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Biomedical subjects

G Gasbarrini

Publications and source records attributed to G Gasbarrini.

At least 487 records · Page 27Linked to original sources

Chronobiological study of factors affecting plasma aldosterone concentration in cirrhosis.

We studied the mechanisms leading to derangement of aldosterone secretion in cirrhosis. The circadian patterns of plasma renin activity (PRA), aldosterone, cortisol, sodium, and potassium were studied in 16 nonazotemic cirrhotics (group 1 without ascites, 7 cases; group 2 with ascites, 9 cases) and 7 healthy controls. Group 1 did not differ from controls in aldosterone, sodium, and potassium mean daily levels (mesors), but had reduced PRA mesor (p less than 0.05). Moreover, minor derangements in circadian patterns of PRA, aldosterone, and potassium were also found. Group 2 not only showed an increased mesor of PRA (p less than 0.05), aldosterone (p less than 0.001), and reduced sodium (p less than 0.005), but also achronia in daily fluctuations of PRA, aldosterone, and potassium. In all groups the mesors of PRA and aldosterone were correlated (r greater than or equal to 0.82; p less than 0.01 or less), but the regression line slopes of patients were steeper than those of controls (group 1, p less than 0.05; group 2, p less than 0.01). Moreover, although in controls and some group 1 patients aldosterone paralleled cortisol rhythmicity, most group 2 patients had aldosterone daily patterns correlated with those of PRA. Finally, no relationships between plasma potassium and aldosterone concentrations were found in patients, whereas they were strictly related in controls. These results suggest that the renin-angiotensin system is the prevalent determinant of aldosterone secretion in cirrhosis.

Adult↗

T lymphocyte subsets implicated in cytotoxicity in autologous hepatocytes in chronic active hepatitis patients with active viral replication.

We investigated inhibitory effect of various monoclonal antibodies on T-cell-mediated cytotoxicity against autologous hepatocytes in 24 patients with hepatitis B surface antigen/hepatitis B e antigen (HBsAg/HBeAg)-positive chronic active hepatitis. A significant reduction of cytotoxicity index occurred after preincubation of T lymphocytes with anti-Leu 7 (killer-natural killer cells), D1/12 (Ia-positive cells), 5/9 (restricted helper/inducer cells), and MLR4 ("activated" and radiosensitive helper cells) monoclonal antibodies (MAb). Anti-Leu 2a (cytotoxic/suppressor cells) and anti-Leu 3a (helper/inducer cells) MAb did not affect cytotoxic activity. This finding supports the hypothesis that the T cytotoxic reaction in this in vitro system is probably due to two mechanisms: first, spontaneous cell membrane cytotoxicity sustained by anti-Leu-7-positive lymphocytes; and second, specific cytotoxicity mediated by activated Ia-positive cells. We also found that the presence of helper/inducer cells (5/9 positive) appears to be a prerequisite for the cytotoxic reaction.

Adult↗

Gluten specific suppressor T cell dysfunction in coeliac disease.

A T lymphocyte direct migration inhibition factor test has been used to investigate the function of the specific suppressor T cell population controlling the immune response to gluten in coeliac disease. The test has been carried out in 21 adult coeliac patients, 22 Mantoux- healthy controls and eight Mantoux+ donors using gluten fraction III and purified protein derivative, as antigens. All coeliacs, but two, were Mantoux-. When gluten fraction III was used a significant migration inhibition was observed in coeliac patients compared to controls; such migration inhibition was abrogated by coculturing in a 1:1 ratio coeliac T cells with T cells from controls or Mantoux+ donors. On the contrary, the addition to coeliac T cells of T lymphocytes from other coeliacs did not abolish migration inhibition to gluten. Pretreatment of normal T cells with mitomycin C prevented their abrogating activity on migration inhibition of coeliac T lymphocytes. When purified protein derivative was used as antigen a significant migration inhibition was observed in Mantoux+ donors compared with healthy subjects and such migration inhibition was abolished by co-culturing T cells from Mantoux+ donors with those from Mantoux- controls and coeliac patients. Our results show that coeliac T cells, while retaining their ability to suppress the immune response to purified protein derivative, cannot suppress the immune response to gluten and are consistent with the hypothesis that a gluten specific suppressor T cell dysfunction, rather than a generalised T lymphocyte defect, may play a role in the pathogenesis of coeliac disease.

