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Biomedical subjects

M González

Publications and source records attributed to M González.

At least 37 records · Page 2Linked to original sources

Study of patients diagnosed with advanced HIV in the HAART era--OMEGA Cohort.

Our objective is to analyse patients diagnosed with late-stage HIV infection in the highly active antiretroviral therapy (HAART) area. A prospective, observational study of all patients with an initial CD4 < 50 x 10(6)/L was carried out. Epidemiological, clinical and HAART-associated data were analysed. Survival rates were estimated and pairs of survival curves were compared. The statistical program used was SPSS (version 10). In all, 349 HIV-infected patients were diagnosed, 117 (33.5%) had late-stage disease, mean CD4 23.9 x 10(6)/L and mean viral load (VL) 5.38 log10. In 98 men, mean age 39.5 years, percentage of AIDS cases at their first attendance was 83.8%. The median follow-up period was 28 months and 27 died. Pneumocystis carinii was the most frequent cause of AIDS (24.4%) and death (18.5%). Survival rates at 12, 24 and 36 months were 95.6%, 85.8% and 72.4%. HAART was started in 82.1%. VLs < 50 copies/mL at one, two and three years of treatment were 55.2%, 55.7% and 58.0%. Resource utilization included 0.58 hospitalization/patient/year and 0.07 events/patient/year. HAART-related complications were as follows: 50% lipodystrophy, 9.7% hypertension, 22.2% hyperglycaemia, 26.4% hypercholesterolaemia, 31.9% hypertrygliceridaemia and 18.1% mixed hyperlipaemia. Over one-third of our patients have advanced HIV infection at diagnosis. However, the outcome is favourable, with a good immunovirological response and few new opportunistic events. HAART-related complications were frequent.

AIDS-Related Opportunistic Infections↗

Atherogenic lipid profile and cardiovascular risk factors in HIV-infected patients (Nétar Study).

We undertook a transverse study of 603 HIV outpatients to determine their atherogenic lipid profile (ALP) and cardiovascular risk (CVR) factors. CVR was estimated from the Framingham score. ALP was defined as a total cholesterol to high density lipoprotein (HDL)-cholesterol ratio > or =5 plus triglycerides > or =150 mg/dL and a CVR >10% at 10 years was considered high. The most frequent CVR factor was smoking. ALP was diagnosed in 26.9% and was related to sex (odds ratio [OR] 2.6; 95% confidence interval [CI], 1.3-5.0; P = 0.0047), protease inhibitor use (OR 3.8; 95% CI, 1.8-7.8; P = 0.0002) and sexual HIV risk (OR 2.4; 95% CI, 1.4-4.0; P = 0.0004). The mean 10-year CVR was 6.2%, was high in 20.4% and was related to sexual HIV-risk (OR 3.8; 95% CI, 2.1-6.8; P < 0.00001) and nadir cell differentiation factor (CD4) (OR 1.0; 95% CI, 1.0-1.003; P = 0.0026). Although the current CVR of our patients is not high, the contribution to the lipid profile of highly active antiretroviral therapy (HAART)-associated factors and the high prevalence of some risk factors may lead to an increased future CVR.

Adult↗

Long-term evolution of liver histopathology in patients with chronic hepatitis C and sustained response.

OBJECTIVE: To evaluate the evolution of histological changes observed in patients with chronic hepatitis C (CHC) and sustained response (SR) compared to non-responders (NR) to antiviral treatment. METHODS: A retrospective study was performed in a total of 176 patients with CHC. These were divided into two groups: 132 SR and 44 NR. All had undergone a basal liver biopsy prior to treatment onset. A second biopsy was performed in 143 patients, 104 SR and 39 NR. Inflammatory activity and the degree of liver fibrosis was measured by Metavir units (MU). The progression and regression index of fibrosis was calculated before and after treatment. The time elapsed between the two biopsies was 5.9 +/- 0.3 years for SR and 6.6 +/- 0.3 years for NR (NS). RESULTS: At baseline, 53% of SR patients had mild, chronic active hepatitis (CAH), while this was moderate in 43% of NR patients (p < 0.0001). The time elapsed between baseline and post-treatment liver biopsies was 5.9 +/- 0.3 years for SR subjects and 6.6 +/- 0.4 years for NR subjects (NS). After antiviral treatment 47% of SR subjects presented a normal liver or minimal changes, whilst mild CAH persisted in 34.4% and moderate CAH in 37.5% of NR subjects. Necro-inflammatory activity decreased by 50% in SR subjects and by 15% in NR subjects (p < 0.0001), and fibrosis decreased by 82% in SR subjects (p < 0.0001) and by 66% in NR subjects (p < 0.001). Fibrosis progression index was 0.14 MU/year in SR subjects and 0.21 MU/year in NR subjects (NS). Fibrosis regression index was -0.11 in SR subjects and -0.14 in NR subjects (NS). CONCLUSIONS: In our series of patients with CHC and SR, we observed histological normalization in approximately fifty per cent of cases during long-term follow-up. NR subjects also showed improvement, especially in the fibrosis score. Both groups showed a marked regression of liver fibrosis after treatment.

