Search PubMed⌕ Search

Biomedical subjects

G Gasbarrini

Publications and source records attributed to G Gasbarrini.

At least 415 records · Page 23Linked to original sources

Interferon-alpha increases prostaglandin E2 production by cultured liver biopsy in patients with chronic viral hepatitis: can non-steroidal anti-inflammatory drugs improve the therapeutic response to interferon?

Arachidonic acid metabolites seem to play an important role in modulating the post-receptorial activity of interferon-alpha. In this study the effect of interferon-alpha on prostaglandin E2 production was evaluated in cultured liver tissue in 18 patients with chronic active hepatitis related to viral infection (9 hepatitis B virus (HBV) and 9 hepatitis C virus (HCV) positive) and in 7 uninfected patients with various liver diseases. The results show that interferon-alpha induces a significant increase in prostaglandin E2 production in both HBV and HCV chronic active hepatitis. Since the inhibition of the cyclooxygenase pathway increases antiviral protein synthesis and prostaglandin E2 has an immunosuppressive activity, this finding seems to suggest that a combined therapy (interferon-alpha plus non-steroidal anti-inflammatory drugs) should be indicated at least for patients who do not respond to interferon therapy alone.

Adolescent↗

Asp57-negative HLA DQ beta chain and DQA1*0501 allele are essential for the onset of DQw2-positive and DQw2-negative coeliac disease.

The genetic predisposition to coeliac disease is associated with the HLA DQw2 allele. Coeliac patients lacking the DQw2 allele are very rare and always exhibit the DR4-DQw3 haplotype. We performed oligotyping of polymerase chain reaction (PCR)-amplified DQA1 and DQB1 genes in six DQw2-negative and 30 DQw2-positive coeliac patients. The DQB analysis showed that all six DQw2-negative patients possessed the DQB1*0302 allele. The other DQB alleles found in five of these patients were DQB1*0501, DQB1*0604 and DQB1*0302. The DQ beta chains encoded from all these alleles have the replacement of aspartic acid residue at position 57 (Asp57), as well as the DQB1*0201 allele which was found in all 30 DQw2-positive coeliac patients. The DQw2-negative proband who lacked the homozygous Asp57 replacement exhibited the DQA1*0501 allele in the DQA1 gene. The DQA1*0501 allele was also found in 27 of the 30 DQw2-positive coeliac patients. Among this group of coeliacs, the four cases lacking the DQA1*0501 allele exhibited the homozygous Asp57 replacement in the DQ beta chain. Our results indicate that Asp57-negative DQ beta alleles are involved in both DQw2-positive and -negative coeliac patients. Moreover, when the Asp57-negative DQ beta chain is encoded from only one of the two DQB1 genes the DQA1*0501 allele is always present.

Alleles↗

In vivo effect of chronic ethanol consumption on the fatty acid composition of phosphatidylinositols in resting and anti-CD3-activated lymphocytes.

Fatty acid composition of phosphatidylinositols was analyzed in peripheral blood lymphocytes from nine alcoholic patients who were well nourished and without severe acute and chronic liver disease, before and after stimulation with anti-CD3 antibody. Six comparable nondrinkers were studied as controls. A reduction in unsaturated fatty acid (mainly arachidonic) and an increase in palmitic and stearic acid molar content were observed in phosphatidylinositol (PI), phosphatidylinositol-4-phosphate (PIP), and phosphatidylinositol-4,5-bisphosphate (PIP2) in unstimulated samples from alcoholic patients in comparison with normal subjects, leading to a significant decrease in the saturated/unsaturated ratio. In controls, anti-CD3 stimulation caused a marked decrease in arachidonic acid relative molar content counterbalanced by an increase in other polyunsaturated fatty acid relative molar content in PI, PIP, and PIP2 fractions. Interestingly, after anti-CD3 stimulation, alcoholic patients show the same trend of modification in the fatty acid composition resulting in a sharp reduction of arachidonic acid relative molar content. These results support the hypothesis of an alteration in nutrients being responsible for immune derangement in alcoholics.

Adult↗

Efficacy and safety of the stepped care medical treatment of ascites in liver cirrhosis: a randomized controlled clinical trial comparing two diets with different sodium content.

