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Biomedical subjects

M Robles

Publications and source records attributed to M Robles.

At least 19 recordsLinked to original sources
PubMed2006

Accurate quantification methods to evaluate cervical cord atrophy in multiple sclerosis patients.

OBJECT: Automatic accurate measurement techniques are needed to increase reproducibility in the quantification of cervical cord area (CCA) with magnetic resonance (MR) imaging in the assessment of central nervous system (CNS) atrophy in multiple sclerosis (MS) patients. MATERIALS AND METHODS: Two segmentation methods were implemented: (1) spatial mean brightness level estimation (SMBLE), and (2) partial-volume modeling (PVM). These were evaluated with the inclusion of spinal cord inclination and/or partial-volume-effect corrections. An averaged manually segmented set was considered as reference. Thirty MR studies were used to compare the different methods. A set of 15 MS patients and 15 control subjects within a two-year longitudinal study were used to evaluate cord atrophy with the best method. Statistical evaluation was made by using an intraclass correlation coefficient and Bland-Altman comparisons. RESULTS: Partial-volume modeling with spinal cord inclination correction and partial-volume spinal-cord contour contribution estimation was the most accurate method. The longitudinal test showed a 4% decrease in CCA in MS patients with no significant reduction in control subjects. CONCLUSION: The automatic PVM cord-segmentation approach, taking into consideration the spinal-cord inclination and partial-volume treatment, provides reproducibility and increased accuracy in the evaluation of cord atrophy, allowing the monitoring of changes in MS patients.

Adolescent↗
PubMed2006

Theoretical scheme for the shear viscosity of Lennard-Jones fluids.

We use the shear viscosity expression from the Enskog theory of dense gases in a perturbative scheme for the Lennard-Jones (LJ) fluid. This perturbative scheme is formulated by combining the analytic rational function approximation method of Bravo Yuste and Santos [Phys. Rev. A 43, 5418 (1991)] for the radial distribution function of hard-sphere fluids and the well known Mansoori-Canfield/Rasaiah-Stell perturbation theory to determine an effective diameter for the LJ fluid. The scheme is reliable on a wide range of temperatures and densities, and is very accurate around the critical point. Using this information, we build an accurate empirical formula for the shear viscosity in the liquid phase, which fits the recent data [K. Meier et al., J. Chem. Phys. 121, 3671 (2004)] in the whole simulation range.

Journal Article↗
PubMed2006

Blast2GO goes grid: developing a grid-enabled prototype for functional genomics analysis.

The vast amount in complexity of data generated in Genomic Research implies that new dedicated and powerful computational tools need to be developed to meet their analysis requirements. Blast2GO (B2G) is a bioinformatics tool for Gene Ontology-based DNA or protein sequence annotation and function-based data mining. The application has been developed with the aim of affering an easy-to-use tool for functional genomics research. Typical B2G users are middle size genomics labs carrying out sequencing, ETS and microarray projects, handling datasets up to several thousand sequences. In the current version of B2G. The power and analytical potential of both annotation and function data-mining is somehow restricted to the computational power behind each particular installation. In order to be able to offer the possibility of an enhanced computational capacity within this bioinformatics application, a Grid component is being developed. A prototype has been conceived for the particular problem of speeding up the Blast searches to obtain fast results for large datasets. Many efforts have been done in the literature concerning the speeding up of Blast searches, but few of them deal with the use of large heterogeneous production Grid Infrastructures. These are the infrastructures that could reach the largest number of resources and the best load balancing for data access. The Grid Service under development will analyse requests based on the number of sequences, splitting them accordingly to the available resources. Lower-level computation will be performed through MPIBLAST. The software architecture is based on the WSRF standard.

Computational Biology↗
PubMed1998

Repin-induced neurotoxicity in rodents.

