Dissolving gallstones.
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Biomedical subjects
Publications and source records attributed to M Malavolti.
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Twenty-five postcholecystectomy (PC) patients who underwent a diagnostic work-up for persistent diarrhea and six control subjects were studied. Fourteen of the 25 patients were also characterized by conditions other than PC which could play a role in the pathogenesis of the diarrhea. However, none of the patients had evidence of ileal disease or resection. The average follow-up of the patients after the study was approximately 4.4 years. Excretion, composition, and aqueous-phase concentrations of fecal bile acids were analyzed using gas-liquid chromatography. Eleven of the 25 PC patients showed an increased fecal bile acid excretion. In three of the 11 patients, the magnitude of the bile acid loss, which ranged from 2.26 to 3.34 mmol/24 hr, indicated the presence of severe bile acid malabsorption. The fecal bile acid composition showed a significant shift from secondary to primary bile acids. In spite of the presence of marked bile acid malabsorption, the aqueous-phase concentrations of the dihydroxy bile acids, chenodeoxycholic and deoxycholic acids, did not, with one exception, reach the secretory level of 1.5 mM. The relatively low aqueous concentrations were the result of low bile acid solubility, due to an acidic fecal pH. Only two of nine patients, one with severe, and the other with equivocal bile acid malabsorption, who were treated with cholestyramine, showed an improvement of the diarrhea. The findings of subsecretory bile acid concentrations in the fecal aqueous phase and of inconsistent therapeutic responses to cholestyramine indicate that, in spite of the presence of bile acid malabsorption, the diarrhea was, with few exceptions, not bile acid-induced. The results of the study also suggest that the diarrhea in many PC patients is multifactorial in origin.
The effects of both apolipoprotein B,E receptor-dependent and receptor-independent uptake of low-density lipoprotein (LDL) in the liver on bile secretion were studied in bile fistula hamsters. Three groups of animals were studied after 4 wk of feeding either a control, chenodeoxycholic acid-, or ursodeoxycholic acid-containing diet. The hepatic receptor-dependent and receptor-independent uptake of LDL was related to both bile flow and biliary lipid secretion. The correlation with bile flow and biliary lipid secretion was positive for the receptor-dependent, but negative for the receptor-independent uptake of LDL. Although the receptor-mediated LDL uptake appeared to exert a strong influence on bile acid-independent bile flow, the receptor-independent uptake showed a significant relation with biliary bile acid excretion. Differences between the two mechanisms of LDL uptake were also evident in the biliary bile acid-cholesterol coupling, which was significantly stronger during receptor-independent than during receptor-dependent uptake of LDL. The effects of LDL uptake on bile secretion were modulated by the experimentally induced changes in both the content and composition of bile acids in the enterohepatic circulation.
Hamsters were fed chenodeoxycholic acid (CDC), ursodeoxycholic acid, (UDC), or no bile acid. [14C]Sucrose-labeled hamster low density lipoprotein (LDL) and methylated human LDL were infused intravenously to study LDL receptor-dependent and LDL receptor-independent organ uptake, respectively, of LDL. Biliary CDC increased during both CDC and UDC treatment. The UDC enrichment of bile after UDC feeding was relatively small. Bile acid synthesis was suppressed after both bile acid treatments. Under the condition of an acute bile fistula, the hamster LDL uptake increased in the liver, heart, and adrenals in the CDC-treated animals. During an intact enterohepatic circulation, the hepatic uptake of hamster LDL, which accounted for a major portion of the total uptake, was increased after UDC treatment. The hamster LDL uptake in the colon, which represented only a small fraction of the total uptake, increased after CDC treatment. When hamster LDL was infused at increasing concentrations, its uptake was significantly higher in the UDC-treated than in the control and CDC-treated animals. The methylated human LDL uptake showed no significant changes in the different treatment groups under either experimental condition. The study shows significantly different effects of CDC and UDC on LDL receptor activity. Since these differences are expressed in spite of a similar suppression of bile acid synthesis, UDC may directly influence LDL receptor activity.
