Pharmacokinetics of single intravenous and oral doses of dolasetron mesylate in healthy elderly volunteers

Dolasetron mesylate (MDL 73,147EF, Anzemet; Hoechst Marion Roussel, Laval, Canada) is a 5-HT3 receptor antagonist undergoing clinical evaluation for use as an antiemetic agent. The pharmacokinetics of dolasetron and its reduced metabolite (MDL 74,156) were studied after administration of single intravenous and oral doses of dolasetron mesylate 2.4 mg/kg in 18 healthy elderly subjects. Expressed as the dolasetron base, this dose was 1.8 mg/kg. Dolasetron was rapidly metabolized to the reduced metabolite, which appeared in plasma within 10 minutes after intravenous or oral administration. The mean half-life (t1/2) of dolasetron was 0.24 hours after intravenous administration and 0.50 hours after oral administration. The pharmacokinetic parameters of the reduced metabolite were similar after intravenous and oral administration. The apparent absolute bioavailability of the reduced metabolite was 89%, and it had an elimination t1/2 of approximately 7 hours and an apparent volume of distribution (Vd beta) of 4.69 L/kg. Dolasetron was not detected in urine. Metabolites were excreted in urine almost completely within 24 hours of administration. The primary metabolite detected in urine was the (+)-enantiomer of the reduced metabolite, which accounted for 25.35% (+/- 7.79%) and 18.88% (+/- 7.65%) of the intravenous and oral doses, respectively. Hydroxylated metabolites accounted for 5% or less of the total dose via either route. The pharmacokinetics of the reduced metabolite after single intravenous or oral doses in elderly volunteers were consistent with pharmacokinetics observed in both young healthy men and cancer patients receiving high-dose cisplatin chemotherapy. Dosage adjustments of dolasetron mesylate on the basis of age do not appear to be necessary.     

Obstructive effect of a closed 12F urethral catheter during the emptying phase of cystometry in patients with a spinal reflex bladder

There is a group of malignant intrascrotal tumours which represent a very small number when compared to testicular neoplasias and which are known as paratesticular neoplasias. More than 90% belong to the sarcomatous species. From a clinical point of view and based on the patient's age, two groups can be distinguished: sarcomas affecting children and adolescents (primarily rabdomiosarcomas) and those occurring in adulthood, the more frequent histopathological variants being fibrosarcoma, leiomiosarcoma and liposarcoma. This work contributes five paratesticular sarcomas (two rabdomiosarcomas, one liposarcoma, one leiomiosarcoma and one fibrosarcoma). The features related to histogenesis, diagnosis (revealing signs and clinical examination), natural history (dissemination routes based on histopathology) and treatment are reported. With regard to treatment, both the local surgery (total orchiectomy by inguinoscrotal approach with or without hemiscrotectomy), and indications for lymphadenectomy and radiotherapy in relation to staging are discussed though insisting on the chemotherapy approach.     

Least-squares fitting by circles

In reflectometry and in the aircraft industry the problem of fitting data points by a circle is relevant. In contrast with other authors we realize a very special iterative method to determine such a circle. Former approximations for the parameters are used as starting values and are improved. Numerical examples are given.     

Clustering of one-dimensional ordered data

A set ofn ordered real numbers is partitioned by complete enumeration intok clusters such that the sum of the sum of squared deviations from the mean-value within each cluster is minimized.     

Matrix exponentials and parallel prefix computation in a quantum control problem

Quantum control plays a key role in quantum technology, in particular for steering quantum systems. As problem size grows exponentially with the system size, it is necessary to deal with fast numerical algorithms and implementations. We improved an existing code for quantum control concerning two linear algebra tasks: the computation of the matrix exponential and efficient parallelisation of prefix matrix multiplication.For the matrix exponential we compare three methods: the eigendecomposition method, the Padé method and a polynomial expansion based on Chebyshev polynomials. We show that the Chebyshev method outperforms the other methods both in terms of computation time and accuracy. For the prefix problem we compare the tree-based parallel prefix scheme, which is based on a recursive approach, with a sequential multiplication scheme where only the individual matrix multiplications are parallelised. We show that this fine-grain approach outperforms the parallel prefix scheme by a factor of 2–3, depending on parallel hardware and problem size, and also leads to lesser memory requirements.Overall, the improved linear algebra implementations not only led to a considerable runtime reduction, but also allowed us to tackle problems of larger size on the same parallel compute cluster.     

The influence of residual stresses induced by plastic deformation on rolling contact fatigue

A general method is first described for finding the optimum residual stress distribution. Cylindrical test specimens were subjected to a prestress cycle which was able to induce a favourable residual stress distribution, all the specimens being fatigue tested after that. The 10% fatigue life of the prestressed test specimens was more than twice that of the baseline group. Fatigue tests carried out on four groups of ball-bearings also confirm both the existence of the optimum residual stress distribution and the possibility of inducing this distribution by a prestress cycle.     

H NMR study of temperature-induced phase transitions in D2O solutions of poly(N-isopropylmethacrylamide)/poly(N-isopropylacrylamide) mixtures and random copolymers

¹H NMR spectroscopy was used to investigate temperature-induced phase transitions in D₂O solutions of poly(N-isopropylmethacrylamide) (PIPMAm)/poly(N-isopropylacrylamide) (PIPAAm) mixtures and P(IPMAm/IPAAm) random copolymers of various composition on molecular level. While two phase transitions were detected for PIPMAm/PIPAAm mixtures, only single phase transition was found for P(IPMAm/IPAAm) copolymers. The phase transition temperatures of PIPAAm component (appears at lower temperatures) are not affected by the presence of PIPMAm in the mixtures; on the other hand, the temperatures of the phase transition of PIPMAm component (appears at higher temperatures) are affected by the phase separation of the PIPAAm component and depend on concentration of the solution. For P(IPMAm/IPAAm) random copolymers, a departure from the linear dependence of the transition temperatures on the copolymer composition was found for a sample with 75 mol% of IPMAm monomeric units.