Arterial and venous effects of serotonin in the forearm of healthy subjects are not age-related

The influence of age on the regional arterial and venous effects of serotonin (5-HT) was investigated in 13 young (aged 22-31 years) and seven older (aged 50-69 years) healthy volunteers. Single-dose infusions of 5-HT (1, 10, and 80 ng/kg/min) and of the 5-HT2 receptor antagonist ritanserin (50, 150, and 500 ng/kg/min) were administered into the brachial artery. Subsequently, the relative arterial and venous effects of the highest dose of 5-HT were investigated. Forearm blood flow (FBF) and maximum venous outflow (MVO) were measured by venous occlusion plethysmography. Heart rate (HR) and intraarterial (i.a.) blood pressure were recorded semicontinuously. In both age groups, 5-HT induced an initial transient arterial dilation, followed by a persistent increase in FBF for the doses of 1 and 10 ng/kg/min and a relative small decrease in FBF for the highest dose. In both age groups, the highest dose of 5-HT induced a similar large reduction in MVO (p less than 0.05 for both). The reduction in MVO was attenuated by ritanserin (500 ng/kg/min, p less than 0.05 for both groups). In the younger subjects, this dose of ritanserin also unmasked an arterial dilator effect of the highest dose of 5-HT (p less than 0.05). The single infusions of ritanserin did not influence FBF significantly in either study group. No significant differences were observed between the age groups. These results show that in the forearm of healthy subjects arterial and venous vascular responses to 5-HT were not age-related. In the arterial vascular bed, 5-HT acted predominantly as a vasodilator; at high doses, mainly venous vasoconstriction was observed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Quality and standardization in blood component preparation with an automated blood processing technique

The use of automated blood processors in combination with bottom and top blood containers has been found to improve the standardization and quality of blood components. A study was performed to validate a new type of processor (Optipress® II) and compare its performance with a first generation processor (Optipress® I).
Primary separation on the Optipress II was investigated on 570 mL (± 10%) of anticoagulated blood in a nonpaired study. In addition, the quality of the products in routine production was compared between the results of the Optipress I and Optipress II. The whole blood units were kept overnight at room temperature (20 ± 2 °C). Separation was performed under conditions to obtain 55 mL buffy coats with a 50% haematocrit (ht). Platelet concentrate preparation was investigated in a paired study and compared to the routine manual method using PAS II additive solution. Parameters studied were volume, red cell, white cell and platelet counts, ht, haemoglobin (hb, total and free).
Primary separation was more efficient in the Optipress II because the platelet count was lower in the erythrocyte concentrates ( P  < 0.0001), platelets were lower in plasma ( P  < 0.0001) and platelet counts were higher in buffy coats ( P  < 0.0001). Buffy coat volume showed less variation (Optipress II VC = 4%, Optipress I VC = 7.4%). Secondary separation did not show differences between the Optipress II and manual method but was advantageous because of the automatic termination of the procedure.
Further improvement of standardization in blood component preparation is possible with an automated blood processor, leading to improvement of the quality of blood products for patient care.     

Chromosomal aberrations in follicular thyroid carcinoma. Case report of a primary tumor and its metastasis

We present the result of a cytogenetic study of a case of follicular carcinoma of the thyroid and its metastasis. Both tumors have a low number of chromosomes. The primary tumor is characterized by a idic(22;22)(p11;p11). The skeletal metastasis has also structural abnormalities of chromosome 22.     

Impairment of phenytoin parahydroxylation as a cause of severe intoxication

A case history is presented of a patient who developed a severe phenytoin intoxication on a "therapeutic" dose of 300 mg/day. This phenomenon could be ascribed to a poor oxidative metabolizing capacity of this patient for phenytoin, as demonstrated by a low para-hydroxyphenyl-phenylhydantoin to phenytoin ratio in the urine. To characterize the specificity of this metabolic defect, debrisoquine and antipyrine oxidation were also studied. Contrary to expectations, this patient was shown to be an extensive debrisoquine metabolizer; the antipyrine clearance was even higher than normal. These findings suggest that phenytoin para-hydroxylation is regulated by an oxidative enzyme complex different from those which oxidize debrisoquine and antipyrine.     

