840
T-cell receptors that use particular Vp Since the total spectrum of Vp families is genes. genetically determined, individuals will vary in their susceptibility to diseases associated with this type of response (autoimmune disorders). Such variation has long been associated with inheritance of certain major histocompatibility complex (MHC) alleles and, although the functional link between that locus and TCR is obscure, it is undoubtedly real.7 Dalgleish et al sought to test the validity of the autoimmune concept of AIDS by searching for evidence of selective involvement of T cells expressing particular TCR Vp genes. Within the limitations of the technology available, they obtained a positive result in that patients in the early stages of HIV-1 infection seem to have expanded the population of lymphocytes bearing T-cell receptors of the Vp5’3 subfamily. It will be considerably more difficult, in view of the general lymphocyte depletion of advanced disease, to show subsequent accelerated elimination of the same population, but the findings accord with the growing body of data pointing to immunopathogenic mechanisms as the key to HIVinduced disease. Although we do not know for certain which components of the virus may behave as alloantigen or superantigen, resolution of the threedimensional structure of the envelope glycoprotein reveals a conserved region with striking homology to the alloactivating determinant of human MHC.88 Dalgleish et al believe their model suggests that the gp 120/41 envelope glycoprotein mimics a conserved domain of MHC class II and class I. Proponents of the autoimmune hypothesis of AIDS still have important questions to answer. In other settings, superantigen or alloantigen responses are blocked rather easily by antibodies directed against the foreign determinant or against TCR or MHC/ So why is the process not aborted in most individuals by one or more of the many antibodies generated in the course of HIV infection? Furthermore, while participation of particular V (3 gene families and MHC alleles in pathogenesis may explain the extreme species specificity of HIV-associated disease, why does the involvement of these polymorphic determinants in man show only relative specificity in the sense that ultimately all CD4 lymphocytes are destroyed irrespective of their TCR characteristics? Similarly, while most autoimmune disorders affect only the susceptible minority, it appears that the great majority of human beings infected with HIV will eventually get AIDS. Those rare individuals who remain well and immunologically intact for ten years or more after HIV seroconversion represent an especially important group for future studies.
expressing
1. Duesberg PH. Human immunodeficiency virus and acquired immunodeficiency syndrome: correlation but not causation. Proc Natl Acad Sci USA 1989; 86: 755-64. Jaffe HW. Duesberg, HIV and AIDS. Nature 1990; 345:
2. Weiss RA, 659-60.
S, Morris C, Sprent J. Extrathymic tolerance of mature T cells: clonal elimination as a consequence of immunity. Cell 1990; 63: 1249-56. 4. Kawake Y, Ochi A. Programmed cell death and extrathymic reduction of V&bgr;6-CD4-T cells in mice tolerant to staphylococcal enterotoxin B. Nature 1991; 349: 245-48. 5. Kappler JW, Roehm N, Marrack P. T cell tolerance by clonal elimination in the thymus. Cell 1987; 49: 273-80. 6. Watson JD, Hopkins NH, Roberts JW, Steitz JA, Weiner AM. Molecular biology of the gene. 4th ed. Menlo Park: Benjamin/ Cummings, 1987: 882-86. 7. Miller A, Hafler DA, Weiner HL. Tolerance and suppressor mechanisms in experimental autoimmune encephalomyelitis: implications for immunotherapy of human autoimmune diseases. FASEB J 1991; 5: 2560-66. 8. Hounsell L, Renouf D, Liney D, Dalgleish AG, Habeshaw JA. A proposed molecular model of the carboxyterminus of gp120 showing structural features of a T cell alloepitope. Mol Aspects Med (in press). 3. Webb
The Helicobacter genus: we are nine
now
Helicobacter, first published in October, 1989, now seems to have justified its creation, encompassing a respectable number of distinct species. H pylori was the first clinically significant organism in the genus, and was cultured initially in Western Australia ten years ago.2-4 The name Campylobacter pyloridis was suggested in 1983,5 but grammatical rules required the change to C pylori.6 It was Marshall,4 recalling Armstrong’s observation that the flagella were sheathed, who suggested that the organism was not a Campylobacter; sheathed flagella are now regarded as the characteristic The new genus name,
