Clinical, hematological, and molecular characterization of sickle cell anemia pediatric patients from two different cities in Brazil

This study focused on clinical, hematological, and molecular aspects of sickle cell anemia pediatric patients from two different cites in Brazil. Seventy-one patients from S?o Paulo and Salvador, aged 3 to 18 years, were evaluated. Hematological analyses, betaS globin gene haplotypes, and alpha2 3.7kb-thalassemia were performed. Numbers of hospitalizations due to vaso-occlusive crises, infections, stroke, and cholelithiasis were investigated. S?o Paulo had more hospitalizations from vaso-occlusion, cholelithiasis, and stroke than Salvador. The Ben/CAR genotype predominated in both cities. Alpha2 3.7kb-thalassemia had a frequency of 28.2% in Salvador, mostly with Ben/CAR genotype (45.0%), while S?o Paulo had 22.5% with similar frequencies of the Ben/ CAR and CAR/CAR genotypes. Sickle cell anemia patients from S?o Paulo also had more episodes of stroke, which was observed among CAR/CAR, atypical, and BEN/CAR haplotypes. In Salvador stroke was only observed in the Ben/CAR genotype. Cholelithiasis had similar frequencies in the two cities. These data suggest a milder phenotype among patients in Salvador, possibly due to genetic, environmental, and socioeconomic factors. Further studies are needed to elucidate modulating factors and phenotype association.     

Protein L-agarose for adsorption of autoantibodies: a potential tool for extracorporeal treatment

This work investigated the adsorption of autoantibodies such as anti-SS-A/Ro, anti-SS-B/La, anti-Sm, and anti-dsDNA on protein L-agarose gel. In order to determine better conditions for IgG adsorption on this matrix, some buffer systems were tested. Adsorption data were analyzed using the Langmuir and Langmuir-Freundlich isotherm models. The experimental isotherms were best described by the Langmuir-Freundlich model, which indicated negative and positive cooperativities for binding in the presence of PBS and HEPES buffers, respectively. The K(d) values for phosphate buffered saline solution (PBS) and hydroxyethylpiperazine ethanesulfonic acid (HEPES) were 2.8 x 10(-7) M and 3.2 x 10(-7) M, respectively, which indicate a high affinity between IgG and the immobilized protein L. The amount of protein adsorbed per amount of protein loaded was high for anti-Sm (44%) and anti-dsDNA (46%), but low for anti-SS-B/La (9%). The amount of albumin adsorbed was lower than 0.06 mg/mL, which may remove the need for a plasma replacement solution in clinical apheresis.     

Systemic administration of propentofylline does not attenuate morphine tolerance in non-injured rodents

Propentofylline is a phosphodiesterase inhibitor that has been shown to attenuate the onset of morphine tolerance when administered intrathecally to rats. The present studies examined whether systemic administration could be effective in attenuating morphine tolerance in non-injured rodents using a similar dosing paradigm. Propentofylline at 10, 30, or 50 mg/kg, administered intraperitoneally once daily for 5 days, was unable to attenuate morphine tolerance established by twice daily administration of 10 mg/kg morphine. These results suggest that direct delivery of propentofylline to the central nervous system (CNS) may be required in order to attenuate morphine tolerance.     

Effects of local nicotinic activation of the superior colliculus on saccades in monkeys

To examine the role of competitive and cooperative neural interactions within the intermediate layer of superior colliculus (SC), we elevated the basal SC neuronal activity by locally injecting a cholinergic agonist nicotine and analyzed its effects on saccade performance. After microinjection, spontaneous saccades were directed toward the movement field of neurons at the injection site (affected area). For visually guided saccades, reaction times were decreased when targets were presented close to the affected area. However, when visual targets were presented remote from the affected area, reaction times were not increased regardless of the rostrocaudal level of the injection sites. The endpoints of visually guided saccades were biased toward the affected area when targets were presented close to the affected area. After this endpoint effect diminished, the trajectories of visually guided saccades remained modestly curved toward the affected area. Compared with the effects on endpoints, the effects on reaction times were more localized to the targets close to the affected area. These results are consistent with a model that saccades are triggered by the activities of neurons within a restricted region, and the endpoints and trajectories of the saccades are determined by the widespread population activity in the SC. However, because increased reaction times were not observed for saccades toward targets remote from the affected area, inhibitory interactions in the SC may not be strong enough to shape the spatial distribution of the low-frequency preparatory activities in the SC.     

An unusual bilateral oblique facial cleft in a newborn

An extremely rare case of asymmetrical bilateral oblique facial cleft presumably secondary to amniotic bands is presented. The cleft on the right side of the patient commenced from the lower lip through the maxillary region of the face to the temporal area and was described as a lower oro-temporal cleft to differentiate it from the previously reported type commencing from the upper lip.     

