The effect of physiological concentrations of bile acids on in vitro growth of Mycobacterium tuberculosis.

BACKGROUND: Intestinal tuberculosis occurs mainly in the terminal ileum and caecum, where the concentration of bile acids is lowest, and rarely in the upper digestive tract. OBJECTIVES: We examined the effect of physiological concentrations of bile acids on the in vitro growth of Mycobacterium tuberculosis (MTB). METHODS: The 4 major bile acids, lithocolic acid, cholic acid, deoxycholic acid and chenodeoxycholic acid, were added to individual Lowenstein-Jensen (LJ) culture media at physiological concentrations. A combined LJ medium was also prepared using all 4 bile acids. These were double-diluted 4 times by the addition of LJ media. Each culture medium was inoculated with the H37Rv strain of MTB and incubated at 37°C for 8 weeks. MTB growth was measured at 2 and 8 weeks in a semiquantitative fashion using cut-offs of >5, >10, >20, >100 colony-forming units. RESULTS: All lithocolic acid cultures showed uninhibited TB growth at 2 and 8 weeks. Chenodeoxycholic acid, deoxycholic acid and cholic acid alone, and in combination, showed concentration-dependent inhibition of MTB growth at 2 and 8 weeks. Four cultures were lost to contamination. CONCLUSIONS: Certain bile acids alone and in combination, at physiological concentrations, inhibit the growth of MTB in vitro. This might explain why intestinal TB occurs in the ileocaecum in the majority of cases and why gallbladder TB is very rare.

Alterations in the cytological composition of the juxta-scar villous mucosa after ulcer therapy with sucralfate or cimetidine.

A comparative light-microscopic morphometric analysis of non-metaplastic mucosa obtained from the pretreatment juxta-duodenal ulcer (DU) villous mucosa of 10 patients and from the first part of the duodenum of 5 normal volunteers revealed a significant increase (P less than 0.01) in the number of goblet cells (GCs) per 100 microns of villous mucosa (GC/100 microns). Such an increase was thought to represent a mucoprotective response by the mucosa to the corrosive lumenal factors that may cause or maintain ulceration. A similar morphometric analysis was performed on the endoscopically healed juxta-scar villous mucosa of 11 patients successfully treated for 6 weeks with sucralfate (5 patients) or cimetidine (6 patients). After treatment with cimetidine, GC/100 microns was reduced to near-normal levels, whereas after sucralfate therapy it was significantly raised (P less than 0.05). The difference in GC/100 microns after treatment with either sucralfate or cimetidine was significant at the P less than 0.02 level. The apparent drug-mediated difference in the cytological composition of the healed mucosa was thought to be a function of the pharmacodynamic mechanisms of action of the two drugs in promoting DU healing. It is proposed that the retention of GC hyperplasia after curative therapy with sucralfate may predisposed patients so treated to extended periods of remission.

Comparative study of sucralfate 2 grams twice daily versus sucralfate 1 gram four times daily in the treatment of benign gastric ulcers in outpatients.

In a double-blind, randomized study, we compared the healing of gastric ulcer during a twice-daily regimen of 2 g sucralfate or sucralfate 1 g q.i.d. Patients receiving the former therapy received the tablets one-half hour before breakfast and at bedtime. Patients receiving sucralfate 1 g q.i.d. received their therapy 30 minutes before breakfast, lunch, and supper, and at bedtime. The study included 52 patients with endoscopically proven gastric ulcer; 41 patients completed the study. Healing was endoscopically assessed at 8 weeks and 12 weeks. After 8 and 12 weeks the healing rate for sucralfate 2 g b.i.d. was 67% and 92%, respectively; the healing rate of sucralfate 1 g q.i.d. was 59% and 71%, respectively. No statistically significant difference was found between the two regimens. The results suggest that 2 g sucralfate twice daily is as effective in the healing of gastric ulcer as 1 g sucralfate q.i.d.

Colonoscopic features of early intestinal tuberculosis. Report of 11 cases.

The colonoscopic findings in 11 patients with early tuberculous colitis included erythema alone in 1 patient (9.1%), mucosal nodules indistinguishable from small adenoma in 8 (72.7%), aphthous ulcers in 3 (27.3%), and a deformed ileocaecal valve in 3 (27.3%). The caecum was the principal site of disease and the ileum was found to be normal in the 4 patients in whom it was entered. In 3 patients (27.3%), skip lesions were present. Acid-fast bacilli were present on histological examination in all cases--in the mucosa of 4 patients and the submucosa or lamina propria in 7 patients.

Symptoms and investigative findings in 145 patients with tuberculous peritonitis diagnosed by peritoneoscopy and biopsy over a five year period.

