Acute myocardial infarction and chronic leukaemia with significant thrombocytopenia

We present a case of a 62 year-old male with acute myocardial infarction, chronic leukaemia and significant thrombocytopenia (50 g/L). The patient underwent primary coronary intervention followed by full antiplatelet and antithrombotic treatment without bleeding complications.     

Risk factors of migraine-related brain white matter hyperintensities: an investigation of 186 patients

Brain white matter hyperintensities are more prevalent in migraine patients than in the general population, but the pathogenesis and the risk factors of these hyperintensities are not fully elucidated. The authors analyzed the routine clinical data of 186 migraine patients who were referred to the Outpatient Headache Department of the Department of Neurology, Medical School, University of Pécs, Hungary between 2007 and 2009: 58 patients with white matter hyperintensities and 128 patients without white matter hyperintensities on 3 T MRI. Significant associations between the presence of white matter hyperintensities and longer disease duration (14.4 vs. 19.9 years, p = 0.004), higher headache frequency (4.1 vs. 5.5 attacks/month, p = 0.017), hyperhomocysteinemia (incidence of hyperintensity is 9/9 = 100%, p = 0.009) and thyroid gland dysfunction (incidence of hyperintensity is 8/14 = 57.1%, p = 0.038) were found. These data support the theory that both the disease duration and the attack frequency have a key role in the formation of migraine-related brain white matter hyperintensities, but the effects of comorbid diseases may also contribute to the development of the hyperintensities.     

Ten kilodalton heat shock protein (HSP10) is overexpressed during carcinogenesis of large bowel and uterine exocervix

In the present study, we evaluated the presence and the level of expression of HSP10 in two carcinogenetic models: the 'adenoma-carcinoma sequence' of large bowel and the 'dysplasia-carcinoma sequence' of uterine exocervix. We found HSP10 was overexpressed during the carcinogenesis of both organs. In particular, HSP10 was overexpressed early in large bowel carcinogenesis, while the expression of this protein in exocervical carcinogenesis gradually increased from normal through dysplastic to neoplastic tissues. The quantitative analysis of immunohistochemistry and the Western blotting confirmed these results. Our previous observations showed overexpression of HSP60 in the same carcinogenetic models. This report correlates the overexpression of HSP10 with that of HSP60 during carcinogenesis in vivo. These results could stimulate further studies on the pathogenetic role of these proteins during the carcinogenesis as well as their use as diagnostic and prognostic tools in oncology.     

Genetic prevention of lymphoma in p53 knockout mice allows the early development of p53-related sarcomas

Homozygous knockout of p53 in mice leads to early mortality from lymphoma, with almost complete penetrance, thus hampering studies of other tumor histotypes related to p53 alterations. To avoid lymphoma development, we crossed p53 knockout mice (BALB-p53 mice) with alymphocytic BALB/c Rag2^−/−;Il2rg^−/− (RGKO) mice. We compared the tumor spectrum of homozygous (BALB-p53^−/−) and heterozygous (BALB-p53^+/−) mice with alymphocytic mice (RGKO-p53^−/− and RGKO-p53^+/−). Lymphoma incidence in BALB-p53^−/− mice exceeded 80%, whereas in RGKO-p53^−/− it was strongly reduced. The prevalent tumor of RGKO-p53^−/− mice was hemangiosarcoma (incidence over 65% in both sexes, mean latency 18 weeks), other tumors included soft tissue sarcomas (incidence ~10%), lung and mammary carcinomas. Tumor spectrum changes occurred also in p53 heterozygotes, in which lymphomas are relatively rare (~20%). RGKO-p53^+/− had an increased incidence of hemangiosarcomas, reaching ~30%, and females had an increased incidence of osteosarcomas, reaching ~20%. Osteosarcomas shared with the corresponding human tumors the involvement of limbs and a high metastatic ability, mainly to the lungs. Specific alterations in the expression of p53-related genes (p16Ink4a, p19Arf, p15Ink4b, p21Cip1) were observed. Genetic prevention of lymphoma in p53 knockout mice led to new models of sarcoma development, available for studies on hemangiosarcoma and osteosarcoma onset and metastatization.     

The effect of dimension and vocabulary age on rapid picture naming in children

This investigation involved measures of the reaction times of normally developing children who were asked to name a series of centrally presented picture stimuli of varying vocabulary age and dimension. Results of the ANOVA on reaction times indicated a significant main effect of vocabulary level and an interaction of Dimension x Vocabulary level for the normally developing children. Post-hoc tests showed significant differences between two- and three-dimensional pictures for higher-level vocabulary items, but not for lower-level vocabulary items. This finding indicates that central operations involved in picture naming are influenced differentially by the physical characteristics of the stimulus items. The finding that two-dimensional higher-level vocabulary items were associated with significantly longer reaction times than the three-dimensional higher-level vocabulary suggests that dimensionality may be a critical feature for rapid lexical access for higher-level picture vocabulary. Clinically, the employment of three-dimensional forms may facilitate access to stored visual object memory for advanced levels of picture vocabulary. Learning outcomes: As a result of this activity, participants will be able to (1) identify the various visual and verbal processes involved in the naming of pictures; and (2) understand the influence of physical characteristics of pictures on reaction time in rapid naming tasks.     

