Absorption of folic acid, water and electrolytes in apparently normal proximal jejunum of patients with Crohn's disease studied by the technique of intestinal perfusion.
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Biomedical subjects
Publications and source records attributed to L M Nelson.
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Clofibrate is known to increase cholesterol saturation of bile and the prevalence of gallstones. We studied 10 healthy volunteer subjects to determine the effect of gemfibrozil (a new lipid-lowering agent) on biliary cholesterol saturation and to compare it with that of clofibrate. Biliary cholesterol saturation indices were calculated on fasting duodenal bile samples collected before and after administration of each drug for 4 weeks using a 4-week "washout" period between each preparation. There was a statistically significant rise in the cholesterol saturation index from a control value, taken as the mean of 2 samples, of 1.226 (0.785--1.526), median (range), to 1.547 (0.807--1.781) after clofibrate, P less than 0.05, but the rise to 1.352 (0.840--2.686) after gemfibrozil was not significant. However, direct comparison of the cholesterol saturation indices on clofibrate and gemfibrozil revealed no statistically significant difference. Only prospective clinical trials will establish definitively the risk of cholelithiasis on gemfibrozil but these results suggest that this drug is unlikely to have an advantage over clofibrate in this respect.
The importance of bile acids in causing gastric mucosal haemorrhage and the protective effect of prostaglandins and antacids has been studied in a series of studies using an animal model. Bile acids alone did not damage the gastric mucosa, but conjugated bile acids together with aspirin and hydrochloric acid may cause gastric mucosal haemorrhage. The prostaglandin analogue 15(R)15-methyl-E2 methyl ester protected the gastric mucosa against damage caused by conjugated bile acids together with aspirin or hydrochloric acid. Gastric mucosal protection was also achieved with antacids, but this effect appeared to be mainly on the aspirin rather than on the bile acid component of the damage. Bile acid binding, if it did occur, did not prevent the bile acid from increasing aspirin-induced gastric mucosal damage.
A high-performance liquid chromatographic method for the quantitation of adrenaline and noradranaline in urine is described, using fluorescence detection. The effluent from the liquid chromatograph is led directly into an analyser to produce the fluorescent trihydroxy-indoles from the catecholamines. The method is more reliable and specific than conventional fluorescence techniques. Both catecholamines can be detected at levels of 0.5 ng on the column.
A direct test of lipid absorption has been developed using [3H]glycerol triether as a lipid marker and [14C]glycerol trioleate as the test lipid. Percentage absorption of triolein is calculated from the isotope ratio ingested and excreted in faeces. The test is independent of a complete faecal collection, reproducible and shows little day to day variation. Absorption in 25 normal subjects ranged from 96.4--100% (mean 98.6, S.D. +/- 1.15). In 24 patients with known pancreatic or small intestinal disease and steatorrhoea absorption ranged from 0.01% to 89.9%. The test has also been assessed by comparison with a standard Lundh test and faecal fat estimation in 34 patients.
Taurodeoxycholic acid increases the incidence of aspirin induced gastric bleeding in rats and in vitro is well bound by Aludrox (aluminium hydroxide) and poorly bound by Maalox (aluminium hydroxide and magnesium hydroxide). We studied the relevance of this binding, as demonstrated in vitro, by observing the effect of the antacids on the occurrence of taurodeoxycholic acid and aspirin-induced bleeding in vivo in rats. Six groups of fasting male Sprague-Dawley rats (n = 24) were intubated and given either water, Aludrox or Maalox and, 30 min later, aspirin or aspirin plus taurodeoxycholic acid. 4 h later the stomachs were examined and rats were scored positive if a lesion greater than 1 mm across was found (incidence of bleeding); a lesion scoring system was also used (severity of bleeding). The incidence of bleeding was increased from 63% with aspirin to 92% with aspirin plus taurodeoxycholic acid (P less than 0.05). The incidence was reduced to 33% and 67% respectively by Aludrox and to 29% (P less than 0.05) and 71% by Maalox. The severity of bleeding (median lesion score, quartiles in parentheses) was increased from 3 (1;6.5) (aspirin) to 10.5 (6;15) (aspirin plus taurodeoxycholic acid); P less than 0.001. These were reduced to 0.5 (0;3); P less than 0.02 and 5 (0.5;9.5); P less than 0.05 respectively by Aludrox and to 0 (0;3); P less than 0.02 and 3 (2;8); P less than 0.02 by Maalox. The severity of bleeding was reduced by both antacids but the effect appeared to be mainly on the aspirin rather than the bile acid component of the damage.
Production of H2 by Azospirillum brasilense under N2-fixing conditions was studied in continuous and batch cultures. Net H2 production was consistently observed only when the gas phase contained CO. Nitrogenase activity (C2H2 reduction) and H2 evolution (in the presence of 5% CO) showed a similar response to O2 and were highest at 0.75% dissolved O2. Uptake hydrogenase activity, ranging from 0.3 to 2.5 mumol H2/mg protein per hour was observed in batch cultures under N2. Such rates were more than sufficient to recycle nitrogenase-produced H2. Tritium-exchange assay showed that H2 uptake was higher under Ar than under N2. Uptake hydrogenase was strongly inhibited by CO and C2H2. Cyclic GMP inhibited both nitrogenase and uptake hydrogenase activities.
