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A new cause of severe transient fitting polyarthritis is described in a patient with primary biliary cirrhosis. Hypercholesterolaemia is thought to provoke acute inflammatory periarthritis and peritendinitis. The clinical features are sudden onset of peripheral joint pain and effusion, with redness of the overlying skin, often precipitated by unusual exercise. Cholestyramine may help to prevent this form of arthritis.
To define the type of dietary fibre of fibre analogue with the greatest potential use in diabetic treatment, groups of four to six volunteers underwent 50-g glucose tolerance tests (GTT) with and without the addition of either guar, pectin, gum tragacanth, methylcellulose, wheat bran, or cholestyramine equivalent to 12 g fibre. The addition of each substance significantly reduced blood glucose concentration at one or more points during the GTT and generally reduced serum insulin concentrations. The greatest flattening of the glucose response was seen with guar, but this effect was abolished when hydrolysed non-viscous guar was used. The reduction in the mean peak rise in blood glucose concentration for each substance correlated positively with its viscosity (r = 0.926; P less than 0.01), as did delay in mouth-to-caecum transit time (r = 0.885; P less than 0.02). Viscous types of dietary fibre are therefore most likely to be therapeutically useful in modifying postprandial hyperglycaemia.
A number of different chronic diseases affect the intrahepatic bile radicles or cholangioles. They include primary and secondary sclerosing cholangitis, primary biliary cirrhosis, chronic cholestatic drug jaundice, atresia, and carcinoma. Aetiological factors include infection, immunological changes, hormones, and congenital defects.Patients with chronic cholestasis have decreased bile salts in the intestinal contents and suffer from a bile salt deficiency syndrome. Failure to absorb dietary fat is managed by a low-fat diet and by medium-chain trigly-cerides which are absorbed in the absence of intestinal bile salts. Fat-soluble vitamin deficiencies are prevented by parenteral vitamins A, D, and K(1). Calcium absorption is defective, and improvement may follow intramuscular vitamin D, medium-chain triglycerides, a low-fat diet, and oral calcium supplements.In partial intestinal bile salt deficiency the anionic bile-salt-chelating resin cholestyramine controls pruritus though steatorrhoea increases. Pruritus associated with total lack of intestinal bile salts is managed by methyl-testosterone or norethandrolone, though the jaundice increases.
Two patients with primary biliary cirrhosis who were increasingly incapacitated by xanthomatous neuropathy are described. Treatment with a low fat diet and cholestyramine was unhelpful but repeated plasmaphoresis by simple venesection in one and plasma exchange using an IBM blood cell separator in the other over a period of several months completely relieved the symptoms of the neuropathy, caused skin xanthomata to recede, and lowered plasma lipid levels in both patients. There was no evidence that this procedure was associated with any deleterious effects on the liver. The size of the cholesterol pool in xanthomata in one patient was estimated to be approximately 35 g, and from the plasma cholesterol response to plasmaphoresis at varying frequency it was suggested that the excess of cholesterol synthesis over degradation was less than 0.3 g/day in one patient and less than 0.4 g/day in the other. On the basis of the response in these patients it is suggested that the turnover rates of lipid pools are relatively slow in biliary cirrhosis and that cholesterol accumulation is more likely to be due to a reduced catabolic rate than to an increased synthetic rate of cholesterol. Plasmaphoresis or plasma exchange are useful methods of treatment for the rare patient afflicted by this resistant and distressing complication of biliary cirrhosis.
Serum bile acid classes have been studied in 15 patients with primary biliary cirrhosis in five patients with cholestasis, and in five patients who had cirrhosis without cholestatic features. Conjugated monohydroxy bile acids (12-35% serum total bile acids) were found in eight of 11 sera from patients with primary biliary cirrhosis, in sera from four patients with cholestasis but not in any of the five patients with cirrhosis. The glycine conjugates/taurine conjugates (G/T) ratio in eight of 11 patients with primary biliary cirrhosis and two of four patients with cholestasis was <1.0. Bile acid concentrations in seven patients with primary biliary cirrhosis were measured before and during cholestyramine therapy. Decreases in serum total bile acid concentrations were observed which were accompanied by small increases in the trihydroxy/dihydroxy ratio and also in the G/T ratio in six of the seven patients. No association was found between the concentration of any particular conjugated or free bile acid and the presence or absence of pruritus.
