History in our lifetime: the changing nature of refractory duodenal ulcer in the era of histamine H2 receptor antagonists.
OBJECTIVE
This prospective cohort observational study, set in a district hospital, presents our experience (1976-1993) of duodenal ulcer refractory to histamine H2 receptor antagonists (defined as not healed after 3 months' treatment) and comments on onset, outcome and spontaneous decline.


METHODS
Patients were treated mainly with cimetidine, the dose being titrated (up to 3.2 g daily) according to response, and followed by serial check endoscopy and clinical assessment.


RESULTS
A total of 782 of the 4032 duodenal ulcer patients seen (19%) were refractory; the incidence declined over time: 1976-1978: 124/379 (33%); 1979-1983: 390/1240 (31%); 1984-1988: 190/1295 (15%); 1989-1993: 78/1118 (7%). A total of 344 were refractory for the first time on their first healing course and 174 on their second. Healing was achieved in two-thirds after a mean of 7 months' treatment with cimetidine 1 g; treatment for 12-18 months with higher doses was needed in the remainder. Relapse occurred in up to three-quarters of patients despite maintenance cimetidine up to 3 g daily. Eventually 47 patients were operated upon but good results (i.e., no ulcer, no symptoms) were achieved in only 11.


CONCLUSIONS
Refractoriness was common until recently. Its incidence has declined dramatically, the fall preceding the newer more powerful treatment with proton pump inhibitors and with Helicobacter pylori eradication. We suggest this phenomenon is a modern example of a spontaneous change in the natural history of the disease.
Rotherham General Hospitals NHS Trust, Moorgate Road, Rotherham, South Yorkshire S60 2UD, UK. bardhan.sec@rothgen.nhs.uk
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Bardhan
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Nayyar
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Royston
D000328:Adult; D002927:Cimetidine / Q000627:therapeutic use*; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004351:Drug Resistance; D004381:Duodenal Ulcer / Q000150:complications / Q000503:physiopathology / Q000628:therapy*; D005260:Female; D005500:Follow-Up Studies; D006635:Histamine H2 Antagonists / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010438:Peptic Ulcer Hemorrhage / Q000453:epidemiology; D010439:Peptic Ulcer Perforation / Q000453:epidemiology; D011446:Prospective Studies; D011899:Ranitidine / Q000627:therapeutic use*; D012008:Recurrence; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology
D006635:Histamine H2 Antagonists; D002927:Cimetidine; D011899:Ranitidine