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Biomedical subjects

E Cordero

Publications and source records attributed to E Cordero.

At least 19 recordsLinked to original sources

Epidemiology of urinary infections in renal transplant recipients.

Urinary tract infection (UTI) remains a significant cause of infectious complications in renal transplant recipients. We evaluated prospectively all the UTIs in 161 kidney recipients transplanted between July 2003 and July 2005. All patients received prophylaxis with sulfadoxine-pyrimethamine. We excluded asymptomatic bacteriuria. Forty-one patients (25%) suffered at least one UTI episode. Ninety-two episodes of infection were confirmed with an incidence rate of 97 UTI episodes per 100 patient-years. The most common clinical features were uncomplicated acute bacterial cystitis, 71 episodes (77%), and acute pyelonephritis, 21 episodes (23%). Microbiological isolation was confirmed in 58 episodes (63%). Bacterial infections were the most frequent etiologies: gram-negative bacilli in 52 (90%), gram-positive cocci in 4 (7%), fungal in 2 (3%), and one viral BK virus (2%) infection. The causative microorganisms were E. coli as the principal isolated agent in 41 cases (71%), including 10 (24%) that were extended-spectrum betalactamases (ESBLEC). All episodes showed a favorable course. The survival rate of the graft at the end of the study period was 90.7%, and the survival rate of the transplant recipients was 97.5%. The incidence of UTI in transplant patients who received antibiotic prophylaxis was high. E. coli (ESBLEC) was the main agent isolated. Uncomplicated UTI, the most frequent post transplantation infection, showed a good prognosis.

Adolescent↗

Usefulness of sputum culture for diagnosis of bacterial pneumonia in HIV-infected patients.

The use of sputum culture in immunocompetent patients with community-acquired pneumonia is controversial. The usefulness of this technique in HIV-infected patients has not been evaluated. A prospective, observational, multicenter, hospital-based study of bacterial community-acquired pneumonia was carried out to analyze the value of sputum culture in HIV-infected patients. Only good-quality sputum samples were cultured. Altogether, 355 cases of bacterial community-acquired pneumonia were included. An etiological diagnosis was obtained in 190 (53.5%) cases. Sputum was cultured in 313 (88.1%) cases, being diagnostic in 108 (34.5%). The microorganism identified in sputum culture was the same as that identified in sterile samples in 26 of 27 (96.3%) cases in which both cultures were diagnostic. The microbiologic findings in sputum and bronchoscopic cultures were concordant in seven of eight (87.5%) cases in which both were positive. These results suggest that sputum culture is a useful technique, given its availability and ease of performance and its good correlation with culture of sterile samples.

AIDS-Related Opportunistic Infections↗

Influence of the response to induction therapy on the rate of progression of cytomegalovirus retinitis in AIDS patients on intravitreal maintenance therapy.

In order to assess whether complete inactivation of retinitis at the end of induction therapy leads to delayed progression during maintenance therapy with weekly intravitreal ganciclovir, the time to the first progression to retinitis was evaluated in 27 AIDS patients (34 eyes) with stable cytomegalovirus retinitis. Data were censored before the introduction of protease inhibitors. Overall, retinitis progressed in 22 of 34 eyes in a median time of 12 weeks (mean +/- SD, 33 +/- 9 weeks). However, retinitis progressed in 15 of 19 eyes in which only partial inactivation was achieved following induction therapy (median time, 10 weeks; mean +/- SD, 17 +/- 4 weeks) but in only 7 of 15 eyes when complete inactivation was obtained (median time, 59 weeks; mean +/- SD, 56 +/- 19 weeks) (P= 0.02). There were no differences between the groups in CD4+ cell counts, drugs, route of induction treatment, or length of induction therapy. Induction therapy should be prolonged until complete inactivation of retinitis is obtained, since achieving only a partial response appears to be a factor in earlier progression when patients are switched to maintenance therapy with intravitreal ganciclovir.

AIDS-Related Opportunistic Infections↗

Cefepime versus cefotaxime for empirical treatment of bacterial pneumonia in HIV-infected patients: an open, randomized trial.

