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Biomedical subjects

A Messori

Publications and source records attributed to A Messori.

At least 19 recordsLinked to original sources
PubMed1992

Pharmacokinetic properties of recombinant factor VIII compared with a monoclonally purified concentrate (Hemofil M). The Recombinate Study Group.

A recombinant FVIII preparation, Recombinate, was compared with a high-purity plasma-derived concentrate, Hemofil M, in 47 hemophilia A patients in a cross-over evaluation of pharmacokinetic properties. The recombinant material showed a significantly lower clearance, volume of distribution, and higher in vivo recovery, but a similar half-life to the plasma-based product. In a comparison with reported data from other standard concentrates, the recombinant preparation exhibited potentially better pharmacokinetic properties in that its clearance was slower and its half-life was longer. We conclude that the recombinant DNA method of preparation does not adversely affect the biological and pharmacological characteristics of the factor VIII molecule.

Adolescent↗
PubMed1992

Pharmacokinetics of two pasteurized factor VIII concentrates by different and multicenter assays of factor VIII activity.

We assessed the pharmacokinetic characteristics of a new high-purity pasteurized FVIII concentrate in comparison with an intermediate purity pasteurized concentrate, produced by the same manufacturer. The study was designed as a cross-over single-dose pharmacokinetic investigation in 8 non-bleeding patients with severe hemophilia A. All patients were given 25 IU/kg of each of the two concentrates, with an interval of at least one week between the two administrations. Decay curves were assessed by collecting 10 serial blood samples over 36 hours following the end of infusion. The concentration of Factor VIII in blood samples was determined in triplicate in three different laboratories using each of the following assay methods: a one-stage clotting assay, a two-stage clotting assay, and a two-stage chromogenic-peptide substrate assay. All pharmacokinetic parameters were calculated by model-independent methods. The two products were found to differ significantly both in the clearance, which was on average 13.8% lower for Haemate P, and in the in-vivo recovery, which was 11.7% lower for Factor VIII:C P on the average. In comparison with previous pharmacokinetic data obtained from other heated Factor VIII concentrates, the clearance of Haemate P was found to be significantly slower, while the half-life of both products was longer. No differences were observed in the Vd-area. These findings indicate that the purification procedures to which both products are subjected do not increase the in-vivo rate of plasma disappearance of Factor VIII.

Adolescent↗
PubMed1992

Smooth-pursuit eye movements: alterations in Alzheimer's disease.

Smooth-pursuit eye movements induced by targets moving at constant velocities (from 5 to 100 deg/sec) were recorded from 13 patients with Alzheimer's disease (AD) and from 11 healthy subjects. Four variables were evaluated to quantify the patients' response to the eye movement tests: (1) average peak velocity of smooth-pursuit; (2) percent target matching index after saccade removal (percent ratio between the area of the velocity curve of smooth-pursuit eye movement after saccade removal and the area of target velocity) which is related to the eye performance for each value of target velocity; (3) total amplitude of anticipatory saccades; (4) total number of anticipatory saccades. Compared to the controls, AD patients were found to have significantly lower values of average peak velocity of smooth pursuit and of percent target matching index and a significantly increased number and amplitude of anticipatory saccades. A discriminant stepwise analysis indicated that 5 oculographic variables were significantly associated with the patient's clinical condition (healthy volunteer or AD patient). These statistics yielded an equation for predicting the patient's status according to which the percentage of cases classified correctly was 82.6% in the overall group (n = 23). The predictive performance was similar between the healthy volunteers subgroup (81.8%, n = 11) and the AD subgroup (83.3%, n = 12). The discriminant score was significantly correlated with the score resulting from the MiniMental test (r = 0.67). A significant correlation was also found between the MiniMental score and the number of anticipatory saccades (r = -0.61). No significant correlation was present between the gain of smooth pursuit and the patients' cognitive decline.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

PKRD: a pharmacokinetic program for least-squares and bayesian analysis of repeated-dose pharmacokinetic curves.

