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The assembly of polyelectrolytes and gold nanoparticles yields stratified multilayers with very low roughness and high structural perfection. The films are prepared by spin-assisted layer-by-layer self-assembly (LbL) and are characterized by X-ray reflectivity (XRR), UV-vis spectroscopy, atomic force microscopy (AFM), and transmission electron microscopy (TEM). Typical structures have four repeat units, each of which consists of eight double layers (DL) of poly(sodium 4-styrenesulfonate)/poly(allylamine hydrochloride), one monolayer of gold nanoparticles (10 nm diameter), and another layer of poly(allylamine hydrochloride). XRR scans show small-angle Bragg peaks up to seventh order, evidencing the highly stratified structure. Pronounced Kiessig fringes indicate a low global roughness, which is confirmed by local AFM measurements. TEM images corroborate the layered structure in the growth direction and nicely show the distinct separation of the individual particle layers. An AFM study reveals the lateral gold particle distribution within one individual particle layer. Interestingly, the spin-assisted deposition of polyelectrolytes reduces the roughness induced by the particle layers, leading to self-healing of roughness defects and a rather perfect stratification.

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The adsorption of a metallo-supramolecular coordination polymer (Fe-MEPE) in the cylindrical pores of SBA-15 silica with pure and carboxylic acid (CA) carrying pore walls has been studied. Fe-MEPE is an intrinsically stiff polycation formed by complexation of Fe(II)-acetate with an uncharged ditopic bis-terpyridine ligand. The adsorption affinity and kinetics of the Fe-MEPE chains is strongly enhanced when the pore walls are doped with CA, and when the pH of the aqueous medium or temperature is increased. The initial fast uptake is connected with a decrease of pH of the aqueous solution, indicating an ion-exchange mechanism. It is followed by a slower (presumably diffusion-controlled) further uptake. The maximum adsorbed amount of Fe-MEPE in the CA-doped material corresponds to a monolayer of Fe-MEPE chains disposed side-by-side along the pore walls. The stoichiometry of Fe-MEPE in the pores (determined by XPS) was found to be independent of the loading and similar to that of the starting material. The mean chain length of Fe-MEPE before and after embedding in the CA-doped matrix was studied by solid-state 15N NMR using partially 15N-labeled Fe-MEPE. It is shown that the average chain length of Fe-MEPE is reduced when the complex is incorporated in the pores.

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The objective of this study was to describe the variation in preparation and administration of cyclophosphamide, mesna, and hydration for the treatment of childhood malignancies within clinical trial protocol documents. All cyclophosphamide-containing cooperative group (Pediatric Oncology Group) protocols that were open at Dana-Farber Cancer Institute in April 1998 were evaluated. Among the 14 active protocols, there were 23 unique cyclophosphamide regimens. Marked variation existed in infusion rate, fluid type, and volume used for admixing cyclophosphamide and mesna, as defined in the "Treatment" section of the protocols that we evaluated. Further variation was found in the type, amount, and rate of infusion of prehydration and posthydration fluid. Internal inconsistency existed within the protocols pertaining to the administration methods described in the "Agent Information," "Treatment," and "Consent" sections of the written documents. Clinical trial protocol documents serve as reference material for health care providers who prescribe, dispense, and administer protocol chemotherapy. Misinterpretation of protocol documents and clinician orders are contributing factors in serious and deadly medication errors. Internal inconsistency within protocol documents and variation in drug administration across protocols is a potential source of error. We recommend improved accuracy, clarity, and internal consistency of protocol documents to improve patient safety and compliance with protocol specifications. In addition, the use of standard concentrations, volumes, and methods of administration of chemotherapeutic agents and accompanying fluids is recommended.

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OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and economic issues associated with sirolimus, the most recent immunosuppressive agent approved for kidney transplantation. DATA SOURCES: A MEDLINE search (1966-June 2000) was completed to identify primary and review articles. In addition, abstracts from recent meetings on transplantation were reviewed for information and research on sirolimus. STUDY SELECTION AND DATA EXTRACTION: Blinded, randomized, controlled studies were the goal, but, as with most newly approved immunosuppressive agents, a significant amount of information on sirolimus is not available in this optimal form. All articles were assessed and all pertinent information was incorporated in this review. DATA SYNTHESIS: Sirolimus is structurally related to the immunosuppressive agent tacrolimus, and retains a pharmacokinetic and drug interaction profile similar to that of the calcineurin inhibitors, cyclosporine and tacrolimus. However, the novel mechanism of action of sirolimus differs significantly from these agents, as does its adverse effect profile. The most significant adverse reaction is hyperlipidemia. Clinical experience with sirolimus has allowed transplant centers to expand its use into other areas of transplantation as well as certain autoimmune disorders. CONCLUSIONS: The definitive role of sirolimus will continue to be determined; however, sirolimus offers an excellent addition to the transplant immunosuppression armamentarium.

