Alessandro Sumberaz

24-hour study of intragastric acidity in duodenal ulcer patients and normal subjects using continuous intraluminal pH-metry

The circadian pattern of intragastric acidity was assessed in 19 healthy subjects and 37 patients with active, endoscopically proven duodenal ulcer using 24-hr continuous intraluminal pH-metry. The median pH 24-hr profiles showed that ulcer patients had lower postprandial pH elevations and a smaller decline in acidity during the early morning hours when compared with controls. The after-lunch and -dinner area under the curve and maximum pH values were significantly higher in controls compared to ulcer patients. In the nighttime, the median pH values in controls were significantly higher during 9 pm to 12 pm (P=0.02), 12 pm to 4 am P=0.01), and 4 am to 8 am (P=0.0008) compared to the ulcer patients. We conclude that the 24-hr acidity is higher in ulcer patients compared to healthy subjects and that the differences are particularly evident in the postprandial and nocturnal periods.

Dna damage in peripheral blood lymphocytes of patients with cirrhosis related to alcohol abuse or to hepatitis B and C viruses

Background Both alcohol abuse and hepatitis B or C virus infections are implicated in the development of hepatocellular carcinoma, but it is still controversial whether the pathogenetic mechanism is epigenetic or genotoxic. Aim Considering that alcohol promotes the generation of reactive oxygen species and both viruses infect peripheral lymphocytes, in this study we investigated the occurrence of DNA fragmentation in peripheral blood lymphocytes from patients with alcoholic cirrhosis and from patients with cirrhosis related to B and C viruses, and analyzed the correlation between the degree of DNA fragmentation and the Child–Pugh score used to assess the degree of hepatic insufficiency. Methods The study population consisted of two groups: group I involved 12 patients with alcoholic cirrhosis; group II involved 25 patients with hepatic B virus or hepatic C virus cirrhosis. The control group involved 20 healthy individuals. The degree of DNA fragmentation in peripheral blood lymphocytes was determined with the alkaline Comet assay that provides two indexes of the frequency of DNA single-strand breaks and alkali-labile sites, the tail length and the tail moment. Results Mean values of both tail length and tail moment were significantly increased (P<0.001) in lymphocytes from 12 patients with alcoholic cirrhosis and in lymphocytes from 25 patients with HBV or HCV cirrhosis, as compared with average tail length and tail moment values of lymphocytes from 20 healthy individuals. A significant positive correlation was found to exist between the degree of DNA fragmentation present in lymphocytes of each of the 37 patients with alcoholic or viral cirrhosis and the corresponding value of the Child–Pugh score. Conclusion The occurrence of DNA fragmentation in peripheral blood lymphocytes reflects a direct genotoxic effect of either alcohol or HBV and HCV and suggests that the same genotoxic effect may operate in the liver and contribute to hepatocarcinogenesis.

Antimony and glass pH electrodes can be used interchangeably in 24-hour studies of gastric acidity

Antimony and glass pH electrodes show almost identical experimental errors in continuously measuring buffer solutions at constant temperature over 24 hr. These errors are lower than the nominal quantization error of the instruments and are not properly described by the 24- hr drift determination. The addition of food particles to the solutions can induce severe reading artifacts. The longer response time reported in vitroof antimony electrodes when moving from pH 1 to pH 7 (3.4 sec vs 0.8 sec with glass electrodes) is irrelevant during in vivopH-metry studies, because we found that the greatest absolute difference between raw fast acquired (4–6 sec) consecutive pH readings of two commonly used devices was 0.7 pH units in circadian profiles obtained from 413 subjects with various clinical conditions. In our in vivo studies, gastric acidity was monitored continuously with two side-by-side minielectrodes, which were variously combined (antimony-glass, A-G; antimony-antimony A1–A2; glass-glass, G1–G2) and applied on groups of 27 subjects matched for clinical condition. The 24-hr pH means and the 24-hr [H+] means calculated from the acidity profiles obtained with the three electrode combinations, lie on the identity line in each group. Using the Bland-Altman technique for assessing measurement agreement, the differences between the 24- hr pH means and the 24-hr [H+] means obtained with the three combined systems are similar (P=.903 and P=0.824, respectively) and their 95% confidence limits are comprised within the range (±) of the reading error of the measuring systems (namely, ±0.3 pH units and ±12 mmolliter in terms of [H+]). These data show that the 24-hr acidity indexes calculated from gastric pH recordings performed with two closely adjacent antimony and glass electrodes are similar, irrespective of their possible combinations. It can be concluded that antimony and glass electrodes provide equivalent results in vivo and can be used interchangeably in the clinical setting.

