[How molecular biology can improve the clinical diagnosis of gliomas?] / Comment la biologie moléculaire améliore le diagnostic clinique des gliomes?

Gliomas are the most common primary brain tumors and include different diagnoses associated with a different prognosis. Histology remains the gold standard for the diagnosis of these tumors. However, pathologists may encounter diagnostic difficulties due to tumor heterogeneity or to the small size of the samples. Recently, major advances in discovery of molecular alterations of these cancers have led to the development of new molecular markers, some with a diagnostic role, others with a prognostic impact and / or predictive of therapeutic response. The testing of different molecular alterations such as 1p / 19q codeletion, mutations of IDH genes, p16 deletion, EGFR amplification or MGMT promoter methylation has been included in the daily practice in order to confirm the diagnosis, assess the patient prognosis and guide treatment choices.

Les gliomes représentent les tumeurs cérébrales primitives les plus fréquentes et regroupent différentes entités au pronostic très différent. L'examen anatomopathologique est le gold standard pour le diagnostic de ces tumeurs. Cependant, les pathologistes peuvent rencontrer des difficultés diagnostiques dues, entre autres, à l'hétérogénéité tumorale ou à la petite taille des prélèvements. Nous avons assisté, ces dernières années, à des avancées majeures dans la découverte des altérations moléculaires de ces cancers, ce qui a mené au développement de nouveaux marqueurs moléculaires, certains avec un rôle diagnostique, d'autres avec un impact pronostique et/ou prédictif de la réponse thérapeutique. Dans la pratique quotidienne, il est donc devenu utile de tester la présence de différentes altérations moléculaires telles que la codélétion 1p/19q, les mutations des gènes IDH, la délétion du gène CDKN2A/p16, l'amplification du gène EGFR ou la méthylation du promoteur du gène MGMT, afin de confirmer le diagnostic, d'évaluer le pronostic des patients ainsi que d'orienter les choix thérapeutiques.

IGF-IR: a new prognostic biomarker for human glioblastoma.

BACKGROUND: Glioblastomas (GBMs) are the most common malignant primary brain tumours in adults and are refractory to conventional therapy, including surgical resection, radiotherapy and chemotherapy. The insulin-like growth factor (IGF) system is a complex network that includes ligands (IGFI and IGFII), receptors (IGF-IR and IGF-IIR) and high-affinity binding proteins (IGFBP-1 to IGFBP-6). Many studies have reported a role for the IGF system in the regulation of tumour cell biology. However, the role of this system remains unclear in GBMs. METHODS: We investigate the prognostic value of both the IGF ligands' and receptors' expression in a cohort of human GBMs. Tissue microarray and image analysis were conducted to quantitatively analyse the immunohistochemical expression of these proteins in 218 human GBMs. RESULTS: Both IGF-IR and IGF-IIR were overexpressed in GBMs compared with normal brain (P<10(-4) and P=0.002, respectively). Moreover, with regard to standard clinical factors, IGF-IR positivity was identified as an independent prognostic factor associated with shorter survival (P=0.016) and was associated with a less favourable response to temozolomide. CONCLUSIONS: This study suggests that IGF-IR could be an interesting target for GBM therapy.

[Peripheral neuropathies, from diagnosis to treatment, review of the literature and lessons from the local experience]. / Les neuropathies périphériques, du diagnostic au traitement, revue de la littérature et enseignements de l'expérience locale.

Peripheral neuropathy implies damages to neurons belonging to the peripheral nervous system which includes cranial nerves, spinal nerves' roots, spinal ganglia, nerve trunks and their divisions, and, the autonomic nervous system. Peripheral neuropathies are frequent in the general population (prevalence: 2,4%). We present a review of the recent literature and highlight diagnostic approaches for certain types of neuropathies particularly the most frequent ones or those requiring peculiar attention in first-line medicine. We also present epidemiologic data and data related to sural nerve biopsies from our centre. The determination of the location and the topography of the affected sites, integrated into the global context of the patient, is essential to provide an etiologic diagnosis. The median nerve compression within the carpal tunnel and polyneuropathies are the most frequent forms of peripheral neuropathies. More than one hundred causes of polyneuropathies are described and they are divided into acquired, genetically determined and idiopathic. We highlight a largely adopted diagnostic strategy concerning polyneuropathies and describe the Guillain-Barre syndrome, the alcohol-related polyneuropathy and the controversies about the benefit of the B vitamin therapy and its dangers. At the Hôpital Erasme, since 2008, more than 1372 patients with peripheral neuropathy were identified. Results of sural nerve biopsies performed in seventeen of them do not largely differ from those of other centres of expertise. We conclude that the diagnosis of peripheral neuropathy usually requires the expertise of a neurologist, but, first line caregivers must be able to recognize and refer patient when needed.

