Castleman disease: surgical cure in pediatric patients

Castleman disease is a rare disorder characterized by lymphoid hyperplasia which rarely manifests in children. We present 2 cases which highlight both histologic variants of this disease, and provide suggestions regarding workup and treatment with the goal of making practitioners aware of Castleman disease in the differential diagnosis of a child presenting with vague symptoms.     

aVR sign as a risk factor for life-threatening arrhythmic events in patients with Brugada syndrome

BACKGROUND: Risk stratification in Brugada syndrome (BS) is controversial, especially in asymptomatic individuals. OBJECTIVE: The aim of this study was to evaluate the significance of lead aVR in patients with BS. METHODS: Twenty-four patients with the electrocardiogram pattern of BS (24 male, mean age 32.1 +/- 13.6 years) and 24 healthy age- and gender-matched controls were studied. RESULTS: Thirteen patients were symptomatic. The R-wave amplitude or R/q ratio in lead aVR was significantly greater in patients experiencing a recurrence compared with those who did not. The aVR sign was defined as R wave >/= 0.3 mV or R/q >/= 0.75 in lead aVR. Most of the recurrences (78%) were in patients with present aVR sign; 84% of BS patients with present aVR sign had events during follow-up. In contrast, only 27% of BS patients with absent aVR sign had events during follow-up. CONCLUSION: Our study shows significant correlation between a prominent R wave in lead aVR (aVR sign) and risk for development of arrhythmic events in BS. In the presence of BS, prominent R wave in lead aVR may reflect more right ventricular conduction delay and subsequently more electrical heterogeneity, which in turn is responsible for a higher risk of arrhythmia.     

A methodological approach to the classification of dermoscopy images.

In this paper a methodological approach to the classification of pigmented skin lesions in dermoscopy images is presented. First, automatic border detection is performed to separate the lesion from the background skin. Shape features are then extracted from this border. For the extraction of color and texture related features, the image is divided into various clinically significant regions using the Euclidean distance transform. This feature data is fed into an optimization framework, which ranks the features using various feature selection algorithms and determines the optimal feature subset size according to the area under the ROC curve measure obtained from support vector machine classification. The issue of class imbalance is addressed using various sampling strategies, and the classifier generalization error is estimated using Monte Carlo cross validation. Experiments on a set of 564 images yielded a specificity of 92.34% and a sensitivity of 93.33%.     

Primary pulmonary mucosa-associated lymphoid tissue lymphoma with associated fungal ball in a patient with human immunodeficiency virus infection

We describe a case of primary mucosa-associated lymphoid tissue lymphoma of the lung in a 44-year-old man with human immunodeficiency virus. Low-grade pulmonary lymphomas in human immunodeficiency virus-positive patients are rare and are described most commonly in pediatric patients. The gross, histologic, and molecular features of this unusual case are described.     

Actinomyces and actinobacillus actinomycetemcomitans-Actinomyces-associated lymphadenopathy mimicking lymphoma

We present 2 unusual cases of long-standing, extensive reactive lymphadenopathy secondary to Actinomyces infection, 1 of which was also accompanied by Actinobacillus actinomycetemcomitans-Actinomyces complex infection. To our knowledge, histologic features of lymph node involvement by these organisms have not been previously reported in the literature. One patient had extensive cervical, posterior mediastinal, and abdominal lymphadenopathy. The second patient presented with a submandibular mass and cervical lymphadenopathy. Clinical features strongly suggested lymphoma. The histologic examination of the lymph nodes from both patients revealed reactive follicular hyperplasia, marked interfollicular and capsular fibrosis, and multiple interfollicular microabscesses. Characteristic Actinomyces colonies were identified at the center of the microabscesses in deep sections. Cultures were obtained from the lymph nodes of 1 patient, and were positive for A actinomycetemcomitans. Both patients had poor dental hygiene. Lymphadenopathy subsided with antibiotic therapy and appropriate dental care.     

