PubMed Health⌕ Search

Biomedical subjects

J L Pérez

Publications and source records attributed to J L Pérez.

At least 19 recordsLinked to original sources

Impaired anti-pneumococcal polysaccharide antibody production and invasive pneumococcal infection following heart transplantation.

An increased risk of invasive pneumococcal infection has been described among adult heart transplant (HT) recipients. Vaccination has been recommended before HT but the appropriate time for revaccination is not known. In a preliminary analysis of a prospective study involving a cohort of 32 HT recipients receiving daclizumab and triple immunosuppresion therapy, a progressive decline in pneumococcal polysaccharide antibody (anti-PPS) levels was observed during the first year after HT. One of the patients who was found to have a decrease in the levels of anti-PPS developed severe pneumococcal meningitis 20 months after HT. Before HT he had received non-conjugated 23-valent pneumococcal vaccine and showed a normal post-immunization anti-PPS production. The data suggest that long-term immunologic monitoring might be useful to recognize impairment of antibody responses under immunosuppressive therapy in HT.

Antibody Formation↗

Formulation in tablets of a cholera whole cells inactivated vaccine candidate.

Licensed as well as candidate cholera vaccines available at the present requires the dose preparation (included buffer) at the moment of application. The aim of this work was to evaluate the presentation in oral tablets of an inactivated cholera vaccine to avoid that inconveniences during application. We have therefore compared inactivated cultures of Vibrio cholerae with tablets formulation vaccine. We obtained that antigenic activity (ELISA) and immunogenicity in animal model (ELISA and vibriocidal tests) of V. cholerae inactivated cell remained unaltered in the final tablet formulation. The results suggest that the oral tablet formulation could be a useful pharmaceutical form in order to produce a new and affordable cholera vaccine.

Administration, Oral↗

Efficacy and potential for resistance selection of antipseudomonal treatments in a mouse model of lung infection by hypermutable Pseudomonas aeruginosa.

Hypermutable Pseudomonas aeruginosa strains are found with high frequency in the lungs of patients with chronic infections and are associated with high antibiotic resistance rates. The in vivo consequences of hypermutation for treatment in a mouse model of lung infection using strain PAO1 and its hypermutable derivative PAOdeltamutS are investigated. Groups of 30 mice were treated for 3 days with humanized regimens of ciprofloxacin (CIP), tobramycin (TOB), CIP plus TOB, or placebo, and mortality, total lung bacterial load, and 4x- and 16x-MIC mutants were recorded. The rates of mutation and the initial in vivo frequencies of mutants (at the onset of treatment) were also estimated and the in vitro- and in vivo-selected mutants characterized. Since both strains had identical MICs, the same pharmacokinetic/pharmacodynamic (PK/PD) parameters were obtained: area under the 24-h concentration-time curve (fAUC)/MIC = 385 for CIP and maximum concentration of drug in serum (fC(max))/MIC = 19 for TOB. Despite adequate PK/PD parameters, persistence of high bacterial numbers and amplification (50,000-fold) of resistant mutants (MexCD-OprJ hyperexpression) were documented with CIP treatment for PAOdeltamutS, in contrast to complete resistance suppression for PAO1 (P < 0.01), showing that conventional PK/PD parameters may not be applicable to infections by hypermutable strains. On the other hand, the efficacy of TOB monotherapy in terms of mortality reduction and bacterial load was very low regardless of the strain but not due to resistance development, since mutants were not selected for PAO1 and were only modestly amplified for PAOdeltamutS. Finally, the CIP-plus-TOB combination was synergistic, further reducing mortality and bacterial load and completely preventing resistance even for PAOdeltamutS (P < 0.01 compared to monotherapy), showing that it is possible to suppress resistance selection in infections by hypermutable P. aeruginosa using appropriate combined regimens.

Animals↗

[Patterns of susceptibility to antibiotics of Enterobacteriaceae causing intra-abdominal infection in Spain: SMART 2003 study outcomes].