Good interobserver and intraobserver agreement in the evaluation of the new ILAE classification of focal cortical dysplasias

Purpose: An International League Against Epilepsy (ILAE) consensus classification system for focal cortical dysplasias (FCDs) has been published in 2011 specifying clinicopathologic FCD variants. The aim of the present work was to microscopically assess interobserver agreement and intraobserver reproducibility for FCD categories among an international group of neuropathologists with different levels of experience and access to epilepsy surgery tissue. Methods: Surgical FCD specimens covering a broad histopathology spectrum were retrieved from 22 patients with epilepsy. Three surgical nonepilepsy specimens served as controls. A total of 188 slides with routine or immunohistochemical stainings were digitalized with a slide scanner to allow Internet‐based microscopy review. Nine experienced neuropathologists were invited to review these cases twice at a time gap of 3 months and different orders of case presentation. The 2011 ILAE FCD consensus classification served as instruction. Kappa analysis was calculated to estimate interobserver and intraobserver agreement levels. In a third evaluation round, 21 additional neuropathologists with different experience and access to epilepsy surgery reviewed the same case series. Key Findings: Interobserver agreement was good (κ = 0.6360), with 84% consensus of diagnoses during the first evaluation (21 of 25 cases). Kappa values increased to 0.6532 after reevaluation, and consensus was obtained in 24 (96%) of 25 cases. Overall intraobserver reproducibility was also good (κ = 0.7824, ranging from 0.4991 to 1.000). Fewest changes in the classification were made in the FCD type II group (2.2% of 225 original diagnoses), whereas the majority of changes occurred in FCD type III (13.7% of 225 original diagnoses). In the third evaluation round, interobserver agreement was reflected by the level of experience of each neuropathologist, with κ values ranging from moderate (0.5056; high level of experience >40 cases/year) to low (0.3265; low level of experience <10 cases/year). Significance: Our study achieved a good and reliable interobserver agreement among the group of expert neuropathologists originally involved in the ILAE FCD consensus classification system. Intraobserver reproducibility in this group was even more robust. These results showed considerable improvement compared to a previous study evaluating the 2004 Palmini FCD classification. Agreement levels were lower in our second group of neuropathologists and were related to their level of access and experience with epilepsy surgery specimens. These results suggested that the more precise ILAE definition of FCD histopathology patterns improves operational procedures in the diagnosis of FCDs. On the other hand, microscopic assessment of FCD is a challenge and requires sustained experience and teaching. The virtual slide review system allowed testing of this hypothesis and reached a widespread group of participating colleagues from different centers all over the world. We propose to further use this tool as a teaching device and also to address other epilepsy‐associated entities still difficult to classify such as hippocampal sclerosis, long‐term epilepsy‐associated tumors, or mild malformations of cortical development (mMCDs), which were not yet covered by current ILAE classification systems.     

Direct and indirect effects of childhood adversity on adult depression

Exposure to adverse events in childhood is a predictor of subsequent exposure to adverse events in adulthood, and both are predictors of depression in adults. The degree to which adult depression has a direct effect of childhood adversity versus an indirect effect mediated by adult adversity has not previously been reported. We report data collected from 210 adult participants regarding childhood and adult adversity and current symptoms of depression. Mediation of the relationship between childhood adversity and adult depression by adult adversity was statistically assessed to evaluate the relative direct and indirect effects of childhood adversity on current depression levels in adults. Both the direct effect of childhood adversity on adult depression and the indirect effect, mediated by adulthood events, were significant. Therefore, partial mediation of the relationship between childhood adversity and adult symptoms of depression by adult adverse events was found in the sample. Implications for treatment are presented.     

Perifollicular fibroma in Birt-Hogg-Dubé syndrome: an association revisited

Background: Mutation in the folliculin gene in Birt–Hogg–Dubé (BHD) syndrome leads to a spectrum of benign tumors of the hair follicle, classically including both fibrofolliculoma and trichodiscoma. In addition, lesions clinically indistinguishable from fibrofolliculoma/ trichodiscoma may show histopathologic findings of perifollicular fibroma or angiofibroma. Although some consider perifollicular fibroma to be a variant of angiofibroma, the specific histopathologic findings of perifollicular fibroma are uncommon. Methods: This is a case series. Results: In 4 patients with multiple facial lesions, recognizing perifollicular fibroma would have been helpful in leading to the diagnosis of BHD syndrome. Conclusion: Perifollicular fibroma is on a spectrum with fibrofolliculoma and trichodiscoma; in a patient with multiple lesions, the diagnosis of perifollicular fibroma is suggestive of BHD syndrome.