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Biomedical subjects

L Tedeschi

Publications and source records attributed to L Tedeschi.

At least 19 recordsLinked to original sources
PubMed1996

Cisplatin-associated anaemia in patients with solid tumours. A retrospective evaluation and considerations relative to erythropoietin administration.

We have reviewed the incidence of cisplatin-induced anaemia in patients affected with solid tumours treated with at least three courses of first-line cisplatin-containing regimens. In our experience, a low percentage (5%) of patients required transfusions of red blood cells. We think it is of the utmost importance to adopt uniform criteria in monitoring and treatment of patients at risk of developing cisplatin anaemia and to identify subsets of patients to eventually treat with erythropoietin.

Anemia↗
PubMed1996

Effect of moderate or severe liver dysfunction on the pharmacokinetics of gamma-hydroxybutyric acid.

OBJECTIVES: To assess the effect of moderate or severe liver dysfunction on the pharmacokinetics of gamma-hydroxybutyric acid (GHB). METHODS: The absorption and disposition kinetics of GHB were studied in eight cirrhotic patients without ascites (Child's class A) and eight cirrhotic patients with ascites (Child's class C), after administration of a single oral dose of 25 mg.kg-1. The liver metabolic function of each patient was evaluated by measuring antipyrine clearance and the formation rate of the lidocaine metabolite monoethylglycinexylidide (MEGX). RESULTS: Compared to those previously determined in eight healthy control subjects given the same GHB dose, mean AUC values were double or greater in the cirrhotic patients. Accordingly, apparent oral clearance was markedly reduced (from 9.1 to 4.5 and 4.1 ml.min-1.kg-1 in nonascitic and ascitic patients, respectively). Terminal half-life (t1/2), was significantly longer in nonascitic patients than in control subjects (32 vs 22 min). A further significant prolongation of t1/2, most likely due to an increased distribution volume, was observed in patients with ascites (56 min). Nonetheless, GHB plasma concentrations fell to either undetectable or negligible levels by the end of the usual dosing intervals (6-8 h). More limited changes were noted in the absorption parameters. The peak level (Cmax) increased only in nonascitic patients, but not proportionally to the increase in AUC. The time to Cmax increased from 30 to 45 min in both cirrhotic groups. These findings are consistent with a slowed rate of GHB absorption in cirrhotic patients. Adverse effects were similar, for intensity and duration, to those recorded in healthy volunteers, i.e., mild and transient. CONCLUSIONS: Although liver cirrhosis causes significant modifications of GHB disposition kinetics, the increase in t1/2 is not such as to cause drug accumulation on repetitive dosing. However, in consideration of the higher mean plasma levels observed in cirrhotic patients, it appears wise to keep the initial GHB daily dose at the lower end of the therapeutic range and to carefully monitor the patients if upward dose adjustments are required.

Aged↗
PubMed1995

Fatality due to gamma-hydroxybutyric acid (GHB) and heroin intoxication.

The first case of fatal intoxication due to ingestion of gamma-hydroxybutyric acid (GHB) and intravenous use of heroin is reported. A 42-year-old man, known to have been a heroin addict and to have taken other psychoactive substances, who had been in treatment with GHB for several months, was found dead. Anatomohistopathologic examination showed generalized visceral congestion, edema and pulmonary anthracosis, chronic bronchitis and chronic active hepatitis. Toxicological findings included fluid and tissue distributions of GHB, morphine and 6-monoacetylmorphine. GHB and morphine concentrations were respectively 11.5 and 0.77 micrograms/mL (blood), 84.3 and 0.3 micrograms/mL (vitreous humor), 258.3 and 1.35 micrograms/mL (urine), 57.0 and 14.3 micrograms/mL (bile), 40.0 and 0.43 micrograms/g (brain), 43.0 and 0.60 micrograms/g (liver), 47.0 and 0.68 micrograms/g (kidney). Blood and urine levels of 6-monoacetylmorphine were 28.5 and 12.1 ng/mL respectively. The presumed mechanism of action and pharmacokinetics of GHB are briefly reviewed, with reference to its therapeutic use and to reports of non-fatal GHB intoxication.

Adult↗
PubMed1994

Drugs-of-abuse testing in urine: statistical approach and experimental comparison of immunochemical and chromatographic techniques.

This study deals with the experimental and statistical comparison of six immunochemical techniques, including noninstrumental on-site and instrumental formats (EIA-EMIT and EZ-SCREEN; FPIA-ADx; RIA-Coat-A-Count; LI-Abuscreen ONTRAK; CBI-Triage), and three chromatographic techniques (TLC-Toxi-Lab; HPLC; HPLC-REMEDi drug profiling system), using GC-MS as a reference technique for analyzing amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, methadone, and opiates in the urine of various kinds of drug users. The study reports (a) the values of sensitivity, specificity, false-positive rates, and false-negative rates of each technique; (b) the results of bayesian statistical analysis, which are based on prevalence values of the samples examined and expressed as positive and negative predictive values and cumulative predictive values for each single technique and for combinations of paired immunochemical and chromatographic techniques; and (c) the results of a rough classification of the various degrees of predictability of these techniques. Lastly, this study proposes a decision-making process for establishing the best combination of analytical techniques for the goals in question, according to the characteristics and facilities of each laboratory.

