Risk factor for irritable bowel syndrome: role of food allergies.
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Biomedical subjects
Publications and source records attributed to G Addolorato.
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OBJECTIVE: Nutritional disorders in alcoholics remain one of the most relevant medical problems in Western societies. As ethanol can supply >50% of the dietary energy in alcoholics, body composition alterations may easily occur. The aim of the present study was to evaluate the influence of chronic alcohol consumption on body composition in alcoholics compared to healthy social drinkers. METHODS: A total of 34 alcoholics defined according to DSM III R criteria, aged 41.6 +/- 9.3 yr and with a body mass index (BMI) 23.8 +/- 3.2 kg/m2, were consecutively enrolled in the study. In addition, 43 healthy male social drinkers were used as controls. Body composition was assessed using dual energy x-ray absorptiometry (DXA), and dietary habits were determined by a 3-day food diary. RESULTS: Mean daily alcohol intake was 194 +/- 62.4 g/day in alcoholics and 35.7 +/- 5.2 in healthy subjects (p < 0.0001). Body weight did not differ between alcoholics and controls (70.1 +/- 9.9 vs 71.8 +/- 6.4 kg). Alcoholics had a lower percent body fat (PBF) than control subjects (18.7 +/- 3.7 vs 23.9 +/- 3.9%; p < 0.01), as well as a lower fat mass content (13.4 +/- 3.8 vs 17.0 +/- 3.7 kg; p < 0.01). BMI was highly correlated with PBF in the patient population studied (R = 0.79; p < 0.0001). Significantly higher waist-to-hip ratios were found in alcoholics than in healthy subjects (p < 0.01). No correlation was found between dose of ethanol or duration of alcohol abuse and any of the variables examined. CONCLUSIONS: Alcoholics showed a reduced fat mass and a good preservation of lean body mass with respect to control subjects, and duration of alcohol use and alcohol dose did not seem to influence body composition. These data suggest that, unlike control subjects, alcoholics cannot store the calories provided by ethanol as fat deposits.
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BACKGROUND: The similarities between the pharmacological effects of the gamma-aminobutyric acid receptor agonist, baclofen, and the alcohol-substituting agent, gamma-hydroxybutyric acid, led us to investigate whether baclofen was capable of reducing (a) ethanol withdrawal syndrome in ethanol-dependent rats and (b) voluntary ethanol intake in ethanol-preferring rats. METHODS: In experiment 1, Wistar rats were rendered physically dependent on ethanol by the repeated administration of intoxicating doses of ethanol for 6 consecutive days. Baclofen was acutely administered intraperitoneally at doses of 10, 20, and 40 mg/kg. In experiment 2, baclofen (0, 2.5, 5, and 10 mg/kg, intraperitoneally) was administered once a day for 14 consecutive days to ethanol-preferring sP rats that had continuous access to ethanol (10%, v/v) and water under the two-bottle free choice regimen. RESULTS: In experiment 1, baclofen dose-dependently decreased the intensity of ethanol withdrawal signs; furthermore, 20 mg/kg of baclofen protected from audiogenic seizures in ethanol-withdrawn rats. In experiment 2, baclofen selectively and dose-dependently reduced voluntary ethanol intake; a compensatory increase in water intake left total fluid intake virtually unchanged. CONCLUSIONS: These results are in close agreement with those of a preliminary clinical study and suggest that baclofen may constitute a novel therapeutic agent for alcoholism.