feature of all members of the Helicobacter genus. H pylori was also shown to have a unique cellular fatty acid profile.By 1988, the Perth microbiology team had sufficient evidence to justify a new genus name, and H pylori was the type species; simultaneously, the ferret gastric spiral organism, H mustelae, was included in the genus.1 Probably the first member of the genus to be cultured was a spiral organism in the lower gut of rats and mice,8 now named H muridarum.9 Five Helicobacter species have been isolated from the stomach, three from the lower gut, and one from both sites. The three other gastric organisms are H felis found in the cat and dog, H nemestrinae in a pigtailed macaque," and "H acim.myx" in cheetahs with gastritis.12 Two human pathogens associated with gastroenteritis were originally put in the Campylobacter genus but are now known as H cinaedi and H fennelliae.l3 "Flexispira rappini"14 was first isolated from aborted lambs15 but has recently been found in human beings with gastroenteritis16 and in the stomachs of beagle dogs. 17 Although this organism shows some phenotypic differences from H pylori, it possesses urease and genotypically should be in the Helicobacter genus as "H rappini".9°13 Most reports of spiral organisms in the stomachs of human beings and animals have not distinguished the shorter, loosely spiralled H pylori from the longer, tightly spiralled "(Mon7/MM AewK’MM", which has not been cultured and characterised and therefore
tightly been cultured and characterised and therefore
841
named. The report of beagle dogst7 showed three electron micrographs-the first was "H rappini", the second H felis, and the third "G hominis". By means of a specific DNA probe for the Helicobacter genus, three more distinct, unnamed species of Helicobacter have been discovered in the faeces of terns, gulls, house sparrows, and pigsl9 and another ferret Helicobacter species distinct from H mustelae has been found in ferret feces. The urease enzymes of gastric helicobactersH pylori, H mustelae, and H felis-have two pH optima, including one at acid pH,2O,21 but the latter is missing from the ureases of helicobacters that colonise the lower gut, such as H muridarum.21 It has been suggested that possession of such a urease is a prerequisite for gastric colonisation. Why should we take an interest in these animal helicobacters? H felis can be inoculated into mice to produce an intense colonisation and inflammation of the stomach.22 Such a model could be used to study the antibacterial effect of single drugs and combinations. Unfortunately, H pylori administered to ferrets that were free of H mustelae did not colonise. However, sparse colonisation followed oral inoculation of H felis into these animals. 23 Many workers have erroneously concluded that minimum inhibitory concentrations of antibiotics determined at neutral pH against H pylori are a reliable guide to therapy. Numerous drugs are much less active at acid pH,24 and single drugs effective in vitro--eg, erythromycin-fail totally in vivo.25 Animal helicobacters and animal models will be required to test any H pylori vaccine; a successful vaccine could prevent H pylori gastritis and its sequelae. Duodenitis due to H pylori is an essential prerequisite for nearly all duodenal ulcers,26 and a high proportion of gastric ulcers are H pylori-associated. In populations at high risk of gastric cancer, H pylori is much more common in children than in low-risk populations, and leads to lifelong infection. 27 Excessive salt intake and a diet low in antioxidants from fresh fruit and vegetables are important factors in the development of gastric cancer, but H pylori infection is a strong candidate for the previously unknown epidemiological factor that characterises not
officially
high-risk populations.27 1. Goodwin CS, Armstrong JA, Chilvers T, et al. Transfer of Campylobacter pylori and Campylobacter mustelae to Helicobacter gen. nov. as Helicobacter pylori comb. nov. and Helicobacter mustelae comb.
