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Biomedical subjects

P Vajro

Publications and source records attributed to P Vajro.

At least 73 records · Page 4Linked to original sources

Failure of expression of the phenobarbital-induced enhancement of UDP-glycosyltransferases in native, sealed endoplasmic reticulum vesicles from rat liver.

Conflicting data have been published regarding the effects of phenobarbital treatment on bilirubin UDP-glucuronyltransferase activity in native liver microsomes. Recent evidence suggests that the bilirubin UDP-glycosyltransferase system faces the interior of microsomal vesicles, and that expression of its activities in sealed microsomes may be rate-limited by transport of UDP sugars across the membrane. These observations raise the possibility that the reported variability in the effects of phenobarbital may reflect differences in integrity of the membrane in microsomal preparations. We examined the effect of phenobarbital on bilirubin UDP-glucosyltransferase and the UDP-glucuronyltransferase activities towards bilirubin, 4-nitrophenol, and 1-naphthol using native rat liver microsomes with verified vesicle integrity. Phenobarbital-induced microsomes in which the membrane permeability barrier was eliminated by pretreatment with detergent displayed markedly higher UDP-glycosyltransferase activities towards all tested substrates compared with activities in similarly disrupted microsomes from untreated rats. In contrast, none of the transferase activities tested were significantly enhanced by phenobarbital treatment when the enzymic activities were assayed in sealed microsomes. Addition to the enzyme assay mixture of UDPGlcNAc, a presumed physiological activator of the UDP-glucuronyltransferases, failed to expose the enhanced UDP-glucuronyltransferase concentration in phenobarbital-induced sealed microsomes. Our findings are consistent with the idea that transport of UDP sugar across the membrane may be rate-limiting for expression of UDP-glycosyltransferase activities in sealed microsomes. Quantitative assessment of membrane integrity is an essential prerequisite in experiments designed to study the regulation of the microsomal UDP-glycosyltransferase system.

Animals↗

Monitoring of serum alpha-fetoprotein levels in children with chronic hepatitis B virus infection.

Changes in serum alpha-fetoprotein (alpha FP) levels were investigated by radioimmunoassay during the follow-up (17 +/- 12 months, two to three times per year) of 50 children with chronic hepatitis B virus infection (mean age of 8 years, 30 males) and of 35 healthy age- and sex-matched controls. Eleven of 50 were healthy carriers; 7 had chronic persistent hepatitis, 29 had chronic active hepatitis, and 3 had cirrhosis-associated chronic active hepatitis. Serum alpha FP levels in controls were found to be always lower than 5 ng/ml (0.1-4.4 ng/ml, mean +/- SD of 1.34 +/- 1.32 ng/ml). Statistical analysis after logarithmic transformation showed a significant difference between mean levels (ng/ml) in controls and in patients [geometric mean = 0.83 C.L. (95% confidence limits of 1.19/0.58) vs. 3.43 (95% C.L. of 4.79/2.45); p = 0.0001]. Mean values of serum alpha FP levels at entry were higher than those found at the end of the follow-up period [geometric mean = 3 (95% C.L. of 4.69/1.92) vs. 1.48 (95% C.L. of 2.13/0.95); p = 0.038]. Only three patients repeatedly showed high alpha FP levels (76.7, 122.8, and 1,600 ng/ml at entry): alpha FP values became normal after a mean follow-up of 17 +/- 7.8 months as well as liver enzymes, with no changes in serum "e" antigen-antibody and anti-delta antibody status being observed. Mean values of serum alpha FP levels in HBeAg-positive patients were significantly higher than in HBeAg-negative patients both at entry and during the follow-up (p = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Incidence of cirrhosis in children with chronic hepatitis.

To determine the incidence of liver cirrhosis in children with chronic hepatitis, we investigated 92 children (64 were girls; mean age was 8 years 2 months) with chronic hepatitis for the presence of cirrhosis by the combined use of laparoscopy and needle liver biopsy, between 1975 and 1985. Forty-six children had hepatitis B virus-related chronic hepatitis; cirrhosis was present in 13 (32%). Cirrhosis was diagnosed by laparoscopy in 14 children and by needle liver biopsy in eight. In six patients, cirrhosis was diagnosed within the first 12 months after the clinical onset of liver disease. Forty-six children had autoimmune hepatitis; cirrhosis was present in 41 (89%). Cirrhosis was diagnosed by laparoscopy in all 41 children and by needle liver biopsy in 23 children. Cirrhosis was already present in all 10 children studied 2 to 5 months after the first sign of liver disease. Our results indicate that the incidence of cirrhosis is high in children with chronic hepatitis, especially of the autoimmune type, and that cirrhosis may occur early, irrespective of cause. A combination of laparoscopy and biopsy is more reliable than biopsy alone for the diagnosis of cirrhosis in children with chronic hepatitis.

