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Biomedical subjects

R Rodriguez

Publications and source records attributed to R Rodriguez.

At least 55 records · Page 3Linked to original sources

Use of a modified American Urological Association Symptom Score for the evaluation of the quality of life of patients with prostate cancer.

OBJECTIVES: To present our experience with the clinical use of a modified American Urological Association Symptom Score (AUASS) and a quality-of-life (QOL) questionnaire in obtaining clinically available information and to investigate whether a relatively short questionnaire, administered in the clinic, can help in identifying symptoms and QOL issues associated with various types of definitive treatments (DTs) for prostate cancer (PCa) and its impact on patients' QOL. METHODS: The AUASS was modified to contain questions on continence and was combined with a short QOL questionnaire. It was administered to control groups and all patients with PCa during their clinic visit. The responses were analyzed and correlated with the DT of PCa. RESULTS: The questionnaire was administered 846 times to 375 patients with PCa and to 170 controls during clinic visits. We found that patients on watchful waiting had symptom scores and QOL responses similar to controls and that DT was associated with worse scores and a reduced QOL. DT with continence was associated with a better QOL than DT with incontinence. Incontinence of either urine or stool, among DT patients, had similar adverse impact on QOL, compared with continent DT patients. CONCLUSIONS: The questionnaire, administered in a clinical setting, provides insight into the QOL and symptoms associated with interventions aimed at curing PCa. The use of such a questionnaire enhances the objective documentation of treatment outcomes of PCa and benefits the patients by increasing their opportunities to express their problems.

Case-Control Studies↗

Navigating the time-space context of HIV and AIDS: daily routines and access to care.

Geographers have shown that daily activities and social networks are constrained by time-space, but there are also enabling facets or opportunities created by daily routines for accessing material and emotional resources, improving quality of life, and even challenging existing power relations. Time-geography in this paper is taken as a starting point to assess how individuals living with HIV and AIDS navigate the complex and often difficult time space contexts defining their access to services. The concept of time space windows of access is offered as a way to understand the opportunities created by daily routines and social network interaction even in highly marginalized social, economic, and political circumstances. Survey data and in-depth interviews conducted with a diverse group of persons living with HIV and AIDS are used to illustrate this conceptual argument. Results indicate that the time space characteristics of daily routines, such as frequency of activities, variety or heterogeneity in activities, and whether activities are self- or social network-oriented, serve to define the availability of temporal and spatial windows of access to services. In addition, daily routines seem to matter for specific types of services, and have a limited role to play in terms of primary medical services or those associated with basic needs. The implications of these findings for theorizing and for enhancing access to services are provided.

Acquired Immunodeficiency Syndrome↗

Prostate cancer gene therapy.

Cancer-specific gene therapy is still in its infancy. Although the first gene therapy trials were initiated in the late 1980s, it was only more recently that the first successful treatment of a genetic disease was reported.3 The current problems with low efficiency of gene transfer coupled with the immunologic difficulties with certain vectors indicate that more effort needs to be directed at the basic science of gene transfer. Ultimately, successful cancer-specific gene therapy will require combinations of the lessons learned from the ex vivo and in vivo paradigms. The next generation of gene therapy trials likely will focus on combination therapy with conventional chemotherapeutic agents, differentiating agents, or radiation therapy. The obstacles to the development of gene-based human therapeutics (i.e., molecular medicine) are formidable, but the benefits are so great that eventually the technical issues of gene transfer methodology will be worked out, and ultimately this will become the standard of care, not only for inborn errors of metabolism, but also for cancer.

Adenocarcinoma↗

Investigation of irradiated soil byproducts.

