The effect of a new symbiotic formulation on plasma levels and peripheral blood mononuclear cell expression of some pro-inflammatory cytokines in patients with ulcerative colitis: a pilot study.

BACKGROUND: During intestinal inflammation white blood cells are recruited from the blood, and they represent the major contributors to tissue perpetuation of inflammation via their production of chemokines and proinflammatory cytokines. OBJECTIVES: Investigate the effect of a symbiotic formulation containing Lactobacillus Paracasei B 20160 versus placebo, on serum levels of interleukin (IL)-6, tumor necrosis factor (TNF)alpha, IL-8, IL-1beta and IL-10 and on mRNA lymphomonocyte expression of TNFalpha, IL-8 and IL-1beta in patients with ulcerative colitis. MATERIALS AND METHODS: Eighteen patients entered the study with histologically proven not complicated ulcerative colitis, treated with mesalazine. Patients were treated for 8 weeks (9 with symbiotic and 9 with placebo). Serum levels of IL-6, TNFalpha, IL-8, IL-1beta and IL-10 were measured using a commercially available sandwich ELISA kit. RT-PCR analysis was performed on total RNA isolated from peripheral lymphomonocytes. RESULTS: In basal condition, there was an increase of serum levels of TNFalpha, IL-6, and IL-8. The treatment with symbiotic significantly decreased serum levels of the last two cytokines (IL-6 and IL-8). In lymphocytes, the treatment with the symbiotic don't significantly reduced the mRNA expression of TNFalpha and IL-1beta, while that of IL-8 was strongly and significantly decreased. CONCLUSION: Our preliminary results suggest that a symbiotic formulation containing Lactobacillus paracasei significantly improves the plasma and lymphocyte content of some proinflammatory cytokines.

Psychological status and depression in patients with liver cirrhosis.

BACKGROUND: Previous studies reported an impairment of both the physical and mental dimensions of quality of life in patients with cirrhosis. Very few data are available on the psychological impact of the disease and its relation to liver function. AIM: To measure the psychological status of patients with cirrhosis in relation to the severity of the liver impairment. PATIENTS AND METHODS: One hundred and fifty-six patients with cirrhosis were studied. Two questionnaires (the Beck Depression Inventory and the Psychological General Well-Being Index) were self-administered in random order. Clinical and laboratory data were collected using standardised forms. RESULTS: The global score of Psychological General Well-Being Index was severely reduced compared to Italian population norm. Among individual domains, the more severely affected was General Health, the less compromised was Positive Well-Being. A negative relation was found between Child-Pugh score (a comprehensive measure of disease severity) and global Psychological General Well-Being Index and several individual subscales. The Beck Depression Inventory scores were indicative of a depressed mood in over 50% of patients, in relation to the presence of clinical symptoms. CONCLUSIONS: Patients with cirrhosis have signs of psychological distress and depression, as assessed by Beck Depression Inventory and Psychological General Well-Being Index, in relation to the severity of liver disease. Accordingly, a non-negligible number of patients warrant treatment.

Improvement of Pap smear sensitivity using a visual adjunctive procedure: a co-operative Italian study on speculoscopy (GISPE).

The present study evaluates whether speculoscopy, a magnified chemiluminescence examination, combined with Pap smear can improve the detection of cervical lesions, as compared with Pap smear alone. The investigation was a prospective practice-based research carried out as a multicentre cohort study throughout the Italian territory. The participants were 3,300 asymptomatic women age > or = 18 years undergoing routine pelvic and cytological screening. All participants were subjected to Pap smear, speculoscopy and colposcopy investigations in succession. The 646 women with positive colposcopy underwent biopsy. Of the 267 women with positive histology 25 were high-grade intraephitelial lesions (HGSIL) and 242 were low-grade intraephitelial lesions (LGSIL). The histological findings were correlated with the results of Pap smear and speculoscopy alone and combined (PPS). Pap smear alone detected 76% of HGSIL, speculoscopy alone identified 84% of HGSIL, and PPS indicated 100% HGSIL. Of the 242 women with LGSIL, Pap smear alone detected 37% of the cases, speculoscopy alone detected 54% of the cases, and PPS identified 91% of the cases. Together, the two tests missed 9% of the LGSIL. The combination PPS was found to increase sensitivity from 40% to 92%, but to lower specificity from 94% to 23%. Speculoscopy combined with Pap smear can yield a higher percentage of women with biopsy-confirmed cervical pathology than the use of Pap smear as a sole screening test. This is particularly true of patients with LGSIL. The mechanisms of pathological detection and the use of speculoscopy should be investigated further.

