Outcome of four weeks' intervention with probiotics on symptoms and endoscopic appearance after surgical reconstruction with a J-configurated ileal-pouch-anal-anastomosis in ulcerative colitis.

OBJECTIVE: Pouchitis is a common and troublesome condition in patients operated on with ileal-pouch-anal-anastomosis (IPAA). A disturbed microecology in the pouch has been suggested as one possible explanation. In a previous double-blind, randomized, controlled study we demonstrated clinical improvement of symptoms in patients with ulcerative colitis (UC) operated on with IPAA, during intervention with live probiotic microbes Lactobacilli and Bifidobacteriae. The aim of the present study was to confirm our previous results in a much larger material, including clinical symptoms, faecal flora and endoscopic evaluation, and to compare the results in UC/IPAA patients with those of patients with familial adenomatous polyposis (FAP) with IPAA and UC patients with ileorectal anastomosis (IRA). MATERIAL AND METHODS: Five hundred millilitres of a fermented milk product (Cultura) containing live lactobacilli (La-5) and bifidobacteriae (Bb-12) was given daily for 4 weeks to 51 UC patients and 10 patients with FAP, operated on with IPAA, and six UC patients operated on for IRA. Stool samples were cultured for examination of lactobacilli, bifidobacteriae, fungi and pH before, during and after intervention. Before, during and after intervention, endoscopic evaluation was performed. Categorized symptomatology was examined prospectively using diary cards in addition to an interview, before and on the last day of intervention. RESULTS: The number of lactobacilli and bifidobacteriae increased significantly during intervention in the UC patients operated on with IPAA and remained significantly increased one week after intervention. Involuntary defecation, leakage, abdominal cramps and the need for napkins (category I), faecal number and consistency (category II) and mucus and urge to evacuate stools (category III) were significantly decreased during intervention in the UC/IPAA group. In the FAP group there was a significant decrease in faecal leakage, abdominal cramps and use of napkins (category I) during intervention. The median endoscopic score of inflammation was significantly decreased during intervention in the UC/IPAA patients. Blood tests, faecal fungi and faecal pH did not change significantly during intervention. CONCLUSIONS: Results of this extended study, showing an effect of probiotics on symptoms and endoscopic inflammation in UC patients operated on with IPAA confirm our previously reported effect of probiotics on clinical symptoms and endoscopic score in a smaller, double-blind, randomized, controlled study. The significantly higher response to probiotics in families with increased risk of IBD will have to be repeated in future studies.

Assessment of mucosal inflammation and blood flow in response to four weeks' intervention with probiotics in patients operated with a J-configurated ileal-pouch-anal-anastomosis (IPAA).

BACKGROUND: Pouchitis is a common and troublesome condition in patients operated on with ileal-pouch-anal-anastomosis (IPAA). A disturbed mucosal perfusion in the pouch has been suggested as a possible cause. Laser Doppler flowmetry (LDF) has been used successfully to measure gastric and colonic mucosal perfusion in humans. In a previous study, we demonstrated a reduced mucosal perfusion in the distal part of the pouch, during probiotic intervention, examined by LDF measurement. The aim of the present study was to confirm our previous results in a much larger material, and to compare the results of LDF measurements and inflammatory activity in ulcerative colitis (UC) patients with those in familial adenomatous polyposis (FAP) patients. METHODS: Five hundred millilitres of a fermented milk product (Cultura), containing live lactobacilli (La-5) and bifidobacteria (Bb-12), was given daily for 4 weeks to 41 UC and 10 patients with FAP, operated on with IPAA. Mucosal perfusion was measured with LDF and the degree of inflammation was examined at predefined levels of the distal bowel by histology and faecal calprotectin measurements both before and after intervention. We also evaluated the applicability of a Pouchitis Disease Activity Index (PDAI). RESULTS: The LDF measurements were reproducible in the pelvic pouch at each of the predefined levels, but did not change during intervention. Mucosal perfusion was significantly reduced in the distal compared to the proximal part of the pouch in the UC group (P < 0.05). The perfusion levels were higher in the FAP patients compared to the UC patientsat all predefined levels (P < 0.05). Calprotectin levels and histological score did not change significantlyafter intervention in any of the groups. The calprotectin level was significantly lower in the FAP compared to the UC group both before and after intervention. The PDAI decreased in both groups from alevel considered diagnostic for pouchitis to a level considered as not active pouchitis. The decreasewas significant for the UC patients. CONCLUSIONS: The results did not demonstrate an effect of probiotics on histology, although a significant effect on the PDAI was achieved, which concurs with the previously reported effect on symptoms and endoscopic score. The significantly reduced blood flow in the UC group compared to the FAP group, operated on with the same procedure, and the significantly increased calprotectin levels in the UC group, are original findings. Both findings may be related to an increased risk for pouchitis among UC patients. The lack of effect of intervention on mucosal perfusion does not exclude a role for reduced circulation as a cause of pouchitis based on the reduced LDF measurements in the distal part of the pouch.

