PubMed Health⌕ Search

Biomedical subjects

R H Dowling

Publications and source records attributed to R H Dowling.

At least 55 records · Page 3Linked to original sources
PubMed1992

Inhibition of human gall bladder mucus synthesis in patients undergoing cholecystectomy.

Hypersection of gall bladder mucus is associated with gall stone formation in animal models. Aspirin inhibits both mucus synthesis and secretion, prevents gall stone formation in animals and reduces gall stone recurrence in man after dissolution therapy. Mucus biosynthesis in human gall bladder mucosal explants is inhibited by aspirin in vitro. We have studied the effects of aspirin in vivo. Fifty five patients with functioning gall bladder and stones have been randomised, 27 to group 1 (aspirin EC 300 mg once daily for seven days before cholecystectomy) and 28 to group 2 (controls). Gall bladder bile composition was analysed and mucus synthesis rates measured using 3H-glucosamine incorporation into mucosal explants cultured for 24 hours. Patient age, sex, and gall bladder histology were similar in both groups. There were no differences in stone composition, gall bladder bile calcium concentration, cholesterol saturation and cholesterol nucleation time. The mean 3H-glucosamine incorporation in aspirin treated patients was 1347 fmol/g wet weight as compared with 2008 fmol/g wet weight in controls (95% confidence interval 222-1100, p<0.005, unpaired t test). This reduction in biosynthesis was associated with gall bladder bile mucus concentrations of 7.6 mg/ml in patients and 7.1 mg/ml in controls (ns). Treatment with aspirin led to a significant reduction in mucus biosynthesis by the gall bladder mucosa. This action is consistent with a role for aspirin in the prevention of gall stones.

Adult↗
PubMed1992

Gallbladder stones--dissolve, blast, or extract? Laparoscopic cholecystectomy versus 'the rest'.

This article reviews selected aspects of the non-surgical/minimally invasive treatments of gallbladder stones (GBS) and discusses briefly the residual role of these treatments in the era of laparoscopic cholecystectomy. In patients with specific, gallstone-related symptoms who wish to retain their 'functioning' gallbladders, there are at least six different management options. They range from rapid but invasive to slow but safe: i) the rotary lithotrite; ii) percutaneous cholecystolithotomy; iii) percutaneous transhepatic or iv) endoscopic retrograde cannulation of the gallbladder followed by instillation (manual or pump-assisted) of contact solvents; v) extracorporeal shock-wave lithotripsy + adjuvant bile acids and; vi) oral bile acids alone. The recommended investigation sequence is i) ultrasound (to diagnose the presence of GBS), followed by ii) oral cholecystography (to assess cystic duct patency, gallbladder anatomy and GBS size, number, lucency, buoyancy, and contour), and iii) regional computed tomography scanning of the gallbladder (to predict stone composition and dissolvability and to plan routes of access to the gallbladder). The decision-making steps are i) choice of some form of active treatment versus no treatment (other than observation); ii) in those with specific symptoms and a patent cystic duct who opt for active treatment, to choose between removing versus retaining the gallbladder; and iii) in those who wish to retain their 'functioning' gallbladder, to offer and select the most appropriate of the alternative options. In conclusion, despite the excellence of laparoscopic cholecystectomy, there remains a place for the non-surgical/minimally invasive approaches in a carefully selected minority of symptomatic GBS patients. Although GBS may recur in approximately 50% of patients, the recurrent stones are often asymptomatic, can be detected 'early' by follow-up ultrasound, and are easily treated. Ultimately, the aim of gallstone research must be to prevent not only recurrent but also primary GBS formation, which would obviate the need for both medical and surgical treatment.

Administration, Oral↗
PubMed1992

Cellular and molecular basis of intestinal and pancreatic adaptation.