Brain cholecystokinin depletion in rats with acute liver failure.

A decrease of both hypothalamic and cortical CCK occurred in the brain of rats killed 8 hours after hepatic artery ligation following portocaval anastomosis. Brain CCK depletion was not reproduced by exogenously provoked hyperammonemia nor by insulin-induced hypoglycemia, thus suggesting a central mechanism for the derangement of the CCKergic system in the course of acute liver failure.

Reduced quality of life in patients with chronic hepatitis C: effects of interferon treatment.

BACKGROUND: Quality of life is an area of increasing interest in hepatology. Studies, so far, have assessed quality of life in patients with chronic virus C-related hepatitis in relation to antiviral therapy by means of generic questionnaires. AIM: To measure quality of life in chronic hepatitis patients without cirrhosis by means of the Nottingham Health Profile questionnaire, a measure of "distress" in comparison with the Medical Outcome Survey SF-36, an index of well-being. PATIENTS: A series of 126 outpatients with chronic hepatitis; 37 on and 89 not on active interferon treatment. METHODS: The two questionnaires were used in random order. Clinical and laboratory data were also collected. The final score of any domain of the two questionnaires, for any individual patient, was compared to age-adjusted normal values obtained in 2 random samples of Italian population. RESULTS: Patients showed a significant modification of 3 domains of Nottingham Health Profile (Energy, Social Isolation and Physical Mobility) and 6 domains of SF-36. In relation to interferon treatment, the Nottingham Health Profile questionnaire was able to detect differences in Energy, Physical Mobility and Pain, which were modified only in treated patients. SF-36 did not show any differences in relation to treatment. In addition, the Nottingham Health Profile demonstrated that treated patients had a lower prevalence of concern for family life, possibly due to expectations of treatment itself. CONCLUSIONS: Active interferon treatment causes considerable distress in chronic hepatitis C patients, adding to the perceived change in health status caused by liver disease.

Reduced quality of life of patients with hepatocellular carcinoma.

BACKGROUND: It has been shown that health-related quality of life is reduced in patients with cirrhosis and with chronic hepatitis in relation to antiviral therapy. No data are available on patients with hepatocellular carcinoma. AIM: To assess health-related quality of life in cirrhotic patients with hepatocellular carcinoma. PATIENTS AND METHODS: Health-related quality of life was assessed in 101 hepatocellular carcinoma patients by means of Short Form-36 and Nottingham Health Profile questionnaires. Final scores of domains for individual patients were compared to age-adjusted normative Italian values, using Z-score and with values obtained in 202 matched patients with cirrhosis, without hepatocellular carcinoma. RESULTS: All Short Form-36 domains and 4 out of 6 Nottingham Health Profile domains were altered. When hepatocellular carcinoma patients were compared with matched cirrhotics, differences were present for Bodily Pain, Role Limitation-Physical, and the Physical Component Summary of Short Form-36, as well as Pain of Nottingham Health Profile. Perceived health status had changed significantly in the year prior to assessment. Health-related quality of life was not primarily related to tumour mass or hepatocellular failure, whereas sleep disorders were selected by logistic regression as strongly associated with poor health-related quality of life. CONCLUSIONS: The present data stress the relevance of pain in poor perceived health status of hepatocellular carcinoma patients, and the importance of minor symptoms, such as sleep disorders.

The Italian experience of a Pap test and speculoscopy based screening programme.

