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Biomedical subjects

J Prieto

Publications and source records attributed to J Prieto.

At least 379 records · Page 21Linked to original sources

Transjugular intrahepatic portocaval shunt after thrombus disruption in partially thrombosed portal veins.

Portal vein (PV) thrombosis increases the risk of variceal bleeding in cirrhotic patients with portal hypertension. Its presence also complicates PV access during transjugular porto-caval shunt (TIPS) placement. We overcame this obstacle by using ultrasound (US) guidance for PV entry. Clot disruption by balloon catheters was then performed before placing the vascular endoprostheses for portal-venous shunting. We treated 3 cirrhotic patients in such fashion with good clinical results. Portal thrombi progressively disappeared after shunting due to both balloon disruption and the rise in portal blood flow velocity.

Catheterization↗

Regression of colon cancer and induction of antitumor immunity by intratumoral injection of adenovirus expressing interleukin-12.

Interleukin-12 (IL-12) has been shown to possess potent immunoregulatory and antitumoral effects. We have evaluated the anti-oncogenic potential and the mechanisms of the antitumoral effect of in vivo adenovirus-mediated transfer of IL-12 gene in a murine model of colon cancer. AdCMVIL-12 was constructed to permit coordinated production of p40 and p35 subunits of IL-12 gene to obtain the maximum IL-12 bioactivity. Infection of murine colon cancer CT-26 cells in vitro with AdCMVIL-12 resulted in the production of high levels of IL-12. In vivo gene therapy of colon cancer nodules by intratumoral injection of AdCMVIL-12 induced a local increase in IL-12 and interferon-gamma levels and a complete regression of the tumor in 26 of 34 (76%) mice. Tumor disappeared between days 7 and 10 after vector administration. The antitumoral effect was mediated by CD8+ T cells and was associated with the generation of cytotoxic T lymphocytes against colon cancer cells. Animals that eliminated the tumor were protected against a second administration of neoplastic cells. Treatment with AdCMVIL-12 of one tumor nodule also caused regression of established tumors at distant sites. These data demonstrate that AdCMVIL-12 is a useful therapeutic tool for established colon cancer in mice and should be considered for application in humans.

Adenoviridae↗

Influence of temperature and concentration on the postantifungal effect and the effects of sub-MIC concentrations of four antifungal agents on previously treated Candida species.

BACKGROUND: The objective of this study was to investigate the impact of different temperatures (22, 35 and 37 degrees C) on the postantifungal effect (PAFE) and the effect of sub-MIC concentrations (1/4 x MIC) on Candida albicans and Candida glabrata in PAFE stage (PAFSE). METHODS: This stage was induced by a 1.5-hour pretreatment with different doses (1 x, 4 x and 8 x MIC) of four antifungal agents that are fundamental to modern candidiasis therapy. RESULTS: The temperature, as well as the dose of the antifungal agent that was applied during the pretreatment, determined the duration of the two studied effects. An increase in the temperature and/or the dose prolonged the duration of the PAFE and PAFSE in both species, independent of the applied antifungal agent. Amphotericin B and 5-fluorocytosine always induced significant PAFEs (0.5-4.8 h and 0.5-3.0 h, respectively), which were increased (0.7-3.4 h and 0.5-3. 2 h, respectively) by posterior exposure to 1/4 x MIC of the respective antifungal agent. In the case of ketoconazole and fluconazole, temperature and concentration were especially important. Although neither antimycotics was able to induce a significant PAFE, posterior exposure to 1/4 x MIC of each of the two azoles led in both yeast species to a significant PAFSE of up to 0.8 h (if the concentrations and/or the temperatures were high enough). CONCLUSION: Factors such as temperature and concentration could be important when choosing an antifungal agent.

Antifungal Agents↗

In vitro killing kinetics and postantibiotic effect of josamycin and other macrolides on several bacteria.

The antimicrobial activity [minimal inhibitory concentration (MIC) and killing kinetics] and postantibiotic effect (PAE) of different concentrations (MIC and 10 x MIC) of josamycin, erythromycin, midecamycin and azithromycin on Streptococcus pneumoniae, Staphylococcus aureus and Escherichia coli were studied in vitro. The MIC and killing kinetics were determined by standard methods. The PAE was measured after 1 h exposure to the drugs, which were removed by diluting the culture 1,000-fold. All tested macrolides had their lowest MIC against S. pneumoniae, and the most active against S. aureus was josamycin. In killing kinetics, using 10 x MIC, the macrolides exhibited a bactericidal effect against S. pneumoniae and E. coli, with reductions of 3 log10 in colony-forming units per milliliter with respect to the initial inoculum, while a bactericidal effect was not observed for S. aureus. The PAEs were concentration dependent, the greatest PAEs being obtained with S. pneumoniae. Although lower, the PAEs induced on E. coli were significant when high concentrations of the drug were tested. The assayed macrolides showed both more activity and PAEs on S. pneumoniae.

