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M C Ragni

Publications and source records attributed to M C Ragni.

17 recordsLinked to original sources

[Lights and shadows on the molecular diagnosis of hepatitis C].

The rational application of molecular biology to clinical diagnostics must take in consideration the economic demands, as the waste of sophisticated and expensive assays is of no use for the physician prescribing the assays and burdensome for the individual or the community paying them. Sometimes it is useless to apply to the molecular biology, and the information obtainable through serology answer our demands. This brief survey of the principal means available today for Hepatitis C diagnosis and monitoring, besides summarising the principles on which the different techniques are based, wants to underline the most noteworthy aspects of the different assays--from general indication to specific application to a single case--in the attempt to improve the efficacy of the test, which may be the right one at the right moment. There are qualitative and quantitative methods for viremia determination, which not always are alternative; on the contrary they must sometimes be complementary in order to obtain a complete clinical pattern. As a matter of fact the clinician should choose according to protocol susceptibility and considering what the expected viremia could be. The risk of false negatives is very dreadful for the clinician, as that of false positives (from contamination) is threatening for the laboratory, which must carry out more work than its capabilities consent. One must not misuse these diagnostic means, but they must be used correctly in order not to transform an important service into a harmful inefficiency with unpleasant consequences both for the physician and the patient.

DNA Probes↗

Perinatal transmission and manifestation of hepatitis C virus infection in a high risk population.

We studied the perinatal transmission of hepatitis C virus (HCV) in 70 high risk mother/infant pairs. Seventy-six percent of the mothers (53 of 70) were coinfected with human immunodeficiency virus (HIV) and 79% (55 of 70) had a history of drug addiction. During the follow-up HCV RNA was detected in 14 of 70 (20%) infants: 12% (2 of 17) in infants born to HIV-negative mothers; and 23% (12 of 53) in infants to HIV-positive mothers. The rate of vertical transmission was significantly higher in vaginally delivered infants than in those delivered by cesarean section (32% vs. 6%; P < 0.05). All 56 uninfected infants lost passively acquired anti-HCV by age 9 +/- 4 months and only 2 of 56 infants (4%) had evidence of HIV infection. Four of 14 HCV RNA-positive infants (29%) had evidence of HIV coinfection. We observed 3 clinical patterns of HCV infection: a transient viremia in 2 infants; an acute pattern in 2 infants; and a chronic pattern in 10 infants. All 4 HIV-coinfected infants had chronic HCV infection. All infants with a chronic pattern, had increased alanine aminotransferase values for more than 6 months and 5 had a liver biopsy that showed signs of chronic persistent hepatitis. HCV perinatal transmission was more frequent in infants born to HIV-coinfected mothers than in infants born to HIV-noninfected women, particularly when delivered vaginally.

Alanine Transaminase↗

Population screening for medium-chain acyl-CoA dehydrogenase deficiency: analysis of medium-chain fatty acids and acylglycines in blood spots.

We have developed methods for the measurement of the medium-chain fatty acids octanoate, decanoate and cis-4-decenoate and the acylglycines n-hexanoylglycine (HG) and 3-phenylpropionylglycine (PPG) in blood spots using gas chromatography and mass spectrometry. Normal ranges were obtained for octanoate and decanoate. HG, PPG and cis-4-decenoic acid were not detected in control blood spots. In blood spots from nine patients (including two newborn) with medium-chain acyl-CoA dehydrogenase (MCAD) deficiency, all metabolites were present in elevated concentrations although PPG was close to the detection limits and there was overlap for octanoate and decanoate. The lack of detection of cis-4-decenoic acid and HG in controls suggests that these are the metabolites of choice for blood spot identification of infants with MCAD deficiency.

Acyl-CoA Dehydrogenase↗

Azelaic and pimelic acids: metabolic intermediates or artefacts?

