How useful is GLUT-1 in differentiating mesothelial hyperplasia and fibrosing pleuritis from epithelioid and sarcomatoid mesotheliomas? An international collaborative study.

OBJECTIVE: Mesothelial hyperplasia (MH) and fibrosing pleuritis (FP) can be difficult to distinguish from epithelioid (MM-E) and sarcomatoid (MM-S) malignant pleural mesotheliomas. GLUT-1 has shown variable results regarding its sensitivity and specificity when used to evaluate mesothelial proliferations. We evaluated the utility of GLUT-1 immunostaining in differentiating MH and FP from MM-E and MM-S. MATERIALS AND METHODS: In this retrospective study, diagnostically well-characterized cases (MH=31, FP=29, MM-E=41, MM-S=29) were collected and manually stained for GLUT-1. All slides were visually scored by 2 pathologists; using the following system: 0%, 1+ 1-25%, 2+ 26-50% and 3+ >51% cells staining. RESULTS: All benign cases (n=60) were negative for GLUT-1 while 45 of 78 (58%) MM [21 of 41 (50%) MM-E, 21 of 29 (72%) MM-S and 3 of 3 biphasic mesothelioma (100%)] had 1+ to 3+ staining. Of the MM-E, 10 had 1+, and 11 had 2+ staining; of the MM-S 3 had 1+, 15 had 2+ and 3 had 3+ staining. Both sarcomatoid and epithelioid components of the 3 biphasic mesotheliomas revealed 1+ staining. All 5 desmoplastic MM were negative. CONCLUSIONS: Positive staining with GLUT-1 is helpful since it is present in half of MM-E and three-quarter of MM-S. Although all reactive mesothelial lesions were negative, the absence of immunoreactivity does not exclude the diagnosis of MM. As with all IHC stains used for diagnostic purposes, GLUT-1 has to be a part of a panel, and the results interpreted in the context of clinical, radiological and histological findings.

Ectopic pancreas presenting with pancreatitis and a mesenteric mass.

Ectopic pancreas is defined by the presence of abnormally situated pancreatic tissue that lacks contact with normal pancreas and possesses its own duct system and vascular supply. Ectopic pancreas in the gastrointestinal tract is not uncommon. Moreover, there are several reported cases of adult ectopic pancreatitis in the literature, but to date, only two cases of pediatric ectopic pancreatitis have been reported. We describe a 15-year-old female with acute right upper quadrant pain and elevated serum lipase and amylase, in whom the radiological diagnosis was mesenteric soft tissue mass with adjacent inflammatory changes. The surgical pathology diagnosis, however, was mesenteric ectopic pancreas complicated by pancreatitis. We advocate for ectopic pancreatitis to be considered in a pediatric patient with acute abdominal pain, laboratory findings consistent with pancreatitis, and imaging findings of a mesenteric mass and normal orthotopic pancreas.

Nucleometric study of anisonucleosis, diabetes and oxidative damage in liver biopsies of orthotopic liver transplant recipients with chronic hepatitis C virus infection.

Anisonucleosis is defined as a morphological manifestation of nuclear injury characterized by variation in the size of the cell nuclei. It has been described in variety of benign conditions and is most pronounced in dysplasia and malignancy. To better understand the pathogenesis of anisonucleosis in liver diseases, this study focused on hepatocyte anisonucleosis in biopsies of liver transplant recipients who developed recurrent chronic hepatitis C virus (HCV) infection. Post transplant surveillance liver biopsy specimens were evaluated employing light microscopy, immunohistochemistry, digital image analysis, and nucleometry for histopathological analyses, measurement of nuclear size, and quantification of tissue expression of oxidative marker 8-hydroxy-2'deoxyguanosine (8-OHdG). Our aim in this study was to determine whether there were any independent associations between hepatocyte anisonucleosis and various clinicopathological parameters. These features included patient age, body mass index, gender, race, donor age, live versus cadaveric donor status, history of diabetes mellitus, history of tacrolimus and cyclosporine therapy, duration post transplant and parameters of hepatitis activity index, fibrosis index, steatosis, and oxidative tissue damage in formalin fixed paraffin embedded (FFPE) liver biopsies as determined by immunohistochemistry using 8-OHdG, an indicator of hydroxyl radical mediated tissue damage. Our findings suggested that in liver transplant recipients with recurrent chronic HCV infection, hepatocyte anisonucleosis is more pronounced in individuals with diabetes mellitus (p = 0.0016), and among those who have heightened hepatic expression of the oxidative damage marker 8-OHdG (p = 0.0053). Further studies are necessary to determine whether anisonucleosis is an independent marker for diabetes or oxidative damage.