Effects of a progesterone-based oestrous synchronization protocol in 51- to 57-day postpartum high-producing dairy cows.

The aim of this study was to investigate the effect of applying a progesterone-based oestrous synchronization protocol at 51-57 days postpartum in high-producing dairy cows. The data analysed were derived from 1345 lactating cows. Cows between 51 and 57 days postpartum were assigned to the groups: control, PRID (receiving a progesterone-releasing intravaginal device for 9 days, and prostaglandin F(2α) 24 h before PRID removal) or GnRH-PRID (the same as the PRID group plus GnRH at PRID insertion). Oestrus was detected by using pedometers and confirmed by examination of the genital tract at AI. Oestrous and conception rates before days 71-77 postpartum, pregnancy loss in early pregnant cows or the cumulative conception rate registered on day 120 postpartum were considered as the dependent variables in four consecutive logistic regression analyses. Based on the odds ratios, the oestrous rate increased by a factor of 1.73 in cows showing oestrus before treatment for each unit increase in the number of previous oestruses; decreased by a factor of 0.44 in the control group with respect to the treatment groups; and by a factor of 0.61 in cows without luteal structures at treatment with respect to cows with corpora lutea. The conception rates of cows inseminated before days 71-77 postpartum remained similar across the groups, whereas the likelihood of pregnancy loss for cows becoming pregnant during this period was 0.11 times lower in the PRID group than in the control. Based on the odds ratio, the likelihood of a higher cumulative conception rate on day 120 postpartum: increased in cows showing oestrus before treatment by a factor of 1.41 for each unit increase in the number of previous oestruses, was reduced 0.56-fold in control cows compared with treated cows, and was also reduced by a factor of 0.98 for each kilogram of milk production increase recorded at treatment. In conclusion, although oestrous synchronization programmes performed in this study did not improve fertility, cows treated with progesterone could be inseminated earlier than untreated cows, such that the treatments increased the cumulative pregnancy rates determined on day 120 postpartum. In addition, fewer pregnancy losses were observed in early pregnant cows in the PRID group than the GnRH-PRID group.

Apparent diffusion coefficient and cerebral blood volume in brain gliomas: relation to tumor cell density and tumor microvessel density based on stereotactic biopsies.

BACKGROUND AND PURPOSE: MR imaging-based apparent diffusion coefficient (ADC) and regional cerebral blood volume (rCBV) measurements have been related respectively to both cell and microvessel density in brain tumors. However, because of the high degree of heterogeneity in gliomas, a direct correlation between these MR imaging-based measurements and histopathologic features is required. The purpose of this study was to correlate regionally ADC and rCBV values with both cell and microvessel density in gliomas, by using coregistered MR imaging and stereotactic biopsies. MATERIALS AND METHODS: Eighteen patients (9 men, 9 women; age range, 19-78 years) with gliomas underwent diffusion-weighted and dynamic susceptibility contrast-enhanced MR imaging before biopsy. Eighty-one biopsy samples were obtained and categorized as peritumoral, infiltrated tissue, or bulk tumor, with quantification of cell and microvessel density. ADC and rCBV values were measured at biopsy sites and were normalized to contralateral white matter on corresponding maps coregistered with a 3D MR imaging dataset. ADC and rCBV ratios were compared with quantitative histologic features by using the Spearman correlation test. RESULTS: The highest correlations were found within bulk tumor samples between rCBV and cell density (r=0.57, P < .001) and rCBV and microvessel density (r=0.46, P < .01). An inverse correlation was found between ADC and microvessel density within bulk tumor (r=-0.36, P < .05), whereas no significant correlation was found between ADC and cell density. CONCLUSION: rCBV regionally correlates with both cell and microvessel density within gliomas, whereas no regional correlation was found between ADC and cell density.

Tenascin-C expression relates to clinicopathological features in pilocytic and diffuse astrocytomas.

