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Biomedical subjects

M Márquez

Publications and source records attributed to M Márquez.

At least 19 recordsLinked to original sources

Molecular profiling and comparison of field transmissible spongiform encephalopathy cases diagnosed in Catalunya.

Molecular profiling of the proteinase K resistant prion protein (PrP(res)) is a technique that has been applied to the characterisation of transmissible spongiform encephalopathy (TSE) strains. An interesting example of the application of this technique is the ability to differentiate, at the experimental level, between bovine spongiform encephalopathy (BSE) and scrapie infection in sheep, and to distinguish between classical and atypical BSE and scrapie cases. Twenty-six BSE cases and two scrapie cases from an active TSE surveillance program and diagnosed at the PRIOCAT, TSE Reference Laboratory (Centre de Recerca en Sanitat Animal, Universitat Autònoma de Barcelona, Catalunya, Spain) were examined by Western blotting. Molecular profiling was achieved by comparing the glycosylation profile, deglycosylated PrP molecular weight and 6H4/P4 monoclonal antibody binding ratio. The results obtained during the characterisation of these field cases indicated an absence of atypical BSE cases in Catalunya.

Amino Acid Sequence↗

Model of an asymmetric DPPC/DPPS membrane: effect of asymmetry on the lipid properties. A molecular dynamics simulation study.

The study of asymmetric lipid bilayers is of a crucial importance due to the great number of biological process in which they are involved such as exocytosis, intracellular fusion processes, phospholipid-protein interactions, and signal transduction pathway. In addition, the loss of this asymmetry is a hallmark of the early stages of apoptosis. In this regard, a model of an asymmetric lipid bilayer composed of DPPC and DPPS was simulated by molecular dynamics simulation. Thus, the asymmetric membrane was modeled by 264 lipids, of which 48 corresponded to DPPS- randomly distributed in the same leaflet with 96 DPPC. In the other leaflet, 120 DPPC were placed without DPPS-. Due to the presence of a net charge of -1 for the DPPS- in physiological conditions, 48 Na+ were introduced into the system to balance the charge. To ascertain whether the presence of the DPPS- in only one of the two leaflets perturbs the properties of the DPPC in the other leaflet composed only of DPPC, different properties were studied, such as the atomic density of the different components across the membrane, the electrostatic potential across the membrane, the translational diffusion of DPPC and DPPS, the deuterium order parameters, lipid hydration, and lipid-lipid charge bridges. Thus, we obtained that certain properties such as the surface area lipid molecule, lipid head orientation, order parameter, translational diffusion coefficient, or lipid hydration of DPPC in the leaflet without DPPS remain unperturbed by the presence of DPPS in the other leaflet, compared with a DPPC bilayer. On the other hand, in the leaflet containing DPPS, some of the DPPC properties were strongly affected by the presence of DPPS such as the order parameter or electrostatic potential.

1,2-Dipalmitoylphosphatidylcholine↗

Immunohistochemical approach to the pathogenesis of bovine spongiform encephalopathy in its early stages.

An immunohistochemical and histochemical study was carried out on the brains of nine cases of BSE-diagnosed cattle as part of the surveillance plan in Catalonia, Spain. The animals had no clinical symptoms reported and were thus at early stages of the disease. The first part of the study consisted of a characterization of PrP(BSE) deposits throughout the encephalon. The behaviour of the different immuno-labelling patterns was analysed and tropism of some patterns towards certain brain areas was described. This tropism is principally directed to the brain stem region; however, an association of the stellate pattern was found with areas where PrP(BSE) is deposited less abundantly, such as the cerebral cortex. Secondly, distinct pathogenesis mechanisms that take place in the early stages of BSE, which would include these cases were investigated. This study describes the glial response to the presence of PrP(BSE) (using antibodies against astrocytic glial fibrillary acidic protein and lectin from Griffonia simplicifolia to identify microglia), the presence of mild oxidative stress phenomena (antibodies against metallothioneins I and II and against nitrated aminoacidic residues: nitrotyrosine), the apparent absence of apoptotic cellular death (cleaved caspase 3) and the preservation of synaptic proteins synaptophysin and small synaptosome-associated 25 kDa protein immuno-labelling. Finally, no alteration of the extra-cellular matrix was detected with the use of Wisteria floribunda agglutinin, a marker for perineuronal nets.

