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E Delgado

Publications and source records attributed to E Delgado.

At least 37 records · Page 2Linked to original sources

High-resolution MRI detects cartilage swelling at the early stages of experimental osteoarthritis.

OBJECTIVE: The progressive early changes in cartilage and subchondral bone in an experimental model of osteoarthritis (OA) were investigated with high-resolution magnetic resonance imaging (MRI) and microradiography. METHODS: Partial medial meniscectomy was performed in the left knee of 16 rabbits. Four normal and four sham-operated additional rabbits were used as controls. Changes in cartilage and subchondral bone were sequentially assessed after surgery with MRI at 0, 2, 4, 6, 8 and 10 weeks, subchondral bone variations quantified postoperatively on microradiographs of sagittal sections at 6 and 10 weeks and the macroscopic alterations graded according to the severity of joint changes. RESULTS: MRI demonstrated a progressive increase in the articular cartilage thickness in the weight-bearing area of the femur at weeks 4, 6 and 8 vs basal. Tibial cartilage thickness only showed a significant increment at week 6. No significant abnormalities were detected on X-rays in subchondral bone when compared to controls. Macroscopically, 4 weeks after the operation OA rabbits had only slight cartilage discoloration. Cartilage eburnation, pitting, superficial erosions and osteophytes were detected at week 6. These abnormalities were more evident at 8 and 10 weeks after meniscectomy. CONCLUSION: The focal increase in cartilage thickness is one of the earliest measurable changes in OA and preceeds subchondral bone remodeling. The measurement of cartilage thickness variations with MRI can be used to follow the course of OA and to evaluate the potential beneficial effect of novel therapies.

Animals↗

Using pressure-limited mechanical ventilation in caring for organ donors.

Pressure-limited (controlled) ventilation is commonly employed to provide mechanical ventilation in the intensive care unit when lung compliance is poor or when airway resistance is irreversibly high. Modification of the inspiratory-expiratory ratio to include inspiratory-expiratory ratio reversal and permissive hypercapnia can also be used when lung disease or injury is severe. Because other donor organs often can be saved for transplantation even when the lungs have been badly damaged, the organ procurement coordinator should adopt pressure-limited ventilation as well as inspiratory-expiratory ratio reversal and permissive hypercapnia as potentially helpful methods while providing mechanical ventilation to selected donors.

Humans↗

Monitoring and humidification during tracheal gas insufflation.

In order to use tracheal gas insufflation (TGI) in a safe and effective manner, it is important to understand potential interactions between TGI and the mechanical ventilator that may impact upon gas delivery and carbon dioxide (CO2) elimination. Furthermore, potentially serious complications secondary to insufflation of cool, dry gas directly into the airway and the possibility of tube occlusion must be considered during use of this adjunct modality to mechanical ventilation. Regardless of the delivery modality (continuous TGI, expiratory TGI, reverse TGI, or bidirectional TGI), conventional respiratory monitoring is required. However, TGI with mechanical ventilation can alter tidal volume and peak inspiratory pressure and can lead to the development of intrinsic positive end-expiratory pressure. Therefore, depending on the gas delivery technique used, it is important to carefully monitor these ventilatory parameters for TGI-induced changes and understand the potential need for adjustments to ventilator settings to facilitate therapy and avoid problems. Optimally, gas insufflated by the TGI catheter should be conditioned by addition of heat and humidity to prevent mucus plug formation and potential damage to the tracheal mucosa. Finally, patients must be closely monitored for increases in peak inspiratory pressure from obstruction of the tracheal tube and should have the TGI catheter removed and inspected every 8-12 hours to assess for plugs.

Airway Resistance↗

Effects of continuous, expiratory, reverse, and bi-directional tracheal gas insufflation in conjunction with a flow relief valve on delivered tidal volume, total positive end-expiratory pressure, and carbon dioxide elimination: a bench study.