Adult↗

Equilibrative nucleoside transporter 2 is expressed in human umbilical vein endothelium, but is not involved in the inhibition of adenosine transport induced by hyperglycaemia.

Human equilibrative, Na(+)-independent nucleoside transport is mediated by membrane proteins sensitive (system es, hENT1) or insensitive (system ei, hENT2) to nitrobenzylthioinosine (NBMPR). Gestational diabetes and elevated extracellular concentrations of D-glucose reduce adenosine transport in human umbilical vein endothelium (HUVEC). We studied hENT2 and hENT1 expression in HUVEC, and the effect of D-glucose on their activity and expression in HUVEC preincubated with 25 mM D-glucose (24 h). hENT2 and hENT1 mRNA were quantified by real-time reverse transcription polymerase chain reaction, and their proteins were detected by Western blotting. hENT2 and hENT1 proteins are co-expressed in HUVEC and are located at the plasma membrane, however, hENT2 was mainly cytoplasmatic and perinuclear in location. D-Glucose reduced hENT1 and hENT2 mRNA expression, but only hENT1 protein abundance at the plasma membrane. Adenosine transport was inhibited by D-glucose and NMBPR (1 microM) in intact cells and membrane vesicles. Hypoxanthine inhibited adenosine transport in the absence or in the presence of 1 microM NBMPR. D-Glucose reduced NBMPR maximal binding in intact cells, membrane vesicles, and plasma membrane fractions. In conclusion, the present study demonstrates that hENT2 and hENT1 are co-expressed in HUVEC, and even when adenosine transport is also mediated by hENT2, the hENT2-mediated transport activity is not involved in the d-glucose-induced down-regulation of total adenosine transport.

Adenosine↗

Copper overload affects copper and iron metabolism in Hep-G2 cells.

Divalent metal transporter #1 (DMT1) is responsible for intestinal nonheme Fe apical uptake. However, DMT1 appears to have an additional function in Cu transport in intestinal cells. Because the liver has an essential role in body Cu homeostasis, we examined the potential involvement of Cu in the regulation of DMT1 expression and activity in Hep-G2 cells. Cells exposed to 10 microM Cu exhibited a 22-fold increase in Cu content and a twofold decrease in Fe content compared with cells maintained in 0.4 microM Cu. (64)Cu uptake in Cu-deficient Hep-G2 cells showed a twofold decrease in K(m) compared with cells grown in 10 microM Cu. The decreased K(m) may represent an adaptive response to Cu deficiency. Cells treated with >50 microM Cu, showed an eightfold increase in cytosolic metallothionein. DMT1 protein decreased (35%), suggesting that intracellular Cu caused a reduction of DMT1 protein levels. Our data indicate that, as a result of Cu overload, Hep-G2 cells reduced their Fe content and their DMT1 protein levels. These findings strongly suggest a relationship between Cu and Fe homeostasis in Hep-G2 cells in which Cu accumulation downregulates DMT1 activity.

Cation Transport Proteins↗

Epithelioid malignant peripheral nerve sheath tumour in a dog.

An unusual morphological variant of malignant peripheral nerve sheath tumour, in which the cells exhibited a predominantly epithelial morphology, was diagnosed in a dog. The animal had a history of progressive ataxia. Post-mortem examination revealed an infiltrative growth in the sublumbar region, encroaching on the L1 and L2 vertebral bodies; additional masses were observed in the kidneys, liver and lungs. Histologically, the subcutaneous mass was composed of a dense population of spindle-shaped cells arranged in fascicles. The internal masses were composed of epithelioid cells arranged in a nodular pattern. Immunohistochemically, the spindle-shaped cells of the subcutaneous mass were positive for S-100, and the epithelioid cells of the internal growths exhibited weak S-100 immunoreactivity.

