Containment of carbapenem-resistant Enterobacterales colonisations and infections: Results from an integrated infection control intervention in a large hospital trust of northern Italy.

PURPOSE: We describe the results of an infection control intervention, implemented in 4 tertiary hospitals in Romagna, Italy, aiming at containing the spread of carbapenem-resistant Enterobacterales (CRE). METHODS: The intervention consisted of rectal screening in patients at risk for CRE; pre-emptive contact precaution waiting for screening results; timely notification of CRE identification and concomitant computerized alert; contact precaution for confirmed CRE-positive patients. We performed an interrupted time series analysis to compare the incidence of CRE bacteraemia, of other CRE infections, and CRE-positive rectal swabs in the pre and postintervention period (January 2015-July 2017 and August 2017-June 2020, respectively). RESULTS: 4,332 CRE isolates were collected. Klebsiella pneumoniae was the most represented pathogen (n = 3,716, 85%); KPC production was the most common resistance mechanism (n = 3,896, 90%). The incidence rate of CRE bacteraemia significantly decreased from 0.554 to 0.447 episodes per 10.000 patient days in the early postintervention period (P = .001). The incidence rate of other CRE infections significantly decreased from 2.09 to 1.49 isolations per 10.000 patient days in the early postintervention period (P = .021). The monthly number of rectal swabs doubled in the postintervention period and there was a significant reduction trend of CRE-positive swabs, sustained over time (P < .001). CONCLUSIONS: The infection control intervention was successful in containing the spread of CRE infections and colonisations.

Gestational weight gain in overweight and obese women enrolled in a healthy lifestyle and eating habits program.

OBJECTIVES: To determine whether changes in lifestyle in women with BMI > 25 could decrease gestational weight gain and unfavorable pregnancy outcomes. METHODS: Women with BMI > 25 were randomized at 1st trimester to no intervention or a Therapeutic Lifestyle Changes (TLC) Program including diet (overweight: 1700 kcal/day, obese: 1800 kcal/day) and mild physical activity (30 min/day, 3 times/week). At baseline and at the 36th week women filled-in a Food Frequency Questionnaire. OUTCOMES: gestational weight gain, gestational diabetes mellitus, gestational hypertension, preterm delivery. Data stratified by BMI categories. RESULTS: Socio-demographic features were similar between groups (TLC: 33 cases, CONTROLS: 28 cases). At term, gestational weight gain in obese women randomized to TLC group was lower (6.7 ± 4.3 kg) versus controls (10.1 ± 5.6 kg, p = 0.047). Gestational diabetes mellitus, gestational hypertension and preterm delivery were also significantly lower. TLC was an independent factor in preventing gestational weight gain, gestational diabetes mellitus, gestational hypertension. Significant changes in eating habits occurred in the TLC group, which increased the number of snacks, the intake of fruits-vegetables and decreased the consumption of sugar. CONCLUSIONS: A caloric restriction associated to changes in eating behavior and constant physical activity, is able to reduce gestational weight gain and related pregnancy complications in obese women.

Growth: healthy status and active food model in pediatrics.

OBJECTIVE: The brain integrates peripheral signals of nutrition in order to maintain a stable body weight. Nutritional status defined as the results of introduction, absorption, and utilization of the nutrients could be interpreted with the base of the relationship between nutritional status and healthy status. In this view, energy balance, body function, and body composition are three entities correlated to each other to the healthy status. AIM: To discuss the nutritional status in relation with healthy status, and its relationship with growth and nutrients. METHODS: A review of the available literature on food patterns and active food model was carried out. RESULTS: In the reviewed studies, strategies that could offer promising results to prevent overweight and obesity were discussed, in particular in the light of functional foods that effect energy metabolism and fat partitioning. CONCLUSION: At this moment it is necessary to proactively discuss and promote healthy eating behaviors among children at an early age and empower parents to promote children's ability to self-regulate energy intake while providing appropriate structure and boundaries around eating.

Accuracy of eight-polar bioelectrical impedance analysis for the assessment of total and appendicular body composition in peritoneal dialysis patients.

