Predictive Factors for Positive Surgical Margins and Their Locations After Robot-Assisted Laparoscopic Radical Prostatectomy

Background: Positive surgical margin (PSM) after radical prostatectomy (RP) has been shown to be an independent predictive factor for cancer recurrence. Several investigations have correlated clinical and histopathologic findings with surgical margin status after open RP. However, few studies have addressed the predictive factors for PSM after robot-assisted laparoscopic RP (RARP). Objective: We sought to identify predictive factors for PSMs and their locations after RARP. Design, setting, and participants: We prospectively analyzed 876 consecutive patients who underwent RARP from January 2008 to May 2009. Intervention: All patients underwent RARP performed by a single surgeon with previous experience of > 1500 cases. Measurements: Stepwise logistic regression was used to identify potential predictive factors for PSM. Three logistic regression models were built: (1) one using preoperative variables only, (2) another using all variables (preoperative, intraoperative, and postoperative) combined, and (3) one created to identify potential predictive factors for PSM location. Preoperative variables entered into the models included age, body mass index (BMI), prostate-specific antigen, clinical stage, number of positive cores, percentage of positive cores, and American Urological Association symptom score. Intra-and postoperative variables analyzed were type of nerve sparing, presence of median lobe, percentage of tumor in the surgical specimen, gland size, histopathologic findings, pathologic stage, and pathologic Gleason grade. Results and limitations: In the multivariable analysis including preoperative variables, clinical stage was the only independent predictive factor for PSM, with a higher PSM rate for T3 versus T1c (odds ratio [OR]: 10.7; 95% confidence interval [CI], 2.6-43.8) and for T2 versus T1c (OR: 2.9; 95% CI, 1.9-4.6). Considering pre-, intra-, and postoperative variables combined, percentage of tumor, pathologic stage, and pathologic Gleason score were associated with increased risk of PSM in the univariable analysis (p < 0.001 for all variables). However, in the multivariable analysis, pathologic stage (pT2 vs pT1; OR: 2.9; 95% CI, 1.9-4.6) and percentage of tumor in the surgical specimen (OR: 8.7; 95% CI, 2.2-34.5; p = 0.0022) were the only independent predictive factors for PSM. Finally, BMI was shown to be an independent predictive factor(OR: 1.1; 95% CI, 1.0-1.3; p = 0.0119) for apical PSMs, with increasing BMI predicting higher incidence of apex location. Because most of our patients were referred from other centers, the biopsy technique and the number of cores were not standardized in our series. Conclusions: Clinical stage was the only preoperative variable independently associated with PSM after RARP. Pathologic stage and percentage of tumor in the surgical specimen were identified as independent predictive factors for PSMs when analyzing pre-, intra-, and postoperative variables combined. BMI was shown to be an independent predictive factor for apical PSMs. (C) 2010 European Association of Urology. Published by Elsevier B. V. All rights reserved.

Alteration of cortical excitability in patients with fibromyalgia

We assessed cortical excitability and intracortical modulation systematically, by transcranial magnetic stimulation (TMS) of the motor cortex, in patients with fibromyalgia. In total 46 female patients with fibromyalgia and 21 normal female subjects, matched for age, were included in this study. TMS was applied to the hand motor area of both hemispheres and motor evoked potentials (MEPs) were recorded for the first interosseous muscle of the contralateral hand. Single-pulse stimulation was used for measurements of the rest motor threshold (RMT) and suprathreshold MEP. Paired-pulse stimulation was used to assess short intracortical inhibition (SICI) and intracortical facilitation (ICF). Putative correlations were sought between changes in electrophysiological parameters and major clinical features of fibromyalgia, such as pain, fatigue, anxiety, depression and catastrophizing. The RMT on both sides was significantly increased in patients with fibromyalgia and suprathreshold MEP was significantly decreased bilaterally. However, these alterations, suggesting a global decrease in corticospinal excitability, were not correlated with clinical features. Patients with fibromyalgia also had lower ICF and SICI on both sides, than controls, these lower values being correlated with fatigue, catastrophizing and depression. These neurophysiological alterations were not linked to medication, as similar changes were observed in patients with or without psychotropic treatment. In conclusion, fibromyalgia is associated with deficits in intracortical modulation involving both GABAergic and glutamatergic mechanisms, possibly related to certain aspects of the pathophysiology of this chronic pain syndrome. Our data add to the growing body of evidence for objective and quantifiable changes in brain function in fibromyalgia. (C) 2010 International Association for the Study of Pain. Published by Elsevier B. V. All rights reserved.