A gas chromatographic method is described for the quantitative determination of urinary normetadrenaline, metadrenaline and 3-methoxytyramine using electron capture detection. The N,O-dipentafluoropropionyl beta-O-ethyl derivatives of normetadrenaline and metadrenaline and the N,O-dipentafluoropropionyl derivative of 3-methoxytyramine were prepared. The amines were purified by ion exchange chromatography and ion pair extraction. Amine derivatives from urine extracts were identified definitively by mass fragmentography. The 24-h excretion value for normetadrenaline in human urine is 167 +/- 95 micrograms (mean +/- S.D.), for metadrenaline is 116 +/- 74 micrograms (mean +/- S.D.) and for 3-methoxytyramine is 82 +/- 68 micrograms (mean +/- S.D.).
The effect of an elemental diet (Vivonex) together with a gluten-free diet on the absorption of water, sodium and chloride in the jejunum was studied in 4 patients with untreated adult coeliac disease before and after a 1-month course of therapy. The morphology of the jejunum was also studied by jejunal biopsy taken at the same time as the intestinal perfusion. The results were compared with those obtained in 4 patients with adult coeliac disease treated with a gluten-free diet alone. No marked improvement was noted in the transportation of water, sodium and chloride after either treatment with Vivonex and a gluten-free diet or after a gluten-free diet alone, and no marked histological changes were found. Clinical improvement occurred in both groups of patients, in that the diarrhoea improved in all patients and they generally felt better. There appears to be no additional advantage of using an elemental diet with a gluten-free diet in the initial management of adult coeliac disease.
1. Rats were fed with the elemental diet Vivonex for 1 or 3 months and their jejunal histology was compared with that of an equal number of rats fed on a normal diet. 2. After 1 month of Vivonex feeding a significant reduction in the ratio of crypt height: villus height (CH:VH) was found in the Vivonex-fed rats (n = 4) compared with the control rats (n = 4) (P less than 0.05). 3. After 3 months the CH:VH ratio was also reduced in the Vivonex-fed rats (n = 18) compared with control rats (n = 18) (P less than 0.002). Villus height was significantly increased (P less than 0.002) and crypt height decreased (P less than 0.05). 4. Jejunal protein content, alkaline phosphatase and disaccharidase activity were also determined in 12 control and 12 Vivonex-fed rats from the 3 months study. 5. Alkaline phosphatase activity was increased from a control value of 201 +/- 8 to 243 +/- 15 munits/cm in the Vivonex-fed rats (n = 12) (P less than 0.05) but no significant changes in lactase, sucrase or maltase activites were found. The observed decrease in the CH:VH ratio suggested an improved survival of the mature enterocyte population during elemental diet feeding.
Three bacterial isolates, a Pseudomonas sp., a Bacillus sp., and an Arthrobacter sp., commonly isolated from a hummocky sedge-moss meadow at Devon Island, N.W.T., Canada, were selected for further taxonomic characterization and for a study of the effects of temperature and limiting carbon source on growth. Pseudomonas M216 resembled P. putida and Bacillus M153, B. carotarum. Arthrobacter M51 had growth-factor requirements which were more complex than those of any named species of that genus. The temperature ranges of growth indicated that Pseudomonas M216 and Arthrobacter M51 were psychrotrophic while Bacillus M153 was mesophilic. Growth in batch culture at limiting glucose concentrations enabled the calculation of Ks and Y values for each isolate. These were similar to those obtained for other organisms and Pseudomonas M216 and Bacillus M153 showed a high affinity for glucose. The nutritional versatility of Arthrobacter M51 and its ability to grow at low temperatures and the high growth rates and affinity of Pseudomonas M216 for low substrate concentrations may account for their competitive abilities in the natural environment, while the inability of Bacillus M153 to grow at low temperatures may limit its activity in tundra soils.
Azospirillum brasilense was grown continuously at various levels of dissolved oxygen (O2) in a nitrogen-free medium containing malates as the carbon source. Steady-state cultures were established only at O2 concentrations less than 0.0150 atm (1 atm = 101.325 Pa) and rates of acetylene reduction (N2 fixation) and efficiencies of N2 fixation were maximal between 0.0050-0.0075 atm dissolved O2. These cultures appeared to be O2- or N2-limited. There was no evidence of a respiratory protective mechanism in this organism. Anaerobic denitrifying steady-state cultures were established with nitrate (NO3-) as the sole nitrogen source with no detectable N2 fixation. N2 fixation, but no denitrification, was observed when NO3- was decreased to 10 microgram N per millilitre at 0.003 atm dissolved O2. In samples removed from the culture vessel, either activity could be induced with a lag of approximately 120 min by incubation under appropriate conditions.
