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Biomedical subjects

E Rodriguez

Publications and source records attributed to E Rodriguez.

At least 19 recordsLinked to original sources

Pediatric renal transplantation: 13 years of experience--report from the Chilean Cooperative Multicenter Group.

Between 1989 and 2002, 178 renal transplants were performed in 168 pediatric patients in Chile. The mean age was 10.9 +/- 3.7 years (range 1 to 17.9). End-state renal disease etiologies were: congenital renal hypoplasia/dysplasia, chronic glomerulonephritis, and reflux nephropathy. Seventy received a graft from a living donor (LD), and 108 from a cadaveric donor (CD). Only 9% received antibody induction. Acute rejection episodes were reported in 76 patients: 38% in LD recipients and 48% in CD recipients (P = NS). One-, 3-, and 5-year graft survivals were 88%, 84%, and 76%, respectively, for LD and 86%, 79%, and 68% for CD recipients. Actuarial graft survival was significantly better among those patients with serum creatinine < 1 mg/dL at 1 year posttransplant compared with those with creatinine > 1 mg/dL (P < .05). The graft survival rate has improved from the first period (1989 to 1996) to the second period (1997 to 2002); (P = .05). Patient survival rates at 1, 3, and 5 years were 98%, 98%, and 98%, respectively, for LD, and 95%, 94%, and 94% for CD. Global height/age Z-score decreased from -0.7 at birth to -1.5 when dialysis started, and to -2.4 at the time of transplantation. The Z-score height/age at 1, 3, and 5 years posttransplantation was -2.25, -2.24, and -2.5. No significant differences were observed in transplant outcomes comparing patients younger than 7 years with those older ones. In conclusion, pediatric renal transplant has been performed in Chile with acceptable morbidity. The patient and graft survivals are similar to the reported international experience. In the last period there was a significant improvement in graft survival.

Adolescent↗

Preclinical testing of three South American antivenoms against the venoms of five medically-important Peruvian snake venoms.

World Health Organization (WHO)-recommended preclinical in vivo and in vitro studies were carried out to compare the efficacy of Brazilian, Peruvian and Colombian antivenoms in neutralizing the venom toxins responsible for the lethal, haemorrhagic, necrotizing, coagulant and defibrinogenating effects of five medically-important Peruvian snake venoms. Overall, the Brazilian antivenom was found to be the most effective followed by the Peruvian and Colombian antivenoms. However, it was concluded that all three antivenoms would be acceptable for use in a randomised clinical trial in envenomed humans in Peru.

Animals↗

Transmission study of Andes hantavirus infection in wild sigmodontine rodents.

Our study was designed to contribute to an understanding of the timing and conditions under which transmission of Andes hantavirus in Oligoryzomys longicaudatus reservoir populations takes place. Mice were caged in test habitats consisting of steel drums containing holding cages, where seronegative rodents were exposed to wild seropositive individuals by freely sharing the same cage or being separated by a wire mesh. Tests were also performed for potential viral transmission to mice from excrement-tainted bedding in the cages. Andes virus transmitted efficiently; from 130 attempts with direct contact, 12.3% resulted in virus transmission. However, if we consider only those rodents that proved to be infectious, from 93 attempts we obtained 16 infected animals (17.2%). Twelve of them resulted from intraspecies O. longicaudatus encounters where male mice were differentially affected and 4 resulted from O. longicaudatus to Abrothrix olivaceus. Experiments using Abrothrix longipilis as receptors were not successful. Transmission was not observed between wire mesh-separated animals, and mice were not infected from excrement-tainted bedding. Bites seemed not to be a requisite for oral transmission. Genomic viral RNA was amplified in two out of three saliva samples from seropositive rodents, but it was not detected in urine samples obtained by vesicle puncture from two other infected rodents. Immunohistochemistry, using antibodies against Andes (AND) hantavirus proteins, revealed strong reactions in the lung and salivary glands, supporting the possibility of oral transmission. Our study suggests that AND hantavirus may be principally transmitted via saliva or saliva aerosols rather than via feces and urine.

Animals↗

Technical skills for weight loss: 2-y follow-up results of a randomized trial.