Effectiveness of diuretic injection on the measurement of differential renal function using Tc-99m DMSA in patients with a dilated renal pelvis

AIM: The aim of this study was to evaluate the effectiveness of diuretic injection for the measurement of differential renal function (DRF) with technetium-99m dimercaptosuccinic acid (Tc-99m DMSA) scintigraphy in patients with a dilated pelvis. MATERIALS AND METHODS: A total of 46 patients who were referred for both technetium-99m-L,L-ethylenedicysteine (Tc-99m L,L-EC) and Tc-99m DMSA imaging and found to have a dilated collecting system on Tc-99m EC scintigraphy were studied. Four to 5 hours after intravenous injection of Tc-99m DMSA, imaging was performed in the supine position, and posterior, anterior, left and right lateral, and left and right posterior oblique views were taken. After this study, furosemide was administered intravenously and 30 minutes later, additional images in the anterior and posterior views were obtained. RESULTS: The kidneys were evaluated into 2 groups. Group 1 comprised 12 kidneys that had an obstructive curve pattern on Tc-99m EC scans. Group 2 comprised 34 kidneys that had a nonobstructive dilated renogram curve pattern. DRF of the kidneys in each patient were calculated, and the values obtained from the standard and diuretic DMSA scans were compared with each other for all patients and each group. Considering all the patients, the values of mean DRF on both standard and diuretic DMSA images were 55.4%+/-21.2% and 55.4%+/-21.5%, respectively. There were no significant differences between DRF values of each kidney obtained by the 2 methods. When we compared the DRF values in groups 1 and 2, there were again no significant differences. In group 1, the values of mean DRF on standard and diuretic images were 51.7%+/-13.7% and 51.6%+/-13.9%, respectively, and in group 2, the values of mean DRF were 56.7%+/-23.4% and 56.7%+/-23.6%, respectively. CONCLUSION: In view of our study, diuretic administration seems to be an unnecessary intervention because it has no effect on the accuracy of DRF measurements using DMSA scintigraphy in patients with a dilated collecting system whether it is obstructed or not.     

Conduction properties of identified neural pathways in the central nervous system of mice in vivo

Various lines of transgenic or knockout mice are now available that have abnormalities in neuron, glial cells or neuron-glial interaction. However, the techniques for quantitative analysis of their pathophysiological functions are still limited. We established an experimental model system to measure the properties of nerve conduction of identified neural pathways in the CNS using anesthetized and immobilized mice. Dorsal column (DC), vestibulospinal/reticulospinal tracts (VRST) and pyramidal tract (PT) were stimulated by inserting stimulating electrodes into the dorsal column nuclei, medial longitudinal fasciculus, and the medullary pyramid, respectively. Volleys were recorded at various segments in the cervical spinal cord with surface electrodes, and their conduction velocities (CVs) and relative refractory periods (RRPs) were measured. The CVs of the DC, VRST and PT were 26.25 +/- 4.96 m/s (n = 7), 51.55 +/- 4.65 m/s (n = 7), 8.89 +/- 1.81 m/s (n = 7), respectively. Data from paired stimulation indicated that the median values of RRPs of the DC, VRST and PT were 10, 2 and 4 ms, respectively, which suggested marked difference among individual tracts. This is the first attempt to measure the conduction properties of the central tracts in mice in vivo. This experimental procedure will give us a physiological measure of CNS functions in normal and genetically manipulated mice and contribute to clarifying the molecular mechanisms and pathophysiology of neurodegenerative diseases such as multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS).     

Expression of non-membranous beta-catenin and gamma-catenin, c-Myc and cyclin D1 in relation to patient outcome in human colon adenocarcinomas

Non-membranous beta-catenin and gamma-catenin, c-Myc and cyclin D1 are key participants in the Wnt cell signalling pathway, in which aberrancies have been associated with malignant cell transformation. We assessed the independent prognostic value of these proteins in a clinical material. Tumours from a series of 162 patients operated on for Dukes' stage A, B and C colonic adenocarcinomas were analysed using semiquantitative immunohistochemistry and the results were related to patient outcome. Patients expressing nuclear beta-catenin in the primary tumour showed reduced survival compared to other patients (log rank p=0.028) and there was also an association with development of metastases follow-up (logistic regression p=0.024). Using multivariate analysis (Cox regression) co-expression of nuclear beta-catenin and c-Myc turned out to be the strongest marker of impaired prognosis (p=0.001, HR 5.26, 95% CI 1.93-14.36). Expression of non-membranous gamma-catenin, cyclin D1 and c-Myc alone failed to have independent prognostic significance in our study.