OBJECTIVES: The main objective of the study was to evaluate if speculoscopy, a magnified chemiluminescent examination, combined with a Pap smear, could improve the detection of early cervical lesions compared with the Pap smear alone. SETTING: Pap tests and speculoscopies were performed in two family planning centres located in the surrounding areas of Modena. Colposcopic investigations and biopsies of the uterine cervix were performed in a second level centre (Gynaecological Prevention Centre of Modena Policlinico). Histological specimens were analysed at the Section of Pathological Anatomy of Modena Policlinico. SUBJECTS: The study population comprised 1000 women aged 25-64 years, invited to undergo a Pap smear every three years in accordance with the screening programme for cervical cancer started in Modena in 1997. METHODS: Midwives performed the Pap smear and speculoscopy in succession. Women with a positive Pap test and/or positive speculoscopy underwent colposcopy and, if colposcopic findings were positive, targeted punch biopsies were performed. RESULTS: A total of 1000 patients were subjected to cytology and speculoscopy examinations. Among these women, 10 had abnormal Pap smear findings whereas 144 had an abnormal speculoscopic pattern. Only three of 59 patients with a histological diagnosis of cervical intraepithelial neoplasia grade I (CIN I)/human papillomavirus and only three of seven patients with CIN II/CIN III had a positive Pap test. CONCLUSIONS: Speculoscopy combined with a Pap test can significantly increase the detection of cervical lesions when included in a screening programme.

Oral BCAA supplementation in cirrhosis with chronic encephalopathy: effects on prolactin and estradiol levels.

The effects of oral BCAA supplementation on fasting levels of prolactin and estradiol were retrospectively analyzed in frozen plasma samples of patients with cirrhosis and chronic hepatic encephalopathy, taking part in a 3-month randomized, double-blind trial. Twenty-five patients had received 0.24g of BCAA per kg body weight, 24 had received an equinitrogenous amount of casein, in addition to a diet providing 0.7-1.0 g/kg of protein. Thirty-eight were males, 11 post-menopausal women. Fasting prolactin did not show any change in the BCAA group, where mental state significantly improved. In the casein group plasma prolactin increased by nearly 50% during the 3-month period. Similarly, estradiol concentrations were unchanged during BCAA supplementation, and increased during casein treatment. The analysis of variance demonstrated significant differences between the 2 treatments. Liver function tests and nutritional parameters (albumin, transferrin, urinary creatinine) supported a superiority of BCAA over casein. These data suggest that the favorable effects of BCAA on mental state are not mediated by changes in cerebral neurotransmission, but are due mainly to maintained liver function, possibly related to improved nutrition.

Omeprazole vs. ranitidine in the short-term treatment of duodenal ulcer: an Italian multicenter study.

A double-blind, double-dummy, randomized Italian multicenter trial was carried out to compare the efficacy and safety of omeprazole 20 mg in the morning and ranitidine 150 mg b.i.d. in short-term treatment of acute duodenal ulcer. One hundred and twenty-one patients (61 in the omeprazole and 60 in the ranitidine group) with endoscopically proven active duodenal ulcer, completed the study. The healing rates after 2, 4 and 6 weeks were 66, 97 and 100%, respectively, with omeprazole and 53, 85 and 92%, respectively, with ranitidine. The difference was statistically significant (p less than 0.05) at weeks 4 and 6. Night and day pain were markedly reduced during both treatments, as also antacid consumption. Both drugs were well tolerated, and the adverse events were infrequent and moderate. In our experience, omeprazole 20 mg once daily seems to be superior to ranitidine 150 mg b.i.d. in the short-term treatment of duodenal ulcer.

Effect of pyridoxine alpha-ketoglutarate (PAK) on ammonia and pyruvic and lactic acid blood levels in patients with cirrhosis.

Administration of PAK to patients with hepatic cirrhosis significantly reduced hyperammonaemia and plasma levels of pyruvic and lactic acid. No significant changes in glycaemia were found. PAK treatment increased plasma levels of glutamic acid and decreased plasma levels of glutamine. This double-blind placebo controlled trial showed that PAK administration has a positive effect on some metabolic disturbances in cirrhotic patients.

Immunostimulating effect of oral glutamine.

