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.

Diagnostic value of lactoferrin analysis in pleural effusions.

Lactoferrin was analysed with an ELISA in pleural effusions from 21 patients with malignant exudative effusions (15 carcinomas and 6 mesotheliomas), 12 patients with non-malignant exudative effusions of unknown aetiology, 11 patients with transudative effusions due to congestive heart failure, 12 patients with exudative effusions secondary to infection, and 2 patients with tuberculous effusions. Median pleural fluid lactoferrin was 133 micrograms/l (range 25-435) in carcinomas, 55 micrograms/l (23-185) in mesotheliomas, 198 micrograms/l (31-530) in non-malignant exudates, 68 micrograms/l (17-205) in transudates, 1815 micrograms/l (1380-2050) in infectious exudates and 107 micrograms/l (88-125) in tuberculosis. Due to a wide overlap between the various groups pleural fluid lactoferrin appears to be of limited value in the routine diagnostic evaluation of non-infectious pleural effusions, but seems to separate infectious exudates from non-infectious exudates.

Relationships among serum iron status markers, chemical and histochemical liver iron content in 117 patients with alcoholic and non-alcoholic hepatic disease.

Histochemical and chemical liver iron and iron status markers (serum (S-) ferritin, transferrin saturation) were determined in 109 patients with various types of liver disease (71 alcoholic, 38 non-alcoholic disease) and 8 normal subjects. In the series as a whole there was a significant correlation between histochemical hepatocyte iron and chemical iron (rho = 0.48, p = 0.0001). Of the iron status markers, only S-ferritin showed clinically significant correlations with histochemical liver iron (rho = 0.54, p = 0.0001) and chemical liver iron (r = 0.45, p = 0.0001) (log vs. log values). The highest correlation was found between S-ferritin and the product of chemical iron x ASAT (r = 0.61, p = 0.0001) (log vs. log values). None of the normal livers had stainable hepatocyte iron; median chemical iron content was 15 mumol/g dry weight (range 8-25). The entire group of alcoholics had a median liver iron content of 21 mumol/g; all patients had a hepatic iron index (hepatic iron/age) of under 1.4. In alcoholic liver disease, median chemical liver iron content was 15 mumol/g (range 3-36) in 35 subjects with grade 0 hepatocyte iron; 24 mumol/g (range 6-90) in 25 subjects with grade 1 + 2 hepatocyte iron; 30 mumol/g (range 14-74) in 11 subjects with grade 3 + 4 hepatocyte iron. Among subjects with alcoholic liver disease and normal liver iron (< 26 mumol/g), 39% had stainable hepatocyte iron vs. 70% in subjects with increased liver iron (> or = 26 mumol/g). The corresponding figures in subjects with non-alcoholic liver disease were 13% and 20%.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Relation between bone marrow hemosiderin iron, serum iron status markers, and chemical and histochemical liver iron content in 82 patients with alcoholic and nonalcoholic hepatic disease.

Bone marrow hemosiderin iron was assessed in 48 patients with alcoholic, and in 34 patients with nonalcoholic liver disease (53 men, 29 women, median age 55 years, range 18-84) and correlated to serum (S)-iron status markers (iron, transferrin, ferritin), as well as to histochemical hepatocyte iron and chemical liver iron content. In a control group of 53 healthy subjects (23 men, 30 women, median age 28 years, range 18-90) marrow hemosiderin iron and iron status markers were evaluated as well. Among liver patients, the marrow iron grade was higher in men than in women (p = 0.03). Correlations were found between marrow iron and histochemical liver iron (rho = 0.38, p = 0.0001) as well as chemical liver iron (rho = 0.33, p = 0.01). Marrow iron was correlated to S-ferritin (rho = 0.53, p = 0.0001), mean red cell volume (rho = 0.34, p = 0.003), and S-transferrin (rho = -0.24, p = 0.02). Alcoholics had a higher marrow iron grade than nonalcoholics (p = 0.001) and controls (p = 0.0001). Among controls, the marrow iron grade was likewise higher in men than in women (p = 0.01). Correlations were found between marrow iron and ferritin (rho = 0.64, p = 0.0001), transferrin saturation (rho = 0.56, p = 0.001), transferrin (rho = 0.53, p = 0.001), S-iron (rho = 0.37, p = 0.01), and hemoglobin in women (rho = 0.38, p = 0.05). The results indicate that alcoholics either have increased marrow hemosiderin iron stores, or display a redistribution of iron in reticuloendothelial cells from soluble ferritin-bound iron to insoluble hemosiderin iron. Among patients with absent marrow hemosiderin iron, 81% had absent hepatocyte hemosiderin iron as well. Among patients with absent hepatocyte hemosiderin iron, 23% had absent and 77% normal or increased marrow hemosiderin iron. Therefore, in patients with iron depletion, assessment of marrow hemosiderin iron yields more relevant information of iron status than assessment of hepatocyte hemosiderin iron.

