Long-term follow-up of children with extrahepatic portal vein obstruction: impact of an endoscopic sclerotherapy program on bleeding episodes, hepatic function, hypersplenism, and mortality

Background: Endoscopic sclerotherapy (ES) has been the standard treatment for children with idiopathic extrahepatic portal vein obstruction (EHPVO). Portosystemic shunts are indicated when variceal bleeding cannot be controlled by ES. Recently, mesenteric left portal vein bypass was indicated as a surgical intervention and preventative measure for hepatic dysfunction in children with long-term EHPVO. Nevertheless, there is a lack Of published data confirming the extent of hepatic dysfunction, hypersplenism, and physical development in children with long-term follow-up. Method: We retrospectively verified the long-term outcomes in 82 children with EHPVO treated with ES protocol, focusing on mortality, control of bleeding, hypersplenism, and consequent hepatic dysfunction. Results: Of the children, 56% were free from bleeding after the initiation of ES. The most frequent cause of rebleeding was gastric varices (30%). Four patients had recurrent bleeding from esophageal varices (4.6%). Four patients underwent surgery as a consequence of uncontrolled gastric varices. There were no deaths. Most patients showed good physical development. We observed a mild but statistically significant drop in factor V motion, as well as leukocyte and platelet count. Conclusion: Endoscopic sclerotherapy is an efficient treatment for children with EHPVO. The incidence of rebleeding is low, and there was no mortality. Children develop mild liver dysfunction and hypersplenism with long-term follow-up. Only a few patients manifest symptoms of hypersplenism, portal biliopathy, or liver dysfunction before adolescence. (C) 2009 Elsevier Inc. All rights reserved.

Lower N-Acetyl-Aspartate Levels in Prefrontal Cortices in Pediatric Bipolar Disorder: A (1)H Magnetic Resonance Spectroscopy Study

Objective: The few studies applying single-voxel(1)H spectroscopy in children and adolescents with bipolar disorder (BD) have reported low N-acetyl-aspartate (NAA) levels in the dorsolateral prefrontal cortex (DLPFC), and high myo-inositol / phosphocreatine plus creatine (PCr+Cr) ratios in the anterior cingulate. The aim of this study was to evaluate NAA, glycerophosphocholine plus phosphocholine (GPC+PC) and PCr+Cr in various frontal cortical areas in children and adolescents with BD. We hypothesized that NAA levels within the prefrontal cortex are lower in BD patients than in healthy controls, indicating neurodevelopmental alterations in the former. Method: We studied 43 pediatric patients with DSM-IV BD (19 female, mean age 13.2 +/- 2.9 years) and 38 healthy controls (79 female, mean age 13.9 +/- 2.7 years). We conducted multivoxel in vivo (1)H spectroscopy measurements at 1.5 Tesla using a long echo time of 272 ms to obtain bilateral metabolite levels from the medial prefrontal cortex (MPFC), DLPFC (white and gray matter), cingulate (anterior and posterior), and occipital lobes. We used the nonparametric Mann-Whitney U test to compare neurochemical levels between groups. Results: In pediatric BD patients, NAA and GPC+PC levels in the bilateral MPFC, and PCr+Cr levels in the left MPFC were lower than those seen in the controls. In the left DLPFC white matter, levels of NAA and PCr+Cr were also lower in BD patients than in controls. Conclusions: Lower NAA and PCr+Cr levels in the PFC of children and adolescents with BD may be indicative of abnormal dendritic arborization and neuropil, suggesting neurodevelopmental abnormalities. J. Am. Acad. Child Adolesc. Psychiatry, 2011;50(1):85-94.

Patients Receiving Physical Rehabilitation: Records of Sexual Function Before the Introduction of Erectogenic Drugs

The objective of this study is to evaluate the entries associated to the sexual function of patients undergoing physical disability rehabilitation, as well as the course of changes and medical approach through a retrospective review of medical charts. Methods: Medical records referring to the period between July and September, 1998 were evaluated. The data was divided into two groups, records containing physician`s entries on sexual function and/or entries of other health care professionals. The following aspects were investigated: whether complaints were spontaneously voiced by the patient, and whether diagnosis had been reached, with corresponding management. Results: Out of 245 medical records investigated, 17 (6.9%) contained clinical observations on the sexual function; out of those, 14 reached diagnosis. Twelve records (4.9%) had information by non-medical healthcare professionals. Out of 17 entries by doctors, 16 referred to male patients, which was found to be significant (p = 0.0202). Conclusions: Records for the sexual function of patients undergoing physical rehabilitation are scarce. In this population, the sexual function of male patients had more extensive investigation on the part of physicians when compared to other health care professionals.