The high dose irradiation of windblown soil deposited onto the surface of spent nuclear fuel is of concern to long-term fuel storage stability. Such soils could be exposed to radiation fields as great as 1.08 x 10(-3) C/kg-s (15,000 R/hr) during the 40-year anticipated period of interim dry storage prior to placement at the proposed national repository. The total absorbed dose in these cases could be as high as 5 x 10(7) Gy (5 x 10(9) rads). This investigation evaluated the potential generation of explosive or combustible irradiation byproducts during this irradiation. It focuses on the production of radiolytic byproducts generated within the pore water of surrogate clays that are consistent with those found on the Idaho National Engineering and Environmental Laboratory. Synthesized surrogates of localized soils containing combinations of clay, water, and aluminum samples, enclosed within a stainless steel vessel were irradiated and the quantities of the byproducts generated measured. Two types of clays, varying primarily in the presence of iron oxide, were investigated. Two treatment levels of irradiation and a control were investigated. An 18-Mev linear accelerator was used to irradiate samples. The first irradiation level provided an absorbed dose of 3.9 x 10(5)+/-1.4 x 10(5)Gy (3.9 x 10(7)+/-1.4 x 10(7) rads) in a 3-h period. At the second irradiation level, 4.8 x 10(5)+/-2.0 x 10(5)Gy (4.8 x 10(7)+/-2.0 x 10(7) rads) were delivered in a 6-h period. When averaged over all treatment parameters, irradiated clay samples with and without iron (III) oxide (moisture content = 40%) had a production rate of hydrogen gas that was a strong function of radiation-dose. A g-value of 5.61 x 10(-9)+/-1.56 x 10(-9) mol/J (0.054+/-0.015 molecules/100-eV) per mass of pore water was observed in the clay samples without iron (III) oxide for hydrogen gas production. A g-value of 1.07 x 10(-8)+/-2.91 x 10(-9) mol/J (0.103+0.028 molecules/100-eV) per mass of pore water was observed in the iron (III) oxide containing clay samples for hydrogen gas production. This value was noticeably larger when the samples were spiked with both KCl and KNO3 salts. The ratio of oxygen to nitrogen gas was observed to increase as a function of absorbed dose particularly in the presence of both KCl and KNO3 salts. The creation of radiolytic byproducts produced an observable but small increase in headspace pressure. Temperature increases during irradiation were not observed. Additionally, KCl and KNO3 salts added to the clays enhanced nitrite production as a function of radiation-dose and the type of clay considered. The addition of aluminum to these samples had no statistically discernable impact at the alpha = 0.05 level. Generation of the irradiation products, hydrogen peroxide and hydrogen gas also depended upon the type of clay irradiated and the presence of both KCl and KNO3 salts and the total dose received.

Aluminum↗

Study of biologic attributes of Cuban dengue 2 virus after serial passage in primary dog kidney cells.

OBJECTIVE: The serial passage of dengue viruses in primary dog kidney (PDK) cells has resulted in selection of attenuated viruses. However, the molecular changes responsible for loss of virulence are not well characterized. This article describes the isolation and biologic attributes of one dengue 2 virulent strain as a first step to allow the study of determinants of virulence at the molecular level. METHODS: A15 dengue 2 Cuban strain was isolated from the viremic plasma of a patient with uncomplicated dengue fever during the 1981 epidemic. This was then subjected to serial passage in PDK cells. Viruses resulting from several PDK passages were compared to the parent strain for plaque size and temperature sensitivity, neurovirulence in newborn mice, and cytopathogenic effects on LLC-MK(2) and C6/36-HT cell lines. RESULTS: A15 dengue 2 Cuban strain was successfully propagated in PDK cells. Primary dog kidney 52 to 53 viruses exhibited several biologic attributes, such as small plaques, temperature sensitivity, reduced mouse neurovirulence, and cytopathic effect in permissive cell lines. CONCLUSIONS: These results represent the first step to allow attenuation of this strain of dengue 2 virus.

Animals↗

Correlates of participation and willingness to participate in anti-tobacco activities among 4th-7th graders.

The purpose of this study was to identify factors associated with participation and willingness to participate in anti-tobacco community activities in 4-7th grade students. A probability sample was drawn from seven regions in Florida (n = 1219). Telephone interviews assessed socioeconomic status, tobacco use, knowledge, and attitudes, and exposure to anti-tobacco school education and media campaigns. Factors related to both participation and willingness included: parental discussion of tobacco use, exposure to school courses with anti-tobacco curricula and a belief that youth could convince their friends to stop smoking. Additional participation correlates included: parental smoking status and student government activity participation. Additional willingness correlates included: exposure to anti-tobacco television campaigns, liking school, and several tobacco-related knowledge and attitudinal questions. These findings suggest that exposure to community-based tobacco control programs and family discussion of tobacco use is associated with regular participation and/or willingness of youth to participate in anti-tobacco activities.

