Pharmacokinetics and pharmacokinetic-dynamic modelling of rocuronium in infants and children

We have determined the pharmacokinetics and pharmacokinetic- pharmacodynamic relationship of rocuronium in infants and children. We studied infants (n = 5, 0.1-0.8 yr) and children (n = 5, 2.3-8 yr), ASA II, in the ICU while undergoing artificial ventilation under i.v. anaesthesia with an arterial cannula in situ and the EMG of the adductor pollicis muscle was monitored. Rocuronium 0.06 (infants) and 0.09 (children) mg kg-1 min-1 was given i.v. over +/- 5 min until 85% neuromuscular block was obtained. Arterial blood samples were obtained over 240 min. Plasma concentrations were measured by HPLC. Pharmacokinetic-dynamic variables were calculated using the Sheiner model and the Hill equation. Statistical analysis was performed using the Mann-Whitney U test (P < 0.05). The mean administered dose was 0.32 (SD 0.08) mg kg-1 and 0.4 (0.1) mg kg-1 for infants and children, respectively. Infants differed from children in plasma clearance (4.2 (0.4) vs 6.7 (1.1) ml min-1 kg-1), distribution volume at steady state (231 (32) vs 165 (44) ml kg-1), mean residence time (56 (10) vs 26 (9) min), concentration in the effect compartment at 50% block (1.2 (0.4) vs 1.7 (0.4) mg litre-1) and the slope of the concentration-effect relationship (5.7 (1.3) vs 3.9 (0.5)). Calculated mean ED90 values were 0.26 and 0.34 mg kg-1 for infants and children, respectively. The time course of neuromuscular block after equipotent doses did not differ.      

Job satisfaction, work ability and life satisfaction among Finnish anaesthesiologists

BACKGROUND: Organizational changes and relative growth of the ageing population together with related health problems seem to have increased stressfulness in the work of anaesthesiologists. However, little is known about their work-related well-being and the factors through which their situation could be improved. METHODS: A cross-sectional questionnaire study of the level and the determinants of job satisfaction, work ability and life satisfaction among female and male anaesthesiologists involved 258 Finnish anaesthesiologists working full time (53% men). RESULTS: The respondents had fairly high job satisfaction, work ability and life satisfaction. No gender differences appeared in these well-being indicators, but their determinants differed by gender. Job satisfaction was only associated with work-related factors in both genders: with job control in women and with job control and organizational justice in men. Work ability correlated with job control and health in both genders and with family life in women. Life satisfaction correlated with individual- and family related factors such as social support and family problems in both genders. Life satisfaction correlated with physical workload in men and health in women. Women had less job control, fewer permanent job contracts and more domestic workload than men. CONCLUSIONS: Job control and organizational justice were the most important determinants in work-related well-being. Work-related factors were slightly more important correlates of well-being in males, and family life seems to play a larger role in the well-being of female anaesthesiologists. Organizational and gender issues need to be addressed in order to maintain a high level of well-being among anaesthesiologists.     

Befunde in den Hauptentwicklungsstufen des Gebisses bei Dysgnathieträgern

Zusammenfassung In dieser Arbeit wurden die Gebisse von 31 männlichen und 45 weiblichen Dysgnathieträgern mit Hilfe des Berliner Meßsystems vermessen und die Ergebnisse mit Hilfe eines Computers ausgewertet. Es erfolgt der Vergleich der Parameter zwischen Probanden mit Progenie, Kreuzbiß, offenem Biß und Schmalkiefer. Die Veränderung der Werte wurden longitudinal in den Hauptentwicklungsstufen Milchgebiß, Wechselgebiß und im bleibenden Gebiß untersucht. Dabei werden auch nach der Behandlung noch zwischen den Anomaliegruppen bei einzelnen Werten signifikante Unterschiede gefunden.

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Summary In this study dental plaster casts of 31 male and 45 female subjects were measured using the Berlin measurement system and evaluated with the aid of a computer. The parameters of subjects with class III malocclusion, crossbite, open bite and class II/1 malocclusion were compared. The changes were studied longitudinally in the main developmental stages, namely the deciduous, mixed and permanent dentitions. Significant differences were found also following treatment between the malocclusion groups.

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Résumé On a mesuré les dentures de 31 hommes et 45 femmes présentant des dysgnathies à l'aide du système de mesure mis au point à Berlin; les valeurs ainsi établies on fait l'objet d'un traitement sur ordinateur. On a procédé à la comparaison des paramètres des sujets atteints de prognathie inférieure, occlusion croisée, béance et endognathie. On a étudié la modification des valeurs de manière longitudinale, en suivant les principales étapes d'évolution: denture lactéale, denture mixte et denture permanente. L'examen a permis, même après le traitement, d'établir, pour chacune des valeurs, des différences importantes d'un groupe d'anomalie à l'autre.