SMART (Study for Monitoring Antimicrobial Resistance Trends) is an ongoing global antimicrobial surveillance program focused on clinical isolates from intra-abdominal infections. The objective of this subanalysis was to assess antimicrobial susceptibility patterns among Entero-bacteriaceae recovered at 13 participating Spanish sites during 2003. Antimicrobial susceptibility testing was performed using broth microdilution techniques according to the CLSI (formerly NCCLS) guidelines for MIC testing. The presence of extended-spectrum beta-lactamases (ESBL) was confirmed in isolates with a MIC of ceftriaxone, ceftazidime, or cefepime>or=2 mg/l by comparing cefepime MICs with and with-out clavulanate. A total of 981 Enterobacteriaceae recovered from 840 patients were tested, of which 398 (41%) were community-acquired. Escherichia coli was the most common isolate (571 isolates; 58%), followed by Klebsiella spp. (153; 16% Enterobacter spp. (97; 10%), and Proteus spp. (63; 6%). A total of 191 isolates (19%) from 176 patients produced inducible beta-lactamases. The carbapenems and amikacin were the most consistently active agents against the Enterobacteriaceae (susceptibility>or=99%). Resistance rates for ceftazidime, cipro-floxacin, and levofloxacin exceeded 10%. ESBLs were detected phenotypically in 61 (6%) isolates, being the most common E. coli (61%), Klebsiella spp. (20%), and Enterobacter spp. (8%). Antimicrobial resistance among Enterobacteriaceae isolated from intra-abdominal infections is a problem in Spain. A significant proportion of inducible beta-lactamase and ESBL-producing Enterobacteriaceae causing intra-abdominal infection were acquired in the community. The carbapenems ertapenem, imipenem and meropenem and the aminoglycoside amikacin were highly active in vitro against Enterobacteriaceae isolated from intra-abdominal sites, including ESBL-producing organisms.

Abdomen↗

Process development for a Cuban cholera vaccine based on the attenuated strain Vibrio cholerae 638.

Genetically modified Vibrio cholerae strain 638 (biotype El Tor, serotype Ogawa) has previously been shown to be immunogenic in animal models and in human trials. Our objective in the work reported herein was to describe the process development methods for the production of the 638 attenuated cholera vaccine. Cell seed bank, culture of biomass, lyophilization and final formulation were processes were developed. The results show kinetics of culture that fulfils a logistical model. The microbiological properties, colonizing capability, immunogenicity and non-toxigenicity of the final product were indistinguishable from the properties of the working seed lot. We conclude that the non-reactogenic, immunogenic and protective strain 638 is robust and can withstand the fermentation processes required for large-scale production of a vaccine.

Animals↗

Effects of lipids and aging on the neurotoxicity and neuronal loss caused by intracerebral injections of the amyloid-beta peptide in the rat.

The influence of diet and age on the area of lesion and on the neuronal density in the cerebral cortex was studied in rats following local injections of the amyloid-beta peptide (Abeta1-40) in PBS vehicle into the left frontal and cingulate cortices and compared with effects of injections of PBS alone into the corresponding regions of the right hemisphere The experiments were carried out in two groups of animals: one group of young adult rats and a second group of aged rats. Each group of animals, depending on the diet received, was divided into high-cholesterol, high-fat, and a control group. In order to evaluate the interaction of Abeta/PBS-cholesterol and of Abeta/PBS-fat, animals without dietary manipulation receiving Abeta and PBS injection were used as controls. The results showed that the greatest area of lesion was at Abeta injection sites in the high-cholesterol fed group of aged animals. The results also revealed a significant variance in the neuronal density by group and by injection type. Thus, high-cholesterol fed animals showed a greater reduction in neuronal density at Abeta and PBS-injected sites than that seen in the high-fat or control groups. The results also indicate that the loss of neurons at the Abeta injection site exceeds that seen in the PBS-injected area. The greatest reduction in the neuronal density was found at Abeta-injected site in the high-cholesterol fed group of aged animals. In conclusion, our findings indicate an interaction between lipids, age, and Abeta neurotoxicity, and might provide insights into the basic mechanisms involved in a short-term (acute-to-subchronic) response to Abeta peptide.

Aging↗

Contribution of clonal dissemination and selection of mutants during therapy to Pseudomonas aeruginosa antimicrobial resistance in an intensive care unit setting.

Rates of antibiotic resistance in Pseudomonas aeruginosa isolates from intensive care unit (ICU) patients are expected to be dependent on the selection of resistance mutations during therapy, the availability of exogenous resistance determinants and their dissemination potential, and the efficiency of transmission of the resistant strains. The relative contributions of these three factors were studied in an ICU with no apparent outbreak in 216 sequential P. aeruginosa isolates recovered from 102 patients between September 2002 and November 2003. Analysis of pulsed-field gel electrophoresis patterns revealed the presence of 82 different clones. Thus, the dissemination of particular resistant clones had a minimal effect on the relatively high overall resistance frequencies found for imipenem (32%), cefepime (25%), ceftazidime (24%), meropenem (22%), ciprofloxacin (18%) and tobramycin (2%). Rates of primary resistance were relatively low, and resistance development during treatment (secondary resistance) was the main factor contributing to the overall high resistance rates. In ICU settings with a low prevalence of epidemic resistant strains, the main strategy for resistance control should focus on the design of targeted regimens to avoid the development of resistance.

