Evidence for inflammation in normal-appearing brain regions in patients with growing sporadic vestibular schwannoma: A PET study.

Background: Nonauditory symptoms can be a prominent feature in patients with sporadic vestibular schwannoma (VS), but the cause of these symptoms is unknown. Inflammation is hypothesized to play a key role in the growth and symptomatic presentation of sporadic VS, and in this study, we investigated through translocator protein (TSPO) positron emission tomography (PET) whether inflammation occurred within the "normal appearing" brain of such patients and its association with tumor growth. Methods: Dynamic PET datasets from 15 patients with sporadic VS (8 static and 7 growing) who had been previously imaged using the TSPO tracer [11C](R)-PK11195 were included. Parametric images of [11C](R)-PK11195 binding potential (BPND) and the distribution volume ratio (DVR) were derived and compared across VS growth groups within both contralateral and ipsilateral gray (GM) and white matter (WM) regions. Voxel-wise cluster analysis was additionally performed to identify anatomical regions of increased [11C](R)-PK11195 binding. Results: Compared with static tumors, growing VS demonstrated significantly higher cortical (GM, 1.070 vs. 1.031, P = .03) and whole brain (GM & WM, 1.045 vs. 1.006, P = .03) [11C](R)-PK11195 DVR values. The voxel-wise analysis supported the region-based analysis and revealed clusters of high TSPO binding within the precentral, postcentral, and prefrontal cortex in patients with growing VS. Conclusions: We present the first in vivo evidence of increased TSPO expression and inflammation within the brains of patients with growing sporadic VS. These results provide a potential mechanistic insight into the development of nonauditory symptoms in these patients and highlight the need for further studies interrogating the role of neuroinflammation in driving VS symptomatology.

Low-dose GBCA administration for brain tumour dynamic contrast enhanced MRI: a feasibility study.

A key limitation of current dynamic contrast enhanced (DCE) MRI techniques is the requirement for full-dose gadolinium-based contrast agent (GBCA) administration. The purpose of this feasibility study was to develop and assess a new low GBCA dose protocol for deriving high-spatial resolution kinetic parameters from brain DCE-MRI. Nineteen patients with intracranial skull base tumours were prospectively imaged at 1.5 T using a single-injection, fixed-volume low GBCA dose, dual temporal resolution interleaved DCE-MRI acquisition. The accuracy of kinetic parameters (ve, Ktrans, vp) derived using this new low GBCA dose technique was evaluated through both Monte-Carlo simulations (mean percent deviation, PD, of measured from true values) and an in vivo study incorporating comparison with a conventional full-dose GBCA protocol and correlation with histopathological data. The mean PD of data from the interleaved high-temporal-high-spatial resolution approach outperformed use of high-spatial, low temporal resolution datasets alone (p < 0.0001, t-test). Kinetic parameters derived using the low-dose interleaved protocol correlated significantly with parameters derived from a full-dose acquisition (p < 0.001) and demonstrated a significant association with tissue markers of microvessel density (p < 0.05). Our results suggest accurate high-spatial resolution kinetic parameter mapping is feasible with significantly reduced GBCA dose.

Rabies pathogenesis update / Atualização sobre a patogênese da raiva

Human rabies continues to be an important public health problem. Our understanding of the disease has been acquired from studies in experimental animal models. There are many unanswered questions in rabies pathogenesis, although there has been recent progress. Rabies virus-infected neurons may not function normally due to degenerative changes involving neuronal processes, including both dendrites and axons. Street rabies virus infection may not be cleared from the central nervous system because immune effectors cannot be delivered into brain tissues as a result of poor blood-brain barrier permeability. No effective therapy is available for human rabies. Therapeutic (induced) coma has failed repeatedly. An improved understanding of rabies pathogenesis may offer new insights for the development of novel therapies for human rabies.

