Detection of Epstein-Barr virus in children and adolescents with Burkitt's lymphoma by in situ hybridization using tissue microarrays

In this retrospective study, we evaluated 53 patients diagnosed with Burkitt's lymphoma (BL). Patients were admitted to the Pediatric Department of Santa Casa de S?o Paulo, Brazil from August 1988 to September 2006. The male gender was found more frequently in the proportion of three males to one female. At the time of the diagnosis, the mean age was 6 years. The most frequent clinical presentation was abdominal (extra nodal) in 42 (79.2%) cases. The patients were treated with chemotherapy using two different treatment methods, 30 cases until September 1994 with BGLTI -87 and the other 23 until September of 2006 with BGLTI -96. According to Murphy's classification, 90.2% of the patients were diagnosed as stages III and VI showing an advanced disease at time of diagnosis. Using Tissue Microarrays (TMA); we searched for the expression of the Epstein-Barr virus (EBV) RNA in 50 patients. The presence of EBV using in situ hybridization was found in 33/50 (66%) and there was no association between the presence of the virus in the tumor cells or patient age, as well as the survival rate. There was 74.5% global survival rate until September, 2005 of 12 years and 8 months. The disease free survival rate was 86.5%. The frequency of the EBV association with this neoplasia in Brazil is intermediate between the endemic and sporadic forms of disease.     

A novel type of familial transthyretin amyloidosis, ATTR Asn124Ser, with co-localization of kappa light chains.

A 68-year-old Italian woman who had a clinical history of thyroidectomy in 2002 presented with slowly progressing renal insufficiency and non-nephrotic proteinurea in 2004. A renal biopsy showed the occurrence of amyloid; the thyroid biopsy previously taken also revealed amyloid infiltration. Other amyloid-containing tissues included bone marrow and heart. The plasma cell level in the bone marrow was found to be less than 5% and both serum and urine samples were positive for a monoclonal kappa light chain band. DNA analysis unexpectedly revealed the presence of a novel transthyretin (TTR) mutation, ATTR Asn124Ser. Histologically, amyloid deposits in the thyroid had a homogeneous appearance with moderate Congophilia. In immunohistochemistry, a kappa light chain antiserum showed positive immunoreactivity with amyloid deposits in the thyroid. Furthermore, a TTR antiserum, anti-TTR50-127, also recognized a number of amyloid deposits stained positive with the kappa light chain antiserum. Overall, the kappa light chain antiserum reacted with most of the amyloid deposits in the thyroid, whereas TTR immunoreactivity was scarcer, with a scattered appearance. In contrast, only the anti-TTR50-127 antiserum labeled amyloid in the kidney, albeit not all deposits. In this study, we report a patient having a novel TTR variant, ATTR Asn124Ser, with co-localization of kappa light chains in the amyloid deposits in the thyroid tissue.     

Factors affecting left ventricular remodelling and mechanics in the long-term follow-up after successful repair of aortic coarctation

AIMS: To identify factors predisposing to abnormal left ventricular geometry and mechanics in 52 patients after successful repair of aortic coarctation. METHODS AND RESULTS: We evaluated left ventricular remodelling, systolic midwall mechanics, and isthmic gradient by echo-Doppler, systemic blood pressure at rest/exercise and by ambulatory blood pressure monitoring, and the aortic arch by magnetic resonance imaging. Echocardiographic findings were compared with those of 142 controls. The patients with aortic coarctation showed an increased indexed left ventricular end-diastolic volume, increased mass index, increased ratio of mass to volume and systolic chamber function. The contractility, estimated at midwall level, was increased in 21 percent of the patients. In 26 (50 percent) of the patients, we found abnormal left ventricular geometry, with 9 percent showing concentric remodelling, 33 percent eccentric hypertrophy, and 8 percent concentric hypertrophy. These patients were found to be older, underwent a later surgical repair, and to have higher systolic blood pressures at rest and exercise as well as during ambulatory monitoring. The relative mural thickness and mass index of the left ventricle showed a significant correlation with different variables on uni- and multivariate analysis. Age and diastolic blood pressure at rest are the only factors associated with abnormal left ventricular remodelling. CONCLUSIONS: Patients who have undergone a seemingly successful surgical repair of aortic coarctation may have persistently abnormal geometry with a hyperdynamic state of the left ventricle. This is more frequent in older patients, and in those with higher diastolic blood pressures.     