In order to clarify debated issues of the medical treatment of ascites in cirrhosis--the usefulness of a low sodium diet and washout period preceding diuretic administration, maximal dosage of antimineralocorticoid to be reached before the addition of a loop diuretic, identifications of factors influencing treatment efficacy--115 hospitalized patients with non-azotemic cirrhosis and ascites were recruited and randomized to receive a diet providing either 40 or 120 mmol of sodium daily. After a washout period from the outpatient diuretic regimen for 7 days (Step 1), increasing dosages of K-canrenoate (200 mg/day every 4th day up to 600 mg) were administered to patients not undergoing spontaneous diuresis (Step 2). Upon the failure of Step 2, K-canrenoate (400 mg/day) and furosemide at increasing dosage (25-50-100 mg every other day) were given (Step 3). Nine percent of patients underwent spontaneous diuresis, and 77% developed a negative sodium balance by the end of Step 2 (69% with a dosage of K-canrenoate < or = 400 mg/day) and 93% by the end of Step 3. Two patients were withdrawn from the protocol due to diuretic side-effects. Univariate analysis showed that the type of diet did not influence the response to treatment. The washout period led to a significant increase in endogenous creatinine clearance; natremia significantly rose in hyponatremic patients. Multivariate analysis showed that creatinine clearance and plasma aldosterone were independent predictive factors of the response to treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Ascites↗

Subclinical celiac sprue. Increasing occurrence and clues to its diagnosis.

We have reviewed the clinical records of 226 consecutive adult patients with celiac sprue diagnosed in our department from 1972 to 1989. The study period has been divided into three subperiods of 6 years each (1972-1977, 1978-1983, 1984-1989). From the first to the third subperiod a significant increase in the number of new diagnoses and of the proportion of patients recognized by minor symptoms has been observed. These patients represent 50% of our series in the last 3 years of the study and 70% in 1989. Diagnosing subclinical forms of celiac sprue has significantly lowered the mean age at diagnosis and the female/male ratio. First-degree relatives of celiac patients; subjects who had a gluten-free diet for a period during childhood; patients with short stature, anemia, or amenorrhea of no obvious cause; or patients with unexplained immunological abnormalities are the groups in which most patients with subclinical celiac sprue have been found and in which potential patients should be sought. Helpful diagnostic tools include antigliadin antibody testing and the observation of absent or reduced Kerckring folds in the descending duodenum in the course of upper gastrointestinal endoscopy.

Adult↗

Serum markers of immune activation and liver allograft rejection.

We monitored the immune response after liver transplantation in 20 patients by measuring the serum levels of soluble interleukin-2 receptor (sIL-2R), soluble CD8 (sCD8), serum amyloid-A protein (SAA), and tumor necrosis factor-alpha (TNF-alpha). In six patients data were available to extend the follow-up period to one year. In all patients mean sIL-2R levels increased in the first month after liver transplantation, and subsequently decreased to values similar to pre-OLT ones, while SAA mean levels rose in the first week after OLT only in patients with rejection. sCD8 levels did not significantly rise after OLT, and TNF-alpha was undetectable in most cases. During episodes of rejection, rejector patients had significantly higher levels of sIL-2R, sCD8, and SAA than stable (without complications) patients. Conversely, no significant difference between rejectors and patients with other complications existed for any of the markers studied. These results diminish the importance of these serum markers of immune activation as laboratory tools in the differential diagnosis of acute rejection from other complications. However, sIL-2R, SAA, and sCD8 levels correlated with the histological grade of rejection and therefore can be utilized to monitor patients with an established diagnosis of acute rejection.

Biomarkers↗

Gliadin immune reactivity is associated with overt and latent enteropathy in relatives of celiac patients.

Antigliadin antibodies have been widely used in the screening of celiac disease. Using this test, candidates for jejunal biopsy were selected from 328 first-degree relatives of 128 adult celiac patients. All relatives geographically available were willing to participate in the study. Twenty-one turned out to be positive for antigliadin antibodies, and in 13 jejunal histology was consistent with celiac disease. In the remaining 8, the morphometric evaluation of jejunal biopsy specimens showed a mean surface to volume ratio that, although in the normal range, was significantly lower than that of other 10 relatives negative for antigliadin antibodies and 16 biopsied controls. It was concluded that antigliadin antibody testing is a valuable method for the screening of celiac disease among family members and that relatives with genetically predisposed gliadin sensitivity, without gross histological lesions but with minor morphometric abnormalities of the jejunal mucosa, may be regarded as subjects with latent celiac disease.