Altered oxidative stress/antioxidant status in blood of alcoholic subjects is associated with alcoholic liver disease

BACKGROUND Oxidative stress is implicated in pathogenesis of alcoholic liver disease (ALD). This study investigated the possible correlation among the erythrocyte indices of oxidative stress, the leukocyte panels of antioxidant proteins (metallothioneins), the serum biochemical parameters and the liver steatosis grade. METHODS A total of 118 cases including 60 alcoholic subjects and 58 controls were enrolled. All the alcoholic subjects were screened for body mass index (BMI), liver steatosis, and blood chemistry and serology. The level of oxidative stress and oxidative stress-related parameters were measured in the blood and correlated with clinical findings. RESULTS Alcoholic subjects showed higher BMI, moderate/severe hepatic steatosis, increase in the levels of triglycerides, cholesterol, glucose, γ-glutamyl-transpeptidase (GGT), alanine aminotransferase (ALT), bilirubin, alpha 1 and beta 2 globulins, iron and a decrease in the levels of aspartate aminotransferase (AST) and beta 1 globulin with respect to the reference values. Moreover, alcoholic subjects showed: (i) an increase in Thiobarbituric Acid Reactive Substance (TBARS) content representing a good estimation of global oxidative stress; (ii) a stimulation of the activities of the antioxidant enzymes catalase and SOD; (iii) a modulation of expression of metallothioneins, with a down-regulation of MT-1A and an up-regulation of MT-1E isoforms. CONCLUSIONS Our data suggest that alcoholism is strongly associated with altered pattern of blood metallothioneins; this parameter combined with the score calculated by an ad hoc implemented algorithm (HePaTest) could offer a non-invasive alternative approach for evaluating alcohol-related damages and could be used in follow-up of alcoholic patients.

Clinical relevance of sampling rate in the characterization and analysis of 24-hour gastric acidity. A report on 413 cases.

Four hundred and thirteen continuous, high-frequency-sampled gastric pH-metries were subdivided into six groups (normal subjects and patients with duodenal ulcer, gastric ulcer, chronic gastritis, prior cholecystectomy, or antisecretory treatment). The frequency distribution of those pH fluctuations that were greater than the quantitation error of instruments did not differ significantly (p greater than 0.30) between groups. Five per cent of these real pH fluctuations lasted less than 3 min. As the sampling rate increased from 1 to 60 min, the percentage of subjects whose 24-h median of pHs differed by no more than +/- 10% from that calculated on the raw high-frequency-acquired data progressively decreased (99.8%-42%). This error propagation was more marked in the case of [H+] integrals (99%-10%). A sampling rate equal to or faster than 1 min is necessary to provide a proper representation of the circadian pH pattern and to calculate accurate acidity indexes, regardless of the physiologic or pharmacologic nature of the profile.

Once and Twice Daily Doses of H2 Antagonists Revisited, Using Continuous Intragastric pH Monitoring

Eight patients with previous duodenal ulcer in symptomatic remission underwent continuous intraluminal pH monitoring on five separate occasions to compare the effects on 24-h intragastric acidity of placebo, 300 mg ranitidine at night, 150 mg ranitidine twice daily, 40 mg famotidine at night, and 20 mg famotidine twice daily. All H2 blocker treatments were superior to placebo (p congruent to 0), whereas the twice daily doses of both ranitidine and famotidine were significantly better (p congruent to 0 and p = 0.00006, respectively) than the single ones in reducing 24-h intragastric acidity. The higher acid inhibitory effect of the twice daily dose regimens than of the single ones was evident during the daytime, whereas no difference between them was found during the nighttime (from 2200 to 0800 h). These data are at variance with those previously published, and the slight effect of the single nightly doses of H2 blockers on daytime acidity seems to confirm further that the suppression of nocturnal acidity may really be the decisive factor in the success of this dosing schedule in treating duodenal ulcer.

