Estimating Potency for the E max-Model Without Attaining Maximal Effects

The most widely applied model relating drug concentrations to effects is the E_max model. In practice, concentration–effect relationships often deviate from a simple linear relationship but without reaching a clear maximum because a further increase in concentration might be associated with unacceptable or distorting side effects. The parameters for the E_max model can only be estimated with reasonable precision if the curve shows sign of reaching a maximum, otherwise both EC₅₀ and E_max estimates may be extremely imprecise. This paper provides a solution by introducing a new parameter (S₀ ) equal to E_max/EC₅₀ that can be used to characterize potency adequately even if there are no signs of a clear maximum. Simulations are presented to investigate the nature of the new parameter and published examples are used as illustration.     

A testosterone-producing tumour in the mesovarium

An androgen-secreting adnexal tumour is presented. The tumour was a steroid cell tumour of the mesovarium, without crystals of Reinke, hence the diagnosis was a steroid cell tumour (lipid cell tumour), not otherwise specified (in this case, because of its location in the mesovarium, an adrenal rest tumour). The clinical presentation, diagnosis, prognosis and differential diagnosis of virilizing adnexal tumours are discussed.     

Rupture of the posterior tibial tendon: CT and surgical findings

Computed tomography (CT) was performed in 42 patients with 49 clinically suspected tears of the posterior tibial tendon. Twenty-eight of the 49 suspected tears were subsequently surgically explored and repaired. Three patterns of tendon abnormalities were recognized on CT scans: type I-intact, hypertrophied, heterogeneous tendon; type II-attenuated tendon; and type III-absence of a portion of a tendon. Types I and II correlated with partial rupture seen during surgery, and type III correlated with complete rupture of the tendon. CT findings were accurate in 96% of the patients who underwent surgery. In four cases (14%), tendon rupture was seen on CT scans, but the extent of the injury was underestimated and the rupture was misclassified. Reactive periostitis of the distal tibia was seen in 71% of diseased tendons and may represent an important factor in the diagnosis of tendon rupture.     

Effects of antidepressants on monoamine transporters

1. Using [3H]antidepressants, high affinity binding sites associated with the neuronal transporter for serotonin, noradrenaline, dopamine and adrenaline have been identified. 2. The association of high affinity [3H]imipramine binding with the serotonin transporter in brain and platelets is well established. Although the exact relationship between the [3H]imipramine recognition site and the serotonin transporter remains to be elucidated, it appears that the [3H]imipramine labelled component of the serotonin transporter represents a novel receptor that functions to modulate serotonin uptake. 3. Most data available to date support the hypothesis that [3H]imipramine binding to platelet represents a biological marker in depression. The majority of studies indicate that the Bmax of platelet [3H]imipramine binding is lower in depressed, untreated patients than in the control population and that this finding is relatively specific to depression. 4. Among the [3H]antidepressant binding sites associated with the other monoaminergic transporters, the recent identification of [3H]desipramine binding to the neuronal transporter for adrenaline offers novel perspectives. Thus, given the high affinity for [3H]desipramine binding to the adrenaline transporter in the frog heart for not only desipramine but also imipramine and the atypical antidepressants mianserin and iprindol, it is possible that an interaction with the adrenaline transporter is of significance to the clinical effects of antidepressant drugs.