Selenium depletion in patients with gastrointestinal diseases: are there any predictive factors?

BACKGROUND: Patients with intestinal disease are at risk of developing selenium deficiency due to impaired intestinal absorption. The aim of the present study was to evaluate selenium status and to identify predictive factors of selenium depletion in patients with gastrointestinal disease. METHODS: The concentration of selenium and the activity of glutathione peroxidase in plasma and erythrocytes were measured by fluorometry and by spectrophotometry. Eighty-six patients with Crohn's disease, 40 patients with ulcerative colitis, and 39 patients with various other gastrointestinal diseases were studied. Twenty-seven patients (16%) received home parenteral nutrition. Stool mass, faecal fat, and vitamin B12 absorption were analysed in 100 patients. RESULTS: The plasma selenium concentration was decreased in 85% of the patients receiving supplementary parenteral nutrition and in 20% of the patients receiving oral nutrition, among them in 26% of the patients with Crohn's disease. Almost all patients with ulcerative colitis had normal selenium levels. A statistically significant correlation was found between plasma selenium and vitamin B12 absorption, stool mass, faecal fat excretion, body mass index, P-albumin, P-zinc, and the length of the remaining small bowel. Stepwise regression analyses showed that the strongest predictors of selenium deficiency were stool mass, vitamin B12 absorption, and the length of the small-bowel resection. CONCLUSION: Selenium deficiency is common in patients with severe gastrointestinal disorders. The deficiency is mainly related to malabsorption, and a low selenium level was almost invariably present in patients who needed parenteral supplementation due to gut failure.

The metabolism of [75Se]selenite in patients with short bowel syndrome.

BACKGROUND: Patients on home parenteral nutrition (HPN) require significantly higher amounts of selenium compared with controls. The purpose of the present study was to investigate if selenium deficiency of patients with short bowel syndrome is caused by selenium malabsorption or by excessive intestinal or renal loss. METHODS: The metabolism of [75Se]selenite was investigated in eight selenium-depleted short bowel patients on HPN and in six control subjects. The isotope was given orally, and in a subsequent study as bolus injection or as 12-hour IV infusion. RESULTS: The fractional intestinal absorption of selenium was significantly reduced in the patients (2% to 58%, median 20%) when compared with the reference group (79% to 91%, median 82%) (p < .001). Within the group of patients we found a positive significant correlation between fractional selenium absorption and the length of the remaining small intestine (r = 0.95, p < .05). After parenteral [75Se]selenite administration, the patients showed a significantly higher fecal loss and a significantly reduced urinary excretion of 75Se when compared with the controls. Bolus injection vs 12-hour infusion of [75Se]selenite did not affect the cumulative fecal or urinary 75Se excretion in the HPN patients. CONCLUSIONS: Reduced intestinal selenium absorption is probably the most important cause of the selenium deficiency reported in patients with short bowel syndrome, but increased endogenous intestinal selenium loss and low selenium intake may also contribute. Despite the renal counterregulation, which results in a low urinary selenium excretion, HPN patients need a supply of selenium with their parenteral nutrition.

Selenoprotein P in patients on home parenteral nutrition.

BACKGROUND: The purpose of this study was to evaluate the use of selenoprotein P as an indicator of selenium status in patients receiving home parenteral nutrition. METHODS: Adult patients (n = 38) who had been on parenteral nutrition with no addition of selenium for 3 to 216 months were included in the study. Plasma samples were analyzed for selenium, selenoprotein P, and extracellular glutathione peroxidase (eGSHPx) using fluorimetry and newly developed radioimmunoassays. RESULTS: The mean plasma (+/- SD) eGSHPx and selenoprotein P in the patients were 1.9 +/- 1.2 mg/L and 0.7 +/- 0.4 arbitrary units, respectively, which corresponds to about 50% of the concentration measured in the plasma of the reference subjects (4.0 +/- 1.0 mg/L and 1.50 +/- 0.17 arbitrary units). The mean plasma selenium concentration was 0.5 +/- 0.4 mumol/L, which was approximately half of the concentration measured in the healthy subjects (1.1 +/- 0.2 mumol/L). Thirty-four (89%) and 20 (53%) patients, respectively, had selenoprotein P and eGSHPx values lower than mean - 2 SD of the reference material. The lowest values observed for selenoprotein P and eGSHPx were 3% and 2% of the reference mean. Selenoprotein P levels correlated significantly to eGSHPx (p = 0.88, p < .0001) and plasma selenium (p = 0.91, p < .0001). CONCLUSIONS: The positive correlations between selenoprotein P and eGSHPX and plasma selenium indicates that selenoprotein P may be used as a marker of selenium status in selenium-depleted patients.