Involvement of the mu-opioid receptor gene polymorphism A118G in the efficacy of detoxification of alcohol dependent patients

INTRODUCTION The A118G (rs 1799971) polymorphism in the mu-opioid receptor gene (OPRM1) has been reported to be associated with alcohol addiction. METHODS In this study 109 patients diagnosed with alcohol dependence in accordance with DMS-IV criteria and 95 healthy subjects were enrolled and everyone has been genotyped. RESULTS The percentage of alcoholic patients with higher than normal gamma-glutamyl transferase (GGT) levels significantly decreased after six months of standard detoxification treatment, both in patients with A/A genotype and in the other ones with A/G genotype. However, the percentage of alcohol dependent patients with the A/A genotype recorded a slight decrease of the GGT and the mean corpuscolar volume of erythrocytes (MCV) combination marker after six months of therapy (30% vs 12%), while subjects with the A/G genotype showed no variation. CONCLUSION This finding suggests that alcohol dependent patients with the A/A genotype could have a faster restoration of their liver function than those ones with the A/G genotype: it might be possible that the presence of G allele confers on these patients a reduced ability in abstaining from drinking alcohol.

Single Morning and Nightly Doses of Ranitidine 300 mg: An Appraisal of Their Antisecretory Effects by Continuous pH Monitoring

Gastric acidity of 12 patients with healed duodenal ulcers was continuously monitored over 24 h in order to assess the antisecretory effects of two different administration times of a single daily dose of ranitidine 300 mg. Each patient orally received either (a) placebo at 08.00 h and 22.00 h; (b) ranitidine 300 mg at 08.00 h and placebo at 22.00 h, or (c) placebo at 08.00 h and ranitidine 300 mg at 22.00 h in randomized and double-blind fashion. Each medication was administered on three separate occasions, with intervals of at least 1 week. Both the morning and the bedtime doses of ranitidine were significantly superior (p less than 0.001) to placebo in controlling 24-hour gastric acidity, while, in the same period, ranitidine nocte was more effective (p less than 0.001) than ranitidine mane. During the night, bedtime ranitidine caused more acid inhibition (p less than 0.001) than morning ranitidine, but the opposite (p less than 0.01) occurred during the daytime. This study shows that the antisecretory effect of morning ranitidine during the daytime is less consistent than that achieved by bedtime ranitidine during the nocturnal period. As similar rates of duodenal ulcer healing have recently been achieved with morning and conventional nighttime administration of H2 antagonists, it becomes clear that antisecretory drugs can also be beneficial with an acid inhibition which is shorter-lasting than that which was previously thought to be necessary or, alternatively, that also daytime acidity is important in ulcerogenesis.

Liver steatosis and antiviral therapy in chronic hepatitis C

To the editor: We have read with great interest the paper by Soresi et al. (1). The authors report genotype 1 is more frequent in patients with mild-moderate steatosis and seems to condition therapeutic response negatively, together with body mass index (BMI) and age. From this work emerges the importance of a better internistic evaluation in order to reach the highest number of sustained virological response (SVR). As confirmation of what was stated by Soresi et al. (2) for us it is a pleasure to remember our recent experience, effected in subjects with recurrent hepatitis C (genotype 1) after liver transplantation and treated with pegylated interferon a-2b plus ribavirin. We have evidenced a strong correlation between BMI, cholesterol (mg/dl), triglycerides (TGC, ng/ml) and hepatic percentage of steatosis. In subjects with BMI o25 and TGC o160, the chance of SVR was 48 times higher than that of no-response. The chances of SVR and sustained biochemical response for patients with percentage of steatosis o 15 were 12 times higher than that with higher percentage of steatosis values (2). The observed diminished response has been hypothesized to be because of decreased interferon bioavailability in presence of hepatic steatosis, which itself is a predictor of poor response to interferon treatment. Moreover, increased expression of suppressor of cytokine that inhibit interferon signalling may be one mechanism by which overweight reduces the interferon response (3). We can conclude how the amount of steatosis can be noted specifically through biopsy examination reports and how the management of dismetabolism, diet and exercise therapy can improve BMI, liver histology and, therefore, admeliorate the response to antiviral therapy.