Glutamine represents the principal metabolic substrate for all rapidly proliferating cells. Since part of the glutamine efficacy could be related to immunoregulating properties, we assessed the effects of orally administered glutamine on serum interleukin-2 (IL-2) levels and intestinal T-cell populations in 48 athymic (nude) mice. Twenty-four mice received a standard diet enriched by glutamine (added to drinking water at a 4% concentration), while the other 24 served as the control group and received the same diet without glutamine. In glutamine-fed animals, we observed a marked increase in IL-2 concentrations after 10 days of treatment in comparison with control group and a modest but significant increase in intestinal T-cell counts. These results suggest that oral glutamine is able to exert local and systemic immunostimulating activity that could be of relevance in the prevention of gut integrity and immune defense loss associated, for example, with trauma, surgery, and starvation.

Effects of chronic oral branched-chain amino acid supplementation in a subpopulation of cirrhotics.

Liver cirrhosis is characterized by low plasma levels of branched chain amino acids (BCAA) and high concentrations of aromatic amino acids (AAA), and this imbalance has been implicated in the pathogenesis of hepatic encephalopathy by the synthesis of altered neurotransmitters. Contrasting results on intravenous or oral BCAA efficacy and metabolic impact have already been reported, but studies reported in the literature were never longer than a few weeks. After oral administration of BCAA and a standard diet to 28 cirrhotic patients for 1 year, no modifications in plasma concentrations of BCAA could be observed up to 3 months of therapy. Our data and an accurate analysis of the current literature lead us to propose the hypothesis that in the impaired nitrogen metabolism following cirrhosis there are neither single metabolic presentations nor many perturbations, but numerous 'subpopulations' of patients who present a homogeneous pattern of alterations that may distinguish them in terms of therapeutic approach.

[Adhesion capacity of Enterococcus faecium (SF 68) and Enterococcus faecalis to various substrates]. / Capacità aderente di Enterococcus faecium (SF 68) e di Enterococcus faecalis a diversi substrati.

The author's studied the adherence ability of Enterococcus faecium SF 68 compared to that of Enterococcus faecalis IM 11f, on various substrates: vascular catheters and cardiac valves of rabbit, immunodepressed rats and diabetic rats. The bacterial adherence test was calculated by the number of bacteria adhered for microscopic field enlarged to 2000. The data obtained by scanning electron microscope SEM (Cambridge Stereoscan 150 MK2) revealed a different adherence action of the two germs on the various substrates. All the adherence tests showed a higher and uniform adherence activity of E. faecalis compared to that of E. faecium.

[Late reactions to a radiologic contrast media (Iopamidol-Bracco). Prospective study]. / Reazioni tardive a un mezzo di contrasto radiologico (Iopamidolo-Bracco). Studio prospettico.

PURPOSE: This prospective, non-randomized study was aimed at evaluating the incidence of Delayed Adverse Drug Reactions (DADRs) to iodinated contrast agents and to evaluate possible risk factors to the development of these reactions. DADRs are those reactions occurring one to 48 hours after contrast medium administration. Their symptoms and frequency are not well defined, but the majority of DADRs are mild in intensity and resolve spontaneously without sequelae. In the literature, DADRs are reported to occur in 1 to 15% of patients undergoing contrast-enhanced examinations. MATERIAL AND METHODS: This prospective, non-randomized trial was carried out on 403 patients undergoing either dynamic CT or urography with iopamidol-300 (Iopamiro-300, Bracco SpA). Before the examination, data were collected regarding patients' anagraphical details, presence of risk factors, allergy, previous exposure and previous adverse reactions to iodinated contrast agent. After the examination, any adverse events occurring between 30 minutes and 48 hours post-dose were recorded, specifying time of onset and duration of symptoms. Studied variables were type of DADRs and risk factors to their development (sex, age, underlying disease, allergy, previous exposure to contrast agent, type of diagnostic examination). Two hundred and sixty-two patients were male (65%), and 141 were female (35%). Mean age was 61 years (+/- 11.8); 192 patients (48%) had underlying disease, and 115 (28%) were allergic. About half of the patients had previously undergone another contrast-enhanced examination. Two hundred and seventy-one patients underwent dynamic CT and 132 urography. RESULTS: A total of 50 patients (12.4%) reported DADRs. Factors associated with a significantly higher incidence of DADRs were found to be allergy (p = 0.001), previous exposure to contrast agent (p = 0.001), female sex (p = 0.001), underlying disease (p = 0.030). The most frequently reported DADRs were nausea and vomiting, drowsiness, rash, itching and headache. All reported reactions were mild and resolved spontaneously without sequelae. DISCUSSION AND CONCLUSIONS: In our experience, though limited and not on large numbers, DADRs to nonionic low osmolality contrast agents such as iopamidol have been few, mild, and not clinically significant. Although there are no absolute contraindications to the use of iodinated contrast agent, the risk/benefit ratio should always be evaluated, especially in patients with allergy, in those with severe renal, hepatic or cardiac insufficiency, and in diabetics.

