Disseminated mucormycosis associated with invasive pulmonary aspergillosis in a patient treated for post-transplant high-grade non-Hodgkin's lymphoma

The incidence of mucormycosis, defined as systemic infection caused by fungi of the class Phycomycetes has been increasing over the past 2 decades, especially in profoundly immunocompromised hosts. We report a new case in a patient presenting with post-transplant high-grade non-Hodgkin's lymphoma who received a prolonged treatment with voriconazole and caspofungin for an invasive pulmonary aspergillosis. Definite diagnosis of mucormycosis was made by liver biopsy of nodules mimicking progressive lymphoma. The patient died 1 week after the diagnosis of mucormycosis despite the administration of liposomal amphotericin B. The role of voriconazole and caspofungin in the emergence of mucormycosis is discussed.     

The influence of mental fatigue on facial EMG activity during a simulated workday

The present study investigated whether facial EMG measures are sensitive to the effects of fatigue. EMG activity of the corrugator and frontalis muscles was recorded during and after a simulated workday. Fatigue was evaluated in four ways: (a) the building up of fatigue effects during the workday, (b) the building up of fatigue during a test period, (c) examination of after-effects of the workday in two test sessions in the evening, and (d) comparison of subjects with a high-and low-score on an Emotional Exhaustion questionnaire. EMG activity decreased during the workday and increased again in the evening. EMG activity also increased during a test period, reflecting increased mobilization to maintain performance. High-score subjects showed a lower level of EMG activity throughout the entire workday. They reported a higher need for recovery, experienced the workday as more fatiguing, and were less well rested when getting up. EMG measures seem to reflect that high-score subjects have problems with investing sufficient energy to maintain performance during a workday.     

Microglial changes accompanying the promotion of retinal ganglion cell axonal regeneration into peripheral nerve grafts

Intravitreal injection of the microglia inhibitor tuftsin 1-3 leads to an increase in retinal ganglion cell axonal regeneration into peripheral nerve grafts and a decrease in phagocytic cells in the retina. However, the relation of phagocytic cells and particularly microglia towards axonal regeneration remains unclear. Initially, to assess this, tuftsin 1-3's effect on axonal regeneration was reexamined by doing a dose-response study. Optimal doses were found to be 2.5 g/ml and 250 g/ml in rats and hamsters respectively. We then studied retinal phagocytic cells in rats. Microglial cells were classified as resting or activated based on their morphology following OX42 immunolabelling. In controls, most microglial cells were in the resting state. Optic nerve cut led to an increase in the total number of microglia and a ten-fold elevation in the proportion of activated cells; changes were more pronounced at the optic nerve stump. Anastomosis of an autologous segment of sciatic nerve to the stump of the freshly cut optic nerve minimized the overall increase in microglia, and combined with 2.5 g/ml tuftsin 1-3, lead to a marked blunting of activation. Preservation within the retina of a higher proportion of resting over active form of microglia, and not the prevention of microglial proliferation per se, may be a crucial factor in allowing additional retinal ganglion cell axons to regenerate into peripheral nerve grafts.     

Positron emission tomography in clinical oncology

A NEW FORM OF MEDICAL IMAGING: Positron emission tomography (PET) is used for the non-invasive in vivo visualisation of biochemical cell processes. It reveals the metabolic characteristics of neoplastic lesions and hence their identification by compensating the lack of lesion specificity of radiological techniques. VARIOUS INDICATIONS: Using the current oncology marker, 18F-fluorodeoxyglucose (FDG), excellent results with PET have been established at all stages of neoplasia, notably for the diagnosis of initial malignancy and the identification of residual lesions and early detection of relapses. Moreover, the fact that the whole of the body can be explored makes PET the tool of choice in the control of the extension and operability of cancers. With the close correlation between imaging and the metabolism of the lesions, PET is the earliest and most precise for assessing the effects of treatment. LIMITS AND PERSPECTIVES: The existence of benign inflammatory FDG binding should lead to the development of markers of other metabolisms directly linked to cell proliferation. The lack of anatomical reference points characteristic of PET does not permit the precise localisation of the lesions detected and could be corrected by combining, in a single apparatus, the PET camera and an X scan, the anatomical resolution of which is irreplaceable. This type of equipment represents the development of a new branch of medical imaging, oncological imaging.     