An open, randomized, multicentre clinical trial was conducted to compare the efficacy and safety of cefepime 2 g iv bd (2 g tds daily in cases of Pseudomonas aeruginosa pneumonia) with cefotaxime 2 g iv tds, in the empirical treatment of bacterial pneumonia in HIV-infected patients. The primary end-point was effectiveness after 3-5 days of treatment, taking success to be when the study drug was continued during this period of time. Clinical and bacteriological responses at end of treatment (EOT) were also evaluated. Analyses of the intention-to-treat population (n = 160) and the as-per-protocol groups (n = 150) were carried out. Treatment groups were comparable with regard to sex, age, HIV status and degree of severity of pneumonia. The primary end-point for cefepime was considered successful for the intention-to-treat and as-per-protocol groups in 85.7% and 93.5% of cases, respectively, and for cefotaxime, in 77.6% and 80.8% of cases, respectively (P = 0.22 and P = 0.02). In the as-per-protocol group, cefotaxime treatment was independently related to failure at the primary end-point. A satisfactory clinical response in the intention-to-treat population was observed in 83.3% of cefepime and 82.9% of cefotaxime patients. Bacteriological cure was obtained in 100% of evaluable cefepime and 93.4% of evaluable cefotaxime patients at EOT. Safety of the study drugs was comparable in both treatment groups. Cefepime 2 g iv bd was at least as effective and as well tolerated as cefotaxime 2 g iv tds in the treatment of bacterial pneumonia in HIV-infected patients.

Adult↗

Intravitreal pharmacokinetics and retinal concentrations of ganciclovir and foscarnet after intravitreal administration in rabbits.

PURPOSE: To perform a detailed pharmacokinetic study and to evaluate the drug levels reached in the retina after the intravitreal administration of ganciclovir and foscarnet to rabbits. METHODS: Retinal and vitreal levels of both drugs were measured by high-performance liquid chromatography at 1, 6, 12, 24, 36, 48, 60, and 72 hours after a single intravitreal injection of 196 microg and 800 microg of ganciclovir and 960 microg of foscarnet to three groups of 24 pigmented rabbits. A noncompartmental pharmacokinetic analysis was used. RESULTS: Both drugs incorporated rapidly into the retina, but no equilibrium was observed between the drug levels in the vitreous humor and retina. Mean ganciclovir levels in vitreous and retina were 179.6 microg/g and 131.3 microg/g (dose of 196 microg), 755.7 microg/g and 381.6 microg/g (dose of 800 microg) at 1 hour after administration, decreasing to 0.1 microg/g, 0.6 microg/g, 0.8 microg/g, and 0.7 microg/g, respectively, by 72 hours. Mean foscarnet levels in vitreous and retina were 944 microg/g and 217.1 microg/g at 1 hour after administration, decreasing to 74 microg/g and 17.1 microg/g, respectively, by 72 hours. Whereas both doses of ganciclovir yielded retinal levels above the mean inhibitory concentration (IC50) of most human cytomegalovirus (CMV) isolates for more than 60 hours, foscarnet retinal levels were lower than the CMV IC50 before 36 hours had elapsed after administration. CONCLUSIONS: The results suggest that the intravitreal administration of ganciclovir has a better pharmacokinetic profile than foscarnet for the treatment of retinitis caused by CMV and other herpes viruses and support the administration of intravitreal ganciclovir twice a week as a treatment for CMV retinitis.

Animals↗

Prospective evaluation and follow-up of European patients with visceral leishmaniasis and HIV-1 coinfection in the era of highly active antiretroviral therapy.

A prospective descriptive study was designed to determine the impact of highly active antiretroviral therapy (HAART) in the evolution of visceral leishmaniasis (VL) in HIV-1 infected patients. Thirty-two patients were treated with meglumine antimoniate or amphotericin B in lipid formulations. Patients who had undergone previous HAART at study entry (n=17) continued with therapy while receiving treatment for VL. Patients who had never undergone HAART started it after VL treatment finished (n=15). Ten patients were lost to follow-up. All of the remaining patients (n=20) continued to receive HAART and were followed for an average of 441 days. Relapses were observed in 5 of 20 patients. These results indicate that HAART neither prevents the incidence of VL relapse nor modifies the clinical picture described in the pre-HAART era.

Adult↗

Haemophilus influenzae pneumonia in human immunodeficiency virus-infected patients. The Grupo Andaluz para el Estudio de las Enfermedades Infecciosas.