Elevation of oxidative stress in the aorta of genetically hypertensive mice

Hypertension is an age-dependent disorder. Oxidative stress has been suggested to play a role in aging and age-dependent disorders. The objective of this study is to examine the oxidant and antioxidant status in the aorta of a mouse model with high blood pressure (BPH). Our results showed that the level of malondialdehyde (MDA) in the aorta of BPH mice was approximately 2.6-fold higher than that of the normal blood pressure (BPN) mice, suggesting an increased in vivo oxidative stress in the arterial wall of BPH mice. In addition, the release of hydrogen peroxide (H2O2) from the aorta of BPH mice was significantly faster than that of BPN mice. To determine if the increased H2O2 release is related to a down-regulation of antioxidant enzymes in the arterial wall, we measured the activities of the major antioxidant enzymes in mouse aortas. We observed that the activities of Cu/Zn-superoxide dismutase (SOD) and glutathione peroxidase-1 in BPH mice were similar to BPN mice. On the other hand, the catalase activity in the aorta of BPH mice was significantly reduced while the activities of Mn-SOD and extracellular (EC)-SOD in the aorta of BPH mice were significantly elevated as compared with BPN mice. These results suggest that increase in SOD activity and decrease in catalase activity might be responsible for the increased release of H2O2 in the arterial wall of BPH mice.     

Integrin alpha2beta1 affects mechano-transduction in slowly and rapidly adapting cutaneous mechanoreceptors in rat hairy skin

The role of a transmembrane protein, integrin alpha2beta1, to modulate the neural responses of cutaneous mechanoreceptors to mechanical indentation was examined using an isolated skin-nerve preparation in a rat model. Skin and its intact innervation were harvested from the medial thigh of the hindlimb and placed in a dish containing synthetic interstitial fluid. Using a standard teased nerve preparation, the neural responses of single slowly or rapidly adapting mechanoreceptors (SA or RA, respectively) were identified and the afferents categorized according to standard protocols (i.e. response to constant stimuli). The most sensitive spot of a mechanoreceptor's receptive field was identified and then stimulated using controlled compressive stress (constant or dynamic loads between threshold and saturation load for SAs and RAs, respectively). Loads were applied before, during, and after passive diffusion into the skin of a function-blocking anti-integrin alpha2 monoclonal antibody (FBmAb) or one of two types of control antibodies (immunoglobulin G or a FBmAb conjugated with a secondary antibody). The sensitivities of both SA and RA mechanoreceptors were profoundly reduced in the presence of the FBmAb, while not changing the waveforms of their action potentials or their adaptation properties. Both control antibodies had no significant effect on mechanoreceptors' sensitivities. Following removal of the FBmAb, the effects in some neurons were partially reversible. Taken together, the data from this study support the hypothesis that integrin alpha2beta1 plays a significant role in modulating mechanoreceptive response to compressive indentation.     

Anti-inflammatory actions of interleukin-13: suppression of tumor necrosis factor-alpha and antigen-induced leukocyte accumulation in the guinea pig lung

The Th2 cytokine interleukin (IL)-13 is believed to play an important role in the development of allergy, although it has also been ascribed anti-inflammatory roles in several experimental models. In this study, we have examined the effects of human recombinant IL-13 on eosinophilic lung inflammation in the guinea pig. IL-13 (1 to 100 ng, given by intratracheal instillation) did not elicit airway eosinophil recruitment. A pronounced accumulation of eosinophils, as well as monocyte/macrophages, was elicited by intratracheal instillation of guinea pig tumor necrosis factor alpha (gpTNF-alpha). Intratracheal administration of IL-13 (1 to 100 ng) given immediately prior to exposure to gpTNF-alpha resulted in a dose-related suppression of eosinophil and monocyte/macrophage accumulation in the airways, as assessed by bronchoalveolar lavage (BAL) and eosinophil peroxidase activity in whole-lung homogenates. IL-13 treatment also reduced BAL fluid (BALF) leukocyte accumulation induced by subsequent aerosol antigen challenge of sensitized guinea pigs. Antigen challenge also resulted in elevated levels of immunoreactive eotaxin and eosinophil-stimulating activity in BALF, although only the latter was reduced significantly by IL-13 instillation prior to challenge. In contrast to the suppressive effects of IL-13, instillation of human recombinant IL-4 (100 ng) alone elicited an increase in BALF monocyte/macrophage numbers, and IL-4 was unable to inhibit gpTNF-alpha-induced leukocyte accumulation. Hence, IL-13 (but not human IL-4) exhibits an anti-inflammatory action in the airways of gpTNF-alpha- or antigen-challenged guinea pigs, by mechanisms that may involve the decreased generation of eosinophil-stimulating activity in the airways.