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In humans, CH4 is produced in the colon by methanogenic archaea and is detected in breath samples from approximately 50% of healthy adults, identified as CH4-excretors. Methanogenesis and sulfate reduction have been described as two mutually exclusive processes, potentially regulated by sulfate availability. To determine whether microbial population balances reflected these apparently co-regulated activities, we compared sulfate-reducing bacteria, methanogenic archaea, sulfate and sulfide concentrations in faeces of 10 CH4-excretors (CH4+) and 9 non-CH4-excretors (CH4-). The mean +/- SE of the logarithm of methanogenic archaea per gram wet weight were 9.0 +/- 0.2 and 4.0 +/- 0.7 for CH4+ and CH4-, respectively (P0.001). Sulfate-reducing bacterial counts were 6.5 +/- 0.1 and 7.3 +/- 0.2, respectively (P0.001). Fecal sulfate and sulfide concentrations did not differ between groups. These results suggest that a competitive interrelation between methanogenic archaea and sulfate-reducing bacteria occurs in the human colon. However, it does not lead to a complete exclusion of the two populations.

The indigenous microflora of the upper digestive tract is poorly developed and consists of microorganisms in transit, originating in the oro-pharynx. Aerobic bacteria, mainly streptococci, predominate. In the normohydrochloric stomach, the mean fasting bacterial concentration is 10(3)-10(4)/ml gastric juice. In the small intestine, levels of up to 10(5) bacteria/ml contents are reached. The essential mechanism which maintains this relative sterility of the upper digestive tract is the gastro-intestinal transit and in particular the interdigestive migrating motor complex. In the terminal ileum, a zone subject to relative stasis, the intraluminal bacterial population rises to 10(8)/ml in one third of subjects, with the appearance of enterobacter and strict anaerobes. In the colon, a zone of physiological stasis, the number of microorganisms per ml of contents is 10(8)-10(9) on the right side and 10(10)-10(12) on the left side. The dominant flora is strictly anaerobic and the subdominant flora optionally aero-anaerobic, consist mainly of Enterobacter, Streptococci and Lactobacilli. The balance between the species of microorganisms in the colonic ecosystem and its stability results primarily from microbial antagonisms. The barrier flora, consisting of groups of anaerobes, either prevent the implantation of exogenous microorganisms (drastic barrier) or limit it to the subdominant flora (permissive barrier). The repression of the subdominant flora by the dominant flora prevents the subdominant flora from spreading to the mesenteric ganglia and then the whole body. Rupture of the barrier flora by a wide-spectrum antibiotic may permit the local multiplication of a pathogenic organism (C. difficile, Salmonella), or the spread of an opportunist organism (Klebsiella pneumoniae).

A double-blind randomized parallel group trial was undertaken to compare the acceptability and efficacy of 2 forms of analgesic treatment, DI-Antalvic (Houde Laboratories, Puteaux, France) (30 mg dextropropoxyphene and 400 mg paracetamol per capsule) and Efferalgan-Codeine (UPSA Laboratories, Rueil Malmaison, France) (30 mg codeine and 500 mg paracetamol per tablet) prescribed for 1 week at doses of 6 capsules/day and 6 tablets/day, respectively, in 141 outpatients with active osteoarthritis of the knee or hip. The principal aim of the trial was concerned with acceptability, with efficacy as its secondary aim. The principal trial criterion was defined as overall assessment of acceptability by the patient at the end of the trial (success or failure) or by treatment dropouts because of an adverse effect (failure). Comparability of the groups was confirmed before any treatment regarding the physical characteristics of the patients, characteristics of osteoarthritis, and the initial level of pain and functional consequences of pain. Results show that the analgesic efficacy of the treatment was similar, but that the acceptability of Efferalgan-Codeine was significantly worse than that of DI-Antalvic: 53% failure with Efferalgan-Codeine versus 29% failure with DI-Antalvic (P = .005). Other trials of the same type would seem necessary (comparison of lower doses, other types of pain) before being able to generally extrapolate such findings.