Russian knapweed is a perennial weed found in many parts of the world, including southern California. Chronic ingestion of this plant by horses has been reported to cause equine nigropallidal encephalomalacia (ENE), which is associated with a movement disorder simulating Parkinson's disease (PD). Repin, a principal ingredient purified from Russian knapweed, is a sesquiterpene lactone containing an alpha-methylenebutyrolactone moiety and epoxides and is a highly reactive electrophile that can readily undergo conjugation with various biological nucleophiles, such as proteins, DNA, and glutathione (GSH). We show in this study that repin is highly toxic to C57BL/6J mice and Sprague-Dawley rats and acutely induces uncoordinated locomotion associated with postural tremors, hypothermia, and inability to respond to sonic and tactile stimuli. We also show that repin intoxication reduces striatal and hippocampal GSH and increases total striatal dopamine (DA) levels in mice. Striatal microdialysis in rats, however, has demonstrated a significant reduction of extracellular DA levels. These findings, coupled with the absence of any demonstrable change in striatal DOPAC levels, suggest that repin acts by inhibiting DA release, a hypothesis that is further supported by our demonstration that, in cultured PC12 cells, repin inhibits the release of DA without affecting its uptake. We believe, therefore, that inhibition of DA release represents one of the earliest pathogenetic events in ENE, leading eventually to striatal extracellular DA denervation, oxidative stress, and degeneration of nigrostriatal pathways. Since the neurotoxic effects of repin appear to be mediated via oxidative stress, and since repin is a natural product isolated from a plant in our environment that can cause a movement disorder associated with degeneration of nigrostriatal pathways, clarification of the mechanism of repin neurotoxicity may provide new insights into our understanding of the pathogenesis of PD.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1998

Noninvasive positive-pressure ventilation in chronic obstructive pulmonary disease.

Interest in noninvasive positive-pressure ventilation both as an alternative to intubation and mechanical ventilation and as a unique therapy has grown over recent years. Clinical and patient acceptance is highest in neuromuscular deficits, but supporting evidence for its use in chronic obstructive pulmonary disease is highly dependent on the application. This review considers the clinical implementation of noninvasive positive-pressure ventilation in acute respiratory failure, as a postextubation weaning alternative, in stable severe hypercapnic chronic obstructive pulmonary disease, in overlap syndrome, and for nocturnal oxygen desaturation. Some applications are well supported, leading to a cautious recommendation for its utilizatip4, whereas for others evidence is starkly conflicting. The clinical efficacy of noninvasive positive-pressure ventilation is vastly dependent on equipment, equipment-patient interface, pressure settings, physician's bedside manner, and experience of the center. Interpretation of the studies must take into account the foregoing factors along with the various ventilatory techniques and differing primary outcome measures. Generalizations can be made regarding indications and contraindications, but this is an area rife with exceptions. The subtle message from the clinical studies describes the importance of the clinical art applied from the palette of science and technology.

Acute Disease↗
PubMed1998

Ethnopharmacology of Mexican asteraceae (Compositae).

Traditional herbal remedies have increased in popularity in Europe and the United States in recent years but have always been important to people living in rural Mexico and to their Mexican American/Chicano descendants in the United States. Mexican American patients will often be ingesting herbal teas at the same time that they are being treated for their ailments with antibiotics or antiinflammatory agents. The plant family Asteraceae (Compositae) has contributed the largest number of plants to this pharmacopoeia; the reasons for the importance of this family include its large number of species in Mexico and its wide array of natural products that are useful in the treatment of the maladies that have afflicted the inhabitants of rural Mexico. These natural products include sesquiterpene lactones, polyacetylenes, alkaloids, monoterpenes, and various phenolics such as flavonoids. In this review, we emphasize the sesquiterpene lactones, a large group of compounds with antiinflammatory properties and the ability to relax smooth muscles and thereby relieve gastrointestinal distress. These compounds also readily form adducts with glutathione or free thiols and can thereby affect the metabolism, activity, and toxicology of a wide array of pharmacological agents.

Animals↗
PubMed1997

Cytotoxic effects of repin, a principal sesquiterpene lactone of Russian knapweed.