OBJECTIVE: To investigate the sustained effectiveness of a novel skill-based intervention for weight loss. DESIGN: Randomized, controlled trial. SUBJECTS: A total of 80 overweight/obese women living in Connecticut. MEASUREMENTS: Absolute weight difference measured in pounds and absolute change in body mass index (BMI). Secondary outcomes included changes in food frequency questionnaire (FFQ) data and waist-to-hip ratio. RESULTS: In all 61, 35, and 34% of study participants completed the 6-, 12-, and 24-month assessments, respectively. At 6 months postintervention, both counseling-based (CBI) and skill-based (SBI) intervention groups had statistically significant decreases in absolute weight (4.0+/-3.6 and 1.7+/-3.0 kg, respectively). Compared to their baseline values, both CBI and SBI groups still maintained weight losses at 24 months (1.1+/-5.8 and 0.59+/-3.3 kg, respectively); however, the differences were not statistically significant. FFQ results showed that, within the SBI group, there was a significant decrease (P<0.05) in percent fat from baseline to 12 months and a nearly significant decrease in saturated fat from baseline to 24 months (P=0.07). CONCLUSIONS: Both the novel SBI and conventional dietary counseling demonstrated some residual weight loss benefit at 2 y. Effects of the SBI on dietary intake patterns are encouraging, and warrant further study.

Adult↗

Comparison of Hilbert transform and wavelet methods for the analysis of neuronal synchrony.

The quantification of phase synchrony between neuronal signals is of crucial importance for the study of large-scale interactions in the brain. Two methods have been used to date in neuroscience, based on two distinct approaches which permit a direct estimation of the instantaneous phase of a signal [Phys. Rev. Lett. 81 (1998) 3291; Human Brain Mapping 8 (1999) 194]. The phase is either estimated by using the analytic concept of Hilbert transform or, alternatively, by convolution with a complex wavelet. In both methods the stability of the instantaneous phase over a window of time requires quantification by means of various statistical dependence parameters (standard deviation, Shannon entropy or mutual information). The purpose of this paper is to conduct a direct comparison between these two methods on three signal sets: (1) neural models; (2) intracranial signals from epileptic patients; and (3) scalp EEG recordings. Levels of synchrony that can be considered as reliable are estimated by using the technique of surrogate data. Our results demonstrate that the differences between the methods are minor, and we conclude that they are fundamentally equivalent for the study of neuroelectrical signals. This offers a common language and framework that can be used for future research in the area of synchronization.

Brain↗

Oxidative stress and lipid retention in vascular grafts: comparison between venous and arterial conduits.

BACKGROUND: Because saphenous vein grafts (SVGs) exhibit greater cellular heterogeneity and worse clinical outcomes than arterial grafts (AGs), we examined oxidative stress and lipid retention in different vascular conduits. METHODS AND RESULTS: In a porcine model of graft interposition into carotid artery, superoxide anion (.O(2)(-)) was measured at 2 weeks after surgery. SVGs demonstrated increased.O(2)(-) production compared with AGs (SOD-inhibitable nitro blue tetrazolium reduction, P<0.01). The NAD(P)H oxidase inhibitor diphenyleneiodonium (P<0.01) abolished SVG-derived.O(2)(-), whereas the inhibitors of other pro-oxidant enzymes were ineffective. The change in oxidative stress was also reflected by lower activity of the endogenous antioxidant superoxide dismutase in SVGs than in AGs (P<0.001). SVG remodeling was associated with increased synthesis of sulfated glycosaminoglycans and augmented expression of a core protein, versican. These changes were accompanied by SVGs retaining significantly more (125)I-labeled LDL than AGs ex vivo (P<0.001). In hyperlipemic animals, lipid accumulation and oxidized epitopes were preferentially noted in the intima of SVGs at 1 month after surgery. CONCLUSIONS: This study demonstrated significant differences in the biology of SVGs and AGS: SVGs exhibited higher oxidative stress, LDL accumulation, and the presence of oxidized epitopes. These findings suggest that proatherogenic changes in SVGs may commence early after surgical revascularization.