respectively. Int J Syst Bacteriol 1989; 39: 397-405. BJ, Royce H, Annear DI, et al. Original isolation of Campylobacter pyloris from human gastric mucosa. Microbios Lett 1984; 25: 83-88. 3. Warren JR. Unidentified curved bacilli on gastric epithelium in active chronic gastritis. Lancet 1983; i: 1273. 4. Marshall B. Unidentified curved bacilli on gastric epithelium in active chronic gastritis. Lancet 1983; i: 1273-74. 5. Skirrow MB. Taxonomy and biotyping. In: Pearson AD, Skirrow MB, Rowe B, Davies JR, Jones DM, eds. Campylobacter II. Proceedings of the 2nd International Workshop on Campylobacter Infections. London: Public Health Laboratory Service, 1983. 33-38. 6. Marshall BJ, Goodwin CS. Revised nomenclature of Campylobacter pyloridis. Int J Syst Bacteriol 1987; 37: 68.
Armstrong JA, Wee SH. Unusual cellular fatty acids and distinctive ultrastructure in a new spiral bacterium (Campylobacter pyloridis) from the human gastric mucosa. J Med
7. Goodwin CS, McCulloch RK,
Microbiol 1985; 19: 257-67. 8.
9.
Phillips MW, Lee A. Isolation and characterisation of a spiral bacterium from the crypts of rodent gastrointestinal tracts. Appl Environ Microbiol 1983; 45: 675-83. Lee A, Phillips MW, O’Rourke JL, et al. Helicobacter muridarum sp. nov.,
microaerophilic helical bacterium with a novel ultrastructure isolated from the intestinal mucosa of rodents. Int J Syst Bacteriol 1992; 42: 27-36. 10. Paster BJ, Lee A, Dewhirst FE, et al. The phylogeny of Helicobacter felis nov., a spiral-shaped bacterium isolated from the gastric mucosa of the cat, Helicobacter mustelae, and related bacteria. Int J Syst Bacteriol 1991; 41: 31-38. 11. Bronsdon MA, Goodwin CS, Sly LI, et al. Helicobacter nemestrinae sp. nov., a spiral bacterium found in the stomach of a pigtailed macaque (Macaca nemestrina). Int J Syst Bacteriol 1991; 41: 148-53. 12. Eaton KA, Radin MJ, Fox JG, et al. Helicobacter acinonyx, a new species of Helicobacter isolated from cheetahs with gastritis. Microb Ecol Hlth Dis 1991; 4 (spec suppl): 104. 13. Vandamme P, Falsen E, Rossau R, et al. Revision of Campylobacter, Helicobacter, and Wolinella taxonomy: emendation of generic descriptions and proposal of Arcobacter gen. nov. Int J Syst Bacteriol 1991; 41: 88-103. 14. Bryner JH. "Flexispira rappini", gen nov sp nov: a motile, ureaseproducing rod similar to Campylobacter pyloridis. In: Kaijser B, Falsen E, eds. Campylobacter IV, Proceedings of the 4th International Workshop on Campylobacter Infection. Sweden: University of Gotëborg, 1987: 440-42. 15. Kirkbride CA, Gates CE, Collins JE, Ritchie AE. Ovine abortion associated with an anaerobic bacterium. J Am Vet Med Assoc 1986; 186: 789-91. 16. Archer JR, Romero S, Ritchie AE, et al. Characterization of an unclassified microaerophilic bacterium associated with gastroenteritis. J Clin Microbiol 1988; 26: 101-05. 17. Henry GA, Long PH, Burns JL, Charbonneau DL. Gastric spirillosis in beagles. Am J Vet Res 1987; 48: 831-36. 18. McNulty CAM, Dent JC, Curry A, et al. New spiral bacterium in gastric mucosa. J Clin Pathol 1989; 42: 585-91. 19. Paster BJ, Dewhirst FE, Seymour C, Fraser GJ, Fox JG. Helicobacter species isolated from bird and swine feces. Microbial Ecol Health Dis 1991; 4 (spec suppl) S107. 20. Taylor MB, Goodwin CS, Karim QN. Two urease activities with different pH optima in Campylobacter pylori and similar organisms. FEMS Microbiol Letters 1988; 55: 259-62. 21. Ferrero RL, Lee A. The importance of urease in acid protection for the gastric-colonising bacteria, Helicobacter pylori and Helicobacter felis sp. nov. Microbiol Ecol Health Dis 1991; 4: 121-34. 22. Lee AL, Fox JG, Otto G, Murphy J. A small animal model of human Helicobacter pylori active chronic gastritis. Gastroenterology 1990; 99: 1315-23. 