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Biomedical subjects

G Järnerot

Publications and source records attributed to G Järnerot.

At least 19 recordsLinked to original sources

Surface properties, connective tissue protein binding and Shiga-like toxin production of Escherichia coli isolated from patients with ulcerative colitis.

Escherichia coli strains isolated from intestinal biopsies of patients with ulcerative colitis (n 146), Crohn's disease and colonic polyposis (n 41) were analysed for binding of collagen I, collagen IV, fibronectin and laminin. Strains expressed varying degrees of binding of one or more of the four connective tissue proteins. Only 32 strains did not express binding of any of the proteins. The strains expressed low or moderate cell surface hydrophobicity. There was no correlation between protein binding and expression of cell surface hydrophobicity. E. coli isolated from inflamed rectal mucosa were slightly less negatively charged than strains isolated from healthy intestinal mucosa. Shiga-like toxins I and II were detected in 32 strains from 28 patients. Of these, 5 strains had been isolated from normal or healed tissue. In patients with inflammatory bowel disease, connective tissue proteins are exposed in intestinal ulcerations. Strains expressing binding of one or several of these proteins may have a selective advantage to colonize these lesions.

Adolescent

Experimentally induced ileal ulcers in rats. Formula diet is a preventive factor.

We recently described an experimental model in the rat to create recurring chronic ileal inflammation including ulceration. This model is dependent on an "in vivo culture" of normal intestinal contents. In the present experimental study we examined the effect of a polymeric and a hydrolyzed formula diet on the formation of ulcerating lesions using our rat model. Two groups of rats (twenty in each group) were fed either one of these formula diets eight weeks prior to the experimental procedure and this diet was continued until sacrifice eight weeks later. Twenty control rats also underwent the experimental procedure but were fed standard rat pellets for the same time periods. At sacrifice 60% of the control rats had developed ileal ulcers. None of the rats fed the formula diets developed macroscopic ileal inflammation or ulceration. The effectiveness of formula diets in inducing remission in Crohn's disease in humans may be linked to alterations in the intestinal microflora. We hypothesize that the formula diets in this experiment exerted a protective effect against ileal ulceration by altering the ileal microflora. Preliminary studies support this hypothesis but need to be expanded.

Animals

IgG subclass distribution in serum and rectal mucosa of monozygotic twins with or without inflammatory bowel disease.

Serum samples from 26 monozygotic twin pairs concordant or discordant with regard to inflammatory bowel disease, and rectal biopsies from 42 twins of the same subject group, were examined for IgG subclasses. They were all compared with normal controls. Almost all affected twins were in clinical remission. Paired immunofluorescence staining of the rectal mucosa showed that those with ulcerative colitis had a significantly higher (p < 0.01) proportion of IgG1 producing mucosal immunocytes than normal controls (78.1% v 55.9%). Conversely, the IgG2 cell fraction was significantly reduced (15.9% v 34.6%). Healthy twins from ulcerative colitis pairs tended to show a raised proportion of IgG1 cells and the IgG2 cell fraction was significantly reduced (p < 0.05). In discordant ulcerative colitis twin pairs, no difference appeared in the cellular IgG subclass pattern between healthy and affected twins. Furthermore, the proportion of IgG1 in these healthy and diseased twins showed good correlation (T = 0.867). The results in rectal mucosa of twins with Crohn's disease were widely scattered and affected twins did not differ significantly from normal controls. Healthy twins, however, showed a marginally raised IgG1 cell proportion, but no correlation was seen between the IgG subclass fractions in discordant Crohn's disease twin pairs. The serum concentrations of IgG1 and IgG2 did not differ from normal controls in twins of either category. These results suggested that in ulcerative colitis, the aberrant mucosal production of IgG1 and IgG2 does not depend on active disease, but is apparently at least partially explained by a genetic impact. Conversely, the mucosal IgG subclass pattern in Crohn's disease appears to be determined mainly by exogenous variables.

Adult

Smoking in Crohn's disease: effect on localisation and clinical course.

