The effects of perfusion conditions on melphalan distribution in the isolated perfused rat hindlimb bearing a human melanoma xenograft

An isolated rat hindlimb perfusion model carrying xenografts of the human melanoma cell line MM96 was used to study the effects of perfusion conditions on melphalan distribution. Krebs-Henseleit buffer and Hartmann's solution containing 4.7% bovine serum albumin (BSA) or 2.8% dextran 40 were used as perfusates. Melphalan concentrations in perfusate, tumour nodules and normal tissues were measured using high-performance liquid chromatography (HPLC). Increasing the perfusion flow rates (from 4 to 8 mi min(-1)) resulted in higher tissue blood flow (determined with Cr-51-labelled microspheres) and melphalan uptake by tumour and normal tissues. me distribution of melphalan within tumour nodules and normal tissues was similar for both Krebs-Henseleit buffer and Hartmann's solution; however, tissue concentrations of melphalan were significantly higher for a perfusate containing 2.8% dextran 40 than for one containing 4.7% BSA. The melphalan concentration in the tumour was one-third of that found in the skin if the perfusate contained 4.7% BSA. In conclusion, this study has shown that a high perfusion flow enhances the delivery of melphalan into implanted tumour nodules and normal tissues, and a perfusate with low melphalan binding (no albumin) is preferred for maximum uptake of drug by the tumour.

Quantification of Regional Left and Right Ventricular Deformation Indices in Healthy Neonates by Using Strain Rate and Strain Imaging

Background: Color Doppler myocardial imaging (CDMI) allows the calculation of local longitudinal or radial strain rate (SR) and strain (epsilon). The aims of this study were to determine the feasibility and reproducibility of longitudinal and radial SR and epsilon in neonates during the first hours of life and to establish reference values. Methods: Data were obtained from 55 healthy neonates (29 male; mean age, 20 +/- 14 hours; mean birth weight, 3,174 +/- 374 g). Apical and parasternal views quantified regional longitudinal and radial SR and epsilon in differing ventricular wall segments. Values at peak systole, early diastole, and late diastole were calculated from the extracted curves. CDMI data acquired at 300 +/- 50 frames/s were analyzed offline. Three consecutive cardiac cycles were measured during normal respiration. The timing of specific systolic or diastolic regional events was determined. Multiple comparisons between walls and segments were made. Results: Left ventricular (LV) longitudinal deformation showed basal differences compared with apical segments within one specific wall. Right ventricular (RV) longitudinal deformation was not homogeneous, with significant differences between basal and apical segments. Longitudinal 3 values were higher in the RV free basal and middle wall segments compared with the left ventricle. In the RV free wall apical segment, longitudinal SR and 3 were maximal. LV systolic SR and epsilon values were higher radially compared with longitudinally (radial peak systolic SR midportion, 2.9 +/- 0.6 s(-1); radial peak systolic epsilon 53.8 +/- 19%; longitudinal peak systolic SR midportion, -1.8 +/- 0.5 s(-1); longitudinal peak systolic epsilon, -24.8 +/- 3%; P < .01). Longitudinal systolic epsilon and SR interobserver variability values were 1.2% and 0.7%, respectively. Conclusion: Ultrasound-based SR and 3 imaging is a practical and reproducible clinical technique in neonates, allowing the calculation of regional longitudinal and radial deformation in RV and LV segments. These regional SR and epsilon indices represent new, noninvasive parameters that can quantify normal neonate regional cardiac function. Independent from visual interpretation, they can be used as reference values for diagnosis in ill neonates. (J Am Soc Echocardiogr 2009;22:369-375.)

Kinetics of elimination and distribution in blood and liver of biocompatible ferrofluids based on Fe(3)O(4) nanoparticles: An EPR and XRF study

In this study, we evaluated the biodistribution and the elimination kinetics of a biocompatible magnetic fluid, Endorem (TM), based on dextrancoated Fe(3)O(4) nanoparticles endovenously injected into Winstar rats. The iron content in blood and liver samples was recorded using electron paramagnetic resonance (EPR) and X-ray fluorescence (XRF) techniques. The EPR line intensity at g=2.1 was found to be proportional to the concentration of magnetic nanoparticles and the best temperature for spectra acquisition was 298 K. Both EPR and XRF analysis indicated that the maximum concentration of iron in the liver occurred 95 min after the ferrofluid administration. The half-life of the magnetic nanoparticles (MNP) in the blood was (11.6 +/- 0.6) min measured by EPR and (12.6 +/- 0.6) min determined by XRF. These results indicate that both EPR and XRF are very useful and appropriate techniques for the study of kinetics of ferrofluid elimination and biodistribution after its administration into the organism. (c) 2007 Elsevier B.V. All rights reserved.

