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Gastrointestinal bleeding and iron absorption in the experimental blind loop syndrome.

Rats with surgically created self-filling jejunal blind loops and the blind loop syndrome manifested gastrointestinal bleeding and hyperabsorption of iron. Although the mean hematocrit and serum iron levels of rats with self-filling blind loops became overtly anemic and manifested low-serum iron levels. It is suggested that the documented gastrointestinal bleeding in these rats with the experimental blind loop syndrome is another manifestation of damage to the intestinal epithelium in conditions of small intestinal bacterial overgrowth.

Animals

Small intestinal mucosal injury in the experimental blind loop syndrome. Light- and electron-microscopic and histochemical studies.

Microscopic (light and electron) and histochemical abnormalities have been demonstrated in the jejunum of rats with the blind loop syndrome. Three groups of animals were studied: normal control animals, and animals with either self-filling (SF) or self-emptying (SE) blind loops. Vitamin B12 malabsorption and bacterial overgrowth occurred only in those animals with SF blind loops. Three jejunal segments were studied: the blind loop segment and the jejunal segments proximal and distal to the blind loop. In the animals with the blind loop syndrome, those with SF blind loops, the most striking findings occurred in the blind loop itself, with similar but less marked changes in the jejunum distal but not proximal to the blind loop segment. Hypertrophy of both crypts and villi was evident with focal abnormalities of villus architecture. Approximately 10 to 20% of the columnar cells in the upper half of the villi were swollen and vesiculated. By electron microscopy microvilli demonstrated a variety of degeneration changes and the glycocalyx and terminal web were disrupted. Mitochondria and endoplasmic reticulum (ER), both smooth and rough, were swollen. Concentric whorls of parallel membranes and long, curvilinear rough ER were present in the cytoplasm. Histochemically, there was loss of enzymatic activity in the epithelial brush border, mitochondria and ER. Inasmuch as bacterial invasion of the jejunal mucosa was not seen, the etiology of these changes is not known but may involve bacterial "toxins" or products of bacterial metabolism. These morphological observations demonstrate that both brush border and intracellular injury occur in the jejunal epithelial cell of rats with the experimental blind loop syndrome.

Animals

Brush border peptidases and arylamidases in the experimental blind loop syndrome of the rat.

Peptidase and arylamidase activities were assessed in purified brush borders from jejunum of rats with surgically created blind loops. The blind loop segment and the jejunum proximal and distal to the blind loop were studied. Comparable jejunal segments from control rats were also studied. The blind loop syndrome was documented by presence of macrocytic anemia. Enzyme activities were determined on purified brush borders. In rats with the blind loop syndromes enzymatic activities hydrolizing sucrose, L-Leucyl-beta-naphthylamide, L-lysyl-beta-naphthylamide, alpha-L-glutamyl-beta-naphthylamide, L-phenylalanyl-alanine and L-leucyl-glycine were significantly reduced as compared to controls (P less than 0.001). After a short course of antibiotic therapy enzymatic activities returned to normal. Our findings suggest a reversible intestinal mucosa damage in the rat with blind loop syndrome.

Aminopeptidases

Functional, biochemical and morphological alterations in the intestines of rats with an experimental blind-loop syndrome.

In rat self-filling blind loops and in the contiguous regions of the intestinal tract, considerable functional impairment, accompanied by pronounced morphological transformations of the mucosa, has been observed. The histological alterations consist of mucosal hypertrophy and a reduction in the villus height: crypt length ratio, which is indicative of a hyper-regenerative change. Various enzyme activities of the epithelial cells are reduced and the absorption otinal juices is greatly altered in favour of the free acids. Two mec,anisms have 0een dicids, or meta0olites from bacterial degradation, on the absorptive epithelium; 2. Reduced cellular maturity in response to the effect of bile acids and/or bacteria on the lifespan of the cells.

Animals

The uptake of vitamin B12 by the sediment of jejunal contents in patients with the blind-loop syndrome.

