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Biomedical subjects

M Esposito

Publications and source records attributed to M Esposito.

At least 181 records · Page 10Linked to original sources
PubMedDate not supplied

Bone metastasis in hepatocellular carcinoma. A report of five cases and a review of the literature.

Hepatocarcinoma occurs frequently throughout the world. Bone metastases are rare although incidence has increased because of progress in diagnosis and treatment. The authors report 5 cases of bone metastases and review the literature. The spine is the most frequent localization of bone metastases. Radiotherapy is the treatment of choice for this lesion. Surgery should be used to prevent and treat complications such as nerve compression and pathologic fracture, only if the coagulative pattern and the conditions of the patient allow it. The authors recommend the use of long intramedullary nailing when localization of the disease is in the femur, with prophylactic stabilization of the neck in diaphyseal metastasis.

Carcinoma, Hepatocellular↗
PubMedDate not supplied

Effect of normal saline on cisplatin pharmacokinetics and antitumor activity in mice bearing P388 leukemia.

The effect of normal saline (NS) on the antitumor activity, toxicity and pharmacokinetic of cisplatin (DDP) was investigated in BDF1 mice bearing P388 leukemia. Tumor-bearing mice received 8 or 16 mg/Kg of DDP dissolved in NS or distilled water (DW) intraperitoneally. Control animals were treated with DW or NS alone. The administration of 8 mg/Kg of DDP+NS produced a significantly better survival (P less than 0.05) compared to that observed in mice receiving DDP+DW. The proportion of long-term survivors was 3.5 times higher in the DDP+NS group (39%) compared to the DDP+DW group (11%). The administration of 16 mg/kg DDP+DW was highly toxic, resulting in early deaths (MST = 5 days) and no long-term survivors. NS protected from DDP toxicity without further improving the survival achieved following the injection of 8 mg/kg DDP+NS. Investigation of platinum pharmacokinetics showed that NS significantly decreases both plasma and tissue concentrations of total platinum, mainly through a decrease in the amount of platinum bound to high molecular weight plasma proteins. HPLC studies indicated that mice receiving 8 mg/kg DDP+NS or DDP+DW fail to show clear differences both in the total ultrafilterable platinum and unchanged DDP in plasma ultrafiltrate. Conversely, mice treated with DDP+NS had higher concentrations of platinum-species in plasma ultrafiltrate than mice receiving DDP+DW. These latter results, together with the observation that NS decreases the amount of platinum bound to plasma proteins, suggest that the effect of NS does not solely depend in vivo on the ability of the chloride ion concentration to stabilize the DDP molecule and suppress the formation of DDP metabolites, but also on its ability to prevent DDP toxicity by reducing the protein binding of DDP aquated products.

Animals↗
PubMedDate not supplied

Plasma and synovial fluid lanthanides in rheumatoid arthritis: variations after intra-articular therapy.

Lanthanides (Ln), or rare earth elements, are detectable in trace amounts in organisms. Increased concentrations of Ln have been observed in rheumatoid arthritis (RA) in plasma (pl) and synovial fluid (Sf). We have evaluated pl and Sf concentrations of Ln (in particular La, Nd, Ce, Yb, Lu, Eu), in rheumatoid arthritis patients, before and after intra-articular steroid injection. Increased pl and Sf concentrations of Ln were confirmed in RA. No detectable synovial fluid concentrations of Ln were observed in healthy controls. A statistically significant Ln reduction (p less than 0.001) was observed in Sf 3 and 6 days after local steroid injection and in pl after 6 days. The decrease in Ln concentrations in Sf and pl, after antiphlogistic therapy, reflects the reduction of the inflammatory condition.

Adult↗
PubMedDate not supplied

Serial determination of platinum, protein content and free sulfhydryl levels in plasma of patients treated with cisplatin or carboplatin.

