Genetic causes of PD: A pathway to disease modification.

The underline neuropathology of Parkinson disease is pleiomorphic and its genetic background diverse. Possibly because of this heterogeneity, no effective disease modifying therapy is available. In this paper we give an overview of the genetics of Parkinson disease and explain how this is relevant for the development of new therapies. This article is part of the special issue entitled 'The Quest for Disease-Modifying Therapies for Neurodegenerative Disorders'.

Physicochemical evaluation of acid-base disorders after liver transplantation and the contribution from administered fluids.

OBJECTIVES: To analyze the mechanism of acid-base disorders in liver transplant recipients and to examine the relationship between these disorders and the fluids administered during surgery. METHODS: This prospective study in a university-affiliated hospital intensive care unit (ICU) included 52 patients admitted to the ICU from December 2009 to January 2011. We examined the contributions of inorganic ion differences, lactate, unmeasured anions, phosphate, and albumin to metabolic acidosis. In addition to laboratory variables, we collected demographic and clinical data. RESULTS: Metabolic acidosis (standard base excess ≤ -2.0 mmol/L) was identified in 37 (71.2%) patients during the immediate postoperative period. The inorganic ion difference was the main determinant of acidosis, accounting for -6.17 mEq/L of acidifying effect. The acidemia was attenuated mainly by the alkalinizing effect of albumin reduction, which contributed +6.03 mEq/L. There was an inverse proportional relationship between the quantity of saline solution used during surgery and the inorganic ion difference during the immediate postoperative period. CONCLUSIONS: Hyperchloremia is the primary contributor to metabolic acidosis in liver transplant recipients. Possibly the use of chloride-rich solutions increases the incidence of this disorder.

Influência das condições ambientais na transmissão da leptospirose entre criações de ovinos e bovinos da região de Sorocaba, SP / The influence of environment conditions on the transmission of leptospirosis between sheep and cattle herds of Sorocaba region, SP, Brazil

Leptospiras excretadas pela urina podem sobreviver por longos períodos em águas de superfície e solos, na dependência do pH e teor de umidade e de matéria orgânica. Investigou-se a influência do meio ambiente na transmissão da leptospirose em dois rebanhos exclusivos de ovinos (A e C) e dois de ovinos consorciados com bovinos (F e H) da região de Sorocaba, SP, no período de dezembro de 2007 a setembro de 2008. Foram examinadas amostras de soro pela reação de soroaglutinação microscópica; de urina, água e solo pelo cultivo para leptospiras e urina de ovinos pela PCR. Condições edafoclimáticas, pH das águas de superfície e solo, granulometria e permeabilidade do solo foram analisadas. Todos os rebanhos apresentaram pelo menos um animal sororeagente para Leptospira spp. Apenas a PCR de um pool de urina de ovinos (H) foi positiva. Leptospira spp. foi isolada do lago de F. O pH das águas de superfície variou entre 6,0-7,0; e nos solos entre 4,5 e 6,8. Os índices de matéria orgânica em A, C e H variaram de 24 a 35 g/dm3, e 63 g/dm3 em F. A composição do solo de A e F mostrou-se franco-argiloarenosa, C argilosa e H franco-siltosa; como texturas mistas são capazes de manter a umidade, principalmente devido a argila. Diante da presença de animais sororeatores e portanto da circulação de Leptospira spp. nos rebanhos, conclui-se que o ciclo de transmissão é dependente da interação sinérgica e antagônica de muitas variáveis; onde o pastejo num habitat com alto teor de umidade parece ser limitante.