     

Langzeitergebnisse nach lumbalen Bandscheibenerkrankungen

The therapeutic results of operatively and conservatively treated patients with lumbar disc syndromes were reviewed in a retrospective study. The patients were treated during a 10-years period (1976-1985). A total of 330 patients with lumbar disc prolapses were treated in the hospital during this period 44% were treated surgically. The data on 100 operated and 100 conservatively treated cases, registered in this random test sample, have been compared with respect to: pain; neurological deficits; subjective problems and sociomedical questions. The average patient age of both groups was about 41 years, and the patients predominant were male (about 70%). The therapeutic results of both operatively and conservatively treated patients were good, which is also by the high percentage of employment (80%-90%) in the two treatment groups. The critical evaluation showed more neurological disturbances and limited vocational activity in the group of cases operated upon. More than 70% of the operated cases showed radicular syndromes of the follow-up examination although it was not of essential functional importance. The period inability to work and the percentage of disablement were also much higher in this group. The pain symptoms were particularly relevant in our examination. Only 12%-16% of the patients in the two groups that took part in the follow-up examinations reported freedom from pain. It was apparent that atypical pain syndromes were correlated with personality psychological disturbances. Nearly one-third of our patients mentioned psychological problems. The prognosis of the conservative treatment of lumbar disc prolapse was equivalent to operative therapy (disregarding the absolute indications for operations). There were no definite advantages found for either of the two methods of treatment. The necessity for a specialized follow-up treatment of patients with sciatica due to herniated lumbar discs is discussed, and differentiated selection for operative therapy is given. Here the treatment of pain should be considered most important.     

Antidiabetic effect of kolaviron,a biflavonoid complex isolated from Garcinia kola seeds,in Wistar rats

Background

Hypoglycaemic effect of kolaviron (KV), (biflavonoid from Garcinia kola) in streptozotocin (STZ)-diabetic rats has been established.

Objectives

To evaluate the possible protective effects of KV on cardiac, renal and hepatic tissues of STZ-diabetic rats.

Methods

This study consists of four groups of 6 rats each. Groups one and two contained non-diabetic and untreated-diabetic rats, respectively. Groups three and four were made up of KV- and glibenclamide (GB) - treated diabetic rats, respectively.

Results

STZ-intoxication caused a significant (p<0.05) increase in the relative weight of liver in diabetic rats. STZ-diabetic rats had significant increase (p<0.05) in the levels of fasting blood glucose (FBG), á-amylase and HbA_1c. A marked and significant (p<0.05) increase in the levels of cardiac, renal and liver marker indices such as serum creatine kinase, lactate dehydrogenase, creatinine, urea and alanine aminotransferase were observed in untreated diabetic rats. Also, untreated diabetic rats had significantly (p<0.05) elevated urinary glucose and protein and, lowered creatinine clearance. In KV- and GB- treated groups, the levels of FBG, á-amylase and HbA_1c were significantly (p<0.05) reduced, while treatment with KV significantly (p<0.05) attenuated the cardiac, renal and liver marker indices.

Conclusion

KV offered significant antidiabetic and tissues protective effects in the rats.     

Mutational analysis of the SOX9 gene in campomelic dysplasia and autosomal sex reversal: lack of genotype/phenotype correlations

It has previously been shown that, in the heterozygous state, mutations in the SOX9 gene cause campomelic dysplasia (CD) and the often associated autosomal XY sex reversal. In 12 CD patients, 10 novel mutations and one recurrent mutation were characterized in one SOX9 allele each, and in one case, no mutation was found. Four missense mutations are all located within the high mobility group (HMG) domain. They either reduce or abolish the DNA-binding ability of the mutant SOX9 proteins. Among the five nonsense and three frameshift mutations identified, two leave the C-terminal transactivation (TA) domain encompassing residues 402-509 of SOX9 partly or almost completely intact. When tested in cell transfection experiments, the recurrent nonsense mutation Y440X, found in two patients who survived for four and more than 9 years, respectively, exhibits some residual transactivation ability. In contrast, a frameshift mutation extending the protein by 70 residues at codon 507, found in a patient who died shortly after birth, showed no transactivation. This is apparently due to instability of the mutant SOX9 protein as demonstrated by Western blotting. Amino acid substitutions and nonsense mutations are found in patients with and without XY sex reversal, indicating that sex reversal in CD is subject to variable penetrance. Finally, none of 18 female patients with XY gonadal dysgenesis (Swyer syndrome) showed an altered SOX9 banding pattern in SSCP assays, providing evidence that SOX9 mutations do not usually result in XY sex reversal without skeletal malformations.      

The ethics of psychopharmacological research in legal minors

Research in psychopharmacology for children and adolescents is fraught with ethical problems and tensions. This has practical consequences as it leads to a paucity of the research that is essential to support the treatment of this vulnerable group. In this article, we will discuss some of the ethical issues which are relevant to such research, and explore their implications for both research and standard care. We suggest that finding a way forward requires a willingness to acknowledge and discuss the inherent conflicts between the ethical principles involved. Furthermore, in order to facilitate more, ethically sound psychopharmacology research in children and adolescents, we suggest more ethical analysis, empirical ethics research and ethics input built into psychopharmacological research design.