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D Gatehouse

Publications and source records attributed to D Gatehouse.

28 records · Page 2Linked to original sources
PubMed1983

The bacterial mutagenicity of three naturally occurring indoles after reaction with nitrous acid.

Three naturally occurring indoles were evaluated for potential nitrosatability using the Nitrosation Assay Procedure (NAP test) as recommended by the World Health Organisation. All three indoles i.e. tryptophan, tryptamine and 5-hydroxy-tryptamine were nitrosated to products which were directly mutagenic for S. typhimurium TA1537. In addition, the products of nitrosation of tryptamine and 5-hydroxytryptamine were also mutagenic for strains TA1538, TA98 and TA1535 without the need for metabolic activation. The sensitivities of the frameshift-detecting strains TA1537, TA1538 and TA98 were of particular interest, since nitroso compounds are characteristically base-substitution mutagens. The mutagenic effects of the products formed after nitrosation of each indole at pH 3.6, were eliminated in the presence of S9 mix. This was not the case when the nitrosation assay was carried out at pH 2.6. At this pH the mutagenicity of the nitrosated products varied in the presence of S9 mix and depended upon the nature of the indole undergoing nitrosation, and the bacterial test strain utilised for the mutagenicity assay. This indicated that more than one mutagenic product was responsible for the observed effects. As well as pH, a number of other factors influenced the formation of mutagenic nitroso products. Most notably, the concentrations of precursor compounds (sodium nitrite, and indole) present in the NAP test were of critical importance. As the sodium nitrite concentration was reduced from that recommended by the W.H.O. (40 mM), so the mutagenicity decreased. For all three compounds significant mutagenic effects were lost at sodium nitrite concentrations below 15 mM. In conclusion the data presented in this paper clearly demonstrates that individuals are chronically exposed to naturally occurring substances which readily nitrosate in excess nitrous acid and yield bacterial mutagens.

Biotransformation↗
PubMed1980

Mutagenicity of 1,2 ring-fused acenaphthenes against S. typhimurium TA1537 and TA1538: structure-activity relationship.

A number of 1,2-ring fused acenaphthenes, together with the parent compounds acenaphthene and acenaphthylene, were evaluated for mutagenicity, using the Pour-Plate Technique with S. tpyhimurium strains TA1538 and TA1537. Although acenaphthene and acenaphthylene were non-mutagenic, all the 1,2-ring fused acenaphthene were found to be indirect frameshift mutagens in strain TA1537. The chemical nature of the 1,2-fused ring did not appear to be important for mutagenic activity against TA1537, however, its nature did affect the mutagenesis of strain TA1538. Only acenaphthenes fused with a pyrimidine or pyrazine ring were capable of mutating the hiD 3052 locus of TA1538. Substitution at the 8-position of the ring system with an amino group rendered the molecule inactive against TA1538, whilst substitution at the 10-position only reduced, but did not eliminate the mutagenic effect against TA1538. Methyl substitution at various sites on the molecule modified the mutagenic activity against TA1537, and indicated the formation of an electrophilic species (epoxide) at the 2,3-position of the acenaphthene nucleus. The incorporation of a competitive substrate for ring hydroxylation (naphthalene) reduced the mutagenic effect of acenaphthopyrimidine against TA1537 and confirmed this assumption. However, naphthalene did not reduce the mutagenic effect of the compound against TA1538, indicating the possible formation of a second metabolite by an alternative enzymic pathway. The fusion of a pyridine ring to the system to give a pentacyclic compound resulted in a molecule sufficiently planar to allow for a weak direct mutagenic effect against TA1537.

Acenaphthenes↗
PubMed1979

One-dose antibiotic prophylaxis against wound infection after appendicectomy: a randomized trial of clindamycin, cefazolin sodium and a placebo.

Two hundred and fifty patients were admitted to a prospective randomized trial of single dosage prophylaxis against wound infection after appendicectomy. There were 12 exclusions, 72 patients received placebo, 81 received 600 mg i.m. clindamycin phosphate and 85 received 1 1 g i.m. cefazolin sodium, the agent being given in the anaesthetic room. Clindamycin produced a significant reduction in the overall rate of wound infection from 33 per cent in the controls to 17 per cent. In cases with a gangrenous or perforated appendix the infection rate in controls was 78 per cent; this was reduced to 44 per cent by a single dose of clindamycin. Cefazolin significantly reduced the number of aerobic organisms isolated from wound infections, but did not significantly reduce the incidence of wound infection. We conclude that anaerobic organisms are more important than faecal aerobic organisms in the pathogenesis of wound infection after appendicectomy.

Adult↗
PubMed1978

Prediction of wound sepsis following gastric operations.

Gastric aspirates were obtained from 12 healthy volunteers, 49 patients with duodenal ulcer, 14 with gastric ulcer and 35 with gastric carcinoma. The mean total viable bacterial counts in these groups were as follows: volunteers 0, duodenal ulcer 3.8 X 10(1), gastric ulcer 6.95 X 10(4), carcinoma 1.9 X 10(7) organisms/ml. The incidence of wound sepsis in patients without antibiotic cover was; duodenal ulcer 17 per cent, gastric ulcer 38 per cent, carcinoma 56 per cent. Regardless of the underlying pathology, patients with counts greater than 5 X 10(6) organisms/ml in the gastric aspirate had a 93 per cent incidence of wound sepsis, compared with 16 per cent in patients with counts of less than 5 X 10(6) organisms/ml (P less than 0.001). In the group with high counts all except one of the wound infections were caused by organisms present in the stomach at the time of operation. There was a good correlation in the bacteriology of apirates obtained during preoperative endoscopy compared with operative nasogastric samples (n = 31) both for viable counts (r = 0.93) and for the counts of individual organisms. Therefore, preoperative endoscopy can be used to identify patients who are at risk of developing wound sepsis after gastric surgery.

Duodenal Ulcer↗
PubMedDate not supplied

A randomized controlled trial to compare anal dilatation with lateral subcutaneous sphincterotomy for anal fissure.

A prospective randomized trial has compared manual dilatation of the anus (MDA)during general anesthesia with lateral subcutaneous spincterotomy (LSS) during local anesthesia for the management of anal fissure in 156 patients. The two groups were similar with respect to age, sex and symptoms. There was no difference in the duration of time off work or early complications of treatment but, four months after operation, 93 per cent claimed to have been improved by MDA compared with 78 per cent after LSS (P less than 0.05). Recurrent fissure was recorded in 13 patients after LSS (29 per cent) compared with four (10 per cent) after MDA (P less than 0.02). There was a significant reduction in anal pressure at four months (P less than 0.02) after MDA, (123 +/- 31 to 97 +/-33) and LSS (127 +/- 36 to 104 +/- 32), but the anal pressure remained unchanged by operation in all patients where pressures were measured with recurrent fissure. These data indicate that MDA gives better results than LSS for treatment of anal fissure and that successful treatment is associated with a reduction in anal pressure.

Adult↗