Metabolic Characterization of Nondiabetic Severely Obese Patients Undergoing Roux-en-Y Gastric Bypass: Preoperative Classification Predicts the Effects of Gastric Bypass on Insulin–Glucose Homeostasis

Introduction Obese individuals may have normal insulin–glucose homeostasis, insulin resistance, or diabetes mellitus. Whereas gastric bypass cures insulin resistance and diabetes mellitus, its effects on normal physiology have not been described. We studied insulin resistance and β-cell function for patients undergoing gastric bypass. Methods One hundred thirty-eight patients undergoing gastric bypass had fasting insulin and glucose levels drawn on days 0, 12, 40, 180, and 365. Thirty-one (22%) patients with diabetes mellitus were excluded from this analysis. Homeostatic model of assessment was used to estimate insulin resistance, insulin sensitivity, and β-cell function. Based on this model, patients were categorized as high insulin resistance if their insulin resistance was >2.3. Results Body mass index did not correlate with insulin resistance. Forty-seven (34%) patients were categorized as high insulin resistance. Correction of insulin resistance for this group occurred by 12 days postoperatively. Sixty (43%) patients were categorized as low insulin resistance. They demonstrated an increase of β-cell function by 12 days postoperatively, which returned to baseline by 6 months. At 1 year postoperatively, the low insulin resistance group had significantly higher β-cell function per degree of insulin sensitivity. Conclusions Adipose mass alone cannot explain insulin resistance. Severely obese individuals can be categorized by degree of insulin resistance, and the effect of gastric bypass depends upon this preoperative physiology.     

Pseudo-angiomatous hyperplasia of mammary stroma: a case with gigantomastia

Pseudo-angiomatous hyperplasia of mammary stroma (PASH) is a histopathological entity which is a microscopic fortuitous finding in mammary biopsies performed for different reasons. It may be symptomatic and appears then as a palpable lump. The term pseudo-angiomatous emphasizes the characteristic aspect of the stroma simulating a vascular tumor. We report a case of PASH in a 71 year-old woman who presented a recurring breast mass with rapid swelling of the mammary gland (70 x 60 x 20 cm) treated by mastectomy. PASH must be distinguished from a well-differentiated angiosarcoma. It is ruled out by immunohistochemistry.     

ALK Expression Defines a Distinct Group of T/Null Lymphomas (“ALK Lymphomas”) with a Wide Morphological Spectrum

The t(2;5)(p23;q35) translocation associated with CD30-positive anaplastic large cell lymphoma results in the production of a NPM-ALK chimeric protein, consisting of the N-terminal portion of the NPM protein joined to the entire cytoplasmic domain of the neural receptor tyrosine kinase ALK. The ALK gene products were identified in paraffin sections by using a new anti-ALK (cytoplasmic portion) monoclonal antibody (ALKc) that tends to react more strongly than a previously described ALK1 antibody with the nuclei of ALK-expressing tumor cells after microwave heating in 1 mmol/L ethylenediaminetetraacetic acid buffer, pH 8.0. The ALKc monoclonal antibody reacted selectively with 60% of anaplastic large cell lymphoma cases (60 of 100), which occurred mainly in the first three decades of life and consistently displayed a T/null phenotype. This group of ALK-positive tumors showed a wide morphological spectrum including cases with features of anaplastic large cell lymphoma “common” type (75%), “lymphohistiocytic” (10%), “small cell” (8.3%), “giant cell” (3.3%), and “Hodgkin’s like” (3.3%). CD30-positive large anaplastic cells expressing the ALK protein both in the cytoplasm and nucleus represented the dominant tumor population in the common, Hodgkin’s-like and giant cell types, but they were present at a smaller percentage (often with a perivascular distribution) also in cases with lymphohistiocytic and small cell features. In this study, the ALKc antibody also allowed us to identify small neoplastic cells (usually CD30 negative) with nucleus-restricted ALK positivity that were, by definition, more evident in the small cell variant but were also found in cases with lymphohistiocytic, common, and “Hodgkin’s-like” features. These findings, which have not been previously emphasized, strongly suggest that the neoplastic lesion (the NPM-ALK gene) must be present both in the large anaplastic and small tumor cells, and that ALK-positive lymphomas lie on a spectrum, their position being defined by the ratio of small to large neoplastic cells. Notably, about 15% of all ALK-positive lymphomas (usually of the common or giant cell variant) showed a cytoplasm-restricted ALK positivity, which suggests that the ALK gene may have fused with a partner(s) other than NPM. From a diagnostic point of view, detection of the ALK protein was useful in distinguishing anaplastic large cell lymphoma cases of lymphohistiocytic and small cell variants from reactive conditions and other peripheral T-cell lymphoma subtypes, as well as for detecting a small number of tumor cells in lymphohemopoietic tissues. In conclusion, ALK positivity appears to define a clinicopathological entity with a T/null phenotype (“ALK lymphomas”), but one that shows a wider spectrum of morphological patterns than has been appreciated in the past.     

Takayasu’s arteritis occurring under TNF blockers in a patient with spondyloarthritis: is it an association or a paradoxical effect?

Coexistence of spondyloarthritis (SpA) and Takayasu’s arteritis is not a common finding, but such cases have been discussed, particularly in the context of choice of therapy. Inhibition of inflammation by tumor necrosis factor inhibitors (TNFi) is a key aspect of the treatment of SpA and also positive effects of such treatment in concomitant large vessel vasculitis have been reported. However, TNFi is also associated with the possibility of initiating vasculitis.The present article based on a case study and the available literature is an attempt to discuss coexistence of these two diseases and the impact of treatment with biological drugs from the anti-TNF group in the course of SpA with Takayasu’s arteritis.     

Preliminary evaluation of particle systems visualization on the skin surface by scanning electron microscopy and transparency profilometry

Background: There is a rising debate concerning the possible side effects arising from the use of particles at nanosize since the production of nanomaterials is increasing worldwide. Nanoparticles are able to enter the body through the skin, lungs or intestinal tract, depositing in several organs, and the risk associated with exposure to them, the routes of entry and the molecular mechanisms of any cytotoxicity need to be well understood. The aim of this work was to evaluate the suitability of skin replica as a method to study the colloidal systems visualization and distribution on skin surface. Methods: Solid lipid nanoparticles (SLN) were used as carrier systems. Skin replicas on healthy volunteers, before and after SLN application, were prepared and visualized using profilometry and scanning electron microscopy (SEM). Results: The results obtained in our study show that skin replica represents a suitable method to study the colloidal systems and their interaction with the skin surface. Conclusion: Profilometry enabled us to observe the systems distribution on a cutaneous texture. In addition, SEM, thanks to its high magnifications and field depth, allowed us to evaluate particles' distribution on the skin texture and the interaction between particles of different compositions and replica silicone.