23. Fox JG, Otto G. Murphy JC, et al. Gastric colonization of the ferret with Helicobacter species: natural and experimental infections. Rev Infect Dis 1991; 13 (suppl 8): S671-80. 24. McNulty CAM, Dent JC, Ford GA, Wilkinson SP. Inhibitory antimicrobial concentrations against Campylobacter pylori in gastric mucosa. J Antimicrob Chemother 1988; 22: 729-38. 25. McNulty CAM, Gearty JC, Crump B, et al. Campylobacter pyloridis and associated gastritis: investigator blind, placebo controlled trial of bismuth salicylate and erythromycin ethylsuccinate. Br Med J 1986; 293: 645-49. 26. Goodwin CS. Duodenal ulcer, Campylobacter pylori, and the "leaking roof" concept. Lancet 1988; ii: 1467-69. 27. Correa P. Is gastric carcinoma an infectious disease? N Engl J Med 1991; 325: 1170-71. a
Warm heart surgery
nov.,
2. Marshall
Lancet readers who
come across
papers
advocating
"warm heart surgery"12 may well be puzzled by this apparent wave of enthusiasm emanating from Canada and the USA for normothermic cardiopulmonary
bypass. The techniques that made cardiac surgery possible developed in the 1950s. Moderate hypothermia to about 30°C was described by a Canadian group3 and perfected at the Middlesex Hospital in London by were
T-cell receptors that use particular Vp Since the total spectrum of Vp families is genes. genetically determined, individuals will vary in their susceptibility to diseases associated with this type of response (autoimmune disorders). Such variation has long been associated with inheritance of certain major histocompatibility complex (MHC) alleles and, although the functional link between that locus and TCR is obscure, it is undoubtedly real.7 Dalgleish et al sought to test the validity of the autoimmune concept of AIDS by searching for evidence of selective involvement of T cells expressing particular TCR Vp genes. Within the limitations of the technology available, they obtained a positive result in that patients in the early stages of HIV-1 infection seem to have expanded the population of lymphocytes bearing T-cell receptors of the Vp5’3 subfamily. It will be considerably more difficult, in view of the general lymphocyte depletion of advanced disease, to show subsequent accelerated elimination of the same population, but the findings accord with the growing body of data pointing to immunopathogenic mechanisms as the key to HIVinduced disease. Although we do not know for certain which components of the virus may behave as alloantigen or superantigen, resolution of the threedimensional structure of the envelope glycoprotein reveals a conserved region with striking homology to the alloactivating determinant of human MHC.88 Dalgleish et al believe their model suggests that the gp 120/41 envelope glycoprotein mimics a conserved domain of MHC class II and class I. Proponents of the autoimmune hypothesis of AIDS still have important questions to answer. In other settings, superantigen or alloantigen responses are blocked rather easily by antibodies directed against the foreign determinant or against TCR or MHC/ So why is the process not aborted in most individuals by one or more of the many antibodies generated in the course of HIV infection? Furthermore, while participation of particular V (3 gene families and MHC alleles in pathogenesis may explain the extreme species specificity of HIV-associated disease, why does the involvement of these polymorphic determinants in man show only relative specificity in the sense that ultimately all CD4 lymphocytes are destroyed irrespective of their TCR characteristics? Similarly, while most autoimmune disorders affect only the susceptible minority, it appears that the great majority of human beings infected with HIV will eventually get AIDS. Those rare individuals who remain well and immunologically intact for ten years or more after HIV seroconversion represent an especially important group for future studies.
