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Background Quality of bowel cleansing in hospitalized patients undergoing colonoscopy is often unsatisfactory. No study has investigated the inpatient or outpatient setting as cause of inadequate cleansing. Aims To assess degree of bowel cleansing in inpatients and outpatients and to identify possible predictors of poor bowel preparation in the two populations. Methods Prospective multicentre study on consecutive colonoscopies in 25 regional endoscopy units. Univariate and multivariate analysis with odds ratio estimation were performed. Results Data from 3276 colonoscopies were analyzed (2178 outpatients, 1098 inpatients). Incomplete colonoscopy due to inadequate cleansing was recorded in 369 patients (11.2%). There was no significant difference in bowel cleansing rates between in- and outpatients in both colonic segments. In the overall population, independent predictors of inadequate cleansing both at the level of right and left colon were: male gender (odds ratio, 1.20 [1.02–1.43] and 1.27 [1.05–1.53]), diabetes mellitus (odds ratio, 2.35 [1.68–3.29] and 2.12 [1.47–3.05]), chronic constipation (odds ratio, 1.60 [1.30–1.97] and 1.55 [1.23–1.94]), incomplete purge intake (odds ratio, 2.36 [1.90–2.94] and 2.11 [1.68–2.65]) and a runway time >12 h (odds ratio, 3.36 [2.40–4.72] and 2.53 [1.74–3.67]). Conclusions We found no difference in the rate of inadequate bowel preparation between hospitalized patients and outpatients.

This study was undertaken to evaluate by anthropmetric measurements the nutritional status of cirrhotic patients at different stages of the disease and to establish intra- and inter-observer variability in the determination of these parameters. In 60 healthy controls and 108 cirrhotics (63 'well compensated' and 45 'decompensated' groups A and B + C on the Child-Pugh classification respectively) two independent experienced observers measured biceps, triceps, subscapular and overiliac skinfold thicknesses and arm circumference three times. Each observer was unaware of the results obtained by the other. No significant intra- or inter-observer variability was found. The study indicates that skinfold thickness measurements are a reliable and reproducible method of assessing the nutritional status of cirrhotics. It was found that more than 50 per cent of the decompensated patients were malnourished, with skinfold values significantly lower than those of the controls. In comparison with skinfold thickness and arm circumference, parameters such as body weight and lean body mass are unreliable, and other indices such as muscle and/or fat arm area do not add any significant information to the evaluation of the nutritional status of cirrhotics.

We sought (i) to validate a new prediction rule of mortality (Progetto Nazionale Emorragia Digestiva (PNED) score) on an independent population with non-variceal upper gastrointestinal bleeding (UGIB) and (ii) to compare the accuracy of the Italian PNED score vs. the Rockall score in predicting the risk of death.We conducted prospective validation of analysis of consecutive patients with UGIB at 21 hospitals from 2007 to 2008. Outcome measure was 30-day mortality. All the variables used to calculate the Rockall score as well as those identified in the Italian predictive model were considered. Calibration of the model was tested using the chi2 goodness-of-fit and performance characteristics with receiver operating characteristic (ROC) analysis. The area under the ROC curve (AUC) was used to quantify the diagnostic accuracy of the two predictive models.Over a 16-month period, data on 1,360 patients were entered in a national database and analyzed. Peptic ulcer bleeding was recorded in 60.7% of cases. One or more comorbidities were present in 66% of patients. Endoscopic treatment was delivered in all high-risk patients followed by high-dose intravenous proton pump inhibitor in 95% of them. Sixty-six patients died (mortality 4.85%; 3.54-5.75). The PNED score showed a high discriminant capability and was significantly superior to the Rockall score in predicting the risk of death (AUC 0.81 (0.72-0.90) vs. 0.66 (0.60-0.72), P0.000). Positive likelihood ratio for mortality in patients with a PNED risk score8 was 16.05.The Italian 10-point score for the prediction of death was successfully validated in this independent population of patients with non-variceal gastrointestinal bleeding. The PNED score is accurate and superior to the Rockall score. Further external validation at the international level is needed.