AIMS: Tenascin-C (TN-C) is an extracellular matrix brain glycoprotein for which conflicting in vitro and in vivo results are reported in the literature dealing with its involvement in astrocytoma aggressiveness, in particular astrocytoma invasion. In view of these conflicting results and the lack of data available on low-grade astrocytomas, the present study focuses on pilocytic World Health Organization (WHO) grade I, and diffuse WHO grade II astrocytomas, that is, two histological entities associated with very different invasive abilities. METHODS: Using real-time reverse transcription polymerase chain reaction and immunohistochemistry, we analysed the TN-C expression in normal brain tissue as well as in a series of 54 pilocytic and 53 grade II astrocytomas. CONCLUSIONS: Our data on normal brain showed that while TN-C is largely expressed in supratentorial white matter, it was largely absent in infratentorial white matter. Paralleling these observations, we showed that TN-C expression in low-grade astrocytomas similarly varies according to tumour site. Cox regression analysis evidenced that TN-C provided an independent prognostic value which is enhanced in the case of grade II astrocytomas for which positive TN-C expression is associated with a higher risk of recurrence. We also analysed TN-C expression specifically in vascular areas of low-grade astrocytomas without demonstrating any prognostic value for this additional feature. RESULTS: Similarly to normal brain, low-grade astrocytomas exhibit variations in TN-C expression with site, and this expression is associated with an independent prognostic value in terms of recurrence.

Tailgut cyst associated with a carcinoid tumor: case report and review of the literature.

We report the case of a 49-year-old woman who presented a tailgut cyst lined by a variety of epithelium including squamous, columnar and transitional. Fortuitously a microscopic carcinoid tumor expressing immunohistochemically neuroendocrine markers was identified in the cystic wall. Tailgut cysts are congenital abnormalities located in the presacrococcygeal area occurring usually in adult patients. Clinical diagnosis is difficult because they are often asymptomatic. Patients may present symptoms resulting from local mass effects or complications. The differential diagnoses include rectal duplication cysts, cystic sacrococcygeal teratomas, epidermal cysts, epidermoid cysts, anal duct or gland cysts. Magnetic resonance imaging has recently become the modality of choice to image the cyst. Malignant transformation is rare; 23 cases including 10 carcinoid tumors have been reported in the literature. To our knowledge, this is the eleventh case of carcinoid tumor arising in a tailgut cyst.

The differential expression of Galectin-1 and Galectin-3 in normal lymphoid tissue and non-Hodgkin's and Hodgkin's lymphomas.

The WHO classification of lymphomas was established on the basis of clinical, morphological, immunohistochemical and genetic criteria. However, each entity displays its own spectrum of clinical aggressiveness. Treatment success varies widely and is not predictable. Since galectins are involved in oncogenesis and the physiology of immune cells, we investigated whether galectin-1 and galectin-3 immunohistochemical expression could differ in 25 normal lymphoid tissues, 42 non-Hodgkins and 14 Hodgkins lymphomas. Immunohistochemical galectin expression was submitted to semi-quantitative and quantitative (computer-assisted microscopy) evaluations. This study is completed by an analysis (by means of quantitative RT-PCR) of galectin-3 mRNA expression in 3 normal lymph nodes, 3 follicular lymphomas (FLs) and 3 diffuse large B-cell lymphomas (DLBCLs). The data show that in normal lymphoid tissue, lymphocytes do not express galectin-1 and rarely express galectin-3. In contrast, galectin-3 was expressed in 8 of the 16 DLBCL cases and in 1 of the 8 FL cases. Furthermore, galectin-3 mRNA was expressed 3 times more in the DLBCLs than in the FLs. While the blood vessel walls of the lymphomas expressed galectin-1, the vessel walls of normal lymphoid tissues did not. This expression of galectin-1 in blood vessel walls was correlated with vascular density. The present study thus shows that DLBCL can be distinguished from normal lymphoid tissue and other lymphomas on the basis of galectin-3 expression.

Ozone quenching properties of isoprene and its antioxidant role in leaves.