Myocarditis with ST-Elevation Myocardial Infarction presentation in young man. A case series of 11 patients

Acute myocarditis may mimic an infarction. Aim is to describe a case series of peculiar myocarditis. From 1997 to 2003, 11 male patients (age 17-39 years) were admitted with diagnosis of acute myocardial infarction, localized ST segment elevation and minimal enzyme release. Ten patients had fever in the 3 days prior to admission. Eight patients underwent coronary angiography showing normal coronary arteries. All remained asymptomatic at long term follow-up. In conclusion, myocarditis with ST elevation myocardial infarction presentation is an acute benign syndrome especially frequent in young males.     

Primary hyperparathyroidism associated to slipped capital femoral epiphysis in a teenager

Primary hyperparathyroidism (PHP) is an uncommon disease in children and adolescents. The association between PHP and slipped capital femoral epiphysis is rare, and so far only four cases have been reported in the literature. Herein, we report a case of PHP due to a parathyroid adenoma, with several painful skeletal deformities and associated with slipped capital femoral epiphysis in an 18-year-old male patient. Laboratory evaluation showed: calcium of 13.6 mg/dL, parathyroid hormone of 1,524 pg/mL and alkaline phosphatase of 3,449 U/L. Deformities were caused by late diagnosis during the growth spurt, and this association is the result of combinations between metabolic and mechanical factors. The patient underwent parathyroidectomy and, in agreement with the literature, since the removal of the adenoma is followed by prompt resolution of the slipped capital femoral epiphysis we decided for a conservative approach. We observed improvement of the pain and normalization of calcium and parathyroid hormone levels.     

Identification and characterization of undifferentiated mast cells in mouse bone marrow

Sequential immunomagnetic isolation with 2 monoclonal antibodies was used to purify and characterize an undifferentiated mast cell in adult mouse bone marrow that had not been previously recognized. This cell represents 0.02% of the cells in the bone marrow, is CD34(+), CD13(+), and c-kit(+), and does not express FcepsilonRI. However, by polymerase chain reaction (PCR) the cell contains message for the alpha and beta subunits of FcepsilonRI, mast cell-specific proteases, and carboxypeptidase A. Morphologically, this cell has a large nucleus, little cytoplasm, few cytoplasmic organelles, and no cytoplasmic granules. In vitro, in the presence of interleukin-3 (IL-3) and stem cell factor (SCF) these cells differentiate only into a granulated mast cell that now expresses CD13, c-kit, mast cell-specific gangliosides, FcepsilonRI, and binds immunoglobulin E (IgE). When injected into lethally irradiated mice, these cells are able to reconstitute the mast cell population in the spleen.     

Increased pituitary vascular endothelial growth factor-a in dopaminergic D2 receptor knockout female mice

Vascular endothelial growth factor (VEGF)-A is an important angiogenic cytokine in cancer and pathological angiogenesis and has been related to the antiangiogenic activity of dopamine in endothelial cells. We investigated VEGF expression, localization, and function in pituitary hyperplasia of dopamine D2 receptor (D2R)-knockout female mice. Pituitaries from knockout mice showed increased protein and mRNA VEGF-A expression when compared with wild-type mice. In wild-type mice, prolonged treatment with the D2R antagonist, haloperidol, enhanced pituitary VEGF expression and prolactin release, suggesting that dopamine inhibits pituitary VEGF expression. VEGF expression was also increased in pituitary cells from knockout mice, even though these cells proliferated less in vitro when compared with wild-type cells, as determined by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium proliferation assay, proliferating cell nuclear antigen expression, and [(3)H]thymidine incorporation. In contrast to other animal models, estrogen did not increase pituitary VEGF protein and mRNA expression and lowered serum prolactin secretion in vivo and in vitro in both genotypes. VEGF (10 and 30 ng/ml) did not modify pituitary cell proliferation in either genotype and increased prolactin secretion in vitro in estrogen-pretreated cells of both genotypes. But conditioned media from D2R(-/-) cells enhanced human umbilical vein cell proliferation, and this effect could be partially inhibited by an anti-VEGF antiserum. Finally, using dual-labeling immunofluorescence and confocal laser microscopy, we found that in the hyperplastic pituitaries, VEGF-A was mostly present in follicle-stellate cells. In conclusion, pituitary VEGF expression is under dopaminergic control, and even though VEGF does not promote pituitary cellular proliferation in vitro, it may be critical for pituitary angiogenesis through paracrine actions in the D2R knockout female mice.     

Effect of high-density lipoprotein cholesterol levels on carotid artery geometry in a Mediterranean female population.

