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Biomedical subjects

A Messori

Publications and source records attributed to A Messori.

At least 145 records · Page 8Linked to original sources
PubMed1983

Pharmacokinetic predictions based on a variable dosage frequency in chronic treatment.

After repeated intramuscular or oral administration, plasma drug levels are predicted by using a programmable calculator. Predictions are based on a one-compartment, open model with first-order absorption. The actual times of dosing are considered, so that the assumption of a constant dosing interval is not required. A brief analysis of the pharmacokinetic consequences that may result from a variable dosage frequency is presented.

Computers↗
PubMed1983

A new programmable calculator procedure for individualizing phenytoin dosage.

A programmable calculator procedure allowing nonlinear least-squares fit to pharmacokinetic data conforming to the Michaelis-Menten model is described. Model parameter estimation is performed according to the iterative Gauss-Newton technique as modified by Hartley. This procedure thus employs the same theoretical approach used by most pharmacokinetic computer programs. No programming skill is needed to run the program described. The proposed procedure is discussed in detail and applied to some sets of pharmacokinetic data.

Computers↗
PubMed1983

Iterative least-squares fitting programs in pharmacokinetics for a programmable handheld calculator.

Programs that perform a nonlinear least-squares fit to data conforming to one-compartment oral or two-compartment intravenous pharmacokinetic models are described. The programs are designed for use on a Hewlett-Packard HP-41 CV programmable calculator equipped with an extended-functions module and one or two extended-memory modules. Initial estimates of variables in the model are calculated by the method of residuals and then iteratively improved by the use of the Gauss-Newton algorithm as modified by Hartley. This modification minimizes convergence problems. The iterative-fitting procedure includes a routine for estimation of lag time for the one-compartment oral model. Clinical applications of the programs are illustrated using previously published data. Programming steps and user instructions are listed. The programs provide an efficient and inexpensive method of estimating pharmacokinetic variables.

Absorption↗
PubMedDate not supplied

Cryoprecipitate and Factor VIII commercial concentrates: in vitro characteristics and in vivo compartmental analysis.

In vitro and in vivo characteristics of cryoprecipitates and three commercial factor VIII concentrates (Kryobulin, Hemofil and Koate) were comparatively studied. Factor VIII:C/VIIIR:Ag ratio was very low in all commercial concentrates without differences among them. Conversely, the decrease of factor VIIIR:WFRCof was proportional to the degree of purity. Factor VIII:C/VIIIR:WFRCof ratio was shown to be a reliable index of factor VIII complex denaturation. Crossed electroimmunoassay showed a faster migration of factor VIIIR:Ag only in commercial concentrates. Using a two-compartmental open model that accounts for endogenous synthesis of factor VIII:C, single-dose kinetics of factor VIII:C were studied in 23 patients with classic hemophilia. Good agreement between measured and fitted values of factor VIII:C plasma concentration was observed. beta half-life was shorter in high purity concentrates and longer in intermediate purity concentrates and cryoprecipitates.

Antigens↗
PubMedDate not supplied

A calculator program for least-squares parameter estimation according to the one-compartment kinetic model with zero-order input.

A calculator program that performs a nonlinear least-squares fit to data conforming to the one-compartment model with zero-order input is described. The program, which is designed for the Hewlett-Packard HP-41 CV calculator, is based on the Gauss-Newton iterative algorithm as modified by Hartley. A subroutine for calculation of initial parameter estimates is incorporated into the program. Plasma concentration data relative to a single oral dose of a sustained-release theophylline formulation are used to demonstrate the practical application of the program.

Computers↗
PubMedDate not supplied

Predictive performance of pharmacokinetic methods for phenytoin dosing: a multi-center evaluation in 282 patients with epilepsy.

A retrospective study was conducted in 282 patients with epilepsy to assess the predictive performance of pharmacokinetic methods for individualizing dosage of phenytoin. Two population-based dosing methods (population clearance method and bayesian feedback method) and one individual-based method (the so-called linearized Michaelis-Menten method) were evaluated, when applicable, for single-point and/or 2-point dose predictions of phenytoin. In single-point predictions, we found a generally low percentage of dose calculations falling inside the +/- 10% range (48.9% and 51.1% for the population clearance and the bayesian methods, respectively). In 2-point predictions, the bayesian method was 'accurate' (dose within the +/- 10% range) in approximately 54.3% or 55.0% of cases (depending on the particular method of implementation adopted). An even worse percentage of 'accurate' dose predictions (38.3%) was obtained by using the linearized Michaelis-Menten method. Our data do not confirm results from previous studies indicating a generally good performance of pharmacokinetic methods for predicting phenytoin dosage.

