Pharmacokinetic profile of Mitoguazone (MGBG) in patients with AIDS related non-Hodgkin's lymphoma

Summary Mitoguazone is a unique chemotherapeutic agent whose activity is believed to result primarily from the competitive inhibition of S-adenosyl-methionine decarboxylase leading to a disruption in polyamine biosynthesis. Initial clinical trials demonstrated that the dose-limiting toxicities (mucositis and myelosuppression) of Mitoguazone were both dose and schedule dependent. Early pharmacokinetic studies of Mitoguazone in man revealed a prolonged half-life. Concurrent with a recent Phase II trial of Mitoguazone in patients with AIDS related non-Hodgkin's lymphoma, the single dose pharmacokinetics of Mitoguazone were characterized. Twelve patients received 600 mg/m² of intravenous Mitoguazone over 30 minutes on an intermittent every 2 week schedule. Blood, urine, cerebrospinal fluid (CSF), pleural fluid and tissue samples were collected and analyzed by HPLC. Mitoguazone was cleared from the plasma triexponentially with a harmonic mean terminal half-life of 175 hours and a mean residence time of 192 hours. Peak plasma levels occurred immediately post-infusion, ranged from 6.47 to 42.8 g/ml, and remained (for an extended period) well above the reported concentration for inhibition of polyamine biosynthesis. Plasma clearance averaged 4.73 l/hr/m² with a relatively large apparent volume of distribution at steady-state of 1012 l/m² indicating tissue sequestration. Renal excretion of unchanged Mitoguazone accounted for an average of 15.8% of the dose within 48 to 72 hours post-administration. Detectable levels of drug were present in random voided samples eight days post-dose. Mitoguazone levels in CSF ranged from 22 to 186 ng/ml post-dose with CSF/plasma ratios ranging from 0.6% to 7%. The pleural fluid/plasma ratio was approximately 1. Tissue levels of Mitoguazone were highest in the liver followed by lymph node, spleen and the brain.     

电感耦合等离子体原子发射光谱法分析珍宝类藏药七十味珍珠丸中汞的5种形态和分布

目的:研究藏药七十味珍珠丸中汞的5种存在形态和分布.方法:将七十味珍珠丸中汞的形态分为水溶态汞、溶于盐酸的无机汞和有机汞、络合汞、单质汞和残渣态汞,通过电感耦合等离子体原子发射光谱(ICP-AES)法分析5种形态汞的含量和分布.结果:藏药七十味珍珠丸中总汞的93.8％是以惰性汞形式存在的硫化汞,6.18％是与锌、铝、钙...     

Decellularized dermis in combination with cultivated keratinocytes in a short- and long-term animal experimental investigation

Decellularized human dermis as a potentially ideal scaffold for dermal substitution in severe burns was examined in a two‐staged animal experiment. In an initial step, an in vitro generated composite graft consisting of human keratinocytes and decellularized dermis (AlloDerm®) was transplanted onto nude mice in a short‐term trial (n = 20, 14 days). Subsequently, a combined one‐step grafting of full thickness wounds with both decellularized dermis (in part preincubated with fibroblasts) and cultivated autologous keratinocytes as a cell suspension in fibrin glue was done in a long‐term porcine animal model (n = 10, 6 months). In both series, macroscopic wound healing was evaluated by planimetry. Histological investigations included morphological as well as immunohistochemical parameters. The short‐term study showed both successful integration of the composite grafts and reduction of wound contraction compared with the control group (epithelial grafts). The long‐term porcine study displayed reduced myofibroblast formation and contraction in the wounds that had been treated with fibroblast‐preincubated dermis. After 4 weeks, a decline of the structural integrity of the dermal matrix could be noticed. The utility of decellularized dermis as template for both dermal reconstitution and keratinocyte delivery vehicle was shown. The closure of full thickness wounds by a single‐step combination of an autologous keratinocyte fibrin sealant suspension and acellular dermis in a pig animal model could be shown. Incorporation of fibroblasts led to reduced wound contraction but could not prevent the loss of dermal integrity. The engineered ‘skin’ remained viable and stable over a period of 6 months.     