Repin is the principal sesquiterpene lactone isolated from Russian knapweed (Centaurea repens), a perennial weed found in many parts of the United States. Ingestion of Centaurea repens by horses has been reported to cause a movement disorder simulating Parkinson's disease (PD) and nigrostriatal degeneration, called equine nigrostriatal encephalomalacia (ENE). To understand the mechanisms whereby ingestion of Centaurea repens induces ENE and a PD-like disorder, repin cytotoxicity was examined to explore its pathogenetic relationship to ENE and to PD. Repin was highly cytotoxic to both PC12 cells and mouse astrocytes in a dose- and time-dependent manner. The cytotoxic effects were accompanied by depletion of glutathione (GSH), a rise in the level of reactive oxygen species (ROS) and damage to cellular membranes. Although repin is a highly reactive electrophile that can readily conjugate GSH, GSH depletion may not be the sole mechanism underlying repin cytotoxicity as shown by our study using buthionine sulfoximine, in which severe GSH depletion did not result in a parallel increase in cell death. However, pre-treatment with GSH-glycoside or with lipoic acid provided significant protection from repin-induced cell death. These data suggest that oxidative stress plays a major role in repin cytotoxicity. Since oxidative stress is considered to play a major role in neuronal degeneration accompanied by depletion of mitochondrial GSH and an increase in lipid peroxides in the substantia nigra of PD, further elucidation of mechanisms of repin neurotoxicity may generate clues regarding not only the mechanisms of neuronal degeneration but also the possible role of environmental factors in the pathogenesis of PD.

Animals↗
PubMed1996

The effects of glutathione glycoside in methyl mercury poisoning.

The use of glutathione glycoside (GSH-glyc), a compound newly synthesized in our laboratory, was highly effective in raising cellular GSH levels both in vitro and in vivo. Based on mass spectrometry and 1H NMR data, the structure of GSH-glyc was determined to be that of an S-glycoside. Rapid GSH uptake was observed by confocal microscopy in both A549 cells and mouse astrocytes following incubation with GSH-glyc. Intraperitoneal (i.p.) and per oral administration of GSH-glyc in C57BL/6J mice raised GSH concentrations in brain and liver to significantly higher levels than normal. Methyl mercury (MeHg) poisoning of mice with multiple doses of methylmercuric chloride (MMC) induced severe toxic effects associated with marked depletion of brain and liver GSH progressing to death in all animals, whereas the animals primed with GSH-glyc and given MMC and GSH-glyc concurrently were devoid of toxic signs. We suggest, on the basis of D-[3H]glucose and [2- 3H]deoxyglucose uptake studies, that the transport of GSH-glyc across the blood-brain barrier may occur through one of the glucose transport pathways. Although the precise mechanism by which GSH-glyc protects against MeHg poisoning is not clear, it is probable that any one of a number of factors, including conjugation of MeHg, scavenging of free radicals, restoration of reactive thiol groups, and enhancement of MeHg efflux, may have been instrumental. GSH-glyc is a nontoxic compound that can be used to transport GSH into cells, including those of brain and liver, and may prove to be useful for prophylaxis and therapy of tissue injury induced by various neurotoxic compounds, particularly when the capacity to synthesize or regenerate GSH has been compromised.

Animals↗
PubMed1996

Phase II and pharmacologic study of docetaxel as initial chemotherapy for metastatic breast cancer.

PURPOSE: Because docetaxel (Taxotere, RP 56976; Rhone-Poulenc Rorer, Antony, France) appeared to be active against breast cancer in phase I trials, we performed this phase II study. PATIENTS AND METHODS: Thirty-seven patients with measurable disease were enrolled. Only prior hormone therapy was allowed, as was adjuvant chemotherapy completed > or = 12 months earlier. Docetaxel 100 mg/m2 was administered over 1 hour every 21 days. Diphenhydramine hydrochloride and/or corticosteroid premedication was added after hypersensitivity-like reactions (HSRs) were seen in two of the first six patients. Pharmacokinetic studies were performed during cycle 1 for correlation with toxicity. RESULTS: Thirty-seven patients were assessable. Nineteen (51%) required dose reductions, usually for neutropenic fever. The median nadir WBC count was 1.4 x 10(3)/microL. HSRs were noted in 20 patients (54%). At a median cumulative dose of 297 mg/m2 (range, 99.6 to 424.5 mg/m2), 30 patients (81%) developed fluid retention, for which 11 (30%) subsequently stopped treatment. The first-cycle plasma area under the concentration-time curve (AUC) did not correlate with toxicity, although an ineligible patient with hepatic metastases (pretreatment bilirubin level 1.8 mg/dL) had an elevated AUC and died of toxicity. Responses were seen at all sites. On an intent-to-treat basis, there were two (5%) complete responses (CRs) and 18 (49%) partial responses (PRs). The overall response proportion (CRs plus PRs) was 54% (95% confidence interval, 37% to 71%). The median time to response was 12 weeks (range, 3 to 15) and the median duration was 26 weeks (range, 10 to 58+). CONCLUSION: Docetaxel is active for metastatic breast cancer. Neutropenia and fluid retention are dose-limiting. The AUC did not predict toxicity, but caution is warranted when treating patients with liver dysfunction. An understanding of the pathophysiology of the fluid retention may facilitate prevention. Frequent HSR may warrant prophylactic premedication.

