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Biomedical subjects

M J Sánchez

Publications and source records attributed to M J Sánchez.

At least 19 recordsLinked to original sources

Reduction in the prevalence and intensity of infection in Onchocerca volvulus microfilariae according to ethnicity and community after 8 years of ivermectin treatment on the island of Bioko, Equatorial Guinea.

Bioko is the only island known in the world with endemic onchocerciasis. The island's rural communities consist of villages and cocoa plantations inhabited by Bubi and Fang ethnic groups. The aim of this study was to evaluate the impact of 8 years of vertical ivermectin distribution on the prevalence and intensity of Onchocerca volvulus infection in the rural population by means of pre- (1989) and post-long term treatment (1998) epidemiological surveys. In both surveys, the entire population of 12 randomly selected communities (1723 and 1082 individuals) was examined. The mean ivermectin therapeutic coverage for the 8 years was 53.2%. Iliac crest skin snips were used for differential diagnosis between O. volvulus and Mansonella streptocerca. The crude O. volvulus infection prevalence before ivermectin intervention was 74.5% (1284/1723); after the intervention it was 38.4% (415/1082). The Community Microfilarial Load (CMFL) before and after ivermectin intervention was 28.29 microfilariae/snip vs. 2.32 microfilariae/snip. The reduction in prevalence and CMFL after eight annual rounds of ivermectin treatment corroborates the drug microfilaricidal activity and good tolerability. In the pre-treatment survey, the prevalence was higher in the Bubi group (77.1%, 1126/1461); post-treatment it was higher among the Fang (51.1%, 92/180). The reduction in prevalence and intensity of O. volvulus infection differed between ethnic groups and communities.

Adolescent↗

Validity of self reported diagnoses of cancer in a major Spanish prospective cohort study.

INTRODUCTION: This study aims to assess the validity of self reported diagnoses of cancer by persons recruited for the Spanish EPIC (European prospective investigation into cancer and nutrition) cohort study and to identify variables associated with correctly reporting a diagnosis of cancer. METHODS: 41 440 members of EPIC were asked at the time of recruitment whether they had been diagnosed with cancer and the year of diagnosis and site. The process of validating self reported diagnoses of cancer included comparison of the cohort database with the data from the population based cancer registries. Cancer diagnostic validity tests were calculated. The association between a correct report and certain sociodemographic, tumour related, or health related variables were analysed by logistic regression. RESULTS: The overall sensitivity of self reported diagnoses of cancer is low (57.5%; 95% CI: 51.9 to 63.0), the highest values being shown by persons with a higher level of education or with a family history of cancer and the lowest values by smokers. Breast and thyroid cancers are those with the highest diagnostic validity and uterus, bladder, and colon-rectum those with the lowest. In both sexes the variables showing a significant association with a correct report of cancer are: higher education level, number of previous pathologies, invasive tumour, and, in women, a history of gynaecological surgery. CONCLUSIONS: The overall sensitivity of self reported diagnoses of cancer is comparatively low and it is not recommended in epidemiological studies for identifying tumours. However, self reported diagnoses might be highly valid for certain tumour sites, malignant behaviour, and average to high levels of education.

Adult↗

Nonvolatile memory with multilevel switching: a basic model.

There is a current upsurge in research on nonvolatile two-terminal resistance random access memory (RRAM) for next generation electronic applications. The RRAM is composed of a simple sandwich of a semiconductor with two metal electrodes. We introduce here an initial model for RRAM with the assumption that the semiconducting part has a nonpercolating domain structure. We solve the model using numerical simulations and the basic carrier transfer mechanism is unveiled in detail. Our model captures three key features observed in experiments: multilevel switchability of the resistance, its memory retention, and hysteretic behavior in the current-voltage curve.

Journal Article↗

Optimization of a solid-phase microextraction procedure for the determination of herbicides by micellar electrokinetic chromatography.

