[14C]D-xylose breath test for small intestinal bacterial overgrowth.
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Biomedical subjects
Publications and source records attributed to J J Rumessen.
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Two new fiber types, pea fiber (PF) and sugar beet fiber (BF), were compared with wheat bran (WB) to investigate the effect on postprandial blood glucose and serum insulin responses in normal subjects. The control meal consisted of 150 g ground beef mixed with 50 g glucose and 20 g lactulose. Only addition of PF (15 g pure fiber) reduced the area under the incremental blood glucose curve significantly (by 65%, p less than 0.05). None of the fibers affected the area under the insulin-response curve significantly although it was reduced by all fibers. Mouth-to-cecum transit time, assessed by the hydrogen breath technique, was decreased by WB and BF, (p less than 0.05) but not by PF. PF is palatable and may prove beneficial as a fiber supplement for diabetics.
The aim of the present study was to determine whether changes in orocaecal transit time (OCTT) affect the magnitude of the breath hydrogen (H2) excretion after ingestion of unabsorbable carbohydrate. We studied eight healthy subjects by interval sampling of end expiratory H2 concentration for 12 hours after ingestion of: (1) 10 g lactulose (L); (2) 10 g L with 20 mg metoclopramide (M) as tablets; (3) 20 g L, and (4) 20 g L with 7.5 mg diphenoxylate (D) as tablets, in random order. In spite of significant changes in OCTT after M and D, there were no significant changes, compared for the same dose of lactulose, with respect to area under the breath H2 excretion curves, peak increments of H2 concentration or timing of the peak increment. We conclude that, within the ranges observed, the OCTT does not significantly affect the shape of the H2 concentration versus time curves. In comparative studies estimates of the degree of carbohydrate malabsorption on the basis of breath H2 concentration may be valid in spite of differences in OCTT.
The effect of dietary fibre on starch absorption was investigated in 8 healthy subjects. Amounts of starch escaping small-bowel absorption was assessed by comparison of breath H2 excretion after test meals and after lactulose (10g). After ingestion of bread made from 100g of wheat flour increases in H2 excretion occurred in all subjects; the calculated fractions of unabsorbed starch ranged from 4% to 17% (median, 8%). Concurrent ingestion of this bread with either wheat bran, sugar-beet fibre, or pea fibre increased the fraction of unabsorbed starch to 12.5% (5-22%) (p less than 0.05), 12.5% (5-20%) (p less than 0.01), and 12% (5-27%) (p less than 0.01), respectively. Bread made from 100 g of low-gluten wheat flour only escaped small-bowel absorption in three subjects with a maximal fraction of 6% (p less than 0.05). All three fibres decreased mouth-to-caecum transit time. We conclude that the dietary fibres used in this impaired the absorption of wheat starch and thereby increased the amount of starch-derived carbohydrate available for colonic fermentation.
Twenty-five patients with functional bowel disease were given fructose, sorbitol, fructose-sorbitol mixtures, and sucrose. The occurrence of malabsorption was evaluated by means of hydrogen breath tests and the gastrointestinal symptoms, if any, were recorded. One patient could not be evaluated because of lack of H2 production. Based on a cut-off level of 10 ppm rise of H2 concentration, malabsorption was apparent in 13 patients, in 7 of which the calculated absorption capacities were below 15 g. In contrast, in patients given 50 g of sucrose, malabsorption could not be detected. Ingestion of fructose caused marked abdominal distress in patients with demonstrable malabsorption. Ingestion of sucrose in these patients gave less pronounced symptoms of abdominal distress. Malabsorption of a 5-g dose of sorbitol could be detected in 8 of 13 patients. Mixtures of 25 g of fructose and 5 g of sorbitol caused significantly increased abdominal distress, and more than additive malabsorption was found in several cases. The present study shows that pronounced gastrointestinal distress may be provoked by malabsorption of small amounts of fructose, sorbitol, and fructose-sorbitol mixtures in patients with functional bowel disease. The findings may have direct influence on the dietary guidance given to a major group of patients with functional bowel disease and may make it possible to define separate entities in this disease complex.
The reliability of end-expiratory hydrogen (H2) breath tests were assessed and the significance of some important pitfalls were studied, using a compact, rapid H2-monitor with electrochemical cells. The H2 response was shown to be linear and stable. The reproducibility of the breath collection technique was determined in 20 patients following ingestion of lactulose. The increment between consecutive means of duplicate samples indicative of a significant rise of H2 concentration never exceeded 10 p.p.m., the mean coefficient of variation of the duplicate samples was below 5%. Fasting H2 levels were studied in 10 healthy adults during a 4-month period and they showed very marked inter- and intra-individual variability (16% above 40 p.p.m.). Initial peaks (early, short-lived H2 rises unrelated to carbohydrate malabsorption) were identified in 25% of the breath tests (in 4% above 20 p.p.m). It is concluded that the technique used for interval sampling of end-expiratory breath samples for H2 concentration gives reliable results. The biological significance of H2 concentration increments can only be evaluated if the limitations of the technical procedures and the individual ability to produce H2 is known.
