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Biomedical subjects

A Bonetti

Publications and source records attributed to A Bonetti.

At least 19 recordsLinked to original sources
PubMed1995

n-Hexane-induced parkinsonism: pathogenetic hypotheses.

n-Hexane, similar hydrocarbons, and derivatives are common environmental pollutants and by-products of lipid peroxidation, and they may have a nigrotoxic effect like that of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. This report describes our second case of parkinsonism in a subject exposed to n-hexane. Positron emission tomography studies demonstrated regional striatal abnormalities of the nigrostriatal dopaminergic system and of glucose metabolism that were different from those found in idiopathic Parkinson's disease.

Air Pollutants, Occupational↗
PubMed1995

Estrogen receptors in 699 primary breast cancers: a comparison of immunohistochemical and biochemical methods.

BACKGROUND: Over the last few years, estrogen receptor (ER) determination by immunohistochemistry (ER-ICA) has been extensively used, but it still remains to be established whether this method can replace the standard biochemical technique using dextran-coated charcoal (ERDCC). PATIENTS AND METHODS: ER were determined by both the dextran-coated charcoal (DCC) method and immunohistochemistry (ICA) in 699 patients with primary breast cancer; other parameters (age, pathological T-pT- and nodal status -pN-, progesterone receptors by DCC, proliferative index by ICA) were also recorded. The 'best' cut-off for ERICA was evaluated by means of Receiver Operating Characteristics (R.O.C.) analysis; logistic regression analysis was used to find adequate 'weights' for stain intensity. RESULTS AND CONCLUSIONS: A significant correlation was found between the two methods (p < 0.001). R.O.C. analysis revealed that the 'best' cut-off for the ERICA score was 45% (sensitivity 0.810, specificity 0.804). Logistic regression analysis showed that an ERICA score which also considers staining intensity does not add any useful information concerning ER content in breast cancers.

Breast Neoplasms↗
PubMed1995

Cisplatin pharmacokinetics using a five-day schedule during repeated courses of chemotherapy in germ cell tumors.

Total and ultrafilterable platinum (Pt) disposition was investigated during 49 courses of chemotherapy in 13 patients with germ cell tumor treated with cisplatin (DDP), 20 mg/m2/day on 5 consecutive days. The following pharmacokinetic parameters were analyzed: distribution (t1/2 alpha) and elimination (t1/2 beta) half-lives, total body clearance (ClT), renal clearance (ClR), and areas under the concentration versus time curve (AUCs). Blood samples were collected immediately before and after DDP infusion (Day 1 through Day 5); in addition, on Day 5, samples were collected at 0.25, 0.5, 1, 8, 24, and 48 h after DDP infusion. Urine was collected during each day of treatment and up to 48 h after the last DDP dose. During each chemotherapy cycle plasma levels of total and ultrafilterable Pt progressively increased from the first to the last day of treatment. At the first cycle, total Pt concentrations ranged from 0.67 to 1.46 micrograms/ml (mean increase, 118%), and those of ultrafilterable Pt from 0.117 to 0.205 micrograms/ml (mean increase, 75%). Mean +/- SD total Pt plasma levels immediately postinfusion increased from 0.67 +/- 0.20 microgram/ml at the first cycle (first day of therapy) to 1.13 +/- 0.21 microgram/ml at the same time point at the fourth cycle. Mean total Pt peak levels were reached at the end of infusion on the last day of each cycle, and increased from 1.46 +/- 0.29 microgram/ml (first cycle) to 1.89 +/- 0.40 microgram/ml (fourth cycle). Total Pt was detectable in plasma before the beginning of all cycles following the first. As a result, AUC significantly increased and ClR significantly decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Lipoprotein(a) and exercise.

Plasma levels of lipoprotein(a), total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, apoprotein A1 and apoprotein B were assessed in 10 healthy, untrained volunteers subjected to a bicycle ergometric exercise equal to 50% of individual VO2max, followed by increasing loads until muscular exhaustion. Blood samples were taken before the exercise, immediately afterwards and then at 12-hourly intervals for a 72 hours period. Subsequently, the same parameters were evaluated for 8 long-distance runners during the XXIII New York Marathon, with blood samples being taken before and after the race, and then after one month of detraining. After the exercise, lipoprotein(a) in untrained subjects began to decrease significantly from the 24th hour on and remained lower than baseline levels up till the 72nd hour. After detraining, lipoprotein(a) in marathon runners increased significantly both with respect to basal values and especially to post-race values. Modifications of the other metabolic parameters evaluated in both tests were negligible and predictable. In the two groups of subjects examined, no correlation was found between lipoprotein (a) and the anthropometrical data and metabolic parameters considered.