Animals↗

Cross-cultural study comparing the association of familism with burden and depressive symptoms in two samples of Hispanic dementia caregivers.

Familism has been pointed out as a key value in Hispanic culture that may or may not be associated with caregiver distress. Although groups included in the Hispanic identity have many common features, differences between Hispanic sub-groups in the relationship of familism with burden and depressive symptoms remain unexplored. The association of familism with burden and depressive symptomatology was examined in 48 Hispanic dementia caregivers from Los Angeles (CA, USA) and 60 from Madrid (Spain) through path analyses. Burden and depressive symptomatology were positively and significantly related in both samples. Familism was significantly correlated with lesser burden in the USA Hispanic caregiver sample, but with higher levels of depressive symptoms in the Spanish sample. Significant differences between Hispanic samples were found in the relationship between familism, burden, and depression, denoting the importance of specific cultural contexts influencing dementia caregiving in Hispanics.

Aged↗

T cell receptor excision circles (TRECs), CD4+, CD8+, and their CD45RO+, and CD45RA+, subpopulations in hepatitis C virus (HCV)-HIV-co-infected patients during treatment with interferon alpha plus ribavirin: analysis in a population on effective antiretroviral therapy.

Interferon (IFN)-alpha induced CD4(+) T lymphopenia is a toxic effect of the treatment of chronic hepatitis C virus (HCV) in human immunodeficiency virus (HIV)-co-infected patients. To increase the knowledge about this secondary effect, we performed an analysis of the evolution of the T cell receptor excision circles (TRECs), CD4(+) and CD8(+) T cells and of their CD45RO(+) and CD45RA(+) subpopulations during the treatment of chronic hepatitis HCV with peginterferon alpha (pegIFN-alpha) + ribavirin. Twenty HCV/HIV-co-infected patients, with undetectable HIV load after highly active antiretroviral therapy (HAART), were treated with pegIFN-alpha + ribavirin. TRECs were determined using real-time polymerase chain reaction. CD4(+) and CD8(+) T cells and their CD45RO(+) and CD45RA(+) subpopulations were analysed by two-colour flow cytometry. Median baseline CD4(+) and CD8(+) T cells were 592 mm(3) and 874 mm(3), respectively. Median baseline CD45RO(+) subpopulation was 48% for CD4(+) T and 57% for CD8(+) T lymphocytes. A progressive decrease in both T cell populations, as well as of their CD45RO(+) and CD45RA(+) subpopulations, was detected, with a difference between the baseline and nadir levels approaching 50%. The evolution of T cell populations and TRECs was independent of the response to the treatment. T lymphocytes and their subpopulations returned to baseline levels at 24 weeks after the end of treatment, with the exception of the T CD4(+) CD45RA(+) subpopulation. The ratio of CD4(+) CD45RO(+)/CD4(+) CD45RA(+) increased from 0.89 (baseline) to 1.44 (24 weeks after the end of the therapy). TRECs/ml did not return to the basal values. In conclusion, a significant reduction of CD4(+) and CD8(+) T cells, and of their CD45RA(+) and CD45RO(+) subpopulations, in HIV/HCV co-infected patients treated with pegIFN-alpha was observed. Both subpopulations increased after the suppression of treatment, but the CD4(+) CD45RA subpopulation did not reach the basal levels as a consequence, at least in part, of a decrease in thymic production.

Adult↗

Impact of highly active antiretroviral therapy on blood pressure in HIV-infected patients. A prospective study in a cohort of naive patients.