A quality network model for the daily care of multiple sclerosis

The urgent need to optimise treatment strategies for patients with Multiple Sclerosis (MS) was recognised by the participants at the 1998 European Charcot Foundation (ECF) symposium in Nice. The 'Nice Declaration' led to the formation of a Task Force Essentials Group charged with developing measures of the quality of MS care in Europe. Algorithms for nine critical domains (disability, spasticity, ataxia, pain, cognition, mood, fatigue, bladder function and sexual activity) and 'educated guesses' have been developed to measure interventions and outcomes which reflect the quality of clinical decision-making processes. A generic model called a 'quality network', consisting of a group of clinics connected to a central server, has been successfully applied to the care of diabetes across Europe. This model will now be developed and applied to MS management, to provide clinicians with longitudinal epidemiological data and, to evolve treatment algorithms and further quality measures. The ECF will next validate the system in a 1-year pilot study using a net of 10 clinics. Finally, an extended European network working in a learning environment will continuously assess, update and improve the quality of care of MS patients. Multiple Sclerosis (2000) 6 231 - 236     

High-performance ion-exchange chromatography with in-line complexation of bisphosphonates and their quality control in pharmaceutical preparations

An ion-exchange chromatographic method using an anion-exchange column was developed for the analysis of a number of bisphosphonates. The bisphosphonates were in-line complexed by copper(II) ions and added to the acidic eluent, to yield an UV-absorbing complex. Chromatographic parameters were studied for eight different bisphosphonates, particularly amino-1-hydroxyalkyl-1,1-bisphosphonates; special attention was paid to the relationship between retention and complex formation. The method was applied to the quality control of pamidronate injection concentrate and olpadronate tablets. The lower detection limit was 8 ng of disodium pamidronate, and the inter-assay precision was 1.0% for both pamidronate and olpadronate standard solutions and 1.8% for a 3 mg ml⁻¹ disodium pamidronate injection concentrate. The method was compared with a previously described ion-exchange chromatographic method with conductivity detection, without copper(II) ions in the eluent.     

Pharmacokinetics and pharmacodynamics of midazolam administered as a concentrated intranasal spray. A study in healthy volunteers

AIMS: To investigate the pharmacokinetic and pharmacodynamic profile of midazolam administered as a concentrated intranasal spray, compared with intravenous midazolam, in healthy adult subjects. METHODS: Subjects were administered single doses of 5 mg midazolam intranasally and intravenously in a cross-over design with washout period of 1 week. The total plasma concentrations of midazolam and the metabolite 1-hydroxymidazolam after both intranasal and intravenous administration were described with a single pharmacokinetic model. beta-band EEG activity was recorded and related to midazolam plasma concentrations using an exponential pharmacokinetic/pharmacodynamic model. RESULTS: Administration of the intranasal spray led to some degree of temporary irritation in all six subjects, who nevertheless found intranasal administration acceptable and not painful. The mean (+/-s.d.) peak plasma concentration of midazolam of 71 (+/-25 ng ml-1) was reached after 14 (+/-5 min). Mean bioavailability following intranasal administration was 0.83+/-0.19. After intravenous and intranasal administration, the pharmacokinetic estimates of midazolam were: mean volume of distribution at steady state 1.11+/-0.25 l kg-1, mean systemic clearance 16.1+/-4.1 ml min-1 kg-1 and harmonic mean initial and terminal half lives 8.4+/-2.4 and 79+/-30 min, respectively. Formation of the 1-hydroxymetabolite after intranasal administration did not exceed that after intravenous administration. CONCLUSIONS: In this study in healthy volunteers a concentrated midazolam nasal spray was easily administered and well tolerated. No serious complications of the mode of administration or the drug itself were reported. Rapid uptake and high bioavailability were demonstrated. The potential of midazolam given via a nasal spray in the acute treatment of status epilepticus and other seizure disruptions should be evaluated.     

Pharmacokinetics of intravenous busulfan in children prior to stem cell transplantation

AIMS: Intravenous formulations of busulfan have recently become available. Although busulfan is used frequently in children as part of a myeloablative regimen prior to bone marrow transplantation, pharmacokinetic data on intravenous busulfan in children are scarce. The aim was to investigate intravenous busulfan pharmacokinetics in children and to suggest a limited sampling strategy in order to determine busulfan systemic exposure with the minimum of inconvenience and risk for the patient. METHODS: Plasma pharmacokinetics after the first administration was investigated in six children using nonlinear mixed effect modelling. RESULTS: Pharmacokinetics showed little variability and were described adequately with a one-compartment model (population estimates CL,av=0.29 l h(-1) kg(-1); V,av=0.84 l kg(-1); t(1/2)=1.7-2.8 h). Combined with limited sampling and a Bayesian fitting procedure, the model can adequately estimate the systemic exposure to intravenous busulfan, which in children appears to be at the lower end of the adult range. CONCLUSIONS: Busulfan systemic exposure in children during intravenous administration can be estimated adequately with limited sampling and a Bayesian fitting procedure from a one-compartment model. Intravenous busulfan pharmacokinetics in children should be the subject of more research.