Leucocyte ascorbic acid (LAA) levels were measured in 138 patients with liver disease. Significantly reduced levels were found in 37 patients with alcoholic liver disease (P less than 0-01) and 25 patients with primary biliary cirrhosis (P less than 0-05). In the primary biliary cirrhosis patients, cholestyramine therapy was associated with significantly lower levels of the vitamin (P less than 0-05). Liver ascorbic acid measured in Menghini needle biopsies in 20 patients was significantly correlated with LAA (r=0-807, P less than 0-001). No significant correlation was found between LAA and haematological indices, conventional liver function tests, or cholesterol levels in any group of patients. Patients with LAA levels below 100 nM/10(8) WBC had significantly higher antipyrine half-lives (mean=28-3 h) than patients with LAA levels above this level (mean=18-6 h) (P less than 0-05). Delayed drug metabolism related to low LAA should be considered when drugs metabolised by the liver are prescribed for patients with alcoholic liver disease or primary biliary cirrhosis.
The (14)C-glycocholic acid test ((14)C-GCA) has been assessed in 27 patients who have had resection of the ileum and colon for Crohn's disease and in 19 patients with unoperated stable Crohn's disease. The incidence of increased breath output of (14)CO(2) and faecal output of (14)C was significantly greater in operated patients. Half the unoperated patients had normal results and, of the others, a modest increase in faecal (14)C was the usual finding. There was no correlation between the (14)C-GCA test, the Schilling test, and the extent and severity of the radiological signs in the unoperated patients. Metronidazole therapy was poorly tolerated and had little or no influence on symptoms but did decrease the excretion of (14)CO(2) in the breath when the (14)C-GCA test was repeated. Cholestyramine therapy was beneficial in the majority of resected patients with diarrhoea and an increased faecal (14)C excretion and, on repeat testing, there was a significant increase in the output of breath (14)CO(2). The beneficial effect was less marked in the unoperated patients and the breath (14)CO(2) output remained normal in those retested. Interruption of the enterohepatic circulation of bile acids did not seem to make an important contribution to the symptoms of patients with stable unoperated (and uncomplicated) Crohn's disease, even when the ileum was extensively involved.
Between 1982 and 1989, the seven day retention of 75SeHCAT was measured in 181 patients with chronic diarrhoea that remained unexplained after full investigation. Altogether 121 of the 181 had a seven day 75SeHCAT retention greater than or equal to 15% and thus had no evidence of abnormal bile acid turnover. Twenty one had a seven day 75SeHCAT retention greater than or equal to 10% but less than 15%. Their clinical features were typical of the irritable bowel syndrome, and none of eight treated with cholestyramine showed symptomatic improvement. Sixteen patients had a seven day retention greater than or equal to 5% and less than 10%, six of whom had improved symptoms after treatment with bile acid chelating agents. The remaining 23 patients had a 75SeHCAT retention of less than 5% at seven days and responded to bile acid chelators. This group had a characteristic illness with intermittent watery diarrhoea, but no constitutional upset. It was not possible to distinguish the patients with bile acid malabsorption exclusively on the basis of the clinical symptoms and investigations, other than 75SeHCAT retention. We conclude that the measurement of 75SeHCAT retention is useful, appropriate, and necessary in patients with unexplained chronic diarrhoea.
