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Biomedical subjects

J Aguilar

Publications and source records attributed to J Aguilar.

At least 19 recordsLinked to original sources

Cost-effectiveness analysis of lamivudine and adefovir dipivoxil in the treatment of patients with HBeAg-negative chronic hepatitis B.

AIM: To estimate the cost-effectiveness over a 4-year duration of lamivudine and adefovir dipivoxil for patients with hepatitis B 'e' antigen-negative chronic hepatitis B. METHODS: A decision analysis model has been used to perform a cost-effectiveness analysis of lamivudine and adefovir dipivoxil from the perspective of the Spanish Public Health System. Data were obtained from clinical trials. RESULTS: For the base-case, the total estimated cost per patient treated with lamivudine or adefovir dipivoxil for 4 years was 11,457 and 21,939 respectively. Virological response at year 4 for the lamivudine arm was 40.4% and 78.0% for the adefovir dipivoxil arm. The average cost-effectiveness ratio (cost per responding patient at year 4) was 28,375 for the lamivudine arm and 28,132 for the adefovir dipivoxil arm. The incremental cost-effectiveness ratio of adefovir dipivoxil vs. lamivudine (cost per additional responding patient with adefovir dipivoxil) was 27,872, demonstrating that this cost was slightly lower than the average cost-effectiveness ratios of adefovir dipivoxil or lamivudine. The sensitivity analysis demonstrated that the factors that most influence the cost-effectiveness were the response to adefovir dipivoxil and lamivudine at year 4. CONCLUSION: Long-term treatment with adefovir dipivoxil is a cost-effective strategy in patients with chronic hepatitis B 'e' antigen-negative hepatitis.

Adenine↗

Temporal relationship between proliferating and apoptotic hormone-producing and endothelial cells in the equine corpus luteum.

The temporal relationship between endothelial cell death, vascular regression and the death of hormone-producing cells in the mare has not been established. To determine the dynamics of cell proliferation and death throughout the luteal phase, corpora lutea were studied at the early, mid- and late luteal phase, and after treatment with cloprostenol in the mid-luteal phase to induce premature luteolysis. Changes in cell proliferation and apoptosis were investigated utilising specific markers (phosphorylated histone-3 and activated caspase-3 respectively). Histone-3 positive cells were most abundant during the early luteal phase, and were mainly present in endothelial cells. Histone-3 activity significantly increased in hormone-producing cells 36 h after cloprostenol treatment. Frequency of activated caspase-3 staining peaked on day 14, and was induced by 36 h after cloprostenol administration in mid-luteal phase. However, cell death occurred simultaneously in the endothelial and hormone-producing cells. These results show that a subset of hormone-producing cells enter the early stages of cell division around luteolysis, while the majority of cells are undergoing cell death. Natural and induced functional and structural luteal regression in the mare can be at least partially attributed to simultaneous apoptosis of endothelial and hormone-producing cells. However, there is no evidence that endothelial cell death is the trigger for naturally occurring luteolysis.

Animals↗

Influence of analytical and biological variation on the clinical interpretation of seminal parameters.

Quality assurance in semen analysis has been questioned recently in this journal. Based on the limited capacity of seminal parameter in the determination of fertility, the authors advocated abandoning methods of quality assurance in semen analysis for clinical situations. In this article, we explore arguments as to why quality assurance in semen analysis for clinical use is not 'a waste of time'. Imprecision and within-subject biological variations are the two major components involved in the dispersion of seminal parameter results obtained by analysis of a semen sample from an individual. As within-subject biological variation is constant across geography, time and population, imprecision is a very important factor in the quality of laboratory test results. We analyse this influence on various seminal parameters and observe that there is an amount of error that can be tolerated without invalidating the medical usefulness of seminal parameter determination. However, there is a maximum allowable analytical error above which the medical usefulness of seminal parameter results is invalidated. The level of performance required to facilitate clinical decision-making is termed quality specification. We comment on different strategies to define the maximum allowable analytical error.