Body composition in patients on home parenteral nutrition.

Dual energy X-ray absorptiometry (DXA) measures and separates three of the principal compartments of the body, fat mass (FM), fat-free mass (FFM), comprising muscle, inner organs and body water, and the total bone mineral content (TBMC). The aim of the present study was to determine body composition by DXA scan in 37 patients who had been on home parenteral nutrition (HPN) for 6-216 months. The height and weight of patients were significantly lower when compared to a group of healthy subjects. The weight, however, was relatively more reduced than the height. This is reflected by a significantly reduced body mass index in young female and male patients (p < 0.05). Fat-free mass and total body mineral content were significantly reduced (p < 0.05) in patients on home parenteral nutrition compared to a group of healthy subjects. However, the percentage of fat-free mass was unchanged. No significant change in fat mass was observed. We conclude that patients, with intestinal failure due to short bowel syndrome, who are on HPN have a smaller body size with a normal relative body composition.

The effect of selenium supplementation on skeletal and cardiac muscle in selenium-depleted patients.

BACKGROUND: The purpose of the present study was to evaluate the effect of sodium selenite on skeletal and cardiac muscular function in patients with severe Se deficiency. METHODS: Skeletal and cardiac muscular function was investigated in 10 selenium depleted patients on long-term home parenteral nutrition because of short bowel syndrome. The following examinations were applied: Skeletal muscle biopsy, muscular force test (Kin-Com dynamometer test), electromyography (EMG) and radionuclide ventriculography. The patients were blindly randomized to intravenous supplementation with selenium 200 micrograms 5 to 7 times per week or placebo for 4 months. Hereafter the examinations were repeated. The patients randomized to placebo received selenium in an open study for a further 4 months and hereafter their skeletal and cardiac function was reevaluated. RESULTS: Plasma selenium increased to normal levels from median .21 mumol/l (range 0-.69) to 1.25 mumol/l (range .9-2.27) following selenium repletion. The muscle biopsies showed only minor abnormalities. The only change after selenium supplementation was a small but statistically significant increase of the mean diameter of fiber type 1. The muscle strength of the quadriceps muscle was unchanged after selenium substitution. EMG did not reveal signs of myopathy. The cardiac function was normal and remained unchanged. CONCLUSION: Despite severe selenium depletion ten patients on long term home parenteral nutrition had normal cardiac function, and no clinically significant signs of skeletal myopathy. The only change after selenium supplementation was a small but statistically significant increase of the mean diameter of muscle fiber type 1.

Effect of intravenous infusion of omeprazole and ranitidine on twenty-four-hour intragastric pH in patients with a history of duodenal ulcer.

The effect on intragastric pH of two different dose regimens of continuous intravenous infusion of omeprazole (4 or 8 mg/h after a bolus of 80 mg), and ranitidine (0.25 mg/kg/h after a bolus of 50 mg) was studied in 10 patients with duodenal ulcer disease in symptomatic remission. The pH was monitored over 24-hour periods during fasting in a cross-over, randomised design including a baseline period. With the high omeprazole dose it was possible to maintain a pH > or = 4 in all patients but 1 and 6 of the patients also maintained a pH > or = 6. The lower dose of omeprazole seemed to be somewhat less effective. Continuous infusion of ranitidine was as efficient as the higher omeprazole infusion although with a tendency to decreased pH levels towards the end of the 24-hour period. Thus, in order to obtain consistently high pH levels of 4-6 over a prolonged period a continuous infusion of omeprazole, an 80-mg bolus plus a continuous infusion of 8 mg/h seem to be needed.

Bone mineral content in patients on home parenteral nutrition.