OBJECTIVE: To establish the accuracy of bioelectrical impedance analysis (BIA) for the assessment of total and appendicular body composition in peritoneal dialysis (PD) patients. DESIGN: Cross-sectional study. SETTING: University Nephrology Clinic. SUBJECTS: In all, 20 PD patients and 77 healthy controls matched for gender, age and body mass index. METHODS: Whole-body fat-free mass (FFM) and appendicular lean tissue mass (LTM) were measured by dual-energy X-ray absorptiometry. 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 of R of arms, trunk and legs. The resistance index (RI) was calculated as the ratio between squared height and whole-body or segmental R. RESULTS: RI at 500 kHz was the best predictor of FFM, LTM(arm) and LTM(leg) in both PD patients and controls. Equations developed on controls overestimated FFM and LTM(arm) and underestimated LTM(leg) when applied to PD patients. Specific equations were thus developed for PD patients. Using these equations, the percent root mean-squared errors of the estimate for PD patients vs controls were 5 vs 6% for FFM, 8 vs 8% for LTM(arm) and 7 vs 8% for LTM(leg). CONCLUSION: Eight-polar BIA offers accurate estimates of total and appendicular body composition in PD patients, provided that population-specific equations are used.

Body water distribution in severe obesity and its assessment from eight-polar bioelectrical impedance analysis.

OBJECTIVE: To measure body water distribution and to evaluate the accuracy of eight-polar bioelectrical impedance analysis (BIA) for the assessment of total body water (TBW) and extracellular water (ECW) in severe obesity. DESIGN: Cross-sectional study. SETTING: Obesity clinic. SUBJECTS: In all, 75 women aged 18-66 y, 25 with body mass index (BMI) between 19.1 and 29.9 kg/m(2) (ie not obese), 25 with BMI between 30.0 and 39.9 kg/m(2) (ie class I and II obese), and 25 with BMI between 40.0 and 48.2 kg/m(2) (ie class III obese). METHODS: TBW and ECW were measured by (2)H(2)O and Br dilution. Body resistance (R) was obtained by summing the resistances of arms, trunk and legs as measured by eight-polar BIA (InBody 3.0, Biospace, Seoul, Korea). The resistance index at a frequency of x kHz (RI(x)) was calculated as height (2)/R(x). RESULTS: ECW : TBW was similar in women with class III (46+/-3%, mean+/-s.d.) and class I-II obesity (45+/-3%) but higher than in nonobese women (39+/-3%, P<0.05). In a random subsample of 37 subjects, RI(500) explained 82% of TBW variance (P<0.0001) and cross-validation of the obtained algorithm in the remaining 38 subjects gave a percent root mean square error (RMSE%) of 5% and a pure error (PE) of 2.1 l. In the same subjects, RI(5) explained 87% of ECW variance (P<0.0001) and cross-validation of the obtained algorithm gave a RMSE% of 8% and a PE of 1.4 l. The contribution of weight and BMI to the prediction of TBW and ECW was nil or negligible on practical grounds. CONCLUSIONS: ECW : TBW is similar in women with class I-II and class III obesity up to BMI values of 48.2 kg/m(2). Eight-polar BIA offers accurate estimates of TBW and ECW in women with a wide range of BMI (19.1-48.2 kg/m(2)) without the need of population-specific formulae.

Comparison of bioelectrical impedance analysis and dual-energy X-ray absorptiometry for the assessment of appendicular body composition in anorexic women.