Effects of bone remodelling on calcium mass transfer during haemodialysis

Background. During haemodialysis, calcium balance can affect, or be affected by, mineral metabolism. However, when dialysate calcium concentration (d[Ca]) is chosen or kinetic models are employed to calculate calcium balance, bone remodelling is rarely considered. In this study, we examined whether bone remodelling affects calcium mass transfer during haemodialysis. Methods. We dialysed 23 patients using a d[Ca] of 1.0, 1.25, 1.5 or 1.75 mmol/L. Calcium mass transfer was measured and associated with remodelling bone factors. Results. Calcium balance varied widely depending on the d[Ca]. Calcium removal was -578 +/- 389, -468 +/- 563, +46 +/- 400 and +405 +/- 413 mg when a d[Ca] of 1.0, 1.25, 1.5 or 1.75 mmol/L was used, respectively (1.0 and 1.25 VS 1.5 and 1.75 mmol/L, P<0.001; 1.5 vs 1.75 mmol/L, P<0.05). Univariate analysis showed that calcium balance correlated with calcium gradient, parathyroid hormone (PTH), osteocalcin and dialysis vintage. Multivariate analysis revealed that calcium balance was dependent on calcium gradient, PTH and osteocalcin. Conclusions. These results suggest that bone remodelling could affect calcium mass transfer during haemodialysis.

Increased number and function of natural killer cells in human immunodeficiency virus 1-positive subjects co-infected with herpes simplex virus 2

P>Natural killer (NK) cells bridge the interface between innate and adaptive immunity and are implicated in the control of herpes simplex virus 2 (HSV-2) infection. In subjects infected with human immunodeficiency virus 1 (HIV-1), the critical impact of the innate immune response on disease progression has recently come into focus. Higher numbers of NK cells are associated with lower HIV-1 plasma viraemia. Individuals with the compound genotype of killer cell immunoglobulin-like receptor (KIR) 3DS1 and human leucocyte antigen (HLA)-Bw4-80I, or who have alleles of KIR3DL1 that encode proteins highly expressed on the NK cell surface, have a significant delay in disease progression. We studied the effect of HSV-2 co-infection in HIV-1-infected subjects, and show that HSV-2 co-infection results in a pan-lymphocytosis, with elevated absolute numbers of CD4+ and CD8+ T cells, and NK cells. The NK cells in HSV-2 co-infected subjects functioned more efficiently, with an increase in degranulation after in vitro stimulation. The number of NK cells expressing the activating receptors NKp30 and NKp46, and expressing KIR3DL1 or KIR3DS1, was inversely correlated with HIV-1 plasma viral load in subjects mono-infected with HIV-1, but not in subjects co-infected with HSV-2. This suggests that HSV-2 infection mediates changes within the NK cell population that may affect immunity in HIV-1 infection.

