Modeling the pharmacokinetics and pharmacodynamics of dexamethasone in depressed patients

Summary Changes in time course effected by cortisol suppression and the relationship of these changes to the plasma dexamethasone concentration of suppressor and non-suppressor patients are described in this report on a combined pharmacokinetic-pharmacodynamic model.Thirteen depressed patients (8 suppressors and 5 non-suppressors) received an intravenous dose (1.5 mg) of dexamethasone. The drug-induced effect changes are found to lag behind, in time, the plasma drug level changes. To accurately relate the temporal relationship of effect changes to plasma dexamethasone levels, a pharmacodynamic model (sigmoid-Emax) was combined with a pharmacokinetic model that incorporated an effect compartment. The magnitude of the time-lag was quantified by the half-time of equilibration between concentrations in the hypothetical effect compartment and the plasma dexamethasone levels (t_&frac;k_eo).The t_&frac;k_eo of the nonsuppressing group was about 50 of that of the suppressing group, indicating that for a given plasma level the onset and termination of effect for the nonsuppressing group is about two times more rapid than for the suppressing group. Moreover, the model can estimate the effect-site concentration that causes one-half of the maximal predicted effect (EC₅₀), a measure of an individual's sensitivity to dexamethasone. The receptor sensitivity (as determined from the EC₅₀ ratio) of the suppressing group was about twice that of the nonsuppressing group.     

Ex vivo estimation of thoracolumbar vertebral body compressive strength: The relative contributions of bone densitometry and vertebral morphometry

The estimation of vertebral fracture risk in individuals with suspected osteopenia is commonly based on measurements of lumbar spine bone density. The efficacy of vertebral size and deformity, as assessed by vertebral morphometry, in the prediction of fractures has been less studied. In an ex vivo investigation the regional relationships between vertebral size, vertebral deformity, bone density and compressive strength throughout the thoracolumbar spine were examined. In 16 vertebral columns (T1–L5) the bone mineral content (BMC) and bone mineral density (BMD) of each segment were measured using lateral projection dual-energy X-ray absorptiometry, and the vertebral cancellous density (VCD) and mid-vertebral cross-sectional area (CSA) measured using quantitative computed tomography. Vertebral body heights were determined from mid-sagittal CT scans, and vertical height ratios calculated for each segment. The failure load and failure stress of the isolated vertebral bodies were determined using a material testing device. Separate analyses were performed for the upper (T1–4), middle (T5–8) and lower (T9–12) thoracic, and lumbar (L1–5) segments. In all regions, failure load was strongly correlated with BMD (r=0.82–0.86), moderately correlated with VCD (r=0.60–0.71) and vertebral height (r=0.22–0.49), and poorly correlated with the height ratios (r=0.04–0.33). Failure stress was best predicted by BMD (r=0.73–0.78) and VCD (r=0.70–0.78) but was poorly correlated with all morphometric variables (r=0.01–0.33). The segmental correlations between BMD and VCD ranged fromr=0.49 tor=0.79. For all regions, BMD and VCD were included in the stepwise regression models for predicting failure load and failure stress. Either the mid-vertebral height or CSA were included in all the failure load models, while mid-vertebral height was included in only one of the failure stress models. The results suggest that vertebral deformity and size (as assessed by vertebral morphometry) make only a minor contribution to the prediction of vertebral strength additional to that provided by bone densitometry alone. The consistent regional relationships between variables appear to support the practice of global fracture risk assessment based on lumbar spine densitometry.     

Editorial

Ohne Zusammenfassung

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Editorial

     

Six cases of travel-associated legionnaires' disease in Ischia involving four countries

Summary The detection of travel-associated legionellosis can be extremely difficult; hence, an extensive case investigation is recommended in pneumonia-striken travellers and tourists, who are particularly at risk of acquiring the disease. On the Island of Ischia (Isola d'Ischia, Naples, Italy) a total of six cases of Legionnaires' disease occurred from 1986 to 1990. All patients (one man and two women from Germany, one Austrian woman, one Swiss man, and one Italian woman) had taken thermal baths and stayed in local hotels; they all experienced severe pneumonia, and three of them died. These cases were associated with hotels, and the hot-water supply was presumed to have transmitted the infection. Remedial procedures were applied to the hot-water plumbing of the hotels according to the WHO recommendations and were proved to be effective. The occurrences described in this paper stress the importance of rapid and accurate reporting of diagnosed cases to the country where the infection was probably acquired, in order to ensure early detection of endemic foci and emerging clusters of legionellosis.

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Sechs Fälle von reiseassoziierter Legionärskrankheit in Ischia unter Beteiligung von vier Ländern

Zusammenfassung Der Nachweis reiseassoziierter Legionärskrankheit gestaltet sich häufig schwierig. Eine Überwachung von Touristen und Reisenden, die ein erhöhtes Legionellose-Risiko haben, ist daher zu empfehlen. Zwischen 1986 und 1990 traten auf der Insel Ischia (Neapel, Italien) insgesamt sechs Fälle von Legionärskrankheit auf. Alle Patienten (ein Mann und zwei Frauen aus Deutschland, eine Österreicherin, ein Schweizer und eine Italienerin), die in Hotels auf der Insel wohnten, hatten Thermalbäder besucht. Sie erkrankten an schweren Pneumonien, wobei drei Todesfälle auftraten. Die Ansteckungsquelle konnte mit Hotels in Verbindung gebracht werden, wobei die Übertragung der Infektion über die Warmwasserleitungsnetze als gesichert anzunehmen war. Desinfektionsmaßnahmen in den betreffenden Hotels, die nach den Empfehlungen der WHO ausgeführt wurden, erwiesen sich als wirksam. Das genannte Infektionsgeschehen weist auf die Notwendigkeit hin, Fälle von Legionärskrankheit so rasch wie möglich dem Ursprungsland unter Angabe der vermuteten Infektionsquelle zu melden, um sicherzustellen, daß eine Früherkennung endemischer Herde bzw. assoziierter Legionellosen bekannt gemacht wird.

     

Bilateral adrenal hemorrhage associated with bilateral renal vein and vena cava thrombosis

Idiopathic bilateral adrenal hemorrhage with thrombosis of both renal veins and inferior vena cava are presented using US and CT in a newborn. To our knowledge such bilateral involvement of the adrenal glands and the renal veins have not been reported previously.     

The anesthesia workstation with autopilot design

Conclusions Many of the resources for the proposed data management system are readily available. It is time to begin to develop and make available such systems.