Patients with Crohn's disease who suffer from longstanding diarrhoea that does not respond to conventional treatment pose a common clinical problem. Bile acid malabsorption is a possible cause, although its prevalence and clinical importance is unclear. This paper explores the clinical indications for referring patients with Crohn's disease for bile acid assessment and the extent of bile acid malabsorption in this selected group of patients. The selenium labelled bile acid SeHCAT was used to assess the effect of disease on the integrity of the enterohepatic circulation. Altogether 76% of the patients referred for bile acid assessment had longstanding diarrhoea that had not responded to conventional anti-diarrhoeal treatment or an increase in steroid therapy as their sole or predominant symptom. Ninety per cent of patients with bowel resections, almost exclusively ileocaecal, had abnormal SeHCAT retention (< 5% at seven days). Twenty eight per cent of patients with Crohn's disease who had not undergone resection 28% had a SeHCAT retention < 5%, signifying bile acid malabsorption. Nineteen of 22 patients given cholestyramine treatment subsequent to the SeHCAT test had a good symptomatic response. In conclusion, the prevalence of bile acid malabsorption in this selected group with Crohn's disease is sufficiently high to justify performing the SeHCAT test in order to separate the various differential diagnoses.
BACKGROUND: Data on collagenous colitis have been based on a limited number of patients. AIMS: To obtain more information on this disease from a register set up at Orebro Medical Center Hospital. PATIENTS AND METHODS: Twenty five Swedish hospitals have contributed to this patient register, which comprises 163 histopathologically verified cases. Clinical data were retrospectively analysed. RESULTS: Collagenous colitis followed a chronic intermittent course in most cases (85%) with a sudden onset in 42%. Symptoms were chronic watery diarrhoea, often nocturnal (27%), abdominal pain (41%), and weight loss (42%). Sixty six patients (40%) had one or more associated diseases. Routine laboratory data were mostly normal. The median age at diagnosis was 55 (range 16-86) years, but 25% of the patients were younger than 45 years. Seven patients died of unrelated diseases. The response rate for sulphasalazine was 59%, and 50% and 40% for mesalazine and olsalazine. Prednisolone was most effective with a response rate of 82%, but the required dose was often high and the effect was not sustained after withdrawal. Antibiotics were efficient in 63%. Cholestyramine and loperamide had response rates of 59% and 71% respectively. CONCLUSIONS: Collagenous colitis follows a chronic continuous course. Symptoms can be socially disabling, but the disease does not seem to have a malignant potential. A plan for the treatment of a newly diagnosed patient with collagenous colitis is proposed.
BACKGROUND: In a retrospective study bile acid malabsorption was observed in patients with collagenous colitis. AIMS: To study the occurrence of bile acid malabsorption and the effect of bile acid binders prospectively in patients with chronic diarrhoea and collagenous colitis. METHODS: Over 36 months all patients referred because of chronic diarrhoea completed a diagnostic programme, including gastroscopy with duodenal biopsy, colonoscopy with biopsies, and the (75)Se-homocholic acid taurine ((75)SeHCAT) test for bile acid malabsorption. Treatment with a bile acid binder (cholestyramine in 24, colestipol in three) was given, irrespective of the results of the (75)SeHCAT test. RESULTS: Collagenous colitis was found in 28 patients (six men, 22 women), 27 of whom had persistent symptoms and completed the programme. Four patients had had a previous cholecystectomy or a distal gastric resection. The (75)SeHCAT test was abnormal in 12/27 (44%) of the collagenous colitis patients with (75)SeHCAT values 0.5-9.7%, and normal in 15 patients (56%). Bile acid binding treatment was followed by a rapid, marked, or complete improvement in 21/27 (78%) of the collagenous colitis patients. Rapid improvement occurred in 11/12 (92%) of the patients with bile acid malabsorption compared with 10/15 (67%) of the patients with normal (75)SeHCAT tests. CONCLUSION: Bile acid malabsorption is common in patients with collagenous colitis and is probably an important pathophysiological factor. Because of a high response rate without serious side effects, bile acid binding treatment should be considered for collagenous colitis, particularly patients with bile acid malabsorption.
