Search PubMed⌕ Search

Biomedical subjects

A Mattioli

Publications and source records attributed to A Mattioli.

At least 19 recordsLinked to original sources
PubMed1996

Adenine arabinoside monophosphate coupled to lactosaminated human albumin administered for 4 weeks in patients with chronic type B hepatitis decreased viremia without producing significant side effects.

A conjugate of adenine arabinoside monophosphate (ara-AMP) with the liver-targeting molecule lactosaminated human serum albumin (L-HSA) was administered by intravenous infusion for 28 days to eight patients with chronic type B hepatitis. The daily dose varied among the patients, ranging from 34 mg/kg to 53 mg/kg (equal to 1.5 and 2.3 mg/kg ara-AMP, respectively). Pharmacokinetic analysis indicated that, at every dose tested, the conjugate was disposed of without accumulation. Viral DNA serum levels fell markedly during treatment; values rose again when treatment was ceased. The L-HSA-ara-AMP conjugate did not cause either the neurotoxic side effects of free ara-AMP or other adverse clinical reactions. It produced a significant increase both in serum alkaline phosphatase activity and platelet number, and a small but significant decrease in erythrocyte number. These laboratory parameters returned to normal levels within 2 months after treatment. The conjugate induced the production of small amounts of antibodies (approximately 20 pmol of conjugate bound by 1 mL of serum) in one patient only. In conclusion, the present results indicate that the L-HSA-ara-AMP conjugate can exert the antiviral activity of ara-AMP in chronic type B hepatitis patients without producing the neurotoxic side effects which hamper a 4-week period of treatment with the free drug.

Adult↗
PubMed1995

Selective delivery to the liver of antiviral nucleoside analogs coupled to a high molecular mass lactosaminated poly-L-lysine and administered to mice by intramuscular route.

In order to obtain hepatotropic conjugates of antiviral drugs suitable for intramuscular administration, three nucleoside analogs (adenine arabinoside monophosphate, ribavirin and azidothymidine) were coupled to a high molecular mass lactosaminated poly-L-lysine. The conjugates had a high molar ratio drug/conjugate and after intramuscular administration to mice, were selectively taken up by the liver and eliminated by the kidney only in minute quantities. The high molar ratio and low renal elimination are important properties not possessed by conjugates previously prepared by using a small molecular mass lactosaminated poly-L-lysine. The conjugate with adenine arabinoside monophosphate (ara-AMP) was found to be devoid of acute toxicity for mice and in spite of its high molecular dimension (Mn = ca. 72,500) did not induce antibodies in this animal after repeated intramuscular injections. This conjugate could have two advantages over a similar complex of ara-AMP with lactosaminated human albumin currently under clinical trials for the treatment of chronic type B hepatitis which must be injected intravenously: it might provide better patient compliance since it is injectable intramuscularly and could introduce larger amounts of ara-AMP into hepatocytes due to its higher drug/carrier molar ratio.

Amino Sugars↗
PubMed1995

Inhibition of woodchuck hepatitis virus replication by adenine arabinoside monophosphate coupled to lactosaminated poly-L-lysine and administered by intramuscular route.

We prepared a hepatotropic conjugate, suitable for intramuscular (IM) injection, of lactosaminated poly-L-lysine with adenine arabinoside monophosphate (ara-AMP), a drug active against hepatitis B virus (HBV). We studied its organ distribution in mice and its antiviral activity in woodchucks that are carriers of woodchuck hepatitis virus (WHV). In mice, after IM administration of a conjugate tritiated in the drug moiety (5.2 micrograms/g equal to 2 micrograms/g of ara-AMP) radioactivity in liver was three times greater than in kidney, spleen, and intestine. On the contrary, after IM injection of unconjugated, tritiated, ara-AMP (5 micrograms/g) the amounts of radioactivity in liver, spleen, and kidney were similar. Unconjugated ara-AMP and the conjugate were administered IM to woodchucks for 13 days. Unconjugated ara-AMP decreased viremia at the daily dose of 5 mg/kg but was ineffective at 2.5 mg/kg. The conjugate at the daily doses of 4.2 and 7 mg/kg (equal to 1.5 and 2.5 mg/kg of ara-AMP, respectively) markedly lowered the viremia, which decreased to undetectable levels in the animals treated with the higher dose. Assuming that in HBV-infected patients the same doses will be active, then the amount of conjugate (soluble at 200 mg/mL) required by a 70-kg patient will be contained in a volume of 1.5 to 2.5 mL, compatible with the IM route. Compared with a similar ara-AMP complex with lactosaminated human albumin, currently being studied in clinical trials for the treatment of chronic type B hepatitis, which must be infused intravenously, the present conjugate might provide more patient compliance because of IM administration.