Isoprene is formed in and emitted by plants and the reason for this apparent carbon waste is still unclear. It has been proposed that isoprene stabilizes cell and particularly chloroplast thylakoid membranes. We tested if membrane stabilization or isoprene reactivity with ozone induces protection against acute ozone exposures. The reduction of visible, physiological, anatomical, and ultrastructural (chloroplast) damage shows that clones of plants sensitive to ozone and unable to emit isoprene become resistant to acute and short exposure to ozone if they are fumigated with exogenous isoprene, and that isoprene-emitting plants that are sensitive to ozone do not suffer damage when exposed to ozone. Isoprene-induced ozone resistance is associated with the maintenance of photochemical efficiency and with a low energy dissipation, as indicated by fluorescence quenching. This suggests that isoprene effectively stabilizes thylakoid membranes. However, when isoprene reacts with ozone within the leaves or in a humid atmosphere, it quenches the ozone concentration to levels that are less or non-toxic for plants. Thus, protection from ozone in plants fumigated with isoprene may be due to a direct ozone quenching rather than to an induced resistance at membrane level. Irrespective of the mechanism, isoprene is one of the most effective antioxidants in plants.

Are infants with orofacial clefts at risk for insecure mother-child attachments?

OBJECTIVE: Several risk factors in the early lives of children with clefts are believed to interfere with their development of secure attachments to parents; however, this possibility has rarely been studied empirically. This study compared 12- and 24-month attachment classifications of infants with cleft palate (CP), infants with cleft lip and palate (CLP), and a comparison group of unimpaired infants (COMP). METHOD: Twenty-two CP infants, 24 CLP infants, and 61 matched COMP infants were assessed at 12 and 24 months of age in an urban children's hospital. At both visits, mothers and infants participated in the Strange Situation, which was videotaped and subsequently coded for patterns of attachment behavior. RESULTS: CP infants displayed a lower rate of 12-month attachment security than infants in the CLP or COMP groups. By 24 months, no diagnostic group differences in attachment classification were found. Stable 12- to 24-month attachment classifications were less likely in the CP group (36.3%) than in the COMP (62.3%) group. CP infants who were insecure at 12 months were more likely to become secure by 24 months than were CLP or COMP group infants. CONCLUSIONS: In contrast to previous theory and clinical speculation, the facial appearance of infants with CLP does not appear to affect the early mother-infant relationship adversely. The infancy period is marked by attachment instability for infants with CP, who demonstrated lower-than-expected rates of security at 12 months. However, these problems resolved in nearly all cases by 24 months of age. Most infants with clefts emerged from the first 2 years of life with secure maternal attachments.

Cognitive and psychomotor development of infants with orofacial clefts.

OBJECTIVE: To compare at ages 3, 12, and 24 months the cognitive and psychomotor development of 29 infants with cleft lip and palate (CLP), 28 infants with cleft palate only (CPO), and a demographically matched comparison (COMP) group of 69 infants; to examine predictors of cognitive status at age 24 months in the cleft group. METHODS: Infants were administered the Bayley Scales of Infant Development (BSID), mother-infant interactions were observed, and medical records were reviewed. RESULTS: CLP and CPO groups scored lower than the COMP group on the BSID, but did not differ from one another. Cleft group infants scored lower than COMP group infants on BSID items assessing nonverbal and expressive language skills. Quality of maternal interaction predicted the 2-year Mental Development Index (MDI) scores of infants with clefts. CONCLUSIONS: Infants with clefts show relative deficits in cognitive and psychomotor development. Cognitive deficits are apparent in nonverbal as well as verbal areas of performance.

Carta aberta aos pais acerca da escolarizacao das criancas com problemas de desenvolvimento

Os autores examinam a historia das escolas especiais ate nossos dias. Trinta anos atraz, essas escolas tinham uma orientacao empirista e repetitiva, o que era um incentivo as perseveracoes e as estereotipias. A partir dai, iniciaram-se esforcos em direcao a escola inclusiva e em direcao a transformacao das escolas especiais. No entanto, as escolas especiais passaram tambem a desdobrar praticas sociais discriminatorias. De outro lado, nas escolas comuns caiu uma avalanche de criancas que apresentam condicoes psiquicas que os docentes nao foram preparados para sustentar. Os autores examinam esses dois desdobramentos e concluem que, seja qual for o caminho a ser adotado, nao se deve esquecer que toda questao escolar, alem de dar lugar a uma crianca, implica trabalhar com um sujeito.

Psychosocial adjustment in twin pairs with and without hemifacial microsomia.