OBJECTIVE: To establish the accuracy of bioelectrical impedance analysis (BIA) for the assessment of appendicular body composition in anorexic women. DESIGN: Cross-sectional study. SETTING: Outpatient University Clinic. SUBJECTS: A total of 39 anorexic and 25 control women with a mean (s.d.) age of 21 (3) y. METHODS: Total, arm and leg fat-free mass (FFM) were measured by dual-energy X-ray absorptiometry and predicted from total and segmental BIA at 50 kHz. The predictor variable was the resistance index (Rl), that is, the ratio of height (2) to body resistance for the whole body and the ratio of length(2)/limb resistance for the arm and leg. RESULTS: Predictive equations developed on controls overestimated total, arm and leg FFM in anorexics (P<0.0001). Population-specific equations gave a satisfactory estimate of total and appendicular FFM in anorexics (P=NS) but had higher percent root mean square errors (RMSEs%) as compared to those developed on controls (8% vs 5% for whole body, 12% vs 10% for arm and 10% vs 8% for leg). The accuracy of the estimate of total and leg FFM in anorexics was improved by adding body weight (Wt) as a predictor with Rl (RMSE%=5% vs 8% and 7% vs 10%, respectively). However, the same accuracy was obtained using Wt alone, suggesting that in anorexics, BIA at 50 kHz is not superior to Wt for assessing total and leg FFM. CONCLUSION: BIA shows some potential for the assessment of appendicular body composition in anorexic women. However, Wt is preferable to BIA at 50 kHz on practical grounds. Further studies should consider whether frequencies >50 kHz give better estimates of appendicular composition in anorexics as compared to Wt. SPONSORSHIP: University of Napoli.

Cross-calibration of eight-polar bioelectrical impedance analysis versus dual-energy X-ray absorptiometry for the assessment of total and appendicular body composition in healthy subjects aged 21-82 years.

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.

Sensitivity and specificity of body mass index and skinfold thicknesses in detecting excess adiposity in children aged 8-12 years.

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.

Accuracy of an eight-point tactile-electrode impedance method in the assessment of total body water.

OBJECTIVE: To establish the accuracy of an eight-polar tactile-electrode impedance method in the assessment of total body water (TBW). DESIGN: Transversal study. SETTING: University department. SUBJECTS: Fifty healthy subjects (25 men and 25 women) with a mean (s.d.) age of 40 (12) y. METHODS: TBW measured by deuterium oxide dilution; resistance (R) of arms, trunk and legs measured at frequencies of 5, 50, 250 and 500 kHz with an eight-polar tactile-electrode impedance-meter (InBody 3.0, Biospace, Seoul, Korea). RESULTS: An algorithm for the prediction of TBW from the whole-body resistance index at 500 kHz (height (2)/R(500) where R is the sum of the segmental resistances of arms, trunk and legs) was developed in a randomly chosen subsample of 35 subjects. This algorithm had an adjusted coefficient of determination (r2(adj)) of 0.81 (P<0.0001) and a root mean square error (RMSE) of 3.6 l (9%). Cross-validation of the predictive algorithm in the remaining 15 subjects gave an r2(adj) of 0.87 (P<0.0001) and an RMSE of 3.0 l (8%). The precision of eight-polar BIA, determined by measuring R three times a day for five consecutive days in a fasting subject, was < or =2.8% for all segments and frequencies. CONCLUSION: Eight-polar BIA is a precise method that offers accurate estimates of TBW in healthy subjects. This promising method should undergo further studies of precision and its accuracy in assessing extracellular water and appendicular body composition should be determined. SPONSORSHIP: Modena and Reggio Emilia University.

Relationship between body composition and bone mineral content in young and elderly women.

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.

Association of waist circumference and body mass index with fasting blood insulin in severely obese children: a cross-sectional study.

We tested whether body mass index (BMI) and waist circumference (WC) are associated with fasting insulin in severely obese children. A number of 391 (204 female and 187 male) obese children were consecutively enrolled in the study at a Paediatric outpatient clinic. They were aged 10+/-3 yr (mean+/-SD; range: 3-17 yr) and had a relative weight for age of 160+/-27% (mean+/-SD). BMI and WC explained respectively 9 and 13% of the variance of log-transformed (lt) insulin (p<0.0001 for both). After correction for age, however, BMI lost its association with lt-insulin (p=NS) and WC explained only 3% (p<0.001) of lt-insulin variance. Sex and pubertal status did not influence the relationship between WC, BMI and lt-insulin (p=NS, ANCOVA). We conclude that in severely obese children: 1) WC is a marginally better predictor of fasting blood insulin than BMI, 2) age has a substantial influence on the relationship between BMI, WC and insulin and, 3) the contribution of BMI and WC to insulin is of doubtful clinical relevance because it leaves a substantial portion (> or = 87%) of lt-insulin variance unexplained.

