Impaired modulation of motor cortex excitability by homonymous and heteronymous muscle afferents in focal hand dystonia.

A decrease of heteronymous median nerve-evoked inhibition of corticospinal projections to forearm extensor muscles was reported in a group of 10 dystonic patients by Bertolasi and colleagues in 2003. Here we tested the excitability of corticomotoneuronal connections to both wrist extensor (ECR) and flexor (FCR) muscles after conditioning stimulation of median and also radial nerve at rest in a group of 25 patients with focal hand dystonia compared to 20 healthy subjects. We also investigated the effect of the wrist dystonic posture, either in flexion or in extension, on the afferent modulation of ECR and FCR motor evolved potentials (MEPs). The heteronymous (median-induced) but also homonymous (radial-induced) inhibitions (interstimuli intervals 13-21 ms) of ECR MEP size observed in healthy subjects were decreased in patients. In addition, homonymous (median-induced) facilitation of FCR MEP size was also decreased in patients while heteronymous inhibition (radial-induced) was not. Neither the involvement of the target muscle in the dystonic posture nor the origin of the afferent volley (from a dystonic muscle) influenced the degree of impairment of afferent modulation of the MEP. These findings support the view that a global abnormal somatosensory coupling in focal hand dystonia may contribute to an inadequate motor command to wrist muscles.     

Fungal infections in cancer patients: An international autopsy survey

In an attempt to estimate the frequency of fungal infections among cancer patients, a survey of autopsy examinations was conducted in multiple institutions in Europe, Japan and Canada. Fungal infections were identified most often in leukemic patients and transplant recipients (25 % each). Fifty-eight percent of fungal infections were caused byCandida spp. and 30 % byAspergillus spp. There was considerable variability in the frequency of fungal infections in different countries. Nevertheless, this study clearly demonstrates that fungal infections represent a common complication in cancer patients, especially in patients with leukemia.     

Per operative localization of a carcinoid tumour of the breast using indium-111 pentetreotide and a nuclear surgical probe

A 69-year-old woman presented with a single enlarged lymph node in the left axilla. Clinical examination and other investigations, including various imaging methods, failed to reveal the primary tumour. However, indium-111 pentetreotide scan revealed a site of uptake in the anterior region of the left thorax. Peroperative imaging with t¹¹¹In-pentetreotide confirmed the tumour uptake and use of a nuclear surgical probe allowed precise localization of the tumour, which was completely resected.     

Comparison of bone mass measured by histomorphometry on iliac biopsy and by dual photon absorptiometry of the lumbar spine

In a prospective study we compared bone mass measured independently by dual photon absorptiometry (DPA) on lumbar spine and by histomorphometry on transiliac biopsy. Measurements were done in 83 patients (23 males, 60 females) with various generalized bone diseases, including spinal osteoporosis, primary hyperparathyroidism and osteopetrosis. Iliac bone density was analyzed on bone biopsy with an automatic image analyzer and expressed as the trabecular bone volume (TBV), the cortical thickness (CT) and the total bone density (TBD) which includes the density of both spongy and cortical bone within the periosteal envelope. The bone mineral content (BMC) and density (BMD) were measured from L2 to L4 with a Novo Lab 22a device. For the 83 patients, there were significant correlations between values given by both methods, with r values ranging from 0.74 to 0.43, according to the bone mass parameters analyzed. In the 37 patients with untreated vertebral osteoporosis, the TBV--but not the CT nor the TBD--correlated significantly with the BMD of the spine (r = 0.53, p less than 0.001). In conclusion, there is a significant correlation between bone density of the iliac crest assessed histomorphometrically and spinal density measured by DPA. Despite the fact that DPA measures both trabecular and cortical bone of the spine, it correlates better with iliac trabecular bone mass than with the overall iliac bone density.     

In vitro metabolism of ferroquine (SSR97193) in animal and human hepatic models and antimalarial activity of major metabolites on Plasmodium falciparum.

Ferroquine (SSR97193) has been shown to be a promising antimalarial, both on laboratory clones and on field isolates. So far, no resistance was documented in Plasmodium falciparum. In the present work, the metabolic pathway of ferroquine, based on experiments using animal and human hepatic models, is proposed. Ferroquine is metabolized mainly via an oxidative pathway into the major metabolite mono-N-demethyl ferroquine and then into di-N,N-demethyl ferroquine. Some other minor metabolic pathways were also identified. Cytochrome P450 isoforms 2C9, 2C19, and 3A4 and, possibly in some patients, isoform 2D6, are mainly involved in ferroquine oxidation. The metabolites were synthesized and tested against the 3D7 (chloroquine-sensitive) and W2 (chloroquine-resistant) P. falciparum strains. According to the results, the activity of the two main metabolites decreased compared with that of ferroquine; however, the activity of the mono-N-demethyl derivative is significantly higher than that of chloroquine on both strains, and the di-N-demethyl derivative remains more active than chloroquine on the chloroquine-resistant strain. These results further support the potential use of ferroquine against human malaria.     

Prostaglandin E2 level in tissue surrounding aseptic failed total hips

Summary Production of inflammatory mediators (IM) by cells and specifically macrophages around loosened implants may be responsible for their loosening. Our hypothesis was that different materials give rise to different amounts of these IM. It is thought that alumina/alumina for total hip replacement (THR), which has been used for 15 years in our orthopedic department, may produce less IM than other systems. We initiated a clinical prospective study to measure the level of prostaglandin E₂ (PGE₂) in tissue surrounding loosened prostheses to quantify PGE₂ production regarding the types of material involved in the friction couple, i.e., alumina/alumina versus metal/polyethylene, and the type of fixation, i.e., cemented versus cementless. A total of 29 THR revisions were performed in 28 patients. Four implant groups were identified: alumina/alumina cemented, alumina/alumina cementless, metal/polyethylene cemented, and metal/polyethylene cementless. For each revision, tissues surrounding the failed implants were harvested and processed, and the PGE₂ was measured in a blind manner using an immunoassay technique. As the measuring technique was difficult, at least three determinations for each sample were necessary. Some samples were excluded from the analysis for various reasons, for example, second or further revisions involving many different materials in the past, conjunction of metallic and alumina debris and samples taken from nonloosened components. Finally, 15 samples were considered adequate for inclusion in this study. Two groups were analyzed and compared: the alumina/alumina couple and the metal/polyethylene couple. Tissue surrounding the first group demonstrated a PGE₂ level of 69 ± 56 fmol/mg wet weight compared to 202 ± 156 fmol/mg for the second. The Wilcoxon test was applied, and there was a statistical difference (P < 0.05). When the alumina/alumina cemented group was compared to the alumina/alumina cementless group, there was a tendency to less PGE₂ with the cemented, but the difference was not statistically significant. Results thus demonstrate that alumina/alumina produces less IM than metal/polyethylene. However, these results do not indicate whether this is related to the type of debris, the amount, or both. This remains a preliminary study. Further studies with more samples, other mediators and growth factors, and a precise comparison to histological findings are still necessary.