OBJECTIVES: To assess the impact of highly active antiretroviral therapy (HAART) on the blood pressure (BP) of naive patients after 1 year of treatment. METHODS: A prospective, observational study of 95 HIV-positive patients in our Unit starting HAART between January 2001 and October 2002 and maintaining the same regimen for 48 weeks of follow-up was carried out. Data on blood pressure (BP) and demographic, epidemiological, clinical, immunovirological and therapeutic characteristics related to HIV infection were collected prior to HAART and at week 48. High blood pressure (HBP) [systolic BP (SBP) > or =140 mm Hg and/or diastolic BP (DBP) > or =90 mm Hg] was defined according to international criteria. RESULTS: Of the 95 patients, 78 were men, 44% had AIDS and 68% were smokers, and their mean age was 40 years. At week 48 the prevalence of HBP was 26% and SBP, DBP and pulse pressure (PP) increased (121.8 versus 116.6 mm Hg, P=0.0001; 76.3 versus 69.7 mm Hg, P=0.004; 46.9 versus 43.8 mm Hg, P=0.001, respectively). Univariate analysis showed that HBP was associated with older age, higher body mass index (BMI), higher baseline lipids, and higher baseline BP. A linear regression model adjusting for age and sex suggested a significant impact of older age, higher baseline SBP, higher baseline hypercholesterolaemia and lower baseline CD4-cell count on SBP increase. CONCLUSIONS: Blood pressure increased after 48 weeks of HAART, leading to an important prevalence of hypertension. The increase in SBP depended on age and baseline lipid profile and immunological status. BP should be periodically measured and treated when necessary in HIV-infected patients on HAART.

Acquired Immunodeficiency Syndrome↗

Effect of antiretroviral therapy on admissions of HIV-infected patients to an intensive care unit.

OBJECTIVES: To analyse the characteristics of HIV-infected patients admitted to an Intensive Care Unit (ICU) and to compare them in the pre-highly active antiretroviral therapy (HAART) and HAART eras. METHODS: All HIV-infected patients who were admitted to the ICU of our hospital between January 1990 and December 2003 were reviewed. Patients were divided into two groups based on whether they were admitted before or after the advent of HAART, the cut-off date being 31 December 1996. RESULTS: Data were collected on 66 patients, 17 in the pre-HAART and 49 in the HAART era. The proportion of HIV-infected patients admitted to the ICU in our HIV-infected population increased after the introduction of HAART (3.8 vs 0.5%; P=0.001), and the largest diagnostic group was respiratory pathology in both periods. More than a third of patients were diagnosed with HIV infection during the ICU income, and only 31.2% were on antiretroviral therapy. The in-hospital mortality was 53.0%, and later survival was high. There were no significant differences between the pre-HAART and HAART eras. CONCLUSIONS: Our results suggest that the characteristics of HIV-infected patients admitted to ICU have not changed: respiratory diseases are still the most frequent cause of admission, in-hospital mortality is high, and later survival rates are good.

AIDS-Related Opportunistic Infections↗

Once-daily antiretroviral therapy: Spanish Consensus Statement.

BACKGROUND: Administration of antiretroviral therapy (ART) once daily is creating extraordinary interest among the members of the scientific community and also among those who receive the therapy. However, in clinical practice, some doubts remain about its use. OBJECTIVES: This document examines the characteristics and possibilities of treatment administered once daily. METHODS: Consensus of 248 Spanish experts in the field. RESULTS: Once-daily dosing is considered an added value which could favour adherence and, therefore, efficacy, as well as the quality of life of certain patients, however, the objective of adequate adherence in the long term is often difficult to achieve regardless of the treatment used. In theory, any patient can receive once-daily therapy, although some patients could particularly benefit from it, e.g. those with unfavourable social or personal circumstances, including drug users, patients whose treatment must be supervised, patients receiving multiple medications, or those who need rescue therapy after multiple treatment failures. At present, it is possible to design once-daily ART using some of the combinations of drugs considered as first-choice in national and international recommendations for antiretroviral therapy, but the options are still limited. The marketing of new drugs with this characteristic could allow us to increase the number and types of patient who can benefit from once-daily regimens, including those patients who need rescue therapy. CONCLUSIONS: Once-daily ART is a good alternative to regimens administered several times each day when a potent combination of active drugs is available.

Anti-HIV Agents↗

Electrophoresis of large polyelectrolyte-coated colloidal particles.