BACKGROUND: Accumulating evidence shows the efficacy of the gamma-aminobutyric acid (GABA(B)) receptor agonist baclofen in reducing alcohol intake in rats, but no studies have been performed in alcoholics. In the present preliminary study we investigated the effect of short-term baclofen administration on craving for alcohol, ethanol intake, and abstinence from alcohol in alcoholic individuals. METHODS: Ten male current alcoholic individuals were admitted to the study. Baclofen was orally administered for 4 weeks, at a dose of 15 mg/day refracted in three times per day for the first 3 days, with the dose increased to 30 mg/day for the remaining 27 days. Each subject was checked as an outpatient every week for the 4 weeks; at each visit (T0-T4) craving level was evaluated by the Alcohol Craving Scale (ACS), and abstinence from alcohol was assessed based on the individual's self-evaluation, family member interview, and the main biological markers of alcohol abuse. A self-reported alcohol intake was recorded as the mean number of standard drinks consumed per day. RESULTS: Nine subjects completed the study; of these, two subjects continued to drink alcohol although they substantially reduced their daily drinks in the first week of treatment, whereas seven maintained abstinence throughout the experimental period. Craving was significantly reduced from the first week of the drug administration (p < 0.01) and remained so throughout the entire treatment period. Participants also reported that obsessional thinking about alcohol disappeared. Values of gamma-glutamyltranspeptidase, alanine aminotransferase, and mean cellular volume significantly decreased by the end of the study. Tolerability was fair in all participants; headache, vertigo, nausea, constipation, diarrhea, abdominal pain, hypotension, increased sleepiness, and tiredness were present as side effects in the first stage of the treatment. No participants showed craving for the drug. CONCLUSIONS: With the limitations of the low number of individuals evaluated and the open design, this preliminary clinical study supports the preclinical evidence on the effect of baclofen in reducing alcohol intake. The anticraving properties of the drug suggest a possible role of baclofen in the treatment of individuals with alcohol problems.
Dicarboxylic acids (DA) are alternate lipid substrates recently proposed in parenteral nutrition. Two new derivatives of DA, a triglyceride of sebacic (TGC10) and one of dodecanedioic (TGC12) acid have been synthesised in order to reduce the amount of sodium given with the unesterified forms. The present paper describes a rapid and direct high-performance liquid chromatographic method (HPLC) for the analysis of these substances in both plasma and urine. Thirty-six male Wistar rats were rapidly injected with 64 mg of TGC10 or 53 mg of TGC12. The triglycerides and their products of hydrolysis were measured in plasma samples taken at different times. For the dose of 500 ng the intra-assay variations ranged from 6. 80+/-0.35% for TGC10 to 18.6+/-3.20% for TGC12 and the inter-assay variations were from 4.44+/-2.21% for TGC10 to 15.0+/-6.72% for TGC12. The detection limit for both triglycerides was 5 ng. This rapid and direct HPLC method could have practical implications in monitoring the concentration of both triglycerides and free forms of DA in biological samples of patients who might benefit from the administration of these substances during parenteral nutrition regimens.
It is still debatable whether anxiety and depression in patients affected by rhinitis could play a role in the genesis of the disease, whether they are a consequence of the symptoms. The aim of this study was to evaluate anxiety levels in both state and trait forms, and depression, in patients affected by allergic (AR) and vasomotor rhinitis (VMR). A total of 45 women, 24 AR and 21 VMR were compared with 64 healthy nonallergic women matched for age and sociodemographic characteristics. All subjects were administered the State and Trait Anxiety Inventory (STAI) and the Zung self-rating depression scale. The percentage of subjects with high levels of state anxiety was significantly higher in AR (p<0.005) and VMR (p<0.01) with respect to controls. The percentage of subjects with high levels of trait anxiety was significantly higher in AR (p<0.001) and VMR (p<0.05) than controls. There was no significant difference in depression between AR and VMR and controls. No significant difference was found in state anxiety, trait anxiety, or depression between AR and VMR. In conclusion, anxiety in patients with rhinitis is present both as a state and as a trait, at least when measured with the STAI.
Gamma-hydroxybutyric acid (GHB) is a drug recently utilized for alcoholism management. It has been shown that GHB has anabolic effects since it can increase growth hormone (GH) release in healthy subjects. At present, there are no studies investigating body composition in alcoholics during long-term GHB treatment. In this study body composition and GH secretion in alcohol dependent subjects was evaluated during addiction and at different time of GHB administration and alcohol abstinence. A total of 45 male alcohol dependent patients (mean age 39.7+/-9.8 yrs, mean height: 171+/-6.8 cm, body mass index--BMI--22.1+/-1.6 kg/m(-2)) were consecutively enrolled. Body composition was assessed by anthropometry, bioimpedance analysis and tritiated water method. A 7-day food diary was collected. Plasma GH levels were determined by radioimmunoassay. A 6-month total abstinence was obtained in 22 patients, by means of psychological support counseling and self-help groups in 9 subjects and also by 50 mg/kg/day of GHB in 13 subjects. At 1, 2, 3 and 6 months of abstinence, the biochemical assessment and metabolic variables were re-examined. Fat-free mass (FFM) and basal GH secretion were similar at the different times of follow-up in both groups of patients. GHB treated patients and those receiving psychological support alone showed similar values in FFM and GH. Both groups of patients did not differ in FFM and plasma GH level from healthy controls at any of the times evaluated. Waist-to-hip ratio did not differ between patient groups, while higher values were shown in alcoholics with respect to control subjects. The present study shows that long-term administration of GHB did not affect muscular mass and did not determine an increase of GH release in chronic alcoholics. This findings could be due to an impairment of the hypothalamic-limbic system and of GABAergic neurotransmission in alcoholics' brain.