Prevalence of Erectile Dysfunction as Defined by the International Index of Erectile Function (IIEF) and Self-Reported Erectile Dysfunction in a Sample of Brazilian Men Who Consider Themselves Healthy

A cross-sectional study was carried out with 288 male blood donors, aged between 40 and 60 years old, with the aim of comparing the prevalence of erectile dysfunction (ED) as defined by the International Index of Erectile Function (IIEF) and that resulting from the simple questioning of the presence of ED. Socio-demographic, clinical, and behavioral factors that are associated with the presence of ED were considered. Erectile dysfunction prevalence in the IIEF was 31.9%, while self-reported ED prevalence was 3.1%. The factors associated to ED, as reported by the IIEF were: professional inactivity, suspected depression and/or anxiety, reduced sexual desired, and self-reported ED.

Expression of smooth muscle and extracellular matrix proteins in relation to airway function in asthma

Background: Smooth muscle content is increased within the airway wall in patients with asthma and is likely to play a role in airway hyperresponsiveness. However, smooth muscle cells express several contractile and structural proteins, and each of these proteins may influence airway function distinctly. Objective: We examined the expression of contractile and structural proteins of smooth muscle cells, as well as extracellular matrix proteins, in bronchial biopsies of patients with asthma, and related these to lung function, airway hyperresponsiveness, and responses to deep inspiration. Methods: Thirteen patients with asthma (mild persistent, atopic, nonsmoking) participated in this cross-sectional study. FEV1 % predicted, PC20 methacholine, and resistance of the respiratory system by the forced oscillation technique during tidal breathing and deep breath were measured. Within 1 week, a bronchoscopy was performed to obtain 6 bronchial biopsies that were immunuhistochemically stained for alpha-SM-actin, desmin, myosin light chain kinase (MLCK), myosin, calponin, vimentin, elastin, type III collagen, and fibronectin. The level of expression was determined by automated densitometry. Results: PC20 methacholine was inversely related to the expression of alpha-smooth muscle actin (r = -0.62), desmin (r = -0.56), and elastin (r = -0.78). In addition, FEV1% predicted was positively related and deep inspiration-induced bronchodilation inversely related to desmin (r = -0.60), MLCK (r = -0.60), and calponin (r = -0.54) expression. Conclusion: Airway hyperresponsiveness, FEV1% predicted, and airway responses to deep inspiration are associated with selective expression of airway smooth muscle proteins and components of the extracellular matrix.

Cholinergic Hyperresponsiveness of Peripheral Lung Parenchyma in Chronic Obstructive Pulmonary Disease

Background: Up to 60% of chronic obstructive pulmonary disease ( COPD) patients can present airway hyperresponsiveness. However, it is not known whether the peripheral lung tissue also shows an exaggerated response to agonists in COPD. Objectives: To investigate the in vitro mechanical behavior and the structural and inflammatory changes of peripheral lung tissue in COPD patients and compare to nonsmoking controls. Methods: We measured resistance and elastance at baseline and after acetylcholine (ACh) challenge of lung strips obtained from 10 COPD patients and 10 control subjects. We also assessed the alveolar tissue density of neutrophils, eosinophils, macrophages, mast cells and CD8+ and CD4+ cells, as well as the content of alpha-smooth muscle actin-positive cells and elastic and collagen fibers. We further investigated whether changes in in vitro parenchymal mechanics correlated to structural and inflammatory parameters and to in vivo pulmonary function. Results: Values of resistance after ACh treatment and the percent increase in tissue resistance (%R) were higher in the COPD group (p <= 0.03). There was a higher density of macrophages and CD8+ cells (p < 0.05) and a lower elastic content (p = 0.003) in the COPD group. We observed a positive correlation between %R and eosinophil and CD8+ cell density (r = 0.608, p = 0.002, and r = 0.581, p = 0.001, respectively) and a negative correlation between %R and the ratio of forced expiratory volume in 1 s to forced vital capacity (r = -0.451, p < 0.05). Conclusions: The cholinergic responsiveness of parenchymal lung strips is increased in COPD patients and seems to be related to alveolar tissue eosinophilic and CD8 lymphocytic inflammation and to the degree of airway obstruction on the pulmonary function test. Copyright (C) 2011 S. Karger AG, Basel