We perform electrophoretic mobility mu measurements of spherical colloidal particles coated with a charged polyelectrolyte shell versus 1:1 electrolyte concentration c. Instead of the expected Smoluchowski scaling law mu approximately c(- 1 / 2) for large kappaa, with kappa the inverse of the Debye length, we find that mu scales as mu approximately c(- 1 / 3). We account for this result using a general theory for the electrophoresis of soft particles [H. Ohshima, Adv. Colloid Interface Sci. 62, 189 (1995)] combined with the salt concentration dependence of the shell thickness, as described by Pincus [P. Pincus, Macromolecules 24, 2912 (1991)].

Journal Article↗

Comparative study of the PrPBSE distribution in brains from BSE field cases using rapid tests.

The distribution of PrP(BSE) in the brain of nine confirmed BSE field cases was analyzed using immunohistochemistry and compared to the levels of PrP(BSE) determined by two rapid tests (Prionics-Check WESTERN and Prionics-Check LIA). Each brain was dissected into 16 areas: spinal cord, medulla oblongata, pons, mesencephalon, thalamus, hippocampus, cerebellar vermis, cerebellar medulla, cerebellar hemispheres, occipital cortex, temporal cortex, parietal cortex, striatum, frontal cortex, piriform lobe and olfactory bulbs. The highest levels of PrP(BSE) were detected in the medulla oblongata, spinal cord and pons, and correspondingly both rapid tests showed 100% correlation with the immunohistochemistry with regard to sensitivity and specificity. Some inconsistencies between the levels of PrP(BSE) determined either by immunohistochemistry or by the rapid tests were found in brain areas with medium to low levels of PrP(BSE). These brain areas included the cerebellar hemisphere, olfactory bulb, and the temporal and parietal cortices. A brain PrP(BSE) distribution curve (BPDC) was designed by plotting the PrP(BSE) signals obtained from the two rapid tests versus the anatomical region along the caudal-rostral axis of the brain. Comparison of the BPDC of the nine BSE cases showed that all cases had a similar PrP(BSE) distribution in the brain but with variable intensities, which could be explained by different stages in the progression of the disease. We propose that the BPDC could be used as a tool to differentiate classical cases of BSE from the recently identified atypical BSE cases.

Animals↗

Electrophoresis of ionic microgel particles: from charged hard spheres to polyelectrolyte-like behavior.

We perform electrophoretic mobility measurements of ionic microgel particles in the deswollen and swollen phases. The results show that microgels behave as charged hard spheres in the first case and as free-draining spherical polyelectrolytes in the latter. A unified theory for the electrophoresis of polyelectrolyte-coated particles [H. Ohshima, Adv. Colloid Interface Sci. 62, 189 (1995)] is shown to contain the essential physics for describing the experiments, upon adequate consideration of the particles swelling behavior and network-solvent friction variations.

Journal Article↗

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↗

Steady cone-jet electrosprays in liquid insulator baths.

This study shows that conducting liquids can be electrosprayed in steady cone-jet mode inside liquid insulator baths. Experimental results show that the current emitted from the meniscus fits well the scaling laws given in the literature for electrosprays in air at atmospheric pressure or vacuum. The technique may be of interest in obtaining fine liquid-liquid emulsions of uniformly sized droplets in the nanometric range.

Journal Article↗

An experimental study of the electrospraying of water in air at atmospheric pressure.

Water solutions with electrical conductivities ranging from that of the deionized water up to 2 S/m have been electrosprayed in air through narrow silica tubes. Results show unambiguously that steady cone jets of water in air without the assistance of glow discharge can be formed for the range of electrical conductivities we have explored. The absence of corona discharge has been proven not only for the good agreement between the experimental results and the scaling laws given in the cone-jet literature but also for the independence of the spray current on the atmosphere (air or CO(2)) in which water was being electrosprayed. Other regimes such as the electric dripping and the assisted glow discharge cone-jet mode that appear in the electrospraying of water in air at room temperature have also been investigated.