Bifidobacterium sp is a natural component of the dominant colonic microflora that was recently introduced into several fermented dairy products. The aim of the present study was to study the fate of this microorganism in the human gut. On the basis of antibiotic resistance characters, a variant of Bifidobacterium sp that could be distinguished from indigenous bifidobacteria in the fecal flora was selected, and its survival and colonization in the colon was examined. This strain was used to ferment milk, and 125 g of the fermented product obtained was ingested by eight healthy volunteers three times daily for 8 days. Stools were recovered and weighed throughout the study. The results showed that the exogenous Bifidobacterium sp appeared in the stools and reached a mean level of 8.8 +/- 0.1 log colony-forming units per gram. This level was maintained as long as the fermented dairy product was consumed. When its ingestion stopped, the exogenous Bifidobacterium sp gradually decreased and was no longer detectable 8 days after cessation. The mean recovered quantity during the 8-day period of administration of the ingested bifidobacteria excreted in stools was 12.1 +/- 0.1 log colony-forming units per gram, i.e., 29.7% +/- 6% of the ingested bacteria, which was similar to the percentage that reached the colon in previous studies. It is concluded that under physiological conditions, exogenously administered Bifidobacterium sp do not colonize the human colon. However, the high fecal concentrations of exogenous bifidobacteria reached are compatible with metabolic "probiotic" activities.

Oro-ileal intubation was performed in 6 healthy volunteers who ingested, either 100 g of a fermented milk containing 10(8)/g Lactobacillus acidophilus and 10(7)/g Bifidobacterium sp or sterilized fermented milk along with a meal in random order. Lactobacillus acidophilus and Bifidobacterium were counted in the ileal fluid which was aspirated continuously for 8 h, and flow rates were calculated using the constant slow infusion of PEG 4000. After ingestion of fermented milk but not after control, hourly ileal flow rates of Lactobacillus acidophilus and Bifidobacterium increased form 4.8 +/- 0.2 and 4.9 +/- 0.6 to 7.2 +/- 0.3 and 8.0 +/- 0.3, respectively (mean +/- SE log10 CFU). 8.3 +/- 0.2 Lactobacillus acidophilus and 8.8 +/- 0.1 Bifidobacterium were recovered in the ileum which represented 1.5 percent and 37.5 percent of the ingested bacteria, respectively. In conclusion, under usual conditions of fermented milk ingestion, a large number of living Lactobacillus acidophilus and Bifidobacterium pass through the upper gastrointestinal tract and reach the colon.

Therapeutic efficacy of mesalazine controlled-release suppository 1 g once daily was compared with that of a placebo during 2 weeks in 50 patients (26 in the mesalazine group, 24 in the placebo group) with ulcerative proctitis, in a double-blind randomized trial. Endoscopic and clinical remission was seen in 69 and 65% of mesalazine-treated patients and in 33 and 25% of placebo-treated patients respectively (Por = 0.01). No side effects were seen. It is concluded that a once-a-day administration of 1 g mesalazine controlled-release suppository is effective for topical treatment of patients with ulcerative proctitis.

The therapeutic efficacy of 1 g 5-aminosalicylic acid enema was compared with that of 90 mg hydrocortisone acetate foam following daily rectal administration to patients with idiopathic proctitis or proctosigmoiditis during two weeks. A total of 199 patients (103 5-aminosalicylic acid, 96 hydrocortisone acetate) were included in a randomized, multicenter trial. Endoscopic and clinical remission was seen in 67 and 69 percent of the 5-aminosalicylic acid-treated and in 50 and 45 percent of the hydrocortisone acetate-treated patients (P less than 0.05), respectively. Mild side effects were seen in 10.7 percent of the 5-aminosalicylic acid-treated patients and in 3.1 percent of the hydrocortisone acetate-treated patients (P = 0.05). After 2 weeks, 5-aminosalicylic acid enemas are more effective than hydrocortisone foam for topical treatment of patients with idiopathic proctitis or proctosigmoiditis.

We report 7 prospectively followed cases of lymphomatous polyposis of the gastrointestinal tract. They were characterized by multiple polypoid lesions affecting several segments of the gastrointestinal tract always involving the colon and the rectum. An ileocecal mass was present in 4 cases. Regional lymph node involvement was constant. Peripheral lymphadenopathy was frequent (5 cases out of 7), as was other extra-digestive extension to the bone marrow (4 cases out of 7) and cavum (3 cases out of 7). The histopathological aspect was that of a small cleaved cells (working formulation) or centrocytic (Kiel classification) non-Hodgkin's lymphoma. The peculiar morphology and phenotype of the tumoral B-lymphocytes suggest their possible follicle marginal zone origin. Lymphomatous polyposis bore a rapidly fatal prognosis in every case (mean survival 20 months). This study of seven patients together with the 20 well-documented cases of the literature confirms the existence of lymphomatous polyposis as a distinctive clinicopathological entity among gastrointestinal non-Hodgkin's lymphoma.