Animals↗

[Lung function in cardiac dysfunction].

OBJECTIVE: The alterations in lung function caused by heart failure were first described some decades ago. The advent of new tools for the diagnosis and investigation of heart disease, such as echocardiography, has subsequently made it possible to classify cardiac dysfunction with greater precision. The objective of this study was to analyze and compare a series of lung function and gas exchange variables in patients who had been classified into 4 groups according to type of heart disease as diagnosed by echocardiography. MATERIALS AND METHOD: Emergency room patients whose main symptom was acute dyspnea caused by cardiac or respiratory disease were included in the study. The final sample comprised 71 patients whose echocardiogram revealed cardiac dysfunction. Spirometry was carried out and resting arterial blood gases measured in this group. RESULTS: Of the 71 patients with cardiopathy, 31 had systolic dysfunction, 27 diastolic dysfunction, 7 cor pulmonale, and 6 primary valve disease. Spirometry revealed a generally obstructive pattern, more marked in the group with cor pulmonale. Analysis of arterial blood gases revealed slight hypoxemia with normocapnia in all groups, but this was more accentuated in the patients with cor pulmonale and diastolic dysfunction. An analysis of the correlations (Pearson's r) between cardiac and pulmonary variables revealed the statistically significant associations between cardiac mass and other variables to be as follows: forced vital capacity r=0.34 (P=.02), forced expiratory volume in one second r=0.526 (P=.0001), forced expiratory volume in one second as a percentage of predicted r=0.3 (P=.037), and forced midexpiratory flow rate r=0.31 (P=.03). The correlation between left ventricular ejection fraction and PaO2 was r=-0.312 (P=.01); the correlation between left ventricular end-diastolic diameter and PaO2 was r=0.369 (p=.006). CONCLUSIONS: In patients with cardiac dysfunction, spirometry reveals a generally obstructive pattern, which is more accentuated in patients with right ventricular dysfunction owing to the existence of prior lung disease. The associations found between the cardiac and lung function variables do not help the physician to determine the predominant diagnosis for a patient more precisely or to establish a prognosis.

Adult↗

[Comparison of arterial blood sample kits].

Most inaccuracies in the analysis of gases and electrolytes in arterial blood samples are due to preanalytic factors, among which is the type of equipment used for blood collection. Our objective was to compare arterial blood gas sample kits used under clinical conditions and to evaluate the impact of delay in estimation on variability in results. In 2 types of study we compared 5 kits (Radiometer's Pico 70, Becton Dickinson's Preset, SIMS Portex's Pro-Vent, SIMS-Concord's Pulsator, and Marquest's Quick ABG). In the first study kitsyringe assignment was randomized for collecting arterial blood samples from 160 consecutive patients to evaluate practical aspects of using them and the presence of bubbles in the samples taken. The second study evaluated the effects of delays of 30 and 60 minutes in estimation and of the type of heparin used in 54 blood samples. The kits which produced the fewest bubbles, gave samples with the greatest stability, and had the least impact on ion concentration were Radiometer's Pico 70 and SIMS-Portex's Pro-vent.

Blood Gas Analysis↗

Biological and economic optimum level of calcium in White Leghorn laying hens.

Calcium is important in eggshell formation; inadequate levels in the diet of laying hens may affect shell quality and egg production. An experiment with 250 Leghorn Hy-Line W-98 hens was conducted to evaluate 5 dietary Ca levels (2.96, 3.22, 3.83, 4.31, and 4.82%) in 3 laying periods. The evaluated variables were egg production (EP), egg mass (EM), average daily feed intake (ADFI), feed conversion (FC), and specific gravity (SG). The biological optimum level (BOL) of Ca for maximum egg production and specific gravity, and the economic optimum level (EOL) to maximize profits were calculated. There was no interaction between Ca level and laying period. The results show that the Ca level of the diet (P < 0.05) affected the intake of this nutrient (3.34, 3.68, 4.26, 4.89, and 5.39 g bird/day), ADFI (113, 114, 111, 113, and 111 g bird/day), and SG (1.080, 1.081, 1.082, 1.083, and 1.083). As the hens aged, EP and SG diminished (P < 0.05). BOL for maximum EP and SG were 4.34 and 4.62%, and EOL was 4.38%.

