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Intestinal permeability in patients with Crohn's disease and their relatives
Commentaries
Intestinal and their
permeability relatives
in patients
with Crohn’s
disease
D. Hollander
1 See related
article
on page
680-5
1
The gastrointestinal tract performs a dual role: it absorbs needed nutrients but, simultaneously, it must prevent the absorption of harmful substances from the lumen into the systemic environment of the body. Its ability to prevent the absorption of potentially harmful substances is referred to as “intestinal permeability”. Substances with the potential to cause harm come from both the external environment and from bacteria in the lumen that produce a wide variety of antigens and secretions. One of the most important functions of the gastrointestinal tract is to maintain an effective barrier against the penetration and absorption of harmful environmental and luminal factors into the body through the gastrointestinal mucosa. This function is called “the barrier function” or the “permeability” of the gastrointestinal tract ’ . Evidence is accumulating that one of the underlying factors in the genesis of Crohn’s disease is a defective permeability barrier that allows antigens from food, the environment and bacteria in the lumen to penetrate through the gastrointestinal surface mucosa into the intestinal wall and the systemic environment 23. Evidence to support this hypothesis includes a marked increase in intestinal permeability of patients with Crohn’s disease and some lo-20% of their clinically healthy relatives 3 4. The increase in permeability both in patients and their healthy relatives is markedly enhanced by the ingestion of acetylsalicylic acid (ASA) 5 6. In contrast, household members, such as spouses, do not show an increase in permeability with the ingestion of ASA ‘. This finding suggests that ASA ingestion influences the genetically determined component of intestinal permeability of patients with Crohn’s disease and their healthy relatives but does not influence environmentally determined permeability characteristics s. A recent report documents the development of clinical Crohn’s disease in one of the relatives who, initially, was clinically normal but did have an increase in their intestinal permeability 9. This finding demonstrates that an abnormality in intestinal permeability is a predisposing factor in the development of active Crohn’s disease in a genetically predisposed relative of patients with Crohn’s disease. Inert, non metabolized, water-soluble probes with
cross-sectional diameters of 4-30 Angstroms are used to measure intestinal permeability. The probes are administered orally to subjects whose urine is collected over the next few hours. Some fraction of the ingested probes penetrates the gastrointestinal mucosal barrier and is excreted in the urine where their concentrations are measured. The greater the permeability the greater the amount of the ingested probes that penetrates the intestinal barrier and appears subsequently in the urine. The co-administration of ASA and the probes accentuate and enhance the abnormal permeability of patients with Crohn’s and their clinically healthy relatives 5 6. Why the accentuation occurs is not known, but one must wonder whether long-term ingestion of ASA or related compounds might not instigate or hasten the onset of Crohn’s disease in those individuals with a genetic predisposition for the disease. The bulk of evidence suggests that clinical measurements of intestinal permeability assess the permeability of the tight junctions between enterocytes and not the permeability of the lipid cell membrane of the enterocytes ’ ‘I. The tight junctions open or close intermittently and allow water, nutrients and luminal antigens to penetrate into the lamina propria of the intestine and to enter the systemic environment 12. The cross-sectional size of the permeability probe and the size of the tight junction seem to determine where the probe transits the intestinal barrier lo. The intestinal tight junctions are smaller and more numerous at the villous tips and larger but less numerous in the crypts between villi. In Crohn’s disease, it is the larger-sized probes, such as lactulose, that demonstrate an increase in permeability. This finding suggests that the abnormality in Crohn’s may reside at the base of the villi and in the crypts but not at the villous tips I. Many spurious factors can influence the rate of intestinal permeability. They include smoking, the ingestion of alcohol, ASA and other non-steroidal anti-inflammatory compounds, and the simultaneous ingestion of food with the probe. In order to avoid errors in the assessment of permeability, the study subjects must abstain from food when the probe is being administered and from smoking, alcohol, ASA and non-steroidal anti-inflammatory drugs (NSAIDs) during the 2 weeks prior to the study IX. The laboratory methods for measuring permeability
649
Commentaries