INTRODUCTION: Tracheal gas insufflation (TGI) can increase total positive end-expiratory pressure (total-PEEP) when flow is delivered in a forward direction, necessitating adjustments to maintain total-PEEP constant. When TGI is delivered throughout the respiratory cycle, additional adjustments are needed to maintain tidal volume (V(T)) constant. OBJECTIVE: Determine if bi-directional TGI (bi-TGI) (simultaneous flows toward the lungs and upper airway) in combination with a flow relief valve eliminates the increase in total-PEEP and maintains a constant V(T), thus simplifying TGI administration. METHODS: Using an artificial lung model and pressure control ventilation, we studied the effect of TGI at 10 L/min on inspired V(T), total-PEEP, and CO(2) elimination during 6 conditions: (1) control (no TGI, no catheter in the airway), (2) baseline (catheter in the airway but no TGI), (3) continuous TGI, (4) expiratory TGI, (5) reverse TGI, and (6) bi-TGI. Each condition was studied under 3 inspiration-expiration ratios (1:1, 1:2, and 2:1). A preset flow relief valve was inserted into the ventilator circuit during all TGI conditions with continuous flow. SETTING: University research laboratory. RESULTS: CO(2) elimination efficiency was similar under all conditions. Total-PEEP increased with continuous TGI and expiratory TGI, decreased during reverse TGI, and was unchanged during bi-TGI. With the flow relief valve in place, and no adjustment in mechanical ventilation, the change in minute ventilation ranged from 0% to 10%, with the least change during bi-TGI (0-5%). During bi-TGI, gas flow was equivalent in both directions during dynamic conditions and the flow relief valve consistently removed gas at 10 L/min under various pressures. CONCLUSIONS: Our data from an artificial lung model support that continuous bi-TGI minimizes the change in total-PEEP seen during other TGI modalities. The flow relief valve compensated for the extra gas volume delivered by the TGI catheter, thereby eliminating the need to make ventilator adjustments. Used in combination with a flow relief valve, bi-TGI appears to offer unique advantages by providing a simpler method to deliver TGI. Further testing is indicated to determine if similar benefits occur in the clinical setting.

Airway Resistance↗

Auto-positive end-expiratory pressure during tracheal gas insufflation: testing a hypothetical model.

OBJECTIVE: The major benefit of tracheal gas insufflation (TGI) is an increase in CO2 elimination efficiency by removal of CO2 from the anatomical deadspace. In conjunction with mechanical ventilation, TGI may also alter variables that affect CO2 elimination, such as minute ventilation and peak airway pressure (peak Paw) and cause the development of auto-positive end-expiratory pressure (auto-PEEP). We tested the hypothesis that TGI-induced auto-PEEP alters ventilatory variables. We predicted that TGI-induced auto-PEEP offsets the beneficial effects of TGI on CO2 elimination and that keeping total PEEP (ventilator PEEP + auto-PEEP) constant enhances the CO2 elimination efficiency afforded by TGI. DESIGN: Prospective study of two series of patients with acute respiratory distress syndrome receiving mechanical ventilation. SETTING: Intensive care units at a university medical center. PATIENTS: Each series consisted of eight sequential hypercapnic patients. INTERVENTIONS: In series 1, we examined the effect of continuous TGI at 0 and 10 L/min on PaCO2, without compensating for the development of auto-PEEP. In series 2, we examined this same effect of continuous TGI while reducing ventilator PEEP to keep total PEEP constant. TGI-induced auto-PEEP was calculated based on dynamic compliance measurements during zero TGI flow conditions (deltaV/deltaP) after averaging the two baseline values for peak Paw and tidal volume and assuming compliance did not change between the zero TGI and TGI flow conditions (deltaVTGI/deltaPTGI). MEASUREMENTS AND MAIN RESULTS: In series 1, total PEEP increased from 13.2 +/- 3.2 cm H2O to 17.8 +/- 3.5 cm H2O without compensation for auto-PEEP (p = .01). PaCO2 decreased (p = .03) from 56.2 +/- 10.6 mm Hg (zero TGI) to 52.9 +/- 9.3 mm Hg (TGI at 10 L/min), a 6% decrement. In series 2, total PEEP was unchanged (p = NS). PaCO2 decreased (p = .03) from 59.5 +/- 10.4 mm Hg (zero TGI) to 52.2 +/- 8.3 mm Hg (TGI at 10 L/min), a 12% decrement. There was no significant change in PaO2; there were no untoward hemodynamic effects in either series. CONCLUSIONS: These data are consistent with the hypothesis that mechanical ventilation + TGI causes an increase in auto-PEEP that can blunt CO2 elimination. In addition to the ventilator modifications necessary to keep ventilatory variables constant when TGI is used, it is also necessary to reduce ventilator PEEP to keep total PEEP constant and further enhance CO2 elimination efficiency.

Aged↗

Tracheal gas insufflation. Limits of efficacy in adults with acute respiratory distress syndrome.