Anti-Bacterial Agents↗

Effect of cervical spinal cord stimulation on regional blood flow and oxygenation in advanced head and neck tumours.

BACKGROUND: Tumour ischaemia leads to decreased delivery of oxygen, chemotherapy and radiosensitisers. Hypoxia in head and neck (H&N) tumours is an important adverse prognostic factor. Spinal cord stimulation (SCS) is a well-established neurosurgical technique in the treatment of several ischaemic syndromes. This prospective study evaluated the effect of cervical-SCS on common carotid artery (CCA) blood flow and tumour oxygenation in patients with advanced H&N cancer. PATIENTS AND METHODS: Sixteen patients with advanced H&N tumours were enrolled. Cervical-SCS devices were inserted subcutaneously prior to commencement of scheduled chemoradiotherapy. Pre- and post-SCS measurements were as follows: (i) tumour oxygenation (mmHg) using polarographic probes; (ii) blood flow quantification (ml/min) and diastolic and systolic velocimetry (cm/s) in the CCA using colour Doppler. RESULTS: After SCS, median tumour oxygenation increased in two-thirds of patients (34%; P = 0.023), all patients had improved CCA blood flow (50%; P <0.001) and almost all patients showed an increased CCA diastolic velocity (26%; P = 0.003) and systolic velocity (20%; P = 0.011). CONCLUSIONS: Cervical-SCS increased tumour oxygenation and CCA blood flow, and could enhance the loco-regional delivery of oxygen, radiosensitising and chemotherapeutic drugs. Cervical-SCS as adjuvant in chemoradiotherapy of these tumours warrants further investigation.

Adult↗

Epidemiological relatedness of methicillin-resistant Staphylococcus aureus from a tertiary hospital and a geriatric institution in Spain.

From January 2000 to June 2002, 24 Staphylococcus aureus isolates were recovered from decubitus ulcers of patients in a geriatric institution, of which 17 (70.8%) were methicillin-resistant S. aureus (MRSA). Antibiotic resistance and DNA macrorestriction (pulsed-field gel electrophoresis; PFGE) patterns of the MRSA isolates were compared with a collection of 161 MRSA isolates from patients admitted to the institution's reference hospital. PFGE revealed the presence of five clonal types (found also in hospitalised patients) among the 17 MRSA isolates. The findings suggest nosocomial acquisition of the MRSA strains by five patients, with subsequent dissemination of the strains within the institution. The high rate of MRSA highlights the need for epidemiological analysis to control the dissemination of MRSA in long-term care facilities.

Aged↗

Prevalence and patterns of polyomavirus urinary excretion in immunocompetent adults and children.

BK and JC polyomavirus infections are acquired commonly during childhood, mainly asymptomatically. These viruses are thought to remain latent in renal tissue after the primary infection and to reactivate under certain conditions. This reactivation leads to urinary excretion of virus particles, which can be detected by a range of methods. However, while this reactivation has been studied in depth in immunocompromised patients, little information is available about healthy individuals. The present study used PCR-based methods to examine urine samples from healthy individuals (51 adults and 15 children), and found that 62.7% of adults and 13.2% of children excreted polyomaviruses in the urine, mostly JC virus (41.2%). JC virus excretion was continuous, while BK virus excretion was mostly occasional.

Adolescent↗

Risk factors in neuroleptic malignant syndrome. A case-control study.

OBJECTIVE: To determine whether environmental temperature, agitation, neuroleptic use, mental retardation, and affective disorders were risk factors for neuroleptic malignant syndrome (NMS). METHOD: Cases and age- and sex-matched psychiatric controls admitted to a regional acute psychiatric unit over a 10-year period. RESULTS: Both uni- and multivariate analysis revealed statistically significant differences between patients with NMS (n=15) and controls (n=45) with regard to the presence of mental retardation, psychomotor agitation, and a number of variables relating to neuroleptic use (newly introduced or increased, intramuscular administration, and dosage). We found no differences between NMS patients and psychiatric controls in respect of changes in environmental temperature. CONCLUSION: Our study supports the need for caution when using intramuscularly administered, abruptly increasing, high-dose neuroleptics, particularly in mentally retarded or agitated patients, regardless of environmental temperature.