Recruitment maneuver in experimental acute lung injury: The role of alveolar collapse and edema

Objective: In acute lung injury, recruitment maneuvers have been used to open collapsed lungs and set positive end-expiratory pressure, but their effectiveness may depend on the degree of lung injury. This study uses a single experimental model with different degrees of lung injury and tests the hypothesis that recruitment maneuvers may have beneficial or deleterious effects depending on the severity of acute lung injury. We speculated that recruitment maneuvers may worsen lung mechanical stress in the presence of alveolar edema. Design: Prospective, randomized, controlled experimental study. Setting: University research laboratory. Subjects: Thirty-six Wistar rats randomly divided into three groups (n = 12 per group). Interventions: In the control group, saline was intraperitoneally injected, whereas moderate and severe acute lung injury animals received paraquat intraperitoneally (20 mg/kg [moderate acute lung injury] and 25 mg/kg [severe acute lung injury]). After 24 hrs, animals were further randomized into subgroups (n = 6/each) to be recruited (recruitment maneuvers: 40 cm H(2)O continuous positive airway pressure for 40 secs) or not, followed by 1 hr of protective mechanical ventilation (tidal volume, 6 mL/kg; positive end-expiratory pressure, 5 cm H(2)O). Measurements and Main Results: Only severe acute lung injury caused alveolar edema. The amounts of alveolar collapse were similar in the acute lung injury groups. Static lung elastance, viscoelastic pressure, hyperinflation, lung, liver, and kidney cell apoptosis, and type 3 procollagen and interleukin-6 mRNA expressions in lung tissue were more elevated in severe acute lung injury than in moderate acute lung injury. After recruitment maneuvers, static lung elastance, viscoelastic pressure, and alveolar collapse were lower in moderate acute lung injury than in severe acute lung injury. Recruitment maneuvers reduced interleukin-6 expression with a minor detachment of the alveolar capillary membrane in moderate acute lung injury. In severe acute lung injury, recruitment maneuvers were associated with hyperinflation, increased apoptosis of lung and kidney, expression of type 3 procollagen, and worsened alveolar capillary injury. Conclusions: In the presence of alveolar edema, regional mechanical heterogeneities, and hyperinflation, recruitment maneuvers promoted a modest but consistent increase in inflammatory and fibrogenic response, which may have worsened lung function and potentiated alveolar and renal epithelial injury. (Crit Care Med 2010; 38: 2207-2214)

Structural alterations in adult rat carotid bodies exposed to hyperbaric oxygenation

Inhibition of carotid body (CB) function is the main mechanism involved in the attenuation of respiratory drive observed during hyperoxia However, only a few studies at 5 0 atmospheres absolutes (ATA) have analyzed carotid body structure or function in hyperbaric oxygenation (HBO(2)) situations We hypothesized that rats will present CB structural alterations when exposed to different lower hyperbaric oxygen doses enough to alter their chemosensory response to hypoxia Methods - Twenty-one adult male Wistar rats, divided into three groups, were maintained in room air or exposed to O(2) at 2 4 or 3 0 ATA for six hours Histological, ultrastructural and immunohistochemical analyses for neuronal nitric oxide synthase (nNOS) and F2-isoprostane were performed in the excised CBs Results - Histological analyses revealed signs of intracellular edema in animals exposed to both conditions, but this was more marked in the 3 0 ATA group, which showed ultrastructural alterations at the mitochondrial level There was a significant increase in the volume density of intraglomic-congested capillaries in the 3 0 ATA group associated with an arteriolar vasoconstriction In the 2 4 ATA group, there was a relative increase of glomic light cells and a decrease of glomic progenitor cells Additionally, there was a stronger immunoreactivity for F2-isoprostane in the 3 0 ATA O(2)-exposed carotid bodies The glomic cells stained positive for nNOS, but no difference was observed between the groups Our results show that high 02 exposures may induce structural alterations in glomic cells with signs of lipid peroxidation We further suggest that deviation of blood flow toward intraglomic capillaries occurs in hyperbaric hyperoxia

Pulmonary function and histological impairment in mice after acute exposure to aluminum dust

