Trends in the incidence rates of tonsil and base of tongue cancer in England, 1985�C2006

INTRODUCTION

The aim of this study was to investigate whether incidence rates of tonsil and base of tongue cancer in England are increasing using data from the UK cancer registry.

SUBJECTS AND METHODS

Cancer registrations for oral cavity and oropharynx cancer from 1985–2006 in England were obtained from the National Cancer Information Service. Population estimates were obtained from the Office for National Statistics. Age-adjusted incidence rates and age-specific incidence rates were calculated. The sexes were considered separately as incidence rates are known to differ significantly between men and women. Linear regression was performed to establish whether there was a relationship between incidence rates and time.

RESULTS

There has been an increase in all oral cavity and oropharyngeal cancer in the study period. Linear regression analysis suggests that approximately 90% of the variance in age-adjusted incidence rates for men and women for tonsil, base of tongue and other oral cavity cancer is explained by the passage of time. For other oropharyngeal cancer, the variance is 62% and 46% in men and women, respectively. The estimated annual percentage change from 1985 to 2006 in age-adjusted incidence rates for tonsil and base of tongue cancer is 5.7% and 6.7% for men, and 4.3% and 6.5% for women, respectively.

CONCLUSIONS

This study confirms a wide-spread clinical impression that there has been an increase in age-adjusted incidence rates, between 1985 and 2006, in all oral cavity cancer in England. The age range 40–69 years has seen the biggest increases in age-specific incidence rates for tonsil and base of tongue cancer. This reflects the findings of similar studies in other countries.     

Cribado combinado del síndrome de Down: validación del riesgo estimado por Fetaltest

Objective

To validate empirically the risk for Down syndrome estimated by Fetaltest using biochemical markers in the first trimester (PAPP-A and free beta subunit of hCG) and nuchal translucency.

Material and methods

We performed a retrospective study of the data from 15,009 pregnant women screened for Down Syndrome in the first trimester, included in the database prospectively maintained by the Fetaltest multicenter study, and completed before December 31, 2007. The study included 39 cases of Down syndrome detected either prenatally or postnatally, and used a previously established analysis method.

Results

The correlation between predicted risk and the observed prevalence of Down syndrome was very high (r = 0.999967).

Conclusions

The risk estimated by Fetaltest agrees closely with the observed prevalence of Down syndrome. Therefore, this calculation system is valid and can be used with confidence when counseling pregnant women in our environment.     

Physiological and behavioral studies of spatial coding in the auditory cortex

Despite extensive subcortical processing, the auditory cortex is believed to be essential for normal sound localization. However, we still have a poor understanding of how auditory spatial information is encoded in the cortex and of the relative contribution of different cortical areas to spatial hearing. We investigated the behavioral consequences of inactivating ferret primary auditory cortex (A1) on auditory localization by implanting a sustained release polymer containing the GABA(A) agonist muscimol bilaterally over A1. Silencing A1 led to a reversible deficit in the localization of brief noise bursts in both the horizontal and vertical planes. In other ferrets, large bilateral lesions of the auditory cortex, which extended beyond A1, produced more severe and persistent localization deficits. To investigate the processing of spatial information by high-frequency A1 neurons, we measured their binaural-level functions and used individualized virtual acoustic space stimuli to record their spatial receptive fields (SRFs) in anesthetized ferrets. We observed the existence of a continuum of response properties, with most neurons preferring contralateral sound locations. In many cases, the SRFs could be explained by a simple linear interaction between the acoustical properties of the head and external ears and the binaural frequency tuning of the neurons. Azimuth response profiles recorded in awake ferrets were very similar and further analysis suggested that the slopes of these functions and location-dependent variations in spike timing are the main information-bearing parameters. Studies of sensory plasticity can also provide valuable insights into the role of different brain areas and the way in which information is represented within them. For example, stimulus-specific training allows accurate auditory localization by adult ferrets to be relearned after manipulating binaural cues by occluding one ear. Reversible inactivation of A1 resulted in slower and less complete adaptation than in normal controls, whereas selective lesions of the descending cortico collicular pathway prevented any improvement in performance. These results reveal a role for auditory cortex in training-induced plasticity of auditory localization, which could be mediated by descending cortical pathways.     

Evidence for apoptosis in the fetal Down syndrome brain.