Hyperlipidaemia in children is most commonly expressed as hypercholesterolaemia. "Normal values" for serum cholesterol, if defined statistically, vary between communities, and levels of cholesterol in childhood above which an increased risk of coronary heart disease in adult life may be expected have not been firmly established. It is suggested that serum cholesterol concentration over 250 mg/dl (6.47 mmol/l) in a child over 1 year of age merits detailed investigation, including full lipoprotein analysis, and levels of serum cholesterol between230 and 250 mg/dl (5.95-6.47 mmol/l) should be repeated with further studies if indicated. Secondary hyperlipoproteinaemia rarely presents diagnostic problems but must always be excluded. The only primary hyperlipoproteinaemia likely to be encountered in childhood is familial hyperbetalipoproteinaemia in its common heterozygous form. The most effective means to date of lowering serum cholesterol in this condition is cholestyramine, but the long-term consequences of therapy are not known and treatment should at present be limited to children from high-risk families. Long-term follow-up is essential and until results of such studies are available population screening is unjustified.
The SeHCAT test was used to investigate possible bile acid malabsorption in 166 patients presenting to a district general hospital with chronic diarrhoea of uncertain cause. Eighty-four (51%) patients had impaired SeHCAT retention. These included 23 of 28 patients with a possible type I abnormality (terminal ileal resection or disease, previous pelvic radiotherapy), 20 of 74 with a possible type II abnormality (idiopathic diarrhoea), 32 of 45 with a possible type III abnormality (post-cholecystectomy, post-vagotomy), and 9 of 19 with diarrhoea associated with diabetes. Patients with severe bile acid malabsorption demonstrated a good response to cholestyramine whereas the response in patients with a mildly abnormal SeHCAT retention was variable. Bile acid malabsorption is an important cause of diarrhoea in patients presenting with unexplained chronic diarrhoea.
In an autoperfused dog ileum preparation, artificial pressure, venous outflow pressure, blood flow, and arteriovenous oxygen difference were measured while bile and bile salt solutions, at physiological concentrations, were placed in the lumen. Intraluminal placement of endogenous bile, synthetic bile, or bile salt solutions increased ileal blood flow (99 +/- 10, 94 +/- 20, and 104 +/- 17%, respectively) and oxygen uptake (30 +/- 5, 36 +/- 9, and 28 +/- 5%, respectively). Endogenous bile pretreated with cholestyramine, a bile salt-sequestering resin, did not alter ileal blood flow, yet increased ileal oxygen uptake by 11 +/- 3%, a response similar to that observed while Tyrode's solution (the vehicle) was in the lumen. Intra-arterial infusion of bile salts increased ileal blood flow in a dose-dependent manner, while not significantly altering ileal oxygen uptake. The results of the present study indicate that bile salts play an important role in the functional (postprandial) hyperemia in the ileum by 1) directly dilating the ileal vasculature and 2) enhancing ileal metabolism during their active absorption.