Adolescent↗

Volume and emptying of the gallbladder in patients with cystic fibrosis.

As in cystic fibrosis (CF), gallbladder (GB) hypokinesia might play a role in the high incidence of either cholelithiasis or atrophic and hypoplastic GBs. We studied the contractility of the GB by ultrasonography (US) in 57 CF patients and in 25 age- and sex-matched healthy controls. We evaluated the status of the GB, the GB volume after an overnight fasting and 30 min after the ingestion of a standardized milk meal, the GB contractility (the percentage of reduction, (%R) of the GB volume after a meal), the presence of gallstones, and finally, the span of the liver. In addition, liver function test results were evaluated in the CF group. We concluded that the mean values of GB contractility in CF patients do not differ from those of healthy controls, the most hypokinetic GBs (%R less than 40%) being observed, however, only in the CF group. Gallstones occur in CF patients with a greater frequency than seen in the normal population, even in early childhood. The CF patients' GB mean volumes in fasting conditions are significantly greater than in healthy controls (13.5 +/- 2 versus 8.5 +/- 1.5 cc, p less than 0.0001).

Adolescent↗

Effect of prednisone on DR-positive T cells in children with chronic active hepatitis B.

The effect of short-term immunosuppressive treatment on the percentage of circulating DR-bearing T cells was investigated in 16 children with HBsAg-positive chronic active hepatitis. DR-positive T cells, thought to represent activated T cells, were significantly increased in all patients as compared to 10 age-matched controls [14.5 +/- 4.2% (mean +/- SD) vs. 0.4 +/- 0.1%, p less than 0.001]. Fifty-six percent of patients showed a decrease in the percentage of DR-positive T cells after 72 h of prednisone therapy. A response did not correlate with the presence of HBeAg, anti-HBeAg, or anti-delta antibodies. There was an inverse relationship (r = -0.56; p less than 0.05) between the decrease of the percent of DR-positive T cells during immunosuppression and pretreatment alanine aminotransferase levels. The persistence of high levels of circulating DR-bearing T cells during therapy may represent the immunological counterpart of more severe disease, and of nonresponsiveness to corticosteroids.

Adolescent↗

Orocoecal transit time in healthy and constipated children.

Orocoecal transit time (OCTT), assessed by means of H2 breath test after lactulose and/or after a semisolid standard meal, was studied in normal and constipated children. Both control subjects and patients with constipation showed a significantly longer OCTT after a standard meal than after lactulose ingestion (p less than 0.01). Whereas the OCTT after lactulose did not differ in the two groups, the constipated patients had a significantly longer transit time after a standard meal when compared to controls (p less than 0.05). No correlation was observed within each group between the OCTT after a standard meal or after lactulose ingestion (r = -0.077; p greater than 0.01). These findings suggest that 1) measurement of the transit of a standard meal instead of a lactulose solution may offer more direct insight into the role of small intestinal transit of food, both in physiological and pathological conditions, 2) gastrointestinal segments other than colon may play a role in chronic non organic constipation of childhood.

Breath Tests↗

Effects of postoperative cholestyramine and phenobarbital administration on bile flow restoration in infants with extrahepatic biliary atresia.

Surgical restoration of bile flow in patients with extrahepatic biliary atresia (EHBA) results in the disappearance of clinical cholestasis in about 30% of cases. It is suggested that early postoperative administration of phenobarbital (PB) or cholestyramine (Ch) may improve this percentage. Eighty patients were randomly divided into three subgroups comprising 27 who were treated with Ch (4 g/d), 27 who were given PB (7.5 to 10 mg/kg/d) during the first 3 postoperative months and 26 untreated patients, who served as controls. Cholestasis was observed to disappear in 38 (group I) patients and to persist in 42 (group II) patients, as judged from their total blood bilirubin levels, the conjugated/total bilirubin ratio, measurements of cholesterol, bile acids and alkaline phosphatase, and of Rose Bengal fecal excretion. Neither Ch nor PB significantly improved the degree or duration of cholestasis in either group.

Barbiturates↗

Iron malabsorption in giardiasis.

