An examination of male and female odds ratios by BMI, cigarette smoking, and alcohol consumption for cancers of the oral cavity, pharynx, and larynx in pooled data from 15 case-control studies.

BACKGROUND: Greater tobacco smoking and alcohol consumption and lower body mass index (BMI) increase odds ratios (OR) for oral cavity, oropharyngeal, hypopharyngeal, and laryngeal cancers; however, there are no comprehensive sex-specific comparisons of ORs for these factors. METHODS: We analyzed 2,441 oral cavity (925 women and 1,516 men), 2,297 oropharynx (564 women and 1,733 men), 508 hypopharynx (96 women and 412 men), and 1,740 larynx (237 women and 1,503 men) cases from the INHANCE consortium of 15 head and neck cancer case-control studies. Controls numbered from 7,604 to 13,829 subjects, depending on analysis. Analyses fitted linear-exponential excess ORs models. RESULTS: ORs were increased in underweight (<18.5 BMI) relative to normal weight (18.5-24.9) and reduced in overweight and obese categories (>/=25 BMI) for all sites and were homogeneous by sex. ORs by smoking and drinking in women compared with men were significantly greater for oropharyngeal cancer (p < 0.01 for both factors), suggestive for hypopharyngeal cancer (p = 0.05 and p = 0.06, respectively), but homogeneous for oral cavity (p = 0.56 and p = 0.64) and laryngeal (p = 0.18 and p = 0.72) cancers. CONCLUSIONS: The extent that OR modifications of smoking and drinking by sex for oropharyngeal and, possibly, hypopharyngeal cancers represent true associations, or derive from unmeasured confounders or unobserved sex-related disease subtypes (e.g., human papillomavirus-positive oropharyngeal cancer) remains to be clarified.

Roles of mGluR5 in synaptic function and plasticity of the mouse thalamocortical pathway.

The group I metabotropic glutamate receptor 5 (mGluR5) has been implicated in the development of cortical sensory maps. However, its precise roles in the synaptic function and plasticity of thalamocortical (TC) connections remain unknown. Here we first show that in mGluR5 knockout (KO) mice bred onto a C57BL6 background cytoarchitectonic differentiation into barrels is missing, but the representations for large whiskers are identifiable as clusters of TC afferents. The altered dendritic morphology of cortical layer IV spiny stellate neurons in mGluR5 KO mice implicates a role for mGluR5 in the dendritic morphogenesis of excitatory neurons. Next, in vivo single-unit recordings of whisker-evoked activity in mGluR5 KO adults demonstrated a preserved topographical organization of the whisker representation, but a significantly diminished temporal discrimination of center to surround whiskers in the responses of individual neurons. To evaluate synaptic function at TC synapses in mGluR5 KO mice, whole-cell voltage-clamp recording was conducted in acute TC brain slices prepared from postnatal day 4-11 mice. At mGluR5 KO TC synapses, N-methyl-D-aspartate (NMDA) currents decayed faster and synaptic strength was more easily reduced, but more difficult to strengthen by Hebbian-type pairing protocols, despite a normal developmental increase in alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-mediated currents and presynaptic function. We have therefore demonstrated that mGluR5 is required for synaptic function/plasticity at TC synapses as barrels are forming, and we propose that these functional alterations at the TC synapse are the basis of the abnormal anatomical and functional development of the somatosensory cortex in the mGluR5 KO mouse.

Cessation of alcohol drinking, tobacco smoking and the reversal of head and neck cancer risk.

BACKGROUND: Quitting tobacco or alcohol use has been reported to reduce the head and neck cancer risk in previous studies. However, it is unclear how many years must pass following cessation of these habits before the risk is reduced, and whether the risk ultimately declines to the level of never smokers or never drinkers. METHODS: We pooled individual-level data from case-control studies in the International Head and Neck Cancer Epidemiology Consortium. Data were available from 13 studies on drinking cessation (9167 cases and 12 593 controls), and from 17 studies on smoking cessation (12 040 cases and 16 884 controls). We estimated the effect of quitting smoking and drinking on the risk of head and neck cancer and its subsites, by calculating odds ratios (ORs) using logistic regression models. RESULTS: Quitting tobacco smoking for 1-4 years resulted in a head and neck cancer risk reduction [OR 0.70, confidence interval (CI) 0.61-0.81 compared with current smoking], with the risk reduction due to smoking cessation after >/=20 years (OR 0.23, CI 0.18-0.31), reaching the level of never smokers. For alcohol use, a beneficial effect on the risk of head and neck cancer was only observed after >/=20 years of quitting (OR 0.60, CI 0.40-0.89 compared with current drinking), reaching the level of never drinkers. CONCLUSIONS: Our results support that cessation of tobacco smoking and cessation of alcohol drinking protect against the development of head and neck cancer.