Some applications of indirect calorimetry to sports medicine.

Some applications of indirect calorimetry to sports medicine are discussed and exemplified by case reports. In particular, it is suggested that oxigen consumption can be employed to assess the effects of physical activity on fat-free tissues and that the respiratory quotient may offer some insights into the food habits of athletes.

Effect of ursodeoxycholic acid on hepatic LDL binding and uptake in dietary hypercholesterolemic hamsters.

Administration of ursodeoxycholic acid (UDCA) has been shown to decrease serum total and low density lipoprotein (LDL) cholesterol in hypercholesterolemic patients with primary biliary cirrhosis. Results of previous studies prompted us to postulate that the cholesterol-lowering effect of UDCA may be due, at least in part, to a direct increment in hepatic LDL receptor binding [Bouscarel et al., Biochem J, 1991;280:589; Bouscarel et al., Lipids 1995;30:607]. The aim of the present investigation was to determine the ability of UDCA to enhance hepatocellular LDL receptor recruitment, as determined by its effect in vivo on LDL uptake, and its effect in vitro on LDL binding, under conditions of moderately elevated serum cholesterol. Study groups consisted of male golden Syrian hamsters fed either a standard chow diet (control), a 0.15% cholesterol-containing diet, or a 0.15% cholesterol-containing diet supplemented with either 0.1% UDCA, or 0.1% chenodeoxycholic acid (CDCA). Cholesterol feeding increased (P<0.01) total serum cholesterol by 44%, and was associated with a 10-fold accumulation of cholesteryl esters in the liver (P<0.01). In vivo, hepatic uptake of [U-(14)C]sucrose-labeled hamster LDL was increased (P<0.05) to a level of 454+/-101 microl in animals fed a cholesterol-containing diet supplemented with UDCA, compared to that either without UDCA (337+/-56 microl), or with CDCA (240+/-49 microl). The hepatic uptake of [U-(14)C]sucrose-labeled methylated human LDL, a marker of LDL receptor-independent LDL uptake, was unaffected by bile acid feeding. In vitro, specific binding of [125I]hamster LDL to isolated hepatocytes was determined at 4 degrees C, in presence and absence of 700 micromol/l UDCA. The K(D) ranged from 25 to 31 microg/ml, and was not affected by either cholesterol feeding or UDCA. In the presence of UDCA, the B(max) was increased by 19% (P<0.05) in cells isolated from control animals and by 29% (P<0.01) in cells isolated from hamsters fed a cholesterol-supplemented diet. In conclusion, in dietary hypercholesterolemic hamsters, both chronic in-vivo and acute in-vitro treatments with UDCA resulted in restoration of hepatic LDL binding and uptake to levels observed in control hamsters.

Effect of dietary oils containing different amounts of precursor and derivative fatty acids on prostaglandin E2 synthesis in liver, kidney and lung of rats.

The availability of the fatty acids which are precursors of prostaglandins is affected by dietary intake. We have studied, in particular, the effects of dietary intake of lipids with different amounts of precursor and derivative fatty acids on the synthesis of prostaglandin E2 (PGE2) in rat liver, kidney and lung. Fifteen-month-old rats were fed for 3 months diets containing different amounts of oleic, linoleic, alpha linolenic, gamma linolenic and stearidonic acids. The fatty acid compositions of total phospholipids and prostaglandin E2 levels of liver, kidney and lung were investigated. In the organs studied, the intake of lipids at different amount of precursor/derivative fatty acids caused variations in the fatty acid composition of phospholipids. PGE2 showed different values which did not seem directly affected by tissue availability of arachidonate but by the effect of dietary lipids on the metabolic pool of polyunsaturated fatty acids (PUFAs).