Animals↗

NMR mapping and secondary structure determination of the major acetylcholine receptor alpha-subunit determinant interacting with alpha-bungarotoxin.

The alpha-subunit of the nicotinic acetylcholine receptor (alphaAChR) contains a binding site for alpha-bungarotoxin (alpha-BTX), a snake-venom-derived alpha-neurotoxin. Previous studies have established that the segment comprising residues 173-204 of alphaAChR contains the major determinant interacting with the toxin, but the precise boundaries of this determinant have not been clearly defined to date. In this study, we applied NMR dynamic filtering to determine the exact sequence constituting the major alphaAChR determinant interacting with alpha-BTX. Two overlapping synthetic peptides corresponding to segments 179-200 and 182-202 of the alphaAChR were complexed with alpha-BTX. HOHAHA and ROESY spectra of these complexes acquired with long mixing times highlight the residues of the peptide that do not interact with the toxin and retain considerable mobility upon binding to alpha-BTX. These results, together with changes in the chemical shifts of the peptide protons upon complex formation, suggest that residues 184-200 form the contact region. At pH 4, the molecular mass of the complex determined by dynamic light scattering (DLS) was found to be 11.2 kDa, in excellent agreement with the expected molecular mass of a 1:1 complex, while at pH >5 the DLS measurement of 20 kDa molecular mass indicated dimerization of the complex. These results were supported by T(2) measurements. Complete resonance assignment of the 11.2 kDa complex of alpha-BTX bound to the alphaAChR peptide comprising residues 182-202 was obtained at pH 4 using homonuclear 2D NMR spectra measured at 800 MHz. The secondary structures of both alpha-BTX and the bound alphaAChR peptide were determined using 2D (1)H NMR experiments. The peptide folds into a beta-hairpin conformation, in which residues (R)H186-(R)V188 and (R)Y198-(R)D200 form the two beta-strands. Residues (R)Y189-(R)T191 form an intermolecular beta-sheet with residues (B)K38-(B)V40 of the second finger of alpha-BTX. These results accurately pinpoint the alpha-BTX-binding site on the alphaAChR and pave the way to structure determination of this important alphaAChR determinant involved in binding acetylcholine and cholinergic agonists and antagonists.

Amino Acid Sequence↗

A critical role for inducible nitric oxide synthase in host survival following coxsackievirus B4 infection.

Coxsackieviral infections have been linked etiologically to multiple diseases. The serotype CB4 is associated with acute pancreatitis and autoimmune type 1 diabetes. To delineate the mechanisms of host survival after an acute infection with CB4 (strain E2), we have investigated the role of nitric oxide (NO), generated by the inducible form of nitric oxide synthase (NOS2), in viral clearance and pancreatic beta-cell maintenance. Mice deficient in NOS2 (NOS2-/- mice) and their wild-type (wt) counterparts were injected with CB4, after which both groups developed severe pancreatitis, hepatitis, and hypoglycemia within 3 days. Within 4 to 7 days postinfection (p.i.), most of the NOS2-/- mice died and at a strikingly higher mortality rate than wt mice. Histological examination of pancreata from both infected NOS2-/- and infected wt mice revealed early and complete destruction of the pancreatic acinar tissue, but intact, insulin-stained islets. When examined up to 8 weeks p.i., neither surviving NOS2-/-mice nor surviving wt mice developed hyperglycemia. However, the clearance of infectious CB4 was different between the mice. The spleens of NOS2-/- survivors were cleared of infectious virus with kinetics similar to that of wt mice, but the livers, pancreata, kidneys, and hearts of the NOS2-/- groups cleared virus more slowly than those of the wt group. This delayed clearance was particularly prominent in the livers of infected NOS2-/- mice, which also showed prolonged histopathological features of viral hepatitis. Taken together, this outcome suggests that NOS2 (and NO) is not required for the prevention of pancreatic beta-cell depletion after CB4 infection. Instead the critical actions of NOS2 apparently occur early in the host immune response, allowing mice to survive and clear virus. Moreover, the data support the existence of an organ-specific dependency on NO for a rapid clearance of CB4.