Clinical Laboratory Techniques↗

Quality specifications for seminal parameters based on the state of the art.

BACKGROUND: The aim of this study was to calculate the analytical goal for seminal parameters based on the state of the art, and then to compare these specifications with those previously obtained by our group based on biological variation. METHODS: All data used for analysis were derived from the Spanish programme of external quality control on semen analysis. Over 90 laboratories participated from 1999 to 2003. Using graphs of the state of the art, we also determined the numbers of laboratories that achieved quality specifications. RESULTS: The total allowable error calculated using state of the art graphs is similar to that calculated using biological variation for concentration and total motility. However, it is much higher for morphology and rapidly progressive motility. Over 80% of the laboratories achieved the minimum quality specification based on biological variation for concentration, total and progressive motility. However, only approximately 30% of the laboratories achieved the minimum quality specification based on biological variation for morphology and rapidly progressive motility. CONCLUSIONS: The study enabled us to identify the state of the art of analytical performance for seminal parameters, and revealed the difficulty inherent in meeting the quality specifications based on biological variation.

Andrology↗

Predictors of eating behaviors in a sample of Mexican women.

The aim of the study was to develop a model of potential risk factors associated to the development of eating behaviors in Mexican women. A structural equation model was carried out on a sample of 425 women: high school and college students (N=425) with a mean age of 19.1 years (SD=3.8). The variables selected for the model were those that obtained significant correlations with the variable "eating behaviors": criticism by father/mother, depressed mood, body mass index, attitudes and beliefs concerning obesity and dissatisfaction with figure. The model fitted the data well, with a non-significant Chi-square. The proportion of variance explained for eating behavior by the other variables was 59, the direct effects of all the variables were significant, while the total effect of all the variables on eating behavior were also significant, particularly the effects of the "dissatisfaction with figure" and, "attitudes and beliefs concerning obesity". The model yielded similar data to the findings in international literature, since they revealed the influence exerted by social pressure on thinness, the internalization of the socio-cultural ideal of thinness and the role of excess weight in increasing the risk of body dissatisfaction and therefore with the development of eating disorders.

Adult↗

Interaction of limestone grains and acidic solutions from the oxidation of pyrite tailings.

To characterise the coatings formed and to analyse element partitioning between the aqueous and solid phase, suspensions were prepared with four grain sizes of limestone and three different amounts of acidic solution from oxidized pyrite tailings. In all cases, red coatings with three different layers covered the grain surface, sealing off the acidic solution. The inner layer was composed mainly of basaluminite, the middle layer of schwertmannite, and the outer layer of gypsum and jarosite. Zn, Cd and Tl were co-precipitated by Fe and Al; As and Pb were co-precipitated almost completely by Fe; and Cu formed mainly Cu sulphates. All trace elements reached almost total precipitation at pH 6.3, but the precipitation of As and Pb tended to decrease as the pH rose. Consequently, liming should be calculated so that the soil pH does not exceed 6.3. This calculation should take into account that the armouring of the limestone grains can cause underestimations in the amount of liming material needed.

Environmental Pollution↗

Treatment of hepatitis C virus with interferon in hemodialysis patients awaiting kidney transplant.

INTRODUCTION: Hepatitis C virus (HCV) infection is associated with worsening disease progression after renal transplant, and to date there is no available treatment for use at this stage. It has therefore been recommended to treat HCV infection with interferon (IFN) during the dialysis period while the patient is on the waiting list for transplantation. METHODS: We analyzed data from 27 patients on hemodialysis awaiting transplant, who were under IFN treatment for chronic HCV infection (dominant genotype, 1b). The starting regime was IFN alpha-2b, 3 MU x 3/week (n = 20) or pegylated IFN alpha-2a, 135 mg/week (n = 7). If there was clearance of HCV RNA in the first 3 to 6 months, we attempted to prolong IFN treatment for 1 year, although in many patients the dose had to be reduced. A sustained response was defined as viral clearance for at least 12 months after the end of treatment. RESULTS: Viremia was negative in 13 patients (48.1%) at the end of treatment, but two of these patients relapsed, to give an overall long-term response rate of 11 patients (40.7%) and incomplete follow-up in three patients. Viral clearance was not achieved in 11 patients. In three patients (12%), IFN had to be suspended before finishing the third month of therapy due to side effects (mainly pancytopenia and intolerance of a previous kidney graft). Seven patients showing a sustained response underwent transplant, maintaining a negative viremia result. CONCLUSIONS: IFN treatment was effective in a high proportion of dialysis patients with HCV infection, with response rates possibly even higher than for the general population. However, its use is restricted by a high incidence of side effects.

