[Severe hypercalcemia of unusual cause, looking for the culprit: Case report and review of the literature]. / Hypercalcémie sévère de cause inhabituelle, à la recherche du coupable : cas clinique et revue de la littérature.

INTRODUCTION: Hypercalcemia is not a rare event and can lead to severe consequences. Its main etiologies are primary hyperparathyroidism and neoplasic conditions. The iatrogenic etiology by vitamin D intoxication is more rarely found. CASE PRESENTATION: A 76-year-old finish woman comes to the emergency room for chest pain. Her medical history is impossible to specify due to the language barrier and initial confusion. She has severe hypercalcaemia (4.14mmol/L), renal insufficiency, cardiac arrhythmia later complicated by an ischemic cardiac episode. Clinic and biologic examinations initially guided the research towards a hematological and neoplasic pathology. The iatrogenic etiology will be permitted by the contribution of details on its medical history and treatment learnt secondly. She was treated for post-surgical hypoparathyroidism by dihydrotachysterol, a vitamin D derivative. The cessation of substitution, treatment with hydration and biphosphonates allowed the rapid correction of hypercalcemia. DISCUSSION: Dihydrotachysterol intoxication is a rare etiology of hypercalcemia. Because of the longer half-life of this molecule, the risk of hypercalcemia seems to be greater than with other vitamin D derivatives. This molecule, withdrawn from the French market in 1982, is not detected by the dosage of 25 and 1.25 OH vitamin D. CONCLUSION: We report an original case of intoxication by dihydrotachysterol. The risk of hypercalcemia encountered with this molecule must be known. The close medical follow-up recommended in case of hypoparathyroidism seems to be particularly necessary in case of supplementation by this molecule.

Long-distance seed and pollen dispersal inferred from spatial genetic structure in the very low-density rainforest tree, Baillonella toxisperma Pierre, in Central Africa.

We analysed the spatial distribution of genetic diversity to infer gene flow for Baillonella toxisperma Pierre (Moabi), a threatened entomophilous pollinated and animal-dispersed Central African tree, with typically low density (5-7 adults trees/km(2)). Fifteen nuclear and three universal chloroplast microsatellites markers were used to type 247 individuals localized in three contiguous areas with differing past logging intensity. These three areas were within a natural forest block of approximately 2886 km(2) in Gabon. Expected heterozygosity and chloroplast diversity were He(nuc) = 0.570 and H(cp) = 0.761, respectively. F(IS) was only significant in one area (F(IS) = 0.076, P < 0.01) and could be attributed to selfing. For nuclear loci, Bayesian clustering did not detect discrete gene pools within and between the three areas and global differentiation (F(STnuc) = 0.007, P > 0.05) was not significant, suggesting that they are one population. At the level of the whole forest, both nuclear and chloroplast markers revealed a weak correlation between genetic relatedness and spatial distance between individuals: Sp(nuc) = 0.003 and Sp(cp) = 0.015, respectively. The extent of gene flow (σ) was partitioned into global gene flow (σ(g)) from 6.6 to 9.9 km, seed dispersal (σ(s)) from 4.0 to 6.3 km and pollen dispersal (σ(p)) from 9.8 to 10.8 km. These uncommonly high dispersal distances indicate that low-density canopy trees in African rainforests could be connected by extensive gene flow, although, given the current threats facing many seed disperser species in Central Africa, this may no longer be the case.

High-risk molecules or insufficient scientific data?

When I was invited to author an ethics policy piece on the "approach to high-risk molecules" as a contribution to the theme of "Innovation in Drug Development" of this Clinical Pharmacology & Therapeutics issue, I thought there was a need to evaluate whether questioning the transition from preclinical to clinical development after the TGN 1412 serious adverse event may freeze the development of innovating tools in drug development.

Fine-scale genetic structure and gene dispersal in Centaurea corymbosa (Asteraceae) I. Pattern of pollen dispersal.

