Malignant granular cell tumor of the lateral femoral cutaneous nerve: report of a case with cytogenetic analysis

Malignant granular cell tumors (MGCTs) are rare neoplasms of uncertain histogenesis. We report a case of MGCT involving a peripheral nerve with peritoneal and omental dissemination in which cytogenetic findings are available. Our results show that MGCTs share some cytogenetic abnormalities with malignant peripheral nerve sheath tumors (MPNSTs), supporting the hypothesis that they may represent histogenetically related lesions.     

TCV-309, a novel platelet activating factor antagonist,inhibits leukocyte accumulation and protects against splanchnic artery occlusion shock

The aim of this study was to evaluate: (1) the accumulation of leukocytes in the ileum and the lung during splanchnic artery occlusion (SAO) shock; (2) the role of platelet-activating factor (PAF) and tumor necrosis factor (TNF-) in this phenomenon. Untreated anesthetized rats subjected to total occlusion of the celiac, superior and inferior mesenteric arteries for 45 min, followed by reperfusion, uniformly died within 90 min after reperfusion. The mean survival time was 93±7 min. The neutrophilic infiltrate was quantitated in the ileum and in the lung using a myeloperoxidase (MPO) assay. MPO activity in the ileum and in the lung averaged 0.05±0.03 and 0.4±0.02 U×10^–3/g protein in animals killed before occlusion. MPO activity did not change in rats killed immediately before reperfusion and was significantly elevated (0.11±0.02 and 1.7±0.6 U×10^–3/g protein in the ileum and the lung, respectively) in those killed 80 min after the beginning of the reperfusion. The histological examination confirmed the accumulation of leukocytes in the mucosa of the ileum and the lung over the 80 min. SAO shocked rats exhibited leukopenia and increased serum levels of TNF-. In order to evaluate the role of PAF and TNF- in SAO shock, a powerful PAF receptor antagonist, TCV-309 (5 g/kg i.v.), was injected 5 min after reperfusion. TCV-309 increased survival time, lowered serum TNF-, reduced MPO activity in both the ileum and the lung and ameliorated leukopenia induced by SAO shock. In addition, the drug significantly reduced ileal necrosis and pulmonary morphological alterations induced by shock. These results suggest an important role for PAF in the adhesion of leukocytes in SAO shock.     

Formoterol provides long-lasting protection against exercise-induced bronchospasm.

BACKGROUND: Patients with exercise-induced bronchospasm (EIB) may benefit from a prophylactic beta2-adrenergic agonist that combines rapid onset with long duration of action. OBJECTIVE: To compare the protective effect against EIB of a single inhaled dose of formoterol powder delivered via the Aerolizer inhaler (Novartis Pharmaceuticals, East Hanover, NJ) with the effect of placebo and albuterol. METHODS: Eighteen patients with EIB were randomized to treatment in a double-blind, placebo-controlled, four-way, crossover study. Seventeen patients completed all four crossover periods. Each patient received in random sequence a single dose of formoterol (12 or 24 microg), albuterol (180 microg), or placebo at intervals of 5 +/- 2 days. Pulmonary function measurements were taken before and after exercise challenge tests (ECTs) at 15 minutes postdosing and at 4, 8, and 12 hours postdosing. RESULTS: Both doses of formoterol produced significantly greater protection against EIB, compared with placebo, at all timepoints (P < or = 0.016). The two doses of formoterol were not significantly different from one another at any time. Protection against EIB with albuterol was clinically significant only for the 15-minute ECT and was statistically superior to placebo for the 15-minute and 4-hour ECTs. Although formoterol and albuterol exhibited a rapid onset of action, formoterol provided longer-lasting protection over the 12-hour observation period. Rescue medication was used substantially less with either dose of formoterol, compared with albuterol or placebo. All treatments were well tolerated. Two-hour postdosing electrocardiograms and vital signs were unremarkable for all study treatments. CONCLUSION: A single dose of formoterol (12 or 24 microg) provides protection against EIB within 15 minutes of dosing and persists for up to 12 hours. Formoterol is safe and well tolerated.     

Monte Carlo simulations of a scintillation camera using GATE: validation and application modelling

Geant4 application for tomographic emission (GATE) is a recently developed simulation platform based on Geant4, specifically designed for PET and SPECT studies. In this paper we present validation results of GATE based on the comparison of simulations against experimental data, acquired with a standard SPECT camera. The most important components of the scintillation camera were modelled. The photoelectric effect. Compton and Rayleigh scatter are included in the gamma transport process. Special attention was paid to the processes involved in the collimator: scatter, penetration and lead fluorescence. A LEHR and a MEGP collimator were modelled as closely as possible to their shape and dimensions. In the validation study, we compared the simulated and measured energy spectra of different isotopes: 99mTc, 22Na, 57Co and 67Ga. The sensitivity was evaluated by using sources at varying distances from the detector surface. Scatter component analysis was performed in different energy windows at different distances from the detector and for different attenuation geometries. Spatial resolution was evaluated using a 99mTc source at various distances. Overall results showed very good agreement between the acquisitions and the simulations. The clinical usefulness of GATE depends on its ability to use voxelized datasets. Therefore, a clinical extension was written so that digital patient data can be read in by the simulator as a source distribution or as an attenuating geometry. Following this validation we modelled two additional camera designs: the Beacon transmission device for attenuation correction and the Solstice scanner prototype with a rotating collimator. For the first setup a scatter analysis was performed and for the latter design. the simulated sensitivity results were compared against theoretical predictions. Both case studies demonstrated the flexibility and accuracy of GATE and exemplified its potential benefits in protocol optimization and in system design.     