The effects of plantar fasciitis and pain on plantar pressure distribution of recreational runners

Background: Plantar fasciitis is the third most frequent injury in runners. Despite its high prevalence, its pathogenesis remains inconclusive. The literature reports overload as the basic mechanism for its development. However, the way that these plantar loads are distributed on the foot surface of runners with plantar fasciitis and the effects of pain on this mechanical factor has not yet been investigated. Therefore, the aim of this study was to evaluate and compare the plantar pressure distributions during running in runners with symptom or history of plantar fasciitis and runners without the disease. Methods: Forty-five recreational runners with plantar fasciitis (30 symptomatic and 15 with previous history of the disease) and 60 runners without plantar fasciitis (control group) were evaluated. Pain was assessed by a visual analogue scale. All runners were evaluated by means of the Pedar system insoles during running forty meters at a speed of 12(5%) km/h, using standard sport footwear. Two-way ANOVAS were employed to investigate the main and interaction effects between groups and plantar areas. Findings: No interaction effects were found for any of the investigated variables: peak pressure (P=0.61), contact area (P=0.38), contact time (P=0.91), and the pressure-time integral (P=0.50). Interpretation: These findings indicated that the patterns of plantar pressure distribution were not affected in recreational runners with plantar fasciitis when compared to control runners. Pain also did not interfere with the dynamic patterns of the plantar pressure distributions. (C) 2010 Elsevier Ltd. All rights reserved.

In-shoe plantar pressure distribution during running on natural grass and asphalt in recreational runners

The type of surface used for running can influence the load that the locomotor apparatus will absorb and the load distribution could be related to the incidence of chronic injuries. As there is no consensus on how the locomotor apparatus adapts to loads originating from running Surfaces with different compliance, the objective of this study was to investigate how loads are distributed over the plantar surface while running on natural grass and on a rigid surface-asphalt. Forty-four adult runners with 4 3 years of running experience were evaluated while running at 12 km/h for 40 m wearing standardised running shoes and Pedar insoles (Novel). Peak pressure, contact time and contact area were measured in six regions: lateral, central and medial rearfoot, midfoot, lateral and media] forefoot. The Surfaces and regions were compared by three ANOVAS (2 x 6). Asphalt and natural grass were statistically different in all variables. Higher peak pressures were observed on asphalt at the central (p < 0.001) [grass: 303.8(66.7) kPa; asphalt: 342.3(76.3) kPa] and lateral rearfoot (p < 0.001) [grass: 312.7(75.8) kPa: asphalt: 350.9(98.3) kPa] and lateral forefoot (p < 0.001) [grass: 221.5(42.9) kPa asphalt: 245.3(55.5) kPa]. For natural grass, contact time and contact area were significantly greater at the central rearfoot (p < 0.001). These results suggest that natural grass may be a Surface that provokes lighter loads on the rearfoot and forefoot in recreational runners. (C) 2008 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

The distribution of naloxone to heroin users

Overdose deaths are a manor contributor to excess mortality among heroin users. It has been proposed that opioid overdose morbidity and mortality could be reduced substantially by distributing the opioid antagonist naloxone to heroin users. The ethical issues raised by this proposal are evaluated from a utilitarian perspective. The potential advantages of naloxone distribution include the increased chance of comatose opioid users being quickly resuscitated by others present at the time of an overdose, naloxone's safety and its lack of abuse potential. The main problems raised by the proposal are: the medico-legal complications of medical practitioners prescribing a drug that is most likely to be administered to and by people other than the one for whom it is prescribed; the economic costs of distributing naloxone sufficiently widely to have an impact on overdose morbidity and mortality; and the potentially greater cost-effectiveness of simpler educational interventions. Given the possible benefits of naloxone distribution, it may be worthwhile considering a controlled trial of naloxone distribution to high-risk heroin users.

Molecular Characterization, Distribution, and Dynamics of Hepatitis C Virus Genotypes in Blood Donors in Colombia

Hepatitis C virus (HCV) is a frequent cause of acute and chronic hepatitis and a leading cause for cirrhosis of the liver and hepatocellular carcinoma. HCV is classified in six major genotypes and more than 70 subtypes. In Colombian blood banks, serum samples were tested for anti-HCV antibodies using a third-generation ELISA. The aim of this study was to characterize the viral sequences in plasma of 184 volunteer blood donors who attended the ""Banco Nacional de Sangre de la Cruz Roja Colombiana,`` Bogota, Colombia. Three different HCV genomic regions were amplified by nested PCR. The first of these was a segment of 180 bp of the 5`UTR region to confirm the previous diagnosis by ELISA. From those that were positive to the 5`UTR region, two further segments were amplified for genotyping and subtyping by phylogenetic analysis: a segment of 380 bp from the NS5B region; and a segment of 391 bp from the E1 region. The distribution of HCV subtypes was: 1b (82.8%), 1a (5.7%), 2a (5.7%), 2b (2.8%), and 3a (2.8%). By applying Bayesian Markov chain Monte Carlo simulation, it was estimated that HCV-1b was introduced into Bogota around 1950. Also, this subtype spread at an exponential rate between about 1970 to about 1990, after which transmission of HCV was reduced by anti-HCV testing of this population. Among Colombian blood donors, HCV genotype 1b is the most frequent genotype, especially in large urban conglomerates such as Bogota, as is the case in other South American countries. J. Med. Virol. 82: 1889-1898, 2010. (C) 2010 Wiley-Liss, Inc.

