Biomedical subjects

S E Walker

Publications and source records attributed to S E Walker.

183 records · Page 11Linked to original sources

PubMedDate not supplied

Early appearance of abnormally migrating serum IgM in control and cyclophosphamide-treated NZB/NZW mice.

An augmented incidence of neoplasms was observed in autoimmune NZB/NZW mice receiving longterm immunosuppressive therapy with cyclophosphamide. This observation afforded a unique opportunity to test for paraproteins in 58 serial samples of serum from 39 mice dying with tumors or with renal disease/vasculitis. In 6 animals, abnormally migrating monoclonal IgM precipitin lines appeared at 40--56 weeks of age and persisted until death. In 3 animals, paraproteins appeared 32 to 43 weeks before reticuloendothelial neoplasms were observed. Three mice with abnormally migrating IgM died with renal disease/vasculitis. Abnormal IgM did not correlate with histologic changes of Sjögren's syndrome, lymphadenopathy, or activity of autoimmune disease. In 1 instance, an IgM paraprotein appeared and persisted in a mouse receiving prolonged treatment with a high dose of cyclophosphamide.

Animals↗

PubMedDate not supplied

Effects of cimetidine and ranitidine on the pharmacokinetics of a chronotherapeutically formulated once-daily theophylline preparation (Uniphyl).

The effects of cimetidine and ranitidine on the steady-state pharmacokinetics, safety, and efficacy of a chronotherapeutically formulated (CTF), once-daily theophylline preparation (Uniphyl) were evaluated in 12 adult patients with asthma. In this randomized, double-blind, three-way crossover study, patients received a fixed dose of CTF-theophylline and concurrent cimetidine, ranitidine, or placebo for a period of 7 days each. Asthma symptoms, drug side effects, and beta 2-agonist inhaler use were recorded daily. Venous blood sampling for pharmacokinetic assessment was done over a complete dosing interval on day 7 of each phase. Coadministration of cimetidine, but not ranitidine, was associated with a significant decrease in the apparent oral clearance of theophylline (2.47 +/- 0.91 vs 1.85 +/- 0.63 L/hr; P = 0.004) and increases in the theophylline area under the curve (233.48 +/- 58.99 vs 307.43 +/- 79.07 mg/L/hr; P = 0.003), peak concentration (13.2 +/- 2.8 vs 16.7 +/- 3.7 mg/L; P = 0.002), and trough concentration (6.4 +/- 2.5 vs 9.0 +/- 3.0 mg/L; P = 0.008). Despite the changes in theophylline pharmacokinetic parameters during cimetidine treatment, no significant differences in asthma symptom scores or side effects were seen when once-daily CTF-theophylline was administered concomitantly with cimetidine, ranitidine, or placebo.

Adult↗

PubMedDate not supplied

Dexamethasone phosphate stability and contamination of solutions stored in syringes.

The stability of 10 mg/mL dexamethasone sodium phosphate injection was evaluated using a validated, stability-indicating liquid chromatographic method during 91 days storage in glass and 55 days storage in plastic syringes with rubber plungers. The presence of accelerators, commonly used in the manufacture of rubber, mercaptobenzothiazole (MBT), tetramethyl thiuram disulfide (TMTD) and tetraethyl thiuram disulfide (TETD), was monitored on day 101 and after 18 months storage. During the 91-day study period there was no significant trend for dexamethasone phosphate concentrations in Glaspak syringes to decrease in solutions stored at room temperature or 4 degrees C. The concentration remaining in each syringe on the final day of analysis was greater than 95% of the initial concentration. In Monject plastic syringes there was no significant decrease in the dexamethasone phosphate concentration over 35 days with 1 mL syringes or 55 days with 3 mL syringes at either room temperature or 4 degrees C. The concentration remaining in each syringe on the final day of analysis was greater than 93% of the initial concentration. Analysis of samples for leachates on day 101 failed to demonstrate any contamination. However, re-analysis of the syringes following 18 months storage indicated contamination by a number of compounds. The results indicate that sorption of dexamethasone phosphate to the syringe barrel or plunger did not occur to a clinically important degree. We conclude that dexamethasone phosphate solutions (10 mg/mL) stored at 4 degrees C or 23 degrees C for up to 91 days in Glaspak syringes or 55 days in plastic Monject syringes will retain more than 93% of the initial dexamethasone concentration. Furthermore after 101 days there was no measurable contamination of the dexamethasone phosphate solution, although after 18 months considerable contamination was observed.

Chromatography, Liquid↗