This article reviews the structural and functional changes which develop in the intestine and pancreas in response to a variety of stimuli and which characterise adaptive hyper- or hypo-plasia. It then discusses the principal physiological mechanisms controlling this adaptive growth. In the gut, these include luminal nutrition, endocrine, autocrine and paracrine hormonal influences, growth factors, enterotrophic components of pancreatico-biliary secretions, neural factors, changes in blood flow and mesenchyme-epithelial interactions. The cell biology of adaptive growth involves cell membrane receptors (first messengers) and a cascade of intracellular second messengers, the best studied of which is changes in polyamine metabolism and in related enzymes. The effects of ornithine decarboxylase (ODC) blockade with difluoromethyl ornithine (DFMO) and of diamine oxidase (DAO) blockade with aminoguanidine, are described. In general, DFMO inhibits or prevents adaptive hyperplasia while in the small bowel, aminoguanidine treatment induces 'supranormal' adaptation. However, both the gut and the pancreas transport 'exogenous' (ingested in food and circulating in the blood stream) polyamines across their apical and basolateral membranes. The influence of this exogenous polyamine transport on 'endogenous' (enzyme-regulated) intracellular polyamine concentrations, is largely unknown. Finally, the molecular biology of adaptive growth is described briefly--as illustrated by the use of a growth hormone transgenic model in which mice develop marked intestinal mucosal hyperplasia and increases in the relative abundance of insulin-like growth factor-I (IGF-I) mRNA in the intestine.

Adaptation, Physiological↗
PubMed1991

Gall bladder emptying patterns in response to a normal meal in healthy subjects and patients with gall stones: ultrasound study.

In this study gall bladder emptying patterns in response to a solid meal were studied using ultrasound. A similar triphasic pattern was seen in eight healthy control subjects and eight patients with gall stones, with 'early' and 'late' net emptying phases separated by a period of net refilling with peak postprandial gall bladder volumes occurring at (mean (SD)) 33.1 (17.9) minutes and 27.4 (18.8) minutes in control subjects and patients, respectively. A phase of slower net emptying followed, which was complete at 146 (33) minutes in control subjects and 125 (33) minutes in the gall stone patients (not significant). Superimposed upon this overall triphasic pattern, postprandial gall bladder emptying was punctuated by repeated short lived episodes of filling and emptying. The mean (SD) estimated postprandial bile outputs were 0.83 (0.34) ml/min in four control subjects and 1.2 (1.1) ml/min in seven patients with gall stones. We propose a 'washout' model to reconcile this large turnover of bile with the concentrating and storage functions of the gall bladder and predict that the extent rather than the rate of gall bladder emptying is important in determining stasis of bile in the gall bladder.

Adult↗
PubMed1991

Gastric carcinogenesis in the rat induced by duodenogastric reflux without carcinogens: morphology, mucin histochemistry, polyamine metabolism, and labelling index.

Chronic duodenogastric reflux induces gastric adenocarcinomas in the rat without the use of carcinogens. Altogether, 186 male Wistar rats were randomised to undergo either a simple gastrojejunostomy or a gastrotomy and sacrificed at eight weekly intervals for 56 weeks. No control animals developed dysplasia or carcinoma. All rats subjected to a gastrojejunostomy showed hyperplasia of the proliferative neck zone, with increased sulphomucin production adjacent to the scar. Low grade dysplasia was found at 16 weeks, and carcinoma was first seen at 32 weeks. Most carcinomas were well differentiated mucin secreting adenocarcinomas of the expanding type, which secreted a mixture of sialomucins and sulphomucins. Duodenogastric reflux was associated with a 100% increase in labelling index (assessed autoradiographically with tritiated thymidine) in the gastric mucosa when compared with corresponding tissue adjacent to a gastrotomy scar. This increase was significant at eight weeks and persisted for 56 weeks after surgery. This study supports the theory that, in this model, hyperplasia precedes the development of carcinoma.

Animals↗
PubMed1991

Molecular differences between human and experimental pancreaticobiliary diversion-induced rat pancreatic neoplasia.

A series of molecular changes are now known to be seen in human pancreatic neoplasia, including the very frequent mutational activation of Kirsten ras oncogene at codon 12, overexpression of the epidermal growth factor receptor, and abnormalities of c-erbB-2 expression. In order to determine whether similar changes can be seen in animal models of pancreatic cancer a molecular analysis of tumours induced in rats by pancreaticobiliary diversion was performed. The polymerase chain reaction was used to amplify portions of the rat Kirsten ras gene and sequence specific oligonucleotide hybridisation was used to define whether sequences were wild type or mutant. No evidence of mutation was found in the Kirsten ras gene at codons 12 or 61, where activating mutations are known to occur. In addition immunohistochemical methods were used to investigate expression of c-erB-2 and the epidermal growth factor receptor but no evidence of abnormal expression was found. We conclude that there are major molecular differences between human and experimental rat pancreatic cancer.

Amino Acid Sequence↗
PubMed1990

Postheparin plasma diamine oxidase in health and intestinal disease.