probes in the urine are difficult and exacting. Furthermore, they vary in their sensitivity and reproducibility. Most rely on column chromatographic separation of the probes and a variety of detection systems. Some of the confusion in the literature regarding the results of permeability studies stems from unreliable laboratory measurement systems. It is useful to correct the results of permeability measurements for transit, collection and assay artifacts by the simultaneous administration of both a small and a large probe and to express the results as a ratio of the two probes. The rationale for expressing the results as a ratio is based on the assumption that confounding extraneous factors, such as gastric emptying, intestinal transit, intestinal blood flow, and urinary clearance, will be eliminated from the results if one probe that is not affected by the disease itself is administered and measured simultaneously with one that is affected by the diseased intestinal wall. Since the permeability of small marker molecules, such as mannitol or rhamnose, is not affected by Crohn’s disease, one or the other is frequently used as a correction factor in expressing the results of permeability studies. Simultaneously, larger molecules, such as lactulose or chromium-labelled ethylenediaminetetraacetic acid (EDTA), are used to assess the influence of Crohn’s disease on permeability itself because the absorption of both molecules is affected by the disease. The final ratio between the small and large probes is used to correct the data for spurious factors, other than the permeability characteristics of the abnormal epithelium itself 14. Polyethylene glycol 400 (PEG 400) was used as a marker molecule in some of the initial studies of permeability in Crohn’s disease 3. The problem with its use is that the different molecular weight species of PEG 400 have the same cross-sectional diameters, and thus traverse the intestine at the same rate, and provide no correlation between their molecular weights and permeability. More reliable results are obtained when either lactulose or EDTA are used as the larger probes and mannitol - or “rhamnose” - are used as the smaller ones and the data are corrected to eliminate artifacts caused by transit time or blood flow.15. The important question of whether the increase in intestinal permeability of relatives of patients with Crohn’s disease is genetically determined or is due to environmental factors has been raised by several research groups x. The issue was raised because some of the spouses of patients with the disease have increased intestinal permeability. It has been clearly demonstrated that ASA accentuates the genetic abnormality found in Crohn’s disease patients and their clinically normal relatives, but when ASA is given to the spouses of patients with Crohn’s disease there is no accentuation of the rate of perme-
650
ability 7. These findings with ASA confirm that the increase in permeability of patients with Crohn’s disease and their clinically healthy relatives is caused by genetic, rather than environmental, factors while spouses of the patients may have increased intestinal permeability because of environmental factors. It has also been demonstrated, recently, that antisaccharomyces antibodies found in healthy relatives of patients with Crohn’s disease are found predominantly in relatives of patients with familial Crohn’s disease rather than those with sporadic Crohn’s disease 16. Since the antibodies would occur due to abnormal permeability of saccharomyces or an antigenic component of the fungus, these findings lend support to the conclusion that an increase in intestinal permeability in the relatives of patients with Crohn’s disease is a genetic and not an environmental factor. In the current issue of Digest Liver Dis (2001;33:6805), investigators from Naples and Pavia report their findings about intestinal permeability in patients with Crohn’s disease and their first-degree relatives who live in the same household 17. The study showed that 11.5% of the relatives had a significant increase in permeability. Since the risk of developing active Crohn’s disease in the relatives of patients with Crohn’s disease is 10 to 15%, the findings of the present study appear to correlate well with what would be expected to be the incidence of permeability abnormalities in the relatives assuming that permeability abnormalities predispose the relatives to the development of the disease. The authors studied a relatively small number of subjects in each of the study groups and used the marker molecules cellobiose and mannitol to study intestinal permeability. Cellobiose is not used by most investigators for permeability studies because it is present in dietary vegetables and fruits and has the potential of being a spurious contaminant of the urine from bacterial enzymatic digestion of cellulose. Most investigators use lactulosa in preferences to cellobiose since lactulose is not a natural contaminant of the intestinal contents. The study subjects abstained from alcohol and drugs for too short a time period. These factors could affect permeability measurements. In most studies of intestinal permeability, subjects are asked to avoid NSAIDs and alcohol for at least 2 weeks prior to the study in order to avoid their effects on permeability measurements 13. Perhaps larger study groups and other marker molecules such as lactulose would sharpen the differences between the study groups. Another approach which could help improve a follow-up study would be to enhance the permeability with ASA 5 6 in order to bring the genetically-related differences between the groups into sharper focus. This study raises the important question of the role of intestinal permeability in the pathogenesis of Crohn’s
Commentaries
disease j. By studying the permeability of the relatives of patients with Crohn’s disease, the authors attempted to clarify the relative importance of genetic versus environmental factors in the genesis of the disease. This study should stimulate us to study larger groups, to use more rigorous methods of assessing permeability, to enhance permeability with ASA, and to prepare the study subjects carefully for the studies in order to avoid spurious factors that could influence the permeability itself.
list
of abbreviations
~ ASA: acetylsalicylic NSAID: non-steroidal L ~~~~~
I acid; EDTA: ethylenediaminetetraacetic anti-inflammatory drug
acid; -~
Address for correspondence Ll. Ho/lander, M.D., I 124 West Carson Street Torrance, 2064 USA. Fax: + l-31 O-222-3603. E-mail: dhollander@ei.
