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Biomedical subjects

E Pisi

Publications and source records attributed to E Pisi.

At least 91 records · Page 5Linked to original sources

Splanchnic vein measurements in patients with liver cirrhosis: a case-control study.

The portal venous system was evaluated by real-time ultrasonography in 100 consecutive cirrhotic patients and 100 pair-matched controls to assess the sensitivity and specificity of ultrasound findings in detecting or excluding cirrhosis. The best discriminant findings were the expiration diameters of the superior mesenteric and the splenic vein and, chiefly, their sum corrected by body surface. In cirrhotics the calibers of the splanchnic veins significantly increase in relation to the extent of esophageal varices, but in individual patients this increase cannot predict the extent of varices, which are the main determinant of the bleeding risk.

Adult↗

Aberrant expression of HLA-DR antigens on bileduct epithelium in primary biliary cirrhosis: relevance to pathogenesis.

Direct immunofluorescence with an avidinbiotin system was used to investigate the expression of MHC molecules HLA-DR and HLA-A,B,C on bileducts in cryostat sections from 10 primary biliary cirrhosis (PBC) patients. Needle biopsy specimens from 55 patients with various chronic liver disorders, surgical biopsy specimens from 2 patients with recurrent secondary cholangitis, and 4 normal livers were used as controls. Normal bileducts did not express DR whereas in 8/10 PBC biopsy specimens there were varying degrees of cytoplasmic DR staining in septal or interlobular bileduct epithelium. In the early histological stages of PBC the aberrant DR expression was multifocal, but in late-stage specimens whatever ducts remained were all positive. This pattern resembles that in focal thyroiditis and suggests that DR expression is an early manifestation of autoimmune cholangitis. In 6/61 control biopsies only weak staining was detected in occasional small interlobular ducts. The class I HLA-A,B,C expression normally seen on biliary epithelium was increased in 8/10 PBC cases and in 19/61 non-PBC biopsies. Perhaps the aberrant expression of HLA-DR antigens on bileduct epithelium in PBC enables these cells to present "self antigens" to sensitised T-lymphocytes and to promote autorecognition, possibly in response to several environmental triggers; the increased HLA-A,B,C, expression may be a means of amplifying T-cell cytotoxic responses.

Adult↗

Insulin-dependent metabolism of branched-chain amino acids in obesity.

The effect of euglycemic hyperinsulinism on branched-chain amino acids (BCAA; valine, isoleucine and leucine) was evaluated in five obese subjects and five controls. A continuous intravenous insulin infusion raised plasma insulin to a steady-state level. An artificial endocrine pancrease that infused glucose was used to sustain euglycemia. Basal and steady-state insulin levels were significantly higher in the obese subjects than in the controls. The amount of glucose infused to maintain euglycemia and its ratio to steady-state insulin levels was significantly lower in the obese subjects, suggesting an impaired insulin action on glucose metabolism. Basal BCAA levels were similar in the two groups of subjects. During insulin infusion the decremental areas of BCAA below basal levels were significantly lower in the obese patients (63 +/- 5 nmol/mL X min v 143 +/- 8 nmol/mL X min, P less than 0.001), as was the ratio of the decremental areas of BCAA to the incremental areas of insulin (1.11 +/- 0.05 nmol/microU v 3.30 +/- 0.24 nmol/microU, P less than 0.001). Our data suggest that insulin resistance in obesity reduces hormonal effects on glucose as well as on BCAA metabolism.

Amino Acids, Branched-Chain↗

The euglycemic clamp technique in patients with liver cirrhosis.

Tissue sensitivity to insulin and insulin metabolic clearance rate were assessed by means of the euglycemic clamp technique in 11 controls and 11 patients with liver cirrhosis. The method was carried out using an artificial endocrine pancreas. The amount of glucose infused to keep euglycemia, as well as the ratio of glucose infused to steady-state insulin level, were significantly lower in cirrhotics as compared to controls (p less than 0.001). The metabolic clearance rate of insulin did not show significant differences between the two groups. Our results confirm that a marked insulin resistance is present in cirrhotics, as previously shown by means of different techniques.

Adult↗

Steroid treatment lowers hepatic fibroplasia, as explored by serum aminoterminal procollagen III peptide, in chronic liver disease.