expressing
1. Duesberg PH. Human immunodeficiency virus and acquired immunodeficiency syndrome: correlation but not causation. Proc Natl Acad Sci USA 1989; 86: 755-64. Jaffe HW. Duesberg, HIV and AIDS. Nature 1990; 345:
2. Weiss RA, 659-60.
S, Morris C, Sprent J. Extrathymic tolerance of mature T cells: clonal elimination as a consequence of immunity. Cell 1990; 63: 1249-56. 4. Kawake Y, Ochi A. Programmed cell death and extrathymic reduction of V&bgr;6-CD4-T cells in mice tolerant to staphylococcal enterotoxin B. Nature 1991; 349: 245-48. 5. Kappler JW, Roehm N, Marrack P. T cell tolerance by clonal elimination in the thymus. Cell 1987; 49: 273-80. 6. Watson JD, Hopkins NH, Roberts JW, Steitz JA, Weiner AM. Molecular biology of the gene. 4th ed. Menlo Park: Benjamin/ Cummings, 1987: 882-86. 7. Miller A, Hafler DA, Weiner HL. Tolerance and suppressor mechanisms in experimental autoimmune encephalomyelitis: implications for immunotherapy of human autoimmune diseases. FASEB J 1991; 5: 2560-66. 8. Hounsell L, Renouf D, Liney D, Dalgleish AG, Habeshaw JA. A proposed molecular model of the carboxyterminus of gp120 showing structural features of a T cell alloepitope. Mol Aspects Med (in press). 3. Webb
The Helicobacter genus: we are nine
now
Helicobacter, first published in October, 1989, now seems to have justified its creation, encompassing a respectable number of distinct species. H pylori was the first clinically significant organism in the genus, and was cultured initially in Western Australia ten years ago.2-4 The name Campylobacter pyloridis was suggested in 1983,5 but grammatical rules required the change to C pylori.6 It was Marshall,4 recalling Armstrong’s observation that the flagella were sheathed, who suggested that the organism was not a Campylobacter; sheathed flagella are now regarded as the characteristic The new genus name,
feature of all members of the Helicobacter genus. H pylori was also shown to have a unique cellular fatty acid profile.By 1988, the Perth microbiology team had sufficient evidence to justify a new genus name, and H pylori was the type species; simultaneously, the ferret gastric spiral organism, H mustelae, was included in the genus.1 Probably the first member of the genus to be cultured was a spiral organism in the lower gut of rats and mice,8 now named H muridarum.9 Five Helicobacter species have been isolated from the stomach, three from the lower gut, and one from both sites. The three other gastric organisms are H felis found in the cat and dog, H nemestrinae in a pigtailed macaque," and "H acim.myx" in cheetahs with gastritis.12 Two human pathogens associated with gastroenteritis were originally put in the Campylobacter genus but are now known as H cinaedi and H fennelliae.l3 "Flexispira rappini"14 was first isolated from aborted lambs15 but has recently been found in human beings with gastroenteritis16 and in the stomachs of beagle dogs. 17 Although this organism shows some phenotypic differences from H pylori, it possesses urease and genotypically should be in the Helicobacter genus as "H rappini".9°13 Most reports of spiral organisms in the stomachs of human beings and animals have not distinguished the shorter, loosely spiralled H pylori from the longer, tightly spiralled "(Mon7/MM AewK’MM", which has not been cultured and characterised and therefore
tightly been cultured and characterised and therefore
841