In this paper a summary of recent work on proton tunneling in intermolecular hydrogen bonds in the condensed phase is presented and its relevance to biological systems is discussed. Dye molecules are used to influence the proton structure in neighboring hydrogen bonds. The optical transitions of the dye serve as a probe of this structure and the dynamics. A variety of optical spectroscopic measurements at low temperatures leads to a determination of the tunneling splitting and the rate of proton transfer in benzoic acid dimers. A theoretical analysis of these data within a simplified model suggests that fluctuadons of the energy difference of the tautomers determine the relaxation behavior and that multiphonon processes dominate the relaxation of delocalized protons. 1.

The mechanism of hypocalcemia was assessed prospectively in 10 gastroenterological hypomagnesemic patients. Baseline serum magnesium was 0.9 +/- 0.1 mg/dl and calcium, 7.2 +/- 0.4 md/dl. Plasma 25-hydroxyvitamin D (25 (OH)D) was low in 5 patients and normal in the others. Plasma parathormone (PTH) and urinary cyclic AMP (ur. cAMP), although twofold above normal values, were inappropriately low and increased sharply after a magnesium bolus injection. There was no renal resistance to PTH as ur. cAMP increased after i.v. bovine PTH bolus injection. Subsequently, patients were randomly divided into 2 groups, each including patients with low or normal levels of 25 (OH)D, receiving either MgCl2 (group I) or 1 microgram/d of 1-alpha (OH)D (group II) for one week. Although magnesium status remained low in group II patients, increase in plasma calcium was identical in both groups. Serum calcium levels in patients receiving combined 1-alpha (OH)D and MgCl2 during a second week of treatment returned to normal. In the 4 tested patients, plasma 1,25 (OH)2D levels were low before, but also after correction of hypomagnesemia, suggesting that low level of 1,25 (OH)2D might not be due to hypomagnesemia. Therefore, treatment with low dosage of 1-alpha (OH)2D associated with magnesium chloride repletion can be recommended to restore normal calcium homeostasis in patients with intestinal hypomagnesemia.

Jejunal secretion of albumin, immunoglobulins and secretory component was studied using the segmental perfusion technique with an occluding balloon, in two patients with common variable hypogammaglobulinemia and one patient with selective immunoglobulin A deficiency. Results were compared with those of twenty-two controls previously studied under the same conditions. In all three cases, jejunal secretion rate of immunoglobulin A was nil and secretion rates of albumin and immunoglobulin G were increased as compared to controls. Jejunal secretion rate of immunoglobulin M was increased in the patient with selective immunoglobulin A deficiency, normal in one case of common variable hypogammaglobulinemia and almost nil in the other case. Secretory component was secreted in the jejunal lumen mostly or exclusively under a free form depending on partial or total absence of immunoglobulin A and M. This study allowed to confirm in vivo that secretion of secretory component is independent of the presence of immunoglobulins. Intestinal perfusion might be a useful tool in the investigation of immunological diseases of the intestinal tract.

SUMMARY We studied the local humoral immunity of histologically non-involved jejunum in patients with Crohn's disease. Normal subjects and patients with ulcerative colitis served as controls. Jejunal fluid samples were collected during segmental jejunal perfusion, under an occluding balloon and the in vivo jejunal secretion of the following proteins was determined: albumin, orosomucoid, transferrin, α2-macroglobulin, secretory component, monomeric and polymeric IgA, IgG, and IgM. The densities and number of IgA-, IgG-, and IgM-containing cells in the lamina propria of the jejunum were measured on perendoscopic biopsies. Jejunal secretion of polymeric IgA and the density of IgA-containing plasma cells in the lamina propria were significantly lower in patients with Crohn's disease than in both control groups. This abnormal intestinal immune response, which was not correlated to the activity of the disease, might be involved in its pathogenesis.