Although Haemophilus influenzae is a common etiologic agent of pneumonia in patients infected with human immunodeficiency virus (HIV), the characteristics of this pneumonia have not been adequately assessed. We have prospectively studied features of H. influenzae pneumonia in 26 consecutive HIV-infected inpatients. Most of these patients were severely immunosuppressed; 73.1% had a CD4+ cell count <100/microL. A subacute clinical presentation was observed in 27% of the patients and was associated with a higher degree of immunosuppression (P=.04). Bilateral lung infiltrates were noted radiographically in 57.7% of the cases. The mortality attributable to H. influenzae pneumonia was 11.5%. Thus, pneumonia caused by H. influenzae affects mainly patients with advanced HIV disease, and since its clinical and radiological features may be diverse, this etiology should be considered when pneumonia occurs in patients with advanced HIV infection. The mortality rate associated with H. influenzae pneumonia is not higher than that occurring in the general population.

AIDS-Related Opportunistic Infections↗

Intravitreal, retinal, and central nervous system foscarnet concentrations after rapid intravenous administration to rabbits.

Retinal, vitreous humor, brain, and cerebrospinal fluid (CSF) foscarnet levels were measured by high-performance liquid chromatography after administration of an intravenous dose of 120 mg/kg of body weight to 32 pigmented rabbits. A pharmacokinetic analysis was done using a two-compartment model. The penetration ratios, defined as ratios of retinal, vitreous humor, brain, and CSF areas under the concentration-time curve from 0 to 2 h were 110% +/- 1%, 12.3% +/- 0.7%, 118% +/- 1%, and 20.2% +/- 2.2%, respectively. These results suggest a good penetration of foscarnet into the retinal and brain tissues, reaching higher concentrations than those estimated from vitreous humor and CSF levels.

Animals↗

Community-acquired bacterial pneumonia in human immunodeficiency virus-infected patients: validation of severity criteria. The Grupo Andaluz para el Estudio de las Enfermedades Infecciosas.

Severity criteria for community-acquired pneumonia (CAP) have always excluded patients with human immunodeficiency virus (HIV) infection. A 1-yr, multicenter, prospective observational study of HIV-infected patients with bacterial CAP was done to validate the criteria used in the American Thoracic Society (ATS) guidelines for CAP, and to determine the prognosis-associated factors in the HIV-infected population with bacterial CAP. Overall, 355 cases were included, with an attributable mortality of 9.3%. Patients who met the ATS criteria had a longer hospital stay (p = 0.01), longer duration of fever (p < 0.001), and higher attributable mortality (13.1% versus 3.5%, p = 0.02) than those who did not. Three factors were independently related to mortality: CD4(+) cell count < 100/microl, radiologic progression of disease, and shock. Pleural effusion, cavities, and/or multilobar infiltrates at admission were independently associated with radiologic progression. A prognostic rule based on the five criteria of shock, CD4(+) cell count < 100/microl, pleural effusion, cavities, and multilobar infiltrates had a high negative predictive value for mortality (97.1%). The attributable mortality for severe pneumonia was 11.3%, as compared with 1.3% for nonsevere disease (p = 0.008). The ATS severity criteria are valid in HIV-infected patients with bacterial CAP. Our study provides the basis for identification of patients who may require hospitalization determined by clinical judgment and the five clinical criteria of shock, a CD4(+) cell count < 100/microl, pleural effusion, cavities, and multilobar involvement. These prognostic factors should be validated in independent cohort studies.

AIDS-Related Opportunistic Infections↗

Activities of the EM10 protein from Echinococcus multilocularis in cultured mammalian cells demonstrate functional relationships to ERM family members.

The ezrin-radixin-moesin (ERM) homolog EM10 is expressed by the larval stage of the parasite E. multilocularis and shows 46.9% overall identity in the primary structure with human ezrin. To determine whether EM10 has similar activities to ERM proteins, we investigated properties of the protein expressed in mammalian cells. In particular, we transiently expressed haemagglutinin-tagged (HA-tagged) versions of the full-length EM10 as well as the amino- and the carboxy-terminal halves of EM10 in HtTA-1 cells. In addition we stably transfected NIH-3T3 cells with untagged full-length EM10. The data demonstrate that EM10 polypeptides behave like their corresponding portions of radixin when transiently expressed in mammalian cells. The full-length and amino-terminal EM10 polypeptides were localized to cortical structures. Cells expressing the carboxy-terminal polypeptide of EM10 showed long actin-filled protrusions. Cells expressing full-length EM10 showed a reduction in endogenous moesin-staining at cortical structures. In stably transfected NIH-3T3 cells EM10 was not crisply localized but rather was diffuse throughout the cytoplasm. These cells showed a conspicuous loss of stress-fibers, a phenotype that was not seen in analogous experiments with ERM proteins. The results demonstrate both similarities and differences between the functional properties of EM10 and ERM proteins expressed in vertebrate cells.