Adolescent↗

Bed-rest-induced hypernatriuresis in cirrhotic patients without ascites: does it contribute to maintain 'compensation'?

Renal function, plasma renin activity, plasma aldosterone concentration and urine excretion of free norepinephrine were evaluated in 13 cirrhotics without previous or ongoing ascites and in 13 healthy subjects, after 6 days of controlled electrolyte intake (40 mmol of Na and 70 mmol of K per day) and during 24 h of recumbency. Plasma concentrations of the atrial natriuretic peptide (ANP) were also measured in 8 patients and 8 controls. Despite a low-normal filtered load of sodium (14.6 +/- 1.2 vs. 17.1 +/- 1.2 mmol/min), cirrhotic patients showed supernormal natriuresis (141.5 +/- 14.1 vs. 78.8 +/- 8.6 mmol/day; p < 0.001). Whereas the fractional excretion of sodium in these patients was twice that of controls (0.70 +/- 0.05 vs. 0.36 +/- 0.04%; p < 0.001), potassium excretion (42.5 +/- 2.7 vs. 43.1 +/- 2.7 mmol/day) and urine volume (1270 +/- 98 vs. 1452 +/- 148 ml/day) did not differ. In cirrhotics, plasma renin activity was reduced (0.50 +/- 0.12 vs. 1.39 +/- 0.33 ng/ml/h; p < 0.02), and plasma aldosterone concentration tended to be lower (66 +/- 10 vs. 86 +/- 9 pg/ml; p = 0.09), while urine norepinephrine excretion did not significantly differ from controls (961 +/- 120 vs. 782 +/- 43 ng/h). ANP was higher in patients than in controls (92 +/- 17 vs. 48 +/- 9 pg/ml; p < 0.05). Natriuresis was directly correlated with ANP (r = 0.69, p < 0.005) and ANP/plasma aldosterone ratio (r = 0.63; p < 0.01) in patients and healthy subjects taken together.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

beta-Galactosidase from Aspergillus niger in adult lactose malabsorption: a double-blind crossover study.

An assessment was made of the efficacy of a beta-galactosidase, obtained from Aspergillus niger and added to intact milk, in decreasing lactose malabsorption and intolerance. Sixteen adult patients with malabsorption and intolerance to this sugar were studied in a double-blind crossover study vs. placebo. A 5-hour hydrogen breath test was used to assess malabsorption of lactose contained in 400 ml milk. When compared with placebo, the addition of exogenous lactase to intact milk caused a statistically significant reduction in the maximum breath H2 concentration (P less than 0.01) and in the cumulative H2 excretion (P less than 0.005). In the same way, the cumulative index for gastrointestinal intolerance was significantly lower (P less than 0.005) after the ingestion of lactase-added milk. This study demonstrates that enzyme replacement therapy, with beta-galactosidases obtained from Aspergillus niger, is effective in decreasing lactose malabsorption and its consequent intolerance in adult subjects with lactase deficiency.

Adult↗

HLA-DP polymorphism in northern Italian celiac patients.

The contribution of HLA-DP genes to celiac disease susceptibility has been investigated in 95 Italian patients, 41 with childhood and 54 with adult disease onset. Polymerase chain reaction amplification, sequence-specific oligonucleotide probe hybridization and restriction fragment length polymorphism analyses have been carried out. All celiac patients and 56 out of 128 random healthy controls were DQw2-positive. The frequency of the DPB1*0101 allele was significantly increased (pc = 0.002, relative risk 5.21) in patients with celiac disease (23.2%) compared to the whole panel of controls (5.5%), but not to the 56 controls bearing DQw2 (10.7%). No significant difference in the frequency of DPB1*0101 was found between celiac patients with pediatric (24.4%) or adult (22.2%) onset. The DPB1*0101 allele was associated with both the DR3-DQw2 and DR7-DQw2 haplotypes. Moreover, our study has not confirmed the association with DPB1*0402 and DPB1*0301 previously reported in celiac children from southern Italy. The linkage of the DPB1*0101 allele with the DQ locus and the observation that the DP but not the DQ association appears to be ethnically dependent strongly support a secondary role of DP molecules in celiac disease susceptibility.

