冲洗量,每筒培养基中加入0.1 mol·L~(-1)硫酸锰溶液3 mL 可去除加替沙星对细菌的抑菌作用。结论:加替沙星具有较强的抑菌活性,通过适当的样品处理、薄膜过滤法和添加硫酸锰溶液作为重金属络合剂,去除加替沙星抑菌活性,可对解决喹诺酮类抗生素无菌检查问题起到较好的参考作用。     

保健食品微生物限度检查的方法学验证

目的:确认对保健食品进行微生物限度检查时,昕采用的细菌、霉菌及酵母菌计数和控制菌检查方法是否适合于该保健食品的微生物限度检查。方法:按2005年版中国药典微生物限度检查法及方法学验证实验要求,对21种保健食品进行了方法学验证。结果:10个品种(血尔口服液、金舒通胶囊、事轻松胶囊、梦玉胶囊等)分别对金黄色葡萄球菌和枯草芽孢杆菌有明显的抑菌作用,阳性对照菌回收率均低于70%。结论:保健食品采用 GB/T4789-2003食品卫生微生物学检查法进行检查时,其检验结果可能不够科学,建议参照2005年版中国药典要求,通过方法验证实验建立合理的检验方法。     

Selenium status of New Zealand infants fed either a selenium supplemented or a standard formula

Objective: New Zealand soils are deficient in the essential micronutrient, selenium. New Zealand infants have low selenium levels at birth and experience a further decline if fed cows milk based formula. This study examined the selenium status of infants fed with a new commercially available selenium supplemented formula.
Methodology Forty-four newborn infants, whose mothers wished to formula feed, were randomized in an open controlled trial to be fed a commercially available selenium supplemented cows milk formula (containing 17 μg Se/L) or an unsupplemented formula (containing 4.6 μg Se/L). Cord, 1 and 3 month blood samples were obtained for selenium status (plasma and red cell selenium and glutathione peroxidase) and thyroid function.
Results Mean plasma selenium and glutathione peroxidase values were significantly higher in supplemented than unsupplemented infants at 1 month (unpaired t -tests; P <0.0001 and P = 0.001 respectively) and 3 months ( P <0.0001 and P = 0.0005). Analysis within treatment groups between time points (paired t -tests) showed that selenium supplementation prevented the fall in plasma selenium from birth to 1 month seen in unsupplemented infants and was associated with a rise in levels between 1 and 3 months ( P = 0.002).
Conclusions Supplementing cows milk formula with selenium to replicate the levels found in breast milk is nutritionally sound. Feeding from a few days of age with a formula containing 17 μg Se/L in infants with low selenium status at birth is sufficient to cause a rise to 80% of adult levels at 3 months of age.     

Radioimmunotherapy with yttrium-90 ibritumomab tiuxetan for patients with relapsed CD20+ B-cell non-Hodgkin's lymphoma

The clinical development and US Food and Drug Administration approval in 1997 of the monoclonal anti-CD20 antibody rituximab have been major treatment advances for patients with B-cell non-Hodgkin's lymphoma (NHL). Rituximab produces responses in approximately 50% of cases of relapsed, low grade NHL. Most of these responses are partial remissions; cure remains elusive. One way to enhance the effectiveness of monoclonal antibodies is to chelate radionuclides such as yttrium-90 ((90)Y) to the antibody. ( 90)Y is a high-energy, beta-emitting radioisotope that delivers most of its radiation over a path length of 2 to 5 mm. Therefore, the antibody delivers, or targets, the radiation only to CD20+ cells, sparing normal cells from the radiation. Ibritumomab is the murine anti-CD20 antibody that was engineered to develop the human chimeric antibody rituximab. Tiuxetan is a linker/chelator that is attached to the antibody to form ibritumomab tiuxetan (Zevalin; IDEC Pharmaceuticals, San Diego, CA). Zevalin can be reacted with (111)indium ((111)In) for imaging and (90)Y for therapy. Phase I studies of Zevalin have determined that patients with a baseline platelet count greater than 150,000 10(6)/L receive 0.4 mCi/kg. Patients with a platelet count of 100 to 149,000 10(6)/L should receive 0.3 mCi/kg. Zevalin has a higher overall response rate (ORR) than its cold antibody counterpart rituximab, as demonstrated in two separate clinical trials. The first trial (IDEC 106-04) randomized 143 rituximab-na?ve patients with relapsed NHL to receive rituximab or Zevalin. The ORR for Zevalin was 80% compared with 56% for rituximab (P = 0.002). The second trial (IDEC 106-06) tested the efficacy of Zevalin in patients who were rituxan-refractory; the ORR was 74%. The main toxicity of Zevalin was reversible myelosuppression. These studies indicate that radiolabeled anti-CD20 antibodies can produce a higher ORR than rituximab. Single-dose Zevalin is another treatment alternative for patients with relapsed low grade NHL. It is well-tolerated even by older adults. The exact role of Zevalin in the therapy of NHL is undetermined. New studies are underway to explore whether patients can safely receive a second dose of Zevalin and to combine Zevalin with high-dose chemotherapy and stem cell rescue. The outcome of these studies will be helpful in deciding how best to integrate this new modality into the treatment paradigm of NHL.     

Treatment with ibritumomab tiuxetan radioimmunotherapy in patients with rituximab-refractory follicular non-Hodgkin's lymphoma.

PURPOSE: Rituximab is commonly used as a single agent or in combination therapy for non-Hodgkin's lymphoma (NHL). Ibritumomab tiuxetan radioimmunotherapy targets the same antigen as rituximab and has demonstrated efficacy in rituximab-na?ve NHL. This study evaluated ibritumomab tiuxetan in the treatment of rituximab-refractory follicular NHL. PATIENTS AND METHODS: Eligible patients were refractory to rituximab; this was defined as no objective response to rituximab (375 mg/m(2) weekly for 4 weeks) or time to progression (TTP) of < or = 6 months. The ibritumomab tiuxetan treatment regimen consisted of pretreatment with rituximab (250 mg/m(2) intravenously on days 1 and 8) to deplete peripheral blood B cells, then yttrium-90 ibritumomab tiuxetan (0.4 mCi/kg; maximum, 32 mCi) intravenously on day 8, administered on an outpatient basis. An imaging/dosimetry dose of indium-111 ibritumomab tiuxetan (5 mCi) was injected after rituximab (day 1) in 28 patients. RESULTS: Fifty-seven patients were treated. The median age was 54 years, 74% had tumors > or = 5 cm, and all were extensively pretreated (median, four prior therapies; range, one to nine). The estimated radiation-absorbed doses to healthy organs were below the study-defined limit in all patients studied with dosimetry. The overall response rate for the 54 patients with follicular NHL was 74% (15% complete responses and 59% partial responses). The Kaplan-Meier-estimated TTP was 6.8 months (range, 1.1 to > or = 25.9 months) for all patients and 8.7 months for responders. Adverse events were primarily hematologic; the incidence of grade 4 neutropenia, thrombocytopenia, and anemia was 35%, 9%, and 4%, respectively. CONCLUSION: Ibritumomab tiuxetan radioimmunotherapy is effective in rituximab-refractory patients. The only significant toxicity is hematologic.