Neoplastic Ascites in Osteosarcoma A Case Report

Background Osteosarcoma is a malignant tumor of connective tissue Whose tumor cells produce bone tissue. It can be classified as osteoblastic, chondroblastic, or fibroblastic, according to the predominant histologic type of cells. Its dissemination is hematogenous; and the lungs are the most frequent site of clinically evident metastasis. Extrapulmonary metastases are rare and more frequently diagnosed at necropsy. We present a case of osteosarcoma with peritoneal dissemination that developed neoplastic ascites. Case A 46-year-old patient came to the hospital with a 4-month history of lumbar pain and weakness in the lower limbs. Computed tomography showed blastic lesions in the L3 vertebral body. Surgical resection and histologic analysis revealed a mixed osteoblastic and chondroblastic osteosarcoma. After only one session of chemotherapy, the patient presented a marked clinical worsening with extensive metastatic dissemination and occurrence of voluminous ascites. The cytologic examination of the ascitic fluid demonstrated frequent poorly differentiated tumor cells. The patient died a little more than 2 months after the diagnosis. Conclusion This case is the only report of osteosarcoma primarily focused on the vertebral column affected by peritoneal metastasis shown by cytologic examination of ascitic fluid. (Acta Cytol 2010;54:845-848)

Myocardial Perfusion Imaging Is a Strong Predictor of Death in Women

OBJECTIVES We sought to assess the prognostic value and risk classification improvement using contemporary single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) to predict all-cause mortality. BACKGROUND Myocardial perfusion is a strong estimator of prognosis. Evidence published to date has not established the added prognostic value of SPECT-MPI nor defined an approach to detect improve classification of risk in women from a developing nation. METHODS A total of 2,225 women referred for SPECT-MPI were followed by a mean period of 3.7 +/- 1.4 years. SPECT-MPI results were classified as abnormal on the presence of any perfusion defect. Abnormal scans were further classified as with mild/moderate reversible, severe reversible, partial reversible, or fixed perfusion defects. Risk estimates for incident mortality were categorized as <1%/year, 1% to 2%/year, and >2%/year using Cox proportional hazard models. Risk-adjusted models incorporated clinical risk factors, left ventricular ejection fraction (LVEF), and perfusion variables. RESULTS All-cause death occurred in 139 patients. SPECT-MPI significantly risk stratified the population; patients with abnormal scans had significantly higher death rates compared with patients with normal scans, 13.1% versus 4.0%, respectively (p < 0.001). Cox analysis demonstrated that after adjusting for clinical risk factors and LVEF, SPECT-MPI improved the model discrimination (integrated discrimination index = 0.009; p = 0.02), added significant incremental prognostic information (global chi-square increased from 87.7 to 127.1; p < 0.0001), and improved risk prediction (net reclassification improvement = 0.12; p = 0.005). CONCLUSIONS SPECT-MPI added significant incremental prognostic information to clinical and left ventricular functional variables while enhancing the ability to classify this Brazilian female population into low-and high-risk categories of all-cause mortality. (J Am Coll Cardiol Img 2011;4:880-8) (C) 2011 by the American College of Cardiology Foundation

Lymphatic Vessel Density and VEGF-C Expression are Significantly Different Among Benign and Malignant Thyroid Lesions

Thyroid cancer is the most frequent endocrine neoplasia worldwide. The route for metastasis and loco-regional invasion preferentially occurs by lymphatic vessels. For this reason, the assessment of lymphatic vessel density (LVD) is supposed to represent both a prognostic parameter and also a potential therapeutic target. In order to evaluate the value of LVD in benign and malignant thyroid lesions, we analyzed 110 thyroidectomy specimens using D2-40, a specific marker for lymphatic vessels and vascular endothelial growth factor C (VEGF-C), the most potent molecule of lymphatic proliferation. LVD was significantly different between papillary and follicular carcinomas in total (p = 0.045) and peritumoral area (p = 0.042). Follicular adenoma and follicular carcinoma showed an important difference of intra- (p = 0.019) and peritumoral (p = 0.033) LVD. VEGF-C was more markedly expressed in malignancies than in benignant lesions (p = 0.0001). Almost all cancers with high positive VEGF-C expression also exhibited increased peritumoral LVD (p = 0.049) when compared with the benignant lesions. Indeed, the high peritumoral LVD of malignant thyroid lesions is an important finding for surgery planning and supports the practice of total thyroidectomy in malignant thyroid neoplasm`s since the lymphatic peritumoral vessels definitely are an escape path for tumor cells.

