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Biomedical subjects

G Budillon

Publications and source records attributed to G Budillon.

At least 73 records · Page 4Linked to original sources

Adult Fanconi syndrome and liver cirrhosis.

A female presenting primary adult Fanconi syndrome and liver cirrhosis of obscure aetiology is described. The only other report of this association appeared over four decades ago and concerned a male patient who, however, was subsequently diagnosed as having Wilson's cirrhosis, a well-known cause of acquired Fanconi syndrome. Therefore, the present report is the first account of primary Fanconi syndrome with authentic cryptogenic liver cirrhosis. Since the chronic urinary amino acid leakage is not a pathogenetic mechanism of the cirrhotic process, we believe that this association in fortuitous.

Fanconi Syndrome↗

Effects of anthracycline therapy on intestinal absorption in patients with advanced breast cancer.

Although cytotoxic chemotherapy for human cancer has been reported to induce alterations in intestinal permeability, its effects on the absorptive process are still controversial. We have studied mediated and nonmediated absorption in 10 patients with metastatic breast cancer before and after treatment with Adriamycin by the use of specific test sugars given orally and their subsequent urinary recovery, as measured by chromatography. Mediated absorption was investigated by the use of D-xylose and 3-O-methylglucose, while lactulose and L-rhamnose were used to study nonmediated permeation. Lactulose is considered a marker of unmediated paracellular (tight junction) permeation, while L-rhamnose explores passage across cell membranes. The test was performed on patients before and on the second and the eighth days after Adriamycin administration, and only once in 22 age-matched healthy women. Under basal conditions, as well as 2 and 8 days after chemotherapy, D-xylose and 3-O-methylglucose absorption was 35% lower in patients than in controls (P less than 0.001). Lactulose absorption was significantly higher in patients than in controls under basal conditions (P less than 0.001); it reached levels three times higher the second day after chemotherapy, and returned to basal levels by the eighth day. The data suggest an early reversible effect of Adriamycin on cellular tight junctions with resulting increased permeabilization. This effect seems of a toxic nature rather than due to increased cell loss. It is interesting that both nonmediated absorption and mediated absorption were already altered before chemotherapy in cancer patients, suggesting a preexisting functional damage of the intestine. The significance of this alteration as a potential mechanism of cancer cachexia is discussed.

3-O-Methylglucose↗

Diagnostic efficiency in discriminating liver malignancies from cirrhosis by serum gamma-glutamyltransferase isoforms.

Total GGT and GGT complexed with low-density-lipoprotein plus very low-density lipoprotein (LDL + VLDL) have been evaluated in sera from 53 healthy subjects, 23 patients with chronic hepatitis, 87 with liver cirrhosis and 50 with liver tumors (primary and metastatic). A cut-off of 20 U/l of GGT complexed with LDL + VLDL results in a diagnostic sensitivity of 84% for liver tumor patients, and a diagnostic specificity of about 80% towards the two groups of patients affected by cirrhosis or chronic hepatitis. This test, because of its high diagnostic efficiency, is a useful addition to the battery of laboratory tests that serve to discriminate cirrhosis and chronic hepatitis from liver malignancies.

Adolescent↗

Effect of nicotinic acid administration on serum levels of bilirubin and iron in patients with porphyria cutanea tarda.

Nicotinic acid (NA) administration in Gilbert's syndrome (GS) patients promotes an increment of bilirubin and of total iron serum levels, dependent on a defective hepatic bilitranslocase function and on a haemolytic effect of NA. In porphyria cutanea tarda (PCT): (1) the effect of nicotinic acid on bilirubinaemia is superimposable to that in controls; (2) a well documented disturbance of iron metabolism occurs; (3) but relationship between bilirubin and iron under NA load has never been investigated. The administration of 5.9 mumol/kg body weight of NA to 12 PCT patients, 10 GS subjects and nine healthy volunteers of comparable age resulted in: (1) normal behaviour of bilirubin parameters in PCT but higher bilirubinaemic values in GS subjects; (2) normal values of serum iron in GS subjects, but higher baseline values and lower sideraemic effect of nicotinic acid in PCT patients; (3) a normal NA half-life in PCT and enhanced in GS subjects. These findings confirm a defective bilirubin uptake and excretion by the liver of GS subjects with a normal iron metabolism. On the contrary, in our PCT patients a normal clearance of bilirubin occurs, but a complex disturbance of iron metabolism is well evident in baseline conditions as well as after NA administration. The latter being probably the consequence of an enhanced excretion of iron extraproduced by the haemolytic effect of NA.

Adult↗

Investigation of intestine function during acute viral hepatitis using combined sugar oral loads.