Pollen dispersal was characterized within a population of the narrowly endemic perennial herb, Centaurea corymbosa, using exclusion-based and likelihood-based paternity analyses carried out on microsatellite data. Data were used to fit a model of pollen dispersal and to estimate the rates of pollen flow and mutation/genotyping error, by developing a new method. Selfing was rare (1.6%). Pollen dispersed isotropically around each flowering plant following a leptokurtic distribution, with 50% of mating pairs separated by less than 11 m, but 22% by more than 40 m. Estimates of pollen flow lacked precision (0-25%), partially because mutations and/or genotyping errors (0.03-1%) could also explain the occurrence of offspring without a compatible candidate father. However, the pollen pool that fertilized these offspring was little differentiated from the adults of the population whereas strongly differentiated from the other populations, suggesting that pollen flow rate among populations was low. Our results suggest that pollen dispersal is too extended to allow differentiation by local adaptation within a population. However, among populations, gene flow might be low enough for such processes to occur.

Postmeiotic cytokinesis and pollen aperture number determination in eudicots: effect of the cleavage wall number.

In eudicot postmeiotic tetrads, apertures are usually joined in pairs in highly conserved areas. These appear to be located at the last points of contact persisting at the end of cytokinesis between the cytoplasm of the future microspores. In order to investigate the relationship between cytokinesis and aperture formation, aperture distribution within postmeiotic tetrads and the progression of meiosis were studied in Nicotiana tabacum cv. Ambalema. This variety (inbred line) produces about 85% tricolporate pollen and 15% tetracolporate pollen grains. In addition, about 7% of tetrads are composed of four equal-sized microspores and a supernumerary pseudomicrospore of small size and an equal proportion of tetrads exhibit unpaired apertures (these apertures are not joined in pairs within tetrads). Observation of cytokinesis indicates that both unpaired apertures and pseudomicrospores could result from the persistence of late communications between microsporocytes. Observations of tetrads indicate that an increase in the number of elements that are separated during cytokinesis is correlated with an increase in microspore aperture number. All data converge to support the hypothesis that aperture site determination is partly controlled by the number of walls formed to separate the different elements of the tetrad.

Pollen aperture heteromorphism. Variation in pollen-type proportions along altitudinal transects in Viola calcarata.

Some species produce pollen grains with different aperture numbers within a single individual (pollen aperture heteromorphism). In the pansy Viola diversifolia, aperture number is positively correlated with pollen germination speed, and negatively correlated with viability. In V. calcarata, young five-aperturate pollen grains germinate faster than four-aperturate ones. Heteromorphism could thus be favoured when pollination is unpredictable, as plants produce both very competitive and long-lived pollen grains. Depending on the efficiency of the pollinators, different proportions of pollen types will be optimal. In insect-pollinated species, such as V. calcarata, pollination efficiency generally decreases as elevation increases. We therefore expect a decrease in mean aperture number as altitude increases. This was found in four transects (out of six). Pollinator activity therefore has a potential impact on pollen morphology.

[Pharmacokinetics of sulindac in aged patients presenting with inflammatory joint disease]. / Pharmacocinétique du sulindac chez des patients âgés présentant une pathologie articulaire inflammatoire.

The kinetic of sulindac and its two metabolites (sulfide and sulfone) was investigated in twelve elderly patients, following multiple oral dose administration of 400 mg/d. Data were compared to those obtained previously in ten healthy volunteers who received the same dosage regimen. Following multiple dose administration, accumulation ratios indicate that sulindac do not accumulate either in elderly patients (R = 1.35; R = AUC0-24 J8/AUC0-24 J1) or in healthy young subjects (R = 1.38; R = U0-24 J1). No significant modification of sulindac and sulfide kinetic parameters was observed. The apparent bioavailability of the inactive metabolite, sulfone, was found to be doubled in elderly patients (p less than 0.05). We conclude that there is no need to modify the dosage regimen of Arthrocine (400 mg once a day) in elderly patients.