We report here the results of serial determinations of free-sulfhydryl, protein content and platinum levels in plasma of cancer patients following either cisplatin (cis-DDP, 3 patients, 60 mg/m2) or carboplatin (JM-8, 3 patients, 300 mg/m2) i.v. administration. After treatment with cis-DDP, significant platinum binding to plasma components with MW greater than 25 kD was observed; the ratio free-sulfhydryls/protein content decreased during the first two hours, returning to normal values at 24 hours after injection. In contrast, no evidence of platinum binding to plasma components with MW greater than 25 kD was noted after JM-8 i.v. administration, and the ratio free sulfhydryls/protein content did not change significantly after treatment. In vitro experiments show that at a molar ratio cis-DDP:JM-8 1:10, the two compounds bind to low MW thiols with the same kinetics. These data seems to suggest different interactions at the plasma level of these drugs, which may be correlated with their different toxicity.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

Serum, urine and peritoneal fluid levels of 5-FU following intraperitoneal administration.

Seven patients with advanced colon cancer, refractory to conventional chemotherapy, and malignant disease confined to the intra-abdominal space received a total of 24 consecutive courses of ip 5-Fluorouracil (5-FU). 5-FU 1000 mg was administered in 2 L of warm (37 degrees C) dialysate daily for five consecutive days every 28 days. 5-FU concentrations in serum, peritoneal fluid and urine were measured by high pressure liquid chromatography (HPLC). The mean disappearance half-life of 5-FU from the peritoneal fluid was 1.6 hours with a mean permeability area product (PA) of 22.4 ml/min. The mean peritoneal AUC was 450 +/- 165 times greater than the mean serum AUC. Ip 5-FU treatment is well tolerated, can be safely administered on an outpatient basis and produces a significant pharmacological advantage over conventional routes of administration.

Adult↗
PubMedDate not supplied

[Severe mental retardation and slight dysmorphism in a child with a bisatellite extrachromosome: inversion duplication (15)?].

A de novo tetrasomy 15 has been reported, in a 6 years old child. The patient had severe mental retardation an minimal physical stigmata, consisting in slight skeletal and facial dismorphism. Cytogenetic analysis showed that extrachromosome, G-like long, was bisatellited and dicentric and was interpreted either as an inversion duplication 15 or as 15; G or D translocation.

Abnormalities, Multiple↗
PubMedDate not supplied

[Aarskog's syndrome (facial-digital-genital syndrome). Study of a family (author's transl)].

A case of Aarskog syndrome in a 6-years old boy is reported. The patient showed clinical pictures typical of the syndrome: characteristic dysmorphic facies, palpebral ptosis, brachyfalangism, abnormality of the scrotum. Minimal stigmata and clinodactyly of 5th finger were present in a sister. Isolated bilateral clinodactyly was found in other 4 members of the family. The significance of this sign in the context of the syndrome has been discussed. Unusual dermatoglyphic patterns were present in the proband, mother and sister.

Blepharoptosis↗
PubMedDate not supplied

[Sensitivity in vitro of 61 strains of Salmonella to aminoglycoside antibiotics and to cephalosporins].

The in vitro susceptibility of 61 strains of Salmonella from pathological specimens was tested by an agar dilution technique to four aminoglycoside and to seven cephalosporin antibiotics. Aminoglycosides were effective against these isolates. Ten strains of Salmonella wien were found resistant to cephapirine, cefazolin, cephaloridine, cephalotin, but susceptible to cepharidine and expecially to cefuroxim.

Aminoglycosides↗
PubMedDate not supplied

Chemical and biological properties of a new cis-diammineplatinum (II) complex containing para-aminobenzoic acid as amino ligand.

In this paper we report on the synthesis, characterization and preliminary pharmacological evaluation of a new platinum (II) complex obtained by reaction of cis-diamminedichloroplatinum(II) (DDP) with para-aminobenzoic acid (PABA). The structure of this platinum compound was defined by UV, IR, 1H-NMR and elemental analysis. DPAB tested in vitro and in vivo against P388 leukemic cells displayed good antiproliferative (IC50 values after 48 h exposure of cells = 3 micrograms/ml) and antitumor activity (T/C% = 150). This compound also possesses desirable physical properties, such as a good solubility and stability in aqueous media, and a low toxicity (LD50 > 1200 mg/kg body weight) combined with a moderate nephrotoxic activity [plasma urea nitrogen (PUN) level: 36 +/- 8(SD) mg/100 ml]. DPAB was cleared from plasma ultrafiltrate (UF-plasma) very rapidly [clearance (CL), 55.3 ml x min-1 x kg-1], showing a half-life of 13.6 min. Platinum exposure (AUC) in the kidney was 2.6 times greater than that found in UF-plasma. AUCS for liver, stomach and UF-plasma were similar, while the AUC value for the spleen was 1.7 times lower than that of UF-plasma. These preliminary results seem to hold interest for further preclinical evaluation of the biological activity of this new platinum compound.