Azelaic and pimelic acids are excreted in elevated amounts in urine in disorders of mitochondrial beta-oxidation and disorders of peroxisomal beta-oxidation, for which they are of significant diagnostic value. We have detected the presence of azelaic, pimelic and even-chain-length dicarboxylic acids (adipic, suberic and sebacic acids) arising artefactually as a result of storage of small sample volumes in plastic containers. Storage of samples for organic acid analysis in glass containers is recommended.

Adipates↗

Impaired response to hepatitis B vaccine in HIV infected children.

Eighteen human immunodeficiency virus (HIV) vertically infected children (HIV group) and 33 seroreverted children (SR group), who had completed hepatitis B vaccination (Engerix B, 20 micrograms dose) were studied. Four out of 18 (22%) HIV children failed to develop protective antibody levels (anti-HBs titres less than 10 mIU ml-1) compared with 1 out of 33 (3%) SR children (p less than 0.05). Magnitude of response among HIV children was significantly lower than among SR children. In HIV children the probability that anti-HBs titres persist above the protective levels was significantly lower than in the SR group at any time during the 24 month follow-up. These results show that HIV children have a suboptimal response to hepatitis B immunization and the protection is less durable. Further studies are needed to determine the optimal protocol for hepatitis B immunization in HIV children.

Child, Preschool↗

Comparison of post-mortem urinary and vitreous humour organic acids.

We have analysed organic acid profiles in 74 samples of post-mortem vitreous humour from the sudden infant death syndrome and compared the profiles to those obtained from the corresponding urine or bladder wall swab. There was a high degree of correlation indicating that vitreous humour analysis in high-risk infants is an appropriate analytical strategy when urine is not available. In our patient sample two infants had evidence of abnormal methylmalonic acid metabolism, one had glyceric aciduria (and elevated levels of vitreous humour glyceric acid), one had evidence of pre-existing liver damage as judged by the presence of 4-hydroxyphenyllactic acid, one had a non-ketotic dicarboxylic aciduria indicating inhibited fatty acid oxidation and two patients had significant long-chain 3-hydroxydicarboxylic acids and evidence of paracetamol ingestion.

Carboxylic Acids↗

When do gut flora in the newborn produce 3-phenylpropionic acid? Implications for early diagnosis of medium-chain acyl-CoA dehydrogenase deficiency.

Urinary excretion of 3-phenylpropionylglycine (PPG) is a diagnostic marker for medium-chain acyl-CoA dehydrogenase (MCAD) deficiency. PPG is derived from 3-phenylpropionic acid (PPA), a product of anaerobic bacterial metabolism in the gut. To determine when the infant gut was colonized with PPA-producing bacteria, we cultured stool in prereduced thioglycollate broth from 93 apparently healthy infants. We analyzed the products of bacterial metabolism by gas chromatography/mass spectrometry for the presence of PPA. Trend analysis demonstrated a significant difference (P less than 0.001) in PPA production between early and later infancy. PPA was not detected in 84% of media isolated from stool collected from infants younger than four months. For older infants, 67% of the samples were PPA-positive. Thus, because the normal gut is not sufficiently colonized with PPA-producing bacteria before three to four months of age, PPG analysis alone is not a sensitive marker for the early detection of MCAD deficiency. Using stable isotope dilution mass spectrometry, we measured PPG and n-hexanoylglycine (HG) excretion in two well newborns with MCAD deficiency. HG, believed to be an endogenous metabolite associated with MCAD deficiency, was consistently above normal in all urine samples.

Acyl-CoA Dehydrogenases↗

Kinetics of chylomicron remnant clearance in normal and in hyperlipoproteinemic subjects.

