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Biomedical subjects

K Wareham

Publications and source records attributed to K Wareham.

4 recordsLinked to original sources

Effects of low-dose cimetidine on nocturnal acid secretion in healthy subjects.

The effects of 100 mg and 200 mg bedtime doses of cimetidine on nocturnal gastric acid secretion were examined in nine healthy subjects in a double blind, placebo controlled, randomised three way crossover study. Treatment was given at 23.00 hours and the gastric contents continually aspirated from midnight until 07.00 hours the following morning. Hourly aliquots were analysed for pH and acid output. Relative to placebo the 100 mg and 200 mg doses of cimetidine respectively increased mean pH by 2.22 and 2.63 units/h (P less than 0.001) with mean acid output decreasing by 0.95 and 0.98 mmol/h (P less than 0.001). Whilst mean pH was higher and mean acid output was lower for 200 mg cimetidine compared to 100 mg cimetidine the difference was not statistically significant. Mean hourly pH was consistently above pH 3 for 100% of the time for both doses of cimetidine whereas mean pH failed to reach this value at anytime on placebo. Low doses of cimetidine taken at bedtime effectively reduced nocturnal gastric acid secretion in healthy individuals.

Administration, Oral

Reversion of the attenuated and temperature-sensitive phenotypes of the Sabin type 3 strain of poliovirus in vaccinees.

Isolates of type 3 poliovirus from vaccine-recipients were characterized in terms of virulence, sensitivity of growth to high temperatures, and differences in genome structure from the Sabin type 3 vaccine strain. These included point mutations in the region of the genome coding for the structural proteins and in the 5' noncoding region, and the presence of type 1 or type 2 poliovirus genomic sequences resulting from intertypic recombination. Isolates from healthy vaccinees resembled those from vaccine-associated cases of poliomyelitis in all of these properties. Suppression of the temperature-sensitive phenotype was strictly correlated with reversion to virulence in nonrecombinant type 3 strains. Recombinant isolates were more attenuated than expected, even when they had lost all mutations known to attenuate the type 3 vaccine strain.

Base Sequence

The temperature sensitivity of the Sabin type 3 vaccine strain of poliovirus: molecular and structural effects of a mutation in the capsid protein VP3.

The growth of the Sabin strain of type 3 poliovirus is reduced at high temperatures compared to that of its virulent precursor strain Leon. Recombinant viruses have been generated from infectious cDNA clones and demonstrate that the temperature-sensitive (ts) phenotype is mainly attributable to a difference in residue 91 of the virion protein VP3. Examination of non-ts mutants derived in vitro or in vivo reveals the existence of second site mutations some of which are clearly able to suppress the ts phenotype. The location of residue 91 of VP3, and of a number of candidate suppressor mutations, in the atomic structure of the virion suggests that the ts phenotype may result in destabilization of the particle and that the suppressors may function by stabilizing specific interfaces. It is not yet clear whether the ts phenotype is expressed at the level of the particle or in the form of defects in assembly or uncoating of the virion, or all three.

Amino Acid Sequence