Adolescent↗
PubMedDate not supplied

Clinical features, pathogenesis and management of drug-induced seizures.

Many classes of pharmacological agents have been implicated in cases of drug-induced seizures. The list includes antidepressant drugs, lithium salts, neuroleptics, antihistamines (H1-receptor antagonists), anticonvulsants, central nervous system stimulants, general and local anaesthetics, antiarrhythmic drugs, narcotic and non-narcotic analgesics, non-steroidal anti-inflammatory drugs, antimicrobial agents, antifungal agents, antimalarial drugs, antineoplastic drugs, immunosuppressive drugs, radiological contrast agents and vaccines. For each of these classes of drugs, this article offers a revision of the literature and emphasises in particular the frequency of the adverse reaction, its clinical presentation, its presumed epileptogenic mechanism and the therapeutic strategy for the management of drug-induced seizures. An attempt is also made to distinguish seizures induced by standard dosages from those provoked by accidental or self-induced intoxication. For some classes of drugs such as antidepressants, neuroleptics, central nervous system stimulants (e.g. theophylline, cocaine, amphetamines) and beta-lactam antibiotics, seizures are a well recognised adverse reaction, and a large body of literature has been published discussing exhaustively the major aspects of the issue; sufficient data are available also for the other classes of pharmacological agents mentioned above. In contrast, several other drugs [e.g. allopurinol, digoxin, cimetidine, protirelin (thyrotrophin releasing hormone), bromocriptine, domperidone, insulin, fenformin, penicillamine, probenecid, verapamil, methyldopa] have not been studied thoroughly under this aspect, and the only source of information is the occasional case report. This review does not address the issue of seizures induced by drug withdrawal.

Animals↗
PubMedDate not supplied

Treatments for newly diagnosed multiple myeloma: analysis of survival data and cost-effectiveness evaluation.

The main therapeutic options currently available to induce remission in newly diagnosed cases of multiple myeloma include: i) melphalan at conventional doses without concurrent administration of interferon; ii) melphalan at conventional dose combined with interferon; iii) autologous bone marrow transplantation (ABMT). We conducted an analysis of the survival data reported in five large-scale published clinical trials and we evaluated the cost-effectiveness ratio. We determined the mean lifetime survival (MLS) for each treatment group using the Gompertz model. The cost data of patients given ABMT or standard chemotherapy were estimated from published information. The values of MLS were 3.47 years per patient for melphalan at conventional doses without interferon, 3.74 years for melphalan at conventional doses combined with interferon, and 7.28 years for ABMT. As compared with conventional melphalan treatment, ABMT yielded a significantly better survival. Survival after melphalan combined with interferon was not significantly different from that following melphalan alone. Using melphalan at conventional doses without interferon as reference term, the marginal cost-effectiveness ratio of ABMT was of about $26,000 per life year gained. For the induction treatment in patients with newly diagnosed myeloma, ABMT seems to be more effective and more cost-effective than the standard treatment with melphalan at conventional doses.

Antineoplastic Agents↗
PubMedDate not supplied

A new method for expressing survival and life expectancy in lifetime cost-effectiveness studies that evaluate cancer patients (review).

The methodology of cost-effectiveness studies that use a lifetime perspective is based on the extrapolation to infinity of the survival curves. However, the research in this methodological area is at an initial phase. Hence, adequate techniques for survival curve extrapolation still need to be devised for handling the different clinical settings that can be analysed by cost-effectiveness survival studies. After a brief overview of the two most commonly used extrapolation methods (Markov decision-tree model and Gompertz technique), we describe a new method for expressing lifetime survival in cost-effectiveness studies that evaluate cancer patients. Our method extrapolates to infinity a traditional survival curve by assigning a normal life expectancy to patients (or long-term survivors). In this way, the value of mean lifetime survival (MLS) for the patient cohort under study can be determined using a lifetime perspective. This value can be employed in lifetime cost-effectiveness analyses that compare different forms of intervention for that disease condition. A separate section of our method compares the overall survival pattern of cured and not cured patients with that of a reference healthy population to assess the impact of the disease on life expectancy. As an example of the application of our method, we reanalysed a survival data set reported by Spinolo et al in 1992, that refers to patients with acute leukaemia who relapsed after their first allogeneic bone marrow transplantation and who received a second transplant (n=17, mean age at relapse = 26 years). The use of our extrapolation method provided the following results: MLS for leukaemia patients = 105.9 months per patient or 8.8 years per patient; MLS for the reference cohort of healthy subjects = 583.8 months per patient or 48.6 years per patient. We conclude that the extrapolation technique described herein can be useful to handle lifetime survival data in cost-effectiveness analysis.