Weight loss and malnutrition are commonly reported in inflammatory bowel disease (IBD), but differences between Crohn's disease (CD) and ulcerative colitis (UC) patients have rarely been pointed out. In this regard, a sample of 102 consecutive patients with a diagnosis of either CD (n = 63, 33 males) or UC (n = 39, 25 males) based on previously reported clinical, morphologic, and histopathologic criteria were studied. Twenty-six anthropometric and metabolic variables were measured upon admission. Body composition was assessed by both anthropometry and bioimpedance measurements, and energy expenditure and substrate oxidation were assessed by indirect calorimetry. The data were subjected to principal-component analysis and to factor rotation to derive a set of a few basic independent descriptors of the metabolic features of each subject. Six descriptors were found to be responsible for greater than 86% of the total sample variability and to associate very well with mutually disjoint subsets of the original variables. The six summarizing factors are listed in order of decreasing percentage of explained variation (size 41.8%, fatness 17.9%, fuel 12.2%, shape 5.4%, energy 5.2%, and steroid 3.9%). CD and UC patients differed significantly with respect to fatness (CD lower, P = .004) and carbohydrate (CHO) fuel preference (CD lower, P = .030). Hence, CD patients showed a reduced fat mass (FM) compared with UC patients, and from a metabolic point of view, too, CD and UC are not superimposable. In fact, the lower CHO oxidation (CHOox) rate and consequent preferential lipid utilization found in CD patients may be taken into account as a contributing cause of lipid tissue wasting and in planning therapeutic enteral regimens.
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BACKGROUND: Inflammatory mediator concentration was found to be increased in active inflammatory bowel disease, and this could be related to an insulin-resistant state. Moreover, glucocorticoids, which are widely used in the treatment of inflammatory bowel disease, are notoriously related to insulin resistance. AIM: To measure body composition, whole body glucose uptake and oxidation in Crohn's disease and ulcerative colitis patients with inactive disease. METHODS: All patients had clinical, ultrasound and biochemical assessment. Body composition was determined by isotopic dilution technique; basal metabolic rate and substrate oxidation were measured by indirect calorimetry. Insulin sensitivity was assessed by the euglycaemic hyperinsulinaemic clamp. Ten patients with inactive Crohn's disease (five males, aged 31.1 +/- 7.0 years) and 10 patients with inactive ulcerative colitis (five males, aged 33.4 +/- 8.8 years) participated in the study. Forty healthy subjects, matched for age and height were used as a control group. RESULTS: Crohn's disease patients showed lower BMI (P < 0.001), fat mass (P < 0.05) and respiratory quotient (P < 0.001) values compared to both ulcerative colitis and control subjects. No difference in peripheral glucose uptake (micromol/kg/min) was found between groups (respectively 42.5 +/- 6.78 in Crohn's disease, 40.2 +/- 8.00 in ulcerative colitis and 41.4 +/- 10.8 in control subjects). Glucose storage and oxidation did not differ between groups. CONCLUSION: Our data showed that inflammatory bowel disease patients in a remission phase of the disease activity had a whole body glucose uptake and oxidation similar to those of control subjects, probably due to fat-free mass preservation and low blood and tissue cytokine concentration.