Adult↗

Ageing and small-bowel mucosa: a morphometric study.

A direct effect of ageing in reducing mucosal surface area of the small intestine is still disputed. The aim of this study was to morphometrically evaluate a panel of jejunal biopsy specimens obtained from 16 elderly patients and 22 younger controls, all complaining of abdominal symptoms but without evidence of malabsorption and/or malnutrition in either group. Quantitative histology was performed by calculating the surface area to volume ratio of jejunal mucosa and the mean enterocyte height. The mean of surface to volume ratios in geriatric patients (97.6 +/- 18), although slightly reduced, did not significantly differ from that of younger controls (107.6 +/- 26) and no significant correlation was found between surface to volume ratio and age in years. The mean enterocyte height in the elderly group (30.1 +/- 1.2 microns) did not significantly differ from that of younger controls (31.3 +/- 2.3 microns). In conclusion, the frequent finding of malnutrition due to malabsorption in the elderly should not be attributed to a reduction of jejunal surface area as a mere consequence of age.

Adolescent↗

Effects of somatostatin on plasma ammonia and amino acid profile during fasting and after protein feeding in cirrhotic patients.

The effects of somatostatin on fasting and absorptive plasma ammonia and amino acids were studied in 12 cirrhotic patients. They received a 6 h intravenous infusion of somatostatin (500 micrograms/h) or saline, starting 90 min before protein feeding. During the fasting period somatostatin significantly reduced plasma ammonia (-18%) and total tryptophan (-39%), increased plasma leucine (+19%), isoleucine (+17%), glutamine (+22%), glycine (+13%), arginine (+14%) and lysine (+12%), and prevented the significant fall of phenylalanine (-8%), tyrosine (-6%), alanine (-8%) and threonine (-9%) seen with saline. The percent changes in ammonia and glutamine concentrations were inversely correlated (r = -80; p less than 0.001) After protein ingestion, somatostatin slowed the maximal plasma increase in ammonia and alpha-nitrogens by at least two hours, but their total 5 h plasma response was not reduced, and even, in some instances, significantly increased (valine, leucine, glutamine, alanine and serine) with respect to saline. The results suggest that in fasting cirrhotics somatostatin reduces plasma ammonia, probably through an impaired intestinal ammoniogenesis from circulating precursors, and inhibits the disposal of branched chain, aromatic (except tryptophan) and gluconeogenic amino acids. Furthermore, it delays, but does not reduce, the plasma increase in nitrogen after protein ingestion.

Adult↗

Correlative scanning electron microscopy in the study of human gastric mucosa.

We studied two aspects of the human gastric mucosa: the surface morphology of mucous cells, as viewed by scanning electron microscopy (SEM); the glycosidic components of intracellular mucins, characterized by means of lectins. The latter were conjugated with fluorescein isothiocyanate and with colloidal gold-silver for the visualization of the reaction products in light microscopy (LM) and in SEM (backscattered mode) respectively. The surface morphology of mucous cells appears to be correlated to the secretory state. In gastric ulcers we found a prevalence of non-secreting cells. A decrease in glycosidic receptors for fucose-binding lectin and galactose-(1-3)-N-acetyl-galactosamine-binding lectin was also observed. This suggests the presence of an impaired mucus secretion which may play a role in the pathogenesis of gastric ulcer. Spiral bacteria, supposed to be aetiologically related to peptic ulcer and gastritis, were easily detected by SEM. Intestinal metaplasia defined "complete" in LM showed surface morphology and glycosidic components different from those of true intestinal mucosa. This implies the necessity of taking into account also these parameters when classifying this lesion. The same applies to polyps. Our data indicate that correlative SEM may contribute further information on the pathogenesis and pathology of gastric diseases.

Adult↗

The renin-angiotensin-aldosterone system in human hepatic cirrhosis.