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.

Pharmacokinetics of 5-aminosalicylic acid in man following administration of intravenous bolus and per os slow-release formulation.

The fate of 5-aminosalicylic acid (5-ASA), which is used in the treatment of chronic inflammatory bowel diseases, was studied in six healthy volunteers receiving doses of 100 mg and 250 mg intravenous bolus as well as 250 mg per os (slow release). Following intravenous administration, the drug was rapidly eliminated with a plasma half-life of about 40 min, mainly due to rapid metabolism. No parent drug was recovered in feces, and the total recovery following oral administration (30%) was significantly lower than following the intravenous doses (77% and 72%). Nonlinear pharmacokinetics were suggested as the 2.5-fold increase in intravenous dose was followed by a significant relative increase (greater than 2.5) in the renal elimination of 5-ASA, as well as a significant decrease (less than 2.5) in the elimination of the metabolite N-acetyl-5-ASA. There was also a trend towards a decreasing total body clearance and metabolic ratio. The present study confirms earlier findings on the pharmacokinetics of 5-ASA and suggests a possible saturation of the N-acetylating system in the dose range studied. This may be of interest in the design of controlled-release formulations and dosage regimes for the treatment of diseases of the small-bowel, where 5-ASA is easily absorbed. Further, for the first time, a marked difference in the intestinal fate compared to the systemic fate of the drug is demonstrated, suggesting alternative presystemic metabolism of 5-ASA, which may bear relevance to its mode of action. Further studies on the pharmacokinetics of 5-ASA, preferably in patients, are warranted.

Fate of the rectum after colectomy and ileostomy for Crohn's colitis.

Eighty-four patients had colectomy with ileostomy and oversewing of the rectum for Crohn's colitis. Seventy-two patients were operated on because of intractable disease, colitis in combination with rectal fistulas, and toxic megacolon. The operative mortality was 6 percent, and neither emergency surgery nor treatment with steroids correlated with operative morbidity. After a median 7.7 years of follow-up, 25 ileorectal anastomoses had been undertaken, 16 of which were successful. Twenty-nine protectomies were performed; the resulting 10-year cumulative risk of proctectomy was 50 percent. While the risk of proctectomy was significantly less among patients with a normal rectum at colectomy compared with patients with proctitis, the initial macroscopic degree of proctitis did not correlate with the risk of subsequent proctectomy. The 5-year cumulative ileal resection rate in 29 patients with a rectum in situ but out of circuit was 29 percent. The possibility of a future ileorectal anastomosis should still be considered in patients with proctocolitis.

Incidence of spontaneous bacterial peritonitis in patients with ascites. Diagnostic value of white blood cell count and pH measurement in ascitic fluid.

During a 21-month period, 65 consecutive patients admitted with ascites were included in a prospective study of the incidence of spontaneous bacterial peritonitis, and paracentesis was performed on admission. The ascitic fluid was cultured, ascitic leucocytes were counted and pH was measured. Bacterial growth was found in five patients with chronic liver disease, who were diagnosed as having spontaneous bacterial peritonitis (SBP), since no intra-abdominal focus could be demonstrated. Thus, the incidence of SBP in this material was 7.7% (95% confidence limits: 2.5-17%). SBP was caused by Escherichia coli (n = 3), coagulase negative staphylococcus (n = 1), and Bacteroides species (n = 1). Abdominal tenderness, abnormal intestinal sounds, fever and hepatic encephalopathy were equally frequent in the group with SBP and in patients with sterile ascites. Infection was not anticipated in any of the patients with SBP. In contrast to several previous studies, neither ascites pH nor ascites leucocyte counts were any help in obtaining a rapid diagnosis. Survival time of patients with SBP was significantly shorter than of patients without SBP.