4-Aminobenzoic Acid↗
PubMedDate not supplied

Cis-diamminedichloroplatinum (II)-procaine pharmacokinetic interaction in mice bearing P388 leukemia.

The distribution and elimination kinetics of cis-diamminedichloroplatinum (II) (DDP) in female BDF1 mice bearing 6-day P388 leukemia were investigated in the presence and absence of procaine hydrochloride (P.HCl) exposure. DDP was administered as a single i.p. dose of 8 mg/kg in a 0.9% NaCl solution 6 days after tumor inoculum. P.HCl was administered as a single i.v. dose of 40 mg/kg immediately after DDP. The combined treatment with P.HCl produced marked changes in the plasma concentration-time profile of Pt. The unbound fraction of Pt was significantly increased both in the ascites fluid and plasma following DDP + P.HCl administration. P.HCl treatment induced a significant reduction (P < 0.01) in the rate constant of the protein-bound of Pt in plasma of tumored mice. Urinary excretion of Pt was unaffected by P.HCl, and there was no significant P.HCl-induced modification in the concentrations of Pt in the P388 leukemic cells. A statistically significant reduction of kidney and spleen Pt content was observed in female mice exposed to a dose of 8 mg/kg DDP + P.HCl. A similar reduction was observed in kidneys and testes of tumored mice receiving 16 mg/kg DDP along with 40 mg/kg P.HCl, which also showed lower renal and testicular cisplatin-DNA adducts after DDP + P.HCl than after DDP treatment. Potential explanations for the ability of P.HCl to interfere with the pharmacokinetics and biodistribution of DDP are discussed.

Animals↗
PubMedDate not supplied

Effect of para-aminobenzoic acid on the pharmacokinetics and urinary excretion of cis-diamminedichloroplatinum(II) in rats.

Para-aminobenzoic acid (PABA) has been previously reported as being an inhibitor of DDP toxicity, and its use did not result in any observable loss in antitumor activity of DDP. The following studies investigated the effect of PABA on the pharmacokinetics and urinary excretion of cis-diamminedichloroplatinum(II) (DDP) in male Sprague-Dawley rats. DDP was injected i.p. at the dose of 7.5 mg/kg in normal saline alone and with a concurrent i.p. injection of PABA (100 mg/kg). The combined treatment with PABA produced a significant increase in the plasma concentrations of total platinum, without affecting the levels of platinum species in the plasma ultrafiltrate. Similar results were also obtained in additional studies in rats receiving the same dose of DDP plus PABA through different routes of administration (i.e. DDP i.v. and PABA i.p.). Both the area under the total platinum plasma concentration-time curve (AUC) up to 60 min and AUC0-120 min were increased by PABA by an average of 113% and 66% respectively. The administration of PABA in rats was followed by a substantial reduction in total urinary excretion of platinum (P < 0.05) and by a significant (P < 0.01) lower concentration of DDP derived platinum in the urine collected during the first 4 h after treatment. The renal clearance of filterable platinum was reduced by PABA by an average of 67.5% from 1.11 to 0.36 ml/min/100 g body wt. Total 24-h urinary excretion of platinum was also decreased, although not significantly, by PABA. Urine volumes from rats treated with DDP+PABA were similar to those from animals receiving DDP alone. HPLC studies indicate that PABA reacts readily with the species generated from DDP in vitro, while the agent is essentially unreactive toward the parent DDP and does not influence its decomposition rate. The overall data of this study suggest that the protective effect exerted by PABA on DDP toxicity may be at least partially due to its ability to interact with aquated DDP as well as to alter the renal excretion of platinum.

4-Aminobenzoic Acid↗
PubMedDate not supplied

Gaschromatography-mass spectrometry analysis of fatty acids in human milk from forty puerperae living in southern Italy.

