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Biomedical subjects

M López

Publications and source records attributed to M López.

At least 37 records · Page 2Linked to original sources
PubMed2005

Dendritic cell immunizations alone or combined with low doses of interleukin-2 induce specific immune responses in melanoma patients.

Dendritic cell (DC)-based therapy has proved to be effective in patients with a variety of malignancies. However, an optimal immunization protocol using DCs and the best means for delivering antigens has not yet been described. In this study, 20 patients with malignant melanoma in stages III or IV were vaccinated with autologous DCs pulsed with a melanoma cell lysate, alone (n = 13) or in combination with low doses of subcutaneous (s.c.) interleukin (IL)-2 injections (n = 7), to assess toxicity, immunological and clinical responses. Monocyte-derived DCs were morphological, phenotypic and functionally characterized in vitro. Peripheral blood mononuclear cells (PBMC), harvested from patients either prior to and after the treatment, were analysed using enzyme-linked immunosorbent spot (ELISPOT). After vaccination, 50% of the patients tested (seven of 13) from the first group and (three of seven) from the second, showed an increase in interferon (IFN)-gamma production in response to allogeneic melanoma cell lines but not to controls. Four of five tested human leucocyte antigen (HLA)-A2(+) patients with anti-melanoma activity also showed specific T cell responses against peptides derived from melanoma-associated antigens. Delayed type IV hypersensitivity reaction (DTH) against melanoma cell lysate was observed in six of 13 patients from the group treated with DC vaccines only and four of seven from the group treated with the combination of DCs and IL-2. Significant correlations were found between DTH-positive responses against tumour lysate and both disease stability and post-vaccination survival on the stage IV patients. There were no toxicities associated with the vaccines or evidence of autoimmunity including vitiligo. Furthermore, no significant enhancement was observed as a result of combining DC vaccination with IL-2. Our data suggest that autologous DCs pulsed with tumour lysate may provide a standardized and widely applicable source of melanoma specific antigens for clinical use. It is safe and causes no significant side effects and has been demonstrated to be partially efficient at triggering effective anti-melanoma immunity.

Antigen Presentation↗
PubMed2005

Regulation of peroxisome proliferator activated receptor-gamma in rat pituitary.

Peroxisome proliferator activated-receptor gamma (PPARgamma) is a member of the nuclear receptor superfamily and, in addition to its relation with obesity and insulin sensitivity, it has recently been localized in human and mice pituitary, indicating a functional significance of PPARgamma in adenopituitary tumours. In the present study, we localized the PPARgamma mRNA and protein in different cell types of rat pituitary. Moreover, using the real-time polymerase chain reaction, we assessed the mRNA expression of PPARgamma in different physiological and pathological settings known to be associated with alterations in anterior pituitary cell proliferation and/or function. Our experiments have shown that PPARgamma mRNA levels were repressed by oestrogen through an oestrogen receptor-alpha effect. However, PPARgamma protein levels were only modified in males but not in females. On the other hand, PPARgamma mRNA expression was increased in dwarf rats in comparison with Lewis rats. Finally, nutritional, thyroid status or pregnancy did not change PPARgamma expression. Taken together, we provide new data regarding the regulation of pituitary PPARgamma mRNA by hormonal and metabolic status.

Animals↗
PubMed2005

Poly (ADP-ribose) polymerase-1 haplotypes are associated with coeliac disease.

In coeliac disease (CD) there is an inflammatory status of the intestinal mucosa because of a high expression of proinflammatory mediators. The nuclear protein poly (ADP-ribose) polymerase-1 (PARP-1) has been implicated in the initial inflammatory response by modulating transcription of inflammation-related genes. The aim of this work was to investigate the role of PARP-1 gene promoter region haplotypes in relation to coeliac disease susceptibility. We analysed a coeliac population consisting of a case-control panel with 120 CD patients and 311 healthy blood donors. A CA microsatellite, as haplotype-defining variant of the whole PARP-1 promoter, was typed using a polymerase chain reaction (PCR) method combined with fluorescence technology. We considered two promoter haplotypes: A defined by short CA alleles (83-87 bp) and B defined by long CA alleles (89-101 bp). Haplotype A was significantly increased within the coeliac patients group (P = 0.007 OR 1.6 95%CI 1.12-2.35). Additionally, we observed a significant dose effect, showing homozygous individuals for haplotype A higher risk for CD susceptibility (P = 0.007, OR 1.79 95%CI 1.14-2.82). Our results provide the first evidence that PARP-1 haplotypes are related with coeliac disease susceptibility.