Bone mineral density analysis in patients with primary hyperparathyroidism associated with multiple endocrine neoplasia type 1 after total parathyroidectomy

P>Objective Limited data have been reported on the effect of parathyroidectomy (PTx) on bone mineral density (BMD) in the setting of patients with hyperparathyroidism (HPT) associated with multiple endocrine neoplasia type 1 (MEN1). This study investigates the impact of total PTx on BMD in patients with HPT/MEN1. Design and patients A case series study was performed in a tertiary academic hospital. A total of 16 HPT/MEN1 patients from six families harbouring MEN1 germline mutations were subjected to total PTx followed by parathyroid auto-implant in the forearm. Measurements Bone mineral density values were assessed using dual-energy X-ray absorptiometry. Results Before PTx, reduced BMD (Z-score <-2 center dot 0) was highly prevalent in the proximal one-third of the distal radius (1/3 DR) (50%), lumbar spine (LS) (43 center dot 7%), ultradistal radius (UDR) (43 center dot 7%), femoral neck (FN) (25%) and total femur (TF) (18 center dot 7%) in the patients. Fifteen months after PTx, we observed a BMD improvement in the LS (from 0 center dot 843 to 0 center dot 909 g/cm2; +8 center dot 4%, P = 0 center dot 001), FN (from 0 center dot 745 to 0 center dot 798 g/cm2; +7 center dot 7%, P = 0 center dot 0001) and TF (from 0 center dot 818 to 0 center dot 874 g/cm2; +6 center dot 9%, P < 0 center dot 0001). No significant change was noticed in the 1/3 DR and UDR after PTx. Conclusions This data confirmed BMD recovery in the LS and FN after PTx in HPT/MEN1 patients. We also documented a significant BMD increase in the TF and no change in both the 1/3 DR and UDR BMD after PTx. Our data suggest that LS and proximal femur are the most informative sites to evaluate the short-term BMD outcome after PTx in HPT/MEN1 subjects.

Validation of a Cutoff Value on Echo Doppler Analysis to Replace Right Heart Catheterization During Pulmonary Hypertension Evaluation in Heart Transplant Candidates

Background. Heart transplantation (OHT) has traditionally been contraindicated in the presence of severe pulmonary hypertension (PH), as detected by right heart catheterization. Noninvasive methods are still not reliably accurate to make this evaluation. Objectives. Determine the efficacy of echo Doppler analysis for the diagnosis of severe PH. Methods. One hundred thirty patients (mean age = 42 +/- 15 years, 82 men) showed severe left ventricular dysfunction (mean ejection fraction = 29 +/- 12%; functional class III-IV). We excluded patients with atrial fibrillation, heart failure secondary to congenital disease, and valvulopathy. The pulmonary parameters defined as severe PH were: systolic pulmonary artery pressure (sPAP) >= 60 mm Hg; a mean transpulmonary gradient >= 15; or pulmonary vascular resistance >= 5 Wood units. Patients underwent a right heart catheterization using a Swan-Ganz catheter to measure hemodynamic parameters and to noninvasively estimate right-sided pressures from spectral Doppler recordings of tricuspid regurgitation velocity (right ventricular systolic pressure [RVsP]). A Pearson correlation of sPAP was obtained with RVsP by; the sensitivity of RVsP for the diagnosis of PH was determined by a receiver operating characteristic (ROC) curve. Results. A good correlation between sPAP and RVsP was obtained by Pearson correlation analysis (r = 0.64; 95% confidence interval [CI] 0.50-0.75; P < .001). The ROC curve analysis showed a sensitivity of 100%, a specificity of 37.2%, (95% CI 0.69-0.83, P < .0001) of a RVsP < 45 mm Hg (cutoff) on the exclusion of severe PH. Conclusions. The cutoff of RVsP < 45 mm Hg, on noninvasive echo Doppler evaluation of PH is an efficient method to replace invasive heart catheterization in OHT candidates.