BACKGROUND AND STUDY AIM: The aim of this study was to assess the prevalence of nonpolypoid lesions (NPLs) in Italy and their risk of containing neoplasia or advanced histology. PATIENTS AND METHODS: This was a multicenter cross-sectional observational study on consecutive patients undergoing total colonoscopy over a 3-month period in 80 Italian centers. RESULTS: In all, 27,400 total colonoscopies were analyzed. Cancer was diagnosed in 801 patients (2.9 %). A total of 6553 precancerous lesions were detected in 5609 patients. Of these, 4154 patients (74.1 %) had polypoid lesions and 1455 patients (25.9 %) had NPLs. Therefore, the prevalence of NPLs was 5.3 % (95 %CI 5.0 - 5.6). NPLs larger than 10 mm were detected in 254 patients (17.5 %). NPLs were more predominant in the proximal colon (OR 2.92, 95 %CI 2.56 - 3.43; P < 0.0001 vs. polypoid lesions). Neoplastic tissue was diagnosed in 79.0 % and advanced histology (high-grade intraepithelial neoplasia or more) in 20.9 % of resected lesions. The risk of advanced histology was similar for polypoid and nonpolypoid lesions when adjusted for size. Depressed lesions had the highest risk of advanced histology (OR 10.56, 95 %CI 6.02 - 18.55; P < 0.0000 vs. flat-elevated). Age was an independent predictor of both neoplasia and advanced histology ( P = 0.0001). CONCLUSIONS: NPLs are relatively common in the Italian population, with a prevalence similar to that in other Western series. NPLs are not more aggressive than polypoid lesions, except for those with depressed morphology. Georg Thieme Verlag KG Stuttgart. New York.

Liver biopsy is used as a gold standard in the diagnosis of chronic liver disease. However, this procedure is not without risk to the patients. This study was aimed to evaluate whether clinical, ultrasonographic, and biochemical variables may discriminate between well-compensated liver cirrhosis and non-cirrhotic chronic liver disease. Logistic regression analysis was used to assess the independent predictive value of each variable. Moreover, the post-test probability of the diagnostic variables was converted into "weights" which positively correlated with the likelihood of diagnosis of liver cirrhosis. We applied a decisional rule based on the diagnostic "weight" of each variable to 412 patients, 278 with well-compensated liver cirrhosis and 134 with non-cirrhotic chronic liver disease, diagnosed by liver biopsy with/without laparoscopy. By adding the diagnostic "weights" of each variable, liver cirrhosis and non-cirrhotic chronic liver disease were correctly diagnosed in 67% and 75% of cases, respectively. This result was validated in a split sample of 100 patients (50 with compensated liver cirrhosis and 50 with non-cirrhotic chronic liver disease) randomly selected from the acquisition sample. Based on this data, diagnosis of well-compensated liver cirrhosis can be reached in over 67% of cases without using invasive procedures. However, a prospective study is needed to confirm the clinical reliability of this method.

The serum increments in unconjugated bilirubin and total iron were determined after intravenous administration of 5.90 mumol/kg body weight of nicotinic acid (NA) in 26 patients with Gilbert's syndrome (GS), seven patients with hemolytic anemia, and 13 healthy volunteers. The hyperbilirubinemic response, expressed as the area under time concentration curve of unconjugated bilirubin (AUCBR, milligrams per deciliter per 240 minutes) was significantly higher (P less than 0.01) in patients with GS than in controls and patients with hemolytic anemia, in whom no difference was observed. In contrast, comparable values of the hypersideremic effect (AUCFe, milligrams per deciliter per 240 minutes) were noticed among the three groups. In seven consecutive patients with GS, seven with hemolytic anemia, and four healthy volunteers, AUCBR, AUCFe, and the NA plasma half-life of the first fast slope of the curve were determined at three different doses of the drug (1.18, 2.95, and 5.90 mumol NA per kilogram body weight). A significant, dose-dependent increase in AUCBR was present in patients with GS, whereas it remained constant both in controls and in patients with hemolytic anemia. The NA plasma half-life was also significantly prolonged in GS with each of the three doses, but remained unchanged in the other two groups. In patients with GS, a linear correlation (r = 0.891, P less than 0.001) was present between AUCBR and NA plasma half-life. In contrast, the AUCFe value remained constant at the different doses used in the three groups.(ABSTRACT TRUNCATED AT 250 WORDS)

