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.     

Unicanalicular stent for nasolacrimal duct obstruction

The authors describe a method for silicone intubation of a single patent canaliculus associated with a nasolacrimal duct obstruction. Although bicanalicular intubation is always preferable when possible, unicanalicular stenting is necessary when only one canaliculus is patent. A chief advantage of this technique is that the lacrimal stent is inaccessible to the child and thus cannot be accidentally pulled out.     

Keratography as a guide to selective suture removal for the reduction of astigmatism after penetrating keratoplasty

After penetrating keratoplasty in 52 eyes, keratography refraction and keratometry were used to select appropriate interrupted sutures for removal in order to reduce astigmatism. All eyes had one continuous and either 12 or 16 interrupted nylon sutures. The keratographs were examined retrospectively and separated into six groups on the basis of similar mire patterns. The removal of single sutures associated with three of these patterns reduced astigmatism by the following average amounts: symmetrical oval pattern, 0.44 diopters (D); D-shaped oval pattern, 2.07 D; and focal indentation pattern, 6.60 D. The other three patterns--mildly disrupted mires, incomplete mires, and uninterpretable mires--did not allow quantification of results. Examples of these keratographic patterns are presented and recommendations are made for their use in the management of astigmatism following penetrating keratoplasty.     

Synthesis and teratogenic action of n-hydroxythalidomide

N-Hydroxythalidomide (1d), a potential metabolite of thalidomide (1a), was synthesized from N-phthalyglutaminic acid anhydride (1b) and O-tetrahydropyraline hydroxylamine, followed by deprotection. The teratogenicity of 1d was studied using the Hen's-Egg-Test model which had been found applicable for 1a. 1d was more teratogenic to chicken embryos compared to 1a. The percentage of teratogenic malformations in the 1d groups was 28-46%, whereas the percentage in the 1a groups was 20-23%. The oxygen protected precursor N-hydroxythalidomide (1c) was less teratogenic (11-15%).     

Mycobacterium ulcerans infection in Ashanti region, Ghana

We describe a series of 96 cases of Mycobacterium ulcerans infection (Buruli ulcer) from a new endemic focus in the Afram valley, north of Agogo, in Ghana. 63 cases were children under 13 years old. Active treatment by excision and skin grafting necessitates long stays in hospital and repeated procedures. Scarring and contracture are frequent. Eyes and other vital organs may be destroyed. In its endemic foci Buruli ulcer is a serious health burden on rural populations. Research is urgently needed, especially in prevention and non-surgical management.     

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.