Is the recommended dose of leflunomide the best regimen to treat rheumatoid arthritis patients?

SIR, The aim of this letter is to show our experience in theuse of leflunomide (LFN) and express our opinion about the recommendeddose [1, 2]. As far as we know, no data exist about a possibleassociation between the loading dose and the presence of adverseevents. Any new suggestion about the use of LFN should be appreciated,specially after the safety of this     

Changes in the microvasculature with age

The microvasculature of various organs of the rat and of the mesentery of the cat were examined for histochemical changes as a function of age, using the periodic acid-Schiff (PAS) reaction. Arterioles, minute arteries, and nonmuscular venules were histochemically unchanged to approximately 17 months of age in the rat and 8 years in the cat. Subsequently, focal areas of PAS-positive material developed in the media of arterioles and small arteries and increased in extent and severity with age. The adventitia of nonmuscular venules normally stains slightly positive due to the mucopolysaccharide coating of collagen fibers. With age this adventitial layer becomes more intensely PAS-positive. In the 26-month-old rat and 19-year-old cat, the media of arterioles and small arteries were extensively hyalinized. Lesions of arteriosclerosis were not present. These observations, in consort with prior observations of others in various mammals, indicate that there is a regular systematic alteration of various elements of the microcirculation with age. A possible relationship between these anatomical changes and tissue exchange is considered.     

Nutrient-specific modulation of gastric mechanosensitivity in patients with functional dyspepsia

Intraduodenal lipid infusion induces symptoms and increases sensitivity to gastric distension in patients with functional dyspepsia. To test whether these effects are specific for lipid, we compared the effects of intraduodenal infusions of either lipid or glucose on symptoms and gastric sensory and motor responses to gastric distension. Eighteen dyspeptic patients and nine controls were studied. The stomach was distended with a flaccid bag during isocaloric infusions (1 kcal/ml) of saline and either 10% Intralipid (nine patients) or 26.7% glucose (nine patients) into the duodenum. Dyspeptic symptoms and sensory thresholds for epigastric fullness and discomfort were assessed. Gastric pressure profiles during distensions were similar during lipid and glucose infusions in patients and controls, but both were significantly lower than during saline infusion. Lower volumes were required to induce fullness and discomfort in the patients compared with the controls. In the controls, the threshold volumes required to induce fullness and discomfort were greater during infusion of lipid and glucose than during saline infusion, but in the patients, the threshold volumes were increased during glucose infusion but further reduced during lipid infusion. Moreover, in the patients, nausea was more common during lipid than glucose infusion and did not occur during saline. The controls did not experience any symptoms during any infusion. In conclusion, intraduodenal lipid but not glucose sensitizes the stomach to distension in patients with functional dyspepsia but not in controls.     

Evidence of vector-borne disease of Early Cretaceous reptiles

A blood-filled sand fly, Palaeomyia burmitis, was recently described from Early Cretaceous Burmese amber. Within the alimentary canal of this sand fly were the amastigotes and promastigotes of a digenetic leishmanial trypanosomatid. Inside the lumen of the thoracic midgut of the fossil sand fly were nucleated blood cells, some of which were intact and others in various stages of lysis and disintegration. The present study identifies these blood cells as reptilian and describes putative developing amastigotes inside spherical to oval whitish vacuoles within some of the fossil blood cells. The significance of this find is discussed, especially regarding the high possibility that Cretaceous dinosaurs were infected by trypanosomatids.     

Analysis of the semantic representations of living and nonliving concepts: A normative study

Current feature-based semantic memory models assume that the semantic representations of concepts differ systematically across living and nonliving categories and that such differences account for the emergence of category-specific semantic deficits in brain-damaged people. To assess some of the different models' main assumptions about structural differences at the semantic feature level in the two major semantic domains, we administrated a feature-listing task to normal young volunteers on 64 concepts drawn from living and nonliving semantic categories. We investigated whether feature correlation, a variable with a crucial role in the emergence of category-specific deficits, should be computed as a concept-dependent or as a concept-independent measure, and we chose the former. We also addressed the issue of a psychological counterpart of feature production frequency. Finally, we analysed the database obtained from the feature-listing tasks, looked at cross-domain differences for correlation, feature frequency, distinctiveness, and feature type, and discussed the implications of these findings for current semantic memory models.