Chronic lung disease in infancy following prematurity

Survival of extremely preterm infants has improved with modern neonatal intensive care. Chronic lung disease of prematurity, however, remains an important clinical problem and this article reviews the changing presentation and discusses new concepts of its aetiology.     

The ACE gene I/D polymorphism is not associated with the blood pressure and cardiovascular benefits of ACE inhibition

The insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene might have consequences for the risks of vascular diseases. We examined the ACE genotype and the effects of a perindopril-based blood pressure-lowering regimen on macrovascular events, dementia, and cognitive decline among hypertensive and nonhypertensive patients with a history of cerebrovascular disease. ACE I/D genotypes were measured in 5688 of 6105 individuals with previous stroke or transient ischemic attack who participated in the PROGRESS trial. The DD genotype was significantly (P<0.0001) less frequent in Asian subjects (Chinese and Japanese, 14.7%) than in non-Asian subjects (32.0%). Controlling for racial background, there were no associations between ACE genotypes and cerebrovascular disease history or cardiovascular risk factors, including baseline blood pressure. The ACE genotype was not associated with the long-term risks of stroke, cardiac events, mortality, dementia, or cognitive decline; neither did the ACE genotype predict the blood pressure reduction associated with the use of the ACE inhibitor perindopril. Similarly, there was no evidence that the ACE genotype modified the relative benefits of ACE inhibitor-based therapy over placebo. This study provides no evidence that in patients with cerebrovascular disease, knowledge of ACE genotype is useful for predicting either the risk of disease or the benefits of perindopril-based blood pressure-lowering treatment.     

P-Glycoprotein Inhibition Leads to Enhanced Disruptive Effects by Anti-Microtubule Cytostatics at the In Vitro Blood-Brain Barrier

Purpose. To investigate whether P–glycoprotein (Pgp) protects the in vitro BBB against the cytotoxic effects of anti–tumour drugs. Methods. In an in vitro BBB coculture model the influence of the anti–microtubule drugs vinblastine, colchicine, paclitaxel and the non–antimicrotubule drugs doxorubicin, fluorouracil and etoposide in the absence or presence of Pgp modulators on the trans–endothelial electrical resistance (TEER), which is an indicator for the integrity, was investigated. Results. In the absence of Pgp modulators vinblastine, colchicine and paclitaxel dose dependently decreased TEER values to less than 20% of control. Non–anti–microtubule drugs did not affect TEER values. Following competitive inhibition of Pgp by various Pgp modulators and substrates, even low concentrations of vinblastine, colchicine and paclitaxel substantially decreased TEER. IC₅₀ values of LY 335979, SDZ–PSC 833, cyclosporin A, and verapamil were 0.03, 0.25, 0.46, and 13.7 M, respectively. Conclusions. These results indicate that Pgp normally protects the in vitro BBB against the disruptive effects of anti–microtubule drugs, but its integrity is lost when anti–microtubule drugs are used in combination with potent Pgp modulators. In addition, this procedure offers the possibility to characterize Pgp modulators and substrates with respect to their efficacy and to elucidate drug interactions at the level of Pgp.     

Conjoint and extended neural networks for the computation of speech codes: the neural basis of selective impairment in reading words and pseudowords

The computation of speech codes (i.e. phonology) is an important aspect of word reading. Understanding the neural systems and mech- anisms underlying phonological processes provides a foundation for the investigation of language in the brain. We used high-resolution three-dimensional positron emission tomography (PET) to investigate neural systems essential for phonological processes. The burden of neural activities on the computation of speech codes was maximized by three rhyming tasks (rhyming words, pseudowords and words printed in mixed letter cases). Brain activation patterns associated with these tasks were compared with those of two baseline tasks involving visual feature detection. Results suggest strong left lateralized epicenters of neural activity in rhyming irrespective of gender. Word rhyming activated the same brain regions engaged in pseudoword rhyming, suggesting conjoint neural networks for phonological processing of words and pseudowords. However, pseudoword rhyming induced the largest change in cerebral blood flow and activated more voxels in the left posterior prefrontal regions and the left inferior occipital-temporal junction. In addition, pseudoword rhyming activated the left supramarginal gyrus, which was not apparent in word rhyming. These results suggest that rhyming pseudowords requires active participation of extended neural systems and networks not observed for rhyming words. The implications of the results on theories and models of visual word reading and on selective reading dysfunctions after brain lesions are discussed.