In animals, the distribution of the enzyme diamine oxidase is confined, almost exclusively, to the small bowel mucosa. In humans, plasma diamine oxidase is at or below assay detection limits but can be liberated into the circulation from binding sites in the intestine by i.v. heparin. Therefore, the authors wished to see if diamine oxidase could be released by a low and safe dose of heparin (5000 U) and if the resultant area under the concentration-time curve would provide a noninvasive marker of segmental intestinal disease. In 17 control subjects, the mean area under the curve (following administration of 5000 U i.v. heparin) was 35.9 +/- 5.0 (SEM) mU.L-1.2 h-1; in 6 individuals studied on two separate occasions, postheparin plasma diamine oxidase profiles were reproducible (r = 0.98; p less than 0.001). The longitudinal distribution of diamine oxidase in the gastrointestinal tract, measured in 12 gastric, 16 jejunal, 6 ileal, and 18 colonic biopsies, was similar in humans to that found in animals. In patients with normal peroral biopsies, there was a linear relationship between jejunal mucosal and postheparin plasma diamine oxidase activities (r = 0.84; p less than 0.01). The areas under the curve in controls were then compared with those in patients with segmental intestinal diseases: 21 with ileal disease with or without colonic Crohn's disease (10 unoperated and 11 with ileal resection), 7 with non-Crohn's ileal resection, 8 with ulcerative colitis, 10 with untreated and 7 with treated celiac disease (6 studied before and after a gluten-free diet), and 5 studied during total parenteral nutrition and again after resumption of oral feeding. The results in the 18 ileectomized patients were subdivided into those with major (arbitrarily greater than 75 cm) and minor (less than 75 cm) resections. Areas under the curve were markedly reduced in nonresected Crohn's patients (6.0 +/- 1.79 mU.L-1.2 h-1; p less than 0.001 vs. controls), correlating inversely, in a first-order relationship, with disease activity (r = 0.82; p less than 0.001) and returning toward normal in 4 patients achieving disease remission. Low areas under the curve in total parenteral nutrition patients (4.5 +/- 0.9; p less than 0.001) were also reversible on resumption of oral feeding. However, areas under the curve were not significantly lower in patients with limited ileal resection (less than or equal to 75 cm), with celiac disease (untreated and treated), or ulcerative colitis than in controls.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1990

Recurrent urticaria and reduced diamine oxidase activity.

An abnormal metabolism of histamine has been suspected in urticaria and the role of diamine oxidase (DAO: histaminase) is therefore of interest. We have studied DAO activity in plasma and jejunal biopsy material and have measured the post-heparin DAO release in 11 control subjects and nine with recurrent urticaria, three of whom had had concurrent episodes of abdominal pain. Two of the nine urticaria subjects had only a minimal rise in plasma DAO activity after heparin, three had a response which was at the lower end of the normal range, and four were normal. In four out of five cases in which jejunal biopsy activity was obtained, there was concordance between mucosal DAO activity and the post-heparin plasma DAO response. Those with abdominal symptoms had abnormally low mucosal DAO activity and the subject who was most severely affected had proven episodes of small bowel oedema.

Adult↗
PubMed1990

Effect of intestinal diamine oxidase (DAO) depletion by heparin on mucosal polyamine metabolism.

The aim of this study was to examine the relative importance of the enzymes ornithine decarboxylase (ODC) and diamine oxidase (DAO) in intestinal polyamine metabolism in normal rats. To study this we measured jejunal and ileal DAO and ODC activities and polyamine levels 2 h after injecting, in non-fasting male Wistar rats, either normal saline (controls) or a large dose of i.v. heparin to deplete intestinal mucosal DAO stores. We found that heparin significantly reduced mean DAO activity (p less than 0.001). As a result putrescine levels increased significantly in both jejunum (p less than 0.02) and ileum (p less than 0.01). Heparin-induced DAO depletion had no significant effect on spermine and spermidine levels at either site. The increased putrescine was associated with reduced ODC activity in both jejunum (p less than 0.01) and ileum (p less than 0.05). ODC activity correlated negatively with putrescine (p less than 0.001). These results suggest that (i) in normal rats, DAO is more important than ODC in regulating mucosal putrescine levels and (ii) putrescine exerts feedback inhibition of ODC.

Amine Oxidase (Copper-Containing)↗
PubMed1990

Role of polyamines in the early adaptive response to jejunectomy in the rat: effect of DFMO on the ileal villus:crypt axis.