Bone mineral content (BMC) was monitored in 15 patients with short bowel syndrome receiving home parenteral nutrition (HPN). Thirteen patients had Crohn's disease and 2 ulcerative colitis (mean age 36 years, range 23-69 years). During the study the patients received HPN for a mean period of 62 months, range 20-106 months. At the time of inclusion the patients had a significantly reduced BMC of lumbar spine and femoral neck compared to normals (Z-scores = -3.35 +/- 3.49, p < 0.05 and Z-score = -2.23 +/- 2.11, p < 0.05). During HPN the Z-score of lumbar spine BMC decreased in 8 patients and increased slightly or was unchanged in 7 patients. The mean Z-score of BMC of lumbar spine declined by 1.46 +/- 2.48 (p < 0.05) and the Z-score of femoral neck BMC declined by 0.831 +/- 1.14 (p < 0.05). This corresponds to a yearly decrease of lumbar spine BMC of 4%. There was no correlation between the decline in BMC during the study and the period of length the patients were on HPN. We conclude that patients on HPN have a low bone mineral density and that the bone loss continues during prolonged HPN.

Selenium depletion in patients on home parenteral nutrition. The effect of selenium supplementation.

Severe selenium (Se) depletion was found in nine patients receiving long-term home parenteral nutrition because of short bowel syndrome. Plasma Se ranged from 0-0.51 (median 0.21 mumol/L), and erythrocyte Se ranged from 0.7-2.6 (median 1.8 mumol/gHgb), which was significantly lower than in the controls. Glutathione peroxidase (GSHPx) in plasma and erythrocytes was also decreased. After bolus injections with 200 micrograms Se/d in the form of sodium selenite for 4 mo, followed by 100 micrograms/d for 8 mo, plasma Se increased to values slightly but significantly higher than in the controls. Erythrocyte Se reached normal levels in most of the patients after 4 mo substitution, but it remained lower than in the controls. Following Se supplementation, plasma and erythrocyte GSHPx did not differ between patients and controls. These data suggest that all patients receiving long-term parenteral nutrition because of short bowel syndrome should receive at least 100 micrograms sodium selenite/d when given as bolus injections to avoid Se depletion.

Selenium status in patients with Crohn's disease.

Twenty-seven of 66 patients with Crohn's disease had reduced concentrations of selenium and glutathione peroxidase in plasma and erythrocytes. When the patients were subgrouped according to the length of resected small bowel, a significant reduction of selenium and glutathione peroxidase in both plasma and erythrocytes was only found in patients with a resection > 200 cm. A highly significant correlation between selenium and glutathione peroxidase was found in plasma (r = 0.81) as well as in erythrocytes (r = 0.62), but no correlation was observed in the control group. A statistically significant correlation was also found between plasma selenium and the Harvey-Bradshaw score (r = -0.44), body mass index (wt/ht2) (r = 0.47), and plasma albumin (r = 0.29). Patients with a small-bowel resection > 200 cm appear to be at risk of developing severe selenium deficiency. These patients should have their selenium status monitored and probably receive selenium supplementation.

[Epilepsy/cardiac arrhythmia? Differential diagnostic problems]. / Epilepsi/kardial arytmi? Differentialdiagnostiske problemer.

In cases of suspected epilepsy the possibility of cardiac arrhythmias should be considered. Two case histories are presented. One patient had grand mal epilepsy combined with Wolff-Parkinson-White syndrome. In the other patient, epilepsy was suspected. However, the final diagnosis proved out to be third degree atrioventricular block. Examination must include an electrocardiogram and in case of doubt, Holter monitoring.

Prophylactic effects of olsalazine v sulphasalazine during 12 months maintenance treatment of ulcerative colitis. The Danish Olsalazine Study Group.

In a Danish multicentre trial we compared the relapse preventing effects of olsalazine and sulphasalazine in patients with ulcerative colitis over a 12 month treatment period. Two hundred and twenty seven patients (118 men) with at least two previous attacks of ulcerative colitis were randomly allocated according to a prearranged treatment schedule to olsalazine 500 mg bd or sulphasalazine 1 g bd in a double blind, double dummy fashion. One hundred and ninety seven patients completed the trial. The relapse rate after 12 month in the olsalazine group was 46.9% v 42.4% in the sulphasalazine group with a 95% confidence interval for the difference in proportions of -9% to 18%. Seven per cent of the patients were withdrawn from the trial because of adverse drug reactions and these were equally distributed between the two groups.

The [14C]-triolein breath test is not valid as a test of fat absorption.