Amino Sugars↗
PubMed1995

Liver targeting of adenine arabinoside monophosphate (ara-AMP) by coupling to lactosaminated human serum albumin.

Adenine arabinoside monophosphate (ara-AMP) is a potent antiviral agent against hepadnaviruses but its use in the treatment of chronic hepatitis B is hampered by severe neurotoxic side effects, which are dose dependent. In order to reduce these adverse reactions and to adopt the lysosomotropic approach to antiviral chemotherapy, ara-AMP was coupled to lactosaminated human serum albumin (L-HSA), a neoglycoprotein which specifically penetrates hepatocytes. In mice with Ectromelia virus hepatitis, ara-AMP coupled with L-HSA was selectively delivered to liver cells in which it was released in a pharmacologically active form. Moreover in woodchucks with WHV hepatitis and in patients with chronic HBV infection, coupled ara-AMP inhibited hepadnavirus replication at a dose (1.5 mg/kg/day) 3-6 times lower than the free drug. A clinical study using a 28-day period of treatment with conjugated ara-AMP at 1.5 mg/kg/day has now been started. In the first 6 patients the treatment has been completed. The conjugate inhibited virus growth without producing any side effects. L-HSA-ara-AMP conjugate must be given by intravenous infusion. New hepatotropic conjugates of ara-AMP have been recently prepared which could be administered by bolus intravenous injection or by intramuscular route. These complexes might assure a better compliance in patients with hepatitis B virus infection for a long lasting liver targeted antiviral treatment.

Amino Sugars↗
PubMed1995

[Surgery of abdominal aortic aneurysm and concomitant disease of the digestive tract].

The incidence of intra-abdominal diseases associated with abdominal aortic aneurysm is increasing, and it is difficult to decide whether to operate the abdominal disease first, the aneurysm first or both simultaneously. Variables used in decision analysis include type, stage and life expectancy of the cancer, rupture rate of abdominal aortic aneurysm. Symptomatic lesion should be treated first. Absolute indication for operation initially on the aneurysm is the presence of symptoms of rupture. Aortic abdominal aneurysmectomy combined with surgical removal of an intestinal disease may present severe risks as infection of the graft and anastomotic leakage, especially during lower abdominal surgery. In this paper authors present four cases of AAA which had intra-abdominal surgical disease. They were treated by one-stage operation with no complications. Criteria to assess timing of surgical treatment of abdominal surgical diseases concomitant to AAA are discussed.

Aged↗
PubMed1994

A conjugate of lactosaminated poly-L-lysine with adenine arabinoside monophosphate, administered to mice by intramuscular route, accomplishes a selective delivery of the drug to the liver.

A conjugate of the antiviral agent adenine arabinoside monophosphate (ara-AMP) with a low molecular mass lactosaminated poly-L-lysine, administered to mice by i.m. route, selectively delivers the drug to the liver. In mice the conjugate is devoid of acute toxicity even at high dose (1.3 mg/g) and injected i.m. for 20 days does not induce antibodies. Moreover it is highly soluble in water; this means that a pharmacologically active dose may be administered in a small volume compatible with the i.m. route. Compared to the similar ara-AMP complex with lactosaminated albumin which must be injected intravenously, the present conjugate might assure a better compliance of patients with hepatitis B virus infection for a long lasting, liver targeted antiviral treatment.

Amino Sugars↗
PubMed1993

Coupling of antiviral nucleoside analogs to lactosaminated human albumin by using the imidazolides of their phosphoric esters.