named. The report of beagle dogst7 showed three electron micrographs-the first was "H rappini", the second H felis, and the third "G hominis". By means of a specific DNA probe for the Helicobacter genus, three more distinct, unnamed species of Helicobacter have been discovered in the faeces of terns, gulls, house sparrows, and pigsl9 and another ferret Helicobacter species distinct from H mustelae has been found in ferret feces. The urease enzymes of gastric helicobactersH pylori, H mustelae, and H felis-have two pH optima, including one at acid pH,2O,21 but the latter is missing from the ureases of helicobacters that colonise the lower gut, such as H muridarum.21 It has been suggested that possession of such a urease is a prerequisite for gastric colonisation. Why should we take an interest in these animal helicobacters? H felis can be inoculated into mice to produce an intense colonisation and inflammation of the stomach.22 Such a model could be used to study the antibacterial effect of single drugs and combinations. Unfortunately, H pylori administered to ferrets that were free of H mustelae did not colonise. However, sparse colonisation followed oral inoculation of H felis into these animals. 23 Many workers have erroneously concluded that minimum inhibitory concentrations of antibiotics determined at neutral pH against H pylori are a reliable guide to therapy. Numerous drugs are much less active at acid pH,24 and single drugs effective in vitro--eg, erythromycin-fail totally in vivo.25 Animal helicobacters and animal models will be required to test any H pylori vaccine; a successful vaccine could prevent H pylori gastritis and its sequelae. Duodenitis due to H pylori is an essential prerequisite for nearly all duodenal ulcers,26 and a high proportion of gastric ulcers are H pylori-associated. In populations at high risk of gastric cancer, H pylori is much more common in children than in low-risk populations, and leads to lifelong infection. 27 Excessive salt intake and a diet low in antioxidants from fresh fruit and vegetables are important factors in the development of gastric cancer, but H pylori infection is a strong candidate for the previously unknown epidemiological factor that characterises not
officially
high-risk populations.27 1. Goodwin CS, Armstrong JA, Chilvers T, et al. Transfer of Campylobacter pylori and Campylobacter mustelae to Helicobacter gen. nov. as Helicobacter pylori comb. nov. and Helicobacter mustelae comb.
respectively. Int J Syst Bacteriol 1989; 39: 397-405. BJ, Royce H, Annear DI, et al. Original isolation of Campylobacter pyloris from human gastric mucosa. Microbios Lett 1984; 25: 83-88. 3. Warren JR. Unidentified curved bacilli on gastric epithelium in active chronic gastritis. Lancet 1983; i: 1273. 4. Marshall B. Unidentified curved bacilli on gastric epithelium in active chronic gastritis. Lancet 1983; i: 1273-74. 5. Skirrow MB. Taxonomy and biotyping. In: Pearson AD, Skirrow MB, Rowe B, Davies JR, Jones DM, eds. Campylobacter II. Proceedings of the 2nd International Workshop on Campylobacter Infections. London: Public Health Laboratory Service, 1983. 33-38. 6. Marshall BJ, Goodwin CS. Revised nomenclature of Campylobacter pyloridis. Int J Syst Bacteriol 1987; 37: 68.
Armstrong JA, Wee SH. Unusual cellular fatty acids and distinctive ultrastructure in a new spiral bacterium (Campylobacter pyloridis) from the human gastric mucosa. J Med
7. Goodwin CS, McCulloch RK,
Microbiol 1985; 19: 257-67. 8.
9.