Assessment of mucosal inflammation and circulation in response to probiotics in patients operated with ileal pouch anal anastomosis for ulcerative colitis.

BACKGROUND: Pouchitis is a common and troublesome condition, and a disturbed microbiological flora and mucosal blood flow in the pouch have been suggested as possible causes. Laser Doppler flowmetry (LDF) has been used successfully to measure gastric and colonic mucosal perfusion in humans. The aim of this study was to evaluate the effect of intervention with probiotics on ileal pouch inflammation and perfusion in the pouch, assessed by endoscopy, histology, fecal calprotectin and LDF. METHODS: A fermented milk product (Cultura; 500 ml) containing live lactobacilli (La-5) and bifidobacteria (Bb-12) was given daily for 4 weeks to 10 patients operated with ileal-pouch-anal anastomosis (IPAA) for ulcerative colitis (UC). Mucosal perfusion was measured with LDF and the degree of inflammation was examined at predefined levels of the distal bowel by endoscopy and histology. Stool samples were cultured for lactobacilli and bifidobacteria and calprotectin were measured before and after intervention. RESULTS: The LDF measurements were reproducible in the pelvic pouch at each of the predefined levels, but did not change after intervention. The mucosal perfusion was reduced in the distal compared to the proximal part of the pouch. Calprotectin levels did not change significantly after intervention. The median endoscopic score for inflammation was significantly reduced by 50% after intervention, whereas the histological score did not change significantly. CONCLUSION: The results suggest that probiotics primarily act superficially, with change of gross appearance of the mucosa at endoscopy, but without significant effect on histological picture, mucosal perfusion or faecal calprotectin, during a relatively short period of 4 weeks.

Assessment of Mucosal Inflammation and Circulation in Response to Probiotics in Patients Operated with Ileal Pouch Anal Anastomosis for Ulcerative Colitis.

BACKGROUND: Pouchitis is a common and troublesome condition, and a disturbed microbiological flora and mucosal blood flow in the pouch have been suggested as possible causes. Laser Doppler flowmetry (LDF) has been used successfully to measure gastric and colonic mucosal perfusion in humans. The aim of this study was to evaluate the effect of intervention with probiotics on ileal pouch inflammation and perfusion in the pouch, assessed by endoscopy, histology, fecal calprotectin and LDF. METHODS: A fermented milk product (Cultura; 500 ml) containing live lactobacilli (La-5) and bifidobacteria (Bb-12) was given daily for 4 weeks to 10 patients operated with ileal-pouch-anal anastomosis (IPAA) for ulcerative colitis (UC). Mucosal perfusion was measured with LDF and the degree of inflammation was examined at predefined levels of the distal bowel by endoscopy and histology. Stool samples were cultured for lactobacilli and bifidobacteria and calprotectin were measured before and after intervention. RESULTS: The LDF measurements were reproducible in the pelvic pouch at each of the predefined levels, but did not change after intervention. The mucosal perfusion was reduced in the distal compared to the proximal part of the pouch. Calprotectin levels did not change significantly after intervention. The median endoscopic score for inflammation was significantly reduced by 50% after intervention, whereas the histological score did not change significantly. CONCLUSION: The results suggest that probiotics primarily act superficially, with change of gross appearance of the mucosa at endoscopy, but without significant effect on histological picture, mucosal perfusion or faecal calprotectin, during a relatively short period of 4 weeks.