Attitude to Health↗

A novel method for the determination of basal gene expression of tissue-specific promoters: an analysis of prostate-specific promoters.

Because the toxicity of suicide gene therapeutics is directly related to basal promoter activity, we developed an assay to test for promoter "leakiness" using a diphtheria toxin mutant. Sequences of 15 prostate-specific gene promoter constructs were cloned in an expression plasmid (pBK; Stratagene, La Jolla, CA) backbone driving expression of an attenuated mutant of diphtheria toxin A (tox176). Low expression levels of the DT-tox176 result in significant protein synthesis inhibition reflected by a decreased expression of the luciferase activity of a simultaneously transfected CMV luciferase construct. ID50 (dose of plasmid with 50% luciferase inhibition) was calculated for each promoter construct in different cell lines. Highest transactivational activity (ID50 <75 ng) was found for the CMV promoter in all cell lines, which is in agreement with the dual luciferase assay findings. Unlike the dual luciferase findings, however, the DT-tox176 assay showed protein inhibition of CN65 (PSA promoter/enhancer) and PSE-hK2 (PSA enhancer and basal human kallikrein 2 promoter) in HEK293 and DLD cells indicating "leakiness" of these promoter constructs. Low basal promoter activity in nonprostate cell lines was found for the minimal PSA promoter, hK2, DD3, and OC promoters. The DT-tox176 assay can better predict basal promoter activity compared to less sensitive dual luciferase assay.

Biological Assay↗

Effects of omapatrilat on blood pressure and insulin sensitivity in an animal model of insulin resistance.

OBJECTIVE: To assess the effects of omapatrilat, fosinopril and placebo on blood pressure, plasma insulin, glucose and triglycerides concentrations in Zucker rats, a model for insulin resistance. DESIGN: Double blind, parallel, prospective trial. METHODS: Forty-two male obese Zucker (falfa) rats (aged 13-18 week) initially weighing 400-600 g were used for the experiments. Omapatrilat (n = 14), placebo (n = 14) or fosinopril (n = 14) were administrated once daily at 10 micromol/kg oral for 15 days. At baseline and at the end of the study, a tail-cuff blood pressure measurement was performed; an oral glucose tolerance test was done at the end of the study. RESULTS: Omapatrilat and fosinopril resulted in significant lower systolic blood pressure compared to the placebo group (p < 0.001). This parameter was significantly lower in the omapatrilat group compared with fosinopril-treated rats (116+/-9 vs 125+/-4 mmHg, p < 0.05). After an overnight fast, there was no difference in the fasting glucose concentrations among treatment groups. The basal and post-glucose challenge insulin concentrations were lower in the omapatrilat group compared to the placebo group. No difference was observed in the fasting triglycerides concentrations between the treatment groups. CONCLUSIONS: Compared to placebo and fosinopril treatment, omapatrilat results in lower arterial blood pressure in an animal model of insulin resistance. The results suggest that omapatrilat may have a positive effect on insulin sensitivity.

Animals↗

Long-term efficiency of catalytic converters operating in Mexico City.