Adult↗
PubMed1994

Separation and detection of herbicides in water by micellar electrokinetic capillary chromatography.

The herbicides linuron, metolachlor, atrazine and metsulfuron were analysed using micellar electrokinetic capillary chromatography (MECC) after a 1000-fold concentration step by solid-phase extraction (SPE). Recoveries ranged from 80 to 92%, depending on the concentration and the number of active substances in the sample. Furthermore, the hydrolysis products of metsulfuron were analysed by MECC and by gas chromatography-mass spectrometry (GC-MS). Representative MECC and GC-MS profiles are shown and the structures of the hydrolysis products are proposed on the basis of their chromatographic and mass spectra features. A tentative pathway for the degradation of metsulfuron is proposed.

Chromatography↗
PubMed1994

An extended-release formulation of methotrexate for subcutaneous administration.

Methotrexate is a cell-cycle phase-specific antimetabolite that requires prolonged exposure for optimal efficacy. However, the in vivo half-life is short, and repeated administrations are required for optimal efficacy. Methotrexate was encapsulated into a lipid-based drug-delivery system to create an extended-release formulation (Depo/methotrexate) for subcutaneous administration. Pharmacokinetics and efficacy studies were done in BDF1 mice. Depo/methotrexate increased the methotrexate plasma half-life by a factor of 190, from 0.53 to 100 h. Plasma peak levels of the encapsulated drug were 120-fold lower than those of unencapsulated methotrexate, whereas the AUCs (areas under the concentration-time curve) were similar. As a consequence of the extended drug release, the single-dose potency of methotrexate against the L1210 leukemia model was increased by a factor of about 130 without producing significant changes in the therapeutic index. In conclusion, Depo/methotrexate appears to have potential usefulness as an extended-release formulation of methotrexate.

Animals↗
PubMed1994

Cisplatin pharmacokinetics in elderly patients.

The treatment of elderly patients with cancer may be difficult because of the narrow therapeutic index of antineoplastic drugs, the decline in the performance of organs and functions, and frequent comorbidity. In these patients, therapeutic drug monitoring may be useful in optimizing chemotherapy. Six patients older than 70 years with a variety of solid tumors received a total of 21 cycles of cisplatin (DDP)-based chemotherapy program (DDP dose, 50-65 mg/m2). Total and ultrafilterable platinum (Pt) were determined in plasma and urine during the first cycle of the therapy by means of atomic absorption spectroscopy. Pharmacokinetic parameters were analyzed with use of a two-compartment open model. The treatment was generally well tolerated. The most important side effects were a significant increase in serum creatinine level (from 0.98 to 1.23 mg/dl) and a decrease in creatinine clearance (from 44.4 to 38.9 ml/min) in comparison with pretreatment values. The mean decrease in hemoglobin levels was slight. The values of the main pharmacokinetic parameters of total Pt agreed well with the data obtained with other adult patients. Total and ultrafilterable Pt had a short distribution phase (t1/2 alpha = 0.35 and 0.54 h, respectively) followed by a prolonged elimination phase (t1/2 beta = 63.08 and 58.91 h, respectively). A reduced ability to clear ultrafilterable Pt (ClT = 123.52 ml h-1 kg-1) was evident and, as a result, the area under the curve increased (15.47 mg h L-1). The limited number of patients and the concomitant use of other agents prevent any firm conclusions.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

High-dose biweekly intraperitoneal cisplatin: an effective way to increase cisplatin dose intensity.