CA, 90502edu
References ’ Hollander D. The intestinal permeability barrier. A hypothesis as to its regulation and involvement ian Crohn’s disease. Stand J Gastroenterol 19921;27:721-6. ? Hollander D. Crohn’s disease - a permeability disorder of the tight-junction? Gut 1988;29:1621-4. 3 Hollander D, Vadheim CM, Brettholz E, Petersen GM, Delahunty TJ, Rotter JI. Increased intestinal permeability in Crohn’s patients and their relatives: an etiological factor. Ann Int Med 1986;105:883-5. -I Katz KD, Hollander D, Vadheim CM, McElree C, Delahunty T, Dadufalza VD, et al. Intestinal permeability in patients with Crohn’s disease and their healthy relatives. Gastroenterology 1989;97:Y)27-3 1.
IBD: how important
are clinical
5 Pironi L, Miglioli M, Ruggeri E, Dallasta MA, Omigotti L, Valpiani D, et al. Effect of non-steroidal anti-inflammatory drugs on intestinal permeability of first degree relatives of patients with Crohn’s disease. Gastroenterology 1992;102(Suppl.):A679. 6 Hilsden RJ, Meeddings JB, Sutherland LR. Intestinal permeability changes in response to acetylsalicylic acid in relatives of patients with Crohn’s disease. Gastroenterology 1996;l IO:1395403. ’ Soderholm JD, Olaison G, Lindberg E, Hannestad U, Vindels A, Tysk C, et al. Different intestinal permeability patterns in relatives and spouses of patients with Crohn’s disease: an inherited defect in mucosal defence? Gut 1999;44:96-100. x Peters M, Geypens B, Claus D, Nevens H, Ghoos Y, Vebeke G, et al. Clustering of increased small intestinal permeability in families with Crohn’s disease. Gastroenterology 1997;113:802-7. y h-vine EJ, Marshall JK. Increased intestinal permeability proceeds the onset of Crohn’s disease in a subject with familial risk. Gastroenterology 2000; I 19: 1740-4. lo Hollander D, Ricketts D, Boyd CAR. Importance of probe molecular geometry in determining intestinal permeability. Can J Gastroenterol 1988;2:A3.5-8. ‘I Hollander D. Permeability in Crohn’s disease: altered barrier functions healthy relatives? Gastroenterology 1993;104:184?51. I2 Diamond JM. Tight and leaky junctions of epithelia: a perspective on kisses in the dark. Fed Proc 1974;33:2220-4. I3 Bjamason I, MacPherson A, Hollander D. Intestinal permeability: an overview. Gastroenterology 1995; 108: 1566-8 1. I4 Travis S, Menzies IS. Intestinal permeability functional assessment and significance. Clin Sci 1992;82:47 l-88. I5 Hollander D. Intestinal permeability in health and disease. In: Kirsner JB, editor. Inflammatory bowel disease, 5th Ed. Philadelphia: WB Saunders Co.; 1999. p. 45-54. lo Joossens S, Vermeire S, Vanderwalle P, Esters N, Sendid B, Poulain D, et al. ASCA (Anti-Saccharomyces cerevisiae Antibodies) in healthy relatives of sporadic and familial Crohn’s disease patients. Gastroenterology 2001;120(Supp1 l):A525. ” Secondulfo M, de Magistris L, Fiandra R, Caserta L, Belletta M, Tartaglione MT, et al. Intestinal permeability in Crohn’s disease patients and their first degree relatives. Digest Liver Dis 2001;33:680-5.
epidemiological
studies?