Traditional risk factors for cardiovascular disease in primary antiphospholipid syndrome (APS) when compared with secondary APS: a study with 96 patients

Objective: To evaluate the prevalence of traditional risk factors in patients with primary antiphospholipid syndrome (APS) in comparison to those with systemic lupus erythematosus-secondary APS. Methods: Transversal study of 96 APS patients (Sapporo`s criteria). Demographic and clinical data, cardiovascular risk factors and drug use were investigated. Results: Thirty-nine Primary APS and 57 secondary APS were included. The groups did not differ regarding age (38.5 +/- 9.9 vs. 39.4 +/- 10.5 years, p=0.84) and female gender (84.6 vs. 96.5%, p=0.06), respectively. Arterial events were more observed in primary than secondary APS (59 vs. 36.8%, p=0.04) patients. No difference was seen concerning venous and obstetric events. In regard to traditional risk factors for cardiovascular disease, both groups were comparable related to current or previous smoking, sedentarism, family history for coronary disease, systemic hypertension, diabetes mellitus, overweight and obesity. The frequencies of altered lipid profiles were alike in the two groups, except for a higher prevalence of low HDL-c levels in primary APS group (84.6 vs. 45.5%, p=0.0001). Concerning drug use, no significant differences were observed related to chloroquine and statin use, however the secondary APS patients had a higher rate of prednisone use (10.2 vs. 57.9%, p<0.001) as well as mean dose of corticosteroid (1.5 +/- 5.7 vs. 9.2 +/- 12.5mg/ /day, p=0.0001). Conclusion: Traditional risk factors for cardiovascular disease are present and comparable between patients with primary and secondary APS, except for a high frequency of low HDL-c in primary APS patients.

Verbal fluency in the detection of mild cognitive impairment and Alzheimer`s disease among Brazilian Portuguese speakers: the influence of education

Background: Verbal fluency (VF) tasks are simple and efficient clinical tools to detect executive dysfunction and lexico-semantic impairment. VF tasks are widely used in patients with suspected dementia, but their accuracy for detection of mild cognitive impairment (MCI) is still under investigation. Schooling in particular may influence the subject`s performance. The aim of this study was to compare the accuracy of two semantic categories (animals and fruits) in discriminating controls, MCI patients and Alzheimer`s disease (AD) patients. Methods: 178 subjects, comprising 70 controls (CG), 70 MCI patients and 38 AD patients, were tested on two semantic VF tasks. The sample was divided into two schooling groups: those with 4-8 years of education and those with 9 or more years. Results: Both VF tasks - animal fluency (VFa) and fruits fluency (VFf) - adequately discriminated CG from AD in the total sample (AUC = 0.88 +/- 0.03, p < 0.0001) and in both education groups, and high educated MCI from AD (VFa: AUC = 0.82 +/- 0.05, p < 0.0001; VFf: AUC = 0.85 +/- 0.05, p < 0.0001). Both tasks were moderately accurate in discriminating CG from MCI (VFa: AUC = 0.68 +/- 0.04, p < 0.0001 - VFf:AUC = 0.73 +/- 0.04, p < 0.0001) regardless of the schooling level, and MCI from AD in the total sample (VFa: AUC = 0.74 +/- 0.05, p < 0.0001; VFf: AUC = 0.76 +/- 0.05, p < 0.0001). Neither of the two tasks differentiated low educated MCI from AD. In the total sample, fruits fluency best discriminated CG from MCI and MCI from AD; a combination of the two improved the discrimination between CG and AD. Conclusions: Both categories were similar in discriminating CG from AD; the combination of both categories improved the accuracy for this distinction. Both tasks were less accurate in discriminating CG from MCI, and MCI from AD.