Familial childhood monosomy 7 and associated myelodysplasia.

SUMMARY: Familial monosomy 7 is defined as bone marrow monosomy 7 occurring as a sole cytogenetic abnormality affecting 2 or more siblings. It manifests usually in childhood with neurologic disorder (cerebellar ataxia or atrophy) and/or hematologic disorder (marrow hypoplasia, myelodysplasia, acute myeloid leukemia, or pancytopenia). Partial or complete monosomy 7 with hematologic disorder has been reported in 13 families/pedigrees to date. Here we report the 14th family.

Safety of high volume lipid emulsion infusion: a first approximation of LD50 in rats.

BACKGROUND: Lipid infusion reverses systemic local anesthetic toxicity. The acceptable upper limit for lipid administration is unknown and has direct bearing on clinical management. We hypothesize that high volumes of lipid could have undesirable effects and sought to identify the dose required to kill 50% of the animals (LD(50)) of large volume lipid administration. METHODS: Intravenous lines and electrocardiogram electrodes were placed in anesthetized, male Sprague-Dawley rats. Twenty percent lipid emulsion (20, 40, 60, or 80 mL/kg) or saline (60 or 80 mL/kg), were administered over 30 mins; lipid dosing was assigned by the Dixon "up-and-down" method. Rats were recovered and observed for 48 hrs then euthanized for histologic analysis of major organs. Three additional rats were administered 60 mL/kg lipid emulsion and euthanized at 1, 4, and 24 hrs to identify progression of organ damage. RESULTS: The maximum likelihood estimate for LD(50) was 67.72 (SE, 10.69) mL/kg. Triglycerides were elevated immediately after infusion but returned to baseline by 48 hrs when laboratory abnormalities included elevated amylase, aspartate aminotransferase, and serum urea nitrogen for all lipid doses. Histologic diagnosis of myocardium, brain, pancreas, and kidneys was normal at all doses. Microscopic abnormalities in lung and liver were observed at 60 and 80 mL/kg; histopathology in the lung and liver was worse at 1 hr than at 4 and 24 hrs. CONCLUSIONS: The LD(50) of rapid, high volume lipid infusion is an order of magnitude greater than doses typically used for lipid rescue in humans and supports the safety of lipid infusion at currently recommended doses for toxin-induced cardiac arrest. Lung and liver histopathology was observed at the highest infused volumes.

A rare case of lipoprotein glomerulopathy in a white man: an emerging entity in Asia, rare in the white population.

Lipoprotein glomerulopathy is a rare entity that predominantly affects the Asian population, mainly the Japanese and Chinese. Lipoprotein glomerulopathy is clinically characterized by proteinuria and progression to renal failure and is caused by glomerular lipoprotein thrombi formation in association with increased levels of serum apolipoprotein E. The disease has a male predominance and can affect virtually any age group. We describe the third reported case, to our knowledge, of lipoprotein glomerulopathy to affect a white patient.

Lactobacillus acidophilus stimulates the expression of SLC26A3 via a transcriptional mechanism.

Clinical efficacy of probiotics in treating various forms of diarrhea has been clearly established. However, mechanisms underlying antidiarrheal effects of probiotics are not completely defined. Diarrhea is caused either by decreased absorption or increased secretion of electrolytes and solutes in the intestine. In this regard, the electroneutral absorption of two major electrolytes, Na(+) and Cl(-), occurs mainly through the coupled operation of Na(+)/H(+) exchangers and Cl(-)/OH(-) exchangers. Previous studies from our laboratory have shown that Lactobacillus acidophilus (LA) acutely stimulated Cl(-)/OH(-) exchange activity via an increase in the surface levels of the apical anion exchanger SLC26A3 (DRA). However, whether probiotics influence SLC26A3 expression and promoter activity has not been examined. The present studies were, therefore, undertaken to investigate the long-term effects of LA on SLC26A3 expression and promoter activity. Treatment of Caco-2 cells with LA for 6-24 h resulted in a significant increase in Cl(-)/OH(-) exchange activity. DRA mRNA levels were also significantly elevated in response to LA treatment starting as early as 8 h. Additionally, the promoter activity of DRA was increased by more than twofold following 8 h LA treatment of Caco-2 cells. Similar to the in vitro studies, in vivo studies using mice gavaged with LA also showed significantly increased DRA mRNA ( approximately 4-fold) and protein expression in the colonic regions as assessed by Western blot analysis and immunofluorescence. In conclusion, increase in DRA promoter activity and expression may contribute to the upregulation of intestinal electrolyte absorption and might underlie the potential antidiarrheal effects of LA.