The amount of cisplatin (DDP) delivered per unit time (dose intensity, expressed in mg/m2/week) may be an important factor in determining the clinical outcome in tumors such as ovarian carcinoma. In this neoplasm, intraperitoneal chemotherapy is an effective form of treatment. In this trial we have explored the tactic of shortening the cycle interval as a way to increase the dose intensity of ip DDP. Sixteen patients with a variety of solid tumors received a total of 77 cycles of DDP 180 mg/m2 instilled ip concurrent with i.v. sodium thiosulfate at the dose of 4 g/m2 as loading dose, followed by 12 g/m2 over 6 hr. Each cycle was repeated every 2 weeks. The number of cycles delayed for 3 or more days was 28 (36%). The mean DDP dose intensity received by these patients was 77% of the planned dose or 69 mg/m2/week (confidence interval 95%, 60.5-77.5). The treatment was generally well tolerated: myelotoxicity was mild, only 1 patient had an increase in serum creatinine to > 2 mg/dl. Five patients (31%) developed symptoms of peripheral neuropathy. All patients were evaluable for response. The overall response rate (complete plus partial) in these heavily pretreated patients was 19%. When DDP is given in high doses by the ip route concurrently with systemic sodium thiosulfate, the dosing interval can be reduced to every 2 weeks permitting a marked increase in DDP dose intensity.

Abdominal Neoplasms↗
PubMed1993

Pharmacokinetics of an extended-release human interferon alpha-2b formulation.

The in vivo half-life of human interferon alpha-2b (hIFN-alpha-2b) is relatively short, and frequent injections over prolonged periods are required for efficacy. An extended-release formulation of hIFN-alpha-2b (Depo/IFN) was created by encapsulation into a lipid-based drug-delivery system. The capture efficiency was 51% +/- 13% and the release half-life in human plasma at 37 degrees C was 16 days. The pharmacokinetics of Depo/IFN was compared with that of unencapsulated standard hIFN-alpha-2b (Std/IFN) in the peritoneal cavity of male BDF1 mice. Depo/IFN exhibited a 13-fold longer intraperitoneal (i.p.) half-life as compared with Std/IFN (20 vs 1.5 h). The release of free hIFN-alpha-2b from Depo/IFN into the peritoneal cavity was slow and protracted, with a 10-fold lower peak concentration and a 13-fold longer apparent half-life being observed in comparison with Std/IFN. The areas under the curve of free hIFN-alpha-2b in the peritoneal cavity were comparable for Depo/IFN and Std/IFN. hIFN-alpha-2b was detectable in plasma only after the i.p. administration of Std/IFN. These data suggest the possibility that Depo/IFN may be useful as an extended-release formulation of hIFN-alpha-2b.

Animals↗
PubMed1993

Dose intensification of cisplatin chemotherapy through biweekly administration.

PURPOSE: Dose intensity (DI, expressed in mg/m2/wk) may be an important factor in the clinical use of cisplatin (DDP). We have explored the shortening of the cycle interval as a way to increase the DI of DDP. PATIENTS AND METHODS: DDP 180 mg/m2 was given intravenously (i.v.) over 4 hours; sodium thiosulfate (STS) was given i.v. in the opposite arm at a loading dose of 4 g/m2, followed by 12 g/m2 over 6 hours. Each cycle was repeated every two weeks. Seventy-five cycles were administered to 28 patients in this clinical trial. RESULTS: In 19 patients who received 2 or more cycles of chemotherapy, a delay of three or more days was required on 17/66 courses (26%); the mean DDP DI actually received by these patients was 83 mg/m2/wk (88% of the planned DI). The major side effect was ototoxicity; this occurred in 9 patients (33%), but none required a hearing aid. Myelosuppression was moderate with thrombocytopenia greater than neutropenia. Nephrotoxicity (creatinine > 2 mg/dl) occurred on only 2 cycles (3%). Three patients (11%) developed symptoms of peripheral neuropathy. In 23 evaluable patients, the overall response rate was 39%. CONCLUSION: It is feasible to give 180 mg/m2 of DDP and STS every two weeks with tolerable nephrotoxicity but without blocking other types of toxicity, such as myelosuppression and ototoxicity. The shortening of cycle intervals resulted in a markedly increased DI.

Adult↗
PubMed1992

Estrogen and progesterone receptors in breast cancer: correlation with clinical and pathological features and with prognosis.

Estrogen and progesterone receptor status was reviewed in 405 patients from prior adjuvant breast cancer trials at the University of Verona. Only 233 patients were actually examined with respect to hormone status and outcome. No relationship between hormone receptor status and most of the commonly followed prognostic signs, i.e. tumor size, nodal status, and age, was found. Overall survival was correlated with hormone receptor positivity for patients with more than 4 positive axillary nodes. Disease-free survival was correlated only with PgR positivity, in premenopausal and in T1 groups.

Breast Neoplasms↗
PubMed1991

Visualization of nimodipine (NIM) binding sites of rat brain by means of a NIM-colloidal gold complex (1-2).

