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We recently reported increased intestinal permeability to polysucrose (PS) 15000 in patients with Crohn's disease and in patients treated with non-steroidal anti-inflammatory drugs (NSAIDs). We have now compared this new macromolecular marker (14,700 D) with the conventional markers, 51Cr-labelled ethylenediaminetetraacetic acid (EDTA) (342 D) and 14C-mannitol (182 D), in healthy humans.Twenty healthy volunteers on four occasions ingested a solution containing PS 15000, 51Cr-EDTA, and 14C-mannitol, the test solution being, respectively, isoosmolar, hyperosmolar, isoosmolar followed by a standard meal, and isoosmolar after 1 week of NSAID treatment. Fractional urinary excretion of the substances was measured over 0-4 h, 4-8 h, and 8-12 h.The excretion of PS 15000 was, like that of 51Cr-EDTA but unlike that of 14C-mannitol, increased by NSAID pretreatment, little affected by hyperosmolar test solution, little correlated to urinary volume, and skew with regard to frequency distribution. Despite being nominally about 40 times lower, the excretion of PS 15000 was highly correlated to that of 51Cr-EDTA but not to that of 14C-mannitol. A standard meal reduced the test variability for all three probes.PS 15000 may be an alternative to 51Cr-EDTA as a small-intestinal permeability marker. Inclusion of a standard meal reduces test variability.

OBJECTIVES--To examine the microflora of the upper small intestine in patients with seropositive rheumatoid arthritis (RA) using a combination of microbial cultivation and tests for microbial metabolic activity. METHODS--Twenty five patients with seropositive RA, 12 achlorhydric control subjects, and 11 control subjects with normal gastric acid secretion were investigated. Disease activity was evaluated in the patients with RA by three different indices. Eight (32%) of the patients with RA had hypochlorhydria or achlorhydria. The acid secretory capacity was determined with pentagastrin stimulation. A modified Crosby capsule was used to obtain biopsy specimens and samples of intestinal fluid from the proximal jejunum; aerobic and anaerobic microbial cultivation of mucosal specimens/intestinal fluid was carried out, and gas production and microflora associated characteristics in jejunal fluid were determined. Additionally, a bile acid deconjugation breath test was performed. RESULTS--Subjects with at least one of the following findings were considered to have bacterial overgrowth: positive bile acid deconjugation test; growth of Enterobacteriaceae; positive gas production; or low tryptic activity. By these criteria half of the patients with RA with hypochlorhydria or achlorhydria and half of the achlorhydric controls had bacterial overgrowth. Thirty five per cent of the patients with RA with normal gastric acid secretion had bacterial overgrowth compared with none of the normal controls. Disease activity indices and rheumatoid factor titres were significantly higher in patients with RA with bacterial overgrowth than in those without. CONCLUSIONS--A high frequency of small intestinal bacterial overgrowth was found in patients with RA; it was associated with a high disease activity and observed in patients with hypochlorhydria or achlorhydria and in those with normal acid secretion.

The effects of oral natural prostaglandin E2 (PGE2) on symptoms, disease activity, and gastrointestinal functions in rheumatoid arthritis (RA) were studied in an open pilot trial. Twelve patients, six taking and six not taking non-steroidal anti-inflammatory drugs (NSAIDs), received 1 mg natural PGE2 three times a day for six weeks. The treatment was tolerated well and the only side effect noted was slightly looser stools in three patients. Half of the patients reported subjective improvement and none had aggravation of symptoms. The Ritchie articular index and several biochemical inflammation markers decreased and were significantly reduced at the end of the treatment period. The thickness of the small intestinal mucosa increased during the PGE2 treatment. The intestinal permeability pattern, measured by urinary excretion of polyethylene glycols (PEG 400), differed between the patients taking and not taking NSAIDs. The initially high urinary PEG 400 excretion values in the patients taking NSAIDs decreased and the initially low excretion values in patients not taking NSAIDs increased during the PGE2 treatment. The jejunal contents became sterile in 5/6 patients not taking NSAIDs and remained sterile in 1/6 patients taking NSAIDs at the end of the treatment. The treatment period was associated with a reduction of lactobacilli in patients not treated with NSAIDs. Thus the treatment appeared to decrease disease activity and to improve small intestinal functions in patients with RA, findings that need confirmation in a controlled trial.