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Liver transplantation in patients infected with hepatitis B virus (HBV) commonly results in reinfection that, if untreated, often compromises the viability of the allograft and negatively influences survival. Posttransplant treatment with hepatitis B immune globulin (HBIG) is now the standard of care, but patients appear to require lifelong treatment to prevent reinfection. In the past several years, new management strategies in patients with HBV have been developed, with an aim to decrease HBV-DNA replication before transplantation. Such an approach should increase the success of transplantation by decreasing the risk of reinfection and thus preventing recurrent disease posttransplantation. Nucleoside analogues, either alone or in conjunction with HBIG, are currently in use and are being studied in clinical trials as a means of preventing viral recurrence. Ganciclovir, famciclovir, and lamivudine all have demonstrated efficacy, although they vary in terms of effectiveness. Resistance may develop with the use of these agents and leads to reinfection by the mutant virus. Combination therapy may minimize the risk of viral mutation. Research continues to search for more effective ways to prevent and, if necessary, treat viral recurrence in patients undergoing liver transplantation for HBV.

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Mycophenolate mofetil (MMF) is the morpholinoethylester prodrug of mycophenolic acid, an agent which inhibits the proliferation of B and T lymphocytes through the noncompetitive, reversible inhibition of inosine monophosphate dehydrogenase, itself a key enzyme in the de novo synthetic pathway of guanosine nucleotides. Currently, MMF is approved for the prevention of acute renal allograft rejection when used in combination with cyclosporin and corticosteroids. Several studies have also demonstrated that this drug is useful in the treatment of refractory rejection in renal, heart and liver transplant recipients.

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Mycophenolate mofetil is the morpholinoethylester prodrug of mycophenolic acid, an agent that inhibits the proliferation of B and T lymphocytes through noncompetitive, reversible inhibition of inosine monophosphate dehydrogenase, a key enzyme in the de novo synthetic pathway of guanine nucleotides. Currently, mycophenolate mofetil is approved for the prevention of acute renal allograft rejection when given in combination with cyclosporine and steroids. Several studies also demonstrated that the agent is effective in the treatment of refractory rejection in renal, heart, and liver transplant recipients, and may have efficacy in the treatment of chronic rejection as well.

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To evaluate the clinical role of amphotericin/20% Intralipid emulsions (ILA), we conducted a Medline search of the English literature to locate the relevant case reports and clinical studies involving the use of this formulation. Due to differences in study design and definitions, we applied a set of treatment outcome definitions to determine the clinical efficacy of this treatment modality. Only 37 patients received ILA for the treatment of documented fungal infections. Using our definitions, four were considered successfully treated, one improved, two failed, and 30 were unevaluable. While infusion-related adverse events and nephrotoxicity were reportedly reduced with ILA, use of adjunctive therapies and concomitant nephrotoxic agents, and comparisons with high infusion concentrations complicate evaluation. Furthermore, incomplete and conflicting data exist regarding the physiochemical stability of ILA. The currently available data do not support recommendations for the use of this formulation for the treatment of systemic fungal infections.

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We examined the expression of interleukin-6 (IL-6) by 12 established human melanoma cell lines. Two constitutively produced low levels of IL-6 protein, as measured by enzyme-linked immunosorbent assay. Cells from these two lines, as well as those from two non-IL-6-producing cell lines, contained IL-6-specific mRNA as demonstrated by Northern hybridization. Treatment of the two IL-6-producing melanoma cell lines with interleukin-1 beta, tumor necrosis factor-alpha, or phorbol myristate acetate caused a marked increase in IL-6 production. These induction signals failed to stimulate IL-6 production in the nonproducing cells, even those that expressed IL-6 mRNA. IL-6 did not appear to act as an autocrine growth factor since the addition of exogenous human recombinant IL-6 or polyclonal anti-IL-6 antibody did not alter cellular proliferation. The production of this multifunctional cytokine by tumors may play a role in tumor-host interactions and this should be recognized in the design of biologic therapy trials.

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Multiple bone marrow aspirations or biopsies and lumbar punctures are a necessary part of the diagnosis and treatment of many pediatric cancer patients. Pharmacologic sedation may decrease the distress associated with these procedures. Midazolam (MDZ, Versed) is a water-soluble, rapid-onset, short-duration benzodiazepine that has not been studied widely in children. We prospectively evaluated safety and recovery parameters for intravenous MDZ used for conscious sedation by oncologists (without an anesthesiologist in attendance) for 70 procedures (bone marrow aspirations, lumbar punctures, or bone marrow aspirations plus lumbar punctures) in 24 ambulatory pediatric cancer patients, aged 1.5 to 15.5 years. MDZ was used alone or in combination with morphine or fentanyl. Respiratory rate, oxygen saturation, blood pressure, and heart rate were monitored. Sedation, anxiolysis, and recovery were assessed with a behavior score and a modified recovery room discharge score. Restraint was not required in 45% of the procedures. In no case was a respiratory rate less than 12 observed. In nine procedures (13%), an oxygen saturation less than or equal to 90 occurred, all within 10 minutes after the last dose of MDZ. Ten procedures (14%) required verbal stimulation to take deeper breaths. Two patients did not respond immediately to verbal stimulation and received face-mask oxygen. Hypoxemia was not correlated with opioid use. Hypoxemia appears to be related to total MDZ dose and may occur with normal respiratory rates; all cases resolved with verbal stimulation or face-mask oxygen without specific airway maneuvers or assisted ventilation. Heart rate and blood pressure remained stable in all 70 procedures.(ABSTRACT TRUNCATED AT 250 WORDS)

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