Leptospires excreted by urine are able to survive for long periods in surface water and soil depending on the pH, humidity and organic matter presence. This paper reported the influence of environment conditions on the transmission of leptospirosis in two sheep-only farms (A and C) and two cattle-sheep farms (F and H) from December 2007 to September 2008. Serum samples were examined by microscopic agglutination test; urine, surface water and soil samples were cultured for leptospires, and ovine urine pools were analyzed by PCR. Regional edaphoclimatic conditions, pH of surface water and soil, granulometry and permeability of soil were analyzed. All herds presented at least one reactor to Leptospira spp. Only the PCR of an ovine urine pool of herd H was positive and Leptospira spp. was isolated from the F lake. The pH of water samples ranged from 6.0 to 7.0; while in soil it was around from 4.5 to 6.8. Soil organic matter were 24 to 35 g/dm3 in A, C e H, and 63 g/dm3 in F. Soil samples of A and F showed loamy-clay texture; C had clay soil, and H loamy-silt soil; as mixed compositions are able to maintain the humidity, mainly where clay is present. As the presence of reactors in all herds indicated the contact with Leptospira spp., it was concluded that the cycle of transmission is dependent on the synergistic and antagonistic interaction of many variables; but the close contact of animals grazing in a high humidity habitat seems to be limiting.

Anatomical indicators of dominance between the coronary arteries in swine.

The interest in experimental use of coronary arteries of swine as a stage towards their application in human hearts justifies the need for obtaining a detailed anatomical understanding of those arteries, particularly to evaluate similarities and differences. However, we did not find any citations about anatomical indicators of coronary dominance among swine in the literature. Many authors have used the crux cordis and the origin of the posterior interventricular branch as references for defining three types of pattern in human hearts: right, balanced and left dominance. We used 30 hearts fixed in 10% formalin from male and female Landrace swine aged five to six months, weighing 80 to 110 kg. The branch corresponding to the subsinuosal interventricular sulcus came from the right coronary artery (96.7%) or from both coronary arteries (3.3%). The subsinuosal interventricular branch presented at least one small branch that went beyond the crux cordis. The apical area presented predominance of the paraconal interventricular (left anterior descending) branch in 43.3%, the subsinuosal interventricular branch in 23.3% and presence of both arteries in 33.3%. The left coronary artery emitted 54.5% of the ventricular branches and the right coronary artery 46.5%. Taking the crux cordis and the subsinuosal interventricular branch as references, the arterial pattern in swine hearts is right dominance. The diversity of the apical pattern and the balance in the distribution of ventricular branches do not allow this to be used as an approach in isolation. The similarities between human and swine hearts also apply to the coronary artery pattern.

Changes in severe accidental tetanus mortality in the ICU during two decades in Brazil.

INTRODUCTION: Tetanus is still a significant health hazard in developing countries, with high associated mortality. OBJECTIVE: Describe the management of patients with severe tetanus in intensive care units (ICUs), in two different periods. SETTING: ICUs of two general hospitals. DESIGN: Concurrent cohort study. METHODS: Follow-up of all patients hospitalized with the diagnosis of severe tetanus in the ICUs from October 1981 to March 2001. We collected data prospectively, regarding the site of injury, clinical features, frequent clinical and infectious complications, concomitant illnesses, and mortality. The patients were divided into two groups according to the treatment protocol used; before 1993 and after 1993. RESULTS: There were 126 patients in group 1 (93 males) with a mean age of 39.0 +/- 18.8 years. There were 110 patients in group 2 (95 males) with a mean age of 48.4+/-17.8 years. Incubation period, onset period, and symptomatic period were higher in group 2 ( P < or = 0.02). The duration of neuromuscular junction blockade, benzodiazepine administration, mechanical ventilation, and ICU stay were longer in group 2, P < 0.001. Infectious complications were more frequent in group 2 ( P < 0.001). The mortality rate in group 1 was 36.5% and in group 2, 18.0% ( P = 0.002). Mortality was directly associated with symptomatic period, acute renal failure cardiac arrest and hypotension, and inversely associated with onset period in the multivariate analyses. CONCLUSIONS: The reduced mortality in severe accidental tetanus patients in group 2 is probably related to advances in ICU management, despite the higher incidence of infectious complications, which are probably related to the longer ICU stay.

Using Geostatistical Analysis to Evaluate the Presence of Rotylenchulus reniformis in Cotton Crops in Brazil: Economic Implications.