In mechanically ventilated adults with acute respiratory distress syndrome (ARDS), peak airway pressures (Paw(peak)) above 35 cm H(2)O may increase the risk of barotrauma or volutrauma. Tracheal gas insufflation (TGI), an adjunctive ventilatory technique, may facilitate a reduction in set inspiratory pressure in these patients, and thereby in the tidal volume (VT) and Paw(peak) used in their ventilation, without a consequent increase in arterial carbon dioxide tension (PaCO(2)). The purpose of this study was to: (1) assess the limits of efficacy of continuous TGI at two levels of decreased mechanical ventilatory support; and (2) determine an appropriate time interval after initiation of TGI at which to evaluate response. We prospectively studied eight adults with ARDS and increased airway pressures (40.2 +/- 2.7 cm H(2)O) who were managed with pressure-control ventilation (PCV). After obtaining baseline ventilatory and hemodynamic measures, we initiated TGI at 10 L/min, adjusting ventilator positive-end expiratory pressure (PEEP) to maintain baseline VT, and decreased the set inspiratory pressure by 5 cm H(2)O. Data were obtained after 30 and 60 min. Set inspiratory pressure was then decreased by an additional 5 cm H(2)O (total: 10 cm H(2)O), and data were again obtained after 30 min. Baseline (zero TGI) measures were then again recorded. Thirty minutes after decreasing the set inspiratory pressure by 5 cm H(2)O with TGI at 10 L/min, there was a 15% decrease in Paw(peak) and a 16% decrease in VT as compared with their baseline values. However, Pa(CO(2)) remained constant (59 +/- 10 mm Hg versus 57 +/- 6 mm Hg) (p = NS). There was no change in Pa(O(2)) or in hemodynamic variables, and no differences between variables, at 30 min versus 60 min in seven subjects. The remaining subject did not tolerate the reduction in set inspiratory pressure for 60 min. Thirty minutes after the set inspiratory pressure was decreased by 10 cm H(2)O with TGI at 10 L/min, there was a 26% decrease in Paw(peak) and a 26% decrease in VT. However, Pa(CO(2)) increased by 19% and Pa(O(2)) decreased by 13%. Six subjects completed this phase of the protocol for 30 min, and one subject completed it for 60 min. TGI can be used to rapidly facilitate a 5 cm H(2)O reduction in set inspiratory pressure without an increase in Pa(CO(2)). The ability to achieve a 5 cm H(2)O reduction in set inspiratory pressure without adverse physiologic effects was evident within 30 min. Attempts to further reduce set inspiratory pressure were not successful.

Acute Disease↗

Virus replication begins in dendritic cells during the transmission of HIV-1 from mature dendritic cells to T cells.

BACKGROUND: To initiate immunity, dendritic cells (DCs) capture antigens or viruses at body surfaces, undergo maturation to express T-cell costimulatory molecules, and then migrate to lymphoid organs. DCs at body surfaces can capture human immunodeficiency virus 1 (HIV-1), but mature DCs do not support replication of the virus unless T cells are added. The initial site for HIV-1 replication remains unknown and it is unclear whether replication can take place in DCs or whether the virus must first be transmitted from DCs to T cells. RESULTS: We generated mature DCs from monocyte precursors. Upon infection with HIV-1, reverse transcription was completed only when T cells were added. When the reverse transcriptase inhibitor azidothymidine was added to the DCs during exposure to HIV-1, the DCs remained fully infectious, as long as the drug was removed just before culturing the DCs with T cells. HIV-1 variants that were engineered to undergo only one cycle of replication were able to infect DCs and replicate once in these cells. When T cells were added, newly produced HIV-1 Gag protein was exclusively localized to the DCs. With wild-type virus, subsequent rounds of replication took place in T cells. Soluble CD40 ligand (CD40L) and CD40L-transfected fibroblasts stimulated HIV-1 replication in purified mature DCs. CONCLUSIONS: Mature DCs provide a drug-resistant reservoir for HIV-1. This reservoir is activated within DCs by CD40L and upon interaction with T cells, and the virus then spreads rapidly to other T cells.

Anti-HIV Agents↗

Acute pancreatitis: evaluation of the prognostic criteria of the latest Balthazar tomographic classification.

The use of prognostic criteria to detect potentially acute pancreatitis can allow us to select patients most in need of special attention. Of the many possible criteria, we used Ranson's clinical analytic criteria and Balthazar's tomographic criteria, and compared them to the latest criteria of Balthazar, in which pancreatic necrosis figures as the principal prognostic factor. Tomographic evaluation of pancreatic necrosis was shown to be the best prognostic marker in acute pancreatitis, with the greatest sensitivity and specificity of all methods used with one-hundred consecutive patients admitted with acute pancreatitis.