Anti-Bacterial Agents↗

Enhancement of the susceptibility of Staphylococcus aureus to phagocytosis after treatment with fosfomycin compared with other antimicrobial agents.

Phagocytosis and intracellular killing of invading pathogens by host cells play the major role in resistance to bacterial infections. In vitro, antibiotics improve the susceptibility of microorganisms to antimicrobial activity of leukocytes, suggesting that this effect may contribute to determine the antimicrobial therapy and safe dosing intervals. The susceptibility of Staphylococcus aureus to phagocytosis and killing by human polymorphonuclear leukocytes (PMNL) in the presence of normal human serum in the postantibiotic phase of fosfomycin were compared with ciprofloxacin, cefotaxime and pristinamycin. Pretreatment of S. aureus for 10 min with 4 x MIC of fosfomycin and ciprofloxacin clearly sensitized the bacteria to leukocytic killing in the presence of normal human serum (10% v/v); cefotaxime and pristnamycin failed to enhance the phagocytic killing.

Anti-Bacterial Agents↗

Influence of human serum on the postantifungal effect of four antifungal agents on Candida albicans.

This study evaluates the influence of both fresh and heated human serum on the postantifungal effect (PAFE) induced by different concentrations of amphotericin B (AmB), 5-fluorocytosine (5-Fc), Ketoconazole (Kz) and fluconazole (Flu) on two strains of Candida albicans. The concentrations were selected in harmony with the pharmacokinetic properties and toxicity of the drugs. Without serum there was no delay in the growth of yeast cultures pretreated with Kz or Flu, leading to negative PAFEs, however with AmB and 5-Fc the PAFEs were positive. When assays were made in the presence of 10% fresh human serum, the duration of the PAFEs increased with all drugs tested, and those induced by azolic agents became positive. In the presence of 10% human serum heated at 56 degrees C for 30 min, the PAFEs of the antifungal agents were similar to those obtained in the absence of serum. Our results suggest that fresh serum positively influenced PAFE which may be an important factor in determining the dosing regimen for infection by yeasts.

Amphotericin B↗

Pharmacodynamic effects of ciprofloxacin, fleroxacin and lomefloxacin in vivo and in vitro.

The present study investigates the postantibiotic effect (PAE) in vivo, and the postantibiotic subinhibitory concentration effects (PA-SE) in vitro and SE in vivo of three 4-fluoroquinolones (ciprofloxacin, fleroxacin and lomefloxacin) against standard strains of Staphylococcus aureus and Escherichia coli. In vivo killing kinetics have also been performed using two different short administrations to study if the PAE duration could cover the time that the antibiotic was below the minimal inhibitory concentration (MIC) in serum. The results show that the three antimicrobial agents induced long PAEs (1.9-3.1 h) against the two microorganisms. Moderate but significant in vitro PA-SEs were also produced (1-->9 h). The in vivo SEs were not significant except when the effect of lomefloxacin on E. coli was assayed (0.54 h). Finally, the in vivo killing kinetics showed that the administrations that included the PAE duration were as effective as the schedule that maintained the antibiotic levels in serum above the MIC. Only when fleroxacin and S. aureus were assayed, this last administration was more effective (+0.9 log10 colony-forming units/thigh).

Animals↗

Effects of antifungal pretreatment on the susceptibility of Candida albicans to human leukocytes.

The aim of this work was to measure the susceptibility of Candida albicans pretreated for 2 or 6 h with fluconazole (Flu), ketoconazole (Ktz), amphotericin B (AmB) and 5-fluorocytosine (5-Fc) to the fungicidal action of human polymorphic leukocytes. The influence of pretreatment was measured by comparing the delay (in hours) and reduction (log10) in growth of pretreated cultures in the presence of leukocytes and serum with that of non-pretreated control cultures. Six-hour pretreatments with Flu, Ktz, AmB and 5-Fc led to growth delays of 1, 3, 3 and 3 h, respectively. No significant differences were found when pretreatment lasted only 2 h. With respect to a reduction in growth, this was larger when the preincubation was 6 h, mainly for 5-Fc and AmB. 5-Fc was seen to be the most effective, followed by Ktz, AmB and finally Flu. It may be concluded that antifungal pretreatment renders this yeast more susceptible to the action of leukocytes. The degree of susceptibility achieved is dependent on the antifungal agent employed.