Along the aluminum refining process, alumina (Al(2)O(3)) constitutes the main source of dust. Although aluminum refinery workers present respiratory symptoms with lung functional changes, no conclusive data about lung function impairment after alumina exposure has been so far reported. We examined the pulmonary alterations of exposure to material collected in an aluminum refinery in Brazil. BALB/c mice were exposed in a whole-body chamber for 1 h to either saline (CTRL, n = 11) or to a suspension (in saline) of 8 mg/m(3) of the dust (ALUM, n = 11) both delivered by an ultrasonic nebulizer. Twenty-four hours after exposure lung mechanics were measured by the end-inflation method. Lungs were prepared for histology. ALUM showed significantly higher static elastance (34.61 +/- 5.76 cmH(2)O/mL), elastic component of viscoelasticity (8.16 +/- 1.20 cmH(2)O/mL), pressure used to overcome the resistive component of viscoelasticity (1.62 +/- 0.24 cmH(2)O), and total resistive pressure (2.21 +/- 0.49 cmH(2)O) than CTRL (27.95 +/- 3.63 cmH(2)O/mL, 6.12 +/- 0.99 cmH(2)O/mL, 1.23 +/- 0.19 cmH(2)O, and 1.68 +/- 0.23 cmH(2)O, respectively). ALUM also presented significantly higher fraction area of alveolar collapse (69.7 +/- 1.2%) and influx of polymorphonuclear cells (27.5 +/- 1.1%) in lung parenchyma than CTRL (27.2 +/- 1.1% and 14.6 +/- 0.7%, respectively). The composition analysis of the particulate matter showed high concentrations of aluminum. For the first time it was demonstrated in an experimental model that an acute exposure to dust collected in an aluminum producing facility impaired lung mechanics that could be associated with inflammation.

Assisted ventilation modes reduce the expression of lung inflammatory and fibrogenic mediators in a model of mild acute lung injury

The goal of the study was to compare the effects of different assisted ventilation modes with pressure controlled ventilation (PCV) on lung histology, arterial blood gases, inflammatory and fibrogenic mediators in experimental acute lung injury (ALI). Paraquat-induced ALI rats were studied. At 24 h, animals were anaesthetised and further randomized as follows (n = 6/group): (1) pressure controlled ventilation mode (PCV) with tidal volume (V (T)) = 6 ml/kg and inspiratory to expiratory ratio (I:E) = 1:2; (2) three assisted ventilation modes: (a) assist-pressure controlled ventilation (APCV1:2) with I:E = 1:2, (b) APCV1:1 with I:E = 1:1; and (c) biphasic positive airway pressure and pressure support ventilation (BiVent + PSV), and (3) spontaneous breathing without PEEP in air. PCV, APCV1:1, and APCV1:2 were set with P (insp) = 10 cmH(2)O and PEEP = 5 cmH(2)O. BiVent + PSV was set with two levels of CPAP [inspiratory pressure (P (High) = 10 cmH(2)O) and positive end-expiratory pressure (P (Low) = 5 cmH(2)O)] and inspiratory/expiratory times: T (High) = 0.3 s and T (Low) = 0.3 s. PSV was set as follows: 2 cmH(2)O above P (High) and 7 cmH(2)O above P (Low). All rats were mechanically ventilated in air and PEEP = 5 cmH(2)O for 1 h. Assisted ventilation modes led to better functional improvement and less lung injury compared to PCV. APCV1:1 and BiVent + PSV presented similar oxygenation levels, which were higher than in APCV1:2. Bivent + PSV led to less alveolar epithelium injury and lower expression of tumour necrosis factor-alpha, interleukin-6, and type III procollagen. In this experimental ALI model, assisted ventilation modes presented greater beneficial effects on respiratory function and a reduction in lung injury compared to PCV. Among assisted ventilation modes, Bi-Vent + PSV demonstrated better functional results with less lung damage and expression of inflammatory mediators.