Heterogeneity of intraepithelial lymphocytes in refractory sprue: potential implications of CD30 expression.

BACKGROUND: Refractory sprue is defined as primary or secondary failure to respond to a gluten free diet in patients with coeliac disease-like enteropathy and may signify cryptic or overt enteropathy associated T cell lymphoma. AIMS: To study in detail jejunal morphology and immunophenotypes in patients with refractory sprue in the search for features that might be useful to predict prognosis. PATIENTS: Seven patients are described, representing all such cases identified in our hospital over a 13 year period. METHODS: Biopsy and/or surgical resection specimens were examined by morphology, immunohistochemistry, including enzymatic and immunofluorescent detection, and molecular biology. RESULTS: All patients had phenotypically abnormal intraepithelial lymphocytes (IELs) that lacked CD8, T cell receptor alpha beta (or gamma delta), and/or expressed CD30 in addition to variable expression of the natural killer cell receptor CD94. A monoclonal T cell population was present in six cases, data from the seventh being inconclusive. Three patients had overt lymphoma with CD30+ tumour tissue intervening between intact mucosa that contained neoplastic IELs. Intriguingly, CD30+ IELs were observed both a long way away from, and in direct continuity with, the tumours in these patients. Such CD30+ cells were hardly detected in patients without tumours, two of which are in good health several years after the initial diagnosis. CONCLUSIONS: Our data suggest that abnormal IELs in patients with refractory sprue are phenotypically heterogeneous. CD30 expression by these cells may indicate a worse prognosis, including the occurrence of overt lymphoma.

Intracerebral abscess caused by Nocardia otitidiscaviarum in a renal transplant patient--cured by evacuation plus antibiotic therapy.

We present a 50-year-old female who experienced generalized convulsion 3 months after a successful cadaveric renal transplantation. The first cerebral CT scan indicated cerebral frontal infarction. Repeat CT some days later revealed progressive lesions, and a highly malignant tumor or abscess was suspected. Antifungal and broad-spectrum antibacterial therapy was initiated. Cerebral MRI could not differentiate between these conditions, but a neutrophil granulocyte scan strongly suggested an infectious process. A stereotactic puncture of the frontal lobe was followed by temporary improvement. A severe progressive left-sided hemiparalysis gave indication for a craniotomy with evacuation of the abscess 9 days later. Culture of aspirated pus yielded growth of a gram-positive, rod-shaped bacterium, later identified as Nocardia otitidiscaviarum by sequencing the 16S rRNA. The patient was treated with meropenem plus rifampicin intravenously for 6 weeks followed by oral ciprofloxacin and rifampicin for 2 months. Due to pharmacokinetic interaction with rifampicin, the prednisolone dose was doubled, and the dose of tacrolimus had to be tripled for maintenance of adequate trough concentrations. Five months following cessation of antibiotic treatment, the patient has regained normal strength and function in her left-sided extremities and has a serum creatinine level of about 160 micromol/l (1.8 mg/dl).

Low frequency of complications in imported falciparum malaria: a review of 222 cases in south-eastern Norway.

