Necrotizing proctitis caused by Streptococcus pyogenes.

We report the case of a 65-year-old patient with peritonitis, septicaemia and toxic shock syndrome in whom the primary focus of infection was acute purulent proctitis with necrosis. Streptococcus pyogenes serotype T28R28 was isolated from blood culture and peritoneal pus. The patient recovered after a prolonged period of intensive therapy and four abdominal operations including anterior resection of the rectum. We believe this to be the first clinical description of streptococcal necrotizing proctitis.

Prospective evaluation of dynamic contrast enhanced magnetic resonance imaging in the evaluation of fistula in ano.

Forty-two patients with a suspected diagnosis of fistula in ano underwent prospective comparison of digital rectal examination, dynamic contrast enhanced magnetic resonance imaging (DCEMRI) and surgical exploration. There were five discordancies: DCEMRI showed an ischiorectal abscess and track with no enteric connection in one patients who at operation was found to have a well epithelialized primary fistula. Four patients with fistulas on DCEMRI had no enteric opening found at surgery and were treated as having sinuses. Long-term follow-up has shown failure to heal in all patients and further surgery confirmed missed fistula. Compared with final outcome measures DCEMRI had a sensitivity of 97 per cent and specificity of 100 per cent in the detection of fistula. DCEMRI also identified more secondary tracks and was more accurate at identifying complex fistulas than either digital rectal examination alone or surgical exploration.

Effect of vitamin C upon gastric mucosal O6-alkyltransferase activity and on gastric vitamin C levels.

The repair enzyme O6-alkyltransferase will repair O6-methylguanine adducts in human DNA. In gastric mucosal DNA these adducts may be formed as a result of exposure to nitrosamines within the gastric lumen. The formation of these nitrosamines may be inhibited by vitamin C. We have examined the effect of oral vitamin C supplementation upon intragastric vitamin C levels and gastric mucosal O6-alkyltransferase levels in 48 patients. Intragastric vitamin C levels were significantly elevated in those patients with normal gastric mucosal histology after treatment, although a variable response in intragastric vitamin C to supplementation was seen in the presence of chronic atrophic gastritis. Gastric mucosal O6-alkyltransferase activities ranged from 100 to 950 fmol/mg protein before vitamin C administration. The range of enzyme activity was similar after the course of vitamin C (62-1137 fmol/mg) but O6-alkyltransferase activities were found to be higher in 33 of the 48 patients following treatment (P < 0.01). Once again this effect was more pronounced in patients with normal gastric mucosa than those displaying evidence of chronic atrophic gastritis. We speculate that inhibition of intragastric nitrosation by vitamin C results in decreased formation of O6-methylguanine-DNA. In consequence, less O6-alkyltransferase is consumed in repairing these adducts resulting in higher tissue levels of this enzyme.

DNA damage as measured by 32P-postlabelling in normal and pre-malignant gastric mucosa.

DNA was extracted from the gastric mucosa of 69 patients and analysed for the presence of DNA adducts by 32P-postlabelling. Adduct levels found in patients with histologically normal gastric mucosa were compared with levels found in patients displaying evidence of chronic atrophic gastritis or intestinal metaplasia, both of which may be considered pre-malignant conditions. Adduct patterns were the same for all patients, but the highest adduct levels were found in the latter two groups. Mean adduct levels were also higher in patients with abnormal gastric mucosa, but there was no statistically significant difference in adduct levels between the normal and pre-malignant groups (P > 0.05, Mann-Whitney U test). Thus DNA adduct levels do not correlate with the presence of histological abnormalities in the stomach and are not useful as a marker of malignant potential.

Effect of vitamin C supplementation on gastric mucosal DNA damage.

The effect of oral vitamin C supplementation on intragastric ascorbate levels and gastric mucosal DNA damage as measured by the 32P-postlabelling assay was assessed in 43 patients. In patients with normal gastric mucosa, treatment with vitamin C resulted in elevation of intragastric ascorbate levels in all cases. In the presence of chronic atrophic gastritis, however, the effect was variable. Gastric mucosal DNA damage was decreased in 28 of the 43 patients after vitamin C supplementation (P = 0.01; Wilcoxon sign rank test). This supports epidemiological evidence that suggests vitamin C may exert a protective effect against the development of gastric cancer.

DNA damage in the stomach after vagotomy measured by 32P-postlabelling.