Over the past 15 years (1974-1989), 126 patients with Crohn's disease received azathioprine (n = 123) or 6-mercaptopurine (n = 3). Seven patients were lost of follow-up during the first month and were not analyzed. Among the 119 patients analyzed (52 men, 67 women, mean age 31.6 years), the median duration of treatment was 9.1 months (range: 8 days to 15 years). Most of the 109 patients with active disease at the beginning of the immunosuppressive therapy were either steroid-dependent (n = 63) or steroid-resistant (n = 23); 19 had frequent relapses and/or extensive involvement of the gastrointestinal tract; 4 had severe perianal disease. Among these 109 patients, 25.4, 51, 60.4 and 64.4 percent were in clinical remission at 3, 6, 9 and 12 months (life-table analysis) respectively. There was no difference in outcome of patients with colonic, ileocolonic or small intestinal involvement. Steroid-resistant patients fared better than steroid-dependent patients (81 percent vs 59 percent of remission within the first year; p less than 0.001). In the 62 patients with quiescent disease treated with azathioprine or 6-mercaptopurine, previous remission had been achieved with immunosuppressive therapy in 52, 8 were treated after a bowel resection which was assumed to be curative; 2 had achieved remission after total parenteral nutrition. In these patients, the percentages of relapse were 15.3 at the end of the first year and 20.3 at the end of the second year. Among the 8 patients treated with azathioprine after bowel resection, only one relapse occurred 1.5 months after surgery. Nineteen percent of the patients had adverse reactions that required discontinuation of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Elevated antibody (Ab) levels to gliadin (GL), the alcohol soluble fraction of gluten, are present in the serum of patients with coeliac disease (CD), an enteropathy caused by hypersensitivity to gluten. The site of production and role of these Abs in the pathogenesis of the disease are poorly understood. In order to evaluate in vivo the secretion of Ig by the jejunal mucosa in CD, we have analysed jejunal fluids collected during a perfusion of a 40cm jejunal segment under an occluding balloon which avoid contamination with other intestinal secretions (1). Diisopropylfluorophosphate (protease inhibitor) was added to the samples Jejunal biopsies and serum were also collected.

purpose: The concentrations of myeloperoxidase (MPO), a neutrophil granule constituent, and eosinophil cationic protein (ECP), a specific eosinophil granule protein, were measured in jejunal perfusion fluid in an attempt to elucidate the neutrophil and eosinophil involvement of the small bowel in health and disease. patients and methods: The control group consisted of 14 males and two females. Ten patients (seven males and three females) with Crohn's disease and seven patients (two males and five females) with celiac disease were also studied; in addition, one patient with relapsing giardiasis, one patient with giardiasis and complete absence of plasma cells in small intestinal lamina propria, and one patient with selective IgA deficiency and no IgA plasma cells in duodeno-jejunal lamina propria were evaluated. Segmental perfusion of the jejunum was performed according to a previously described method. MPO and ECP were measured by radioimmunoassays. results: In healthy control subjects, the concentrations of both granule proteins were in a narrow range and much higher than would have been anticipated from passive leakage from circulating blood. In patients with celiac disease, the perfusion fluid concentrations of MPO and ECP were on average 3.5 and eight times, respectively, higher than the values seen in the controls. The jejunal segment perfused in patients with Crohn's disease was endoscopically and histologically normal. The perfusion fluid concentrations of MPO and ECP were increased 3.5 and two times, respectively, compared with that in the control subjects. Both patient groups and the control group had similar perfusion fluid concentrations of albumin. Data on MPO and ECP expressed as jejunal secretion rates gave the same differences between patients and controls as just described for the jejunal fluid concentrations. Immunohistochemical studies of jejunal biopsy specimens from another group of patients with celiac disease demonstrated a prominent extracellular deposit of ECP in the lamina propria of the atrophic intestinal mucosa, whereas the release of neutrophil constituents (cathepsin G, MPO) was scarce. In Crohn's disease, an extracellular degranulation ECP and, to a lesser extent, of cathepsin G was observed in relation to ulcerations only. conclusion: Data obtained indicate that the local release of neutrophil and eosinophil granule components is enhanced in the jejunal tissue from patients with celiac sprue and Crohn's disease. The prominent extracellular deposit of eosinophil granule constituents with cytotoxic properties at the site of inflammatory intestinal lesions in celiac sprue might reflect a pathophysiologic mechanism. The deposit of eosinophil and neutrophil granule components in ulcerated areas in Crohn's disease suggests that granulocytes may contribute to the inflammatory lesions also in this disease.