A microcomputer program is presented which analyses multiple-dose pharmacokinetic curves using either a least-squares nonlinear analysis or a bayesian fit. The least-squares subroutine is designed to fit retrospective pharmacokinetic curves and can generate the so-called population pharmacokinetic parameters using the Standard Two-Stage method. The bayesian subroutine can instead be used prospectively to individualise the dosage regimen of a patient based on the concentrations measured in the initial phases of the drug treatment. All the pharmacokinetic subroutines of the program use the one-compartment model with either constant-rate intravenous infusion or oral route with zero-order absorption. The program was tested in a series of ten bone marrow transplantation patients treated with cyclosporine. The least-squares estimates of the one-compartment parameters, calculated by the program, were compared with those generated by the SIMKIN program.

Adolescent↗
PubMed1992

Effects of oxcarbazepine and carbamazepine on the central nervous system: computerised analysis of saccadic and smooth-pursuit eye movements.

Oxcarbazepine (OXC) is a new anti-epileptic agent structurally related to carbamazepine (CBZ). OXC seems to have a similar efficacy and a better tolerability profile than CBZ. In the present study we compared the subclinical side-effects on the CNS of OXC and CBZ using a computerised analysis of saccadic and smooth-pursuit eye movements. Six healthy male volunteers (mean age 29 yrs) participated in the study, which was conducted by a double-blind cross-over design. Each subject was given a single dose of either CBZ 400 mg or OXC 600 mg (according to the random assignment) after which the drug effects on eye movements were evaluated. One week later, the trial was repeated using the other drug. The parametrisation of both saccadic and smooth-pursuit eye movements was carried out by measuring a series of performance parameters [e.g. the maximum saccade peak velocity (MSPV) and the typical target velocity (TTV)]. OXC was found to induce a lesser degree of alteration on the values of both MSPV (p = 0.07) and TTV (p less than 0.03) than CBZ. In particular, the TTV values were virtually unaffected by OXC administration, while the effects of CBZ on both variables were particularly evident at 8 and 10 h after dosing which correspond to the time at which the plasma concentrations of CBZ and of its 10,11-epoxide reach the peak. In conclusion, our preliminary results indicate that OXC induces negligible alterations, if any, on the eye movement parameters evaluated in our study.

Adult↗
PubMed1992

Iron lung treatment of subjects with COPD in acute respiratory failure. Evaluation of short- and long-term prognosis.

We evaluated retrospectively the short-term and the long-term prognosis of 105 patients with COPD and prolonged respiratory insufficiency admitted to our respiratory intensive care unit from 1976 to 1980 for acute respiratory failure. All subjects underwent intermittent negative pressure ventilation by means of an iron lung to overcome the acute episode. Twelve patients died during hospitalization, six were lost after discharge, while 87 were successfully weaned and were included in a follow-up lasting five years. All relapses of ARF were treated by INPV. The survival rates after one and five years were 82 percent and 37 percent, respectively and were significantly influenced by factors such as age, chronic cor pulmonale, FEV1/VC, PaCO2 on admission. The survival rate observed in our patients was better than that reported previously by other authors in COPD patients with ARF submitted to mechanical ventilation after intubation. These results suggest that INPV can improve survival in this category of patients, but a controlled clinical trial will be needed to address this issue.

Acute Disease↗
PubMed1991

Reproducibility of one-stage, two-stage and chromogenic assays of factor VIII activity: a multi-center study.

This study was aimed at assessing the reproducibility of Factor VIII assays between different laboratories using the same reagents. A total of 176 post-dose plasma samples were obtained from 8 Italian subjects with hemophilia-A treated with a single dose of Factor VIII concentrates. Three laboratories (in FRG, Italy, and Sweden) participated in the study. Frozen aliquots of each sample were dispatched to each of the laboratories, where the aliquots were assayed using the same one-stage, two-stage and chromogenic methods. The one-stage and the chromogenic methods were well reproducible between the three centers: pairwise correlation analyses yielded r-values ranging from 0.88 to 0.91 for the one-stage method and from 0.91 to 0.96 for the chromogenic method. The agreement between these two assays was less evident in samples with activity below 200 IU/L in which the one-stage gave, on average, higher Factor VIII concentrations than those provided by the chromogenic method. The two-stage method was not well reproducible, and the pairwise r-values ranged from 0.48 to 0.73. Our study emphasises the need to develop multi-center quality control programs to verify the reproducibility of Factor VIII assays.