Does the perception of downloading speed influence the evaluation of web-based lectures?

Medical schools put little emphasis upon education on public health, even though public health has played an important role in this century. One way to harness its benefit in order to improve global health in the 21st century is to globally share lectures on public health through the Internet. We have developed the Supercourse comprising of web-based learning modules on epidemiology in a standardized format with the size of each web page less than 10 kilobytes. A cross-sectional observational study was conducted to investigate the association of the perception of the access speed to Web-based lectures by teachers with their perception of lecture quality. There were 223 teachers who rated the lectures: 72% were from North America or Western Europe, 40% had taught epidemiology, and 14% reported that the speed of access was slow. Odds ratio of above-average rating among those who reported that the speed of access was fast relative to those who reported that the speed of access was slow was 4.25 (2.03-8.91; P = 0.001). The odds ratios were similar and significant after taking into account several other factors, including the variation of rating across lectures, region, and experiences in teaching epidemiology. The results indicate that the perception of the quality of Web-based lectures is related to the speed of access to a web page. The speed of access may be as important, if not more important, as the content itself. This suggests that, to share educational materials on the Web globally for teachers, one must consider not only the content, but also how people at local sites gain access to the Internet.     

Pulmonary embolism after hip or knee replacement: postoperative changes on pulmonary scintigrams in asymptomatic patients

Serial pulmonary imaging has proved to be effective in the evaluation of patients undergoing total joint arthroplasty. A clinical dilemma arises in asymptomatic patients whose postoperative pulmonary images differ from the preoperative images. The authors prospectively evaluated 403 patients with serial imaging to determine the significance of changed postoperative images in asymptomatic patients undergoing total hip or knee arthroplasty. Twenty-two (5.5%) patients had significant changes on postoperative images. Seventeen were asymptomatic; all but one underwent pulmonary angiography. Documented pulmonary emboli were demonstrated in 100% of patients whose postoperative images changed to indicate a high probability of pulmonary embolism, 71% whose images changed to a moderate probability, and 0% whose images changed to indeterminate probability. Overall, pulmonary emboli occurred in 76% of all asymptomatic patients with significantly change postoperative images. Asymptomatic pulmonary embolism is a significant occurrence after total hip or knee repair, and a changed lung scan with appropriate clinical evaluation is an accurate indicator of pulmonary emboli in asymptomatic postarthroplasty patients.     

Prostatic cancer therapy: comparison of external-beam radiation and I- 125 seed implantation treatment of stages B and C neoplasms

Of 179 patients with stage B or C adenocarcinoma of the prostate, 106 underwent iodine-125 seed-implant therapy (I-125 SI) and 73 received external-beam radiation therapy (EB). A retrospective analysis determined disease-free survival rate, local tumor control, and complication rate for each treatment group. The 5-year disease-free survival rates for SI-treated patients were 75% for stage B and 30% for stage C groups. Corresponding rates for EB-treated patients were 75% and 40%, respectively. The rate of local tumor control for stage B patients was 85% for SI-treated and 88% for EB-treated patients. The corresponding rates for stage C tumors were 75% for SI-treated and 92% for EB-treated patients. The rate of long-term complications in each group was approximately 10%. For stage B cancer of the prostate, I-125 SI treatment is an acceptable alternative to EB therapy; our data are inconclusive regarding stage C treatment, but EB therapy is preferred.     

Adverse reactions to xenon-enhanced CT cerebral blood flow determination

Fourteen institutions performed 1,830 computed tomographic (CT) cerebral blood flow (CBF) examinations with 32% inhaled stable xenon. Respiratory rate delay greater than 10 seconds occurred in 3.6% of patients, with 83% of the delays lasting 10-15 seconds. There was no incident of prolonged respiratory difficulty. Headache (0.4%), seizures (0.2%), nausea and vomiting (0.2%), and change in neurologic status (0.1%) were uncommon, and there were no transient ischemic attacks. The CT CBF method with 32% inhaled stable xenon is thus associated with an acceptably low incidence of adverse reactions.