L'etude concerne la metastase ganglionnaire d'un carcinome medullaire de la thyroide, evoluant depuis 9 ans, chez une jeune fille de 16 ans. Le tableau clinique etait domine par l'existence d'une diarrhee motrice et d'un flush syndrome. L'examen histologique a confirme la structure particuliere de cette tumeur a stroma amyloide. La microscopie electronique montre des grains d'aspect neurosecretoire dans le cytoplasme, et des fibrilles qui semblent etre excretees dans le milieu extracellulaire et participer a la formation de l'amyloide. Il est generalement admis, depuis les travaux de Williams (1966) que ce carcinome deriverait des cellules C ou parafolliculaires, secretant la thyrocalcitonine. Cette activite secretoire ne rend pas compte des symptomes souvent associes, en particulier de la diarrhee; on peut suspecter l'association a la thyrocalcitonine de substances a activite vasopressive, telles que les kinines, la serotonine ou la 5 hydroxytryptamine.

Jejunal aqueous solubilisation of vitamin D3 was assessed in eight normal subjects, after ingestion of a standard liquid test meal. Percentages and total concentrations of vitamin D3 in the aqueous phase were significantly higher in the first post-prandial 30 minutes than during the following two hours, as were bile salts, total lipids, and free fatty acids. As shown by partial correlation analysis, a statistically significant relationship was found between aqueous concentrations of free fatty acids and of vitamin D3 in the jejunal content during all the 2 1/2 hours of the study. From these data it is concluded that, in healthy man, vitamin D3 is solubilised in vivo in mixed micelles only, and is governed in the aqueous phase.

The pathological and clinical features of alpha-chain disease, its immunological diagnosis, the structural abnormalities of the abnormal immunoglobulin A compared with those of proteins of gamma and mu heavy chains diseases, the course of the disease and its present treatment, the epidemiological factors involved and their influence on pathogenesis and finally, the relationship with the "Mediterranean abdominal lymphoma" or IPSID are successively described. The stress has been placed on the latest data which refine but no not modify the first description of the disease. In the same way as studies on the synthesis and structure of proteins in heavy chain diseases will provide new data on the biosynthesis of normal immunoglobulins, so the elucidation of sequential events leading from a plasmocytic stage reversible by antibiotic therapy alone to a highly malignant immunoblastic stage should improve our knowledge of the genesis of human lymphomas.

A progressive neurological syndrome with cerebellar signs, abnormal proprioception, areflexia and Babinski response was observed in a child with chronic intestinal malabsorption. There was no ophtalmoplegia or retinitis pigmentosa. Electromyography and biopsy showed no axonopathy or myopathy. Two other members of the family were also affected. The serum Vitamin E corrected the serum Vitamin E levels within a few months and led to secondary neurological improvement. The authors underline the importance of searching for Vitamin E deficiency and its cause in patients, especially children, with signs of spino cerebellar degeneration. Substitative therapy may have a favorable influence on the neurological condition even when administered late.

The aim of this work was to study the role of gut associated lymphoid tissue in the control of bacterial translocation. Two strains of Escherichia coli were orally inoculated to 71 axenic mice. Ten days after, the 2 initial strains and 2 others, resulting from plasmidic exchanges, were present in the digestive tract of the mice which were divided in two groups: the first group (n = 41) received one intraperitoneal injection of cyclophosphamide 100 mg/kg; the second control group (n = 30) received isotonic saline. The following parameters were studied 3, 5 and 9 days after the injection: the population level of the 4 strains in the caecum, their translocation to mesenteric lymph nodes, liver, spleen and circulating blood, the density per unit surface of lamina propria plasma cells and intraepithelial lymphocytes in duodenal and caecal mucosae. The population in each strain found in the caecum was different from the 3 others but similar within the two groups of animals and remained unchanged with time. In the control group, bacterial translocation to the mesenteric lymph nodes decreased (p less than 0.01), while the density of plasma cells increased (p less than 0.01) from the 3rd to the 9th days. In the cyclophosphamide treated group, translocation to the mesenteric lymph nodes increased (p less than 0.01), while the density of intestinal plasma cells decreased (p less than 0.05) from the 3rd to the 9th days. Density of intraepithelial lymphocytes did not vary with time in each group and from one group to another. Bacterial translocation to liver, spleen and systemic blood was weak and did not increase in the treated group.(ABSTRACT TRUNCATED AT 250 WORDS)