To study the role of the polyamines putrescine, spermidine and spermine and of the enzymes controlling their synthesis (ornithine decarboxylase; ODC) and degradation (diamine oxidase; DAO) along the villus:crypt axis at the crucial early stage of the ileal adaptive response to jejunectomy, we measured polyamine concentrations and the activities of ODC, DAO and alkaline phosphatase (a marker of enterocyte maturity) in epithelial cells isolated by the Weiser technique from villus tips, mid villi, lower villi and crypts 4 days after surgery in transected control (TRC) and jejunectomised rats untreated or given the specific ODC blocker, alpha-difluoromethyl ornithine (DFMO, 2% in drinking water beginning 3 days before surgery). In the TRCs, there was a diminishing villus tip-to-crypt gradient not only in alkaline phosphatase but also in ODC and DAO activities. After jejunectomy, there were up to 93% increases in mean enterocyte ODC activity when compared with the corresponding cell fractions from the TRCs, but in both the control and jejunectomised rats, DFMO treatment markedly inhibited ODC activity (p less than 0.05-0.01) and reduced spermidine and particularly putrescine concentrations (p less than 0.005-0.001) in all four cell fractions. Only 4 days post-operation, jejunectomy stimulated a significant increase in ileal wet weight but DFMO treatment completely prevented this adaptive response and significantly reduced segmental intestinal weight (mg/cm) in the TRCs. These results (i) extend our knowledge of polyamines and related enzymes along the villus:crypt gradient in the normal intestine, (ii) provides the first data on these variables after resection, and (iii) lend further support to the hypothesis that changes in enterocyte ODC activity and in putrescine and spermidine concentrations play an important role in initiating the ileal adaptive response to proximal small bowel resection in the rat.

Adaptation, Physiological↗
PubMed1990

Effect of fasting and feeding on polyamines and related enzymes along the villus: crypt axis.

Fasting and feeding have profound effects on crypt cell production and small bowel mucosal growth but the mechanism whereby food stimulates villus tip enterocytes to influence crypt cell production is unknown. We therefore measured the activities of ornithine decarboxylase (ODC), diamine oxidase (DAO) and alkaline phosphatase (ALP--a marker of enterocyte maturity) and polyamine concentrations in epithelial cells from villus tips, mid villi, lower villi and crypts of small intestine in non-fasted controls and 18-24 h fasted rats. Fasting reduced crypt cell production and caused villus hyperplasia, DAO activity (mU/g) increased in control villus tips from 9.6 +/- (SEM) 0.8 to 12.3 +/- 1.5 after fasting (NS), from 7.6 +/- 0.4 to 13.9 +/- 3.0 in mid villi (p less than 0.01), from 5.7 +/- 1.0 to 10.4 +/- 7.4 in lower villi (p less than 0.01) and from 5.4 +/- 0.9 to 12.8 +/- 1.5 in the crypts (p less than 0.001). ALP showed a similar pattern of results. In contrast, fasting lowered ODC activity (pmol/mg protein/h) dramatically from 319 +/- 82 in control villus tips to 16.7 +/- 3.0 during fasting, from 297 +/- 59 to 10.7 +/- 3.6 in mid villi, from 224 +/- 45 to 6.3 +/- 2.8 in lower villi and from 150 +/- 31 to 5.8 +/- 3.3 in the crypts. Fasting reduced putrescine concentrations in all fractions but particularly in the crypts and in general was associated with increases in spermidine and spermine concentrations. The role of DAO in the maintenance of low putrescine concentrations during fasting is unclear.

Alkaline Phosphatase↗
PubMed1990

Is the intestine the sole source of heparin-stimulated plasma diamine oxidase? Acute effects of jejunectomy, ileectomy and total enterectomy.

The assumption that the intestine is the sole/major source of post-heparin diamine oxidase (DAO) has been tested only once by Kobayashi et al. in 1969. In this study we tested whether the intestine is indeed the sole/major source of post-heparin plasma DAO and furthermore we studied the relative contribution of jejunum and ileum to post-heparin plasma DAO. We measured non-fasting plasma DAO before and every 15 min for 2 h after i.v. heparin (4,000 U/kg BW) and compared the resultant areas under the concentration-time curves (AUCs: mU/l X 2 h) in unoperated controls, jejunectomised, ileectomised and totally enterectomised (from gastro-oesophageal to colorectal junctions) male Wistar rats. Total enterectomy virtually abolished the post-heparin rise in plasma DAO, the mean AUC falling from 55.3 +/- (SEM) 10.2 in controls to 2.1 +/- 1.1 after enterectomy (p less than 0.001). The mean AUCs after jejunectomy and ileectomy were 25.6 +/- 5.5 and 10.75 +/- 2.42, respectively. Therefore in acute jejunal and ileal resection the AUCs were 2.1 and 5.4 times, respectively, lower than those seen in the controls (p less than 0.02 and p less than 0.001). The difference in mean AUC values between jejunectomy and ileectomy groups was also statistically significant (p less than 0.05). We conclude that total enterectomy abolishes the post-heparin rise in circulating DAO activity, confirming that the intestine is the major source of post-heparin plasma DAO. The ileum contributes more than the jejunum to this post-heparin rise in plasma enzyme activity.