Acute Disease↗

Strategic control of fasciolosis in the inter-Andean valley of Cajamarca, Peru.

Fasciolosis is recognised as a major problem in dairy cattle in Cajamarca, Peru. The infection has an annual cycle, with the major period of infection from January to March. A control programme, involving two doses of the fasciolicide triclabendazole aimed at reducing the passage of Fasciola hepatica eggs on to the pasture, together with the use of the molluscicide, niclosamide, was evaluated against traditional treatment programmes. The double treatment regimen did not significantly reduce the overall parasite burden, as measured by faecal egg counts, but did control the parasites to a level similar to that achieved by traditional programmes averaging 3-7 treatments per year. The cows' eosinophil counts and serum liver enzyme activities were significantly lower than in animals treated by the traditional programmes. The use of niclosamide in addition to the triclabendazole treatments gave no clear advantage, although there was a significant reduction in the number of intermediate host snails after the application of the molluscicide.

Animal Husbandry↗

The effect of repetitive magnetic stimulation on localized musculoskeletal pain.

Current magnetic coil stimulators can efficiently activate neural structures without deep electrode placement and the local discomfort associated with transcutaneous electrical stimulation used in pain control. We tested the possibility of reducing pain in patients with localized musculoskeletal processes by applying repetitive magnetic stimulation on the tender body region. Thirty patients were randomized to receive 40 min of real or sham magnetic stimulation. After a single session, real magnetic stimulation significantly exceeded the sham effect: a 101-point pain score decreased by 59% in the treated group and 14% in sham-treated patients (z = -3.26, p = 0.001). The pain relief attained regularly persisted for several days. Results indicate that powerful magnetic coil stimulation can efficiently reduce pain originating from localized musculoskeletal injuries.

Adult↗

Mature dendritic cells respond to SDF-1, but not to several beta-chemokines.

Immature dendritic cells (DCs) are highly motile, but after differentiation they stop migration. Chemokines are chemotactic cytokines that direct leukocyte trafficking, therefore we looked for the expression and function of chemokine receptors in immature and mature DCs. As a model, we used the human DCs that develop from CD14+ peripheral blood monocytes cultured with GM-CSF and IL-4. After 6-7 days in culture, these cells have the characteristics of immature DCs, but can be induced to mature further by inflammatory stimuli or by monocyte conditioned medium (MCM). Immature DCs express mRNA for CXCR4, CCR3 and CCR5. The receptors are expressed on the cell surface, as assessed with monoclonal antibodies, and are functional (with the exception of CCR3) as assessed by CA++ mobilization in response to specific chemokines. Further differentiation and maturation of DC in MCM causes a downregulation of expression and function of the beta-chemokine receptors, while CXCR4 still remains, and signals a calcium flux on mature DCs. We argue that the downregulation of beta-chemokine receptors during maturation helps to stop DC movement after T cells have been identified in lymphoid organs or at sites of delayed-type hypersensitivity.

Calcium↗

Immature dendritic cells selectively replicate macrophagetropic (M-tropic) human immunodeficiency virus type 1, while mature cells efficiently transmit both M- and T-tropic virus to T cells.

Dendritic cells (DCs) can develop from CD14+ peripheral blood monocytes cultured in granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 4 (IL-4). By 6 days in culture, the cells have the characteristics of immature DCs and can be further induced to mature by inflammatory stimuli or by monocyte-conditioned medium. After infection with macrophagetropic (M-tropic) human immunodeficiency virus type 1 (HIV-1), monocytes and mature DCs show a block in reverse transcription and only form early transcripts that can be amplified with primers for the R/U5 region. In contrast, immature DCs cultured for 6 or 11 days in GM-CSF and IL-4 complete reverse transcription and show a strong signal when LTR/gag primers are used. Blood monocytes and mature DCs do not replicate HIV-1, whereas immature DCs can be productively infected, but only with M-tropic HIV-1. The virus produced by immature DCs readily infects activated T cells. Although mature DCs do not produce virus, these cells transmit both M- and T-tropic virus to T cells. In the cocultures, both DCs and T cells must express functional chemokine coreceptors for viral replication to occur. Therefore, the developmental stage of DCs can influence the interaction of these cells with HIV-1 and influence the extent to which M-tropic and T-tropic virus can replicate.

Cell Communication↗

Evaluation of mixtures of wild-type HIV-1 and HIV-1 with resistance point mutations against reverse transcriptase inhibitors.

