Giuseppe Francesco Stefanini

Inflammatory Bowel Disease: A Study of the Association between Anxiety and Depression, Physical Morbidity, and Nutritional Status

BACKGROUND The etiology of inflammatory bowel disease is unclear, and the role played by anxiety and depression is highly controversial. Anxiety and depression in patients with inflammatory bowel disease could be secondary to disabling symptoms, but the interaction between physical morbidity and psychologic illness in these subjects has not been sufficiently investigated. Patients with inflammatory bowel disease are nevertheless frequently undernourished, but there are no studies on the association between anxiety and depression and malnutrition. This study was designed to characterize anxiety and depression in subjects affected by inflammatory bowel disease and to establish the influence of physical morbidity and/or nutritional status on psychologic disorders. METHODS Seventy-nine consecutive patients, 43 with Crohns disease (CD) and 36 with ulcerative colitis (UC), were enrolled in the study. An index of the disease activity and physical morbidity was obtained by the simplified Crohns Disease Activity Index and Truelove-Witts criteria and using the Clinical Rating Scale. Thirty-six healthy volunteers were studied as controls. All the subjects were given the State and Trait Anxiety Inventory (STAI) test and the Zung self-rating Depression Scale. RESULTS The percentage of subjects with state anxiety was significantly higher in the CD (P < 0.001) and UC (P < 0.001) groups than in control subjects. There was no significant difference in trait anxiety among groups. The percentage of subjects with depression was significantly higher in the CD (P < 0.05) and UC (P < 0.05) groups than in control subjects. State anxiety and depression were significantly associated with physical morbidity and correlated with malnutrition in CD and UC patients. CONCLUSION Anxiety and depression in patients with inflammatory bowel disease could be reactive to the disabling symptoms and to malnutrition. As measured with the STAI, personality trait of anxiety does not seem to play an important role in inflammatory bowel disease.

Oral Cromolyn Sodium in Comparison with Elimination Diet in the Irritable Bowel Syndrome, Diarrheic Type Multicenter Study of 428 Patients

BACKGROUND In a significant number of patients affected by the irritable bowel syndrome, an adverse reaction to food is proposed to be a causative factor. A diet that eliminates the offending foods is the obvious treatment for such adverse reactions. Compliance with a dietetic regimen is often poor and sometimes not completely free from risks. METHODS Since the diarrheic type of irritable bowel syndrome seems mainly affected by food intolerance, and previous observations suggested that oral cromolyn sodium is effective in such patients, a multicenter therapeutic trial in the diarrheic type of irritable bowel syndrome was carried out in 346 of 409 patients with this disease, to evaluate the effects of oral cromolyn sodium and compare its efficacy with that of an elimination diet. RESULTS Symptoms related to the irritable bowel syndrome improved in 60% of patients treated with elimination diet and in 67% of those treated with oral cromolyn sodium (1500 mg/day) for 1 month. Moreover, in both groups clinical results were significantly better in the patients positive to the skin prick test than in the negative ones. CONCLUSIONS These results confirm the high prevalence of adverse reactions to foods in diarrheic irritable bowel syndrome and the usefulness of cromolyn sodium treatment in these patients.

Gross pathologic types of hepatocellular carcinoma in Italian patients. Relationship with demographic, environmental, and clinical factors.

Background. The prevalence of the different hepatocellular carcinoma (HCC) macroscopic types, and the association between these types and age, gender, blood group, alcohol and coffee intake, smoking habit, hepatitis virus markers, underlying cirrhosis, and cancer histologic type were retrospectively assessed in 416 unselected patients (321 with cirrhosis).

A case of gamma-hydroxybutyric acid withdrawal syndrome during alcohol addiction treatment: utility of diazepam administration.

Gamma-hydroxybutyric acid (GHB) is an emerging drug for alcoholism therapy. We present a case of GHB withdrawal syndrome secondary to GHB addiction during alcoholism treatment. A complete disappearance of drug withdrawal syndrome was achieved with oral diazepam and the symptoms resolved without sequelae. GHB has been used for alcoholism therapy for only a few years now, but the trend is increasing, and other cases similar to this one are foreseeable. This risk could be higher in some countries in which GHB use is increasing not for alcoholism therapy, but for its euphoric and anabolic effects. The present experience indicates that administration of benzodiazepines would seem to be sufficient to achieve total regression of the withdrawal syndrome in a short time, at least if recognized early.