Aging↗

Human platelet antigen systems in allogeneic peripheral blood progenitor cell transplantation: effect of human platelet antigen mismatch on platelet engraftment and graft-versus-host disease.

BACKGROUND: Alloimmune incompatibility in allo-geneic stem cell transplantation (ASCT), pregnancy, and blood transfusion might trigger an immune response with clinical consequences. Human PLT antigens (HPAs), which play a significant role in pregnancy or blood transfusion-associated alloimmune thrombocytopenia, are also expressed on the surface of tissues affected by GVHD. Thus, HPA mismatch in HLA-identical ASCT could play a potential role in PLT engraftment and GVHD. STUDY DESIGN AND METHODS: We studied the HPA-1, -2, and -5 genotypes in Caucasian donors and patients involved in 77 HLA-identical ASCTs. We evaluated the association of HPA compatibility with clinical outcome, analyzing the relevance of host-versus-donor HPA incompatibility in PLT engraftment and donor-versus-host HPA incompatibility in GVHD. RESULTS: PLT engraftment and transfusion require-ments were similar in HPA-compatible and HPA-incompatible ASCT. Cases with severe thrombocytopenia or significant delayed PLT engraftment did not display host-versus-donor HPA incompatibility. Moreover, the incidence of GVHD did not correlate with HPA compatibility. CONCLUSION: Our results support no role for these antigens in immune complications of ASCT: PLT engraftment, requirement of PLT transfusions, and GVHD.

Adolescent↗

[Variables associated with functional recovery and post-discharge institutionalization of elderly cared in an average stay geriatric unit].

BASIS: To describe the evolution and results of the rehabilitation of elderly disabled cared in an average stay geriatric unit, and to define the factors associated with functional improvement and post-discharge institutionalization. PATIENTS AND METHOD: Observational longitudinal study in 459 patients with functional disability consecutively hospitalized between May 2000 and December 2001. Basal variables collected included the clinical, functional, mental, and sociodemographic manifestations previous to the admission. The favorable functional response (defined as a functional gain during the admission of > or = 20 points in the Barthel index) and the post-discharge institutionalization were regarded the main result variables. RESULTS: The average age of patients was 80.56 (SD: +/- 7.45) years, 64.9% were women and 81% came from acute hospital units; the main cause of disability was stroke (48.5%) followed by orthopedic pathology (26.2%) and immobility for different causes (23.5%). 72.5% of patients get functional improvement and 16.4% were institutionalized after the discharge. The main independent risk factors for poor functional response found in the multivariate analysis were a scoring in Pfeiffer's cognitive test of 5-7 points (OR: 0.42; 95% CI: 0,22-0.78) and > or = 8 (OR: 0.29; 95% CI: 0.12-0.71), and a scoring in Barthel's index < 60 prior to the deterioration (OR: 0.36; 95% CI: 0.14-0.93). Independent risk factors for institutionalization after the discharge were age (OR: 1.06; 95% CI: 1.01-1.12), and a scoring in the Gijon's sociofamiliar scale > or = 9 (OR: 6.83; 95% CI: 1.91-24.47). A functional disability after the discharge in the Barthel's index < 40 also was independently associated to post-discharge institutionalization (OR: 3,07; 95% CI: 1.04-10.06). CONCLUSIONS: Most of elderly with recent disability benefit functionally from care in specific hospital geriatric units. Moderate or severe cognitive deterioration after hospitalization is associated to lower recovery probability. Very advanced age, higher social precariousness and severe disability after discharge are associated with higher risk of institutionalization.

Aftercare↗

Developmental expression of neurotensin in thyrotropes and gonadotropes of male and female rats.