Serum aminoterminal type III procollagen peptide (sPIIIP) has been proposed as an index of hepatic fibroplasia. sPIIIP was retrospectively evaluated in 34 treated and five untreated patients affected by chronic active hepatitis with or without cirrhosis by an RIA test. Serum samples taken before and after 6 months of treatment were tested in all cases. In 15 of the treated and all untreated patients, 6-20 (median 13) sera, corresponding to a median follow-up of 43 months were studied. Before treatment, the sPIIIP median value was 18.6 ng/ml; after 6 months of treatment, it decreased to 13.6 ng/ml (p less than 0.005). Follow-up sPIIIP levels were significantly lower in treated than in untreated patients (p less than 0.05), at each interval considered, except for the last control (39 months). In seven patients, treatment was discontinued: sPIIIP rose rapidly in six; four of them were retreated and this was followed by a new decrease. In four patients, sPIIIP was tested weekly from the onset of the treatment: it reverted to normal values within the first week in all cases, while GOT decreased later. sPIIIP is significantly and rapidly reduced by steroids. Steroid withdrawal is generally followed by a rebound, with a new decrease when treatment is restarted. Since sPIIIP is more rapidly lowered than GOT levels, the above data support the hypothesis that steroids can directly affect collagen metabolism.

Adolescent↗

Antibodies to gliadin in adult coeliac disease and dermatitis herpetiformis.

Antibodies to gliadin, searched for by indirect immunofluorescence and a micro-ELISA, were detected in 16 (64%) of 25 sera from patients with adult coeliac disease and in 13 (45%) of 29 with dermatitis herpetiformis. Although the sensitivity of the two tests was relatively low in the whole groups, it increased when only cases with severe jejunum abnormalities were considered (93% for coeliac disease and 81% for dermatitis herpetiformis). A significant correlation was found between antigliadin antibodies and the severity of jejunum damage in both diseases. Moreover, most coeliac and dermatitis herpetiformis patients with antigliadin antibodies were on normal diet. The specificity of the tests was 100% for the immunofluorescence and fairly good for the micro-ELISA, as only 5 (11%) of the 46 disease control patients (Crohn's disease, ulcerative colitis) were positive for antigliadin antibodies. R1-reticulin antibody test was equally specific but less sensitive in both groups. We conclude that antigliadin antibodies are useful in the diagnosis of patients with active adult coeliac disease and dermatitis herpetiformis with gluten-sensitive enteropathy. Moreover, the two tests make it possible to monitor the compliance to gluten-free diet in both diseases.

Adolescent↗

R1 reticulin antibodies: markers of celiac disease in children on a normal diet and on gluten challenge.

R1 reticulin antibodies were found in sera from patients with childhood celiac disease (CCD). Although the overall sensitivity of R1 in the diagnosis of CCD was relatively low (16/43 = 37%), when only those cases in an active phase of the disease were considered, the sensitivity increased (16/24 = 67%). In spite of its low sensitivity, the R1 assay did show a high degree of specificity, as this antibody was not found in children with post-enteritis syndrome or in healthy controls. R1 antibodies, when found in active CCD, always turned out to be positive when tested on human liver as substrate. While this fact did not enhance the sensitivity of the test, it strengthened its specificity, since R1, found in pathological conditions other than CCD, was nearly always negative on human tissue. Although the R1 reticulin antibody test cannot replace jejunal biopsy in the diagnosis of CCD, its assay, particularly on human liver as substrate, can be considered a useful tool in the screening of celiac patients.

Animals↗

Liver cell surface expression of the antigen reacting with liver-kidney microsomal antibody (LKM).

To test the hypothesis that liver membrane antibodies, found in all liver-kidney microsomal antibody (LKM) positive sera from patients with chronic active hepatitis, were directed against antigens shared by both hepatocellular endoplasmic reticulum and plasma membranes, absorption experiments have been performed using viable isolated hepatocytes and liver microsomes as antigens. Results are in agreement with the above hypothesis, LKM, which displays a restricted organ specificity, is thus able to react with antigenic determinants expressed on the liver cell surface, as it has been demonstrated for strictly organ specific antibodies directed against thyroid, adrenal and gastric parietal cell microsomes.