The use of a different optimization procedure that involves Experimental Design (ED) and Artificial Neural Networks (ANN) for the off-line coupling solid-phase microextraction-micellar electokinetic chomatography (SPME-MEKC) is presented. This combination of ED and ANN, mathematical tools not previously used in SPME-MEKC optimization, allowed us to obtain good extraction efficiencies in the SPME procedure for the determination of a group of eleven triazine herbicides in groundwater samples. Both extraction and desorption steps were carried out by solution stirring at 900 rpm. Optimal conditions for the off-line SPME procedure were: extraction with a poly(dimethylsiloxane)/divinylbenzene SPME fiber for 120 min, 10% (w/v) NaCl, desorption time 40 min, and 70% (v/v) of methanol/buffer as desorption mixture. Detection limits lay between 0.80 microg L(-1) and 4.89 microg L(-1). Finally, the optimized method was applied to the determination of these compounds in spiked and non-spiked groundwater samples using a previously optimized MEKC separation.

Chromatography↗

Lifetime body mass index and risk of oral cavity and oropharyngeal cancer by smoking and drinking habits.

The influence of body mass index (BMI) on oral cancer risk was evaluated in 375 incident cases and 375 age-gender-matched hospital-based controls. Low BMIs at diagnosis and 2 years before diagnosis were associated with significantly elevated odds ratios (OR for BMI < or =22 vs >26 kg m(-2); 3.64; 95% confidence interval, CI: 2.27-5.82 and 3.31; 95% CI: 2.04-5.39, respectively). The association with low BMI, however, tended to be weaker and nonsignificant among never smokers and never drinkers.

Adult↗

Bilateral paravertebral blockade for conventional cardiac surgery.

This prospective observational study aimed to assess the feasibility and efficacy of bilateral continuous paravertebral blockade combined with general anaesthesia in "on-pump" cardiac surgery. One hundred and eleven elective patients had two paravertebral catheters inserted: one either side of the midline within 2.5 cm of the spinous process of the third or fourth thoracic vertebrae, through which a mixture of ropivacaine and fentanyl was infused during and after surgery. In the first 47 patients, haemodynamic and analgesia data were recorded. In all patients, time to tracheal extubation, length of stay in the intensive care unit and the hospital, morbidity and mortality, and any complication attributable to the regional blockade were recorded. The technique was associated with good haemodynamic stability, good postoperative analgesia and short times to tracheal extubation, with few significant complications.

Adult↗

Thoracic epidural analgesia in coronary artery bypass graft surgery: seven years' experience.

OBJECTIVE: To evaluate the risk of neurologic complications caused by an epidural hematoma in a series of patients who had coronary artery bypass graft surgery with cardiopulmonary bypass under combined general and thoracic epidural anesthesia (TEA). DESIGN: Prospective observational study. SETTING: General hospital associated with a university. PARTICIPANTS: Seven hundred fourteen patients who had coronary artery bypass grafting surgery over a 7-year period. INTERVENTIONS: An epidural catheter was inserted at T(1)-T(3) as soon as the patient was in the operating room and local anesthetic was administered as a bolus and then as a continuous infusion throughout the operation and postoperatively. A set of safety guidelines was routinely followed. A protocol for postoperative neurologic evaluation was used to rule out any signs of spinal compression. MEASUREMENTS AND MAIN RESULTS: Preoperatively, a battery of coagulation tests was systematically performed including APTT, platelet count, and prothrombin time. Antiplatelet drugs (aspirin) were stopped at least 7 days before surgery. No patient required parenteral opiates postoperatively. Seventy-five percent of the patients were extubated in the operating room. No clinical epidural hematomas were detected. CONCLUSION: In this study, some of the benefits previously reported during cardiac surgery under TEA, such as excellent analgesia and early extubation, were confirmed. In addition, the series adds further evidence that adherence to a set of standard safety measures, in this setting, averts the occurrence of symptomatic epidural hematomas.

Aged↗

Oral and oropharyngeal cancer in Spain: influence of dietary patterns.

Cancer of the oral cavity and oropharynx is a major public health problem in Spain. Tobacco and alcohol have been identified as the two major risk factors for oral cancer in most western populations. Other risk factors include diets low in fruits and vegetables, but the impact of dietary habits on the risk of these cancers has never been assessed in Spain. The objective of this study was to elucidate the role of dietary habits in oral and oropharyngeal cancer, a multicentric case-control study was conducted in three areas of Spain (Barcelona, Granada and Sevilla) between 1996 and 1999. Cases were 375 patients (71 women), with incident, histologically confirmed cancer of the oral cavity or oropharynx, and controls were 375 subjects (71 women) admitted to hospitals for conditions unrelated to smoking or alcohol drinking. Data were analysed using multivariate logistic regression procedures. After allowance for education, tobacco and alcohol use, a significant inverse association with the risk of oral and oropharyngeal cancer was found for total consumption of total green vegetables (OR 0.54, 95% CI = 0.34-0.87) and total fruit (OR 0.52, 95% CI = 0.34-0.79) with significant trends in risk. We found that the protective effect of each of these food items was consistently larger among current smokers and among heavy alcohol drinkers, following a multiplicative effect model. In conclusion, this study provides further support to the beneficial effect of high intake of vegetables and fruits on the risk of developing cancers of the oral cavity and oropharynx in Spain, particularly among current smokers and heavy alcohol drinkers.