V. Binder
1 See related
article
on page
686-92
The prognosis of a disease - the life prospect for the patient - is, of course, of great importance, both for the individual patient as well as for the medical profession and, indeed, the community. The basis for such estimations, however, is often lacking. The “clinical experience”, which has, until recent years been the standard knowledge, has obvious limitations, and depends pri-
marily on which part of the disease spectrum, a given doctor will normally see and treat. As an example of the limitations of this general experience, a study was carried out twenty years ago - before the era of Helicobacterpylori - concerning the prognosis of peptic ulcer disease in a regional cohort of patients. The study was a follow-up of a regional group of patients, 10 years after their first diagnosis of peptic ulcer, with the aim of describing the clinical course during that lo651
Intestinal and their
permeability relatives
in patients
with Crohn’s
disease
D. Hollander
1 See related
article
on page
680-5
1
The gastrointestinal tract performs a dual role: it absorbs needed nutrients but, simultaneously, it must prevent the absorption of harmful substances from the lumen into the systemic environment of the body. Its ability to prevent the absorption of potentially harmful substances is referred to as “intestinal permeability”. Substances with the potential to cause harm come from both the external environment and from bacteria in the lumen that produce a wide variety of antigens and secretions. One of the most important functions of the gastrointestinal tract is to maintain an effective barrier against the penetration and absorption of harmful environmental and luminal factors into the body through the gastrointestinal mucosa. This function is called “the barrier function” or the “permeability” of the gastrointestinal tract ’ . Evidence is accumulating that one of the underlying factors in the genesis of Crohn’s disease is a defective permeability barrier that allows antigens from food, the environment and bacteria in the lumen to penetrate through the gastrointestinal surface mucosa into the intestinal wall and the systemic environment 23. Evidence to support this hypothesis includes a marked increase in intestinal permeability of patients with Crohn’s disease and some lo-20% of their clinically healthy relatives 3 4. The increase in permeability both in patients and their healthy relatives is markedly enhanced by the ingestion of acetylsalicylic acid (ASA) 5 6. In contrast, household members, such as spouses, do not show an increase in permeability with the ingestion of ASA ‘. This finding suggests that ASA ingestion influences the genetically determined component of intestinal permeability of patients with Crohn’s disease and their healthy relatives but does not influence environmentally determined permeability characteristics s. A recent report documents the development of clinical Crohn’s disease in one of the relatives who, initially, was clinically normal but did have an increase in their intestinal permeability 9. This finding demonstrates that an abnormality in intestinal permeability is a predisposing factor in the development of active Crohn’s disease in a genetically predisposed relative of patients with Crohn’s disease. Inert, non metabolized, water-soluble probes with
cross-sectional diameters of 4-30 Angstroms are used to measure intestinal permeability. The probes are administered orally to subjects whose urine is collected over the next few hours. Some fraction of the ingested probes penetrates the gastrointestinal mucosal barrier and is excreted in the urine where their concentrations are measured. The greater the permeability the greater the amount of the ingested probes that penetrates the intestinal barrier and appears subsequently in the urine. The co-administration of ASA and the probes accentuate and enhance the abnormal permeability of patients with Crohn’s and their clinically healthy relatives 5 6. Why the accentuation occurs is not known, but one must wonder whether long-term ingestion of ASA or related compounds might not instigate or hasten the onset of Crohn’s disease in those individuals with a genetic predisposition for the disease. The bulk of evidence suggests that clinical measurements of intestinal permeability assess the permeability of the tight junctions between enterocytes and not the permeability of the lipid cell membrane of the enterocytes ’ ‘I. The tight junctions open or close intermittently and allow water, nutrients and luminal antigens to penetrate into the lamina propria of the intestine and to enter the systemic environment 12. The cross-sectional size of the permeability probe and the size of the tight junction seem to determine where the probe transits the intestinal barrier lo. The intestinal tight junctions are smaller and more numerous at the villous tips and larger but less numerous in the crypts between villi. In Crohn’s disease, it is the larger-sized probes, such as lactulose, that demonstrate an increase in permeability. This finding suggests that the abnormality in Crohn’s may reside at the base of the villi and in the crypts but not at the villous tips I. Many spurious factors can influence the rate of intestinal permeability. They include smoking, the ingestion of alcohol, ASA and other non-steroidal anti-inflammatory compounds, and the simultaneous ingestion of food with the probe. In order to avoid errors in the assessment of permeability, the study subjects must abstain from food when the probe is being administered and from smoking, alcohol, ASA and non-steroidal anti-inflammatory drugs (NSAIDs) during the 2 weeks prior to the study IX. The laboratory methods for measuring permeability
649
Commentaries