The presence of resistance-related mutations in 185 serial proviral DNA samples from 108 HIV-infected patients was monitored using the line probe assay (LiPA). The proportions of wild-type and mutant virus in each sample were determined. Subsequent samples from the same patient were analysed. Resistance mutations were detected in 58 of 108 patients studied (53.7%), 53 of 73 (72.6%) treated with antivirals and 5 of 35 (14.2%) untreated. The mutations were against zidovudine (51), lamivudine (1), zidovudine and lamivudine (4), zidovudine and zalcitabine (1) and zidovudine and didanosine (1). Among the 58 patients with resistant virus, 168 related mutations were observed: 161 to zidovudine (90 in codon 70, 25 in codon 41 and 46 in codon 215), 5 to lamivudine (codon 184), 1 to zalcitabine (codon 69) and 1 to didanosine (codon 74). Mixtures of wild-type and resistant mutants were detected in 76 of 90 (84.4%) mutated at codon 70, 28 of 46 (60.8%) mutated at codon 215 and in 21 of 25 (84%) mutated at codon 41. The mutations at codon 184 were mixtures of wild-type and resistant in 4 of 5 samples. The agreement between LiPA and sequencing was 96.5%. LiPA was more sensitive for the detection of mutants that were present at low frequency. The analysis of sequential samples from the same patient allowed evaluation of the dynamics of appearance of the resistant mutants.

Anti-HIV Agents↗

Exendin-4 agonist and exendin(9-39)amide antagonist of the GLP-1(7-36)amide effects in liver and muscle.

The GLP-1 structurally related peptides exendin-4 and exendin(9-39)amide were found to act, in rat liver and skeletal muscle, as agonist and antagonist, respectively, of the GLP-1(7-36)amide effects on glucose metabolism. Thus, like GLP-1(7-36)amide, exendin-4 increased glycogen synthase a activity and glucose incorporation into glycogen in both tissues and also stimulated exogenous D-glucose utilization and oxidation in muscle. These effects of GLP-1(7-36)amide and exendin-4 were inhibited by exendin(9-39)amide. Our findings provide further support to the proposed use of GLP-1, or exendin-4, as a tool in the treatment of diabetes mellitus. Thus, in addition to the well-known insulinotropic action of the peptides, they act both in liver and in muscle in a manner most suitable for restoration of glucose homeostasis, with emphasis on their positive effects upon glycogen synthesis in the two tissues and on the stimulation of exogenous glucose catabolism in muscle.

Animals↗

Utilisation rates and expenditure for public and private, curative-care services in semi-urban Guatemala.

In November 1994, a retrospective survey was conducted for two purposes; to investigate patterns of health-care uptake for childhood and maternal illness in semi-urban Guatemala; and to gain an insight into the expenditure incurred by the subjects when they consulted the various health-care providers. The subjects, who all belonged to a semi-urban ladina community, had easy geographical access to the health-care providers, of all types, operating in Sacatepequez, in the central highlands of Guatemala. The community was divided into clusters of roughly equal population size and 20 of these were selected. Within each selected cluster, eight households that had at least one young child (< 5 years of age) were investigated. Mothers belonging to each household were asked whether, how frequently, and where they had sought outside help for any health problem that had possibly affected them or their children during the past year. Subsequently, they were also invited to recall the expenditure incurred on the last visit, if any, to each type of health-care provider established in the area. The crude utilisation rates, for all providers combined, were 1.0/women.year and 0.8/child.year. Overall, 61% of women had no uptake of curative care for themselves and 12% of families no such uptake for their children. Lay curers and clinics run by non-governmental organizations were hardly utilised. Drug vendors accounted for 38% of contacts by women and 26% by children, private physicians for 34% and 38%, and public services for 22% and 33%, respectively. The utilisation rate of the official sector attained roughly 0.3/person.year in both women and children. Dissatisfaction with the treatment received and the lack of drugs were often given as reasons for not attending public services. The median total expenditure incurred per curative, health-care contact ranged from 0 quetzales in the official health centres to 63 quetzales with private physicians (a U.S.$ being equivalent to 5.5 quetzales at the time of the study). Although for each type of provider (except the health centres), expenditure was nearly equal for a woman or for a child contact, it consisted of a different mix of cost elements (consultation fee, drugs and transport) for each of the various categories of provider. The willingness for a more prominent role of the public sector. It would seem that there is, in the socio-economic environment of semi-urban Sacatepequez, room for experimenting with alternative modes of health-care financing to increase the quality and attractiveness of public services and their utilisation.

Adult↗