OBJECTIVE: To compare the psychosocial adjustment of children with and without hemifacial microsomia (HFM). DESIGN: This cross-sectional pilot study investigated psychosocial adjustment of twin pairs in which one twin was affected with HFM and the other was unimpaired. Data were analyzed using paired t tests. SETTING: The dental medicine clinic of a large urban children's hospital, serving a multistate area. PARTICIPANTS: Participants were six twin pairs aged 9 to 15 years and their parents. Data were also collected from classroom teachers. MAIN OUTCOME MEASURES: Outcome measures included: the Child Behavior Checklist (CBCL), the Teacher Report Form (TRF), the Coopersmith Self-Esteem Inventory (SEI), and a structured self-concept interview (the Self-Interview). RESULTS: Children with HFM had significantly higher CBCL and TRF total behavior problem scores and lower SEI general self-esteem scores than their unimpaired twins. No differences were found in CBCL competence scores. Interview data revealed concerns among the HFM group related to appearance, negative social responses, and fear of hospital procedures. Children also reported positive aspects of coping with HFM. CONCLUSIONS: The results of this study suggest that, similar to other craniofacial conditions, HFM is associated with an elevated risk for childhood psychosocial difficulties. Replication of specific findings with a larger sample is needed. Multicenter, collaborative studies are a crucial next step for this field.

Training resident surgeons in combat: an experience during the Persian Gulf War.

The Persian Gulf War necessitated the activation of many Army Reserve and National Guard physicians, including a number in residency training. No prototype existed for the continued training of resident surgeons in a combat setting. The 159th Mobile Army Surgical Hospital (MASH) deployed in support of the Allied invasion of Iraq. A structured training program for two general surgery residents attached to the 159th MASH was developed and implemented. This program combined supervised operating room experience, perioperative management, morbidity and mortality conferences, and orthopedic grand rounds, all with careful professional documentation. A planned reading program could not be realized, due to the physical setting of wartime. Residents and attending staff interacted positively and the residents were able to continue their formal training as an integral part of the hospital. The model developed by the 159th MASH is a practical method of continuing structured resident training in a combat setting.

Excisäo tangencial em queimadura profunda de mäos: apresentaçäo de caso / Tangential excision in deep burns of the hand: a case report

É descrito um caso de queimadura profunda de dorso de mäos, tratado cirurgicamente através de excisäo tangencial, e apresentada uma análise crítica da técnica em questäo, à luz dos resultados cirúrgicos obtidos, dos dados da literatura, e da comprovaçäo anatomopatológico. Conclui-se pela total eficácia da técnica, apesar de sua imprecisäo no que se refere à profundidade do corte na pele queimada a ser excisada

Observaçöes clínicas e anátomo-patológicas na excisäo tangencial em queimadura de mäos / Clinical and anatomo-pathological observations in tangential excision in burn of hands

Relata-se um caso de queimadura profunda de dorso de mäos, tratado cirurgicamente através da excisäo tangencial e apresenta uma análise crítica da técnica em questäo, à luz dos resultados cirúrgicos obtidos, dos dados da literatura e da comprovaçäo anátomo-patológica. Conclui que pela total eficácia da técnica, apesar de sua imprecisäo no que se refere à profundidade do corte na pele queimada a ser excisada

Upwelling of hydrothermal solutions through ridge flank sediments shown by pore water profiles.

High calcium ion and low magnesium ion concentrations in sediment pore waters in cores from the Galápagos Mounds Hydrothermal Field on the flank of the Galápagos Spreading Center are believed to be due to a calcium-magnesium exchange reaction between circulating seawater and basement basalt. The nonlinearity of the calcium ion and magnesium ion gradients indicates that these discharging hydrothermal solutions on the ridge flank are upwelling at the rate of about 1 centimeter per year through the pelagic sediments of the Mounds Field and at about 20 centimeters per year through the hydrothermal mounds themselves.

Silastic sponge implants in retinal detachment surgery.

Two hundred consecutive primary rhegmatogenous retinal detachments repaired with Silastic sponge implants were evaluated. A primary reattachment rate of 94% and an overall reattachment rate of 95% were achieved. Two of the successful repairs became detached after six months giving a redetachment rate of approximately 1%. Eight of the 12 failures were due to massive periretinal proliferation (MPP) (overall incidence of MPP = 4%). To date, only one Silastic sponge has had to be removed because of late infection. No cases of extrusion or erosion occurred. We recommend this procedure as safe and effective.