We performed a retrospective study of 222 cases of falciparum malaria diagnosed in Oslo and Akerhus counties, Norway, from January 1988 to December 1997. Except for 12 cases, all had acquired the disease in sub-Saharan Africa. Sixty-four (28.8%) cases occurred in assumed non-immune individuals; of these, 41 (64.1%) were compliant to recommended antimalarial chemoprophylaxis. The mean time lag from first symptom to diagnosis (total diagnosis delay) was 4.6 d (median 3 d, range 0-30 d) and the mean time from presentation to diagnosis (doctor's delay) was 1.3 d (median 0 d, range 0-25 d). There were no fatal cases, and only 8 (3.6%) had a complicated course. The following factors were significantly associated with development of complicated disease: higher age, non-immunity combined with chemoprophylaxis non-compliance, prolonged doctor's delay and prolonged total diagnosis delay (p < or = 0.05). Our data suggest that complicated disease in imported falciparum malaria may largely be prevented by high chemoprophylaxis compliance rates in non-immune travellers and a high index of suspicion in physicians evaluating febrile travellers.

Accuracy of IgG serology and other tests in confirming Helicobacter pylori eradication.

BACKGROUND: In this study we assessed the accuracy of IgG serology and other tests in confirming Helicobacter pylori eradication. METHODS: The outcome of anti-H. pylori therapy was established by at least two of the following tests: rapid urease test (RUT), culture, 14C urea breath test (non-capsule or capsule UBT), and IgG serology (Orion Diagnostica Pyloriset New EIA-G). RESULTS: Successful H. pylori eradication was confirmed in 698 of 794 patients (88%). The percentage decrease in IgG antibody titre was related to the patients' pre-treatment IgG titre and time interval after treatment. A decrease in IgG titres of 40% or more confirmed H. pylori eradication with 100% specificity, whereas the sensitivity was 82%, 90%, 98%, and 98% 3, 4, 5, and 6 months after therapy, respectively. The 40% cut-off confirmed eradication 3 to 6 months after therapy in 328 of 339 patients (97%) with pre-treatment IgG titres of >700, in 36 of 45 patients (80%) with pre-treatment titres of 300-700, and in 5 of 12 patients (42%) with pretreatment titres of <300. The sensitivity and specificity of the other tests 2 months after treatment were as follows: RUT, 84% and 100%; culture, 88% and 100%; non-capsule UBT, 100% and 89%; and capsule UBT, 100% and 97%. CONCLUSION: A decrease in IgG antibody titre of 40% or more 3 to 6 months after therapy and the capsule 14C UBT at the 2-month follow-up were both highly accurate in confirming H. pylori eradication.

Accuracy of seven different tests for the diagnosis of Helicobacter pylori infection and the impact of H2-receptor antagonists on test results.

BACKGROUND: In this study we compared the accuracy of seven diagnostic tests in diagnosing Helicobacter pylori infection. METHODS: Over 1 year 351 consecutive dyspeptic patients were tested for H. pylori infection by means of antral biopsy specimens for the rapid urease test (RUT), culture, microscopy (acridine stain), and the laboratory urease test (LUT) and, in addition, with 14C urea breath test (UBT), IgG serology, and IgA serology (Orion Diagnostica Pyloriset New EIA-G and New EIA-A). The criterion for H. pylori infection was a minimum of three positive tests. Before being tested, 38% of the patients had used an H2-receptor antagonist (H2RA). RESULTS: Two-hundred and twenty-four patients (64%) were H. pylori-positive. The sensitivity and specificity of the tests were as follows (percentages): RUT, 85, 99; culture, 93, 100; microscopy, 81, 98; LUT, 80, 100; UBT, 95, 95; IgG serology, 99, 91; and IgA serology, 88, 91. The accuracy of the RUT and LUT was reduced in patients receiving H2RA therapy (P=0.04 and 0.01, respectively). CONCLUSIONS: Culture, UBT, and IgG serology were all superior to the other four tests in diagnosing H. pylori infection. Invasive urease-based tests were less accurate in patients receiving H2RAs.

Topical metronidazole treatment in pouchitis.

