Dysmorphology and the orbital region: a practical clinical approach

Dysmorphology is the field of medicine focusing on congenital developmental abnormalities due to exogenous teratogens, chromosomal anomalies, or to a defect in a single gene. Numerous syndromes have been reported and a growing number of genes or chromosomal anomalies are identified. The clinical observation of the face remains an essential part of the clinical evaluation of the patients. The orbital region, as other regions of the face, should be systematically evaluated. Orbital malformations can be isolated or part of a syndrome. In the diagnostic process, the orbital anomaly can be classified as a major feature (essential for the diagnosis), a moderate feature (important but not essential for the diagnosis), or a minor feature (contributing weakly to the diagnosis). The diagnoses of the main orbital anomalies in dysmorphology are reviewed and illustrated with relevant examples of syndromes that are presented as well as the usual landmarks used in clinical practice. Abnormal position of the eyes in syndromes such as hypertelorism, hypotelorism, primary or secondary telecanthus, asymmetry, and proptosis are discussed. Eyelid anomalies, such as cryptophthalmos, ablepharon, blepharophimosis, euryblepharon, or anomalies at the level of the eyelashes and eyebrows are described.     

Prognostic stratification of Dukes B colon cancer by a neoglycoprotein

Disease progression of tumors is accompanied by structural changes of the glycan chains of cellular glycoconjugates. Within the concept of the sugar code the presence of complementary receptors such as lectins translates changes in ligand presentation into biological effects, for example in growth regulation and adhesion. By introducing neoglycoproteins to histopathological colon cancer analysis the questions are addressed as to whether specific binding sites for main N- and O-glycan components are present and whether they harbor potential for prognostic predictions. Synthetic conjugation of fucose, lactose, and mannose derivatives to a carrier protein yielded neoglycoproteins for glycohistochemical analysis. The tumor panel included routinely fixed tissue sections from 67 cancer cases (15 Dukes A, 20 Dukes B, 15 Dukes C, and 17 metastatic tumors) and 6 hepatic metastases as well as 20 normal biopsy specimens as control. Quantitative image analysis determined the labeling index and the mean optical density in each case, separating tumor and peritumoral connective tissue. Specific carbohydrate-dependent binding with inter-individual heterogeneity was observed. The distinct staining profiles were not associated with disease stage or metastasis formation. Strong expression of lactose-binding sites in the peritumoral connective tissue especially in terms of the labeling index was significantly correlated with reduced survival in Dukes B patients (p=0.02). A similar tendency was observed in the Dukes C group. In conclusion, the application of the synthetic markers aimed at lectin detection defines lactose binding as new prognostic marker. It has potential relevance for improving the benefit from adjuvant therapy in Dukes B colorectal cancer patients. Technically, chemical ligand immobilization to an inert carrier can find useful application beyond glycosciences in the quest to extend the panel of tumor markers.     

Psychiatric disorders in oncology: recent therapeutic advances and new conceptual frameworks

PURPOSE OF REVIEW: Major advances achieved in anticancer treatment have resulted in significant increases in cancer patients' survival periods. At the same time, growing awareness of the psychologic impact of the diagnosis and treatment of cancer on quality of life has created the need for deeper insights into the adjustment process, its disorders, and effective strategies for the treatment of psychiatric morbidity. The wider availability of brain imaging techniques and other neurobiologic tools is creating major opportunities for a scientific understanding of psychodynamic processes. RECENT FINDINGS: Several elements indicate a stress-system activation in response to cancer. The existence of traumatic stress-like syndromes has received increasing support. Structural brain imagery has revealed volumetric alterations of the amygdala, a major participant in emotional and fear responses. Hypotheses about functional modifications at the hypothalamic-pituitary-adrenal axis level may have significant implications for the identification, treatment, and even prevention of psychopathology. Finally, longitudinal studies assessing psychologic adjustment confirm the need for psychosocial and pharmacologic interventions. SUMMARY: Our understanding of the cancer experience at the emotional and cognitive levels remains insufficient, leading to weakly positive results of psychosocial intervention models. The use of antidepressant medication has received substantial empiric and scientific support, but a risk of antidepressant-induced carcinogenesis has not been excluded, which should keep clinicians from overprescribing attitudes. Finally, improving the quality of doctor-patient communication and the psychologic impact of carrying a genetic marker of cancer risk should be the focus of further attention.     