Besides its potential roles as a central neuromodulator or a hypothalamic neurohormone, neurotensin (NT) may also have endocrine function in the anterior pituitary of mammals. We previously found that NT immunoreactivity is present in the secretory granules of gonadotropes and thyrotropes in both male and female rats, where its levels of expression are under the control of sex steroids. In this work, using immunocytochemistry and in situ hybridization, we have studied the postnatal development of NT-like immunoreactivity (NTir) and the mRNA encoding NT (mRNA-NT) in specific anterior pituitary cells of both male and female rats. NT expression starts after birth and displays an identical pattern in both sexes until sexual maturity, with mRNA-NT being detected from day 2 of postnatal life in thyrotropes localized in the central portion of the anterior lobe. This pattern of expression develops progressively throughout the 2nd and 3rd weeks in both sexes. By the beginning of the 3rd week, mRNA-NT can also be detected in gonadotropes localized in the periphery of the gland coinciding with a rise in serum estradiol concentrations in both sexes, and by day 21, mRNA-NT is extensively present in both the periphery and the central region. NTir is observed from days 5-6 in thyrotropes predominantly localized in the central portion of the anterior lobe, and by day 21, NTir is also detected in gonadotropes localized in the periphery of the gland. This pattern remains similar in both sexes until the time of puberty, when female rats start displaying plastic changes in NT expression according to the stage of the estrous cycle. These findings indicate that NT expression in the rat anterior pituitary is cell specific, and develops from birth to adulthood under the control of sex steroid hormones. In addition, preliminary data showing the presence of NT receptors in rat pituitary cells support the hypothesis of a paracrine or an autocrine role for this peptide within the pituitary.

Aging↗

Field and in vitro assay of three methods for freezing ram semen.

Glycerol has been the most widely used cryopreservation agent for spermatozoa and a wide range of factors affect its action on sperm viability and fertilizing capacity. We tested three methods for freezing ram semen packed in 0.25 ml straws (final cellular concentration: 100 x 10(6) spz/ml). Method M1: Two-thirds of the final volume of diluent was added as solution A (without glycerol) to the pure semen at 35 degrees C. The sample was cooled to 5 degrees C (-0.30 degrees C/min), one-third of final diluent volume was added as solution B (final concentration of glycerol 4%) and the sample was maintained at 5 degrees C for 2h. It was then frozen in a programmable biofreezer (-20 degrees C/min down to -100 degrees C). Method M2: The sample was diluted with a specific solution at 35 degrees C (final concentration of glycerol 3%), cooled to 5 degrees C (-0.20 degrees C/min) and left for 2h. After that, it was frozen in nitrogen vapours. Method M3: Semen was diluted 1:1 in a specific solution (concentration of glycerol 2%) and cooled to 5 degrees C (-0.25 degrees C/min). The sample was then diluted again in the same solution to the final cellular concentration (final concentration of glycerol 4%). It was left for 1h at 5 degrees C and then frozen in a programmable biofreezer (-20 degrees C/min down to -100 degrees C). Best total motility (TM) and progressive motility (PM) (75.8 and 55.18%) were obtained using Method M3. Methods M1 and M3 gave significantly higher values (P<0.05) for kinetic parameters: average path velocity (VAP) (81.3 and 85.2 microm/s), straight-line velocity (VSL) (72.8 and 77.3 microm/s) and linearity (LIN) (66.6 and 68.8%). Method M2 showed the lowest kinetic parameters of motility (VAP 74.4, VSL 67.3 and LIN 62.5) and the highest percentage of cells with damaged plasma membrane (53.8%). Method M1 gave the worst results in viability and acrosome status assessed using fluorescence probes (31.3%-dead cells with damaged acrosomes-versus 25.4% in M2 and 23.3% in M3). A field trial carried out on fertility showed a significantly higher percentage of pregnant or lambing ewes (P<0.05) with Method M3 (67.3% versus 51.1% for M1 and 58.8% for M2). We concluded that the use of a simple dilution medium (test-fructose-glycerol-egg yolk) with the addition of glycerol (to 2% at 35 degrees C and to 4% at 5 degrees C) in two steps together with a programmable biofreezer was a productive method for freezing ram semen.

Acrosome↗

Expanded bed adsorption processing of mammalian cell culture fluid: comparison with packed bed affinity chromatography.

A comparison between expanded bed adsorption and conventional packed bed Protein A Fast Flow to purify the anti-rHBsAg mAbs from feedstock is presented in this work. Direct capture by STREAMLINE expanded bed adsorption chromatography resulted in 92% product recovery and sevenfold more concentrated product with similar purity levels compared to that obtained by the standard packed method. The process time and buffer consumption were reduced in the expanded bed adsorption method not only with the binding-elution conditions but also with the use of NaOH during the cleaning-in-place step. The latter is the most widely accepted agent in downstream processing, being a cost effective technique that provides not only efficient cleaning but also sanitizes complete column systems and destroys pirogens.