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OBJECTIVE: The aim of the present study was to investigate and compare the effects of two proton-pump inhibitors, lansoprazole (Limpidex 30 mg, Sigmatau) vs pantoprazole (Peptazol 40 mg, Boehringer Mannheim), included in a three-day antibiotic therapy regimen with azithromycin (Zitromax 500 mg, Pfizer) and tinidazole (Fasigin 500 mg, Pfizer). DESIGN: Seventy consecutive, H. pylori-positive patients were randomly pre-treated with lansoprazole 30 mg o.d. (once daily) or pantoprazole 40 mg o.d. for two days, and subsequently respectively assigned to one of the two following treatment regimens, given for only three days: regimen A (LAT) comprising lansoprazole 30 mg o.d. plus azithromycin 500 mg o.d. and tinidazole 500 mg b.i.d. (bis in die), or regimen B (PAT) comprising pantoprazole 40 mg o.d. plus azithromycin 500 mg o.d. and tinidazole 500 mg b.i.d. H. pylori status was evaluated by means of histology and rapid urease test at entry, and by 13C-urea breath test alone 8 weeks after treatment. MAIN OUTCOME MEASURES: Sixty-nine of the enrolled patients completed the study: 34 in the LAT group and 35 in the PAT group. One patient in the LAT group was lost to follow-up. In the LAT group, after the end of treatment, 28/34 patients were H. pylori-negative (per protocol: 82%; intention-to-treat: 80%). In the PAT group, after treatment, 29/35 patients were H. pylori-negative (per protocol and intention-to-treat: 83%). Mild or slight side-effects occurred in only one patient in the LAT group and in one in the PAT group. CONCLUSIONS: From this study there is no evidence that either of the two proton-pump inhibitors used is preferable in a three-day antibiotic regimen with azithromycin and tinidazole. The excellent side-effect and tolerability profiles, associated with acceptable eradication rates, make the two treatment regimens we tested particularly useful when patient compliance is difficult to achieve.
BACKGROUND: At present few data are available on the total body water (TBW) content and in particular on the distribution of water in the intra- and extracellular compartments (ICW and ECW) of alcoholics. The aim of this study was to evaluate TBW, ICW, and ECW in chronic alcoholic patients. METHODS: Thirty-six alcoholics meeting DSM-III-R criteria for diagnosis (20 men, 16 women; body mass index [BMI] 22.3+/-2.57 kg/m2) were enrolled. Fifty-four healthy social drinkers (31 men, 23 women; BMI 23.7+/-1.68 kg/m2) matched for age and height were used as controls. Systolic and diastolic blood pressure was measured for all cases. All patients were assessed using specific anthropometric measurements. The waist-to-hip ratio (WHR) was used as an indicator of body fat distribution. TBW was measured by isotopic dilution by giving 100 microCi of tritiated water. ICW and ECW were assessed by multifrequence bioelectric impedance analysis (BIA). Basal metabolic rate (BMR) was measured by indirect calorimetry. RESULTS: Body weight was lower in the alcoholics than in the controls (61.9+/-5.5 kg vs. 65.8+/-5.2 kg;p < 0.01), essentially due to a reduction in fat mass. Significantly higher WHR values were found in both male (p < 0.001) and female (p < 0.001) alcoholics than in healthy subjects. A higher ECW/TBW ratio was found in the alcoholics compared with the controls, both as a whole (0.53+/-0.04 vs. 0.41+/-0.03; p < 0.0001) and separated by gender (p < 0.001). CONCLUSIONS: The increased ECW could derive from an increase in cellular permeability related to endothelial damage linked to the vasoconstriction present in the alcoholics and/or to a direct toxic effect of ethanol on cellular membranes. In addition, because the high ECW volumes correlated positively with WHR in the alcoholics, a potential association of these two factors in determining an increased risk of liver disease, hypertension, and cardiovascular disease may exist. Finally, the lower TBW characteristic of women may be one of the reasons for the observed greater rate of toxic effects of ethanol that occur in women.