The bicompartmental kinetics of nicotinic acid (NA) and rifamycin-SV (R-SV)--2 organic anions that probably share a common hepatic uptake mechanism--were studied in 7 cases of Gilbert's syndrome (GS) and in 7 healthy controls matched for sex and age. In GS the NA and R-SV uptake constants (K21) were significantly decreased. In GS patients, simultaneous loads of NA and R-SV, the latter at increasing doses, produced: 1) a progressive lowering only of R-SV K21; and 2) an increase in R-SV hepatic plasma reflux (K12). Changes in biliary excretion ( Kee ) and hepatocellular pool (Ke) of both NA and R-SV probably depend on the rates of uptake and reflux constants of the two anions. The study of the parameters of compartmental kinetics of NA and R-SV confirms that the two organic anions, which have different metabolic routes and/or a different affinity for intracellular carriers, share common uptake mechanisms.

This study concerns the family of a girl affected by type 2 Crigler-Najjar syndrome; a brother and a sister died of kernicterus a few months after birth. The father and two living siblings had moderate unconjugated hyperbilirubinemia. The patient's liver uridine-diphospho-glucuronyl-transferase activity (UDPGT) was markedly reduced. All the family members underwent nicotinic acid (NA) load to test hepatic uptake capacity. This test, and NA half-life were normal in the patient and in her mother, and altered in the other relatives. The extent of the hyperbilirubinemic response to NA load, and of the NA half-life, together with physical examination over a one-year period were in good agreement with the diagnosis of Gilbert's syndrome in the patient's father and siblings. Our conclusion is that different impairments of hepatic handling of organic anions may be present in members of families with non-hemolytic bilirubinemia.

When considering urogenital complaints occurring during diabetic autonomous neurotherapy , three clinical situations are important due to their frequency and the clinical situation, the considerable effect they have on quality of life. In addition they may also be responsible for severe complications as in the case of diabetic cystopathy . This syndrome is the cause of considerable subjective disturbances even though it may be diagnosed instrumentally in its early, completely asymptomatic stage. The complaint evolves inevitably towards bladder denervation, chronic urinary retention and more or less severe septic complications. Retrograde ejaculation may lead to the loss of procreative ability as in the case of neurogenic impotence in diabetics. These three autonomous neuropathic situations occur quite frequently, especially in older subjects who have suffered from diabetes for more than ten years. Often the three syndromes are interconnected or linked to autonomous or peripheric neuropathic complaints affecting other areas. The few therapeutic measures practised have not proved very conclusive. Only a diligent examination of signs and symptoms with the aim of early diagnosis and the maintenance of good glycometabolic balance are considered to be at all effective as preventive measures.