Phillips MW, Lee A. Isolation and characterisation of a spiral bacterium from the crypts of rodent gastrointestinal tracts. Appl Environ Microbiol 1983; 45: 675-83. Lee A, Phillips MW, O’Rourke JL, et al. Helicobacter muridarum sp. nov.,
microaerophilic helical bacterium with a novel ultrastructure isolated from the intestinal mucosa of rodents. Int J Syst Bacteriol 1992; 42: 27-36. 10. Paster BJ, Lee A, Dewhirst FE, et al. The phylogeny of Helicobacter felis nov., a spiral-shaped bacterium isolated from the gastric mucosa of the cat, Helicobacter mustelae, and related bacteria. Int J Syst Bacteriol 1991; 41: 31-38. 11. Bronsdon MA, Goodwin CS, Sly LI, et al. Helicobacter nemestrinae sp. nov., a spiral bacterium found in the stomach of a pigtailed macaque (Macaca nemestrina). Int J Syst Bacteriol 1991; 41: 148-53. 12. Eaton KA, Radin MJ, Fox JG, et al. Helicobacter acinonyx, a new species of Helicobacter isolated from cheetahs with gastritis. Microb Ecol Hlth Dis 1991; 4 (spec suppl): 104. 13. Vandamme P, Falsen E, Rossau R, et al. Revision of Campylobacter, Helicobacter, and Wolinella taxonomy: emendation of generic descriptions and proposal of Arcobacter gen. nov. Int J Syst Bacteriol 1991; 41: 88-103. 14. Bryner JH. "Flexispira rappini", gen nov sp nov: a motile, ureaseproducing rod similar to Campylobacter pyloridis. In: Kaijser B, Falsen E, eds. Campylobacter IV, Proceedings of the 4th International Workshop on Campylobacter Infection. Sweden: University of Gotëborg, 1987: 440-42. 15. Kirkbride CA, Gates CE, Collins JE, Ritchie AE. Ovine abortion associated with an anaerobic bacterium. J Am Vet Med Assoc 1986; 186: 789-91. 16. Archer JR, Romero S, Ritchie AE, et al. Characterization of an unclassified microaerophilic bacterium associated with gastroenteritis. J Clin Microbiol 1988; 26: 101-05. 17. Henry GA, Long PH, Burns JL, Charbonneau DL. Gastric spirillosis in beagles. Am J Vet Res 1987; 48: 831-36. 18. McNulty CAM, Dent JC, Curry A, et al. New spiral bacterium in gastric mucosa. J Clin Pathol 1989; 42: 585-91. 19. Paster BJ, Dewhirst FE, Seymour C, Fraser GJ, Fox JG. Helicobacter species isolated from bird and swine feces. Microbial Ecol Health Dis 1991; 4 (spec suppl) S107. 20. Taylor MB, Goodwin CS, Karim QN. Two urease activities with different pH optima in Campylobacter pylori and similar organisms. FEMS Microbiol Letters 1988; 55: 259-62. 21. Ferrero RL, Lee A. The importance of urease in acid protection for the gastric-colonising bacteria, Helicobacter pylori and Helicobacter felis sp. nov. Microbiol Ecol Health Dis 1991; 4: 121-34. 22. Lee AL, Fox JG, Otto G, Murphy J. A small animal model of human Helicobacter pylori active chronic gastritis. Gastroenterology 1990; 99: 1315-23. 23. Fox JG, Otto G. Murphy JC, et al. Gastric colonization of the ferret with Helicobacter species: natural and experimental infections. Rev Infect Dis 1991; 13 (suppl 8): S671-80. 24. McNulty CAM, Dent JC, Ford GA, Wilkinson SP. Inhibitory antimicrobial concentrations against Campylobacter pylori in gastric mucosa. J Antimicrob Chemother 1988; 22: 729-38. 25. McNulty CAM, Gearty JC, Crump B, et al. Campylobacter pyloridis and associated gastritis: investigator blind, placebo controlled trial of bismuth salicylate and erythromycin ethylsuccinate. Br Med J 1986; 293: 645-49. 26. Goodwin CS. Duodenal ulcer, Campylobacter pylori, and the "leaking roof" concept. Lancet 1988; ii: 1467-69. 27. Correa P. Is gastric carcinoma an infectious disease? N Engl J Med 1991; 325: 1170-71. a
Warm heart surgery
nov.,
2. Marshall
Lancet readers who
come across
papers
advocating
"warm heart surgery"12 may well be puzzled by this apparent wave of enthusiasm emanating from Canada and the USA for normothermic cardiopulmonary
bypass. The techniques that made cardiac surgery possible developed in the 1950s. Moderate hypothermia to about 30°C was described by a Canadian group3 and perfected at the Middlesex Hospital in London by were