Animals↗

Correlation between Ito cells and fibrogenesis in an experimental model of hepatic fibrosis. A sequential stereological study.

The relationship between Ito cells and hepatic fibrogenesis has been investigated in an experimental model: intraperitoneal injection of heterologous serum in rats leads to the appearance of fibrous septa within 5 weeks. Groups of rats were sacrificed at various intervals (from 2.5 to 20 weeks), saline-injected rats being used as controls. Liver fragments were prepared for light and electron microscopy and determination of hydroxyproline. Ito cells were identified by defined morphological criteria on 1 micron sections. The volume density (VD) of Ito cells and fibrous septa, and the Ito cell index were determined. Ito cells represent a very relevant component of early septa. In later stages, the VD of cells with morphological features of Ito cells falls to very low values. This might be related to modulation of Ito cells to fibroblasts. The increase of tissue hydroxyproline is delayed with respect to the peak VD of septal Ito cells, actually corresponding to the fall in the VD of septal Ito cells. The striking increase in the VD of total Ito cells cannot be related to a theoretically possible increase in the volume of single Ito cells, as VD always parallels the Ito cell index. These data suggest a hyperplastic reaction, possibly associated with a cellular migration from the lobules to early septa.

Animals↗

Plasma amino acid response to protein ingestion in patients with liver cirrhosis.

The metabolic effects of a protein-rich meal were studied for 3 h in 10 controls and in 20 cirrhotic patients. After protein ingestion, blood glucose did not vary significantly. Insulin and glucagon levels rose in controls and, more markedly, in cirrhotics. Aromatic amino acids and tryptophan increased more in cirrhotics as a result of their decreased liver function. Similarly, branched-chain amino acids increased by 153 +/- 14 nmol/ml X min (mean +/- SE) in controls and by 259 +/- 27 nmol/ml X min in cirrhotics (p less than 0.02), in the presence of a markedly increased insulin response. Branched-chain amino acid metabolism mainly occurs in skeletal muscle under insulin control; in cirrhosis, it might be reduced as a consequence of insulin resistance. To support this hypothesis, the effects of the protein meal were compared with those of an oral glucose load in 15 cirrhotic patients. Branched-chain amino acid response to protein ingestion significantly correlated with blood glucose response to oral glucose (r = 0.714), and with insulin resistance during the glucose tolerance test, when assessed by the insulinogenic index (r = 0.628). Similarly, in 8 patients, increased branched-chain amino acid response also correlated with the index of tissue sensitivity to insulin obtained by means of the glucose clamp technique during continuous insulin infusion (r = -0.809). We conclude that liver cirrhosis is characterized by an abnormal branched-chain amino acid response to protein ingestion, which matches the well-known intolerance to oral glucose. Both alterations are possibly due to decreased peripheral insulin activity on substrates.

Amino Acids↗

Antibodies to cardiac conducting tissue and abnormalities of cardiac conduction in rheumatoid arthritis.

The prevalence of antibodies to cardiac conducting tissue and cardiac conduction electrocardiographic abnormalities were studied in 60 patients with rheumatoid arthritis (RA). Complete or incomplete right bundle branch block (RBBB) was found in 21 patients (35%). Antibodies to cardiac conducting tissue were found in 16 (76%) of the 21 with RBBB and in eight (21%) of the 39 without RBBB. Cardiac conducting tissue antibodies (CCTA) were found only in one of 42 patients with RBBB unrelated to RA and in two out of 60 normal subjects. This newly documented immunological abnormality is thus correlated with disorder of conducting tissue.

Adolescent↗

Evaluation of serum rosette inhibitory factors in chronic liver disease.