One fifth of all cases of A virus hepatitis (AVH) have symptoms of gastroenteritis at the onset. This study investigated the mediated intestinal absorption of D-xylose (D-xyl) and 3-o-methyl-D-glucose (3-omG) and the non-mediated permeation of lactulose (Lacl, mol wt 342) and L-rhamnose (L-rh, mol wt 164) during acute and remission phases of AVH. Ten patients with AVH were given an oral load containing these sugars (5 g D-xyl: 2.5 g 3-omG, 1 g L-rh, 5 g lacl in 250 ml water) once during the acute phase and again during remission. The same load was given once to a group of 22 healthy controls. The mean concentration of D-xyl in urine and the ratio of D-xyl to 3-omG in plasma and urine were normal in both the AVH phases, ruling out intestinal malabsorption even in the acute phase. This study showed a significant increase in non-mediated permeation to Lacl, but not to L-rh, during the acute phase. These data indicate that the barrier function of the intestine is compromised in AVH infection while the absorptive function is not. An abnormally low concentration of D-xyl and 3-omG in plasma at one hour was found in all patients during the acute phase. This finding cannot be explained by alterations in intestinal absorption, but could be accounted for by increased space distribution of the sugars because of increased diffusion into tissue cells and/or expansion of the extracellular space by fluid retention.

3-O-Methylglucose↗

Metabolic fate of plasma diamine oxidase: evidence of isolated and perfused rat liver uptake.

After injection of an intravenous bolus of heparin (15,000 IU) in two groups of subjects, 10 normal volunteers and 6 subjects with external biliary drainage, blood and urine samples were collected; in the latter group bile samples were collected also. All samples were assayed for diamine oxidase (DAO). Persistently high values of this enzyme were found in plasma of both populations after heparin stimulation, while no increase in enzymatic activity was detected in bile and urine. In order to confirm and support the hepatic clearance of DAO, liver uptake of the enzyme derived from porcine kidney, human plasma and human placenta was studied by perfusion of isolated rat liver. Disappearance curves of the enzyme derived from three different sources showed a prompt liver uptake: activity decreased by about 50% in 10 min (endocytic uptake) and a slower but constant reduction during the remaining 110 min of perfusion was observed. These data suggest the hypothesis of liver metabolism of plasma DAO.

Adult↗

Evaluation of heparin toxicity in the isolated and perfused rat liver.

A plasma increase of liver enzymes has been recently reported in patients receiving heparin therapy. In this study we have evaluated the toxic effect of heparin infusion in the whole rat and in the isolated and perfused rat liver. No variation of plasma enzymes was observed in heparin-treated rats (10 IU per gram body weight, daily for 12 days). The heparin addition in the perfusion medium (5,000 IU in all) has shown no difference in the kinetics of hepatic enzymes release and in the other parameters of liver function. These data do not confirm a liver-toxic effect of heparin in the rat.

Alanine Transaminase↗

Investigation of intestine and liver function in cirrhosis using combined sugar oral loads.

Active and passive intestinal absorption and the efficiency of hepatic galactose clearance were studied in 12 patients with liver cirrhosis and 8 healthy control subjects using differential absorption techniques in which paired sugar markers were ingested simultaneously. Such differential absorption procedures overcome the effects of variation in gastric emptying, intestinal transit, distribution space and renal clearance which could invalidate tests incorporating a single marker only. In the cirrhotic group, active absorption of D-xylose (D-xyl) compared with that of 3-O-methyl-D-glucose (3-OMG), indicated by the ratio of D-xyl/3-OMG concentration in plasma, showed no reduction in respect to the control group. The passive intestinal permeability to lactulose (lac) compared with that of L-rhamnose (rham), indicated by urinary lac/rham excretion ratio, was not raised. These findings indicate no dysfunction of small intestinal mucosa in cirrhotic patients in spite of the clinical evidence of portal hypertension. Urinary galactose (gal) excretion after oral load was 10 times higher in the cirrhotic group (P less than 0.001). The gal/3-OMG excretion ratio correlated well with galactose elimination capacity as assessed by an intravenous method. Estimation of plasma D-xyl/3-OMG concentration and both urinary lac/rham and gal/3-OMG excretion ratios after appropriate oral loads provided a convenient and simultaneous evaluation of intestinal absorption, permeability and hepatic galactose elimination.

Adult↗

[Blood amino acids in chronic HBsAg positive liver disease].

Typical changes in blood aminoacid concentrations have been described in patients with severe liver disease. In this study we measured the serum amino acid levels, by Beckman Aminoacid Analyzer, in 11 healthy subjects and 24 HBsAg-positive patients with biopsy-proven liver disease (4 CPH, 10 CAH, 10 cirrhosis). A significant decrease in total aminoacids was observed in CAH and cirrhosis groups (-24% and -22% respectively). The three branched chain aminoacids (BCAA = val + leu + isoleu) were reduced by 24% (P less than 0.002) and 37% (P less than 0.001) in the CAH and cirrhosis groups respectively. Tyrosine was the only of the aromatic aminoacids (AAA) to increase in cirrhotics (+ 34%, P less than 0.02). The molar ratio BCAA/AAA was 3.6 in controls, 3.8 in CPH, 3.1 in CAH (P less than 0.025) and 1.9 in cirrhosis (P less than 0.001). A linear correlation was found between molar ratio BCAA/AAA and serum albumin in all patients (P less than 0.001). These results document the presence of specific quantitative changes in serum aminoacids of HBsAg positive patients, which appear related to severity of liver disease and comparable to the alterations described in non viral chronic liver disease.