Antiviral Agents↗

Evaluation of the BCR sequential extraction procedure applied for two unpolluted Spanish soils.

The procedure of BCR sequential extraction has been applied to five samples from two unpolluted soils in southern Spain. Total concentrations of different elements have been calculated as the sum of the three fractions of BCR and the residue has been measured for each. Also, a total analysis based on INAA or total-digestion techniques has been performed for the same samples. BCR and total analysis closely agreed for As, Pb and Cd. For Cu, Co, Cr and Zn the comparison of the results did not provide definitive conclusions concerning the capability of BCR in measuring total concentrations. On the other hand, in these cases, a certain correlation was found between the concentrations measured and some soil characteristics, especially the clay, organic-matter and CaCO(3) contents. BCR proved incapable of providing accurate measurements for Ni.

Chemical Fractionation↗

Soil pollution by a pyrite mine spill in Spain: evolution in time.

Soil pollution was studied after the spill of the Aznalcóllar pyrite mine between 1998 and 2001, analyzing As, Zn, Cd, Cu and Pb both in total concentrations as well as in soluble and bioavailable forms. The main remediation measures were: clean-up of the tailings and polluted soils, plus application of amendment materials (liming). The results indicate that, after three years, 50-70% of the acidic soils and 25-30% of the basic soils are still highly polluted in total arsenic. The limit of 0.04 mg kg(-1) for water-soluble arsenic is exceeded in 15-20% of all soils. The EDTA-extractable arsenic (bioavailable) exceeds the limit of 2 mg kg(-1) only in the acidic sectors. After clean-up, the homogenization of the upper 20-25 cm of the soils appears to be the most recommended measure in the reduction of pollution.

Biological Availability↗

Soil pollution by oxidation of tailings from toxic spill of a pyrite mine.

On the 25th April 1998, toxic water and tailings from a pyrite mine of Aznalcóllar (southern Spain) spilled into the Agrio and Guadiamar River Basin affecting some 40 km2. In five sectors throughout the basin, we monitored the physical and chemical properties of the tailings as well as the degree of pollution in the soils on four different sampling dates: 5 May, 20 May, 4 June and 22 July 1998. The characteristics of the tailings deposited on the soils are shown to be related to distance from the spill. The oxidation rate of the tailings and the solubilization of the pollutant elements were more pronounced in the middle and lower sectors of the basin, where the particle size was finer, the sulfur content higher and the bulk density less. The increases in water-soluble sulfates, Zn. Cd and Cu were very rapid (the highest values being reached 25 days after the spill) and intense (reaching 45% of the total Cu, 65% of the total Zn and Cd). Meanwhile, the increases in water-soluble As, Bi, Sb, Pb and Tl were far lower (ranging between 0.002% of the total Tl and 2.5% of the total As) and less rapid in the case of As, Bi and Pb (the highest values for these elements being reached 40 days after the spill). These soluble elements infiltrated the soils with the rainwater, swiftly augmenting the soil pollution. Twenty-five days after the spill, when the rainfall ranged between 45 and 63 mm, the first 10-cm of the soils in the middle and lower sectors of the basin exceeded the maximum concentration permitted for agricultural soils in Zn, Cu and Tl. At 40 days after the spill, when the rainfall ranged between 60 and 89 mm, all the soils reached or exceeded the maximum permitted concentrations for As and Tl. Nevertheless, the pollutants tended to concentrate in the first 10 cm of the soils without seriously contaminating either the subsoil or the groundwaters. Consequently, a rapid removal of the tailings and the ploughing of the first 25-30 cm of the soils would be urgent measures to diminish pollutant concentration in the soils affected by the spill.