Patients with pouchitis usually respond to oral metronidazole treatment, but side effects of the treatment are common. Eleven patients with pouchitis were given local treatment by instillation of metronidazole in doses of 40-160 mg daily into the reservoir. The effects of the treatment on the bacterial flora and short-chain fatty acids in reservoir contents, morphology of the ileal mucosa, and serum concentrations of metronidazole were studied. All patients responded to local administration of metronidazole. Three patients with chronic pouchitis remained well for 6 months, 3 years, and 4 years, taking 40 mg metronidazole daily. Three patients had one single treatment course, and four had repeated courses when they had recurrences. In one patient a continent reservoir had to be removed owing to a persistent ulcer causing chronic blood loss. The bacterial flora of reservoir contents showed no significant differences between patients with and without pouchitis. The number of anaerobic microorganisms and the concentration of short-chain fatty acids were reduced after metronidazole treatment. Serum concentrations of metronidazole were very low, and no patients experienced any side effects of the treatment. In conclusion, topical application of small doses of metronidazole relieved symptoms in most cases of pouchitis and was well tolerated, even as long-term treatment.

Susceptibilities of Norwegian Candida albicans strains to fluconazole: emergence of resistance. The Norwegian Yeast Study Group.

All Candida albicans isolates in Norwegian microbiological laboratories in 1991 judged clinically important (except vaginal isolates) were collected. The isolates were tested for susceptibility to fluconazole with an agar dilution test and a commercially available agar diffusion test. A total of 212 strains (95%) were susceptible to fluconazole, and MICs for most of the strains (92%) were < or = 1.56 micrograms/ml. The agar diffusion test using a 15-micrograms tablet and a 48-h incubation period separated resistant from susceptible strains with a wide margin. The only exception was a strain for which the MIC was 6.25 micrograms/ml. The difference in zone size between the resistant and the susceptible populations of strains was 11 mm. Accordingly, it appears that the agar diffusion test is an appropriate method for detecting fluconazole resistance. The 12 fluconazole-resistant isolates originated from eight AIDS patients with oral or esophageal Candida infections. Seven of the patients had been given fluconazole for 1 month or more, often as self medication. Four had infections that were clinically resistant to fluconazole; one additional patient responded only when the dose was increased. All isolates recovered from these patients were analyzed by multilocus enzyme electrophoresis. The 12 C. albicans isolates belonged to five electrophoretic types, but three of four patients attending one hospital had isolates belonging to one electrophoretic type. One possible explanation for this finding could be that a nosocomial spread of resistant strains has occurred.

Breath methane and colorectal cancer.

The association between colorectal cancer and breath methane is controversial. We compared a group of 59 patients with unresected colorectal cancer with a group of control subjects matched for age and sex. We also studied 43 of the cancer patients before and 3-6 months after resection. Sixty-three per cent of the patients with unresected carcinoma and 56% of the control subjects were methane excretors (NS). We found no significant change in methane excretion status after resection. Because recent colonic cleansing has been shown to influence methane production in the colon, 15 breath methane excretors were studied immediately before the start of cleansing, on the day of colonoscopy, and on the 7th day thereafter. Forty per cent became breath-methane-negative on the day of colonoscopy, but all 15 were excretors with a median of 60% of the precleansing concentration on the 7th day. The present study does not confirm an association between breath methane and colorectal cancer. It is unlikely that colonic cleansing procedures influenced the results of this study.

[Cytomegalovirus disease in the gastrointestinal tract]. / Cytomegalovirussykdom i gastrointestinaltractus.

Cytomegalovirus infections in immunocompromised patients may cause serious illness, particularly in patients with HIV-disease and in transplant recipients. There is an increasing number of reports of cytomegalovirus infections involving the alimentary tract, especially colitis. Diagnosis of cytomegalovirus disease is at present based on specific histological findings. Antibody findings can be difficult to interpret. The slow growth of cytomegalovirus in cultures makes this method less useful in the acute setting of diagnosis. It is important to recognize cytomegalovirus colitis as a differential diagnosis to idiopathic inflammatory bowel disease. In fulminant disease, colectomy should be considered in addition to antiviral treatment.