Cost-Benefit Analysis↗
PubMedDate not supplied

Treatment of large cell lymphoma with the Fi2 regimen (doxorubicin, vincristine, cyclophosphamide, bleomycin and prednisone): 25-year experience.

The CHOP protocol is the reference treatment for large cell lymphomas, but several other schemes of different intensity have recently been studied with controversial clinical findings. We report here the results obtained at our institution with a CHOP-like regimen called Firenze 2 (Fi2), which is characterised by an original scheduling of chemotherapy administration. A total of 225 patients, who were diagnosed from 1974 to 1996, were included in this retrospective study. All patients received the Fi2 regimen as a first-line intervention. One-hundred and sixty-two (72%) achieved complete remission; the overall survival at 120 months was 51% with a disease-free survival of 67% (median follow-up = 78 months). The survival curve showed a stable plateau of 42% after 16 years, which remained stable for further 4 years. In a multivariate survival analysis, achievement of complete remission (p<0.001) and IPI index of 0 or 1 (p=0.05) were significantly associated with a better survival. Overall, the outcome of our patients was similar to that reported by others, but the distinguishing feature of our study is the very long follow-up of the patients. Our study confirms that first generation regimens are effective and can cure a substantial proportion of patients. The long-term results of our study are helpful to retrospectively identify high-risk patients whose prognosis is poor and who can be candidates for more aggressive schemes of chemotherapy.

Aged↗
PubMedDate not supplied

Clinical data and therapeutic approach in elderly patients with Hodgkin's disease.

The present study was undertaken to investigate the clinico pathologic features of Hodgkin's disease in a series of 114 elderly patients (age greater than 60 yrs), with particular reference to prognosis and treatment. Mixed cellularity (63.2%) was the most frequent histologic subtype. Clinical presentation was characterized by superficial lymphadenopathy (92%) and the presence of general symptoms (40.4%); mediastinal involvement was observed in 16.6% of cases; 17.5% of patients had a primitive infradiaphragmatic presentation. Thirty-eight patients were treated with radiotherapy alone (33.4%), 69 with chemotherapy alone (60.5%), while 7 received combined treatment. Complete remission was obtained in 85 patients (74.6%), 25 of whom relapsed. Elderly patients had an overall 5-year survival rate of 61.8% (considering only disease progression as a cause of death). Proportional-hazard multi variate statistics showed that survival was strongly influenced by the achievement of complete remission (P less than 0.001) and stage (P = 0.011). The achievement of complete remission was also significantly linked to the presence of constitutional symptoms, advanced stage and age greater than 70 yrs, as demonstrated by discriminant statistical analysis. The actuarial incidence of second cancer (28.7% at 15 yrs) was slightly higher than that previously reported in younger patients. Overall, our data indicate that the treatment of elderly patients with Hodgkin's disease should be aimed at achieving a cure, using the same therapeutic modalities commonly employed in younger subjects.

Aged↗
PubMedDate not supplied

Hyperprolactinemia and 5-alpha-reductase activity.

A number of experimental data indicate that hyperprolactinemia inhibits the activity of 5-alpha-reductase; however, no information is available about the time required for this enzyme to re-activate after prolactinemia has returned to normal values. In the present study, five normal caucasian men, whose fertility had previously been proven, were given HCG (5000 IU/day by intramuscular route for three days) both in basal conditions and after sulpiride-induced hyperprolactinemia (dosage = 200 mg/day for ten days). In both conditions, the plasma levels of prolactin (PRL), testosterone (T), dihydro-testosterone (DHT), 17-beta-estradiol (E2), and dehydroepiandrosterone sulfate (DHAS) were monitored during the treatment with HCG and for an additional 24 hrs after HCG discontinuation. All hormones were assayed by RIA. Our results demonstrate that hyperprolactinemia causes a marked decrease (58%) of DHT, a less marked decrease (39%) of T, an increase (43%) of DHAS whereas only a small increase (2%) of E2 was observed. Steroids were shown to behave differently after the HCG tests performed in the two experimental conditions. In particular, the levels of DHT had a much more pronounced increased after HCG in the second test than in the first; in contrast, both DHAS and E2 had a less marked response after the second test. Our data, on the one hand, confirm that 5-alpha-reductase is inhibited by hyperprolactinemia; on the other hand, the hyperprolactinemia-induced block of this enzyme appears to be rapidly reversible because the enzyme is reactivated within 48-72 hrs after normalization of prolactin levels. (Normal values of prolactin were on the average achieved on the 4th day after sulpiride discontinuation).(ABSTRACT TRUNCATED AT 250 WORDS)

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