Environmental Monitoring↗

Development and application of monoclonal antibodies for the detection of white spot syndrome virus of penaeid shrimp.

Monoclonal antibodies (MAbs) were produced against white spot syndrome virus (WSSV) of penaeid shrimp. The virus isolate used for immunization was obtained from China in 1994 and was passaged in Penaeus vannamei. The 4 hybridomas selected for characterization all produced MAbs that reacted with the 28 kD structural protein by Western blot analysis. The MAbs tested in dot-immunoblot assays were capable of detecting the virus in hemolymph samples collected from moribund shrimp during an experimentally induced WSSV infection. Two of the MAbs were chosen for development of serological detection methods for WSSV. The 2 MAbs detected WSSV infections in fresh tissue impression smears using a fluorescent antibody for final detection. A rapid immunohistochemical method using the MAbs on Davidson's fixed tissue sections identified WSSV-infected cells and tissues in a pattern similar to that seen with digoxigenin-labeled WSSV-specific gene probes. A whole mount assay of pieces of fixed tissue without paraffin embedding and sectioning was also successfully used for detecting the virus. None of the MAbs reacted with hemolymph from specific pathogen-free shrimp or from shrimp infected with infectious hypodermal and hematopoietic necrosis virus, yellow head virus or Taura syndrome virus. In Western blot analysis, the 2 MAbs did not detect any serological differences among WSSV isolates from China, Thailand, India, Texas, South Carolina or Panama. Additionally, the MAbs did not detect a serological difference between WSSV isolated from penaeid shrimp and WSSV isolated from freshwater crayfish.

Animals↗

Biochemical characterization of the 2-ketoacid reductases encoded by ycdW and yiaE genes in Escherichia coli.

Glyoxylate is an important intermediate of the central microbial metabolism formed from acetate, allantoin or glycolate. Depending on the physiological conditions, glyoxylate is incorporated into the central metabolism by the combined actions of the activity of malate synthase and the D-glycerate pathway, or alternatively it can be reduced to glycolate by constitutive glyoxylate reductase activity. At present no information is available on this latter enzyme in Escherichia coli, although similar enzymes, classified as 2-hydroxyacid dehydrogenases, have been characterized in other organisms. A BLAST search using as the query sequence the hydroxypyruvate/glyoxylate reductase from Cucumis sativus identified as an orthologue the yiaE gene of E. coli encoding a ketoaldonate reductase. Use of this sequence in a subsequent BLAST search yielded the ycdW gene as a good candidate to encode glyoxylate reductase in this bacterium. Cloning and overexpression of the ycdW gene showed that its product displayed a high NADPH-linked glyoxylate reductase activity, and also catalysed the reduction of hydroxypyruvate with a lower efficiency. Disruption of the ycdW gene by a chloramphenicol acetyltransferase ('CAT') cassette did not totally abolish the glyoxylate reductase activity, indicating that another enzyme accomplished this function. The similarity with YiaE led us to test whether this protein was responsible for the remaining glyoxylate reductase activity. Purification of YcdW and YiaE proteins permitted their kinetic characterization and comparison. Analysis of the catalytic power (k(cat)/K(m)) disclosed a higher ratio of YcdW for glyoxylate and of YiaE for hydroxypyruvate.

Alcohol Oxidoreductases↗

Cytidine (5') diphosphocholine-induced decrease in cerebral platelet activating factor is due to inactivation of its synthesizing enzyme cholinephosphotransferase in aged rats.