The [14C]-triolein breath test is used as a test of fat absorption. However, its validity has not been established. The aim of this study was to investigate, whether the absorption of [14C]-triolein could be estimated from the breath test, and whether the breath test could be useful as a clinical test. The [14C]-triolein absorption was estimated from faecal measurements, using 51CrCl3 as non-absorbable marker. The breath test was done according to the standard technique with hourly estimations of the 14CO2 expiration. Fifty-one patients participated. A nearly perpendicular, curvilinear relation between the 6-h cumulative 14CO2 expiration and the [14C]-triolein absorption was found, and no obvious cut-off level for normal 14CO2 expiration could be identified. Accordingly, the diagnostic sensitivity of the breath test was 80% at the expense of a specificity of 45%. In 19 patients duplicate measurements were done. A high intra- and inter-individual variation in the fraction of absorbed [14C]-triolein, expired within 6 h, was found. It is concluded that expiration of 14CO2 is influenced by factors other than the absorption of [14C]-triolein, and that the [14C]-triolein breath test is not useful as test of fat absorption.

[Severe prolonged hypotension after the first dose of enalapril in a patient with essential hypertension]. / Svaer langvarig hypotension efter første dosis af enalapril hos en patient med essentiel hypertension.

A case of severe and prolonged hypotension following intake of 10 mg enalapril in a patient with slight hyponatraemia is described. Despite administration of isotonic NaCl and treatment with dopamine infusion, it did not prove possible to maintain a stable blood pressure. Adrenaline and ephedrine were required intravenously on repeated occasions on account of symptom-producing hypotension with a systolic pressure as low as 60 mmHg. On account of the increasing use of ACE-inhibitors, it is recommended that the specific antidote, angiotension II, should be registered in Denmark and should be available in all hospitals.

A triple isotope technique for estimation of fat and vitamin B12 malabsorption in Crohn's disease.

A test for simultaneous estimation of vitamin B12 and fat absorption from stool samples was investigated in 25 patients with severe diarrhoea after operation for Crohn's disease. 51CrCl3 was ingested as a non-absorbable marker, 58Co-cyano-cobalamin as vitamin B12 tracer, and 14C-triolein as lipid tracer. Faeces were collected separately for 3 days. Some stool-to-stool variation in the 58Co/51Cr and 14C/51Cr ratios was seen. When the 58Co-B12 and 14C-triolein excretion was estimated in samples of the two stools with the highest activities of 51Cr, the variations of the estimates were less than +/- 10% and +/- 15% of the doses ingested, respectively. Twelve of the 25 patients were not able to collect faeces and urine quantitatively and separately. However, in all patients faeces with sufficient radioactivity for simultaneous estimation of faecal 58Co-B12 and 14C-triolein excretion from stool samples were obtained.

Absorption studies after ileal J-pouch anastomosis for ulcerative colitis. A prospective study.

Absorption studies were performed in 17 patients with ulcerative colitis operated on with colectomy and an ileal two-limbed J-pouch anastomosis. The patients were studied 3 and greater than or equal to 18 months after closure of the temporary ileostomy. Increased stool mass (median, 609 g/24 h) was found in all patients and was unchanged with time. Moderate steatorrhoea was present in 29% of the patients 3 months postoperatively, but faecal fat excretion normalized with time. Calcium absorption was normal in all but one patient regardless of time after operation. An abnormal bacterial deconjugation, evaluated by a 14C-glycocholic acid breath test was present in 27% of the patients and increased significantly with time. Forty per cent of the patients had increased faecal bile acid excretion. B12 malabsorption was present in 29-35% of the patients. In conclusion, ileal J-pouch anastomosis for ulcerative colitis causes increased stool mass in all patients and produces moderate bile acid deconjugation and malabsorption in about one-third to half. Substitution therapy with vitamin B12 is necessary in about one-third of the patients. Intestinal adaptation as far as absorption is concerned is minimal after the first 3 postoperative months.

Pancreatic function in Crohn's disease.

We investigated exocrine pancreatic function in a population of patients with Crohn's disease in order to correlate the pancreatic function with clinical and laboratory variables. A total of 143 patients affected by Crohn's disease and 115 control subjects were studied. All had a Lundh meal test. As a group patients with Crohn's disease had significantly decreased activity of both amylase (p less than 0.02) and lipase (p less than 0.001) in duodenal aspirates. In patients with Crohn's disease enzyme activities were not correlated to duration of disease or to extent or localisation of previous bowel resection. The lowest enzyme values were found in patients with the most extensive bowel involvement, and they were significantly lower (p less than 0.05) than in patients with disease confined to the terminal ileum. The differences between enzyme values in other subgroups of patients were not significant. For the patient group as a whole no correlation was found between disease activity and enzyme values, but for the most uniform group of patients, those with terminal ileitis, pancreatic function was significantly lower (p less than 0.05) in patients with moderate and severe disease compared with patients with mild disease. Thus at least two factors seem to be responsible for impaired pancreatic function in Crohn's disease: firstly disease activity and secondly localisation or extent of disease.