The Genoa Method in Alcohol Dependence Treatment

Alcohol consumption is a major public health problem in Europe, resulting in 3.8% of all deaths and 4.6% of years of life lost due to disability [1]. The overall cost of alcoholic disease is more than that of smoking tobacco [1, 2]. Currently in the European Union, only 10% of alcohol dependence (AD) patients are treated. In the United States, this happens in 25% of cases [1]. It is evident that a new way of working is necessary. As indicated in our previous papers [1, 3], the treatment of AD will be increasingly aimed at a truly tailored therapy that takes into account the type of AD (Cloninger or Lesch’s), the type of craving (reward, relief and obsessive), the presence of other addictions, the presence of comorbidities both internistic and psychiatric, and the pharmacogenomics [4]. In literature, there is only one report about a new way of treatment in AD patients [5]. Siva [5] showed a new way of working within AD. It is to ensure rapid access to a specialist detox center (rapid access to acute alcohol detoxification referrals: RADAR). This modified way of working has been at the San Martino Hospital in Genoa since 2005. The approach is an immediate action multidisciplinary clinic with the offer of immediate self-help groups for patients and family members. In addition, the monitoring of the activity and, therefore, the outcome has been put in relation to the period of sobriety and the onset of liver cirrhosis. The recent retrospective evaluation (2005 2010) of a group of young patients under the age of 25 took over as the immediate task of receiving hospital care in combination with self-help groups to ensure the best outcome. One hundred one young patients with a mean age of 22 years (20 24 years) were enrolled rapidly (within 24 h after acute) and put into a multidisciplinary care pathway. The team was accompanied by self-help groups. This group was compared with 130 younger patients with a mean age of 22 years (20 24 years), which for various reasons followed a traditional route. The diagnosis of AD was carried out through the DSM-IV. After 5 years, we evaluated some variables by univariate analysis of the period of sobriety, and the onset of cirrhosis and hepatocellular carcinoma (HCC). With multivariate analysis, the sobriety variable was linked to the onset of cirrhosis. The diagnosis of cirrhosis was carried out through a clinical laboratory assessment and through the histological evaluation and/or the use of quantitative elastographic features. Since June 2015, the elastography assessment has been performed with Share Wave (RS80 with Prestige Samsumg Electronics, Italy). The diagnosis of HCC with two imaging techniques is concordant (contrast enhanced ultrasound plus computed tomography and/or magnetic resonance) [6, 7]. Univariate and multiple logistic regression analysis was performed to identify the demographic variables and outcomes associated with self-help groups (JMP, SA, NC, USA). The covariates were significant at 0.10 in the univariate analysis and were further top evaluated for inclusion in multivariable regression models, using a stepwise algorithm. All the tests were two-tailed, and a P-value < 0.05 was determined to represent statistical significance. It has emerged that an early enlistment in combination with the presence of a self-help group will guarantee a period of sobriety longer in years than in a group with conventional treatment: 6 (4 7) vs. 3 (3 6) (P < 0.0001). Cases of cirrhosis (20.7% vs. 26.15%) and HCC (9% vs. 13%) tend to be lower. Multivariate analysis found that sobriety reduced the risk of cirrhosis by 23 times: LR 301.06, Chi-square (P < 0.0001), odds ratio (95% CI): 23.5 (1.15 2.26) (P < 0.0001). In the literature, approaches of this kind are not described. They are to be proposed at the international approach RADAR and Genoa with the advice of a real involvement already in the initial stages of a self-help group (within 24 h). The synergy of the rapid intervention multidisciplinary associations of selfhelp may be particularly important for maintaining abstinence over time and reducing healthcare costs.