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Biomedical subjects

K W Somerville

Publications and source records attributed to K W Somerville.

At least 19 recordsLinked to original sources
PubMed1997

The inhibition of colon-26 adenocarcinoma development and angiogenesis by topical diclofenac in 2.5% hyaluronan.

Topical diclofenac in 2.5% hyaluronan inhibits basal cell carcinoma, actinic keratosis, and murine colon-26 growth in vivo. colon-26 tumor growth was preceded by angiogenesis and reduced apoptotic and mitotic indices. Diclofenac reduced proliferation and viability in vitro, and stimulated apoptosis. Hyaluronan inhibited proliferation and viability at 1 mg/ml but was inactive below this level. Topical application of diclofenac inhibited tumor prostaglandin synthesis and retarded angiogenesis and tumor growth (ratio of treatment:control, 0.174). The mitotic index remained unaltered in vivo, whereas the apoptotic index and necrosis were increased. Topical vehicle exhibited slight antitumor and antiangiogenesis activity. The substantial quantities of diclofenac delivered locally in hyaluronan may exhibit antitumor activity in similar fashion to those seen in vitro and explain its clinical efficacy.

Adenocarcinoma↗
PubMed1994

Endocarditis due to high level gentamicin resistant Enterococcus faecium.

We describe the first reported case in the literature of bacterial endocarditis caused by Enterococcus faecium that was highly resistant to gentamicin. The case is unusual in that it followed a successfully treated Streptococcus sanguis endocarditis. The micro-organism was susceptible only to the glycopeptide antibiotics, vancomycin and teicoplanin and to agents such as pristinamycin and daptomycin which are not routinely available for treatment. It illustrates the therapeutic dilemma posed by serious infections with such micro-organisms and supports previous observations that early heart valve replacement surgery may be necessary to achieve cure of endocarditis due to enterococci which are highly resistant to gentamicin. It further emphasises the importance of screening for high-level aminoglycoside resistance in enterococci in all life threatening enterococcal infections, including endocarditis, septicaemia and meningitis when aminoglycoside-penicillin synergy is required for successful treatment.

Aged↗
PubMed1988

Prophylaxis of aspirin-induced gastric mucosal bleeding with ranitidine.

The ability of ranitidine to protect the human gastric mucosa against aspirin-induced damage was investigated by timed measurements of blood loss collected by gastric washing. Ranitidine (150 mg) 1 h or 5 h before 900 mg aspirin (5 doses of each) over 48 h reduced subsequent mean bleeding from 7.7 microliters/10 min to 2.6 microliters/10 min or 3.4 microliters/10 min, respectively. Both regimens were antisecretory at the time of aspirin administration, as judged by a rise in the pH of the aspirated washings. The prolonged protection against aspirin-induced bleeding achieved with twice daily dosing with ranitidine has clinical potential in the management of patients taking anti-inflammatory drugs.

Adult↗
PubMed1987

Twenty-four-hour intragastric acidity and clinical trial of bedtime enprostil 70 micrograms compared with ranitidine 300 mg in duodenal ulcer.

The effects of bedtime 70 micrograms and twice daily 35 micrograms doses of enprostil on 24-hour intragastric acidity were investigated in nine duodenal ulcer patients in remission. Median nocturnal acidity decreased significantly by 30% with 35 micrograms twice daily, and by 48% with 70 micrograms at bedtime. In a clinical trial using bedtime dosing, 102 duodenal ulcer patients randomly received either ranitidine 300 mg or enprostil 70 micrograms. More ulcers healed after 4 and 8 weeks treatment with ranitidine than with enprostil (76% ranitidine vs 52% enprostil, at 4 weeks p = 0.0065 and 94% vs 68%, respectively at 8 weeks, P = 0.0007). However, 6 months after cessation of treatment there was no material difference in overall outcome. Despite combining mucosal protection with acid inhibition enprostil treatment conferred no advantage over simple acid inhibition.

Adult↗
PubMed1987

Oral phenytoin pharmacokinetics during omeprazole therapy.

1. In a double-blind crossover study 10 healthy males received either placebo or omeprazole (40 mg day-1) for 9 days, a single dose of phenytoin (300 mg) being taken on the seventh day. 2. Omeprazole significantly increased the area under the curve (0 to 72 h) of phenytoin (mean +/- s.e. mean) from 121.6 +/- 14.0 to 151.4 +/- 13.6 micrograms ml-1 h) (P less than 0.01). 3. The peak concentration, and apparent elimination half-life of phenytoin also tended to be increased though not significantly. 4. The omeprazole-phenytoin interaction observed may be clinically important because of the low therapeutic index associated with phenytoin.

Administration, Oral↗
PubMed1986

Reduction by enprostil of aspirin-induced blood loss from human gastric mucosa.

Enprostil's ability to protect human gastric mucosa against aspirin-induced damage was investigated in a controlled study. Damage was assessed as blood loss into gastric washings measured spectrophotometrically using orthotolidine in the presence of hydrogen peroxide. Phenol red was used to correct for recovery rates. Five doses of aspirin, 600 mg, given over 48 hours increased blood loss ninefold compared with placebo. Administration of enprostil 35 micrograms twenty minutes before each dose of aspirin halved this blood loss. After enprostil administration, the pH of both aspirated gastric juice and washings was significantly elevated, suggesting that an antisecretory dose had been used. Increased losses of phenol red occurred following both aspirin and enprostil administration, suggesting enhanced gastric emptying or possible absorption of phenol red as a result of aspirin damage. Side effects related mainly to the alimentary system were associated with enprostil treatment. Enprostil reduced aspirin-induced mucosal blood loss but the mechanism is unclear.