Fatty acid (FA) composition of breast milk, an important factor in newborn nutrition, may change in relation to maternal diet and individual metabolic characteristics. This study was carried out on a group of 40 puerperae who lived in Southern Italy, delivered at term and feeded with common mediterranean diet. End-milk samples were collected between the 15th and 40th day (in mean at 27th day) after delivery. Analysis of fatty acids was performed using high resolution gaschromatography and mass spectrometry. It has been reported 37 different fatty acids including 6 branched chain fatty acids (BCFA).

Adult↗
PubMedDate not supplied

[Lipiodol with and without Gelfoam in primary liver tumors. Plasma levels of Mitoxantrone and clinical results].

Transcatheter chemoembolization with various drugs is employed for palliative treatment of hepatocellular carcinoma. Thirty-seven patients (33 with Child A or B cirrhosis) were treated with 14 mg/m2 of Mitoxantrone and up to 20 ml of Lipiodol, followed by Gelfoam embolization as indicated. Sixty-nine cycles were given, with mean (+/-SD) Lipiodol and emulsified Mitoxantrone doses of 11.3 +/- 3.8 ml and 11.8 +/- 5.2 mg, respectively. Thirteen, 16, and 8 patients received one, two, and three cycles, respectively, with time intervals of 123 +/- 60 days. Thirty patients had Gelfoam embolization at the first cycle, 9 at the second and 4 at the third. At the first cycle, 10 patients underwent serial measurements of serum Mitoxantrone up to two hours after a full dose of emulsified drug. Drug levels resulted much lower than those reported after plain arterial infusion, with AUC levels (+/-SE) of 5924 +/- 1015 and 4381 +/- 429 ng/ml x 120 min in 6 and 4 cases treated with and without Gelfoam, respectively. No treatment related deaths occurred. Complications were mild and transient, including nausea vomiting in most cases, fever > 38 degrees C 67%, pain 74%, ascites 8% jaundice 3%, bleeding 3%, pancreatitis 3%, myelosuppression 44%, diarrhea 5%. Treatment response rate was 49% (including 16% minor response) with 16% early progressions. With a median follow-up of 12 months, the 12-month response duration and survival rates were 56% and 79% respectively. Transcatheter chemoembolization with Mitoxantrone deserves further evaluation in randomized studies.

Aged↗
PubMedDate not supplied

Activity of high dose 24 hour 5-fluorouracil infusion plus L-leucovorin in advanced colorectal cancer.

BACKGROUND: Modulation of 5-fluorouracil (5-FU) by leucovorin (L-LV) in patients (pts) with advanced colorectal cancer has been demonstrated to produce a highly significant benefit over single-agent 5-FU in terms of tumor response rate, but this advantage does not translate into an evident improvement of overall survival. To improve the clinical efficacy of the 5-FU plus L-LV regimen a phase II study of weekly 24-hour high-dose 5-FU infusion with L-LV was undertaken. PATIENTS AND METHODS: Seventy advanced colorectal patients were enrolled and treated by a weekly outpatient combination regimen according to the following schedule: L-LV 100 mg/sqm by 4 hours i.v. infusion followed by 5-FU 2600 mg/sqm over a 24 hours infusion combined with a fixed dose of oral L-LV (50 mg) every 4 hours for 5 times. Forty-four pts did not receive any previous CT and 26 pts were pretreated with fluoropyrimidines. RESULTS: The overall objective response rate (OR) was 35.3%; 7 CR and 11 PR (42.8% OR) were observed in the group of untreated pts, and 6 PR (23% OR) were reported among previously treated pts. Major side effects were represented by diarrhoea (grade III: 26%, grade IV: 1%), hand-foot syndrome (grade III: 4%, grade IV: 1%) and mucositis (grade III: 4%); however, this did not significantly influence the therapeutic programme. Median 5-FU dose intensity was 100% and 80% at 4 weeks, 87% and 75% at 8 weeks in untreated and pretreated pts, respectively. CONCLUSIONS: L-Leucovorin modulation of weekly short-term continuous infusion of high-dose 5-fluorouracil appeared a well-tolerated outpatient regimen; it demonstrated a high activity in advanced colorectal cancer, both in untreated pts and in pts resistant to 5-FU-based chemotherapy.

Adult↗