Amine Oxidase (Copper-Containing)↗
PubMed1990

Aminoguanidine blocks intestinal diamine oxidase (DAO) activity and enhances the intestinal adaptive response to resection in the rat.

The aim of this study was to assess the effect inhibiting diamine oxidase (DAO) activity on intestinal adaptation after 80% proximal small bowel resection in the rat. Aminoguanidine (AG), a DAO inhibitor, was administered subcutaneously (25 mg kg-1 day-1) to rats for 11 days after small bowel transection (n = 6) or resection (n = 6). Two additional groups of animals (n = 6) served as transection or resection controls and received normal saline subcutaneously for the same period. On day 12 after operation, the animals were sacrificed, mucosal homogenates prepared from the ileal remnants (or from the control ileum), analysed for DAO and ornithine decarboxylase (ODC) activities, and the concentrations of the polyamines putrescine, spermidine, spermine, and the indices of mucosal mass (wet weight, protein and DNA) measured. The results were expressed both per unit length intestine and per milligram mucosal DNA. AG treatment completely inhibited DAO activity in both the transection control and resected rats. In the AG-treated resection group, inhibition of DAO activity was accompanied by increases (p less than 0.005) in all three indices of mucosal mass (wet weight, protein and DNA per centimetre intestine), putrescine concentrations (p less than 0.05) and ODC activity per centimetre intestine (p less than 0.001) when compared with the saline-treated resection controls. The results of this study suggest that inhibition of the putrescine-degrading enzyme, DAO, enhances the adaptive response to intestinal resection. Therefore, DAO may play a major role in regulating adaptive intestinal mucosal growth. Furthermore, inhibition of DAO activity could be important therapeutically in patients with the short bowel syndrome.

Adaptation, Physiological↗
PubMed1990

Calcium binding by bile acids: in vitro studies using a calcium ion electrode.

In this study, we compared in vitro calcium binding by the taurine and glycine conjugates of the major bile acids in human bile: cholic (CA), chenodeoxycholic (CDCA) and deoxycholic (DCA) acids, together with the cholelitholytic bile acids ursodeoxycholic (UDCA) and ursocholic (UCA) acids. At physiological total calcium (CaTOT) (1-15 mM) and bile acid (BA) (10-50 mM) concentrations, all the bile acids caused concentration-dependent falls in [Ca2+], suggesting calcium binding. Except for glycine-conjugated CDCA, all the other calcium-bile acid complexes were soluble in 150 mM NaCl. The calcium binding affinities followed the pattern: dihydroxy (CDCA, UDCA and DCA) greater than trihydroxy (CA and UCA) bile acids, and glycine conjugates greater than taurine conjugates. The glycine conjugate of UDCA, which increases during UDCA treatment, had the highest calcium binding affinity. Ten-20 mM phospholipid modestly increased calcium binding by CA conjugates, but not by CDCA, UDCA, and DCA conjugates. Phospholipid also prevented the precipitation of glyco-CDCA in the presence of calcium. Bile acid-calcium biding was pH-independent over the range 6.5-8.5. The different calcium binding affinities of the major biliary bile acids may partly explain their varying effects on biliary calcium secretion. The results also suggest that neither precipitation of calcium-bile acid complexes nor impaired calcium binding by bile acids is important in the pathogenesis of human calcium gallstone formation.

Alkanesulfonates↗
PubMed1990

Final outcome of ursodeoxycholic acid treatment in 126 patients with radiolucent gallstones.

