Search PubMed⌕ Search

Biomedical subjects

A Mattioli

Publications and source records attributed to A Mattioli.

At least 55 records · Page 3Linked to original sources

[Cervico-mediastinal goiter].

The descent of a cervical goiter below the plain of the thoracic inlet to become substernal in location, is fairly rare, but not exceptional, with an incidence, derived from several large series of operated patients, ranging from 1.7% to 13.1%. The importance of this particular location of the goiter is chiefly due to the fact that the thyroid is growing in a limited space with many surrounding structures, that unavoidably, sooner or later, will be compressed or strained. This provokes respiratory symptoms (such as cough, dyspnea, stridor) or difficulty in swallowing or determines a superior vena cava syndrome with venous stasis in the neck and in the upper thorax, and with facial oedema. The substernal location, that already constitutes a complication of the basic thyropathy, is further aggravated by the incidental malignant transformation of the substernal goiter or by the development of a thyrotoxicosis due to hyper-functioning intra-thoracic thyroid tissue. For all these reasons the presence of a substernal goiter represents in and of itself a precise indication for a surgical treatment. This study is aimed at examining the series of 19 substernal goiters observed at the Institution of General and Cardiovascular Surgery, University of Milan, from 1967 to 1987, particularly analyzing the progresses in the diagnostic procedures, the adopted surgical therapy and the observed complications.

Adult↗

Inhibition of hepatitis B virus replication by vidarabine monophosphate conjugated with lactosaminated serum albumin.

Vidarabine (ara A) produces severe dose-dependent side-effects. To examine whether its monophosphate ester (ara-AMP) can be effective in the treatment of chronic hepatitis B when given in reduced dosage as a conjugate with lactosaminated human serum albumin (L-HSA), which selectively enters hepatocytes, five patients with chronic type B hepatitis (HBsAg/HBV-DNA positive for at least 2 years) were treated with the conjugate. The daily dose of conjugate given (35 mg/kg) contains 1.5 mg ara-AMP, whereas the usual daily dose of free ara-AMP is 5-10 mg/kg. In three patients HBV-DNA fell to undetectable levels and remained negative in two; in one of them anti-HBe developed. In the other two patients HBV-DNA decreased but was detectable during treatment--one received three cycles of therapy, and became HBV-DNA negative and anti-HBe positive 45 days after the end of treatment; the other remained HBeAg/HBV-DNA positive. No adverse effects were observed, and biochemical variables (including aminotransferases) remained unchanged or decreased with viraemia. No antibodies (IgM and IgG classes) that bound the conjugate were detected. Thus L-HSA-ara-AMP inhibits HBV replication as well as free ara-AMP but at a third to a sixth of the dose.

Adult↗

Targeting of antiviral drugs bound to protein carriers.

The value of antiviral drugs would be improved by their selective delivery into infected cells. This goal can be achieved by conjugating the drug to a protein which is taken up specifically by the cells where the virus grows. Conjugates will be pharmacologically effective in these cells if the bond linking the drug to the carrier does not suppress the activity of the drug or if the bond is broken down with consequent intracellular release of the drug. Experiments on this approach to antiviral chemotherapy have been directed mainly at selectively delivering antiviral agents into hepatocytes in order to increase their chemotherapeutic index in the treatment of chronic hepatitis B.

Albumins↗

Distribution of a conjugate of 9-beta-D-arabinofuranosyladenine 5'-monophosphate (ara-AMP) with lactosaminated albumin in parenchymal and sinusoidal cells of rat liver.

9-beta-D-Arabinofuranosyladenine 5'-monophosphate (ara-AMP) coupled to lactosaminated human albumin (L-HSA), injected i.v. into rats, selectively enters the liver. The conjugate concentration in parenchymal and sinusoidal hepatic cells, isolated by collagenase perfusion, was found to be practically equal in both cell types. This indicates that the high uptake of L-HSA-ara-AMP complex by the whole liver also corresponds to a high conjugate concentration in hepatocytes where ara-AMP should be targeted in order to increase its chemotherapeutic index in chronic hepatitis B treatment.