Laparoscopic right hemihepatectomy for hepatolithiasis

Background Liver resection is the definitive treatment for unilateral hepatolithiasis [1]. Recently, laparoscopic major hepatectomias have become more common and are being performed in highly specialized centers [2-4]. However, few laparoscopic liver resections for hepatolithiasis have been reported. Chen et al. [5] reported two cases of laparoscopic left lobectomy for hepatolithiasis, but to our knowledge, right hepatectomy has never been reported to date. This video demonstrates technical aspects of a totally laparoscopic right hepatectomy in a patient with hepatolithiasis. Methods A 21-year-old woman with right-sided nonoriental primary intrahepatic stones [1] was referred for surgical treatment. The operation followed four distinct phases: liver mobilization, dissection of the right portal vein and right hepatic artery, extrahepatic dissection of the right hepatic vein, and parenchymal transection with harmonic shears and linear staplers for division of segment 5 and 8 branches of the middle hepatic vein. No Pringles` maneuver was used. In contrast to liver resection for other indications, the right bile duct was enlarged and filled with stones. It was divided during parenchymal transection and left open. After removal of the surgical specimen, the biliary tree was flushed with saline until stone clearance, under radioscopic surveillance, was complete. The right hepatic duct then was closed with running suture. Results The operative time was 240 min, and the estimated blood loss was 120 ml, with no blood transfusion. The hospital stay was 5 days. At this writing, the patient is well and asymptomatic 7 months after the procedure. Conclusion Laparoscopic liver resection is safe and feasible for patients with hepatolithiasis and should be considered for those suffering from intrahepatic stones.

Genotypic distribution of hepatitis C among hepatitis C and HIV co-infected patients in Brazil

Information on hepatitis C virus (HCV) genotypic distribution among HIV-HCV co-infected patients is lacking in Brazil as well as other Latin American countries. The objective of this study was to evaluate the level of exposure to different risk factors associated with HCV transmission among a group of co-infected patients and to characterize the genotypic distribution of HCV in this cluster. A series of 100 HIV-HCV co-infected patients was analysed. The data to be analysed were collected from specific laboratory tests. Information was collected through a questionnaire. HCV genotyping was carried out by sequencing the 5 ` non-coding region of HCV. Chi-square and Fischer association tests or Kruskal-Wallis test were used to study the association between HCV transmission-related variables and the established genotypes. In conclusion, exposure to multiple risk factors associated with HCV transmission was common among HIV co-infected patients and an association between HCV genotype 3 and intravenous drug user was observed.

Narrowed lumen of the right coronary artery in chronic chagasic patients is associated with ischemic lesions of segmental thinnings of ventricles

Thinning of myocardial segments, mainly at the apex and basal posterior region of left ventricle, are frequent lesions in chronic chagasic cardiopathy (CCC), but still without a well determined etiology. Previously we found severe myocardial microvascular dilatation that could cause ischemia in watershed regions. In this study we analyzed whether narrowness in epicardial coronary arteries in CCC might explain these thinned ventricular lesions. Two groups of dilated hearts with similar weights were compared: eleven hearts from patients with CCC versus four hearts from patients with dilated cardiomyopathy (IDCM). As normal controls we studied three non dilated normal weight hearts. There were no atherosclerotic plaques in the main branches of epicardial coronary arteries and cross-sectional luminal areas of proximal and distal segments were histologically measured. It was found that CCC hearts presented a lower mean luminal area in the right coronary artery (RCA) branch than IDCM, in proximal (4.3 +/- 1.4 vs 6.6 +/- 2.0 mm(2); p = 0.02) and in distal (1.6 +/- 1.0 vs 3.4 +/- 0.9 mm(2); p = 0.01) segments, with no statistical differences with normal hearts (2.7 +/- 1.3 and 1.5 +/- 0.3 mm(2)) in proximal (p = 0.2) and distal (p = 0.11) sections. In conclusion thinning of ventricular wall in CCC patients seems to be ischemic lesions in the peripheral territory irrigated by the right coronary artery, possibly due to a steal phenomenon by the left coronary, induced by micro vessels dilatation.