Animals↗

Role of the extracellular matrix in myelination of peripheral nerve.

Assembly of the extracellular matrix (ECM) has been tightly linked to compact myelin formation in the peripheral nervous system. We recently demonstrated that myelination of dorsal root ganglion (DRG) axons by Schwann cells may occur in the absence of basal lamina. We have now determined whether laminin deposition occurs around myelinating SC, even though basal lamina has not been assembled. DRG/SC co-cultures were prepared from E15 rat embryos and incubated in fully defined medium (B27) with and without ascorbic acid for 21-24 days. Cultures were stained with a rabbit anti-laminin antibody and examined by laser confocal fluorescence microscopy. Myelination occurred in both groups. In the presence of ascorbic acid, there was dense even laminin staining around myelinating SC. In the absence of ascorbic acid, laminin staining was also present but was irregular and less dense. DRG and SC were co-cultured without ascorbic acid in the presence or absence of a function blocking anti-beta(1) integrin receptor antibody. The antibody completely inhibited myelination. Finally, DRG/SC co-cultures were prepared both with and without ascorbic acid and incubated under control conditions or in the presence of continual, gentle motion. Movement in the absence of ECM significantly inhibited myelination. This demonstrates that laminin deposition on the surface of SC but not ECM assembly is required for formation of compact myelin. ECM is required to provide mechanical stability during the process of myelination.

Animals↗

IL-4 triggers autoimmune diabetes by increasing self-antigen presentation within the pancreatic Islets.

Several findings have recently questioned the long held hypothesis that cytokines belonging to the Th2 pathway are protective in T-cell-mediated autoimmunity. Among them, there is our previous report that pancreatic expression of IL-4 activated islet antigen-specific BDC2.5 T cells and rendered them able to trigger insulin-dependent diabetes mellitus in ins-IL-4/BDC2.5 mice (Mueller et al., Immunity, 7, 1997). Here we analyze the mechanisms underlying IL-4-mediated activation of the self-reactive BDC2.5 T cells. IL-4 is mainly known as the Th2-driving cytokine. However, IL-4 is also critical for DC maturation and upregulation of antigen uptake and presentation by macrophages. In our model, we found that pancreatic expression of IL-4 activated self-reactive BDC2.5 T cells by increasing islet antigen presentation by macrophages and dendritic cells. IL-4 could have triggered self-antigen presentation within the pancreatic islets both by driving maturation of DC from a tolerizing to a priming state and by increasing self-antigen uptake by macrophages.

Animals↗

The role of preoperative radial artery ultrasound and digital plethysmography prior to coronary artery bypass grafting.

OBJECTIVE: Doppler ultrasound and digital plethysmography are used at our institution to determine the suitability of the radial artery for harvest prior to coronary artery bypass grafting (CABG). The purpose of this study is to determine the value of this preoperative evaluation. METHODS: A retrospective analysis of non-invasive radial artery testing was performed on 187 CABG patients. Criteria used to exclude radial arteries from harvest were anatomic abnormalities (size<2 mm, diffuse calcifications), and perfusion deficits during radial artery occlusion (>40% reduction in digital pressure, non-reversal of radial artery flow, or minimal increase in ulnar velocity). A questionnaire was used to determine the incidence of postoperative hand ischemia or rehabilitation. RESULTS: In 187 patients, 346 arms were evaluated. Ninety-four arms (27.1%) were excluded for harvesting. Anatomical abnormalities included size<2 mm (1.5%), diffuse calcifications (8.7%), congenital anomalies (2.3%), and radial artery occlusion (0.3%). Circulatory abnormalities included non-reversal of flow (7.2%), abnormal digital pressures (5.5%), and inappropriate increase in ulnar velocity (1.7%). A total of 116 radial arteries were harvested. There were no episodes of hand ischemia. No patient required hand rehabilitation. CONCLUSIONS Doppler ultrasound and digital plethysmography identifies both perfusion (14.5%) and anatomical (12.7%) abnormalities that may make the radial artery less suitable as a bypass conduit.

Collateral Circulation↗

Combinatorial biosynthesis of antimicrobials and other natural products.