The utility of two brands of 20 ml plastic syringes for storage of hydrogen (H2) samples as obtained in H2 breath tests were studied. Plastipak syringes were found to be significantly better with regard to the stability of the H2 concentration and the variability between the H2 samples. Storage of the H2 samples in Plastipak syringes at 5 degrees C significantly improved the H2 retention, whereas refrigeration of H2 samples stored in Once syringes did not reduce H2 loss. Storage of H2 samples in refrigerated plastic syringes is efficient and reliable for several days if syringes with minimal sample variation are used.
Hydrogen breath tests were performed on 10 healthy adults after they had ingested a mixture of sorbitol and fructose, in which these substances were present in amounts corresponding to the individual absorption capacities. A significant malabsorption of this mixture was evident in 7 of 10 subjects. The mixture caused mild to severe gastrointestinal distress in five subjects. When the carbohydrates were given separately, symptoms were absent. There was a significant correlation between the individual absorption capacities of fructose and of sorbitol. A mixture containing a similar amount of fructose, but given as sucrose, and a similar amount of sorbitol was further given to four of the seven subjects showing malabsorption of the fructose-sorbitol mixture. Malabsorption now failed to appear, and symptoms were absent. These findings are of potential importance for the understanding of the physiologic processes involved in fructose absorption and suggest that in healthy adults the presence of sorbitol interferes with fructose absorption and/or vice versa. An interaction between small amounts of fructose and sorbitol causing malabsorption and abdominal distress has not been demonstrated previously. Gastrointestinal discomfort must be suspected to occur in sensitive individuals at a rather limited daily intake of fructose- and sorbitol-containing foodstuffs.
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Amiodarone has proved very effective in the treatment of otherwise resistant cardiac tachyarrhythmias. The use of amiodarone has, however, been limited due to its serious side-effects. A patient with cholestatic hepatitis due to amiodarone treatment is presented below and a review of the hepatotoxicity of amiodarone is given. It is concluded that solid evidence exists of hepatic injury due to amiodarone treatment, including steatosis, alterations resembling alcoholic hepatitis, cholestatic hepatitis and micronodular cirrhosis of the liver. Patients receiving amiodarone should be regularly screened with respect to hepatic enzyme levels. Therapy should be discontinued on the suspicion of cholestatic injury or hepatomegaly.
The capacity to absorb fructose in 10 healthy adults was investigated by means of hydrogen breath analysis. Fructose absorption was quantified with lactulose standards. Significant hydrogen production (greater than or equal to 20 ppm rise of breath hydrogen) was found after challenge with 10% solutions of 50, 37.5, 25, 20, and 15 g fructose in eight, seven, five, four and one subjects, respectively. One subject showed malabsorption after a 10 g dose and possibly also 5 g fructose. In contrast, no malabsorption could be detected in any of the 10 subjects after ingestion of 100 g, 75 g, or 50 g sucrose or a mixture of 50 g glucose and 50 g fructose. After ingestion of mixtures of 50 g fructose +25 g glucose and 50 g fructose +12.5 g glucose malabsorption was present in three and seven subjects, respectively. Symptoms during all challenges were mild, or absent. It is concluded that in the healthy state the absorption capacity of fructose given alone ranges from less than 5 g to more than 50 g. The absorption capacity of fructose given as sucrose is much higher. Glucose stimulates fructose uptake in a dose dependent fashion. The possible existence of more than one intestinal transport system for fructose is considered. The elucidation of the clinical relevance of the findings is important.
In muscularis externa of mouse small intestine, cells with ultrastructural features of macrophages were invariably observed in three layers: in the subserosal layer, between the circular and longitudinal muscle layers, and in association with the deep circular plexus. These macrophage-like cells (MLC) had a single indented nucleus, perinuclear Golgi complex, smooth and rough endoplasmic reticulum, many pits (coated and uncoated) in the plasma membrane, coated vesicles, light vesicles, and primary lysosomes, but rather few heterogeneous lysosomal vacuoles. MLC were partially enveloped by processes of interstitial cells of Cajal. FITC-dextran used in combined fluorescence stereo microscopy, fluorescence microscopy, and electron microscopy was employed as a tracer to study the endocytic qualities of the MLC. The mice were killed 5, 15, 30, and 60 min, 1 day, and 4 days after dextran administration. By fluorescence microscopy after 1 or 4 days MLC were observed as a constant cellular population with a strikingly regular distribution. By electron microscopy dextran-containing vacuoles were conspicuous after 1 h or more. MLC of the subserosal layer and between the circular and longitudinal muscle layers could be distinguished with respect to general appearance, pattern formation, and apparent dextran contents.
