Recurrent glioblastoma: which treatment? A real-world study from the Neuro-oncology Unit “Regina Elena” National Cancer Institute

Neurological Sciences - The majority of patients with glioblastoma (GBM) experience disease progression. At recurrence, treatment options have limited efficacy. Many studies report a limited and...     

Magnetic resonance imaging of solitary brain metastases: main findings of nonmorphological sequences

Purpose

This study was done to investigate the usefulness of diffusion-weighted (DWI), perfusion-weighted (PWI) and proton magnetic resonance (MR) spectroscopy imaging in characterising solitary brain metastases.

Materials and methods

Fifty-nine solitary brain metastases were evaluated with conventional and nonmorphological MR imaging: DWI, PWI and MR spectroscopy. We evaluated size, signal intensity and contrast enhancement and calculated apparent diffusion coefficient (ADC), relative cerebral blood volume (rCBV), percentage of signal intensity recovery (PSR) and maximum values of N-acetylaspartate (NAA), choline (Cho), creatine (Cr), lipids (Lip), NAA/Cr and Cho/Cr. The nonmorphological parameters were compared with those from the literature for brain lesions that frequently enter the differential diagnosis with metastases.

Results

Signal intensity and contrast enhancement patterns were variable. There was a wide range of ADC values: min:max 0.59×10^?3:1.88×10^?3. Compared with normal white matter, rCBV was higher in lesions (3.30±1.59) and lower in perilesional oedema (0.42±0.15). Mean and minimum PSR were 57% and 48%, respectively; lip and Cho were elevated and NAA reduced.

Conclusions

Conventional MR findings of solitary metastases are heterogeneous, and some values of nonmorphological sequences are similar to those of other brain lesions. PWI seems to be the nonmorphological MR technique that may best contribute to the diagnosis of brain metastases.     

Ultrastructural localization of salivary mucins MUC5B and MUC7 in human labial glands

Piras M, Hand AR, Tore G, Ledda GP, Piludu M. Ultrastructural localization of salivary mucins MUC5B and MUC7 in human labial glands. Eur J Oral Sci 2010; 118: 14–18. © 2010 The Authors. Journal compilation © 2010 Eur J Oral Sci
As a result of their presence throughout the mouth in the submucosa or between muscle fibers, minor salivary glands secrete directly and continuously into the oral cavity, providing mucosal surfaces with highly glycosylated proteins that are active in bacterial aggregation and in oral tissue lubrication. In this study, we investigated the ultrastructural localization of the MUC5B and MUC7 mucins in human labial glands by means of a postembedding immunogold technique. Thin sections of normal human labial glands, obtained during surgery, were incubated with polyclonal antibodies to human salivary mucins MUC5B and MUC7, and then with gold-labeled secondary antibodies. Specific MUC5B reactivity was found in the secretory granules of mucous cells of all glands examined, and was associated with the luminal membrane of duct cells. MUC7 labeling was observed in the granules of both mucous and seromucous secretory cells of the glandular parenchyma. Quantitative analyses demonstrated that seromucous granules have higher immunogold labeling densities for MUC7 than mucous granules. Our immunohistochemical data extend the results of previous light microscopic studies of MUC5B and MUC7 localizations, pointing out the significant contribution of human labial glands in the secretion process of these two mucins.     

What is semantic in semantic dementia? The decay of knowledge of physical entities but not of verbs,numbers and body parts

Background: Conceptual knowledge does not decay randomly in patients with cerebral damage, suggesting that dedicated neural substrates may support different categories of knowledge. Semantic dementia is an optimal natural model for studying the organization of semantic memory. Nevertheless, in a pathology primarily characterized by a semantic memory disorder categorical- and modality- specific effects are not obvious findings. In fact, there is no clear evidence of categorical effects, at least concerning two broad categories of knowledge, that is, natural items and artifacts. Furthermore, transmodal deficits do not seem to be the rule in SD. Also quite robust is the observation that some conceptual domains are relatively spared in this pathology, that is, numerical knowledge, abstract words, and action verbs.

Aims: To explore category specific and modality specific deficit in SD and to support the evidence that semantic degradation in SD primarily involves knowledge of the objects in the real world, whereas categories of knowledge whose items can be less easily identified by surface attributes, such as verbs, numbers and body parts, are more preserved.

Methods and Procedures: We investigated the semantic impairment in 8 patients with Semantic Dementia (SD). Voxel-based morphometry (VBM) in each patient was also obtained

Outcomes and Results: In some patients manmade objects were significantly more preserved than natural items, verbs more preserved than nouns and the number system entirely preserved; the body parts category was the least impaired in all subjects; finally, in three patients visual semantic knowledge was significantly more preserved than verbal semantic knowledge. VBM showed that atrophy of the anterior inferior temporal regions was insufficient to impair knowledge about verbs, numbers and body parts, whose impairment was associated with more widespread atrophy. In subjects whose verbal semantic knowledge was significantly more impaired than visual semantic knowledge, atrophy was principally distributed in the left hemisphere. In patients with significant impairment for natural items compared to manmade objects, atrophy was not confine in the temporal lobes.