Autoimmune Diseases↗
PubMed2005

[Evaluation of refractive prognosis factors in myopic LASIK].

PURPOSE: Our objective was to evaluate myopic Lasik refractive results according to preoperative refraction findings. METHODS: In 200 eyes, classified into 4 groups according to preoperative sphere and cylinder findings, different postoperative refractive parameters were compared: predictability, visual acuity (VA), security index (SI) and efficacy index (EI). RESULTS: Grouped by sphere: spherical correction was better than cylindrical correction. Highest negative spheres resulted in undercorrection (p<0.0171). The residual astigmatism was similar and the predictability within +/- 1.0 D was lower for the most myopic groups. Grouped according to cylinder: the higher the cylinder, the more cylinder undercorrection (p<0.05) and more sphere overcorrection was achieved (p=0.0469). Between the lowest and highest cylinder levels, the residual astigmatism difference was of -0.32 x 90 degrees and predictability +/-1.0 D was of 98 and 94% for the sphere and 96 and 88% for the cylinder respectively. Defocus Equivalent <1 D for the lowest and highest myopic groups was 74 vs. 46% for the cylinder and 82 vs. 38% for the sphere respectively. Pre and postoperative VA were lower for higher spheres or cylinders. SI >1.0 was similar to EI (+/-0.9), for preoperative sphere and cylinder groups. Best corrected visual acuity (BCVA) of 20/25 by sphere was 100% vs. 60% and of 20/30 by cylinder was 100% vs. 83%, for lower and higher myopic groups respectively. CONCLUSIONS: Analysis by grouping preoperative refractive errors is helpful for establishing its influence and improving LASIK prognosis and treatment. This procedure is effective and safe for all groups, and its inaccuracy is due more to astigmatism than to spherical error. As astigmatism increases, less spherical and higher cylindrical ablation should be performed.

Humans↗
PubMed2005

Treatment with pegylated interferon alpha-2b and ribavirin in patients unresponsive to previous treatments with standard interferon as monotherapy or combined with ribavirin.

BACKGROUND: Little information is available on the effect of pegylated interferon (PEG) and ribavirin (RBV) in patients with chronic hepatitis due to virus C (CHC) who were non-responders to previous treatment. OBJECTIVES: To evaluate response to treatment in patients who were non-responders to previous treatment. METHODS: One hundred and twenty-four patients who were non-responders to previous treatment were included. All patients were treated with PEG alpha 2b interferon (dose: 1.5 mg/kg body weight) and RBV (weight-dependent dosage). A qualitative PCR of virus C after six months was evaluated. In those in whom this was positive, treatment was discontinued; in those who were negative treatment was continued to the end of the year. RESULTS: Response following treatment (RFT) was 35.4% (44 patients), and sustained viral response (SVR) 29.8% (37 patients). No relation was observed between RFT, SVR and any previous treatment. RFT was dependent on low initial viremia and SVR was significantly and independently related to low serum hepatitis C RNA and a non-1 genotype. In general, treatment was well tolerated. Medication was discontinued in 5 patients, and doses reduced in 18. CONCLUSION: On retreatment with PEG and RBV a SVR of 29.8% was achieved in patients who had not responded to previous treatment, so its use in this group of patients is indicated.

Adult↗
PubMed2004

A possible role of neuropeptide Y, agouti-related protein and leptin receptor isoforms in hypothalamic programming by perinatal feeding in the rat.