Adult↗

Serum aminopeptidase A activity of mice is related to dietary fat saturation.

A high intake of monounsaturated fat has been proposed to be a dietary factor that can decrease the incidence of cardiovascular disease and hypertension. In addition, increasing dietary fat saturation has been shown to increase plasma total cholesterol and elevate systolic and diastolic blood pressures. We demonstrated previously that cholesterol selectively increases in vitro aminopeptidase A activity, which is related to angiotensin metabolism. In this study, we investigated the effect of different degrees of dietary fatty acid saturation on serum aminopeptidase activities in vivo. Serum total cholesterol concentrations were also measured. Five groups of male Balb/C mice were fed for 10 wk diets containing 2.4 g/100 g of sunflower oil, fish oil, olive oil, lard or coconut oil. We measured alanyl-, arginyl-, cystinyl-, pyroglutamyl-, aspartyl- and glutamyl-specific aminopeptidase activities using arylamides as substrates. Serum total cholesterol levels were higher in mice fed diets containing saturated oils (lard and coconut) than in those consuming sunflower oil, which is unsaturated. Two of the serum aminopeptidase A activities (aspartyl and glutamyl aminopeptidase) increased progressively with the degree of saturation of the dietary fatty acids; activities were significantly greater in mice fed coconut oil than in those fed sunflower or fish oil. Therefore, the substrates hydrolyzed by this activity as well as their functions may be similarly affected. These results may have some implication for the treatment of cardiovascular disease.

Aminopeptidases↗

Selective rescue of early haematopoietic progenitors in Scl(-/-) mice by expressing Scl under the control of a stem cell enhancer.

The stem cell leukaemia gene (Scl) encodes a basic helix-loop-helix transcription factor with a pivotal role in both haematopoiesis and endothelial development. During mouse development, Scl is first expressed in extra-embryonic mesoderm, and is required for the generation of all haematopoietic lineages and normal yolk sac angiogenesis. Ectopic expression of Scl during zebrafish development specifies haemangioblast formation from early mesoderm. These results suggest that SCL is essential for establishing the transcriptional programme responsible for the formation of haematopoietic stem cells and have focused attention on the transcriptional regulation of Scl itself. Previous studies have identified a panel of Scl enhancers each of which directed expression to a subdomain of the normal Scl expression pattern. Among them, a 3' enhancer directed expression during development to vascular endothelium and haematopoietic progenitors but not to Ter119(+) erythroid cells. The expression in haematopoietic stem cells, however, remained undetermined. We demonstrate that this 3' enhancer directs lacZ expression in transgenic mice to most foetal and adult long-term repopulating haematopoietic stem cells, and therefore functions as a stem cell enhancer. Consistent with these results, expression in Scl(-/-) embryos of exogenous Scl driven by the stem cell enhancer rescued the formation of early haematopoietic progenitors and also resulted in normal yolk sac angiogenesis. By contrast, erythropoiesis remained markedly deficient in rescued embryos. This observation is consistent with the inactivity of the stem cell enhancer in erythroid cells and reveals an essential role for SCL during erythroid differentiation in vivo.

Animals↗

Enhancement of persistent currents due to confinement in metallic samples.

Confinement and surface roughness (SR) effects on the magnitude of the persistent current are analyzed for ballistic bidimensional metallic samples. Depending on the particular geometry, localized border states can show up at half-filling. These border states contribute coherently to the persistent current and its magnitude is enhanced with respect to their value in the absence of confinement. A linear scaling of the typical current I(typ) with the number of conduction channels M is obtained. This result is robust with respect to changes in the relevant lengths of the samples and to the SR. Possible links of our results to experiments are also discussed.