In Down syndrome, enhanced apoptosis (programmed cell death) may play a role in the pathogenesis of characteristic early mental retardation and precocious neurodegeneration of Alzheimer type. Various apoptosis-associated proteins (Bax, Bcl-2, Fas, p53, Hsp70, neuronal apoptosis inhibitory protein-like immunoreactivity) were investigated in four different cortical regions and the cerebellum of one fetal Down syndrome (35 weeks' gestation) postmortem brain sample compared with a control brain sample. The most impressive finding was an at least fivefold elevation of Bax protein together with decreased Bcl-2 values in all Down syndrome cerebral regions investigated. In addition, antiapoptotic, presumably caspase-inhibitory, principles like heat shock protein 70 and neuronal apoptosis inhibitory protein were also reduced. Whereas Fas protein, an important member of receptor-mediated apoptosis, was inconsistently altered, a rather surprising finding was reduced proapoptotic, regulatory protein p53 in four of five regions. The findings are in good agreement with the proposed role of the Bcl-2 protein family in regulating developmental (naturally occurring) apoptotic neuronal death and further suggest that developmental apoptosis may be inappropriately commandeered by so far undefined pathologic processes in Down syndrome.     

Pineal germinoma: MR imaging

Magnetic resonance (MR) imaging characteristics of pineal germinomas are described in seven patients imaged with MR and computed tomography (CT). In patients with symptoms of an enlarging process in the quadrigeminal plate cistern, MR imaging was as sensitive as CT scanning in detecting the mass. MR imaging did not detect a normal-sized, calcified neoplastic gland. Germinoma, germinoma with embryonal cell carcinoma elements, and pineoblastoma demonstrated different MR signal characteristics. Although direct coronal and sagittal MR images were useful in defining the relationship of the tumor to the posterior third ventricle, Sylvian aqueduct, and vein of Galen, the ease, rapidity, and sensitivity of CT scanning suggest that CT should remain the modality of choice for initial evaluation and screening of the pineal region, especially in the younger pediatric population, in whom detection of calcification may provide the only clue of an abnormality.     

A miRNA signature for defining aggressive phenotype and prognosis in gliomas

Gliomas represent a disparate group of tumours for which there are to date no cure. Thus, there is a recognized need for new diagnostic and therapeutic approaches based on increased understanding of their molecular nature. We performed the comparison of the microRNA （miRNA） profile of 8 WHO grade II gliomas and 24 higher grade tumours （2 WHO grade III and 22 glioblastomas） by using the Affymetrix GeneChip miRNA Array v. 1.0. A relative quantification method （RT-qPCR） with standard curve was used to confirm the 22 miRNA signature resulted by array analysis. The prognostic performances of the confirmed miRNAs were estimated on the Tumor Cancer Genome Atlas （TCGA） datasets. We identified 22 miRNAs distinguishing grade II gliomas from higher grade tumours. RT-qPCR confirmed the differential expression in the two patients＇groups for 13 out of the 22 miRNAs. The analysis of the Glioblastoma Multiforme （GBM） and Lower Grade Glioma （LGG） datasets from TCGA demonstrated the association with prognosis for 6 of those miRNAs. Moreover, in the GBM dataset miR-21 and miR-210 were predictors of worse prognosis in both univariable and multivariable Cox regression analyses （ HR 1.19, P = O. 04, and HR 1.18, P = 0. 029 respectively）. Our results support a direct contribution of miRNAs to glioma cancerogenesis and suggest that miR-21 and miR-210 may play a role in the aggressive clinical behaviour of glioblastomas.     

Differential alteration of hippocampal excitatory synaptic transmission by cannabinoid ligands

Cannabinoid compounds affect synaptic activity and plasticity in numerous brain areas by activating CB1 receptors (CB1). In hippocampus, varying results have been obtained on the extent and site of cannabinoid actions on excitatory transmission, ranging from no effect to complete obliteration of synaptic responses. Here we used the rat hippocampal slice preparation to study and compare the effect of various synthetic and endogenous CB1 ligands on excitatory synaptic transmission. The full CB1 agonist WIN55212-2 (WIN2) greatly decreased excitatory synaptic transmission by 62%. The effect of WIN-2 was concentration dependent (EC50 of 200 nM) and completely prevented by CB1 antagonists. The nondegradable partial CB1 agonist R1-methanandamide (mAEA) decreased transmission by 25% and the endocannabinoids 2-arachidonylglycerol (2-AG) and anandamide (AEA) had no significant effect. The action of AEA was improved by inhibiting its degradation but not its transport. The effect of 2-AG was enhanced upon inhibition of COX-2 but remained unchanged with blockade of monoacylglycerol lipase (MAGL). The observed effects were prevented by CB1 antagonists regardless of the ligand used, and paired-pulse paradigms pointed to presynaptic mechanisms of cannabinoid action. Our results show that cannabinoid effects on neuronal activity differ widely according to the CB1 ligand used. We observed large differences between full (synthetic) and partial (endogenous) CB1 agonists in altering synaptic transmission, notably because of the involvement of active degradation mechanisms.