Trisomy 8 in myelodysplasia and acute leukemia is constitutional in 15-20% of cases.

The trisomy 8 found in malignancies may derive from a constitutional trisomy 8 mosaicism (CT8M), and in these cases the trisomy itself may be regarded as the first mutation in a multistep carcinogenetic process. To assess the frequency of CT8M in hematological dysplastic and neoplastic disorders with trisomy 8, an informative sample of 14 patients was collected. The data ascertained included chromosome analyses of fibroblast cultures and of PHA-stimulated blood cultures in patients with normal blood differential count, as well as possible CT8M clinical signs. One patient showed trisomy 8 in all cell types analyzed and undoubtedly has a CT8M; a second patient consistently showed trisomy 8 in PHA-stimulated blood cultures when no immature myeloid cells were present in blood and should be considered as having CT8M; a third patient, with Philadelphia-positive chronic myelocytic leukemia, was more difficult to interpret, but the possibility that she had CT8M is likely. A few clinical signs of CT8M were also present in these three patients. Our data indicate that the frequency of CT8M in hematological dysplastic and neoplastic disorders with trisomy 8 is approximately 15-20%.     

Identification of cerebral networks by classification of the shape of BOLD responses

Changes in regional blood oxygen level dependent (BOLD) signals in response to brief visual stimuli can exhibit a variety of time-courses. To demonstrate the anatomical distribution of BOLD response shapes during a match to sample task, a formal analysis of their time-courses is presented. An event-related design was used to estimate regional BOLD responses evoked by a cue word, which instructed the subject to attend to the motion or color of an upcoming target, and those evoked by a briefly presented moving target consisting of colored dots. Regional BOLD time-courses were adequately represented by the linear combination of three orthogonal waveforms. BOLD response shapes were then classified using a fuzzy clustering scheme. Three classes (sustained, phasic, and negative) best characterized cue responses. Four classes (sustained, sustained-phasic, phasic, and bi-phasic) best characterized target responses. In certain regions, the shape of the BOLD responses was modulated by the instruction to attend to the target's motion or color. A left frontal and a posterior parietal region showed sustained activity when motion was cued and transient activity when color was cued. A right thalamic and a left lateral occipital region showed sustained activity when color was cued and transient activity when motion was cued. Following the target several regions showed more sustained activity during motion than color trials. In summary, the effect of the task variable was focal following the cue and widespread following the target. We conclude that the temporal patterns of neural activity affected the shape of the BOLD signal.     

Efficacy and safety of sublingual immunotherapy.

OBJECTIVE: To review the available published data concerning the use of sublingual immunotherapy (SLIT) in respiratory allergy to primarily evaluate the clinical efficacy and safety of the treatment and to secondarily consider the mechanisms of action and any unresolved questions. DATA SOURCES: Articles in the medical literature (starting from 1986 up to November 2003) derived from searching the MEDLINE database with the keywords sublingual immunotherapy, respiratory allergy, asthma, and rhinitis. Sources included review articles, randomized controlled clinical trials, postmarketing surveillance studies, and relevant reports from meeting proceedings. STUDY SELECTION: Articles concerning safety, efficacy, and mechanisms of SLIT published in English-language, peer-reviewed journals. RESULTS: SLIT proved effective and safe in adults and children. As with traditional subcutaneous immunotherapy, SLIT has long-lasting efficacy and a preventive effect on new sensitizations. CONCLUSION: SLIT is a viable alternative to subcutaneous immunotherapy. Its use in pediatric patients seems to be particularly promising.     

Presymptomatic diagnosis of SMA III by genotype analysis

Linkage analysis and prenatal prediction in families segregating autosomal recessive spinal muscular atrophy (SMA) has become feasible since the assignment of the locus responsible for type I-III SMA to region 5q12-q13.3. We have performed a segregation study of SMA in Italian families using molecular probes and highly informative PCR-based polymorphic markers. In one family, a 7-year-old boy affected with type III SMA and an 8-year-old apparently healthy brother had identical haplotypes. These findings prompted us to reexamine the apparently unaffected child. His neurological exam was normal. However, the electromyography (EMG) showed a pattern consistent with chronic SMA. To our knowledge this is the first example of presymptomatic diagnosis of SMA based on genotype analysis. © 1993 Wiley-Liss, Inc.     

Could mitochondrial haplogroups play a role in sporadic amyotrophic lateral sclerosis?

Mitochondrial impairment has been implicated in the pathogenesis of the amyotrophic lateral sclerosis (ALS). Furthermore, mitochondrial-specific polymorphisms were previously related to other neurodegenerative diseases, such as Parkinson, Friedreich and Alzheimer disease. To investigate if specific genetic polymorphisms within the mitochondrial genome (mtDNA) could act as susceptibility factors and contribute to the clinical expression of sporadic ALS (sALS), we have genotyped predefined European mtDNA haplogroups in 222 Italian patients with sALS and 151 matched controls. Individuals classified as haplogroup I demonstrated a significant decrease in risk of ALS versus individuals carrying the most common haplogroup, H (odds ratio 0.08, 95% confidence interval 0.04-0.4, p < 0.01). Further stratification of the dataset by sex, age and site of onset of disease and survival failed to reach significance for association. Our study provides evidence of the contribution of mitochondrial variation to the risk of ALS development in Caucasians. Further it may help elucidate the mechanism of the mitochondrial dysfunction detectable in ALS, and may be of relevance in development of strategies for the treatment of this disease.