The serum increments in unconjugated bilirubin and total iron were determined after intravenous administration of 5.90 mumol/kg body weight of nicotinic acid (NA) in 26 patients with Gilbert's syndrome (GS), seven patients with hemolytic anemia, and 13 healthy volunteers. The hyperbilirubinemic response, expressed as the area under time concentration curve of unconjugated bilirubin (AUCBR, milligrams per deciliter per 240 minutes) was significantly higher (P less than 0.01) in patients with GS than in controls and patients with hemolytic anemia, in whom no difference was observed. In contrast, comparable values of the hypersideremic effect (AUCFe, milligrams per deciliter per 240 minutes) were noticed among the three groups. In seven consecutive patients with GS, seven with hemolytic anemia, and four healthy volunteers, AUCBR, AUCFe, and the NA plasma half-life of the first fast slope of the curve were determined at three different doses of the drug (1.18, 2.95, and 5.90 mumol NA per kilogram body weight). A significant, dose-dependent increase in AUCBR was present in patients with GS, whereas it remained constant both in controls and in patients with hemolytic anemia. The NA plasma half-life was also significantly prolonged in GS with each of the three doses, but remained unchanged in the other two groups. In patients with GS, a linear correlation (r = 0.891, P less than 0.001) was present between AUCBR and NA plasma half-life. In contrast, the AUCFe value remained constant at the different doses used in the three groups.(ABSTRACT TRUNCATED AT 250 WORDS)

The hyperbilirubinemia induced by nicotinic acid (NA) is well correlated to 14C-bilirubin clearance, and is utilized to diagnose Gilbert's syndrome (GS). However, NA produces a number of vascular prostaglandin-mediated side effects. In an attempt to improve the NA test we evaluated the influence of pretreatment with Indomethacin, a PG-synthetase inhibitor, both on side effects and hyperbilirubinemia. NA (5.9 mumoles/kg of body weight i.v.) was administered on two separate occasions, before and one hour after i.m. injection of 100 mg Indomethacin in 11 GS males and 11 controls matched for sex and age (age range 18.34 years). The hyperbilirubinemic effect of NA was not modified by Indomethacin in any subject; the side effects were either significantly reduced or completely abolished. We suggest that patients undergoing the NA test for the diagnosis of GS be pretreated with Indomethacin.

To study the 3' immunoglobulin heavy-chain regulatory region (3'RR) enhancer complex, active in class switching recombination and in B-cells, in Crohn's disease.A total of 167 patients [79 females (47.3%) and 88 males (52.7%)] affected by Crohn's disease were enrolled in the study. As a control, we included 64 healthy subjects, age and sex matched, from the same geographical area. Blood tests were performed on all subjects to determine their antibody levels and to detect the presence of any possible infections. We conducted a selective PCR, which amplified the hs1.2-A region. The nested second PCR to amplify the polymorphic core of the enhancer was performed.No differences between cases and controls were observed with respect to sex distribution (43.8% females among controls and 49.5% among cases), age, tTG IgA, RF, serum or secretory IgA, IgG1, IgG2 and IgG3. No correlation was found between both seric and secretory immunoglobulins levels, with except of statistically significant differences between cases and controls with respect to IgA and IgG ASCA positivity (p0.001), serum IgG4 (p0.001) and IgD (p=0.001).We have demonstrated that in Crohn's disease, the HS1,2 immunoglobulins enhancer is not implicated in the disease pathogenesis. Moreover, we have found that IgG4 levels are lower in Crohn's disease patients than in controls; these data may be related to an impairment of number and function of Tregs, further linked to the presence of tissue inflammation. Crohn's disease is a complex multifactorial disease. The pathogenesis of Crohn's disease is incompletely understood although it is clear that the disease involves multiple interacting agents.

