Biomedical subjects

E Nestaas

Publications and source records attributed to E Nestaas.

5 recordsLinked to original sources

PubMed2005

Aminoglycoside extended interval dosing in neonates is safe and effective: a meta-analysis.

OBJECTIVES: To review the evidence from controlled clinical trials of neonates given equal daily aminoglycoside doses as extended interval dosing (dosage interval typically 24 hours in term and 36-48 hours in immature neonates) compared with traditional dosing (dosage interval typically 8-12 hours in term and 12-24 hours in immature neonates). DESIGN: Systematic review and meta-analysis of controlled trials found in electronic databases, trial registers, and references in reviews and selected trials. SETTINGS: The selected trials were blinded and assessed for methodological quality. Each trial's own predefined criteria for treatment failure, nephrotoxicity, ototoxicity, and therapeutic serum drug concentrations were used. SUBJECTS: Controlled trials of neonatal aminoglycoside treatment in which equal aminoglycoside daily doses were given at traditional and extended dosage intervals. MAIN OUTCOME MEASURES: Serum drug concentrations outside the therapeutic range. Treatment failure and toxicity. RESULTS: Sixteen trials involving 823 neonates met the inclusion criteria for the systematic review. Twelve trials involving 698 neonates were included in the meta-analysis of the pharmacokinetics. Compared with traditional dosing, extended interval dosing was associated with a significantly lower risk of both peak (summary risk ratio 0.50, 95% confidence interval 0.26 to 0.94) and trough (0.36, 0.25 to 0.56) serum drug concentrations outside the therapeutic range. Accurate information on treatment failure was obtained in nine trials involving 555 neonates. One trial reported treatment failure. In this trial two neonates in the traditional dosing group did not respond to treatment within 72 hours. Nephrotoxicity was investigated in 589 neonates in 12 trials and ototoxicity in 210 neonates in four trials, with no significant differences between the two dosing regimens. CONCLUSIONS: Extended interval dosing of aminoglycosides in neonates is safe and effective, with a reduced risk of serum drug concentrations outside the therapeutic range.

Aminoglycosides↗

PubMed2000

Capillary zone electrophoresis of a recombinant adenovirus.

Adenovirus preparations are used as vectors in a number of gene therapy clinical development programs. The success of commercial production of adenovirus will strongly depend on the development of methods to define the recombinant virus product by analysis as opposed to being defined by the manufacturing process. While most analytical techniques examine portions of the virus, e.g. proteins or DNA, ion-exchange chromatography has been used to separate intact virus at low efficiency. A free zone capillary electrophoretic method was developed for high-efficiency separations of adenovirus 5. Experimental conditions such as buffer pH and concentration were explored which produced a high-efficiency separation in less than 20 min. The virus band was identified by collection of CE fractions and examination using a cell based assay. Initially, a single virus peak is found in fresh virus samples. After as little as one freeze-thaw in 1 x phosphate-buffered saline with 2% sucrose, the active virus migrates as a regular series of peaks. The nature of the virus modification leading to the differing electrophoretic mobilities is presently under investigation.

Adenoviridae↗

PubMed1999

Reversed-phase high-performance liquid chromatographic assay for the adenovirus type 5 proteome.

An RP-HPLC assay was developed for a recombinant adenovirus type 5. During chromatography, intact adenovirus dissociated into its structural components (DNA and proteins) and the viral proteome was separated yielding a characteristic fingerprint. The individual components were identified by matrix-assisted laser desorption ionization time-of-flight mass spectroscopy, N-terminal sequencing and amino acid composition. The assay was utilized to measure adenovirus particle concentration through quantification of structural proteins. Each structural protein provided independent measurement of virus concentration allowing verification of accuracy. The assay sensitivity is at or below 2 x 10(8) particles. Contrary to the benchmark spectrophotometric assay, the RP-HPLC assay was shown to be insensitive to contaminants common for partially purified adenovirus preparations.

Adenoviruses, Human↗

PubMed1998

A novel sensitive and selective bioassay for human type I interferons.

We describe a novel MxA gene-induction assay for type I interferons (IFN-alpha and IFN-beta) based on the specific induction of the MxA gene in cultured human cells. Accumulated intracellular MxA protein is determined by immunologic measurement by a rapid method using commercially available materials. IFN activity can be measured accurately over a concentration range of 0.1-30 IU/ml. In contrast, type II IFN and other cytokines are not significantly detected. The MxA-induction assay has advantages in terms of specificity, reliability, and sensitivity over other methods for assaying type I IFN. It has also been adapted and validated for measuring the titers of anti-IFN-beta neutralizing antibodies in human sera.

Antiviral Agents↗

PubMed1998

A novel bioassay for the determination of neutralizing antibodies to IFN-beta1b.

We have adapted the new MxA gene-induction bioassay to measure neutralizing antibodies to interferon-beta1b (IFN-beta1b, the active ingredient in Betaseron) in sera from patients treated with Betaseron. This antibody assay has been validated to quantify neutralizing titers of 1:20 and above, with a precision of +/- 0.20 in log10. We have used this MxA gene-induction antibody assay to reinvestigate serum samples from multiple sclerosis (MS) patients treated with Betaseron. The titers measured were closely comparable to those obtained in antiviral assays. Data obtained by both methods show that neutralizing antibodies may appear and subsequently disappear over time in the sera of some patients treated with Betaseron. Sera from some patients contain binding antibodies to IFN-beta1b. It was shown that binding antibody titers do not correlate quantitatively or qualitatively with neutralizing antibody titers, and indeed, a number of patients develop high levels of binding antibodies but never form measurable levels of neutralizing antibodies.

Antigen-Antibody Reactions↗