Amphotericin B↗

[The immunotherapy potential of agonistic anti-CD137 (4-1BB) monoclonal antibodies for malignancies and chronic viral diseases].

Pharmacological intervention on the immune system to achieve more intense lymphocyte responses has potential application in tumour immunology and in the treatment of chronic viral diseases. Immunostimulating monoclonal antibodies are defined as a new family of drugs that augment cellular immune responses. They interact as artificial ligands with functional proteins of the immune system, either activating or inhibiting their functions. There are humanized monoclonal antibodies directed to the inhibitory receptor CD152 (CTLA-4) that are being tested in clinical trials with evidence of antitumoural activity. As a drawback, anti-CTLA-4 monoclonal antibodies induce severe autoimmunity reactions in a fraction of the patients. Anti-CD137 monoclonal antibodies have the ability to induce potent immune responses mainly mediated by cytotoxic lymphocytes with the result of frequent complete tumour eradications in mice. Comparative studies in experimental models indicate that the antitumour activity of anti-CD137 monoclonal antibodies is superior to that of anti-CD152. CD137 (4-1BB) is a leukocyte differentiation antigen selectively expressed on the surface of activated T and NK lymphocytes, as well as on dendritic cells. Monoclonal antibodies acting as artificial stimulatory ligands of this receptor (anti-CD137 agonist antibodies) enhance cellular antitumoural and antiviral immunity in a variety of mouse models. Paradoxically, anti-CD137 monoclonal antibodies are therapeutic or preventive in the course of model autoimmune diseases in mice. In light of these experimental results, a number of research groups have humanized antibodies against human CD137 and early clinical trials are about to start.

Animals↗

[Antiphospholipid syndrome].

Antiphospholipid syndrome is a well-defined clinical and serological entity characterized by arterial and/or venous thrombosis, recurrent abortion and thrombocytopenia. Anticardiolipin antibodies and lupus anticoagulant are autoantibodies directed against negatively charged phospholipids, which represent the serologic criteria for the diagnosis of the antiphospholipid syndrome. In this review the pathogenic mechanisms of anticardiolipin antibodies, their clinical findings and the current therapeutical strategies are discussed.

Abortion, Habitual↗

[McArdle's disease. Apropos of a case].

McArdle's disease (glycogenosis type V) is a metabolic disorder of hydrocarbons, inherited with autosomic recessive pattern. Biochemically is defined by a myophosphorylase deficiency; clinically it is characterized by exercise intolerance, due to the impossibility of providing energetic substrate to the muscle, myalgias and stiffness. We present a case report of a patient with McArdle's disease and we comment the diagnostic procedures and current therapeutic options.

Adult↗

Infection control. Dazed and confused.

This research project aims to uncover the practical concerns of health care staff on a hospital ward while attempting to implement isolation precaution guidelines for patients with Clostridium difficile-associated diarrhoea (CDAD) and methicillin-resistant Staphylococcus aureus (MRSA). The project is still in progress so this article describes the research methods used and some preliminary findings.

Attitude of Health Personnel↗

[Neurophysiological study of thin myelinated and unmyelinated fibers].

INTRODUCTION: Standard neurophysiological techniques evaluate thick myelinated fibers. Yet, peripheral nerves are equally composed of thin myelinated and unmyelinated fibers. The latter are responsible for autonomic function as well as temperature and pain perception. DEVELOPMENT: Microneurographic studies are restricted to investigation laboratories. Since the techniques are complex and invasive, their performance is still poor for clinical purposes and some of the components to be analyzed, such as cardiovagal, cannot be directly recorded. The clinical need to evaluate the functions regulated by the autonomic nervous system (ANS) had led to devising a series of tests which, in most cases, rely on reflex responses evoked by already known standardize stimuli. The battery chosen has to be non invasive, reproducible, specific, providing relevant data to the investigated function, with a readily available technology, which has to be managed being aware of the physiological and pathological factors that might bear an influence on the results. The recent development of heart rate and blood pressure power spectral analysis, provides a new interesting insight for quantification of ANS abnormalities. The study of thermography and thermometry of body surface brings forward evidence on the activity of other thin and unmyelinated fibers components of the peripheral nerve spectrum. CONCLUSION: The adequate management of the above mentioned tests gives rise to a more extensive and appropriate knowledge of the whole peripheral nerve fiber spectrum.

Arrhythmias, Cardiac↗