Adult↗
PubMed1996

[Gastroenteritis due to Aeromonas in pediatrics].

OBJECTIVE: In recent years the incidence of gastroenteritis due to Aeromonas spp has increased significantly. The purpose of this study was to investigate the etiology and clinical manifestations of this disease. PATIENTS AND METHODS: In the period between 1986 and 1992, we found Aeromonas spp in seventy patients (88 samples) between 0 and 16 years of age. We were able to analyze 53 of these samples. RESULTS: Of all of the patients, 66% were males and 58.5% were younger than two years old. We found a pattern in the disease with 83% of the cases occurring in summer and autumn. The infection was polymicrobial in 43% of the patients. The clinical manifestations most often found were fever (71%), vomiting (62.5%) and abdominal pain (9.4%). Diarrhea was watery in 71.7% and 64% of the cases lasted less than a week. The number of stools was 5 to 10 per day in 58% of the patients. Forty patients (75.5%) required hospitalization, with the stay being longer than 10 days in 25%. There were 30% of the patients that required antibiotic therapy, mostly due to concomitant infections and not due to the diarrheic episodes, with all of them having a satisfactory evolution.

Acute Disease↗
PubMed1996

[Streptococcus pyogenes: in vitro susceptibility to several antimicrobials in two date periods].

BACKGROUND: The frequency of Streptococcus pyogenes infections with deep tissue invasion and toxic shock syndrome has increased in the last decade throughout the world. AIM: To compare antimicrobial susceptibility of S. pyogenes strains isolated during 1986 and during 1994-95. MATERIAL AND METHOD: Eighty two S. pyogenes strains isolated in 1986 and 67 strains isolated in 1994-95, were studied. MIC 50 and 90 were determined by and agar dilution method for penicillin, ampicillin, cefazolin, cefuroxime, erythromycin, roxithromycin and miocamycin. RESULTS: Eighty eight strains came from skin of soft tissues, 19 from surgical wounds, 18 from invasive infections, 15 from pharyngeal swabs and 9 from other locations. All strains were susceptible to penicillin, ampicillin, cefazolin, cefuroxime, roxithromycin and miocamycin. Ninety nine percent of strains were susceptible to erythromycin. Strains isolated in 1995-95 had a higher MIC 50 and 90 for erythromycin than those isolated in 1986. CONCLUSIONS: The changes in susceptibility to erythromycin of recently isolated strains could be due to the widespread use of macrolides in Chile.

Adolescent↗
PubMed1995

Recent studies on the zoopharmacognosy, pharmacology and neurotoxicology of sesquiterpene lactones.

Aspects of recent research on the biological activities of sesquiterpene lactones (SQLs) are presented. Several SQLs have been identified as important constituents of plants consumed by animals for presumed medicinal value and is a focus of research in zoopharmacognosy. Recent in vivo antitumor studies with parthenin and eupatoriopicrin are discussed as well as the reports of the antiulcer activity of dehydroleucodin. Helenalin has recently been reported to have cardiotonic activity. Research on the neurotoxicity of repin, a compound reported to cause a Parkinson's-like disease in horses, is also highlighted.

Animals↗
PubMed1992

Human monoclonal antibody recognizing an antigen associated with ovarian and other adenocarcinomas.