It is described a new method to visualize the binding sites of the Ca(2+)-antagonist nimodipine (NIM) on brain cryostatic sections. NIM was bridged to colloidal gold sols by a suitable amphophilic detergent, and used according to autoradiographic procedures. A detailed mappage of vascular and neuronal NIM binding sites was allowed by silver-intensification of the NIM-gold complex bound to the nervous tissue. Selective distribution patterns were visualized in the main cerebral and cerebellar areas, suggesting that the drug potentially may act on multiple, different targets in the CNS.

Animals↗
PubMed1991

[Postsurgical gastric bezoar: presentation of a case of esophageal impaction].

A possible late sequel of gastric surgery is the formation of a phytobezoar in stomach. The phytobezoar can undergo fragmentation and the fragments can migrate causing obstructions. We present a case of proximal migration and esophageal obstruction. Surgical treatment was needed. We analyze the causes which produce this disorder and current therapeutic measures. The literature is reviewed.

Adult↗
PubMed1989

Co-infection with human immunodeficiency virus-type 1 (HIV-1) and cytomegalovirus in two intravenous drug users.

A mononucleosis-like illness is frequently recognized retrospectively as the first manifestation of infection with human immunodeficiency virus-type 1 (HIV-1). This acute but transient retroviral syndrome may include symptoms such as malaise, fever, sweats, myalgia, arthralgia, maculopapular rash, diarrhea, and lymphocytic meningitis. We observed two intravenous drug users who developed a severe, febrile illness with subsequent oral thrush (one also had biopsy-proven esophageal candidiasis). Both patients had weight loss, arthralgia, myalgia, and fatigue. These symptoms occurred two weeks after needle-sharing and persisted for 7 weeks in one patient and 10 weeks in the other. Both patients had serologic evidence for both acute HIV-1 and cytomegalovirus infection. Cytomegalovirus enhances HIV-1 replication in vitro, presumably by stimulating HIV-1 gene expression. Thus, the observed syndrome suggests that this viral interaction may be clinically significant because it appears to cause severe additional morbidity, which is not typical for primary infection with HIV-1. After 6 months of follow-up, one patient is completely asymptomatic but shows markedly reduced CD4+ lymphocytes. The other patient developed persistent lymphadenopathy after the acute illness, but is feeling well 21 months after infection.

Acquired Immunodeficiency Syndrome↗
PubMed1989

[Clinical counseling and management of HIV-positive patients--secondary individual prophylaxis in patients with HIV infection].

In patients with HIV infection, secondary prophylaxis should prevent HIV-associated complications caused by opportunistic infections and psychosocial morbidity. This overview presents the possibilities of chemoprophylaxis and control of transmission to prevent opportunistic and non-opportunistic infections. Indications for immunization in HIV-positive patients are also discussed. Both medical treatment and psychological and social support are equally important for optimal patient care.

Anti-Bacterial Agents↗
PubMed1989

The influence of ubiquinone (Co Q10) on the metabolic response to work.

Ubiquinone (Co Q10) is a natural substance suitable for therapeutic use in cardiology and in the treatment of some muscular diseases. It might therefore be used during strenuous exercise (as in athletic competitions), especially in the presence of metabolic modifications which may justify its use. For this purpose, we have evaluated the effect of prolonged treatment with Co Q10 (100 mg/day per os for one month) on the biological changes induced by prolonged work on an ergometer bicycle (equal to about 50% of the single VO2max per 60 m'), immediately followed by exhaustive work (25 watts increase every 2 m'). From the venous blood of 12 healthy untrained subjects (students, volunteers, mean age 25.7 and body mass index 23.3) we examined some biological parameters [free fatty acids (FFA), free glycerol, lactate, glucose, insulin, CK] before, at the end of aerobic work, at the end of exhaustive work, and after 30 and 60 m' of the recovery phase. The same indexes, measured after identical times and work, were evaluated after one month of treatment with Co Q10. The only relevant modifications observed were those concerning FFA: at the end of aerobic work and after the administration of the drug, lower levels were reached (before, 1011 +/- 329 microEq/l; after 790 +/- 392; p less than 0.05); the same trend was observed at the end of the exhaustive work (1031 +/- 320 microEq/l vs 826 +/- 387; p less than 0.05). At the subsequent times, as well as for the other biological parameters examined, we did not observe any variation before or after the period of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