Background & Aims Helicobacter pylori have become resistant to antimicrobial agents, reducing eradication rates. A 10-day sequential regimen that contains levofloxacin was efficient, safe, and cost saving in eradicating H pylori infection in an area with high prevalence of clarithromycin resistance. We performed a noninferiority randomized trial to determine whether a 5-day levofloxacin-containing quadruple concomitant regimen was as safe and effective as the 10-day sequential regimen in eradicating H pylori in previously untreated patients. Methods We randomly assigned patients with H pylori infection to groups that were given 5 days of concomitant therapy (esomeprazole 40 mg twice daily, amoxicillin 1 g twice daily, levofloxacin 500 mg twice daily, and tinidazole 500 mg twice daily; n=90) or 10 days of sequential therapy (esomeprazole 40 mg twice daily, amoxicillin 1g twice daily for 5 days followed by esomeprazole 40 mg twice daily, levofloxacin 500 mg twice daily, and tinidazole 500 mg twice daily for 5 more days; n=90). Antimicrobial resistance was assessed by the E-test. Efficacy, adverse events, and costs were determined. Results Intention-to-treat analysis showed similar eradication rates for concomitant (92.2%; 95% confidence interval [CI], 84.0%–95.8%) and sequential therapies (93.3%; 95% CI, 86.9%–97.3%). Per-protocol eradication results were 96.5% (95% CI, 91%–99%) for concomitant therapy and 95.5% for sequential therapy (95% CI, 89.6%–98.5%). The differences between sequential and concomitant treatments were 1.1% in the intention-to-treat study (95% CI; −7.6% to 9.8%) and −1.0% in the per-protocol analysis (95% CI; −8.0% to 5.9%). The prevalence of antimicrobial resistance and incidence of adverse events were comparable between groups. Concomitant therapy cost $9 less than sequential therapy. Conclusions Five days of levofloxacin-containing quadruple concomitant therapy is as effective and safe, and less expensive, in eradicating H pylori infection than 10 days of levofloxacin-containing sequential therapy.

UnlabelledThe aim of the present work was to test the potential of Proton Transfer Reaction Time-of-Flight Mass Spectrometry (PTR-ToF-MS) in the diagnosis of liver cirrhosis and the assessment of disease severity by direct analysis of exhaled breath. Twenty-six volunteers have been enrolled in this study: 12 patients (M/F 8/4, mean age 70.5 years, min-max 42-80 years) with liver cirrhosis of different etiologies and at different severity of disease and 14 healthy subjects (M/F 5/9, mean age 52.3 years, min-max 35-77 years). Real time breath analysis was performed on fasting subjects using a buffered end-tidal on-line sampler directly coupled to a PTR-ToF-MS. Twelve volatile organic compounds (VOCs) resulted significantly differently in cirrhotic patients (CP) compared to healthy controls (CTRL): four ketones (2-butanone, 2- or 3- pentanone, C8-ketone, C9-ketone), two terpenes (monoterpene, monoterpene related), four sulphur or nitrogen compounds (sulfoxide-compound, S-compound, NS-compound, N-compound) and two alcohols (heptadienol, methanol). Seven VOCs (2-butanone, C8-ketone, a monoterpene, 2,4-heptadienol and three compounds containing N, S or NS) resulted significantly differently in compensate cirrhotic patients (Child-Pugh A; CP-A) and decompensated cirrhotic subjects (Child-Pugh B+C; CP-B+C). ROC (Receiver Operating Characteristic) analysis was performed considering three contrast groups: CP vs CTRL, CP-A vs CTRL and CP-A vs CP-B+C. In these comparisons monoterpene and N-compound showed the best diagnostic performance.ConclusionsBreath analysis by PTR-ToF-MS was able to distinguish cirrhotic patients from healthy subjects and to discriminate those with well compensated liver disease from those at more advanced severity stage. A breath-print of liver cirrhosis was assessed for the first time.