Thermoregulatory Efficiency is Increased after Heat Acclimation in Tropical Natives

To evaluate the effects of heat acclimation on sweat rate redistribution and thermodynamic parameters, 9 tropical native volunteers were submitted to 11 days of exercise-heat exposures (40 +/- 0 degrees C and 45.1 +/- 0.2% relative humidity). Sudomotor function was evaluated by measuring total and local (forehead, chest, arm, forearm, and thigh) sweat rates, local sweat sodium concentration, and mean skin and rectal temperatures. We also calculated heat production (H), heat storage (S), heat exchange by radiation (R) and by convection (C), evaporated sweat (E(sw)), sweating efficiency (eta(sw)), skin wettedness (w(sk)), and the ratio between the heat storage and the sum of heat production and heat gains by radiation and convection (S/(H+R+C)). The heat acclimation increased the whole-body sweat rate and reduced the mean skin temperature. There were changes in the local sweat rate patterns: on the arm, forearm, and thigh it increased significantly from day 1 to day 11 (all p<0.05) and the sweat rates from the forehead and the chest showed a small nonsignificant increase (p=0.34 and 0.17, respectively). The relative increase of local sweat rates on day 11 was not different among the sites; however, when comparing the limbs (arm, forearm, and thigh) with the trunk (forehead and chest), there was a significant higher increase in the limbs (32 +/- 5%) in comparison to the trunk (11 +/- 2%, p=0.001). After the heat acclimation period we observed higher w(sk) and E(sw) and reduced S/(H+R+C), meaning greater thermoregulatory efficiency. The increase in the limb sweat rate, but not the increase in the trunk sweat rate, correlated with the increased w(sk), E(sw), and reduced S/(H+R+C) (p<0.05 to all). Altogether, it can be concluded that heat acclimation increased the limbs` sweat rates in tropical natives and that this increase led to increased loss of heat through evaporation of sweat and this higher sweat evaporation was related to higher thermoregulatory efficiency. J Physiol Anthropol 29(1): 1-12, 2010 http://www.jstage.jst.go.jp/browse/jpa2 [DOI: 10.2114/jpa2.29.1]

Normal metabolite levels in the left dorsolateral prefrontal cortex of unmedicated major depressive disorder patients: A single voxel (1)H spectroscopy study

Few proton magnetic resonance spectroscopy ((1)H spectroscopy) studies have investigated the dorsolateral prefrontal cortex (DLPFC), a key region in the pathophysiology of major depressive disorder (MDD). We used (1)H spectroscopy to verify whether MDD patients differ from healthy controls (HQ in metabolite levels in this brain area. Thirty-seven unmedicated DSM-IV MDD patients were compared with 40 HC. Subjects underwent a short echo-time (1)H spectroscopy examination at 1.5 T, with an 8-cm(3) single voxel placed in the left DLPFC. Reliable absolute metabolite levels of N-acetyl aspartate (NAA), phosphocreatine plus creatine (PCr+Cr), choline-containing compounds (GPC+PC), myo-inositol, glutamate plus glutamine (Glu+Gln), and glutamate were obtained using the unsuppressed water signal as an internal reference. Metabolite levels in the left DLPFC did not statistically differ between MDD patients and HC. We found an interaction between gender and diagnosis on PCr+Cr levels. Male MDD patients presented lower levels of PCr+Cr than male HC, and female MDD patients presented higher levels of PCr+Cr than female HC. Moreover, length of illness was inversely correlated with NAA levels. These findings suggest that there is not an effect of diagnosis on the left DLPFC neurochemistry. Possible effects of gender on PCr+Cr levels of MDD patients need to be further investigated. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Cerebrospinal fluid levels of chemokines in HIV infected patients with and without opportunistic infection of the central nervous system