Sixteen patients with radiolucent gallstones were treated with a combination of chenodeoxycholic and ursodeoxycholic acids for an average of 19 months. Liver tests remained normal in all patients. In nine of 15 patients (60%), in whom the gallbladder visualized during an oral cholecystogram, gallstones dissolved after one year, in eight of them, partially, and in the remaining one, completely. After two years, partial dissolution became complete in three patients, and partial dissolution occurred in 1 additional patient. Changes in lithogenic index and bile acid pool size were statistically not significant. Biliary content of chenodeoxycholic acid increased significantly from 25.7 +/- 3.53 to 45.2 +/- 3.31 (mean +/- SE)% and that of ursodeoxycholic acid from 2.6 +/- 0.52 to 34.6 +/- 2.45%. There were no discernible changes in serum triglycerides, total cholesterol, and HDL cholesterol. The findings suggest that the chenodeoxycholic-ursodeoxycholic acid combination provides a safe and efficacious treatment for some cholesterol gallstones.
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Three types of bile acid-induced diarrhoea can be distinguished. The best documented and most common entity is represented by type I bile acid malabsorption, which occurs as the result of a pathologically, anatomically defined ileopathy. Type II bile acid malabsorption is found in the setting of a morphologically completely normal ileum. This primary disorder of bile acid transport, which has been described in only a few paediatric and adult patients, appears to be rare. The third variety of bile acid malabsorption is characterized by the history of a previous cholecystectomy and/or by the presence of other gastroenterological conditions. Severe bile acid malabsorption is relatively uncommon in the type III syndrome. Even in the presence of severe bile acid malabsorption, patients with this condition are rarely found to have secretory concentrations of faecal bile acids, and/or rarely respond satisfactorily to cholestyramine. Present data suggest that bile acids play no significant role in the pathogenesis of idiopathic diarrhoea. A careful history, the measurement of stool weight and pH, a therapeutic trial of cholestyramine and the performance of a bile acid test, such as a bile acid breath test, can be used to establish the diagnosis of bile acid diarrhoea. Cholestyramine is the treatment of choice and is virtually always effective in this syndrome.
Fecal bacterial biotransformation studies of chenodeoxycholic acid were performed. Incubations were carried out for 30-s to 12-h time intervals. delta 6-Lithocholenic acid was isolated by thin-layer chromatography. Its structure was confirmed by gas-liquid chromatography and mass spectrometry. The proportion of chenodeoxycholic acid biotransformed to delta 6-lithocholenic acid consistently ranged from 5.5 to 14.0%.
The aim of this study was to investigate whether the cathartic effect of chenodeoxycholic acid (CDCA) could be helpful in the management of chronic constipation. Twenty cholesterol gall-stone patients with chronic constipation were randomly treated with either CDCA (750 mg/day in three divided doses at meals) or placebo for a period of 4 weeks. The administration of CDCA produced a significant increase of stool frequency and a decrease of stool consistency, while placebo was not effective in improving the bowel habit of the patients. As some patients complained of diarrhoea, and some had no modification of bowel frequency, further studies are needed to determine the most appropriate dose for each patient.
In a double-blind crossover design we compared dihydroxydibutylether (DHBE) with placebo in ten patients with cholesterol gallstones. The results showed that DHBE reduced (p less than 0.01) the bile saturation index (SI). The bile lipid composition demonstrated that the reduced SI was due to a decrease (p less than 0.01) in the molar percentage of cholesterol. There was no significant modification in biliary acid and phospholipid molar percentage.
