MALIGNANT ECTOMESENCHYMOMA IN CHILDHOOD

Five childhood malignant ectomesenchymomas are reported from three centers in three countries. The children were all younger than 3 years (four less than 12 months), four were boys, and four tumors were sited in the pelvis or external genitalia. All tumors had distinctive light microscopic features of rhabdomyosarcoma and three also demonstrated small numbers of included neuronal cells. Immunohistochemical studies and transmission electron microscopy revealed the additional presence of neurogenic components in the remaining two patients. An additional epithelial component was found by immunohistochemistry in one tumor, which suggests a pluripotential origin that still requires karyotypic investigation. Aggressive chemotherapy and adequate surgical excision have thus far been effective in providing disease-free follow-up for periods of 7 to 50 months. It is implied that because the biological behavior and morphology closely resemble those of rhabdomyosarcoma and because the neurogenic component is often inconspicuous, many malignant ectomesenchymomas may be misdiagnosed as rhabdomyosarcomas.     

Experimental study of the metastatic spread of tumor cells in embryonated chicken egg. Distribution, histology and ultrastructural aspects of tumorous focuses (author's transl)

The injection of mouse ascite Ehrlich carcinoma cells into a vein in the chorioallantoic membrane of chick embryos at the eleventh day of incubation permits the observation of tumoral focuses analogous to metastasis in intra- or extraembryonic viscera, in 70% of embryos, dead or killed between the seventeenth and the twenty first day of incubation. A very clear selectivity can be observed in the invasion of the different organs by the carcinoma cells. The liver is injured most, with a level of metastasis of about 25%, while the spleen is almost never injured. Between these two extremes are ranged the brain, heart, nephros and lungs. The frequency of tumoral nodules in the chorioallantoic membrane, and the richly vascularized mesenchymatous structure of this organ allows for some aspects of tumoral invasion to be analyzed, particularly the relationship between cancer cells and blood vessels. As shown by electron microscopy, the passage of the cancer cells through the capillary barrier is achieved successively by apposition to the outer wall of the vessel, distribution of the basal membrane, endothelialisation and then immediate embolisation without associated thrombosis.     

Morbidity and cost of rotavirus infections in France

BACKGROUND: Rotavirus is the most common cause of severe diarrhea in children. Morbidity and mortality related to rotavirus infection is not well known in temperate countries in general, and in France in particular. OBJECTIVES: The aim of this study was estimate the morbidity, mortality, and cost related to the rotavirus infection in France, in order to assess the potential impact of a vaccination program. METHODS: A birth cohort was followed until 5 years of age using a decision tree model. Rotavirus infection incidence rates were modeled according to age, seasons, and breast-feeding status. RESULTS: Based on estimates from a decision model, we found that in France, rotavirus infection was responsible for 300,000 annual episodes of acute diarrhea, 138,000 visits to general practitioners, 18,000 hospitalizations, and 9 deaths. The annual direct cost related to rotavirus infection care was estimated at 28 million euros. CONCLUSION: This study demonstrates the high morbidity and cost of care associated with rotavirus infection in France. The decision tree model developed in this study could be used in the future to estimate the potential effectiveness, cost and cost-effectiveness of childhood vaccination strategies using new rotavirus vaccines.     

Neurons in the lateral sacral cord of the cat project to periaqueductal grey, but not to thalamus

Previous work of our laboratory has shown that neurons in the lateral sacral cord in cat project heavily to the periaqueductal grey (PAG), in all likelihood conveying information from bladder and genital organs. In humans this information usually does not reach consciousness, which raises the question of whether the lateral sacral cell group projects to the thalamus. After wheatgerm agglutinin-horseradish peroxidase (WGA-HRP) injections into the sacral cord, anterogradely labelled fibers were found in the thalamus, specifically in the ventral anterior and ventral lateral nuclei, the medial and intralaminar nuclei, the lateral ventrobasal complex/ventroposterior lateral nucleus, and the nucleus centre median, lateral to the fasciculus retroflexus. Much denser projections were found to the central parts of the PAG, mainly to its dorsolateral and ventrolateral parts at caudal levels and lateral parts at intermediate levels. In a subsequent retrograde tracing study, injections were made in those parts of the thalamus that received sacral fibers, as found in the anterograde study. Labelled neurons were observed in the sacral cord, but not in the lateral sacral cell group. In contrast, a small control injection in the caudal PAG resulted in many labelled neurons in the lateral sacral cord. These results suggest that afferent information regarding micturition and sexual behaviour is relayed to the PAG, rather than to the thalamus.     

New dosing strategies for antibacterial agents in the neonate

Dosing of antibiotics in neonates requires finding a delicate balance between maximal efficacy and minimal toxicity. There is a lack of data on efficacy of currently used antibiotics in neonates, and rational dosing therefore needs to be based on gestational- and postnatal-age-dependent pharmacokinetics in combination with surrogate markers. These surrogate markers are: (i) the area-under-the serum concentration time curve to minimum inhibitory concentration ratio (AUC/MIC); (ii) peak concentration to MIC ratio (Cmax/MIC); and (iii) the time the concentration remains above the MIC (T>MIC). Whereas the efficacy of beta-lactam antibiotics (including carbapenems) depends on T>MIC, the efficacy of most other antimicrobials (including aminoglycosides and fluoroquinolones) is related to AUC/MIC and Cmax/MIC. Most modern dosing regimens are adequate when these concentration effect relationships are taken into account. Dosing adjustments in neonates are suggested, based on these relationships. Several antimicrobial combinations for treatment of meningitis and necrotizing enterocolitis exist. Empiric treatment should be based on efficacy, concerns about resistance as well as information from institutional microbiological surveillance.     

Stereological analysis of microvascular parameters in a double transgenic model of Alzheimer's disease

Morphological alterations in microvasculature occur as a common finding in the brains of non-demented aged persons and patients with Alzheimer's disease. Quantifying the extent of this vascular pathology, however, has been complicated by systematic error (bias) associated with the applications of assumption- and model-based morphometric techniques to human and animal tissues. The current study used novel assumption- and model-free stereological approaches to quantify capillary parameters in the corpus callosum of a double amyloid precursor protein/presenilin-1 transgenic murine model of Alzheimer's disease. The results revealed significant reductions in the total number of capillary segments in white matter of transgenic mice compared to non-transgenic littermates, with no differences in total capillary length. These findings support the view that the expression of mutant human genes for beta-amyloid peptides alters the normal architecture of cerebral capillary vessels in the white matter of mouse brain, which may model microvasculature changes reported in Alzheimer's disease.