In recent years, the productivity of cotton in Brazil has been progressively decreasing, often the result of the reniform nematode Rotylenchulus reniformis. This species can reduce crop productivity by up to 40%. Nematodes can be controlled by nematicides but, because of expense and toxicity, application of nematicides to large crop areas may be undesirable. In this work, a methodology using geostatistics for quantifying the risk of nematicide application to small crop areas is proposed. This risk, in economic terms, can be compared to nematicide cost to develop an optimal strategy for Precision Farming. Soil (300 cm(3)) was sampled in a regular network from a R. reniformis-infested area that was a cotton monoculture for 20 years. The number of nematodes in each sample was counted. The nematode number per volume of soil was characterized using geostatistics, and 100 conditional simulations were conducted. Based on the simulations, risk maps were plotted showing the areas where nematicide should be applied in a Precision Farming context. The methodology developed can be applied to farming in countries that are highly dependent on agriculture, with useful economic implications.

[Multiple recurrences of cardiac myxomas with acute tumoral pulmonary embolism]. / Múltipla recorrência de Mixomas Cardíacos com embolia pulmonar aguda.

We report the case of a 42-year-old female with a second recurrence of cardiac myxoma. Her first diagnosis was at the age of 24 years, when cardiac tumors were withdrawn from her right ventricle and left atrium. Her first recurrence was at the age of 36 years, when tumors were removed from the left and right atria, and the right ventricle. Six years later, the patient was admitted to the Hospital das Clínicas de Porto Alegre complaining of sudden dyspnea, dry cough, and pain in the right hypochondrium, which bore no relation to breathing. The transesophageal echocardiography showed a small tumor in the interatrial septum, close to the superior vena cava, and 2 larger tumors in the right ventricle, 1 close to the outflow tract and the other almost completely obstructing the right branch of the pulmonary artery. The patient was referred to surgery, in which myxomas were removed from the right atrium and ventricle with extension to the right pulmonary artery. The postoperative period was uneventful.

Expiratory washout versus optimization of mechanical ventilation during permissive hypercapnia in patients with severe acute respiratory distress syndrome.

The aim of this study was to compare three ventilatory techniques for reducing PaCO2 in patients with severe acute respiratory distress syndrome treated with permissive hypercapnia: (1) expiratory washout alone at a flow of 15 L/min, (2) optimized mechanical ventilation defined as an increase in the respiratory frequency to the maximal rate possible without development of intrinsic positive end- expiratory pressure (PEEP) combined with a reduction of the instrumental dead space, and (3) the combination of both methods. Tidal volume was set according to the pressure-volume curve in order to obtain an inspiratory plateau airway pressure equal to the upper inflection point minus 2 cm H2O after setting the PEEP at 2 cm H2O above the lower inflection point and was kept constant throughout the study. The three modalities were compared at the same inspiratory plateau airway pressure through an adjustment of the extrinsic PEEP. During conventional mechanical ventilation using a respiratory frequency of 18 breaths/min, respiratory acidosis (PaCO2 = 84 +/- 24 mm Hg and pH = 7.21 +/- 0.12) was observed. Expiratory washout and optimized mechanical ventilation (respiratory frequency of 30 +/- 4 breaths/min) had similar effects on CO2 elimination (DeltaPaCO2 = -28 +/- 11% versus -27 +/- 12%). A further decrease in PaCO2 was observed when both methods were combined (DeltaPaCO2 = -46 +/- 7%). Extrinsic PEEP had to be reduced by 5.3 +/- 2.1 cm H2O during expiratory washout and by 7.3 +/- 1.3 cm H2O during the combination of the two modes, whereas it remained unchanged during optimized mechanical ventilation alone. In conclusion, increasing respiratory rate and reducing instrumental dead space during conventional mechanical ventilation is as efficient as expiratory washout to reduce PaCO2 in patients with severe ARDS and permissive hypercapnia. When used in combination, both techniques have additive effects and result in PaCO2 levels close to normal values.

A scanographic assessment of pulmonary morphology in acute lung injury. Significance of the lower inflection point detected on the lung pressure-volume curve.