Extrahepatic deposition and cytotoxicity of lithocholic acid: studies in two hamster models of hepatic failure and in cultured human fibroblasts.

Effects of bile acids on tissues outside of the enterohepatic circulation may be of major pathophysiological significance under conditions of elevated serum bile acid concentrations, such as in hepatobiliary disease. Two hamster models of hepatic failure, namely functional hepatectomy (HepX), and 2-day bile duct ligation (BDL), as well as cultured human fibroblasts, were used to study the comparative tissue uptake, distribution, and cytotoxicity of lithocholic acid (LCA) in relation to various experimental conditions, such as binding of LCA to low-density lipoprotein (LDL) or albumin as protein carriers. Fifteen minutes after i.v. infusion of [24-(14)C]LCA, the majority of LCA in sham-operated control animals was recovered in liver, bile, and small intestine. After hepatectomy, a significant increase in LCA was found in blood, muscle, heart, brain, adrenals, and thymus. In bile duct-ligated animals, significantly more LCA was associated with blood and skin, and a greater than twofold increase in LCA was observed in the colon. In the hepatectomized model, the administration of LCA bound to LDL resulted in a significantly higher uptake in the kidneys and skin. The comparative time- and concentration-dependent uptake of [14C]LCA, [14C]chenodeoxycholic acid (CDCA), and [14C]cholic acid (CA) in cultured human fibroblasts was nonsaturable and remained a function of concentration. Initial rates of uptake were significantly increased by approximately tenfold, with decreasing hydroxylation of the respective bile acid. After 1 hour of exposure of fibroblasts to LCA, there was a significant, dose-dependent decrease in mitochondrial dehydrogenase activity from 18% to 34% of the control, at LCA concentrations ranging from 1 to 20 micromol/L. At a respective concentration of 100 and 700 micromol/L, CDCA caused a 35% and 99% inhibition of mitochondrial dehydrogenase activity. None of the bile acids tested, with the exception of 700 micromol/L CDCA, caused a significant release of cytosolic lactate dehydrogenase into the medium. In conclusion, we show that bile acids selectively accumulate in nonhepatic tissues under two conditions of impaired liver function. Furthermore, the extrahepatic tissue distribution of bile acids during cholestasis may be affected by serum lipoprotein composition. At a respective concentration of 1 and 100 micromol/L, LCA and CDCA induced mitochondrial damage in human fibroblasts, after just 1 hour of exposure. Therefore, enhanced extrahepatic uptake of hydrophobic bile acids during liver dysfunction, or disorders of lipoprotein metabolism, may have important implications for bile-acid induced cytotoxic effects in tissues of the systemic circulation.

Serum lipid and lipoprotein patterns in patients with liver cirrhosis and chronic active hepatitis.

BACKGROUND: An impaired lipid metabolism is often found in patients with chronic liver diseases. Unfortunately, few studies are available concerning serum lipid and lipoprotein levels in patients with liver cirrhosis and chronic active hepatitis (CAH). OBJECTIVES: To evaluate low-density lipoprotein (LDL), high-density lipoprotein (HDL), very low-density lipoprotein (VLDL), and total cholesterol serum levels in patients with cirrhosis and CAH and control patients and to relate the findings to the severity of the cirrhosis (Child classification). METHODS: We measured the serum lipid pattern in 34 consecutive patients with liver cirrhosis (15 men and 19 women; mean [+/-SD] age, 55 +/- 14 years; Child classes: 14 in A, 9 in B, 11 in C; patients with biliary cirrhosis were excluded), 34 patients with CAH, and 34 control patients. The 3 groups were matched for sex and age. Total serum, HDL cholesterol, and triglyceride levels were measured by enzymatic methods; serum LDL and VLDL levels were calculated. RESULTS: In patients with cirrhosis, there was a significant decrease in LDL, HDL, and total cholesterol serum levels compared with both the patients with CAH and the control patients, while the VLDL cholesterol level in patients with cirrhosis was significantly lower compared with the control patients alone. A significant decrease in total cholesterol levels was also observed in the CAH group when compared with the control patients. In patients with cirrhosis, levels of LDL, HDL, and total serum cholesterol were progressively lower when comparing patients in Child class A with patients in class C. CONCLUSIONS: In this study, the striking decrease in the level of serum LDL cholesterol in patients with liver disease was related to the increasing severity of the disease. Accordingly, the assessment of the serum LDL cholesterol level is important for an effective treatment and prognostic evaluation of patients with chronic liver disease.