AIM/HYPOTHESIS: Perinatal overfeeding predisposes humans and rats to obesity and diabetes in later life. One classical model for studying the effect of early feeding is manipulation of the size of rat litters. Rats growing up in small litters gain more weight than rats growing up in normal-sized litters. Interestingly, these obese rats maintain this phenotype in adulthood. Conversely, rats raised in large litters show a delay in growth and a decrease in body weight. The aim of this work was to assess the hypothalamic control mechanisms of food intake regulated by perinatal feeding. METHODS: Leptin levels were analysed using RIA. Leptin receptor mRNA levels were analysed using RT-PCR. Neuropeptide mRNA levels were analysed using in situ hybridisation. RESULTS: Perinatally overfed neonatal male rats exhibited hyperleptinaemia and a decrease in hypothalamic mRNA levels of the long isoform of the leptin receptor (OB-Rb), explaining their leptin resistance. Moreover, this obese model showed an increase in the mRNA expression of cocaine- and amphetamine-regulated transcript, neuropeptide Y and agouti-related protein in the hypothalamic arcuate nucleus (ARC). In contrast, perinatally underfed neonatal male rats with hypoleptinaemia showed an increase in hypothalamic mRNA of the short isoforms of the leptin receptor. Furthermore, they exhibited an increase in expression of neuropeptide Y and agouti-related protein in the ARC. CONCLUSIONS/INTERPRETATION: Rats overfed during early postnatal life show a leptin-resistant state mediated by down-regulation of the hypothalamic OB-Rb. These data, together with the increased expression of neuropeptide Y and agouti-related protein in specific neurons in the ARC, might indicate the existence of regulated programming in this nucleus and may provide a new aetiopathogenic concept in susceptibility to obesity.

Aging↗
PubMed2004

Development and validation of a reversed-phase liquid chromatographic method for analysis of D4T (Stavudine) in rat plasma.

An improved and simplified high-performance liquid chromatographic (HPLC) method at UV detection 265 nm is presented for the determination of d4T in rat plasma. The mobile phase consists of methanol-distilled water-acetic acid in the 23:77:0.2 (v/v) ratio. Quantification is achieved by the peak-area ratio method with reference to the internal standard. This paper presents linearity, accuracy, precision, limit of quantification and limit of detection, specificity-selectivity and sample stability data. Based on the intra and inter-day validation, all coefficients of variation (CV) were found less than 15%. The assay is sufficiently rapid and sensitive and was applied in a pharmacokinetic study in rats.

Animals↗
PubMed2004

Mutant prevention concentration: comparison of fluoroquinolones and linezolid with Mycobacterium tuberculosis.

OBJECTIVES: The mutant prevention concentration (MPC) has recently been defined to characterize the capacity for severely restricting the selection of resistant mutants during antibiotic treatment. We determined this parameter for ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin and linezolid in Mycobacterium tuberculosis clinical isolates in our setting. METHODS: We determined the antibiotic concentration that prevents the selection of resistant mutants following inoculation with a high mycobacteria inoculum on Middlebrook 7H11 plates with serial dilutions of the antibiotics in 224 M. tuberculosis isolates. RESULTS: Fifty percent of the strains exhibited values of MPC (MPC(50)) lower than 0.8, 0.6, 0.4, 0.4 and 0.6 mg/L for ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin and linezolid, respectively. If 90% of the strains are considered (MPC(90)), the values are seen to rise to 2, 1.8, 1, 1.2 and 1.2 mg/L, respectively. CONCLUSIONS: When we compare this parameter with the drug levels in serum and tissue, it can be seen that ciprofloxacin is the least useful of the fluoroquinolones studied, whereas moxifloxacin appears to be the most active. Linezolid exhibits excellent activity against this microorganism (MPC(90) 1.2 mg/L and AUC 140.3 mg.h/L) and this makes us consider that its usefulness in the treatment of this pathology should be thoroughly evaluated.

Acetamides↗
PubMed2004

The stability of 2-acetoxy-4-trifluoromethylbenzoic acid (Triflusal) in micellar pseudophase.

The new platelet antiaggregant Triflusal or 2-acetoxy-4-trifluoromethylbenzoic acid presents a structural analogy to acetylsalicylic acid (ASA). Alkaline hydrolysis of triflusal was studied in the presence and absence of cationic micelles of N-cetyl-N-ethyl-N,N-dimethylammonium bromide (CDEABr) at different KOH concentrations and different temperatures (25, 30, and 37 degrees C) using a spectrophotometric method. The influence of potassium bromide concentration upon alkaline hydrolysis at 25 degrees C is also discussed. At constant [KOH] pseudofirst-rate constant (k(obs)) decreased with increasing [CDEABr] at concentrations greater than the CMC and also decreased with increasing [KBr] at constant [KOH] and [CDEABr]. To explain the effect of cationic micelles of CDEABr upon alkaline hydrolysis, the pseudophase ion exchange model was used. The values of the micellar properties such as the critical micelle concentration, the degree of micellar ionization and the neutralized fraction of the head group obtained by conductivity measurements were determined previously.