Journal Article↗

Phase I trial on sms-D70 somatostatin analogue in advanced prostate and renal cell cancer.

Plasma concentrations and tolerability of a novel somatostatin analogue sms-D70 were studied in patients with metastatic hormone-resistant prostate cancer (HRPC) or metastatic renal cell cancer. To overcome the limitations of the octapeptides having affinity only to somatostatin receptor subtypes 2 and 5, HRPC expressing mainly somatostatin receptors 1 and 4, a somatostatin derivative based on the natural somatostatin having affinity to all five somatostatin receptor subtypes, was developed. The in vivo stability of this dextran-conjugated derivative, somatostatin-D70, was confirmed previously in animal studies, and the nanomolar "panaffinity" has been shown in in vitro receptor binding studies on cell lines transfected with the somatostatin receptor genes. Sms-D70 was given with subcutaneous injection once a week at dose levels of 5, 10, 20, 35, and 50 mg. For pharmacokinetic studies, sms-D70 was labeled with 131I. Fourteen patients were treated, of whom 10 had prostate and 4 renal cell cancer. The kinetic data revealed high stability with a long half-life in the blood. The drug was well tolerated, and no grade 4 (WHO) toxicity was observed. The maximal tolerated dose could not be established due to the lack of dose-limiting toxicities. Objective PSA responses were not recorded in these heavily treated patients, but subjective stabilization of pain was observed and urinary symptoms were alleviated in four patients. Three patients with metastatic HRPC received 5-10-mg intravenous injections of sms-D70 once weekly for 4-14 months on a compassionate use basis. In all cases, serum PSA values decreased more than 50% from the pretreatment level, but these results are difficult to interpret due to concomitant treatments given to these patients. In conclusion, sms-D70 was well tolerated in the treatment of metastatic prostate and renal cell cancer, but no responses were found in these heavily treated patients.

Adult↗

Gender differences and outcome in schizophrenia: a 2-year follow-up study in a large community sample.

This study examined gender differences in the short-term (2 years) course of schizophrenia in a sample of 200 schizophrenic (DSM-IV criteria) outpatients (74 women and 126 men). Number and length of hospitalizations during the prospective follow-up were recorded. After 2 years, men were found to have more hospitalizations and longer stays than women. Among subjects who had at least one hospitalization (12 women and 38 men), men had greater length of hospitalization. In conclusion, schizophrenic women had a significantly better short-term outcome.

Adolescent↗

Alcoholism in 274 patients with panic disorder in Spain, one of the main producers of wine worldwide.

BACKGROUND: Though panic disorder (PD) and alcoholism have been found in epidemiologic studies to often co-occur, the influence of cultural factors on the order of onset of the disorders has not been frequently addressed. METHODS: A sample of 274 patients with PD was assessed and compared according to the presence of alcohol use disorder (AUD) (alcohol abuse or dependence), employing several clinical scales. RESULTS: A total of 26 subjects were diagnosed from AUD. In 73.1% of patients, onset of alcohol use was previous to PD onset. PD subjects with AUD were found to have an earlier age at PD onset. They were more likely to be males, to have a family history of alcoholism, to abuse other drugs and to experience a more severe PD (more attacks in the last month, higher scores in anticipatory anxiety). CONCLUSIONS: Patients with PD and alcoholism may represent a distinct clinical subgroup. Our finding of an uncommon order of onset for both disorders may reflect cultural influences. CLINICAL IMPLICATIONS: (i)The study of panic disorder patients with comorbid alcoholism may help to better characterize this subgroup of patients. (ii) Patterns of alcohol use and the order of onset of both disorders may be influenced by cultural factors, with important practical implications. (iii) Patients with panic disorder and alcoholism may represent a distinct clinical subgroup, with an earlier age at panic disorder onset and greater clinical severity of anxiety. LIMITATIONS: (i) Our results refer to a clinical sample, which may not be representative of the general population. (ii) Alcoholic patients with a history of other drug abuse or dependence were not excluded. (iii) Owing to the small sample size, patients with alcohol dependence and with alcohol abuse were not separated.

Adult↗