The kinetics of chylomicron metabolism have been studied by measuring retinyl palmitate in chylomicrons and their remnants for 10-12 hr following oral administration of vitamin A and Lipomul in three groups of adult male subjects: A) normal plasma triglyceride levels (n = 7); B) endogenous hypertriglyceridemia (n = 12); C) apolipoprotein E (apoE) phenotype E2/2, with Type 3 hyperlipoproteinemia (n = 4) or normal plasma lipids (n = 1). A multicompartmental model was developed using SAAM 27 to characterize the appearance, intravascular metabolism, and clearance from the plasma of retinyl palmitate-labeled dietary lipoproteins. The half-times for retinyl palmitate clearance from the chylomicron remnant fraction (T1/2 REMNANT) were 14.1 +/- 9.7 min in Group A; they were prolonged in Group B (50.7 +/- 20.8 min) and were extremely prolonged for Type 3 subjects in Group C (611.9 +/- 419.9 min). One subject with the apoE 2/2 phenotype and normal plasma triglycerides had a T1/2 REMNANT of 66.8 min. T1/2 REMNANT was highly correlated with fasting plasma triglycerides in Group A and B (r = 0.77, slope = 0.15), and in Group C (r = 0.97, slope = 0.85). These results support the interpretation that delayed chylomicron remnant clearance in subjects with endogenous hypertriglyceridemia may be largely secondary to overproduction of VLDL particles, whose remnants compete with chylomicron remnants for removal by the liver via apoE receptor-mediated endocytosis. The subjects with apoE 2/2 have an additional defect in the removal of chylomicron remnants presumably due to the structural abnormality in their apoE.

Adult↗

The effect of phenobarbital on theophylline disposition in children with asthma.

The disposition of theophylline was examined in seven children with asthma on two occasions before and on one occasion after chronic phenobarbital dosing (2 mg/kg/day). There was little intrapatient variability in apparent theophylline clearance between the two baseline assessments (0.081 versus 0.073 L/hr/kg). After 19 days of phenobarbital therapy, there was a significant increase in apparent theophylline clearance (0.104 versus 0.077 L/hr/kg), accompanied by a 30% decrease in the mean steady-state serum theophylline concentration (12.0 versus 8.4 micrograms/ml). The inducing effect of phenobarbital on theophylline metabolism may require theophylline dosage adjustment in patients with asthma who receive both drugs concurrently to maintain a given average steady-state theophylline concentration.

Asthma↗

[The role of delta agent in particularly severe acute hepatitis B and non-A, non-B hepatitis in HBsAg carriers].

Role of delta agent in course of acute hepatitis B of particular severity and of hepatitis nAnB in carriers of HBsAg. Eighty-four cases of acute viral hepatitis have been studied with regard to the positiveness for delta antigen and anti-delta antibody in the Laboratory of clinical-chemical and microbiological analyses of the Hospital "L. Sacco" of Milan. The cases have been grouped in two classes: acute B hepatitis with prothrombin time of less than 40% acute viral hepatitis nAnB in chronic carriers of HBsAg. The prevalence of delta hepatitis was of 47.1% in the first class, while it was of 22% in the second class.

Antibodies, Viral↗

The aetiology of acute hepatitis in Zimbabwe.

The cause of acute viral hepatitis in 141 patients admitted to both Infectious Diseases Hospitals in Harare (Zimbabwe) was hepatitis A in 44, hepatitis B in 86 and hepatitis Non-A Non-B in 11. The wide distribution of hepatitis A and B viruses and early exposure to both in Zimbabwe are shown by the high positivity rate for anti-HAV antibody in patients under 10 years old (87.5%) and for anti-HBs antibody in patients over 20 (60%). Among the 86 hepatitis B cases, e and delta systems were also investigated: 66 patients (76.5%) were HBeAg positive, six (7%) anti-HBe positive and 14 (16.5%) negative for both; only one was anti-delta positive. Two cases of fulminant liver failure (both occurring in HBsAg and anti-HBc IgM positive, but delta-markers negative patients) and five cases of hepatoma (only one of whom was negative for all HBV markers) are described.

Acute Disease↗

[Generalized and persistent lymphadenopathy in drug addicts: clinical and epidemiological aspects].