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.

Identification and quantification of serum proteins secreted into the normal human jejunum.

The in vivo transfer of serum proteins to the human intestinal lumen was characterized by crossed immunoelectrophoretic analyses of intestinal perfusates from four healthy volunteers. Serum proteins with molecular masses below 100 kDa and the immunoglobulins were found in human jejunal perfusates. Larger serum proteins were either absent (alpha and beta lipoproteins) or present in small amounts (alpha 2-macroglobulin, haptoglobulin and ceruloplasmin). These results demonstrate the existence of a selective transfer of serum proteins to the intestinal lumen under physiological conditions. The intestinal clearance rate was 0.1 ml serum per hour per 10 cm jejunum for albumin, prealbumin, alpha 1-antitrypsin, orosomucoid, transferrin and haemopexin. The rate of secretion of total protein to the jejunal lumen was 100 mg protein per hour per 10 cm jejunum. About 45% was due to immunoglobulins and further 10-15% due to the remaining serum proteins. It is suggested that the serum proteins pass through the epithelium by a transcellular mechanism.

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.

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.

Ulcerative colitis and Crohn's disease of the colon. Is there a macroscopic difference?

The diagnostic reliability of currently accepted gross pathologic signs in patients with ulcerative colitis and Crohn's disease of the large intestine was evaluated. Of 198 patients who had colectomy or proctocolectomy because of inflammatory bowel disease, 52% had ulcerative colitis and 37% had Crohn's disease, 11% were indeterminable according to histologic evaluation of the surgical specimens. Cobblestone mucosa was most common in Crohn's disease (P less than 0.001) and pseudopolyposis in ulcerative colitis (P less than 0.01), but there was considerable overlap. Strictures and skip lesions occurred in both diseases with a similar incidence. It is concluded that the differential diagnosis between ulcerative colitis and Crohn's disease of the large intestine should not be made from macroscopic examination of the resected specimens.

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.

Effect of a long acting somatostatin analogue SMS 201-995 on jejunostomy effluents in patients with severe short bowel syndrome.

The effect of a long acting somatostatin analogue SMS 201-995 on stomal effluents in patients with severe short bowel syndrome was investigated in a double blind placebo controlled balance study. Six patients, five with Crohn's disease and one with radiation enteropathy were studied. Five patients had a jejunostomy and one an ileostomy. The patients had a normal food intake, but because of severe malabsorption had received home parenteral nutrition for several years. Faecal mass was reduced (p less than 0.005) and intestinal net sodium absorption was increased (p less than 0.005) by intravenous infusion of SMS 25 micrograms/h. Net absorption of potassium, calcium, magnesium phosphate, zinc, nitrogen and fat was not influenced. Subcutaneous injections of 50 micrograms SMS every 12 hours had a similar effect on net intestinal absorption of sodium and water. Four patients continued with a five to six months open follow up study when subcutaneous SMS in the same dose was administered by the patients at home. The effect on faecal sodium loss persisted, but in one patient faecal mass gradually increased and finally exceeded pretreatment values. SMS may decrease net absorption of water and sodium following reduced secretion of digestive juices rather than by increasing absorptive capacity. SMS may be useful as an antidiarrhoeal drug in patients with high output jejuno- or ileostomies, but in patients who need permanent parenteral nutrition the effect is too small to significantly alter management.

Somatostatin treatment of gastrointestinal fistulae.

Output from gastrointestinal fistulae to the skin was measured in five patients during total parenteral nutrition and restricted oral intake. Supplemental infusion of somatostatin during six days caused a significant reduction in discharge in all patients compared to the pretreatment level, but none of the fistulae closed as a result of the treatment. Somatostatin may be considered an adjuvant drug to parenteral nutrition and restricted oral intake in the conservative treatment of external fistulae from the gastrointestinal tract.