Sampling efficiency in the diagnosis of Helicobacter pylori infection and chronic active gastritis.

The methods and sampling procedures used in the diagnosis of Helicobacter pylori infection and chronic active gastritis were evaluated. Five biopsy specimens for bacteriological cultivation and three specimens for histological examination were obtained endoscopically from a defined area of the gastric antral mucosae of 83 patients. An increase in the number of biopsy specimens for cultivation from one to five revealed only one more H. pylori-infected patient. H. pylori was isolated from 31 of 83 patients. Three technically adequate samples for histological examination were obtained from each of 74 patients. Of these 74 patients, chronic active gastritis was diagnosed by demonstration of typical histological changes in all three specimens from each of 20 patients, in two of three specimens from each of 3 patients, and in one of three specimens from 1 patient. The results indicate that one biopsy specimen is sufficient for the isolation of H. pylori, whereas several specimens may be necessary for the histological diagnosis. Chronic active gastritis was found in four patients not infected with H. pylori; on the other hand, H. pylori was isolated from nine patients who showed no signs of chronic active gastritis in any of three samples.

Fatal cytomegalovirus (CMV) colitis in a patient receiving low dose prednisolone therapy.

Cytomegalovirus (CMV) colitis is uncommon in patients who are not gravely immunodepressed. We report a case of fatal CMV colitis in a 54-year-old woman on low dose steroid therapy. She was admitted to hospital after sudden onset of abdominal pain and hemorrhagic watery diarrhea. After 25 days in the hospital, treatment with high dosage of methylprednisolone was started for presumed ulcerative colitis. Her condition worsened and she died 52 days after admission. It is important to recognize CMV colitis as differential diagnosis to inflammatory bowel disease, particularly when the colitis is refractory to immunosuppressive treatment.

Campylobacter pylori infection and its relation to chronic gastritis. An endoscopic, bacteriologic, and histomorphologic study.

Campylobacter pylori was isolated from 27 of 61 gastric antral biopsy specimens and from 8 of 61 duodenal biopsy specimens. A significant correlation between the occurrence of C. pylori and chronic active gastritis was demonstrated. However, the presence of the bacterium on normal mucosa weakens the theory of C. pylori as a primary causal organism. There was a significant correlation between isolation of C. pylori and erosive lesions in the antral mucosa as diagnosed by endoscopy. No correlation was found between endoscopic findings and histologically verified chronic active gastritis. The microbiologic examinations in this study showed a high degree of homogeneity between the isolated strains of C. pylori. A 3-OH-octadecanoic acid of the bacterial cell wall seemed to be specific for this organism and was identified in all our isolates and in the type strain of C. pylori. We therefore conclude that all Campylobacter-like organisms isolated in this study belonged to one taxonomic unit.

Bacteria of the gastric antrum and their relation to chronic gastritis.

Biopsy samples from the gastric antrum were taken from 61 patients. On bacteriological culture, Campylobacter pylori was isolated in 27 subjects. Thirty-four patients had chronic gastritis, as seen in routine-stained histological sections. By means of the May-Grünwald-Giemsa (MGG) staining technique, bacteria were demonstrated in sections from 26 subjects. Of these, 22 had gastritis histologically. In 13 subjects, structures similar to Campylobacter pylori were found in MGG-stained sections, 11 of these having chronic active gastritis histologically. Scanning electron microscopy demonstrated bacteria with the typical appearance of Campylobacter pylori, but other types of bacteria were also found, both on electron microscopy and on bacteriological culture. The study confirms that there is an increased frequency of histological gastritis when Campylobacter pylori is present in the samples (p = 0.009). However, a causative role of the bacteria could not be demonstrated in this study, and bacterial penetration into the epithelium was not observed.