BACKGROUND: Benzodiazepine has been shown to be one of the most effective class of drugs in the management of alcohol withdrawal syndrome (AWS). Gamma-hydroxybutyric acid (GHB) has recently been introduced in the treatment of alcohol problems, including AWS. At present there are no comparative studies between benzodiazepines and GHB in AWS treatment. The aim of the present randomized, controlled, single-blind study was to evaluate the efficacy and safety of GHB compared with diazepam in the treatment of AWS. METHODS: Sixty alcoholics affected by AWS were enrolled in the study. Diazepam (0.5-0.75 mg/kg body weight for 6 days, tapering the dose 25% daily until day 10) was administered orally to 30 patients (25 males, 5 females; mean age 44.3 +/- 10.9 years); GHB (50 mg/kg body weight for 10 days) was administered orally to 30 patients (26 males,4 females; mean age 41.7 +/- 10.4 years). The Clinical Institute Withdrawal Assessment for Alcohol-revised scale (CIWA-Ar) was used to evaluate the AWS physical symptoms. The State Anxiety Inventory test for current anxiety assessment and the Zung self-rating Depression Scale for current depression assessment were performed. RESULTS: Eight patients (26.6%) in the diazepam group and 4 patients (13.3%) in the GHB group dropped out. Both treatments were effective in reducing AWS. No significant difference was found between the groups in CIWA-Ar total score at baseline and at the different times of observation. Considering the CIWA-Ar subscore and Zung scale, a significant reduction of anxiety on day 4 (p < 0.02), agitation on day 5 (p < 0.02) and time of recovery of depression on day 5 (p < 0.02) was observed in the GHB group with respect to the diazepam group. Drowsiness and vertigo developed after initial drug administration in the GHB (19.2%) and diazepam (36.4%) groups and quickly resolved in both groups. CONCLUSIONS: GHB is as effective in the management of AWS as benzodiazepine and it seems to be quicker in reducing anxiety, agitation, and depression. Both drugs are safe and well-tolerated in AWS management.
An impairment of nutritional status up to real malnutrition can frequently be associated to gastrointestinal diseases. The diseases of the gastrointestinal tract can be divided into five groups: those hampering the nutrient physiological transit (especially neoplastic diseases); those affecting the intestinal mucosa (such as chronic inflammatory bowel disease); those determining intraluminal maldigestion; the hepato-biliary diseases and finally, the diseases of the pancreas. In order to correctly evaluate the nutritional status of an individual, besides the determination of the common biochemical parameters, body composition by direct and indirect techniques and energy metabolism by indirect calorimetry should be measured. Patients affected by Crohn's disease showed a lower fat mass content along with higher lipid oxidation compared to patients affected by ulcerative colitis. Patients with coeliac disease at diagnosis had a reduction in both fat and fat-free mass content along with an increased utilisation of carbohydrates as fuel substrate. There are many factors potentially leading to severe malnutrition in pancreatic diseases, especially in the acute form. Due to the primary role played by the liver in the metabolism of energy substrates, an impaired nutritional status might be commonly found in cirrhotic patients. In this connection, our group reported an increased energy expenditure and lipid oxidation, and an insulin-resistant state in compensated liver cirrhotic patients. These alterations seemed to precede and probably to lead to liver-disease-related malnutrition.
One of the major complications found in patients affected by malignancy of the gastrointestinal tract is represented by an alteration of nutritional status, up to real cachexia. The factors responsible for the severe nutritional deficiencies are: metabolic alterations, which involve carbohydrate, lipid and protein metabolism; the reduced availability of nutritional substrates, due to neoplastic growth that, by expanding locally or destroying the affected organ, determines alterations of deglutition, digestion and food absorption; the effects of surgical therapy, radiotherapy and chemotherapy, which are able to cause temporary or permanent nutritional deficiencies; the effects of immunological mediators, and above all of tumor necrosis factor-alpha (TNF-alpha). In fact, TNF-alpha is considered the main mediator of cancer cachexia as it is responsible for different metabolic alterations, both directly and by the activation of other mediators, such as lipid mobilizing factor (LMF) and protein mobilizing factor (PMF). In addition, a negative energy balance in cancer patients could occur as a consequence of increased energy requirements. In this connection, patients with different neoplasia localisation, show high or within the normal range energy expenditure values. These data indicate that the increase in energy metabolism is not likely to represent the main determining factor in neoplastic cachexia. In conclusion, since patients affected by malignancy of the gastrointestinal tract showed a reduction in body weight, fat and fat-free mass, accurate evaluation of nutritional status should be useful in the management and follow-up of these patients.