Adolescent↗
PubMed1991

Comparative evaluation of the pharmacokinetics of three monoclonal factor VIII concentrates.

Hemofil M, Monoclate HT, and Monoclate P are high-purity Factor VIII concentrates, obtained from plasma by immunoaffinity chromatography with monoclonal antibodies specific for Factor VIII (Hemofil M) or von Willebrand Factor (Monoclate HT and Monoclate P). The concentrates are subjected to virucidal treatments: a solvent/detergent method (TNBP/Na-cholate) for Hemofil M, heating in the lyophilized state and in solution (pasteurization) for Monoclate HT and Monoclate P, respectively. Since these differences in the manufacturing process might result in different in vivo characteristics of the concentrates, we compared their in vivo behavior in a cross-over, single-dose, pharmacokinetic study performed in 10 non-bleeding patients with severe hemophilia A. The experimental conditions (Factor VIII dose, number and timing of blood sampling, Factor VIII assay methods, calculation of pharmacokinetic parameters) were identical for the three products. The results showed that the clearance, the mean residence time, and the volume of distribution did not differ among the three products.

Factor VIII↗
PubMed1991

Percutaneous twist-drill craniostomy for the treatment of chronic subdural haematoma.

A consecutive series of 65 adult patients with chronic subdural haematoma was reviewed to ascertain the efficacy of twist-drill craniostomy and closed-system catheter drainage. In all patients but two the percutaneous evacuation of the haematoma alone was enough to bring about their recovery. Infections or neurological complications were never observed. Pneumocephalus was likewise absent in all patients. Therefore this technique should be recommended as the "first intention" management of the disease, particularly in elderly patients.

Aged↗
PubMed1991

A new method for analyzing smooth-pursuit eye movements. Description of a microcomputer program and evaluation in healthy volunteers.

The study of ocular movements has been increasingly used to detect subtle pathological modifications, caused by a wide variety of neurological diseases. We have developed a new microcomputer-based method for the analysis of smooth-pursuit ocular movements induced by constant velocity targets moving unpredictably at different velocities (including velocity values as high as 100 deg/s). The ocular movements are recorded by an electro-oculographic technique using silver-silver chloride electrodes fixed near the inner and outer canthi of both eyes. The signals are amplified by two DC amplifiers after a low-pass filtering (50 Hz), sampled at 250 Hz and digitized in a 12-bit form by an analog/digital converter. For each patient's evaluation, a series of 20 sweeps of the target is generated. The data analysis, which is performed automatically by the microcomputer, is based on the calculation of four parameters: average peak eye velocity (APEV); typical target velocity (TTV); percent target matching index after saccade removal (PTMI); typical matching target velocity (TMTV) after saccade removal. APEV is calculated as the average of the peak velocities estimated from the 20 sweeps. The purpose of TTV, which is defined as the value of target velocity at which the percent gain has decreased to slightly more than one third of the maximum percent gain, is to provide an overall index of the rate at which the percent gain decreases as the target velocity increases. PTMI describes the eye performance for each value of target velocity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Comparison of two nonlinear models for fitting saccadic eye movement data.

Saccadic eye movements are rapid shifts in the direction of gaze which are being studied increasingly for clinical and pharmacological purposes. The evaluation of the relationship between amplitude and peak velocity of these ocular movements (the so-called 'main sequence' plot) is particularly useful for characterising the saccade pattern in individual patients. This relationship is nonlinear and the peak velocity tends to achieve an asymptote for high values of amplitude. Since a standard parametrisation of the main sequence based on specific mathematical models has not yet been achieved, in the present study two simple models based on the Michaelis-Menten equation and on an exponential equation are proposed together with their implementation on a microcomputer. Two microcomputer programs are described which estimate the model parameters from the experimental data of the patients using a weighted nonlinear least-squares fit. The two procedures have been tested and compared in a series of 23 healthy volunteers. The following results (mean +/- S.D.) were obtained: Michaelis-Menten model. Km (degrees) = 31.2 +/- 7.7, Vmax (degrees/s) = 841.0 +/- 165.5, root-mean-squared error(%) = 6.0 +/- 1.6; exponential model. K (degrees) = 23.4 +/- 4.6, Vmax (degrees/s) = 578.0 +/- 97.4, root-mean-squared error(%) = 5.4 +/- 1.6. The two techniques of parametrisation provided similar indices of intra-individual variability in 4 healthy volunteers. In conclusion, our methods for saccade parametrisation can be regarded as simple but efficient tools for facilitating research on these ocular movements.