This study analysed gastric mucosal DNA by 32P-postlabelling in a series of patients who have had previous vagotomy for benign peptic ulcer disease. DNA adduct levels were found to be significantly higher in patients who had had previous truncal vagotomy than in those who had had previous highly selective vagotomy (p < 0.001). Intragastric bile concentrations were also considerably higher in patients after truncal vagotomy but there was no correlation between intragastric bile concentrations and DNA adduct levels. These results suggest that, although duodenogastric reflux may be a cause of gastric mucosal DNA damage in the stomach after vagotomy, measurement of total intragastric bile does not accurately reflect genotoxic insult.

O6-alkyltransferase activity in normal and abnormal gastric mucosa.

The activity of the DNA repair enzyme O6-alkyltransferase has been studied in a series of stomachs with abnormal gastric mucosa and the activities found compared with those in normal stomachs. Enzyme activities found in stomachs with the macroscopic abnormalities of gastric ulcer, duodenal ulcer or gastric cancer were not significantly different from normal. In those stomachs where there was histological evidence of chronic atrophic gastritis or intestinal metaplasia however enzyme activities (mean 398 fmole/mg) were significantly higher than normal (mean activity 228 fmole/mg activity P < 0.001). We speculate that the conditions which stimulate these histological changes also give rise to induction of O6-alkyltransferase.

Smoking-related DNA adducts in human gastric cancers.

DNA was extracted from the tumour tissue of 26 patients (18 smokers, 8 non-smokers) undergoing surgery for gastric cancer, and analyzed for the presence of DNA adducts by the 32P-post-labelling method. Adducts were detected in all samples tested, and adduct levels ranged from 2 adducts/10(8) nucleotides to 60 adducts/10(8) nucleotides. In male subjects, adduct levels were significantly greater in the DNA of smokers than in that of non-smokers. These results support epidemiological data suggesting that smoking is a risk factor for gastric cancer.

O6-alkyltransferase activity in normal human gastric mucosa.

The spectrum of activity of the DNA repair enzyme O6-alkyltransferase has been studied in a large series of normal stomachs in order to establish the baseline range of values for this enzyme. Sixty-eight patients with histologically normal stomachs were biopsied during the course of upper gastrointestinal endoscopy and the biopsies assayed for O6-alkyl-transferase activity. A wide spectrum of activity was found with values ranging from 38 fmol O6-guanine extracted/mg protein to over 400 fmol/mg. This suggests that there may be wide inter-individual differences in susceptibility to alkylating actions in the human gastric mucosa.

Aortic root triangulation as a cause of sudden death.

We have reviewed an autopsy series of thirty-six patients who died suddenly after receiving a Starr--Edwards aortic valve prosthesis. In fifteen of the thirty-six explanted valves, the aortic outlet was narrowed with the three-legged prosthetic cage causing a triangular distortion of the wall. In the remaining twenty-one patients, the cause of sudden death was not related to failure of the mechanical valve. Although aortic root triangulation would appear to be an uncommon complication with the Starr--Edwards prosthesis, these findings emphasise the need to carefully size the aortic root diameter at the time of surgery, whilst the known problems of morbidity and mortality with mechanical heart valves should continue to stimulate those developing conservative valve reconstruction.

Selection of resistance to gentamicin and netilmicin in the faecal flora following prophylaxis for colo-rectal surgery.

The selection of aminoglycoside-resistant bowel flora, following the administration of either gentamicin or netilmicin in combination with metronidazole for prophylaxis, during colo-rectal surgery in 88 patients has been examined. Both antibiotic regimens resulted in the selection of an aminoglycoside-resistant flora in a total of 57 (65%) of patients: in half of the patients there was a net gain in the aminoglycoside-resistant flora, and in 13 (15%) one aminoglycoside-resistant strain present prior to prophylaxis was displaced by another following operation. Three patients (3%) lost aminoglycoside-resistant strains after prophylaxis. Most of the resistant organisms selected were considered to be of little importance as potential pathogens, at least in the short term. In only a small minority (5%) of patients were aminoglycoside-resistant enterobacteria isolated. Aminoglycoside-resistant Staphylococcus aureus was not isolated. Of the resistant enterobacteria, only one strain, an isolate of Enterobacter cloacae selected in a patient receiving gentamicin, carried a resistance determinant which was self-transmissible to Escherichia coli.