A raiva humana continua sendo um problema de saúde pública. O nosso conhecimento acerca da doença tem sido construído por meio de estudos em modelos animais experimentais. Há muitas perguntas não respondidas envolvendo a patogênese da raiva, a despeito de termos observado um avanço nos últimos tempos. Os neurônios infectados pelo vírus da raiva podem não operar normalmente devido às mudanças degenerativas envolvendo processos neurais, incluindo dendrites e axônios. As infecções por vírus de rua não podem ser extirpadas do sistema nervoso central, uma vez que os efetores imunes não podem ser transportados aos tecidos do cérebro devido à pequena permeabilidade da barreira hematoencefálica. Não existe uma terapia eficaz contra a raiva humana. O coma terapêutico (induzido) tem falhado sistematicamente. Uma melhor compreensão da patogênese da raiva pode oferecer novas ideias para o desenvolvimento de modernas terapias contra a raiva humana.

Nutrition in early life - "long term effects" - Keynote Address

Most estimates indicate that during the next 20 years most of the morbidity and mortality in the world will be related to chronic diseases, such as cardiovascular disease, diabetes mellitus, some cancers and mental health. The aetiology of each condition is complex and multifactorial, but recent evidence shows that nutritional exposure during early life might be critical in determining individual susceptibility to a range of other environmental factors in the generation of chronic disease in adulthood. It is proposed that the underlying susceptibility originates through "programming" during fetal and early infant life. Thus, in response to a limited availability of nutrients the fetus adapts and this adaption results in a permanent change in organ structure and metabolic function, giving rise to the hypothesis of "Fetal Origins of Adult Disease". Across Britain there is a two-fold variation in cardiovascular disease which cannot be adequately explained by variations in lifestyle. Early studies suggested they may be explained by differences in the physique and growth of young women, the growth of their babies in utero and during infancy, and the consequent lifelong differences in the physiology and metabolism of the offspring. Novel epidemiological studies by Barker and colleagues in Southampton allowed exploration of these ideas using detailed maternity and health visitors records which have been kept from the early years of this century. Babies born fifty years ago were traced and their size at birth and one year of age related to the occurrence of cardiovascular disease in later life. Amongst 10,000 men in Hertfordshire who had lower birthweight and remained lighter than average at one year of age the risk of death from heart disease was three times that of men at the upper end of normal. Small size at birth is also associated with high blood pressure and diabetes, high serum cholesterol and disordered blood coagulation. The lightest babies at birth were ten times more likely to develop the metabolic syndrome of hypertension, impaired glucose tolerance and raised blood lipid levels than those who were heaviest at birth. Stroke is also increased in those with a lower birth weight. These relationships are even more evident in babies in whom growth is disproportionate, thus thinner babies are more likely to develop non-insulin diabetes mellitus as adults.(Au) [truncated at 2500 characters]

Rabies without nwgri bodies: detection of rabies virus at autopsy by immunohistochemistry and in situ hybridization / Rabia sin cuerpos de Negri. Detección del virus rábico en autopsia por inmunohistoquímica y por hibridación in situ

El patólogo puede diagnosticar rabia en autopsia cuando reconoce cuerpos de Negri o si documenta la presencia de antígeno del virus por inmunofluorescencia en tejido fresco o congelado. Técnicas moleculares recientes permiten llegar al diagnóstico en ausencia de estos marcadores. Un muchacho de 13 años fue mordido por un perro rabioso y murió veinte días después a pesar de haber recibido un curso completo de vacuna antirrábica. En la autopsia se encontraron infiltrados inflamatorios en cerebro y médula espinal pero un extenso muestreo no reveló cuerpos de Negri. El cerebro y la médula habían sido fijados en formol y no había tejido fresco para inmunofluorescencia. Se identificó antígeno del virus de la rabia por tinciones con inmunoperoxidasa en cerebelo, hipocampo, bulbo y médula espinal. Se detectó asimismo la presencia de RNA genómico del virus y mRNA de la glicoproteína viral por hibridación in situ usando sonda tritiadas de RNA. En este caso se logró un diagnóstico específico de rabia mediante el uso de métodos de inmunohistoquímica y de hibridación in situ. Estas técnicas pueden ser de utilidad en estudios retrospectivos en material de archivo y particularmente cuando se carece de tejido fresco o congelado para inmunofluorescencia