Adult↗
PubMed1986

Effect of famotidine on oxidative drug metabolism.

Famotidine, a new H2-receptor antagonist was tested for drug interactions using 14C-aminopyrine and antipyrine. Elimination of these model drugs was studied before and during 8 days of famotidine dosing in 8 healthy volunteers. Famotidine 40 mg b.d. did not inhibit aminopyrine 14CO2 half-life or antipyrine clearance although an unexpected mild enzyme inducing effect could not be excluded. It is unlikely that famotidine will inhibit hepatic drug metabolism during routine clinical use as the daily dose is expected to be 40 mg/day but interactions should be looked for if more prolonged or larger doses are used.

Adult↗
PubMed1986

Strategies for preventing aspirin-induced gastric bleeding.

Prostaglandins protect the gastric mucosa in animals, but the evidence of an effect independent of pH changes in man is not overwhelming. Gastrointestinal bleeding because of non-steroidal anti-inflammatory drugs is a major clinical problem, which we have investigated in a model system measuring bleeding rates caused by short-term administration of aspirin. Of the various strategies tested, only those that elevated intra-gastric pH reduced aspirin-induced bleeding.

Animals↗
PubMed1985

Somatostatin in treatment of haematemesis and melaena.

630 patients with haematemesis and melaena were randomly allocated to treatment by a constant intravenous infusion of either somatostatin or an apparently identical placebo in a double-blind controlled trial. Rebleeding was less common in treated patients (70 episodes in 315 individuals compared with 89 episodes in 315 controls) but the difference was not significant. Operation rates were virtually identical (35 treated patients and 34 controls), while there were slightly more deaths in the treated group than in the controls (31 and 25, respectively). These results are in clear disagreement with those of other smaller series. Though it is not possible to be completely sure that treatment is not useful in some individuals, earlier claims of marked benefit seem unlikely to be justified.

Clinical Trials as Topic↗
PubMed1985

L-643.441: an H2-receptor antagonist with potent and long-lasting effects in man.

Submaximal dose pentagastrin tests conducted in normal male volunteers with L-643.441, a novel histamine H2-receptor antagonist, indicate that it is a potent and long-acting inhibitor of gastric acid secretion. The effect appears dose-dependent and single doses of 50 mg are sufficient to reduce secretory potential by at least 50% when examined 24 h after drug administration. No adverse effects attributable to treatment were observed.

Adult↗
PubMed1985

The effects of sucralfate upon phenytoin absorption in man.

The possible influence of sucralfate on phenytoin absorption was investigated in a double-blind, placebo controlled study. Concomitant administration of 1 g sucralfate reduced the absorption of 300 mg phenytoin capsules by 20% as measured by the area under the curve from 0-48 h. This could be of significance in epileptic patients stabilised on phenytoin in whom sucralfate is used in ulcer treatment.

Adult↗
PubMed1985

Intravenous omeprazole rapidly raises intragastric pH.

Twenty four hour intragastric acidity was measured in five duodenal ulcer patients studied at least three times. The effects of different dosage regimens of intravenous omeprazole was compared with placebo. Mean intragastric acidity from 1000 to 0800 was 34.3 +/- 4.3 mmol/l on placebo. After omeprazole 80 mg at 0900 and 40 mg at 1700 mean acidity was 2.1 +/- 0.9 mmol/l and after omeprazole 80 mg at 0900 and 80 mg at 1700 it was 0.7 +/- 0.2 mmol/l. pH remained above 4.0 for about 80% of recordings with these regimens and for only 5% with placebo. Three of the five patients also received omeprazole 80 mg at 0900, 40 mg at 1700 and 40 mg at 0100 when pH remained above 4.0 for 90% of recordings with 99% inhibition of acidity. Omeprazole rapidly raised intragastric pH in all patients and maintained a gastric pH of greater than 4.0 for most of the time. Large doses of IV omeprazole were required compared with studies using the oral compound.

Adult↗
PubMed1985

Stones in the common bile duct: experience with medical dissolution therapy.

Thirty-one patients with radiolucent common bile duct stones received medical treatment. Nineteen had Rowachol, a terpene preparation, eight (42%) achieving complete stone disappearance within 3 to 48 months. Fifteen (including 3 of the above) took Rowachol with bile acid (chenodeoxycholic in 11, ursodeoxycholic in 4) for 3 to 60 months: 11 (73%) achieved complete dissolution within 18 months. Persistent symptoms and complications settled on conservative management: 8 (25%) patients required admission (2 biliary colic, 1 obstructive jaundice, 4 cholangitis, 1 pancreatitis). One patient died of a myocardial infarction during recovery from pancreatitis; the other continued treatment, 2 achieving complete dissolution/disappearance. Oral dissolution therapy with Rowachol and bile acids should be considered when endoscopic sphincterotomy or surgery is not feasible, but careful attention to potential complications is required while stones persist.

Adult↗