Portal hypertension is accompanied by hyperdynamic systemic and splanchnic circulation. Serum bile acids (BAs), which are elevated in portal hypertension and have vasodilatory properties, have been proposed as mediators of this hyperdynamic circulation. In this study, portal hypertensive rats [accomplished by partial portal vein ligation (PVL)] were gavaged with cholestyramine (PVL-CH) to decrease circulating BA levels. A control group of rats was gavaged with an inert suspension of Metamucil (PVL-ME). The following hyperdynamic parameters were found to be similar in PVL-CH and PVL-ME: mean arterial pressure (119 +/- 6 vs. 124 +/- 5 mmHg), portal pressure (13.2 +/- 0.6 vs. 14.5 +/- 0.5 mmHg), cardiac index (0.33 +/- 0.04 vs. 0.34 +/- 0.03 ml.min-1.g body wt-1), splanchnic blood flow (1.4 +/- 0.13 vs. 1.6 +/- 0.1 ml.min-1.g body wt-1), portosystemic shunting (82 +/- 8 vs. 92 +/- 3%), peripheral arteriolar resistances (344 +/- 74 vs. 387 +/- 29 mmHg.min.ml-1.g body wt), and splanchnic arteriolar resistances (75 +/- 14 vs. 72 +/- 6 mmHg.min.ml-1.g splanchnic wt; 1,471 +/- 150 vs. 1,325 +/- 120 mmHg.min.ml-1.g body wt). BA in PVL-ME (84 +/- 9 microM/l) were similar to those previously observed in untreated PVL and significantly greater than those measured in PVL-CH (25 +/- 4 microM/l; P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
The study objective was to determine whether and to what extent sterol 27-hydroxylase, the initial step in the "acidic" pathway of bile acid biosynthesis, is regulated by bile acids. Rats were fed diets supplemented with cholestyramine (CT, 5%), cholate (CA, 1%), chenodeoxycholate (CDCA, 1%), or deoxycholate (DCA, 0.25%). When compared with paired controls, sterol 27-hydroxylase and cholesterol 7 alpha-hydroxylase specific activities increased after CT administration by 188 +/- 20% (P < 0.05) and 415 +/- 36% (P < 0.01), respectively. Similarly, mRNA levels increased by 159 +/- 14% (P < 0.05) and 311 +/- 106% (P < 0.05), respectively. Feeding CA, CDCA, or DCA decreased sterol 27-hydroxylase specific activity to 57 +/- 6, 61 +/- 8, and 74 +/- 8% of controls, respectively (P < 0.05). By comparison, the specific activity of cholesterol 7 alpha-hydroxylase decreased to 46 +/- 7 , 32 +/- 10, and 26 +/- 8% (P = 0.001). mRNA levels and transcriptional activities for sterol 27-hydroxylase and cholesterol 7 alpha-hydroxylase transcriptional activity were changed to the same extent as the specific activities after CT or bile acid feeding. We conclude that sterol 27-hydroxylase and cholesterol 7 alpha-hydroxylase are subject to negative feedback regulation by hydrophobic bile acids at the level of transcription. However, the responses of sterol 27-hydroxylase to manipulation of the bile acid pool are less prominent than those of cholesterol 7 alpha-hydroxylase. During the diurnal cycle the specific activities of sterol 27-hydroxylase and cholesterol 7 alpha-hydroxylase changed in tandem, suggesting that both may be under control of glucocorticoids.
OBJECTIVE: To report an attempt to shorten the preparation interval before radioactive iodine administration using plasmapheresis in a 77-year-old woman with a history of papillary thyroid carcinoma with local recurrence and lung metastases, in whom the administration of a high dose of radioactive iodine was intended as a desperate rescue procedure. METHODS: The patient was initially started on cholestyramine. Two days later, plasmapheresis was performed. RESULTS: Plasmapheresis rapidly decreased free tri-iodothyronine (FT(3)) and free thyroxine (FT(4)). Serum FT(4) subsequently remained low, while FT(3) recovered the next day. Thyroid-stimulating hormone (TSH) reached 25 mIU/l in 14 days, which is within the time frame required to reach the target TSH level by withdrawing levothyroxine alone. CONCLUSION: Plasmapheresis is very effective in eliminating thyroid hormones from the circulation. However, it does not seem to accelerate thyrotroph recovery to a considerable extent after prolonged suppression.
Both alone and in combination with other lipid-lowering drugs, the bile acid sequestrants cholestyramine and colestipol, are excellent agents for lowering circulating low-density lipoprotein (LDL) cholesterol levels. They have been shown to lower the incidence of new coronary events and to retard the progression of coronary atherosclerosis. They also induce qualitative changes in lipoproteins whose significance requires further investigation but may be of significance in coronary disease prevention. While side effects may be bothersome for some patients, they can generally be managed effectively. In particular, modest lowering of dosage may preserve considerable LDL cholesterol lowering and virtually eliminate side effects. Sequestrants appear to be among the safest and most effective drugs in the cholesterol-lowering armamentarium.