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Index of papers about Mycobacterium paratuberculosis and Crohn's disease.

On this page I have listed all of the papers for which the full text has been provided on this web site, organized by category. All of these papers are available in full text, and most have their accompanying diagrams.




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Title Historical overview and current approaches in determining a mycobacterial etiology of Crohn's disease.
Author R. Chiodini
Journal In: Mulder and Tytgat GNJ (eds): Is Crohn's disease a mycobacterial disease. Dordrecht: Kluwer Academic Publishers, 1992, pp 1-15
Comments This review paper was written in 1991, and presented at a conference in the Netherlands. It is written by Dr R Chiodini, the founder of the International Association for Paratuberculosis, a group of 200 researchers from around the world who focus on Mycobacterium paratuberculosis, established in 1989. This review, much shorter than other review papers he has written, gives a thorough and highly readable overview of the history of research in the field, and the state of current research in 1991.

Title Crohn's disease and the mycobacterioses: a review and comparison of two disease entities..
Author R Chiodini
Journal 1989 Jan. Clinical Microbiology Reviews:2:90-117
Comments This is the most extensive review that Dr Chiodini has written. It discusses the subject from many different angles, mostly technical. It includes a complete history of the field, a detailed list of all of the main research efforts, and detailed discussions of evidence in those areas. However, because it was written in 1991, it was only up to date at that time. It stretches to many pages.

Title Mycobacteria and the aetiology of Crohn's disease.
Authors J. Hermon-Taylor, M. Tizard, J. Sanderson, K. Kempsell, N. Sumar, D. Milar, M. Loughlin, J. Ford and S. Withey.
Journal Inflammatory Bowel Disease, 1994.
Comments This paper describes Mycobacterium paratuberculosis in terms of its evolution and in terms of it's relationship with other disease-causing mycobacteria, such as tuberculosis and leprosy.

Title The Causation of Crohn's Disease and Treatment with Antimicrobial Drugs..
Author J. Hermon-Taylor
Journal Ital J Gastroenterol Hepatol. 1998 Dec;30(6):607-10
Comments This updated review from Prof. J. Hermon-Taylor reviews more recent developments in research relating to MAP and Crohn's Disease.

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Antibiotic treatment

Title Antimicrobial Agents and Crohn's disease: Do they have a therapeutic role?
Authors R.J. Chiodini.
Journal 1999 Ital J Gastro
Comments In this comprehensive and readable editorial, Dr. Chiodini discusses the role of antibiotics in Crohn's Disease, both as Supportive Therapy and as Curative Therapy.

Title Two-year outcomes analysis of Crohn's Disease treated with rifabutin and macrolide antibiotics
Authors G.P.H. Gui, P.R.S.Thomas, M.L.V.Tizard, J.Lake, J.D.Sanderson and J.Hermon-Taylor.
Journal 1997 Mar. Journal of Antimicrobial Chemotherapy, 39(3):393-400
Comments The principal author of this paper is Professor J Hermon-Taylor, one of the co-discoverers of the IS900 sequence, a genetic "fingerprint" that is unique to Mycobacterium paratuberculosis, and which is only way that this organism can be definitively distinguished from other Mycobacterium avium subspecies. This paper was the first to describe the results of treating Crohn's disease patients with a multi-drug regime which included macrolide antibiotics.

Title Clarithromycin against Mycobacterium avium complex infections.
Author LB Heifets
Journal 1996. Tubercle and Lung Disease:77:19-26
Comments This paper reviews the use antibiotics in the treatment of Mycobacterium avium complex(MAC) infections, "complex" meaning that it encompasses several distinct subspecies of Mycobacterium avium. These organisms are closely related to Mycobacterium paratuberculosis, the correct classification of this organism being Mycobacterium avium subspecies paratuberculosis. It describes how antibiotic treatment for MAC infections only became effective when the macrolide antibiotic clarithromycin was introduced, and that previously used anti-tuberculosis antibiotic regimes were ineffective in the treatment of MAC infection. This might explain why trials of antibiotic treatment for Crohn's disease, which have used anti-tuberculosis regimes, have failed. This paper also discusses other aspects of treatment, including the development of antibiotic resistance, possible companion drugs, etc.