Background and aims Antimicrobial drug resistance is a major cause of the failure of Helicobacter pylori eradication and is largely responsible for the decline in eradication rate. Quadruple therapy has been suggested as a first-line regimen in areas with clarithromycin resistance rate >15%. This randomised trial aimed at evaluating the efficacy of a levofloxacin-containing sequential regimen in the eradication of H pylori -infected patients in a geographical area with >15% prevalence of clarithromycin resistance versus a clarithromycin-containing sequential therapy. Methods 375 patients who were infected with H pylori and naive to treatment were randomly assigned to one of the following treatments: (1) 5 days omeprazole 20 mg twice daily + amoxicillin 1 g twice daily followed by 5 days omeprazole 20 mg twice daily + clarithromycin 500 mg twice daily + tinidazole 500 mg twice daily; or (2) omeprazole 20 mg twice daily + amoxicillin 1 g twice daily followed by omeprazole 20 mg twice daily + levofloxacin 250 mg twice daily + tinidazole 500 mg twice daily; or (3) omeprazole 20 mg twice daily + amoxicillin 1 g twice daily followed by omeprazole 20 mg twice daily + levofloxacin 500 mg twice daily + tinidazole 500 mg twice daily. Antimicrobial resistance was assessed by the E-test. Efficacy, adverse events and costs were determined for each group. Results Eradication rates in the intention-to-treat analyses were 80.8% (95% CI, 72.8% to 87.3%) with clarithromycin sequential therapy, 96.0% (95% CI, 90.9% to 98.7%) with levofloxacin-250 sequential therapy, and 96.8% (95% CI, 92.0% to 99.1%) with levofloxacin-500 sequential therapy. No differences in prevalence of antimicrobial resistance or incidence of adverse events were observed between groups. Levofloxacin-250 therapy was cost-saving compared with clarithromycin sequential therapy. Conclusion In an area with >15% prevalence of clarithromycin resistant H pylori strains, a levofloxacin-containing sequential therapy is more effective, equally safe and cost-saving compared to a clarithromycin-containing sequential therapy.

The effect of α-interferon (α-IFN) and ribavirin (RBV) treatment on oxidative status in chronic hepatitis C (CHC) is unknown. Aim: To study the time course of oxidative status in patients with CHC during α-IFN and RBV administration, and to evaluate the role of oxidative status in order to predict the therapeutic response. Patients and methods: Fifty one patients with CHC were studied. All received a combination of α-IFN and RBV for 6 or 12 months in relation to the type of response. The hydroperoxides concentration in serum test samples by D-ROM test was measured in all of the patients before therapy. In 27 patients, hydroperoxides were also measured during the treatment and during the 12 subsequent months. Results: Cross-sectional analysis demonstrates that patients with a successive long-term response had a lower basal serum hydroperoxide concentration than non-responders (280 ± 40.8 vs 337 ± 83 CARR Units, p < 0.05). This resulted to be an independent factor predictive of long-term response in the multi-varied analysis. Longitudinal observation on 27 patients showed that the mean hydroperoxide concentration decreased significantly during treatment (T0 329 ± 79.2 vs T12 272 ± 34.5 CARR Units) and that the decrease in the mean values was mainly due to variations in the relapsers group. Conclusions: Normal basal hydroperoxide concentration helps to predict long-term response to combination therapy. The D-ROM test may be used for screening patients before treatment. © 2004 Taylor & Francis Ltd.

GOALS: The authors conducted a study to verify whether supplementation with an antioxidant-rich tomato-based functional food reduces anemia during pegylated interferon and ribavirin therapy for chronic hepatitis C. BACKGROUND: Oxidative stress plays a major role in the physiopathology of hemolytic anemia during ribavirin therapy. The efficacy of antioxidant supplementation with vitamins C and E as pure compounds, is still controversial. METHODS: A functional food with a high content of natural antioxidants and with high carotenoid bioavailability was developed. The authors enrolled 92 patients with chronic hepatitis C, treated with standard combination therapy. Forty-six of them received a daily dose (100 g) of functional food (group 1), and 46 did not (group 2). The effect of antioxidant activity was assessed comparing compliance with the full dose of ribavirin and hemoglobin levels during the first 3 months of treatment. RESULTS: Only 8.7% of patients in group 1 had to reduce their daily ribavirin dose, whereas ribavirin reduction was necessary for 30.4% of patients in group 2 (P = 0.09). Hemoglobin levels showed significant differences at 15, 30, and 90 days during the observation time. CONCLUSION: Results demonstrated that the authors' functional food reduces the severity of ribavirin-related anemia and improves the tolerance to the full dose of ribavirin in patients with chronic hepatitis C.