Phacomatoses et tumeurs génétiquement déterminées: la transition enfant-adulte [Phacomatosis and genetically determined tumors: the transition from childhood to adulthood]

Les phacomatoses regroupent des maladies du développement du neurectoderme, engendrant des manifestations cutanées ou du système nerveux central. Les symptômes de ces maladies peuvent affecter les individus atteints à différents moments de leur vie. Il s'agit de maladies, héréditaires ou congénitales, qui sont transmises de façon variable. Effectivement, certaines, telles que la neurofibromatose, la sclérose tubéreuse ou la maladie de von Hippel-Lindau sont autosomiques dominantes, alors que d'autres, telles que la maladie de Sturge-Weber sont sporadiques. Des transmissions autosomiques récessives liées à X ou des formes mosaïques existent également. Une revue de la littérature, comprenant les cinq phacomatoses les plus fréquemment vues par un neurochirurgien (neurofibromatose de type I et II, sclérose tubéreuse de Bourneville, maladie de Sturge-Weber-Krabbe, maladie de von Hippel-Lindau) a été effectuée en se centrant sur le diagnostic, la variabilité de la symptomatologie selon l'âge du patient et son traitement. Les cas de patients adultes et pédiatriques vus aux consultations de neurologie et neurochirurgie de l'hôpital de Lille (France) et Lausanne (Suisse), de 1961 à nos jours, ont été revus pour illustrer les différentes pathologies rencontrées, selon l'âge des patients atteints. Le phénotype de ces maladies se modifie avec l'âge, car les gènes incriminés sont des gènes impliqués dans la différentiation tissulaire et sont activés à des âges différents suivant les tissus. Le rôle du neurochirurgien sera variable selon l'âge et le syndrome du patient. Il importe de connaître les variations du phénotype de ces maladies avec l'âge ainsi que les conséquences à long terme des traitements pour proposer au patient un suivi neurochirurgical personnalisé. Phacomatoses, or neurocutaneous disorders, are a group of congenital and hereditary diseases characterized by developmental lesions of the neuroectoderm, leading to pathologies affecting the skin and the central nervous system. There is a wide range of pathologies affecting individuals at different moments of life. The genetics is variable: while neurofibromatosis 1 and 2, tuberous sclerosis and von Hippel-Lindau disease are all inherited as autosomal dominant traits, Sturge-Weber syndrome is sporadic. Other neurocutaneous disorders can be inherited as autosomal recessive traits (i.e., ataxia-telangiectasia), X-linked (i.e., incontinentia pigmenti) or explained by mosaicism (i.e., hypomelanosis of Ito, McCune-Albright syndrome). In this review, we discuss the major types of neurocutaneous disorders most frequently encountered by the neurosurgeon and followed beyond childhood. They include neurofibromatosis types 1 and 2, tuberous sclerosis, Sturge-Weber syndrome and von Hippel-Lindau disease. In each case, a review of the literature, including diagnosis, genetics and treatment will be presented. The lifespan of the disease with the implications for neurosurgeons will be emphasized. A review of cases, including both pediatric and adult patients, seen in neurosurgical practices in the Lille, France and Lausanne, Switzerland hospitals between 1961 and 2007 is presented to illustrate the pathologies seen in different age-groups. Because the genes mutated in most phacomatoses are involved in development and are activated following a timed schedule, the phenotype of these diseases evolves with age. The implication of the neurosurgeon varies depending on the patient's age and pathology. While neurosurgeons tend to see pediatric patients affected with neurofibromatosis type 1, tuberous sclerosis and Sturge-Weber syndrome, there will be a majority of adult patients with von Hippel-Lindau disease or neurofibromatosis type 2