Mara Bozzoli

Prevalence rates of gallstone disease in Italy - The Chianciano population study

The prevalence of gallstone disease and associated factors in the entire population of subjects aged 15–65 years born and resident in Chianciano Terme (Siena — Tuscany) was examined in the years 1985 and 1986. The investigation included gallbladder ultrasonography, administration of a questionnaire on personal and family history, physical examination and blood chemistry. A total of 1809 subjects (attendance rate 87.7%) participated in the study. Personal history and physical examination showed that Chianciano inhabitants have a low prevalence of obesity (4.3%) and only 4.4% of the female population had more than two pregnancies. Overall prevalence of gallstone disease (cholecystectomy + cholelithiasis) was 5.9% (3.7% for males and 8.4% for females). Age standardized relative risk of gallstone disease for females was 2.25 (95% confidence limits=1.68−2.68). Prevalence of cholelithiasis was 3.5% (2.7% for males and 4.2% for females). Prevalence of gallstone disease increased with increasing age in both sexes, being extremely low in the age interval of 15–29 years (0.25%). The overall gallstones/cholecystectomy ratio was found to be lower (1:1) in females than in males (2.7:1). Although subjects with gallstones reported more frequently biliary colics and nonspecific dyspeptic symptoms, the diagnostic power of all symptoms in identifying cholelithiasis was very poor due to low sensitivity. Only one third of subjects with gallstones was aware of having the disease. Age, obesity and number of pregnancies were positively associated with gallstone disease in univariate analyses. The association with obesity and parity disappeared in multivariate analysis. Blood lipids and glucose were not associated with the disease both in univariate and multivariate analyses. Our data show that the prevalence of gallbladder disease in Chianciano is lower than that previously reported in Italy. This difference could be related to a lower prevalence of obesity and to a smaller number of pregnancies or to the effect of environmental and genetic factors.

Effect of diabetic autonomic neuropathy on gall bladder kinetics in insulin-dependent diabetic patients

Objective: To evaluate the relationship between autonomic nervous system involvement and gall bladder contraction in insulin-dependent diabetic patients. Patients and methods: Fasting gall bladder volume and gall bladder emptying in response to a standard liquid meal were evaluated using ultrasonography in 10 normal subjects and in 35 patients with insulin-dependent diabetes: 10 without, 15 with asymptomatic and 10 with symptomatic autonomic neuropathy (AN). Gall bladder volumes were calculated from ultrasonographic images, taken during fasting and at regular intervals after a standard meal, using the sum of cylinders method. Evaluation of the presence and degree of AN was based on standard tests and clinical history. Results: In controls, the mean fasting gall bladder volume was 17.6±3.7ml, while respective values for residual volume, per cent emptying and emptying rate were: 3.63±1.69ml, 77.3 ± 10.7% and 0.0356±0.0121 min-1. Compared with controls, diabetic patients had a slightly higher fasting gall bladder volume (19.1 ± 5.6ml), while values for residual volume, per cent emptying and emptying rate were significantly altered at: 9.79±5.90ml, 50.7 ± 18.2% and 0.0155±0.0070 min-1, respectively (P<0.01). When diabetic patients were grouped according to the degree of AN, values for fasting gall bladder volume were significantly higher in those with symptomatic AN (22.0±7.7 ml) compared with controls (P<0.05). When compared with controls, patients without AN had a significantly (P<0.01) higher residual volume (5.58±1.96ml), a significantly lower value for per cent emptying (65.3 ±11.3%) and a prolonged emptying rate (0.0213 ±0.0055 min-1). Call bladder motility deteriorated progressively in diabetic patients with asymptomatic and symptomatic neuropathy. In the latter group, gall bladder emptying was greatly compromised, with a residual volume of 15.22±8.10ml, and per cent emptying and emptying rate of 32.8 ±19.8% and 0.0060 ±0.0030 min-1, respectively (P<0.01 versus controls and diabetic patients with and without asymptomatic AN). Conclusions: Impairment of gall bladder contraction in diabetic patients seems to be dependent on the presence of AN. However, the presence of an alteration in gall bladder motility in those without neuropathy suggests that other factors could also play a role in gall bladder contraction in diabetic patients.

Cytotoxic and Protective Effects of Bile Salts in Vitro

Toxicity and cytoprotective effects of bile salts were studied in the human Hep G2 cell line, grown for 24 up to 72 hours with free and conjugated bile salts at increasing concentrations. Toxicity was observed with 300 μmol deoxycholate and chenodeoxycholate and was enhanced in a dose and time dependent manner. Cell viability inversely correlated with enzyme release, whereas a decrease in DNA synthesis occurred at lower doses. Free hydrophobic bile salts appeared to be more toxic than their conjugates. In delipidated media the toxic effect of bile salts was enhanced and became evident at lower doses. Addition of 50–100 μmol ursodeoxycholate significantly reduced the hepatotoxicity of deoxycholate 350 μmol. The protective effect was similar with cholate and with tauroursodeoxycholate. Higher doses of hydrophilic bile salts added to 350 μmol of deoxycholate resulted always less toxic than equimolar doses of deoxycholate alone. Cytotoxicity of bile salts is correlated to their physico-chemical properties and is enhanced by reduction of lipid availability in the media. Toxicity of deoxycholate is significantly reduced by addition of low doses of hydrophilic bile salts.