Flutamide-induced toxic hepatitis. Potential utility of ursodeoxycholic acid administration in toxic hepatitis.

Flutamide is a nonsteroidal antiandrogen commonly used in the treatment of prostate cancer. Hepatic toxicity associated with flutamide has been reported with an incidence from less than 1% to about 5%. Ursodeoxycholic acid (UDCA), a hydrophilic bile acid, has been widely used in the treatment of cholesterol gallstones and of several liver diseases, but few data are now available concerning its use in the management of drug-induced hepatitis. The case of a patient who presented severe hepatitis with jaundice following use of flutamide is reported. UDCA treatment was started on admission and, contemporaneously, flutamide was withdrawn. Clinical and biochemical improvement was progressively observed, and the patient was discharged six weeks after the admission. Since fatal flutamide-related hepatitis has been reported, monitoring of serum liver tests is advocated during flutamide administration, and the effectiveness of UDCA in the treatment of drug-induced hepatotoxicity requires further study.

Formation, absorption, and biotransformation of delta 6-lithocholenic acid in humans.

delta 6-Lithocholenic acid was identified in small amounts in fecal samples in vitro after incubation with ursodeoxycholic acid and in vivo in controls and after chenodeoxycholic and ursodeoxycholic acid ingestion. Fourteen to 45.0% of delta 6-[24-14C]lithocholenic acid was biotransformed in vitro in feces within 30 s. After colonic instillation of delta 6-[24-14C]lithocholenic acid, 50% of the radioactivity appeared in bile acids, most of it in lithocholic acid, within 3 h. Jejunal perfusions with delta 6-[24-14C]lithocholenic acid showed 33-92% absorption. One hour after jejunal instillation of 1 mmol, 4.4-27.5% of the biliary radioactivity was found in ursodeoxycholic, chenodeoxycholic, lithocholic, and 7-ketolithocholic acids. A sulfated glycine conjugate of delta 6-lithocholenic acid was identified in bile. One hour after intravenous injection of delta 6-[24-14C]lithocholenic acid, 40.1-42.6% of biliary radioactivity appeared in 7-ketolithocholic, chenodeoxycholic, lithocholic/isolithocholic, and ursodeoxycholic acids. The studies show that delta 6-lithocholenic acid is 1) formed in colonic lumen from chenodeoxycholic and ursodeoxycholic acids, 2) well absorbed in small intestine, and 3) biotransformed in both the colonic lumen and liver. The studies also identified delta 6-lithocholenic acid as a new intermediate in formation of lithocholic acid. Finally, the studies showed that a small portion of delta 6-lithocholenic acid is excreted as a sulfated glycine conjugate in bile.

Bile acid dissolution therapy of gallbladder stones.

Oral cholelitholytic bile acid therapy has become established treatment for selected patients with cholesterol gallstones. The treatment finds its clinical application both alone and in combination with ESWL. UDCA alone or, less commonly, a combination of this bile acid with CDCA is used. Optimal results can be expected only in carefully selected patients. Bile acid dissolution therapy is most successful in patients with radiolucent gallstones which are < or = 0.5 cm in diameter or are shown by OCG to be floating. Dissolution is seldom seen when the stones are > 1 cm in size. Cholelitholytic treatment in combination with ESWL yields optimal results in single radiolucent gallstones which are not greater than 2 cm. ESWL thus makes it possible to use medical treatment effectively in single 1-2 cm gallstones when bile acids alone would not be successful. Bile acid treatment is extremely safe, especially if UDCA is given without the addition of CDCA.