Gamma-hydroxybutyric acid versus naltrexone in maintaining alcohol abstinence: an open randomized comparative study.

Maintaining abstinence from alcohol is the main goal in the treatment of alcohol dependence. Naltrexone (NTX) and gamma-hydroxybutyric acid (GHB) have proved able to maintain alcohol abstinence in alcoholic subjects. The aim of our study was to evaluate the efficacy of GHB compared with NTX in maintaining abstinence from alcohol after 3 months of treatment. A total of 35 alcohol-dependent outpatients were randomly enrolled in two groups: the GHB group consisted of 18 patients treated with oral doses of GHB (50 mg/kg of body weight t.i.d) for 3 months; the NTX group consisted of 17 patients treated with oral doses of NTX (50 mg/day) for 3 months. At the end of the study, a statistically significant difference (P=0.02) was found in the number of abstinent patients between the GHB and the NTX groups. In patients who failed to be abstinent, no relapses in heavy drinking were observed in the NTX group, while in the GHB group all patients relapsed. The results of the present study show that GHB is more effective than NTX in maintaining abstinence from alcohol in a short-term treatment period; on the other hand, NTX confirmed its ability to reduce alcohol relapses.

Prenatal exposure to ethanol in rats: effects on liver energy level and antioxidant status in mothers, fetuses, and newborns.

The fetal alcohol syndrome is a clinical condition that affects newborns from alcoholic mothers. It is not clear, however, whether ethanol consumption during gestation can affect liver functions of fetuses and newborns. In this study, we aimed to assess the effects of ethanol administration on body weight, liver energy level, and antioxidant status of mothers, fetuses, and newborns. Pregnant rats were exposed to ethanol during the third week of gestation. Body weight, survival, and liver concentration of gluthatione (GSH) and adenosintriphosphate (ATP) were measured. No differences were observed in body weight or in liver ATP and GSH between mothers exposed to ethanol and control animals. Conversely, fetuses from rats exposed to ethanol showed a marked decrease in GSH, ATP, and body weight when compared to those from control rats. Newborns exposed prenatally to ethanol were no different from those born to control mothers. This study suggests that an amount of ethanol that is not sufficient to determine a significant effect on mothers can, nevertheless, cause a marked decrease in growth and in liver antioxidant and energy status in fetuses. These parameters, however, return to control value one week after ethanol discontinuation.

γ-Hydroxybutyric acid in the treatment of alcoholism: dosage fractioning utility in non-responder alcoholic patients

Gamma-hydroxybutyric acid (GHB) has recently been introduced in clinical practice for alcoholism management, due to its utility in inducing abstinence from alcohol. In the present study we investigated the usefulness of greater dosage fractioning of GHB in non-responder alcoholics to the usual three administrations per day. A total of 154 alcoholics were admitted to the study and were treated with GHB (50 mg/Kg orally administered three times per day) for 8 weeks (phase 1); the patients who continued to drink alcohol in phase 1 were administered the same dose of GHB divided into six times per day for another 8 weeks (phase 2). Of the 154 patients, 115 completed phase 1; 78 (67.8%) of these began and maintained abstinence (group A) while 37 subjects (32.2%) continued to drink alcohol (group B) showing a craving significantly higher than group A at the end of phase 1 (P < 0.001); in these patients the major fractioning of the drug in phase 2 caused a significant reduction in craving (P < 0.005) and 26 (70.2%) began and maintained abstinence. Moreover no significant differences in final craving score between group A and B was observed. Within the limits of an open study, our data show that non-responder subjects to the conventional fractioning of GHB seem to benefit from the greater fractioning of the drug and seem to indicate the need for a slow-release form of GHB with a prolonged action.

Biomarkers to assess the genetic damage induced by alcohol abuse in human lymphocytes

Alcohol abuse is a major risk factor for cancer of the upper alimentary tract, the upper respiratory tract, and liver. Chromosome damage is used as early effect biomarker in the surveillance of human exposure to genotoxic carcinogens. In the present study, two genetic markers, namely chromosome aberrations (CAs) and micronuclei (MN), were used to evaluate genetic damage in peripheral lymphocytes from 20 alcoholics, 20 abstinent alcoholics, and 20 controls. Composition of the three groups was fairly similar as regards sex, age and smoking habits. A highly significant increase was observed in the frequencies of CA and MN in lymphocytes of alcoholics as compared both with controls and abstinent alcoholics. However, no correlation was found between the length of alcohol abuse and the frequencies of either biomarkers in alcoholics. CA and MN frequencies in abstinent alcoholics were similar than those in controls. Our data indicate that CA and MN can be two useful biomarkers to assess genetic damage associated with alcohol abuse. They could be included in programs for cancer prevention in alcoholics. Abstinence appears to normalize the frequency of both MN and CA. This could offer therapists another tool to help alcoholics change their lifestyle.