Chemokines are chemoattractant cytokines involved in the immune response of a wide variety of diseases. There are few studies assessing their role in opportunistic infections in HIV-infected patients. In this study, we measured CC and CXC chemokines in cerebrospinal fluid (CSF) samples obtained from 40 HIV-infected patients with or without opportunistic infections of the central nervous system (CNS). CSF samples were also analyzed for quantification of total protein, cell count and HIV-1 RNA. HIV+ patients with cryptococcal meningitis had higher levels of CCL2, CCL3, CCL5, CXCL9 and CXCL10 when compared to patients without opportunistic neurological infections. Furthermore, HIV+ patients with associated cryptococcal meningitis had higher levels of CCL3, CXCL9 and CXCL10 when compared to HIV+ patients with associated toxoplasmic encephalitis. CCL3 and CXCL9 levels were positively correlated with CSF HIV-1 RNA levels, CSF protein concentration, and CSF cell count. CXCL10 level was correlated with the CSF viral load and the CSF cell count and CCL5 level was correlated with the CSF cell count. In conclusion, the profile of chemokines in CSF of HIV patients may differ according to the modality of the presented opportunistic infection and according to other biological markers, such as viral load in CSF. These differences are probably related to different patterns of neuroinflammatory responses displayed by patients with different opportunistic neurological infections. (C) 2009 Elsevier B.V. All rights reserved.

Final height of adults with childhood-onset steroid-responsive idiopathic nephrotic syndrome

The aim of this study was to evaluate the final stature of adults with childhood-onset steroid-responsive idiopathic nephrotic syndrome (INS) and the influence of disease-related issues on the achievement of their target heights. We analyzed 60 (41 male) patients and/or their records, with a minimum age of 19 years or at a Tanner`s pubertal stage 4 for boys or status postmenarche for girls, and normal glomerular filtration rate. Mean age at first and last consultation was 5.3 +/- 2.4 years and 20.5 +/- 3.1 years, respectively. Mean follow-up period was 15.10 years. Mean cumulative dose of prednisone was 1254 +/- 831.40 mg/kg. Mean initial and final height Z scores (HtZ) were, respectively, -0.60 +/- 1.0 and -0.64 +/- 0.92 (p = 0.72). The final HtZ showed a significant correlation only with the initial HtZ and the target HtZ (THZ). Six patients achieved a final HtZ below -2, which in male patients correlated strongly to the initial HtZ and THZ. A strong correlation was demonstrated between final HtZ, initial HtZ, and THZ. INS-related issues did not prevent the final stature to reach the predicted target height.

Molecular cloning and characterization of a ripening-induced polygalacturonase related to papaya fruit softening

Pulp softening is one of the most remarkable changes during ripening of papaya (Carica papaya) fruit and it is a major cause for post-harvest losses. Although cell wall catabolism has a major influence on papaya fruit, quality information on the gene products involved in this process is limited. A full-length polygalacturonase cDNA (cpPG) was isolated from papaya pulp and used to study gene expression and enzyme activity during normal and ethylene-induced ripening and after exposure of the fruit to 1-MCP. Northern-blot analysis demonstrated that cpPG transcription was strongly induced during ripening and was highly ethylene-dependent. The accumulation of cpPG transcript was paralleled by enzyme activity, and inversely correlated to the pulp firmness. Preliminary in silica analysis of the cpPG genomic sequence revealed the occurrence of putative regulatory motifs in the promoter region that may help to explain the effects of plant hormones and non-abiotic stresses on papaya fruit firmness. This newly isolated cpPG is an important candidate for functional characterization and manipulation to control the process of pulp softening during papaya ripening. (C) 2009 Elsevier Masson SAS. All rights reserved.

Ultrasound evaluation of prognosis in fetuses with posterior urethral valves

Purpose: The aim of this study was to evaluate the ability of prenatal ultrasound markers to predict postnatal renal prognosis in fetuses with posterior urethral valves. Methods: Medical files on fetuses with prenatal diagnosis of posterior urethral valves from 2000 to 2006 were reviewed retrospectively. Data from prenatal follow-up included gestational age at diagnosis, ultrasound renal parenchyma evaluation, and presence and time of oligohydramnios onset. Prenatal parameters studied were correlated to postnatal renal function. Results: Thirty-one male fetuses were included. Six pregnancies were terminated. Of the remaining 25 pregnancies that were continued, 4 children had abnormal creatine and 21 normal creatinine levels at follow-up. Presence and time of oligohydramnios onset did not differ between groups (P = .43). Ultrasound detected bilateral renal abnormalities in 3 fetuses (75%) with altered renal function, and 10 fetuses (55%) with normal creatinine, at follow-up. Conclusions: None of the ultrasound parameters evaluated were able to reliably predict postnatal renal function. (C) 2011 Elsevier Inc. All rights reserved.