Calcium absorption and bone mineral content in patients subjected to ileal bypass because of familial hypercholesterolaemia.

Calcium absorption and bone mineral content were studied prospectively in 30 patients with familial hypercholesterolaemia subjected to partial ileal bypass surgery. One-third of the patients were followed up for 10 years after the operation. Six months postoperatively calcium absorption decreased significantly, from a median of 16% to 13%. The effect persisted up to 5 years of follow-up study. Ten years after the operation the absorption of calcium (median, 14.5%) was not significantly different from the preoperative calcium absorption (median, 16%). Bone mineral content, measured in 76% of the patients, was retained in all patients studied. A significant correlation was present between calcium absorption and urinary calcium. The reduction in calcium absorption did not correlate with increases in faecal fat. Other long-term side effects were persistent diarrhoea and moderate steatorrhoea. A significant weight loss was slowly regained in most patients. An increase of renal oxalate excretion was only small and transient in most patients. The study shows that bypass of the terminal 200 cm of ileum for familial hypercholesterolaemia causes moderate diarrhoea and steatorrhoea in most patients but only a slight reduction of intestinal calcium absorption and apparently no risk of bone demineralization. A benefit of a postoperative calcium and vitamin D supply cannot be excluded.

Catheter-related sepsis in long-term parenteral nutrition with Broviac catheters. An evaluation of different disinfectants.

From April 1976 to January 1988, 58 patients received home parenteral nutrition for 2-138 months, median 36 months, corresponding to a total treatment period of 233 patient years. Before 1980 and after 1985, 0.5-2% iodine tincture or 0.5% chlorhexidine in 70% ethyl alcohol were used to disinfect the exit site of the catheter and the connections of the infusion line. In these periods the sepsis incidence was 0.25-0.28 per catheter year, corresponding to one episode of sepsis per 3.6-4.0 catheter years. In the period 1980 to 1985, 10% povidone-iodine (Isobetadine) was used, and the incidence in this period was 0.58, corresponding to one episode of sepsis per 1.7 catheter year. This suggests that 10% povidone-iodine may be inferior to iodine-tincture and chlorhexidine alcohol in this type of catheter care. The incidence of catheter sepsis was 0.32 per catheter year when the catheter was placed on the chest and 0.86 per catheter year with the catheter on the thigh. Klebsiella pneumoniae was the most common microorganism grown when the catheter was placed on the thigh, while coagulase-negative staphylococci were most common when the catheter was placed on the chest.

Short-chain fatty acids in bowel contents after intestinal surgery.

Short-chain fatty acids are produced in the human colon by bacterial fermentation of dietary fibers and other saccharides escaping absorption in the small bowel. Short-chain fatty acid concentrations were determined together with production rates in 6- and 24-h incubations of intestinal outputs from 56 patients with various types of intestinal resections. Concentrations and 6- and 24-h production rates in feces from 9 healthy persons (controls; median +/- SD) were 98.9 +/- 21.4 mmol/L and 17.2 +/- 5.1 and 9.3 +/- 1.5 mmol/L.h, respectively. Colectomized patients with short bowel syndrome had extremely low concentrations (0.8 mmol/L) compared with controls (p less than 10-5), patients with ileostomy (p = 0.003), and ileal reservoirs (p less than 10-5), and showed low 6- and 24-h production rates (1.5 and 0.9 mmol/L.h, respectively; p less than 10-5 vs. controls). Short-chain fatty acids in ileostomic digesta (11.1 mmol/L) were decreased (p = 0.011) compared with outputs from ileal reservoirs (51.5 mmol/L), although production rates were in the same order of magnitude--all below control values (p less than 0.001). Patients partially colectomized and patients with small bowel bypass or short bowel syndrome with preserved colon had normal fecal concentrations with decreased production rates of short-chain fatty acids vs. controls (p less than 0.01). Only minor changes in ratios between individual acids were found. Reciprocal values of short-chain fatty acid concentrations correlated to volumes of outputs from both small intestine (r = 0.86, p less than 10-6) and colon (r = 0.79, p less than 10-6) when results were cumulated. It is concluded that partial resections of colon and the small bowel do not influence the fecal concentration level of short-chain fatty acids as long as colon is not totally resected.