Implications of prevalent and incident diabetes mellitus on left ventricular geometry and function in the ageing heart: The MONICA/KORA Augsburg cohort study

Background and Aim: It is unclear to what extent diabetes modulates the ageing-related adaptations of cardiac geometry and function. Methods and Results: We examined 1005 adults, aged 25-74 years, from a population-based survey at baseline in 1994/5 and at follow-up in 2004/5. We compared persistently non-diabetic individuals (ND; no diabetes at baseline and at follow-up, n = 833) with incident (ID; non-diabetic at baseline and diabetic at follow-up, n = 36) and with prevalent diabetics (PD; diabetes at baseline and follow-up examination, n = 21). Left ventricular (LV) geometry and function were evaluated by echocardiography. Statistical analyses were performed with multivariate linear regression models. Over ten years the PD group displayed a significantly stronger relative increase of LV mass (+9.34% vs. +23.7%) that was mediated by a more pronounced increase of LV end-diastolic diameter (+0% vs. +6.95%) compared to the ND group. In parallel, LA diameter increased (+4.50% vs. +12.7%), whereas ejection fraction decreased (+3.02% vs. -4.92%) more significantly in the PD group. Moreover, at the follow-up examination the PD and ID groups showed a significantly worse diastolic function, indicated by a higher E/EM ratio compared with the ND group (11.6 and 11.8 vs. 9.79, respectively). Conclusions: Long-standing diabetes was associated with an acceleration of age-related changes of left ventricular geometry accumulating in an eccentric remodelling of the left ventricle. Likewise, echocardiographic measures of systolic and diastolic ventricular function deteriorated more rapidly in individuals with diabetes. (C) 2009 Elsevier B.V. All rights reserved.

Circulating levels of brain-derived neurotrophic factor: correlation with mood, cognition and motor function

Brain-derived neurotrophic factor (BDNF) is the most widely distributed neurotrophin in the CNS, where it plays several pivotal roles in synaptic plasticity and neuronal survival. As a consequence, BDNF has become a key target in the physiopathology of several neurological and psychiatric diseases. Recent studies have consistently reported altered levels of BDNF in the circulation (i.e., serum or plasma) of patients with major depression, bipolar disorder, Alzheimer`s disease, Huntington`s disease and Parkinson`s disease. Correlations between serum BDNF levels and affective, cognitive and motor symptoms have also been described. BDNF appears to be an unspecific biomarker of neuropsychiatric disorders characterized by neurodegenerative changes.

Posttranslational mechanisms associated with reduced NHE3 activity in adult vs. young prehypertensive SHR

Crajoinas RO, Lessa LMA, Carraro-Lacroix LR, Davel APC, Pacheco BPM, Rossoni LV, Malnic G, Girardi ACC. Posttranslational mechanisms associated with reduced NHE3 activity in adult vs. young prehypertensive SHR. Am J Physiol Renal Physiol 299:F872-F881, 2010. First published July 14, 2010; doi:10.1152/ajprenal.00654.2009.-Abnormalities in renal proximal tubular (PT) sodium transport play an important role in the pathophysiology of essential hypertension. The Na(+)/H(+) exchanger isoform 3 (NHE3) represents the major route for sodium entry across the apical membrane of renal PT cells. We therefore aimed to assess in vivo NHE3 transport activity and to define the molecular mechanisms underlying NHE3 regulation before and after development of hypertension in the spontaneously hypertensive rat (SHR). NHE3 function was measured as the rate of bicarbonate reabsorption by means of in vivo stationary microperfusion in PT from young prehypertensive SHR (Y-SHR; 5-wk-old), adult SHR (A-SHR; 14-wk-old), and age-matched Wistar Kyoto (WKY) rats. We found that NHE3-mediated PT bicarbonate reabsorption was reduced with age in the SHR (1.08 +/- 0.10 vs. 0.41 +/- 0.04 nmol/cm(2)xs), while it was increased in the transition from youth to adulthood in the WKY rat (0.59 +/- 0.05 vs. 1.26 +/- 0.11 nmol/cm(2)xs). Higher NHE3 activity in the Y-SHR compared with A-SHR was associated with a predominant microvilli confinement and a lower ratio of phosphorylated NHE3 at serine-552 to total NHE3 (P-NHE3/total). After development of hypertension, P-NHE3/total increased and NHE3 was retracted out of the microvillar microdomain along with the regulator dipeptidyl peptidase IV (DPPIV). Collectively, our data suggest that the PT is playing a role in adapting to the hypertension in the SHR. The molecular mechanisms of this adaptation possibly include an increase of P-NHE3/total and a redistribution of the NHE3-DPPIV complex from the body to the base of the PT microvilli, both predicted to decrease sodium reabsorption.