One hundred and twenty-six patients with radiolucent gallstones in 'functioning' gallbladders were treated with 8-10 mg ursodeoxycholic acid (UDCA) kg/day and followed to a treatment conclusion. Complete or partial gallstone dissolution was achieved in 74 (59 per cent). However, only 22 achieved complete gallstone dissolution, as judged by two normal oral cholecystograms; ultrasonograms were performed in 16 of these patients, and all were normal. UDCA was stopped in 76 patients: because of cystic duct obstruction (n = 12), severe biliary pain (n = 13), non-response (n = 25) or partial stone dissolution with arrested progress (n = 26). Life-table analysis showed that complete gallstone dissolution rates at four years were 25-30 per cent (two normal oral cholecystograms) and 17-19 per cent (two normal oral cholecystograms plus one ultrasonogram). All patients with complete gallstone dissolution had shown partial stone dissolution at 6-12 months; of those with partial stone dissolution at six months, only 25 per cent went on to complete gallstone dissolution, and then always within two years. Efficacy correlated inversely with stone size but not with age, sex, obesity or on-treatment saturation indices. Acquired surface gallstone calcification developed in 13 patients (life-table analysis 22 +/- 7 per cent at four years); none of these patients achieved complete gallstone dissolution and only five achieved partial stone dissolution. Thus, despite relatively high partial gallstone dissolution rates, the ultimate efficacy of UDCA in achieving complete gallstone dissolution is low.

Adult↗
PubMed1989

Cholestasis of total parenteral nutrition: bile acid and bile lipid metabolism in parenterally nourished rats.

As food in the intestine "drives" the enterohepatic circulation and bile acids influence bile flow, we postulated that the cholestasis of total parenteral nutrition might be due to bile acid changes, and the cholelithiasis and biliary sludge of total parenteral nutrition to bile lipid changes. We therefore studied bile acid and bile lipid metabolism in the following groups of rats, with and without bile fistula: (a) nonfasted, orally fed controls, (b) orally fed controls fasted for 20 h, and (c) after 7 days of total parenteral nutrition. Biliary bile acid concentration (35.4 +/- 2.5 mM) and secretion (253 +/- 20.0 mumol/100 g body wt.24 h) increased significantly in the rats on TPN and the rats fasted for 20 h (38.8 +/- 2.5 and 243 +/- 23.4 mM, respectively) when compared with the orally fed controls (26.5 +/- 2.5 and 178 +/- 23.5 mM, respectively). Bile flow, however, was unchanged. Bile acid pool size (Eriksson washout technique) also increased from 43.4 +/- 3.0 mumol/100 g body wt in the controls to 50.5 +/- 4.8 in the group fasted for 20 h and 65.6 +/- 5.3 in the TPN group (p less than 0.05-0.01). Similar bile acid pool sizes (carcass extraction method) were found in the nonfistulated animals. Biliary cholesterol secretion and saturation were significantly less in the TPN rats than in the other two groups. Liver microscopy indicated only minimal fatty change, but serum bile acid and alkaline phosphatase levels were increased in the TPN group (p less than 0.05). Thus, during TPN bile acids stagnate within the enterohepatic circulation, increasing biliary bile acid concentration and secretion rates and expanding the pool size. However, the absence of an associated choleresis, together with abnormal liver function tests, suggest that alterations in bile acid metabolism cause a relative cholestasis in this model.

Animals↗
PubMed1989

Ursocholic acid: bile acid and bile lipid dose response and clinical studies in patients with gall stones.

The biliary bile acid and bile lipid responses to six weeks treatment with approximately 5, 10, and 15 mg/kg/day of ursocholic acid (UCA) were studied in 11 gall stone patients. Maximum enrichment of bile with UCA (24 (SE) 4.9%) occurred with 15 mg UCA/kg/day. The maximum reduction in biliary cholesterol saturation was seen with the 10 mg/kg/day dose when the moles % cholesterol fell from 14 (2.4)% before treatment to 5.6 (0.83)% (p less than 0.02) and the saturation index fell from 1.4 (0.23) to 0.77 (0.13) (p less than 0.05). Clinical studies of the safety and efficacy of UCA in dissolving gall stones were carried out in 13 patients treated for up to two years with a dose of approximately 10 mg/kg/day. Diarrhoea caused withdrawal of treatment in three patients. There were no significant changes in liver function or haematology tests but fasting serum cholesterol tended to rise during treatment. Of nine patients treated for greater than 6 months, only one showed complete gall stone dissolution. As UCA may cause diarrhoea and hypercholesterolaemia, has only a modest effect on biliary cholesterol saturation and low gall stone dissolution efficacy, it is unlikely to replace existing forms of gall stone dissolution therapy.

Aged↗