Following preincubation of intrinsic factor- (IF-) bound 57CoB12 with the jejunal sediments of 6 patients with the blind-loop syndrome, the mean uptake by the sediments of IF-57CoB12 (28.1 percent plus or minus 4.2 percent S,E.M.) was significantly higher than the mean uptake by jejunal sediments from 5 control patients (5.8 per cent plus or minus 3.5 percent) (p smaller than 0.01). The uptake by the sediments significantly decreased when the incubations were carried out in the presence of lincomycin and neomycin. The jejunal sediments from the patients with the blind-loop syndrome inhibited the uptake of IF-57CoB12 by perfused rat intestinal segments (p smaller than 0.01), whereas the sediments from the control patients had no such inhibitory effect (p smaller than 0.5).

Aged

Enterotoxigenicity of colonising coliform bacteria in tropical sprue and blind-loop syndrome.

The enterotoxigenicity of strains of Klebsiella pneumoniae, Enterobacter cloacae, and Escherichia coli, which represented the predominant coliform species isolated from the jejunum of 12 patients with tropical sprue and 5 with the blind-loop syndrome, was quantitatively assessed in terms of the ability of toxin preparations to induce water secretion as assayed by in-vivo perfusion in the rat jejunum. All 12 patients with sprue harboured 1 or more highly toxigenic strains--14 of the 16 strains isolated from this group produced heat-labile and/or heat-stable toxins which were as potent as toxins derived from strains isolated from persons with acute diarrhoea and documented as toxigenic. None of the 9 strains isolated from patients with the blind-loop syndrome produced potent toxins. This difference between the coliform bacteria in sprue and the blind-loop syndrome probably accounts, at least partly, for the different intestinal response in these two disorders to contamination by these organisms.

Acute Disease

Pathogenesis of mucosal injury in the blind loop syndrome.

Bacterial extracts were prepared from cultures originating in chronic self-filling intestinal blind loops in rats. Their ability to remove active maltase molecules from isolated brush border membranes was studied in vitro. Twelve strains in 51 tested, belonging to one of three species, Bacteroides fragilis, Clostridium perfringens, and Streptococcus fecalis, possessed maltase-releasing activity. The ability to remove maltase correlated well with the ability to hydrolyze p-nitrophenyl-tert-butyloxycarbonyl-l-alaninate (NBA), an ester substrate rapidly hydrolyzed by elastase, but not with substrated favored by tryhsin and chymotrypsin. Maltase-releasing activity from C. perfringens was strongly inhibited by soybean trypsin inhibitor and to a lesser extent by lima bean trypsin inhibitor. Of four chloromethylketone active-site directed inhibitors tested with specificities for elastase, trypsin, and chymotrypsin, inhibition was maximal with elastase-specific inhibitors. In two species, activity was shown to be heat sensitive, and to be inhibited by concentration of the extract. In one species maltase-releasing activity was shown to be due to an enzyme of molecular weight at least 66,000 with the capacity to remove lactase, sucrase, and alkaline phosphatase, as well as maltase. The results indicate that anaerobic or facultatively anaerobic species, previously identified with the pathology of of the blind loop syndrome, contain proteases which are capable of removing components of the intestinal surface membrane. These proteases appear to have elastase-like substrate specificity and may be involved in the etiology of disaccharidase deficiency in bacterial overgrowth syndromes.

Animals

Sensitivity of bile acid breath test in the diagnosis of bacterial overgrowth in the small intestine with and without the stagnant (blind) loop syndrome.

The bile acid breath test was studied to examine its sensitivity for establishing the diagnosis of bacterial overgrowth in comparison to that of the Schilling test and small-intestinal cultures in 12 patients with a stagnant (blind) loop syndrome, as well as in 38 patients who had other conditions with suspected bacterial contamination of the small intestine. The presence of bile acid malabsorption was excluded in all 50 patients by studies of fecal excretion of radioactively labeled bile acids. The bile acid breath test was positive in 100% (12/12) of the patients with a stagnant (blind) loop syndrome, whereas 92% (11/12) had a positive Schilling test and 75% (9/12) a positive small-intestinal culture. The abnormal tests improved only in 2 of 4 patients treated with tetracycline. In the group of 38 patients without demonstrable dilated or blind loops of small bowel who were suspected of having bacterial contamination of small bowel, the bile acid breath test was positive in 53% (20/38), the Schilling test in 39% (15/38), and the small-intestinal culture in 45% (17/38). The difference in the incidence of positive results between the tests in the two patient groups was statistically not significant. The findings of these studies have the following diagnostic implications: (1) Bile acid breath test, Schilling test, and cultures of aspirates from the upper small bowel are of comparable sensitivity in the detection of bacterial overgrowth in the small intestine. (2) A negative bile acid breath test makes the diagnosis of a stagnant (blind) loop syndrome very unlikely.