This study analysed clinical features and laboratory investigations in 145 patients with tuberculous peritonitis diagnosed by peritoneoscopy at this hospital between 1984 and 1988. Tuberculous peritonitis was found in 2% of all patients with tuberculosis and in 59.8% of all those with abdominal tuberculosis admitted to the hospital during the study period. Tuberculous peritonitis was more common in women than men (1.4:1) and was most frequently encountered in the third and fourth decades of life. The commonest presenting symptoms were abdominal swelling (73.1%), fever and night sweats (53.8%), anorexia (46.9%), weight loss (44.1%), and abdominal pain (35.9%). The mean duration of symptoms was 1.5 months. Ascites was the commonest (95.2%) physical sign. Tuberculin skin testing was positive in 57.6% of patients (n = 118). The mean erythrocyte sedimentation rate was 75 mm/1st hour (n = 58). Chest radiography on 98 patients showed pleuropulmonary pathology in 40 patients (40.8%). Sputum examination confirmed active pulmonary tuberculosis in 26 patients. The ascitic fluid was an exudate in 96.4% and a transudate in 3.6% of patients, with 91.3% showing a straw coloured ascites. Cirrhosis, detected by biopsy specimen, was a finding in 6.2% of patients.

Gastrointestinal tuberculosis in patients with pulmonary tuberculosis.

Proven or suspected intestinal tuberculosis was diagnosed in 23 (46 per cent) of 50 patients with smear-positive, cavitating pulmonary tuberculosis. The diagnosis was regarded as proven in 14 patients and suspected in the remaining nine. The frequency of proven gastrointestinal disease increased with the severity of the pulmonary tuberculosis. Small intestinal disease was encountered in only two patients. Small mucosal lesions in the caecum were the most commonly detected pathological features. Colonoscopy was of particular value in establishing the diagnosis, which could not be predicted from the patients' abdominal signs or gastrointestinal symptoms.

Incidence of Campylobacter pylori in patients with upper gastro-intestinal symptoms.

Antral mucosal biopsy specimens were examined microbiologically and histologically for the presence of Campylobacter pylori in 224 patients with upper gastrointestinal symptoms. The gastric mucosa of 183 patients (82%) were found to harbour C. pylori. C. pylori was strongly associated with the presence of histological gastritis (93%) and was detected in only 10% of 30 patients in whom histological examination of gastric biopsy specimens was negative. Endoscopically diagnosed duodenal lesions were more strongly associated with the presence of C. pylori than gastric lesions (P less than 0.001). The histological demonstration of spiral bacteria in biopsy specimens was a more sensitive method for the diagnosis of C. pylori than culture (80% v. 65%).

A comparative study of misoprostol and ranitidine in the healing of duodenal ulcers. A double-blind controlled trial.

This study was undertaken to evaluate the safety and therapeutic efficacy of the prostaglandin E1 analogue, misoprostol, when compared with ranitidine in the healing of duodenal ulcers. Sixty patients with endoscopically proven duodenal ulcers participated in a double-blind controlled randomised trial comparing misoprostol 400 microgram and ranitidine 150 mg, both given twice daily orally for up to 8 weeks. Patient characteristics at entry into the trial were similar in the two treatment groups, except that there were 6 women in the ranitidine-treated group and none in the misoprostol-treated group. Ulcers were 0.3 - 2.0 cm in length. Healing was determined by endoscopy at 4 weeks; if ulcers were not healed, endoscopy was repeated at 8 weeks. All patients were given antacid tablets to be used as needed for pain up to a maximum of 8 tablets per day. Healing rates at 4 weeks for a total of 58 evaluate patients in the two treatment groups were: misoprostol (15/29; 51.7%) and ranitidine (20/29; 69.0%). Healing rates at 8 weeks for a total of 55 evaluable patients in the two treatment groups were: misoprostol (21/27; 77.8%) and ranitidine (24/28; 85.7%). The healing rate for misoprostol did not differ significantly from that for ranitidine at both the 4-week (P = 0.28) and the 8-week assessment (P = 0.68). Diarrhoea was the most common side-effect but was usually mild. It occurred in 11 patients on misoprostol and 1 patient on ranitidine. These results indicate that misoprostol 400 micrograms was taken twice daily orally for up to 8 weeks is effective and safe for the treatment of duodenal ulcer.

Diagnosis of tuberculosis by detection of mycobacterial antigen in pleural effusions and ascites.

We describe a method for the diagnosis of pleural and peritoneal tuberculosis by the detection of tuberculous antigens using an enzyme-linked immunosorbent assay. Eleven tuberculous pleural fluid and 10 tuberculous ascitic fluid samples were studied by this technique, using 10 non-tuberculous pleural fluid and 14 non-tuberculous ascitic fluid samples as controls. An absorbance value of 0.3 was found to separate the tuberculous groups from their controls to a statistically significant extent (ascitic fluid P less than 0.05; pleural fluid P less than 0.01).

Dysphagia and dystrophia myotonica. A case report.

A 26-year-old Indian man who presented with a long history of vomiting, upper abdominal pain and dysphagia is described. The dysphagia had been largely overlooked and investigation delayed. The diagnosis of dystrophia myotonica (DM) was apparent on clinical examination and his symptoms responded well to phenytoin therapy. The cause of his symptoms is discussed and the importance of recognizing dysphagia and other gastro-intestinal manifestations of DM is emphasized.