Adsorption↗

Gaseous emissions from ceramics manufactured with urban sewage sludge during firing processes.

The re-use of sewage sludge without any treatment as primary material-mixed with clays-in order to obtain structural ceramics for buildings has been successfully improved. In the Ecobrick project, the firing of a mixture of specific percentages of three components (clays, sludges and forest debris) resulted in a lighter and more thermal and acoustic insulating brick, compared with conventional clay-bricks. Volatile organic compounds (VOC) emission from the manufacturing of ceramics is the most important aspect to control. In the Ecobrick project VOC emissions were monitored by using a bench-scale furnace. The study was conducted using an EPA recommended sampling train and portable sampling tubes that were thermally desorbed and analyzed by gas chromatography/mass spectrometry. Drying of raw sewage-sludge and firing processes were considered separately. In this paper, we present VOC emissions coming from the firing step of the Ecobrick production.

Air Pollution, Indoor↗

Incomplete DJH rearrangements as a novel tumor target for minimal residual disease quantitation in multiple myeloma using real-time PCR.

The hypervariable regions of immunoglobulin heavy-chain (IgH) rearrangements provide a specific tumor marker in multiple myeloma (MM). Recently, real-time PCR assays have been developed in order to quantify the number of tumor cells after treatment. However, these strategies are hampered by the presence of somatic hypermutation (SH) in VDJH rearrangements from multiple myeloma (MM) patients, which causes mismatches between primers and/or probes and the target, leading to a nonaccurate quantification of tumor cells. Our group has recently described a 60% incidence of incomplete DJH rearrangements in MM patients, with no or very low rates of SH. In this study, we compare the efficiency of a real-time PCR approach for the analysis of both complete and incomplete IgH rearrangements in eight MM patients using only three JH consensus probes. We were able to design an allele-specific oligonucleotide for both the complete and incomplete rearrangement in all patients. DJH rearrangements fulfilled the criteria of effectiveness for real-time PCR in all samples (ie no unspecific amplification, detection of less than 10 tumor cells within 10(5) polyclonal background and correlation coefficients of standard curves higher than 0.98). By contrast, only three out of eight VDJH rearrangements fulfilled these criteria. Further analyses showed that the remaining five VDJH rearrangements carried three or more somatic mutations in the probe and primer sites, leading to a dramatic decrease in the melting temperature. These results support the use of incomplete DJH rearrangements instead of complete somatically mutated VDJH rearrangements for investigation of minimal residual disease in multiple myeloma.

DNA Primers↗

Incomplete DJH rearrangements of the IgH gene are frequent in multiple myeloma patients: immunobiological characteristics and clinical implications.

DH-JH rearrangements of the Ig heavy-chain gene (IGH) occur early during B-cell development. Consequently, they are detected in precursor-B-cell acute lymphoblastic leukemias both at diagnosis and relapse. Incomplete DJH rearrangements have also been occasionally reported in mature B-cell lymphoproliferative disorders, but their frequency and immunobiological characteristics have not been studied in detail. We have investigated the frequency and characteristics of incomplete DJH as well as complete VDJH rearrangements in a series of 84 untreated multiple myeloma (MM) patients. The overall detection rate of clonality by amplifying VDJH and DJH rearrangements using family-specific primers was 94%. Interestingly, we found a high frequency (60%) of DJH rearrangements in this group. As expected from an immunological point of view, the vast majority of DJH rearrangements (88%) were unmutated. To the best of our knowledge, this is the first systematic study describing the incidence of incomplete DJH rearrangements in a series of unselected MM patients. These results strongly support the use of DJH rearrangements as PCR targets for clonality studies and, particularly, for quantification of minimal residual disease by real-time quantitative PCR using consensus JH probes in MM patients. The finding of hypermutation in a small proportion of incomplete DJH rearrangements (six out of 50) suggests important biological implications concerning the process of somatic hypermutation. Moreover, our data offer a new insight in the regulatory development model of IGH rearrangements.

Clone Cells↗