Journal Article↗

Phase II study of ifosfamide plus vinorelbine in metastatic breast cancer patients previously treated with combination chemotherapy.

Forty-six patients were included in a phase II study to evaluate the response rate and toxicity of a combination of ifosfamide and vinorelbine in metastatic breast cancer patients previously treated with one or more regimens of chemotherapy. Treatment consisted of ifosfamide 1.6 g/m(2) IV days 1-3 (with mesna) and vinorelbine 25 mg/m(2) IV days 1 and 8, every 3 weeks up to 6 cycles. The median age was 55 years (range 40-76), the World Health Organization (WHO) performance status was 0-1 in 93% of the patients and 2 in the remaining 7%. In all, 43% had received two or more previous lines of chemotherapy, and 91% had been treated with anthracyclines. Forty-four patients were evaluable for response, and all patients for toxicity. The overall response rate was 36.4% [95% confidence interval (CI) 22.4-52.2]. Stabilization was observed in 20.4% and progression in 43.2%. The median time to progression was 25 weeks (95% CI 14-36). Median relative dose intensity (=actual received dose intensity/planned dose intensity) was 0.99 for ifosfamide and 0. 80 for vinorelbine. The main toxicity was hematological, with 63% of the patients experiencing grade 3-4 neutropenia. With a moderate toxicity, this is an active regimen that may be taken into consideration in pretreated metastatic breast cancer patients when further chemotherapy is indicated.

Adult↗

Separation and quantitation of debrisoquine and 4-hydroxydebrisoquine in human urine by capillary electrophoresis and high-performance liquid chromatography.

A comparative study on the use of reversed-phase high-performance liquid chromatography (RP-HPLC) and capillary electrophoresis (CE) for the determination of debrisoquine (D) and its metabolite, 4-hydroxydebrisoquine (4-HD), in human urine is presented. Four different urine pre-treatments are compared for purification of samples prior to their injection in HPLC and CE. The use of a solid-phase extraction with a C18 cartridge provides the best results for the urine sample treatment, with good recoveries, i.e., 94.5% for D and 93.4% for 4-HD, and high reproducibility, i.e., R.S.D. N = 10 values of 1.7% and 1.2%, respectively. Under our separation conditions it is shown that CE is twice as fast and provides slightly better analysis time reproducibility than HPLC for this type of sample. Both the sensitivity and peak area reproducibility are better when HPLC is used. The two techniques show good agreement when employed for determination of phenotypes for hydroxylation, which seems to corroborate the usefulness of CE for this type of study.

Antihypertensive Agents↗

Nitric oxide production during the hyperacute vascular rejection.

A complete understanding of the biological mechanisms that take part in the hyperacute vascular rejection is necessary to prevent its development. Nitric Oxide (NO) release by the graft could be one of those mechanisms as cytokine induction of NO synthase in reticuloendothelial cells produces NO with cytotoxic activity. We have performed 20 heterotopic pig-to-dog kidney xenotransplantations in order to determine if cytotoxic NO is released during the hyperacute rejection. Nitrites and cGMP levels were determined in plasma samples taken from the graft artery and vein until vessel thromboses. NO synthase activity was measured in pieces from renal artery and renal tissue. The results show that after discordant xenotransplantation, inducible NO synthase is activated in the transplanted organ, indicating that NO can mediate host tissue damage during the hyperacute rejection.

Acute Disease↗

Characterization of the first definitive hematopoietic stem cells in the AGM and liver of the mouse embryo.

At day 10 in mouse gestation, the intraembryonic aorta-gonads-mesonephros (AGM) region generates the first definitive hematopoietic stem cells (HSCs) of the adult blood system. By 11 days postcoitum, the liver contains such HSCs. While HSCs of the adult bone marrow and late-stage fetal liver have been extensively characterized for cell surface markers, there has been no phenotypic description of the first HSCs during embryo development. We report here the temporal cell surface phenotype of HSCs from the AGM region and early fetal liver and show that all HSCs reside in the c-kit+ population. c-kit+ HSCs from AGM and liver are mainly CD34+ and in the AGM are in both Mac-1+ and Mac-1 fractions. These results demonstrate that during mouse ontogeny the first definitive HSCs are similar in cell surface phenotype to the HSCs of adult bone marrow but that spatial localization and developmental time are critical factors in the phenotypic assessment of this functional cell population.

Animals↗