MS2B6, a human monoclonal antibody derived from a patient with advanced ovarian cancer, has been used to study the distribution and characteristics of its target antigen. The MS2B6 antigen was detected by immunoperoxidase studies in 41 of 41 epithelial ovarian cancers and in the majority of nonovarian adenocarcinomas. Among normal tissues the MS2B6 antigen was found in the adult epithelia of the fallopian tube, endometrium, endocervix, colon, bronchus, breast, sweat duct, and large renal ducts. No detectable antigen was found in peritoneal epithelia, tissue stromal cells, spleen, thymus, or blood-borne cells. Immunoblotting analysis showed that the MS2B6 epitope resides on polypeptides of 38, 44, and 60 kd. The cellular location of the MS2B6 antigen was studied with immunoperoxidase and immunofluorescent staining and immunoelectronmicroscopy of ovarian cancer ascites tumor cells. The results suggest that in ascites tumor cells the MS2B6 antigen is located in a layer of the peripheral cytoplasm beginning just below the cell membrane. MS2B6 may be useful as an imaging or therapeutic agent.

Adenocarcinoma↗
PubMed1992

Once-weekly oral doses of fluconazole 150 mg in the treatment of tinea corporis/cruris and cutaneous candidiasis.

Ninety-five adult out-patients with tinea corporis and/or tinea cruris participated in a multicentre open non-comparative study investigating the safety and efficacy of 1-4 once-weekly doses of oral fluconazole 150 mg. Trichophyton rubrum was isolated most frequently (67 of 86 mycologically evaluable patients). A mean of 2.6 doses of fluconazole was administered; patients infected with Candida albicans or Epidermophyton floccosum required an average of 2 doses compared to 3-4 doses in patients infected with other organisms. Clinical cure was obtained in 85 of 92 (92%) patients at the last post-treatment evaluation, with the remaining seven patients being substantially improved. At long-term follow-up, 28-30 days after the last dose, 80 of 91 (88%) patients were assessed as clinically cured, three (3%) patients were improved and eight (9%) patients failed. Among the long-term clinical failures, there was one diagnosis of tinea corporis (3% failure rate) and seven diagnoses of tinea cruris (12% failure rate). Mycological evidence of infection occurred in only 1 of 86 patients assessed at the last post-treatment follow-up. Mycological relapse occurred in nine (11%) patients at long-term follow-up; one patient was infected with Trichophyton mentagrophytes and eight patients were infected with T. rubrum. Relapse occurred in 2 of 29 (7%) patients with tinea corporis and eight of 57 (14%) patients with tinea cruris (one patient who relapsed had both tinea corporis and cruris). There was no correlation between the number of doses received and the mycological response or relapse rates at long-term follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1992

Once-weekly oral doses of fluconazole 150 mg in the treatment of tinea pedis.

Seventy adult out-patients with tinea pedis participated in a multicentre open non-comparative study of the safety and efficacy of once-weekly doses of oral fluconazole 150 mg. A mean of 3 doses of fluconazole was administered; patients infected with Candida required an average of 2 doses compared to 3-4 doses in patients infected with other organisms. Clinical cure was obtained in 45 of 61 (74%) evaluable patients at the last post-treatment evaluation, with 15 patients being substantially improved and one patient failing clinically. At long-term follow-up, 28-30 days after the last dose was administered, 46 of 60 (77%) patients were clinically cured, 13 (22%) patients were improved and one patient failed. Trichophyton rubrum was isolated most frequently (47 of 60 mycologically evaluable patients). Mycological evidence of infection was eradicated from 52 of 60 (87%) patients post-treatment. At the long-term follow-up, infection was eradicated from 46 of 59 (78%) patients, persisted in five (8%) patients and relapsed in eight (14%) patients, six of whom were infected with T. rubrum and two of whom were infected with both T. rubrum and Candida. The number of doses received did not correlate with either the mycological response or relapse rates at long-term follow-up. The subgroup of 16 patients with infection of the sole of the foot, which is often considered to be more difficult to eradicate, responded similarly. Only 5 of 70 (7%) fluconazole-treated patients reported adverse effects, which were mild to moderate in severity, transient and did not result in discontinuation of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