Liver targeting of antiviral nucleoside analogs can be obtained by conjugating these drugs with the hepatotropic molecule lactosaminated serum albumin. We describe a new coupling procedure which uses the imidazolides of the phosphoric ester derivatives of the drugs in an alkaline medium. By this procedure conjugates are obtained with a high drug/carrier molar ratio and without the unwanted protein chemical changes produced by carbodiimides usually employed for this coupling.

Animals↗
PubMed1993

[The physiopathology and therapy of esophageal diverticula].

The authors report their experience in the management of 14 patients affected by esophageal diverticula and surgically treated (9 had cervical diverticula, 2 had epibronchial diverticula and 3 had epiphrenic diverticula). All these patients underwent a diverticulectomy: in 3 cases the diverticulectomy was associated with a subdiverticular myotomy. In the last three cases the resection of the diverticulum was performed using an automatic stapler. The follow-up of these patients was prolonged for a period of 5 years with clinical, radiographic and endoscopic evaluations performed at 6 monthly intervals. The most recently operated patient has a minimum follow-up of 22 months. There were no operative deaths and none of the patients complained of recurrence of the diverticulum or of the preoperative symptomatology. No significant complications were observed in the postoperative period in the patients who underwent a simple diverticulectomy or in the cases in which a subdiverticular myotomy was associated. The scant number of observed patients does not allow us to draw any conclusion about the necessity maintained by most authors of an associated myotomy. It is however evident that this adjunctive procedure doesn't cause any further difficulty and is not loaded with an increased risk of complications. Finally the authors believe in the usefulness of performing the diverticulectomy with an automatic stapler, these devices allow in fact a considerable reduction of the surgical time and prevent dangerous contaminations of the operative field.

Adult↗
PubMed1993

[Primary lymphoma of the gastrointestinal tract].

Lymphomas of the gastrointestinal tract are rare tumors with unusual features and few characteristics. Clinical, radiological and endoscopic diagnosis is difficult, because they may be confused with inflammatory or neoplastic forms, especially in primary involvement of the gastrointestinal tract. From 1965 we observed 4 patients with primitive gastrointestinal tract lymphomas. Prognostically important features for GI lymphomas were: stage, site of the primary disease, histological type. Authors report on the clinical findings, diagnostic procedures, surgical treatment and results.

Adolescent↗
PubMed1993

[Functioning paraganglioma].

Pheochromocytomas and functioning paragangliomas are rare tumors arising from indifferent cells of the primitive neural crest. These tumors produce clinical symptoms (pheochromocytoma syndrome) related to catecholamine production. The pheochromocytoma syndrome, constituted by arterial hypertension, headache and sweating, is due in 80% of cases to adrenal pheochromocytomas and only in 20% of cases is due to extra-adrenal secreting paragangliomas. The diffused localization of the Paraganglion System and the common embryologic origin, can explain the occasional identification of multicentric tumors (10%), and the association with multiple endocrine neoplasms (MEN), especially in familial occurrence. Careful follow-up of patients, in order to detect the later development of multicentric or metachronous neoplasms is necessary. The Authors present their experience with 80 patients affected by neoplasms involving the adrenal medulla and the multicentric paraganglion system, surgically treated during the last 25 years. Eight patients (10%) were affected by functioning extra-adrenal paragangliomas: 7 patients (87.5%) had solitary extra-adrenal tumors (6 abdominal and 1 thoracic) with a classic pheochromocytoma syndrome, and 1 patient (12.5%) had a double asymptomatic abdominal paraganglioma.

Adult↗
PubMed1993

[Mediastinal functioning paraganglioma. A case report].

Functioning paraganglioma of the mediastinum is an uncommon tumor of the paraganglion system. We report a case of a 26 year-old woman with a 6 month history of hypertension refractory to therapy. Urinary catecholamine excretion and plasma noradrenaline concentration were elevated. Chest radiograph and computed tomography (CT) scan revealed high-density mass located on the posterior mediastinum. An mIBG scan showed uptake by the mediastinal tumor. At thoracotomy a 5 cm lesion was resected. Histological examination confirmed that it was a paraganglioma. Authors refer on the clinical finding and diagnostic procedures of this rare disease.

Adult↗
PubMed1992

The pathogenesis of vacuoles produced in rat and mouse liver cells by a conjugate of adenine arabinoside monophosphate with lactosaminated albumin.