Conclusion: We conclude that in SD semantic decay primarily involves the real-world items whose knowledge is processed by surface sensorifunctional features and that this is the type of knowledge stored in the temporal lobes. Our data support a model that associates a semantic hub with modality/category specific neural substrates.     

Effects of chronic antidepressant treatments in a putative genetic model of vulnerability (Roman low-avoidance rats) and resistance (Roman high-avoidance rats) to stress-induced depression

Introduction

The Roman low- (RLA) and high-avoidance (RHA) rats were selectively bred for, respectively, poor versus rapid acquisition of active avoidance in a shuttle box and, under aversive conditions, display reactive (RLA) versus proactive (RHA) coping behaviors. In the forced swim test (FST), RLA rats exhibit a depression-like behavior characterized by greater immobility and fewer climbing counts when compared with their RHA counterparts. Furthermore, subacute treatments with clinically effective antidepressant drugs decrease immobility and increase climbing or swimming in RLA rats but do not modify the performance of RHA rats.

Objective and methods

Because chronic treatment with antidepressants is usually required to produce clinical effects, the present study was designed to compare the behaviors of RLA and RHA rats in the FST after subacute (1 day) and chronic (15 days) administration of desipramine, fluoxetine, and chlorimipramine.

Results

In RLA rats, subacute treatments with low doses of desipramine, fluoxetine, and chlorimipramine (2.5–5 mg/kg) were ineffective whereas chronic treatments with the same doses of all three antidepressants decreased immobility and also increased climbing (desipramine) or swimming (fluoxetine). By contrast, neither subacute nor chronic treatments with these antidepressants induced significant changes in the behavior of RHA rats in the FST.

Conclusions

RLA and RHA rats represent two divergent phenotypes, respectively susceptible and resistant to develop depression-like behavior under aversive environmental conditions that may be used to identify genetically determined neural substrates and mechanisms underlying vulnerability and resistance to stress-induced depression.     

Subcellular localization of epidermal growth factor receptor in human submandibular gland

The subcellular distribution of the epidermal growth factor receptor (EGFr) was demonstrated in the normal human submandibular gland by means of immunogold cytochemistry. EGFr labelling appeared in both acinar and ductal cells, where strong immunoreactivity was associated with a tubulovesicular system near the basolateral surfaces. In addition, groups of reactive vesicles were highlighted among secretory granules of both serous and mucous cells and at the apex of ductal cells. Basolateral vesicles were interpreted as being a result of EGFr internalization after activation by an exogenous ligand, although the functional meaning of those located apically remains unclear.     

Morphological and functional MR imaging of Lhermitte-Duclos disease with pathology correlate

Lhermitte-Duclos disease (LDD) is a rare benign lesion of uncertain pathogenesis characterised by distortion of the normal cerebellar laminar cytoarchitecture. We report a case of LDD thoroughly characterized by advanced magnetic resonance imaging techniques, with diffusion-weighted, perfusion-weighted and post-gadolinium sequences. Imaging showed restricted diffusion consistent with high cellularity, high degree of vascularity and preserved blood-brain barrier permeability, correlating with pathology.     

Peripheral blood lymphocyte response to recombinant and non-recombinant interleukin 2 in previously treated patients with Hodgkin's disease, long-time off-therapy

13 patients with Hodgkin's disease (HD) previously treated, 9 of whom were long-time (more than 2 yr) off-therapy, were studied for peripheral blood lymphocyte response to interleukin 2 and for lymphocyte subpopulations by means of in vitro cultures and monoclonal antibodies. The aim of the study was to ascertain the role played by interleukin 2 in the impaired cell-mediated immunity of HD patients. The results show a response of peripheral blood mononuclear cells of HD patients to either the T cell-specific polyclonal mitogens PHA and Con A or to the T cell-dependent, although B cell-specific, PWM, most significantly decreased compared to the normal response. As far as the interleukin 2 involvement in HD is concerned, our study suggests: an impaired endogenous interleukin 2 production by T lymphocytes, a most probable deficiency of the interleukin 2 receptor (Tac) expression and 3) a decrease of the number and/or of the function of NK cells no longer responsive in vitro to interleukin 2. The phenotypic analysis of peripheral blood mononuclear cells showed a slight decrease of total T cells (T3+), of the helper/inducer subset (T4+) and of the T4+/T8+ cells ratio. Our data seem to support the rationale for a therapeutical approach with interleukin 2 in controlled clinical trials also in HD patients, according to the experiments in progress in solid tumor patients.