A 1999 ordinance by the Government of Mexico City bans 1993 model-year vehicles from on-road operation if their catalytic converters are not replaced with new ones. To validate the benefits of this action, we examined three issues related to exhaust emissions of vehicles equipped with catalytic converters. After selecting representative fleets of in-use vehicles, a comparison between emissions and catalyst efficiency in cars with two categories of exhaust emission limits was carried out. For that purpose, two fleets were selected, each made up of 10 vehicles run under similar conditions. A third, larger fleet with emissions control systems was used to evaluate and simulate real-world conditions of vehicles in a controlled laboratory. Finally, the aging effect on the catalytic converter was studied on vehicles run for 100,000 km, replacing their old emission control devices for new ones. The 1991-1992 model-year vehicles showed a high percentage of compliance with the corresponding emissions standard (90%) in comparison with 1993 model-year and later vehicles (Tier 0). However, NOx emissions were higher for the newer vehicles. Fifty percent of the 1991-1992 model-year vehicles evaluated under the official inspection/maintenance (I/M) procedure did not meet the regulated emissions standard when the results were compared with those of the U.S. Federal Test Procedure FTP-75. Our results suggest that the replacement of old catalytic converters with new ones will have little effect on decreasing polluting emissions because these vehicles were in very bad mechanical condition. Results of catalytic activity as a function of mileage indicated inefficient catalyst performance for the fleets tested. All pollutant conversions were below 90% efficiency, and they deteriorated by an average of 30% after the vehicles were run for 100,000 km.

Air Pollutants↗

Development of a monoclonal antibody specific to a recombinant envelope protein from dengue virus type 4 expressed in Pichia pastoris.

A mouse monoclonal antibody (MAb, 4B6) was able to recognize dengue virus type 4 envelope (E) protein both as a recombinant protein in Pichia pastoris and when it was present in infected brains of suckling mice. 4B6 was characterized by enzyme-linked immunoadsorbent assay (ELISA), hemaglutination inhibition, neutralization, and immunoblot. The MAb was isotyped as IgG2a. It was serotype 4 specific and it inhibited hemaglutination and neutralized homologous virus. It did not enhance infection of P338D1 cells by dengue type 4 virus strain H-241 strain. This MAb was reactive with recombinant E protein and dengue 4 virus, as revealed by Western blot. In vivo, MAb 4B6 conferred passive protection in mice challenged with homologous virus. Currently, this MAb is being used to purify recombinant E protein for further studies.

Animals↗

Circulating soluble adhesion molecules in ANCA-associated vasculitis.

BACKGROUND: To evaluate whether changes in concentrations of soluble (s) E-selectin, sP-selectin, sL-selectin, intercellular adhesion molecule 1 (sICAM-1), and vascular cell adhesion molecule 1 (sVCAM-1) reflect disease activity in patients with ANCA-associated vasculitis and whether serum levels of these adhesion molecules are related to the degree of renal failure in patients with chronic renal failure (CRF). SUBJECTS AND METHODS: A sandwich ELISA was used to measure these soluble adhesion molecules in (i) sera from 20 patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (10 patients with Wegener's granulomatosis (WG) and 10 patients with microscopic polyangiitis (MPA)), obtained at the time of diagnosis and during the remission period; (ii) sera from 40 patients with CRF not undergoing haemodialysis. RESULTS: At the time of diagnosis, serum levels of sE-selectin, sICAM-1 and sVCAM-1 (88+/-42 ng/ml, 437+/-184 ng/ml, 1720+/-1174 ng/ml respectively) were significantly higher in patients with ANCA-associated vasculitis than in healthy controls (P<0.0001, P=0.002 and P=0.001 respectively). Serum sP-selectin values did not differ from those obtained in normal donors. In contrast, sL-selectin levels (940+/-349 ng/ml) were significantly lower in patients than those recorded in healthy controls (P<0.0001). A significant decrease in concentrations of sE-selectin, sP-selectin, sICAM-1, and sVCAM-1 was observed between active and remission phases (P<0.0001, P=0.002, P=0.001 and P=0.001 respectively). No significant differences were observed in sL-selectin levels between active and remission phases. sL-selectin concentrations (802+/-306 ng/ml) during the remission phase remained lower than those observed in healthy controls (P<0.0001). No correlation was observed between serum creatinine and sE-selectin, sP-selectin, sICAM-1 and sVCAM-1 in patients of the CRF group. A slight negative correlation was established between creatinine and sL-selectin concentration. CONCLUSIONS: Increased serum levels of sE-selectin, sICAM-1, and sVCAM-1 and decreased levels of sL-selectin in active ANCA-associated vasculitis, and the normalization of sE-selectin, sICAM-1, and sVCAM-1 during the remission phase suggest that the concentration of soluble levels of these adhesion molecules reflects disease activity. The decrease in sP-selectin levels between active and inactive phases also suggest that this receptor may reflect clinical activity. The lack of correlation between serum levels of sE-selectin, sP-selectin, sICAM-1, and sVCAM-1 and the degree of renal failure in patients with CRF suggests that the mechanism of clearance of these molecules is not renal.