Adult↗

[Endomyocardial fibrosis. Presentation as a right ventricular tumor].

Endomyocardial fibrosis is an uncommon disease in Spain, with the most frequent clinical feature being congestive heart failure syndrome. Complete atrioventricular block is exceptional. Two-dimensional echocardiography is a fundamental investigation achieving the diagnosis. Surgical treatment is recommended in symptomatic patients. We present a patient with heart failure secondary to endomyocardial fibrosis with complete atrioventricular block and an infrequent echocardiographic image of a polycystic mass in the free right ventricular wall.

Cardiomyopathies↗

Efficacy of interferon for chronic hepatitis C virus-related hepatitis in kidney transplant candidates on hemodialysis: results after transplantation.

OBJECTIVES: Interferon-alpha (IFN) may have undesirable effects on a functioning graft. The aim of this study was to evaluate IFN treatment in kidney transplant candidates during the hemodialysis period as well as the results after transplantation. METHODS: A total of 29 noncirrhotic hemodialysis patients with chronic hepatitis C virus (HCV) infection (based on long-term rise in ALT, HCV serology, HCV RNA by polymerase chain reaction methods, and histological evidence) were included. Tolerability to IFN treatment, pre- and posttransplantation therapeutic results, and long-term outcome were recorded. IFN regimen consisted of 3 million units (MU) times per week after hemodialysis sessions for 6 months, followed by 1.5 MU after each hemodialysis session for an additional 6 months. All patients gave informed consent for participation. RESULTS: IFN therapy was fairly well tolerated. Adverse effects due to IFN toxicity, renal disease, or causes related to the immunological properties of IFN were observed in 24% of patients. At the end of treatment, ALT had normalized in 23/28 patients (82.1%), and HCV RNA had cleared in 23/28 patients (82.1%). During follow-up, HCV RNA was persistently negative in 18 patients (64%, including transplant recipients). A total of 14 patients (nine HCV RNA-negative) received a kidney transplant. Mean follow-up after the procedure was 41 +/- 28 months. In all, 12 patients had a functioning graft, one had acute vascular rejection, and one died of carcinoma. All transplanted patients maintained normal ALT levels, and eight remained HCV RNA-negative. CONCLUSIONS: Treatment results in our study population were better than those observed in the general population. The long-term response achieved, which was maintained after transplantation, supports the use of IFN for HCV hepatitis in kidney transplant candidates under hemodialysis.

Adult↗

Passive protection of serum from volunteers inoculated with attenuated strain 638 of Vibrio cholerae O1 in animal models.

As part of the studies to obtain an oral vaccine against cholera disease, the protective effect of serum from volunteers inoculated in a controlled trial with a candidate live attenuated vaccine of Vibrio cholerae O1, El Tor Ogawa (638; CTX&phi; mutant, hap::celA), was tested. It was confirmed that the serum, as well as the purified IgG and IgA from the volunteers had a protective effect in both of the animal models used, although the purified antibodies needed the presence of complement to be protective. These results emphasize the expectations about the protective potential of the candidate in challenge studies in humans to be conducted very soon.

Animals↗

[Evaluation of four rapid methods for the investigation of the toxigenic capacity of Clostridium difficile strains isolated in a selective medium].

BACKGROUND: Use of selective Clostridium difficile culture as a diagnostic method for C. difficile associated disease requires to prove the toxigenic ability of the isolates. Toxin B detection by cell culture assay after growing the microorganism in enriched broth is the standard method, but it delays the final diagnosis for 3-5 days. This study compares retrospectively four rapid techniques for detecting these toxigenic C. difficile strains. METHODS: 106 clinical isolates of C. difficile (72 toxigenic and 34 non-toxigenic), these and 16 clinical strains of other species of Clostridium were investigated. The four methods were performed directly from colonies growing on solid agar. They were: a) cytotoxin detection in cell culture; b) two PCR amplifications of toxin A and toxin B, respectively, and c) toxin A detection by an immunoenzymatic method (VIDAS CDA2). All these procedures were completed within a normal working day. RESULTS: Only the 72 toxigenic C. difficile strains gave positive results by cell culture and PCR techniques (sensitivity and specificity: 100%). A total of 14 out of 49 toxigenic C. difficile strains showed negative results by the VIDAS assay in the first run, but all them were positive in repeated tests. CONCLUSIONS: Although all methods performed well, the cytotoxicity assay done directly on colonies growing in CCFA is a simple and rapid technique, and appears to be well-suited for use in laboratories with access to cell cultures.

Agar↗