Algorithms↗
PubMed2004

Pseudo-angiomatous stromal hyperplasia presenting as a breast mass: imaging findings in three patients.

The authors review the mammographic, ultrasonographic and magnetic resonance (MR) imaging findings in each of three patients with a breast tumor corresponding to the characteristics of pseudo-angiomatous stromal hyperplasia (PASH). Imaging findings are indistinguishable from those of the more common type of fibroadenoma, and they are categorised as BIRADS type 3 lesions (probably benign lesions). Their benign condition and behaviour compared with other similar cases, allows the recommendation that surgical excision be avoided, and the patients monitored with periodic follow-up. The diagnosis can be confidently established by sampling with a breast core biopsy in the case of any doubt about whether the lesion is benign if the patient is anxious.

Adult↗
PubMed2004

Use of cytological specimens for p53 gene alteration detection in oral squamous cell carcinoma risk patients.

AIMS: Recurrence and multifocal nature are two important characteristics of oral squamous cell carcinoma. Leukoplakia is the most frequent pre-cancerous oral lesion and, in most cases, it is not possible to predict malignant capacity. The objective of this study is to identify p53 alterations in cells taken from the oral cavity of at-risk patients. MATERIALS AND METHODS: The following samples were collected from 34 patients with oral leukoplakia with and without previous carcinoma: oral rinse, a brush swabbed over the lesions and hair roots. Mutational analysis of the p53 gene was performed by single-strand conformation polymorphisms and confirmed by DNA sequencing. RESULTS: We detected 11 mutations in p53 gene in oral cytological specimens. These alterations were observed only in brush cytology samples in patients without previous carcinoma, and in both samples (rinse and brush) in patients with previous carcinoma. Three of these patients had disease recurrence. CONCLUSION: This non-invasive technique may be useful in the follow-up of at-risk patients, and introduces new possibilities to analyse molecular markers before malignant lesions are clinically apparent.

Adult↗
PubMed2004

Prevalence of sexual dysfunctions in Argentina.

The objective of this study consisted in assessing the prevalence of erectile dysfunction (ED) and other sexual dysfunctions in a group of men who attended a prostate awareness week campaign. In total, 2715 men attended to 'Semana de la Prostata 2001' campaign and received an additional questionnaire on sexual health. The prevalence of ED, desire and ejaculatory disorders was of 41.7, 33.8 and 49.3%, respectively; however, not all of them lived these difficulties as a real sexual problem because only 918 men (37.8%) acknowledged having 'any sexual difficulty'. Only 13.7% of the attendees consulted a physician for this reason in the past. This first Argentinean study proves the high prevalence of sexual dysfunctions in our population.

Adult↗
PubMed2004

CA microsatellite polymorphism of the nuclear factor kappa B1 gene in celiac disease.

In the present work, we investigate the possible effect of a CAn microsatellite polymorphism in the nuclear factor kappa B1 (NFKB1) gene on predisposition to celiac disease (CD). Seventy-eight Spanish families with CD were genotyped using a polymerase chain reaction (PCR)-fluorescent method, and the transmission patterns of different CAn alleles were analysed. Furthermore, in order to type the CAn polymorphism more accurately, samples between 126 and 144 bp were cloned and sequenced. A trend of association with the 132-bp allele was found (P = 0.02). This allele was more frequently transmitted to affected sibs, although the results of statistical tests were not significant after correction for multiple comparisons. After sequencing, we found that the 132-, 138- and 142-bp alleles had two As at the end of the CA microsatellite, with the other alleles presenting the described pattern (NCB1 nucleotide U60337) for the microsatellite repeats. These results suggest that the NFKB1 CAn microsatellite does not play a major role in CD susceptibility. In addition, a more detailed molecular characterization of the CA microsatellite is described.

Base Sequence↗
PubMed2004

Stabilization of a freeze-dried recombinant streptokinase formulation without serum albumin.