Adolescent↗

Diminished active T rosette levels and increased spontaneous B lymphocyte blastogenesis in hepatitis B virus positive chronic active hepatitis.

The present investigation was designed to detect abnormalities in CMI and the presence of polyclonally activated B cells in patients with HBV positive CAH. We studied the peripheral levels and 3H-thymidine incorporation of three lymphocyte subsets: B lymphocytes, as well as two T cell subsets that are either active or late rosetters with high and low affinity receptors respectively for sheep red blood cells (SRBC). In patients the level of peripheral T active cells was decreased, but they exhibited elevated B cell activation. There was also a significant correlation between the decreased levels of T active cells and increased 3H-thymidine incorporation by B lymphocytes. Taken together, our results are consistent with the hypothesis that patients with HBV positive CAH have a severe impairment of T cell function that may lead to an abnormal B cell activation. The increased B cell activity may account for the presence of circulating immune complexes and the variety of autoantibodies often observed in patients with HBV positive CAH.

Adult↗

The cholecystokinin effect on human intestinal permeability: influence of chenodeoxycholic and ursodeoxycholic acid administration.

The influence of CDCA and UDCA administration on human intestinal permeability to lactulose, as disclosed by intravenous CCK, has been investigated. For this purpose the fraction of lactulose excreted in the urine during 5 h after an oral load of the disaccharide in hypertonic solution was measured in 12 healthy subjects, with and without intravenous CCK. The lactulose test was performed in each subject before and after a 7-day course of oral CDCA or UDCA (750 mg/day). Under basal conditions CCK induced a 100% increase in lactulose excretion. CDCA treatment further augmented the response to CCK by 33% (p less than 0.001) but UDCA produced no significant change. Finally, the effect of CDCA or UDCA added directly to the lactulose test solution was investigated in 4 subjects following oral and duodenal administration. CDCA only produced an increase in lactulose excretion (more than 100%) when given in hypertonic solution. The possible reasons for these findings are discussed.

Administration, Oral↗

Changes in intestinal permeability to lactulose induced by cytotoxic chemotherapy.

Intestinal function during cytotoxic therapy was studied in nine patients with nonintestinal lymphoma. An early, marked, and rapidly reversible increase in passive permeability, as disclosed by the lactulose test, was observed without concomitant changes in active absorption or in intestinal histology. The possibility of a toxic effect by cytotoxic drugs on intestinal intracellular junctions is discussed.

Antineoplastic Agents↗

Cholecystokinin and human intestinal permeability.

The effect of intravenous cholecystokinin (CCK) on intestinal permeability in normal subjects and patients after cholecystectomy has been studied by measuring the fraction of orally administered lactulose excreted in the urine. CCK induced a marked increase in lactulose excretion in normal subjects when given in a hyperosmolar solution (49.4 mg lactulose during 5 h rising to 114.3 mg with CCK, p less than 0.001). CCK failed to affect lactulose excretion when given to normal subjects in an isosmolar solution, and also when given to post-cholecystectomy patients in either hyper- or isosmolar solutions. The 'CCK effect' is therefore related to gallbladder emptying. It is suggested that conjugated bile acids released following gallbladder contraction can affect intestinal permeability by enhancing the action of hypertonic solutions on the small intestinal mucosa.

Adult↗

Peritoneoscopy in chronic hepatitis. A retrospective evaluation of its role in the management of the asymptomatic patient.

The course of chronic hepatitis was retrospectively evaluated in 26 patients in whom both peritoneoscopy and liver biopsy were initially performed. At entry all patients were clinically asymptomatic and showed mild or moderate histological and chemical abnormalities, so that none of them needed steroid treatment. The duration of the follow-up ranged from 24-82 months. At the end of follow-up liver biopsy was obtained in all patients. In a few patients peritoneoscopy was also ultimately performed. In six patients in whom initially chronic persistent hepatitis (CPH) was diagnosed both by peritoneoscopy and liver biopsy, the subsequent course of the disease was benign. In all the nine patients in whom initially peritoneoscopy suggested CPH, in contrast to the histological diagnosis of chronic aggressive hepatitis (CAH), chemical and morphological parameters of liver disease activity did not worsen to require steroid treatment. In five of six patients in whom both liver biopsy and peritoneoscopy initially showed CAH, chemical and morphological abnormalities progressed so that steroids had to be initiated. Finally in four of five patients in whom initially peritoneoscopy showed CAH and liver biopsy CPH, steroid treatment was ultimately required because of chemical and morphological worsening. In conclusion peritoneoscopy may be a useful aid in the management of the asymptomatic patient with moderate chemical and histological features of chronic liver disease.

Adolescent↗