Persistent unexplained lymphadenopathy with intermittent fever, weight loss, night sweats and malaise was observed in the period from March 1983 to April 1984 in 66 intravenous drug addicts living in Milan. A high percent of these subjects showed cellular immunity alterations, with significant decrease of total lymphocyte count (p less than 0.001) and of OKT4+ cells (percent and absolute number) (p less than 0.001) OKT8+ cells were augmented in percent, but not in absolute count. OKT4/OKT8 cell ratio were inverted, with significant reduction versus the healthy controls (p less than 0.001). IgG mean concentrations were significantly higher than the normal (p less than 0.001). Anergy or hypoergy to recall skin testing were evidenced in 58/66 patients. Cases of persistent unexplained lymphadenopathy associated with abnormalities of cellular immunity are considered as a possible prodrom of AIDS and were frequently observed in high risk populations. The occurrence of this clinical syndrome in a urban area may be premonitory of further progression to the epidemic. It will be necessary to assess whether this clinical and immunological picture will result in some of these patients in full blown acquired immunodeficiency syndrome.

Acquired Immunodeficiency Syndrome↗

ELISA antibodies to cytomegalovirus in pregnant patients: prevalence in and correlation with spontaneous abortion.

Prevalence of seroimmunity to cytomegalovirus (CMV) infection was tested by detecting ELISA IgG antibodies in 230 pregnant subjects from low socioeconomic backgrounds. Seroimmunity increased from 64.3% to 92.0% between the ages 15-20 and 35-40. Furthermore, ELISA IgM antibodies were detected during hospitalization in a group of 56 women whose pregnancies ended in spontaneous abortion and in a paired matched-control group. The overall percentage of IgM-positive reactions was 5.35% in the group with abortion. The percentage for only second trimester abortions amounted to 18.75%. There was no IgM-positive reaction in the control group.

Abortion, Spontaneous↗

The effect of obesity on apparent volume of distribution of theophylline.

An oral theophylline product was given to eight lean, normal subjects and eight obese subjects (four with asthma and four normals) in a single-dose study. The mean apparent volume of distribution (Vd) was 0.472 +/- 0.08 liters/kg for the lean group and 0.321 +/- 0.063 liters/kg for the obese group (P less than 0.001). When Vd wax expressed in liters, there was no difference between the two groups (lean:26.9 +/- 6.0 liters, obese: 28.5 +/- 6.3 liters). An inverse relationship existed between the ratio of total body weight to ideal body weight (TBW/IBW) and Vd expressed in liters/kg. One obese subject was studied before and after a weight loss of about 32 kg. The values of Vd in this subject were 32.1 and 34.9 liters, respectively. These data indicated that theophylline is not extensively distributed into adipose tissue and that loading-dose calculations should be based on ideal body weight. No difference in clearance of theophylline was seen between the two groups.

Adipose Tissue↗

Theophylline pharmacokinetics in the young infant.

The pharmacokinetics of theophylline were investigated in 13 infants, 4 to 18 months of age. An inverse relationship was found between theophylline half-life and age. Volume of distribution did not differ from that reported by other authors in similarly aged infants. Our data suggest that childhood clearance rates of elimination can be achieved by 6 months of age. The decreased theophylline elimination observed in the smaller infant indicates that the usual pediatric dosing recommendations cannot be used routinely. Until more specific data are available in the infant under 6 months, the authors reaffirm individualization of theophylline dosage to maintain therapeutic levels and avoid toxicity.

Age Factors↗

Viral antibodies in serum and cryoprecipitate of patients with essential mixed and secondary cryoglobulinemia. Preliminary results.

Antibodies to measles virus, CMV, HSV1, HSV2 and EBV have been tested in 9 patients with essential mixed cryoglobulinemia (EMC) and 24 patients with cryoglobulinemia associated with lymphoproliferative, autoimmune or hepatic diseases (secondary cryoglobulinemia, SC). The assays were performed in serum, cryoprecipitate and supernatant by using immunoenzymatic methods. The highest prevalence was observed in the supernatant of both EMC and SC patients. Antibodies to measles virus show a serum/cryoprecipitate ratio higher than that of the other viral agents. Statistically significant differences between EMC and SC patients in the positivity of the various viral antibodies were not shown.

Antibodies, Viral↗