The effects of smoking on the localisation and clinical course of Crohn's disease is evaluated in 231 patients. Heavy smokers (greater than 10 cigarettes/day) had an increased risk of operation at least once--odds ratios for heavy smokers compared with never smokers after five and 10 years were 1.14 and 1.24 respectively (p = 0.03 and p = 0.017). The risk of further operations was even higher and after 10 years the odds ratio was 1.79 (p = 0.015). The accumulated number of fistulae and/or abscesses was higher for smokers than for never smokers (p = 0.046). Patients with a high life time tobacco exposure (greater than 150 cigarette years) and heavy smokers (greater than 10 cigarettes/day) had small bowel disease more often than patients with lower life time exposure (less than or equal to 150 cigarette years) and patients smoking less than or equal to 10 cigarettes/day (p = 0.002 and p = 0.045 respectively). The course of Crohn's disease analysed in different ways was unfavourable for smokers, especially heavy smokers. Patients with Crohn's disease should be dissuaded from smoking.

Abscess

Antibody (IgG, IgA, and IgM) to baker's yeast (Saccharomyces cerevisiae), yeast mannan, gliadin, ovalbumin and betalactoglobulin in monozygotic twins with inflammatory bowel disease.

To assess whether dietary antigens play a role in inflammatory bowel disease, 26 monozygotic twin pairs with inflammatory bowel disease and 52 healthy controls were investigated for serum antibodies (IgA, IgG, IgM) against ovalbumin, betalactoglobulin, gliadin, whole yeast (Saccharomyces cerevisiae) and yeast cell wall mannan. The twins were made up of five pairs concordant and nine pairs discordant for Crohn's disease, and two pairs concordant and 10 pairs discordant for ulcerative colitis. Two patients with Crohn's disease had a slight increase in disease activity, the others were in clinical remission. Two striking observations were made: first, individuals with ulcerative colitis were indistinguishable from healthy twins, and controls except for the response to gliadin. Both healthy and diseased twins had higher IgA levels to gliadin than controls. Second, twins who had developed Crohn's disease displayed higher antibody titres towards yeast cell wall mannan in particular, but also to whole yeast (Saccharomyces cerevisiae) of all antibody types (IgA, IgG, and IgM). In contrast, the response to gliadin, ovalbumin, and betalactoglobulin did not differ from healthy twins and was even lower than in the controls. The results argue against an increased systemic antigen presentation caused by an impaired mucosal barrier in the inflammatory bowel disease. Rather, they suggest that yeast cell wall material--that is, mannan, or some antigen rich in mannose and cross reacting with mannan, may play an aetiological role in Crohn's disease, but not in ulcerative colitis. The increases in IgA and IgM, as well as IgG suggest that local and systemic immune systems are selectively activated by antigen(s) present in the cell wall of baker's yeast.

Adult

Has smoking changed the epidemiology of ulcerative colitis?

The influence of smoking on the risk of developing ulcerative colitis is well documented. Compared with lifetime non-smokers, the risk is reduced in smokers and increased in ex-smokers. During the past 50 years general smoking habits have changed considerably. The proportions of smokers and ex-smokers among men and women have undergone significant changes and, consequently, probably also their risk of ulcerative colitis. A review of 56 earlier epidemiologic studies of ulcerative colitis from 1930 to 1990 showed that the sex distribution in ulcerative colitis has changed from an earlier female predominance that has now been replaced by a male predominance. In contemporary pediatric studies no such changes were seen. We propose that these changes in adults are not related to the disease per se but to an extrinsic factor affecting adults but not children--namely smoking.

Colitis, Ulcerative

Ulcerative proctocolitis in Orebro, Sweden. A retrospective epidemiologic study, 1963-1987.

In a retrospective epidemiologic study of the period 1963 to 1987 the annual incidence of definite ulcerative proctocolitis increased from 3.3 to 14.9/10(5), and during the last 10 years the mean incidence was 13.1/10(5) population. The incidence of extensive and total colitis was fairly stable, whereas an increase of ulcerative proctitis and distal colitis was seen. The increase in incidence is probably an artefact caused by better retrieval of cases in the latter part of the study. The prevalence on 31 December 1987 was 234/10(5) inhabitants. The male to female ratio was 1.59:1, compared with 0.96:1 in the general population. The median age at diagnosis was 33 years and increased almost 7 years by the end of the study, probably caused by an increased proportion of ex-smokers, who at diagnosis were, on average, 9 years older than lifetime non-smokers. The highest age- and sex-specific incidence was found in middle-aged men, who were ex-smokers to a significantly higher extent than women. No specific birth cohort was at an increased risk, and no second incidence peak in older age groups was seen.