Adult↗

Increased serum concentrations of tumour necrosis factor in beta thalassaemia: effect of bone marrow transplantation.

AIMS: Serum concentrations of tumour necrosis factor-alpha (TNF) were determined in beta thalassemic patients before and after bone marrow transplantation (BMT) to evaluate whether changes in TNF concentrations after BMT were related to immune mediated complications. METHODS: Serum TNF concentrations were determined by enzyme linked immunoassay (EIA) in paired samples from 71 patients with beta thalassemia before and after BMT. Serial samples from 13 patients were also studied for up to six months after BMT. Forty one normal healthy children matched for sex and age were studied as controls. RESULTS: beta thalassemic patients had high serum TNF concentrations before transplantation compared with controls. These were not related to sex, age, duration of disease, number of blood transfusions, transferrin concentrations or splenectomy. DQw1 positive patients showed significantly lower TNF concentrations than non-DQw1 cases. Patients with severe liver fibrosis had significantly higher TNF concentrations. No correlation was found between TNF values and BMT outcome before transplantation but TNF alpha values fell significantly after BMT. The decrease persisted only in patients with successful engraftment. In serial samples studied for up to six months after BMT, TNF values decreased but in four out of five patients with graft rejection and in all five with acute graft versus host disease (GVHD) sharp increases occurred at the time of clinical symptoms. No correlation was found between the degree of GVHD and serum TNF-alpha concentrations nor between TNF-alpha concentrations after BMT and the presence of bacterial, viral, and fungal infections. CONCLUSIONS: About 50% of beta thalassemic patients have increased serum TNF, and the changes after BMT are related to the occurrence of immune mediate complications. The persistence of low TNF concentrations after successful engraftment may be due to the preparative regimen and the lack of adverse immune reactions.

Bone Marrow Transplantation↗

Serum amyloid A protein concentration in bone marrow transplantation for beta thalassaemia.

AIMS: To investigate whether serum amyloid A protein (SAA) and C-reactive protein (CRP) concentrations could be used in the management of beta thalassaemic patients undergoing bone marrow transplantation (BMT). METHODS: Serum SAA and CRP concentrations were determined in paired samples from 66 patients with beta thalassaemia before and after BMT. Serum SAA concentrations were determined by an enzyme linked immunoassay (EIA); serum CRP concentrations were determined by a nephelometric assay. RESULTS: Serum SAA concentrations before transplantation were significantly higher in the group that subsequently rejected the transplant than the group without complications. SAA concentrations increased after BMT in acute graft versus host disease (GvHD) and rejection. No significant increase in SAA or CRP was found in chronic GvHD. Increases in serum in SAA and CRP concentrations were not related to concomitant infection episodes. CONCLUSIONS: The different acute phase response in acute GvHD and rejection compared with chronic GvHD suggests that different immunopathogenic mechanisms are responsible.

Acute Disease↗

Oral disodium cromoglycate treatment on irritable bowel syndrome: an open study on 101 subjects with diarrheic type.

Several studies on the usefulness of oral disodium cromoglycate (DSCG) in the treatment of systemic adverse reaction to foods have been performed, with less attention to gastroenterological symptoms. In the present study, we selected 101 patients with diarrheic-type irritable bowel syndrome which improved after an elimination diet and worsened after a challenge with specific food(s). All patients were then tested for 48 commercial alimentary antigens by skin prick test (SPT) and underwent 8 wk of oral DSCG (500 mg three times a day), and the results were evaluated by means of a semiquantitative subjective and objective score. We observed an improvement of the symptoms in 67% of the 74 SPT-positive patients, whereas only 41% of the 27 SPT-negative patients showed a positive response to DSCG (p less than 0.05). These data confirm the protective role of DSCG in food-dependent diarrheic-type irritable bowel syndrome with food allergy features.

Administration, Oral↗