Chromatography↗
PubMed1994

Stages I and II non-Hodgkin's lymphoma of the gastrointestinal tract. Retrospective analysis of 79 patients and review of the literature.

We reviewed the medical records of 79 patients with primary gastrointestinal lymphoma (GI-NHL), defined according to the criteria of Dawson et al. (without involvement of liver, spleen, peripheral or mediastinal lymph nodes, or bone marrow), observed and treated in our institution between 1973-90. The most common disease site was the stomach (70 patients), followed by the small bowel (five patients) and the large bowel (four patients). The stage was IE in 36 cases and IIE in 43. Radical surgery or surgical debulking was the main therapeutic approach (67 patients); 12 patients received only chemotherapy, eight of whom had tumors considered unresectable at laparotomy. After surgery, most of the patients received chemotherapy; radiotherapy (RT) was given to only four patients. Surgically calculated overall survival (OS) rates at 5 years for the patients treated with surgery plus chemotherapy were 64% (radical surgery) and 46% (surgical debulking with microscopic lymphoma residue). For the 12 patients treated with chemotherapy alone, OS at 5 years was 0%. Our findings, in accordance with most published data, suggest that surgery, together with stage and tumor size, remains an important prognostic factor of survival in primary GI-NHL, especially when it is radical. In patients with negative prognostic factors (bulky disease, high-grade histologic type, microscopic residue, and stage II), postoperative chemotherapy and RT decrease the risk of distant failure and local recurrence.

Adult↗
PubMed1994

Impact of interferon at induction chemotherapy and maintenance treatment for multiple myeloma. Preliminary results of a multicenter study by the Italian non-Hodgkin's Lymphoma Cooperative Study Group (NHLCSG).

In 1990 the Italian Non-Hodgkin's Lymphoma Cooperative Study Group (NHLSG) started a multicenter study on the role of interferon (IFN) in multiple myeloma (MM). The schedule of treatment was based on the assumption that melphalan plus prednisone (MP) would be better for good-prognosis patients, whereas poor-prognosis patients would benefit from polychemotherapy. Accordingly, IFN was included randomly for the induction treatment of good-prognosis patients and randomly as maintenance of the response achieved in both groups. Up to now 78 patients of the 124 enrolled have completed the induction treatment and are evaluable for response and response duration. The overall response rate was 59%. Sixty-two percent of good-prognosis patients obtained objective response, 9/14 (64%) with MP and 9/15 (60%) with MP+IFN. Up to now, with a median follow-up of 9 months from the evaluation of response, no difference has been recorded between the maintenance and no maintenance groups on relapse rate, neither in good- nor in poor-prognosis patients.

Aged↗
PubMed1993

Dose-dependent absorption and elimination of gamma-hydroxybutyric acid in healthy volunteers.

Gamma-hydroxybutyric acid (GHB) is effective in treatment of the alcohol and opiate withdrawal syndromes. Its absorption and disposition kinetics have been studied in 8 healthy male volunteers following oral administration of single doses of 12.5, 25 and 50 mg kg-1. The AUC increased disproportionately with the dose and so the apparent oral clearance decreased significantly as the dose was increased, whereas the terminal half-life and mean residence time increased. The peak plasma concentrations normalised to the lowest dose fell significantly with increasing doses, whilst the corresponding peak times increased. These findings suggest that both the oral absorption and the elimination of GHB are capacity-limited processes. GHB did not bind to significant extent to plasma proteins over the therapeutic concentration range. The pharmacokinetic parameters in healthy volunteers were not significantly different from those previously observed in alcohol-dependent patients with compensated alcoholic liver disease.

Absorption↗
PubMed1993

Simultaneous identification of amphetamine and its derivatives in urine using HPLC-UV.

An HPLC-UV method for the simultaneous identification of amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine (MDA) and 3,4-methylenedioxymethamphetamine (MDMA) in urine is described. It includes a rapid extraction procedure of the 4 analogs from urine using Extrelut 3 columns, derivatization with sodium 1,2-naphthoquinone-4-sulphonate (NQS) to obtain highly chromophoric UV-VIS derivatives, and a final HPLC analysis using an ion-pair reversed-phase technique with eluent monitoring at 480 nm. Structural characterization of the derivatives obtained by mass spectrometry is reported. Recoveries of the amphetamines were in the range 80-85% at concentrations of 300 ng/ml. Practical detection limits were 40-60 ng/ml (S/N ratio = 10) for all derivatives. The chromatographic peaks of the NQS derivatized amphetamines are fairly narrow and well resolved. The method is simple, rapid, quite sensitive, and specific for convenient confirmation of preliminary positive results obtained with immunoassays.

3,4-Methylenedioxyamphetamine↗
PubMed1993

Therapeutic gamma-hydroxybutyric acid monitoring in plasma and urine by gas chromatography-mass spectrometry.