Three months of abstinence from alcohol normalizes energy expenditure and substrate oxidation in alcoholics: a longitudinal study

Objective:The aim of this study was to evaluate the energy expenditure, substrate oxidation, and body composition in alcoholics during addiction and after several months of abstinence.Methods:A total of 32 alcoholics without liver cirrhosis and malabsorption were consecutively recruited. A total of 55 social drinkers, matched for gender and height, were studied as a control group. Anthropometry and bioimpedance analysis were performed to assess body composition, and indirect calorimetry was used to measure basal metabolic rate (BMR) and substrate oxidation. Total abstinence was then achieved in 15 subjects. At 1, 2, 3, and 6 months of abstinence, the metabolic variables and the energy intake were re-examined.Results:At enrollment (T0) alcoholics compared to controls showed a significant decrease in body mass index (22.2 ± 2.71 vs 23.6 ± 1.3 kg/m2; p < 0.05), fat mass (14.1 ± 4.5 vs 16.7 ± 3.3 kg; p < 0.01), an increased BMR normalized by fat-free mass (34.5 ± 3.7 vs 32.1 ± 2.01 kcal/kg/day; p < 0.01), a lower nonprotein respiratory quotient (npRQ: 0.76 ± 0.03 vs 0.83 ± 0.03; p < 0.001), with a consequently higher lipid oxidation (0.08 ± 0.02 vs 0.04 ± 0.02 g/min; p < 0.01), and a lower carbohydrate oxidation (0.05 ± 0.02 vs 0.10 ± 0.03 g/min; p < 0.01). Although at 1 and 2 months of abstinence the metabolic parameters had improved, only after 3 months of abstinence did alcoholics show values of body mass index (23.2 ± 2.6 kg/m2), fat mass (17.0 ± 5.34 kg), BMR/fat-free mass (33.1 ± 2.78 kcal/kg/day), npRQ (0.82 ± 0.02), lipid oxidation (0.05 ± 0.03 g/min) and carbohydrate oxidation (0.11 ± 0.04 g/min) comparable to those of controls; these values remained constant at 6 months.Conclusions:Three months of abstinence from alcohol could represent the minimum time necessary to obtain a normalization of the metabolic variables considered and of the nutritional status for these patients, probably related to a regression of the functional alterations of the microsomal ethanol oxidizing system and of mitochondria secondary to chronic ethanol abuse.

Circulating microRNAs, miR-939, miR-595, miR-519d and miR-494, Identify Cirrhotic Patients with HCC

The performance of circulating biomarkers for the diagnosis of hepatocellular carcinoma (HCC) is sub-optimal. In this study we tested circulating microRNAs as biomarkers for HCC in cirrhotic patients by performing a two stage study: a discovery phase conducted by microarray and a validation phase performed by qRT-PCR in an independent series of 118 patients. Beside miRNAs emerged from the discovery phase, miR-21, miR-221, miR-519d were also tested in the validation setting on the basis of literary and tissue findings. Deregulated microRNAs were assayed in HCC-derived cells in the intracellular compartment, cell culture supernatant and exosomal fraction. Serum and tissue microRNA levels were compared in 14 patients surgically treated for HCC. From the discovery study, it emerged that seven circulating microRNAs were differentially expressed in cirrhotic patients with and without HCC. In the validation set, miR-939, miR-595 and miR-519d were shown to differentiate cirrhotic patients with and without HCC. MiR-939 and miR-595 are independent factors for HCC. ROC curves of miR-939, miR-595 and miR-519d displayed that AUC was higher than AFP. An exosomal secretion of miR-519d, miR-21, miR-221 and miR-1228 and a correlation between circulating and tissue levels of miR-519d, miR-494 and miR-21 were found in HCC patients. Therefore, we show that circulating microRNAs deserve attention as non-invasive biomarkers in the diagnostic setting of HCC and that exosomal secretion contributes to discharging a subset of microRNAs into the extracellular compartment.