Maternal alcohol consumption may influence cord blood ascorbic acid concentration: findings from a study of Brazilian mothers and their newborns

Studies that have investigated ascorbic acid (AA) concentrations in cord blood have pointed to significant associations with maternal blood AA concentrations. smoking, age, diet, type of delivery, duration of gestation, fetal distress and birth weight. The aim of the present study was to determine the relationship between cord blood AA concentrations in newborns and maternal characteristics. A total of 117 Brazilian healthy parturients were included in this cross-sectional study. The concentrations of AA in blood were determined by the HPLC method. Data concerning socio-economic, demographic, obstetric, nutritional and health characteristics of the parturients, including alcohol consumption and smoking habit, were assessed by a standardised questionnaire. A FFQ was used to investigate the intake of foods rich in vitamin C. Cord blood AA concentration was significantly correlated with per capita income (r 0.26; P=0.005), maternal blood AA concentration (r 0.48; P<0.001) and maternal vitamin C-rich food intake score (r 0.36; P<0.001). The linear regression model including maternal AA concentration, alcohol consumption, smoking, parity, vitamin C-rich food intake score and per capita income explained 31.13% of the variation in cord blood AA concentrations in newborns. We recommend further experimental studies to assess the effects of ethanol on placental AA uptake, and epidemiological cohort studies to evaluate in detail the influence of maternal alcohol consumption on cord blood AA concentrations.

Lower cytokine secretion ex vivo by natural killer T cells in HIV-infected individuals is associated with higher CD161 expression

Objective: Natural killer T (NKT) cells are efficiently targeted by HIV and severely reduced in numbers in the circulation of infected individuals. The functional capacity of the remaining NKT cells in HIV-infected individuals is poorly characterized. This study measured NKT cell cytokine production directly ex vivo and compared these responses with both the disease status and NKT subset distribution of individual patients. Methods: NKT cell frequencies, subsets, and ex-vivo effector functions were measured in the peripheral blood mononuclear cells of HIV-infected patients and healthy controls by flow cytometry. We measured cytokines from NKT cells after stimulation with either a-galactosyl ceramide-loaded CD1d dimers (DimerX-alpha GalCer) or phorbol myristate acetate and ionomycin. Results: The frequencies of NKT cells secreting interferon-gamma and tumor necrosis factor-alpha were significantly lower in HIV-infected patients than healthy controls after DimerX-alpha GalCer treatment, but responses were similar after treatment with phorbol myristate acetate and ionomycin. The magnitude of the interferon-gamma response to DimerX-alpha GalCer correlated inversely with the number of years of infection. Both interferon-gamma and tumor necrosis factor-alpha production in response to DimerX-alpha GalCer correlated inversely with CD161 expression. Conclusion: The ex-vivo Th1 responses of circulating NKT cells to CD1d-glycolipid complexes are impaired in HIV-infected patients. NKT cell functions may be progressively lost over time in HIV infection, and CD161 is implicated in the regulation of NKT cell responsiveness. (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins

Anterior cingulate volumes associated with trait impulsivity in individuals with bipolar disorder