probes in the urine are difficult and exacting. Furthermore, they vary in their sensitivity and reproducibility. Most rely on column chromatographic separation of the probes and a variety of detection systems. Some of the confusion in the literature regarding the results of permeability studies stems from unreliable laboratory measurement systems. It is useful to correct the results of permeability measurements for transit, collection and assay artifacts by the simultaneous administration of both a small and a large probe and to express the results as a ratio of the two probes. The rationale for expressing the results as a ratio is based on the assumption that confounding extraneous factors, such as gastric emptying, intestinal transit, intestinal blood flow, and urinary clearance, will be eliminated from the results if one probe that is not affected by the disease itself is administered and measured simultaneously with one that is affected by the diseased intestinal wall. Since the permeability of small marker molecules, such as mannitol or rhamnose, is not affected by Crohn’s disease, one or the other is frequently used as a correction factor in expressing the results of permeability studies. Simultaneously, larger molecules, such as lactulose or chromium-labelled ethylenediaminetetraacetic acid (EDTA), are used to assess the influence of Crohn’s disease on permeability itself because the absorption of both molecules is affected by the disease. The final ratio between the small and large probes is used to correct the data for spurious factors, other than the permeability characteristics of the abnormal epithelium itself 14. Polyethylene glycol 400 (PEG 400) was used as a marker molecule in some of the initial studies of permeability in Crohn’s disease 3. The problem with its use is that the different molecular weight species of PEG 400 have the same cross-sectional diameters, and thus traverse the intestine at the same rate, and provide no correlation between their molecular weights and permeability. More reliable results are obtained when either lactulose or EDTA are used as the larger probes and mannitol - or “rhamnose” - are used as the smaller ones and the data are corrected to eliminate artifacts caused by transit time or blood flow.15. The important question of whether the increase in intestinal permeability of relatives of patients with Crohn’s disease is genetically determined or is due to environmental factors has been raised by several research groups x. The issue was raised because some of the spouses of patients with the disease have increased intestinal permeability. It has been clearly demonstrated that ASA accentuates the genetic abnormality found in Crohn’s disease patients and their clinically normal relatives, but when ASA is given to the spouses of patients with Crohn’s disease there is no accentuation of the rate of perme-
650
ability 7. These findings with ASA confirm that the increase in permeability of patients with Crohn’s disease and their clinically healthy relatives is caused by genetic, rather than environmental, factors while spouses of the patients may have increased intestinal permeability because of environmental factors. It has also been demonstrated, recently, that antisaccharomyces antibodies found in healthy relatives of patients with Crohn’s disease are found predominantly in relatives of patients with familial Crohn’s disease rather than those with sporadic Crohn’s disease 16. Since the antibodies would occur due to abnormal permeability of saccharomyces or an antigenic component of the fungus, these findings lend support to the conclusion that an increase in intestinal permeability in the relatives of patients with Crohn’s disease is a genetic and not an environmental factor. In the current issue of Digest Liver Dis (2001;33:6805), investigators from Naples and Pavia report their findings about intestinal permeability in patients with Crohn’s disease and their first-degree relatives who live in the same household 17. The study showed that 11.5% of the relatives had a significant increase in permeability. Since the risk of developing active Crohn’s disease in the relatives of patients with Crohn’s disease is 10 to 15%, the findings of the present study appear to correlate well with what would be expected to be the incidence of permeability abnormalities in the relatives assuming that permeability abnormalities predispose the relatives to the development of the disease. The authors studied a relatively small number of subjects in each of the study groups and used the marker molecules cellobiose and mannitol to study intestinal permeability. Cellobiose is not used by most investigators for permeability studies because it is present in dietary vegetables and fruits and has the potential of being a spurious contaminant of the urine from bacterial enzymatic digestion of cellulose. Most investigators use lactulosa in preferences to cellobiose since lactulose is not a natural contaminant of the intestinal contents. The study subjects abstained from alcohol and drugs for too short a time period. These factors could affect permeability measurements. In most studies of intestinal permeability, subjects are asked to avoid NSAIDs and alcohol for at least 2 weeks prior to the study in order to avoid their effects on permeability measurements 13. Perhaps larger study groups and other marker molecules such as lactulose would sharpen the differences between the study groups. Another approach which could help improve a follow-up study would be to enhance the permeability with ASA 5 6 in order to bring the genetically-related differences between the groups into sharper focus. This study raises the important question of the role of intestinal permeability in the pathogenesis of Crohn’s
Commentaries
disease j. By studying the permeability of the relatives of patients with Crohn’s disease, the authors attempted to clarify the relative importance of genetic versus environmental factors in the genesis of the disease. This study should stimulate us to study larger groups, to use more rigorous methods of assessing permeability, to enhance permeability with ASA, and to prepare the study subjects carefully for the studies in order to avoid spurious factors that could influence the permeability itself.
list
of abbreviations
~ ASA: acetylsalicylic NSAID: non-steroidal L ~~~~~
I acid; EDTA: ethylenediaminetetraacetic anti-inflammatory drug
acid; -~
Address for correspondence Ll. Ho/lander, M.D., I 124 West Carson Street Torrance, 2064 USA. Fax: + l-31 O-222-3603. E-mail: dhollander@ei.