Title Effects of Clarithromycin and Rifabutin Alone and in Combination on Intracellular and Extracellular Replication of Mycobacterium avium.
Authors N Mor, J Vanderkolk, N Mezo, And L Heifets
Journal December 1994. Antimicrobial Agents and Chemotherapy:38:2738-42
Comments This paper is a technical report of the activity of clarithromycin and rifabutin against Mycobacterium avium, and demonstrates that this combination is a highly effective one.

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Crossing the species barrier

Title Mycobacterium paratuberculosis Cervical Lymphadenitis followed five years later by terminal ileitis similar to Crohn's Disease.
Authors J Hermon-Taylor, N Barnes, C Clarke, and C Finlayson.
Journal Feb 1998. British Medical Journal:315:449-453.
Comments This paper was the first to describe the isolation of Mycobacterium paratuberculosis in bacillary form from in a human being, demonstrating that this organism is capable of mutating and crossing the species barrier to infect and cause disease in humans. The paper is in the form of a "Grand Round", i.e. a discussion between doctors of a clinical case. The case in question is that of a seven-year old boy, from whom the bacillary form Mycobacterium paratuberculosis was isolated. The boy went on to develop an Inflammatory Bowel Disease which the same as Crohn's disease.

Full text of this paper, with diagrams, also available from the British Medical Journal Website.

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Genetic research

Title On the Etiology of Crohn Disease.
Authors D. Mishina, P. Katsel, S.T. Brown, E.C.A.M. Gilberts, R.J. Greenstein.
Journal September 1996. Proceedings National Academy of Sciences USA:93:9816-9820.
Comments This paper was the first to describe the use of RNA techniques to search for paratuberculosis in people with Crohn's disease. RNA can only be produced by viable and multiplying organisms. The researchers found Mycobacterium paratuberculosis RNA in 100% of Crohn's disease patients, compared with 0% of controls. This paper also describes the split of Crohn's disease into the "Awareness &" and "Contained" forms, a characteristic which shared with other mycobacterial diseases, such as tuberculosis and leprosy.

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Mycobacterium paratuberculosis in food

Title Long-term sequelae to foodborne disease
Authors R.M. McDowell & M.D. McElvaine
Journal 1997. Rev. sci. tech. Off. int. Epiz:16(2):337-341
Comments This paper, written by two scientists from the United States Department of Agriculture, discusses, among other subjects, the link between Crohn's disease and Mycobacterium paratuberculosis and how ".... foodborne exposure would probably be the major source of human contamination [with Mycobacterium paratuberculosis]".

Title IS900 PCR To Detect Mycobacterium Paratuberculosis in Retail Supplies of Whole Pasteurized Cows' Milk in England and Wales.
Authors D. Millar, J. Ford, J. Sanderson, S. Withey, M. Tizard, T. Doran, and J. Hermon-Taylor.
Journal Sept 1996. Applied and Environmental Microbiology, p 3446-3452.
Comments This describes finding the genetic "fingerprint" (the IS900 sequence) of Mycobacterium paratuberculosis in retail supplies of cows milk in England and Wales. The paper uncovers substantial evidence that the not all of the Mycobacterium paratuberculosis bacteria detected were dead, i.e. that some of the bacteria were still alive.

Title Thermal Tolerance of Mycobacterium paratuberculosis.
Authors N. Sung and MT Collins.
Journal Mar 1998. Applied and Environmental Microbiology:64(3):999-1005.
Comments This is the most thoroughly conducted study in the thermal tolerance of Mycobacterium paratuberculosis. Sung and Collins used food microbiology techniques to determine the thermal tolerance of this organism, and found that it was capable of surviving commercial pasteurization, when there are more than 10 bacteria per millilitre in raw milk. The principal author of this paper, Dr Michael T. Collins, is the current President of the International Association for Paratuberculosis.

Title Effect of high-temperature, short-time (HTST) pasteurization on milk containing low numbers of Mycobacterium paratuberculosis.
Authors I.R. Grant, H.J. Ball and M.T. Rowe
Journal March 1998. Letters in Applied Microbiology 26 (2), 166-170.
Comments This laboratory simulation research, conducted by researchers at the Department of Food Science at Queen's University, Belfast and the Northern Ireland Department of Agriculture, concludes that Mycobacterium paratuberculosis is capable of surviving commercial pasteurization when there are more than ten bacteria per millilitre in raw milk.