AIM: To evaluate the stability and content homogeneity of a new freeze-dried and albumin-free formulation of recombinant streptokinase (SKr) that has recently been approved by the Cuban National Center for the Quality Control of Medicaments. MATERIALS AND METHODS: The new formulation was stored at the intended recommended storage temperature of 4 degrees C, and under accelerated storage conditions (37 degrees C). The stability of the product was also examined after reconstitution and storage at room temperature (28 degrees C) for 24 h. Samples were periodically subjected to biological activity assays (S-2251 chromogenic-substrate method or in vitro clot-lysis assay), sodium dodecyl sulphate/polyacrylamide gel electrophoresis (SDS/PAGE), pyrogen and sterility testing, abnormal toxicity screening, organoleptic evaluation, and measurement of residual moisture and pH. RESULTS AND DISCUSSION: Accelerated storage (37 degrees C) data showed biochemical stability of SKr throughout the 6-month study with activity, remaining between 90 and 110% of its nominal value (0.75 x 10(6) IU/mL). SDS/PAGE-determined purity showed that SKr remained above 97 %. Furthermore, the formulation was non-pyrogenic, non-toxic, sterile and organoleptically acceptable. Real-time storage data confirmed the excellent biochemical long-term (30 months) stability of the new formulation of SKr. Comparison with other freeze-dried preparations showed that the new formulation was organoleptically better. The formulation was stable after reconstitution and storage at 28 degrees C for 24 h. The content homogeneity of this new formulation was also satisfactory. CONCLUSIONS: This study demonstrated the stability and the content homogeneity of this formulation, despite the absence of albumin as stabilizer.

Chemistry, Pharmaceutical↗
PubMed2004

[Interstitial pneumonitis associated with sirolimus administration in a renal transplantation patient: a clinical case].

Sirolimus is an immunosuppressive drug which has proved its effectivity to reduce the incidence of acute rejection in renal transplantation receptors. As this drug lacks nephrotoxic effects, its simultaneous use with other anticalcineurinic drugs allows the use of reduced doses. Thrombocytopenia and hyperlipidemia are the best known side-effects of sirolimus administration. Alterations in hepatic biochemistry results are also common. Some instances of interstitial pneumonitis associated to its use have been recently reported. In this paper we present a clinical case related to this rare but already confirmed adverse side-effect, which apart from the other more common nosologies occurring in immunosuppressed patients, should be taken into account in the differential diagnosis of interstitial pneumonitis in patients who are being administered this drug.

Aged↗
PubMed2003

Primary ovarian trabecular carcinoid tumour: a case report with an immunohistochemical study and a review of the literature.

INTRODUCTION: Primary ovarian carcinoid tumours are uncommon neoplasias. There are distinct histological types with different behaviours: insular, trabecular, mucinous and mixed. The trabecular subtype is very rare and unlike other carcinoid subtypes, it is characterised by the absence of a clinical carcinoid syndrome and has been related with a better prognosis than the others. No distant metastases have yet been reported. CASE REPORT: We present a case of a 76-year-old woman diagnosed with a left ovarian tumour. She underwent a radical hysterectomy with bilateral salpingo-oophorectomy and regional lymph node clearance. Histology revealed an ovarian trabecular carcinoid tumour and no adjuvant treatments were performed. The patient is alive and free of disease 70 months following diagnosis. DISCUSSION: Immunohistochemical staining for p53 protein, and a comparative study with other subtypes of ovarian carcinoid tumours (insular and mucinous) is discussed in this report.

Aged↗
PubMed2003

Ovarian metastases caused by cholangiocarcinoma: a rare Krukenberg's tumour simulating a primary neoplasm of the ovary: a two-case study.

INTRODUCTION: Ovarian metastases represent 10% of all ovarian malignancies. They are characterized by their ability to occasionally reproduce mimicking the clinical and morphological appearance of primary tumours, making diagnosis difficult. Most of these tumours originate in the digestive tract, the best known being Krukenberg's tumour in the stomach. Cholangiocarcinomas are rare neoplasias that very rarely affect the ovary. Their retroperitoneal location and low histological specificity in the ovary may lead to a misdiagnosis. This makes it necessary to accurately assess all clinical, radiological and morphological symptoms so as to avoid inappropriate treatments in affected patients. CASE REPORT: Two cases of biliary cholangiocarcinomas simulating an ovarian neoplasia are reported.

Adult↗