Bayesian applications of belief networks and multilayer perceptrons for ovarian tumor classification with rejection

Incorporating prior knowledge into black-box classifiers is still much of an open problem. We propose a hybrid Bayesian methodology that consists in encoding prior knowledge in the form of a (Bayesian) belief network and then using this knowledge to estimate an informative prior for a black-box model (e.g. a multilayer perceptron). Two technical approaches are proposed for the transformation of the belief network into an informative prior. The first one consists in generating samples according to the most probable parameterization of the Bayesian belief network and using them as virtual data together with the real data in the Bayesian learning of a multilayer perceptron. The second approach consists in transforming probability distributions over belief network parameters into distributions over multilayer perceptron parameters. The essential attribute of the hybrid methodology is that it combines prior knowledge and statistical data efficiently when prior knowledge is available and the sample is of small or medium size. Additionally, we describe how the Bayesian approach can provide uncertainty information about the predictions (e.g. for classification with rejection). We demonstrate these techniques on the medical task of predicting the malignancy of ovarian masses and summarize the practical advantages of the Bayesian approach. We compare the learning curves for the hybrid methodology with those of several belief networks and multilayer perceptrons. Furthermore, we report the performance of Bayesian belief networks when they are allowed to exclude hard cases based on various measures of prediction uncertainty.     

Flow-cytometric cellular allergen stimulation test in latex allergy

BACKGROUND: The use of flow-cytometric basophil activation to different allergens has been recommended in recent years. In this study, we analyzed the diagnostic reliability of the flow-cytometric allergen stimulation test (FAST) after latex-specific stimulation in vitro. The diagnostic reliability of the technique was assessed as well as its correlation with other in vitro diagnostic parameters. METHODS: 43 patients allergic to latex with a positive history and skin test participated in the study. Thirty subjects (20 of them exposed to latex) with a negative history, skin tests and serum-specific IgE determination to latex were used as controls. In FAST the percentage of basophils that express CD63 as an activation marker after in vitro stimulation with allergen (latex) is determined by flow cytometry, following double labelling with the monoclonal antibodies anti-CD63-PE and anti-IgE FITC. RESULTS: Intraclass correlation coefficient in FAST with latex was 0.995 (p < 0.0001), which demonstrates the excellent reproducibility of this technique. Taking a cutoff point of 10% by means of ROC curves, FAST yields a sensitivity of 93% and a specificity of 100%. The FAST positive predictive value in latex allergy was 100% and the negative predictive value was 99.9%. We found a positive and significant correlation between FAST and specific IgE (CAP) with the histamine release test and specific sulphidoleukotriene production [cellular allergen stimulation test (CAST); p < 0.05]. CONCLUSIONS: FAST is a highly reliable technique (93% sensitivity and 100% specificity) in the in vitro diagnosis of IgE-mediated latex allergy.     

Two cases of neurocysticercosis mimicking brain tumor

Neurocysticercosis is an infectious disorder of the central nervous system caused by Taenia solium larvae. We report two misleading cases, mimicking high grade glioma on radiology. Two patients, aged 14 and 29 respectively, developed seizure, associated with left facial paralysis in the second. For each case, radiological data revealed a solitary lesion highly suggestive of high grade glioma. Microscopically, within an important inflammatory process, a characteristic cystic formation allowed a definite diagnosis of cysticercosis. Then, for both patients, a history of migration from endemic area was demonstrated later. These cases highlight the necessary pathological examination when neurocysticercosis mimics a brain tumor.