Adolescent

Behavioral medicine treatment in chronic constipation with paradoxical anal sphincter contraction.

Nine women and five children with severe chronic constipation received behavioral medicine therapy. Before treatment, all patients had a paradoxical contraction of the external anal sphincter at defecation attempts as demonstrated with electromyography and/or anorectal manometry. An electromyographic biofeedback device connected to an anal probe was used for the training that was performed on a regular toilet seat during five 1-hour sessions. Thirteen of the patients improved considerably and could learn to defecate spontaneously, and the use of laxatives ceased or diminished. Simultaneously with improvement, the paradoxical anal contraction disappeared. The results remained after 6 months, although two of the patients had received booster sessions of biofeedback training during follow-up.

Adolescent

Colonic glycoproteins in monozygotic twins with inflammatory bowel disease.

Colonic glycoprotein composition was evaluated in monozygotic twins with inflammatory bowel disease using ion-exchange chromatography. Fifty-three individuals, 12 pairs and 1 single twin with ulcerative colitis and 14 pairs with Crohn's disease, were evaluated. Seven twin pairs were concordant for the presence of ulcerative colitis or Crohn's disease, whereas twin siblings of 10 ulcerative colitis probands and 9 Crohn's disease probands were not known to have inflammatory bowel disease. Content of one chromatographically defined component of colonic mucin, designated HCM species IV, was reduced in both patients with ulcerative colitis (1040 +/- 300 cpm/10,000 cpm total HCM) and their apparently healthy twins (1340 +/- 540 cpm/10,000 cpm total HCM) compared with control subjects (4030 +/- 1,000 cpm/10,000 cpm total HCM). Composition of mucin in Crohn's disease patients and their nonaffected twins was not significantly different than in controls. These observations suggest that altered profiles of mucin glycoprotein may be present before the onset of ulcerative colitis and may be genetically defined. Conversely, it appears that alterations in glycoproteins only are not sufficient to initiate mucosal inflammation.

Adolescent

Endoscopic treatment of anastomotic strictures in Crohn's disease.

The results of endoscopic balloon dilatation in 27 patients with anastomotic strictures caused by Crohn's disease are reported. All patients had obstructive symptoms not responding to corticosteroids and of such a degree that resection or strictureplasty was considered necessary. The patients were followed up for 7 to 38 months after their first dilatation. Eighteen patients were more or less free from obstructive symptoms while the results were less favourable in the remaining nine patients. The median time after the latest surgical intervention was seven years in the group with a successful outcome and 1.6 years in the group with a poor outcome, which may indicate that some patients have a more aggressive form of Crohn's disease where balloon dilatation is only of moderate value. However, all patients experienced at least a temporary effect, so that balloon dilatation can be considered for use in situations where it is desirable to postpone surgery.

Adult

[Medical treatment of inflammatory intestinal diseases].

What possible treatments are there for inflammatory intestinal diseases, and on what scientific grounds do we treat these patients? A survey shows that the considerable decline in mortality which has occurred as regards ulcerous colitis ensued rather via trial and error than as a result of regular clinical tests.

Colitis, Ulcerative

Colonoscopy during an attack of severe ulcerative colitis is a safe procedure and of great value in clinical decision making.

Thirty-four patients who had severe ulcerative colitis had a colonoscopic examination during the attack. The indications were resistance to therapy and/or differential diagnostic purposes. Total colonoscopy was performed in 25 cases and less extensive examination in nine. Biopsy was taken in 22 cases. No clinically significant complications occurred. The procedure helped us to postpone immediate surgical intervention in 19 cases. Fourteen of these patients have maintenance treatment and are still well after a follow-up median time of 5 yr (6 months to 10 yr).

Acute Disease

Prevalence of primary sclerosing cholangitis in patients with ulcerative colitis.

All patients greater than or equal to 16 years old with a diagnosis of ulcerative colitis were identified in five well-defined catchment areas, representing 12.7% of the Swedish population. Exactly 1500 patients were retrieved, giving a point prevalence of 170/10(5) inhabitants. It was possible to obtain liver function test results less than 2 years old in 94% of the patients and to obtain endoscopic retrograde cholangiographic results in 65 of the 72 patients with abnormal serum alkaline phosphatase values. Primary sclerosing cholangitis was diagnosed in 55 of the patients (3.7%). The prevalence of the disease was 5.5% in patients with substantial colitis and 0.5% in patients with distal colitis. There was a marked male predominance in cholangitis patients compared with colitis patients without cholangitis. Ninety-five percent of the patients with cholangitis had substantial colitis, which was more than the 62% of patients without cholangitis who had colitis. Female patients with cholangitis were older than male patients at the time of diagnosis of both cholangitis and colitis, which contrasted to the equal age at diagnosis of colitis in male and female patients without cholangitis.