Changes in the renin-aldosterone axis have long been recognized as occurring in patients with liver cirrhosis; different patterns are encountered during the different stages of the disease. Patients in whom ascites has not yet developed usually show depressed plasma renin activity or concentration. The low levels may be due to effective extracellular fluid volume expansion, although this view is not accepted by all authors. According to the overflow theory of ascites formation, sodium retention should occur before the appearance of ascites and, hence, volume expansion should ensue. Since plasma aldosterone concentration is usually normal or even depressed at this stage, increased sodium retention can only be explained by an enhanced renal tubular sensitivity to mineral-corticoid hormone. Mounting evidence suggests that such an abnormality is present in nonascitic patients and progresses as the disease worsens. This abnormality also explains why greater than 50% of patients with ascites and avid renal sodium retention have plasma renin activity and aldosterone within the normal range. In the late stages of the disease, the development of massive compartmentalization of fluid as ascites, along with changes in cardiovascular homeostasis (reduced peripheral resistances, opening of arterovenous shunts, and reduced efficiency of the sympathetic nervous system), lead to striking activation of the renin-angiotensin-aldosterone system. The system is responsible for sodium retention and for the maintenance of arterial pressure, and can be involved, at least in part, in reducing renal perfusion.

Aldosterone↗

A multicenter double-blind controlled trial comparing lidamidine HCl and loperamide in the symptomatic treatment of acute diarrhoea.

The efficacy of 1-(2,6-dimethylphenyl)-3-methyl-amidinourea hydrochloride (lidamidine HCl, WHR-1142 A) an aryl-substituted amidinourea recently synthesized, was compared with that of loperamide in 32 patients with acute diarrhoea. The results of the study show that lidamidine HCl and loperamide had comparable effects in the pharmacological treatment of acute non-specific diarrhoea. Lidamidine HCl was also shown to be well tolerated; side-effects were generally minor and self-limiting.

Acute Disease↗

S.E.M. study I: Gastric and duodenal lesions induced by non-steroidal anti-inflammatory drugs (aspirin, piroxicam) in man.

A scanning electron microscopy (SEM) study was performed on the gastric and duodenal mucosa of 14 patients treated with Aspirin or Piroxicam. Six patients with normal mucosal morphology were treated with either 1.5 g/day of Aspirin (3 patients) or 20 mg/day or Piroxicam (3 patients) for one month. In addition, 8 rheumatic patients were treated with a similar dose of Aspirin (4 patients) or Piroxicam (4 patients) for at least 4 months. SEM was used to evaluate the following parameters: mucosal structure, cellular exfoliation and anisocytosis, alteration of the microvilli (blebs). The mucosa showed various aspects of alterations ranging from minimal changes (microvillar alteration) to a completely subverted structure both in the stomach and in the duodenum. Mucosal changes, both on the edge of the macroscopic lesions and at a distance from these, were visible with SEM even when endoscopy was normal. Piroxicam appeared slightly less damaging than Aspirin, and no difference was observed between short-term and long-term treated patients, either with Aspirin or with Piroxicam.

Adult↗

S.E.M. study II: Protective effect of ranitidine against gastric and duodenal lesions induced by non-steroidal anti-inflammatory drugs.

The effect of Ranitidine on the gastric and duodenal lesions induced by Aspirin or Piroxicam was studied by scanning electron microscopy (SEM). Twelve patients were entered into the study. The first group consisted of 6 patients with normal basic morphology, of which 3 were treated with 1.5 g of Aspirin and Ranitidine 300 mg/day, and 3 with 20 mg of Piroxicam and Ranitidine 300 mg/day, for one month. The second group was composed of 6 rheumatic patients, 3 of which took 1.5 g of Aspirin and the other 3 received 20 mg of Piroxicam per day for at least four months. Ranitidine (300 mg/day) was then administered concomitantly for one month to all these 6 patients. Overall, Ranitidine appeared to have a positive effect in preventing the development of gastroduodenal lesions induced by these anti-inflammatory drugs in the first group of patients. No differences were observed in the ability of Ranitidine to promote the healing of lesions induced by chronic treatment. Ranitidine, however, appeared to be more effective in preventing lesions induced by Aspirin rather than those induced by Piroxicam.

Adult↗

Liver-specific autoantibodies in chronic hepatitis B virus infection.

Anti-liver-specific protein (LSP) antibody and liver membrane autoantibody (LMA) have been evaluated in 88 patients with hepatitis B virus (HBV)-induced chronic liver disease by means of radioimmunoprecipitation and immunofluorescence. Among our patients, 38 presented circulating HBe antigen while 43 had HBe antibody and seven were negative for both. Anti-LSP was mainly found in HBeAg positive chronic active hepatitis (CAH), anti-HBe in positive CAH and in anti-HBe positive chronic persistent hepatitis (CPH). Similar prevalences of LMA (range 13-33%) were detected in the various groups studied. Taking into account the histological diagnosis of disease activity (periportal inflammation and piecemeal necrosis) no significant differences were found between active and inactive patients. Taking into account the HBeAg/anti-HBe status, no significant differences were found between the patients positive for 'e' antigen or 'e' antibody. Humoral autoimmune reactions may also play a role in HBV-induced chronic (active) liver disease irrespective of HBeAg/anti-HBe status and hence of the viral replication activity of the patients.