Development of a digital hearing aid to meet the Brazilian Government`s Ordinance 587 (APAC) - Health Department

The treatment of sensorineural hearing loss is based on hearing aids, also known as individual sound amplification devices. The hearing aids purchased by the Brazilian Government, aiming at fulfilling public policies, are based on dedicated components, which bring about benefits, but also render them expensive and may impair repair services after manufacture`s warranty expires. Aim: to design digital behind-the-ear hearing aids built from standardized components coming from the very supply chain of these manufacturers. Study design: experimental. Materials and Methods: to identify the supply chain of these manufacturers, request samples and set up hearing aids in the laboratory. Results: The developed hearing aids did not show lesser electroacoustic characteristics when compared to those acquired by the Government, also being tested by the same reference international technical standard. Conclusion: It is possible to develop digital behind-the-ear hearing aids based on off-the-shelf components from hearing aid manufacturers` supply chain. Their advantages include low operational costs - for acquisition (with clear advantages for the Government) and service (advantage for the patient).

Vascular density and distribution of vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 (Flk-1) are significantly higher in patients with deeply infiltrating endometriosis affecting the rectum

Objective: To analyze vascular density and immunolocalization of angiogenic vascular endothelial growth factor (VEGF) and its receptor Flk-1 in the proliferative and secretory eutopic human endometrium. and in three different sites of endometriosis: the ovary, bladder, and rectum. Design: Prospective study. Setting: University hospital. Patient(s): Thirty women with endometriosis (10 ovarian, 1.0 bladder, 10 rectal) and 32 control women (10 proliferative endometrium, 10 secretory endometrium, 4 normal ovary, 4 normal bladder, 4 normal rectum). Intervention(s): Normal endometrial samples were obtained from women during laparoscopic ablation of subserous myoma, and biopsy specimens of endometriosis were obtained from patients undergoing surgery for the diagnosis and treatment of endometriosis. Normal tissues of ovary, bladder, and rectum were obtained from these organs beside the lesions of endometriosis. Main Outcome Measure(S): Blood vessels were quantified according to the number of von Willebrand factor-positive endothelial cells. The VEGF and Flk-1 distribution were evaluated semiquantitatively by immunohistochemical staining. Result(s): More blood vessels were found in cases of endometriosis, particularly rectal endometriosis, compared with the respective control samples and with the eutopic endometrium, and they were localized in endometrial stroma around the glands. The VEGF and Flk-1 expression levels were also higher in cases of endometriosis, especially rectal endometriosis. Conclusion(s): Vascularization and VEGF and Flk-1 expression are significantly higher in deeply infiltrating endometriosis affecting the rectum, reinforcing the hypothesis that antiangiogenesis therapy may constitute a new modality of treatment, especially in cases of deep endometriosis involving the rectum.

Primary ciliary dyskinesia: evaluation using cilia beat frequency assessment via spectral analysis of digital microscopy images

Olm MA, Kogler JE Jr, Macchione M, Shoemark A, Saldiva PH, Rodrigues JC. Primary ciliary dyskinesia: evaluation using cilia beat frequency assessment via spectral analysis of digital microscopy images. J Appl Physiol 111: 295-302, 2011. First published May 5, 2011; doi:10.1152/japplphysiol.00629.2010.-Ciliary beat frequency (CBF) measurements provide valuable information for diagnosing of primary ciliary dyskinesia (PCD). We developed a system for measuring CBF, used it in association with electron microscopy to diagnose PCD, and then analyzed characteristics of PCD patients. 1 The CBF measurement system was based on power spectra measured through digital imaging. Twenty-four patients suspected of having PCD (age 1-19 yr) were selected from a group of 75 children and adolescents with pneumopathies of unknown causes. Ten healthy, nonsmoking volunteers (age >= 17 yr) served as a control group. Nasal brush samples were collected, and CBF and electron microscopy were performed. PCD was diagnosed in 12 patients: 5 had radial spoke defects, 3 showed absent central microtubule pairs with transposition, 2 had outer dynein arm defects, 1 had a shortened outer dynein arm, and 1 had a normal ultrastructure. Previous studies have reported that the most common cilia defects are in the dynein arm. As expected, the mean CBF was higher in the control group (P < 0.001) and patients with normal ultrastructure (P < 0.002), than in those diagnosed with cilia ultrastructural defects (i.e., PCD patients). An obstructive ventilatory pattern was observed in 70% of the PCD patients who underwent pulmonary function tests. All PCD patients presented bronchial wall thickening on chest computed tomography scans. The protocol and diagnostic techniques employed allowed us to diagnose PCD in 16% of patients in this study.