Levels of cerebral platelet activating factor (PAF) result from the balance between the activities of its synthesizing enzyme dithiothreitol (DTT)- insensitive cholinephosphotransferase and its degradative enzyme PAF acetylhydrolase. Cerebral fractions of aged rats (19 months) displayed higher levels of PAF acetylhydrolase isoenzymes (P<0.05; n=4), unaltered levels of DTT-insensitive cholinephosphotransferase and lower PAF levels than young animals (2 months). Cerebral fractions of aged rats treated with cytidine (5') diphosphocholine displayed lower DTT-insensitive cholinephosphotransferase (55% after 8 days of treatment with 350 mg/kg per day, P<0.05; n=4), unaltered levels of PAF acetylhydrolase and lower PAF levels than untreated control animals. Thus our data would indicate that decrease of cerebral PAF may be attributed to an activation of PAF acetylhydrolase in ageing, and to an inactivation of DTT-insensitive cholinephosphotransferase in cytidine (5') diphosphocholine treated animals.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

Multicenter randomized study comparing initial daily induction with high dose lymphoblastoid interferon vs. standard interferon treatment for chronic hepatitis C.

One hundred fifty-five chronic hepatitis C patients were assigned at random to receive natural lymphoblastoid interferon (IFN)alpha-n1, s.c., for 13 months in one of three treatment regimens: initial daily induction with 10 million units (MU) followed (group 1, n = 50) or not (group 2, n = 52) by 1 month of rest and then three times weekly 10 MU (2 months), 5 MU (2 months), and 3 MU (8 months); group 3 (n = 53) received tiw 5 MU (2 months) followed by 3 MU (11 months). By intention-to-treat analysis, ALT normalization at completion of treatment was greater in patients who received continuous IFNalpha-n1 therapy with initial daily induction (group 2: 24/52, 46%) compared with those given intermittent therapy with initial daily induction (group 1: 17/50, 34%) and those who received standard IFNalpha-n1 therapy (group 3, 18/53, 34%; P not significant). The sustained ALT response was 26%, 27% and 21% and the sustained virological response was 20%, 27%, and 19%, in groups 1, 2, and 3, respectively. A trend was observed towards a higher biochemical and virological end-of-treatment response in patients given induction therapy (17%) compared with standard therapy (6%, P = 0.053). Sustained biochemical and virological responses were 20%, 27%, and 17% in groups 1, 2, and 3, respectively. Platelet and leukocyte counts decreased following daily high-dose treatment and remained low until therapy cessation (P < 0.001). The data suggest that daily s.c. induction with 10 MU IFNalpha-n1 followed by intermittent or continuous maintenance therapy for 1 year does not improve the results achieved with the standard 1-year IFNalpha course in the treatment of chronic hepatitis C patients.

Adolescent↗

Microwaves as an energy source for producing beta-SiC.

This work describes the production of silicon carbide using microwaves as the energy source, which was supplied by means of variable power, up to 2000 Watts, magnetron operating at 2.45 GHz. The obtained samples were analyzed by means of X-ray diffraction and observed with electron microscopy (SEM). Temperatures achieved were around 2000 degrees C, which is the upper limit for the beta-SiC growth regime, before getting other SiC polytypes. Analysis of different portions of the sample showed that beta-SiC was the only formed compound, although free SiO2 and graphite were also present. Observations made by SEM demonstrated different crystal growth regime, meaning that thermal conditions were not totally uniform. The amount of beta-SiC found and the relative simplicity of the device prove that production of this material from silica and graphite is possible by applying microwaves as an energy source.

Carbon Compounds, Inorganic↗

Value of 99mTc-MIBI scintimammography in women with impalpable breast lesions seen on mammography.