PRIMARY OBJECTIVE: The study aimed to evaluate the sensitivity (SN) and specificity (SP) of body mass index (BMI) and skinfold thicknesses in detecting excess adiposity in children. RESEARCH DESIGN: Cross-sectional. MATERIALS AND METHODS: 986 children (500 females and 486 males) aged 10 +/- 1 years (mean +/- SD; range: 8-12 years) were studied. All underwent anthropometric measurements and bioelectrical impedance analysis (BIA). Dual-energy X-ray absorptiometry (DXA) was performed in 52 children to develop a population-specific algorithm for the assessment of fat-free mass (FFM) from BIA. The algorithm was applied to the remaining 934 children to estimate their FFM. Fat mass (FM) was obtained by subtracting FFM from weight (Wt). Values of FM:Wt were transformed in Z-scores and converted into 19 percentile categories (from 5 to 95 in steps of 5). The same procedure was performed with BMI and the log-transformed sum of four skinfold thicknesses (triceps, biceps, subscapular and suprailiac; lt-4SF). Excess adiposity was defined as a level of FM:Wt greater than the internally derived 85th percentile. SN and SP of each internally derived percentile of BMI and lt-4SF in detecting excess adiposity were calculated. RESULTS: In the pooled sample (n = 934), SN and SP were 0.39 and 0.99 for the 95th percentile of BMI, 0.65 and 0.95 for the 85th percentile of BMI, and 0.75 and 0.94 for the 85th percentile of lt-4SF. CONCLUSIONS: BMI percentiles employed in the present study have a high SP but a low SN in detecting excess adiposity in 8-12-year-old children. The use of the sum of four skinfolds has the potential to increase the SN of a screening programme for excess adiposity in children of this age.
PRIMARY OBJECTIVE: To study the relationship between bone mineral content (BMC), lean tissue mass (LTM) and fat mass (FM) in a large sample of young and elderly women. RESEARCH DESIGN: Cross-sectional. METHODS AND PROCEDURES: BMC, LTM and FM were measured by dual-energy X-ray absorptiometry in 2009 free-dwelling Caucasian women aged 63 +/- 7 years (mean +/- SD; range: 37-88 years). The majority of women were postmenopausal (96%). RESULTS: LTM explained 13% more variance of BMC than FM (R(2)(adj) = 0.39 vs 0.26, p < 0.0001) but weight (Wt) explained 5% more variance of BMC than LTM (R(2)(adj) = 0.44, p < 0.0001). The prediction of BMC obtained from LTM and FM (R(2)(adj)= 0.46, p < 0.0001) was only slightly better than that obtained from Wt. After the effects of age, Wt and height (Ht) on BMC were taken into account by multiple regression, the contribution of LTM and FM to BMC was just one-fifth of that of Wt (R(2)(adj) for full models < or =0.56, p < 0.0001). After a further correction for bone area (BA), the contribution of LTM and FM to BMC was just one-tenth of that of BA and not different from that of Wt and Ht on practical grounds (R(2)(adj) for full models = 0.84, p < 0.0001). Thus, after inter-individual differences in age, Wt, Ht (and bone size) are taken into account, the relationship between body composition and BMC is substantially weakened. CONCLUSIONS: In Caucasian women, (1) LTM is a stronger predictor of BMC than FM, but (2) Wt is a better predictor of BMC than body composition for practical purposes, and (3) Wt and body composition are not able to explain more than 46% of BMC variance.
AIM: To calibrate eight-polar bioelectrical impedance analysis (BIA) against dual-energy X-ray absorptiometry (DXA) for the assessment of total and appendicular body composition in healthy adults. RESEARCH DESIGN: A cross-sectional study was carried out. SUBJECTS: Sixty-eight females and 42 males aged 21-82 years participated in the study. METHODS: Whole-body fat-free mass (FFM) and appendicular lean tissue mass (LTM) were measured by DXA; resistance (R) of arms, trunk and legs was measured by eight-polar BIA at frequencies of 5, 50, 250 and 500 kHz; whole-body resistance was calculated as the sum R of arms, trunk and legs. RESULTS: The resistance index (RI), i.e. the height(2)/resistance ratio, was the best predictor of FFM and appendicular LTM. As compared with weight (Wt), RI at 500 kHz explained 35% more variance of FFM (vs 0.57), 45% more variance of LTM(arm) (vs 0.48) and 36% more variance of LTM(leg) (vs 0.50) (p < 0.0001 for all). The contribution of age to the unexplained variance of FFM and appendicular LTM was nil or negligible and the RI x sex interactions were either not significant or not important on practical grounds. The percent root mean square error of the estimate was 6% for FFM and 8% for LTM(arm) and LTM(leg). CONCLUSION: Eight-polar BIA offers accurate estimates of total and appendicular body composition. The attractive hypothesis that eight-polar BIA is influenced minimally by age and sex should be tested on larger samples including younger individuals.