The potential role of C-reactive protein in distinguishing cytomegalovirus from tuberculosis and bacterial infections in renal transplant recipients

Introduction: The delay in the diagnosis of infections can be deleterious in renal transplant recipients. Thus, laboratory tests leading to an earlier diagnosis are very useful for these patients. Purpose: To assess the behavior of C-reactive protein (CRP) in renal transplant recipients with a diagnosis of cytomegalovirus (CMV) infection, tuberculosis (TB) and bacterial infection (BI). Methods: A retrospective analysis of 129 patients admitted at our hospital, from 2006 to 2008 because of CMV, TB or BI, was carried out. Appropriate statistical analysis was done and values were expressed as medians, range. Results: When CRP levels were compared among the groups with CMV disease, TB or BI, the group with CMV disease presented lower levels of CRP (18.4 mg/L, 0.28-44 mg/L) than the TB and BI (p < 0.05) groups. The area under the receiver-operating characteristics curve, distinguishing CMV disease from TB/BI, was 0.96 (p < 0.0001), resulting in 100% sensitivity and 90.63% specificity to detect CMV disease when CRP < 44.5 mg/L. The subgroup analysis of CMV infection showed increasing levels of CRP (0.28, 16 and 29.5 mg/L) in the asymptomatic, symptomatic and invasive disease subgroups, respectively (p < 0.05). Conclusion: The measurement of CRP levels may be a useful tool for differentiating CMV infection from the other types (bacterial or TB) of infection in kidney transplant recipients.

Assessment of a New Experimental Model of Isolated Right Ventricular Failure

We assessed a new experimental model of isolated right ventricular (RV) failure, achieved by means of intramyocardial injection of ethanol. RV dysfunction was induced in 13 mongrel dogs via multiple injections of 96% ethanol (total dose 1 mL/kg), all over the inlet and trabecular RV free walls. Hemodynamic and metabolic parameters were evaluated at baseline, after ethanol injection, and on the 14th postoperative day (POD). Echocardiographic parameters were evaluated at baseline, on the sixth POD, and on the 13th POD. The animals were then euthanized for histopathological analysis of the hearts. There was a 15.4% mortality rate. We noticed a decrease in pulmonary blood flow right after RV failure (P = 0.0018), as well as during reoperation on the 14th POD (P = 0.002). The induced RV dysfunction caused an increase in venous lactate levels immediately after ethanol injection and on the 14th POD (P < 0.0003). The echocardiogram revealed a decrease in the RV ejection fraction on the sixth and 13th PODs (P = 0.0001). There was an increased RV end-diastolic volume on the sixth (P = 0.0001) and 13th PODs (P = 0.0084). The right ventricle showed a 74% +/- 0.06% transmural infarction area, with necrotic lesions aged 14 days. Intramyocardial ethanol injection has allowed the creation of a reproducible and inexpensive model of RV failure. The hemodynamic, metabolic, and echocardiographic parameters assessed at different protocol times are compatible with severe RV failure. This model may be useful in understanding the pathophysiology of isolated right-sided heart failure, as well as in the assessment of ventricular assist devices.

Contrast-enhanced magnetic resonance imaging identifies focal regions of intramyocardial fibrosis, in patients with severe aortic valve disease: Correlation with quantitative histopathology

Background Chronic aortic valve disease (AVD) is characterized by progressive accumulation of interstitial myocardial fibrosis (MF). However, assessment of MF accumulation has only been possible through histologic analyses of endomyocardial biopsies. We sought to evaluate contrast-enhanced magnetic resonance imaging (ce-MRI) as a noninvasive method to identify the presence of increased MF in patients with severe AVD. Methods Seventy patients scheduled to undergo aortic valve replacement surgery were examined by cine and ce-MRI in a 1.5-T scanner. Cine images were used for the assessment of left ventricular (LV) volumes, mass, and function. Delayed-enhancement images were used to characterize the regions of MF. In addition, histologic analyses of myocardial samples obtained during aortic valve replacement surgery were used for direct quantification of interstitial MF. Ten additional subjects who died of noncardiac causes served as controls for the quantitative histologic analyses. Results Interstitial MF determined by histopathologic analysis was higher in patients with AVID than in controls (2.7% +/- 2.0% vs 0.6% +/- 0.2%, P =.001). When compared with histopathologic results, ce-MRI demonstrated a sensitivity of 74%, a specificity of 81%, and an accuracy of 76% to identify AVD patients with increased interstitial MF There was a significant inverse correlation between interstitial MF and LV ejection fraction (r = -0.67, P <.0001). Accordingly, patients with identifiable focal regions of MF by ce-MRI exhibited worse LV systolic function than those without MF (45% +/- 14% vs 65% +/- 14%, P <.0001). Conclusions Contrast-enhanced MRI allows for the noninvasive detection of focal regions of MF in patients with severe AVD. Moreover, patients with identifiable MF by ce-MRI exhibited worse LV functional parameters. (Am Heart J 2009; 157:361-8.)