Autoantibodies↗

DR and non-DR Ia allotypes are associated with susceptibility to coeliac disease.

We have studied the frequency of HLA-DR, -MT, and -MB antigens in adult patients with coeliac disease and in a group of healthy controls, evaluating the strength of the observed associations by measuring the aetiologic fractions. Among the antigens significantly associated with coeliac disease, MB2 (DQw2) showed an aetiologic fraction higher than those of DR3 and DR7. Our results suggest that MB2, as associated more frequently than other specificities with a hypothetical disease predisposing gene, may play a role in the pathogenesis of coeliac disease. The significant association of DR3 and DR7 with coeliac disease may be ascribed to linkage disequilibrium of these antigens with MB2.

Adolescent↗

Renal function impairment induced by change in posture in patients with cirrhosis and ascites.

The assumption of upright posture by patients with liver cirrhosis leads to striking activation of adrenergic and renin-angiotensin systems. The tilting-induced modifications in renal function of eight healthy controls and 14 untreated patients with liver cirrhosis and ascites were related to plasma concentrations of noradrenaline, renin activity and aldosterone. All patients had preserved renal blood perfusion. All parameters were evaluated during bed rest for two hours and in the sitting posture for one hour. Basal plasma renin activity (0.1 greater than p greater than 0.05), aldosterone and noradrenaline concentrations (p less than or equal to 0.01) were raised in cirrhotics. The renal function tests (creatinine clearance, filtered sodium, tubular rejection fraction, urinary sodium excretion) were significantly reduced in cirrhosis. Under basal conditions, in cirrhotic patients tubular rejection fraction and urinary sodium excretion were inversely related to both noradrenaline and aldosterone concentrations. After tilting, the noradrenaline and aldosterone integrated outputs (sigma delta) were significantly greater in cirrhosis. All renal function tests significantly decreased in cirrhotics, whereas creatinine clearance only significantly decreased in controls. Patient's tubular rejection fraction of sodium and sodium excretion were related to sigma delta aldosteronaemia (r = -0.72; p less than 0.01), but no longer to sigma delta plasma noradrenaline.

Adult↗

Quantitative assessment of the mucosal architecture of jejunal biopsy specimens: a comparison between linear measurement, stereology, and computer aided microscopy.

Fifty jejunal biopsy specimens obtained from normal subjects and from untreated and treated patients with coeliac disease were assessed blindly by three independent observers, each of them using different morphometric techniques-namely, linear measurement, stereology, and computer aided microscopy. In two of 26 control biopsy specimens linear measurement was not possible because of distortion of villi. Highly significant (p less than 0.001) correlation coefficients were found between the different techniques. With all methods significant differences between controls and patients with coeliac disease and between treated and untreated coeliac patients were found. Only by stereology, however, was there no overlap between results for patients and those for controls. In view of the limitations of linear measurement and the high cost and complexity of computer aided microscopy, we propose that a simple stereological technique using an eyepiece graticule is the method of choice in the quantitative assessment of mucosal architecture in jejunal biopsy specimens.

Biopsy↗

Importance of plasma aldosterone concentration on the natriuretic effect of spironolactone in patients with liver cirrhosis and ascites.

23 cirrhotics with ascites and sodium retention, whose aldosteronemia had been evaluated after an equilibration period at controlled sodium intake at the occasion of previous studies, were retrospectively investigated. The dosage of spironolactone needed to induce a negative sodium balance correlated significantly with plasma aldosterone concentration: r = 0.64; p less than 0.001. However, in cases with plasma albumin concentration less than 3 g/dl, glomerular filtration rate less than 80 ml/min, and plasma sodium concentration less than 136 mmol/l such a relationship was no longer significant. The diuretic response to spironolactone is mainly linked to plasma aldosterone concentration. Factors affecting the removal of ascites from the peritoneal cavity and renal sodium handling can influence the expected diuretic response to the drug.

Aldosterone↗