Among 10 children with giardiasis, eight had iron deficiency; iron deficiency anemia was the main complaint in three. Evaluation of iron absorption by the oral iron load test demonstrated a subnormal response (i.e., increase in serum iron levels of less than 100 micrograms/dl) in all eight patients with iron deficiency. In contrast, in two iron-sufficient patients with giardiasis the response to an oral iron load was normal. Xylose absorption was abnormal in five of the 10 patients. After metronidazole dosing, iron absorption became normal in seven patients but remained abnormal in one patient, who also had IgA deficiency. Xylose absorption became normal in all five patients who underwent a second test, but remained abnormal in the patient with IgA deficiency. Concomitant morphologic-studies of jejunal biopsy material from these patients revealed moderate changes in the intestinal mucosa of two patients. We conclude that malabsorption of iron is a complication of giardiasis.

Anemia, Hypochromic↗

Inefficacy of immunosuppressive treatment in HBSAg-positive, delta-negative, moderate chronic active hepatitis in children.

The efficacy of immunosuppressive treatment was evaluated in a group of 15 children (aged 2-10 years) affected by clinically asymptomatic, biochemically mild, HBSAg-positive, delta-antibody-negative, histologically moderate, chronic active hepatitis (CAH). Clinical, biochemical, serological, and histological features of chronic hepatitis B virus (HBV) infection were studied during a follow-up of 2 years. Eight of 15 patients received immunosuppressive treatment (prednisone plus azathioprine); seven received a placebo. No significant differences were found among treated and untreated patients, an overall improvement of nearly all parameters of disease (aminotransferases, albumin, prothrombin time, immunoglobulins, bromsulphalein at 45 min, and bile acid serum levels) being found in both groups. Treated patients showed an improvement in aminotransferase levels only at the first 3-month checkup. This finding, however, was not statistically significant in our study and disappeared at subsequent follow-up examinations. A high incidence of HBeAg was noted at entry into the study (10 of 15 patients checked). HBeAg seroconversion was observed in two of the six HBeAg-positive treated patients and in two of the four HBeAg-positive untreated patients. Finally, the histological picture showed similar patterns in both groups of patients studied. Our data suggest that no benefit from immunosuppressive therapy can be proven at this time in asymptomatic, moderately active, HBsAg-positive, delta-negative CAH in children.

Azathioprine↗

Infection with the delta agent in children.

Serological evidence of infection with the hepatitis B virus associated delta agent (delta) was found in 34 of 270 Italian children with HBsAg-positive liver disease. In different histological forms of chronic HBsAg hepatitis the prevalence of delta infection increased in parallel with the activity of the disease and was maximal in children with cirrhosis. During two to seven years of follow up the hepatitis deteriorated in 38% of the 34 patients with delta infection and ameliorated only in 9%. By contrast the disease usually ran a mild course in the 236 delta-negative carriers of HBsAg, with remission in 55% of these children and deterioration in only 7%. The outcome of chronic hepatitis associated with delta infection was not influenced by treatment with steroids and azathioprine. Chronic delta infection in children is usually accompanied by serious liver disease, that has a tendency to progress and is unresponsive to conventional immunosuppressive treatment.

Adolescent↗

Gas chromatographic quantitation of breath hydrogen and carbon monoxide for clinical investigation in adults and in children.

A simple and suitable method of breath sampling and the gas chromatographic determination of H2 and CO in breath of children as well as of adults are described. The analytical system allows the measurement of concentrations of H2 and CO as low as a few ppm. The proposed method of breath collection (tedlar bag with low resistance valve face mask) appears particularly useful for long storage purposes, because it eliminates the need for additional manipulations and the possible associated sample dilution. Normalization of H2 breath amounts to internal standard O2 to obtain reliable and precise measurements is particularly useful in non-collaborating patients whose observed H2 peak values increase by 15% after the correction. The overall procedure is fast, inexpensive and accurately recognizes adult or children lactose malabsorbers as well as subjects exposed even to low levels of CO.

Adult↗

Immunoregulatory T subsets in chronic active viral hepatitis: characterization by monoclonal antibodies.

Immunoregulatory T subsets, defined by monoclonal antibodies, were enumerated in children affected by HBsAg-positive chronic active hepatitis. The helper to suppressor/cytotoxic cells ratio was lower in patients than in age-matched controls. The lower ratio was mainly due to an increase of lymphocytes of the suppressor/cytotoxic phenotype. Helper cells were even fewer in severe chronic hepatitis patients, thereby lowering still further the helper/suppressor ratio. Therapy seemed to influence the ratio in patients affected by moderate active chronic hepatitis, for four of eight children treated with azathioprine and prednisone had a ratio within -1 SD of normal values. The increase of the suppressor/cytotoxic cells in patients affected by chronic hepatitis might be a means for limiting virus-induced cell hyperactivity.

Adolescent↗