Adult↗

Intrinsic resistance of Mycobacterium smegmatis to fluoroquinolones may be influenced by new pentapeptide protein MfpA.

The fluoroquinolones (FQ) are used in the treatment of Mycobacterium tuberculosis, but the development of resistance could limit their effectiveness. FQ resistance (FQ(R)) is a multistep process involving alterations in the type II topoisomerases and perhaps in the regulation of efflux pumps, but several of the steps remain unidentified. Recombinant plasmid pGADIV was selected from a genomic library of wild-type (WT), FQ-sensitive M. smegmatis by its ability to confer low-level resistance to sparfloxacin (SPX). In WT M. smegmatis, pGADIV increased the MICs of ciprofloxacin (CIP) by fourfold and of SPX by eightfold, and in M. bovis BCG it increased the MICs of both CIP and SPX by fourfold. It had no effect on the accumulation of (14)C-labeled CIP or SPX. The open reading frame responsible for the increase in FQ(R), mfpA, encodes a putative protein belonging to the family of pentapeptides, in which almost every fifth amino acid is either leucine or phenylalanine. Very similar proteins are also present in M. tuberculosis and M. avium. The MICs of CIP and SPX were lower for an M. smegmatis mutant strain lacking an intact mfpA gene than for the WT strain, suggesting that, by some unknown mechanism, the gene product plays a role in determining the innate level of FQ(R) in M. smegmatis.

Alleles↗

Comparison of anti-PR3 capture and anti-PR3 direct ELISA for detection of antineutrophil cytoplasmic antibodies (ANCA) in long-term clinical follow-up of PR3-ANCA-associated vasculitis patients.

A total of 118 sera from 11 patients with anti-neutrophil cytoplasmic antibodies against proteinase-3- (PR3-ANCA) associated vasculitis were retrospectively screened by anti-PR3 capture and anti-PR3 direct ELISA tests. We studied the relationship between capture and direct ELISA scores and the clinical activity of PR3-ANCA-associated vasculitis patients during follow-up. We also studied the ability of the anti-PR3 capture ELISA to detect positive values of PR3-ANCA in clinical vasculitis relapses. Only capture ELISA presented a significant relationship (p < 0.05) with clinical activity of PR3-ANCA-associated vasculitis patients over time. Capture ELISA appears to be a reliable method for detecting clinical relapses in this group of patients. Our results indicate that the new capture ELISA test is more effective than direct ELISA in the follow-up of patients with PR3-ANCA-associated vasculitis and in the detection of relapses.

Adult↗

DNA damage after chemotherapy correlates with tumor response and survival in small cell lung cancer patients.

To explore the induction of chemotherapy (CT) DNA damage and its correlation with tumor response and patient survival, we undertook the present study in 20 small cell lung cancer (SCLC) patients. All patients underwent the same treatment based on CT courses of carboplatin and etoposide. Blood samples were taken before and immediately after CT and every 12 weeks during follow-up. Nuclear DNA damage was determined through the variations in three mitochondrial pseudogene mutations in DNA of peripheral blood mononuclear cells. They were detected by mutation-specific PCR and assessed by a semiquantitative method. The relative level of mutation rose after chemotherapy in all cases. Among the 11 patients (55%) with higher relative levels of mutations, 9 (82%) of them achieved a complete response. In contrast, of the 9 patients (45%) with lower relative levels of mutations, only 2 (18%) achieved a complete response, displaying a statistically significant difference (P=0.02). The overall survival for patients with marked genomic damage was 18 months (range 10-24), and for patients with low degree of DNA damage, it was 12 months (range 5-15) (P=0.002). Genomic damage detected after chemotherapy treatment correlates positively with tumor response and patient survival.

Adult↗