Adult↗
PubMed1990

Bioavailability of intramuscular ciclosporin in the pig.

We conducted a cross-over single-dose pharmacokinetic study in 4 pigs to measure the bioavailability of ciclosporin (CS) after intravenous and intramuscular administration. Each animal was given 5 mg/kg i.v. followed by 20 mg/kg i.m. after 1 week. Serial blood samples were taken over 36 h after each dose, and the concentration of CS was assayed by radioimmunologic methods. The pharmacokinetic parameters after intravenous administration were (mean +/- SD; n = 4): clearance = 327 +/- 21 ml/h/kg; volume of distribution = 7.2 +/- 2.8 liters/kg. The same parameters after intramuscular dosing were: clearance = 326 +/- 59 ml/h/kg; volume of distribution = 6.9 +/- 2.1 liters/kg. The percent bioavailability of intramuscular CS was 101.9 +/- 13.3 with a mean absorption time of 10.6 +/- 2.7 h. Our results indicate that following a single dose, the percent bioavailability of intramuscular CS in pigs is considerably greater than that reported in previous studies.

Animals↗
PubMed1989

Evaluation of factor VIII pharmacokinetics in hemophilia-A subjects undergoing surgery and description of a nomogram for dosing calculations.

The pharmacokinetics of factor VIII were studied in a series of 20 hemophilia-A patients undergoing surgery. Regardless of the type of operation, elimination of factor VIII was shown to be increased only in ten cases (50%) during the post-operative period. In this subgroup of patients, factor VIII half-life, measured immediately after surgery, was considerably shorter (mean = 9.6 hr, n = 10) than that determined in the same individual during the late operative period (mean = 17.8 hr, n = 10). These findings indicate that identification of patients with increased postoperative consumption of factor VIII can be of value in reducing the risk of hemorrhage in these subjects and in exposing other subjects with no postoperative increase in factor VIII clearance to less of the deficient factor. Data from 20 subjects were analyzed to construct a nomogram allowing individualized prediction of factor VIII dosing requirements. The nomogram, which is based on the "single point after a single dose" method, uses a value of factor VIII concentration measured at 10 hr after preoperative loading dose to predict the regimen producing the desired average steady-state concentration of factor VIII (30, 60, or 90 units/dl).

Adolescent↗
PubMed1989

Combined surgery and chemotherapy for the treatment of primary gastrointestinal intermediate- or high-grade non-Hodgkin's lymphomas.

Fifty-five consecutive patients with primary gastrointestinal intermediate or high grade non-Hodgkin's lymphoma were analysed to assess the efficacy of chemotherapy following surgical tumour resection. Histological subtypes were high grade (n = 18), intermediate grade (n = 36) and unclassified (n = 1). The majority of patients had gastric presentation (71%) and localised disease (84%). Surgery consisted of radical resection in 25 patients (45%) and partial or palliative excision in the remaining cases (22 and 8 respectively). Four subjects died within 3 months of surgery, two patients refused adjuvant chemotherapy and 49 completed the postoperative chemotherapeutic programme. Chemotherapy included either Fi2/74 (adriamycin + vincristine + bleomycin + cyclophosphamide + prednisone) or Fi3/74 (adriamycin + VM26 + bleomycin + cyclophosphamide + prednisone). Excluding the group who underwent radical tumour resection, postoperative chemotherapy induced complete remission in 81% of the remaining 30 patients. The 10-year cause-specific survival for the 53 treated patients was 76% (median follow-up 58 months) with a stable curve plateau after 80 months. Proportional-hazard multivariate statistics showed that survival was influenced by type of surgical resection (P less than 0.05) and stage (P less than 0.05), whereas age, sex and histological subtype were not influential. Our data indicate that chemotherapy following surgical resection of gastrointestinal lesion induces long-term remission in primary gastrointestinal lymphomas.

Adolescent↗