Fetal hemodynamic changes following maternal betamethasone administration in pregnancies with fetal growth restriction and absent end-diastolic flow in the umbilical artery

Objectives. To examine the effects of betamethasone administration on umbilical artery (UA), middle cerebral artery (MCA) and ductus venosus (DV) Doppler flow. Design. Longitudinal prospective study. Setting: Fetal Surveillance Unit, Department of Obstetrics and Gynecology, University of Sao Paulo, Sao Paulo, Brazil. Population. Thirty-two singleton pregnancies complicated by fetal growth restriction with absent end-diastolic flow in the UA. Methods. Pulsatility index (PI) of the UA, MCA and DV was measured from 26 to 34 weeks prior to and within 24 or 48 hours after starting betamethasone treatment course. Analysis of variance for repeated measures was used to determine the changes in the fetal hemodynamic Doppler flow following maternal corticosteroid administration. Main outcome measures. Improvement of UA-PI within 24 hours and DV-PIV (venous pulsatility) within 48 hours from the first betamethasone dose. Results. Mean gestational age at delivery was 29.3 (1.8) weeks and birthweight was 806.6 (228.2) g. A reduction in the UA-PI was observed in 29 (90.6%) cases, with return of end-diastolic flow in 22 (68.7%). The mean UA-PI were 2.84 (0.52) before corticosteroid administration, 2.07 (0.56) within 24 hours and 2.42 (0.75) after 48 hours, with a significant difference along the evaluations (p0.001). No significant changes in the MCA Doppler were observed. DV-PIV decreased from 1.06 (0.23) prior corticosteroids administration to 0.73 (0.16) within 24 hours and 0.70 (0.19) after 48 hours (p0.001). Conclusions. There was reduction in the umbilical artery and in the DV pulsatility indices within 24 hours from betamethasone administration that was maintained up to 48 hours.

Genetic Analysis of Age-at-Onset for Cardiovascular Risk Factors in a Brazilian Family Study

Background/Aims: Statistical analysis of age-at-onset involving family data is particularly complicated because there is a correlation pattern that needs to be modeled and also because there are measurements that are censored. In this paper, our main purpose was to evaluate the effect of genetic and shared family environmental factors on age-at-onset of three cardiovascular risk factors: hypertension, diabetes and high cholesterol. Methods: The mixed-effects Cox model proposed by Pankratz et al. [2005] was used to analyze the data from 81 families, involving 1,675 individuals from the village of Baependi, in the state of Minas Gerais, Brazil. Results: The analyses performed showed that the polygenic effect plays a greater role than the shared family environmental effect in explaining the variability of the age-at-onset of hypertension, diabetes and high cholesterol. The model which simultaneously evaluated both effects indicated that there are individuals which may have risk of hypertension due to polygenic effects 130% higher than the overall average risk for the entire sample. For diabetes and high cholesterol the risks of some individuals were 115 and 45%, respectively, higher than the overall average risk for the entire population. Conclusions: Results showed evidence of significant polygenic effects indicating that age-at-onset is a useful trait for gene mapping of the common complex diseases analyzed. In addition, we found that the polygenic random component might absorb the effects of some covariates usually considered in the risk evaluation, such as gender, age and BMI. Copyright (C) 2008 S. Karger AG, Basel

Chemokine Receptors Expression on T Cells and Response to HAART Among Chronic HIV-1-Infected Subjects

Chemokines receptors are used by HIV-1 for entry into CD4(+) T cells. The chemokines are capable of inhibiting HIV replication. This study determined the CCR5 and CXCR4 expression on T cells in HIV-1-infected patients treated with HAART. The successfully treated group ( plasma viral load 400 copies/mL), when compared with the failure group ( plasma viral load >400 copies/mL), had higher median CD4+ T cells count ( 583 and 245 cells/mm(3); respectively, p<0.0001). The failure patients had higher numbers and intensity of CCR5 and CXCR4-expressing T cells. Successfully treated patients were able to normalize the co-receptors expression-over on T cells. The viremic group showed higher CCR5 expression on CD4+ T cells and lower number of cells; CCR5 expression was normalized in the aviremic group; the naive group showed lower CCR5 expression and higher numbers of CD4 T cells; all groups showed normal CXCR4 expression compared to healthy controls. These findings may have clinical implications, since down-regulation of these co-receptors could be an adjuvant strategy for anti-HIV treatment.