The goal of this study was to assess lung morphology in patients with acute lung injury according to the presence or the absence of a lower inflection point (LIP) on the lung pressure-volume (P-V) curve and to compare the effects of positive end-expiratory pressure (PEEP). Eight patients with and six without an LIP underwent a spiral thoracic CT scan performed at zero end-expiratory pressure (ZEEP) and at two levels of PEEP: PEEP1 = LIP + 2 cm H2O and PEEP2 = LIP + 7 cm H2O, or PEEP1 = 10 cm H2O and PEEP2 = 15 cm H2O in the absence of an LIP. The volumes of air and tissue within the lungs were measured from the gas-tissue ratio and the volumes of overdistended and normally, poorly, and nonaerated lung areas were determined by the analysis of the frequency histogram distribution. In the ZEEP condition, although total lung volume, volume of gas, and volume of tissue were similar in both groups, the percentage of normally aerated lung was lower (24 +/- 22% versus 55 +/- 12%, p < 0.05) and the percentage of poorly aerated lung was greater (40 +/- 12% versus 23 +/- 8%, p < 0.05) in patients with an LIP than in patients without an LIP. Lung density histograms of patients with an LIP showed a unimodal distribution with a peak at 7 Hounsfield units (HU). Lung density histograms of patients without an LIP had a bimodal distribution, with a first peak at -727 HU and a second peak at 27 HU. Total respiratory system and lung compliances were lower in patients with an LIP whereas all other cardiorespiratory parameters were similar in the two groups. In both groups, PEEP induced an alveolar recruitment that was associated with lung overdistension only in patients without an LIP. The amount of lung overdistension was related to the volume of lung parenchyma, characterized by a CT number less than -800 HU before PEEP implementation (y = 0.52x + 4, R = 0.87, and p < 0.0001). This study shows that the presence or the absence of an LIP on the lung P-V curve is associated with differences in lung morphology. In patients without an LIP on the lung P-V curve, normally aerated lung areas coexist with nonaerated lung areas and increasing levels of PEEP result in lung overdistension rather than in additional alveolar recruitment. In patients with an LIP, air and tissue are more homogeneously distributed within the lungs and increasing levels of PEEP result in additional alveolar recruitment without lung overdistention.

A simple automated method for measuring pressure-volume curves during mechanical ventilation.

Measurement of respiratory compliance is advocated for assessing the severity of acute respiratory failure (ARF). Recently, the administration of an automated constant flow of 15 L/min was proposed as a method easier to implement at the bedside than supersyringe or inspiratory occlusions methods. However, pressure-volume (P-V) curves were shifted to the right because of the resistive properties of the respiratory system. The aim of this study was to compare the P-V curves obtained using two constant flows-3 and 9 L/min-during volume-controlled mechanical ventilation with those obtained with the supersyringe and the inspiratory occlusions methods. Fourteen paralyzed patients with ARF were studied. The supersyringe and the inspiratory occlusions methods were performed according to usual recommendations. The new automated method was performed during volume-controlled mechanical ventilation by setting the inspiratory:expiratory ratio at 80%, the respiratory frequency at 5 breaths/min, and the tidal volume at 500 or 1,500 ml. These peculiar ventilatory settings were equivalent to administering a constant flow of 3 or 9 L/min during a 9.6-s inspiration. Esophageal and airway pressures were recorded. P-V curves obtained by the 3-L/min constant-flow method were identical to those obtained by the reference methods, whereas the P-V curve obtained by the 9-L/min constant flow was slightly shifted to the right. The slopes of the P-V curves and the lower inflection points were not different between all methods, indicating that the resistive component induced by administering a constant flow equal to or less than 9 L/min is not of clinical relevance. Because the 3-L/min constant-flow method is not artifacted by the resistive properties of the respiratory system and does not require any other equipment than a ventilator, it is an easy-to-implement, inexpensive, safe, and reliable method for measuring the thoracopulmonary P-V curve at the bedside.

A lung computed tomographic assessment of positive end-expiratory pressure-induced lung overdistension.