A conjugate of adenine arabinoside monophosphate with lactosaminated albumin produced vacuoles in hepatic cells of rats and mice when given at doses 5-10 times higher than that (35 mg/kg) capable of inhibiting hepatitis B virus replication in patients with chronic hepatitis B. The vacuoles were due to the swelling of secondary lysosomes probably caused by incapacity of the lysosomal enzymes to rapidly digest large amounts of conjugate into products able to cross the lysosomal membrane. Although vacuoles progressively disappeared when conjugate administration was discontinued, the present observation suggests caution in giving the conjugate to man at daily doses higher than 35 mg/kg.

Animals↗
PubMed1992

[Profundaplasty as the only revascularization procedure in ischemia of the leg. Clinical contribution].

The profunda femoris artery is the primary source of collateral flow to the lower extremity in the presence of superficial femoral and/or popliteal occlusion. The arteriosclerotic disease involvement of this segment is relatively less frequent and in the majority of the cases localized on the ostium and reaches to the first branch. Profundaplasty to relieve limb-threatening ischemia is infrequently employed as an isolated procedure. However many Authors reported their experience on this treatment, in case of critical limb ischemia in patients without significative lesions of the aortofemoral district. Our late four year experience concerns of 22 patients (18 male, 3 female). All the patients had severe ischemia of the lower limbs, with serious symptoms, such as invalidating claudicatio (13), rest pain (7) and gangrene (2). Twenty-two profundaplasty were performed as the only reconstructive procedure. There was no postoperative mortality. Two patients had above knee amputations (15 days and 14 months after the revascularization). All of the other patients improved and follow-up extended to 48 months shows a limb salvage rate of 90%. In conclusion, on the basis of our experience, we think that the operation is recommended, whenever possible, in patients with critical ischemia when the possibilities of more extensive revascularization procedures are considered to be poor.

Aged↗
PubMed1992

[Isolated aneurysms of the internal iliac artery. A clinical contribution].

Five patients with isolated aneurysms of the internal iliac artery were identified and submitted to surgical procedure. Two patients were operated on in election, three in emergency with aneurysmatic rupture. The natural course of this pathology is one of progressive expansion and rupture. This lesion is often asymptomatic, but sometimes we found associated, compression symptoms of genito-urinary, intestinal tract and venous and neurological structures. Echography, CT scan and angiography are the most common and useful diagnostic procedure. Endoaneurysmectomy with proximal and distal suture of the stumps is the appropriate treatment in the majority of the cases.

Aged↗
PubMed1991

[The surgical prevention of pulmonary embolism. Comments on 100 patients treated by different methods].

A series of 100 patients suffering from deep venous thrombosis with prior episodes of pulmonary embolism or ilio-caval floating thrombi, submitted to surgery for the prevention of new embolic episodes, is analysed. Indications are discussed together with the various prevention techniques adopted over the past 5 years. Special attention is paid to the analysis of 11 patients operated on in the last 2 years by thrombectomy of the infra- and suprarenal vena cava.

Adolescent↗
PubMed1991

Adenine arabinoside monophosphate and acyclovir monophosphate coupled to lactosaminated albumin reduce woodchuck hepatitis virus viremia at doses lower than do the unconjugated drugs.

The woodchuck was selected to study the efficacy of liver-targeted antiviral drugs on hepadnavirus replication. Nineteen woodchucks chronically infected with woodchuck hepatitis virus were treated with adenine arabinoside monophosphate or acyclovir monophosphate, either free or conjugated with the liver-targeting molecule lactosaminated human serum albumin. Circulating woodchuck hepatitis virus DNA levels remained unchanged in untreated animals and in those receiving the carrier lactosaminated human serum albumin alone; in contrast, they were consistently lower after 5 days of treatment with the antiviral drugs. Free and conjugated adenine arabinoside monophosphate were active at doses of 10 and 0.75 mg/kg, respectively, and free and coupled ACVMP were active at doses of 20 and 2.6 mg/kg, respectively. These results indicate that the dosages of adenine arabinoside monophosphate and acyclovir monophosphate required to inhibit hepadnavirus growth can be sharply reduced by coupling the drugs to lactosaminated human serum albumin.

Acyclovir↗