CA, 90502edu
References ’ Hollander D. The intestinal permeability barrier. A hypothesis as to its regulation and involvement ian Crohn’s disease. Stand J Gastroenterol 19921;27:721-6. ? Hollander D. Crohn’s disease - a permeability disorder of the tight-junction? Gut 1988;29:1621-4. 3 Hollander D, Vadheim CM, Brettholz E, Petersen GM, Delahunty TJ, Rotter JI. Increased intestinal permeability in Crohn’s patients and their relatives: an etiological factor. Ann Int Med 1986;105:883-5. -I Katz KD, Hollander D, Vadheim CM, McElree C, Delahunty T, Dadufalza VD, et al. Intestinal permeability in patients with Crohn’s disease and their healthy relatives. Gastroenterology 1989;97:Y)27-3 1.
IBD: how important
are clinical
5 Pironi L, Miglioli M, Ruggeri E, Dallasta MA, Omigotti L, Valpiani D, et al. Effect of non-steroidal anti-inflammatory drugs on intestinal permeability of first degree relatives of patients with Crohn’s disease. Gastroenterology 1992;102(Suppl.):A679. 6 Hilsden RJ, Meeddings JB, Sutherland LR. Intestinal permeability changes in response to acetylsalicylic acid in relatives of patients with Crohn’s disease. Gastroenterology 1996;l IO:1395403. ’ Soderholm JD, Olaison G, Lindberg E, Hannestad U, Vindels A, Tysk C, et al. Different intestinal permeability patterns in relatives and spouses of patients with Crohn’s disease: an inherited defect in mucosal defence? Gut 1999;44:96-100. x Peters M, Geypens B, Claus D, Nevens H, Ghoos Y, Vebeke G, et al. Clustering of increased small intestinal permeability in families with Crohn’s disease. Gastroenterology 1997;113:802-7. y h-vine EJ, Marshall JK. Increased intestinal permeability proceeds the onset of Crohn’s disease in a subject with familial risk. Gastroenterology 2000; I 19: 1740-4. lo Hollander D, Ricketts D, Boyd CAR. Importance of probe molecular geometry in determining intestinal permeability. Can J Gastroenterol 1988;2:A3.5-8. ‘I Hollander D. Permeability in Crohn’s disease: altered barrier functions healthy relatives? Gastroenterology 1993;104:184?51. I2 Diamond JM. Tight and leaky junctions of epithelia: a perspective on kisses in the dark. Fed Proc 1974;33:2220-4. I3 Bjamason I, MacPherson A, Hollander D. Intestinal permeability: an overview. Gastroenterology 1995; 108: 1566-8 1. I4 Travis S, Menzies IS. Intestinal permeability functional assessment and significance. Clin Sci 1992;82:47 l-88. I5 Hollander D. Intestinal permeability in health and disease. In: Kirsner JB, editor. Inflammatory bowel disease, 5th Ed. Philadelphia: WB Saunders Co.; 1999. p. 45-54. lo Joossens S, Vermeire S, Vanderwalle P, Esters N, Sendid B, Poulain D, et al. ASCA (Anti-Saccharomyces cerevisiae Antibodies) in healthy relatives of sporadic and familial Crohn’s disease patients. Gastroenterology 2001;120(Supp1 l):A525. ” Secondulfo M, de Magistris L, Fiandra R, Caserta L, Belletta M, Tartaglione MT, et al. Intestinal permeability in Crohn’s disease patients and their first degree relatives. Digest Liver Dis 2001;33:680-5.
epidemiological
studies?
V. Binder
1 See related
article
on page
686-92
The prognosis of a disease - the life prospect for the patient - is, of course, of great importance, both for the individual patient as well as for the medical profession and, indeed, the community. The basis for such estimations, however, is often lacking. The “clinical experience”, which has, until recent years been the standard knowledge, has obvious limitations, and depends pri-
marily on which part of the disease spectrum, a given doctor will normally see and treat. As an example of the limitations of this general experience, a study was carried out twenty years ago - before the era of Helicobacterpylori - concerning the prognosis of peptic ulcer disease in a regional cohort of patients. The study was a follow-up of a regional group of patients, 10 years after their first diagnosis of peptic ulcer, with the aim of describing the clinical course during that lo651