The aim of this study was to assess positive end-expiratory pressure (PEEP)-induced lung overdistension and alveolar recruitment in six patients with acute lung injury (ALI) using a computed tomographic (CT) scan method. Lung overdistension was first determined in six healthy volunteers in whom CT sections were obtained at FRC and at TLC with a positive airway pressure of 30 cm H2O. In patients, lung volumes were quantified by the analysis of the frequency distribution of CT numbers on the entire lung at zero end-expiratory pressure (ZEEP) and PEEP. In healthy volunteers at FRC, the distribution of the density histograms was monophasic with a peak at -791 +/- 12 Hounsfield units (HU). The lowest CT number observed was -912 HU. At TLC, lung volume increased by 79 +/- 35% and the peak CT number decreased to -886 +/- 26 HU. More than 70% of the increase in lung volume was located below -900 HU, suggesting that this value can be considered as the threshold separating normal aeration from overdistension. In patients with ALI, at ZEEP the distribution of density histograms was either monophasic (n = 3) or biphasic (n = 3). The mean CT number was -319 +/- 34 HU. At PEEP 13 +/- 3 cm H2O, lung volume increased by 47 +/- 19% whereas mean CT number decreased to -538 +/- 171 HU. PEEP induced a mean alveolar recruitment of 320 +/- 160 ml and a mean lung overdistension of 238 +/- 320 ml. In conclusion, overdistended lung parenchyma of healthy volunteers is characterized by a CT number below -900 HU. This threshold can be used in patients with ALI for differentiating PEEP-induced alveolar recruitment from lung overdistension.

Improvement in wall motion after pindolol: a mechanism for the preservation of left ventricular function in coronary artery disease.

1. In order to evaluate the mechanism by which beta blockers with intrinsic sympathomimetic activity preserve left ventricular systolic function at rest, 46 patients with coronary artery disease were studied by right and left heart catheterization and left ventriculography. Patients were studied using a double-blind, randomized protocol before and after a single intravenous dose of 3 mg propranolol (N = 22) or 0.5 mg pindolol (N = 24). 2. Mean right atrial pressure increased similarly after both drugs. Mean pulmonary artery pressure, left ventricular end-diastolic pressure, mean aortic pressure, and peripheral vascular resistance did not change significantly after either drug. Cardiac index (before: 3.0 +/- 0.7 (mean +/- SEM); after: 2.8 +/- 0.2 1 min-1 m-2) and heart rate (before: 78 +/- 15; after: 72 +/- 12 bpm) decreased only after propranolol administration. 3. Ejection fraction decreased only after propranolol (48 +/- 16 to 41 +/- 15%). Improvement in segmental wall motion abnormalities was noted (23 of 47 segments) only after pindolol. The total left ventricular wall motion score improved after pindolol and worsened after propranolol (P less than 0.05). In patients with impaired left ventricular function, pindolol administration resulted in improved resting ejection fraction. 4. Thus, the acute hemodynamic consequences of pindolol administration differ from those of propranolol owing to the preservation of left ventricular systolic function which seems to be related to the intrinsic sympathomimetic effect of pindolol on areas of reversible wall motion abnormality.

Improvement in wall motion after pindolol: a mechanism for the preservation of left ventricular function in coronary artery disease

In order to evaluate the mechanism by which beta blockers with intrinsic sympathomimetic activity preserve left ventricular systolic function at rest, 46 patients with coronary artery disease were studied by right and left heart catheterization and left ventriculography. Patients were studied using a double-blind, randomized protocol before and after a single intravenous dose of 3 mg propanolol (N = 22) or 0.5 mg pindolol (N = 24). Mean right atrial pressure increased similarly after both drugs. Mean pulmonary artery pressure, left ventricular end-diastolic pressure, mean aortic pressure, and peripheral vascular resistance did not change significantly after either drug. Cardiac index (before: 3.0 + or - 0.7(mean + or - SEM); after: 2.8 + or - 0.2 1 min **-1 m**-2) and heart rate (before: 78 + or - 15; after: 72 + or - 12 bpm) deveased only after propranolol administration. Ejection fraction decreased only after propranolol (48 + or - 16 to 41 + or - 15%). Improvement in segmental wall motion abnormalities was noted (23 of 47 segments) only after pindolo. The total left ventricular wall motion score improved after pindolol and worsened after propranolol (P<0.5). In patients with impaired left ventricular function, pindolol administration resulted in improved resting ejection fraction. Thus, the acute hemodynamic consequences of pindolol administration differ from those of propranolol owing to the preservation of left ventricular systolic function which seem to be related to the...