Post on 10-Jun-2019
transcript
J. TACK, M.D., Ph.D.
TARGID
University of Leuven
Leuven, Belgium
www.targid.eu
PEPTIC ULCER DISEASEFrom stress to infection
Animal research
Clinical observations: Higher prevalence in taxi drivers
Higher prevalence in officers than in soldiers at the war front
PEPTIC ULCER DISEASEArguments in favor of stress
• Born 1951 Kalgoorlie, Australia• Graduated Medical school in Perth,
Australia, 1975• Internship and residency at Queen Elizabeth
II Medical Centre, Perth 1975-1979
• Training in internal medicine at Royal Perth Hospital from 1979 onwards; aimed at becoming a rheumatologist
• Gastroenterology division 1981; proposal to do some research project:
• Analysis of 20000 endoscopy reports or• Collaborate with Dr. Warren on bacteria
in the stomach
HELICOBACTER PYLORIBarry Marshall
• 1979: noticed bacteria on gastric biopsies showing chronic gastritis
• Showed the biopsies to 2 colleagues who "did not see any bacteria"
• Confirmed presence by electron microscopy
• Searched for similar cases; collected them and observed bacteria
• Met with Barry Marshall 1981
HELICOBACTER PYLORIRobin Warren
• Found the bacteria in 13/13 patients with duodenal ulcer and 24/28 patients with gastric ulcer
• After 6 months, Barry Marshall moved to the hematology ward. Meanwhile, they set up a 100 patient trial
• In June 1982, Barry Marshall was to be rotated to Port Hedland, 2000 km north of Perth
• Aim of the trial:• Presence in health and diseased stomach• Correlation with type and severity of disease• Culture• Follow-up of disease and infection status
HELICOBACTER PYLORIWarren & Marshall
• All attempts to culture failed• Easter 1982: sample left for 5 days (instead
of routine 2); culture growth obtained• Trial finalised May 1982
• Barry Marshall took the data to Port Hedland and analysed them there:• Significant correlation with presence of gastritis
• Significant correlation with presence of peptic ulcer (gastric but especially duodenal)
HELICOBACTER PYLORIWarren & Marshall
HELICOBACTER PYLORIWarren & Marshall
Duodenal ulcer Gastric ulcer
H. pyloriNSAIDCancer (Zollinger Ellison)Other
92% 70%
5% 1%2%
25%
3%
2%
• Data presented in October 1982 at local College of Physicians meeting; largely negative responses
• Barry Marshall took a job as senior registrar Gastroenterology at Fremantle Hospital end of 1982
• Drafted letter for Lancet; decided to submit two letters: one with Warren’s initial observations of bacteria and one with Warren & Marshall’s joint work
• Letters published June 1983
HELICOBACTER PYLORIWarren & Marshall
• Wrote abstract for Gastroenterological Society of Australia in Perth, February 1983: rejected
• Applied for NHMRC grant: rejected• Looked for grants from manufacturers of
ulcer drugs: rejected, except for manufacturer of bismuth preparation DeNol
• Confirmed antimicrobial effect of DeNol in cultures, not with cimetidine
• Submitted 100 patient paper to Lancet January 1984
HELICOBACTER PYLORIWarren & Marshall
• Confirmed antimicrobial effect of DeNol in cultures, not with cimetidine
• April 1983: small prospective treatment study with DeNol vs. Cimetidine; histology improvement with DeNol
• Observed synergism of bismuth with metronidazole
HELICOBACTER PYLORIWarren & Marshall
Special stain (modified Steinert) showing Helicobacter pylori colonies on the surface and in the pits
1. The organism must always be found in diseased subjects but not in healthy ones
2. The organism must be isolated from diseased animals and grown in pure culture away from the animal
3. The organism isolated in pure culture must initiate and reproduce the disease when reintroduced into susceptible subjects
4. The organism should be re-isolated from the experimentally infected animals
CHRONIC GASTRITISKoch’s postulates
• Attempts to infect pigs failed• Marshall inoculated himself in 1984
• No approval from EC or spouse
• initial biopsy was negative• he inoculated himself with H. pylori
cultured from a patient with excellent response to metronidazole
• He became sick after 7 days (nausea, vomiting, epigastric pain)
• New endoscopy on day 10: positive
CHRONIC GASTRITISKoch’s postulates
1. The organism must always be found in diseased subjects but not in healthy ones
2. The organism must be isolated from diseased animals and grown in pure culture away from the animal
3. The organism isolated in pure culture must initiate and reproduce the disease when reintroduced into susceptible subjects
4. The organism should be re-isolated from the experimentally infected animals
CHRONIC GASTRITISKoch’s postulates