Indomethacin distribution in acute pharmacological response among rats

A detailed examination of quantitative relationships of pharmacological action with plasma and tissue concentrations of indomethacin has been undertaken in the rat, after single oral administration of two sustained release preparations. In this study, drug was assayed by high performance liquid chromatography, whereas antiinflammatory response was assessed through the carrageenin-induced edema test. Significant linear correlations (p less than 0.001) were found between logarithmically transformed percent inhibition of edema and logarithmically transformed plasma, as well as tissue levels of indomethacin. However, the lack of significance for partial correlation regarding tissue concentration, contrary to plasma concentration, suggests that pharmacological response is more closely related to the latter, indicating that antidematous effect is mediated via the circulating drug rather than a local action in target tissues. This assumption is further discussed from the equivalence point of view. The relevance of this type of study in the case of topical administration of indomethacin is addressed as well. Taking into account the predictive value of the rat paw edema test for clinical efficacy, relationships similar to those observed are to be expected in man. The high correlation existing between plasma concentration of indomethacin and its pharmacological effect justifies the development and use of sustained release preparations in order to improve the outcome of treatment with this nonsteroidal antiinflammatory drug.     

Distribution of tyrosine-hydroxylase (TH)-immunoreactive neurons in the diencephalon of the pigeon (Columba livia domestica)

The distribution of tyrosine-hydroxylase (TH)-immunoreactive cell bodies and fibers in the diencephalon has been investigated with immunohistological techniques in the pigeon. The results suggest that TH is present in a number of morphologically distinct neuronal systems. Preoptic and hypothalamic TH neurons were subdivided into a medial periventricular and a lateral group. The medial group starts with a rostral collection of small cells in the preoptic region. A significantly larger collection of TH neurons occupies the paraventricular nucleus (PVN) (stratum cellulare internum) and mainly consists of large multipolar cells. Further caudally, the main concentration of cells is in the hypothalamic posteromedial and the periventricular regions of the tuberoinfundibular (arcuate) nucleus. No TH neuron was found in the ventral and lateral parts of the tuberoinfundibular region, suggesting that the prominent tuberoinfundibular dopaminergic system described in mammals is absent in the pigeon. This further substantiated by the relative scarcity of TH immunoreactive fibers and varicosities in the neurohemal zone of the median eminence (ME). The caudalmost components of the medial group appear to be continuous with the large population of TH neurons distributed in the midline of the mesencephalon. Tyrosine-hydroxylase-immunopositive cells have not been found in the paraventricular organ. The lateral group consists of TH neurons loosely arranged in the lateral hypothalamus, including regions of the supraoptic nucleus and hypothalamic posterolateral nucleus. Tyrosine-hydroxylase containing neurons vary widely in size, shape, and dendritic arborization in each diencephalic region. However, it is possible to distinguish two main cell types. Small bipolar neurons with two simple arborizing dendrites were concentrated in the medial periventricular system. The second type of cell is large, multipolar with four to five branching dendrites. This latter cell type occurs mainly in the lateral system and in the PVN. Major fiber bundles containing TH immunoreactivity were identified in the lateral and periventricular hypothalamus. The paraventricular organ and the organum vasculosum laminae terminalis contained the densest arborization of fibers and varicosities. In the ME, dense innervation was found in the subependymal layer. Dense arborizations of TH positive fibers and varicosities were located in the septal nuclei and the paleostriatum augmentatum.     

Demonstration, by the cartographic test, of an unusual reaction to intermittent light stimulation in patients with migraine

Topographic electroencephalography was carried out to study reaction to photic stimulation in 29 normal volunteers, and 12 patients who had presented frequent clinically confirmed migraines for at least 3 years. In the group of migraineurs photic stimulation resulted in an increase in the alpha band power. The difference between the two groups was statistically significant. This reaction to photic stimulation is of help in diagnosis and suggests that a diagnosis and therapeutic orientation might be possible in patients for whom clinical diagnosis is not clear. The specificity of the migraineur's reaction to photic stimulation and its possible origin are discussed.     

The clinical encounter as local moral world: Shifts of assumptions and transformation in relational context

In this study we consider the process of the clinical encounter, and present exemplars of how assumptions of both clinicians and their patients can shift or transform in the course of a diagnostic interview. We examine the process as it is recalled, and further elaborated, in post-diagnostic interviews as part of a collaborative inquiry during reflections with clinicians and patients in the northeastern United States. Rather than treating assumptions by patients and providers as a fixed attribute of an individual, we treat them as occurring between people within a particular social context, the diagnostic interview. We explore the diagnostic interview as a landscape in which assumptions occur (and can shift), navigate the features of this landscape, and suggest that our examination can best be achieved by the systematic comparison of views of the multiple actors in an experience-near manner. We describe what might be gained by this shift in assumptions and how it can make visible what is at stake for clinician and patient in their local moral worlds—for patients, acknowledgment of social suffering, for clinicians how assumptions are a barrier to engagement with minority patients. It is crucial for clinicians to develop this capacity for reflection when navigating the interactions with patients from different cultures, to recognize and transform assumptions, to notice ‘surprises’, and to elicit what really matters to patients in their care.