OBJECTIVE: To find out if 99mTc-methoxyisobutylisonitrile scintimammography (MIBI) is useful in the evaluation of impalpable breast lesions in women referred for biopsy after mammography screening. DESIGN: Observational and prospective study. SETTING: Radiological screening campaign in Spain. PATIENTS: 36 patients referred between September 1997 and June 1998 (37 biopsies) with impalpable breast lesions referred consecutively from a screening campaign. Ages ranged from 50 to 64 years. INTERVENTIONS: Mammography, ultrasound, MIBI, and wire-guided biopsy. MAIN OUTCOME MEASURES AND RESULTS: Mean values for sensitivity, specificity, positive predictive value, and negative predictive value for scintimammography were 78.9, 72.2, 75, and 76.5 respectively (p = 0.002). The logistic regression analysis showed that 99mTc-MIBI scintimammography result predicted (p = 0.003) the risk of breast cancer in this group of patients (odds ratio: 9.75), particularly infiltrating ductal carcinoma. CONCLUSIONS: MIBI scintimammography in patients referred for biopsy after mammography screening does not so much rule out cancer as confirm the diagnosis. Its practical benefit would be not so much avoiding biopsy for these patients as aiding in planning the radicality of their excision.

Aged↗

Usefulness and reproducibility of cytomorphologic evaluations to differentiate myeloma from monoclonal gammopathies of unknown significance.

We attempted to differentiate monoclonal gammopathies of unknown significance (MGUS) and multiple myeloma (MM) on morphologic grounds and to determine interobserver reproducibility of the differentiation. Cytologists blindly evaluated bone marrow smears from 154 patients with bone marrow plasmacytosis for the proportion of plasma cells with predefined cellular atypias. The single morphologic characteristic that most strongly differentiated MM from MGUS was the presence of nucleoli. The percentage of plasma cells, cytoplasmic contour irregularities, and anisocytosis also predicted a diagnosis of myeloma in multivariate analysis. Six cytologists independently evaluated 68 consecutive cases to determine sensitivity and specificity of these cytomorphologic features. The interobserver coefficient of variation for the plasma cell count was 33%. On consideration of the diagnosis, 36 of 41 MGUS cases and all 24 cases of myeloma were classified correctly. The use of a predesigned score system did not present such a bias, although it did not improve overall efficiency. The plasma cell count is the most predictive characteristic of myeloma from a cytologic viewpoint, but the interobserver variability is high. Interobserver variability is also high in the assessment of morphologic atypia, and atypical traits are not uncommon in plasma cells in MGUS.

Blood Cell Count↗

Lemniscal recurrent and transcortical influences on cuneate neurons.

Intracellular recordings were obtained from cuneate neurons of chloralose-anesthetized, paralysed cats to study the synaptic responses induced by electrical stimulation of the contralateral medial lemniscus. From a total of 178 cells sampled, 109 were antidromically fired from the medial lemniscus, 82 of which showed spontaneous bursting activity. In contrast, the great majority (58/69) of the non-lemniscal neurons presented spontaneous single spike activity. Medial lemniscus stimulation induced recurrent excitation and inhibition on cuneolemniscal and non-lemniscal cells. Some non-lemniscal neurons were activated by somatosensory cortex and inhibited by motor cortex stimulation. Some other non-lemniscal cells that did not respond to medial lemniscus stimulation in control conditions were transcortically affected by stimulating the medial lemniscus after inducing paroxysmal activity in the sensorimotor cortex. These findings indicate that different sites in the sensorimotor cortex can differentially influence the sensory transmission through the cuneate, and that the distinct available corticocuneate routes are selected within the cerebral cortex. From a total of 92 cells tested, the initial effect induced by low-frequency stimulation of the sensorimotor cortex was inhibition on most of the cuneolemniscal neurons (32/52) and excitation on the majority of the non-lemniscal cells (25/40). The fact that a substantial proportion of cuneolemniscal and non-lemniscal cells was excited and inhibited, respectively, suggests that the cerebral cortex may potentiate certain inputs by exciting and disinhibiting selected groups of cuneolemniscal cells. Finally, evidence is presented demonstrating that the tendency of the cuneolemniscal neurons to fire in high-frequency spike bursts is due to different mechanisms, including excitatory synaptic potentials, recurrent activation through lemniscal axonal collaterals, and via the lemnisco-thalamo-cortico-cuneate loop.A corticocuneate network circuit to explain the results is proposed.

Animals↗