A gas chromatographic-mass spectrometric (GC-MS) method for the determination of therapeutic levels of gamma-hydroxybutyric acid (GHB) in plasma and urine samples is described. GHB is converted to its lactonic form gamma-butyrolactone (GBL) which is extracted from biological fluids after the addition of the internal standard delta-valerolactone. Final GC-MS analysis is obtained under electron impact selected ion monitoring (SIM) conditions. Mean relative recoveries of GHB from plasma and urine are 75.5% (RSD% = 2.2) and 76.4% (RSD% = 2.4), respectively. The assay is linear over a plasma GHB range of 2-200 micrograms ml-1 (r = 0.999) and a urine GHB range of 2-150 micrograms ml-1 (r = 0.998). Intra- and inter-assay relative standard deviations (n = 5) determined at 10 and 100 micrograms ml-1 are below 5%. The method is simple, specific and accurate, and may be applied for analytical purposes related to pharmacokinetic studies and therapeutic drug monitoring.

4-Butyrolactone↗
PubMed1992

High dose alpha-2b interferon + folinic acid in the modulation of 5-fluorouracil. A phase II study in advanced colorectal cancer with evidence of an unfavourable cost/benefit ratio.

The combination of folinic acid (FA) and 5-fluorouracil (5FU) is the most active systemic chemotherapy against advanced colorectal cancer. Experimental and clinical studies have suggested that the activity of 5FU can be improved by the addition of alpha-interferon (IFN). To evaluate the possibility of a double modulation of 5FU, a pilot study was conducted in the period July 1989-December 1989 with the following regimen: FA (200 mg/m2 i.v. bolus x 5 days) + 5FU (400 mg/m2 i.v. in 15 min x 5 days) + alpha-2b IFN (10 x 10(6) IU subcutaneously on alternate days). FA and 5FU administrations were repeated every 28 days; IFN was administered every week. In the 16 treated patients, 4 partial responses, 4 no changes, and 8 with progression of disease were observed, with an objective response rate of 25% (95% CI, 7.8%-55.1%). Median duration of response was 9.5 months, as was overall survival. Toxicity (fever, fatigue, neurotoxicity, stomatitis and diarrhea) was considerable and led to a reduction in IFN doses in 10/16 patients. Due to the unfavorable cost/benefit ratio, the study was closed and a new trial, with different doses and schedule of IFN, was started within the GISCAD (Italian Group for the Study of Digestive Tract Cancer).

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Pharmacokinetics of gamma-hydroxybutyric acid in alcohol dependent patients after single and repeated oral doses.

1. The pharmacokinetics of gamma-hydroxybutyric acid (GHB) were studied in 10 alcohol dependent subjects after single and repeated therapeutic oral doses (25 mg kg-1 every 12 h for 7 days). 2. GHB was readily absorbed and rapidly eliminated (tmax = 20-45 min; mean t1/2z 27 +/- 5 s.d. min). Urinary recovery of unchanged GHB was negligible (less than 1% of the dose). gamma-butyrolactone was not detected in either plasma or urine, indicating that lactonization of GHB does not occur in vivo. 3. The multiple-dose regimen resulted neither in accumulation of GHB nor in time-dependent modification of its pharmacokinetics. 4. In five subjects, the data were consistent with nonlinear elimination kinetics of GHB. Administration of a 50 mg kg-1 dose to these subjects resulted in significant increases in dose-normalized AUC, t1/2z and mean residence time. 5. Doubling of the dose also resulted in a significant increase in tmax with little change in Cmax. 6. At the administered doses, GHB did not accumulate in the plasma and caused no serious side effects.

Administration, Oral↗
PubMed1983

Confirmed activity of FAM polychemotherapy in advanced gastric carcinoma.

During a 3-year period at our hospital, 54 consecutively observed patients with parametric, locally advanced, metastatic gastric carcinoma were treated with fluorouracil + adriamycin + mitomycin C. Of 47 evaluable patients, 44.6% had an objective response (complete + partial response) and 29.7% had stabilized disease. The median duration of response was 7.5 months. The median survival was 8.9 months for all patients. In particular, the survival of responders (greater than 12 months) and of patients with stabilized disease (8.6 months) was significantly longer than that of patients with progressive disease (4.5 months). Toxicity was limited and reversible, which allowed treatment also of patients in poor general condition (PS 3-4 of the Zubrod scale).

Adult↗
PubMed1980

Chemotherapy of soft tissue sarcomas.

The medical treatment of advanced soft tissue sarcomas in adults is reviewed. Response rates of 40--50% are obtainable after various polychemotherapies, mainly containing doxorubicin and dacarbazine. Response to secondary treatment is very poor and indicates the need for further clinical research in these infrequent malignant tumors.

Antineoplastic Agents↗
PubMed1979

Amino acid content in fresh sperm and sperm stains.

Seminal fluid was studied biochemically for sperm identification in stains. The qualitative and quantitative distribution of amino acids in samples of fresh sperm has been alayzed. These findings were compared to the results of a similar study of fresh samples and stains of urine, saliva, vaginal fluor, and sweat. The results obtained show a specific and relatively constant level of amino acids in each of five biological liquids. There was no significant variation in results between fresh samples and stains.

Amino Acids↗