BACKGROUND: Controversy remains on the relationship between high-density lipoprotein cholesterol (HDL-C) and atherosclerotic cerebrovascular disease. METHODS: Over 5000 women living in the area of Naples, Southern Italy, were recruited for a prospective study on the etiology of cardiovascular disease in the female population (the 'Progetto ATENA' study). A sample of 310 participants underwent high-resolution B-mode ultrasound examination and the intima-media thickness and diameters of common carotid artery were measured. In addition to routine biochemical tests, these women also had oxidation markers determined. RESULTS: Women in the upper HDL-C quartile (HDL-C>1.89 mmol/L) had significantly lower body mass index and waist-to-hip ratio values, and triglycerides concentrations when compared with women in the first three quartiles. A linear negative association was found between HDL-C and carotid intima-media thickness (1.07+/-0.16 mm for the IV quartile versus 1.10+/-0.20 mm for the III quartile, 1.15+/-0.26 mm for the II quartile and 1.19+/-0.23 mm for the I quartile; P<0.01 by ANOVA). No difference was found between groups with regard to carotid diameters and oxidation markers. After adjustment for other cardiovascular risk factors, women in the highest quartile of HDL-C had a decreased risk of carotid intima-media thickening (OR 0.42, 95%CI 0.23-0.94). CONCLUSIONS: In asymptomatic middle-aged women, HDL-C levels were independently and negatively associated with preclinical atherosclerotic changes of the carotid artery wall.     

Adequate energy-protein intake is not enough to improve nutritional and metabolic status in muscle-depleted patients with chronic heart failure

BACKGROUND: An adequate energy-protein intake (EPI) when combined with amino acid supplementation may have a positive impact on nutritional and metabolic status in patients with chronic heart failure (CHF). METHODS AND RESULTS: Thirty eight stable CHF patients (27 males, 73.5+/-4 years; BMI 22.5+/-1.4 kg/m2), with severe depletion of muscle mass and were randomised to oral supplements of essential amino acids 8 g/day (EAA group; n=21) or no supplements (controls; n=17). All patients had adequate EPI (energy> or =30 kcal/kg; proteins >1.1 g/kg). At baseline and 2-months after randomisation, the patients underwent metabolic (plasma lactate, pyruvate concentration; serum insulin level; estimate of insulin resistance by HOMA index), nutritional (measure of nitrogen balance), and functional (exercise test, walking test) evaluations. Body weight increased by >1 kg in 80% of supplemented patients (mean 2.96 kg) and in 30% of controls (mean 2.3 kg) (interaction <0.05). Changes in arm muscle area, nitrogen balance, and HOMA index were similar between the two treatment groups. Plasma lactate and pyruvate levels increased in controls (p<0.01 for both) but decreased in the supplemented group (p<0.01 and 0.02 respectively). EAA supplemented patients but not controls improved both exercise output and peak oxygen consumption and walking test. CONCLUSIONS: Adequate EPI when combined with essential amino acid supplementation may improve nutritional and metabolic status in most muscle-depleted CHF patients.     

Silent cerebral white matter lesions and cognitive function in middle-aged essential hypertensive patients

BACKGROUND: An association between midlife blood pressure levels and late-life cognitive impairment has been reported. Hypertension is one of the most important factors related to the presence of cerebral white matter lesions, which is a prognostic factor for the development of cognitive impairment. Studies have shown a relationship between white matter lesions and cognitive decline in elderly hypertensive patients. The aim of the present study was to evaluate cognitive function in asymptomatic middle-aged hypertensive patients according to the presence or absence of white matter lesions. METHODS: Sixty never-treated essential hypertensive patients (38 men, 22 women), aged 50 to 60 years (mean age, 54.4 +/- 3.8 years), without clinical evidence of target organ damage, were studied. All patients underwent brain magnetic resonance imaging to establish the presence or absence of white matter lesions, using the Rotterdam criteria. Cognitive function was evaluated by a neuropsychologic test battery measuring attention, memory, intelligence, anxiety, and depression. RESULTS: Twenty-three hypertensive patients (38%) were found to have white matter lesions on brain resonance. These patients exhibited a significantly worse performance on digit span forward, a standardized measure of attention than hypertensives without white matter lesions (4.86 +/- 1.14 v 5.51 +/- 0.97; P =.027). Hypertensive patients with white matter lesions showed no differences on both visual and logical memory tests when compared with patients without lesions. CONCLUSIONS: We conclude that the presence of silent cerebral white matter lesions in middle-aged hypertensive patients is associated with a mild decline in basic attention.