Bacteria

Osteomalacia complicating a blind loop syndrome from congenital megaesophagus-megaduodenum.

A young female with osteomalacia complicating a blind loop syndrome associated with congenital megaduodenum is described. In this case, the correction of vitamin D malabsorption by administration of antibiotics highlights the role of massive intraluminal bacterial overgrowth from destruction of vitamin D, or decreased unicellar solubilization due to deconjugation of biliary acids. The importance of cutaneous vitamin D synthesis in patients with osteomalacia of gastrointestinal origin is emphasized. The detection of megaduodenum and megaesophagus in the patient's father may be the first report of a familial association of these gastrointestinal abnormalities.

Abnormalities, Multiple

Protein digestion and absorption in the blind loop syndrome.

Protein digestion and absorption was studied in rats with 6-week-old surgically constructed self-filling intestinal blind loops and steatorrhea, ie, blind-loop animals and controls were fed a 14C-labeled protein meal containing a nonabsorbable marker, 51CrCl3, and sacrificed 1 or 2 hr later. Intestinal contents were analyzed for 14C, 51Cr, protein, trypsin, and the products of digestion. At 1 hr, 14C absorption was greater in controls, but at 2 hr there was no difference in absorption between the two groups. Marker studies showed that blind-loop filling resulted in a delay of the progression of intestinal contents distally. Intraluminal trypsin and porteolysis were similar in the two groups. Endogenous protein was greater in the blind-loop animals. The early stages of the blind-loop syndrome may be characterized by delayed protein absorption secondary to blind-loop filling, which is compensated for by the distal gut resulting in an absence of overall protein malabsorption.

Animals

[The blind-loop syndrome after side-to-side anastomoses of the gut (author's transl)].

The postoperative blind-loop syndrome can occur after side-to-side, end-to side or by-pass anastomoses of the gut and presents clinically as malabsorption syndrome. Pathogenetically, stasis or slowing of the bowel movements will cause a rapid increase of pathogenic bacteria in the small intestine. Malabsorption is characterized by 3 symptoms: Loss of weight, anemia, steatorrhoea. The method of choice for therapy is to perform a new, end-to-end, anastomosis of the intestine in order to re-establish a physiological situation. During the last 6 years 14 patients with malabsorption syndromes of varying degrees were operated upon: 6 had pure small intestinal anastomoses, 7 anastomoses between the small and large intestine and 1 patient had a side-to-side sigmoidal anastomosis. In all patients the side-to-side or by-pass anastomoses could be reversed.

Adolescent

Intestinal blind pouch- and blind loop- syndrome in children operated previously for congenital duodenal obstruction.

A follow-up study of 27 children operated for congenital duodenal obstruction (CDO) in the years 1953--71 is presented. Nine children belonged to the intrinsic and 18 children to the extrinsic group of CDO. A total of 7 retrocolic, isoperistaltic, side-to-side duodeno-jejunostomy, 7 Ladd's operation, 8 duodenolysis, 2 reduction of midgut volvulus, 2 duodenostomy a.m. Morton and one gastro-jejunostomy were performed at the age of 1 day--15 years. The clinical and radiological examinations were performed 3--21 years (mean 10 years 2 months) after these operations. In 3 cases there was a moderate duodenal dilatation, but reoperation was not necessary. During the follow-up period, one boy, now aged 8 years, developed a blind pouch-syndrome in the I portion of the duodenum containing a 5 x 5 cm phytobezoar 4 1/2 years after duodeno-jejunostomy. The frequency of blind pouch-syndrome after duodeno-jejunostomy was thus 1:7 or 14%. One girl, now aged 9 years, developed a blind loop-syndrome in the ileocaecal segment 3 months after side-to-side ileotransversostomy, which was performed from adhesion-obstruction after duodenolysis for malrotation I and CDO. Both the blind pouch- and the blind loop-deformation were resected and the children recovered well. To avoid blind-pouch- and blind loop-deformations in the intestines, the anastomosis must be made wide enough, and especially in the surgery of the jejuno-ileo-colic region an end-to-end anastomosis is preferable.

Bezoars