3T3 Cells↗

[Clinical and immuno-virologic efficacy of the expanded access use of protease inhibitors for HIV-1 advanced disease].

OBJECTIVE: To compare the efficacy and tolerance of additive therapy with protease inhibitors (PI) in patients with advanced HIV infection previously treated with retro-transcriptase inhibitors (RTI). METHODS: Eighty patients with prior antiretroviral therapy with RTI (zidovudine, ddI or ddc) for more than 6 months were included. Fifteen patients received indinavir, 42 ritonavir and 23 saquinavir. Data were collected at 4, 12 and 24 weeks and included clinical events, tolerability, plasma HIV-1 RNA viral load and CD4+ cell counts. Virologic response was defined if a viral load reduction > 1 log was achieved. RESULTS: Virological response was observed in 45 patients (56.5%) at 4 weeks and was maintained in most of them at 24 weeks. Viral load below limit of detection was achieved in 11 (15%) patients at 12 weeks. Adverse effects were not uncommon, specially with ritonavir, and 10 patients (12.5%) discontinued treatment. Indinavir was the most efficient drug and statistical differences in decreasing viral load were reached in pairwaise comparison with saquinavir at any time and with ritonavir at 12 and 24 weeks. CD4+ cell counts increased with all three drugs parallel with the decrease of viral load. Four patients died and 12 had opportunistic infections. Proportion of patients without infections in the follow-up was associated with virological response over treatment (p < 0.01). CONCLUSIONS: The additive therapy with PI in advanced HIV patients can achieve a sustained reduction of viral load and a persistent recovery of CD4+ cell counts with clinical benefits. Within the limits of this study, indinavir seems more interesting in this group of patients in terms of probability pursuit of treatment because of better efficiency and fewer adverse effects.

Adult↗

NHE-RF, a regulatory cofactor for Na(+)-H+ exchange, is a common interactor for merlin and ERM (MERM) proteins.

We have identified the human homologue of a regulatory cofactor of Na(+)-H+ exchanger (NHE-RF) as a novel interactor for merlin, the neurofibromatosis 2 tumor suppressor protein. NHE-RF mediates protein kinase A regulation of Na(+)-H+ exchanger NHE3 to which it is thought to bind via one of its two PDZ domains. The carboxyl-terminal region of NHE-RF, downstream of the PDZ domains, interacts with the amino-terminal protein 4.1 domain-containing segment of merlin in yeast two-hybrid assays. This interaction also occurs in affinity binding assays with full-length NHE-RF expressed in COS-7 cells. NHE-RF binds to the related ERM proteins, moesin and radixin. We have localized human NHE-RF to actin-rich structures such as membrane ruffles, microvilli, and filopodia in HeLa and COS-7 cells, where it co-localizes with merlin and moesin. These findings suggest that hNHE-RF and its binding partners may participate in a larger complex (one component of which might be a Na(+)-H+ exchanger) that could be crucial for the actin filament assembly activated by the ERM proteins and for the tumor suppressor function of merlin.

Amino Acid Sequence↗

Comparison of two methods for the assessment of delayed-type hypersensitivity skin responses in patients with human immunodeficiency virus infection.

We compared two techniques for detecting delayed-type hypersensitivity (DTH) skin responses in 359 patients infected with human immunodeficiency virus (HIV) (mean CD4+ lymphocyte count, 387/microL). DTH responses were assessed with use of two antigenic panels administered simultaneously: tuberculin purified protein derivative (PPD) plus three control antigens (Candida albicans, mumps antigen, and tetanus toxoid) administered by the Mantoux method and by a multiple-puncture device delivering seven antigens percutaneously (MULTITEST CMI; Institut Mérieux, Lyon, France). Eighty-three patients (23%) were anergic, 216 (60%) reacted to both panels, 55 (15%) did not react to MULTITEST CMI but did react to the antigens administered by Mantoux method, and only five (1%) reacted to MULTITEST CMI without reacting to antigens administered by the Mantoux method (P < .001, McNemar's test). Each of the three possible combinations of PPD plus two control antigens administered by the Mantoux method were also superior to MULTITEST CMI for classifying patients as nonanergic (P < .001, McNemar's test). We conclude that the application of antigens by the Mantoux method is more efficient than MULTITEST CMI for detecting DTH skin responses in HIV-infected patients.

Adolescent↗