In 60 consecutive patients clinically suspected of having chronic pancreatitis the serum concentration of the immunoglobulins (IgA, IgG, IgM), the IgG- and IgA-type non-organ-specific autoantibodies against nuclear material (ANA), smooth and striated muscle, mitochondria, basal membrane, and reticulin, and the IgG- and IgA-type pancreas-specific antibodies against islet cells, acinus cells, and ductal cells (DA) were estimated blindly. In 23 of the patients chronic pancreatitis was verified, whereas chronic pancreatitis was rejected in 37 patients (control group). IgG and IgA were found in significantly higher concentrations in the patients with chronic pancreatitis than in the control group but within the normal range. ANA and DA occurred very frequently in both groups but with no statistical difference. Other autoantibodies only occurred sporadically. The findings of this study do not support the view of an immunological pathogenesis in chronic pancreatitis.
Sixty consecutive patients suspected of having bacterial overgrowth of the small intestine (BOG) had aerobic and anaerobic bacterial cultures made of fasting upper jejunal fluid and also a 14C-D-xylose breath test (XBT). Culture-proven BOG was present in 23 patients. In another 15 patients the presence of BOG was ruled out (diagnoses: irritable bowel syndrome, 8; chronic diarrhoea, 6; and lactose malabsorption, 1). These patients were used as controls. The other 22 of the 60 patients could not be placed in either group owing to the presence of factors known to predispose for BOG; none of them had abnormal jejunal cultures, but several had strong clinical suspicion of BOG. An abnormal XBT, defined as values exceeding upper 90% confidence limits (upper range) of the 15 patient control values within a 4-h period, was observed with the following frequencies in the 23 patients with BOG: after 60 min, 35%; after 120 min, 44%; after 180 min, 61%; and after 240 min, 65%. An abnormal XBT was observed in 41% of the 22 patients with normal jejunal cultures but with predisposition for, and clinical suspicion of, BOG. It is concluded that, compared with a relevant control material, the XBT tends to be rather insensitive and that a negative outcome of jejunal cultures is inadequate to exclude the presence of BOG.
The zinc iodide/osmic acid (ZIO) method was used in a modification that selectively stained nerves and associated interstitial cells of Cajal (ICC) of muscularis externa. Due to its selectivity the method allowed a detailed stereoscopical analysis of whole mounts with respect to the topography and morphology of these elements. The method thus assisted and expanded our ultrastructural studies. The ZIO staining allowed a distinction of four morphologically different interstitial cell types (ICC-I-IV) confined to four compartments. The stained components were: (1) A rich plexus of highly ramified interstitial cells (ICC-II) in the subserous layer. (2) Auerbach's plexus with an associated extensive plexus of interstitial cells (ICC-I) in close contact with tertiary fasciculi. (3) Nerve fasciculi of the outer division of the circular muscle layer. These formed a nerve plexus in a well-defined plane in the outermost cell layers (plexus muscularis superficialis), with few fasciculi located internal to this plexus. A few bipolar interstitial cells (ICC-IV) were associated with nerve fasciculi of this region. (4) A nerve plexus located in the region between the two subdivisions of the circular muscle, plexus muscularis profundus (PMP). PMP was revealed throughout the small intestine as a continuous network of elongated, circularly oriented meshes. The pattern of connections between PMP and the other enteric plexuses was studied stereoscopically. Ganglion cells intrinsic to PMP occurred widely scattered. Interstitial cells associated with PMP (ICC-III) were arranged in a plexiform manner; their morphology and relations to nerves were investigated in great detail. A selective innervation of ICC-III via axons of PMP was strongly supported.
The ultrastructure of plexus muscularis profundus (PMP) of the mouse small intestine was investigated subsequent to vascular perfusion with ruthenium red-containing and routine aldehyde fixatives. Four types of nerve terminals were revealed. Type I: numerous 500-A agranular vesicles and few 1,000-A granular vesicles. Type II: predominantly large (1,000-1,500 A), granular vesicles and fewer 500-A agranular vesicles. Type III: an abundance of mitochondria and many flattened vesicles (300 A X 700-1,300 A). Type IV was identified by abundant smooth cisternae 200 A in width. Types I-III formed close (200 A), synapse-like contacts to interstitial cells of Cajal (ICC-III). Presynaptic densities were frequent in type I endings. A direct innervation of muscle cells via PMP was only very occasionally suggested. ICC-III possessed a basal lamina and numerous caveolae associated with subsurface SER-cisternae. Mitochondria were very abundant in ICC-III-processes. ICC-III formed multiple, large gap junctions with outer circular-muscle cells and with other ICC-III. Also reflexive gap junctions were observed. Fibroblastlike cells (FLC) were distinguished by their prominent GER, the frequent presence of lipid droplets, and the lack of caveolae and a basal lamina. FLC never participated in synaptic arrangements or gap junctions. Macrophage-like cells were occasionally encountered. It is concluded that possible efferent and afferent nerve terminals in PMP may chiefly, if not exclusively, innervate ICC-III, the ultrastructure of which is compatible with efferent and/or afferent modulatory actions.
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