Objective: Impulsivity is associated with the clinical outcome and likelihood of risky behaviors among bipolar disorder (BD) patients. Our previous study showed an inverse relationship between impulsivity and orbitofrontal cortex (OFC) volume in healthy subjects. We hypothesized that BD patients would show an inverse relationship between impulsivity and volumes of the OFC, anterior cingulate cortex (ACC), medial prefrontal cortex, and amygdala, which have been implicated in the pathophysiology of BD. Methods: Sixty-three BD patients were studied (mean +/- SD age = 38.2 +/- 11.5 years; 79% female). The Barratt Impulsiveness Scale (BIS), version 11A, was used to assess trait impulsivity. Images were processed using SPM2 and an optimized voxel-based morphometry protocol. We examined the correlations between BIS scores and the gray matter (GM) and white matter (WM) volumes of the prespecified regions. Results: Left rostral ACC GM volume was inversely correlated with the BIS total score (t = 3.95, p(corrected) = 0.003) and the BIS motor score (t = 5.22, p(corrected) < 0.001). In contrast to our hypothesis, OFC volumes were not significantly associated with impulsivity in BD. No WM volume of any structure was significantly correlated with impulsivity. No statistical association between any clinical variable and the rostral ACC GM volumes reached significance. Conclusions: Based on our previous findings and the current results, impulsivity may have a different neural representation in BD and healthy subjects, and the ACC may be involved in the pathophysiology of abnormal impulsivity regulation in BD patients.

Performance of Brazilian long and short IQCODE on the screening of dementia in elderly people with low education

Background: Dementia screening in elderly people with low education can be difficult to implement. For these subjects, informant reports using the long (L) (26 items) and short (C) (16 items) versions of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) can be useful. The objective of the present study was to investigate the performance of Brazilian versions of the IQCODE L, S and a new short version (SBr) (15 items) in comparison with the Mini-mental State Examination (MMSE) for dementia screening in elderly people with low education. Methods: Thirty-four patients with mild to moderate dementia, diagnosed according to ICD-10 criteria, and 57 controls were evaluated and divided into three groups based on their socioeconomic status and level of education. Patients were evaluated using the MMSE and the informants were interviewed using the IQCODE by interviewers blind to the clinical diagnosis. Results: Education was correlated with MMSE results (r = 0.280, p = 0.031), but not with the versions of the IQCODE. The performance of the instruments, evaluated by the ROC curves, was very similar, with good internal consistency (Cronbach`s alpha = 0.97). MMSE correctly classified 85.7% of the subjects while the three IQCODE versions (L, S and SBr) correctly classified 91.2% of the subjects. Conclusions: The long, short and the new short Brazilian IQCODE versions can be useful as a screening tool for mild and moderate patients with dementia in Brazil. The IQCODE is not biased by schooling, and it seems to be an adequate instrument for samples with low levels of education.

The frequency of anti-beta(2)-glycoprotein I antibodies is low and these antibodies are associated with pulmonary hypertension in mixed connective tissue disease

The objective of this study is to evaluate the prevalence of antiphospholipid antibodies, mainly anti-beta(2)-glycoprotein I (anti-beta(2)-GPI), and their possible clinical and laboratory relevance in mixed connective tissue disease (MCTD). This study included 39 consecutive patients with MCTD (Kasukawa`s criteria) from January, 2005, to March, 2007, and compared them with 21 age- and sex-matched healthy controls. IgG and IgM anticardiolipin (aCL) and anti-beta(2)-GPI were measured by ELISA. Lupus anticoagulant (LA) was detected by functional coagulation tests. Medium to high titres of aCL and anti-beta(2)-GPI antibodies were found in sera from four (10.2%) MCTD patients. One of these patients was found to be positive for IgM aCL, IgM anti-beta(2)-GPI and LA antibodies simultaneously. Additionally, this patient had a previous history of foetal loss in the second trimester and new-onset pulmonary arterial hypertension (PAH). The other three patients had none of the manifestations of antiphospholipid syndrome (APS) or PAH. The mean value of IgG anti-beta(2)-GPI was higher among those MCTD patients with PAH than in the group without PAH (34.2 +/- 46.8 vs 12.3 +/- 9.1, P = 0.018). None of the controls were positive for antiphospholipid antibodies. High to moderate titres of anti-beta(2)-GPI as well as APS were rare in MCTD, and these antibodies may be correlated with the development of PAH in these patients. Lupus (2009) 18, 618-621.