BACKGROUND and AIMS: The major obstacle to 100% effective eradication of Helicobacter pylori infection is represented by antimicrobial-resistant H. pylori strains. This randomized study was designed to evaluate whether regimens based on pretreatment susceptibility testing were more effective and cost saving compared with standard nonsusceptibility testing-based therapy in the eradication of H. pylori infection. METHODS: We studied 150 consecutive H. pylori-infected dyspeptic subjects. Patients were randomly assigned to omeprazole 20 mg twice daily, clarithromycin 500 mg twice daily, and metronidazole 500 mg twice daily for 7 days or to omeprazole 20 mg twice daily and 2 antimicrobials chosen based on susceptibility testing. H. pylori status was reevaluated 12 weeks after the end of treatment by the (13)C-urea breath test. RESULTS: Susceptibility testing-based regimens led to the following results. (1) Eradication rates were 97.3% (95% confidence interval [CI], 91.2%-99.5%) (71 of 73) and 94.6% (95% CI, 87.6%-98.3%) (71 of 75) in the per-protocol and intention-to-treat analysis, respectively. These were significantly higher (P < 0.005) than eradication rates obtained without susceptibility testing, that is, 79.4% (95% CI, 69.1%-87.6%) (58 of 73) and 77.3% (95% CI, 66.9%-85.7%) (58 of 75) in the per-protocol and intention-to-treat analyses, respectively. (2) There were savings of approximately $5 U.S. per patient compared with standard triple therapy. CONCLUSIONS: Pretreatment antimicrobial susceptibility testing is more effective and cost saving and, in health systems that confirm cost advantage, microbial susceptibility testing should be routinely used for eradication of H. pylori infection.

Even though the association between liver cirrhosis and glucose tolerance alterations has been well documented, no data are available on the incidence of this association. In this paper we firstly report the results of a 4-year prospective longitudinal study performed on well-compensated cirrhotic patients with a normal glucose tolerance, in order to evaluate the incidence of glucose tolerance alterations with respect to liver efficiency during the time. The incidence of a diabetic response to a standard OGTT was 4.4% after a 1-year and 21.2% after a 4-year follow-up in stable cirrhotics. These figures are significantly higher than in the general population of our country. This large incidence was even significantly higher in cirrhotics with worsening liver efficiency at the end of the study (35.3%, P < 0.0001). Sex, family history of diabetes, alcoholic aetiology of the cirrhosis, and increment of portal hypertension do not seem to have any significant influence on the frequency of altered glucose tolerance. Therefore, we propose that liver cirrhosis and its worsening play a primary role as diabetogenic risk factors.

The diagnostic value of the nicotinic acid (NA)-induced hyperbilirubinaemia was compared with that resulting from caloric restriction in 40 patients with Gilbert's syndrome (GS) and 20 controls. Both tests resulted in a significant higher level of serum bilirubin in GS than in controls (P less than 0.001). When the serum bilirubin level 240 min after NA administration (5.9 mumol/kg i.v.) was higher than 18 mumoles/l, this test had a specificity and sensitivity of 100%, both in males and females with the syndrome. The discriminatory value of the test was lower when either the area under the time concentration curve or the maximal increment of serum unconjugated bilirubin were used. Reduction in caloric intake (400 calories/day) showed a lower specificity and sensitivity than the NA test, particularly in females. An increment of bilirubin at 24 h greater than 15 mumoles/l was more diagnostic than an increase by 100% or more over the pre-diet value. The efficacy was not improved by prolonging the test for additional 24 h. From these data we conclude that NA-induced hyperbilirubinaemia and, in particular the concentration of the pigment 240 min after drug administration, is more efficient than fasting-induced hyperbilirubinaemia in the diagnosis of the Gilbert's syndrome both in males and in females.