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Three isolates, a Pseudomonas sp., a Bacillus sp. and an Arthrobacter sp., which had been isolated from a meadow soil at Devon Island, Canada, were subjected to starvation under varying conditions. The viabilities of the three isolates during starvation for 30 days in a carbon-free medium was assessed after the organisms had been grown continuously at varying rates in carbon- and nitrogen-limited media at 5 and 15 degrees C. Pseudomonas M216 was the most resistant to starvation stress, Bacillus M153 the least, and Arthrobacter M51 was intermediate in its response. Cells grown and starved at 5 degrees C survived longer than those at 15 degrees C. Carbon-limited Bacillus and Arthrobacter cells grown at high rates prior to starvation survived longer than those grown slowly, while in nitrogen-limited Arthrobacter the reverse was observed. The pattern of endogenous metabolism of the three isolates during starvation at 15 degrees C for 10 days was similar to that observed in other organisms. Levels of endogenous substrates such as carbohydrate and protein showed a rapid decrease in the initial 20 h of starvation, followed by a gradual decline over the remainder of the starvation period. The rates of endogenous metabolism of the isolates were positively correlated with their survival rates during starvation.
Three isolates, a Pseudomonas sp., Bacillus sp., and Arthrobacter sp., which had been isolated from a meadow soil at Devon Island, Canada, were subjected to freezing and thawing at low rates under various conditions. When cells were frozen in sand or soil, survival was dependent on moisture level, storage time, and thaw rate. Pseudomonas M216 was most susceptible to freeze-thaw damage under these conditions. Arthrobacter M51 was the most resistant of the three isolates when frozen in sand or soil and when frozen at a high rate after growth at varing rates at 5 and 15 degrees C in carbon-or nitrogen-limited media. Pseudomonas M216 was more sensitive to freeze-thaw damage when NaCl was present in the freezing menstruum, even at low freezing rates. Survival of cells frozen in growth medium, water, saline, and soil extract was not affected by the freezing rate when it was less than 1 degrees C min-1. Soil extract did not protect cells from freeze-thaw damage any more than water and for Arthrobacter M51 survival was decreased when it was frozen in soil extract.
We have previously shown that the prostaglandin analogue 15(R)15 methyl-prostaglandin E2 methyl ester (Me-PGE2) when administered at a dose of 50 microgram per kg significantly inhibits aspirin-induced gastric mucosal erosions in the rat. In this study we have investigated the effect of cimetidine under similar circumstances. Cimetidine in a dose of 50 mg per kg significantly inhibited gastric mucosal erosions induced by aspirin (192 mg per kg) in the rat, reducing the incidence from 70% of 20 rats to 9.5% of 21 rats, the mean lesion score was reduced from 9.3 +/- 2.1 (mean +/- SEM) to 0.4 +/- 0.3. We then compared the effect of the above doses of Me-PGE2 and cimetidine on gastric erosions induced by aspirin (192 mg per kg) with the hourly addition of 160 mM HCl. The incidence of erosions in the aspirin + HCl group was 100% of 20 rats (mean lesion score 27.4 +/- 2.4). This was not significantly reduced by cimetidine, the incidence being 90% of 20 rats (mean lesion score 19.7 +/- 3.4). The incidence of erosions in the presence of Me-PGE2 was significantly less than that in both the other groups, 13% of 23 rats, (mean lesion score 3.1 +/- 0.8) P less than 0.01 in both instances. These results suggest that, whereas cimetidine protects the gastric mucosa through acid inhibition, Me-PGE2 appears to have a protective effect independent of acid inhibition.
The effect of a low fat containing elemental diet (Vivonex) on faecal bile acid excretion was studied in six patients with cholerheic diarrhoea, two normal controls, and four patients with non-cholerheic diarrhoea. The total faecal bile acid excretion for the patients with bile acid-induced diarrhoea was significantly reduced fron 6-37+/- 1-64 mmol/24 h (mean +/- SEM) to 2-70 +/- 1-12 mmol/24 h during Vivonex treatment (p less than 0-05). A marked improvement in the diarrhoea of these patients occurred; the number of stools per day decreased and there was less urgency associated with the diarrhoea. No significant reduction in faecal bile acid excretion was observed for the control and non-cholerheic diarrhoea groups. An elemental diet of this type may be of value in the management of patients with bile acid-induced diarrhoea unresponsive to other forms of therapy, and may be of particular value in patients with Crohn's disease.
Intrapartum fetal bleeding from an anomalous umbilical cord vessel has been associated with a perinatal mortality rate of over 50%. Fetal blood volume is relatively small. Thus, an insignificant hemorrhage by adult standards may quickly lead to fetal shock and death. This paper documents the fetal heart rate (FHR) response to acute intrapartum hemorrhage. The onset of fetal bleeding is marked by a tachycardia followed by a bradycardia with intermittent accelerations or decelerations. Small amounts of vaginal bleeding associated with FHR abnormalities should raise the suspicion of fetal hemorrhage. This condition demands prompt delivery and immediate reexpansion of the neonatal blood volume.