Combinatorial biosynthesis utilizes the enzymes from antibiotic (and other natural product) biosynthetic pathways to create novel chemical structures. The manipulation of modular polyketide synthases (PKSs) has been the major focus of this effort and has led to the production of, for example, several erythromycin analogs. Many new tools for manipulating and studying these multifunctional enzymes have been developed. These include multiple hosts and expression systems, enzymology tools for in vitro study, and ways to engineer pre-PKS and post-PKS pathways. The result is more rational and faster methods of engineering new compounds for the development of chemotherapeutic agents from natural products. The most significant recent advances in combinatorial biosynthesis are outlined.

Anti-Bacterial Agents↗

The brainweb: phase synchronization and large-scale integration.

The emergence of a unified cognitive moment relies on the coordination of scattered mosaics of functionally specialized brain regions. Here we review the mechanisms of large-scale integration that counterbalance the distributed anatomical and functional organization of brain activity to enable the emergence of coherent behaviour and cognition. Although the mechanisms involved in large-scale integration are still largely unknown, we argue that the most plausible candidate is the formation of dynamic links mediated by synchrony over multiple frequency bands.

Animals↗

Do social programmes contribute to mental well-being? The long-term impact of unemployment on depression in the United States.

BACKGROUND: Important evidence about the mental health effects of unemployment exist; however, little is known about the possible protective effects of various social interventions or about their long-term impact. This study examines the long-term consequences that different types of social programmes, i.e. entitlement and means-tested benefits, might have as regards ameliorating a negative mental health impact of unemployment among women and men. METHODS: Multiple regression models were used to analyse panel data collected in the National Survey of Families and Households in 1987 and 1992. In all 8029 individuals interviewed in both 1987 and 1992 were included in the analysis. A depression index was created from the responses to 15 items from the Center for Epidemiological Studies' Depression Scale-D (CES-D) which were included in the survey. RESULTS: The receipt of government entitlement benefits by unemployed women is associated with a reduction of depression symptoms in the long term. Men and women not working and receiving means-tested or welfare benefits are more likely to report depression in both the short and long term. CONCLUSIONS: The study underscores the need for monitoring the impact of welfare reform on mental health.

Depressive Disorder↗

An economical method for (15)N/(13)C isotopic labeling of proteins expressed in Pichia pastoris.

We report a new and cost-effective approach to prepare (15)N/(13)C labeled proteins for NMR using the Pichia pastoris expression system. Four protocols (P1 to P4) were defined and compared using recombinant Ovine interferon-tau (rOvIFN-tau). Our results demonstrate that in order to get full incorporation of (15)N and (13)C, the isotopes are not totally required during the initial growth phase of P. pastoris culture. The addition of small amounts of (15)N and (13)C compounds 6 h prior to the methanol induction phase is sufficient to obtain 99% incorporation of heavy isotopes into the protein. Our optimized protocol P4 is two-thirds less costly than the classical method using (15)N and (13)C isotopes during the entire growth phase.

Animals↗

Breast reconstruction among inner city women with breast carcinoma.

Despite the known benefits of breast reconstruction, the numbers of patients undergoing breast reconstruction remains lower than expected. The goal of this study was to survey systematically the experience of inner city breast cancer patients with regard to breast reconstruction in an urban public hospital setting. Between July 1999 and April 2000, 60 patients attending the Kings County Hospital Center Outpatient Breast Cancer Clinic were enrolled in this study. A multidimensional questionnaire was designed to explore the factors that determine breast reconstruction among inner city women. Demographic analysis failed to show any difference in education, insurance status, and economics between women who undergo breast reconstruction (N = 11) and nonreconstructed patients (N = 49). Patients who have undergone reconstruction are satisfied with their results. Reconstructed women have a higher rating of satisfaction with their sex life than nonreconstructed women (p = 0.041). The women without breast reconstruction had a tendency toward more embarrassment when undressing in front of a partner and lower partner satisfaction with their bodies. The most commonly sited reason patients did not undergo breast reconstruction was the lack of knowledge about breast reconstruction before mastectomy. This emphasizes the importance of educating patients on all the options in the management of breast carcinoma.

Adult↗