Serum rosette inhibitory factors (IF) were detected in 61% of 18 sera from HBsAg negative and in 78% of 14 sera from HBsAg positive chronic active liver disease (CALD) patients, who were not under immunosuppressive treatment. In CALD patients, who were under treatment for at least 6 months, IF were detected in 66% of the HBsAg positive patients and only in 18% of the HBsAg negative ones. After precipitation of the serum gamma-globulins by ammonium sulphate, IF were found in the supernatant only in HBsAg positive sera, while completely disappeared in HBsAg negative ones. A significant correlation between serum IF and factors reacting in immunofluorescence (IFL) with a T enriched preparation of lymphocytes was documented only in HBsAg negative cases. No correlation was found between serum IF and circulating immune complexes (IC) or lymphocytotoxins in any of the sera tested. From all these data it is concluded that serum IF detectable in HBsAg negative CALD cases are probably immunoglobulins. Our data would favour the hypothesis that they are anti-T lymphocytes antibodies, since no correlation was found between serum IF and circulating IC. Similar factors, detectable in HBsAg positive sera, are, at least in part, different. The role of such factors in the modulation of the immune response in CALD patients is discussed.

Adolescent↗

Muscle protein breakdown in uncontrolled diabetes as assessed by urinary 3-methylhistidine excretion.

In an attempt to evaluate muscle protein catabolism in patients with uncontrolled diabetes, urinary excretion of 3-methylhistidine was measured in eight diabetic subjects, during poor control and after achievement of satisfactory control. The results were compared with the excretion values of ten healthy subjects fed a similar amount of meat. In the diabetic patients in poor metabolic control, 3-methylhistidine excretion was significantly increased compared with the healthy subjects, and returned to normal when a satisfactory glycaemic control was achieved. No significant differences were observed between ketonuric and non-ketonuric uncontrolled patients. Improved glycaemic control reduced 3-methylhistidine excretion in both insulin-dependent and non-insulin-dependent diabetes. These results suggest increased protein catabolism causing muscle protein loss and negative nitrogen balance in diabetic patients with poorly controlled disease.

Adult↗

Branched-chain amino acids and alanine as indices of the metabolic control in type 1 (insulin-dependent) and type 2 (non-insulin-dependent) diabetic patients.

Alterations in plasma branched-chain amino acids (valine, isoleucine and leucine) and alanine have been described in patients with insulin-dependent diabetes mellitus who have poor metabolic control. To assess the relevance of these abnormalities as indices of metabolic control, we sequentially evaluated plasma amino acids in 14 poorly controlled diabetics (seven Type 1 (insulin-dependent) and seven Type 2 (non-insulin-dependent) patients) until good control was achieved. The sum of branched-chain amino acids in both groups of uncontrolled diabetic patients was significantly increased compared with the values for the same subjects in good metabolic control. No statistically significant differences were present between ketotic and non-ketotic uncontrolled patients. The amelioration of the diabetic state with either insulin treatment or oral hypoglycaemic agents, reduced progressively branched-chain amino acids. The sum of valine, isoleucine and leucine strictly correlated with daily urinary glucose (r = 0.73), but less well with fasting blood glucose (r = 0.43), non-esterified fatty acids (r = 0.46) and glycosylated haemoglobin (r = 0.38). Alanine did not show any statistically significant differences at various stages of diabetic control. Branched-chain amino acids, but not alanine, may be used as indices of short-term diabetic control.

Alanine↗

Ammonia-induced changes in pancreatic hormones and plasma amino acids in patients with liver cirrhosis.

The contribution of hyperammonemia to plasma amino acid imbalance in patients with liver disease was assessed in 10 subjects with chronic hepatitis and in 17 advanced cirrhotics. Insulin, glucagon, and plasma amino acids were determined both in the basal state and 45 min after oral ammonium chloride, at doses used in the ammonia-tolerance test. In cirrhotics, ammonia increased to 3 times basal values, in association with a rise in insulin and, more marked, in glucagon. Aromatic amino acids and free tryptophan further increased, while a significant fall in branched-chain amino acids and glutamate was observed. The increase in ammonia levels strongly correlated with the increase in glucagon (r = 0.707). Two patients, with large esophageal varices, showed signs of disturbed consciousness, in association with a marked rise in ammonia and in the ration of free tryptophan to the sum of neutral amino acids. In patients with chronic hepatitis, whose ammonia levels rose slightly, minor variations in pancreatic glucoregulatory hormones and plasma amino acids were observed, as also happened in 10 healthy subjects following ammonium chloride ingestion. Our data fit with the hypothesis that the plasma amino acid imbalance of cirrhotics may be partly due to ammonia-induced changes in pancreatic hormones.

Adult↗