Long-term effects of Enterococcus faecium SF68 versus lactulose in the treatment of patients with cirrhosis and grade 1-2 hepatic encephalopathy.

In 40 patients with cirrhosis on a dietary protein regimen of 1 g/kg b.w., we determined the effect on chronic hepatic encephalopathy of long-term administration of Enterococcus faecium (SF68) versus lactulose. The patients received one of the two treatments for three periods of 4 weeks, each separated by drug-free 2-week intervals. The efficacy of treatment was assessed by arterial blood ammonia concentration, mental status, number connection (Reitan's part A) test and flash-evoked visual potentials. At the end of the third period the reduction in both blood ammonia concentrations and Reitan's test times was more enhanced in patients on SF68 than in patients on lactulose. Furthermore, while patients on lactulose tended to return to basal values during drug-free intervals, responders in the SF68 group maintained improvement throughout the study. In conclusion, SF68 is at least as useful as lactulose for the chronic treatment of chronic hepatic encephalopathy; it has no adverse effects, and treatment can be interrupted for 2 weeks without losing the beneficial effects.

[Role of Enterococcus faecium SF 68 in experimental infection in mice]. / Ruolo dell'Enterococcus faecium SF 68 nell'infezione sperimentale del topo.

The normal intestinal flora is an important defence against various infectious agents. It also allows important metabolic stages in the host. The Authors studied the ability of Enterococcus faecium SF 68 to protect the mice (Swiss strain) from infection by Salmonella typhi and its role when used with penicillin in infection by Staphylococcus aureus. Our results showed that SF 68, determined a good protection against infection. Moreover the association E. faecium SF 68-antibiotic lowers the mortality rate in the infected mice compared with the control group.

Free amino acids in plasma and skeletal muscle of patients with liver cirrhosis.

Free amino acids were measured under postabsorptive conditions in plasma and intracellular water of skeletal muscle obtained by needle biopsy in nine healthy controls and 14 subjects suffering from clinically stable liver cirrhosis. The aromatic amino acids phenylalanine and tyrosine in cirrhotics were elevated to the same extent in plasma and in muscle water. Branched-chain amino acids were uniformly reduced in plasma, but in muscle water only valine was significantly lower (222 +/- 92 mumoles per kg intracellular water vs. 368 +/- 82, p less than 0.001), while isoleucine (142 +/- 63 vs. 103 +/- 30), leucine (223 +/- 88 vs. 226 +/- 36) and branched-chain amino acids as a whole (589 +/- 186 vs. 681 +/- 88) were normal or elevated with an increased muscle:plasma ratio (3.12 +/- 2.03 vs. 1.41 +/- 0.37, p less than 0.05 for isoleucine; 3.00 +/- 1.28 vs. 1.85 +/- 0.27, p less than 0.025 for leucine; 2.24 +/- 0.64 vs. 1.69 +/- 0.13, p less than 0.05 for total branched-chain amino acids. Our data show that, in cirrhosis, plasma concentrations of branched-chain amino acids do not reflect their levels in muscle cellular water; only the intracellular pool of valine is severely depleted. This suggests that higher amounts of valine supplementation may be useful in nutritional treatment of liver cirrhosis. The elevated muscle:plasma gradients for branched-chain amino acids may result from abnormalities in their transport through muscle-plasma membrane.(ABSTRACT TRUNCATED AT 250 WORDS)