Adolescent

Epidural morphine delays gastric emptying and small intestinal transit in volunteers.

The influence of a painful stimulus and lumbar epidural morphine on gastric emptying, the orocecal transit time and small intestinal transit were studied in nine healthy volunteers. Acetaminophen absorption was used as a measure of the rate of gastric emptying. Orocecal transit time was determined by measuring the end-expiratory hydrogen concentration. Small intestinal transit was calculated from measurements of the orocecal transit time and gastric emptying. Cold pain stress with intermittent immersion of the feet in ice-cold water was used as a painful stimulus. Each volunteer was investigated on 3 different days: once after receiving 4 mg of epidural morphine and during cold pain; once during cold pain; and once under control conditions without pain and epidural morphine. Immersion of the feet in ice-cold water was always very painful, but was more tolerable during epidural morphine analgesia. The increase in blood pressure which accompanied the cold pain was the same whether this pain was induced without or during epidural morphine analgesia. Gastric emptying, orocecal transit time and small intestinal transit were delayed during epidural morphine analgesia compared with the findings under the control and plain cold pain conditions. Cold pain stress alone did not influence gastric emptying, orocecal transit time or intestinal transit. To conclude, epidural morphine in itself delayed gastric emptying, orocecal transit and transit through the small intestine in healthy volunteers.

Adult

Newer 5-aminosalicylic acid based drugs in chronic inflammatory bowel disease.

Since the discovery that 5-aminosalicylic acid (5-ASA) is the active moiety of sulphasalazine in the treatment of chronic inflammatory bowel disease, several new 5-ASA based drugs have been developed. These consist either of slow- or delayed-release formulations of plain 5-ASA or sulpha-free azo compounds of 5-ASA. The different formulations and compounds have varying bioavailabilities, which makes it possible to use them alternatively in different clinical situations. A review of the literature is given, together with suggestions as to how the new drugs might be used in different clinical situations.

Administration, Oral

Clinical significance of manometric assessment of both pancreatic duct and bile duct sphincter in the same patient.

In this study both pancreatic and bile duct sphincter pressures were measured on the same occasion by means of endoscopic manometry in 42 patients with long-standing upper abdominal pain. Nine (53%) of the 17 patients with abnormal sphincter function had a marked difference between the pancreatic duct sphincter pressure (PSOP) and the bile duct sphincter pressure (BSOP): 6 patients with a clinical diagnosis of biliary dyskinesia showed elevated BSOPs, whereas the PSOPs were normal. The reverse, an abnormal PSOP but normal or only a slightly elevated BSOP, was registered in the three patients with chronic pancreatitis. These findings indicate that a motor abnormality may be restricted to only one of the sphincters. Thus, when the sphincter of Oddi is investigated only from the pancreatic duct, manometry may either fail to show an abnormal BSOP in some patients with biliary dyskinesia, or it may falsely suggest this diagnosis in patients with unrecognized pancreatitis.

Adult

Serum albumin reserve for bilirubin binding during pregnancy in healthy women.

The concentrations of serum albumin and albumin reserve for bilirubin binding were studied in 24 healthy women during and after pregnancy, using monoacetyl-4,4'-diamino-diphenylsulphone as a deputy ligand for bilirubin. In the first trimester, the serum albumin concentration was already diminished. Likewise, the serum reserve albumin for bilirubin binding was reduced gradually during pregnancy. These reductions were evident as early as the 20th week of gestation, and at delivery the level averaged 53% of the nonpregnant level. The reduction in bilirubin binding capacity was partly dependent on the decreasing serum albumin concentration, but a reduction in the albumin molecule's binding capability was also shown. This binding defect, which is also present in neonates, is not fully explained. The reduction in bilirubin binding capability probably reflects a reduced degree of protein binding for many protein-bound drugs during pregnancy, which may contribute to pharmacokinetic alterations in pregnancy.

Bilirubin