Title Pasteurization of Mycobacterium paratuberculosis in whole milk.
Authors AF Hope, PA Tulk, and RJ Condron
Journal In: Proceedings of the Fifth International Colloquium on Paratuberculosis, Chiodini R. J., Hines, M., Collins MT (eds), pp 368-373.
Comments This research used a commercial pasteurizer unit to study the survivability of Mycobacterium paratuberculosis, and found that some of the organisms survived at temperatures up 82oC for 15 seconds, a full 10.3 oC above the HTST pasteurization temperature of 71.7oC.

Title Heat Inactivation of Mycobacterium paratuberculosis in Raw Milk: Are Current Pasteurization Conditions Effective?
Authors J. R. Stabel, E. M. Steadham, and C. A. Bolin
Journal Dec 1997. Applied and Environmental Microbiology. p. 4975-4977
Comments This the highly controversial research conducted by veterinarians at the United States Department of Agriculture which found that Mycobacterium paratuberculosis did not survive pasteurization.

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Epidemiology of Crohn's disease

Title Crohn's Disease in Olmsted County, Minnesota, 1940-1993: Incidence, Prevalence, and Survival.
Authors EV Loftus, Jr., MD. Silverstein, WJ. Sandborn, WJ. Tremaine, WS. Harmsen, and AR. Zinsmeister
Journal 1998. Gastroenterology:114:1161-1168.
Comments This paper describes the strong and continuing rise in the incidence and prevalence of Crohn's disease in the United States. This paper contains the most recent data available at this time.

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Immunotherapy for Crohn's disease

Title Immunotherapeutical approaches to Crohn's disease in view of a possible pathogenic role of Mycobacterial antigens.
Authors A. Stronkhorst, G.N.J. Tytgat, S.J.H. van Deventer.
Journal In: Mulder and Tytgat GNJ (eds): Is Crohn's disease a mycobacterial disease. Dordrecht: Kluwer Academic Publishers, 1992, pp 35-45.
Comments This paper is the first to raise the possibility that Crohn's disease might be treated by antibodies to Tumor Necrosis Factor-alpha (TNF-alpha). Elevated levels of TNF-alpha are a common symptom of mycobacterial diseases, and are a well documented feature of Mycobacterium paratuberculosis infection in animals. Elevated levels of TNF-alpha are also present in Crohn's disease. This fact is the basis of the new experimental treatment for Crohn's disease from Centocor Pharmaceuticals called Infliximab(Avakine). It is important to note that treatment with antibodies to TNF-alpha only attempts to reduce the levels of TNF-alpha in the body, it does not address the underlying cause of the disease, that results in the high levels of TNF-alpha in the first place.

Title Is immunotherapy with Mycobacterium vaccae appropriate to Crohn's disease?
Authors J.L. Stanford
Journal In: Mulder and Tytgat GNJ (eds): Is Crohn's disease a mycobacterial disease. Dordrecht: Kluwer Academic Publishers, 1992, pp 64-69.
Comments This paper discusses the the use of vaccination with harmless mycobacterium (Mycobacterium vaccae) in the treatment of the mycobacterial diseases tuberculosis and leprosy, and how this strategy might be applicable to Crohn's disease also.

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Johne's disease

Title Ruminant Paratuberculosis (Johne's disease): The current status and future prospects
Authors R.J. Chiodini, H.J. Van Kruiningen, and R.S. Merkal
Journal July 1984. Cornell Veterinarian:74(3):218-262.
Comments This extensive review of the state of Johne's disease research, written in 1984, is probably the most extensive review article on the subject ever written. Even though it is 14 years old, little has changed since that time, mostly due to lack of funding for research. Note that this paper is not hosted on this web site, but on the web site of the International Association for Paratuberculosis, an organization of 200 scientists from many different countries whose sole focus is Mycobacterium paratuberculosis, Mycobacterium avium and other related species of mycobacteria.

Title Johne's Disease - The International Perspective.
Authors M.T. Collins and E.J.B. Manning.
Journal Proceedings of the 99th Annual meeting of the United States Animal Health Association.
Comments This paper discusses the epidemiology of Mycobacterium paratuberculosis on a global basis. It discusses the prevalence of Johne's disease on a continent by continent and a country by country basis. The principal author of this paper, Dr Michael T. Collins, is the current President of the International Association for Paratuberculosis.

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