Haze Development After Photorefractive Keratectomy: Mechanical vs Ethanol Epithelial Removal in Rabbits

PURPOSE: To compare mechanical and ethanol epithelial removal with respect to myofibroblast development and haze formation after photorefractive keratectomy (PRK). METHODS: Seventeen rabbits underwent mechanical or ethanol debridement, and the opposite eye of each rabbit served as an unwounded control. In both groups, the epithelium was removed with a spatula and discarded. A -9.00-diopter PRK was performed in each eye. The level of haze in each cornea at 4 weeks was graded at the slit-lamp microscope according to the Fantes scale. Myofibroblast generation was detected with immunocytochemistry for alpha-smooth muscle actin (alpha-SMA) and cells were quantitatively analyzed. RESULTS: No difference was noted between the two groups in alpha-SMA + myofibroblasts 4 weeks after surgery (43.6 +/- 2.0/400X field and 45.7 +/- 4.8/400X field in ethanol and mechanical groups, respectively) (P=.10). A slight difference was noted but did not reach statistical significance with regard to stromal haze between ethanol and mechanical groups (2.0 +/- 0.5 and 2.3 +/- 0.4, respectively, P=.063). The ethanol and mechanical groups were statistically different when compared to controls regarding stromal haze and alpha-SMA+ cells (P <.0001 for all comparisons). CONCLUSIONS:No difference was noted in clinical haze or myofibroblast generation between corneas that had PRK with mechanical,or ethanol epithelial debridement. [J Refract Surg., 2008;24:923-927.]

Differences in the inflammatory response between patients with and those without diabetes mellitus after coronary stenting

Background: Patients with diabetes mellitus who undergo coronary stenting are at increased risk of restenosis. It is known that inflammation plays a crucial role in restenosis. Objective: We assessed the inflammatory response to elective coronary stent implantation (CSI) in stable diabetic and nondiabetic patients. Methods: C-reactive protein (CRP), soluble (s) P-selectin, and soluble intercellular adhesion molecule (sICAM)-1 plasma levels were determined in diabetic (n = 51) and nondiabetic (n = 56) patients before and 48 hours and 4 weeks after bare metal stenting (BMS). Results: Diabetic patients presented significantly higher inflammatory marker levels before and after CSI. Nonetheless, diabetic and nondiabetic patients had postintervention peak of markers attained within 48 hours. At baseline, diabetic and nondiabetic patients presented CRP levels of 5.0 +/- 20.1 (P <= 0.04) and 3.8 +/- 9.4 mu g/ml and, at 48 hours postintervention, 22.0 +/- 20.2 (P = 0.001; P = 0.002) and 12.6 +/- 11.3 (P <= 0.0001) mu g/ml. Regarding sP-selectin, diabetic and nondiabetic patients obtained levels of, at baseline, 182 +/- 118 (P <= 0.04) and 105 +/- 48 ng/ml and, at 48 hours, 455 +/- 290 (P = 0.001; P <= 0.01) and 215 +/- 120 (P <= 0.04) ng/ml. For diabetic and nondiabetic patients, sICAM-1 levels were, at baseline, 248 +/- 98 (P <= 0.04) and 199 +/- 94 ng/ml and, at 48 hours, 601 +/- 201 (P = 0.001; P <= 0.01) and 283 +/- 220 (P = 0.001) ng/ml. At 4 weeks, for all patients, markers returned to preprocedural levels: versus before PCI: *P = 0.001, P <= 0.0001; versus nondiabetic patients: ^#P <= 0.04, P = 0.002, ^UpsilonP <= 0.01. Conclusions: Diabetic and nondiabetic patients exhibited a temporal inflammatory response after an elective BMS. However, diabetic patients present higher preprocedural levels of CRP, sP-selectin, and sICAM-1 and reveal a further exacerbated inflammatory response after intervention. The differences in inflammatory response may have implications in restenosis within these two sets of patients.