Animals↗

Drug targeting in antiviral chemotherapy. A chemically stable conjugate of 9-beta-D-arabinofuranosyl-adenine 5'-monophosphate with lactosaminated albumin accomplishes a selective delivery of the drug to liver cells.

With the aim of improving the chemotherapeutic index of 9-beta-D-arabinofuranosyl-adenine 5' monophosphate (ara-AMP) in the treatment of chronic hepatitis B, this drug was conjugated with lactosaminated serum albumin (L-SA), a neoglycoprotein which only enters into hepatocytes. We used a L-SA-ara-AMP conjugate which, in contrast to those previously employed, has the advantage of remaining soluble after lyophilization. We found in mice that: (I) this new conjugate was quite stable in the bloodstream where only a small part of ara-AMP was released; (II) after administration of the conjugate labelled in the drug moiety both acid insoluble and soluble radioactivities were several times higher in liver than in other organs; (III) in mice with Ectromelia virus hepatitis, the conjugate inhibited virus DNA synthesis in liver without affecting cellular DNA synthesis in intestine and bone marrow; (IV) the conjugate did not display any recognizable sign of acute toxicity even at doses several fold higher than those pharmacologically active; and (V) when prepared with homologous albumin it was not immunogenic.

Animals↗

A study on the pharmacokinetics in mouse of adenine-9-beta-D-arabinofuranoside 5-monophosphate conjugated with lactosaminated albumin.

In plasma of mice injected with adenine-9-beta-D-arabinofuranoside monophosphate (ara-AMP) coupled to human lactosaminated serum albumin (L-HSA) some of the ara-AMP molecules are enzymatically released, whereas others remain linked to L-HSA. Evidence has been obtained that ara-AMP is not deaminated when it is conjugated to L-HSA, in contrast to the free drug which is rapidly metabolized to its hypoxanthine derivative.

Animals↗

Selective penetration and pharmacological activity of lactosaminated albumin conjugates of adenine arabinoside 5-monophosphate (ara-AMP) in mouse liver.

With the aim of improving the chemotherapeutic index of adenine arabinoside 5-monophosphate (ara-AMP) in the treatment of chronic hepatitis B, this drug was conjugated with lactosaminated serum albumin (L-SA), a neoglycoprotein which only enters into hepatocytes where it is digested in lysosomes. In mice, the L-[3H]SA-ara-AMP conjugates, intravenously injected, selectively penetrated the liver, only small quantities were taken up by cells of spleen, bone marrow, intestine, and brain. After administration of the conjugate to mice with Ectromelia virus hepatitis, ara-AMP was selectively concentrated in liver in a pharmacologically active form. If L-SA-ara-AMP conjugates behave in man as in mouse, their administration to patients with chronic hepatitis B should result in a selective concentration of ara-AMP in liver with a more efficient inhibition of virus replication accompanied by lower toxicity for other tissues.

Amino Sugars↗

Targeting of antiviral drugs by coupling with protein carriers.

Side effects of antiviral drugs might be circumvented by their selective delivery into infected cells. This targeting can be obtained by conjugation of the drugs to macromolecules which are taken up specifically by the infected cells. The experiments reviewed, on this approach to antiviral chemotherapy, are mainly directed at improving the chemotherapeutic index of adenine arabinoside (ara-A) in the treatment of chronic hepatitis B by its coupling to galactosyl terminating glycoproteins.

Albumins↗

[Current indications for lumbar ganglionectomy. Analysis of a series of cases].

Data concerning a personal surgical series covering the last 10 years have been collected as far as cases regarded lumbar gangliectomy. The operative indication and incidence of this type of operation, performed for sclerotic obliterating arteriopathy of the lower extremities, out of total admissions and out of total direct reconstructive surgery operations, are analysed. Postoperative and long-term results of this type of surgery are then discussed. The data collected confirm the indication for lumbar gangliectomy alone or in association with other revascularization procedures in an albeit small number of patients, represented essentially by high risk cases or patients with extremely peripheral lesions.

Arterial Occlusive Diseases↗